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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 till 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.

The prime job of cardiologists is to restore coronary blood flow in an emergency fashion. While we do this with reasonable success ,there is still a missing link between our Initial aim and achieved goal.

It’s all too common situation in any busy cath lab , to see two similar STEMI patients with identical time window & proximal LAD as IRA , in totally different scenarios. In the first patient we find a trickle of flow in LAD , who is relatively comfortable  with normal LV function (In whom , emergency primary PCI might appear redundant.) While the other patient , even after rapidly established TIMI 3 flow , LV wouldn’t look good at all . All our efforts to reperfuse is found wanting.  Ultimately LV goes in a downward spiral , ends up in irreversible cardiogenic shock or fatality inspite of Impellas, ECMOs and other LV asssit exotica !

 

intra-coroanry-thrombus (2)

I can promise , you can never guess from the angiogram whether this ACS patient was very much comfortable or he is in cardiogenic shock on ventilator  unless I reveal the history. Am I right ? That is the mystery of coronary circulation and hence its so critical to serve the myocardium what it wants ? Never treat a coronary artery in isolation !

What is the possible explanation ?

The first trickle (Say TIMI 1 which is usually spontaneous or lytic related ) is the one that’s going keep the muscle viable and possibly prolong the time window for the subsequent reperfusion strategies .Hence it is the timely TIMI 1 or 2 is much more critical than delayed TIMI 3 (Still rapid).

Time window woos :

Who fixed the reperfusion  time window as  6 to 12 hours ? Do you know on what basis  the acceptable delay of 30 to 60 mts related to primary PCI ? was made acceptable by  cardiology community ?  If you analyse the published data both are highly contentious and empirical. ( Suggest you scrutiny the data from DANAM2 , PRAGUE and AIR PAMI and come to your own conclusion) (*These are the 3 sacred studies done with few thousand patients  that redefined our approach  to STEMI and gave the licence to waste the golden hour ! )

I remember reading  the Robins pathology book (Bible of  pathology William Boyd as well ) in early days of medical school myocardium may die even within 1 hour with wavy necrosis, contraction bands etc. Looking back some times I  wonder how the clinicians have conveniently prolonged time window with whims and fancies of science Intact.

Concurring with the pathologists , we have learnt some harsh lessons inside the cath labs. One of them is that even ultra fast pPCI can fail to salvage  myocardium, meaning that time is not the ultimate thing in our race. (There should be other important determinants )

A brief journey back into our pathology classes : Have a look at this table 

Time window in stemi 6 hour 12 hour or 90 minutes

Please note, Irreversible Injury might happen any time after 30 minutes .Of course it can vary . But, the question is how are you going to identify these patients with  ultra short  time windows? source : Robbins Basic Pathology 9th Edition.Elsevier

Other factors that influence myocardial cell survival

Re-perfusion is not a single edged sword 

We may wish the concept of re-perfusion Injury is a myth : Unfortunately it is not ! Myocardium doesn’t relish (not always) the return of circulation in full dose. (May be it’s laying and taking the much needed rest with the initial Injury!)

Reperfused myocardium

Sudden gushes of blood leads to extravasation into the interstitium (due to damaged capillaries)  increases the Intra myocardial resistance and obstructs the microvascular flow. We have  witnessed more than a handful of patients going for cardiac arrest once IRA is opened (of course,  we might be  able to resuscitate many of  them )

Myocardial hypoxia resistance time

Please realise ,true  STEMI clock starts not with onset of symptoms but with time of total occlusion.There is more than subtle difference between the twoOnset of total occlusion to symptom time is not a well explored or understood Interval. We take it for granted that the onset of symptoms coincides with total occlusion.

But in multi vessel CAD, even a CTO can cause a STEMI through loss of distal collaterals. Further ,the presence and absence of pre-infarction angina (PIA*) , ischemic pre-conditioning (IPC*) sensitizing effect of  remote CAD , manifest vs recruitable  collaterals  all these make the fixed time windows with which we did our land mark studies of PCI / lysis academically  questionable.

