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

Endurance exercise,aortic stiffness,Windkessel effect

The beneficial effect of prolonged endurance aerobic exercise on the aortic and great vessels may be as  important or more important that its effects on diastolic function and favorable remodeling. 

First the aorta is not  a stiff pipe. One  model used to explain aortic function and the shape of  the aortic pressure waves is the Windkessel effect model which considers the aortic and large elastic arteries as if it were an elastic buffering chamber which provides a cushioning or reservoir effect providing blood flow during diastole and damping the pulsatile flow. This reservoir effect flow is said to be as much as 40% of the stroke volume. The large elastic arteries act as capacitors , storing energy during systolic while bulging  a bit and then pushing back  or recoiling during diastole maintaining  a more or less steady flow of blood and offering protection to the vulnerable arterial vessels of the brain and kidney to which excessive pulsatile flow may be harmful. The capacitance effect does not eliminate pulsatilty,of course ,the textbook normal diastolic blood pressure is 80 and  not zero which is what it would be if  the aorta were a lead pipe. 

With aging,and arguably more so with sedentary aging,the elastic vessels become less elastic, stiffer and provide less of the Windkessel effect reflected in higher systolic blood pressure, lower diastolic blood pressure (increased pulse pressure) and more rapid blood flow. This   can measured  by noninvasive measurement of pulse wave velocity with an higher velocity indicating stiffer arteries.Loss of the reservoir  function. i.e.. a stiffer aorta and other great vessels  increase the left ventricular afterload predisposing to left ventricular wall thickening. 

It is easy to find data supporting the claim that exercise will improve aortic compliance.As early as 1973 a report from the Baltimore  Longitudinal Study on Aging (BLSA) (ref 1) indicated improved pulse wave velocity ,augmentation index and systolic blood pressure in older endurance athletes as compared with sedentary controls.

Other more recent detailed physiologic studies have confirmed that finding. Gates et al(2) studied men with varying exercise histories in three different age groups and reported that the regular endurance trained subjects has lower large artery stiffness as measured by a reduced aortic pulse wave velocity.

An excellent, detailed exposition of the physiology of the adaptation of the aorta to endurance exercise can be found in full free text in reference 3.


1)Vaitkevicius, PV et al Effect of age and aerobic capacity or arterial stiffness in healthy adults.Exp Physiology 2005:90.645-651

2)Gates PE,Left ventricular structure and diastolic function in human aging. Europen Heart Journal 2003,24, 2213-2220

3) Montero, FJC Adaptation of the aorta to training.Physiological perspective.
Apunts,Medicena de L'esport. 2017:52 (193): 3-9

"All models are wrong, some are useful" George Box  1976

Football lineman may be damaging hearts as well as brains

Dr. J Kin along with Dr. Aaron Baggish, who directs the Cardiovascular Performance Program at MGH, studied a group of NCAA Div.1 college football lineman and compared results with non-lineman over the course of a single season. (1)

They reported that the lineman were all normotensive preseason while post season , 30% had developed Stage one hypertension and 60% developed pre-hypertension. The non-lineman improved their Global Longitudinal Strain measurement (as determined by speckle echocardiography)while the lineman worsened theirs.Concentric hypertrophy was noted in the lineman while the non-linemen displaced eccentric hypertrophy.

This was after a single season.Consider that many high school player play for four years and a number then have a college career.

The authors concluded:

... participation at a lineman field position may lead to a form of sport-related myocardial remodeling that is pathologic rather than adaptive. Future study will be required to determine if targeted efforts to control blood pressure, minimize weight gain, and to include an element of aerobic conditioning in this subset of athletes may attenuate this process and translate into tangible downstream health benefits."

I have blogged before about the occurrence of CTE in collegiate football players quoting a study from the Boston University CTE center. The authors reported 48 cases who only played high school and college ball.

There have also been several articles reporting imaging abnormalities in young players with both concussive and subconcussive head trauma.Now we seem to have evidence of subclinical heart damage  that like subconcussive blows might lead to downstream health problems.


