Steve Stiles
Posted: 07/17/2012

July 17, 2012 (Updated July 18, 2012) (Mountain View, California) — The FDA has approved the weight-loss drug Qsymia (formerly named Qnexa; Vivus, Mountain View, CA), which now joinslorcaserin (Belviq, Arena Pharmaceuticals, San Diego, CA) as the first anti-obesity medications to enter the US market since 1999. News of the agency's decision was announced late Tuesday.

Qsymia, a controlled-release preparation of phentermine andtopiramate in one capsule, is now indicated for use in adults with a body mass index (BMI) >30 kg/m2 or adults with a BMI of >27 kg/m2and at least one weight-related condition such as hypertension, type 2 diabetes, or dyslipidemia.

The approval is accompanied by a Risk Evaluation and Mitigation Strategy (REMS), including a medication guide advising patients about important safety information and specific requirements for prescriber training and pharmacy certification. The drug "will only be dispensed through specially certified pharmacies," according to the FDA statement. Of special note, the drug must not be used during pregnancy; details about the risk of the drug combo in pregnant women are included.

The agency's statement also notes that the drug can increase heart rate, which warrants regular monitoring, and should be used with caution in people with recent unstable heart disease or stroke. The sponsor will be required to conduct a long-term, postmarketing cardiovascular outcomes trial to assess the effect of Qsymia on the risk of major adverse cardiac events.

In February, an FDA advisory panel voted overwhelmingly in favor of the drug's approval for obesity, despite some concerns about possible adverse effects, as reported by heartwire .

The agency then took the step--not unusual in such cases--of giving the company a three-month extension on the period during which it could review its application, which ended today. That allowed the FDA to consider the REMS for Qsymia that Vivus had submitted on April 4.

Many on the advisory panel had stated that their vote favoring Qsymia--it was ultimately 20 to 2--assumed that the company would in fact submit and implement a REMS, parts of which Vivus described at the hearing. That regulators granted an extension to facilitate that process was as good a sign as any that it was leaning toward a positive decision.

Both the FDA and its advisory committee had decided against approval of Qsymia during its first round of consideration in October, 2010, pending a more comprehensive safety assessment. Lorcaserin had followed a similar path in the premarket process, having been denied approval the same week for similar reasons; the agency approved lorcaserin just a few weeks ago.

Many people eagerly watching the web for breaking news on the FDA's decision were confused by a mid-day story by USA Today announcing approval: apparently a 'best guess' story, prewritten, that accidentally went live online before the final word came down.

That story proved prescient, but was not confirmed until much later in the day.

Obtained from MedScape...
MARCH 19, 2012
Lisa Nainggolan 

London, UK - A 23-year-old British soccer player remains in critical condition in the hospital today after suffering a cardiac arrest during a game on Saturday evening. Fabrice Muamba, who plays midfield for the club Bolton Wanderers, collapsed in the 41st minute of the match at Tottenham in London and was quickly attended by doctors for both clubs, as well as a consultant cardiologist who happened to be in the crowd, Dr Andrew Deaner(London Chest Hospital), who reportedly insisted that the player be taken to his specialist unit.

Muamba received prolonged resuscitation on the ground and en route to the hospital, where his heart eventually started working. The quick treatment he received has been praised. He is still under sedation in intensive care at the London Chest Hospital.

The case has received unprecedented media attention and led to calls for universal national screening of soccer players and other athletes in the UK, as is done in Italy. However, as it's likely that Muamba—as an elite soccer player—would have been screened, one cardiologist told heartwire she believes he may have a very rare condition.

Dr Sarah Clarke (Papworth Hospital, Cambridge, UK), vice president of education and research at the British Cardiovascular Society, says: "[Muamba] would have been deemed fit and healthy from what we can gather; his heart is to all intents and purposes normal, so this has to be more of an electrical or electrolyte imbalance or an ion-channel abnormality, one of those rare genetic problems that can present in this way." It's important to note that "less than 1% of cardiac arrests that occur out in the community will be this healthy-heart/ion-channel electrical-abnormality group, of which we are surmising—from what we know—that he is likely to fall into," she says.

Dr Stephen Cox (Cardiac Risk in the Young [CRY], Tadworth, UK) told heartwire that, in the UK, 12 people under the age of 35 die every week, or 600 per year, from sudden cardiac death.

