About 5 million people in the United States suffer from heart failure (HF). While some reports indicate that changes to diet can reduce HF risk, few large, prospective studies have been conducted. In a new study researchers observed over 14,000 participants for more than 13 years and found that whole grain consumption lowered HF risk, while egg and high-fat dairy consumption raised risk. Other food groups did not directly affect HF risk. The results are published in the November 2008 issue of the Journal of the American Dietetic Association.Diet is among the prominent lifestyle factors that influence major HF risk factors: coronary artery disease, obesity, diabetes and insulin resistance and hypertension. Using data from the Atherosclerosis Risk in Communities (ARIC) study, researchers from the Division of Epidemiology and Community Health, University of Minnesota and the Department of Epidemiology and Cardiovascular Diseases Program, University of North Carolina, analyzed the results of baseline exams of more than 14,000 White and African American adults conducted in 1987-89, with follow-up exams completed during 1990-92, 1993-95, and 1996-98. Four field centers participated in the study: Forsyth County, NC; Jackson, MS; northwest Minneapolis suburbs, MN; and Washington County, MD. The study also collected demographic characteristics and lifestyle factors, as well as other medical conditions such as cardiovascular disease, diabetes and hypertension.

Writing in the article, Jennifer A. Nettleton, Ph.D., states, “Although risk estimates were modest (7% lower risk per 1-serving increase in whole grain intake; 8% greater risk per 1-serving increase in high-fat dairy intake; 23% greater risk per 1-serving increase in egg intake), the totality of literature in this area suggests it would be prudent to recommend that those at high risk of HF increase their intake of whole grains and reduce intake of high-fat dairy and eggs, along with following other healthful dietary practices consistent with those recommended by the American Heart Association.”

Researchers have new insight into the mechanisms that underlie a pathological increase in the size of the heart.  The research, published by Cell Press in the October 24th issue of the journal Molecular Cell, may lead to the development of new strategies for managing this extremely common cardiac ailment that often leads to heart failure.

High blood pressure, heart valve disease and heart attacks can lead to a abnormal thickening of the heart muscle, called myocardial hypertrophy.  At the molecular level, signals driving myocardial hypertrophy, such as elevated levels of catecholamine hormones (i.e. adrenaline), activate the Myocyte Enhancer Factor (MEF) proteins.  This alters gene expression in heart muscle cells and induces an adverse developmental paradigm known to cardiologists as the “fetal gene response”.

“Previous research has shown that the signaling pathways leading to MEF2 are altered during pathological cardiac hypertrophy,” says senior study author Dr. John D. Scott, a Howard Hughes Medical Institute Investigator from the Department of Pharmacology at the University of Washington.  “Although we know that enzymes called histone deacetylases (HDACs) control MEF2 activity, it was not clear that HDACs and MEF2 were integrated into a larger signaling unit.”

To further identify the molecular mechanisms associated with cardiac hypertrophy, Dr. Scott and colleagues studied cardiac A-Kinase Anchoring Proteins (AKAPs), which are known to play a critical role in organizing signaling complexes in response to catecholamine hormones and transmitted signals within cells.

The researchers found that AKAP-Lbc functions as a scaffolding protein that selectively directs catecholamine signals to the transcriptional machinery to potentiate the hypertrophic response.  “Our study supports a model where AKAP-Lbc facilitates activation of protein kinase D, which in turn phosphorylates the histone deacetylase HDAC5 to promote its export from the nucleus.  The reduction in nuclear HDAC5 favored MEF2 transcription and the onset of cardiac hypertrophy.”

These studies reveal a role for AKAP-Lbc in which increased expression of the anchoring protein selectively amplifies a signaling pathway that drives cardiac muscle cells to a pathophysiological outcome.  “It will be important to explore the role of the AKAP-Lbc/PKD/HDAC5 signaling pathway in whole animal models to establish whether AKAP-Lbc is a valid biomarker for hypertrophic cardiomyopathy and to determine which genes are initiated upon up-regulation of the anchoring protein,” offers Dr. Scott.

Randomized, controlled trials have shown that nurse-led disease management for patients with heart failure can reduce hospitalizations. However, there is less evidence about the cost-effectiveness of these programs. Researchers looked at cost data from a randomized trial of 203 usual care patients versus 203 nurse-managed patients with heart failure. The study consisted mainly of black and Hispanic patients with lower socioeconomic status. Patients in the nurse-managed group maintained better physical functioning throughout the 12-month intervention than did usual care patients. In addition, nurse-led case management was cost-effective (it cost $20,000 per additional year of survival in good health). Researchers concluded that nurse-led disease management was a reasonably cost-effective way to reduce the burden of heart failure in an ethnically diverse urban setting. The results might not apply to patients in other communities.

New data, generated by David Ornitz and colleagues, at Washington University School of Medicine, St. Louis, have indicated a crucial role for signaling pathways that involve the protein sonic hedgehog in maintaining the blood vessels that supply the mouse heart and keep it beating.  These data have implications for drug development as they suggest that antagonists of hedgehog signaling pathways, such as those being developed as anticancer therapeutics, might have unwanted side effects.

In the study, mice lacking the ability to mediate hedgehog signaling in cells that form part of the blood vessels that supply the heart were found to die of heart failure.  This was because in the absence of hedgehog signaling the blood vessels of the heart were lost, meaning that the heart cells were no longer supplied with enough oxygen and died.  Although these data indicate a need for caution when developing clinical antagonists of hedgehog signaling, it is possible that the degree of inhibition needed to have a clinical effect on tumor development might not have the effect on blood vessels of the heart that completely eliminating expression of the protein does.

The potentially fatal heart disease LQT-2, which is characterized by the prolongation of a specific interval of time (known as the QT interval) in the heart’s electrical cycle, is caused by mutations in the HERG gene. What triggers the changes in the electrical activity in the heart (and therefore in the beating of the heart) has not been completely determined, although loud noises and emotional stress can be triggers. In a new study, a team of researchers from the Academic Medical Centre, The Netherlands, and the University of Wisconsin, Madison, has revealed that fever can also trigger life-threatening changes in the electrical activity in the heart of patients with LQT-2.

The team, led by Arthur Wilde and Craig January, measured the electrical activity in the heart over time (something that is recorded in an ECG) of two LQT-2 patients with the same HERG mutation (A558P), and found that fever was associated with prolonged QT intervals in these individuals. When this mutation was introduced into a cultured human cell line, the cells exhibited temperature-dependent characteristics, including altered electrical currents across their cell membranes at high temperatures. The authors therefore conclude that similar changes in electrical currents occur in heart cells at the high temperatures associated with fever and that fever is a potential trigger of the potentially lethal changes in the electrical activity in the heart of patients with LQT-2.