Category: Blog

 

 

You must appreciate that more than 70 lakh people die of a heart attack in a year, almost 2 persons every second. No wonder so much rime and effort has gone into analysing the cause and management of this disease. The maximum number of research papers still deal with heart attacks. More people die because of a heart attack than those who died in the 2 World Wars, last century. Compared to heart attacks only 300 people have died so far because of the novel corona virus, or the 2019-nCoV. All deaths have taken place within China with the first out side death reported from Philippines this morning. This was a 44 years old man who had returned from China, was doing reasonably well the past few days but suddenly deteriorated in the last 24 hours and perished. He was diagnosed with “severe pneumonia” due to 2019-nCoV. There have been cases reported from other countries but no mortality. The situation however is fluid, we know little about the virus as of today. The clinical picture is evolving and the coming week will provide more information. Today it is clear that the virus has sprung from Wuhan, ion fact a meat market that sold just about everything that moved; including cats and wolves, pea cocks and rats, raccoons and snakes. The 2019-nCoV most probably resided in bats or snakes, and from there leaped into humans consuming wild animals or being in close proximity to them. But the virus has the capability of launching an attack on other humans who never ever visited the meat market that now has been closed down, in other words is is transmissible.

 

 

 

There is a report from Germany that a German male citizen (of 33 years) who had a business meeting with an symptomatic Chinese lady, came down with fever, sore throat, chills and muscle ache. His throat swab and a sputum sample confirmed that he was infected by the new virus. Quantitative reverse-transcriptase-polymerase-chain-reaction assay was employed for confirmation.Interestingly the Chinese woman developed symptoms on her way back to China. The German then infected another 3 colleagues . Fortunately all of them had mild symptoms, none came down with severe pneumonia. This means 2019-nCoV can spread from asymptomatic carriers. A person can harbour the virus, and yet may not develop fever or cough; but still infect another perfectly healthy person. The fact that there are symptomatic carriers of the disease means that we still do not know the true prevalence of the problem. Also the number of patents who will die is still unknown, mortality is still a moving target. But the clinical picture keeps getting clarified by the day.

 

 

The study with the largest cohort of only 99 patients reports that the mean age of those affected was 55 years and 70% were males. Almost half of these patients had visited the notorious meat market of Wuhan. 2019-nCoV was confirmed by real time RT-PCR test that takes from 24 – 48 hours to get back. More than 80% of patients presented with fever and cough. One third had breathing problems. 75% had bilateral pneumonia while almost 15% had a ground glass appearance on chest CT scan. 17% developed acute respiratory distress syndrome (ARDS) and 11% of patients died of multi organ failure. There is one patient with pneumothorax.This is the highest recorded mortality so far; it matches that of SARS. The researchers emphasise that more men than women were infected, probably because women are more adept in fighting off infection by virtue of the X chromosome and their sex hormones. Also half of those infected by the new coronavirus had underlying diseases such as heart disease and diabetes. Older petiole with weaker immunity are more susceptible to 2019-nCoV.

 

In most patients lymphocytes ( a type of white blood cell) were reduced in number indicating that the new virus attacks them, especially T lymphocytes. The 2019-nCoV particles spread from lung mucosa into other cells and generate a variety of immune responses. Some patients rapidly develop ARDS and septic shock, followed by multi organ failure. Th researchers recommend administering intravenous immunoglobulin in severely ill patients; and steroids (methylpredinisolone 1-2 mg/kg per day). A low lymphocyte count not only is a prognostic marker but may also be used for early diagnosis in the clinic. Secondary infections included A.baumannii, K pneumonia, A flavus, C glabrata, and C albicans.

 

 

The only confirmed US citizen case is a 35 years male who visited his family in Wuhan, China. He complained of cough with fever for the previous 4 days.The patient was a non smoker and had no prior history off any disease. His chest auscultation revealed rhonci, but his chest X Ray was normal. His naso-pharyngeal and oropharyngeal swabs tested positive for 2019-nCoV by real time RT-PCR assay. The patient was hospitalised for persistent dry cough and 2 day history of nausea and vomiting. He however had no shortness of breath or chest pain. A stool test also confirmed 2019-nCoV infection by Rt-PCR but his blood sample was negative for the virus. He received supportive treatment. His white cells were low, and so was the platelet count. Liver enzymes were raised. Blood cultures were negative. A second X Ray showed pneumonia of the lower left lobe of the lung.The patient was treated with vancomycin (i gram intravenous 8 hourly) and cefepime( IV 8 hourly). The patient developed rhoncis while in hospital and so an antiviral was initiated ( IV remdesivir; a novel nucleotide analogue prodrug in development) on day 7 in hospital, with no adverse effects. The patient began recovering from day 8.

 

There are still many gaps in the understanding of this new virus, which the WHO has delved a global emergency. The virus was rapidly multiplying and transmitting probably all of November and December last year. The initial response by the Chinese government was tardy, but this may have been because of local bureaucratic inertia. But once officially reported on the last day of the last decade, the Chinese efforts have been stupendous. There has been swift transmission of data and information. A 1000 bedded new hospital has been constructed in a mere 10 days! This will function from tomorrow with 1400 health workers in attendance (from the military). Another equally large hospital is being made, to mange the imminent epidemic. More than 60 million people are still under lock down, their entry and exit shut down. A quarantine off this magnitude has not been witnessed before. It is a moot point whether this will stem the flow of virus transmission. The root cause needs to be tackled, this mandates a cultural shift, easier said than done. How do you convince hundreds of millions of people to stop eating wild animals. The meat markets selling wild animals have to be shut down forever if one seriously wants to prevent another novel virus outbreak. The WHO has done to declare global emergency, because if one third of patients need intensive care admission the best off health systems can be put under tremendous strain. The many low and medium income countries will just not be able to cope. Hence the disease needs to be contained with great vigour.

 

There is no need for panic. The army need not be called in. Common sense measures such as frequent washing of hands with soap and water will go a long way in prevention. Sneeze or cough in a tissue and throw it into a bin, avoid a manifestly sick person, consult your doctor if you have fever with cough, especially if you have come into contact with a person from China or a person who been in contact with a person from China. As they say constant vigilance is the price both of freedom and especially public health. So stay alert against any viruses of any kind, particularly viral tweets and Whatsapp messages that are invariably devoid of any science. Stick to the WHO for information or peer reviewed medical journals.

 

 

2020 will be considered a seminal year for ushering in the new but deadly Coronavirus and the CAA. The silver lining probably is the new kid on the block number 4, Shreyas Iyer who has emerged as the number 4 batsman in limited over cricket by playing some breathtaking shots in consecutive innings against big teams such as Aussie ( in India) and Kiwis ( in New Zealand). Astonishingly the young man was not even thought of during the last World Cup inspite of a gaping black hole in the middle order. Importantly, Iyer ensured the Delhi IPL team reached the semis for the first ever time in the last IPL tournament, Delhi had all these years nestled in the bottom. There is captaincy potential in the lad; he without any doubt is a special talent.

 

The government has set the cat among the pigeons with the CAB and NRC. No Indian needs any elaboration on the acronyms, we have a raging bull in the China shop, only this time the shop is very much Indian. It is quite manifest the current rulers want to pulverise the constitution; they were absent when it was made; so therefore the onslaught now to make amends. Current thinking is not to care a hoot about minorities , women or the less privileged. If they had their way they would raze JNU, Jamia, and AMU to the ground and any other university that whispers any protest. Stephen’s too is up in arms. Few know the Quit India was almost launched from Stephen’s College. The then Vice Chancellor then mercifully looked the other way despite concerns of the Viceroy. The IIM’s and IIT’s have expressed their strong disapproval of the JNU fiasco, which of all things demonstrated the current dispensations penchant for cracking open heads of girl students. Gallantry at its best by the intrepid Delhi police.

 

The economy persists in lurching from disaster to another, it in fact is plummeting quicker than a tear-gas grenade hurled into a library. Hence, some learned chaps have cautioned us of diversionary tactics by the government. Divert and distract seems to be the current mantra of there government. But to fathom the working of the government it is critical that one reads up the biographies of Savarkar and Golwalkar, if not Doctorji Hedgewar. All three were very clear that Muslims at best can be second class citizens within the boundaries of Mother India, and that this privilege should be considered to be a favour. Christians too could settle for runners up if they were serious about settling in the local habitat. This is the core principle of Hindutva, that Hinduism is a more than a cut above the rest of the pack. Hence the brazenness in the current acceleration of transmitting the finer print in the party’s manifesto; comparable to the transmission of the new corona virus evolving from central China. A noted historian has rightly stated that our contemporary image abroad is mud or something to that affect. Not untrue, but there may be a tinge of exaggeration, for why would the West really care what transpires within our shores. They have their own problems, and serious ones at that. The Republic Day parade tomorrow will be watched by the Brazilian president who has gone on record that he wished all indigenous folks of Brazil should have been exterminated. A brilliant choice for chief guest; an amazing resonance of our current mindset.

The last day of the last decade provided the information that a brand new viral disease had emerged in Wuhan, China. Within a week a new virus was recognised, which the WHO has named “2019-nCoV”. I wish some one in the WHO had had the common sense to call this new virus “2020”, which sounds as deadly as the old “ 303” rifle the Indian soldiers had to employ in the 1962 Chinese conflict. 2019-nCoV sounds like an ISRO satellite. Any way the new virus has an RNA core and belongs to the corona virus family, corona means crown or the halo surrounding the sun. The arteries supplying oxygen to the heat are also called coronary arteries because the heart is considered the crown. This new RNA virus is called corona because under the electron microscope it is round in shape with spikes poking out from its periphery. Coronavirus are famous for producing that sniffling cold you get, but that is self limiting without any residual affects. The common cold by itself is benign. However, coronavirus have been incriminated in the severe acute respiratory syndrome or SARS, and also the Middle East respiratory syndrome or MERS. SARS carried a mortality rate of 10%, which is more than a heart attack treated in a city hospital. The mortality rate for MERS has been reported as high as 37%. The take home message is clear, the coronavirus is associated with considerable lethality. This is there reason the entire medical world is carefully looking at China. The Chinese have already reported 56 deaths, and more than 1500 confirmed cases. The mortality rate target is unclear right now, but is close to 5%, but this can vary for little is known about the toxicity of the virus or the response of a victim.

 

This week’s lancet carries the first clinical report that is quite disturbing. The cohort is just about 40 patients, of which one third landed up in the intensive care unit; and as many as 15% of these succumbed to the infection. Almost all patients present with fever, more than two thirds had cough and almost 50% suffered from weakness or muscle ache. More than half complained of shortness of breath. The paramount reason for breathless is the fact that this new virus attacks the lungs and not just the throat. Patients so far have not presented with a sore throat, the reason being that the 2019-cCoV launches an attack at the intraepithelial cells of lung tissue. 2019-nCoV not unlike other virus disease presents with low white cells and reduction in lymphocyte count, and raised liver transaminase levels.Where did this new virus suddenly come from? The internet is already awash with conspiracy theories that the virus already has a patent with a vaccine ready for administration. This is of course nonsense. The American Supreme Court has already declared that because virus are precent in nature there can be no patent for a virus sequence. Also there is absolutely no vaccine, neither is there a vaccine for SARS or MERS. The origin of the virus responsible for both SARS and MERS is the bat. In the case of SARS the concerned virus jumped from an infected bat to a civet and from that to humans. The MERS virus similarly vaulted from bats to camels and thence to humans.

 

The New England Journal of Medicine has published a paper, which defines the genome sequence of the 2019-nCoV. The genome will go a long way to understand the origin and evolution of the virus. And therefore a step however small has been made to construct a vaccine. Interestingly there are reports that the 2019-nCoV probably also originates from bats. But the intermediary animal is as yet not known. Some scientists are pointing fingers at a Chinese snake or the cobra. Crucially ground zero is a sea food market in Wuhan that sells just about any meat, the Chinese have a very diverse and heterogenous menu. The lesson for now is to refrain from eating exotic meats.

 

 

The 2019-NCov attacks the lungs with development of multiple pneumonia in both lungs. Soon the lungs adopt a ground glass appearance on a CT scan. This is when matters have gotten very grim for the patient can now die. There is no specific treatment, management being supportive. Treat fever with paracetamol, and when the lungs begin to fail intubate there patient and attach him to a mechanical ventilator hoping for the best. There is no proven antiviral treatment for the coronavirus. A combination of lopinavir and ritonavir did show some promise in patients with SARS, but this was in the lab and not in humans.A randomised study is being done in Saudi Arabia in patients with MERS ; a combination of lopinavir, ritonavir and recombinant interferon beta-1b versus placebo; the results are awaited. But no effective treatment has been developed for the new virus for obvious reasons, it is clinically less than a month old. The genome sequence has established birth of the virus as recently as October-November of 2019. The new virus genome sequence suggests its is 80% similar to the SARS virus. The 2019-nCoV virus has already been detected in Taiwan, South Korea, Japan,Vietnam and as close as Nepal. Cases have been reported from the USA and Europe. There is no reason to believe that 2019-nCoV is not already in India. We have scores of students studying medicine in China apart from people in the business community.

 

 

The WHO has swung into action by providing simple guidelines for prevention, wash your hands as often as possible with soap, stay clear of people with fever and cough, do not eat uncooked meats, if you have fever with cough and breathlessness consult a doctor as soon as possible. The new virus is capable of being transmitted from human to human, manifesting in global spread. Management is still unclear, but in the event of pneumonia admission to an ICU is warranted if not isolation. It was imperative that scientists, physicians, researchers and health workers crystallise a blueprint to diagnose, treat and contain 2019-NCoV. This is easier said than done; likewise the vigil regarding CAA and NRC will be a formidable task. The treatment for the latter understandably much more difficult. As for the 2019-nCoV infection, we  now have 1600 confirmed cases, world wide, surely a conservative estimate. There have to be many more sub clinical patients, or those with less severe symptoms and therefore have not bothered to walk to a physician. Huwan is under lockdown, which implies no one is allowed to leave it unless there is an emergency. Railway stations and airports are closed. Two doctors treating patients with the new virus have died, one from a heart attack. Wuhan today is a ghost city. The Daily Mail (UK) carries a story that 90,000 people have been infected by 2019-nCoV in China.