See reference 2 for a good summary and commentary regarding Kin's article.or see herehttps://www.sciencedirect.com/science/article/pii/S1936878X16307197?via%3Dihub


1)Lin, J Blood pressure and left ventricular remodeling among American style football players.
JACC,vol 9, number 12 dec. 2016.

2) Zoghbi WA , Cardia remodeling in American style football player. Field Position Matters. JACC
2016 Dec 9 9 (1) 1377-1379    


addendum 1/31/19 Zoghbi reference added.          

Cleveland Clinic article says the more fit live longer

Dr. Kyle Mandsager and colleagues at the Cleveland Clinic reported on the long term mortality  ( median followup of 8.4 years)  on 122,007 patients who were referred for symptom limited exercise treadmill testing.They were stratified by age and sex  into five cardiorespiratory  performance groups .(low,below average,above average,high and elite expressed as metabolic equivalent units (METs) which is 3.5 ml 02 uptake/kilogram/minute) which was estimated by treadmill incline and speed.

The 25th, 50th,75th and 97.7 percentiles were tabulated for age and sex .Low is defined as less than 25 th percentile and elite as greater than 97.7 th percentile.

They found that cardiorespiratory fitness (CRF) was "inversely associated with long term mortality with no observed upper limit of benefit. Cardiorespiratory  fitness is a modifiable indicator of long term mortality …"


We have another coarse grain study that could be used to support  the thesis that exercise is good and lots of exercise is better and you will live longer. I don't believe it is that simple.

 This study does not correlate exercise history with longevity rather it correlates exercise performance with longevity. Admittedly exercise performance or capability does correlate with exercise history but they are not exactly the same thing.  Further, while it may well be the case that CRF is modifiable and  that one can actually improve mortality by improving one's CRF their data does not direct address those point although I like to believe that proposition is true.

What is shown impressively in their Figure 1, is  the 10 year survival probability for the above average or the high group is about 95% ( just by my eyeballing the chart) versus the low group where the survival probability is slightly less than 80%

So how low is the low group in terms of exercise capability.For example in the 70-79 year age group the low group had a MET of less than 6. Some one in that category(assuming a reasonably functioning orthopedic and neuromuscular system)  could likely walk a mile in 15 minutes or complete Stage 1 of the Bruce treadmill protocol. 

What about a 40 year old? Subjects in the 40-49 year old group had a MET levels of less than 9.8. This corresponds to being able to finish Stage 2 and a bit into Stage 3 and be able to run a 12 minute mile.

Someone in the high category would have a MET value of 12.5 to 14.6 which corresponds to being able to reach Stage 5 on the Bruce  protocol and run a mile in 9 minutes.

The authors made comments that are headline attractors.  "The increase in all cause mortality associated with reduced CFR (low versus elite:adjusted HR,5.04:95% CI, 4.10--6.20;p<.002) was comparable to or greater than traditional risk factors." See figure 2 in their artcle for details of that comparison.<0 .001...was="" 2="" comparable="" compared="" diabetes="" esrd.="" factors.="" factors="" figure="" greater="" hypertension="" nbsp="" or="" p="" risk="" see="" smoking="" than="" the="" their="" to="" traditional="">

Skeptics of the thesis that there is a "U -shaped"curve relating risk of death to exercise level will perhaps find some comfort in their finding : "There was also no evidence to suggest relative harm associated with extreme levels of fitness in these subgroups of patients"In fairness I should add that no one has claimed that excessive fitness is deleterious but rather the claim has been that excessive exercise may be harmful, again realizing that fitness levels and exercise levels are highly correlated. 

I don't think anyone has claimed that being too fit is harmful to health or lowers longevity. 

Nitpicking aside, their data provide more fuel to the argument that exercise ( or at least CRF) is good and apparently the more the better.

1)Mandsager,k et al "Association of cardiorespiraory fitness with long-term mortality among adults undergoing exercise treadmill testing" JAMA Network open, 2018 1 (6)Oct 19

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Changing status for use of aspirin in primary prevention of heart disease

In the not too distant past based in part  on the results of the Physicians Health Study (1989) and the Women's Health Study (2005) it seemed reasonable to recommend aspirin for cardiovascular disease prevention. Recommendations were typically based on various guidelines that were estimates of a person's risk based on various risk factors such as cholesterol level,Blood pressure, smoking status, family history, etc. Since age is a major risk factor many of elderly are taking low dose aspirin with or without a physicians's advice.Is that still a good idea?

