Archive for the ‘cardiac failure’ Category

I am unable to answer this question confidently even after spending 25 years in the specialty of cardiology. I thought, the answer was yes. Reality is definitely different. Such is the complexity in the biology of the fluid and circulatory systems. The heart’s function doesn’t seem to end with just pumping 6 liters of blood every minute, ultimately, it has to handle a huge load of water as well with delicate coordination with the kidney. (ANP,& RASS feedback). It is fascinating to note, that the heart transforms into a powerful endocrine organ as and when it is necessary.

Read further, with a caution: (There is no specific physiological /molecular answer attempted)

About 28 of the 42 liters of fluid in the body are inside the 100 trillion cells and are collectively called the intracellular fluid. Thus, the intracellular fluid constitutes about 40 percent of the total body weight in an “average” person. Still, cells are somehow protected from the edema creating hemodynamic force until the very late stages. Fortunately, the Interstitium is the place all excess fluid stagnates. This is a great biological adoption. The simplest explanation is (Na /K+pump never sleeps  ) Bi-directional osmotic forces keep the cell dry even in adverse cellular milieu. Can’t imagine the implications, if every cell begins to swell in early heart failure. Still, it does happen to some degree I guess. We never quantified this.( Andrew Boyle,et al  Myocellular and Interstitial Edema and Circulating Volume Expansion as a Cause of Morbidity and Mortality in Heart Failure)


What happens to massive Intra cellular compartment size in HF? If renal perfusion is compromised (As one would expect in any significant heart failure) How does it affect this fluid distribution over that of heart failure? If the lymphatics’ final destination is the right heart how does this interfere with interstitial space clearance?

Practical implications

Though local factors operate, edema* in heart failure is a reflection of a more serious systemic plumbing issue. Even, subclinical fluid collection can interfere with cell function and contribute to unexplained fatigue which is an early sign of heart failure. No doubt, NYHA  gave much importance to this non-specific symptom in heart failure. Further, Individual organ functions may react in a different fashion with respect to water logging.Hepatic, portal splanchnic congestion directly affect GI function and intermediate energy metabolism.

.(*HF with zero edema so-called dry CHF  is a bigger mystery, is discussed elsewhere on this site)

When does the cardiac failure become a disorder of sodium & water metabolism 

Though the heart is a mechanistic pump when it fails it soon becomes a neuro-metabolic-endocrine problem. We are not clear whether heart failure retains sodium and water equally?  In renal failure-free water, accumulation is less than sodium. What happens in cardio-renal syndrome. These have practical implications as both hyponatremia and hypernatremia can be a feature with water content modulating it.(Now the term dysnatermia is more often used)

If RASS is activated net gain in sodium is expected. It doesn’t really happen. (Even with secondary hyperaldosteronism  sodium knows how to escape from the kidney). Vasopressin antagonist was considered a new innovation for hyponatremia associated with HF. To know the current role of V2 receptor antagonists Tolvapan, read here. 

Can we get rid of this excess water by any other means 

We do have powerful diuretics. It can unload the heart rapidly but can be harmful due to intracellular dehydration and electrolyte imbalance. When I asked an experienced Nephrology colleague  “Does excessive diuretics deplete ICF or ECF space? and how to quantify? , he was honest enough to accept, that it is primarily guesswork in a given patient and clinical assessment is supreme.

It is understood now, that there is a role for ultrafiltration of pure water in refractory hydrophilia. Bart B.A  (RAPID-CHF) trial. J Am Coll Cardiol. 2005; 462043-2046

Imaging subclinical edema in heart failure 

How to catch Heart failure early before clinical edema ? NT pro-BNP is a good option (>400pg/l) but physiologists armed with new generation imaging are working on how and where the fluid is accumulating in early heart failure. Nailfold video capillaroscopy (NVC) and confocal laser scanning microscopy (CLSM).  Wish, these modalities are really useful and do not end up as fancy tools and hike up the heart failure treatment costs. 


