Is the link between atrial fibrillation and obesity epicardial fat?

The epicardial fat pad image on chest x-rays was long regarded as nothing more than a barely  interesting incidental finding of no clinical importance. That no longer appears to be the case.

The epidemiologic data having   established a  sound correlation between obesity and risk of atrial fibrillation , the electrophysiologic (EP) cardiologists  began to speculate on possible mechanistic explanations. These so far have included activation of pro-fibrotic pathways,atrial fibrosis, abnormal connexin, ( gap junction proteins necessary for heart cell action potential propagation) diastolic dysfunction , paracrine effect due to proximity of epicardial fat to myocytes,  and more recently  detailed scrutiny of  the role or roles  of epicardial fat to which has been assigned the ironic designation, of  EAT (epicardial adipose tissue) in deleterious remodeling of the left atrium.

At least as early as 2003 cardiac fat  acting like an endocrine organ was identified as a source of inflammatory cytokines ( Il-6,TNF-alpha, etc) that could  possibly promote coronary artery disease. Mazurek et al (2) found higher levels of inflammatory cytokines in patients with significant CAD.

Now EAT is accused of playing a role in the genesis of AF.

Dr, Mahajan and co-workers from Australia  studied 27 obese patients and 27 non obese patients who underwent AF ablation for AF. The obese groups demonstrated evidence of electroanatomical remodeling (global reduction in conduction velocity and increased electrogram fractionation) .The obese group had increased EAT and low atrial voltage in the posterior aspect of the left  atrium adjacent to EAT.

Author quotes:

" obesity related conduction abnormalities were most prominent in the posterior left atrium which was in close contact with the epicardial fat. "

"Obesity results in expansion of EAT and marked electroanatomical remodeling of the left atrium,creating a substrate for AF"



1)Mahajan, R etl al Electroanatomical Remodeling of the atria in Obesity. Impact of adjacent epicardial Fat.JACC, clinical electrophysiology vol 4, no 12, 2018 ,p 1531.

2)Mazurk, T et al Human Epicardial adipose tissue is a source of inflammatory mediators.
Circulation 2003, 108 r122-128

Did a third randomized trial for PSA screening reconcile the conflict betwen the first two?

Did the third RCT settle the issue of the efficacy of PSA screening for prostate disease?  The short answer is no - that settling purportedly was   achieved by another statistical analysis. ( see reference # 2 for that) at least for a while .

There are now three large RCTs (1) that have addressed the subject.

1) the PLCO
2) The ERSPC
3) the Cluster Randomized Trial of PSA testing for Prostate Cancer.

Only the ERSPC demonstrated reduction in cancer in an "invitation to screening"  with PSA setting.

So did the two out three being negative settle the issue? Not even close.

In 2012, faced with two conflicting RCTs the USPSTF decided to recommend against screening with PSA.Then a third RCT was completed showing no difference in mortality in the PSA screened group.

So if the score was 2 to 1 showing no benefit for PSA screening why did the USPSTF recant and return to their recommendation of "shared decision making" in 2018?

 The answer seems to be that Tsodikov from the University of Michigan ( and 21 other authors from various institutions)   did some adroit statistical footwork (2) in an effort to reconcile the disparate findings. Their work appears successful with the conclusion
being that when the proper type analysis is done (taking into account mean lead time) both the PLCO and the ERSPC both demonstrated approximately the same decrease in mortality with PSA screening.
Note the original analysis did not show a benefit to screening .

So now the score is two RCTs in favor of screening with one against and the current USPSTF recommendation is for shared decision making.


1)A blueprint for cancer screening and early detection :Advanced screening's contribution to cancer control. Wender RC et al . Ca,A Cancer Journal for Clinicians, Vol 49, no 1 Jan/Feb 2019 ( This is an excellent review of screening for cancer detection in average risk, asymptomatic adults including breast,cervix,colorectal,endometrial,lung and prostate.}


2)Tsodikov, A Reconciling the effects of screening on prostate cancer mortrality in the ERSPC and PLCO trials, An Intern Med. 2018, 168 608


"Life is short,art long,opportunity fleeting, experience treacherous,judgment difficult."Hippocrates.

Left bundle branch block -a really big deal part 2

Left bundle branch block (LBBB) is associated with a contraction pattern(s), that are dyssynchronous in regard to the pattern of left venricular (LV) relaxation and contraction.

The first "big deal " I commented on was the observation that the ventricular dyssynchrony associated with LBBB per se can lead to heart failure. See here.

The next big deal is that the pattern of ventricular dyssynchrony typical of "true" LBBB is determinative of a favorable clinical response to CRT and the presence of a LBBB EKG pattern does not necessary indicate a underlying LBBB dyssynchronous pattern.


Risum et al (1) list 3 criteria for the typical contraction pattern of a "true"LBBB
(these apply to description of a longitudinal stain curve in a 4 chamber 2-D strain echocardiogram)

1)early shortening of one or more segment in the ventricular septal wall and early stretching in one or more segments in the lateral wall
2)early septal peak shortening
3)lateral wall peak shortening after aortic valve closure

The early shortening of the septum is recognizable on standard echocardiography and referred to as "septal flash". "Apical rocking" is another echo finding in which there is a rocking motion  of the LV apical  myocardium perpendicular to the long axis. These two findings seem to be the findings on routine echo exams that correspond at least to some degree  (possibly large degree) to the Risum's criteria from strain echocardiography and  perhaps share to some degree the predictive power as regards outcomes of cardiac resynchronization therapy (CRT).