* Both PIA  IPC are master confounders in the true time window calculations .We don’t know whether its due to ischemia tolerating myocytes or pain tolerating nerve fibres  responsible for this varying presentations.But the mystery is certain , when we  realise the angiographic  spectrum of ACS can range from silent ATOs to painful CTOs

Final message

Is timely reperfusion (and its favorable effect ) lies in God’s domain ? If you we  believe myocardial susceptibility , arrhymogenicity and recovery to hypoxia is genetically determined ,then the difference between fate and science Is much narrower than we think .Its appears we can change the former with the later with both positive and negative outcomes. So ,the  “f”  word may not be a forbidden at-least in the STEMI management. It resides not only  within the human genomic codecs written with double-helical nucleic acid fonts . . . but also  in the nimble and restless hands of both novice and experienced interventionists !

                       

A study proposal 

Let me make a hypothetical statement .A significant subset of patients with STEMI have ultra short myocardial survival and we are unable to identify these hypoxia challenged hearts where primary PCI related delay could be a myocardial sin. Any one willing to prove or disprove this hypothesis ? If some body take this quixotically important study in STEMI management please give me some credit as a contributor !

 

 

 

 

 

We learn from basic physiology  lessons that human body is made up of 60 % water. What about heart ? There is no reason for the heart should behave differently from rest of the body . If my  assumptions are correct when the normal heart weighs 300g  , 180g of which should be  be water. The same thing could be applicable for LV mass( * Reference requested)

Is there myocardial congestion in cardiac failure ?

Genesis of edema in any tissue depends on local hydrostatic pressures, tissue resistive forces, osmotic balance, and cell membrane permeability. In the myocardium individual contribution of above factors are not known. Apart from total myocardial water content  , myocardial water logging depends upon the trans myocardial venous gradient and the coronary sinus exit pressure in right atrium.Technically ,any severe right heart failure should lead to myocardial congestion at least to some degree.Unlike the lungs , the myocardial edema fluid doesn’t produce crackle , (May cause S -3 gallop instead) . However ,we have modern technology to image water inside the myocardium. Yes, it is called proton / hydrogen imaging or simply called MRI .

This is especially evident In chronic kidney disease , where in the fractional water content within the myocardium is expected to increase further as the whole body is water logged.

 

myocardial edema by mri in ckd 2

We have seen time and again patients with CKD  improve in LV function immediately  after dialysis . It happens like a magic . The mechanism  is simple .The over-hydrated cardiac Interstitium  threatening to drown the myocytes  is promptly dehydrated by dialysis. This was my wild guess  until I came across this paper which proved the exact points.

myocardial edema in ckd chronic renal failure recovery of lv function after dialysis

 

Other situations  where myocardial edema may play a significant clinical Impact  (*Includes increased permeability of myocardial capillaries)

  1. Myocarditis
  2. Transplant rejection
  3. Stress cardiomyopathy (Takotsubo)
  4. Congestive heart failure
  5. Acute ischemic injury
  6. No Reflow situation after PCI

Final message

Myocardial interstitial edema in cardiac failure is a grossly under diagnosed  entity.  A water-logged myocardium is classical at least in CKD. We know it can severely compromise the LV function especially, the diastolic function that explains the all too common flash pulmonary edema in CKD.

The number of studies in this  topic (Myocardial Hydrology !)  is minuscule compared to other areas of research in cardiology literature.There is a need to involve both  Nephrologist and cardiologists to explore this curious concept of  dialysable  left ventricular mass in CKD/Cardio renal syndromes !

medical quotes new idea

One more area of research 

It is reasonable to believe,  cardiomegaly in cardiac failure  is primarily related to the increased end diastolic volumes .Still , we are not clear whether there is net increase in cardiac mass as the surface area of the heart increases with dilatation. (Even in DCM ? ) Whenever myocardial mass increases relative increase water is likely. Does the beneficial effect of diuretics in cardiac failure , and the restoration of  LV dimension is due to myocardial interstitial diuresis as well ?

