Feeds:
Posts
Comments

It is likely, that the biggest Impact & influence in current medical research may not come from the IQ of our scientists, their concepts, or the sophistication of the laboratory. Then what? Can you guess? It is the man-made mathematic sub-specality called statistics. We are going to either ratify or reject any research work ( on which we toil) based on the quality of numbers we generate. Such is the critical value of this specialty. Just pause a moment, and think over. How much importance do we give to the credibility and “quality of the interpretation” of any study? We have conveniently left it to our esteemed mathematical colleagues and some other invisible forces for a proxy inference.

I don’t think we will ever find an answer for this. Whether facts are made by statistics or statistics are made by facts ?

In recent times, one technique called propensity matching and scoring is used to conduct medical research where multiple covariables and confounders play.

What does the word propensity mean?

Oxford defines this word /prəˈpɛnsət̮i(pl. propensities) (formala tendency toward a particular kind of behavior

What is propensity matching in medical research?

In simple terms, it is doing a study without a true control group. It is a statistical gimmick where in we create an Imaginary or virtual patient arm What a way to conduct a scientific study? Those days, if someone suggests a study without a true control arm, it will go straight to the dustbin. (Of course, the concept came into vogue because we can’t have controls for ethical reasons or the rarity of the condition ) We do have  many other conventional covariable analytical methods available A well-written reference  (Ellicott C. Matthay, SSM – Population Health, 2020,)

Who created this propensity score?

I thought It was a new concept.No, it was proposed by Rosenbaum et al in 1983. (Ref 1) The extreme popularity it enjoys today is unexplainable. I think it is the simplicity, joy of doing a study without a troublesome control population, and the subsequent herd behavior of medical researchers.

Read here the pros and cons

Final message

Only two questions need to be answered before crowning the “propensity score” to glory in the statistical world. 1. Who has the final authority to define, what amounts to a confounding effect?  2, What are the statistical chances of missing an important confounder in toto due to baseline ignorance? 

Most statistical methodologies are like Holywood movies, some strike gold for no reason in spite of a lot of flaws. A few examples are meta-analysis and non-inferiorly trials. Propensity matching with a synthetic control arm could be a useful methodology in very selected situations.  It is unfortunate it has become a fancy tool and doesn’t deserve the wholesome approval for doing away with the true control arm.

Statistics may be great science, but it seems to work fine, only in the absence of continuous, unpredictable biological interference with mathematics.

Lastly, can propensity score take into account of confounding effects of the non-academic mindset of many researchers in senior positions? What shall we do with many important therapeutic guidelines created apparently based on solid evidence created with poorly created virtual (propensity) matches?

Postamble

Experience-based medicine, wild logical guesses, empiricism, and trial of error methods,  all these are unavoidable in medical care and research. We have to move ahead with all the uncertainties in-situ and take our patients to a positive destination. 

Reference

1.Rosenbaum, Paul R.; Rubin, Donald B. (1983). “The Central Role of the Propensity Score in Observational Studies for Causal Effects”. Biometrika70 (1): 41–55. doi:10.1093/biomet/70.1.41.

2.Wang J. To use or not to use propensity score matching? Pharm Stat. 2021 Jan;20(1):15-24. doi: 10.1002/pst.2051. Epub 2020 Aug 10. PMID: 32776719.

Propensity score in cardiology research 

 

Who is the guiding the guidelines, which have become omnipresent & omnipotent ?

I don’t know really. Some good people I guess. But, the doubt creeps in when they try to coerce it on us.

A brief conversation between an elite consultant and his fellow. (Caution: Grade 2 harsh language) 

Hey Doc, why is this guy’s name not found in today’s angiogram list? Any Insurance issues?

No sir, he has every requirement. Thrombolysis was very successful, ST has regressed well and it is nearly isoelectric and only T is inverted. His LV function is normal. In fact, I am not able to pick up any WMA.

Aren’t you aware, that being fine is never a contraindication for a PCI ? Which book teach you like that?

