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.
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.
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.
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.
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.
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.
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.
A video clip distributed recently in a Whatsapp group of doctors featured a senior cardiac surgeon promulgating to a group of bored and confused journalists that good doctors have magic in their hands. Now that certainly may be true for surgeons but not for the entire profession. No one will argue that equally (if not far more importantly) is the quality of the mind that a good doctor carries. A decent professional needs above all a mind that can recall, crunch numbers, analyse signs and symptoms and to take decisive action in the form of intervention or medical treatment. The scriptures too concede that above the senses is the brain, upon the brain is the mind, which in turn is regulated by the consciousness. Emphasising the vital importance of both brain and mind. Let us for the time being stick to the mind, especially with news that the SPRINT-MIND study was presented in the annual meeting of international Alzheimer’s Association last Wednesday.
Almost 3 years ago I had expressed my concern that the SPRINT trial on hypertension generated wide spread publicity in the lay media even before publication in a peer reviewed journal. Every American newspaper and TV channel was bubbling with excitement about the news that intensive lowering of blood pressure to 120 mm Hg systolic would cut down death, heart attack, stroke, acute coronary syndrome, and heart failure significantly. The details of the data were however were largely unknown. The spin was on relative reduction but the actual numbers of events were not provided.
A committee of distinguished Indian cardiologists have to be congratulated for their endeavour in bringing out an Indian perspective on the definition, diagnosis and prevention of contrast induced acute kidney injury ( CI-AKI). The well written manuscript is however severely handicapped by lack of data regarding CI-AKI in Indian conditions. Only one citation from India is provided , which is the Madras Mission Scoring system of risk stratification from a total of 22 references adorning this manuscript. The conclusions drawn by the authors are entirely from Western literature . An Indian viewpoint in the absence of Indian data will have little impact; very much like pace bowling without the assistance of swing, albeit such conditions will favour Indian batsmen in the next 6 weeks of test cricket in England.
The incidence of contrast induced kidney injury depends upon risk factors such as age greater than 75 years, chronic kidney disease, diabetic nephropathy, and heart failure. Prevention of contrast induced kidney injury revolve around managing renal vasoconstriction and tissue hypoxia, direct cytotoxicity, increased blood viscosity and raised oxidative stress.
Every interventional cardiologist has grappled with kidney injury subsequent to diagnostic angiography or a percutaneous coronary intervention procedure. It can be a nerve shattering experience with considerable morbidity and mortality. Contrast nephropathy is a serious problem that has to be treated judiciously.
The working clinical definition of contrast induced AKI remains an elevation of serum creatinine by a relative 25% or an absolute 0.5 mg% in the 48-72 hours following a procedure. The incidence of CI-AKI ranges from 2%-10% depending upon the study you examine. It has been reported as high as 30% in patients with compromised kidney function at base-line. It is also recognised that there are biomarkers indicating damage to nephrons as early as 6 hours post procedure. These biomarkers indicate kidney damage in the absence of elevated serum creatinine. Neutrophil gelatinase associated lipocalin ( NGAL) and Cystain C are sensitive biomarkers reflecting kidney injury but are currently a trifle too expensive for routine clinical use. The Indian “experts” recommend that iso osmolar contrast is to be preferred to low osmolar contrast in patients with compromised kidneys. Hydration with saline is the best preventive measure against CI- AKI ; and that N acetylecysteine (NAC) should be upgraded to recommendation 2A from 2 B.
The 2 most important papers on CI- AKI published in 2017 seem to have completely escaped the notice of the Indian committee. Both papers have been acknowledged as t highlights of research conducted in 2017 in acute coronary syndrome by the European Society of Cardiology. It is well recognised that CI-AKI is a consequence of the administration of intravascular iodinated contrast media use during radiological procedures and PCI. The mechanism is supposed to be direct nephrotoxicity by free radicals or renal vasoconstriction. Dialysis may be required in more than 5% of patients developing AKI due to contrast. Preventive strategies continue to be unclear because trials done in the past included variable population groups, variability in treatment strategy and end points employed. Crucially these studies were powered for CI-AKI and not for hard endpoints like death or requirement of dialysis.