Reference

myocardail edema water content congestion mri n myocardial diuresis interstitial

2.Andrés-Villarreal, M., Barba, I., Poncelas, M., Inserte, J., Rodriguez-Palomares, J., Pineda, V., & Garcia-Dorado, D. (2016). Measuring Water Distribution in the Heart: Preventing Edema Reduces Ischemia-Reperfusion Injury. Journal of the American Heart Association5(12), e003843. doi:10.1161/JAHA.116.003843

3.Cardiovascular magnetic resonance of myocardial edema using a short inversion time inversion recovery (STIR) black-blood technique: Diagnostic accuracy of visual and semi-quantitative assessment Darach O h-Ici, John P Ridgway, Titus Kuehne , Journal of Cardiovascular Magnetic Resonance 2012, 14:22  

 

Evening cardiac clinic is generally a relaxing place until an occasional patient  with vague chest discomfort present with this sort of an ECG .

He was a 68 y old hypertensive and was on Tablet Amlodipine .After a cursory look at his ECG , eyes wandered to look for some specifics. Suddenly ,my  ECG reading skill was stretched . Is it really LVH ? or Ischemia ? I asked for any old ECG which he couldn’t provide. I had to blink  more than a moment , before asking him to describe his chest pain in detail one more time . I got almost convinced it was not ACS  since he was having only localized pain over left side of chest. Still , I didn’t have the courage to send him home. An Echo was done.

Curious to know what the Echo showed ?

 

Yes , you also probably guessed right . It is LVH and there is no wall motion defect either.

How to differentiate between Ischemia and LVH ?

This is a common question asked in the board exams.There are number of ECG clues to differentiate the two .Mostly it will help  fellows  to pass exams. Academics rarely comes to your rescue when patients land with  chest pain  especially at odd hours.

Find the answer in this link

https://drsvenkatesan.com/2009/12/12/how-to-differentiate-lv-strain-pattern-from-primary-lv-ischemia/

 

Now comes the real twister , Does presence of LVH  exclude Ischemia in any way ?

Why can’t be ACS in a patient with LVH ?

When I posed these questions , some one suggested global longitudinal strain  with speckle  tracking to rule out ischemic wall motion defect, my resident suggested  high sensitivity Troponin and Ischemia modified albumin.

Whatever is the technological assistance , one thing  is certain,  we need to finally fall back  on patient’s symptoms . Unstable angina is neither an ECG diagnosis nor biochemical  or Echo diagnosis . (Its all about patient description about his angina , that clinches the  diagnosis !)

It remains a fact normal spot Troponin can never rule out  ACS on time ,( Even patients with unstable angina who  harbor  tight  LAD lesion can be both ECG /Enzyme negative )

When we are not sure ,the traditional coronary care dictum  shall operate .It demands admit, observe, with serial ECGs and enzymes. This protocol cant’t be followed strictly for a variety of reasons . We may have to rely entirely on our clinical Intuition accrued over the years.

A modern-day cardiologist might have a different dictum .The simplest solution in such situations is a diagnostic radial snap shot coronary angiogram .It is an easy way out  . . . , and avoids the trouble of spending wasteful minutes of personal conversation with the patient .The ethics of outsourcing history taking , patient record review or even clinical examination has pushed the definition of professional competence in coronary care into murky grey zone.

One more reason we should hesitate to rush these patient to cath lab is the detection of  incidental insignificant CAD (Which will loom larger than life when they are wheeled in from  ER)  that will  lead on to  further inappropriate chain of events.

How relevant is clinical acumen in modern era ?

Clinical acumen in medicine can never be taught in class rooms or read in text books. It is the innate ability to  combine  knowledge, experience ,skill  and  lastly (and most importantly) courage to ignore conflicting and pervasive data from new generation Investigations. Instead of helping us ,they often directly affect our increasingly vulnerable native medical cognition.