No sir, It’s already beyond 48 hrs sir. What is the purpose of knowing IRA status now? If it is open, well and good.If it is partially closed, again little to gain, right? 

Don’t expose your Ignorance. … haven’t you heard of the pharmaco-invasive strategy & open artery hypothesis. Always learn to respect science.

But sir, then why does late PCI of IRA in otherwise stable patients come under class 3 recommendation, if I understand the guidelines correctly, it is a contraindication, am I, right sir? But, this patient got stabilized by us still, why he is compelled to undergo another procedure exposing and adding further risk?  

That shows your immaturity. Doing an angiogram is never forbidden. It is the inappropriate late revascularisation of IRA that is the issue.

 Agreed sir, how confident are we, that we will stop just with an angiogram after visualizing a tempting lesion in either IRA or non-IRA? (My brief experience as a fellow doesn’t tell a fair story) 

 Now, you are trespassing into prohibited non-academic zones of cardiology practice. Instead, talk about FFR, OCT, multivessel angioplasty, and ( deferred or instant ) complete revascularization. Think like a true scientist don’t get spoiled at a young age in your career with all this ethical stuff. 

Final message 

Never allow an ACS to stabilize by medical management, if he is otherwise eligible and affordable for a procedure. You are not authorized to do that. 

This write up was triggered after encountering a patient who instructed his cardiologist to remove an incidentaly found block in Right coronary artery. 

Oftentimes, It is a funny & futile world out there in modern medicine. Revealing the complete truths or accepting ignorance in critical decisions to their patients, make the Doctors feel that, their academic modesty and reputation are at stake. 

Still, many patients expect (and think) the doctors to be 100 % transparent and want to understand the nuances of disease better than the doctors themselves. The current fad of online & offline health education for patients is not an accident of technology. Though some benefits exist, I feel, It is an intentionally promoted, maliciously motivated patient empowering movement, trying to disarm the true professionals.

Dear colleagues, always realize, never allow the default ignorance to become patients’ knowledge and ask them to take decisions on behalf of you. (I know, this is diagonally opposite to current principles of the practice of medicine) Fortunately, this issue doesn’t arise in most public hospitals in our country.

This paper was written 30 years ago with great foresight.

 

So, act with tact. You can’t hide behind the patient’s preferences in deciding the treatment choice. It can be “as unethical as” any activity that goes against the interest of the patients under which we are taking our oath. I don’t, recall anywhere in the Hippocratic oath, that we pledge to listen to the patient’s choice of treatment. (Rather, we assure to work in their interest always)

Final message 

Let us sharpen our own skills first. We shall think about how to distill and consume the muddy knowledge emanating from the current mess of premature research spilling all over academia. Don’t try to educate too much to your patients. There is nothing called academic empathy because leaving it to our patients will ultimately end up equivalent to medical negligence.

Forget about the patient-guided treatment menu card. Think about this, if ordering a trendy new medical investigation purely on a patient’s demand is declared as medical negligence, How many doctors on this planet will be left non-negligent.(Stop. then what is a master health check-up? Who is the master ?) 

(Hope this write-up is taken from a proper perspective. No intent to create a chasm between patients and doctors relationship )

Reference 

Drane JF, Coulehan JL. The concept of futility. Patients do not have a right to demand medically useless treatment. Counterpoint. Health Prog. 1993 Dec;74(10):28-32.

Postamble & Counterpoint

It all sounds good on paper. The consequence of not listening to our patients, especially if they land up with complications, will look awkward, is it not?  So, I always go by patients’ desires.

Patients tend to believe in fancy investigations and machines and not me, what to do?

No, it is wrong. You can’t justify it. Regarding your concern and impact on our reputation, nothing can be done. The medical judiciary desperately needs some reforms, understand the reality to protect us  I always tell my patients they have to accept me as a whole. (Do you enter the Aeroplane’s cabin and check the pilot’s mental and physical acumen every time you board a flight. It is trust,.. complete trust, that drives our life right !)