Dr. Paul Ridker in an editorial in the NEJM (1) questions whether the old advice is still justified in light of more recent clinical trial data  and perhaps a changing risk baseline for the population in general. More people now are on medication for blood pressure,fewer smoke and many more now are taking statin drugs than they were at the times of the PHS and WHS.

In the same issue of NEJM 3 primary prevention trials were published. Only the trial in diabetic patients (the ASCEND trial) was there shown to be a statistically signficiant reduction in vascular events with asprin. A 12% reduction is vascular events was countered by a 29% increase in major bleeding and the all-cause mortality was the same in the control and the treatment groups.

The ARRIVE trial was  a primary prevention trial in"high risk " subjects The intention-to-treat analysis showed that the primary outcome was the same in the control and aspirin groups. The primary outcome was a composite of stroke,heart attack,unstable angina,TIAs and death from CV causes.Gi bleeding was twice as common in the aspirin group.

The ASPREE trial was a primary prevention trial in subjects 70 years of age and older who were free of CV disease ,dementia or disability on entry into the study. After five years of 100 mg aspirin a day versus placebo there was no CV benefit .There was more GI bleeding with aspirin ( Hazard ratio of 1.39).

So unlike aspirin's well established  role in secondary CV disease prevention the benefit-risk ratio in primary prevention is ( in Ridker's words) "exceptionally small" . Dr. Ridker has been an advocate of statin use and it is not surprising  that he ends his commentary with: "Thus beyond diet maintenance,exercise, and smoking cessation,the best strategy for the use of aspirin in the primary prevention of cardiovascular disease may simply be to prescribe a statin instead."


1) Ridker, PM Should Aspirin be used for primary prevention in the post-statin era? NEJM 379;16 oct 18 2018. 1572

More physical activity may be needed to prevent HF than some other CVD events

 The title is a reworded version of the title of the article which is designated as reference 2 in the footnotes.

There are  2 (at least 2) epidemiologic studies that indicate a linear dose-response relationship between physical activity (PA) and the risk of heart failure. While one study ( Pandy et al see below) does demonstrate a "modest" reduction in HF risk at a lower levels of PA, both studies report a more robust reduction in HF at higher exercise levels.

Pandy et al (Circulation 2015,, see ref 1 below) did a meta-analysis involving about 370  thousand subjects , 20 thousand of which developed HF over a 13 years period.They compared the HF risk in 3 categories based on level of exercise, namely 500 MET-min per week ,1000 MET-min per week and 2000 MET-min per week.

500 MET-min per week is equivalent to 2.5 hours of "moderate" exercise per week or 1.25 hours of "vigorous" exercise per week.Moderate is defined a exercise requiring 3-5.9 MET and vigorous as about 7 METS. (It requires about7 METS to run a 15 minute mile or to finish Stage 2 on the Bruce protocol treadmill exercise tests. One should be able to walk a fifteen minute mile with a 02 consumption of 5 METS.)

1000 MET-hrs per week is 5 hours of moderate or 2.5 hours of vigorous exercise per week and 2000 as twice that or 10 hours of moderate exercise per week. Yes, that does seem like a lot,

Both the 2008 US exercise  guidelines and the 2018 guidelines recommend at least 500 but state that more benefits accrue with higher levels .

Pandy reported a linear dose response with a "marked reduction in risk at very high doses of PA ( about 35%) at 2000 MET-min per week".This would be 10 hours of moderate or 5 hours ofvigorous aerobic activity.