 

 

 

 

There is something toxic with the Indian intelligence agencies. Its still too early to know how deep the rot is but it cannot be less than considerable. The question hovering around now is whether national security has gone septic now or whether it had been so for some time now. Even at first sight the arrest of Mr. Devinder Singh, DSP from Kashmir promises more than a sniff of a policeman gone corrupt. . Mr.Singh was remarkably nabbed ferrying not 2 but 3 terrorists in a car probably directed towards Delhi. Crucially the Republic Day is around the corner. Apparently the terrorists began their fantastic voyage form Mr.Singh’s home., a quaint coincidence. The Wire has reported that Afzal Guru had actually written a letter in broken English describing some strange events. Afzal Guru subsequent to being mercilessly tortured by Mr Singh, and coughing up Rupees 80,000 to him, was urged by Mr Singh to ferry Mr Mohammad (who did not speak Kashmiri) to Delhi. Afzal Guru was instructed by Mr.Singh to provide accommodation for Mr. Mohammad in Delhi, in fact Afzal Guru also helped Mr Mohammad purchase a car form Karl Bagh. The same Mr Mohammad was among the 5 terrorists shot dead in the Parliament Attack. Incidentally my Father was in Parliament that fateful day, and was quite unfazed when he got home. Afzal Guru wrote that both he and Mr Mohammad had mobile phones that received calls from our Mr Singh before the Parliament attack. The credibility of this letter is on thin ice because a man sentenced to hanging (until dead ) can clutch at straws. But Mr Singh has with great pride publicly acknowledged torturing Afzal Guru while the man was in his custody. Mr Singh was also posted in Pulwama, and till a few days before getting arrested was a part of the anti hijacking team at Srinagar airport. Why would a senior police man , an important component in the security apparatus of Kashmir , get conveniently caught escorting chaps from Hizbul Mujahideen? His chutzpah is breathtaking; it was as if he has been doing this on a regular basis; it is too audacious for a cop gone rogue. There is obviously much more than that meets the eye. It certainly a bit more complex than senior journalists attempting to tidy up the clutter around us. In the process they reveal their naiveté.

 

The Indian public knows little of “false flags.” Simply put the classic False Flag is to stage or actually attack one own asset, property or installation in order to agitate the public to the extent that people demand action. One of the first false flag operation was done by the Germans who attacked their own transmitter station, but alleged the Poles had done it; to subsequently launch an all out attack against Poland. The German people were indignant enough to egg their forces on with tremendous gusto; little realising a World War had been ignited, which ultimately would result in the death of millions and the ruin of Germany itself. The Japanese had staged a demolition job on its own railway to invade China, alleging the Chinese were behind the railway sabotage.

 

The Russians have been incriminated in a number of recent false flag attacks; the Russians are experts in false flag cyber attacks. Russian intelligence recently launched several hackings into 20 countries , mostly in the Middle East. Iran was the suspect but actually it was Russian intelligence , mercifully there was no attack against Iran then. The Russians probably never intended Suleimani’s assassination. A False Flag cyberattack is when a hacker stages an attack in such a way that the victim or people at large blame the state being framed.

 

Sony Pictures was hacked in 2014, with huge amounts of personal data being flung out in the open. The ‘Guardians of Peace” took initial responsibility but forensics finally figured out that the North Koreans were behind the hacking. Pro Russian hackers in Ukraine penetrated sensitive data of the (pro West) Ukraine government and also NATO to release information that deeply embarrassed the Americans and the EU. You have to admire the Russians, who took over an Iranian hacking team without the Iranians having a clue. “Tulra” (Russian)took over “Oilrig”(Iranian). The Russians were masquerading as Islamists. The Iranians were running a hacking ship minus their own flag but a fake flag; as and when possible they merrily cyber attacked vulnerable countries. Russian intelligence however penetrated the Iranian ship and used the Iran flag to assault whom they wished; the victims after rigorous investigation concluded the culprit was Iran ! What a False Flag by the Russian !Its not the Russians alone, the Americans and Israelis are equally adept and nimble with False Flags.

 

The New York Times published an Opinion piece on the bombing of 2 oil tankers in the Gulf of Oman. The Americans claimed the attacks were done by Iranians. The Iranians immediately issued a firm denial. According to the Americans Iranians had placed a bomb on the side of the oil tankers. They had video evidence of the dark deed. But careful scrutiny by independent security experts failed to confirm the American version. The opinion article highlights “The Gulf Of Tonkin incident.” The Americans had accused the North Vietnamese of attacking American destroyers in 1964, this enabled president Lyndon Johnson to persuade the Congress to permit escalation of American military intervention. Historians however have concluded that no American destroyer was attacked, it was a False Flag operation to ensure greater American military involvement in Vietnam. The 26/11 Mumbai attack was not a False Flag however much conspiracy theorists may advocate, because the government of the day did not stand to benefit in any way, moreover it did not, the dastardly attack in fact proved very embarrassing for the Congress party.

 

The Kashmir DSP’s arrest is a cause of concern; are we on the brink of further shock.Sepis is feared for exactly this, patients if not treated quickly enough go down the slippery slope of shock. Sepsis is the deranged and dysregulated life threatening response of the human body to infection, accompanied by acute organ dysfunction. The body begins to attack itself in defence against the infection. The risk of death is high, in fact in many cases more than an acute heart attack. Once the qSOFA score exceeds 2 or if 2 of 3 conditions are present the chances of dying become 10%; the conditions are 1)altered mental status, 2) systolic blood pressure less than 100 mm Hg or 3) respiration rate more than 22/min. The patient ism considered to be in shock if she needs inotropic support to keep mean blood pressure over 65 mm Hg or have serum lactate greater than 2 mmol/L. This week’s Lancet has published an excellent article reporting the global burden of sepsis. As expected incidence and mortality are greatest in low and middle income group countries, India has slipped into the low income group.

 

In 2017 almost 50 million or 5 crore people suffered from sepsis across Earth. Sepsis kills more people than cancer, and kills 5 times more people than treat cancer in America. Of the nearly 50 million sepsis patients more than 11 million or 1.1 crore patients died in 2017, that is every 3 seconds one patient dies (Lancet 2020; 395: 200–11).

 

 

The incidence in 2017 is however less than in previous years, as there were more than 60 million cases in 1990. The recent figures rely own death certificates that may not be reliable, hence the figure of 50 million patients in one year could be a conservative estimate. The paper has been published by the Institute of Health Metrics and Evaluation at the University of Washington in Seattle. Half of the patients were children, the leading cause was diarrhoea for sepsis, while pneumonia caused most deaths. Recent guidelines underline the importance of sepsis being a harbinger of death that therefore mandates immediate response with broad spectrum antibiotics and intravenous fluids. Both gram positive (Staphylococcus aureus) and gram negative (Pseudomonas or E.coli) are responsible for most sepsis cases. The most important underlying cause was infection, followed by injury and non communicable disease.

 

 

The editorial applauds the first comprehensive world report on the epidemiology of sepsis; and urges that individual countries put up their own surveillance programs and protocols for treatment. Sepsis continues to be major cause of serious disease globally with there highest burden in low income nations.is not a disease but a syndrome that requires. Ironically the body mortally attacks its own organs while responding to an infection, a variant of a False Flag, bacteria frame the organs as the enemy, and the human body unleashes deadly chemical arsenal to destroy itself. Remember the bacteria has acquired its stealth after hundreds of million years of evolution; we are around a mere 200,ooo years old; puny compared to our co habitants of the planet. The bacteria hack is far superior to the Russians or the Americans; they delude us into believing that are own organs are the culprits, the result is total mayhem; the mother of all False Flags. No wonder 20% of all deaths in the world, due to illness, are because of sepsis. A victim , ladies and gentlemen, kicks the bucket, every 3 seconds.

 

 

 

It happened more than a decade ago but even now seems odd that as thousands of Tamil Sri Lankans were being slaughtered during the last days of the Sri Lankan civil war no concern was expressed by any Hindu organisation within our borders. More 100000 civilians lost their lives courtesy the Seri Lankan forces is the conservative estimate provided by the UN and observers. It got queerer when Prabkakaran’s only 12 year old child was shot dead by Sri Lankan forces after providing him a snack a couple of hours before; not a whisper from our humble God fearing folks; after all is fair in love and war, including pumping 5 bullets in a 12 year old form point blank range. Maybe the Scriptures prescribe cold blooded killing of the children of your enemies. Conceivably the little boy and his mother had followed the tenets of the Roman Catholic faith. His mother too was cut down in cold blood. So was his sister.I wonder what spin our television and You tube savvy Gurus provided then or will deliver now, regarding the killing of the children. The Upanishads or the Gita do NOT endorse the murder of innocent children or women. Astonishingly and appallingly despite being the largest cohort of refugees within in our shores , Tamils who fled the worst possible genocidal onslaught in living memory are not included in the CAA. To add to their infinite misery the Rajapaksa are back in complete control of Sri Lanka.To many the CAA is fair game.

 

 

Let us recollect the high profile murder of of one of Sri Lanka’s most distinguished journalists, Lasantha Wickrematunge in January 2009. Mr. Wickrematunga wrote a remarkable editorial that was published after he was killed.”In the name of patriotism you have trampled on human rights, nurtured unbridled corruption and squandered public money like no other president before you,” Mr Wickrematunge’s editorial said to Percy Mahendra Rajapaksa. It was not uncommon for dissenting voices to be harassed , intimidated or even murdered in Sri Lanka as recently as 10 years ago. “When finally I am killed, it will be the government that kills me,” he wrote, in a more than 2000 word edit republished by the Guardian and New Yorker and attracted international scrutiny of the harassment faced by Sri Lankan journalists. Alas Lasantha who presciently wrote “I hope my murder will be not seen as defeat of freedom but an inspiration”, seems largely ignored by the Indian media. As far as I am concerned absolute and utmost respect to one of the bravest journalists the world has ever known. I would urge you, no beseech you to read Lasantha Wickremtunge’s edit ( freely available online). It is a must read in today’s times. His is a biopic worth making. His is a name worthy of being taught to every school going child on the planet.

“But there is a calling that is yet above high office, fame, lucre and security. It is the call of conscience. Our commitment is to see Sri Lanka as a transparent, secular, liberal democracy.” We need Lasantha right now and right here.

 

 

Now to an equally important subject. The commonest valvular disease in the Western world is aortic stenosis. All cardiac societies agree that severe aortic valve stenosis can only be treated by intervention that is surgical aortic valve replacement (SAVR) or trans catheter aortic valve replacement (TAVR). The intervention however should be done only if the stenosis has become severe and the person concerned is symptomatic. Symptoms consist of chest pain, shortness of breath or syncope ( giddy spell). The aortic valve is considered severe when its are is less than 1cm2 or the flow across the aortic valve exceeds 4m/sec or the mean gradient is more than 40 mm Hg. A small randomised trial from Korea published this week makes the case of intervening in patients who have not yet become symptomatic. This trial randomised 145 patients with very severe aortic stenosis ( defined as aortic valve area equal or less than 0.75cm2 with either an aortic jet velocity of attest 4.5 m/s or a mean gradient of 50 mm Hg), to early surgery or conservative care as currently recommended. The primary end point was a composite of surgical mortality (death due to surgery upto 30 days) or death from cardiovascular causes. The followup extended to 8 years. The primary endpoint was significantly greater in the conservative cohort, it was 1% at 4 years and 1% at 8 years n the early surgery group versus 6% at 4 years and 26% at 8 years in the conservative group. Sudden death had occurred in 4% at 4 years and 14% at 8 years in the conservative group. The researchers have concluded that the composite of operative mortality or cardiovascular deaths are significantly lower when patients with very severe aortic stenosis are treated by surgery even though they are asymptomatic ( N Engl J Med 2020;382:111-9).

 

The study will however not change current guidelines because a few caveats shall have to be kept in mind. Firstly only 145 patients have been studied, and all of them belong to the Korean peninsula. The average age of these patients is relatively young at only 63-65 years. Most patients undergoing TAVR are nearly 2 decades older; and being older carry the burden of other co morbidities or illness with them. None of the TAVR randomised trials have included patients with bicuspid valve, while the Korean paper has more than half the patients suffering from bicuspid aortic valves (54% in the conservative group and 67% in the early surgery group).

 

 

Randomised trials in patients with severe symptomatic aortic valve stenosis undergoing TAVR have reported equal if not better results in patients with low surgical risk, we therefore our moving into an area where TAVR can be considered a suitable alternative in almost all patients with symptomatic severe aortic stenosis. The age of the patient best suited for TAVR is still to be ascertained, because the life of the TAVR valve (tissue valve) is not as yet clear. TAVR is hence best suited in patients who have crossed their mid seventies because of the durability question; consequently TAVR in a patient in her sixties would be questionable.

 

The editorial on the Korean paper highlights the fact that 22% of patients in the conservative group never underwent surgery. So how does one best tease out asymptomatic patients with very severe aortic stenosis for surgery? That may be clarified by completion of ongoing large TAVR randomised trials such as “AVATAR”, “ESTIMATE”, and “EARLY TAVR”, which are trials comparing TAVR in asymptomatic severe aortic stenosis versus watchful waiting.

