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A young man aged around 40 years, had a STEMI was promptly thrombolysed in a small hospital located about 40 KM away in the suburbs of my city Chennai. They did an awesome job of saving the patient life and salvaging the myocardium.

Now begins the story . . . one of the non-medical person who is the owner of the hospital has an unfortunate working  business relationship with a frighteningly big nearby hospital  which had signed a memorandum of irresponsible understanding . It demanded any  patient who arrives in the small hospital with MI should be transferred at earliest opportunity to them.

So, an ambulance was arranged  and the patient (with a fairly well reperfused heart ) was shifted  in an emergency fashion . It reached desired destination after nicely chugging along the choked chaotic Chennai evening traffic for 45 minutes.

The guy was taken directly to cath lab through the side doors to perform a second salvage  procedure on a successfully opened IRA. Young cardiology consultants  in designer cath suite welcomed the smiling ACS patient to their posh new lab .Did few rapid radial shots, mumbled among themselves for few minutes,  decided to stent  a minimal LAD lesion for a patient who was in  zero distress with well-preserved LV function.

*The relatives of the patients were curious when they were asked sign a fresh set of consent which elaborately  mentioned about possible life risk during the procedure.

The patient’s wife  was clearly  amused and she pointed out to the superior cardiologists about  the earlier briefing by the Inferior freelance cardiologist who treated him in the previous hospital. She recalled , “I was told in confident terms  that  Initial thrombolysis  has been spectacularly  successful and bulk of the treatment is over and risk of complication has dramatically reduced”.

Then why is this distressing risk taking story again ,  she asked ?

The doctors hurriedly explained ,”this procedure is different. We are sorry to say we have no other option but to add  further risk to you” ! but , its all for your good !

Why should I ?  If the initial lysis is very successful  why do you want to meddle with it again ?

No Madam , you are ill-informed , you can’t talk like that .This is what modern  science  is all about. Leave the professional decision to us. We need to check immediately  whether the lysis is really successful .We can’t rely on the ECG.Further, true success lies in stenting the lesion as we fear the ill-fated site may close again.We are  taught to practice protocols based on standard scientific guidelines. This hospital has highest rating in-terms of quality care. That’s why we got updated ISO 2000  NABH accreditation

The women who is a soft ware engineer was smartly and  scientifically silenced in 5 minutes flat !

Post-amble :

What happened  to the patient then ? (When you fear something it happens is in’t the  Murphy’s law ?)

The apparently asymptotic and comfortable patient had uneventful PCI. A  long drug eluting  stent  was  implanted in recanalized  lesion in LAD with around 30 % narrowing that ended with an innocuous looking diagonal pinch. The procedure was uneventful , however next day he developed some fresh ECG changes and chest pain . The worried team took him for another angio found  stent was patent But , ultimately after a stressful 3 days of stay , some thing went wrong he ended up with new LV dysfunction.He got discharged fine with a caution  that , his stent needs to intensively monitored for the next 1 year since technically he had recurrent ACS !

Lessons we don’t learn from such cases.

When two procedures are done to accomplish the same aim (Reperfusion) , but with  differing success rates, expertise, time ,and unpredictable hazards , the benefits from them may not add together. There is clear knowledge deficit here. Scientific data can never provide fair answers to  these questions  as all real life cofounders can never be recreated in study population.

While we expect 1+1 to become  two in pharmaco-Invasvie strategy  ,one should realise it may end up with  either zero or even  – 2 .

1 -1 = 0

-1 + (-1)=  -2 ?

Learning cardiology from lay persons 

The patient’s shrewd wife threw this question ,

After two modes of re-perfusion done sequentially in my  husband’s  heart ,  at a total cost of Rs4.5Lakhs Why he  is  still left with significant LV dysfunction (Which was  around 40% EF.)

The query raised by the lady appeared much more crucial and logical than the ones discussed in many top-notch live interventional workshops we attend every few months!

As usual , I started mulling over the issue. There is something wrong with the way , we  understand  the pharmaco invasive approach-PIA .You go with it only if  initial pharmacological  approach has failed.

Of Course ,there is one more modality possible ie Pharmaco -Angio strategy where in, you look at the coronary anatomy and take a call ! This sounds good , the only issue is taking a right call ! My experience suggests wrong calls are the rule and  exceptions are rare. Then a whole new issue erupts about all those non IRA lesions

Final message

So,  til we have gain complete self-control over our evolved ignorance and evolving knowledge , it is better to follow this proposed  funny new ACS algorithm called “Pharmaco -non invasive” approach (PNIA)  in asymptomatic ACS patients  who have had apparently successful lysis.

*Please note, Incidentally  PNIA actually  refers to simple good old traditional stand alone thrombolysis.

Counter point

No one can deny Interventional cardiology carries a risk of untoward effects.Don’t blow this out of proportion. Do you know, how many lives have been saved by routine Pharmaco -Invasive approach ?

I am not sure , my experience may be limited.Let me ask the readers. Is routine PIA is warranted in all asymptomatic , successfully lysed STEMIs ?