Their data:
exercise level                                HF RF

500 MET minutes  per week            0.9 (0.87-0.92)
1000 "  " " " " " " " "                       0.81(0.77-0.80
2000 "  "   "   "" """""                     0.65 (0.58-0.73)

Quoting the authors; "Only a moderate reduction ( about 10%) risk in HF noted at the minimal ( US guidelines) recommended level,"

The authors offer a mechanistic explanation namely that CAD event risk reduction occurs at a lower level of exercise by reducing the usual suspect Risk factors (BP,Lipids,blood sugar control) while HF risk reduction occurs at a higher levels of exercise perhaps  by altering cardiac function and structure, i.e beneficial remodeling,perhaps mitigating the age related loss of left ventricular compliance

An earlier article Patel K, (Int J Cardiol 2013 see ref 2) had reached generally similar conclusions regarding the levels of exercise needed to decrease HR risk versus the amount adequate to  reduce general  CV risk,

Patel et al studied 5503 patients age 65 and older
During the 13 years of follow up incident HF developed in:
26% of those with little or no regular exercise
23% of those with "low"level of exercise
20% of those with "moderate"
19 % of those with high .

Low was defined a 1-499 Met-min per week
medium as 500-999
high as greater than 1000

The HRs for incident HF were:
low level exercise     0.87 (0.71-1.06)
medium                     0.68 (0.54-0.85) stat sig 
high                            0.60 (0.49-0.74) stat sig 

All exercise level groups had reduced HR for incident MI, stroke, and cardiovascular mortality but the lowest level group did not have a statistically significant  decrease in HF risk.

These 2 studies indicate that more exercise is associated with greater reduction in HF risk, although some  HF decrease was noted in the lowest exercise group in the Pandy study.

Now for something completely different. A different type of study published by CR de Fillippi from the Cardiovascular Health study ( reference 3) provides an interesting  insight regarding possible mechanism(s) by which more exercise is better in terms of HF risk reduction. 

They studied 2, 9333 subject free of HF at the onset and  who had normal values for two biomarkers, NT-Pro BNP and cTnT (troponin).They then measured these markers every 2 to 3 years and compared incident increase in those markers in groups divided by their exercise levels.(They quantitated exercise using  a particular system and used numerical scores to define groups and I was not able  to translate those values in to MET hrs to compare with the other 2 articles)

 They found compared with the participants with the lowest PA activity scores those with the highest (i.e. more exercise) had an low odds ratio of 0.50 (0.33-0.77) for a significant increase in NT proBNP and an OR of 0.3 for and increase in troponin.  Quoting  the authors "increased levels of NTProBNP and cTnT may reflect pathological precursors of hemodynamic stress and injury that are prevented by PA at some as yet more precisely defined level.

So how to put all this together.

An  appealing ( at least to me) mechanistic explanation is that an overall decrease in CV mortally and arguably a slight reduction in HF risk  can be brought about by modest exercise and even  perhaps slightly less  than modest levels  by reducing the usual suspect,traditional CVD risk factors.Modest here refers to about 500 MET hrs per week. but some studies have shown a decreased heart attack risk at even lower exercise levels.

A more robust risk reduction in HF risk (perhaps 20-35%) seems  to require higher levels of exercise  ( in the 1000 Met-hrs per week range and higher) by perhaps bringing about an advantageous remodeling of the heart or at least a mitigation of the deleterious remodeling of the heart than occurs with sedentary aging which in turn may predispose to the development of heart failure with preserved ejection fraction (HFpEF).

To the extent that CVD risk factor reduction can decrease heart attacks and the  accompanying reduction in   heart function some reduction in HF risk would be likely, i.e.some reduction in heart failure with reduced ejection fraction ( HFrEF). But at least half of cases of HF are not associated with decreased systolic function ( at least as measured by the ejection fraction  (EF)) but by the echocardiographic findings of decreased left ventricular compliance and distensibility which according to the work of Dr. Ben Levine and others at SW  Medical School in Dallas predispose to diastolic heart failure  (HFpEF) .That group suggests that at least 30 minutes of exercise 4 to five times a week might be sufficient to prevent that age related loss of cardiac compliance. ( see ref 4 below for more on this argument) and perhaps prevent at least some cases of HFpEF. It would be nice if as little as 30 minutes 5 times a week would be sufficient.