 

 

 

Is Delhi burning? Not exactly but a couple of buses did get torched yesterday in south Delhi by angry protestors against the Citizenship Amendment Act. The Assamese too are more than irate at the new “Citizenship Amendment Bill “that was recently successfully thrust though the Indian parliament. Remarkably, there was little or no unrest while with National Register of Citizens exercise was going on in Assam. The affected folks were of course terrified.There was little to write home about after 19 lakh people were declared non residents or “illegal” occupants of the land. Even the realisation that of the these 19 lakh “illegal migrants” 15 lakhs were Hindus did not appear to cause great concern. The government however was obviously deeply concerned and swiftly moved into action. The “Citizenship Amendment Bill” got approved by both houses of parliament and shall soon be autographed by the president in Rashtrapati Bhawan. The citizens of Assam seem now to be acutely aware that the NRC exercise has served to purpose, they are back dealing with the same people they wanted out in the first place. Worse this time they shall not be dealing with “illegals” but those officially converted to “legals”, courtesy CAB. Small wonder the short lived sense of NRC relief has turned into a rage that has translated into violent protests, including the death of at least 5 people so far.

“The point is that it makes 200 million Muslims feel as if somehow their religion is not as valid or as Indian as the others. That’s not a good recipe for harmony.” That is Professor and Nobel Laureate Venky Ramakrishnan (2009 chemistry Nobel winner) on CAB  in his interview to The Quint. He went on to say despite not being a local citizen he has “deep affection” for India and he wants ‘India to do well.”

 

It is impossible to be bored in modern India, every new day is an event. Probably diversion is needed from the mundane narrative of a rapidly declining economy, they say sales of both toothpaste and underwear are down; forget about selling a house. More than 10 lakh flats lie unsold in major cities of the country. There manifestly is no money going around and hence little appetite for consumption. Apparently unlike the Chinese economy that is based on manufacturing , Indian fiscal health depends on purchase. But what do you buy when you are broke ?

 

 

A much smaller seismic event has taken place in the world of cardiology with little notice by the Indian media. It concerns the left main (LM) coronary artery, which is the most important artery of the heart because it supplies good to more than two thirds of heart muscle. It divides into the left anterior descending and left circumflex coronary arteries. Blockage in the left main artery is of great concern because death is imminent if no treatment is provided. This is one blockage that mandates intervention either by coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI) by stenting. Stents are tiny metallic tubes inserted into blocked arteries to make them patent. For many years CABG had been the only option for LM blockage or disease. Randomised trials done in the eighties of the last century had established superiority of CABG over medical treatment. The situation is much the same despite substantial improvement in medical therapy; left main disease can only be tackled by intervention; medicines do not work. The last decade however has witnessed the emergence of stenting as a viable alternative to CABG in the treatment of LM blockage or disease. Both American and European cardiology associations recommend PCI with stenting in LM disease of mild or moderate complexity based on the SYNTAX score, the recommendations are made based on clinical outcomes of high quality clinical trials. The first such trial to demonstrate equipoise between CABG surgery and PCI with stenting was the SYNTYAX trial, which randomised almost 800 patients of LM disease to CABG or stenting. The ten year long followup was recently published in the Lancet; the results suggested that mortality was the same whether a patient with left main disease underwent surgery or stenting. There was no significant difference in the death rate, even after 10 years.

 

 

 

The other big trial called “EXCEL”, however has become a huge controversy. The BBC beamed a documentary on accusations made by an author of the paper that vital data was concealed while publishing the paper in the prestigious New England Journal of Medicine journal. Professor David Taggart has been the “whistle blower” ; Taggart has withdrawn his name from the authorship of the paper because he believes that the incidence of heart attack has been withheld by the other investigators involved with the EXCEL paper. According to Taggart there were more heart attacks and more deaths in the stenting group as compared to patients undergoing CABG surgery, and that this data has been deliberately buried by the investigators of the EXCEL paper. EXCEL published its 5 years follow up recently, it recorded no significant difference in heart attack or death between CABG or stenting. Taggart’s allegations have been taken quite seriously by the European Association of Cardio-thoracic Surgeons (EACTS), which has gone to the extent of no longer supporting guidelines recommending stenting as an alternative to CABG.

 

The EXCEL trial was led by Professor Greg stone; it included almost 19005patients with left main disease; randomised them to CABG or stenting; and concluded that at the end of 5 years there was no difference in the composite of death, heart attack or stroke between CABg and stenting. Death of any cause occurred more frequently with stenting than CABG (13% versus 10%), but importantly definite cardiovascular deaths were similar (5% versus 4.5%). Heart attacks too were similar , around 10% in both groups. This is the data provided in the New England Journal of Medicine paper.

 

 

So how do we adjudicate the allegations made by Professor Taggart ( who by the way is a cardiac surgeon) and the BBC Newsnight investigation. Actually it is not too complicated. The problem lie not in the stars but in the definition of heart attack. You will be astonished to learn that even now there is no clarity as to what constitutes a heart attack. In simplest terms a heart attack implies that heart muscle is damaged to the extent that it is dead our necrotic; a small or large part of heart muscle gets damaged when an artery large or small gets completely blocked. One can therefore have a small or a large heart attack, which is measured by the amount chemicals or cardiac enzymes released by the necrotic heart muscle cells. The larger the damage the greater in quantum the release of these enzymes. There are largely 2 types of enzymes; creatine kinase MB (CKMB) and troponin (Tr). So far so good. The problem is that there is “Universal Definition” of heart attack and there is also a heart attack definition proposed by the Society for Cardiovascular Angiography and interventions (SCAI). The SCAI definition, to put it lucidly has a higher threshold or a higher bar; SCAI defines a heart attack subsequent to a PCI or CABG as an increase of CKMB ten times above the normal limit or a Tr increase by 70 above the upper limit. The “Universal” definition has a much lower threshold or bar to define a heart attack; the 2018 version defines a procedure related heart attack as a troponin level increase of 5 times more than the upper normal limit accompanied by ECG changes, 2 D echo demonstration of a new ischemic segment or the presence of (on coronary angiography) a blocked vessel, dissection of an artery or distal embolisation). So a heart attack is present with a lower bar when the “Universal” definition is employed; hence more patients will be classified as having a heart attack following a procedure. The SCAI definition on the contrary, with the higher bar, will identify fewer heart attacks. Professor Taggart and BBC Newsnight is deeply concerned that investigators of the EXCEL trial have used the SCAI definite and not the “Universal” definition, and therefore the allegation that had the “Universal” been used there would have been 80 times more attacks in the stenting group. These heart attacks were as explained involved a small area of the heart with little clinical significance. The Australian investigators reported that almost half of heart attacks using the “Universal”definition were due to occlusion of arteries < 1mm.

 

The response of Professor Greg Stone was swift; he put up a lengthy mail explaining the position of the Excel investigators. In a nutshell he emphasises the different thresholds of the 2 heart attack definitions. The riposte has already been explained by an elegant Australian study done a few years ago. The investigators of this trial used both SCAI and the Universal definitions in patients undergoing stenting. The patients were divided into a group with procedure related hear attack or a group without procedure related heart attack.They found that albeit more procedure related heart attacks were noted using the “Universal” definition than with the SCAI definition, at the end of 2 years the number of deaths or heart attacks were significantly greater with the SCAI definition ( 25% with positive SCAI versus 11% with negative SCAI). There was however no significant deaths/heart attack at the end of 2 years in patients identified as having stenting related heart attack when a rise in troponin was used (“Universal”). The Australian investigators reported that almost half of heart attacks using the “Universal”definition were due to occlusion of arteries < 1mm. Professor Greg stone in his explanation has underlined the fact that he and his co investigators considered the SCAI definition more suitable in the EXCEL trial. There was in the EXCEL trial no difference in heart attack at the end of 5 years with application of there SCAI definition. But the data on heart attack as per the “Universal” definition will be published also to further clear the air. He also made the point that the European association of cardiac surgeons should have sought an explanation from him before withdrawing from the left main revascularization guidelines.

 

The European Society off Cardiology however has not changed it’s recommendations regarding stenting in left main disease despite the BBC Newsnight investigation. Professor Taggart being a cardiac surgeon may be a bit sceptical about stenting and shall need to be satisfied by revealing the “Universal” heart attack numbers in ESCEL at the earliest. The BBC has pointed out that Professor Greg Stone has heaps of conflicts of interest. Stone is connected to nearly 20 stent/device companies as an adviser or other financial treated positions. The EXCEL rial was first presented at the TCT meeting , which one of the largest interventional cardiology conferences in the world. The TCT meeting is supervised by Professor Greg Stone , the lead author of EXCEL, and also millions of dollars are provided to TCT by nearly all major interventional cardiology product (stent) manufacturers of the world. EXCEL was supported by ABBOT , the maker of everolimus eluting stents used in EXCEL. Worse , one of the authors of the EXCEL paper has moved on to become the vice president of Medtronic, which is a giant stent manufacturing company. It will take some time for the air to clear; the issues involve life and death of thousands of left main disease patients.

 

 

It is important to mention a meta analysis of 24 prospective studies including almost 45,000 patients published in the current issue of EuroIntervention that concludes even 3 fold increase in troponin above the upper limit is associated with all cause mortality. The authors of this large meta analysis do not however discuss cardiovascular mortality; also studies that were included albeit prospective were not randomised. The editors of Eurointervention have issued a disclaimer that responsibility of the contents of this paper lies with the authors.

 

For now stenting should be considered for patients with the least complex left main blockage, and CABG surgery for more complex lesions; for the air to clear we may have to wait for another BBC Newsnight investigation. The SYNTAX trial is remarkable for concluding that even after 10 years there was no difference in mortality between stenting and CABG; and especially so because the stents used in SYNTAX were the paclitaxel eluting ones that are currently considered obsolete.

 

 

The evidence is surely chilling. The time to play the blame game is long past. Also, there is absolutely no need to point fingers because we probably have achieved the point of no return.The World Health Organisation seems rio have fixation for India. As per their latest data base , levels of PM 2.5 ( ultra fine particles smaller than 2.5 microns) are the highest in India. We currently have 16 of the world’s 30 most polluted cities. Remarkable figures that surely should be the discussed fiercely on all TV channels every night. Granted the dismantling of Article 370 and the majoritarian Supreme Court verdict on Ayodhya merit serious debate but the air around us is a killer. More people will die in this country each year than all the wars put together. Maybe even more than those slaughtered during Partition. Yet one does not perceive a proportionate outcry by the citizens of Delhi.Mercifully according to the WHO, the most polluted city on the planet is in Nigeria, a port named Onitsha. But Delhi cannot be far behind. Delhi recently bore the brunt of farm burning across adjoining states. The air quality was horrendous then, but is still potentially carcinogenic today. In fact I doubt there will be a single day in Delhi when we will be safe from bad air in the future. The population keeps rapidly climbing, construction work continues unabated and unchecked, and there is absolutely no solution for vehicular pollution. Ironically the slash in car and 2 wheeler sales could not have come at a better time, but the streets of Delhi are infested with traffic that churns out toxic air every minute of the day.

 

 

Somehow the consequences of bad air do not appear to sink in. We are indeed a stoic people, with the Mahabharata marvelling at the fact that we carry on living without the slightest acknowledgement of our imminent death. It has become a stale cliche to enumerate the horrible ways one can suffer by this toxic air around us. The list keeps increasing. We now know that just about every cancer in the body can be due to Delhi’s air because the 2.5 particles can affect every cell of the human body. It was already well known that bad air causes asthma, bronchitis and of course lung cancer. By penetration into blood these toxic particles affect the entire cardiovascular system; a chronic inflammatory condition is created. The person concerned becomes acutely vulnerable to high blood pressure, heart attack, heart failure and stroke. You are therefore looking at astronomical mortality figures. The biggest killer in the world continues to be cardiovascular disease, we are talking about more than 15 million deaths a year. A significant fraction of cardiovascular deaths are due to air pollution. The WHO is clear that air pollution kills around 7 million people each year. More than 80% people who live in cities monitoring air quality are exposed to toxic air around the world. The stats are staggering, while the response of people who matter in this country continues to be jaw dropping. As recently as August this year data showing independent associations between short term exposure of only 2 days to PM 2.5 and PM 10 ( particles 10 microns in diameter) and daily all cause , cardiovascular , and respiratory mortality has been published. The study included from m ore than 650 cities across the planet. A mere increase of 10 micrograms per cubic meter air in PM 2.5 and PM 10 was associated with a 36% increase in cardiovascular death and 47% increase in respiratory mortality. These mortality figures are from regions in the Northern hemisphere; the situation in India must be much more dire.

 

 

 

The connection between particulate air pollution and mortality was recorded as long as 70 years ago. There was clear evidence even then that number of deaths increased with higher levels of particulate matter (PM). The Dutch Environmental Longitudinal Study reported association of particulate matter pollution and mortality. Conversely the Chinese have very elegantly shown that bringing down particulate air pollution reduces stroke mortality. Air pollution ranked as the 11th most important risk factor of death and disability in the United States, while chronic obstructive pulmonary disease (COPD) is the third most common cause of death and disability. Crucially half of COPD patients have the disease because of poor lung growth rather than declining lung functions; every child in Delhi breathing toxic fumes is susceptible to developing chronic lung disease later on, part from having sub-optimally functioning lungs. There goes your future Olympic champion. Delhi had an Air Quality Index greater than 500 on 1st November 2019, that is 50 times more than the safe value of 50. The AQI was literally a stunner, because dear readers bad air adversely affects the human brain, by inducing depression, reducing intelligence and promoting dementia. Brain cancer too is on the list; it is a moot point whether dementia or brain cancer is worse.

 

 

 

 

We should be scrambling to tackle the mess we have created. This is not only a serious matter , it is downright deadly. Lakhs of lives are at stake besides increasing incidence of disabling and lethal disease. The problem is the public refuses to appreciate the looming danger. The time for the canary test is long past, right now Yama has comfortably settled himself in the largest sofa in the room, and he is larger than any known elephant. But he is not the one spewing out dirty air, for him it is collection time.

