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Treating a patient with shock can be an extremely daunting task for any clinician. Shock is a common reason for admission into an intensive care unit. Shock is accompanied with low blood pressure that is invariably raised by vasopressors and inotropes. Two thirds of patients entering an intensive care unit septic shock, which is a distributive type of shock. Other albeit uncommon causes of distributive shock are drug/toxin induced, anaphylactic shock, endocrine shock (Addison crisis) and neurogenic shock. Every protocol on spec shock mandates administration of norepinephrine at 0.2 mcg/kg/min (recommneded first line) and if need be vasopressin at 0.3 units /min. Norepinephrine can be combined with epinephrine, both having combined vasopressor and inotropic effects. The latest vasopressor to be found effective is angiotensin II. Angiotensin II acts by Gq protein stimulation in vascular smooth muscle. The ATHOS -3 (N Engl J Med 2017;377:419-30) randomised trial comparing angiotensin II with placebo in 344 patients with vasodilatory shock (80% had sepsis), showed that significantly more patients had their mean blood pressure raised more than 75 mm Hg at 3 hours with angiotensin II than placebo against background conventional vasopressor therapy ( 70% versus 23%). It must be noted that all these patients were suffering from vasodilatory shock defined as cardiac index greater than 2.3 litresb per minute per square meter or as central venous oxygen saturation greater than 70% coupled with central venous pressure more than 8 mm Hg, with mean arterial pressure between 55 and 70 mm Hg.

 

 

Cardiologists on the other hand are confronted with cariogenic shock where low blood pressure is a result not of dilated peripheral arteries but inability of the heart to pump adequately. Poor pumping of the heart is usually due to acute myocardial infarction, and in other instances due to mechanical failure (valvular dysfunction, ventricular septal defect, atrial myxoma), and arrhthmias. Initial treatment includes inotropic support with dobutamine and vasopressor support with norepinephrine. Vasodilatory shock by itself is very difficult to treat, but cariogenic shock is even more so because of the fact that too much vasopressor administration can be detrimental to the already struggling heart. No sweet spot has so far been determined for vasopressor/inotrope dosage, and hence patients of cariogenic shock will need supportive treatment consisting of the intraaortic balloon pump (IABP), Impella, or extracorporeal membrane oxygenation (ECMO).

Continue reading “IMPELLA IS YET TO OUTSCORE THE INTRA-AORTIC BALLOON PUMP IN SEVERE CARDIOGENIC SHOCK”

 

It has become impossible to get a happy story on diabetes. Every succeeding story is grimmer than the preceding one. We yet again learn that Asian patients with diabetes are exquisitely vulnerable to the disease. More than 230 million people in Asia suffer from type 2 diabetes, which is more than half of the world population. A recent study on Asian patients with diabetes  has established that in a follow up of 12.6 years 148,868 participants died. The study included more than a million (10 lacs) individuals from China, Japan, India, Bangladesh and South Korea. Individuals with diabetes had twice the number of deaths as compared to those without diabetes. The risk of relative mortality far exceeded that seen in Western populations. The researchers concluded that Asian people with diabetes were at increased risk of dearth due to a variety of causes. You just cannot take diabetes lightly (JAMA Netw 0pen 2019:2(4):e192696). Therefore the recommendation for urgent need for Asia-centric diabetes management strategies. It is against this background of a looming diabetes epidemic that one needs to become aware of newer more effective medicines to tackle diabetes; albeit they will be outside the reach of most Indian patients.

 

Type 2 diabetes is a complex problem with multiple underlying pathophysiological mechanisms. It therefore makes sense to administer combined therapy. Treatment with an SGLT2 inhibitor may increase production of glycogen even as it reduces glucose level via the kidney. Semaglutide a GLP 1 receptor agonist on there other hand not only kick starts insulin production by the pancreatic islet cells but also tone down glycogen delivery. The recently published SUSTAIN 9 trial ( Lancet Diabetes Endocrinol 2019;7:356-67 ) employed addition of once weekly injection of semaglutide in addition to daily ingestion of an SGLT 2 inhibitor in patients of type 2 diabetes. The primary outcome of this trial was change in HbA1C at 30 weeks while the secondary outcome was change in weight.

 

Patients with an HbA1c ranging from 7% – 10% despite 3 months of an SGLT2 inhibitor were randomised to subcutaneous 1 mg of semaglutide or placebo once weekly. Semaglutide dose was gradually increased from O.25 mg to 0.5 mg to eventually 1 mg per week. Apart from randomised medication and SGLT2 inhibitor, 70% patients were on metformin and about 13% were taking a sulfonylurea. SUSTAIN 9 showed that addition of semaglutide to existing therapy with SGLT2 inhibitor resulted in significantly greater reduction in HbA1C and fasting glucose levels. Moreover almost 80% of patients got their HbA1C level down to less than 7%.

Continue reading “SEMAGLUTIDE SWINGS IN FOR PATIENTS WITH DIABETES.”

