Functional MR is a term used , when it occurs due to defective LV function, ie LV dysfunction. This happens in spite of normal mitral leaflets and intrinsically normal mitral valve apparatus. The above statement can be instantly disputed because LV muscle is also a part of the apparatus. Then realistically, functional MR occurs due to dysfunctional LV and infact becomes a part of primary. Then, logically we need to replace the term functional MR to dysfunctional MR .A classical double oxymoron isn’t.
Image source : Barbara Brzezińska and Krystyna Łoboz-Grudzień from the Book : Structural Insufficiency Anomalies in Cardiac Valves Mechanism of functional mitral regurgitation. (A) Balance of closing and tethering forces acting on mitral leaflets during systole. (B) Disrupted balance of closing and tethering forces due to local LV remodeling (dark shading). LA: left atrium; LV: left ventricle; PM: papillary muscle; Ao: aorta; ME: mitral regurgitation.
Why fight with nomenclature ?
Classification and nomeclature are the foundation for any medical entity .Since, we build our knowledge over it, If it goes wrong, everything grows out of it is problamatic. This is exactly, is the reason we are blinking at the diagonally opposite results with COAPT & MITRA-FRtrials. Ofcourse , it is not a pleasnt job to shake the foundation often as well,as it has its own side effects.
It is expected in cardiology academic forums, we use the term secondary MR. While secondary MR is preferable, I guess myocardial MR may be a more apt term. We know secondary MR is further subdivided into ischemic and non-ischemic.
Need for a combined New entity : Combined Primary and Secondary(cps-MR)
This occurs in two situations
MR begets MR: If primary MR is severe, it invokes LV dilatation and dysfunction of LV . Then it becomes cps-MR by default.
Ischemic MR causing structural damage to chordae: If Ischemic MR ends up in chordal disruption or severe destruction of papillary muscle , it doubles up as combined primary & secondary MR
Final message
What is “functional” in functional MR ?
Nothing.Everything is dysfunctional. The only good thing is that the leaflets are structurally normal. (Please note, any of the other 5 components of MV may still be abnormal) Semantics and nomenclature should not bother us, as long as we understand the mechanism of MR and the principles of its management. Understanding the concept of cps-MR could throw more light on why the intermediate and long term outcome of MVR can be as unpredictable as a tropical storm in nay given case of secondary MR.
Postamble : If LV is part of mitral valve apparatus, then, let us realise the same thing will apply for RV as well. This would imply, right ventricle is a component of tricuspid valve apparatus .(at least to a lesser extent) This fact, is rarely taught to cardiology fellows.There is evidence for progresssive RV dysfunction, to worsen the TR, inspite of the reduced contractlity .The fact,TR begets TR, is less popular among us for no obvious reasom (Rana BS et al Echo Res Pract. 2019 )
Welcome to 2025 and best wishes for a great academic journey to all readers .
Collected from ACC website (Arranged in three heading) These are the creamy academic extract of whatever happened over the last one year. Thanks to ACC for compiling it. While the first one,(Trials) will be under scrutiny, the other two , ie the cardiology news stories and magazine reviews are absolute gem of learning resource.
What happened to top 10 cardiology research papers of 2023 ?Did we follow up ? what is the Impact of them in the bed side ?
For some reason, we have a strong belief , that randomized control trials (RCT) are the only way science can express itself and move forward . This is a much more sacred rule in cardiology. In that sense, every year, we see more than 100s of RCT get released various research centers with varying credibility. If every RCT is taken at its face value, we should have conquered much of cardiology secrets long ago. Unfortunately, that can not be the case.
As an Intelligent, interventional cardiologists we are extremely talented (From tackling a left main dissection, to recapture a runaway TAVI and reimplant it ) .But, we have to admit, many (?most) of us lack the expertise of picking the genuine , winning research especially in the arena of new drugs and devices. Some times, I wonder, whether we have sort of outsourced the job of interpreting the results to invisible third parties. No escape from this ,this is the way science has to grow.
Final message : One study from 2024 really bothers
The PREVENT trial of 2024 is suggesting a tectonic shift in the way we should manage CAD. It is asking for stenting all non-flow limiting lesion , if found, to carry high risk plaques by intracoronary Imaging. We have a come full circle, from vulnerable plaque to vulnerable patient and let us hope, we do not become a vulnerable cardiologist.
