No new drug for systolic heart failure (HF) has been approved by the FDA for more than a decade; the last one being eplerenone (an aldosterone antagonist) which was approved in 2003. In 2005 a combination drug of hydralazine –isosorbide dinitrate was cleared for (HF) for African Americans who persisted with symptoms despite evidence based treatment. Finally after so many years of research a new combination tablet has made head lines across the globe for significant reduction in mortality in HF patients already on standard treatment including 10 mg twice a day of enalapril. The novel drug has been given the rather mundane name of LCZ696, and consists of a combination of a neprilysin inhibitor (sacubitril) and the angiotensin receptor blocker (ARB) valsartan (160 mg).
The recently concluded European Society of Cardiology 2014 Conference (one of the largest cardiology meetings in the world) in Barcelona, Spain was dazzled by a striking study that showed dramatic efficacy of an experimental drug in patients with heart failure. The new drug, with the tonguetwisting name of ‘LCZ696’, reduced both deaths due to cardiovascular disease and hospitalization due to heart failure in patients already prescribed standard life saving medication by a whopping 20%. This study (PARADIGMHF) included more than 8000 heart failure patients (1). Heart failure affects more than 26 million (260 lakh) people globally and is the leading cause of hospitalization in Europe and the US. A patient with heart failure is unable to pump blood adequately to different organs of the body, because of a weakened heart due to a variety of reasons such as heart attack and hypertension. This leads to breathlessness, tiredness, salt retention, and swollen feet and eventually, if not treated, death. The new drug has therefore created a buzz among physicians across the world; but it will cost around $ 2,500 annually as opposed to $ 50 a year spent on available heart failure medicines. It will be therefore a multi-billion dollar bonanza for the drug company that has made the new drug ‘LCZ696’. Fiscal profit, albeit justifiable, is the driving force behind pharmaceutical research for new drugs. There have been hundreds of rigorously controlled randomized trials on drugs and devices in cardiovascular disease; acute heart attack in fact is not only the most extensively studied disease in the world but has also turned into a multi billion dollar industry. There is, however, sparse randomized data on the role of diet in prevention of heart attack and stroke. The public is repeatedly bombarded with anecdotal or observational nutritional information on prevention of cardiovascular disease.
Percutaneous coronary intervention has rapidly evolved in the last 38 years from the the first from percutaneous balloon angioplasty (BA) done in 1977, insertion of bare metal stents (BMS) in the eighties, to deployment of metallic drug eluting stents (DES) since 2000. It was realized in the eighties that coronary stents were mandatory in most cases of PCI to prevent catastrophic coronary artery recoil following BA, to tack up dissection, and to reduce restenosis. Second generation DES with much finer struts have now become the norm because they reduce restenosis and stent thrombosis in stable angina and acute coronary syndrome patients as compared to earlier DES and BMS. All second generation DES however still carry the risk of chronic inflammation by the polymer that holds and elutes the drug, and the phenomenon of late neoatheroslerosis. The metallic stent moreover jails the concerned artery preventing vascular reactivity and blunting coronary dilation and constriction; they can also block a significant side branch if inserted at a bifurcation. These potential disadvantages led to hectic research on a fully bioresorbable scaffold capable of melting away in 2-3 years.
Recently a 45 year-old man was admitted for gross congestive heart failure (HF) due to non-ischemic cardiomyopathy (normal coronary arteries) and right bundle branch block (RBBB). He had been hospitalized before for breathlessness at rest. It was agreed that he was in NYHA class IV; he had a left ventricle ejection fraction of about 20%; the QRS was a little more than 120 msec. The junior consultants were keen to implant a biventricular pace- maker; till I patiently explained to them that cardiac resynchronization therapy (CRT) was yet not an indication because the patient was not ambulatory class IV, and he moreover had an RBBB. I had to draw their attention to the 2013 European Society of Cardiology guidelines on CRT therapy that provides a level of recommendation of II b in the event of RBBB, but the patient must be in NYHA class II – ‘ambulatory’ IV. Ambulatory class IV implies that the patient has not been admitted for heart failure electively or as an emergency in the previous one month. This patient had not only been admitted the previous week but currently was in hypotension mandating inotropes.