 

 

The WOEST trial ( Lancet 2013; 381:1107-15) was the first randomised study to show that a combination of a vitamin K antagonist (VKA) and a P2Y12 inhibitor when employed inn a patient of atrial fibrillation undergoing PCI resulted in significantly less bleeds than a triple combination of VKA, aspirin and a P2Y12 inhibitor. The study however randomised less than 600 patients. At the end of a year major bleeds were reduced from 45% in the triple therapy group to 20% in the double therapy group; p<0.0001). The conclusion was that use of clopidogrel minus aspirin was associated with a significant reduction in bleeding complications, without an increase in thrombotic events. The study was not powered to assess changes in ischemic events or mortality.

 

Atrial fibrillation (AF)s the commonest arrhythmia in adults and therefore more than 10% of patients suffering from acute coronary syndrome are found to be in AF. The aim is to prevent ischemic events such as myocardial infarction or stent thrombosis, and also simultaneously prevent thromboembolism because of AF. Ischemic events can be avoided by dual anti platelet therapy (DAPT) while embolism (stroke) is prevented by an oral antocaogulant (OAC). The problem is that combining DAPT with an OAC increases the risk of major bleeding considerably. Choosing antithrombotic treatment for an AF patient suffering also from acute coronary syndrome becomes quite a challenge.

 

Apart from WOEST, 2 more randomised trials comparing a new oral anticoagulant (NOAC) plus a P2Y12 inhibitor with triple therapy consisting of VKA, aspirin and P2Y12 inhibitor showed a lower incidence of bleeding with double regimen therapy without aspirin. These 2 rials were not powered to assess whether lower bleeds were due to avoidance of aspirin or due to use of a NOAC.

Continue reading “APIXABAN FOR PATIENTS WITH ATRIAL FIBRILLATION UNDERGOING CORONARY STENTING”

 

 

 

All said and done the promise of ultra thin strut stents with biodegradable polymer to cut down the incidence of stent thrombosis and neoatheroscelrosis remains to be fulfilled. Drug eluting stents (DES) have indeed reduced restenosis but have been hampered by development of late stent thrombosis and neoatherosclerosis. In order to improve clinical results ultra thin stents were developed in which strut size is a mere 60 microns. These stents are made of the allow cobalt chromium and are covered by a polymer that is only 5 microns in thickness. Moreover the polymer is biodegradable, which means that it melts away in a few months to a year, having done its job of preventing smooth muscle proliferation or restenosis. Crucially the stent left behind behaves like a bare metal stent that is incapable of inducing inflammation in the coronary artery wall. The situation that we have currently is that every ultra thin strut stent in the market carries biodegradable polymer (BP). All randomised studies done with the ultrathin strut stent have compared them with the durable polymer (DP) everolimus eluting stent ( or the Xience stent). The Xience stent has a strut thickness of 80 microns, which is also quite thin. The Xience stent and other thin strut stents with a durable polymer have provided excellent clinical outcomes compared to earlier generation drug eluting stents, but results have flattened. Second generation DP-DES have a lower risk of stent thrombosis, restenosis, myocardial infarction and death in comparison with bare metal stents. The latest ultra thin strut BP-DES also provide clinical outcomes comparable to second generation BP-DES but no randomised trial has shown superiority.

 

The latest trial comparing BP-DES with DP-DES ( the TALENT trial) reported similar outcomes by 12 months (Lancet 2019,393:987-97). TALENT studied 1435 patients and the primary endpoint was a composite of death, myocardial infarction or clinically indicated target vessel revascularization. At the end of one year both groups had an incidence of about 5%. Participating centres were from Europe.

Continue reading “MORE ON THE ULTRA THIN STENT WITH BIODEGRADABLE POLYMER”

 

 

Trans catheter aortic valve replacement (TAVR) is an established technique that has been found to be a viable alternative to surgical valve replacement (SAVR) in patients of severe aortic stenosis (AS) at high risk or moderate risk for death following SAVR. Severe AS includes patients of AS who have a valve area equal or less than 1cm2 ( equal or less than 0.6 cm2 per square meter of body surface area) or mean gradient greater than 40 mm Hg or Doppler flow across the aortic valve exceeding 4 meter per second, assessed by 2D echo performed at rest.

 

Aortic stenosis can become as life threatening condition once symptoms develop. The aortic valve becomes narrowed, obstruction blood flow from the heart to the rest of the body. Patients develop breathlessness, chest pain and can even faint. Open heart surgery in which a mechanical valve with solid carbon leaflets is inserted has been the mainstay of treatment for the last half century. The mechanical valve however requires life long anticoagulation or blood thinners. Biological valves made from cow and pig heart tissue are also implanted when anticoagulation is undesirable, such as in patients who are old (more than 65 to 70 years, pregnant women, and in those who are incapable of takin blood thinners for life).

 

It was inevitable that the next target would be patients of severe AS at low risk defined as predicted 3% risk of death by 30 days. We now have 2 large studies that have taken the interventional cardiology world by a storm. In fact the entire audience at the latest American College of Cardiology Meeting was left breathless the presentation of these 2 studies; both studies were published simultaneously by the New England Journal of Medicine.

 

 

The first trial to be discussed used a self expanding valve in more than 1400 severe AS patients (N Engl J Med March 17). The researchers compared outcomes of SAVR ( in which the chest and heart are opened in the operation room) versus the far less invasive procedure of TAVR, in which the aortic valve is inserted via the groin. All patients were considered ow risk ( predicted death less than 3% at 30 days); 65% were male while mean age was 74 years.

