Fatty fish and fish oils could lower HF risk in men

Medical Tribune June 2009 P5
David Brill

Moderate consumption of fatty fish and marine omega-3 fatty acids may help to protect against heart failure (HF), a study of Swedish men has found.

Eating fatty fish once a week reduced the chances of developing HF over 6 years by 12 percent, while consuming around 0.3 grams a day of marine omega-3 fatty acids reduced the risk by 33 percent (adjusted hazard ratios 0.88, 95 percent CI 0.68 – 1.13; and 0.67, 05 percent CI 0.50 – 0.90).

The apparent protective effect did not grow stronger with increasing consumption, however. Eating more than moderate amounts, in fact, restored HF risk almost to that of men who did not consume any fatty fish or marine omega-3 fatty acids.

The researchers conducted food questionnaires in 39,367 men aged 45 to 75, and followed them up in inpatient and cause-of-death registries from 1998 to 2004. A total of 597 men developed HF in this time, 34 of whom died. [Eur Heart J 2009 Apr 21; Epub ahead of print]

“Our study shows that a moderate intake of fatty fish and marine omega-3 fatty acids is associated with lower rates of HF in men, but that the men did not gain a greater benefit by eating more of these foods,” said lead author Dr. Emily Levitan, a cardiology research fellow at Harvard Medical School, US.

“This study reinforces the current recommendations for moderate consumption of fatty fish. For example, the Swedish National Food Administration recommends consuming fish two to three times per week, with one of those portions being fatty fish. Similarly, the American Heart Association recommends eating fish, preferably fatty fish, twice a week,” she said.

Omega-3 fatty acids, which are found in fish oil, have been previously shown to reduce blood pressure, triglycerides and platelet aggregation, and to benefit heart rate and endothelial function. Consumption of fatty fish, such as salmon, herring and mackerel, has also been shown to confer cardiovascular benefits: one such study found that moderate consumption reduced the risk of coronary death by 36 percent and total mortality by 17 percent. [JAMA 2006 Oct 18;296(15):1885-99]

The reason for the U-shaped association between consumption and HF risk in the present study is unclear, said Levitan, although she speculated that men with poor health may be eating more fish in an attempt to improve their wellbeing.

“It will be important to replicate these findings in other populations, particularly those including women, as our study was conducted in men only,” she added.

Omega-3 fatty acids may also have a protective effect against age-related macular degeneration (AMD), a recent study of elderly Australians suggests. One serving of fish per week reduced AMD risk by 31 percent, with a similar magnitude observed for consumption of long-chain omega-3 polyunsaturated fatty acids. [Arch Ophthalmol 2009 May;127(5):656-65]

The OMEGA (Randomized trial of omega-3 fatty acids on top of modern therapy after acute myocardial infarction) trial, however, found that daily consumption of omega-3 fatty acids had no benefit for preventing sudden cardiac death after acute myocardial infarction, in a cohort of 3,851 patients with 1-year follow-up. The results were presented recently at the Annual Scientific Session of the American College of Cardiology.

CRT holds promise for atrial fibrillation in heart failure

Medical Tribune April 2009 P9
David Brill

The benefits of cardiac resynchronization therapy (CRT) for heart failure could extend to those sicker patients who have atrial fibrillation (AF), according to a leading Hong Kong cardiologist.

Although more randomized controlled studies are needed, observational data so far appear to support the use of CRT for these patients said Dr. Jeffrey WH Fung, director of cardiac electrophysiology and pacing services at the Prince of Wales Hospital, Chinese University of Hong Kong.

Fung estimated that up to 30 percent of heart failure patients have AF, but noted that guidelines currently exclude this group from the class I indications for CRT. This top-level recommendation is presently reserved for those who are in sinus rhythm, while AF patients are grouped under class IIa indications – reflecting a lower level of evidence in support of the treatment.

Fung, however, pointed to a recent paper from the Multicentre Longitudinal Observational Study (MILOS) group – the largest study so far to address the use of CRT in AF patients. After a median of 34 months following CRT, all-cause and cardiac mortality were similar between the 243 AF patients and the 1,042 sinus rhythm patients. [Eur Heart J 2008 Jul;29(13):1644-52]

Further support for these findings comes from a meta-analysis of 5 observational studies involving 1,164 patients, which showed that AF and sinus rhythm patients had similar mortality 1 year after CRT initiation. Improvements in New York Heart Association functional class were also comparable for the two groups. [J Am Coll Cardiol 2008 Oct 7;52(15):1239-46]

“It seems that sinus rhythm and AF patients behave similarly after receiving CRT,” Fung summarized. He noted that sinus rhythm patients appear to fare better on quality of life measurements, but said that this finding is “consistent with other heart failure studies which show that AF patients are much sicker than those who remain in sinus rhythm, no matter what therapies they receive.”

Besides the clinical benefits, CRT also seems to offer comparable improvements between the two patient groups when it comes to echocardiographic parameters, he added.