More widespread screening would help identify more affected individuals and save lives, he says. But he too believes Muamba would "have been screened because he was a [Football AssociationAcademy player, and they have a strong screening program, and it's not just ECG, he would have had ECG and echo as a routine. They are one of the few sports [in the UK] to have instigated it to that level."

But "there are certain conditions that will not be detected through screening," Cox added. CRY's consultant cardiologist, Dr Sanjay Sharma (St George's Hospital, London), who runs Britain's only cardiac unit for sportspeople and who is official cardiologist to the London 2012 Olympic Games, told the Independentnewspaper that 80% of conditions causing sudden death will be picked up by screening. "I am surprised the heart problem was not picked up. The medical screening these players get is extremely comprehensive".

Muamba was born in Kinshasa, Democratic Republic of the Congo, and came to the UK at the age of 11 after his father was granted political asylum here. Asked whether Muamba's background might hold any clues as to what happened on Saturday, Cox said that any heart damage, such as myocarditis from rheumatic heart disease, would have been seen on echo: "Something like that would have been identified on screening."

Cox added that one of the areas of research at his organization involves looking at ethnicity and how this affects the interpretation of ECG and other screening.

In 2005, the European Society of Cardiology recommended screening of young people taking part in competitive sport, a move that was then endorsed by the International Olympic Committee (IOC), says Cox.

Obtained from heartwire... 

MARCH 12, 2012
Lisa Nainggolan

Boston, MA - Sugary drinks are associated with an increased risk of coronary heart disease (CHD) as well as some adverse changes in lipids, inflammatory factors, and leptin, according to a new analysis of men participating in the Health Professionals Follow-up Study, reported by Dr Lawrence de Koning (Children's Hospital Boston, MA) and colleagues online March 12, 2012 in Circulation [1].

"Even a moderate amount of sugary beverage consumption—we are talking about one can of soda every day—is associated with a significant 20% increased risk of heart disease even after adjusting for a wide range of cardiovascular risk factors," senior author Dr Frank B Hu (Harvard School of Public Health, Boston, MA) toldheartwire. "The increased risk is quite substantial, and I think has important public-health implications given the widespread consumption of soda, not only in the US but also increasing very rapidly in developing countries."

The researchers did not find an increased risk of CHD with artificially sweetened beverages in this analysis, however. "Diet soda has been shown to be associated with weight gain and metabolic diseases in previous studies, even though this hasn't been substantiated in our study," says Hu. "The problem with diet soda is its high-intensity sweet taste, which may condition people's taste. It's still an open question whether diet soda is an optimal alternative to regular soda; we need more data on this. "

Hu says water is the best thing to drink, or coffee or tea. Fruit juice is "not a very good alternative, because of the high amount of sugar," he adds, although if diluted with water, "it's much better than a can of soda," he notes.

And Hu says although the current results apply only to men, prior data from his group in women in the Nurses' Health Study [from 2009] were comparable, "which really boosts the credibility of the findings."

Inflammation could be a pathway for impact of soda upon CHD risk
Hu and colleagues explain that while much research has shown a link between the consumption of sugar-sweetened beverages and type 2 diabetes, few studies have looked at the association of these drinks with CHD.

Hence, they analyzed the associations of cumulatively averaged sugar-sweetened (eg, sodas) and artificially sweetened (eg, diet sodas) beverage intake with incident fatal and nonfatal CHD (MI) in 42 883 men in the Health Professionals Follow-up study. Beginning in 1986 and every two years until December 2008, participants answered questionnaires about diet and other health habits. A blood sample was provided midway through the study.

There were 3683 CHD cases over 22 years of follow-up. Those in the top quartile of sugar-sweetened-beverage intake had a 20% higher relative risk of CHD than those in the bottom quartile (RR 1.20; p for trend <0.001) after adjustment for age, smoking, physical activity, alcohol, multivitamins, family history, diet quality, energy intake, body-mass index, preenrollment weight change, and dieting.

Adjustment for self-reported high cholesterol, high triglycerides, high blood pressure, and diagnosed type 2 diabetes only slightly attenuated these associations, which suggests that drinking soda "may impact on CHD risk above and beyond traditional risk factors," say the researchers.

Consumption of artificially sweetened drinks was not significantly associated with CHD (multivariate RR 1.02; p for trend=0.28).

Intake of sugar-sweetened drinks, but not artificially sweetened ones, was also significantly associated with increased triglycerides and several circulating inflammatory factors—including C-reactive protein, interleukin 6 (IL-6), and tumor-necrosis-factor receptor 1 (TNFr1)—as well as decreased HDL cholesterol, lipoprotein (a) (Lp[a]), and leptin (p<0.02).