1)Pandy,A "Linear,dose dependent inverse association between PA(physical activity) and heart failure risk Circ. 115.132 p 1786-1794

2.Patel K. "Prevention of heart failure in older adults may require higher levels of physical activity than needed for other cardiovascular events." Int J Cardiol. 2013, Oct 168 (3) 1905-1909)

3)de Fillippi, CR "Physical activity, change in biomarkers of myocardial stress and injury, and subsequent heart failure risk in older adults. JAm Coll Cardiol.. 2012 Dec. 18;60 (24), 2539-47

4) Bhella, PS  "Impact of lifelong exercise "dose" on left ventricular compliance and distensibility"J Amer coll cardiology. 2014 , 64, no 12,p 1267  


Addendum 7/13/20 In the table of Pandy's data I had erroneously type Met hr instead of Met minutes.

2018 U.S. exercise guidelines-or how exercise is good for just about everything

The 2018 Physical Activity Guidelines Advisory Committee issued its report to the Secretary of HHS in February 2018.See here for link to full report.

Their prescription for exercise was unchanged from their 2008 recommendations.  They recommend 2.5 to 5 hours of moderate to vigorous exercise per week. This can also be expressed as 500 to 1000 Met-minutes per week. "Moderate" is defined as exercise requiring between 3 and 5.9 METS and "vigorous" as greater than 6 METS.

To put those numbers into perspective , consider than it would require about 7 METS to run a fifteen minute miles and about 5 METs to walk a fifteen minute mile and about 9 METS to run a 12 minute mile. It requires about 7 METS to complete Stage 2 on the Bruce treadmill protocol .A MET is 3.5 ml of oxygen per kilogram weight per minute. 

Now, about how exercise (physical activity or PA) is good for just about everything. 

The 2008 exercise guidelines reported that PA could lead to a reduction in risk of breast cancer and colon cancer . The 2018 reports adds the following cancers to those whose risk is reduced by PA :
bladder, lung, esophagus, endometrium and stomach.But reduction in heart disease risk is the major selling. point for an exercise program as well as decrease in diabetes and hypertension risk. 


The publication also offers evidence of a risk reduction for dementia and depression.

If the benefits of exercise could be achieved by a daily  pill, everyone would be taking it.

The impressive and alarming success of the American Board of Internal Medicine Foundation

The American Board of Internal Medicine Foundation (ABIMF) is not the largest,most heavily endowed nor the best known of the many non-profit organizations who  function as advocates for various aspects of health care and medical practice. However, its success in promulgating concepts and influencing medical practice and health care seems disproportionately greater than one might expect based on its size. ABIMF's "greatest" achievement may be the development and promulgation of the notion of Medical Professionalism and its major tenets: patient welfare,patient autonomy and social justice. The insertion of the later tenet into medical ethics is a major departure from traditional ethics and is destructive to the physician patient relationship

The first two tenets were long standing pillars of medical ethics and practice and dealt with the relationship between the physician and patient but in 1992, their efforts along with the ACP Foundation and a European Group proclaimed that part of medical professionalism included what they believed was the proper relationship between the physician and society

This  manifesto was published in the Annals of Internal Medicine in 1992 in a paper entitled Medical Professionalism in the New Millennium-A Physician Charter. The ABIF has continued after the 1992 paper to promote the primacy of patient welfare,patient autonomy and social justice and to advocate for "a just and cost effective distribution of finite resources".


 The notion of a co-duty,one to the patient and one to society,was not previously a part of western medical ethics.The 1991 edition of the AMA ethical code did not mention social justice or stewardship of society's resources. Cost effective care is the major thrust of the foundation's recent initiative called "choosing wisely" .  By 2012 over 100 other medical professional organizations had signed on to the Charter and education along those lines apparently is taking place in a number of medical school according to a 2012 article in the Annals of Internal Medicine.

It is the ABIM's MOC  ( Maintenance of Certification program ) that has caused the most angst for internists and reliable reports of its very questionable financial activities have triggered an unprecedented uprising  which surprisingly has had more than a little success.( Much credit for this is due to Dr. Wesby Fisher who on his blog has reported activities of the ABIM and the ABIMF that are  egregious and arguably illegal.)