Those patients with a ekg pattern of LBBB and these findings on strain echo are much more likely to have a favorable clinical response to CRT.

Not all patients with a typical LBBB EkG pattern have what Risum refers to as the typical LBBB contraction pattern which is predictive of likelihood of favorable response. to CRT.This seems to hold true in regard to both the standard criteria for LBBB and the newer Strauss criteria .


Quoting Risum : "It seems reasonable to believe that the main mechanism underlying the differential effect from CRT according to QRS morphology is whether a significant activation delay is present in the LV". ( my underlining)

Question: Does the presence of septal flash and apical rocking predict likelihood of success with CRT as good or better than Risum's criteria? Have the two set of criteria been directly compared? While I could find no direct comparison ,Stankovic et al (2) published data that indicated apical rock and septal flash could predict reverse remodeling with a sensitivity of 84 % and 79% and the absence of both was associated with unfavorable long term survival.

Bottom line from Risum's work is that a patient may have EKG criteria for LBBB  (either the standard criteria or the new criteria proposed by Strauss) and not have the mechanical dyssynchrony pattern described by Risum  and not respond well to RCT.

So is the evidence strong enough to recommend pre-implantation 2d strain echo and not proceed with Bi-V pacing if the Risum criteria are not met? Is the absence of apical rock and septal flash reason to not proceed with Bi-v (or His Bundle) implantation?



1) Risum , N Identification of typical left bundle branch block contraction by strain echocardiography is additive electrocariography in prediction of long-term outcome after cardiac resynchronization
J Amer Coll of cardiology, 2015, vol 66, no. 631-641

2)Stankovic, I Relationship of visually assessed apical rocking and septal flah and long term survival following cardiac resynchronization therapy (PREDICT-CRT) Eur Heart J Cardiovasc Imaging. 2016,Mar 17 (3)262-9

addendum 1/30/19 reference to the Stankovic paper added

Once I thought I knew how to advise people how to eat to reduce heart disease risk , Now....

Read this recent brief overview of diet and fats and carbs and and cholesterol levels  and heart disease risk and see if you would presume to advise patients on how to eat. I am glad that I am out of that business.

I have written several times on medical hubris . In light of what we think we "know" now and what I advised ten years ago,I think "who is without sin....." I believed I had the answer while having answers was little more than parroting the recommendations of boards and organizations.

You have to remember the lawyer's classic query "Doctor, where you wrong then or are you wrong now/"

Neither the pre-operative beta blocker debacle nor the post menopausal use of estrogen and progesterone missteps seem to be a teaching moment for the population medicine devotees. The pop med folks , as explicated here would presume to take funds away from the treatment of some to fund preventive program to others which would "after a few generations" bring about a utilitarian gain by some metric even as some might suffer now.

At the time of this writing serious doubt has been cast on the previously widely disseminated advice about how to eat to avoid heart disease and who should take aspirin for primary prevention of coronary artery disease and who , if anyone, shovel be screened to detect low vitamin D levels, just to name a few of the ever changing array of medical recommendation to prevent disease and death. 

The internist who once upon a time was thought to be the physician trained to diagnose and treat complex complicated medical conditions has to extent  that she is now a ambulist ( at least those who are not now hospitalists) sends her time in part giving advice about how to prevent disease. How to eat,how often to get a cervical cancer screening test or a colonoscopy , who should take statins of aspirin or vitamins  and how much to exercise. For this you did not need to study four years in medical school and then three of more years of internal medicine training.You just need to subscribe to a service ( an app on your IPAD) to keep you up to date on the latest, and every changing, recommendation of various panels.

"Some people do not deserve health care reform?what would Maimonides have said?

The notion of someone "not deserving medical care reform" has appeared at least twice in writings by physicians. KevinMD taked about it here as he called attention to a commentary by Dr Edwin Leap. Dr.Leap is a long time medical blogger and ER physician and submitted this essay to an online version of a newspaper.

My first cursory reading of the essay and KevinMD's comments I erroneously read it to say " "Do some people not deserve medical care"


Sometime ago I wrote about a wonderful essay by Dr. Lawrence J. Hergoff published in JAMA which seems to address this line of thought.


Near the end of his current manuscript he quotes part of the Oath of Maimonides:

"May I never see in the patients anything but a fellow creature in pain."
I added:

Not as someone who deserves his dyspnea because of cigarette use defying years of advice to quit, not as someone whose ascites is his just due from profligate use of alcohol, not as someone who should not be in this country at all, not as someone who would not be having the myocardial infarction at all if he had done what his doctors told him to do and not as someone who is taking "scarce medical resources" from someone who deserves them more or for whom the treatment could be more cost effective but as a fellow human whose is in need of what physicians spent so many years of their lives preparing themselves to be able to offer.

The oath ( Maimonides) should remind us that being face to face with a fellow human in need

..makes judgment beyond the biomedical not only unnecessary but inappropriate.

Comments on the "Extreme Exercise Hypothesis"

Dr. THM Eijsvogels  from the Netherlands has written extensively about the relationship between endurance exercise levels and various cardiovascular outcomes and findings.

His  recent (1) review with an annotated references list  is available in full text on line.

Maybe the first question should be "what do you  mean "extreme'?

U.S. National and WHO guidelines  recommend 250 minutes of moderate exercise per week or 125 minutes of vigorous ( greater than 7 METS) per week based on in part a well established  reduction in cardiovascular mortality and morbidity as well as numerous other health benefits. However ,US guidelines also state that exercise above that levels is associated with added benefits. But how far "above" should one go. Can you go too far?