Future of Cardiac Hydraulics management.
1. Afterload reduction, 2. Preload optimization, and 3.Inotropics. We have been playing with these three famous principles in heart failure treatment for quite some time. We must admit, nothing really worked to our expectations. “Total body water management” is a new hope. It will revolve around a mechanical fluid management system as this overview from circulation tantalizingly discuss. DRI2P2S  (Circulation heart failure 2020)

Final message 

Edema in HF is primarily extracellular and interstitial until the end stage. Fortunately, the ionic and osmotic forces along with capillary hemodynamic forces keep the excess fluid within a safer interstitial compartment. However, we must realize each organ swells in a different manner depending upon cell membrane responsiveness to neural and humoral factors. The mechanism and content of edema fluids are different in heart vs kidney failure. It is also true, that every cardiac failure patient has a renal component and vice versa.

That’s it. I know it was a superficial attempt to understand water distribution in HF. Someone needs to break the complete truth about H2O metabolism in cardiac failure.

Postamble & a Non-academic trail

 Should we really bother to know where does fluid accumulate in HF ?  In a pragmatic sense the answer is “No” Let it accumulate anywhere, just push inj. Lasix, or if refractory add Metolazone and Torsemide, (I need to rush to the cath lab for the next angioplasty for that angina-free RCA stenosis, you know !)


This 37-page landmark review about fluid dynamics will help you find many queries raised here. (Tough read though)




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An Interaction in IMCU

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

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

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

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

“Good, You have done a nice job”

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

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

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

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

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

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

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

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

Loop diuretics 

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

The meteoric rise of SGLT-2 Inhibitors 

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

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

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

Final message 

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


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

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

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


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

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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.


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.

ESC 2020 Update

RATE-AF study reinforces value of Digoxin in AF rate control.




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


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.

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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 ?


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  


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This cartoon succinctly  depict all the options we have in our fight against end stage heart failure .We know , a failing heart is often compared to a sick , aged and tired horse.

cardiac failure cartoon tired horse whicpping lionel opie book

Image courtesy Heart Physiology: From Cell to Circulation :Lionel H. Opie Lippincott Williams & Wilkins, 2004


1.Don’t whip the horse (Except in emergency)

  • Avoid all Inotropics ( Doubutamine and Milrinone were shown to improve quality of life marginally but  with dramatic reduction in quantity of life ! However , the same thing does not apply for Digoxin as it is the  the only Inotropic with a soothing para-sympathetic comfort  !
  • Please be reminded, CRT wires could act as  “multiple whip equivalents” right inside the heart , especially in advanced class 3 or just recovered class 4 patients. Beware!

2.Unload the horse



3.Slow the horse

  • Never exert too much (Not more than 70% of capacity)
  • Beta blockers
  • Ivabradine (Slow the sinus node and expect a reduction in MVO2 )

4.Change the horse

  • Heart transplant may be the best solution

5.Switch to an Artificial Horse(Tractor )

  • ie  LV assist device

6.Finally try to heal the horse (Still largely in research labs!)

  • Genetic engineering
  • Tissue repairing
  • Stem cells
  • Holistic and spiritual healing etc (Has really  worked in few )

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I used to tell my students ,the relationship between the heart and kidney  is so close , it is never justified for  the  two departments of Nephrology and Cardiology  are  physically away by two blocks in our institute .

Kidneys are vital to maintain the volume and pressure of body fluids and heart is responsible for keeping this fluid circulating.

In clinical setting  it is a well known secret ,most deaths in patients who are on dialysis is cardiac while  most  deaths in patients  with CHF are renal.

It remains a mystery  why kidneys were   ever considered as a circulatory organ  , when  our medical pundits de-compartmentalised  human organ systems !

CKD is pre-cardiac failure and CHF is pre-renal failure

The Heart /Kidney affair is so intimate in many  pathological situations both either succeed or fail  simultaneous or sequentially.

While CKD  results in and pressure and volume overload of heart , cardiac failure cause pressure and volume under load (pre-renal  factor) which worsen the renal function and aggravate cardiac function alter.

In essence,  it is vicious cycle of two  serial organs  performing  the vital circulatory function with body fluids playing a  role of diligent mediator.Whenever the kidney  fails heart  is stretched and stressed  to its Frank starling limits by the volume  as well as the accompanying HT load.

While text books link these two organ as simple cardio-renal syndrome it is not happening at the level of patient’s bed side.

Cardiologists and  Nephrologists must realise they need do work in tandem like  their  respective  departmental  organs  which accomplish this task easily !