Even if some one is blessed with a good clinical acumen it seems to have little value many times as power of Investigations and fear of missing a event will prevail over it ! I have been victim of this phenomenon many times and not able to follow what my mind preach me !

What happened to this patient ?

I had to admit him against my  wish (Of course I was safe!)  He too got admitted reluctantly and was observed till morning , spent Rs 5000 for pack of investigations and stay , was discharged without any issues with a diagnosis of simple Hypertension and LVH.

The non academic bug  didn’t stop there  . . . again  contrary to my conscience  I had to suggest  optional coronary angiogram to rule out true CAD as a precautionary statutory advisory !

 

Counterpoint 

How do you know this is really not CAD  ? I won’t believe unless and until I see the CAG and its normal.

Ok, Let me post his angiogram if he decides to  undergo it.

We know pleural effusion (hydrothorax) is disproportionately more common on right side in cardiac failure.Though its a well observed phenomenon, the mechanism of which  has not been clear to us. It could be due to multiple  anatomical , physiological factors.

 

*The are  right and left lymphatic (Thoracic) ducts that drain the corresponding lungs and pleural space . There can be overlap and contribute to the differential occurrence of pleural effusion

 

Reference 

A meticulous paper written some 75 years ago (1946) from Harvard medical school teach us some important points in this phenomenon.

There is still lot, to be understood about pleural effusion in cardiac failure. We need to know why some pleural effusions tend to occur independent of hydrostatic forces.  It is also noted long-standing transudative effusions can become true exudates. Role of local pleural capillary hypoxia resulting increasing permeability is underestimated.Hepatic congestion and trans-abdominal seepage of fluid is a distinct possibility.

One more area we are not clear is  the relationship  between the  genesis of  pericardial effusion in cardiac failure and concomitant pleural effusion. Post operatively , after univentricular repair (as in Fontan ), pleural effusions can be much problematic with high venous pressure interfering with  pleural drainage.

Impact on symptoms

Finally, even mild pleural effusion can increase the work of breathing and result in dyspnea which is out of proportion to cardiac dysfunction.While we expect the diurteics to clear the effusion of cardiac failure, it doesn’t happen always arguing for a non transudative mechanism in at least some of them.

Further reading

Discerned readers are advised to study the pleural space dynamics in detail.

Link to the original Article of Edgar Mcpeak and Levine 1946

 

 

 

Though heart is known primarily as a pump, it is the four cardiac valves that ensures the critical , non-stop unidirectional flow that sustain the circulation . It is to be recalled these valves originate in the very early days of cardiac development when the primitive heart tube loops , even as the chambers expand from primitive ventricle. Mesenchymal differentiation controlled by various genes that cleaves the valve from myocardial tissue.

While heart by itself is the supreme vascular organ ,  its surprising  few structures inside the heart , like the valves are quiet avascular ( or is it really so ?)

The valves that beat average of 30 billion time in life time ,seem  to get its nourishment from Nowhere ?

Layers of heart valve 

 

Image source : Huk D., Lincoln J. (2017) Oxidative Stress in Cardiac Valve Development. In: Rodriguez-Porcel M., Chade A., Miller J. (eds) Studies on Atherosclerosis. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Boston, MA

It’s primarily made up of  complex stratified connective tissue covered by endothelial cells with intervening interstitial cells. The extracellular matrix (ECM) layers are rich in elastin proteoglycan (spongiosa) and collagen (fibrosa). It has been found myocytes and dormant fibroblasts are scattered in the valve leaflets. This forms the basis of focal origins of  Cuspal Ventricular tachycardia J Cardiovasc Electrophysiol. 2002 Jun;13(6):551-6.  from electricaly activated myocytes.

Is there a dynamic cell turnover within the valve tissue ? Where does it get the nourishment ? What is the effect of  aging and CAD on valve tissue ? 

