Archive for the ‘Uncategorized’ Category

The New England Journal of Medicine (NEJM) the premier journal in medicine originated two centuries ago, in 1811, when  John Collins Warren, a Boston physician, along with James Jackson, submitted a formal prospectus to establish the New England Journal of Medicine and Surgery and Collateral Branches of Science as a medical and philosophical journal. 

Subsequently, the Massachusetts Medical Society (MMS) purchased the Journal for US$1 and, in 1928, renamed it to The New England Journal of Medicine.

NEJM’s New Journey

It is 2022, after 200 years of providing explosive knowledge in medical science, MMS  starts a new journal, fresh and bold. It is called NEJM Evidence. Can you guess, what is the need for such a journal now? I think the most battered word in science in current times is probably “ evidence”.  It has a unique character of appearing most sacred as well as scandalous at the same time.

NEJM has remained the torchbearer of almost all advances in the medical field seen in the last two centuries.  It is heartening to note the newborn is named as NEJM evidence. It has come at a critical juncture. I am sure, everyone will acknowledge that we are at difficult crossroads. Overwhelmed with unregulated scientific discoveries and publications, struggling to deal with self-inflicted knowledge pandemic. In the process, we have lost “not only” the ability to ignore trivial health issues “but also” failed to provide simple, cost-effective care to the real patients who desperately need it.

Let us hope, (& wish,) NEJM’s new prodigy will guide medical science towards a successful, meaningful, and ethically fulfilling journey for mankind. Meanwhile, let us pray for every medical scientist to be blessed with the required strength and courage to steer in the right direction, weeding off both academic and non-academic contaminants.



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What is in store for the future of cardiology as of 2022?

Here is one of the rare lectures (A grand rounds by Houston Methodist)  by legendary cardiologist Dr. Euegne Braunwald who shares his wisdom, vision, and research and finally his advice for the generation next cardiologist.


For those, who are short of time to listen to the father of modern-day cardiology, let me share a preview. The talk is divided into 6 subsets.

  1. Polygenic risk score (PRS)  Dr. Braunwald talks about how genetic risk profiling and risk factor interaction will help us identify susceptible populations. Here, he stresses also the importance of clinical risk assessment.
  2. Primordial prevention of CAD: 
  3. Anti-lipid strategies: He introduces a new concept of  Cumulative LDL score &  CHD threshold.  Dr. Braunwald argues rigorous lipid control should go beyond statins and suggest once a year Injection Inclisiran(Small interfering RNA that prevents PCSK synthesis) will reset the lipids levels by 40% and prolong life by 30 years.
  4. Anti -Inflammatory strategies: He reminds us Atherosclerosis is equally an inflammatory disease and new anti-inflammatory drugs like Canakinumab’s role could be vital.
  5. Artificial Intelligence: Will be the guiding force in the future of preventive cardiology, as well as treatment. He tells us predicting Atrial fibrillation and even LV function from the resting ECG is possible.
  6. Clonal hematopoiesis independent potential (CHIP) is a new risk factor by somatic mutations in leukocytes that accelerate atherosclerosis proven by canonical risk predicting models

    It was a great one hour to spend on a Sunday, under Covid Lockdown.  However, It was a surprise, the biggest Innovation in cardiology in the last century, PCI, and other exotic coronary and noncoronary interventions could not find a place in his one-hour lecture. I think there is a hidden message here. 

He signs off with some important advice for the generation next cardiologist.

Thanks, Methodist for bringing  this to us.


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Surprised to find this site, in the 5th slot in the global rankings by feedspot search engine.

Never Imagined, when I started my scribblings way back in 2008 , It will be listed along with American heart asssociation, BMJ and others in top 10.

I need to thank the readers who make this happen.

Thank you all.

(PS :I am not sure on what basis these rankings were done though, still it adds some energy, that keeps this site running)


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A new year brings “New hope”

After a hectic two years , let us pray & believe, the good old times will be back in our life.

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     If anyone asks to shortlist the best papers that were, ever published in clinical cardiology, I am sure, this one will reach the top ten. It was 1979, the field of cardiology is just waiting to explode. CAD was managed primarily with drugs and occasional CABGs.  Coronary angiograms were an academic luxury. Both thrombolysis and PCI were unknown. Fortunately, Clinical cardiology was still alive and kicking. Dr. George Diamond and  Dr. James Forrester from  Cedars Sinai, New York worked together to bring this masterpiece. How and when to suspect CAD in the general population? For the first time probability was applied as a diagnostic tool. 