To tackle this much  maligned  cardio-renal conundrum

Consider CKD as CHF equivalent  and CHF as CKD’s

I would recommend this concept to be infused  right in the third year medical school and  try de- compartmentelise  clinical  medicine.

Need of the hour : How to Moderate ACEI dosing in CKD

ACEI has been a major pharmacological   revolution in controlling and reversing the adverse events of cardiac failure . Some where along ,  a significant fear complex arose regarding the damage it could cause to kidneys.

Recently , we know the role of  ACEI in CKD made U turn(Like what  Beta  blockers did to CHF) .Now, it is presumed ACEI are indeed  safe in most CKD and may  even regress  CKD. Still this concept  has not been fully disseminated  into general physician domain.

Let cardiologist and Nephrologist sit together and sort out this issue.

I guess ,  ACEI controversy is  a sort of  ongoing ego clash  between Nephrologist and Cardiologist . Both like it , both make fuss about it ! In my observation , if  a cardiologist titrate it upwards  Nephrologist would  lower it  and reverse happens if cardiologist express caution about it ! Do you agree ?

Final message

Mankind has  accrued  great benefits  from stunning break throughs in modern medical science . . . but it has come  only at a huge  cost ! Medical knowledge has completely fragmented the physician mind-set .Every good therapeutic concept is  hanging aloof .It requires periodic de-fragmentation (As we do it to our PCs by anti-viral soft ware !)

To begin with , let us  consider   CKD and CHF as single sequential circulatory  entity !

Let us vouch to  create new generation medical professional  devoid of skewed  medical vision !


Guidelines for ACEI in CKD

NKF national kidnye foundation


acc aha  accf guidelines chf 2013

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Obesity is a major cardio vascular risk factor.We earnestly  believe  this  by  evidence from Framingham and other studies.However , epidemiological  truths   can be dissociated from individuals .

We now understand  some  of the obese  patients fare better in CHF outcomes  apparently because of the obesity ! Even patients who undergo PCI show some benefits.This concept  is being proved in large data base of  > 200,00 patients.

Possible mechanisms

The lay man’s logic may apply (Science hidden somewhere !) Obese persons  have basically a  large heart with better cardiac reserve and  muscle mass .These hearts are  pre-conditioned to extra burden of MVO2  in it’s life time . So it  is able to tackle  hypoxia better, takes more time  to get fully exhausted .After all heart can consume fatty acids for it’s energy requirement.

Adipose tissue may also  secrete favorable anti-inflammatory  chemicals , though majority of adipocytokines are detrimental  except adiponectin .Paradoxically  the tumor necrosis factor TNF  (Same as cachectin or Interleukin 6)  is less  in obese patients .



obesity paradox

obesity paradox 3

obesity paradox 4

obesity paradox 3 jama archives of internal medicine


The landmark Lancet article that first raised the question of obesity paradox



Counter to the  concept

obesity pardox does it exist


Obesity   paradox applies in stroke too ! This study (TEMPIS) from Berlin  Germany  suggest controversially though


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What   are the factors other than EF %  that determine  functional capacity in cardiac failure ?

In our experience we have found the following factors  contribute immensely to the functional capacity of cardiac failure patients

  1. LV  filling  defects  (30 % of DCM have significant LV relaxation defects )*
  2. Integrity of  RV  function
  3. Mitral valve  competence(Even a mild MR can be important .It lowers the threshold for pulmonary congestion  )
  4. Severity of Pulmonary hypertension
  5. Lung Function *(Restrictive PFT common , gross cardiomegaly can reduce lung space )
  6. Basal exercise capacity .
  7. Skeletal muscle  function (Mitochondrial training )*
  8. High body weight
  9. Will power and self esteem *
  10. Spouse support and motivation

* May  have  major Impact on functional capacity

Final message

Physicians and even cardiologists are   obsessed  with EF %  to a large extent . My guess is , it   is not likely to end in the near future . The irony is ,  we have passed it  to our  colleagues  (Like anesthetists !)  and patients as well .(  for various reasons )

                        Please remember  , there are at-least 10 factors  that are  important  in the genesis of  symptoms of heart failure  . The list can extend  further  if we include  like associated renal  dysfunction , hemoglobin concentration  , etc .