"Inflammation is a key factor in the pathogenesis of cardiovascular disease and cardiometabolic disease and could represent an additional pathway by which sugar-sweetened beverages influence risk," say Hu et al.

Cutting consumption of soda is one of easiest behaviors to change
Hu says that one of the major constituents of soda, high-fructose corn syrup, is subsidized in the US, making such drinks "ridiculously cheap" and helping explain why consumption is so high, particularly in lower socioeconomic groups.

"Doctors should set an example for their patients first," he stresses. "Then, for people who already have heart disease or who are at high risk, physicians should be advising them to cut back on sugary beverages; it's almost a no-brainer, like recommending that they stop smoking and do more exercise. The consumption of sugary beverages is a relatively easy behavior to change."

And although this particular study included mostly white subjects and there are few data on the risk of cardiovascular disease associated with the consumption of soda in people of other ethnicities, there are data on its effect on type 2 diabetes in these groups, he says.

"It has been shown for minority groups—such as African Americans and Asians—that they are more susceptible to the detrimental effects" of sugary drinks on diabetes incidence, he notes.

Obtained from heartwire... 

Howard S. Weintraub, MD
Posted: 03/06/2012


I am Dr. Howard Weintraub, a cardiologist at the New York University Langone Medical Center, where I am Clinical Director for the Center for Prevention of Cardiovascular Disease. I want to thank Medscape for asking me to comment on what is probably a very important recent US Food and Drug Administration (FDA) decision. They called it a "crucial decision" that offers a reworking of the product insert for a very important class of drugs: statins.

The use of statins has expanded to phenomenal proportions in this country and around the world. This class of drugs has been very influential in allowing for reductions in the development of cardiovascular disease -- stroke and myocardial infarction (MI) -- by slowing the progression of atherosclerotic plaque and preventing mortality from stroke and MI.

Use of statins is no longer confined to older individuals or patients whom you would think of as "older." Statins are used more widely in individuals in their 20s, 30s, and certainly in their 40s and 50s. Individuals are now being treated with statins in adolescence. The safety of this class of drugs has very important implications when it is being prescribed to patients who haven't reached their 20th birthday.

The concerns voiced by the FDA were fourfold. One concern was that we should abandon compulsory performance of liver function tests. Many of us in the cardiology community have known about this for years. When you look at the mortality from liver disease in patients with previously normal livers who then start taking statins, this number is infinitesimally small. In their infinite wisdom, the FDA recognized this and chose to remove this obligation. They do request that a blood test looking at liver functions be performed before the drug is started.

The FDA also calls attention to data that show that statins may raise blood glucose and hemoglobin A1c levels. The latter are more long-term blood sugars that provide a better idea of the 24-hour balance of blood sugars over the course of days, weeks, and months. This is very important because when a single blood test is performed in the fasting state, patients can prepare for this blood test and eat the right way in the hours before the test and perhaps have an inappropriately low blood sugar that does not reflect their true glycemic risk.

Nonetheless, the possibility of raising blood glucose is concerning, certainly for younger individuals, but particularly for those who are at risk of developing diabetes, and this has raised many questions. However, the unambiguous data show that in patients with and without diabetes, as well as in those whom we can call "diabetics in training" (those with metabolic syndrome), evidence for the benefits of statin drugs has been unambiguous and very forceful. Ultimately, despite a mild change in certain laboratory parameters, where the rubber meets the road, we want to prevent heart attacks and strokes, prevent the development of atherosclerosis or slow its progression, and reduce mortality.

The third concern, something that also affects younger individuals, is cognitive impairment. I find that people who are particularly worried about taking medicines in general are focusing on this with even greater intensity because they want to use any excuse they can to avoid taking a drug. I can understand this fully; however, at the same time, we have to hark back to the benefits of statins and hope that the physician has put the patient on the statin drug for a good reason.

Nonetheless, isolated reports (not based on mechanism of action because this has not been established) maintain that in some people on statins, cognition slows, and they may develop some changes in short-term memory. This can occur as early as 1 day after starting the statin, according to some reports; but more commonly it takes longer -- up to 1 year -- after the drug is initiated.

The good news is that these changes are generally mild and tend to disappear within 2-3 weeks of stopping the drug in patients in whom the statin is not a hugely important issue. However, you don't want patients who just received a stent or had an MI or a stroke to go on and off statin drugs without a very good reason. Most people who are taking statins for the prevention of disease can safely come off the statin for a couple of weeks to see if the symptoms that have been troubling them abate. If not, it may simply be that the patient is living in a very stressful environment, and their cognition may be impaired as a consequence of their stress levels or other issues.

