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Is the new professionalism and ACP's new ethics really just about following guidelines?

The Charter ( Medical Professionalism in the New Millennium.A Physician's Charter) did not deal with just the important relationship of ...

Friday, May 12, 2017

An increasing cardiac calcium score may not mean increased CVD risk

The coronary calcium score (  for example as done with a EBCT heart scan) is well recognized as a tool to estimate  cardiac risk, a higher score meaning a higher risk.

Coronary calcification is by definition coronary artery disease. Calcification may be in the media of arteries or in the intima. Intimal calcification may be dense as is  found in fibrous, basically stable plagues which are not prone to rupture and cause an acute coronary event. Spotty calcification can be found in soft, vulnerable plaques that are at risk of rupture.

Serial calcium scans on patients taking statins have shown increase in coronary calcification and yet there is more than abundant  evidence that statins ( at least in secondary prevention) can reduce plaques and  decrease the risk of coronary events,a situation referred to by some as the "statin paradox" or the "plaque paradox".

A possible explanation  to this alleged paradox may be found in a study (1) from Cleveland Clinic in which the authors analyzed intravascular ultrasound images of patients from 8 clinical trials.

Patients with coronary artery disease treated with statins show an increase in coronary calcification.The so-called high intensity statins bring about more increase in calcification while also causing the greatest regression of plaques. The increase in calcification may be one mechanism by which statin therapy stabilizes plagues and makes them less likely to rupture. So serial calcium scans in a patient taking a statin demonstrating increased calcification may not be a warning of increased risk at all.

Quoting Cleveland Clinic's  Dr . Steve Nissen:

"This is an important observation that tells us statins work to stabilize plaques by converting softer,cholesterol -laden plaques that are prone to rupture into more stable calcified plaques that are relatively inert.It explains the paradox of why serial measurements of calcium doesn't necessarily work to track the progression of disease and it explains to some extent how statins work.

Internists who like to talk about mechanisms and how things work may find this a compelling story but as an accompanying editorial (3) said this is a hypothesis generating study,causality cannot be inferred and the techniques used have multiple limitations. Human are pattern seeking story telling creatures and this story might catch on-at least until something better comes along.


Shifting gears-there are at least 3 articles that have reported that long time endurance exercisers have higher calcium scores than age matched  sedentary controls controls,an observation offered by some authors as  more proof that too much exercise is not good. Juxtaposed to that is the epidemiologic evidence that longtime endurance exercise decreases the risk of a coronary event and that elite athletes life longer than sedentary colleagues and yet more calcium in the athletes.Another plaque paradox?

Merghani and co-authors studied 152 maters athletes ( ages 51-63) They found that "most" )( 60%)  of the lifelong exercisers  has a normal CT coronary angiogram as did a similar number of the controls. However they also reported that the male athletes were more likely to have a CAC score of 300 or more compared to the sedentary controls.The plaques in  the athletes were predominately calcific.

Similar results were reported by V.L. Aengevaeren et al (2) who studied 284 lifelong exercisers. In regard to their findings they said:

"The most active group did however had a more benign composition of plaques with fewer mixed plaques and more often only calcified plaques.These observation may explain the increased longevity of endurance athletes  despite the presence of more coronary atherosclerotic plaques in the most active participants ".

Eijsvogels and co-workers published an excellent, detailed and extensively referenced  review( 4) of the possible harmful effects of acute and chronic exercise .  They only briefly mention what was then the preliminary evidence that longtime runners have higher calcium scores as their review preceded Puri's work as well as that of Aengevaren and Merghani

1.Puri, R Impact of statins on serial coronary calcifications during atheroma progression  and regression. J Am Coll Cardio 2015;65, 1273-1282


2 Aengevaren VL et al The Relationship between lifelong exercise volume can coronary atherosclerosis in Athletes. Circulation 2017 april 27

3. Shaw LJ The Never Ending story on Coronary Calcium.Is it predictive,punitive or protective? Editorial Comment J of Amer Coll Cardio, 2015 ,65 no 15 1283-1285

4. Eijsvogels,TMN et al Are there deleterious cardiac effects of acute and chronic endurance exercise? Physiol Rev 96 99-125,2015

Tuesday, May 09, 2017

The annualized decrease in exercise capacity may be even worse than we thought

The longitudinal decline in aerobic capacity is typically said to be 5 -10% per decade from age 40 to about age 70  then a more rapid decline occurs. Data from the Baltimore Longitudinal study of Aging (BLSA) (1) suggests that the decline is not constant across age ranges  but rather" accelerates markedly   with each successive age decade".