Even though LV pump primarily determines  the ultimate outcome in cardiac failure ,  it is unwise  to  blame the EF %  for all the suffering  . If only  we realise this fact , one  can take  appropriate  measures .

**   Paradoxically modalities aimed to improve LVEF by positive inotropics has never been shown to improve the outcome .In-fact , there is more evidence for the contrary !

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Caution: This is a fairly lengthy article . Optimal Reading time  15  minutes

Cardiac failure is a progressive systemic disease  ,  even though the primary problem originates in the heart .Most of the symptoms and clinical features are related to Neuro-Endocrine activation instigated by poor pumping function.When the diminishing cardiac function exceeds the compensatory mechanisms , full blown cardiac failure sets in and get into a vicious downward spiral unless  intervened.

The conventional treatment model involves  on three targets.

  • Reduction in pre -load(Diuretics)
  • Improving  contractility (Inotropics)
  • Reduction in afterload  (Vaso- dilators)

Though the concept looked attractive  there are many missing links . Medical treatment   lags far  behind  the desired goals. Still , it  can stabilize most of the patients with cardiac failure till they reach very late stages.


Inadequately  treated  CHF is not  synonymous  with refractory failure  . But  ,  practically it is the commonest cause for refractionaries . Hence  , every patient must be scrutinised meticulously for adequacy of treatment.

Primary mitral  , aortic valve  lesions causing cardiac failure need  not be considered as refractory  cardiac failure . In the strict sense myocardial disease /damage  either  idiopathic or secondary to CAD  would form  bulk of refractory failure .

(For example a patient with critical aortic stenosis with severe LV dysfunction is   technically  refractory cardiac failure but functionally it could be a  simple  expression of  after load mis- match )

COPD -Cor pulmonale /Primary pulmonary  hypertension  / End  stage congenital  heart disease  and   Eisenmenger syndromes   form separate  group of  CHF and would not be discussed  here.

The valves , the fibrous skeleton, the  pericardium are integral parts  of the heart . Individual disease process can affect these compartments in a differential pattern .

When we  refer to  refractory heart failure   it amounts only two  large disease groups.Ischemic and idiopathic  cardiomyopathy.The whole myocardium is a single unit. If it is destined to fail  it will fail in toto.  There can be reversible factors that can be addressed.

The coronary artery   though not a part of heart has a major say in the outcome of cardiac failure as they determine the cardiac muscle  integrity.In every patient with refractory cardiac  failure , an attempt must be made to rule out  any  re-vascularisible  lesions.

The primary difference between ischemic and Idiopathic DCM   is ,  in ischemic DCM left ventricular  segments  are predominantly involved . RV function  is relatively   preserved until very late stages.

Patient factors

Age , gender, body weight , systemic illness that increase metabolic demands have an adverse impact . Diabetic patients fare poorly .

Fluid management  and  diuretics

In refractory cardiac failure the renal blood flow is reduced .Diuretics usage will further worsen this if ECF is depleted .

So it is obvious we have to use it very judiciously .

Why only  certain patients with cardiac  failure   develop significant edema while others do not ?

This lies in the response of neuro -humoral  activation of secondary RASS system.

Both inadequate  and excess diuretic can perpetuate the  status.

Intra vascular hypovolemia and effective renal blood flow reduced

Diuretic strategies

  • Increasing the dose
  • Adding another ( Switching over to another loop diuretic like Bumetanide, or Toresemide  can be tried )
  • Sequential nephron blockade ( Add  metalazone a powerful thiazide acting in proximal tubule  to be used with caution risk of hypokalemia)
  • Continuous IV infusion  is an option

Ultra filtration  can be  used  in severely volume over loaded  patients.

Refractory diastolic failure .  How common is that ?

The incidence of significant LV filling defect are more commonly observed.There is no specific  drugs  available to tackle this .It may be argued digoxin and other positive inotropes worsen diastolic dysfunction.This  may not be true in the bed side.Unless severe  LV restriction feature are present  digoxin can be continued.