Yet the sea change in the discussion about medical ethics and professional behavior importantly driven by the same folks who gave us MOC  may in the long run be even more damaging.

Is the minimal level of recommended exercise sufficient to decrease the risk of heart failure?

In January 2017, I posted a blog commentary entitled " The minimum exercise levels of  the 2008 guidelines won't prevent heart failure". See here.

The gist of that commentary   was that the adherence to the minimal exercise levels indicated by the guidelines had been demonstrated by ample epidemiologic studies to reduce the incidence of cardiovascular disease (CVD) but  exercise at that level had not been demonstrated to reduce   heart failure (HF) incidence and that a higher amount of exercise was needed.

Since then I have more carefully studied a 2015 epidemiologic paper  by Pandy,which I had read before but obviously not with adequate attention , and a detailed physiologic comparison of cardiac function by Bella et al  in 4 groups of healthy subjects who varied  in their long term exercise levels to which I also had not paid appropriate attention. 

These considerations   resulted in a major revision my 2017 headline to " Adherence to the 2008 guideline will reduce HF incidence but more exercise will reduce HF risk significantly more"

Note: I have added an addendum to the 2017 posting  stating the headline is simply wrong 

So now to try and clean up the earlier erroneous  commentary .

First a review of some background:

The 2008 US and WHO guidelines recommend a minimum of 150 minutes of moderate exercise per week or 75 minutes of vigorous exercise. This corresponds to 500 MET minutes  per week or 8.3 MET hours .The US panel also said that further gain could be made by increasing that level to twice that amount. Moderate intensity was defined as requiring between 3 and 5.9 METS and vigorous greater than 6 METS.Note-the panel was addressing the risk of cardiovascular disease in general and not heart failure risk per se .

There is universal agreement that aerobic exercise will decrease heart disease risk ( and according to some studies-dementia,some cancers and type 2 diabetes) but there is disagreement as regards how little exercise  might be  sufficient to reduce cardiovascular risk  and how much exercise might be harmful. I leave those 2  questions  to another time.

In regard to HF:

Patel et (1) published a 2013 review of 5503 subjects age 65 and older from the Cardiovascular Health Study .They divided participants into inactive ,low level exercise ( 1-499 METS),Medium (500 to 999 METS )and high was defined as  greater than 1000 METS 

The hazard ratio (HR) for the low group was a non-statistically significant 0.87 (0.71-1.06,p=0.170.

The medium groups HR 0.68 (0.54-0.85)p=0.001

The high group HR 0.60(0.49-0.74, p=0.026<0 .001.="" p="">

Note that  the low and medium groups overlap the 500 level so  no conclusive verdict regarding HF risk reduction with 500 MET level can be made. You can say that the lowest exercise group enjoyed no reduction in HF risk but we do not know how many subjects were closer to the 1 than to the 500 level. We can say that the medium and high level  did demonstrate a HF  risk reduction but can conclude  nothing about the value of exercising at the 500 MET min level,which is the minimal level recommended by the 2008 panel. 

However, from Pandy's 2015 meta-analysis (2) that there demonstrable risk reduction  in HF in a group of subjects exercising at the 500 MET level. The authors examined data that included over 20 thousand HF events among 370 thousand participants in some 12 prospective cohort studies. 

The 500 MET-min  per week group had a reduction in HF risk ( HR-0.9 (0.81-0.92). However, a greater risk reduction was found in the 1000 MET Min per week group ) HR-.81 (0.77-0.86) and even greater reduction 0.65 (0.58 -0.73 ) in the group at the 2000MET min per week which corresponds to 10 hours of moderate exercise per week or 4 times the minimal amount suggested by the 2008 guidelines.

So the epidemiology  data indicate  that the lower level of recommended exercise will cause a measurable decrease in HF risk but in that regard more does seem to be better.Now to consider Bella's (3) physiological data which is consistent with Pandy's analysis.

 The following  2 paragraphs are copied from my earlier blog commentary.