Courtesy : A news clip from The Guardian , UK 26th December2024.
Can any one dare to stop this prescription medication with significant metabolic side effects ,being flashed in the New York bill board ?
Semaglutide is a GLP 1 agonist, (Glucagon like peptide) primarily used in diabetes where it competes with glucagon and modulates its adverse action. By some unknown mechanism this drug reduces body weight. The consequences of which is not clear. Meanwhile this drug got cleared as a magic bullet , as a weekly shot injection in obesity .We don’t yet know the long term effects of this drug. But, already it is promoted in social media, (as if it is a Pepsi or Coke) bypassing the physicians. It is a new low in pharma marketing strategies. (No one bothers, rather, no one wants to bother.)
Final message
The primary issue here is, not about the quick buck of profit, these companies want to make. It is about the potential Injury it can cause to patient’s ,(rather, healthy peoples’)metabolic landscape.
Prosthetic valve assessment is complex, thought process intensive examination. Not every echocardiographer can do it efficiently. It needs a good knowledge of anatomy, physiology of inter & Intra valvular hemodynamics .It demands thorough understanding of principles of Doppler echocardiography and also the hidden truths( ie, How we take liberty with the mighty Bernoulli equation for granted )
In spite of the number of imaging and doppler parameters we are able to gather ,still, we need to analyze them with reference to the clinical presentation. Mind you, even an innocuous episode of fever, associated dyspnea, and tachycardia can elevate the mitral gradient and sound a false alarm.
Depending solely on prosthetic valve gradients to diagnose obstruction is the biggest error we commit. We have seen this, even from elite hospitals. Echocardiography is not the final say, one may require cine fluoroscopy, CT scan or even PET (Infected peri prosthetic abscess) in appropriate situations.
Absolutely yes. The number of studies with such wrong aims is staggeringly higher than we could imagine. “Wrong aim” is probably not the right word to describe them. Rather, we can call them obsolete, duplicate, illogical, unproductive, intentionally fraudulent studies, or studies with a prefixed conclusion.
There is an estimate, that says 95% of papers in nearly 5,000 medical journals, is either junk or written for the sake of publication related to mandatory academic positions or promotions as a budding scholar or faculty. Science has to survive on the shoulders of those rare & genuine 5% souls.
Final message
What is the true “Aim for your study” , I want a very honest answer ?
Yes sir, I agree ,the primary aim is to publish my damn paper and get that promotion !
A related post
There was a brief post about this in the year 2008, 15 years ago. Is it still relevant? Find out for yourself.
Here is astate of the art review article on peripartum cardiomyopathy from NEJM that came out in Jan 2024. It is one of the comprehensive article on the topic. Everyone will relish, and would like to preserve it as well . Click on the image for the PDF of the article .Sharing here purely for the academic purpose with the courtesy and thanks to NEJM group.
In this post, I wish to highlight two statements that occur in tandem in the latter half of the article‘ They are picked with one important academic purpose and a discussion on the combined entity of PIH associated PPCM.
I hope , you could appreciate the two lines (under the red bracket) to appear as antagonistic statements. Read the cross- references and try to understand yourself. They are not wrong statements for sure . It only reflects the complexity of the interaction of PIH with PPCM.
A 26 year old woman with PIH was about to deliver in one month, went on to develop another serious complication. Her echocardiography revealed LV dilatation with mild LV dysfunction. One reputed hospital labeled her as peripartum cardiomyopathy (flagged her as very high sub-set as well, since the PPCM has occurred in the antenatal period).
The family was in distress and blaming their fate. I happened to see her for a consult. It is true ,she fulfilled the criteria for PPCM with the available records. When I examined the patient, she was in class 2 and her BP was yet to be controlled fully. I added alpha methyl dopa for two weeks. I know it is just an afterload mismatch that has dilated her LV .Assured the family they need not panic, and she is going to have a good outcome if we control the BP tightly. The worried family was very much relieved and her husband wanted to know how I could give a good outcome when everyone was saying his wife was suffering from double complication.