The simple and effective way to improve LV filling in the presence of diastolic filling defect ,  is to slow down the heart rate. At low heart rates  diastolic filling period prolongs and dysfunction tend to vanish.Beta blockers usefulness  in   DCMs  is attributed to this phenomenon

Specific  therapeutic targets

RV dysfunction

RV dysfunction is responsible for systemic congestion .RV function improvement alone can improve the functional class in  many .Controlling and targeting pulmonary hypertension is beneficial . There can be a role for off  label use for chronic pulmonary hypertension associated with DCM.

Importance of  weight reduction :

We can comprehend  complex equations  in  cardiac failure  , still we often  forget a simple logic  . Body wieght is an  indirect but powerful determinant of aortic after load.  A 80kg body needs more heart power than a  body with a 40 kg  mass. If a  patient with EF of  25 %  loses 50 % of his body mass,   his heart can serve  his body  for   100 % longer duration.   (Of course ,  this happens  in certain patients  by a mechanism  called  cardiac  cachexia !  shall we call  it as  natural adaptation ?  )

 Inflammation   control

Tumor necrosis factors and Interleukins are responsible for systemic reaction . These levels are high in CHF. Anti -Inflammatory drugs and diet would help. Statin usage is shown to be beneficial.

Metabolic modulation

ATPs ,fatty acid are fuels for the  heart .Ailing hearts  require  it in plenty. Certain drugs like Trimetazidine, L carnitine has been shown to be useful .

Cardio-Renal syndrome

This is nothing but raising renal parameters  as heart failure worsen .This  essentially  involves fluid and electrolyte management.

Natural course of refractory cardiac failure

It is sort of a  delayed near death sentence . 5 year survival is comparable to many cancer inflicted patients.Basic medical care  remain the corner stone. CRT /ICD*  , LV  assist devices are slightly more effective with substantial  risks and cost involved. Indicated only for  rich  and  insurance infested  population who can tolerate both scientific and  financial excesses.

ICDs* do prevent sudden electrical deaths.

 There is a  fundamental flaw  of  electrical and mechanical device concepts  in refractory heart failure .It  forgets  ,  CHF is a  systemic disease .A  cardio centric approach rarely works to perfection .

Cardiac transplantation  is the ultimate . It works well beyond any doubt. In best centers  like  Stanford 85 %   for 5 year survival is expected. Heart transplantation is limited by donor  availability and  surgical infra structure.Total artificial heart is a distant dream , but will be definitely accomplished

Role of surgery

CABG ( Strictly Indicated only in absolutely deserving .The habit of  revascularising scarred, akinetic DCMs to be abandoned )

Ventricular reduction( Batisda -seems to work only in Brazil!)

Mitral valve  interventions

Some  exotic interventions in cardiac failure

Mitral splinting to  reduce secondary mitral regurgitation in DCM


Newer drugs  and experimental drugs

Nesiritide, (Synthetic Brain naturetic peptide )  Tolvapton ( Vasopressin antagonist) are used with varying  success .

20  point bed side prescription tips  for refractory failure.

  1. Correct the  underlying causes  and triggers.Try to correct any  critical coronary lesion if any by PCI /CABG ( Not a major game changer ! )
  2. Restrict activities (Better to remain in class 3)
  3. Admit  only if  persistent  class 4 .(Intermittent class 4 does not require admission )
  4. Do not try vigorously to move up to class 2  with inotropes  you may  end up in class 4 !
  5. Advice mild passive and active movements. (6 minutes walk > 300 -400meters)
  6. Educate the entire  family / Ask them to shun Internet  (Internet acquired half baked medical knowledge is more injurious to health )
  7. Restrict salt intake
  8. Continue  Digoxin till toxicity develop  or maximum  dose  is reached  (Milrinone /Amrinone make  no major difference )
  9. Optimse diuretics.  Add Metalazone to Frusemide.
  10. Maintain good hemoglobin level (Erythropoitin does not work !)
  11. Add beta blockers  in every one including many of the  class 4 (Not necessarily Carvidilol)
  12. ACEI remain a key drug . Titrate to maximum tolerated dose. (Additional ARBs not much useful)
  13. Aldosterone antagonist has  unique role (Anti-fibrotic ? )  Caution required in diabetic patients  in monitoring renal function .
  14. At-least One metabolic modulator like  Trimetazide  could be tried (ATP utilisation amplified)
  15. Fatty acid metabolism enhancer  L carnitine  may be useful (Recall 1st year medical school basics  . . . Heart thrives on fat energy more  !)
  16. Nephrologist consult  is recommended if electrolyte / ECF status fluctuations are more.
  17. Avoid dobutamine infusions unless patient  insist.
  18. Narcotics like morphine can be used liberally in terminal heart failure  (Both for hemo-dynamic  and  neural benefits )
  19. As far as possible do not send these  patients  to big tertiary hospital unless heart transplantation is planned.
  20. Don’t  be a party  in  exhausting the  personal finance resources of the patient by ordering exotic investigations . Let him not suffer from additional worry ! (By the way . . .  having a hefty health insurance limit  is not an excuse  . Depleting  it  for futile purposes   would make the national economy weaker ! )