100% occlusion of a coronary artery result in STEMI.This includes both thrombus and mechanical component .We are very much blinded till we touch , feel and see the lesion with a wire or IVUS to quantify the mechanical component’s  contribution in the genesis of  STEMI.It is generally believed (True as well ) thrombus is the chief culprit .It can even be 100 % thrombotic STEMI with  just a residual endothelial  erosion and hence
zero mechanical component .However , the point of contention that non flow limiting lesion is more likely to cause a thrombotic STEMI than a flow liming
lesion  seems to be biased and misunderstood scientific fact .

What happens once 100 % occlusion take place ?

Sudden occlusion , is expected to evoke a strong fire fighting response within the coronary artery.The immediate reaction is the activation of  tissue plasminogen system. In this aftermath  few succumb . ( Re-perfusion arrhythmia  generated as VF ) .The TPA system activates and tries to lyse the clot.The volume , morphology, attachment, content of thrombus ,  and the elasticity of fibrin mesh , location of  platelet core would determine the life and dissolvablity of thrombus. Even a trickle flow can keep the distal vessel patent .(Please note a timely TIMI 2 flow can be a greater achievement than a delayed TIMI 3  flow !)

thrombus propgation
What happens to the natural history of thrombus in STEMI ?
Thrombus formed over the culprit lesion can follow any of the following course

  •  Can remain static
  •  Get lysed by natural or pharmacological means
  •  Progress distally (By fragmentation or by moving en-mass )
  •  Grow proximal and and involve more serious proximal side branch obstruction
  • Organise and become a CTO

Factors determining thrombus migration

The interaction between the hemodynamic  forces that push a thrombus distally and hemo-rheological factors that promote fresh proximal thrombus formation are poorly understood. The altered intra-coronary milieu with a fissured plaque covered by  platelet vs RBC / fibrin core,  totally of obstruction,  reperfusing forces , re-exposure of raw areas and  the distal vessel integrity all matters.

While, logic would tell us,  thrombus more often migrates  distally  assisted by the direction of blood flow, an  opposite concept also seeks attention , ie since the blood flow is sluggish  in the proximal (to obstruction site )more thrombus forms in segments proximal to obstruction.

(In fact, its presumed  in any acute massive proximal LAD STEMI , it takes hardly few minutes for the thrombus to  queue up proximaly and  clog the bifurcation and spill over to LCX or even reach left main and result in instant mechanical death.)

What is the significance of length and longitudinal resistance of the thrombotic segment in STEMI ?

If thrombus is the culprit let us get rid of it , this concept looks nice on paper , but still  we don’t  know why thrombus aspiration in STEMI is not consistently useful. We also know little about  the length of the thrombotic  segment .When a guide wire is passed over a STEMI ATO it may cross smoothly like  “cutting a slice of  butter” in some , while in few we struggle and  end up with severe no-reflow inspite of great efforts .Why ?

What is the Impact of distal collateral flow in flushing fresh thrombus ?

The efficacy of collateral flow in salvaging myocardium is underestimated. Distal vessel flow if perfused partially by acute collaterals the thrombus load is not only less it’s soft and fail to get organised early that would help cross the lesion easily.

Mohandas Karam Chand Gandhi ,  father of my country , India , made these observations in year 1925  about the  fundamental constituents of  violence in society . These words of monumental wisdom came when he was  addressing young Indians in a country- side rally .

mahatma gandhi quotes medical science humanity

Note, his finger points to , what  exactly is relevant to our profession ! He emphasized this  nearly  100 years ago, when medical science was at its infancy .One can only guess what would be Mahatma’s comment about our profession in it’s  current form !

Should we include moral, behavioral and ethical classes  right from the first year of medical  school along with Anatomy , physiology and bio chemistry.Medical council of India obviously need to burn more mid night oil , I wish it happens in my life time. !

Here is a  video recipe  !

Please click here to  see more videos from my you tube site

Prosthetic valve implantation has revolutionized the management of  valvular heart disease . The original concept valve  was a ball in a cage valve  , still considered as a  fascinating discovery.  It was conceived by the young Dr Starr and made by Engineer Edwards  .This was followed   by long hours of arguments,  debates and  experiments that ran into many months . The  silent corridors of  Oregon hospital Portland USA remain the only witness  to their hard work and motivation.  At last,  it happened , the first human valve was implanted in the year 1960. Since then . . . for nearly  50 years these valves  have done a seminal  job for the mankind.

With the advent of  disc valve and bi-leaflet valve in the  later decades of 20th century , we had to say a reluctant good-bye to this valve.

There is a  lingering question among many of the current generation cardiologists and surgeons why this valve became extinct ?

Starr and Edwards with their child !

We in India , are witnessing these old warrior inside the heart functioning for more than 30 years.From my institute of Madras medical college  which probably has inserted more Starr Edwards valve than any other  during the 1970s and 80s by Prof . Sadasivan , Solomon victor , and Vasudevan and others .

It is still a mystery why this valve lost its popularity and ultimately died a premature death.The modern hemodynamic  men  working from a theoretical labs thought  this valve was  hemodynamically  inferior. These Inferior valves worked  like a  power horse  inside the hearts  the poor Indian laborers  for over 30 years.