Cardiac resynchronisation therapy (CRT) or biventricular pacing has rapidly evolved as the bedrock for treating patients with severe hear failure on optimal medication (beta blockers, aldosterone antagonists, and ACE inhibitors). It has been observed that CRT improves ejection fraction, quality of life, symptomatic status and above all it significantly reduces mortality. It is most effective in patients of systolic heart failure in NYHA functional class III – ambulatory IV, having LV ejection fraction less than 35%, and QRS duration greater than 120 ms . Crucially the patient should be able to live at least one year. The mechanisms by which CRT improves cardiac function are complex but the paramount reason is it’s ability to synchronise contraction of the failing left ventricle. Left bundle branch block leads to dyssynchrony in left ventricle contraction, which means that all segments of the chamber do not contract uniformly. There is also dyssynchrony in contraction between the right and left ventricles. With establishment of chaotic contraction there is compromise in stroke volume and also cardiac output. CRT also improves b-adrenergic responsiveness and other cellular functions.
The MADIT CRT randomised 1820 patients to CRT and no CRT therapy against the background of optimal medical therapy. Continued follow up for 7 years shown that in patients with left bundle branch block there was 41% reduction in death, an absolute reduction of 11% as compared to patients not on CRT. The substantial reduction in mortality was seen in patients already on beta blockers and ACE inhibitors ( and angiotensin receptor blockers). The MADIT -CRT trial included patients in NYHA class I and II.
More than 10 years ago the COURAGE trial (N Engl J Med 2007;356: 1503-16) had randomised more than 2,200 patients of stable angina to percutaneous coronary intervention (PCI) plus optimal medical therapy or optimal medical therapy alone. Medical therapy consisted of statins, beta blocker, long acting calcium blocker or long acting nitrate. All patients needed to have a 70% stenosis of at least one epicardial coronary artery accompanied with objective of evidence myocardial ischemia. Surprisingly at the end of almost 5 years there was no difference in death or myocardial infarction. In patients with stable angina there was no advantage of PCI and optimal medical therapy over medical therapy.
A few months ago the ORBITA trial (Lancet 2018;391:31-40) reported that there was no significant increase in exercise time when PCI was compared to a sham PCI procedure in stable angina patients with a single artery that was blocked significantly. The difference was only an insignificant 16.6 seconds at 6 weeks follow up. There were loud cries of changing guidelines in the treatment of stable angina following the presentation of ORBITA data. Medical therapy when prescribed optimally was as good as an invasive procedure in patients with stable angina. The study included only 220 patients and had a brief follow up of only 6 weeks.
Heart failure (HF) is an awful disease, there are lakhs of patients in this country who barley get treated. A considerable proportion of HF patients have systolic dysfunction or reduced ejection fraction of there left ventricle. Thus is also known as heart failure with reduced ejection fraction or HFrEF. The burden of severe heart failure continues to escalate . Just about every practicing physician regularly comes across a heart failure patient needing careful treatment and probable admission in hospital. Once hospitalised almost 30% to 40% patients need re-hospitalisation within 6 months. Almost patients are dead due to worsening heart failure or sudden arrhythmia. The majority of current physicians will just not be able to appreciate that as recently as the mid ninety eighties there was no effective treatment for heart failure apart from diuretics and digoxin. Neither diuretics or digoxin are known to reduce death in HF. Despite reduction in hospitalisation by angiotensin converting enzyme (ACE) inhibitors, spironolactone and digoxin, the incidence of admission for worsening HF remains quite grim.
The 1990’s witnessed substantial progress in reduction of HF hospital admission. Beta blocker treatment in addition to ACE inhibitors and digoxin reduced risk of hospitalisation by 20% to 30%. The early studies on beta blockers assessed efficacy in patients with mild to moderate HF. The effects of beta blockers on morbidity in patients with severe HF were yet to follow. The COPERNICUS ( N Engl J Med 2001;344:1651) trial was one such pioneering trial that established the role of carvedilol in patients with severe HF. COPERNICUS was a prospective double blind placebo controlled trial that studied the effect of carvedilol on mortality and morbidity in severe HF. Severe HF was defined as breathlessness or fatigue at rest or on minimal exertion, and a left ventricle ejection fraction less than 25%. Patients were already on diuretics (>95%), an ACE inhibitor (>95%), digoxin (65%), spironolactone (20%) or amiodarone (15%). The trial was stopped early after a mean duration of follow up of 10.4 months, because of a highly significant benefit on survival with carvedilol. Notably in this short follow up 24% of patients in there placebo group were admitted for worsening HF as compared to 17% in the carvedilol group, indicating the severity of HF in this trial. Moreover there was no incidence of worsening of HF by carvedilol during start of treatment.