Finally, the FDA made what I feel to be a very well-deserved change in the product insert for lovastatin. You may recall that lovastatin's "stable-mate," simvastatin, received a similar going-over (appropriately, I think), and use of the drug in its very highest dose (80 mg) was limited on the basis of 2 studies (SEARCH and A TO Z). Lovastatin, which is very similar to simvastatin, should not be used in combination with many of the antiretrovirals, antifungals, and certain macrolide antibiotics and their derivatives.

Also important for internists and cardiologists are the restrictions on other antihypertensive drugs, particularly calcium channel blockers like verapamil, amlodipine, and diltiazem. In my opinion, with the other drugs that are generically available in the statin class, this should steer us to other safer and probably more potent statin drugs, the same way that we have begun to steer away from simvastatin in individuals who require 40 or 80 mg and are on confounding medications.

I want to encourage physicians to not become spooked by this change in the product insert. I want to even more strongly encourage patients to not even think about coming off medications without discussing it with their healthcare practitioner. You should have a good relationship and a bond with this individual so you can talk with him or her about what is best for long-term and short-term prognosis. It is very important to not change these medications because, in many individuals, the degree of lowering of low-density lipoprotein cholesterol and triglyceride, and small elevation of high-density lipoprotein cholesterol, can't be duplicated with lifestyle modifications (diet and exercise).

These drugs have been shown to be phenomenally safe. If you look at the history of these drugs, there was concern early on that lovastatin might cause cataracts. This, too, was dispelled. We rely on this class of drugs. In the setting of rampant obesity, and with type 2 diabetes ascending, these drugs have managed to keep mortality and the development of cardiovascular disease at the levels that we have now.

It is important that we listen to these recommendations and to calm, sensible knowledge, and understand that statins are very good drugs that should be continued in appropriate patients.
Obtained From MedScape... 
Lisa Nainggolan 

January 19, 2012 (Houston, Texas) — New advice indicates that sexual activity is safe for the majority of heart disease patients and that doctors--as well as patients and their partners--should endeavor to bring up the subject of sex in discussions [1]. The guidance comes from the first-everAmerican Heart Association (AHA) scientific statement to address the issue, which is published online today in Circulation.

Lead author Dr Glenn N Levine (Baylor College of Medicine, Houston, TX) told heartwire that the recommendations are probably the most comprehensive on the subject to date and have been compiled by experts from various fields, including cardiology, exercise physiology, sexual counseling, and urology. Physicians, patients, and partners are reluctant to talk about sexual activity, but it is something "that is important to quality of life for most people, and we would not want to see patients refraining from sex out of undue concern about precipitating a heart attack or sudden death," he observes.

We would not want to see patients refraining from sex out of undue concern about precipitating a heart attack or sudden death.

The only patients who should refrain from sex are those with unstable heart disease or severe symptoms; they should be assessed and stabilized with appropriate treatment before engaging in sexual activity, says Levine. And drugs that can improve cardiovascular symptoms or survival should not be withheld due to concerns that they may have an impact on sexual function, he notes.

He also stresses that while use of phosphodiesterase-5 (PDE-5) inhibitor erectile-dysfunction drugs, such as sildenafil (Viagra, Pfizer) are generally safe for men who have stable cardiovascular disease, these agents are absolutely contraindicated in patients receiving nitrate therapy, either long-acting preparations or sublingual ones.

Fear, Anxiety, and Depression Can Underlie Avoidance of Sex

The AHA guidance gives general recommendations for sexual activity and CVD but also advice pertaining to patients with specific conditions: coronary artery disease; heart failure; valvular heart disease; those with arrhythmias and/or pacemakers or implantable cardioverter defibrillators (ICDs); congenital heart disease; and hypertrophic cardiomyopathy. And it covers cardiovascular drugs and sexual function as well as pharmacotherapy for sexual dysfunction.

One of the main purposes of the statement "is to make physicians and healthcare providers aware that this is a real issue that is not appropriately addressed with the patient and partner and truly should be," says Levine.

"At the same time--because we are getting a lot of lay press attention to this issue--we hope to make patients and their partners aware that sexual activity is something they should feel free to discuss with their healthcare providers during an office visit or before hospital discharge.