 

 

 

 

The much awaited ISCHEMIA trial was presented yesterday at the American Heart Association Meeting in Philadelphia, and the results were as anticipated by any common sense carrying doctor. Patients with stable angina , that is chest pain occurring only on walking, running or any other effort did not stand to benefit by coronary bypass (CABG) surgery or percutaneous coronary intervention (PCI) over and above optimal medical treatment (OMT). This was the important conclusion drawn by the 100 million dollars worth “International Study of Comprehensive Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) trial done over 10 years. This was by any standards a mammoth study and the inferences reached infinitely far important than the result of the current cricket test series between Bangladesh and India. In fact the ramifications of the ISCHEMIA study will be as sweeping and widespread as the Ayodhya verdict by the Indian Supreme Court, that has awarded the concerned spot of land for construction of a Temple and 5 acres nearby for a Mosque to be built. The judgment is clearly in tune with majority sentiment and despite mummers of deep concern is unlikely to be reviewed. The ISCHEMIA trial on the other hand just may be replicated but the results of the experiment will not change. There is little to achieve in incremental manner by coronary stenting in a patient of stable angina already on optimal medical therapy. Readers must be warned that the more than 5000 patients included in the ISCHEMIA trial had stable angina; they were NOT patients of acute coronary syndrome (ACS). They did not suffer from an acute heart attack or unstable angina, which is severe or moderate chest pain at rest occurring with increasing frequency. The importance of urgent coronary angiography followed by an appropriate intervention strategy (CABG or PCI) cannot be over-emphasised. Unstable Angina is a complete different ball game that needs rapid intervention, particularly in the case of a ST segment elevation myocardial infarction (STEMI).

 

The ISCHEMIA study included 5,179 patients with stable angina with preserved ejection fraction, in 320 sites in 37 countries. The patients needed to haver moderate to severe ischemia as assessed by a nuclear perfusion scan, almost 50% patients had severe inducible schema at baseline , 33% had moderate , and around 12% had mild ischemia. Patients were randomised to CABG or PCI over optimal medical treatment or to initial optimal medical therapy alone. Importantly, almost two thirds of patients underwent a blinded CT coronary scan to rule out left main disease or to confirm there was a block of at least 50% in other coronary artery branches. Patients with blocks less than 50% or blocks not accompanied with ischemia were also excluded. The patients excluded for left main blocks numbered 434, and 1,218 patients were excluded for having non critical disease. After a median of 3.3 years there was no significant difference in the composite endpoint of mortality, heart attack, resuscitated cardiac arrest, admission for unstable angina, or admission for heat failure, between the 2 groups. Patients included in the ISCHEMIA trial had inducible ischemia ranging from 5% to 10%.

 

Prior to the ISCHEMIA trial , the COURAGE study too had shown no superiority of an invasive strategy over optimal medical therapy in patients with stable angina. The COURAGE trial however was done more than a decade ago with most patients in the PCI group receiving bare metal stents, now considered inferior or obsolete. The ISCHEMIA trial had the advantage of some of the best stents in the business being used (cobalt chromium everolimus eluting) and the latest CABG techniques.

 

The take home messages are simple. Do not rush to coronary angiography if one is having stable angina with a normally contracting heart. Everet patient with moderate to severe ischemia need not sprint to the Cath lab.In the case of worsening frequency, duration and intensity of chest pain, especially if accompanied with impaired left ventricle ejection fraction, coronary angiography is the logical option. But what about the patient with a left main artery block who has few symptoms? Remember significant left main stenosis is helped only by early coronary intervention (CABG or PCI). But how does one rule out left main disease without undertaking a CT coronary angiogram ? The ISCHEMIA trial failed to show improved survival with coronary intervention as compared to optimal medical treatment but there was significant improvement in frequency of angina, and thereby quality of life. Along with the ISCHEMIA trial , results of the ISCEMIA-CKD trial too were presented; the ISCHEMIA-CKD trial also did not show any difference in clinical outcome s with PCI or CABG compared with medical treatment in patients with advanced chronic kidney disease and stable angina.

 

Normally a trial of the magnitude of ISCHEMIA gets simultaneously published in either the LANCET or the New England Journal of Medicine; but this however has not happened this time. Maybe the reason is that ISCHEMIA is a “negative” trial; but BIG PHARMA hardly stands to lose, it surely will enjoy greater sales, crucially justifiably so. The ISCHEMIA trial will eventually be published sooner than later, but November of 2019 will be be best remembered for the Supreme Court verdict in India and the ISCHEMIA trial presentation in Philadelphia. Also it is all very well to talk about optimal medical therapy, the reality is that only 41% patients in the ISCHEMIA trial were on high level optimisation therapy, despite careful follow up ! The lead investigator of the ISCHEMIA trial, Prof Judith Hochman, very rightly states that the “challenge in medicine is to get people to comply with their medicines and change lifestyles to reduce risk factors.”

 

To summarise this latest study did not find increased heart attack or mortality with medicines alone than in those who also received bypass surgery or stents. But if a patient continues to have chest pain despite optimal medicines, the person must consider a coronary angiogram. In India, a patient invariably lands up with the unstable form of the disease; stable angina can be, remarkably, ignored for months why the Indian people, much like the polluting air of Delhi is disowned and disregarded.

 

 

 

 

The leading cause of kidney failure across the planet is type 2 diabetes. Patients with diabetes who develop reduction in estimated glomerular filtration rate (eGFR) to less than 60 mL/min per 1.73 m2 or albuminuria, or both over a period of 3 months, are considered to be suffering from chronic kidney disease (CKD). A ratio of urinary albumin (mcg/L to creatinine (mg/l) of less than 30 is normal, a ratio between 30-300 suggests microalbuminuria, and a value greater than 300 is macroalbuminuria. A patient with diabetes and also CKD has a much graver prognosis than a patient of diabetes without CKD. Herein lies the importance of regularly checking for eGFR and morning urinary albumin creatine ration (UACR) because the aim of treating diabetes kidney disease is to reduce albuminuria and progressive reduction in eGFR. Blocking the renin-angiotensin aldosterone system (RAAS) with angiotensin converting enzyme inhibitor and angiotensin receptor blockers has been a reasonable strategy for the last 2 decades. There was little else to manage diabetic kidneys apart from RAAS inhibitors, till serendipitous data on a new class of glucose lowering data appeared. Sodium glucose co-transporter 2 (SGLT2) inhibitors have been found to have the added benefit of arresting and reversing kidney disease in patients with diabetes. Randomised trials with SGLT2 blockers have shown substantial reduction in clinical cardiovascular events such as cardiovascular mortality and hospitalisation for heart failure. Now mercifully we find that an SGLT2 blocker can favourably affect kidney disease in patients with diabetes apart from its glucose lowering effect.

 

More than 26 lakh patients received dialysis or kidney transplantation in 2010. This number will double by 2030. Five to 10 million people are estimated to die from kidney disease worldwide every year.As already mentioned ACE inhibitors and ARB’s prevent adverse kidney outcomes in patients with diabetes and therefore are recommended by all clinical practice guidelines in patients with diabetes with kidney disease or at high risk of developing kidney disease. Crucially end stage kidney disease carries a high risk of mortality, fewer than 50% on dialysis will be alive at the end of 5 years. The risk of death and heart disease is exponentially increased in patients with less severe kidney disease with any incremental lowering of eGFR or increase in albuminuria. Three large randomised trials with SGLT2 inhibitors , EMPA-REG OUTCOME ( empagliflozin), CANVAS Program (Canagliflozin) and DECLARE (dapagliflozin) included patients with type 2 diabetes and known cardiovascular disease (60%), or with multiple cardiovascular risk factors (40%). Each of these trials demonstrated significant reduction in composite kidney disease outcomes (defined as either doubling of serum creatinine or a 40% reduction in eGFR), end stage kidney disease , or death because of kidney disease. But fewer than 17% of patients had a baseline EGFR less than 60 mL/L/ 1.73m2. Thew mean baseline eGFR in all 3 trials was greater than 74 mL/L per 1.73 m2.

 

But the CREDENCE with canagliflozin studied patients with type 2 diabetes having microalbuminuria and baseline eGFR of 56 Ml/L per 1.73 m2, and showed a 30% relative reduction in composite kidney outcome of end-stage kidney disease (dialysis for at least 30 days, transplantation, or eGFR <15 ml per minute per 1.73 m2 for 30 days), doubling serum creatinine or death from kidney disease or heart disease ( N Engl J Med 2019;380:2295-306). Four thousand four hundred patients with diabetes and established kidney disease received 100 mg of canagliflozin for placebo in a double blind manner in addition to an ACE inhibitor or an ARB. There was also a 20-30% reduction in cardiovascular outcomes. Glycated hemoglobin was reduced more by canagliflozin, as were blood pressure and body weight. Fractures and lower limb amputations were similar in the canagliflozin and placebo groups, but diabetic ketoacidosis was more in the canagliflozin cohort (2.2 vs. 0.2 per 1000 patients years). The mechanism of action most probably is efferent arterioles vasoconstriction that reduces glomerular perfusion and intra-glomerular pressure. There is reduction in eGFR initially but this soon stabilises.

 

 

 

A large meta analysis including 37,723 participants looking specifically at kidney outcomes with an SGLT2 blocker has reported significant reductions in the primary kidney composite outcomes of need for dialysis or transplantation or death due to kidney disease (relative risk 0.67, p=0.0019) ( Lancet Diabetes Endocrinol 2019; published on line September 5,2019).

 

The robust reduction in kidney outcomes was independent of baseline albuminuria and use of an ACE inhibitor or ARB. Reduction was greater when baseline eGFR ranged between 45 and 60 ml per min per 1.73 m2 ( 45% relative reduction) than when baseline eGFR was between 30 and 45 ml per minute per 1.73 m2 (30% relative reduction). These findings strongly suggest that SGLT2 blockers work better when eGFR is less attenuated. Importantly, acute kidney injury was lowered by 25% (p < 0.0001) in the CREDENCE trial.

 

In summary the latest meta analysis supports the principle that SGLT2 inhibitors provide protection to the kidney in a broad range of patients with type 2 diabetes; in patients with both preserved and compromised eGFR, independent of their glucose lowering effect. SGLT 2inhibitors reduce risk of dialysis, transplantation, or death due kidney disease in patients with type 2 disease and provide protection against acute kidney injury. SGLT2 inhibitors are available in India.

 

 

 

I was amused on learning that a senior administrator of a large private hospital in Delhi publicly expressed his dismay on consultants not wearing white coats while on duty. His anguish apparently was perceptible, he sincerely believed that insisting on doctors putting on white coats was the done thing. Check out medical marketing websites and you will be struck by the number of photographs off doctors with white coats, but than getting snapped with a white coat for a website is completely different from putting on a white coat in a hospital. Most administrators and also doctors in this country are blissfully unaware that white coats are not permitted in the United Kingdom and frowned upon by most hospitals in the West. In fact while coats got banned by the government in the UK more than a decade ago, not just last week. No doctor is permitted to slip into a white coat whilst on duty in England. Neither is she or he allowed to wear a watch, a tie, a bracelet or a ring. The reason is quite scientific, it is impossible to avoid settling germs on the white coat. Importantly less than 1% of medical personnel get their white coats washed every alternate day or even once a week. More than 15% white coats were found to harbour the deadly round bacteria named staphylococcus aureus, including the infamous methicillin resistant staph aureus (MRSA). More than 40% of white coats were found to be infected by gram negative rods. A randomised trial clearly showed that coats with long sleeves had significantly greater association with viral DNA transfer than coats with short sleeves. No wonder most Western hospitals insist that doctors go around with their responsibilities in scrubs or half sleeve shirts. If a tie has to be worn it should be a bow tie. Scrubs are mandatory in the intensive care units, for obvious reasons of sterility. Walking around computing blood reports and blood gas reports while examining patients in white coats would be worse than hazardous it would be deadly. Patients in the ICU are sick, weak and severely immune compromised. The last thing they need is a cross infection spread by a shirt or a white coat sleeve. It is time a “ bare below the elbow policy “ is adopted in our hospitals too. This would be easy during hot summers but a difficult to employ during winters of north India. Undoubtedly the white coat has been a symbol of skills, privilege, dedication and right training. A lot of patents still do respect white coats on a doctor, but in the final analysis once explained to her the patient would always prefer compassion, knowledge and less fear of becoming an unnecessary victim of cross infection from another patient or the good doctor himself. And then there is “white coat hypertension” in which almost 30% of patients with hypertension have their blood pressure shoot up by almost 30-40 mm Hg when confronted by a doctor with a white coat. The same patient has a significant drop in blood pressure on reaching home. Yes, the white coat can be quite intimidating to quite a few. Ironically the white coat was established to prevent infection being transmitted to patients and the doctor herself. The hard truths are that white coats are teeming with deadly pathogens; these germs can be transmitted to the patient by the doctor, and visa versa.

 

 

 

More than 25 million people (2.5 crores) suffer from heart failure (HF); and about half of them have heart failure with reduced ejection fraction (HFrEF) or systolic HF. Reduced ejection fraction implies that that the heart is unable to pump out blood with adequate force, and hence less blood is pumped out. In order to improve its function the heart tends to enlarge, and thereby increase force of contraction, this is also called remodelling. This remodelling alas is unsuccessful and if left untreated the heart can become as big as a football, before finally succumbing to death. The only drugs to stop this enlargement or remodelling of the heart are ACE inhibitors and ARB’s or angiotensin II receptor blockers. Note that ACE inhibitors or ARB’s are only capable of stopping or arresting the remodelling, but significantly improve quality of life and also reduce mortality. Beta blockers on the other hand also cut death rates of patients with HFrEF, but also have the ability to reverse remodelling, which means a beta blocker can actually shrink the failing heart to a certain extent. The champion device to reverse remodelling of the failing heart is the bi-ventricular pacemaker or cardiac resynchronisation therapy (CRT); a fairly complex and expensive procedure not without it’s share of morbidity and complications.