Continue reading “TRANS CATHETER AORTIC VALVE REPLACEMENT FOR THE LOW RISK PATIENT”

 

 

The introduction of first generation drugs eluting stents ( 1G- DES) sub substantially reduced rates of in stent restenosis (ISR) as seen with bare metal stents (BMS). Bare metal stents had significantly cut down plain balloon angioplasty complications such as emergency coronary artery bypass grafting surgery and restensis, but were associated with stent thrombosis (ST). ST is a dreaded complication of coronary stenting that apart from killing a patient, invariably results in a large myocardial infarction. Improved anti platelet therapy in the form of dual anti platelet therapy (DAPT) and improved stent technology with better implantation techniques did reduce early ST events (less than 30 days). In stent restenosis with BMS was due to neo intimal hyperplasia, and this pathological phenomenon paved way for the entry of the IG-DES. The IG-DES significantly reduced in stent restenosis but became associated with late ST (30 days to 1 year), and with very late ST (later than 1 year) ST. Late ST necessitated development pf more powerful anti platelet medication, administered for prolonged duration, which in turn brought in the spectre of increased bleeding.

 

Delay in re-endotheliazation is considered the primary substrate for late and very late ST. Optical coherence tomography (OCT) has revealed that stent malapposition and rupture of a neoatherosclerotic plaque are nearly always associated with late and very late stent thrombosis. In a few cases uncovered struts are the cause. Delayed re-endotheliazation is due to the anti proliferative effect of the drugs released by the 1G-DES.

 

Another phenomenon to explain late ST was a chronic inflammatory reaction induced by the polymer attached to the stent struts, and even the stent struts themselves. The stent itself essentially has 3 components, the metallic platform, the polymer (drug carrier) and the pharmacological agent.

Continue reading “THE TALENTED ULTRATHIN STRUT DRUG ELUTING STENT KICKS IN”

 

 

 

Let us  consider  randomized trials comparing paclitaxel eluting stents (PES) with the newer generation everolimus eluting stent ( EES); the COMPARE trial randomized PES to EES in 1800 patients to report that the composite of death, MI and target vessel revascularisation  by the end of 1  year was significantly better with the newer generation EES ( Lancet 2010;375:201-9). By 2 years the difference was almost 5 % ( 13.7% versus 9%); with stent thrombosis lower by 77% and MI reduced by 45%( 7.5% versus 3.9%) ( J Am Coll Cardiol 2011;58:11-18). The SPIRIT IV trial ( N Engl J Med 2010;362:1663-74) too found that the composite of death, MI and target lesion revascularisation was significantly less with EES as compared to PES in 3687 randomized patients, at one year follow up.

The ENDEAVOUR III trial, albeit randomized only 436 symptomatic  patients with single vessel disease to zotarolimus eluting stent ( ZES) versus sirolimus eluting stent ( SES); at the end of 5 years death/ MI was significantly less with ZES than with SES ( 1.3% versus 6.5%). The simple conclusion was that death/ MI  was less with ZES than with SES ( JACC Cardiovasc Inter 2011;4: 453-50).

 

 

The message is clear, earlier generation stents are inferior to the newer generation stents where clinical outcomes are concerned. The newer stents with much thinner struts induce less inflammation of vessel walls, and therefore are clinically more durable. 

 

The  FREEDOM Follow On trial with a median 7.5 years follow up should be assessed against the above backdrop. FREEDOM randomised 1900 patients ( mean age 63 years)  with diabetes to either CABG or PCI. Eighty three percent had 3 vessel disease with SYNTAX score of 26; but 33% of patients had a high SYNTAX score greater than 33. About 35% of patients had a low SYNTAX score of less than 22. It should be noted that the majority of patients studied had a high or intermediate score; all guidelines proscribe PCI in such patients of multivessel disease with intermediate and high SYNTAX scores.The extended follow up of FREEDOM at  reports significantly less death in the CABG cohort as compared to PCI ( 18% versus 24%, p=0.01). An absolute decrease of 6% and a relative decrease of 25%. CABG showed better results in every subgroup and crucially provided better results in younger patients (JACC 10.1016/j.jacc.2018.11.001).

 

The FREEDOM trial however must be carefully analysed. The number of patients available for following by the researchers were a mere half of the original groups, a substantial mitigation in the number studied. 

Continue reading “REVISITING THE “FREEDOM FOLLOW ON STUDY””

 

There are almost 10 million new cases of tuberculosis (TB) in a calendar year with around 1.7 million deaths. Worse we now have more than half a million patients of multi drug resistant TB ( MDR TB) ,with 10% of these being extensively drug resistant TB ( XDR TB). The definition of MDR TB is drug resistance of TB bacilli to rifampicin and isoniazid, while XDR TB constitutes added resistance to quinolones and second line injectables like amikacin and capreomycin. Successful treatment of MDR TB is quite difficult with an average success rate of less than 50%. Treatment is of long duration and extends for at least 20 months. Mercifully, WHO has come out with a revised simpler protocol for managing MDR-TB.Medicines have been regrouped based on latest clinical evidence.

 

Group A : medicines to be prioritised , Levofloxacin, bedaquiline, linezolid.

 

Group B: medicines to be added next: cycloserine, terizodone, clofazimine.