Link to the NEJM Paper

The paper begins by analysing basic clinical symptoms, risk factors, then gradually dwell deep into the population-based likelihood ratio, of CAD with the help of stress ECG, Thallium, and fluoroscopic coronary calcium. It finally ends up with a magical fusion of the  Bayesian theorem into clinical medicine. It essentially taught us how to accrue scattered knowledge, clinical judgment, and diagnostic acumen among physicians in a community and aggregate them to a powerful statistical evidence base.

A popular Inference from the DK model still asked in cardiology boards

It’s more than four decades since this paper was published. There have been some concerns about DF classification in the current era.  It was compared with the new Duke risk and found to be less valuable in the low-risk CAD population.(Wasfy MM, et all AJC 2011)  The concept of pre-test probability deciding the diagnostic value of screening tests is very much valid. We need to recalibrate the DF scale for the current population and new generation screening methods like MDCT etc..(Gibbons et al Jamanetwork 2021 )

Forget the pros and cons, DF study told us the importance of clinical judgment in the decision making process. Now, we are living in a glamorous new world of cardiology. Cath labs have become our 24/7 office suits, always in hot pursuit for instant fix solutions. Still, we often find ourselves desperately blinking at the doors of EBM, for the elusive answers to some critical queries. Why the same intervention seems to work in one large study and totally go wanting in another? (MITRA-FR vs COAPT)

Where are we erring?

The problem is the way evidence is created. It is often made up of data collected from poorly framed questions and methods, which are incompletely collected or wrongly interpreted. I wish, Bayesian theorem derivatives also address the probability of how pure is the pre-test (research) evidence base available in a scientific community. The core of truth in statistical science lies in, how we understand and define the number needed to treat, (NNT) and the number needed to harm (NNH) with any treatment or diagnostic modality.

Final message 

Artificial intelligence and machine learning are projected to be the next big thing in medical science However, the probability of machines prevailing over, human clinical acumen, backed by a sound knowledge base and observation skills appears very minimal. Let us see. Meanwhile, I wish every young cardiologist to go through this paper by D&F to get enlightened.  


1.Diamond GA, Forrester JS. Analysis of probability as an aid in the clinical diagnosis of coronary-artery disease. N Engl J Med. 1979 Jun 14;300(24):1350-8. doi: 10.1056/NEJM197906143002402

2,Wasfy MM, Brady TJ, Abbara S,  Comparison of the Diamond-Forrester method and Duke Clinical Score to predict obstructive coronary artery disease by computed tomographic angiography. Am J Cardiol. 2012 Apr 1;109(7):998-1004. doi: 10.1016/j.amjcard.2011.11.028. 

3.Gibbons RJ, Miller TD. Declining Accuracy of the Traditional Diamond-Forrester Estimates of Pretest Probability of Coronary Artery DiseaseTime for New MethodsJAMA Intern Med. 2021;181(5):579–580. doi:10.1001/jamainternmed.2021.0171

Further reading 

1.The Duo of D & F didn’t stop with that. They went on to make produce another fabulous paper on the hemodynamic classification of STEMI. Which is discussed elsewhere

Dr. Diamond & Dr . Forrester



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There are a whole lot of scientists trying to jailbreak and expose the limitations of the hugely popular ISCHEMIA trial which put the emergency breaks in the way we used to practice cardiology. Not everyone is happy. While few are ready to apply the brake, many continue to love the accelerator.

This study (Ref 1)  talks about an important issue. How much of the CAD  populations in the real world will match the ISCHEMIA trial population? It concludes it is just 32%.  It suggests caution to the cardiologists to understand this trial from a proper perspective. Don’t give too much importance, lest we may end up with Inappropriate non-intervention. 

Sounds too good? 

But is it real?

The authors of ISCHEMIA have countered this claim. (Ref 2)If we include all mild and moderate symptom cohort Ischemia study population is very much relevant in the true world and, actually constitutes about 68 % .

Final message 

Clinical trials are the greatest gift of science and EBM. But why is that …it never fails to confuse us at each and every step, while we accumulate tons and tons of evidence.

I wish someone do a mega four-limbed study on what really our patients are getting in the overall CAD care.

  1. Inappropriate non-intervention 
  2. Appropriate Interventions 
  3. Inappropriate interventions
  4. Appropriate non-Intervention.

I could easily guess the winning theme of this hypothetical trial. (That’s not good news though) However, response 4  If practiced in the right spirits would have the maximum impact on global cardiovascular health in terms of both healing and saving.


1.Chatterjee S, Fanaroff AC, Parzynski C, et al. Comparison of patients undergoing percutaneous coronary intervention in contemporary U.S. practice with ISCHEMIA trial population. J Am Coll Cardiol Intv. 2021;14:2344-2349.

2.Maron DJ, Bangalore S, Hochman JS. The glass is at least half full. J Am Coll Cardiol Intv. 2021;14:2350-2352.