 

 

A recent observational trial has thrown up a tantalising challenge to CRT. The new combination drug consisting of valsartan (an ARB) and sacubitril (Neprilysin inhibitor) has shown significant increase left ventricle ejection fraction (LVEF) along with substantial reduction in left ventricle volumes. The PROVE-HF trial enrolled 794 patients with HFrEF, NYHA II-IV and followed them for a year. The biomarker N terminal pro B type natriuretic peptide (NTpBNP) an indicator of left ventricle stretch fell from 816 pg/ml to 455 pg/ml by 12 months, importantly the fall in NTproBNP levels was correlated with reduction in left ventricle diastolic and systolic volumes. Left ventricle ejection fraction increased from a median of 28% to almost 38% (p < 0.001). We now know the reason for the significant reduction in cardiovascular mortality and heart failure admissions with valsartan-sacubitril in the large double blind randomised PARADIGM heart failure trial, as compared to enalapril. Based on the clinical outcomes of the PARADIGM trial valsartan-sacubitril has become a class I indication for patients with systolic Hf or HFrEF. In the PROVE-HF trial fall in NT-proBNP levels was rapid and occurred within a fortnight, with the valsartan-sacubitril combination drug particularly effective in patients with new onset heart failure. Even sub optimal doses were effective. Crucially more than 95% of patients were on beta blockers and almost 70% had been on an Ace inhibitor or an ARB; while 30% were on a mineralocorticoid receptor antagonist. The LVEF increased on an average by 5.2% by 6 months and 9.4% by 12 months. Around 25% of patients had an absolute increase in LVEF by 13% or greater by one year. A major limitation the trial is its observational nature that creates a doubt whether the valsartan-sacubitirl combination alone is responsible for the substantial rise in ejection fraction(JAMA. 2019;322(11):1085-1095. doi:10.1001/jama.2019.12821). The most frequent adverse effects were hypotension (18%), dizziness (17%), hyperkalemia (13%) and worsening kidney function (12%). But the important thing to remember is that an intervention that reverses remodelling of a failing heart dramatically cuts down mortality. The PROVE-HF had 30% females studied and median age of all patients was around 65 years; and 30% patients were black.

 

I would most certainly wait for a while before implanting a bi-ventricular pacemaker in a patient with HFrEF who can tolerate tablets of valsartan-sacubitril. But one has to hope that the valsartan in the combination pill used in the HOPE-HF trial and available in the market is not manufactured in China or India. Also what could be the boost to the left ventricle ejection fraction if both valsartan-sacubitril and bi-ventricular pacing are used in a patient with systolic heart failure?

 

 

 

High blood pressure or hypertension is a huge problem both in the world and India. The prevalence of hypertension has shown some decline in high income countries but continues its ascent in low and medium income nations. At least a third of worlds population above 18 years has hypertension; the prevalence in India is staggering, with more than a quarter of the adult population suffering from hypertension. Worse, apparently less than 50% of people in India are aware that they have hypertension. Moreover less than 13% are on antihypertensive medication and less than 10% have their blood pressure under control. Hypertension is an important risk factor for heart attacks and stroke, the first is he largest killer on the planet while stroke is the third leading cause of death. In India, the prevalence is high, but awareness by subjects or adequate control low. This grim situation persist despite anti hypertensive pills being reasonably inexpensive. The prevalence of hypertension in people as young as 18 to 25 years is around 12%. Systolic and diastolic blood pressure was measured 3 times using an Omron device, with at least 5 minutes difference between each reading. Crucially the definition of blood pressure was 140/90 mm Hg. The new American College of Cardiology /American Heart Association definition of stage 1 hypertension is systolic 130 mm Hg (or more) or diastolic 80 mm Hg (or more) ! One can safely presume that the prevalence of hypertension with the latest definition would exceed 35% of adult population. I still consider hypertension as blood pressure exceeding 140/90 mm Hg. Anything below this level or around this level should be best managed by life style modification; I have discussed these changes extensively in the past. Interestingly Chhatisgarh and Nagaland had high prevalence go hypertension, whereas Jammu and Kashmir and Kerala were considered “role models” by the researchers. So must for Article 370. Uttar Pradesh had a prevalence of 14.4% but in absolute numbers it had 14,267,516 hypertensives. India currently has 18% of the worlds population but in the next 5 years will haver the largest number of people on the plant.(PLoS Med 16(5): e1002801. https://doi.org/10.1371/journal. pmed.1002801).

 

 

 

So we now know that a very large number of people have hypertension in thIs country; but less than 10% are getting optimal treatment; despite reasonably cheap blood pressure pills freely being available in the market. The next important question is when should these pills be taken? There is scant data on the timing of taking these pills. Generally, because cardiac events take place in the early morning hours, advice has been that blood pressure pills be taken first thing in the morning. We now have a large randomised trial including 19,000 people with high blood pressure that assessed whether pills should be taken in the morning or at night. The conclusion is that blood pressure pills work much better if taken at night, rather than when consumed in the morning. Cardiovascular events such as heart and attack and stroke were almost reduced by a half by the night time dose. The reasoning is that the same medic at the same dose works differently in the body depending upon the time of the day or the night. The ability of the drug to be absorbed and then circulate within the human body apparently is superior at night. 19000 patients were divided into 2 groups, one group got the pills in the morning while the second group took them at night. Patients who took night pills had a 56% lower risk of cardiovascular death; 49% reduced risk of stroke and a 44% lore risk of heart attack, after adjusting for age, sex, diabetes, kidney disease or smoking. Importantly people who took their pills at night had better kidney function and lipid profile. Median follow up was for 6.3 years. The researchers of the Hygia Chronotheraspy Trial concluded that the modestly reduced systolic sleep blood pressure was the most important marker for reduced clinical events, far more important than diabetes, male sex, advanced age, low HDL cholesterol, smoking and kidney disease (European Heart Journal (2019) 0, 1–12 doi:10.1093/eurheartj/ehz754). The big limitation of this study is data restricted to people between 15 and 49 years, most people with high blood pressure are their 50′ to 70’s.

 

About 25% of patients were on ACE inhibitors, 30% were on calcium channel blockers, 20% were on beta blockers and 45% were on a diuretic. The most commonly dual therapy was a combination of an ARB/ACEi with a diuretic (hydrochlorthiazide) at 43% or ARB/ACEi with a calcium channel blocker at 26%. There was no significant difference in intake of low dose aspirin or a statin.Crucially, more than 50% of patients in this trial were on angiotensin receptor blockers or ARB’s. The reader must be informed that a small storm has been brewing the last almost 12 months. Three ARB’s ( valsartan, irebsratan and losartan) have been found to be contaminated by nitrate salts that are potentially precancerous. There have been therefore massive recalls of these pills. Unacceptable levels of N-Nitrosodimethylamine (NDMA) were first found in valsartan tablets. Most of these ARB’s are manufactured in China and India; it is feared that these precancerous molecules develop during the manufacturing process. There is no direct link of ARB’s with cancer. The risk of developing cancer is minute but the danger however small is there. Industry claims that the risk is as low as 1 in 100,000 cancer cases over 70 years. But the reality is that voluntary recall has been demanded by FDA, which has issued a warning letter to the India based Torrent pharmaceutical company. Torent manufactures losartan potassium tablets ; one of the 3 ARB’s facing recalls since last December.

 

 

 

The purpose of mentioning potential carcinogens in ARB’s is certainly NOT to advise against blood pressure pills. Blood pressure pills, on the contrary ,are mandatory if one has high blood pressure apart from life style alterations. Do NOT stop taking your blood pressure pill under any circumstance; consult your treating physician to prescribe an alternative. Controlling blood pressure is crucial, keeping in mind the scandalously high prevalence of hypertension in Indians, and the fact that very few take optimal treatment for the problem. There are a variety of effective blood pressure pills available; also there are other effective ARB’s without NDMA.

 

 

Sir Roger Bannister etched his name in history by breaking the 4 minute barrier for the mile in Oxford on 6th May 1954, after coming fourth in the Helsinki 1952 Olympics in the 1500 m finals. Sir Roger was a junior doctor then and went on to become a consultant neurologist. His training sessions were light compared to todays standards, but was most probably practicing what is now called high intensity interval training. But when asked what was his proudest achievment he is supposed to have replied his academic contribution as a clinical neurologist. He almost gave up running when he missed a medal in Helsinki. It should be borne in mind that competitive middle distance and long distance running in those years was largely done by Europeans; the Africans must have been definitely running but were not noticed as their participation in track events was extremely thin. But all said and done Sir Roger’s feat will stay in human sporting history for eternity. He ran on primitive earthy sort of a track albeit with pacers, but the last 300 m were tough bet cause of a cross wind. After the race young Roger still gasping for breath said he was “glad” the 4 minute barrier was shattered in Oxford and not in the USA. The current 1500 m record for men stands in the name of Hichem el Guerrrouj of Morocco at 3 min 26 secs set in Rome more than 20 years ago in 1998. The fastest Indian at 1500 m is Jinsen Johnson who has clocked 3:35.24 last month in Berlin. The 1500m record is bound to be broken but Bannisters run will always be a reference point for every middle distance runner on the planet.

 

 

 

This brings us to another historic moment in distance running, the day Eliud Kipchoge became the first human to run 26.2 miles also called the “marathon” below 2 hours. This is a phenomenal sporting feat that shall be talked about for hundreds of years by everyone attached to sports in general and running in particular. Vienna was the lucky city to witness the extraordinary marathon by Kipchoge. Guess who have been born in Vienna? My favourite is Lisa Meitner, the woman who figured out that when a heavy nuclear particle divides there is always some loss in mass that actually always converts to energy. No wonder Lisa Meitner famously quoted that “You must not blame us scientists for the use which war technicians have put our discoveries.” She was referring to the atom bomb and the Manhattan Project; Lisa Meitner never got a Nobel for physics despite being manifestly deserving. Einstein called her the “German Marie Curie.” Yes the Nobel committee has goofed up many a times. The Nobel prize for literature this year is considered by many close to a disgrace. We however must stick to Kipchoge’s run. The run had numerous adjuncts that a trained athlete will keep in consideration, The route was almost flat and 90% straight. Kipchoge had world class pace setters along with him, who also protected him from any breeze or wind. Vienna was selected for its languid conditions and mild weather. A fancy green laser was constantly directed on the road in front of Kipchoge to enhance running efficiency and importantly he wore the most advanced running Nike shoes ever that have a trampoline effect. The shoes or “Vaporflys’ are reckoned to give almost a 90 seconds advantage to an elite marathon runner.But all these assisting devices cannot mitigate or in any way shadow the accomplishment. Even this record will eventually be broken but Kipchoge made history as he dazzled the world with the first ever sub 2 hour marathon. His time 1:59.40.2 ! This is mythical. I wonder how many Indians fed on 24 X 7 cricket have any idea about the Kenyan’s run.

 

 

We need to shift to something quite different but life saving. For decades it was anathema to consider any treatment other than CABG surgery for patients with what is termed “left main” disease. The left main coronary artery divides usually into the left anterior descending and left circumflex arteries, and thus supplies most of the heart muscle. Life is under great threat if the left main coronary artery gets blocked more than 50 %. Coronary bypass surgery had been the only option, earlier randomised trials had clearly shown that surgery was far superior to medical therapy in patients with left main disease. Also percutaneous coronary intervention (PCI) was never considered as an alternative. A paradigm shift has taken place in the last week or so. Two mammoth randomised trials have shown that left main patients do equally well with PCI (ptca and stenting) when compared to CABG surgery. The trials are big by any standards and there follow up as long as 10 years, which is pretty long. The SYNTAX trial (Lancet 394;1325-34 ) has reported that all cause mortality was more or less similar whether patients with left main disease underwent stenting with first generation paclitaxel eluting stents or CABG surgery. In fact after 10 years mortality in the PCI group was 26% versus 28% in the CABG cohort, so actually there were fewer deaths with PCI albeit this was not significant. Also it did not matter if patients suffered diabetes.More than half of the patients in the left main group had distal disease and 50% block was taken as the cut-off. Hence PCI is a suitable alternative to CABG with similar 10 year death rates. Information was available in almost 95% of the 1800 original patients randomised in the SYNTAX trial. There were 705 patients with left mason disease studied in SYNTAX.

 

 

The other big trial (N Engl J Med ; published September 28,2019) named EXCEL reported 5 year follow up of 1905 left main disease patients. There was no difference in cardiovascular mortality whether patients were subjected to PCI or CABG ( 5% vs. 4.5%) or in myocardial infarction (10.6% vs. 9.1%). Patients had to have left main block of 70% or if the block was between 50% and 70% they needed to have physiological schema confirmed by stress test to FFR. More than 80% had distal left main disease while stents used were the newer durable polymer everolimus stents. The researchers failed to detect a significant difference in the composite rate of death, stroke, or myocardial infarction at 5 years in patients with low or intermediate complexity (SYNTAX score of 32 or less). As in SYNTAX results were no different if diabetes was present. The message is lucid, PCI is a viable alternative to CABG surgery in patients with left main coronary artery disease. Both PCI and CABG unlike a quadruple ton in a cricket test match or a sub 2 hour marathon save human lives.