There is growing evidence for valvular extra cellular  matrix are indeed dynamic. This explains valvular lesions in connective tissue disorders like Rheumatoid arthritis. Progressive degenerative changes of aging  involves  remodelling , tissue engineering . Calcification of cardiac valves in endocrine disorders like  hyperparathyroid states implies  cardiac valvular interstitium is in continuum of systemic metabolic pool. There has been very little published evidence  correlating  CAD and Ischemic degeneration of valve.

Evidence for vascularity of valves

It is surprising , this simple question of  vascular supply to cardiac valves has  confronted the scientists for too long.

1.Histopathological and  autopsy studies have revealed vascular channels.(Harper 1938 BMJ)

2.X-ray projection microscopy was used to image the valves after injecting radio opaque microparticles in the ascending aorta. This is probably the one of the few original studies done in UK in 1968 (Clarke et al ) it revealed significant  vascularity of the valve .It was found 16 % the tricuspid valve, in 10% of the mitral valve, and was maximum in Aortic valve (24%).

3.The fact that statins reach the Aortic valve tissue in lipomatous Aortic stenosis indicate significant vascular port of entry to valves.

Direct evidence : Why don’t we ask the surgeon ?

When I asked my surgical colleagues  Does the valve  bleed  as they cut it  ? Most of them were amused with my query , still Iam not sure I got the answer right. At least one of them said since the heart is on pump ,  it won’t bleed any way !

 

Conclusive evidence : From a 1968 study 

It is academically humiliating to note we have to go back 50 years in time to get a proof for vascularity in cardiac valve.(Or anything new I am missing ? readers may share !) I think , this is strongest proof  for valve cusps are supplied by end coronary arteries. However the penetrance is not deep into all layers of the valve and distally

Is hematogenous spread of Infective endocarditis(IE) occur ?

How does systemic infection reach the valves ? We still believe the IE is due to direct colonisation from circulating blood .Hematogenous spread of IE do occur but difficult to prove. It seems infection of valves primarily happen from outside initiated by  endothelial injury over the valves .

*There seems to be a contribution from  systemic bacteremia  reaching  from within through the pre-existing capillary twigs as well.(Evidence elusive !)

 

Final message

Is cardiac valves vascular ?  It is curious even in this era , we struggle to answer this query with certainity.

Yes, they are vascular structures , but at best it has partial vascular capillary network. It is also possible  the valves can live a durable life even without these vascular Innervation.(I haven’t heard of a condition called mitral valve infarct or necrosis in RCA/LCX STEMI which supply the base of the heart)

Still, this partial  vasculaity can become Important at times of pathology like infection or degeneration. Expecting more research in this unique area of valvular heart disease

Reference

1.JOHN A. CLARKE AN X-RAY MICROSCOPIC STUDY OF THE BLOOD SUPPLY TO
THE VALVES OF THE HUMAN HEART BY   From the Department of Anatomy, University of Glasgow, Glasgow Brit. Heart J., 1965, 27, 420

2.https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC1252531&blobtype=pdf

3.Dow, D.R. and Harper, W.F. The vascularity of the valves of the human heart. J Anat193266610–617

4.Ritter, S.A., Gross, L., and Kugel, M.A. Blood vessels in the valves of normal human hearts: from a study of 700 human hearts. Am Heart J19283433–446

5. Saini N, Saikia UN, Sahni D, Singh RS.  Vascularity of human atrioventricular valves: a myth or fact? J Thorac Cardiovasc Surg. 2014 Jan;147(1):517-21. 

Cardiologist are always worried about the supply side of coronary blood flow. It’s fair enough, we can condone our brain for this one way thinking , afterall arterial supply remain the life-line for the heart. Some of us could (should) realise the importance of these  humble coronary veins which are anatomically and physiologically tied together.Its existence is as unique as their arterial counterpart.Coronary blood flow of about 250 ml traverses both the arms every minute.Imagine the scenario if the veins refuse to clear the blood from previous cardiac cycle . . . total hemodynamic chaos right ? Luckily such situations are rare !