Is there a U-shaped curve when you plot health risk of the Y axis and exercise training volume on the x axis? If so, can the inflection point be defined?

Arem (2015) combined data from six prospective population based cohorts ( 661,137 individuals).Maximal all-cause mortality risk reduction was noted at exercise level of 3-5 times current recommendations and even  those exercising at 10 times current recommendation had a lower mortality risk  ( HR 0.69, 95% CI 0.59-0.78). But at the highest level the degree of risk reduction was  less than that achieved by lower exercise levels,

Ten times would be 25 hours ( one full day) of moderate exercise per week,I suggest very few exercise at that level while many preparing for a marathon would likely exercise  as much as 7 or 8 hours a week (3-5 the recommend levels). Olympic rowers might exercise as much as 17-18 hours a week .The relatively few exercisers at the highest volume make the confidence intervals for HR estimation at that exercise level so large as to not be reliable or useful.

Eijsvogels summarizes the quest for "what do mean by extreme" with this understatement:

" Based on limited current evidence and numerous potential confounders, it is difficult to delineate an upper limit for the for the benefits of physical activity at this time."

So there is no epidemiologic support for a U shaped relationship between exercise volume and health risk at least as measuring all-cause mortality. But what about certain medical conditions that have been reported to be increased in long time endurance athletes at levels said to be higher than those who exercise less.

The usual suspects include 1) atrial fibrillation 2)cardiac fibrosis 3)coronary artery calcifications.

I have commented on atrial fibrillation before ( see here) and will likely have more to say later and have blogged about the coronary  calcification paradox before( see here).

Cardiac or myocardial fibrosis (MF) is detected by cardiac MRI imaging with injection of gadolinium  and  is referred to as late gadolinium enhancement (LGE).There is a recognized pattern of LGE designating the  localized fibrosis following a heart attack. The  LGE pattern at issue in endurance athletes is something different-, i.e. a non-ischemic pattern. .

Van de Schoor et al did a systematic Pub Med search (2) and identified 65 athletes with MR imaging. A subgroup (30 subjects) were identified in an MRI study of 509 athletes.

The most frequent pattern was that located near the interventricular septum  and right ventricular insertion points. The significance of this type of myocardial fibrosis is unclear.

Levine (3) et al have suggested that LGE in endurance athletes may not represent irreversible fibrosis and note that a similar pattern of LGE at the insertion points is seen in hypertrophic cardiomyopathy and also pulmonary hypertension.

Chan et al (4) described the histopathology in patients with hypertrophic cardiomyopathy (HCM). In a multi institutional study of 1293 HCM 10% demonstrated small areas of LGE in the area of  ventricular insertion into the ventricular septum. Biopsies showed " greatly expanded extracellular space" with intestinal fibrosis and disorganized myocyte patterns." The authors emphasized the pattern was not that of myocyte death and replacement fibrosis.

Perhaps a similar histologic pattern would be found in the endurance athletes but to my knowledge that information is not available.

LGE has been reported in participants in various sports , the first case was a soccer player. Its significance and underlying mechanism  ( repetitive microtrauma, transient pulmonary artery pressure over load ??) are  not known.

 I have to agree with Eijsvogels' summary statement :  )"There is limited evidence that supports the "extreme exercise hypothesis",the most compelling relating to the increased risk of atrial fibrillation at high volume of exercise. 2) cardiac abnormalities may be present in a small proportion of the most active veteran athletes …"






1)Eijsvogels, TMH, er al The "Extreme Exercise Hypothesis:Recent findings and cardiovascular
health Implications. C"urr Teat Options Cardio Med 2018 20:84

2)Van de Schoor, F ,et all Myocardial Fibrosis in athletes . Mayo Clin Proc 2016,2016

3)Abdullah, Sm Lifelong Physical Activity regardless of does is not associated with myocardial
fibrosis. Circ Cardiovas Imaging. 2016 9,:e005511 (ful text)

4)Chan R, et al Significance of late gadolinium enhancement at right ventricular attachment to ventricular septum in patients with hypertrophic cardiomyopathy. Am J cardiol. 2015:116 436

The concept of medical commons is a bogus and dangerous concept

A fundamental concept of the various types of egalitarianism is. neither coherent,correct and operationally meaningful. .. That concept is : Individually possessed  resources or assets should be considered as part of a collective pool owned by everyone and that all have an equal right to some share of the pool.

In regard to a private property system the rights of the owner in general terms are clear. The owner has the right to use his property,exclude others from us of the property and dispose of the property through sale,gift or inheritance.

 In contrast , the rights are in a common ownership system are vague and indeterminate. Feser said it is not clear how one can be said to "own" something if no one in principle is excluded from making a claim on that something.

Even a  cursory survey of the twentieth century reveals how tragic and unsuccessful were attempts to build a society based on the notion of common ownership and the abolition of private property. The Bolshevik revolution promised peace,freedom ,equality and prosperity and delivered mass murder and starvation.Communist China's attempt in that regard were no better .The dramatic nighttime photograph of the Korean peninsula showing darkness in the north and countless points of light in the south tells the story of the difference between the two systems of ownership..

Yet the movement to consider medical or health care resources as a central pool or a medical commons has had surprisingly wide acceptance in certain medical organizations and medical academia and among health care planners and policy wonks.