A Starr Edwards valve rocking inside the heart in mitral position

The cage which gives  a radial support* mimic  sub valvular apparatus, which none of the other valves can provide.

* Mitral  apparatus has 5 major  components. Annulus, leaflets, chordae, pap muscle, LV free wall.None of the artificial valves has all these components.  Though , we would love to have all of them technically it is simply not possible.  The metal cage of Starr Edwards  valve partially satisfies this  , as  it acts as a virtual sub valvular apparatus.Even though the cage has no contact with LV free wall, the mechano hydrolic  transduction of  LV forces to the annulus  is possible .

Further , the good hemodyanmics of this valve indicate , the cage ensures co axial blood  flow  across the mitral inflow throughout diastole. .Unlike the bi-leaflet valve ,  where the direction of  blood flow is determined by the quantum of leaflet excursion  in every beat . In bileaflet valves  each leaflet has independent determinants of valve  motion . In Starr Edwards valve the ball is the leaflet . In contrast to bi-leaflet valve , the contact area  of the  ball and the blood in Starr Edwards  is a smooth affair  and  ball makes sure  the LV forces are equally transmitted to it’s surface .

The superiority of bi-leaflet valves and disc valves  (Over ball and cage ) were  never proven convincingly in a randomized fashion . The other factor which pulled down this valve’s popularity was the supposedly high profile nature of this valve. LVOT tend to get narrowed in few undersized hearts.  This  can not be an  excuse , as no consistent  efforts were made to miniaturize this valve which is  distinctly possible.

Sudden deaths from  Starr Edwards valve  .

  • Almost unheard in our population.
  • The major reason  for the long durability of this valve is due to the  lack of  any metallic moving points .
  • Absence of hinge  in this  valve  confers  a huge mechanical  advantage with  no stress points.
  • A globe / or a ball  has  the universal hemodynamic advantage. This shape makes it difficult for thrombotic focus to stick and grow.

Final message

Science is considered as sacred as our religion Patients believe in us. We believe in science. A  good  durable valve  was  dumped from this world  for no good reason. If commerce is the  the main issue ( as many still believe it to be ! )  history will never  forgive those people who were  behind the murder of this innocent device.

Cardiologists and Cardio thoracic surgeons are equally culpable  for the pre- mature exit of this valve from human domain.  Why didn’t they protest ?  We  can get some solace  ,  if  only we can impress upon  the current valve manufacturers  to  give a fresh lease of life to this valve .

http://www.heartlungcirc.org/article/S1443-9506%2810%2900076-4/abstract

It is often said life is a cycle , time machine rolls without rest and reach  the same  point  again and again . This is  applicable for the  knowledge cycle as well .

We  live a life ,  which is infact a  “fraction of a time”(<100years) when we consider the evolution of life in our planet for over 4 million years.

Man has survived and succumbed to various natural and  self inflicted diseases &  disasters. Currently,  in this  brief phase of life  , CAD is the major epidemic , that confronts  modern  man.It determines the ultimate  life expectancy . The fact that ,  CAD is a new age  disease   and  it was  not  this rampant ,   in our ancestors  is well known .The disease has evolved with man’s pursuit for knowledge and wealth.

A simple example of how the management of CAD over 50 years will  help assess the importance of  “Time in medical therapeutics”

  • 1960s: Life style modification and Medical therapy  is  the standard of care in all stable chronic  CAD The fact is medical and lifestyle management remained the only choice in this period as   other options were not available. (Absence of choice was  a blessing as we subsequently realised  ! read further )
  • The medical  world started looking for options to manage CAD.
  • 1970s : CABG was  a major innovation for limiting angina .
  • 1980s: Plain balloon angioplasty a revolution in the management of CAD.
  • 1990s: Stent scaffolding of    the coronaries  was  a great add on .Stent  was too  dangerous  for routine use  was to be used only in bail out situations
  • Mid 1990s : Stents  reduced restenosis. Stents are  the greatest revolution for CAD management.Avoiding stent in a PCI  is unethical , stents  should be liberally used. Every PCI should be followed by stent.
  • Stents have potential complication so a good luminal dilatation with stent like result (SLR)  was  preferred so that we can avoid stent related complications.
  • 2000s: Simple  bare metal stents are not enough .It also has significant restenosis.
  • 2002: BMS are too notorius for restenosis and may be dangerous to use
  • 2004 : Drug eluting stents are god’s gift to mankind.It eliminates restenosis by 100% .
  • 2006:  Drug eluting stents not only eliminates restenosis it eliminates many patients suddenly by subacute stent thrombosis
  • 2007 : The drug is not  the culprit in DES it is the non bio erodable polymer that causes stent thrombosis. Polymer free DES  or   biodegradable stent , for temporary scaffolding  of the coronary artery  (Poly lactic acid )  are likely to  be the standard of care .
  • All stents  are  potentially dangerous for the simple reason any metal within the coronary artery  has a potential for acute occlusion.In chronic CAD it is not at all necessary to open the occluded coronary arteries , unless  CAD is severely symptomatic in spite of best  medical therapy.
  • 2007: Medical management is superior to PCI  in most of the situations in chronic CAD  .(COURAGE study ) .Avoid PCI whenever possible.
  • 2009 :The fundamental principle of CAD management  remain unaltered. Life style modification,  regular  exercise ,  risk factor reduction, optimal doses of anti anginal drug, statins and aspirin  is the time tested recipe for effective management of CAD .