See how the the two coronary arteries and its branches interwine with the 4 major coronary veins.

J. M. Bourgery from Atlas of Human Anatomy and Surgery / Atlas d’antomie Humaine et de Chirurgie by Jean Marc Bourgery (1797-1849) Los Angeles: Taschen, 2005. Atlas Case QM 25 .B67 2005

Is the LAD flow coupled with Great cardiac venous flow ?

It is curious to see the LAD  hugging its spouse great cardiac vein within the anterior Inter-ventricular groove , but directing the flow exactly in the opposite direction . One should  wonder is it the same stream of blood from LAD ?(Near 100% So2) goes out into myocardial tissue comes back with 30 % *saturation in GCV ? If this is true , one can measure the “LAD micro-circulatory bed” integrity by computing the arrival time of levo phase blood in GCV.

J. M. Bourgery from Atlas of Human Anatomy and Surgery / Atlas d’antomie Humaine et de Chirurgie by Jean Marc Bourgery (1797-1849) Los Angeles: Taschen, 2005. Atlas Case QM 25 .B67 2005

* Its an important physiological fact the most desaturated blood(30%) in the body is from coronary veins as the aerobic organ extracts maximum oxygen .(For comparison IVS/SVC saturation is around 75% )

What happens to GCV flow in LAD  STEMI ? or CTO ?

In  ATOs of LAD there is temporary collapse of GCV. If it prolongs it may end up in complete thrombotic occlusion of GCV which has implication in slow flow , no reflow and poor myocardial salvage.

What happens when there is  acute  coronary venous occlusion ?

Nothing alarming happens. God’s masterly protection  ? Yes it is .Still its a mystery , sudden death is not the rule if we clip the coronary sinus as  thebesian venous system take over which drain direct to chambers.The fact that obstruction of  these veins may not result in acute coronary syndrome brings  less attention to this circulation , in spite of vital hemo dynamic role . Acute venous infarct due to coronary sinus infarction is still  possible.

Is there chronic coronary veno occlusive disorder ?

We know ,venous system is Intrinsically prone for thrombosis  in susceptible individual as the flow velocity is sluggish . Almost every venous system right from portal, hepatic pulmonary , renal cortical venous , experience this pathology. It’s surprising to note coronary venous system is largely devoid of this.(or at least it’s not recognised as often !)

Some of the patients with chronic CAD with syndrome X /Y show extreme slow flow with normal epicardial coronary arteries.We need to study them for sluggish coronary venous flow syndromes.

Assessment of coronary venous hemodynamics 

Coronary venous circulation integrity is critical component of  coronary micro -circulation.We have done original studies in the timing of filling of coronary sinus that reflects integrity  coronary micro circulation.( Sangareddi V, Alagesan R. Coronary sinus filling and emptying time: A new parameter to assess coronary microcirculation by a simple angiographic frame count. 59th Annual Conference of the Cardiological Society of India December 7–10, 2008. (Abstract).)

Microscopic analysis of coronary venous debris following PCI is our future area of study to assess the mechanisms of no reflow.

Clinical utility of  coronary venous circulation 

  • Coronary veins are popular with  electrophysiologist.The typical CS catheter is used to record intracardiac ECG around the AV groove .
  • They also provide an alternate site for ventricular pacing and cardiac resynchronisation therapy. However the efficacy of CRT is related directly to the coronary venous finger print .Unless it matches with the scar free areas of ischemic cardiomyopathies the response is likely to be less. So essentially EPs are at the mercy of these veins and scars.
  • Coronary veins can be used for retrograde perfusion of myocardium in diffuse obstructive  coronary arterial CAD where CABG is not possible with some success.
  • There is one trial (COSIRA) which suggested increased microvascular perfusion if we narrow the CS diameter with a device .This is hemodynamically Ironical though as coronary  perfusion gradient is increased still because of stagnation suggest some improvement in perfusion( Verheye S ,NEJM 2015)

Reference

Coronary venous circulation has an Integral link with micro circulatory bed .It will be of huge importance to understand the highly unpredictable response of PCI with reference to myocardial salvage in STEMI and revascularisation in chronic CAD.Youngsters are encouraged to dwell deeper into the mystery of coronary microcircualtion .