Even though the concept of a collective pool of individually possessed resources is basically void of meaningful operational content a derivative metaphor-that of the physician as a steward of the mythical medical resources-has been promulgated and to some a surprising degree accepted and has become part of a major  and growing effort to control medical care and has become part of the discourse about health care policy.

The rules by which a collective of healthcare resources  would be allocated are not defined, but  those who advocate the physician as steward of these resources have several things in mind to make the metaphor operationally meaningful, the most important of which is the purported ethical requirement of physicians to adhere to guidelines which in their most at least superficially justifiable  analytical form are based on a cost benefit analysis and in their least evidence based form , expert opinion.

Cost effective analysis has been smuggled into the professionalism package in the trojan horse of social justice. This is bogus as well. The utilitarian mantra of the greatest good for the greatest number is not necessarily a part of the concept of social justice.The basis of social justice is equal respect for all humans while utilitarians would favor policies that benefit the aggregate though some individual may loose. The prominent egalitarian John Rawls rejected utilitarian allocations because they ignored the separateness of individuals and in his mythical behind- the- veil contract he believed that individuals would not sign up for a society that would sacrifice them for some aggregate benefit.

High value? Fuzzy concept? who gets to decide?

"Some measures are golden, but mostly those that we have tested. We have a responsibility as a profession to challenge this concept without seeing clear evidence that patients benefit from labeling some measures as value. Value and quality are fuzzy concepts. How can one oppose using value and quality? No one opposes the concept, but we all should demand that the implementation of measures does improve patient outcomes. We should all worry." From a blog commentary by Dr. Robert Centor. Yes, we should all worry.

Value and quality have be become buzz words-  to be blended into "value statements" and purported goals .

Classical economists ' notion of value as something imparted into a good by the labor expended in its production was overturned by economists in the late 1800s when Menger and others introduced the idea of  marginal subjective value. The value of a good or service was subjective,that is in the eye of the beholder, and was made "at the margin".The value of the tenth piece of apple pie is less to a person than is the value of the first piece. Great effort and artistic skill might be expended in the production of an artistically beautiful pogo stick but labeling it a high value product would not  bring about large sales of such a product. Few potential consumers would value such a product.

Marx 's labor theory of value is  resurrected in the payment system  for medicare "The doc fix" carried that archaic misconception  further. The Medicare payment scheme contains elements likely to be admired by the old time Soviet Union central planners.

Third party payers embrace the notion of high value medical care . The words quality and high value are  loose, vague and indeterminate  but seem to have considerable rhetorical value . They are found to a degree making them worthless in myriads of value and missions statements of various organizations whose actual activities and goals have nothing to do with those statements.

Some measures are golden, but mostly those that we have tested. We have a responsibility as a profession to challenge this concept without seeing clear evidence that patients benefit from labeling some measures as value. Value and quality are fuzzy concepts. How can one oppose using value and quality? No one opposes the concept, but we all should demand that the implementation of measures does improve patient outcomes. We should all worry.

Sha

- See more at: http://www.medrants.com/archives/8118#comments

Some measures are golden, but mostly those that we have tested. We have a responsibility as a profession to challenge this concept without seeing clear evidence that patients benefit from labeling some measures as value. Value and quality are fuzzy concepts. How can one oppose using value and quality? No one opposes the concept, but we all should demand that the implementation of measures does improve patient outcomes. We should all worry.

Sha

- See more at: http://www.medrants.com/archives/8118#comments

Some measures are golden, but mostly those that we have tested. We have a responsibility as a profession to challenge this concept without seeing clear evidence that patients benefit from labeling some measures as value. Value and quality are fuzzy concepts. How can one oppose using value and quality? No one opposes the concept, but we all should demand that the implementation of measures does improve patient outcomes. We should all worry.

Sha

- See more at: http://www.medrants.com/archives/8118#comments

What happens to your heart in you train really hard for a year or two may depend on your age

First -what happened to the hearts of young men and women who trained intensively for one year in preparation for a marathon.See below for changes noted in older subjects.

Dr.Benjamin Levine (1) and colleagues at the Institute for Exercise and the Environment performed extensive physiologic studies on 12   subjects ( aged 29 +/- 6 years) and provided valuable insight into the functional and structural change in their hearts over  one year.

The training program was intensive and progressive and was divided into four 3 months periods or segments. The third quarter included 2 hour long runs and 4 th quarter involved 7 -9 hours per week  with 3 hour long runs and interval training.

The cardiovascular system of the trained endurance athlete differs in a number of ways from the untrained person.These include:

1.increased red blood cell mass and blood volume

2.increased numbers of mitochondria and capillaries in leg muscles.

3.lower peripheral arterial resistance

4.lower systolic and diastolic blood pressure during exercise.

What distinguishes the elite endurance athlete's heart from other equally well trained athletes is the very large stroke volume which in turn depend on a very large end diastolic left ventricular volume (LVEDV). A  very compliant left ventricle is the key (.It may be more accurate to state "compliant heart" as that would include a more easily stretched pericardium facilitating diastolic filling.)

The maximal 0xygen uptake increased from 40.3 =/-1.6 to 48.7  =/-2.5. (The 02 max for elite marathoners is typically 70 to 80 plus).  Maximal stroke volume increased from 98 to 113 ml.

A key finding was that both right and left ventricular mass increased to levels similar to those seen in elite athletes but the LV volume did not change until six months of training. In the first 6 months of training when training did not include significant high intensity training the left ventricle remodeling was concentric and eccentric remodeling ( i.e. increased LV volume) did not occur more intense exercise was part of the regimen.The right ventricle began "eccentric" hypertrophy early on. Question -is the eccentric pattern dependent on the addition of some HIT or interval training in addition to the moderate intensity exercise.