 How so?

In cross sectional studies " each succeeding age decade  represents a more highly selected group than it predecessor, thus healthy 70 to 90 year-olds may have been physiologically superior to current 20-40 years olds when they were on a similar age. In other words there is inherent selection bias in cross sectional data.

I will not attempt to explain the statistical model used but here are their values for the reduction  in men in peak O2 uptake expressed in ml/kil0/min for various decades:

age
30- 39 minus 7
40-49  minus 10
50-59  minus 15
60-69 minus 20
over 70 minus 26
                    
 A similar pattern was found in women.

They found that the oxygen pulse (oxygen consumed per heart beat) rate of decline mirrored the rate of decline in peak 02 .Since oxygen pulse is a function of stroke volume and peripheral muscle uptake of oxygen it is not possible to determine if it is cardiac output or muscle uptake that is largely responsible for the decline.

Caveat-The published results are from a mixed-effect prediction model and the median followup was only 7.9 years and prediction is the operative word. Though the study is "longitudinal" numbers in their tables do not represent for example following the same people over a lifetime and noting the per decade change in oxygen uptake. Still their data suggest that the often quoted 5-10 % decrease per decade may be too optimistic and rates of changes likely accelerate with aging.The confidence intervals for each age range are quite large and you have to wonder what are the mechanisms responsible for such wide variation in loss of exercise capacity within a age range. If subendocardial  fibrosis is the ( or a) culprit what are the actors that accelerate or retard that process.



1) Fleg, JL Accelerated Longitudinal Decline or Aerobic Capacity in Healthy Older Adults"
Circulation 2005, 112: 674 -682.

Sunday, April 23, 2017

"Para Hisian Pacing" as well as selective Bundle of His pacing may bring about a hyper response

I have written before about a sub group of Cardiac resynchronization patients (CRT)   who have a hyper response with marked improvement in indices of cardiac   function, e.g. ejection fraction and end diastolic volume.

Such responses have been reported with Biventricular pacing  (Bi-V) and  His Bundle Pacing ( HBP). There are two forms or types of HBP: 1) pure HBP also known as selective and 2) Para Hisian pacing also known as non  selective HBP.

The QRS is normalized with selective HBP while in nonselective although the widened QRS duration is significant reduced it may not be restored to the pre  bundle branch block  configuration. There is both activation of the His Bundle fibers and adjacent ventricular septal muscle giving a fused or fusion ventricular activation pattern. 

According to Lida et al writing in the December 2016 Journal of Arrhythmia (1) "there seems to be no significant clinical difference between selective HBP and non selective HBP because both do not alter physiological impulse conduction and possibly maintain rapid and synchronous LV ( left ventricular) activation "

A similar case report was published by Ajijola et al  from UCLA in 2015 (2)

His Bundle pacing seems to gaining momentum both as an alternative to right ventricular pacing and as a method of cardiac resynchronization.

1)Lida, Y et al Successful resynchronization by permanent His-bundle pacing in patient with pacing -induced cardiomyopathy' J Arrhythmia , 2016 Dec. 32(6), 499-501

2)Ajijola,O et al Hyper-response to cardiac resynchronization with permanent His bundle pacing:Is parahisian pacing sufficient? Heart Rhythm Society, open access article http://dx'doi.org/19.10.hrcr.2015.05.006

Addendum:  5/26/2017  Several papers presented at the May 2017 meeting of the Heart Rhythm Society indicated that His Bundle pacing is ready for prime time.  See Dr. John Mandrola's  article on Medscape entitled " His Bundle pacing hits the mainstream at HRS 2017".
On a personal note-It is now almost two years since I was implanted with a Pacemaker with Bundle of His pacing before the practice became more mainstream. I had developed a left bundle branch block and an exercise induced second degree heart block. The LBBB had  markedly decreased my exercise tolerance. My LBBB was "fixed" and after getting over a few complications of the procedure my exercise tolerance was back to my pre LBBB level .