Doctor, are you sure? My obstetrician says it is a deadly combination, but you ask us to take it casually.
No, I am not asking you to take it casually. It is indeed high-risk pregnancy, but the outcome is not as bad as we predict, especially in your wife’s case (A combo of PIH with PPCM ) where we have a target to treat .
As I expected (with all concealed anxiety) the mother delivered a normal baby with a little bit of lung congestion in the immediate postpartum period .However , she recovered fast , discharged doing fine in follow-up. LV shrunk back to normal dimension two weeks.
Is PIH and PPCM are pathophysiologically linked ?
Peripartum cardiomyopathy is a complex primary/secondary cardiomyopathy with varied outcomes. It is a neurovascular and hormonal disorder, affecting the heart and possibly the entire vascular system. It is important to note, this happens in a rare population of genetically predisposed individual, who harbor molecular defects in cardiac structural muscle proteins and gap junctions.
It shares some of its pathologies with PPCM and affects the placental, uterine, and microcirculatory vascular bed, impacting the perfusion of the growing fetus. In the process, it gives false autoregulatory signals to the mother’s circulation, which responds with a dramatic increase in late pregnancy trying to perfuse the baby , reflecting natural mother-baby evolutionary survival model. This includes the RASS system , and for this reason only ACEI are an absolute contraindication in pregnancy.
PPCM is a rare but not a mystery diagnosis,. Obstetricians out of anxiety and compulsion refer to cardiologists every case of pregnancy ,(of course in your case it is a must, since it is established PIH ) Further, the current echo machines are too sensitive to pick up mild abnormalities. It is very important patients should be relaxed during echo. If the resting BP is high, LV wall will be stressed, global hypokinesia can occur . Often times , we have wrongly labeled transient LV dysfunction due to sudden spikes in BP as serious cardiac muscle diseases. This concept is called afterload mismatch.
This process can have drastic effects on the mother’s heart, as the response to raised afterload is unpredictable. This disease affects the maternal circulation primarily by increasing the BP. What is the heart’s response to this ? It can be a fight mode with development of LVH or a flight (fear) mode, ie dilatation of LV that may end up in echocardiographic LV dysfunction or clinical failure. We are comfortable in labeling this as a type of PPCM. Many such mothers do well once the baby is out and when the BP is normalized.
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Final message
PIH increases the incidence of PPCM in the general population. While the prevalence of PIH in PPCM is 22%, the incidence of PPCM in PIH is a far lower(.05 to 1%) The outcome of PPCM is often dismal (18-56% Ref JAMA 2000) with mean mortality reaching 30 to 40%.
Though PIH appear in the adverse list, what we find find in the real world is , PPCM that is associated (most likely triggered) by PIH/preeclampsia has a much more favorable prognosis than other mysterious /idiopathic forms of PPCM. However ,the degree of LV dysfunction determine the ultimate recovery ,even in PIH associated PPCM.
In this era of Artificial ignorance , using mathematical models for biological risk prediction can be tricky or even misleading .PIH and PPCM are two high risk subsets, when looked in isolation, but when they occur together, the risks actually need not add up. Infact, it is plausible , LV dilatation in severe PIH could be a marker of utilization of cardiac reserve mechanism, which has crossed its limits transiently.
A post amble paradox
PPCM, if it occurs in the antenatal period, obviously It is more risky, because the mother has to pass through the test of labor or cesarean with a dysfunctional heart. Ironically, most of the PIH-related PPCM is expected to occur in the antenatal period, which may ultimately carry a better outcome
Ventricular tachycardia can be a killer arrhythmia that can arrest the heart within seconds or behave like your pet, gently cuddling the heart and terminating spontaneously. The latter phenomenon we call it casually as benign non-sustained VT. Such VTs are more common in the out flows, fascicles or in HCMs. Most of us do not have time, to wonder why some of these blessed arrhythmias are not able to sustain.
Of course, the definition of non sustained VT can be challenging and keep changing with time. We have examples for both extremes , ie hemodynamically stable sustained VTs as well as unstable , but still, not sustained one.
Coming back to the mechanism behind these VT ,Let me provoke an answer from the readers.