Cardiac catherization data derived measures of LV compliance improved but did not approach those typically observed in elite athletes. The "Starling Curves" which plot pulmonary capillary wedge pressure (PCWP) which is an index of left ventricular filling pressure on the x axis versus stroke volume on the y axis shifted up and to the left suggesting an improvement in left ventricular compliance, i.e a ventricle more easily filled.


Their morphology measurements which  were done by cardiac MR ( generally thought to be more accurate than echocardiographic measurements) did not conform with the Morganroth hypothesis (1975) which stated that endurance exercise lead to eccentric hypertrophy which is a balanced increase in wall thickenss and ventricular volume while strength training leads to concentric hypertrophy with an increase in wall thickness with no significant change in cavity size.

Levine's subjects first had a LV concentric pattern and only after more intense ( volume and intensity) exercise was part of the program did the classic endurance athletes eccentric pattern become evident. A certain level of  intensity of exercise seemed to be necessary for aerobic exercise to cause eccentric hypertrophy. This seems to run contrary to the notion  that endurance exercise is simply a "volume overload event".

Levine's group has also reported on a similar project (2) involving older ( age 68-74) subjects and although their training program was vigorous it was less intense than the young subjects.The 02 max increased on average by 19%,arterial elastance decreased, LV mass increased with no change in the mass volume ratio ( i.e physiologic remodeling) but the Staring curves did not indicate a more compliant left ventricle.So good things happened but improved LV compliance was not one of them.

The third publication (3) in Levine's hat trick involves similar measurements of  heart function and structure in middle age subjects over  a two year period.The details are complex and interested readers can find details in ref 3 which has  entire text without firewall.

The two year training program involved at least 30 minute session of moderate exercise 4-5 times  per week with at least one high intensity exercise session ( the Norwegian 4x4).
The authors were able to show an improvement in compliance using the techniques ( The Starling curves) mentioned above .The data offer the hope that "middle age" is not too late to start .

Levine suggests that sedentary aging effect of the heart has 3 stages; 1) loss of relaxation 2)loss of compliance or stiffening of the myocardium and 3) remodeling.This sedentary aging may predispose  to heart failure with preserved ejection fraction (HFpEF) perhaps when confronted  by another "hit" such as hypertension,obesity,and diabetes. Levine's data suggests that some doable amount of endurance exercise might retard or mitigate the process . (Whether high intensity exercise is a necessary component is still an open question)

t





1) Arbab-Zadeh, A  "cardiac remodeling in  response to 1 year of intensive endurance training.
Circulation 2014, 130 (24) 2152

2)Fujimoto,N Cardiovascular effects of 1 year of progressive and vigorous exercise training in previously sedentary individuals older than 65 years of age. Circ. 2010, 122 (18), 1797

3) Howden EJ et al Reversing the cardiac effects of sedentary aging.A randomized 
trial.Circulation,2018 137; (full text available on line without firewall)

addendum 2/17/19 Comment about pericardium added.

Left Bundle Branch block cardiomyopathy-incidence

 Altered cardiac function has been recognized in Left Bundle Branch Block (LBBB) as early as 1989 (1).

 In 2005,Blanc et al  (2)described five patients with dilated cardiomyopathy whose cardiac function was "normalized" by cardiac resynchronization therapy (CRT) suggesting that longstanding LBBB could cause a cardiomyopathy that was potentially reversible by CRT.Prior to Blanc's paper, animal studies had demonstrated that LBBB could cause progressive cardiac structural and  functional loss that could be to some degree reversible with CRT.Blanc suggested that his paper introduced "a new concept of left ventricular dyssynchrony-induced cardiomyopathy"

In 2013 Vaillant (4) et al published data with similar cases  that tended to support  Blanc's thesis.
.

The topic of concern here is so called isolated LBBB  as a cause of cardiomyopathy. i.e LBBB not associated with ischemic heart disease or other recognized causes of a cardiomyopathy , LBBB as a cause of a dyssynchronopathy.

HV Barot et al (3) from Lahey clinic  identified patients with LBBB ,without evidence of coronary artery disease or other recognized  cause of cardiomyopathy  and an LVEF greater than 45% and followed them for 40 +/- 24 months. Of a total of 94 patients meeting the entry criteria, 13 developed  a  significant decrease in EF to 31+/-7 % .

All lone LBBB instances are not created equal.The degree of dyssynchrony and the patterns of altered depolarizations vary as does the resultant degree of loss of LV function and the likelihood and rate  of progression of a cardiomyopathy.

From a clinical point of view several questions are important. What factors indicate that a asymptomatic patient with LBBB will develop heart failure? What should the clinical management be when a patient with LBBB develops a significant decrease in ejection fraction?

The experience reported by Wang et al (5)  strongly suggests that the usual heart failure package of medications is not very effective in LBBB induced heart failure.At what point should CRT ( either BI-V or His Bundle pacing) be considered ?



