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Posts Tagged ‘diastolic dysfunction’

We presume  ECG  fails miserably against echocardiography for assessing hemodynamics , while  echocardiogram  has  little value  when it comes to studying   electrophysiology .  Ironically ,  we often  ignore  the fact  ,   ECG can  provide  important long-term   hemodynamic  data . The pattern of  chamber enlargement  give us  vital clues to the prevailing hemodynamic  stress and loading conditions. While echo  can be termed as an  anatomical and  physiologic   modality  , ECG  apart from  its unique capacity to record cardiac  electrical finger prints ,  it  provides  useful ,  anatomical ,  hemodynamic information too !

While Doppler is a  fascinating modality to measure hemodynamic data in a moment to moment fashion it can never ever tell us  , what has been going around in the preceding months or years. This  is were chamber size helps which  give us chronic physiological information (Chronic  Doppler ?)

A simple E:A reversal  in  mitral inflow doppler can be a  innocuous  finding in isolation  . If it is associated with even   minimal grades of  LAE  it gains huge importance. That is why left atrial size is  funnily referred to as HB A1C of diastolic dysfunction ( A marker of chronicity  of  diastolic dysfunction)

If LAE is so important to diagnose diastolic dysfunction , why  we are so  obsessed  with doppler filling profiles  of mitral valve ,pulmonary veins, mitral annular tissue Doppler and what not ! .Many of these sophisticated doppler methods are extremely operator dependent  and are  subjected  to technical and mathematical errors. Especially , with  tissue doppler where we  magnify the errors as we  filter  extremely  slow tissue motion .

For  many  decades  we  have failed  to impress ourselves  , about the importance of subtle P wave abnormalities in the  ECGs   of  hypertensive patients.

In fact those  innocuous looking  slurs and notches   in P waves ,  suggest the left atrial  stress and a definite marker of underlying LV diastolic dysfunction .

P wave is the only electrical wave that occur in diastole .Hence there is no surprise  ,i  gives us enormous information about this phase of cardiac cycle .

If only we look  at them carefully, zoom it (Now it is made easy with so many softwares)  analyse critically we can find a wealth of information about the atrial behavior in hypertension.

Experience from our hypertension clinic  with periodic echocardiograms suggest ,  the following  ECG  findings   can be   good markers  of significant  diastolic dysfunction .

  1. Notched P wave
  2. Wide  P waves
  3. Slurred  P wave
  4. Bi-phasic P waves

* Surprisingly  , these abnormalities correlated with at least grade 1 diastolic dysfunction even in the absence of  for LAE or LVH by echocardiogram.

** In an  occasional patient  P waves  can widen due to inter atrial block or conduction delay. This a rare exception for wide P waves without LAE.

Final message

A well recorded and   analysed   ECG can  predict diastolic dysfunction  with fair  degree of accuracy .This fact need to be emphasized  by every one  .  Next to ECG ,  LA size and volume  by 2d echo are excellent parameters  to assess diastolic function in a long term fashion. Sophisticated  but  error prone ,  momentary doppler parameters are getting too much attention  at the cost of simple ,  shrewd ECG and 2D echo  !

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Heart is mainly perceived  as  a pumping organ but it need to be realised it  also has a   reservoir function  (Temporarily though , for  about .5 seconds every beat ) . Contrary  to the popular belief heart is not  continuously and tirelessly working  .For every contractile  beat it takes  a brief period of rest .This is called diastole. But , even here it is not a complete rest , as  it has to receive the blood from the atria and get filled and be ready for the next beat.

Many think diastole is an active energy-consuming process . . . but it can be debated still ,  as passive elastic properties may contribute substantially to cardiac relaxation blunting the energy requirement

God is so scientific (Greatest scientist !)  he  made it sure   the resting phase(Diastole)   is slightly more  than the contractile phase (Systole ).

This makes the organ relax a bit more than it stresses  in its entire life time . At  any  given heart rate diastole will be slightly  more than systole  , peculiarly  for the same reason  during tachycardia  diastole suffers more than systole.

What happens in diastolic dysfunction ?

Pathologically the ventricles become stiff  and rigid and the filling of the  ventricle is impaired . The commonest cause for diastolic dysfunction are  hypertension, diabetes, and  ischemic  CAD some forms of myopathies  .In systole ,the calcium  is pumped into actin myosin complex  while in diastole the  same calcium molecules  (Or different !)   are ejected back into the cytosol and sarcoplasmic reticulum. The later process is impaired in many situations of diastolic dysfunction.