 

 

 

 

 

Now that Gandhi Jayanti is over here are some charming facts regarding the tribe called “manual scavengers”. Apparently they have existed a,ingest us for generations, in fact have been considered a vital and essential component of the Indian social fabric. The manual scavengers responsibility is to engage directly with human excreta. He ensures sewers are kept operational in the towns of our land. He also is entrusted to tackle septic tanks, manholes and of course sort out dry latrines across the length and breadth of the country. There are thousands of them, more than 50,000 as per official records. A New York Times report placed the figure at 300,00 if not 900,000! More than 800 have died in the last 2 decades. These are conservative figures. Some responsible agencies go to the extent of stating that a manual scavenger dies every fifth day. This may or may not be an exaggeration, but pictures speak for themselves. There will be a young able bodied male entering or exiting a sewer/ man hole with absolutely no protective gear. Deaths are because of poisonous gases produced in sewers. The main stream media including TV channels provide scanty information, they barely scratch the surface. Little wonder there is little or no outrage over the delightful job of engaging with human excreta in the twenty first century. India has the unique distinction of nurturing this band of men. There numbers have actually increased in some North Eastern states including West Bengal. Maximum deaths have occurred in Tamil Nadu, and now hold your breath , the silver medal winning state is Gujarat. Almost 18,000 crore rupees are spent per year in the Swachh Bharat Abhiyaan project, but less than 63 crores were provided by the government for the rehabilitation of our sewer gladiators in the last 4 years. Ironically publicity money for the Swachh Bharat Abhiyaan project ( electronic and print media) during this time exceeded 500 crore rupees. There was recently an uproar in the BBC when a breakfast TV host of Indian origin expressed her anger and frustration on being a target of racism in the UK. The BBC management in its infinite wisdom reprimanded her for disclosing personal views, but was promptly attacked by numerous British journalists for its bigotry. It struck me whether these manifestly decent journalists had any clue about our sewer gladiators who handled excreta possibly with bare hands on a daily basis, without the slightest whisper from the community at large. There is stunning insensitivity where manual scavengers are concerned, one could go further to say there is tacit approval by society. This stunning acquiescence is embedded in culture, for the volunteers to tackle dry latrines and blocked sewers come from a particular section of Indian people. A recent report describes 3 gladiators dying one after the other while tackling a sewer, there was no one prepared to give them water as they were dying(scroll.in). What can be more horrific than this? That Justin Trudeau may lose the next Canadian election because of the crime of polishing his face black is laughable. Canadian, or for that matter the Brits have absolutely no idea of the systemic debasement inflicted on fellow humans in this part of the planet. Mr. Bill Gates are you listening? Indian scientists have an orbiter encircling our moon right now, it shall do so for some years. Very soon they will surely drop a rover on its surface too. They almost did it last month. “Vikram” the rover named after the famed scientist Mr. Vikram Sarabhai travelled nearly almost 380,400 km or more from earth; thats quite a brilliant feat. Less than a handful of nations have achieved that. It is odd to say the least that we are incapable of producing robotic devices that can replace the manual scavenger. Why on earth is there no directive issued to our engineers to construct a robotic system that can clear sewers and man holes of this country ? The Supreme Court has definitely prohibited employment of manual scavengers, this came about as recently as 2013, but this is a toothless law, which is conveniently gone around by Indian culture. Is a sustained media campaign needed to sensitise the general public on this subject? There is little money to be gained from it and also possibly meagre fame. We don’t even have canaries to check out toxic sewers; maybe the first manual scavenger to enter a pit serves as the canary in the mine. There are no middles in national newspapers on this scented subject. Unremarkably no Bollywood icon or corporate honcho has uttered a word.

 

 

 

 

We therefore have the unique situation where there are thousands of manual scavengers operating and at the same time we produce world standard heart valves and latest generation coronary stents. The Lancet has published just yesterday a paper on the superiority of an ultra thin biodegradable polymer sirolimus eluting ultrathin strut stent over a durable polymer everolimus eluting stent in the setting of ST elevation myocardial infarction (STEMI). More than 1300 patients with a STEMI or acute heart attack were randomised; after a follow ups of one year the biodegradable polymer sirolimus eluting stent performed better, it significantly reduced the clinical endpoint of target lesion failure from 6% to 4%. Cardiac death and target vessel myocardial infarction remained the dame in both groups, but target vessel revascularisation or re-intervention was 1% in the biodegradable polymer sirolimus eluting stent group versus 3% in the durable polymer everolimus eluting stent group. Importantly this is the first randomised trial comparing a second generation with a third generation drug eluting stent in patients of acute heart attack or STEMI. I am reporting this study called the BIOSTEMI trial, which is the first ever trial comparing a biodegradable polymer coronary stent with a durable polymer coronary stent for a particular reason. The reason is that we produce world class biodegradable polymer coronary stents in India. We even produce them in a small town called Faridabad, I have in fact visited the factory in Faridabad manufacturing these third generation stents. These stents have struts only 60 microns in thickness. One micron is a millionth of a meter. A human hair is 75 microns while a human red cell is 5-6 microns across. The largest bacteria is 3 microns in size. You can appreciate the precision demanded in producing an ultra thin stent. Not only are Indians manufacturing these stents but a randomised trial published in The Lancet in February this year showed that the Indian biodegradable polymer sirolimus eluting stent was equivalent in clinical performance with the ‘gold standard’ Xience stent ( or a durable polymer everolimus eluting stent). At one year followup there was no difference in death, myocardial infarction or target vessel reintervention.

 

 

 

 

So we now have a charmingly odd situation. We can launch satellites, attempt a robotic landing on the moon’s surface, and also develop an intercontinental ballistic missile that can cover more than 5000 kms. We call it the “Agni V”. The intent is to keep Beijing in sight. We are the only country apart from the US, Russia, China and North Korea with such advanced ICBM’s. Moreover more than $130 billion is to be spent in modernising our armed forces in the coming 4 to 5 years. This is above and beyond the I.6% of the GDP allocated to defence this year; about 3.2 lakh crore Rupees. But, astonishingly we don’t seem to have a roadmap to eliminate the job of the manual scavenger in this country. The sweeping absence of flush toilets and sewer lines in this country ensures that a particular community is compelled to clean up other people’s excreta with their bare hands. No law however stringent shall eradicate this dehumanisation… till we develop a mechanised way to do this work.

 

 

 

 

 

 

Sodium glucose co-transporter 2 inhibitors (SGLT2i) are weak agents where sugar lowering is concerned in patients with type 2 diabetes. They have at best a modest lowering effect on HbA1C levels; they lower blood glucose by preventing reabsorption in the kidney, at the same time they also ensure that sodium too is not absorbed but excreted by the kidney. Empagliflozin has shown significant reduction in cardiovascular mortality and also hospitalisation for heart failure in patients with type 2 diabetes on background anti diabetes medication. In fact considerable data is now emerging that SGLT2i prevent heart failure in patients with and without atherosclerotic disease, with and without heart failure, across a range of impaired kidney function, and even in patients without diabetes. The mechanism for correcting heart failure is still mystery, it is independent of glucose lowering mechanisms. It is conjectured that improved kidney haemodynamics is associated with a salutatory effect on heart muscle; or maybe there may be a direct positive effect on cardiac muscle metabolism. They also of course act as an expensive diuretic, but the mechanism is quite unique.

 

Conventional diuretics reduce preload and congestion by reducing intra-intra-vascular volume, while SGLT2i deplete interstitial fluid rather than fluid in the vasculature. Afterload is lowered by SGLT2i by reducing blood pressure and vascular stiffness. In heart failure heart cells rely on non -esterified fatty acids for metabolism. SGLT2i increase ketones levels that are considered to be ‘super fuels’ superior to glucose and fats acids for energy production by the mitochondria. The third hypothesis is that SGLT2I interfere with the hydrogen ion exchange pump system and thereby cut down both sodium and calcium in heart cells, resulting in better mechanics. Both fibrosis and collagen synthesis is prevented by SGLT2I, improving cardiac function.

 

 

Now a new large randomised trial has demonstrated that the diabetes drug dapagliflozin (an SGLT2i) substantially improves clinical outcomes in patients with established reduced ejection fraction heart failure, remarkably improvement was also seen in non diabetic patients of heart failure N Engl J Med September 19, 2019). There was a 26% lowering in a composite of time to cardiovascular death, heart failure hospitalisation or urgent heart failure visit requiring intravenous treatment, when dapagliflozin was added to standard therapy, over a median if 18.2 months. Primary outcome was reduced with dapagliflozin from 21% to 16%, p < 0.001.The authors concluded that among patients with heart failure and reduced ejection fraction, the risk of worsening heart failure or death from cardiovascular causes was lower with dapagliflozin as compared to placebo, regardless of the presence of or absence of diabetes. Fifty five percent of patients in this trial did not have diabetes.Standard therapy consisted of an ACE inhibitor/ ARB and a beta blocker in almost 95% of patients, a mineralocorticoid inhibitor in more than 60% , and a sacubitril/valsartan inhibitor in one third patients. Dapagliflozin reduced all cause mortality by 17%. The DAPA HF is being noticed by heart failure specialists around the world. SGLT2i are known to prevent heart failure in type 2 diabetes, but the DAPA HF trial has shown that an SGLT2i can also be used to treat congestive heart failure, as an add on medicine. Earlier both empaglifozin and canagliflozin have significantly prevented heart failure hospitalisation in patients with diabetes.Emagliflozin substantial cut down mortality and hospitalisation for heart failure without reducing the risk of myocardial infarction and stroke.

 

 

Another small double blind randomised trial (DEFINE -HF Trial ) including 263 patients with reduced ejection fraction heart failure has shown significant improvement in symptoms and quality of life as early as 3 months, with addition of dapagliflozin ( Circulation. 2019;140:00–00. DOI: 10.1161/CIRCULATIONAHA.119.042929 ). Crucially there was no difference in NT-proBNP levels over 12 weeks of treatment. The researchers concluded that dapagliflozin produced meaningful clinical improvement in heart failure patients without affecting mean NT-proBNP levels. Benefits of 10 mg dapagliflozin per day were seen both in diabetics and patients without type 2 diabetes. It should be borne in mind that dapagliflozin was used over and above standard heart failure medication. Patients in the trial had to have an NT-proBNP more than 400 pg/ml and eGFR >30/ml/min/1.73m2. The median NT-proBNP level was 1400 pg/ml. Number needed to treat over the course of 2 years was 21 only to reduce the primary composite end points. Diuretics were provided to 94% patients, ACE inhibitor or ARB to almost 90%, Sacubitril-valsartan to 11%, beta blocker to 96%, aldosterone blocker to 72% and digoxin to 19% patients. More than 50% patients were on metformin and 28% were on insulin.

 

There were few adverse effects, no significant increase in hypotension or hypoglycaemia.Serious renal adverse effects were uncommon and significantly less common in the dapagliflozin group. But this was small sized trial. We have to wait for more randomised trials with SGLT2i to make their prescription mandatory. The prevalence of heart failure is humungous; and the accompanying morbidity and mortality well known. The DEFINE HF has too few patients, follow up too short, and it was not powered to detect mortality or hospitalisation for heart failure. The number to treat for improvement in clinical symptoms and quality of life was only 10. The fact that there was little or no change in NT-proBNP level strongly suggest that dapagliflozin did not merely operate as a diuretic. Another icing with SGLT2i is their reno-protective capabilities. Nearly all patients in the DEFINE-HF trial were on ACEi’s, ARB and a beta blocker, 60% were on aldosterone blockers,, while 30% were on a sacubitril/valsartan. Importantly about 35% were on a biventricluar pacemaker. There was no significant increase in 6 minute walking distance nor was there any significant change in weigh.

 

 

 

Unlike the DEDFINE-HF trial, DAPA HF included 4744 patients of heart failure with reduced ejection fraction. Mean left ventricle ejection fraction was approximately 31%, 45% patients had diabetes, and 41% had chronic kidney disease. Dapagliflozin reduced death by 18%, heart failure hospitalisation by 30% and risk of worsening heart failure by 30%. It will however not be easy to optimally mix dapagliflozin with a prescription containing a beta blocker, an aldosterone antagonist, and Sacubitril/valsartan. There will be the problem of drug interaction and also issues with adherence. The researchers of the DAPA Hf trial have not provided details of dosage of the standard treatment given, the optimal prescription will always therefore be a painstaking guess.

 

We are looking at a world where in a patient with reduced ejection heart failure will be teated by a combination of beta blocker, sacubitril/valsratin ( ARNI) , spironolactone and an SGLT2i. A diuretic may not be needed, patients however will need to be carefully chosen. A new era in treatment of heart failure has certainly begun. Time will tell us how safe an SGLT2i is in the long run. The FDA has granted FAST Track designation for the development of dapagliflozin to reduce cardiovascular death or hospitalisation for heart failure. The long term adverse effects are unknown where SGLT2i is concerned. Initially there is a drop in eGFR that improves within a year, but long term effect on eGFR is yet to be ascertained. Fractures have been associated with SGLT2i’s because of mineral changes and the problem of lower limb amputation persists, albeit associated only with canagliflozin but no confirmation of causality. Genital fungal infection can be a problem but this is early treatable.

 

 

 

 

Percutaneous coronary intervention (PCI) consisting of PTCA with stenting remains the cornerstone for effective treatment in patients with acute myocardial infarction. There is rapid restoration of blood flow in the completely occluded culprit coronary artery, that is not only life saving but also improves left ventricle function, and which goes a long way in improving quality of life. More than 17.7 million people die annually because of cardiovascular disease. Heart disease and stroke kill more people than any other disease. In India alone more than 7 lakh people die of a heart attack each year, and the list is growing.

 

It is often found that 50% of patients with an acute ST segment elevation myocardial infarction (STEMI) that coronary arteries apart from the culprit are also significantly blocked. They have what is termed multi vessel disease. There are additional narrowed arteries apart from the coronary artery causing the heart attack.It was unclear whether tackling all concerned coronary arteries was the way to go or whether treating the culprit vessel and managing the remaining blocked vessel by pills ( and intervening only if symptoms developed) was a better option. Observational trials suggested treating all blocked vessels was the better alternative, but no large randomised trial has shown significant reduction in mortality.

 

A Danish trial randomised more than 600 patients to culprit vessel only PCI or directional flow reserve (FFR) dependent intervention of other coronary arteries to conclude that there was significant reduction in reintervention of non culprit vessels on more than 2 years of follow up, but no reduction in death ( lancet 2015;386:665-71). Another slightly larger randomised trial also came up with a similar recommendation, that intervention of all involved vessels in acute heart attack patients cut revascularisation but not the hard end points of death or myocardial infarction (N Engl J Med 2017;376:1234-44). More than 800 patients of STEMI with multi vessel disease were involved in this trial, both groups had FFR evaluation but the group with culprit alone PCI was unaware of the results ( both patients and the cardiologists).