Friday, April 14, 2017

If peak load is the determing parameter runners should have more osteoarthritis

Perhaps it seems counter intuitive that runners do not have a higher incidence of knee osteoarthritis or so the preponderance of epidemiologic data contents.After all the peak load of the articular cartilages in running is much higher than in walking or so the kinesiologists tell us and would not the cumulative higher peak load after many miles of running wear out and maybe chew up the articular cartilages.

Or maybe the explanation does not lie in the peak load.

 Ross H Miller from the Department of Kinesiology at the University of Maryland offers an alternative view (1) and an alternative analysis of the relevant forces conspiring to "wear out" the knees.

He suggested that peak load is not the relevant variable but rather it is the "average load per distance traveled"  which is said to be surprisingly low and purportedly similar to walking.

Ross also discussed the notion of cartilage conditioning .Knee cartilage glycosaminoglycan content( which affects lubrication and shock absorption ) has been  shown in one study to be greater in recreational runners and even greater in high volume runners.

"... a man hears what he wants to hear and disregards the rest" Paul Simon.The Boxer



1) Miller, RH "Joint loading in runners does not initiate knee osteoarthritis" Exerc Sports Sci  Rev 45(2), 87-95,4 2017

Thursday, March 23, 2017

CRT-non-responders, responders and the rare super responder

About one third of patients with heart failure (HF) do not benefit appreciably or respond to cardiac resynchronization treatment (CRT). Some other have a clinical benefit with physiological confirmation in the form of echocardiographic demonstration of reduction in heart size and increase in the ejection fraction. A relatively small subset show a marked improvement both symptomatically and in terms of impressive  improvement in terms of ejection fraction and reduction in left ventricular size.

Neither EKG nor echocardiographic  patterns accurately predict who will respond and to what degree. However, patients with a LBBB EKG pattern -particularly using the new criteria suggested by Strauss (1 )- are much more likely to have a favorable response.  In fact CRT basically "treats" the electric and associated mechanical dyssynchrony imposed by the left bundle branch block.Some of the variables influencing response include how much myocardial damage may have already occurred in the patient  ( e.g. heart attacks) and the location of the left ventricular lead in relationship to left ventricular scar(s).

The most dramatic example of super responders was reported  by Vaillent et al in 2013. (2). They described 6 patients with a diagnosis of LBBB without evidence of coronary or other heart disease and an EJ of greater than 50% at the time of diagnosis. Over a period of five to 21 years all developed  heart failure severe enough to warrant referral for CRT. Following CRT, ejection fraction improved greatly , five of the six within 3 months .Mean EJ increased from 31 to 56.In one patient , from 26 to 60.Other cardiac functional indices improved as well

The authors suggest that these cases "strongly support the concept of LBBB-induced cardiomyopathy".This idea was apparently suggested earlier by Blanc et al in 2005 (4)

LBBB induced heart failure represents a vary small percentage of patient who are treated with CRT. Ghani et al (3) report on the predictors of long term outcome of "super-responders to CRT which they define as Left ventricular EF (LVEF) greater than 50% ( mean of 54.9%, +/-6) on follow-up echocardiogram.The group whose EF was between 30 and 50% were labelled as "responders"

They describe 56 patients from a group of 347 patients with primary CRT D indication. The predictors were female sex,nonischemic  etiology,higher EF at baseline and wider QRS duration.

Vaillant's patients , when compared to Ghani's patient, perhaps could be considered "super super" responders.


1. Strauss DG et al, Defining Left Bundle Branch block in the Era of Cardiac Resynchronization Therapy. American J Cardiology 2011,Vol 107 pg 927-934

2. Vaillant C et al. Resolution of left bundle branch block induced cardiomyopathy by cardiac resynchronization therapy. J. Amer College of Cardiology 2013,vol 61, p 1089

3. Ghani, S  et al  Predictors and long term outcome of super-responders to cardiac resynchronization therapy. Clin Cardiology 2017

4.Blanc J et al. Evaluation of left bundle branch lock as a reversible cause of non-ischemic dilated cardiomyopathy with severe heart failure. A new concept of left ventricular dyssynchrony-induced cardiomyopathy. Europace 2005;7,604

Sunday, March 19, 2017

Do low levels of cardiovascular fitness predispose to cardiac hypertrophy?