The AFFIRM trial ( N Engl J Med 2002; 347:1825-33) had randomised more than 4000 patients with atrial fibrillation (AF) to rate control and rhythm control groups. The researchers had concluded that there was no difference in mortality between the 2 groups, in fact adverse events were similar while deaths were actually a bit more in the rhythm control group. A total of 4060 patients were included in the trial with two thirds having hypertension while the remainder had coronary artery disease. There were 356 deaths in the rhythm control group versus 310 deaths in the patients assigned to rate control by 5 years follow up. More patients in the rhythm control group needed to be hospitalised. Anticoagualation was recommended in both groups. Rhythm control was achieved by amiodarone, disopyramide, flecainide, morcizine, procainamide, propafanone, quinidine, sotyalol and a combination of these drugs. Rate was controlled below 100/min by beta blockers, verapamil, diltiazem, digoxin or a combination of these drugs. The average age of patients studied was 70 years.
The next randomised trial comparing rate versus rhythm control was published more than a decade later ( N Engl J med 2016;374:1911-21). This studied AF developing post cardiac surgery. Rhythm control was achieved with amiodarone. New onset post operative atrial fibrillation occurred in almost 700 patients of the 2109 patients enrolled in this trial. Total number of hospital stay was the same in both groups. There was no significant difference in rates of death or over all serious side effects. At 60 days more than 94% patients in both groups had a stable without AF for the previous 30 days. The researchers of the trial concluded that a sizeable number of patients develop new onset AF after cardiac surgery, but there was no discernible difference in hospital stay, mortality or other complications. The strategy of rhythm control did not provide any clinical advantage over rate control in patients with post heart surgery AF.
I had wanted to write on the treatment of acute coronary syndrome-unstable angina, but I woke up this morning to learn that the world had turned more unstable, than it had ever been since World War II. Donald Trump has scrapped the Iran Nuclear Deal not because he did not consider it worthwhile but probably more because it was the singular foreign policy achievement of his predecessor. Obama was rightly proud of the Iran Deal because it has stopped the Iranian nuclear program . Iran was no longer feverishly making a nuclear bomb, it had cut down its centrifuges from 20,000 to around 500, uranium stockpile had been reduced from 8 tons to just 4%. Crucially verification by international atomic energy agencies were considered “robust”, which means Iranian nuclear establishments were open to inspection whenever necessary. Trump by reneging on American promise will instigate the Iranians to pursue their making the atom bomb program with a vengeance despite any form of sanctions. The Middle East may once plunge into wars, American lives put to danger, and above all put India in a delicate and vulnerable position.India buys considerable amount of oil to fuel its economy from Iran, and that too not in Dollars but Euros. Why would the North Koreans believe the Americans on any deal? Trump has already reneged on the Paris Climate and Trans Pacific Partnership trade deals. Some now say that Americans rarely take deals signed by them seriously. The Brits, French and Germans are scrambling to salvage the fractured deal. Mr. Putin is yet to issue a statement. The world waits with bated breath for the Iranian response. Do the Iranian resume their military nuclear program? Does the position of their moderate president become untenable? Do the hard liners in Iran strengthen their grip over their government?
We however ned to concentrate on acute coronary syndrome. Acute coronary syndrome (ACS), apart from ST segment elevation myocardial infarction (STEMI), consists of unstable angina and non ST segment elevation myocardial infarction (NSTEMI). Unstable angina is worsening stable angina that occurs more frequently, on lesser exertion or at rest. Unstable angina is not associated with a rise in troponin levels or other cardiac enzymes but has ECG changes of T wave invasion or ST segment depression. Troponion and cardiac enzyme levels are raised in NSTEMI. Routine coronary angiography followed by PCI if needed has been shown to provide improved clinical outcomes by multiple randomised trials. The optimal timing for intervention in patients with unstable angina or NSTEMI was clarified by the large TIMACS trial. TIMACS randomised 3030patients with ACS to undergo either routine early intervention (less than 24 hours) or delayed coronary angiography more than 36 hours after randomisation.The primary outcome was death, myocardial infarction or stroke at 6 months. The secondary outcome was death, myocardial infarction o refractory schema at 6 months. Primary angiography was performed in 98% of the early intervention group (median time, 14 hours) and 96% in the delayed intervention group (median time ,50 hours) . At 6 months there was no significant difference in the primary endpoint. There was a 28% relative reaction in secondary endpoint of death, MI or refractory schema in the early intervention versus delayed intervention group, which was significant (10% versus 13%, p=0.003). Early intervention improved outcome in patients at highest risk (one third) but not in the intermediate o low risk groups.