 

 

 

 

A smaller British trial had shown that clinical outcomes were better with complete revasularisation than with culprit only intervention during pCI in STEMI patients. The CvLPRIT trial enrolled 296 patients in 7 UK centres and followed them for one year only. There was no significant reduction in death or myocardial infarction, but total MACE consisting of death, recurrent myocardial infarction, heart failure or repeat revascularisation was significantly less ( J Am Coll Cardiol 2015;65:963-72). The authors suggested that larger trials were warranted to confirm their findings.

 

 

 

 

But now we have a large adequately powered trial that assigned more than 4000patients with STEMI  having multi vessel disease to culprit vessel only PCI or multi vessel PCI ( N Engl J Medicine 2019; September 1st). In the multi vessel group ,non culprit coronary arteries with either 70% or greater block or stenoses between 50 and 69% with an FFR value less than 0.80 were subjected to PCI. Percutaneous intervention of non culprit vessels in the multi-vessel group was done as long as 45 days after index procedure with a median of 3 weeks. The primary end point of cardiovascular death or myocardial infarction at the end of 3 years was significantly less in the complete revascularisation cohort than in the culprit vessel intervention group; (7.8% vs 10.5%, p=0.004). The difference albeit significant was driven largely by a cut in myocardial infarction, mortality remained unchanged. The secondary end point of a composite of death, myocardial infarction or re-intervention was lowered significantly in the complete revasularisation group by an almost 50%. The researchers concluded that in STEMI patients undergoing PCI clinical outcomes were substantially superior in those who had complete revascularisation as compered to the culprit lesion only group. Only 13 patients were needed to be treated by complete revascularisation to prevent re intervention in a follow up for 3 years, also only 37 patients required complete revascularisation to prevent death or myocardial infarction.

 

 

I saw a female patient just yesterday who had undergone successful primary PCI for a nasty acute inferior wall ST segment elevation accompanied by shock and heart failure a few months ago. During the index procedure she had multi vessel disease with greater than 70% blocks of the left anterior descending and left circumflex coronary arteries. The patient was advised intervention for the non culprit vessels at discharge but she was lost on follow up. She decided to consult me again because of symptoms of giddiness that did not seem to be related to her heart or the vasculature system. But armed with data from the COMPLETE trial I suggested to her to get the remaining coronary vessels tackled. The COMPLETE trial strongly suggests that despite no significant cut in mortality, there is substantial lowering of myocardial infarction and future re intervention if all involved coronary vessels are tackled during or soon after the index procedure. Importantly there were no major differences noted regarding acute kidney injury, stroke, bleeds or stent thrombosis.

 

 

Every patient of STEMI with multi vessel disease may not benefit by complete revasularisation, because some may have complex lesions ( long calcified block, chronic total occlusion or bifurcation stenoses) that may be difficult to treat percutaneously. Suitable non culprit vessels however should surely be treated. There is no urgent need to rush in because the non culprit vessels can be tackled subsequently after a couple of weeks and even later. One does not have to treat every vessel in the middle of the night, the entire cardiac team of the doctor, the nurse and technicians can get drained soon after opening up the culprit vessel at 2 am in the night. Crucially, COMPLETE studied more than 4000 patients of STEMI, while the SYNTAX score was around 16; hence extrapolating to more complex lesions may not be easy. But the COMPLETE trial will definitely have some impact on contemporary management of acute heart attack accompanied with multi vessel disease. Thousands of recurrent heart attacks could be prevented across the planet

 

 

 

 

I kept advising this young man; all of 23 years only, not to make public his watertight views on religion and Karl Marx. But he is more than obstinate or why would he insist despite all shades of warnings to jot down such inflammatory phrases that religion is the opium of the masses or that religion has served little service apart form providing untold miseries to people. Worse, he noted, one must be wary from the control of machines or people with machines wishing to control men. He had already thought of the title, “ Jail Notebook and Other Writings.” Worse, he is a firm atheist. Not for him the slightest participation in any ritual of Hindu or Sikh mythology. Ladies and gentlemen I present who else but one of the greatest revolutionary’s the world has ever seen, Shaheed Bhagat Singh, who was hanged by our colonial masters 8 days after the Ides of March in 1931. Remarkably the morning he was hanged Shaheed Bhagat Singh was reading a book on Lenin, the architect of the Russian revolution. He did not want a scripture or a sermon uttered the day he died, he could not be bothered.He went to the gallows without a single prayer in his lips, along with his comrades, Sadguru and Sukhdev. Shaheed Bhagat Singh had been charged primarily for the assassination of the policeman John Saunders ( 17 December 1927), who in turn had led the charge that eventually killed Lala Lajpat Rai. Saunders however had not been the intended victim, the target was James Scott the superintendent of police who had ordered the deadly charge. Ironically , Shaheed Bhagat Singh in todays times may be charged an atheist plus a dangerous an urban Naxal. He would certainly today be a subject of the ire of a great number of people .

 

 

Ironically, Vinayak Damodar Savarkar ji too was an atheist and clearly desired that after he died no rituals were to be performed. He in fact most probably did not attend his wife funeral and ensured she went into an electrical crematorium, as he himself would be. Savarkar ji vehemently objected to orthodox Hindu beliefs. He was completely against the caste system, and had had 2 boys of the tailoring community as his best friends. Crucially Savarkar ji was against cow worship, which he dismissed as superstition. He believed that worship of the cow was a consequent to her utility in providing milk and numerous edibles from that milk. He would never hesitate to protect the cow but was reluctant to worship her as a goddess. But despite being an atheist he was of the firm opinion that he was a Hindu just as others who were monists, pantheists, and theists. He attacked the caste system all his life and would have been surely deeply dismayed by the (repeated) contemporary assaults against Dalits; he most certainly would not have kept silent (Savarkar: Echoes From a Forgotten Time by Vikram Sampath). Savarkar ji demanded full and complete independence more than 20 years before the Congress party took up the cause; but curiously met almost all the players who participated in the murder of The Mahatma, a few days before that sad evening of 30th January 1948.

 

 

Remarkably, Madan Lal Pahwa ( of the failed bomb attack on Gandhi ji) had been arrested 10 days before, and interrogated by the police in custody; Pahwa was a member of the gang that eventually participated in the killing of Gandhi ji ; it is difficult to believe that the police of those days was unable to extract information on the imminent mortal attack; also almost the entire top Bombay police brass had been informed of the impending murder ( including the premier of Bombay), and yet no adequate security was provided to Gandhi ji. Some serious investigative journalism is required for this humongous intelligence lapse. Despite having Pahwa, a close associate of Nathu Ram Godse, in the cooler for 10 days , the police had no clue what was about to happen at Birla House on 30 January 1948. Utter incompetence or something murkier than that. But more to the point; Savarkar ji would have felt awkward in today’s season of Hindutva, that he had almost single-handedly conceived. Careful rigorous reading on Shaheed Bhagat Singh and Veer Savarkar ji will reveal that it is near impossible to compare the two or even club them together, the only common factor would be their immense unease amid contemporary political currents.

 

 

 

 

German investigators, however, had the easier task of comparing head to head two powerful anti platelet agents, enjoying a class 1 recommendation during percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS); that is patients admitted for unstable angina, ST segment elevation Myocardial infarction (STEMI) or non ST segment elevation myocardial infarction (NSTEMI). The ISAR React 5 trial included more than 4000 ACS patients and assigned them in a randomised manner to either ticagrelor or prasugrel. Both ticagrelor and prasugrel are P2Y12 inhibitors that are not only more powerful than clopidogrel but also act quicker. When combined with aspirin or what is termed DAPT (dual antiplatelet therapy ) they significantly prevent ischemic events such as heart attacks, death or stroke after PCI. They also prevent stent thrombosis that can be fatal in quite a few cases. The researchers had anticipated that ticagrelor would come out tops because of past data. Ticagrelor was the favourite to be the winner because of its superior record when compared with clopiodogrel. The PLATO study ( N Engl J Med 2009;361:1045-57) had shown superior efficacy with ticagrelor when compared to clopidogrel in ACS patients. Prasugrel on the other hand has been found to be wanting when given before coronary angiography in patients with non ST elevation myocardial infarction in the ACCOAST trial.There was no advantage with before angiography prasugrel administration but in fact there were significantly more bleeds. More than 4000 patients were randomised in this trial ( N Engl J Med 2013;369:999-1010).

 

 

 

Prasugrel was unable to trump clopidogrel in the TRILOGY ACS trial that included more than 7000 ACS patients who not subjected to PCI, but given medical therapy. There were no differences in ischemic clinical endpoints or bleeding complications when Prasugrel was compared to clopidogrel in such patients. The researchers of the ISAR REACT 5 were therefore taken aback when their data revealed that prasugrel was in fact superior to ticagrelor without increasing clinical significant bleeds ( N Engl J Med September 1st, 2019).

 

 

 

Primary end point, a composite of death, myocardial infarction, or stroke at I year was 6.9% with prasugrel versus 9.3% with ticagrelor. Moreover stent thrombosis was almost halved with prasugrel (0.6%) versus ticagrelor 1.1%. The authors were compelled to conclude that in patients of acute coronary syndrome with or without ST segment elevation myocardial infarction, incidence of death, myocardial infarction or stroke was significantly lower among those given prasugrel as compared to ticagrelor. Prasugler was administered as a 60 mg bolus dose followed by 10 mg maintenance daily dose. In people more than 75 years or having weight less than 60 Kg daily Prasugrel was reduced to 5 mg. Ticagrelor was given as 180 mg bolus and 90 mg twice a day maintenance dose. Prasugrel was not given before coronary angiography in NSTEMI patients. The ISAR REACT 5 trial is the first ever head to head comparison of ticagrelor with prasugrel. Forty one percent patients enrolled had ST elevation myocardial infarction, 46% had non ST segment elevation myocardial infarction, and 12% were admitted for unstable angina.

 

 

The results of ISAR React 5 are yet to sink in. It is however well known that prasugrel is once a day regimen while Ticagrelor has to be taken twice day. In India a weeks course of ticagrelor is almost Rupees 700 while a 10 day course of prasugrel is around Rupees 100 only. The reaction of professional societies remains to be seen, but the makers of ticagrelor must be surely scrambling for a suitable response. For now unlike a choice between Shaheed Bhagat Singh and Veer Savarkar ji, the choice between ticagrelor and prasugrel ( in patients with acute coronary syndrome) appears far clearer. Prasugrel is the victor. Remember more than 700,000 people suffer with acute coronary syndrome (heart attack or close to one) for the first time in a year with around 333,000 having a recurring episode the same year, in the United States (Circulatiuon 2019;139(10):e 56-e528). The numbers from India are bound to be substantially greater; a shot in the arm for a diminishing GDP. The importance of an effective anti platelet agent cannot be overestimated. Nor can Veer Savarkar’s diktat that no crow was to be fed after he died ( ‘Savarkar: The True Story of the Father of Hindutva’ by Vaibhav Purandare).

 

 

The majority of Indian cardiologists including myself will now have to rethink on the role of prasugrel during percutaneous intervention in patients with acute coronary syndrome. Between the ages 30-69 years in 2015 there we’re 1.3 million ( 13 lakhs) deaths in India due to cardiovascular disease. About 70%b were because of heart attack while 30% due to stroke.Cardiovascular disease resulted in 2.1 million deaths ( 21 lakhs) in all ages in 2015. The ISAR REACT 5 trial, it should be noted was not sponsored by the industry, but further confirmation of prasugrel’s superiority will be difficult in the near future, because an adequately powered randomised trial is both hard work and expensive. As far as Bhagat Singh and Veer Savarkar are concerned; both were atheists till the end, Shaheed Bhagat Singh a Marxist till his last breath and Veer Savarkar anti caste activist. Would they have felt comfortable today when the cow is worshipped and  while poor school children are served rotis (bread) with salt in their mid day meals. Importantly, however, probably the biggest difference between the 2 was that Savarkar in attempting to get back non-Hindus into what he described the Hindutva peoples, he actually was driving deep wedge between Hindus and non-Hindus. He insisted that oil-Hindus accept India not only as their Father land but also as their holy land. By insisting on Hinduism as a religion he ceased to be as described some to be an agnostic or an atheist. Bhagat Singh on the contrary steered away from religion upto his last breath.

 

 

 

 

 

 

Triglycerides (Trigs), which are fats in the blood, have not received rigorous attention enjoyed by the ‘bad” cholesterol also called low density lipoproteins (LDL). Trigs when raised in blood ,much like LDL, are also quite capable of triggering a heart attack or stroke. Some trigs are naturally produced by the liver and some by the calories or food we ingest. The more calories you indulge in the greater the Trig level. A level higher than 200 mg% is considered an increased risk for a cardiovascular event such as a heart attack or stroke. Very high levels exceeding 500 mg% can cause acute inflammation of the pancreas. People with high Trigs are usually overweight or have diabetes. Hypothyroidism can also raise Trigs levels. Excercise, reduction of weight, cutting down on alcohol are good ways to cut down Trigs in the blood. One is compelled to resort to medication if life style alterations do not work. Earlier trials with fibrates and niacin did not enjoy much success in reducing Trigs levels and were thus abandoned.

 

 

A lot of work has been done with fish oils containing there omega 3 fatty acids (3FA) eicosapentaenoic acid (EPA) and docosohexaenoic acid (DPA). Numerous previous trials with 3FA’s also have not shown clinical benefits regarding cardiovascular disease. A meta analysis of 10 randomised trials ( JAMA Cardiol 2018;3:225-34) including 78,000 patients did not show any improvement in major adverse cardiovascular events with 3FA when compared to placebo. The ASCEND trial ( N Engl J med 2018; 379:1540-50) that tested 840 mg of 3 FA’s in patients with diabetes also did not report any difference. The VITAL trial that examined 25000 participants with vitamin D and 3FA versus placebo did not show lowering of the incidence of the primary outcome of death, myocardial infarction, or stroke ( N Engl J Med 2019;380:23-32).