" Dr Paul Bhella and his  associates  did extensive physiological studies on four groups of healthy volunteers over the age of 64. Four groups were designated   on the basis of their exercise history for the preceding 25 years. (not a typo) 1) sedentary-no more than one exercise session per week  2) casual exerciser-2-3 session per week 3) "committed" exercisers-4-5 session per week and 4)competitive master level athletes -6-7 session per week and competed regularly.  All had normal systolic function ( as defined by a normal resting ejection fraction) but groups one and two has decreased left ventricular compliance while the committed and competitive groups had left ventricular pressure volume curves and left ventricular masses similar to young healthy controls. ( see here for my  further comments and a few caveats regarding this paper including reference to Tanaka's work that challenges the notion that long term endurance exercise  does in fact preserve  ventricular compliance)

Quoting Bhella ". . at least 30 minutes of dynamic exercise per session for 4-5 days per week over a lifetime can  sufficiently prevent most of the decreases in LV compliance and distensibility observed with sedentary aging"

It appears that training at triathlon or marathon levels is not necessary to decrease long term risk of heart failure but the exercise has to be persistent. The term "lifelong "used by Bella may be an exaggeration but his subjects had a 25 year history of regular aerobic exercise.

Bella's data seems to confirm the notion that the 2/12 hours per week recommendation just might decrease the risk of HF with the caveat " if done over a long period of time". The same  group has subsequently published data showing that beginning a  more intense exercise program in a person's 60s or 70's will not result in improved left ventricular compliance but , of course, one would expect  health benefits.

I quote a key paragraph from Bella:

"This study's key finding is the novel observation tcompliance that at least 30 minutes of dynamic exercise per session 4  to 5 days per week over a lifetime can sufficiently prevent most of the decrease in and distensibility observed  with sedentary aging.
This finding holds important implications for global health as ventricular stiffening has been implicated in the pathophysiology of many common CV conditions affecting the elderly."

Contrary to my earlier commentary the minimal levels of exercise may well be enough to decrease the risk of HF but exercise at about twice that levels is likely to bring about a more significant reduction. Note that Bella's comment of 30 minutes 4-5 days a week corresponds to the minimal recommendation of 150 minutes of moderate exercise per week.

1)Patel,K et al Prevention of heart failure in older adults may require higher levels of  physical activity than needed for other cardiovascular events.Int j Cardiol 2013 1905,-1909.

2)Pandy, A Dose Response relationship  between physical activity and risk of heart failure.A meta-analysis. Circulation 2015 132 1786-1794

3)Behlla,P Impact of lifelong exercise "dose"on left ventricular compliance and distensibility. JACC 64 1257-1267 2014  

Does the notion that people have a duty to be healthy shatter traditional medical ethics

First lets define what we mean by traditional medical ethics.This would include the medical ethical precepts that constituted medical ethics before the announcement of the "New Professionalism" by the ACP and others. Basically and stating it informally it is that the physician has a fiduciary duty to the patients, and he should place the patients interests before his and of course first do no harm.

Keeping those precepts in mind, consider the following statement which is typical of a growing trend in medical commentaries .

People ( patients) have a duty to be healthy ( practice "healthy behaviors" and eschew "unhealthy behaviors") and comply with medical advice for the good of healthy population.

Drs. JF Wharam and D. Salmasy, writing in the Jan. 14,2009 issue of JAMA. In their discussion of P4P arrangements they state:

...policy makers, health care executives,disease advocates, and scientists with clinical or epidemiological expertise effectively choose population-level goals and thus impose obligations in a manner that might ( my italics) infringe on patient and physician autonomy. Without fair deliberation,such goals, however wise, cannot claim legitimacy

I suggest that the word "might" be deleted from the above quote. It will infringe. Further, it is not clear what would constitute "fair" deliberation.When someone begins to talk about being fair,watch out.So with "fair deliberation " such claims ( if wise) are , according to the authors therefore  legitimate.



When physicians get some of their income by meeting certain population based goals( e.g. have x% of patients with a hemoglobin A1c under some number) patients who might seem to eat too much or not always take their medicine or whatever else might  be perceived  by the physicians as getting in the way of the population based goals and keeping  the doc from her bonus.Again it is issue of serving two masters,the real life patient in the exam room  versus some insurance based collective construct.