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Check out these two posters* for are a quick reference on HOCM with current updated evidence. The first one details about  Echo evaluation. The second one illustrates the genetic screening flow chart of the HOCM families.

Some of the queries, you will find the answers from these posters are,

1. How to recognize Intrinsic mitral valve defect by MR jet morphology?

2. How to cross-check the true LVOT gradient from MR jet?

3. When to do a provocative test to document the LVOT gradient?

4. What are the standard pre-myectomy measurements by Echo?

5. How to screen a family member of HCM?  Pros and cons of  Phenotypic vs Genotyping screening 


The poster is created by: Karan Kapoor, MD; Allison G Hays, MD, FASE. Design and illustration by medmovie.com.


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With deep regret, reporting the demise of Dr. KA Abraham, cardiologist, par excellence in our part of the world (Chennai, Tamil Nadu, India.) He was a man of great knowledge,  wisdom, and integrity and was an inspiration to generations of cardiologists like us.

Dr.K.A Abraham 1942-2021

A life, that was fully dedicated to all those heart patients, many of them sick children in his den, the Railway hospital, Chennai for three decades. Though, never had the privilege to be associated with him either directly, nor does he knew me, one could feel instantly the greatness and simplicity in him. It’s 1994-95, vividly recall, the early morning classes, he took in the small auditorium in the Railway hospital,(For which, we used to rush to the far away Perambur from MMC in the peak Chennai traffic). His passion for teaching the basics of cardiac catheterization was phenomenal. Somehow, I used to think he was in the league of the Nobel trio of “Forssman, Richards & Cournand” who invented cardiac catheterization.

Those were ordinary days when the quest for knowledge and teaching was pure and Dr. Abraham was one of the great souls in pursuit of genuine and quality cardiac care. No surprise, his services were recognized and conferred a top award of India,  Padmashree.

Yes, India truly lost a pioneering cardiologist. 




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“Your husband is really lucky, his heart attack got spontaneously aborted. His ECG is near normal now. The angiogram is normal.No lysis, no stent is required. He secreted his own TPA and got rid of the clot. We will discharge him to tomorrow.”

Thank you very much, Doctor. How did this happen, doctor?

Don’t thank me. Definitely, I don’t have an answer. Spontaneous successful thrombolysis (Ref 4) happens up to 15 % of ACS. All I can say is he has a very disciplined  fibrinolytic system backed up with an agile mast cell and basophil function.

Vascular events: Pathobiology

Vascular highway accidents that happen due to the sudden freezing of blood in any vital organs consume more human lives than any other disease. This can happen with or without a trigger from the vessel wall, the phenomenon which Virchow’s taught us a century ago.

By the way, who is keeping the 5 liters of blood in our body in a fluid status life long?

Blood coagulation and lysis is a fascinating balance of two pairs opposing hematological forces.

  1. Coagulant system (The 13-factor Intrinsic /extrinsic clotting cascade )
  2. Anticoagulation system  (Antithrombin, protein  C and S, and tissue factor pathway inhibitor (TFPI) )
  3. The fibrinolytic system (Commander in chief is Plasmin, It has the ability to feed and digest clots just like that It comes from plasminogen the activation of this the core concept of thrombolytic or fibrinolytic agents)
  4. Anti-fibrinolytic system  Haemostasis 1986;16:16–20

* Among the blood component cells platelet is the only cell that plays a critical role in the clotting process. Paradoxically the fiery red clot, that is loaded with RBCs has a little direct role in the clotting process while biochemical molecules like fibrinogen, thrombin plays a major role. The fact that blood is liquid forever, tells us a compelling fact, that innate anticoagulation and the fibrinolytic system are more critical than the extensively understood clotting mechanisms. 

Are you aware we all have some amount of naturally secreted heparin in blood?

Circulation, Volume XXIII, April 1961

Which cells secrete heparin? 

Basophils of blood and mast cells continuously secrete heparin that keep the blood fluid. Heparin is normally present in human plasma in values ranging from 10 to 24 units percent (1 to 2.4 mg. per liter). The range of average values is from 1.53 to 1.77 mg. The native heparin secretion by mast cell population is directly related to the anticoagulation activity (Bill Eksp Biol Med. 1984 Feb;97(2):131-4. Russian. PMID: 6230117.)

Where does TPA come from?

TPA normal levels not only confers the capacity to spontaneously abort  a vascular event, but it is also a critical determinant of how streptokinase is going to act as this drug can’t act alone it simple accelerates the action of Tpa complex

Mind you, the basal levels of TPA are injected instantly into the coronary thrombus with a zero-second time window. Now guess what is the potency of this enzyme cascade and who directs it?

