Heart Failure’s Surprises Keep Coming

Heart failure has historically been one of the most poorly understood and hard to treat cardiovascular diseases, and many reports at the annual congress of the European Society of Cardiology in London hammered home how many mysteries remain about heart failure and how many tricks it still keeps up its sleeves.

Probably the most high-profile example was the stunning result of the SERVE-HF trial, reported as a hot-line talk and published concurrently (N Engl J Med. 2015 Sep 1. doi: 10.1056/NEJMoa1506459). The trial randomized more than 1,300 patients with heart failure with reduced ejection fraction and central sleep apnea presenting as Cheyne-Stokes respiration to nocturnal treatment with adaptive servo-ventilation. The idea was simple: These heart failure patients have trouble breathing while asleep, so help them with a ventilator.

^{Wellcome Images/Wikimedia Commons/CC BY 4.0, changes made}

“We had a technology that could alleviate central sleep apnea, and we just wanted to prove how large the benefit was,” said Dr. Martin R. Cowie, the trial’s lead investigator. But in results that “surprised us completely,” said Dr. Cowie, ventilation not only failed to produce a significant benefit for the trial’s primary, combined endpoint, it also showed a significant deleterious effect for the secondary endpoints of death by any cause and for cardiovascular death. In short, treating these patients with a ventilator was killing them. “We don’t understand what’s going on here,” Dr. Cowie said. He characterized the outcome as a “game changer” because many physicians had already begun using this form of ventilation on patients as it made such perfect sense.

“It’s unbelievable. We thought it was a slam dunk,” commented Dr. Frank Rushitka when he summed up the congress’ heart failure program at the end of the meeting.

Dr. Athena Poppas, who delivered the invited commentary on SERVE-HF, highlighted the “complexity” of heart failure and how “poorly understood” it is. “We’ve seen so many times where we saw something that we thought was bad [and treated] without fully understanding the mechanisms,” she said in an interview.

A great example was the misbegotten flirtation a couple of decades ago with inotropic therapy. It was another no-brainer: drugs that stimulate the heart’s pumping function will help patients with impaired cardiac output. But then trial results showed that chronic inotropic treatment actually hastened patients’ demise. “Patients felt better but they died faster,” Dr. Poppas noted.

Heart failure’s surprises keep coming. During the congress, heart failure expert Dr. Marriel L. Jessup said, “We used to think the reason why patients with acute heart failure were diuretic resistant was because of poor cardiac output. Now we know that they have a lot of venous congestion that impacts the kidneys and liver.”

Another researcher, Dr. John C. Burnett Jr. added, “It’s not just plumbing” that harms the kidneys and liver, but also “deleterious molecules” released because of venous congestion that causes organ damage. The identify of those molecules is only now being explored. And recognition that liver damage is an important part of the heart failure syndrome occurred only recently.

Heart failure continues to reveal its mysteries slowly and reluctantly. Clinicians who believe they know all they need about how to safely and effectively treat it are fooling themselves and run the risk of hurting their patients.