Featured Post

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 ...

Tuesday, June 12, 2018

age related decline in exercise capacity is not just decrease in 02 max

It has been suggested that the study of the physiology (pathophysiology?) of aging might be informed by the study of aging athletes.

Analyzing information about Ed Whitlock,thought by some to be the greatest "ancient marathoner" ever, may offer some interesting insights.See here for more regarding Whitlock.

02 max measurements were made on Whitlock at age 70 (52.8 ml,/kilo/min)) and age 81 (54ml/kilo/min).

At age 72 he ran a 2:54 marathon and at age 82 his marathon time was 3:41.So his running time decreased significantly from 6.62 minutes per mile to 8.4 minutes per mile.His speed decreased from 9 miles per hour to 7.11 miles per hour, a 20% decrease.  Yet during that same time period his measured maximal oxygen uptake was unchanged. We also know from  published interviews  that his training did not significantly diminish. So what was the cause(s) of his decreased running speed?

The decade of the the 70s is generally said to be one in which the age associated decrease exercise capacity seems to accelerate. and 15 to 20% decrement per ten years have been reported.A reasonable assumption is that a major factor in that decrease is decrease in 02 max. Yet Whitlock's 02 max was unchanged while his running speed decreased in the range typically said to occur in normal humans.

Similar data on other runners have demonstrated that running speed for distance running decreases proportionally greater than the temporal decrease in 02 max.However, in cyclists a different pattern is seen with the 02 max and speed decreasing more proportionately .

It is tempting  to evoke the role of the pounding of the legs in running versus cycling. The long time distance runner and exercise physiologist, Tim Noakes ,has opined about the long term effect of "pounding" on decline in exercise capacity.The constancy of Whitlock's 02 max and the 20% decrease in marathon times from early 70s to early 80 reminds one of the high school coach's aphorism "you are  only as young as your legs".

Could some answers be found in study of titin and its isoforms?Titin (aka connection) is the body's largest protein and is said to act like a spring for muscles, recoiling the sarcomere after it is stretched.

There is a short,stiff isoform ( N2B) as well as other more elastic isofroms ( e.g. N2BA ) . The phosphorylation of titn results in a post translational modification of titin with production of more elastic isoforms. Beta adrenergic stimulation may increase the phosphorylation of titin.

The stiffer ventricular muscles of patients with diastolic heart failure have less of the more elastic titin isoform and more of the shorter stiffer titin isoform.

Titin may or may not play a role -probably more than one factor conspire by a number of mechanisms to cause runners in their seventies to loose much of the "spring in their steps."even if their cardiac output changes little even though a constant cardiac output over that 10 years period is likelyvery far out on the curve.






Friday, May 11, 2018

Is ablation better than drugs for A FIb? What did CABANA trial show?

The results of the Cabana trial were presented at the Heart Rhythm Society meeting in May 2018. The full results will be published later. Here is Larry Husten's reporting in Forbes.

The intention-to-treat (ITT) analyses indicated there was no statistically significant difference between ablation and drug treatment in regard to the primary outcome which was the total of death,disabling stroke, serious bleeding and cardiac arrest.

On the other hand the per-protocol analysis (PPA) gave different results indicating  an advantage to the ablation group.

It got down to a battle of the Packers. Dr Doug Packer,who presented the data,said that the per protocol analysis should trump the ITT, while Dr. Milton Packer seemed to think that venerable epidemiologic principles would be violated if one did not follow the ITT analysis.

There is already talk of the need for a sham trial  and EP cardiologists talking about sub-group analysis (ablation maybe better in those under 65 years of age and in those with heart failure) and touting the quality of life benefits of ablation .

One obvious problem (many more will likely be talked about) was the drug treatment group was not homogenous-it  included both rate and various rhythm  control strategies.  

Since there seems to be a battle between the ITT folks and the PPA supporters ,for those who might want to drive deeper into the issue , here is a place to start.

Thursday, May 03, 2018

Argument for aerobic exercise in patients with Parkinson's disease.

There ae no randomized clinical trials that demonstrate the benefit of regular aerobic exercise in delaying the progression of Parkinson's disease  (PD) nor in the decrease in the risk of development of dementia.However the Mayo Clinic has published an excellent review of the literature regarding  the beneficial effect of exercise on various brain areas and functions. See here.