 

Group C: medicines to complete regimen or when drugs from groups A and B cannot be used; ethambutol, pyrazinamide, delamanid, ethionamide, prothionamide, PAS, streptomycin, meropenam, imipenam.

 

Kanamycin and capreomycin are no longer recommended because of relapse, toxicity and treatment failure.

 

 

 

 

A shorter regimen lasting 9 to 12 months has been observed to have similar efficacy as with the longer schedule, but with a higher chance of relapse. Quinolone, bedaquiline and linezilod have become top priority drugs while the injectables have been downgraded if not removed entirely from the list. Delamanid comes in group C because of limited data regarding its efficacy. Continue reading “TACKLING MULTI-DRUG RESISTANT TUBERCULOSIS IN THE TWENTY FIRST CENTURY”

 

 

The advantages of an arterial graft during coronary artery bypass graft operation is well recognised; largely because of the fact that an internal mammary graft will remain patent as long as 20 or more years. It has been known for decades that more than 90% single internal mammary artery graft (SIMA) are patent into the third decade post CABG, while more than two thirds of venous grafts get blocked by 10 years. A systematic review and meta analysis had previously documented significantly reduced mortality with bilateral internal mammary grafting (BIMA) as opposed to SIMA accompanied by venous grafts, albeit this included observational studies that had a collective cohort of more than 15,000 BIMA patients. The mean follow-up was around 4 years only. It was explained that the reduced mortality was a consequence of greater patency associated with BIMA ( N Engl J Med 2016;375: 2540-46).

 

 

Despite the promise of prolonged survival associated with BIMA less than 5% North American cardiac surgeons use bilateral internal mammary graft technique, the statistic from Europe being marginally better, around 10% surgeons employ BIMA ( Circulation 2014;130:539-45).A meta analysis with a 10 year follow up also demonstrated reduced mortality when BIMA is used as opposed to SIMA, but surgeons continued to be hesitant. The reasons for their reluctance were largely that BIMA was far more challenging and the incidence of sternal infection was markedly increased. Also there was little or no randomised data.

 

Another meta-analysis of 29 observational studies including almost 90,000 patients noted that overall the BIMA group had significantly better long term survival than the SIMA cohort (HR 0.78; p< 0.00001). The BIMA group also had significantly lower in hospital mortality, cerebrovascular accidents, and requirement for revascularization. However the incidence of deep sternal wound infection was significantly more in the BIMA cohort ( 1.8% vs. 1.4%, p = 0.0008), (Heart 2017;103:1419-26).

Continue reading “THE ‘ART’ OF BILATERAL INTERNAL MAMMARY GRAFT VERSUS SINGLE INTERNAL MAMMARY GRAFT”

 

 

Patients of type 2 diabetes will be relieved and even downright happy to learn that finally a double blind randomized trial using an oral insulin preparation has been published. The researchers report that an oral insulin preparation developed by the company funding the trial was found to be as defective as an injection of basal insulin in reducing fasting glucose level. Insulin was developed more than a century ago, the big downside despite saving lives was the needle prick. The early injections must have been an ordeal, but over the years we have pen filled insulin preparations with very fine needles that are almost not felt. Yet a needle prick once or twice a day every day for years is not a prospect one looks forward to, and there are lakhs and lakhs of patients with diabetes.

 

 

The latest Lancet endocrinology issue carries the first randomized trial on oral insulin ( Lancet Diabetes Endocrinol ; published online Jan 21, 2019;) and also an editorial applauding the effort of the researchers. Fifty patients of type 2 diabetes who were insulin naive but not controlled adequately on metformin or other oral anti diabetic medication were randomized to injection insulin glargine or a basal oral insulin preparation ( I338). Twenty five patients got the oral insulin once a day only and a dummy subcutaneous injection while the remainder received insulin glargine injection plus a once a day dummy oral preparation. At the end of 2 months fasting glucose had dropped to a similar extent in both groups (43 mg% and 47 mg %) . There was also no differences in the drop in HbA1C level in both groups (0.75% with oral insulin and 1.05% with injection.

Continue reading “ORAL INSULIN SHOWS CLINICAL PROMISE FOR THE FIRST TIME”

 

 

Rightly or wrongly it is being suggested that cardiologists begin managing patients with diabetes with the realisation that 2 new classes of drugs have a beneficial effect on cardiovascular outcomes. Albeit oral hypoglycaemic agents have been used for decades in the treatment of diabetic patients no clear signal indicating salutatory cardiovascular effects has ever been recorded. The United Kingdom Prospective Diabetes Study (UKPDS) studied metformin versus diet control ( only) in overweight diabetics ( > 120% of ideal body weight)and came to the conclusion that metformin significantly reduced mortality as compared to diet alone therapy. Metformin also reduced mortality when compared to a sulfonylurea or insulin. But when metformin was added to sulfonylurea treatment there was increased mortality.

 

Metformin has been considered all these years as the go to therapy in patients with diabetes, especially because it induces less hypoglycaemia and less increase in weight. The problem with the UKPDS study is that only 342 patients got studied on metformin, this number would be considered a pittance in contemporary clinical research.