1) Grines,CL et al Functional abnormalities in isolated left bundle branch block.The effect of interventricular  asynchrony.Circulation 1989:79, 845

2) Blanc,JJ et al Evaluation of left bundle branch block as a reversible cause of non-ischemic dilated cardiomyopathy with serve heart failure. A new concept of left ventricular dyssynchroncy-induced cardiomyopathy. Europace. 2005,7 604-610

3)Barot, HV Incidence of Left bundle branch block-associated cardiomyopathy. Journal of Cardiac Failure August 2017, vol 23, issue 8, supplement, p S55

4) Vaillant, C. et al Resolution of left bndle branch block-induced cardiomyopathy by cardiac resynchronization therapy. J Am Coll. Cardiol. 2013:61, 1089

5)Wang,NC et al New onset left bundle branch block-associated idiopathic nonischemic cardiomyopathy and time from diagnosis to cardiac resynchronization therapy. The NEOLITH II study PACE 2018 Jan 4

Variably unreliable information form Pacemaker technicians

 In the first three  years of of having a pacemaker (PM) implanted, the following instances of misinformation,lack of proper oversight or misdiagnosis occurred.I did not need that having a titanium foreign body crammed under my left chest wall muscle attached to wires coursing to various parts of my heart was quite enough to ramp up my anxiety level to at least sub-panic attack levels.

1)In October 2015 I had a pacemaker implanted- one  which is designed for bi-ventricular pacing  the most common form of CRT (cardiac resynchronization therapy).

 2)The technician who assisted and provided technical advice to the EP cardiologist at the time of the implantation told me on the following day that my home -bedside PM communication device  would send a recording every night to the manufacturer's web site  and then to the hospital PM center.

Only 6 months later was I informed by him , in reply to a question from me, that no -that was not true and that arrangement was only for devices with a defibrillator  which I did not have.  So for six months I made a effort  to be near  near by communication device device each night.

2.In October of 2016 my device recorded several episodes designed as AF/AT  (atrial fibrillation/atrial tachycardia) Episodes of AF are thought to be common  ( at least 30% by three years in patients with a PM- according to one data base).This lead to to my fairly extensive literature review of the issue of AHRE ( atria high rate episode). I learned that the topic is controversial and opinion varies as to what if any threshold there is for "signficiant volume of AF" to justify anticoagulation. (There are 2 randomized clinical trials underway that are designed to try and answer that question)

Also, All AHREs so designated by the PM's algorithms are  not in fact AF. The phenomenon of far field r wave sensing and  and a less common and more obscure PM rhythm disturbance known as  recurrent, non reentrant ventricular atrial synchrony (RNRVAS)  are capable of mimicking AF.The technician at the hospital PM center  who is tasked with screening the remote interrogation report had not recognized that the rhythm was FFA and apparently did not feel that the issue required calling the matter to the attention of the EP cardiologist.

I send an email to my EP cardiologist  and I was  told  the issue of short episodes of possible AF are very controversial and I  did not need to come any sooner or consider taking anticoagulants. He apparently did not address the possible issue of FFS or RNRVAS) or actually review my interrogation report until months later even though I has asked in my email if the data really indicated AF.

 However three months later, at routine office followup a  Medtronic technician said  that the earlier interrogation did not actually show AF but rather FFS  the reoccurrence of which he intended to prevent  by increasing the sensitivity threshold(i.e making detection less sensitive) on the atrial lead. The EP cardiologist  agreed, and I later leaned that FFS is not an uncommon cause of AHREs particularly so in the type of lead placement that I have. (Placement in the Bundle of His which in my case is higher up in the ventricle than the standard apical placement of the RV lead-sometimes the His Bundle Lead is in the atrium)


3)At an August 2018 in office PM interrogation, the technician and I entered into a conversation about battery life estimation  and she wondered if the estimate of battery life was disproportionately shorter than what may have  been expected on the basis of the settings .She forwarded the data to the home office and the engineers found nothing to do to improve the settings.Her concern and interest was appreciated but ..

In talking to her I quoted the section of  the device manual in regard to the device powering down a bit with several settings once three months has passed after the recommended replacement time ( RRT date). She said no that was not the case with my particular model However, I contacted the pacemaker company  technical support and they confirmed the manual's description was correct. 

4)Issue of high left ventricular (LV)  threshold occurring on multiple of the every three month reports.It was not until October 2017 (2 years after implantation ) that the left ventricular management system was switched to "monitor". I can only speculate as to the degree to which battery life was shortened by  what seems to be the less than prompt attention to that issue. 

The interrogation report is fairly long and reviewing it requires considerable technical knowledge about  cardiology,PMs in general as well as certain details regarding the specific brand,various programmable setting and particular model and various lead placement configurations .Being a retired physician I have had the time and interest to spend a fairly large amount of time and effort into learning about PM lore and in particular the interrogation reports. The somewhat  shaken confidence in the folks monitoring the wires in my heart has certainly provided incentive to learn how  to read the reports. 

Cardiovascular function and muscle studies on "lifelong" exercisers

Gries et al from Ball State Human Performance Lab have published the results of a study of cardiovascular  function and muscle enzyme levels on long term aerobic exercisers who did aerobic exercise for fifty (50 !) years and compared them to non exercisers of comparable age and to young exercisers.

The life time exercisers were divided into 2 groups based on the intensity of lifelong exercise  with the "performance" group consisting on competitive runners and the others called the "fitness" group which I take to mean they exercised to be fit and were not competitive athletes.Both subgroups of the
lifelong exercisers exercised 5 days per week with an impressive 7 hours of exercise per week.

The maximal oxygen consumptions values were , (expressed as ml/kilo/min):

performance group 38.1 +/-1
fitness group  27.1 +/- 2
young exercisers 53 +/- 3

Not surprising that the competitive group would have a significantly higher 02 max.In regard to muscle enzyme levels there were no differences between the competitive and fitness groups and levels were similar to the values seen in the young group.