Quoting the authors : "This aggregate literature provides a compelling argument for regular aerobic exercise and cardiovascular fitness attenuating PD progression."


h/t to Dr. Robert Donnell at his blog "Notes from Dr. RW" .


Monday, April 09, 2018

People who are more fit have less atrial fibrillation and less strokes if they develop AF


Individuals who are more fit ( have a higher functional aerobic capacity) are less likely to develop atrial fibrillation (AF) and if they do develop AF they are less likely to have a stroke or die.

These are the conclusions from a long , large study from Mayo Clinic.See https://www.ncbi.nlm.nih.gov/pubmed/29221502. ref 1

The final study cohort included 12043 patients referred for a treadmill exercise test and were followed for a median time of 14 years (9-17).They were classified into four groups based on functional aerobic capacity (FAC) .Each 10% increase in FAC was associated with an decreased risk of incident AF ,stroke and mortality by 7 %.

Was the decreased risk observed in the more fit due to a direct physiological effect of exercise or a result of the reduction in the standard risk factors observed in the more fit individuals  or is that a distinction without a difference?

Folks who may be accused of exercising too much may find some satisfaction in the data revealing no level of fitness above which there was an increased risk of AF.In other words they found no "U-shaped curve" regarding level of exercise ( or more properly of fitness as this study did not measure exercise level) and AF risk.




1)Hussain, N, Impact of cardiorespiratory fitness on frequency of atrial fibrillation,stroke and all cause mortality. Am J Cardiol 2018, Jan 1, 121 41-49

Thursday, April 05, 2018

More on the "lying"or at best really stupid electronic medical record

My medical record at a well known medical center -which shall remain nameless-has labelled me as having atrial fibrillation and it seems to be written in indelible electronic ink refractory to my attempts to erase it.

It came about because of two computers conspiring  together. The first was the computer inside of my pace maker.Its algorithm to detect atrial fibrillation detected signals which were interpreted at "AT/AF", meaning atrial tachycardia/ atrial fibrillation. It was a false positive call , tricked by a Pacemaker phenomenon called far field sensing. This occur when the sensing lead in one cardiac chamber senses activity in the other chamber and miscounts it. Ultimately the Medtronic tech recognized it and adjusted the atrial lead sensitivity so that the double counting would not occur. Problem fixed but..

The second computer, my electronic medical record (EMR) latched on to the "diagnosis of atrial fibrillation and will not let go. I have written my "patient portal" with a full explanation indicating that my EP cardiologist concurred.

Recently, I met with my new primary care internist and we discussed my Blood pressure, my pacemaker and no mention was made of AF.He never said the words atrial fibrillation.I gave him two of my old EKGs which did not show atrial fibrillation . Yet when he gave me a copy of my patient visit summary my current health issues were said to be 1.pacemaker 2.atrial fibrillation.

Did the computer write the second diagnosis on its own. Did the doc see it, did he even read what was printed out? I cannot believe he even saw it. I cannot believe a board certified internist of over 25 years experience would not have asked why was I not taking an anticoagulant as my CHADS2-VASc score of 3 would warrant anticoagulation according to all guidelines.In the days of the paper medical record can one imagine an internist handing a patient a report that said he had atrial fibrillation when he was aware of no evidence that he in fact had AF?

Of perhaps less significance, my printout also listed a physician who I had never seen, never heard of before and apparently is a pediatrician not even affiliated with the hospital.

The computer systems with which physicians try to make "meaningful use" were  designed to assist coding and quality reporting and have little to do with really improving patient care and often have the opposite effect and not infrequently are harmful.




Tuesday, March 20, 2018

If endurance exercise is the fountain of youth how much do you have to drink?

The arc (s?) of the normal aging heart -

One of the stories told  by physiologists and cardiologists regarding the age related downhill course of cardiac function is something like this.

One way to simplify  cardiac function is to consider the two parts of the cardiac cycle,1) contraction and ejection of blood and 2) relaxation and the refilling of the ventricle.

There are data indicating that the first signs of an impending problems are seen in the filling phase ie. diastole.From extensive echocardiographic and invasive physiologic measurements in humans the following sequence can be sketched out.