So the CAD  therapeutic  journey  found  it’s  true  destination  ,  where it started in 1960s.

Final message

Every new option of therapy must be tested  against every past option .There are other reverse cycles  in cardiology  that includes the  role of diuretics  in SHT , beta blockers in CHF etc. It is ironical , we are in the era  of rediscovering common sense with sophisticated research methodology .What our ancestors know centuries ago , is perceived to be great scientific breakthroughs . It takes  a  pan continental , triple  blinded  randomised trial   to prove physical activity is good  for the heart .(INTERHEART , MONICA  studies etc) .

Medical profession is bound to experience hard times in the decades to come ,  unless we  look back in time and “constantly scrutinize”  the so called  scientific breakthroughs and  look  for genuine treasures for a great future !

Common sense protects more humans than modern science and  it comes free of cost  too . . .

NSTEMI  constitutes a  very heterogeneous population .The cardiac   risk   can vary  between very low to very high .  In contrast ,  STEMI patients  carry  a high risk for  electro mechanical complication including   sudden death .They all need immediate treatment  either with  thrombolysis or PCI to open up the blood vessel  and salvage the myocardium.

The above concept , may  be true in   many situations  ,  but what we fail to recognize   is  that ,   STEMI   also  is  a heterogeneous clinico pathological  with varying risks and outcome !

Let us see briefly ,  why this  is very important  in the management of STEMI

Management of STEMI  has undergone great  change  over the past 50 years and  it is the standing example of evidence based coronary care in the modern era ! The mortality  ,  in the early era was around 30-40% . The advent of coronary care units, defibrillators, reduced the mortality to around 10-15%  in 1960 /70s . Early use of heparin , aspirin   further improved the outcome .The inhospital mortality  was greatly  reduced to a level of  7-8% in the thrombolytic  era. And ,  then  came the interventional approach, namely primary PCI ,  which is now considered the best form of reperfusion when done early by an experienced team.

Inspite of this wealth of evidence   for the   superiority  of PCI  , it is only a fraction of  STEMI patients get  primary PCI   even in some  of the  well equipped centers ( Could be as low as  15 %)

Why ? this paradox

Primary PCI   has   struggled  to establish itself  as a global  therapeutic concept  for STEMI ,   even after   20 years of it’s introduction (PAMI trial)  .  If we  attribute ,  lack of   infrastructure  , expertise are  responsible for this low utility of primary PCI , we are mistaken ! There are so many institutions , at least in developing world ,   reluctant to do primary PCI  for varied reasons.( Affordability , support system , odd hours ,and finally perceived fear of untoward complication !)

Primary PCI may be a great treatment modality , but it comes with a inherent risk related to the procedure.

In fact the early hazard could exceed the potential benefit in many of the low risk STEMI  patients !

All STEMI’s are not  same , so all does not require same treatment !

Common sense and logic would   tell us any medical condition should be risk stratified before applying the management protocol. This will enable  us to avoid applying “high risk  – high benefit”  treatments in low risk patients . It is a great surprise,  the cardiology community has extensively researched to risk stratify NSTEMI/UA   ,  it has  rarely  considered risk stratification of STEMI before  starting the treatment.

In this context , it should  be emphasized  most of the clinical trails on   primary PCI  do not address  the clinical  relevance and the  differential outcomes   in various  subsets of  STEMI .

Consider the following two cases.

Two young men with STEMI  , both present within  3  hours   after  onset of symptoms

  1. ST elevation in V1 -V6 , 1 , AVL   ,  Low blood pressure , with severe  chest pain.
  2. ST elevation in 2 ,3, AVF , hemodynamically stable , with minimal  or no  discomfort .

In the above example,   a  small inferior  MI by a distal RCA occlusion  ,  and a proximal LAD lesion jeopardising entire anterior wall , both  are  categorized as STEMI !

Do you want to advocate same treatment  for both ?  or Will you  risk stratify the STEMI and treat individually ?  (As we do in NSTEMI !)

Current guidelines , would  suggest PCI for both situations. But , logistic ,  and real world experience would clearly favor thrombolysis for the second patient .

Does that mean,  the second patient is getting an inferior modality of treatment ?

Not at all . In fact there is a strong case for PCI being inferior in these patients as the risk of the procedure may far outweigh the benefit especially if it is done on a  random basis  by  not so well experienced cath lab team.

(Note : Streptokinase  or TPA does not  vary it’s action ,  whether given by  an ambulance drive or a staff nurse or even a  cardiologist !  .In contrast ,  the infrastructure and expertise have the  greatest impact on the success and failure  of PCI )

Final message

So , it is argued the world cardiology societies(ACC/ESC etc)  need to risk stratify STEMI (Like we do in NSTEMI ) into low risk, intermediate risk and high risk categories and advice primary PCI only for high risk patients.