 There is evidence  that suggests low levels of cardiac fitness predispose to maladaptive cardiac remodeling  typically manifest as concentric remodeling and concentric hypertrophy and increased ventricular stiffness and diastolic dysfunction.

Lovic and Kokkinos and co workers correctly point out that the cardiac hypertrophy consequent to  high blood pressure differs from the typical physiological cardiac hypertrophy of the endurance athlete realizing that  extreme examples of the latter can be difficult to distinguish from the former.

Lovic et al  makes the following  argument in a 2016 issue of the Journal of Hypertension.

Low fitness level individuals will reach a systolic blood  pressure of 150 at low levels of exercise, e.g. 4-5 METS , which are  levels commonly encountered in some activities  of everyday living.
150 systolic  blood pressure is necessary to trigger cardiac remodeling. Individuals, who are more fit, are able to do that level of work without that degree of BP rise. So individuals with low fitness may spend considerable  time each day with a BP of sufficient magnitude to trigger hypertrophic changes in  the left ventricle. even though their BP as measured in their doctor's office may be normal.

Their data (1) found an inverse relationship between exercise capacity, blood pressure response to exercise and  left ventricular mass.Further, they have published data that showed 16 weeks of aerobic training resulted in subjects having  a significantly lower blood pressure  level when they  exercised at the every day activity level of 3-5 METS. A reduction in previously elevated left ventricular mass was also shown.

Other data consistent  with this notion comes from a study by Brinker et al ( 2) from Southwestern Medical School in Dallas. They studied subjects aged 42 -67 years of age with stress testing and echocardiography. Those individuals in the lowest fitness category ( they divided the group into 3 fitness levels ) had 40 % concentric hypertrophy as well as a 9% prevalence of diastolic dysfunction ( as defined  by the e/a ratio on mitral valve echo flow studies)

Data from the Dallas group and others have outlined the concept of there being two distinct cardiac phenotypes related to the development of both heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF).They are:

1)Subclinical systolic dysfunction (EF may be normal but abnormalities detectable by measurement of global strain with speckle echocardiography)),with eccentric cardiac hypertrophy with increased LV diameter)-the proposed precursor to HFrEF

2)Subclinical diastolic dysfunction with concentric LV hypertrophy; with increased relative wall thickness (RWT) -the proposed precursor to diastolic heart failure (HFpEF)

Increasing data strongly suggest that low fitness levels predispose to the precursors of HFpEF.
Lovic's work suggesting that exercise induced elevated blood pressure in the unfit may be one possible mechanism involved.



1)Lovic, D et al Left ventricular hypertrophy in athletes and hypertensive patients.J Clin Hypertension 2017,

2) Brinker SK et al. An association of Cardiorespiratory Fitness with left ventricular remodeling and diastolic dysfunction. JACC Heart Failure., Vol 2, no 3, 2014, p 238


5/1/17 An embarrassingly large number of typos and misspellings were corrected and again on 5/16/17.

Wednesday, February 22, 2017

Cardiac remodeling -some old and new theory and some data


Following the 1975 echocardiographic study by Morganroth (1) of endurance athletes and resistance exercise athletes and several cross sectional studies that seemed to validate his work the  "Morganroth  Hypothesis" became  the standard exercise physiology party line.

The story goes like this:

Endurance exercise brings about a volume overload or a preload stimulus to the ventricle that lead to eccentric hypertrophy which is an increase in ventricular cavity size and only slight increase in wall thickness. Resistance exercise brings about a pressure overload or an afterload stimulus which leads to concentric hypertrophy in which there is little change in cavity size but thickening of the ventricular wall.,The 2 types can be defined  by the relative wall thickness (RWT) which is 2 x the posterior wall thickness divided by left ventricular diastolic diameter with  a value greater than 0.42 indicating  concentric hypertrophy.

Skeptics have argued that echo studies have inherent  methodological error  ranges too great   to separate groups whose absolute values are not that far apart and MR is a much more precise method and that cross-sectional studies have limited ability  to sort out group differences that  are due to training  from other causes of individual differences. So, what did a longitudinal study with MR imaging show.