 

 

A Japanese study (JELIS) done more than a decade ago did show improved clinical outcomes with 1.8 grams of EPA plus a statin; a 19% reduction in cardiovascular events (Lancet 2007;369:1090. The American Heart Association as recently as last week come out with an advisory recommending prescription EPA for safe reduction of Trigs by administering prescription EPA alone or a prescription combination of EPA + DPA ( Circulation ;19 August 2019). The researchers have based their conclusions upon analysis of 17 clinical trials, but the weight of the recommendation is based largely on the REDUCE-IT trial. The FDA has already approved prescription 3FA’s to treat very high Trig levels >500 mg%

 

 

The REDUCE-IT rial randomised more than 8000 patients in a double blind manner to 4 grams of icosapent ethyl ( prescription EPA) plus statin or placebo. Patients that were included had to have established cardiovascular disease or diabetes plus another risk factor. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, unstable or myocardial re-vascularization. Secondary end point was a composite of cardiovascular death, myocardial infarction or stroke). At the end of 5 years a primary end point event occurred in 17.2 % of patients in the icosapent ethyl group as compared with 22% in the placebo group 9 P<0.001).This is an absolute 20% reduction meaning only 20 patients are needed to be treated for 5 years to prevent a cardiovascular event. Overall 60% patients had diabetes , at base line LDL cholesterol was well controlled ( median value 75 mg%) while Trigs were slightly raised ( median value 216 mg %). These staggering results have raised eyebrows because as mentioned earlier trials have not shown these levels of efficacy. The researchers were themselves at a loss to explain a 25% reduction in clinical outcomes. They also concede that they cannot pin down the exact reasons driving such improved outcomes. There may be an anti thrombotic effect in view of increased bleeding with the icosapent ethyl as compared to placebo. Or there may be an anti inflammatory effect, which stabilises the cap covering the atherosclerotic plaque. It is well to remember that it is not the extent of blockage in a coronary artery but the instability of the cap of the block that is more lethal.

 

 

 

The REDUCE-IT trial however used a mineral oil containing capsule in the placebo group; being a double blind study the mineral oil capsule had to masquerade as the treatment fish oil; 3FA. It is quite possible that the mineral oil interfered with statin absorption as also with other heart medicines in the placebo and therefore results got tilted in favour of the 3 FA treated group. Also LDL cholesterol went up by more than 10% and Trigs were up by 2.2% in the placebo group; once again advantage icosapent ethyl group. By 2 years C reactive protein had gone up a s high as 32.3% in the placebo group. But far more patients in the treated group developed atrial fibrillation requiring hospitalisation (3.1% vs. 2.1%; p=0.004). The authors concluded that among patients with raised Trigs despite intake of statins risk of cardiovascular ascetic events are substantially lower with 4 grams of icosopent ethyl taken daily as compared to placebo. The REDFUCE-IT trial was sponsored by industry that was responsible for collection and management of there data; the lead author of the trial however is a top cardiologist with impeccable academic credentials.

 

More trials are needed to confirm the conclusions of REDUCE-IT that icosapent ethyl significantly prevents cardiovascular events in people with an LDL as low as 75 mg% but slightly raised Triglycerides. Maybe a better option at least for non vegetarians would be to consume a fatty fish like salmon, tuna or a mackerel. Icopent ethyl on the other hand is a synthetic derivative of EPA and thus can be safely taken by vegetarians. The FDA is yet to approve icosopent ethyl for cardiovascular protection; the agency plans to hold an advisory committee meeting in November this year. Currently icospent ethyl is only approved for severe hypertriglyceridemia of > 500 mg%. The REDUCE-IT trial did not use fish oil supplements available overt the counter but a prescription medicine.

The last big meta analysis including 10 randomised trials with more than 75000 patients (mentioned earlier) concluded that  the 2016 European Society of Cardiology and European atherosclerosis Society guidelines for prevention of cardiovascular disease ere unconvinced that omega3 FA’s provide protective effects (JAMA Cardiol 2018;3:225-234). The American Heart association ( Circulation 2017; 135(15) e8670-e884)  on the contrary recommended that omega 3 FA’s are justified for cardiovascular protection in patients with prior heart disease and those with reduced ejection fraction heart failure. But the meta analysis found that use of 1 gram per day of omega 3 FA’s was ineffective in prevention of heart attack, death or any other vascular event, in patients with prior cardiovascular disease. The authors of this meta analysis are prudent enough to suggest that a higher dose of 3-4 grams per day of EPA may be be effective in cutting risk of major vascular events. The REDUCE-It trial has so far filled the gap, but  there shall  be more certitude with  completion of the higher dose EPA/DPA omega 3 FA’s  randomised trials.

 

 

 

Considerable progress has been made in the treatment of chronic heart failure, with multiple randomised trials reporting significant reduction in mortality, improvement in quality of life, reduction in symptoms, bettering of functional capacity and arresting further remodelling of the heart. All guide lines recommend that chronic HF be initiated by an ACE inhibitor or angiotensin receptor blocker (ARB) along with a beta blocker in patients with reduced left ventricular ejection fraction lower than 35%. If the combination dos not prove effective, a mineralocorticoid (spironolactone or eplerenone ) should be added. Further ratcheting of treatment in the event of failure of the above cocktail becomes interesting. Ivabradine may be added in case heart rate persists more than 70 per minute despite full dose of a beta blocker. Ivabradine suppresses the funny cells of the sinus node. A bi-ventricular pace maker (CRT) can be implanted in case there is left bundle branch block with the QRS width more than 120-130 msec. Also if the cocktail does not work there is a new medicine in the market; a combination of valsartan (ARB) and sacubitril (neprilysin inhibitor) or ‘ARNI’ should replace the ACE inhibitor or ARB in the original cocktail of 3 drugs. In fact latest guidelines suggest that ARNI could replace an ACE inhibitor or ARB even if they are effective because of substantial incremental benefit with ARNI as shown in the large PARADIGM trial.

 

Chronic heart failure afflicts almost 1-2% of adult population in developed countries. The prevalence in India also must be in the millions and crores. Morbidity and mortality are sadly quite high. Once hospitalised 10-15% patients have worsening of heart failure and on discharge as many as 10-15% die within 6 months. Congestive heart failure is obviously as “malignant” as any “malignant cancer”. As many as 7% of people above 70 years are affected. But as with hypertension treatment less than 25% patients of heart failure take full dose optimal therapy, largely because treating physicians are unaware or nervous about providing full dose treatment. Treatment of course should be begun at a “low dose”, administered “slow” but “aiming high”. Always look out for hypotension and any alteration in kidney function. The European Society of Cardiology guidelines appreciate high prevalence of chronic kidney disease in patients with heart failure. Usage of loop and thiazide diuretics mandate caution in context of declining renal function; however continuation of an ARB or ACE inhibitor is encouraged unless there is significant decline in kidney function.

 

Continue reading “NO TREATMENT YET FOR ACUTE HEART FAILURE”

 

 

 

We are most certainly living in momentous times, the world has changed as never before, the proof being the scrapping of Articles 370 and 35A from the state of Jammu and Kashmir on a single morning of this month. This naturally created a humongous furore both within Parliament as also the entire nation. The prime minister rightly stated from the ramparts of Red Fort that what could not be done in 70 years he did in 7 weeks. Brutal no doubt but the truth. To his credit the BJP manifesto for decades had underlined abrogation of the above Articles. Modiji had the crucial majority in both Houses to push the Bill through, spectacularly assisted by the home minister. The opposition was left both stunned and speechless. Remarkably Pakistan did not haver a clue ; this includes their infamous ISI that repeatedly has staked claims of being the finest in the business and whose very existence is based on ensuring “freedom” to “Indian Held Kashmir.” On closely examining the photographs published of their military high command one thing is obvious, both the army chief and the ISI head look perplexed, almost confused and tense. Only a few days earlier they had returned from a triumphant visit to the United states, with the promise of a big IMF loan and renewal of spare parts for their F16s. Mr Imran Khan was ecstatic declaring that he felt he had won the Cricket World cup once more. In his mammoth public meeting with Pakistani expatriates he had screamed he would ensure that AC’s and televisions of jailed Mr Nawaz Sharif and Mr Zardari were cut off, to loud cheers from the Pakistani American audience. The newspaper Dawn could not help commenting on the stunning success of Mr Imran Khans successful visit. This collective hubris was however short-lived but in the mean time Mr Khan got Mr Sharif’s daughter Maryam Sharif also incarcerated in a cell. In fact right now the apex of almost the entire Pakistani opposition languishes in jail. So when the “selected prime minister” of Pakistan wails about the 2 former chief ministers of Kashmir being put under house arrest he sounds a bit rich. Also most of the media is directly under the control of Pakistani regulators. The Pakistani media is however putting up a robust fight unlike our chaps who excel in toeing the government line. One of the brightest journalist of the subcontinent has had a defamation suit slapped against him by Mr Khan. Mercifully Seth keeps coming up with his excellent takes on matters in Pakistan. His independent day message to his countrymen is a must watch; its on YouTube. He puts great emphasis on Pakistan resetting its relations with India. He cannot but concede that the economic gap between India and Pakistan has become insurmountable. Pakistan as of now remains on Finacial action Task Force (FATF) grey list of countries recognised as laundering money to support terrorist activities. To get the 6 billion dollars loan agreed by the IMF, Pakistan has to get out of this FATF list or face complete fiscal collapse. Pakistan’s foreign exchange is depleting  fast. No wonder Mr Khan finds himself between a rock and a very hard place. He cannot launch a military operation nor a jihadi movement. His mentor the army chief had accompanied him to the USA and knows every line of the IMF deal.

Continue reading “TENTATIVE STEPS IN KASHMIR AND IN TREATMENT OF XDR TUBERCULOSIS”

 

I wonder if you noticed that at least 3 cricketers in the last 2-3 years developed a sore throat, requiring a cough syrup. Sore throats are pretty common , last 5- 7 days, with a virus being usually the cause. It really needs no treatment as the course is self limiting. Drinking warm beverages or warm saline gargling brings considerable relief. A pain killer can be taken in case of excessive discomfort, but never give aspirin to a child ( as this may trigger Reye’s syndrome). But our cricketers were found to have taken terbutaline by the BCCI ( the exalted Indian cricket board), which then slapped bans effective from a back date. So an 8 month ban actually became effective for as little as 4 months. No wonder the Sports Ministry of the government of India has tried its best to make the BCCI realise that it cannot be jury and executioner, not cannot and should not check for banned performance enhancing drugs on its own and then slap strange back dated bans on the culprits. There is obviously a conflict of interest apart from the fact that the testing may neither be robust enough or worse the burden not large enough. Apparently a little ore than 200 samples were sent by the BCCI to a national doping laboratory that detected 5 positive samples; there is no record of how these 5 cricketers were dealt with; or whether they were dealt with at all. The sports ministry is therefore keen to bring the process of checking for doping under the National Anti-Doping Agency or NADA, which operates under the regulatory authority of WADA or the World Anti-Doping Agency. Every Indian sport federation is subject to NADA’s testing; the BCCI insists for some strange reason to be outside NADA’s ambit. It believes that its own system for checking doping is robust enough.

 

A sore throat may be because of streptococcal bacteria , in which case an antibiotic is administered to resolve the infection. This too rarely lasts a more than a week. There is neither science nor logic in administration of terbutaline to an athlete for a sore throat. Remarkably Mr Yusuf Pathan when nabbed with terbutaline in his urine sample , in all wisdom confessed that he had to take terbutaline for a sore throat; the BCCI as customary handed him a back dated ban. Mr Pathan made a statement of how proud he was to play for his state and his Motherland. One can only hope that he does not use terbutaline again while playing for the next edition of the IPL. Or at least does not get caught.

 

 

Continue reading “TERBUTALINE TURBOCHARGED CRICKET”

 

 

 

 

Recently many cardiovascular  professional bodies pulled down the high blood pressure threshold, needing treatment , from 140 mm Hg systolic and 90m mm Hg diastolic to 130 mm Hg systolic and 80 mm Hg diastolic. The impetus for lowering blood pressure threshold from 140/90 to 130/ 80 was largely based upon a single trial, albeit a large randomised one that showed slight improvement in clinical outcomes but accompanied with the offshoot of serious adverse effects, when blood pressure was lowered below 130 mm Hg systolic. I have never been a great admirer of the “SPRINT” study and have stuck out my neck by expressing my views in the past. I am more comfortable keeping the threshold at 140/90 because I am not convinced that there is incremental advantage in lowering it below 130/80 as many of my colleagues would recommend on the basis of international guidelines. By lowering the threshold millions more people get branded as hypertensives, and hence obviously many millions of tablets get prescribed, with little advantage. Someone somewhere is raking in a lot of moolah. However it is well known that almost 600,000 people die of heart attack or stroke in the US alone in a year.

 

An interesting study, published last week( N Engl J med 2019;381: 243-51) has received little attention. In fact it has gone completely under the radar. Maybe because it has not shown any difference in the composite of myocardial infarction (heart attack), ischemic or hemorrhagic stroke in more than 1 million middle aged people followed for almost 8 years. The researchers pored through data on more than 36 blood pressure readings of 1.3 million or 13 lakh participants. There were almost 19% participants who could be labeled as hypertensive when the 140/90 threshold was employed, but this jumped to 43.5% with 130/80. The prevalence of people with high blood pressure thus more than doubles with the lower threshold label. Results demonstrated that both systolic and diastolic blood pressure measurements influenced clinical outcomes. There was an increase of 18% in clinical outcomes when the systolic threshold was breached, and an increase of 6% with raised diastolic blood pressure. Crucially, researchers found similar increase in risks with both thresholds of 140/90 or 130/80.I must dilate on this, there was no increase in death or stroke with the 140/90 cohort versus the 130/80 group.

 

Continue reading “SHOULD BLOOD PRESSURE THRESHOLD BE LOWERED FROM 140/90 TO 130/80 ??”