It should  also be realised not every one with diastolic dysfunction  has a  calcium release /unloading defect .Many  have structural diastolic dysfunction  like interstitial fibrosis  .Here the mechanism goes beyond  calcium kinetics.These are the patients who get maximum  benefit out of heart rate reduction.

It is all Time  . . . Time as a  lusiotropic  drug !

If the ventricle finds difficult to relax  (or slow /sluggish to relax )  we have  two  options to tackle this .

  • To make relaxation  faster( ie positive lusiotropism )*
  • To  prolong the diastole  itself  .

Prolonging diastole makes it certain , the LV relaxation process is completed   as the excess time compensates for  the slowness of calcium reuptake into the sarcoplasmic reticulum . In fact , we have observed at slow heart rates (<60)  it is very difficult to document diastolic dysfunction  by doppler .

In many of  dilated  cardiomyopathies  the beneficial effect of  beta blockers , could be linked to simple reduction in heart rate and prolongation of diastole .(Note In DCM about 30-40 % have restrictive filling )

Final message

As we have no specific drugs to  augment the  process  of   cardiac diastole,  currently heart rate reduction  could be the simple and best method*  to improve diastolic function  .In many cases  diastolic dysfunction  simply vanishes  at low heart rate.Bradycardia  and  diastolic dysfunction   will remain as foes  forever !  Please give the benefit of this simple concept to all your patients with diastolic dysfunction .Your patients  can breath lot more easier !

*Apart from controlling the underlying cause like DM, SHT and CAD  , anti fibrotic drugs,  interstitial relaxants ,selective cardiac   collagen uncouplers  are the  future areas of research .

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Diastolic dysfunction  as concept  has  come a  long way after  initial hiccups . Now,  it is a well established  left ventricular pathology  , and has   a  sound physiological and molecular basis. Even though there are variety of methods available to quantify  LV diastolic function,  echocardiogram is the simple method to identify and grade diastolic dysfunction.

There are 4 grades of diastolic dysfunction

1.Impaired relaxation  (without elevated filling pressure)

Some  describe another grade  1 a  with elevated filling pressure

2.Pseudonormal mitral inflow

3.Restrictive -Reversible

4.Restrictive -irreversible

What is pseudo normal pattern ?

The grade 1 is the  most common type  diagnosed  . It is diagnosed when the  A  velocity is more  than E velocity . This  simply implies ,  ventricular filling needs greater assistance from atrial contraction than in resting conditions. It is so common , especially in elderly ,  many thought it should not be considered a pathology . In youngsters it is definitely pathological especially if it is persistent.

The issue that  really concerns  us  is  this  : When the diastolic dysfunction  progress  from grade 1  to grade 2  ,  the mitral the inflow  doppler pattern ,  instead of showing any  new changes simply nullifies the changes that occurred in grade 1 and  records a normal E : A velocity .

So , a person with grade 2 diastolic dysfunction will have a near normal pattern .Of course  deceleration time, and IVRT is shorter than in grade 1 but it is not very useful in differentiating it from normal .

Pseduonormal is  actually  equivalent to moderate diastolic dysfunction , but the abnormality is masked  as near normal  filling is restored with atrial assistance . So,  technically it a  assisted LV filling . A  superficial  look at the doppler pattern may exactly mimic normal . But there will be a  2 D echo  abnormality  that makes the patient  pathological . Our eyes need to look  beyond  doppler  ( in coherence with  2 D ) to differentiating  normal or pseudo normal.

It is learnt  ,  2D abnormality of LV or LA occurs in nearly 90 % of grade 2 diastolic dysfunction .(There can be a pure functional grade 2 diastolic dysfunction  without structural changes in LA/LVH in minority -This is poorly understood form of silent sub clinical CAD manifesting only as diastolic dysfunction  )

Traditionally  there are few methods taught  in echocardiaographic schools  all over the world to differentiate normal from pseudonormal

1.Pulmonary vein  doppler

2.Response to valsalva maneuver

3.Tissue doppler etc

One simple echo feature  that is   often forgotten , that can be really useful in differentiation of  normal from pseudo normal is    left atrial dimension

While patient with pseudonormal who  have  progressed   into  stage 2  will show a  definite left atrial abnormality .

When does a left atrium begins to enlarge in diastolic dysfunction?

  • It depends  on LA thickness  and  LA afterload (LVEDP is the afterload for LA)
  • It is generally believed  LAE  will be there in almost all cases of grade 3  diastolic dysfunction.
  • It is present in  majority of patients  with grade 2 as well . But the degree  of LAE may be less  ( 4-4.5cm)

It is yet unclear ,  the onset of LA enlargement in diastolic dysfunction .This is potentially a research topic for the fellows !