The jury is still out, however, on whether AF patients should undergo atrio-ventricular junction (AVJ) ablation alongside CRT, said Fung. The MILOS study found that ablation improved survival compared to CRT alone but other studies have produced inconsistent results, he said, cautioning that AVJ ablation renders patients device-dependent for the rest of their lives and should not be done unless necessary.

“I think we need a properly randomized study to try to ascertain the merits of ablation or pharmacological rate control and understand which one is really preferred in patients with heart failure and permanent AF,” he said.

“We should try to maximize drugs and sometimes maybe if there is a very low percentage of pacing you may ask the patient to undergo AVJ ablation. But looking in our database it seems that most of the patients are doing fine with more than 90 percent pacing just with drugs,” he concluded.

Exercise beneficial for heart failure patients, experts say

Medical Tribune December 2008 P9
David Brill

Exercise training is safe and of great benefit to patients with heart failure (HF), experts concluded following the recent presentation of a new study.

HF-ACTION*, the largest-ever randomized trial to assess the effects of exercise in HF patients, was greeted as a success despite failing to meet its primary endpoint.

Participation in a structured exercise program produced a modest reduction in all-cause mortality or hospitalization, which only achieved significance after adjustment for prognostic factors (adjusted hazard ratio 0.89; P=0.03).

Exercise training also improved quality of life among HF patients, a substudy of the trial showed.

Discussing the findings of HF-ACTION, which involved 2,331 patients with an average age of 59, Professor Philip Poole-Wilson of Imperial College, London, UK, said that the data were "compelling" and had wide implications.

"They missed their primary endpoint and there are those who would say ‘well that’s the end of it, let’s go home.’ I think that would be a very wrong interpretation," he said.

"I think that this trial does support the use of exercise and will strengthen the guidelines for both primary care and for the treatment of HF.

"The one thing this trial does not show is what type of exercise to advocate, and I think we’re going to see a lot more studies in that area," he added.

HF-ACTION was conducted at 82 sites in Europe, Canada and the US, with patients followed up for an average of 2.5 years.

A 15 percent reduction in the risk of cardiovascular mortality and HF hospitalization – a secondary endpoint of the study – was also seen after adjustment (adjusted hazard ratio 0.85; P=0.03).

"The HF-ACTION study results support a structured exercise training program for patients with reduced left ventricular function and HF symptoms in addition to evidence-based therapy," said Professor Christopher O’Connor, the study’s principal investigator who presented the findings to the media.

He added that the additional benefits of exercise in HF-ACTION came on a background of excellent medical and device therapy – superior to that seen in any previous HF clinical trial population. More than 90 percent of the patients were on optimal medical therapy and around 40 percent had implantable cardioverter defibrillators, he said.

The exercise program comprised 36 supervised sessions, after which patients were given an exercise bike or treadmill for use at home and encouraged to undertake five weekly sessions of 40 minutes each.

After 3 months, 52 percent of patients were completing at least three such sessions per week. At one-year follow-up, just 25 percent of patients were completing the full five sessions each week.

O’Connor, director of the Heart Center at Duke University Medical Center, US, stressed that adherence is much harder to achieve in lifestyle intervention trials than drug trials, noting that by the conclusion of the study most patients were exercising for just 50 or 60 minutes per week.
Professor Mariell Jessup, a HF specialist from the University of Pennsylvania, said that for many years it was thought that the best treatment for HF was to go to bed and avoid exertion.

"Exercise in HF-ACTION was safe and it improved outcomes so it’s a very encouraging and positive trial. Now when patients come into the office you can say that you need to exercise and it’s perfectly safe for you to do so."


*HF-ACTION: Heart Failure – A Randomized Controlled Trial Investigating Outcomes of Exercise Training.

Routine NT-proBNP screening could tackle heart failure burden

Medical Tribune December 2008 SFVI
David Brill

The incidence of heart failure could be reduced by adopting routine screening for N terminal pro-B-type natriuretic peptide (NT–proBNP), an international group of experts has advised.

The biomarker offers important information on both diagnosis and prognosis, and "holds great promise" for screening high-risk populations, the panel wrote in a consensus statement published earlier this year.

"We need to shift from a reactive to a proactive mode," the
group’s co-chairman Dr. James Januzzi told Medical Tribune.

"Rather than just waiting for the disease to show itself we’re now shifting our focus upstream in the process to better recognize the earliest changes in the heart prior to this very high-risk situation developing."

Januzzi, who spoke recently on the topic at the 17th ASEAN Congress of Cardiology in Hanoi, Vietnam, said that patients with diabetes, hypertension, left ventricular hypertrophy and men aged over 65 would benefit most from routine screening.

He added that NT-proBNP testing is more cost-effective than echocardiography which, although a useful tool for detecting heart failure, is not widely available and requires extensive training to operate. Chest X-ray and physical examination are neither sensitive nor specific for the condition, he said.

