Author: admin

 

 

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”