FFR is the ultimate hemodynamic test that measures the physiological Impact of lesions. Just pass a manometer tipped wire across the lesion and note the pressure drop (with or without Adenosine) All you have to remember is two cut off values  .8 for FFR and .9 for IFR. Abracadabra . . . yes you got the answer , whether to proceed with PCI or not? It’s as simple as that. We are no longer blind to physiology to which many coronary purists often criticize us.

ffr ifr fame study

Coronary physiology simplified

Now , answer this question.

Is FFR heart rate dependent? If yes, how significant it is?

This simple question on coronary physiology caused the maximum distress  to  a large expert cardiologist group

Some of the answers

  1. No, it doesn’t.
  2. I think it may be affected.
  3. Yes for sure, but it’s not significant
  4. Yes, it’s an important limitation

My Answer

It has to be yes, right, however minimal it may be. My interpretation of truth in FFR is, it can have a massive influence* . (*Unless you are sure (we can never be ) about achieving maximum hyperemia or this hyperemia is the same as physiological exercise.) In fact, the whole concept of FFR lies in the fact that it should induce enough HR raise that should be used as a surrogate marker for maximum hyperemia. Ideally, like stress testing, we need to test FFR at maximum heart rate and minimal heart rate. The difference could be documented as FFR max-min. This will throw new light into the physiology of microcirculation.

Should we need to create a heart rate corrected FFR?

Yes , I think we need to do it or else should report at what HR we are reporting the FFR. If FFR falls at a high heart rate and maintains at low it implies a significant lesion. So don’t get fooled with FFR of .9 measured at an inadequate heart rate.

IFR to replace FFR : On what basis?

Meanwhile, new generation coronary flow quantification tool IFR jettisoned Adenosine and simply measure diastolic instantaneous flow at resting state. This makes a mockery of coronary physiology, without a true debate about heart rate dependence of trans-lesional flow.

Impact on clinical practice

Even as we struggle to answer the fundamental question of the influence of Heart rate on FFR, many landmark studies had been done. They have ratified FFR as the most physiological modality to assess coronary lesion. Important guidelines have been written based on these studies. No one will ever know, the true impact on the current cardiology care,  had we included heart rate adequacy /correction as an essential criteria in those FAMEd studies we hype about.

Counterpoint.

All is well with FFR.It has been tested with various heart rates.

FFR at peak hyperemia means there is no further HR rate induced potential microvascular reserve. So a properly administered optimal Adenosine augmented FFR should not bother the HR variability. (But its only theory)

If FFR is ok . . . IFR should not be ok is it not?, For the simple reason, there is no hyperemia in IFR , what is the use of knowing resting flow reserve (RFR)

Reference

 

Postamble with a slice of History 

FFR is as old as the concept of PTCA. In fact, the original balloons used by the great Gruentzig’s * had a central port for pressure recording through which he measured both proximal and distal pressure curves to guess the significance of obstruction. After each inflation, he checked  whether both curves are drawn together which he speculated to indicate a successful procedure physiologically.

*What a stunning scientific mind the father of Interventional cardiology was blessed with, still inadequate for the Nobel committee to get convinced.

Rules of the PCI game 

  • Mind the physiology. It is the new norm in selecting the lesions for stenting.
  • Now, If physiology is ok, you have to mind the Anatomy and vice versa.
  • If Anatomical (severity of block )is ok, then, you have to mind the morphology and vulnerability.
  • Finally. and most importantly mind the patient’s symptoms and clinical scenario.

So what should we do in a case of 70 % LAD with  .9 FFR ? (Still shabby looking, eccentric plaque, looks vulnerable  with a thin cap on OCT)

  1. I will stent, no doubt.
  2. I shall wait, and treat with Intensive optimal medical management (OMT).High dose statins will surely seal the cap.
  3. I will defer and watch.
  4. I will teach the patient and their family the basics of coronary hemodynamics and accept their decision.
  5. I simply leave the LAD for God to heal.

Which is correct?

All can be fair depending upon the clinical scenario.

In the ACS setting, one can’t afford to ignore these lessons.

Many would argue even in CCS setting it need to be tackled with PCI.

But isn’t also a fact, (maybe, we have been taught wrong as well ) non-flow-limiting lesions are more at risk in terms of ACS risk.

Hmm . . . then why we Insist to celebrate the concept of FFR  and its magic cut off of .75?

Do we practice coronary care at its height of confusing times ? or Am I make it appear so? 

Watch this, (https://rutherfordmedicine.com/videos )It might help you to get a better answer. Its called FORZA study. freshly delivered at TCT 2019, San Francisco.It compares FFR vs OCT guided PCI

 

 

The term Ischemic cardiomyopathy(ICM) was originally coined by Dr. Burch from Tulane University, New Orleans, USA in 1970. For many decades there was skepticism regarding the existence of such entity. WHO classification over the years never included this term. ESC working group of 2008 (Elliott P, European Heart 29(2):270–276) decided not to include CAD as a cause for cardiomyopathy. Even the current MOGES system doesn’t invoke CAD as a cause for cardiomyopathy. But, I am sure, most of practicing cardiologists would agree, there is a need for such an entity.