It is not uncommon  to find   LA enlarge  like a balloon even in stage 2  of diastolic dysfunction. So , in patients who are suspected to have  pseduonormal  doppler profile , look for the presence of LAE  , (however mild it may be !)  , there is no business for LA to enlarge in normal persons.

Ofcourse , if  you are a echo expert one can measure A reversal in PV doppler, tissue doppler echo etc .But remember a simple 2D echo feature like a LA dimension / LVH   may score over the sophisticated (Also read complex  . . .) parameters  in the grading of diastolic dysfunction

Final message

While  we  immerse  ourself  in   sophisticated doppler methods  to differentiate normal from psedunormal pattern, the fact that  , normal persons will  have normal hearts  is often forgotten , and    presence of left  atrial enlargement (Which is all too common in pseudonormal !)  straightaway   settles the issue . Detailed diastolic function studies are warrented only if the LA size is normal .

*Correction: in table A reversal in normal is less than 35cm/sec

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It is a well known fact  ,   CABG and PCI  provides immediate relief  for patients with angina ,  which is refractory to medical therapy. Of course , this happens only if a critical occlusion of  at least one epicardial coronary artery is  opened . It need to be realised ,  angina  due to  microvascular  disease can not be cured by maintaining  epicardial  patency .

While angina  relief is prompt ,  dyspnea is not ! . If we  believe,  opening  up a  coronary artery  in a patient with LV dysfunction will  restore the LV function  ,  it  is grossly mistaken !

Why is it so ?

Angina  relief requires  simple  restoration  of  oxygen supply and correction of local ischemia .  This happens without any issue as the blood  seeps in to the ischemic cells and soothes the ischemic nerve fibres that trigger the pain signals   . While  ,  for LV function to improve , the blood flow has to be converted to mechanical activity in the form of myocyte actin/myosin interaction. For this,   there need to be an intact  cellular contractile mechanism . The myocyte architecture should be appropriate .In post MI ventricles we know there is  zig zag  orientation of myofibrils due to myocyte slippage that interfere with mechanical recruitment . Further , integrity of  extracellular matrix  namely the collagen frame work is also vital . Note ,  angina relief  is not concerned with any of the above .

And now ,  we also realise  dyspnea  in failing ventricles  is vitally  dependent on diastolic function ,  which is also very much  impaired in ischemic DCM .There is little proof for  PCI/CABG  to correct the  molecular   mysteries in  diastolic dysfunction !

Dysfunctional LV means what ? (read the link )

It is a collection of  variety of myocardial tissues . Viz : Fully  necrosed , partially necrosed ,  ischemic viable, non ischemic viable, ischemic non viable, non ischemic non viable , Apart from this patchy necrosis, patchy ischemic, areas are common. Finally , necrosed segments   may  also be perfused normally by  spontaneous reopening of an IRA.

One can imagine the complexity  of events in these segments  once we do the  PCI /CABG . The response  is highly variable and unpredictable. The major concept we  , the physicians  believe or ( to be precise made to believe !) is  the  sanctity  devoted to  the viable myocardium .For  many us ,  it is considered a  holy  exercise  to identify viable myocardium in patients following MI and then revascularise them if  found to have significant viable myocardium (Atleast 20% of infarcted area )

A full 2 decades were lost or (shall  we   say wasted on this futile exercise !) as   we have since  realised most of the cardiologists do not follow this rule .

Now , even a scarred myocardium is revascularised in the hope of recovery .As such , we have reached a stage where  there is no contradiction for not doing a PCI /CABG   with reference to LV dysfunction.

Now every  patient  with post MI  LV dysfunction  is considered to  have  some amount of viable myocardium that is  fit   enough  for revascularization

Are we justified in doing  this ?

Many clinical  trials  have revealed  , the  recovery of LV function  in these segments  has not been consistent at all .

The most surprising discovery is  a viable myocardium need not  be ischemic   .It might get adequate blood supply either  from invisible collaterals or trickle of antegrade flow .  Hence an adequately  perfused myocardial segment can  still be   non contractile . This shatters the myth  that  revascularisation must have a dramatic effect on the recovery of contractility in all viable segments.

The other major finding is  ,  even ischemic   viable   myocardium ( documented by metabolic activities PET etc)  need not regain it’s original contractility  after the ischemia is fully corrected .