A 2011 MRI longitudinal study, Spence et al (2) provided interesting data from which one might conclude that endurance exercise does bring about eccentric hypertrophy but resistance exercise does not increase wall thickness-at least not in the small group of resistance exercisers who worked out three times a week for six months reported in this publication


It is certainly possible that the six months training program in Spence's study was  not enough to bring about concentric hypertrophy. A more recent  meta analysis supplies data and analysis that indicate that there is a typical pattern for endurance exercisers and a pattern for resistance exercise more or less consistent with Morganroth's hypothesis  and a in- between pattern for those who engage in activity in which there is both significant amount of volume and pressure overload such as rowing and cycling.

 Plium et al (3)analyzed echocardiographic data  on 1451 athletes gathered up from some 59 studies.All subjects were  under the age of forty, older athletes excluded so as to not muddy up the data with the effects of aging on heart function and structure.

 Basically the data conformed with Morganroth's hypothesis. Quoting the author's conclusions;

"Divergent cardiac adaptations do occur in the athletes performing dynamic and static sports..However,the classification as an endurance trained heart or a strength-trained heart is not an absolute and dichotomous concept but rather a relative concept."

So a stereotypical runner will have a different  pattern from a wrestler or body builder  but ventricular volume changes and wall thickening occur in both  to varying degrees with the runner tending to a eccentric hypertrophy-remodeling pattern and the wrestler to a concentric pattern while athletes such as cyclists and rowers demonstrate the most marked changes both  in ventricular volume and wall thickness. 

More surprisingly and maybe more importantly  is the observation that a sedentary life style may evoke a remodeling pattern  characterized  by concentric changes, i.e.  no increase in ventricular volumes and a tendency to develop diastolic dysfunction.

This is what was reported by Brinker et al (4) from Southwestern Medical School in Dallas in their study of  cardiac function and structure in 2900 subjects from the Cooper Center Longitudinal Study.The subjects age ranged from 42 to 67 years of age and all were either self referred or physician referred to the clinic  and had a normal stress test.Based on the exercise levels achieved on the stress test four fitness levels were designated.  They found that the lowest fit subjects ( presumably  those with a sedentary lifestyle) had a higher prevalence of concentric remodeling as well as diastolic dysfunction than the fitter subjects. There was a 40% prevalence of concentric hypertrophy and 9 % prevalence of diastolic dysfunction ( defined as an E/A ratio greater than 1) in the lowest fit group versus less than 20 % concentric change and 2% diastolic dysfunction in the most fit group. So it is not an all on none thing and fitness does not seem to immunize against concentric  hypertrophy and diastolic dysfunction but made both less likely.

 Both resistance and endurance training cause cardiac remodeling but there may also   be a "inactivity remodeling", as might occur in a sedentary lifestyle The ventricles remodel  whether  you exercise or have a sedentary lifestyle and Brinker's group suggest that the inactivity remodeling may be a precursor to diastolic heart failure (aka HFpEF) and further suggest that long term exercise might be preventive.

That is a thesis I would like to believe. I would be more convinced if it were not for the fact that while  66% of the low fit group were hypertensive so were  only 38% of the fittest group were hypertensive. You wonder if that might not play a role in the concentric hypertrophy. I discussed other work by the Dallas group (see here) which,IMO, provides better evidence for the idea that long term aerobic exercise can reduce the risk of diastolic heart failure.


1. Morganroth, J et  al. Comparative left ventricular dimensions in trained athletes.Annl Int Med. 1975,82(4), 521-524

2. Spence,A et al .A prospective randomized longitudinal MRI study of left ventricular adaptation to endurance and resistance exercise J of Physiology 14 nov 2011

3.Pluim,B The Athlete's Heart. A Meta-analysis of cardiac structure and function. Circulation 1999:100: 336

4.Brinker, SK et al. Association of Cardiorespiratory Fitness with Left Ventricular Remodeling and diastolic dysfunction. JACC Heart Failure.Vol 2, no.3, 2014, p238

"Humans are pattern-seeking, story-telling animals and we are quite adept at telling stories about patterns,whether they exist or not" Michael Shermer.