 

 

One should be wary of metformin in patients with diabetes having impaired kidney function. American guidelines proscribe use of metformin when creatinine is greater than 1.5 mg%, while British guidelines urge caution with metformin once GFR is less than 45 ml/ min/ 1.73 m2. It should be noted that insulin also requires reduction in dosage when GFR gets below 50ml/ min. Similarly most if not all sulfonylureas should be avoided in the presence of impaired renal function. Glimeride is not to be used if the GFR <60 ml/min, as also glibeclamide and glyburide are contraindicated with GFR <60 ml/min.The only sulfonylurea to be used safely in diabetics with impaired kidney function is glipizide as it is largely eliminated by the liver (Clinics 2016:71: 47-53).

Continue reading “TWO NEW AGENTS TO TREAT HEART DISEASE ASSOCIATED WITH DIABETES.”

 

 

 

There is unanimous agreement that intervention is needed once a patient with severe valvular aortic stenosis (AS) becomes symptomatic. Valvular AS is not uncommon in the western world with a prevalence as high as 3 % in people over 70 years. Prevalence amongst Indians is unknown but no where near the Western statistic. Te usual risk factors associated with atherosclerosis are linked to aortic stenosis but so far no method for prevention has been identified. Nor is anything known about arresting progression of mild AS to severe AS.

 

Severe AS is defined as a mean gradient across the aortic valve greater than 40 mm Hg, peak flow on Doppler echo more than 4 m/sec, or valve area less than 1 cm2. The 3 key symptoms associated with severe AS are angina, syncope and dyspnea. Life span is considerably shortened once symptoms set in and may be as short as 2 years with onset of breathlessness. It should be remembered that incidence of sudden death hovers around 1-1.5% per year.

 

Currently surgical aortic valve replacement (SAVR) carries mortality as low as 1 to 2% in most experienced centres. Transcatheter aortic valve replacement (TAVR) has over the years become an established alternative to SAVR in a substantial number of cohorts. There is no significant difference in mortality between SAVR and TAVR I patients with both high risk and intermediate risk patients with AS. Surgical risk for AS is anticipated best with the Society of Thoracic Surgery (STS) Risk Score. A predicted risk score by STS of 4% to 8% mortality (by 30 days) is considered intermediate risk, an STS more than 8% is high surgical risk, while less than 4% is low risk. Randomised trials in intermediate risk and high risk patients have confirmed that TAVR is equivalent to SAVR. There were more vascular complications and pacemaker implantation with TAVR, while SAVR was linked with more need for blood transfusion, acute kidney injury and atrial fibrillation. A small Nordic study has demonstrated equivalence between TAVR and SAVR in patients with low risk also, but larger randomiser trials obviously need to confirm this. Contemporary guidelines recommend that patients with intermediate and high risk can be offered both SAVR and TAVR. Patients with very high operation risk (‘inoperable’) should be offered TAVR instead of SAVR, and patients with low risk undergo SAVR for now.

 

Continue reading “CARDIAC MRI MAY TEASE OUT PATIENTS WITH SEVERE AORTIC STENOSIS FOR EARLIER INTERVENTION”

 

 

Lets face it, Indians are a sedentary people. Were they like tis from the beginning one does not know. It is quite possible that life is too hard for most people, they just do not have the luxury of going out for a run or play a game of football. Have you watched a game of hockey being played in your neighbourhood park in the recent or distant past? I doubt it. For a city of more than 20 million people Delhi has an extreme paucity of decent parks. In fact there may not be more than a handful. The neighbourhood parks enjoy some bustle in the mornings when people can be seen going about their morning walks; quite a few still attached to their smart phones. The pace is leisurely without any one breaking out in sweat. These parks are deserted and forlorn the rest of the day. The weather too can be blamed for not providing the right incentive to play a sport. Its just too hot for most of the year, while winters have become periods of discontent with the awful pollution it brings along.

 

 

I highlight the laid back nature of Indian folks because the scenario is a little different in the West. The Westerner has a pathological interest in sports of all kinds. The British swear by football, The Yanks cannot stop discussing baseball, while the average Aussie considers life minus sports unbearable. Thousands endure pain running ultra marathons. An ultra marathon is any distance more than the 26.2 miles of a marathon. There is a saying , ‘ If you want to run, run a mile. If you want to experience a different life, run a marathon . If you want to talk to God, go for an ultra marathon.’

Continue reading “CAN TOO MUCH EXERCISE BE BAD FOR YOU ? MAYBE NOT”

 

 

Cervical cancer, with 500,000 new cases each year, accompanied by 250,000 annual deaths, is not a disease to be trifled with. It happens to be the second most common cancer in women (1). Almost all cases of cancer of the cervix are due to infection with the human papillomavirus (HPV). The biggest culprits are HPV type 16 and 18. Two vaccines are available on sale against the HPV 16 and HPV 18, one of them is also effective against HPV 6 and HPV 11 , responsible for genital warts. The vaccine is administered as 3 intramuscular injections over 6 months(2-4). The human papillomavirus is sexually transmitted, which means females who have attained puberty are particularly susceptible. Persistence infection with HPV results in alterations of cervical epithelial cells after a period of 5 years. Around 10% of infected women go on to develop histological changes graded as cervical intraepithelial neoplasia (CIN 1), CIN 2 and CIN 3. The next grade is termed carcinoma in situ or CIS. The chances of developing full blown cervical are increased considerably once the cellular changes develop, but are still are as low as 1% to 10%, which means that a substantial number of females with precancerous cellular changes resolve spontaneously. Invasive cervical cancer arises over many years , peaking between 35 and 55 years of age (5). The HPV vaccine has no role once a person has become infected. Substantial reduction in HPV infection have been recorded, but effect on cervical cancer remains to be established due to the long lag time in development of invasive cancer subsequent to HPV infection. A systemic review of HPV vaccination of at least 50% in high income countries reported that HPV 16 and 18 infections significantly deceased by 68%, while anogenital warts decreased significantly by 61% in girls 13 to 19 years. Another recent meta analysis of observational studies on quadrivalent HPV vaccination has reported maximal reductions of approximately 90% for HPV 6/11/16/18 infection, approximately 90% for genital warts, approximately 45% for low grade cytological cervical abnormalities, over a 10 year period (6-8).