Final message

 Three  principles of  management in  refractory  cardiac failure  

  1.   Systemic approach  is the key .
  2.   De-mystifying   cardio centric  interventions  is essential.
  3.   Psychological support is vital .

Functional capacity   has a  poor correlation with LV contractile function . The skeletal  muscle  integrity , blood flow , and its  metabolism has critical say in this. Optimal medications  , properly regulated  locomotion  , weight reduction   can have a major impact.

The secrets of living a good quality of life    in  cardiac failure   ,  lies  not in modern technology  but in the  rare commodities  called  common sense and compassion.

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The term cardiomyopathy generally denotes a  progressive disease  in clinical cardiology.There was a time   diagnosis  of dilated cardiomyopathy (DCM )  was synonymous with a  delayed death sentence !  Of course , the situation has vastly improved over the years  with the availability of  new medical , interventional and surgical management. Still ,  there is no denying the  fact  ,  DCM continues to  have a grave outcome  especially when it occurs without any identifiable cause .

While we have  variety of aggressive DCMs , we also  have  patients with relatively benign forms of   dilated and dysfunctional hearts  which recover totally .

This reversible forms of DCM is observed in  the following  situations.

Hypertensive dilated cardiomyopathy . The left ventricle  in  some of the  patients with severe SHT  respond to the stress (Increased  after load) by dilatation rather than hypertrophy. This is especially common after an episode of LVF.  If we do an acute echocardiogram the LV function is severely impaired and the LV may  also be dilated. With good control of BP and fluid management the ventricle promptly return  to it’s baseline dimension. The recovery is complete in many . (The mechansim of LV dysfunction acute severe Hypertension is referred to as Pre-load /After load mismatch) Link to concept of Pre load mismatch .

* Note in the past these entities were not called as  cardiomyopathy .

Peri partum cardiomyopathy.

This is a serious disorder of cardiac muscles that occur during pregnancy  few months before  or few months after delivery  . There is correlation between PIH and this entity. Prognosis varies between very bad to excellent. Very few cardiac entities  have a  natural history like this one disease of women.Most of the pregnant women regain their original cardiac status within  year or so. It should be recalled there is high chances of recurrence in next pregnancy.

Alcoholic cardiomyopathy.

The toxic response to alcohol or the additive cobalt can result in DCM .There is overlap  between holiday heart syndrome and alcoholic DCM , where atrial fibrillation is the major problem. Wet Beri beri is the advamced form of clinical DCM that respond to vitamin B therapy.

Tachycardic cardiomyopathy.

This is also a common entity that occur during persistent sinus tachycardia or AF , thyrotoxicosis.Beta blockers are  of great use here.  Recovery is usual if the primary cause is correctable.

Toxic and drug related  reversible LV dysfunction

Adriamycin cardiomyopathy

Tako -Subot  Cardiomyopathy canbe termed as classic form of reversible  stress cardiomyopathy

Miscellaneous conditions

Diabetes and chronic kidney disorders are known to have a reversible form of cardiomyopathy

Some rare toxins  , scorpion envenomation , selenium deficiency can result in reversible DCM

**Ischemic DCM are partially  correctable in many , still  we don’t include it as cause for reversible DCM

*** Many episodes of acute myocarditis can have transient or short term LV dialtation and  dysfunction.they are classified as myocarditis .But there is little  difference (Except acadmeic . . .)  between chronic myocarditis with LV dysfucntion  and cardiomyopathy.

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