This one from Dr. Muller ,Florida  is a perfect review to start with.


A good review about the venous anatomy with reference to electrophysiology

Thousands of delegates* converge annually in glittering convention centers on a regular basis to present high quality research. It’s all about overflowing seminar halls, stunning speeches , Intense questions , adoring debates , cozy discussions in grand dinner nights . The meet continues further, as news breaks in global TV shows, spreads in non-stop handles of twitter after igniting the face books.

Finally , it ends over the week-end ! (It has to you know ! ) . . . Every one flies back, only to come back next year to ponder “almost the same issue”  all over again. (Some times the questions are left unanswered for decades ! Not getting an answer is okay , after all research is a  journey towards  truth   but sustaining a confusion or creating new one has been a norm in recent times.)

*Sorry , If am provocative , I need to be genuine in my expression.

Coming to the topic, Aspirin is one wonder drug which made a big impact on CAD risk . We know there is something great with this cheapest and humble Dual COX  blocker.The only weak point is ,it lacks the glamor quotient like that of newer antiplatelets, NOACs  and their clones.

Its my perception ,big breaking research has tried to ditch this drug for quiet a while .But ,it was all too difficult to go for the kill.So these studies circumnavigate the real issue. and end up with  suspicious conclusions  (or Inconclusions !) always trying to hide behind sinister statistics of course with a questionable caveat !

What’s new in the topic of Primary prevention of CAD ?

Two major studies were released recently in August 2018

Both studies suggest caution for Aspirin. If Aspirin is really  bad it would (and should) have buried long ago. We should be thankful even in these testing times for truth ,this humble drug is fighting  back and forth .(Digoxin is another close  cousin of Aspirin fighting for the existence  crisis in cardiology  ! ) 

So what is the role of Aspirin in primary prevention of CAD ?

This question doesn’t make sense in many clinical situations.

Primary and secondary prevention are defined with reference to manifest vascular event. We will not know how much of silent CAD exist in asymptomatic persons.Primary prevention of CAD itself could be a misnomer as most elderly do carry at-least some form of CVD. For example, If a patient with manifest peripheral arterial disease (PAD) and takes Aspirin , its  secondary prevention for PAD but becomes primary prevention for CAD . . . isn’t  ?

Final message

We know Aspirin  continues to be the flag bearer of  all DAPT regimen.I wish it remains a star in primary prevention as well. It looks like(for me)  these studies  are another attempt to pull down Aspirin in primary prevention .I think ARRIVE failed to reach the desired conclusion. Aspirin is a warrior and it will never allow that to happen and ASCEND to glory again !

Postamble

Modern drug research appears to pursue a study till the desired conclusion is reached. We need important  drugs in many vital areas of cardiology .Our energy should be focused to find new molecules. It is worrying trend(if its true !) if efforts are wasted to finish off humble generic drugs with proven worthiness. Doing research in established concepts is the most silly thing to do. Its duplication of knowledge.

Counterpoint

It’s scientific blasphemy to criticise  studies without analysing it in a professional manner.It appears all too brutal to take a biased view and questioning the motive of researchers. Yes agreed , I may be prejudiced , . . but , why a doctor of this caliber make a statement of this sort ?

Its a fact  , there are so many true scientist doing their job right, my query is simple why we are not getting clear answer in many common issues In spite of great research ?

Is it the limitation of science or vagaries of research ? I think it’s more of a  Intellectual insufficiency  aided by  malfunctioning regulators !