Similar values for 02 max in  longterm exercisers were reported  (1) by Benjamin Levine's group from Southwestern. They also reported a significant higher 02 max in the competitive subgroup versus the non-competitive subgroup ( 39.5+/- 5.3 versus 32.5+/-5)

These two studies present data on two subgroups of long time or "lifelong" exercisers with the competitive groups having significantly higher maximal oxygen uptakes. Both subgroups exercised for many hours a week but presumably the competitive group in each study exercised at a higher intensity. Is the difference in measured maximal oxygen uptake due to the intensity of training or is the difference due to the competitive group having the genetic endowments that  bestow a super compliant left ventricle capable of rapidly  filling and allowing a higher exercise stroke volume.

1) Bhella PS , Impact of lifelong exercise "dose"on left ventricular compliance and distensibility
JACC vol 64 2014

More use restriction for fluroquinolones from FDA

FDA recommends against use of  fluroquinolones for 1) acute bacterial sinusitis, 2) acute exacerbations of chronic bronchitis.and 3) uncomplicated urinary tract infection because of  increasing concerns about adverse effects.

The warning emphasized the adverse effects of hypoglycemia and various psychiatric symptoms.

For possible mechanisms regarding fluroquinolone   related hypoglycemia see this detailed review.

Milton Friedman's " 4 ways to spend money" and health care spending

Milton Friedman spoke of the four ways people could spend money based on the funding source and the recipient of the goods or services and the associated mind sets,incentives and constraints that each arrangement supports. In his book "Free to Choose" he presented a four quadrant diagram, a version of which can be found here.

The left upper quadrant  represents the situation in which you spend your own money on yourself, a situation where one typically exerts some degree of prudence a thought not found to same degree in the other arrangements.

In the RUQ you spend someone else's money on yourself.

Much (most ?) health care spending seems to be in the RUQ which is clearly the case with Medicare and Medicaid spending and from one view point employees spending their employer based health insurance money.Although you could consider that type of insurance basically part of the employee's compensation so maybe that should be in the LUQ ,folks tend to act as if they are spending someone else's money so I'll leave that in the RUQ.

The LLQ denotes your spending their money on someone else, such as Aunt Hattie buying a birthday gift for her niece in which getting what the niece really wants may not be the determining factor.

The RLQ represents you spending some one else's money on someone else.Think of a welfare program dispensing money .

The concern over high and rising health care costs is sometimes (and in my view correctly) focused on the governmental spending on health care. However, increasingly pundits and health care policy wonks and "thought leaders" frame the issue as one in which total health spending is a threat to nation's fiscal solvency. .

The argument that government spending is out of control, relies on foreign funding and the national debt is growing to a dangerous level resonates across the political spectrum of views. Regardless of the validity of various elements of that sentiment how would spending in the LUQ relate those concerns?

Would not individual spending their own money on things (even medical care)for themselves increase the C part of the GDP formula? Would not increase in spending be exactly what economists of the Keynesian view prescribe to bolster a economy lacking in the right type of "animal spirits"? Why would policy wonks want to limit personal spending? Are they really basing their proposal for more control over individual actions on legitimate concerns for the future economic safety on the country? Or is it the progressive view ( as well the NeoCons view) that society is best managed by wise leaders ?

If there is increased coronary calcification in some long time endurance atheletes,is that a good or bad thing?

If there is increased  coronary calcification in long time endurance athletes,is that a good thing or a bad thing? Also if true is it true only in white males? The Cardia Study (1) found an increased risk of coronary calcification in white men ( depending on what statistical model was used) but not black men.

 Funnily enough a similar question can be asked in regard to the use of statins with  more calcification reported in users of the more potent ( in terms of LDL lowering power) statins.(I am aware of no racial differences reported in that regard)

So is the absolute worse thing you, as a white male could do would be to run excessively for 30 years and take the most potent statin ever?



1) Laddu DR 25-year physical activity trajectories and development of coronary artery disease as measured by coronary artery calcification.

Is the key to prevention of post ablation atrial fibrillation risk factor modification?

Dr. Rajeen Pathar (1) and co researchers from Adelaide Australia seem to think so.

Hypertension,diabetes,obesity, sleep apnea and smoking are recognized risk factors for the development of atrial fibrillation (AF).The authors reasoned that the same risk factors might predispose to  recurrence of AF after a successful atrial fibrillation ablation and that aggressive risk factor reduction just might decrease the recurrence rate. Their published data (1) tends to support that hypothesis.

A excellent discussion of risk factor importance in AF  by Dr. John Mandrola on Medscape can be found here.



1) Pathak,RK Aggressive risk factor reduction study for atrial fibrillation and implications for the outcome of ablation.The Arrest-AF study. JACC2014 Dec 2;64 (2) 2222

kids fredquently getting hit the head is not a good idea

More data accumulate indicating MR changes in the brain are associated with sub concussive blows in youth football in a single season.

Functional MR studies (fMr) have shown changes in both gray and white matter correlated with the number of blows  to the head  as measured by impact detecting systems placed inside football helmet's.

The immediate and long term effect on the young brain is not known and the relationship to CTE is speculative.

Maybe the developing brain is more vulnerable to harm from multiple mini traumas or maybe it is more adaptive .

Meanwhile the  experiments continue in youth football leagues and under Friday Night Lights.

