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Archive for December, 2021

An Interaction in IMCU

How is Mr. K, who was shifted from ward 102 ?

Yes sir, It was acute decompensated LV failure, Patient was in impending pulmonary edema. In fact, he developed. He is fine now,

How did he come around? He was too sick I thought.

“Just pushed 60 mg Frusemide IV, luckily he also had good BP, so with an infusion of NTG, titrated Carvedilol a little bit, he came out nicely. I guess it is Ischemic DCM”.

“Good, You have done a nice job”

“Don’t make me embarrassed sir. It is such a routine in our ER. 

To make him curious, I asked “Which drug do you think that saved him”?

“Obviously, Frusemide sir. He was frothing out. I thought he will require a ventilator. It was a matter of 20 minutes, sort of flushing out 500 ml lung fluid through the urine”.

“No, you are wrong. As a professor and cardiologist, I need to tell you this. Diuretics never save lives heart failure. 

Sir, I guess, you are not kidding. Does this statement apply to acute heart failure? We have saved 100s of lives with Frusemide,  both in acute, acute on chronic, and even in chronic cardiac failures with metolazone.

Hmmm, I agree with you my dear student, Frusemide has saved not hundreds but lakhs of lives in the past decades in all forms of heart failure. It continues to do this fabulous job even now. But, don’t say it in exams or scientific forums. It has no evidence to show survival benefits. You can’t credit a drug without evidence. Also realize, saving lives by unscientific means by a cheap generic is not something to boast upon. We need the blessings of RCTs, or Kaplans Mayer curves, or Forrest blobbograms. Unfortunately . that is the current principle of practice of medicine.

But sir, who is preventing whom, to do such studies. Why they are not comparing diuretics one to one with these modern drugs of inotropes, calcium modulators, or SGLTis, etc? 

I am not sure. My guess is, there are no good friends in the cardiac failure research community for this old warrior drug. 

Loop diuretics 

Till 1960s, toxic mercurial compunds was the only option to drain water in heart failures. The Invention of  Na+/K+ /Cl channel blocker Frusemide, ( In the thick ascending limb of the loop of Henle) is the single most important event, that changed the way we manage cardiac failure in both acute and chronic settings. Still, the current evidence creators hesitate to call it a life-saving drug,

The meteoric rise of SGLT-2 Inhibitors 

Meanwhile, a few micrometers down the hairpin bend of Henle, drugs called phlorizin are doing wonders. These Apple root barks derivatives were since been invaded by Glyflozins Industry. They are made into a powerful glycosuric drug that drags water out of the system along with glucose. This seems to be the biggest revolution in cardiac pharmacology ever since DaVinci drew the heart and Harvey made it functional. I think we need a supercomputer to count the number of papers and analyze the data from Dapa & Empaglyflosin. It is now concluded officially, as an evidence-based life saver in HF.

I asked one Gen X Pharma-geek, “How do these magic drugs perform this miracle in heart failure”? He said beamingly, It is not merely Glyco-diuresis, as you academicians think, it is some mystery action from heaven, still not decoded. What a revelation I thought.

Continuing Medical Education: Choosing the correct path is never easy!

Final message 

Loop diuretics are powerful drugs that aid the failing heart to reduce both pre and after-load. It is a fact, indiscriminate use of these drugs leads to some electrolytes and metabolic issues. But, hiding behind a hazy and shaky evidence base, and trying to ridicule these life-sustaining drugs, is the height of senselessness in cardiac failure literature.

Reference 

(There is a tug of war of evidence between benefits and risks. I guess someone will bring out the truth, which is written clearly on the walls)

1. Chris J Kapelios, Konstantinos Malliaras, Elisabeth Kaldara, Stella Vakrou, John N Nanas, Loop diuretics for chronic heart failure: a foe in disguise of a friend?, European Heart Journal – Cardiovascular Pharmacotherapy, Volume 4, Issue 1, January 2018, Pages 54–63https://doi.org/10.1093/ehjcvp/pvx020

2.Faris R, Flather M, Purcell H, Henein M, Poole-Wilson P, Coats A. Current evidence supporting the role of diuretics in heart failure: a meta-analysis of randomized controlled trials. Int J Cardiol. 2002 Feb;82(2):149-58. doi: 10.1016/s0167-5273(01)00600-3. PMID: 11853901.

Postamble

It is to be noted,Eplerenone (EPHESUS trial )  & Finerinone  (FIDELIO-DKD trial) are new generation  K + sparing diuretics and mineralocorticoid antagonists may have better cardioprotection in cardiac failure.(Part of RAAS blockade)

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Link to PDF download 

Good news: Nothing much has changed since 2008

  • Recognizing the clinical importance of AF and the need to rule out a systemic cause is the key, Further, a genuine bedside debate about the pros and cons of simple vs aggressive treatment discussion is welcome.
  • The nomenclature issue of valvular vs non-valvular has finally seemed to have settled. The latter is banished for good reason. (Funny to note Aortic valve  was considered as not a valve for  so long !)
  • The rate vs rhythm control debate still favors the former. (AFFIRM/RACE)
  • Stroke prevention is the concern  &  anticoagulation is the mainstay. OAC/DAPT /triple therapy has evolved a little more in the last decade. Though stoke is a major concern, we rarely see neurologists & cardiologists debate closely on risk profiling issues of such patients. (at least in this part of the world.)
  • Whether we have conquered AF or not we have become experts in creating an unlimited number of bleeding risk scores. Understanding and applying them at the bedside need special memory and expertise.
  • On the combative front, ablation strategies, however, advanced they look, are vested with the risk of injuring the surrounding structures. My biased opinion is that the risks are prohibitive except in very refractory and troublesome AFs. (with all these 4D, contact, cryo, etc)  Recall the CABANA study. We are beginning to understand, the true embryological face of pulmonary veins insertion points is so variable, and residual sleeves are very rampant that will sustain the AF even after an apparently successful ablation.
  • LAA appendage closure studies again don’t look rosy as the device itself is prone to thrombus at least in the early periprocedural period. (Watchman requires more security and protection than the Inmates !)

Final message 

AF is a simple arrhythmia in 9/10 patients. Please, let us not complicate it. We must ensure, systemic and non-permanent forms of AF should not drain our cardiac resources. We shall follow basic principles of managing a cardiac arrhythmia that will suffice in the majority. An occasional patient needs to be referred to an EP specialist.  

A new look at AF risk estimation for stroke

doi:10.1001/jamacardio.2021.3709

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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.  

Reference

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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