 

Cervical cancer is the second common cause of cancer mortality in women in India, with more than 122,000 new patients each year accompanied by almost 70,000 deaths.In fact 85% of cervical cancer cases are in low and middle income countries. Twenty five percent of cervical cancer deaths in the world occur in India. Despite the dire statistics the Ministry of Health and Family Welfare continues to mull over the decision to include the HPV vaccine in the national immunisation program. The reluctance of the government is largely because of a 2012 writ petition (public interest) filed against the vaccine in the Supreme Court, and political pressure by one of its own affiliates. With a single dose costing almost $ 50 in India, any Indian government would blanch at the idea of putting in billions of dollars on a single vaccine. The HPV vaccine is however available commercially in the private sector.

 

An excellent randomised study from India (9) reported that a single round of screening for HPV involving more than 130,000 women substantially reduced the incidence of advanced cervical cancer and cervical related mortality within 8 years. Screening therefore would be essential in women aged 25-40 years to manage pre cancerous cervical lesions and also cancer itself. A much earlier and probably the best intervention would be preventing infection by HPF; this is where a vaccine comes into play. We already have data demonstrating significant reduction in HPV infection by the vaccine.

Continue reading “HPV VACCINE SPLITS COCHRANE BOARD WIDE OPEN”

 

 

 

 

Millions across the globe suffer form congestive here failure with enormously high rates of morbidity and mortality. A significant proportion of deaths are due to sudden death despite the best guideline based treatment. Crucially in numerous patients with dilatation of the left ventricle the mitral annulus dilates, disallowing optimal coaptation of mitral leaflets. The enlarging heart pulls the valve apart.The altered architecture of the mitral valve apparatus results in regurgitation of blood into the left atria further aggravation the situation. Patients feel exhausted, and hit a stage where they can barely walk a room’s length. They also get short of breath on slightest exertion, worse they are breathless even when they attempt to sleep. They often have to sit up during nights in order to catch their breath. The failing heart tries to compensate by expanding but this only makes matters worse, by increasing the leak (or regurgitation ) across the mitral valve.

 

 

 

It is still unclear whether mitral regurgitation is a sequel of the failing and enlarging left ventricle or whether it actually contributes to the pathophysiology of congestive heart failure. Mitral regurgitation subsequent to a failing left ventricle is termed secondary mitral regurgitation (earlier called functional regurgitation). Surgical intervention in the form of mitral valve replacement or surgical repair has not altered prognosis so far. Degenerative or primary mitral regurgitation, on the other hand can be treated with surgical valve replacement or valve repair.

 

 

Continue reading “DOES THE “MITRACLIP” REALLY WORK ?”

 

 

 

 

 

India apart from being an ancient civilisation never misses a chance to embraces a good humour. You have these massive jokes flying around all the time. For instance anchors of TV channels were given an extra lobe of the lung by the Almighty, but then He had to remove the spine in order to fit the lobe in. A doctor in Delhi states that rather than supporting corporate hospitals, doctors must support smaller hospitals run by a trust or a doctor.The good doctor seems oblivious of the fact that ,in reality,  more than 90% referrals for coronary angiography by doctors in Delhi are to corporate hospitals. The reasons for the referrals are manifold but the primary cause or incentive for this referral pattern is well known to most, and need not be dilated upon. So much for supporting small and medium sized hospitals.

 

The manifestly plump chief coach of the Indian cricket team wants us to believe that the current cricket team is the best traveling team for the last 15 years, despite knowing very well that Dravid managed to win a series in England while Ganguly drew one. A 4-1 hammering in a cricket series cannot possibly suggest that the losing team is the ‘best’. Remarkable interpretation by a remarkable coach. But purists in sports will remind us that cricket is played by less than a dozen countries and so it really dos not matter if we get whitewashed in 3 consecutive series in England. They have a point. Especially when we are inching our way up in athletics, which involves the entire world. To have the best middle distance runners in Asia is no mean feat. To beat Japanese ,Chinese Middle Easter athletes in a 1500 m race or an 800 m finals is a terrific achievement by any standards.