It is true, that medical professionals must be always under a continuous quality* control regimen.  The consequences of consulting less shrewd medical personnel, their errors in judgment, the stress of work, patients need to accept* just like a side effect of a drug or a natural history of a disease.

*, Unlike the engineering field, defining & controlling quality in medical therapeutics is a mystery exercise with multiple agendas!

CPR with BLS and ACLS is time tested method of cardiopulmonary resuscitation. The automatic external defibrillator(AED) was a real breakthrough. Still, complete recovery eveN in “in-hospital cardiac arrest”  is at best 10-15 % . (Brindley PG, CMAJ. 2002. )Here is a technology in-progress story, now I understand FDA has approved this device for emergency resuscitation in cardiac arrest.

The principle is simple. In the early minutes following cardiac arrest, it is the survival of the myocardium and brain that matters. So, occluding Aorta transiently and continuing CPR infuses more life into the brain and heart, and the possibility of revival they say is significantly increased.

Mind you, this is not for the layperson or public but can become a game-changer for the ER crew and in ambulances or even in the cath lab. Emergency insertion of ECMO is never easy and a Neurescue balloon may come in handy in the meantime.

 

The attraction is the simplicity of the device, just inserted through the femoral artery. Don’t know how successful we would be, in centering the collapsed femoral artery though. The balloon actually doesn’t really impede the lower limb flow.It senses and relaxes as and when necessary. 

Final message

The concept behind neurescue looks like a bedside emergency partial IABP-like (IABO-Intra aortic balloon occluder rather) but appears promising. What I understood grossly is, that potential extremity Ischemia is acceptable if it’s going to save a life! Also realize, it is not a magic device that brings back life in every cardiac arrest. It gives us more time to act so that we can do other measures to bring back circulation. 

Reference

Medical science has evolved over 2000 years and moved far away, from the spiritual cure times at the temple of health at Kos islands to the Imaginations of Davicini. We are now in an era, where we can, not-only take stunning live photographs of individual organs but also go inside, assisted by  X RAYs, Ultrasound, CT  MRI, and Optical fiber. Now, a new kid is entering ie Holography. (We may expect haptics very soon).

 

How about a cardiologist operating with a virtual  3D beating heart hanging in front of him?

Yes, it is possible in a scientific fiction movie . No. it’s real. True view, an innovative medical Imaging company from Israel doesn’t think it is a fiction story. The immediate clinical use comes  in electrophysiology labs

Senti-AR command EP system is cleared for clinical use. 

 

Final message

Breaking new frontiers in medicine is becoming the norm, especially in digital imaging. No doubt, we have entered a  new medical world. However, we should be able to realize, that all the excitement is justified, if and only it makes a positive impact on humankind. Even as we are deeply immersed in medical technology, let us remind ourselves, how a tiny virus is teaching all of us, some hard lessons in basic principles and practice of medicine.

Reference

Jennifer N. Avari Silva, Michael K.Southworth, Walter M.Blume, et al. First-In-Human Use of a Mixed Reality Display During Cardiac Ablation Procedures. JACC: Clinical Electrophysiology. Volume 6, Issue 8, August 2020, Pages 1023-1025. https://doi.org/10.1016/j.jacep.2020.04.036.

Bifurcation PCI is a modern-day Cardiologist’s fascinating professional adventure within coronary arteries. Of course, one of their Intentions is to do good for the patient. Bifurcation lesions (BFL) are a special subset of lesions, that looks challenging, more because of the potential biological aftermath following the delicate construction of a grade separator at a critical site. Mind you, it’s done within a live flowing artery and subsequently needs lifelong maintenance.