We hope to make patients and their partners aware that sexual activity is something they should feel free to discuss with their healthcare providers.

"The important thing to emphasize is that the risk of heart attack with sexual activity is only extremely modestly increased during sexual activity and represents only a miniscule amount of a person's overall risk."

Levine also wants to highlight the fact that anxiety and depression should be important considerations in patients with cardiovascular disease and can contribute to reduced or impaired sexual activity. "Sexual counseling of CVD patients and their partners is an important component of recovery; unfortunately, it is rarely provided," he and his coauthors observe.

Advice Should Help All Doctors to Advise CVD Patients on Sex

The scientific statement has been published in a cardiology journal, Levine notes, because "the cardiologist is going to be asked to comment on this, and frequently the GP will often refer the patient to the cardiologist to address issues" relating to sexual activity, he notes. For example, one subject he is frequently consulted about by other doctors is whether patients can use erectile-dysfunction drugs.

Levine hopes, however, that the new recommendations will embolden other specialists to confidently advise patients: "One of the aims is to allow GPs, family doctors, and others to, at least for the majority of patients, give reasonable guidance."

Another important consideration raised in the AHA statement--which is also endorsed by the American Urological AssociationSociety for Cardiovascular Angiography and InterventionsSociety of Thoracic Surgeons,American Association of Cardiovascular and Pulmonary RehabilitationInternational Society of Sexual MedicineAmerican College of Cardiology FoundationHeart Rhythm Society, and Heart Failure Society of America--is that cardiac rehabilitation and regular physical activity can reduce the risk of cardiovascular complications in people with heart disease.

Exercise testing can also provide additional information as to the safety of sexual activity in patients with indeterminate or unclear risk, the authors note.

They conclude that further research is needed on sexual activity in specific cardiovascular conditions, particularly with regard to the effects in females and in older adults.

Levine has reported that he has no conflicts of interest. Disclosures for the coauthors are listed in the paper.

Obtained from Medscape... 
Loma Linda, CA - Aortic stenosis (AS) progresses more rapidly in patients who have milder degrees of stenosis initially, and who also smoke, have hypercholesterolemia, and have elevated serum creatinine and calcium levels. These findings may lead to further insights into the mechanism of AS progression and eventual strategies to retard this common disease, investigators write in the May 30, 2000 issue of Circulation.1

To determine predictors of AS progression, Dr Sanjeev Palta and colleagues (Loma Linda VA Medical Center University and Loma Linda University) retrospectively studied 170 consecutive subjects who had any degree of AS and who had paired echocardiograms 3 or more months apart. The majority of the study cohort (78%) was men and subjects' ages ranged from 62 to 80. Aortic stenosis progression was assessed according to the yearly rate of reduction in aortic valve area (AVA). Clinical and biochemical data, including history of current smoking, serum calcium, creatinine, and cholesterol levels, were also obtained.

High cholesterol doubled rate of AVA reduction
The rate of AS progression varied widely from patient to patient, with a mean annual rate of AVA reduction of 0.10 0.27 cm2 or 7% 18%. Smoking and male sex were two of the clinical characteristics that were associated with faster AS progression, but hypertension, diabetes, and age were not. Larger initial AVA, high serum cholesterol, and high levels of serum creatinine and calcium were also associated with more rapid progression of AS. Individuals whose cholesterol levels were higher than 200 mg/dL had a rate of AVA reduction that was roughly twice that of those with a lower cholesterol level, Palta and colleagues wrote.

As has been found previously, progression of AS was slower in severe stenosis. The investigators speculate that the "stretching effect of a larger gradient in patients with more severe AS retards progression." Higher left ventricular (LV) outflow tract velocity also accelerated the advance of AS, leading the investigators to comment on the potential importance of mechanical factors in disease progression. "Clearly, the effect of LV size, function, and mechanical influences on the aortic valve need further evaluation."

The effect of hypercholesterolemia is "new"
Palta et al. note that their finding that high cholesterol levels were linked to more rapid disease progression is "new", although its association with AS progression in the bicuspid valve has been documented in cases of familial hypercholesterolemia.

The investigators caution that theirs is a retrospective study and that the population is too small to exclude the contribution of other risk factors to AS progression. Although several new risk factors, including elevated serum creatinine and calcium, have emerged, the mechanisms by which they operate are not clear and require further elucidation.

They conclude that the rate of AS progression is unpredictable in a given patient and that modifying known cardiovascular risk factors, such as smoking and cholesterol, and managing other biochemical factors may be important for secondary prevention in these patients.