Continue reading “THE LOOMING CARDIOVASCULAR DISEASE EPIDEMIC IS NEITHER A GOOGLY NOR A DOOSRA, IT CAN BE TACKLED IF ONE POSSESSES THE WILL”

 

There is little data backing advice regarding congenital long QT syndrome (LQTS) and competitive sports. LQTS is a channelopathy characterised by abnormal QT interval prolongation on the ECG. LQTS defined by an abnormally prolonged QT interval (corrected QT interval >440 ms in men and >460 ms in women) with or without morphological abnormalities of T waves is a common cause of cardiac arrest. The prolonged QT interval due to decreased outward potassium currents or increased inward sodium currents predisposes to early after depolarizations and torsade de pointes ventricular tachycardia (VT). LQTS affects one in 2000 individuals. The annual rate of sudden cardiac death (SCD) is estimated to be between 0.33% and 0.9%, while the rate of syncope is 5%.

 

Twelve different genes are involved in inherited LQTS. The first 3 ; LQTS 1, LQTS 2, LQTS 3 account for > 90% of genotyped cases. Symptoms of seizure, syncope , or cardiac arrest usually appear at mean age of 12 years. Patients with LQTS 1 usually have symptoms with physical exercise and especially with swimming. Diving into water triggers the sympathetic system , while hitting cold water triggers the parasympathetic system due to apnea. The LQTS 3 is quite different in that VT is triggered while asleep or during rest. Emotional stress or ringing of a bell triggers VT in the LQTS 2 cohort. A corrected QT interval > 500 ms poses a high risk for a cardiac event. Beta blockers are indicated for all patients with syncope and also for asymptomatic with significant QT prolongation. Beta blockers are very effective in LQTS 1. The role of beta blockers in LQTS 3 is still not established, but symptomatic patients should receive beta blockers. Implantable cardioverter-defibrillator is indicated for secondary prevention of cardiac arrest and for patients with syncope despite beta blocker treatment.

 

It should be borne in mind that the QT interval is longer in athletes than in non athletes because of the lower heart rate connected with training. But the corrected QT interval remains in the normal range albeit towards the upper limit. Corrected QT interval must be measured manually from the beginning of the QRS complex to the end of the T wave. The end of the T wave is defined as point where a tangent line to the steepest part of the descending portion of the T wave intercepts the isoelectric line. The QT interval is best measured in lead II or V5.

Continue reading “LONG QT SYNDROME AND COMPETITIVE SPORTS”

 

There was really nothing to do with a patient with acute myocardial infarction in my times as a junior doctor in Delhi. We did not even know that aspirin by itself if given on time lowered deaths by 25%. I worked in one of there largest teaching hospitals in town. Thrombolytic therapy was to come almost half a decade later. I in fact was the first doctor to administer intravenous streptokinase in a woman admitted for acute inferior myocardial infarction in 1983; I was by now a resident at G B pant Hospital, Delhi. The dose given was homeopathic by todays standards, only 500,000 units of streptokinase, but the drug seemed to work because there was substantial resolution of the ST segments. An angiogram done some days later demonstrated a patent right coronary artery. In those days the only hospital doing coronary angiograms apart from AIIMS was G B Pant Hospital. But there was still no treatment for cariogenic shock (CS) complicating acute myocardial infarction (AMI). In the late eighties I realised in a randomised study that intravenous streptokinase opened just about 25%  of the culprit arteries while intracoronary streptokinase could recanalise more than two third culprit vessels in patients with AMI.

 

 

 

The SHOCK investigators presented data on the role of revascularisation in patients with AMI accompanied with shock for the first time in 1999 (N Engl J Med 1999; 341: 625-34). The researchers reminded the cardiological community that the incidence of shock ranged from 7% to 10% of all AMI patients. Also that cardiogenic shock carried the dreaded mortality figures of 60 to 80%. There seemed to be no effective treatment for AMI accompanied by CS till the SHOCK data got published. No significant difference in morality was seen at 30 days between patients treated with revasularisation and those treated medically ( 47% and 56% ; p=0.11) .But by 6 months the researchers found a significant absolute 13% reduction with revasularisation compared to medical treatment ( 50% vs. 63%; p= 0.027). It should be clarified that the majority of patients underwent balloon angioplasty alone with a third getting coronary stents. About one third patients with extensive coronary disease underwent coronary bypass graft surgery. The authors strongly recommended urgent revascularisation in patients of AMI complicated with CS.

 

Continue reading “TACKLING CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION”

 

 

 

 

Heart failure (HF) is a humungous problem all over the world that carries extraordinary morbidity and mortality. Every doctor has participated in the treatment of an HF patient during training and practice. There was little or no treatment for patients with heart failure with reduced ejection (HFrEF) fraction before the mid nineteen eighties. By definition HFrEF is accompanied by a left ventricle ejection fraction (EF) of less than 40 %. The bedrock of treatment of HFrEF used to be a combination of digoxin and diuretics albeit neither reduced mortality. The aim of treatment continues to be improvement symptoms, raising quality of life and of course cutting down mortality. Mortality was seen to e reduced for the first time in the mid eighties with a combination of hydrazine and isosorbide di nitrate was compared to placebo with the background of digoxin and diuretic therapy. Mortality was reduced from 35% to 25% (an absolute reduction of a solid 10%) by the vasodilator combination therapy in a randomised trial. This was published in 1986 in the NEJM. Soon after a randomised trial comparing enalapril (an ACE inhinitor) with isosorbide di nitrate plus hydralazine reported further reduction in mortality from 25% to 18% approximately. Enalapril 10 mg twice a day became standard treatment for HFrEF patients. There was also significant reduction in hospitalisation for HF.