Strategies for BFL

  1. Strictly committed* single stent strategy (Irrespective of what may come, LCX or LAD  pinching let me take care . Don’t worry strategy *May sound dangerous, but still, it doesn’t make other strategies less ominous) 
  2. Provisional single stent strategy with elective cross-over for truly poor result /cosmetic/peer satisfaction  purpose
  3. Provisional single stent with bail-out cross-over. Often happen as an emergency  (Not all techniques are amenable for this)
  4. Elective planned two stents (Still, flexible  to revert to single stent if the situation allows)
  5. Elective, strictly committed, prefixed  two-stent strategy  (No going back strategy/ Not really a professional PCI )
  6. Always remember, SYNTAX or no SYNTAX CABG is the safe & best bet for many severely symptomatic patients, with complex as well as non-complex BFL lesions esp in diabetic patients.

Wait, there are two more.

7. Please note, there is one benign strategy, that is always available, but hiding deep in the interventional cardiologist’s sub(non)conscious minds. It is a zero radiation, zero contrast, and almost zero cost strategy. Yes, It is “No stent strategy’ also called exclusive medical management, currently referred to as OMT/GDMT. In our analysis of symptom- lesions significance at least 30% of BFL are eligible for exclusive medical management.(FFR & IFRs ? Less we say about it, is better!) 

8. One more option for those patients (&cardiologists) who wants to travel the middle path is POBA or a Glorified POBA ie DEB  (Ref  Corballis NH,. PLoS One. 2021)

Whatever the treatment, bifurcation PCI  cannot be taken lightly. One exclusive club is debating this topic in Europe every year (EBC) for the past 10 years. Currently, Double kiss and crush (DK crush) is considered superior to others. Mini crush and Culotte are good alternatives in specific circumstances (Definition 2, NORDIC, BBC 2)

Something about DK crush (Shao-Liang Chen Nanjing, China first modified mini crush to DK crush)

Best video resource for DK crush 

 

In DK crush every step appears to be double. Apart from the double stent, it is a double wire cross, double crush, double kiss, and double POT (or even more). All must happen in a specific sequence. One may add double Imaging (Pre and Post PCI IVUS or OCT) to the list.  Finally and funnily not to miss the realistic possibility of double complications over the provisional strategy.

I am not sure which of the 10 steps in DK crush is most important. When we go through the physics of  BFL intervention it appears, that proper crushing and kissing may be the key to success. Though kissing is an integral part of any two stent strategies, in DK crush it happens in a unique interface between balloons /balloons with a stent and finally between two stents. In fact 

The physics of bifurcation kissing includes balloon hugging diameter, area, and pressure. Added to that is the intervening metal layer.

Can’t take the kissing in a casual manner. The Morino & Mitsuda model tells us more about the physics of kissing. In BFL interventions, kissing can happen with various layers that include one layer of the balloon with a crushed and non-crushed stent, carina. While we are mastering the techniques, we must realize, Kissing is aimed at stabilizing the carinal basement, still, there is a distinct possibility, that what may appear as innocuous kissing may undo all the good work we have done in previous steps. I guess, no harm in missing the final kissing if everything is ok in OCT.

Dr. Anonio Colombo’s take on kissing 

 

Final message

So, we have both simple and complex modalities for BFL. Evidence and experience reveal that 90 -95 % of patients with BFL would be eligible for the easy path. In one sense, we are indeed wasting our energy and resources in tackling this negligible CAD burden located at the summit of the global CAD pyramid with a gigantic base. However, we can feel scientifically happy, that we have gained considerable expertise in tackling complex lesions with multiple stent strategies in recent times. Still, we are far away from a true vision, of what really might follow such a niche & expertise-intensive procedure.

Let us hope, that modern metallurgy in combination with physics & hydrology would ultimately beat Biology.

Reference 

1.Dr Colomo article (For personal use only)

2..Morino Y, Yamamoto H, Mitsudo K, . Functional formula to determine adequate balloon diameter of simultaneous kissing balloon technique for treatment of bifurcated coronary lesions: clinical validation by volumetric intravascular ultrasound analysis. Circ J. 2008 Jun;72(6):886-92. doi: 10.1253/circj.72.886. PMID: 18503211.

Postamble

Does evidence create expertise?