The International Collaborative of NT-proBNP (ICON) study showed that when using age-related cut-off points, NT-proBNP testing was 90 percent sensitive and 84 percent specific for detecting acute heart failure. Using a standard cut-point of 300 pg/mL, the test had a 98 percent negative predictive value for ruling out the condition. [Eur Heart J 2006 Feb;27(3):330-7]

NT-proBNP testing is particularly relevant for primary care doctors, Januzzi said, since the majority of the at-risk population falls into their hands.

"Having an objective means to say that their patient is at high risk and thus, despite their adjustments in medication, should probably be sent to a specialist, is yet another example of where the value of this marker is going to be heading," he said.

NT-proBNP, which is primarily released by the cardiac ventricles in response to the stretching of myocytes, has been studied extensively as a prognostic indicator for patients with established heart failure and acute coronary syndromes but is not yet widely accepted as a diagnostic screening tool.

The consensus statement, which comprises a series of reviews on the different applications for NT-proBNP, was published in The American Journal of Cardiology.

Heart failure is responsible for around 1 million hospital admissions each year in the US alone, and is thought to cost the health-care system there around US$60 billion.

The Massachusetts General Hospital, Boston, US, has already begun implementing NT-proBNP screening said Januzzi, who is director of the cardiac intensive care unit and an associate professor of medicine at Harvard Medical School.

"We need to have a much, much higher level of suspicion for this very common diagnosis, which is only going to get more common as the population ages. Testing for natriuretic peptide – contrary to many other diagnostics that seem to come and go – is here to stay," he said.

Quality of life in heart failure not affected by defibrillators

Medical Tribune October 2008 P3

Implantable cardioverter-defibrillators (ICDs) do not decrease quality of life for patients with stable heart failure, a study from Duke University Medical Center, US, has concluded.

The randomized trial involved 2,521 patients – all receiving optimal medical therapy along with either a single-lead ICD, amiodarone or a placebo. Physical functioning did not vary significantly between the groups at baseline, 3, 12 or 30 months, while psychological well-being was significantly improved in the ICD group at 3 and 12 months but not at 30.

Receiving a shock in the month preceding assessment, however, was associated with a reduced quality of life. [N Engl J Med 2008 359(10):999-1008]

Identifying causes of hospitalization could optimize heart failure care

Medical Tribune July 2008 P11
David Brill

The factors that precipitate hospitalization for heart failure (HF) are independent predictors of clinical outcomes, a large multicenter study from the US has found.

HF patients who were hospitalized with pneumonia, worsening renal function or ischemia had the highest in-hospital mortality, whereas those with uncontrolled hypertension had the lowest. Ischemia and worsening renal function were also most strongly associated with mortality following discharge.

“Identifying these precipitating factors can be helpful for clinicians and give us targets for therapy addressing some of these precipitating factors, which are preventable,” said Professor Gregg Fonarow, principal investigator for the study and associate chief of the division of cardiology at the University of California, Los Angeles.

“This can help improve clinical outcomes, improve care and avoid future hospitalizations, and be important in optimizing the management of this high-risk, high-morbidity and high-mortality patient population.”

The study, part of the ongoing Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure (OPTIMIZE-HF), included data on 48,612 patients from 259 US hospitals with 60 to 90 days of follow-up for each case. Almost two-thirds of patients (61.3 percent) were identified as having at least one factor that had led to hospitalization. [Arch Intern Med 2008 Apr 28;168(8):847-54]

The risk-adjusted odds ratios (ORs) for in-hospital mortality were 1.6 for patients hospitalized
with pneumonia, 1.48 for worsening renal function, 1.2 for ischemia, and .74 for uncontrolled hypertension – a factor which was also linked to a lower overall risk of death or rehospitalization following discharge (hazard ratio .71). ORs for mortality during followup were 1.52 for ischemia and 1.46 for worsening renal function.

In light of these findings, Fonarow advised hospital doctors who are treating HF patients to read through the history, determine which factors may have contributed to their worsening in symptoms and take steps to rectify them.

Dr. Kenneth Ng from the Novena Heart Centre in Singapore agreed that identifying and addressing precipitating factors is important for preventing a recurrence of hospitalization for HF.

“In (Singapore’s) National Healthcare Group hospitals we have a built-in protocol to vaccinate
all our HF patients against influenza and pneumonia,” Ng said. He added that: “every effort
should be made to monitor renal function closely, especially when starting and titrating angiotensinconverting enzyme inhibitors and angiotensin receptor blockers”.

Ng admitted, however, that he was “a little disappointed” with the modest nature of the study’s results – when the researchers compared all patients with one or more precipitating factors against those with none, the adjusted OR for inhospital mortality was .88 (95 percent
CI .78 – 1.00) with a borderline P-value of .046. There was no significant difference in follow-up mortality when comparing these patient groups.