It ia an established fact that an ST-segment elevation myocardial infarction (STEMI)is due to rupture of an atherosclerotic place and the resultant platelet rich thrombus that completely blocks the coronary artery. By 2003 based upon 23 randomised trials it had become clear that primary percutaneous coronary intervention (PPCI) resulted in significantly fewer deaths, re-infarction, and stroke, as compared to fibrinolysis or thrombolytic therapy. PPCI is superior because of greater achievement of TIMI 3 antegrade flow than thrombolysis and stabilisation of the ruptured plaque. There are less chances of a re-infarction, greater salvage of myocardium and significantly fewer intracranial bleeding with PPCI as compared to thrombolysis. PPCI therefore has become the treatment of choice for STEMI if done in time and by experienced operators.
Experimental studies indicate that amount of myocardial salvage depends on the speed in which the occluded coronary artery is opened up; the sooner PPCI is done the greater the benefit. Hence the cardiac adage “ time is muscle.” Cardiologists became greatly interested in a combination strategy of thrombolysis followed by PCI or “ facilitated PCI.” Facilitated PCI was also called “pharmaco-invasive PCI” by some. It was theorised that by administering a thrombolytic agent as early as possible after symptom onset there would me more infarct related arteries open to some extent by the time PCI was attempted in the cath lab. However early studies combining thrombolytic therapy with immediate PCI reported increased rates of death, coronary occlusion and hemorrhagic complications. The biggest dampener was the ASSENT-4 PCI trial (Lancet 2006;367:569) that randomised 4000 patients of STEMI less than 6 hours duration to PPCI or to standard PCI soon after full dose tenectaplase. All patients got aspirin and a bolus of unfractionated heparin. The safety monitoring board had to abort the study because of significantly greater stroke during hospital stay, reinfarctiron and repeat target vessel revascularisation within 90 days in the study group. The researchers concluded that full dose tenectaplase with thrombolytic co therapy (preceding PCI by 1-3 hours) cannot be recommended.
In the same issue of the Lancet (2006;367:579-588) a review of randomised trials comparing primary and facilitated PCI for STEMI was published. The authors identified 17 trials of STEMI that included a little more than 4500 patients of STEMI. Despite 2-fold increase in the number of patients with TIMI 3 flow in the facilitated PCI group compared to the PPCI group, there was significantly more mortality, re-infarction and urgent target vessel revasularisation. Facilitated PCI was associated with higher rates of major bleeds. The conclusion drawn was that facilitated PCI offers no benefit over primary PCI in the treatment of STEMI, and should be actually avoided. The meta analysis which included data from the ASSENT-4 PCI trial, showed that increased mortality was restricted to studies that used full dose thrombolytic therapy as part of the facilitated strategy. The FINESSE trial randomly assigned 2453 patients in a 1:1:1 treatment allocation to half dose reteplase with abciximab (GP 2b/3a inhibitor), abciximab alone or to primary PCI. At 60-90 minutes patients assigned to facilitated therapy had more ST segment resolution and more patent arteries with TIMI 3 flow before PCI. These benefits however did not translate to lesser death, heart failure, or cariogenic shock through 90 days. There was increased intracranial haemorrhage and significantly more major bleeds in the facilitated PCI groups.A patent artery does not guarantee myocardial perfusion. In fact even though 90% of patients may have TIMI 3 flow after primary PCI, only 29 % have normal myocardial perfusion. Potential explanations for impaired myocardial perfusion despite an open infarct related coronary artery may be distal embolisation of atherosclerotic debris, capillary edema, myocardial edema compressing microvasculature, and plugging by inflammatory cells.