Why there is much reluctance to diagnose Ischemic cardiomyopathy as a distinct entity?

It is because of the basic principle, that cardiomyopathy should be a primary disease of cardiac muscle. (or at least secondary ).The presumption is, Ischemia per se doesn’t lead to muscle disease as such. It is just nutrition deprival.

Does this justify?

No, not at all. When a cardiac muscle is chronically deprived of nutrients it goes for necrosis, dilatation, scarring and dilatation, and progressive LV dysfunction. At some stage, it becomes true muscle disease or its equivalent (Secondary cardiomyopathy).In fact, adverse remodeling, Infarct expansion, extension lead to myocyte disarray, slippage and apoptosis, and cellular and interstitial fibrosis. All these changes are similar to Idiopathic (Postmyocarditis)cardiomyopathy.

What happens in the real world?

Even though there was some hesitation to diagnose ICM in the past, gradually the term shrugged of its taboo in academic circles. In heart failure clinics the only question seems to matter for everyone is, Is it Ischemic or non-ischemic DCM? Surgeons and EP guys also actively pursued the term Ischemic cardiomyopathy while they are selecting patients for CABG or CRT/ICD etc.

Further, in the research world involving community-based heart failure cohort, they required a basic distinction between the group of Ischemic from Non-Ischemic cardiac failures.

DUKE university definition (By Felker et al)

I think DUKE ended the controversy in the Nomenclature of Ischemic cardiomyopathy. It suggested the following to diagnose ICM (Read REF 2)

  1. LV dysfunction < 40% EF
  2. >Atleast one significant proximal coronary lesion (Usually 2 or more)
  3. With the history of MI or Revascularisation

* We are analyzing our data (Madras medical college, Chennai India) and propose to write WHO/WHF to include the following additional criteria to diagnose ICM.

4. At least 6 months should be elapsed between the MI and diagnosing Ischemic cardiomyopathy,

5. Must have significant LV dilatation & global Hypokinesia(With or without regional variation).

6. At least one episode of clinical heart failure is required before labeling it as Ischemic cardiomyopathy.

Other definitions that endorsed Duke

STITCH criteria *Surgical therapy in ischemic DCM study ICM was defined CAD with cut off EF < 35% with triple or double vessel disease.

iFAQs in Ischemic cardiomyopathy

1. Can we diagnose ICM without a history of MI?

This is tricky. As we all aware its very much possible as in silent MI of diabetes. One more possibility is even chronic coronary syndrome with microvascular dysfunction can lead to ICM.

2. Can Ischemic cardiomyopathy present as HFpEF or RCM?

While most Ischemic Cardiomyopathy present as DCMs with HFrEF, It is currently not clear how much of Ischemic heart failure present as HFpEF and if so they can’t be included technically as Ischemic cardiomyopathy in spite of the fact they present as HF.(as EF would be >50%)

3.When does a Post MI failure become Ischemic cardiomyopathy?

If the definition of STITCH or DUKE is applied, any acute STEMI can fulfill criteria of ICM. Hence it advisable to have a time limit say 6 months following MI to be referred to as Ischemic DCM. Pathologically to call it true cardiomyopathy, scarring, dilatation is required. Myocytes should be in independent self-destruction mode irrespective if hemodynamic conditions.

Response to treatment

The only purpose to diagnose ICM is to try to remove the I from ICM( ie Ischemia) Unfortunately, it is not an easy task. (While correcting Ischemia in ACS seems to be such an easy job.)

Following principles apply.

  • Medical management of HF/Ischemia is the key.
  • It is advisable every patient with cardiomyopathy should undergo coronary angiogram to rule out ICM.
  • Effect of revascularisation remains equivocal.
  • Viability of remaining muscle mass must be documented. (At least one-third of total cardiac mass should be viable.(Not very easy to prove though)One may use Doubutamine /Nuclear stress/PET etc) .It’s very important to realize even if the viability is demonstrated, the area that shows viability must be supplied by an artery that has a revascularisation eligible lesion.
  • STITCH can be called as a negative study (meaning positive outcome for patients if the patient doesn’t receive CABG in mulitvessel CAD and LV dysfunction ).However , STICHES (Extension of stich showed some long term benefits) The probable reason for CABG not helping much in ICM is the muscles didn’t get further useful life, either because it’s fully dead or extremely viable, that revascularisation made no impact.
  • CRT/ICD is known to prevent SCD and improve the functional class.
  • Heart transplantation is a life-modifying specific strategy.

Final message

I agree, many times our valuable time is wasted in renaming /Altering /relabeling a disease /process or pathology without any useful purpose. Medical nomenclature and classifications are done to make diagnosis simpler, choose an appropriate therapeutic modality and make a positive impact on the outcome.

In that sense, segregating ICM from other causes of cardiac failure do help in choosing a specific management strategy.

Let us welcome MOGES, It is the most comprehensive cardiomyopathy classification system (Like TNM classification for cancer). Still, I am not clear why it hasn’t included CAD in that system. Thanks to Dr. Burch who thought of this 50years ago.