Murugeson from Southwestern Medical School in Dallas  presented data at recent  RSNA  meeting demonstrating functional MR changes in a single season of high school football correlated with sub concussive head blows.So these are kids who had no reported concussion.  Data from a Wake Forrest study indicated majority of sub concussive blows occurring during practice.

will regular exercise help keep your thymus from shrinking keeping immune system "younger"

Researchers (1) from University of Birmingham present evidence supporting that proposition. 

Remember  the T lymphocytes,they arise from the bone marrow and trek to the thymus where they multiply and prosper then traveling to the lymph nodes and play a essential role in immune function.Decreased immune function and shrinkage  of the thymus are well known effects of aging.

The authors studied immune function in 125 subjects aged 55-79 who had exercised regularly ( cycling) for many years.These were not elite athletes .They also studied age matched non exercisers and young adults.

The active group had higher T cell levels and higher levels of something called RTE which stands for recent thymic emigrants than did the less active control group and these levels were the same as the healthy young controls .



This finding lead some of the lay press to hype the findings in terms such as having the immune function of a 20 year old when you are 80 but only a selected aspect of immune function seemed well preserved and the authors found other aspects of the immune system (including numbers of B Cells) were the same in the active and the inactive group and not similar to the young controls.

So, 80 year old  master cyclists may not have the immune function of a 20 year old but do have some aspects of immune function better preserved than the age matched sedentary controls and there is still another reason why active aging is different from sedentary aging .

1)Duggal NA, Major features of immunosenescence including thymic atrophy are ameliorated
by high levels of physical activity in Adulthood. Aging Cell 2018 Apr 17(2) Online published March 8 2018

20 years from demonstration of AF origin in pulmonary veins to a clincal trial with controversial results

 In 1998, Haissaguerre et al (1) described atrial ectopy or premature atrial beats within the pulmonary veins as the trigger for atrial fibrillation.It seemed to be a particularly attractive theory for the origin of paroxysmal AF (PAF) and has also been proposed as a facilitator of continuation of AF to persistent AF.

This lead to the idea that electrical isolation of the pulmonary veins by burning atrial tissue would keep the ectopy from reaching the rest of the atrium .

And so Pulmonary vein isolation (PVI) really caught on being used for not only PAF but for persistent AF as well  and ever since  the electrophysiology world has awaited a randomized clinical trial answering the question does PVI decrease mortality in atrial fibrillation (AF). It is accepted dogma,backed by considerable experience that PVI is superior to medication treatment in suppressing AF and there is general agreement that restoration of sinus rhythm improves quality of life .A  unanswered question was does PVI decrease risk of death associated with AF.

The Long-awaited CABANA trial was supposed to  or at least hoped would  provide an "Answer" to that question.

When the results of this large (2204 subjects) multi-center,multi national (https://www.acc.org/latest-in-cardiology/clinical-trials/2018/05/10/15/57/cabana) were announced there was no widespread celebration in the EP community. When the data were analyzed according to the standard statistical method used in randomized superiority clinical trials ( namely the "intention to treat" (ITT)) method), there was no difference in the primary outcome which was the combined end points of death,disabling stroke,serious bleeding or cardiac arrest  between the ablation group and the treated with drugs group.Further using ITT analysis there was no significant difference between the two treatment arms for each of the components of the combined end point .

For ablation versus drug therapy :8% vrs. 9.2%  with a hazard ratio of 0.86 (0.65-1.15, ) p=0.3 in regard to the primary endpoint.

There was no difference in death nor in serious stroke between the two arms of the study.

However looking at secondary outcomes- In regard to the category of death or cardiovascular hospitalization  there was a significant difference.

 There is more than one way to analyze data and results of the "per protocol " analysis gave  consolation to the EP cardiologists.

The per protocol analysis showed: a significant decrease in the composite primary end point with ablation  -ablation 7% versus  drug10.9 %  ( HR 0.57 , 0.50 -0.89) and decrease in all cause mortality in the ablation group , 7.5 % for drugs versus 4.4 % for ablation.

So intention to treat analysis indicated that ablation was not superior while per protocol analysis indicated that ablation was superior.Something for everyone.

Though heralded by some as a "game changer", I see nothing in the results changing any game. EP cardiologists are not likely to change their practice in any meaningful way  Just look at the final sentence in the Conclusion slide presented at the American College of Cardiology meeting in August 2018:

"Ablation is an accepted treatment strategy for treating AF with low adverse event rates even in higher risk patients."
.

 Since the study confirms what other data have shown namely that ablation converts AF to sinus rhythm more often than drugs and since sinus rhythm is associated with a better "quality of life" and the results are more durable why would EP docs  change the way they are practicing ?



 1)Haissaguerre M, Jais P, Shah DC, Takahashi A, Hocini M, Quiniou G, Garrigue S, Mouroux AL, Metayer PL, Clementy J. Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med.1998;339:659

Is aerobic endurance training even better for the muscles than the heart?

Aerobic exercise capacity is strongly linked to 02 max which is the product of the cardiac output ( stroke volume X heart rate) multiplied by the A-v 02 difference.

Five middle aged men who underwent aerobic training at age 20 in 1966 participated in a 6 month endurance training program in 1996.Their average 02 max increased 14% but there was no change in their maximal cardiac outputs. Their A-V 02 difference did increase by 10% accounting for the  entire improvement in their aerobic power.

The increase in mitochondrial function brought about by aerobic exercise is well documented and the more mitochondrial the higher the 02 uptake by the exercising muscles.






1)McGuire, DK et al A 30 year followup of the Dallas Bedrest and training Study11Effect of age on cardiovascular adaptation to exercise training. Circulation2001 Sept 18 104 (12) 1358-66