*reference for  both the above statements are available from variety of sources including real life experiences .(Type C evidence )

Final message

  • Do a PCI/CABG promptly for patients with refractory angina.
  • Never  advocate PCI/CABG  for  a primary relief of dyspnea .  (Never is a harsh word,  let it be  “use it  with caution ” ! and  the  patient  should be  revealed  the whole facts  about  what we know and what we do not know regarding the complex  hemodyanmic events  in  revascularisation   )

Counter point

If  the above statements are really true ,   How does PCI/CABG   help  relieving  dyspnea  and functional class  what is your answer for thousands of patients  with CAD and ischemic DCM who have greatly benefited from CABG ?

The answer could  be  simple , The revascularization  piggybacks  over the   medical management (which , these patients pursue vigorously)     like  ACEI,  statins, salt restriction, betablockers  , optimal diuretics and tend to hijack the credits from the poor  drugs !

Read a related blog

Revascularisation for ischemic DCM

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Diastolic dysfunction is a common clinical cardiac problem which has no specific therapy.It can occur either in isolation or in combination with systolic dysfunction.The later may  be more common.

Isolated diastolic dysfunction

  • Hypertensive heart disease.
  • Aortic valvular stenosis
  • Restrictive cardiomyopathy
  • Early stages of CAD
  • Pericardial disorders
  • Idiopathic stiff ventricles

In association with systolic dysfunction

  • Dilated cardiomyopathy (20%)
  • In any form of cardiac failure some degree of diastolic dysfunction is noted .

General principles of management

Even though there is no specific drugs to tackle diastolic dysfunction the following measures may have significant impact.

  1. Correct the underlying problem.(HT/CAD etc)
  2. Reduce the basal  heart rate .At lower heart rates as diastole is prolonged , the stiff muscles has  extra time to relax and stretch itself  longer.
  3. Regular isotonic exercise  preconditions the muscle  for smooth contraction  relaxation .
  4. Optimise diuretics (Excessive diuretics has an  adverse effect on the  diastolic pressure profile across the AV valves)
  5. Avoiding positive inotropic agents like digoxin .This will not be possible in combined dysfunction.
  6. ACE inhibitors, ARBs, Aldosterone have some benefits as they could prevent tissue proliferation in the cardiac interstitium
  7. Milrinone (The non digoxin positive inotrpic)show some promise

What are the  treatments in the horizon ?

Antifibrotic drugs   ,Antiproliferative drugs

Collagen breakers ,

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  • Skeletal muscle relaxants – Available
  • Smooth muscle relaxants -Available
  • Cardiac muscle relaxants -Not available !

Cardiac failure is the number one killer of mankind.  So far we have believed the major function of the heart is to contract . Relaxation was thought to be a passive process  .Now we know,   for myocardium to relax properly the calcium which was  pumped in to acto myosin complex, has to be taken back into the  sarcoplasmic reticulum during diastole  .This is mediated by SERCA 2 , Phospholamban  the active  calcium uptaking kinase.Clinical diastolic dysfunction as a concept has been disputed for too long that has delayed our knowledge  gap .

Myocardial relaxation is much more complex than  we think !

We have given too much importance to calcium kinetics and diastolic dysfunction .While impaired relaxation and diastolic dysfunction are used interchangably by both researchers and clinicians  resting myocardial stiffness is an important parameter that has been overlooked .

The myocardium is made up of not only myocytes  , in fact it has more non myocytic components than myocytes themself. Myocytes constitute only 33 % of cardiac mass . The interstitial cells, fibroblasts  the extracellular matrix (This is in fact a vague terminology in use !) It is nothing but  sheets of tissues made up of collagen criss crossing the myocardial planes.  The type 1 collagen is as powerful as stainless steel . Type 3 collagen is little more flexible. The issue here is , how to flex these rigid collagens without compromising it’s contractile role. One can realise , how  ignorant   it would be be ,  if we thought altering calcium kinetics within the myocardium is the ultimate answer to tackle diastolic dysfunction .

So our aim is to reduce  the resting stiffness of  cardiac muscle in pathological states like SHT/LVH/CAD etc  . . .

How to do augment myocardial relaxation ?

Altering calcium kinetics within the cell is one option. But as we have discussed  much of the stiffness comes from cells which do not have calcium at all  (Fibroblasts) or from life less molecules like collagen etc

The proliferation of interstitial cells and fibroblasts  make the myocardium stiff.So drugs which inhibit these reactive events may help.ACE inhibitors, ACE receptor blockers, anti aldosterone (Spirinolactone) are vigorously tried by respective patent holders to bring in another indication for these drugs namely positive  lusiotropic agents .But the crux of the issue and the fact of the matter is we have not made any break through in finding a positive lusiotropic drug. (Milrinone was shownto have some promise !)