Reference

1.Burch, G. E., Giles, T. D., & Colcolough, H. L. (1970). Ischemic cardiomyopathy. American Heart Journal, 79(3), 291–292.

2.Felker G.M, Shaw L.K, O’Connor C.M (2002) A standardized definition of ischemic cardiomyopathy for use in clinical research. J Am Coll Cardiol 39:210218

History of cardiomyopathy classification

The landmark thoughts originated in 1972 .When Goodwin and Oakley defined cardiomyopathies as the heart muscle diseases of unknown cause and described them as dilated (DCM), hypertrophic (HCM), and restrictive (or obliterative) (RCM) cardiomyopathy types.

WHO adopted it mostly and suggested Primary and Secondary cardiomyopathy in 1980. In 1995 WHO revised it.

The current MOGES classification doesn’t mention about Ischemic etiology

Caution : Non-Academic stuff

Anti hypertensives, lipid-lowering drugs along with antiplatelet drugs always find a proud place in most cardiac prescriptions. The toxic rivalry between various drugs and their creators is a well-known secret. However, the current fight among the antiplatelet agents is reaching comical proportions. The punches and reverse punchs on and off the podium is there for everybody to see.

It all started with clopidogrel two decades ago which was crowned after conquering then-popular Ticlopidine. It was followed by Prasugrel and Ticagrelor. Ticagrelor seems to taste its own medicine from Prasugrel, which brought back memories of the same knock out punches both of them gave to clopidogrel in the past. I guess the ISAR bruised Ticagrelor is just taking a time out, expected to REACT with fresh vigor in the next bout vs Prasugrel.

While these financial heavyweights struggle to keep the bull run, in the multi-billion-dollar stent maintenance market . Aspirin, the aged warrior is enjoying the theatrics silently. While Aspirin is repeatedly shown ( shown literally means shown: Mind you, It is not a synonym for a proven fact ) that it is inferior in stented patients.For stable CAD Aspirin still in the very much in the reckoning. Let the Twilight shine soon. Don’t get a shock of your life, if Aspirin regains the championship one day.

 

Final message

Let us hope the fight gets over till another Grelor  crash lands from nowhere. Meanwhile, we shall strive hard as professional physicians to increase the per-capita antiplatelet drug consumption in  every acute and chronic coronary syndrome (with or without PCI). This will help keep Homosapien’s coronary artery eternally patent.

 

For pure Academics  (Conclusions in science is a misnomer . . . )

 

 

 

Master health checks* , superficially look like a perfect modality to practice the greatest medical concept ie “Prevention is better then cure” .Let us detect all human diseases early , prevent its progression, regress it or completely cure it . Absolute bliss is it not?

Why then articles such as this one should ever get published, that too in one of the prestigious journal of medicine?

*Master health check .( Also referred to as annual General health checks.)

Master health check up geenral cochrane bmj editorial

While the title itself is provocative, it adds a tag line which is still more a shocker.

There are specific well-researched reasons for this preventive health check fiasco.The masters, who were originally the guardians of health soon became disease mongers.In the process, the primary aim of propagating the doctrine of “prevention is better than cure”, could not reach its desired goals. Instead of ignoring and reassuring the minor deviation of biological data and Imagery generated, they became a perfect feed for the hunters who are after the trivial and non-existing illness.

Final message

Good intentioned health checks are always welcome in selected high-risk population say pregnant women/children of developing a world (As in endemic countries of rheumatic fever) Also cancer , CAD , screening in people with a positive family history can be critical.

However, when these masters of health deviated and started making a living out of apparently healthy people. ( The side effects reached monstrous proportions hiking global health cost in a meaningless way).People, especially in counties with poor resources, are the ultimate sufferers, as the cost and efforts are diverted, to fix the health of healthy, while people with true illness continue to struggle.

Will the WHO* wake up and intervene against this skewed practice of routine master health checks in healthy, that are rampant in both rich and poor countries. Ideally, doctors should order preventive health assessment for those who may need it.

There are enough grounds for public Initiated periodic walk-in health checks to be banned (or at least restricted)

*WHO is world health organization

William Withering the British Botanist of 18th century now laid to rest in the St Barthomlew Churchyard ,Edgbaston is known for his astonishing isolation of the wonder moelcule Digoxin from Foxglove. (Of course, let us not forget original old lady Ms. Hutton from Shropshire who was treating epidemic dropsy with a concoction of herbal Tea ) He reported this in the seminal paper “An account of Foxglove’ in the year 1750 and subsequently became a fellow of Royal college of science.

(The story of Withering and Digoxin is extensively researched and written by Dr Dennis M, Krikler in a classic review article of 1985 JACC )

Near-death experience of Digoxin

After 250 years , saving millions of life, modern science has killed this warrior (inadvertently ?) by a minuscule study with serious flaws called DIG trial *published in NEJM 1997. It exposed the truth that science in flimsy forms can misrepresent fact. Actually many wouldn’t agree its a bad study. But , everyone realised , the conclusion was misinterpreted and disproportionately given weight to one aspect.The conclusion was worded in such a fashion, which sort of implied a negative bias.