Yamada R, Yamada S, Ishii A, Sasamata M, Watanabe S. Association between tissue plasminogen activator and serum lipids in healthy volunteers. Ann Med. 1990;22(5):313-8. doi: 10.3109/07853899009147913. PMID: 2127223.

Final message

If we think with a hematologic acumen, all vascular accidents are triggered by temporary aberrant behavior of blood or the interaction of its components with the immediate tissue interface. It is the inability to either prevent or fight the sudden occurrence of thrombus that is a primary problem than the tendency of the blood to clot spontaneously. The basal levels of natural Heparin, TPA, or anti thrombins and the way in which they get activated are much more important than the procoagulant forces, which we tend to blame often. (the famous vulnerable plaque vs vulnerable patient need to be reignited) 

I think it’s time we dwell deeper into the native lytic mechanisms. This will throw an important vision on how we can replicate it in a pharmacological way. If only we have a drug that melts intravascular clots locally, vascular deaths of many vital organs can be prevented. The research in newer lytic agents has almost ceased & needs fresh Impetus.(TPA is a 25-year-old Invention) 


1.Longstaff, C. & Kolev, K. Basic mechanisms and regulation of fibrinolysis. J. Thromb. Haemost. 13(Suppl 1), S98-105.  

2. Wiman B. Predictive value of fibrinolytic factors in coronary heart disease. Scand J Clin Lab Invest Suppl. 1999;230:23-31. PMID: 10389198.

3.Wiman B, Andersson T, Hallqvist J, Reuterwall C, Ahlbom A, deFaire U. Plasma levels of tissue plasminogen activator/plasminogen activator inhibitor-1 complex and von Willebrand factor are significant risk markers for recurrent myocardial infarction in the Stockholm Heart Epidemiology Program (SHEEP) study. Arterioscler Thromb Vasc Biol. 2000 Aug;20(8):2019-23. doi: 10.1161/01.atv.20.8.2019. PMID: 10938026.

4.Kovacs IB, Yamamoto J. Spontaneous thrombolysis: a forgotten determinant of life or death. Clin Appl Thromb Hemost. 2006 Jul;12(3):358-63. doi: 10.1177/1076029606291410. PMID: 16959691


I think we have a problem with our basic science teaching methods. Tried a fact check. When I asked a few passing-out medical graduates, they could rattle everything about clotting factors but struggled to recall any anti-clotting mechanisms. We are still a long way to go, understanding the mysteries of how the blood keeps itself fluid, but always on the alert mode to clot whenever necessary.

DIC: The sine-qua-non of lytic dysfunction

DIC is one of the famous diagnoses in critical care medicine. It is a perfect example of defective fibrinolysis. (Also referred to as acute fibrinolytic shutdown*) classically occurs in septic shock and related conditions. We still lack good criteria to diagnose non-overt DIC-prone patients. A good review was written in 1999, still helps us understand the core concept. 

*Both shutdown as well as Inappropriate activation 

Levi M, Ten Cate H. Disseminated intravascular coagulation. N Engl J Med. 1999;341(8):586–92.

Return to ref 3 in article





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This is not a breaking news story. It’s the same old secret that was exposed in JUPITER  trial with Rosuvostatin 14 years ago. Yes, I am talking about the relationship between the usage of statin and the occurrence of diabetes. Now, we have this huge study on possible diabetes progression with statins. It’s not from a small journal to ignore. 

83 thousand patients data, the world’s largest series on link between statin therapy and diabetes.


This study has this to conclude

Diabetogenic statins

Something* happens as the statins antagonize the HMG COA  enzyme that resides within the delicate membranes of the endoplasmic reticulum inside the most specialized cells in our human body, called hepatocytes.

*What is that something?

Image source Umme Aiman et al Journal of Pharmacology and Pharmacotherapeutics 5(3):181-5DOI: 10.4103/0976-500X.136097

How to go about this issue?

With-holding statin in as many as possible is the best thing for such diabetic  (non-diabetic?) patients. But, the more pragmatic option is to ignore these negative studies, and instead intensify diabetes management if it worsens. After all, we can’t afford to lose the prodigious evidence-based cardio-vascular protective effects of statins and earn the wrath of our patients and peers you know!

Further Interest

1.Mansi IA, Chansard M, Lingvay I, Zhang S, Halm EA, Alvarez CA. Association of Statin Therapy Initiation With Diabetes ProgressionA Retrospective Matched-Cohort StudyJAMA Intern Med. Published online October 04, 2021. doi:10.1001/jamainternmed.2021.5714

2.Aiman U, Najmi A, Khan RA. Statin induced diabetes and its clinical implications. J Pharmacol Pharmacother. 2014 Jul;5(3):181-5. doi: 10.4103/0976-500X.136097. PMID: 25210397; PMCID: PMC4156828.


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