Obtained from
By Salynn Boyles
Reviewed by Laura J. Martin, MD
Jan. 17, 2012 

Having high blood pressure in middle age is a major risk factor for developing atrial fibrillation later in life, and now new research links high-normal-range blood pressure with an increase in risk.

More than 2 million mostly older Americans have the heart rhythm disorder known as atrial fibrillation, which greatly increases their risk for stroke,heart failure, and death.

Researchers followed about 2,000 Norwegian men for an average of 30 years, during which time 270 developed atrial fibrillation.

Men whose systolic blood pressure (the upper number) was in the high-normal range at the start of the study were 50% more likely than men with normal blood pressure to develop the heart rhythm condition.

An earlier study in women who were followed for an average of 14 years also showed high-normal blood pressure to be associated with a higher risk for atrial fibrillation.

Prehypertension and Atrial Fibrillation
In the United States, high blood pressure is defined as a systolic reading of 140 or higher and a diastolic reading of 90 or more.

High-normal blood pressure, also known as prehypertension, is generally defined as having a systolic reading of between 120 and 139 and/or a diastolic reading of 80 to 89.

Atrial fibrillation is characterized by an irregular -- and sometimes rapid -- heartbeat resulting when the two upper chambers and two lower chambers of the heart are not contracting in sync.

Symptoms can include heart palpitations, shortness of breath, general weakness, or no symptoms at all.

In an effort to determine if the earlier findings in women also applied to men, researcher Irene Grundvold, MD, and colleagues from Norway’s Oslo University Hospital analyzed data from a study of men who were in their 40s and 50s when first examined in the early- to mid-1970s.

The men were followed for up to 35 years.

The study revealed that:
  • Men with systolic blood pressure readings of 140 or higher when they entered the study had a 60% increased risk of developing atrial fibrillation over the next three decades, compared to men with systolic readings below 128.
  • Men with systolic readings of 128 to 138 at at the start of the study had a 50% increase in risk.
  • Men with diastolic readings of 80 or higher were 79% more likely than those with lower diastolic blood pressure to develop atrial fibrillation over the next three decades.
High-Normal BP Is Patient Wake-Up Call, Says Doctor
On average, the men who developed atrial fibrillation did so around two decades after entering the study.

The findings appear in the February issue of the American Heart Association (AHA) journal Hypertension.

Prehypertension is common in people with metabolic syndrome, which is a group of risk factors associated with an elevated risk for heart disease, stroke, and type 2 diabetes.

“This study is another example of a metabolic syndrome trait being associated with higher [heart disease and stroke] risk,” says AHA spokesman Roger Blumenthal, MD, who directs the Johns Hopkins Ciccarone Preventive Cardiology Center.

Blumenthal says the findings should serve as a wake-up call for those with blood pressure readings in the high-normal range, adding that people with systolic blood pressure readings in the 130s and diastolic readings in the 80s should be counseled to make lifestyle changes that can improve the numbers.

“That means revving up your diet and exercise schedule and losing weight if you areoverweight,” he says.

Obtained from WebMD Health News...
Clinical Context
Regular exercise can increase life expectancy by an average of 7 years compared with a sedentary lifestyle, according to an editorial by Sharma and Zaidi, which accompanies the current study. Even modest doses of exercise can reduce the risk for mortality.

Endurance athletes may perform physical activity at levels 5 to 10 times greater than the exercise recommendations for preventing coronary atherosclerosis. Previous research suggests that athletes maintain indices of systolic and diastolic function associated with healthy cardiac function, although up to half of marathon runners can demonstrate elevated levels of serum cardiac troponin (cTnI).

This finding, along with a higher risk for atrial fibrillation among endurance athletes, has led to questions regarding whether endurance training among athletes is truly heart healthy. The current study by La Gerche and colleagues examines cardiac function among endurance athletes to address this issue.

Study Synopsis and Perspective
Intense physical exercise appears to cause transient dysfunction of the right ventricle, and while the short-term recovery is complete, researchers say the ventricle, often neglected in cardiac research in favor of the more-often-studied left ventricle, could be a weak point in endurance athletes [1].

"For athletes, they want their heart functioning as well as possible for as long as possible," lead investigator Dr André LaGerche (University Hospitals Leuven, Belgium) told heartwire . "The athletes we work with are very keen to know what the long-term implications of sport are on their heart. To put this in context, I don't think this study provides any answers yet, but it does raise some very important questions and focuses our attention on the right ventricle. We really do believe it's sort of the Achilles' heel in the athlete's heart."