First there is impaired relaxation following by decreased elastic recoil and later diminished  compliance ( which is to say increased stiffness) and then -at least according to work from the EEM group- remodeling of hearts with thicker walls and smaller ventricular volumes).Simply put a sedentary ageing  lifestyle leads to a small stiff heart and long time endurance exercise leads to a larger more easily filled heart.The contractile function of the heart is well preserved with ageing , at least as indicated by measurement  of the ejection fraction.

This is largely consistent with the mainstream echocardiographic model which proposes a predictable,progressive process beginning with impaired relaxation,followed by decreased compliance and ultimately- as a compensation- elevated filling pressures.This model describes three phases of diastolic dysfunction indentifiable by combination of echo findings believed to reflect  how well or poorly blood flows into the ventricles from the atrium. This model recognizes that the various indices ( e.g E/A ratio, IVRT,maximal E wave velocity and the time constant of isovolumic pressure decay (Tau) change with age so that what would be abnormal in a 20 year old is normal in a 75 year old.It is thought that that filling pressure can be estimated by use of this model. NOTE-see end note 1 for reference to data that challenges the mainstream model by in part  providing data that cardiac cath measurements of left sided pressures do not regularly correspond with the three echo defined stages of diastolic dysfunction)

Now we look at what I have labelled as the "Dallas or EEM theory" of cardiac ageing. see end note 2

A series of articles from the University of Texas Southwestern Medical School and the EEM have provided extensive invasive and noninvasive data regarding cardiac function at various ages and the effect of longtime endurance exercise versus sedentary ageing on  cardiac structure and function.

Levine et al first demonstrated that lifelong endurance athletes ( 25 years or more of running a lot) had left ventricular compliance virtually identical to those of sedentary 20-30 years olds. Then they compared ventricular compliance in four groups of 25 each of people who exercised at various levels over a 25 years period. These were all subjects over the age of 64 and were screened to excluded pre-existing heart disease.Group 1 was sedentary people who exercised no more than one session per week. Group 2 were labelled "causal exercisers" and exercised 2-3 times per week. Group 3 (Labelled as committed exercisers}worked out 4-5 times per week and the "competitive" group trained 6-7 times per week and regularly raced.The racers had the most elastic ventricles while group 3 was "very close" in terms of ventricular compliance while groups 1 and 2 has significantly stiffer hearts.

Next Levine studied a group of 70 year old subjects  and an exercise program was unsuccessful in improving the reduced compliance observed in that group. Next a study was able to show that middle aged subjects with a year long exercise program ( that involved in part high intensity interval training) was able to increase their ventricular compliance.


My main question in this regard is "how much exercise "is sufficient to maintain a healthy compliant left ventricle." Levine's amazingly compliant  (pun intended) subjects not only stuck with program for a full year but after the first 6 months participated in a hig intensity interval program using the 4X4 workout program that involves 4 minutes of exercise at 95% of maximal heart rate followed by 4 minutes of rest done four times.


End note 1. Grant et al (Grant A, Grading diastolic function by echocardiography:hemodynamic validation of existing guidelines.Cardiovascular Ultrasound 2015 513 :28) compared echocardiography results with  left heart catherization data in 460 patients.The data demonstrated that there were no differences in regard to left ventricular pressures between patients with normal diastolic function and those with grade 1 or 2 diastolic dysfunction but there were differences between normal and grade 3 diastolic dysfunction in patients with reduced ejection fraction.In those patients with preserved EF, there is no statistical difference between normal and any grade of diastolic dysfunction. (see figure 5 of their article which graphically illustrates the lack of the "predictable, progressive process "which characterizes the  current paradigm.)If the detection of elevated LV pressures which generally correlates with exertional shortness of breath is in part the goal of echo studies of diastolic function it appears to not be reached based on Grant's data.