*Yes , flaws were discussed in one of our detailed journal club meeting .

DIG trial

This one study was good enough to smear this drug with a knockout punch as if we are administering poison to a patient with heart failure.Thus a grand old drug became an object of ridicule in academic forums. Subsequent offline real-world scrutiny clearly indicated reduced hospital rate admissions and preventing worsening of HF was directly improving the mortality for which there were no takers. At least occasionally we need to realize there is foolish face for statistics. Now we are beginning to restore some lost sense.

 

What’s happening in 2019

The same scientific methodology finds Digoxin to have great value . JACC.  Awais Malik from Veterans Affairs Medical Center, Washington DC and others try to  dig out a truth.

screenshot_2019-08-24-23-37-54-789_com1423849373.png

Whoever is blaming this as a withdrawal study are requested to go through the basics of how adding a drug doesn’t help but stopping it worsens. Another group has a different issue. There is a tendency among the scientific community, to look down on studies done in VA hospitals as if they have lesser academic value. I strongly object to that if it’s true. Never have preformed opinion about a study by its source.

How does Digoxin act?

Mind you, Digoxin was working all alone in CHF in the past without the help of all-powerful loop diuretics which was discovered 200 years later, This adds more credit to Digoxin since it has a combined the action of diuretic, anti sympathetic and vagal modulating action, and AV nodal regulation. The only issue with Digoxin could be its safety profile, which if carefully taken care can be overcome. (Afterall, we are trained for this job ) One may call it a most comprehensive drug amongst others in cardiac failure.

Final message

Ignore the greatness of old drugs at your own peril. Foxglove blossoms again, after a gap of 30 years. Please don’t crush it this time! Let Willaim Withering smile from deep inside his resting place at Barthomlew Church along with millions of heart failure patients.

 

Reference

1.

2.History of William Withering

3.Ahmed A, Rich MW, Love TE, et al. Digoxin and reduction in mortality and hospitalization in heart failure: A comprehensive post hoc analysis of the DIG trial. Eur Heart J. 2006;27(2):178-186

Postamble 

A funny business Idea

I guess Parke Davis those days had wholesome rights for Digoxin. May I suggest few tips for the industry how to capitalise this newly generated enthusiasm. Please ensure this drug sounds anything other than Digoxin which seems to have a stigma attached for the modern guys.

Try renaming this drug , a sodium-potassium ATPase blocker, as DiNaKatban and patent  it as a unique weekly depot Injection with an attractive  499$ price tag. Another option is to add Digoxin ,Neprilysin and Frusemide,  possibly an ARB  ( Dinephrimab) and project it as polypill for HFrEF . Publish it in NEJM with a huge non Inferiority trial,break it in  ESC or ACC .Consider selling it on all heart failure clinics with a special launch. I am sure, the same guys who ridiculed this drug for so long, will ask their patients to stand first in the queue. Call me, if this new generation Digoxin doesn’t vanish like hot cakes from these pharma malls.

 

 

Preamble

Hey dudes, will you stent this 76 year old  fragile man’s Aortic valve ?  It looks shaggy and it seems to be leaking as well.Iam not sure its really tricuspid or not .It is so distorted . By the way , he also has a left main lesion with no protection.What shall we do ? Will the Jena valve do the trick ? My experienced collegue threw this question to a flock of freshly hatched senior residents of a upscale cardiac center. 

After rapidly feeding the necessary risk predicting numericals, clinical and hybrid imagery data , they dug deep into the iOS-powered gadget, loaded with latest TAVR app fused with SYNTAX 2 and FAME 2 overlay for few minutes and started responding one by one.

Yes sir , no Issues, we can comfortably stent it , Its class 2 A / with level B evidence according to JACC intervention article, but, I must say , it was class 2B just a month ago. Another fellow interfered, no sir, ESC says it’s still class 3 but the evidence is C so I am  not sure how to interpret it. The third fellow who usually is a quiet guy, came up with this, but sir, It seems TCT and EURO-PCR  has just released an update, the indication is currently upgraded to class 1 backed by level A evidence

Are you talking about TAVR or Left main? the confused consultant quipped… that’s EBM at its best !

Evidence-based errors in cardiology 

Evidence is the most sacred word in current medical practice. How much of our practice is evidence-based ? It is considered as a quality check. But, today we harshly understand, the evidence to which our conviction clings has a very short expiry date. Apart from expiry , the evidence thing comes with serious invisible manufacturing  defects as well. It may become null and void  even before its fully disseminated into the patient domain.(Please mind, your patient’s life is tied to this clueless evidence !)

So, how to tackle this dangerous dissemination of premature wrong evidence from injuring the patient ?

We don’t have a definite answer  . . . except to say, use the available evidence carefully and cautiously. If necessary (it will often be) throw it to the nearest dustbin by your own evaluation assisted by intuition, and a liberal dose of learned empiricism. Mind you, to do this you must be blessed with enough knowledge, wisdom, and courage as you need to overcome strong pressure to do the opposite.

My prediction is, bulk of the future problems in medicine would come from failure to dispose evidence based errors in medicine.