The study, published online December 7, 2011 in the European Heart Journal, included 40 athletes who recently completed an endurance event that lasted anywhere between three and 11 hours, such as a marathon, triathlon, or alpine-skiing event. To heartwire , La Gerche said that biochemical abnormalities, such as troponin elevations, have long been documented in endurance athletes, but echocardiography often showed the heart was normal. In addition, most of the current research has been directed toward the effects of exercise on left ventricular function, with studies showing that there is some chronic left ventricular remodeling resulting from long-term endurance training, but it is not associated with adverse outcomes.

"In 2004, we were basically doing a similar thing," said La Gerche. "We wanted to see what the heart function was like, and we were looking at the left ventricle, and it all looked fairly normal. But then we noticed that in some people the right ventricle looked quite terrible. It was almost an incidental finding at the beginning, and then over the years we've built evidence showing that we think the right ventricle is the problem."

Measures of Right Ventricular Function in 40 Athletes
In this study, the researchers measured cTnI and B-type natriuretic peptide levels and assessed 3-D volume, ejection fraction, and systolic strain rate with echocardiography, as well as quantified myocardial fibrosis on cardiac magnetic resonance (CMR) imaging using delayed gadolinium enhancement, in the 40 athletes immediately and one week after their endurance event.

Relative to their baseline measurements, right ventricular volumes increased and all other measures of right ventricular function decreased following the endurance event. In contrast, left ventricular volumes were reduced and function was preserved from baseline.

B-type natriuretic peptide and cTnI both increased following the endurance event and were correlated with the reduction in the right ventricular ejection fraction, but not with the left ventricular ejection fraction. Right ventricular ejection fractions were reduced in athletes who were involved in longer endurance events and in individuals with highest measurements of VO2 max. All right ventricular function measurements returned to normal after one week.

On CMR imaging, five athletes had evidence of delayed gadolinium enhancement, and this was confined to the intraventricular septum, "in the vicinity of the right ventricular attachment," according to the researchers.

To heartwire , La Gerche said that in strenuous physical exercise, such as in marathons or Ironman triathlons, pulmonary arterial pressure increases, more so than in systemic circulation, and with this increased strain the right ventricle is "bearing the brunt" of the workload. "If the right ventricle is having to work hard, and it has to do this for three, five, eight, or 10 hours, we would expect that this would create greater fatigue and have the potential for damage."

In an editorial accompanying the study [2], Drs Sanjay Sharma and Abbas Zaidi (St George's University, London, UK) note that there are more than 500 marathon races in the US and Europe each year, and this figure is only increasing. The past 30 years have been somewhat paradoxical in the sense that obesity and morbidity caused by lack of exercise is on the rise, yet the number of individuals participating in ultra–long-distance events has increased. Regarding the current study, Sharma and Zaidi say that more detailed studies are needed, including longitudinal studies, to determine the long-term effects of endurance activities in some athletes.

Unsure of the Implications Right Now
Right now, La Gerche and colleagues are unsure of the implications of the right ventricle enlargement, although there are some causes of concern. Animal studies have shown that strenuous physical exercise caused right ventricular changes, and these were associated with serious arrhythmias. In humans, there are no prospective studies evaluating the effects of right ventricular changes, but one study, led by Dr Hein Heidbüchel (University Hospitals Leuven, Belgium), also an author of this paper, found complex right ventricular arrhythmias in cyclists, said La Gerche.

"There is a bunch of circumstantial evidence all pointing to the right ventricle," he said.

  1. La Gerche A, Burns AT, Mooney DJ, et al. Exercise-induced right ventricular dysfunction and structural remodelling in endurance athletes. Eur Heart J 2011; DOI:10.1093/eurheartj/ehr397. Available at:
  2. Sharma S, Zaidi A. Exercise-induced arrhythmogenic right ventricular cardiomyopathy: Fact or fallacy? Eur Heart J2011; DOI:10.1093/eurheartj/ehr436. Available at:

Study Highlights
  • 40 well-trained endurance athletes participated in the trial. All were free of cardiac symptoms and had no structural or electrophysiologic abnormalities during stress echocardiography.
  • Researchers examined athletes 2 to 3 weeks before an endurance race, immediately after the race, and 6 to 11 days after the race. Participants received CMR, biochemistry studies, and echocardiography.
  • The main study outcomes were changes in cardiac performance and testing profiles before and after the endurance race.
  • The mean age of participants was 37 years, and 90% were men. The average amount of training was more than 16 hours per week.
  • Systolic right ventricular function was reduced after the race compared with baseline, with a 9% average reduction in ejection fraction.
  • However, measurements of left ventricular function were generally unchanged, although left ventricular eccentricity increased after the race. Post-race left ventricular diastolic filling was impaired.
  • Whereas serum cTnI levels were detectable in 9 athletes at baseline, all participants had detectable troponin levels after racing. There remained a slight increase in troponin levels from baseline at 6 to 11 days after the race.
  • Greater reductions in right ventricular function correlated with higher post-race increases in troponin and brain natriuretic peptide levels.
  • Longer events and higher exercise capacity, but not age or weekly training volume, were associated with greater reductions in right ventricular ejection fraction.
  • There was evidence of increased cardiac fibrosis in 12.8% of participants. This fibrosis was limited to the interventricular septum. Participants with cardiac fibrosis had been competing longer in endurance sports compared with other participants.
Clinical Implications
  • Regular exercise, even at modest doses, can improve life expectancy, but research among endurance athletes had demonstrated a higher risk for atrial fibrillation as well as an increase in serum cTnI concentrations after exercise.
  • In the current study of endurance athletes by La Gerche and colleagues, the right ventricle ejection fraction declined after a race, whereas the left ventricular ejection fraction did not.
Obtained from Medscape... 
By Richard N. Fogoros, M.D.
Updated November 13, 2011

For years it has been “common knowledge” that people who are under a lot of stress have an increased risk of heart disease. But is this common knowledge correct? And if so, what kinds of stress increase the risk of heart disease, how does it increase your risk, and what can be done about it?Sorting out the effects of stress on the heart has been complicated by at least three factors: 1) people mean different things by “stress;” 2) some types of stress appear to be worse for the heart than others; and 3) how you respond to stress may be more important than the stress itself. In recent years we have learned a lot about stress and heart disease. This article and the links it provides will help you learn what you need to know about it.

What Do People Mean When They Say Stress Causes Heart Disease?

When people refer to “stress,” they are often talking about two different things: physical stress, or emotional stress. Most of the medical literature on stress and heart disease refers to physical stress. But most people are referring to the emotional variety when they talk about stress and heart disease.Physical StressPhysical stress -– exercise or other forms of physical exertion –- places measurable and reproducible demands on the heart. This physical stress is generally acknowledged to be good. In fact, the lack of physical stress (i.e., a sedentary lifestyle) constitutes a major risk factor for coronary artery disease. So this kind of “stress” is usually considered to be good for the heart.If you have significant underlying heart disease, however, too much physical stress can be potentially dangerous. In a person who has coronary artery disease, exercise that is too intense can place demands on the heart muscle that the diseased coronary arteries cannot meet, and the heart becomes ischemic (i.e., starved for oxygen.) The ischemic heart muscle can cause either angina (chest pain), or a heart attack (actual death of cardiac muscle).

So physical stress -- that is, exercise -- is generally very good for you, and is generally to be encouraged (with appropriate precautions, if you have heart disease). And unless the exercise is extraordinarily excessive, physical stress does not actually cause heart disease.

Emotional Stress
Emotional stress is generally the kind of stress people are talking about when they say that stress causes heart disease. “It’s no wonder she died,” you’ll hear people say, “with all the trouble he put her through.” But is it true? Did Ed really kill Elsie with all his gambling and drinking and staying out all hours of the night?Everyone –- even doctors -– have the notion that emotional stress, if it is severe enough or chronic enough, is bad for you. Most even believe that this kind of stress can cause heart disease. But scientific evidence that it actually does so has been hard to come by.

Recently, however, enough evidence has accumulated to be able to say that certain kinds of emotional stress, in certain people and under certain circumstances, appears to contribute to heart disease. Under the right (or rather, wrong) circumstances, emotional stress may contribute to the development of chronic heart disease, or can help precipitate acute cardiac problems in people who already have heart disease.

Denollet, J, Brutsaert, DL. Reducing emotional distress improves prognosis in coronary heart disease: 9-year mortality in a clinical trial of rehabilitation. Circulation 2001; 104:2018.

Rozanski, A, Bairey, CN, Krantz, DS, et al. Mental stress and the induction of silent myocardial ischemia in patients with coronary artery disease. N Engl J Med 1988; 318:1005.

Obtained from Heart Health Center...