Looking at the whole issue of complex PCI philosophically, no technique may really be superior based on accrued evidence. In fact, when expertise becomes the key determinant, the evidence goes to the background. It is really surprising we are too much dependent on hasty and often biased evidence to ratify our expertise, technique, or hardware. I know, one of my colleagues can cross any lesion with one or 2 wires.

To insist, that a particular technique must be followed may not be academically correct always. It is similar to telling a coach driver in advance when to apply a brake or accelerator when he is negotiating multiple hairpin bends in hilly terrain on a rainy day, based on clinical trials done with different drivers on different routes. Ultimately, the outcome is decided by the expertise of the driver, the condition of the vehicle, the road, and not least, the destiny of the passenger.

Murmurs are audible noises from within the Heart or vascular tree when blood flow loses its laminar flow and becomes turbulent. There are many factors responsible for it (Recall Reynold’s number ).It is obvious, that when there is hyperdynamic circulation, even in physiology one may hear a murmur. Pregnancy is a classical example and Innocent (still murmur) in children is another one.

Duroziez murmur: A brief history 

In this post let us dwell on something about a classical murmur that occurs in the peripheral circulation away from the action-packed organ heart. It was originally described by French physician  Dr Duroziez  two centuries ago. (In his own words it was called a double crural murmur ). This happened shortly after Lennec’s new era of auscultation began. When everyone was concentrating on the heart Dr. Duroziez was curiously auscultating the legs and found this crural murmur. For this out-of-the-box thinking, he is still being remembered.

In significant aortic regurgitation, we know a substantial amount of blood regurgitates back into LV. This backflow though happens in the chest and into the LV,  it is reflected all over the vascular tree. It so happens, the entire aortic forward flow for a moment slows in end-systole or even reverses at the end-systole and early diastole when the Aortic valve leaks. Almost all peripheral signs of AR are due to this. It is critical to remember, that these signs are heavily modified by arterial distensibility, associates obstruction, LV  contractility, and peripheral vascular resistance.

Is there real reflux of blood back towards the heart* ? 

Duroziez’s murmur remained controversial both for its mechanism and intriguing questions about, whether the blood really travels back in early diastole in the limbs or is just an acoustic illusion from a  pressure wave. The debate was so intense it demanded a curious animal study. The femoral artery of Dogs with induced AR was injected with contrast and retrograde blood reflux was documented up to the iliac artery and Aorta.(NEJM 1965 Ref 1) 

* While retrograde reflux of blood in the femoral artery is real, which manifests as EDM, we must understand antegrade diastolic flow murmurs or even continuous murmurs are common in hyperdynamic circulation over narrowed peripheral arteries and veins (venous hum)

**For Advanced readers: Some of the issues are not clear. Whether Duroziez murmur is truly decrescendo (Like its EDM counterpart in the Aortic area) or Is it mixed with antegrade diastolic flow murmur over the femoral artery due to hyperdynamic circulation.

Echocardiographic correlates of Duroziex murmur 

Now, we are able to document bizarre hemodynamics that happens the entire length of the vascular tree that is responsible for this murmur.(A related post 😦 In AR the run-off is central or periphery ?_)

Image courtesy: medmastery https://www.youtube.com/watch?v=eVhEXCO13ys 

 

 

Phoncardiography with ECG correlation, help us to  time the murmur exactly and also demonstrates reversal of flow in femoral artery  by color flow doppler.

Importance of Duroziez’s murmur & A research proposal 

Though it’s of historical interest, it is still discussed in exams. It may be amusing for the busy clinical cardiologist to auscultate over the legs, when they may be contemplating a  TAVI for leaky Aortic valve  (Arias EA,  Interv Cardiol. 2019). But, for students, it is a different story. If anyone wants to beat the acumen and curiosity of Duroziez, they may assess the length of this murmur and correlate it with descending aortic flow reversal, aortic ERO, and regurgitant fraction. The fate of Duroziez’s murmur after Aortic valve replacement may also be studied.