We need to try new concepts instead of  trying the existing band of drugs .

The following are some  of the options

Collagen  – The interstitial collagen may be modified.The so called MMP matrix metalloprotinase which lyse collagen cross linkages can make the myocardium agile and fit.Tissue inhibitors of MMP has a role.

One should remember we can not afford to play the dangerous game of manipulating  myocardial structural protein frames . If  the myocardium becomes too flabby it will forget it’s  primary job  that is contraction

Final message

There are thousands of  articles in cardiology literature that cry fowl over diastole and few  hundred of them   devoted to quantify diastolic dysfunction by various imaging technique .

It is unfortunate  there is no single drug or intervention that has a meaningful impact  on this entity. We look forward for cardiac scientists to divert the resources to find an answer to this problem instead of simply  documenting the presence of it .

Common sense has taught us the most effective  method that can reverse established diastolic dysfunction is  by simple , regular exercise .Exercise  not only make the skeletal muscles  agile & fit it does the same to cardiac muscle too !

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The long standing controversy about diastolic heart failure is settled !

The perception that diastolic heart failure ( Now renamed as heart failure with preserved EF ) is less dangerous than systolic HF has been exposed by this land mark study by Owan TE, in 2006 (nejm) But unfortunately this information is not yet fully disseminated among the physician community. Hence this post, with due acknowledgment to NEJM & Owan et all.

Experts from the article

“The nosology of heart failure has been the
subject of much current debate, and some extreme
positions have been taken. The observation
that 22 to 29 percent of patients with diastolic
heart failure die within one year of hospital
discharge, and 65 percent die within five years,
is a reminder that we are facing a lethal condition,
regardless of its name. Owan et al. also
show that, in recent years, there has been little
improvement in survival rate among patients with
diastolic heart failure, in contrast to the improvement
in survival rate over time among patients
with systolic heart failure”

Have a look at the survival curve below, almost similar , surprise surprise ! DHF survival is not only worse ( in many ), than systolic CHF and further they respond poorly to treatment, compared to conventional systolic CHF .

Click below for the link to full text article

Short abstract :

Trends in prevalence and outcome of heart failure with preserved ejection fraction.

Cardiorenal Research Laboratory, Mayo Clinic College of Medicine, Rochester, Minn 55905, USA.

BACKGROUND: The prevalence of heart failure with preserved ejection fraction may be changing as a result of changes in population demographics and in the prevalence and treatment of risk factors for heart failure. Changes in the prevalence of heart failure with preserved ejection fraction may contribute to changes in the natural history of heart failure. We performed a study to define secular trends in the prevalence of heart failure with preserved ejection fraction among patients at a single institution over a 15-year period. METHODS: We studied all consecutive patients hospitalized with decompensated heart failure at Mayo Clinic Hospitals in Olmsted County, Minnesota, from 1987 through 2001. We classified patients as having either preserved or reduced ejection fraction. The patients were also classified as community patients (Olmsted County residents) or referral patients. Secular trends in the type of heart failure, associated cardiovascular disease, and survival were defined. RESULTS: A total of 6076 patients with heart failure were discharged over the 15-year period; data on ejection fraction were available for 4596 of these patients (76 percent). Of these, 53 percent had a reduced ejection fraction and 47 percent had a preserved ejection fraction. The proportion of patients with the diagnosis of heart failure with preserved ejection fraction increased over time and was significantly higher among community patients than among referral patients (55 percent vs. 45 percent). The prevalence rates of hypertension, atrial fibrillation, and diabetes among patients with heart failure increased significantly over time. Survival was slightly better among patients with preserved ejection fraction (adjusted hazard ratio for death, 0.96; P=0.01). Survival improved over time for those with reduced ejection fraction but not for those with preserved ejection fraction. CONCLUSIONS: The prevalence of heart failure with preserved ejection fraction increased over a 15-year period, while the rate of death from this disorder remained unchanged. These trends underscore the importance of this growing public health problem. Copyright 2006 Massachusetts Medical Society.

Other interesting article

Heart failure with preserved ejection fraction: dangerous, elusive, and difficult.

Eur Heart J. 2008 Feb;29(3):339-47. Nielsen OW, Køber L, Torp-Pedersen C.

BMJ editorail 2009

http://www.bmj.com/cgi/content/full/338/jan27_1/b52?ijkey=c7a29d35dc9d9dddf7d0e75c5b8d05014315c564

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