Why some VTs are non sustained ?
A. The forward head of VT energy front is weak.
B. Source-Sink mismatch and tissue fatigue .
C.Disconnect between upper & lower loop of VT
D.Rate induced functional Exit or Entry block in the circuit
E. All of the above
F. None of the above , it is largely decided by the fate of the patient
While most EP specialists are busy taming the sustained one, very few are actively doing research about the mechanisms underlying the non-sustainability of VT. Here is interesting paper that discusses possible mechanism of termination of re-entrant VT.
The clinical importance of this question is, if we can convert sustained VT to non-sustained ones with drugs, it is indeed a therapeutic success. Drugs can slow down or terminate the arrhytmia circuit by acting in any of the four phases of action potential. The research in the field of anti-arrhythmic drugs has almost stopped in the last four decades for some unexplained reason. I think, we (Pharma companies?) decided to close the doors of anti-arrhythmic drugs after Dronedarone or Ibutilide . Renewed interest in Mexiletine, Norpace and Sotolol is a welcome move though. My suggestion is, oral forms of cardio specific lignocaine analogues could be a game changer in the filed of cardiac arrhythmias. Phenytoin sodium is old warrior drug, could make a comeback.
If only we had tried more, we might have produced more powerful drugs ( One obvious reason being cardiologists have decided to take on cardiac arrhythmias with electrical and mechanical weaponry in the hope of avoiding drugs. But, that aim has not really been accomplished except in AVNRT/AVRT. We still need the assistance of drugs in many classes of VT, even after ablation as well as an ICD.
Final message
As far as the answer to the MCQ, is concerned, response E is correct. If we look at the question again, quixotically, we may need to agree response F, (ie none of the above) is also right. Destiny decides the presence or absence of factors A to D in a given patient.
Fixing the target LDL, in both primary and secondary prevention is becoming more & more complex . The reason being, there is a huge healthy population ( with zero risk factor) , but showing insignificant or minimal coronary plaques. This subset of population is anxiously unmasked by inclusion of CT angiogram in many master health check-up programs.
A case profile& a debate
What does the guidelines say ?
If you have any athero-sclerotic cardio vascular disease(ASVD) documented by clinical or Imaging , you belong to very high risk category. It clearly says the target is 55mg both in primary and secondary prevention.
LDL is not only the enemy of the coronary artery. Fatty streaks in the coronary artery begin in the fetal stage itself. In adults, some of these streaks become prominent locally and turn out to be plaque. The argument for intensive statin therapy is to stabilize these plaques. We would not know if the plaque is stable or not. We can’t do OCT imaging, an invasive test, to know about the vulnerability. So, for the sake of safety, everyone advises intense statin therapy. The irony is ACS continues to occur at any level of LDL.
Final message
Is my cardiologist right about the LDL target of 55 mg ?
If you look at the above table of risk categorization, your cardiologist may be right. But the deeper issue is whether such a recommendation is correct or not. In our opinion LDL 70mg is good target to achieve. Lowering further, has its own risk. I am sorry, you can’t escape from the guidelines as of now, Further you don’t have any other risk factors to treat as well. Then, this question, will always hang above your shoulders , why the hell I got this plaque over there?
I think ,its time ,we need ask more questions that are difficult to answer ?
1.Does ASVD includes even 10-20 % plaques by CT angiogram ? How specific these X RAY – stitched slices of CT scans done on moving heart. Then ,what about luminal irregularities ? Should it to be counted as ASCVD as well ?
2.Do we need to refine the definition of by introducing a new term significant ASCVD?
3.Also like subcategorization of clinical ASCVD from image-based ASCVD with reference to target LDL?
Dear patient, wait, there can be more shocking advisories soon. With the famous PREVENT trial (Lancet 2024), results are waiting on the sidelines trying to penetrate the fragile barriers of various guideline writing committee offices. By the way, PREVENT study demands an OCT for all non-flow limiting plaques, and stents if they are found be vulnerable.( Read about The TCFA story)
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Please Note
The author acknowledges all the queries posted by the readers and wishes to answer them .Due to logistic reasons only few could be responded. Inconvenience caused is regretted.
Dr.S.Venkatesan MD 