Roberto Calasso in his enchantingly moving book ‘Ka’ quoted the contemplation by ancient Indians that the world “only exists if consciousness has perceived it as existing. And if a consciousness perceives it, within that consciousness there must be another consciousness that perceives the consciousness that perceives.” The same consciousness also called “Atman” is defined in the Upanishads as “that which sees you without being seen, that which hears you without being heard, that which feels you without being felt, and that knows you without being known.” Repeatedly the Vedas, the Upanishads and the Bhagwad Gita remind man that this consciousness cannot be attained by power, piety, wealth or penance.
Recently my 94 years old Dad who suffers from hypertension ischemic cardiomyopathy (left ventricle ejection fraction of 22 %) Addison’s disease an enlarged prostate and internal hemorrhoids complained of sudden onset palpitations when I returned from hospital in the evening. The palpitations had been on for the last 2 hours and made him both weak and breathless. I realized his heart rate was quite fast and for a moment my heart was in my mouth as I anticipated ventricular tachycardia; but very soon I realized the pulse was irregularly irregular and moreover reasonably well felt. He was in atrial fibrillation (AF). I told him to hang in while I got in reinforcements. I actually drove to Prayag Hospital (5 minutes away from home) and borrowed a cardiac monitor that they gave me without a moment’s hesitation. I also quickly bought 3 ampules of injection amiodarone; a vac of 5% dextrose for dilution and a 20 cc syringe.
We have in the past 2 decades witnessed hundreds of thousands of runners participating in marathons across the globe. Last year Dennis Kimetto set the world record in the Berlin Marathon at 2:02:58. Kimetto not only beat every body who ran in that marathon but every one else who had ever shown up before any where as he blazed his way to a sub 2 hour 3 minutes record time. His record is still intact. The world has rapidly decided to run longer and at the fastest pace possible. The current mantra is to run many miles at blistering speed in the belief that this will cut down disease and death. Recent data however suggest that this may not be the case; and is actually a partial truth. Running undoubtedly is one of the best methods to significantly reduce mortality, heart disease, hypertension, osteoporosis, diabetes, depression and probably cancer. But the question is how much running is therapeutic or healthy. Phidippides was possibly the first running courier to run 26 miles from a battlefield close to the city of Marathon to Athens to deliver the momentous news of victory against the Persians in 490 BC; but the man collapsed almost immediately after and died. Running too much over decades at race speed is now being considered over dosage; much like intake of excessive medicines resulting in harm to the human body.
They reckon the population of Delhi NCR is over 20 million and that two thirds of these are young people. One can safely presume that around half are in their thirties and forties; that is almost 10 million people. Epidemiological data indicates that more than a fourth of these young people suffer from hypertension defined as blood pressure exceeding 140/90 mm Hg. That is a sizable population at risk for heart disease and stroke. There is substantial evidence that treating moderate and severe hypertension significantly lowers death, heart disease and stroke. But when you enter the area of mild hypertension the evidence has been equivocal. Mils hypertension is defined as systolic blood pressure 140 to 159 mmHg and diastolic between 90 to 99 mm Hg.
The European Society of Cardiology, unlike the US guidelines that recommend dual anti-platelet therapy (DAPT) consisting of aspirin and a P2Y12 inhibitor such as prasugrel, ticagrelor or clopidogrel be used for at least 12 months subsequent to a percutaneous coronary intervention (PCI) procedure, has reduced DAPT duration to only 6 months for drug eluting stents (DES). One month of DAPT is advised for bare metal stent (BMS) deployment (class I), and less than 6 months in patients with high bleeding risk who receive newer generation DES (class II b). It must be noted that randomized clinical trials (RCT) have not demonstrated benefit from prolonged DAPT. The American College of Cardiology/American Heart Association guidelines advise 12 months of DAPT in patients treated with DES, who are not at high risk of bleeding.
Recently a middle-aged man presenting with non ST-segment elevation myocardial infarction (NSTEMI) with significant distal left main disease involving ostia of the left anterior descending (LAD) and left circumflex (LCX) arteries consented for percutaneous coronary intervention (PCI). He underwent successful distal left main stenting with TAP stenting for the LCX lesion, but almost immediately developed a large thrombus in the LAD artery, that was managed with an intra-coronary high dose tirofiban injection. The patient had been pre-loaded both with aspirin and 60 mg of prasugrel before coronary angiography. This case suggested the futility of pre-loading with prasugrel but raised other questions such as the role of upstream glycoprotein IIb/IIIa inhibitors (GPI), particularly in patients with distal left main disease.