Final message 

Duroziex murmur is not just a vintage cardiac auscultatory sign meant for exam halls. Looking deep into it, we may get more insights into the behavior of the peripheral circulatory system in normal physiology as well as in patients with AR.  

Reference

1.Duroziez PL. Du double souffle intermittent crural, comme signe de l’insuffisance aortique. Arch Gen Méd 1861; 17: 417–443,588–605.

2. N Engl J Med 1965; 272:1207-1210

3.Jama.1933.Blumgart and Ernstene

 

Some physics: Why is blood under pressure? 

In perfect vascular climatic conditions, the human circulatory system is comparable to a smooth flowing river irrigating 100 trillion cells, traversing many kilometers of the capillary network, to the far away tissue bed. One major difference in the river analogy is, that in human biology, the entire blood has to return back to the heart in about 30 seconds. (The fact that the venous system does this in style with near-zero pressure head is the greatest wonder in circulatory physiology)

The force per unit area, that drives the blood is the blood pressure. It is expressed in kilo pascals. (16/10 Kpa one Kpa is 7.5 mmHg. It has two components streaming pressure as well the lateral pressure. What we measure by conventional BP apparatus is the lateral pressure on the vessel, which is what we are worried about most times. But, the forward driving head is equally important because the branch points bear the brunt of this pressure head. Sudden surges and spikes attack the grade separators more. This is one of the reasons, the arterial branch points are more prone to atherosclerosis. Though we believe onward pressure head does all the damage, it is also worth knowing the velocity of blood flow can also be defining factor in vascular Injury. The flow velocity is surprisingly low in physiological conditions, about 4-6km/h something similar to our walking speed. 

What is normal blood pressure?

We don’t know. The search is going on. But, what is important is the net lifetime BP harming effect on blood vessels. Of course, BP is not a mono player, it interacts with other risk factors like lipids, diabetes, and smoking, along with genetic susceptibility, and epigenetic vulnerability, making cardiovascular events perfectly polygenic.  

How do we define and grade systemic HT?

A dozen different societies keep defining this (ACC/AHA. ESC, ISH, British, whatever be the normal,  one set of numbers is permanently etched in our mind ie 120/80 as the cut-off. 

A more philosophical definition would be, that high BP is defined as the BP at which our blood vessels feel the stress and strain and begin to wear out. We may never ever know that in a given patient. Now, we are adding more twists to this already confusing normality data. Namely nocturnal BP.

Why 24 hr /Nocturnal BP important?

If the average human lived for 75 years, he or she will be spending  25 years in sleep. What does our circulatory system do in those 25 years? We don’t know. We believe if the brain sleeps the vascular tree takes rest as well. How can it be?  The reticular activating system should go off mode, still the vasomotor centers should be vigilant enough to keep vital organ perfusion. Ironically, sleep can be stressful for some. During recumbent posture the fluid compartment redistributes and ECF expands especially in patients with renal and cardiac compromise. (Recall the mechanism of PND) .Add on to this, the ever-fluctuating sympathetic tone with REM/NREM sleep phases. One of the offshoots of widespread use of ambulatory BP monitoring is (ABPM)is the new term nocturnal hypertension. 

Defintion of nocturnal HT

The definition of nocturnal hypertension is, night-time BP ≥120/70 mm Hg (Now it is more stringently defined as >110/65 mm Hg by the 2017ACC/AHA guidelines. I am not sure, but I think this is applicable to anyone with or without HT irrespective of treatment.

Two more entities exist to confuse us. Just don’t bother. (Fellows can’t escape from this though). A Clinic and morning home BP of <130/80 mm Hg is defined either as masked nocturnal hypertension or masked uncontrolled nocturnal hypertension if they are already on drugs.

Night time BP patterns

Normally we expect 10 -20% dip in BP is expected.

