An Ounce of Prevention: Benefits of Early Treatment in Stage B HF

Studies of Left Ventricular Dysfunction trial finds that ACE inhibitors prevent progressive maladaptive changes in LV structure and function.

If there’s one key lesson healthcare professionals should glean from the Studies of Left Ventricular Dysfunction (SOLVD) Prevention Trial, it’s the fact the early recognition and treatment can mean a world of difference when it comes to stage B heart failure.

Those were the words spoken by Barry H. Greenberg, MD, University of California, San Diego, Tuesday at a session entitled “Prevention of Heart Failure Progression: New Insights for Stage B Management” at the HFSA 14th Annual Scientific Sessions. Greenberg, a founder member of the Heart Failure Society of America, reviewed key findings from the groundbreaking trial, which began enrolling asymptomatic patients with evidence of LV dysfunction in the early 1980s, and would have an enormous impact on the clinical research of heart failure.

Perhaps the most critical finding from the study was the ability of ACE inhibitors to prevent progressive maladaptive changes in LV structure and function.

“This study put us on the right road for clinical trials,” said Greenberg, adding that substudies were built into the design and a registry was added to help broaden the researchers’ perspective of HF.

Prior to SOLVD, focus on cardiovascular conditions paid little attention to systemic responses or interplay between the heart and other organs. The therapies used at the time were inotropic agents, diuretics, and vasodilator agents.

ACE inhibitors, researchers believed, “appeared to be most promising treatment of heart failure,” since they were shown to “counteract some of the major adverse hormonal and vasoconstrictor mechanisms, relieve symptoms, diminish cardiac dilatation after myocardial infarction and improve exercise capacity and ejection fraction” in short-term studies. It was chosen as the treatment that would be used at the 23 centers participating in SOLVD, according to Greenberg.

Of the nearly 7,000 patients included in the study, most were white males had prior myocardial infarction, and only 4% had atrial fibrillation. The average age was 59.

The key implications of the study were the focus on the early stages of heart failure in order to determine natural history; the idea that early treatment with therapies that target renin-angiotensin (RAS) activation could favorably impact natural history; and the use of beta blockers in asymptomatic LV dysfunction. Researchers determined that when ACE inhibitors are added to standard therapy, outcomes were improved in patients with asymptomatic LV dysfunction, and that improvements can accrue over time.

It was also found that structural changes in LV volume and mass progression are associated with increased risk for poor outcome, and that LV mass is a potent predictor of outcome in patients with low or high ejection fracture. As a result of the trial, neurohormonal activation emerged as key mechanism in HF progression.

Also of great importance was the finding that racial differences exist in mortality rates among heart failure patients, said Greenberg, noting that African American patients experienced marked differences in mortality rates, and experienced little effect when treated with ACE inhibitors. Consequently, the concept of using dilators in African American patients gained ground as a treatment in HF patients, he said.

It was also found that physical bindings are strong implications of prognosis; presence of diabetes can increase mortality risk in patients with ischemic cardiomyopathy; and presence of renal abnormalities is a potential risk factor. And as a result of the research, the staging system for HF was revised to include four stages: A, B, C, and D.

“We found that by understanding pathophysiology, we can treat patients and inhibit progress to class C and class D,” said Greenberg, who believes that the findings related to prevention can greatly impact the study of heart failure going forward.

“The future in heart disease research is prevention,” he said.