end note 2. Dr Ben Levine is the founder and director of the Institute for Exercise and Enviromental Medicine (EEM) housed at the Texas Health Presbyterian Hospital Dallas and professor at University of Medicine Southwestern. His group have done a series of comprehensive physiological studies on subjects recruited from the Dallas Heart Study, a population based sample of 6100 subjects in Dallas .
In a nut shell the concept is that everyone with aging develops some degree of diastolic dysfunction related to impaired relaxation and loss of diastolic suction,Later aging (particularly sedentary ageing) is associated with loss of ventricular compliance ( AKA increased stiffness). A long term endurance exercise program is capable of mitigating the changes in compliance but not the decrement in relaxation and diastolic suction. EEM's studies  further indicate that a sedentary lifestyle may lead to a small stiff heart which may be the precursor to heart failure with preserved ejection fraction (HFpEF) ) and the Dallas group suggest that an appropriated amount of endurance type exercise begun no later than early middle age may play an important role in the prevention of HFpEF.

"Humans are pattern-seeking story -telling animals and we are quite adept at telling stories about patterns, whether they exist or not".Michael Shermer.
In 2008, Shermer coined the term "patternicity" -the tendency to find meaningful patterns in meaningless noise. I am not suggesting that the extensive,very carefully done research referenced above is meaningless noise.I just really like the quote but I certainty hope the "Dallas hypothesis" ( my term) proves to be of significant value, having spent a lot of time running a lot over the years.

Sunday, March 18, 2018

Mitochondrial function in octogenarian endurance athletes

Scott Trappe from Ball State University and colleagues from the Karolinska Institute studied 9 lifelong endurance athletes 80 years of age or older  with 6 healthy 80 years olds who did no regular exercise. Aerobic capacity and muscles biopsies -done to measure levels of oxidative enzymes- were compared between the two groups.

The muscle biopsies showed high levels of citrate synthase and beta hydoxyacyl-Co A dehydrogenase in the athletes said to reflect the oxidative potential of the mitochondria. These values were similar to those from untrained young subjects.Quoting the authors: " It is important to note that mitochondrial function normally declines with age and this decline does not appear to be reversible with endurance training in sedentary adults greater than 80 yr old or very old animals." This implies that one has to start earlier and maintain some level of regular aerobic exercise to keep your muscle mitochondrial young.

I have commented  before on the impressive aerobic capacity of select elite older athletes.see here.Trappe'sathletes had measured maximal oxygen uptakes of 38 +/- 1 while the healthy controls averaged 21+/1/ .(O2 max in the range seen in the athletes would roughly correlate to the levels seen in someone able to run a 26.2 marathon in 4 to 4/1/4 hours,A 21 02 Max should allow someone to finish stage 1 of the Bruce treadmill protocol and into the second stage but likely not to completion of Stage 2.)Stage 1 Bruce protocol corresponds to 5 Mets roughly equivalent to walking a 15-16 minute mile and  to be able to finish Stage 2 corresponds to 7 Mets roughly equivalent to jogging a 15 minute mile.

Trappe's article is entitled "New Records" but as amazing as these guys were aerobic wise an Englishman transposed to Canada is one rung above on the aerobic scale. Ed Whitlock at age 80 finished the Toronto Marathon in 3 hours and 15 minutes.Using table 2.3 from Tim Noakes's book ,4 th edition The Lore of Running this time would correspond to an estimated  V02 Max of 50-55! See end note 1





1) Trappe S Et al New Records in aerobic power among octogenarian lifelong endurance athletes.J. Applied Physiology 114.3-10 2013.

End note 1.Rather than considering estimated 02 max from a table we can see actual measured values done on Ed Whitlock on two occasions. From the excellent blog entitled "Canute's efficient Running Site" we learn that just before his 70th birthday Whitlock's measured V02 max was 52.8 and at age 81 it was measured at a physiology lab at McGill to be 54!. Assuming that the difference between 52.8 and 54 was just normal test-retest variation, Whitlock seemed to loose no aerobic capacity over a ten year period. Conventional   wisdom and more than a little data indicate that the 70-80 decade is typically a time period in which there is an accelerated decline in 02 max,perhaps twice that of the 10 % per decade decline than is widely quoted. Whitlock did not get the memo.The VDOTvalues that are referenced on Canute's website and found in detail on Jack Daniel's VDOT Running Calculation web site appear to give more realistic estimates of running times that those that I have been using for comparison with exercise testing comparison that those  found on Noake's table.


addendum: End note 1 was completely redone after discovering Canute's web site.