The following are four nocturnal BP patterns defined:

  1. Dipper: 10-20 %;
  2. Extreme dipper, more than 20%;  
  3. Non-dipper: less than 10%, 
  4. Riser: 0%.or + side  (I think, this is the same as the reverse dipper )

 

An Important resource from HOPE Asia net work on ABPM Kazuomi Kario Journal of clinical hypertension.https://doi.org/10.1111/jch.13652 While everything looks ok, that blue line amuses us the most. These guys are also called reverse dippers.

Nocturnal dipping: Is it systolic, diastolic, both or mean?

Most studies documented as systolic dippers. Dipping is expected to Impact both systolic and diastolic BP similarly. But, we know it need not be. systolic BP is more volume-dependent, while diastolic BP is resistance is related. I think the concept of diastolic vs systolic non-dipper is yet to be evaluated.

How to measure? How many readings? 

  • Ambulatory BP monitoring equipment is the key. Few companies have defined and have patented software (Omran HEM series is the leader, Micro life is another one )
  • The night-time BP is calculated as the average of night-time BPs (from going to bed to arising) measured by ABPM The number of night-times BP measurements required may be ≥6.
  • The methodology is getting standardized. Errors in measurement are considerable. Posture, temperature, and inflation triggered awakening all matters. 
  • Substantial technology is still evolving. Remote wireless monitoring is possible (Apple and Google are keenly watching the global BP market potential !)

Management issues

Though there are 4 subsets in nocturnal BP patterns,  currently, Identifying non-dippers is the key target that will help diagnose more resistant HT. 

How to convert non-dippers into dippers?

  • Night-time dose of antihypertensive drugs to be encouraged.
  • Salt restriction in the evening diet 

How to prevent excessive dipper (>20%)

The reverse of the above advice is true in this subset. 

Isolated nocturnal  hypertension

I think it is an overzealous concept in sleep medicine. Let us wait and observe. Stojanovic, M., Deljanin-Ilic, M., Ilic, S. et al. Isolated nocturnal hypertension: an unsolved problem—when to start treatment and how low should we go?. J Hum Hypertens 34, 739–740 (2020).

Is there a J curve phenomenon  among dippers ?

We cant generalize,  pro-dipping forces are good & non-dipping forces are bad. Should we consider labeling excessive dippers as nocturnal hypotension? Considering the fact both non-dippers and excessive dippers carry more CVD risk. Like any other biological variables with dynamic safety margins, we are clueless about what is ideal dipping .(A nocturnal J curve)

Clinical trials on nocturnal hypertension 

  • JHOP study Kario K, Hoshide S, J Clin Hypertens 2015 from Japan is a very popular one on this topic.
  • While this elegantly done Finish study  (J.Hypertension 2004 ) stressed the importance of home BP monitoring. 

What is new in nocturnal HT management?

Melatonin, administered as circadian hormone therapy is expected to play a useful role as a night watchman in BP control (Frank et al Hypertension 2004)

Final message

Nocturnal hypertension is trying to emerge as a new cardiovascular risk factor. Understanding this condition and intervening seems to be important, considering the well-known fact, that cardiovascular events are clustered in the early morning hours.

Still, routine ABPM to know the status of nighttime BP in all hypertensive individuals is not warranted. However, people who had an event or who have secondary hypertension may need to do so. The simple truth is if you have a peaceful day and a perfect sleep, your BP is bound to dip naturally. So, the message to all those active and energetic men and women who are carrying a tag of hypertension need not worry about this dipping and non-dipping stuff. Instead, maintain a healthy lifestyle. There is a thin line separating awareness and anxiety.

Reference 

1.Yano, Y., Kario, K. Nocturnal blood pressure and cardiovascular disease: a review of recent advances. Hypertens Res 35, 695–701 (2012). https://doi.org/10.1038/hr.2012.26

2,Cuspidi, C, Sala, C, Tadic, M, et al. Clinical and prognostic significance of a reverse dipping pattern on ambulatory monitoring: An updated review. J Clin Hypertens. 2017; 19: 713– 721. https://doi.org/10.1111/jch.13023

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 !)

Reference

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