 

The era of manipulating neurohormonal modification began with a vengeance because for the first time there was substantial lowering of death in heart failure patients. The next break through came by the Swedes who successfully demonstrated improved symptoms and lower mortality with a beta blocker. It appeared intuitively implausible but a number of randomised trials reported incremental reduction in mortality by adding a beta blocker to a cocktail of an ACE inhibitor, diuretic and digoxin. Bisoprolol, metoprolol and carvedilol clearly were effective in preventing deaths in patients with heart failure. Cardiac societies were advocating an ACE inhibitor and a beta blocker as a class 1 recommendation for patient with HFrEF. Beta blockers reduced death by a relative 35% and an absolute 3% to 4 %.

 

The third big player was the mineralocorticoid receptor antagonist. The RALES trial with spironolactone concluded that the addition of spironolactone to a combination of an ACE inhibitor and a beta blocker (along with diuretic and digoxin ) brought down mortality from 45% to 35%. The patients of HFrEF patients included in the RALES rial were obviously quite sick, the average EF was less than 30%. Soon eplerenone, another MRA , reduced mortality from 16% to 13% in the EMPHASIS trial that included NYHA class II patients. Cardiac societies therefore strongly recommended that all patients with heart failure be treated with an ACE inhibitor, a beta blocker and an MRA. The recommendation was that treatment be initiated with an ACE inhibitor, if symptoms persisted a beta blocker was to be added. The reverse could be employed too, a beta blocker begun first with addition of an ACE inhibitor in case symptoms persisted. An MRA was indicated in the event of symptoms despite a combination of an ACE inhibitor and a beta blocker. This was the protocol till 2016/2017 when both American and European societies included an ANRI (angiotensin receptor neprilysin inhibitor) and ivabradine in the scheme of things. Both societies recommend that if symptoms persist on a combination of an ACE inhibitor and beta blocker plus an MRA, then if the patient can tolerate an ACE inhibitor or an ARB, an ANRI should be added to the treatment.

 

 

The addition of or ‘switching’ to an ANRI is now a class I recommendation based entirely on the randomised PARADIGM heart failure trial that included more than 8400 patients with an EF less than 40%. The combination of valsartan ( angiotensin receptor blocker) and sacubitril ( neprilysin inhibitor) was found to further reduce cardiovascular mortality by 20% in patients already on enalapril (100%), beta blocker (95%) and an MRA (55%). Readmission for heart failure was also significantly reduced by 20%. Hypotension was the only serious problem with ANRI, surprisingly kidney impairment was not greater than placebo.

Continue reading “LOOKING FOR AN ‘MBA’ TO TREAT PERIPARTUM CARDIOMYOPATHY”

 

 

More than a decade ago a brilliant American marathoner form the United States collapsed and died 5 and a half miles into a marathon trial run for the Beijing Olympic Games. Ryan Shay was a world class long distance runner whose own Dad was a running coach. When Ryan was only 14 years old it had been noticed that his heart was a bit larger than most children, but this was ignored by everyone including his parents because he excelled in sports. Ryan had run numerous marathons before his death and was therefore presumed to be supremely fit. His death sent tectonic waves across the running world of north America. His legacy endures today with a prestigious annual mile race named after him. I had wondered aloud the on the cause of his death, and wrote so in the Times of India, Delhi edition then. I was afraid that maybe a drug had dome him in. The autopsy report was released more than 4 months after Ryan’s sad death. The report stated that Ryan did indeed have an enlarged heart but with dome scar tissue. It was surmised that viral myocarditis some time in the past accounted for the fibrosis in the young athletes heart. Ryan Shay died when only 28 years old. The normal electrical impulse of the heart is obstructed by fibrosis or scar tissue; it is rendered chaotic resulting in arrhythmia (irregular heart beat) ,which in turn can be fatal. The autopsy report of Ryan Shay concluded that fibrosis due previous viral myocarditis led to sudden cardiac arrest (SCA). There was no trace of hypertrophic cardiomyopathy in Ryan’s case, nor any evidence of a performance enhancer.

 

 

Most data on sudden cardiac arrest points out that the leading cause of death in young sportsmen is hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy is a genetic disease (not rare) in which the heart muscle is thickened disproportionately in an erratic manner at the cellular level. The heart muscle cells are not arranged in an orderly fashion under the microscope, there is no brick by brisk pattern of a wall seen in hypertrophic cardiomyopathy. The cells are completely chaotic like an imaginary Van Gogh painting if drunk; this is the microscopic hallmark of hypertrophic cardiomyopathy apart from an obviously thickened heart , which can at times be asymmetric as well. The thickened heart muscle can be recognised on 2 D echocardiography by a reasonably trained doctor, or even a technician. One does not have to wait for a post mortem to confirm obstructive cardiomyopathy. But it should be remembered that elite athletes especially endurance athletes may have enlarged hearts too, accompanied by changes in the their ECG. An astute physician or cardiologist would be required to distinguish physiological heart enlargement from the pathological genetic one.

Continue reading “PRE-SCREENING SHOULD BE A MUST FOR YOUNG INDIAN ATHLETES”