Incident heart failure higher over 10 years

Patients with sarcoidosis had elevated long-term risk of adverse cardiac events compared with controls, a retrospective analysis of national Danish health data found.

In addition, people with sarcoidosis and heart failure had elevated mortality compared with people who had heart failure but not sarcoidosis, reported Adelina Yafasova, MB, of Copenhagen University Hospital, and co-authors, in Journal of the American College of Cardiology.

For the primary outcome of heart failure incidence in those with sarcoidosis versus matched population controls, absolute 10-year risks of heart failure were 3.18% (95% CI 2.83%-3.57%) for sarcoidosis patients and 1.72% (95% CI 1.58%-1.86%) for controls.

Excluding first-year data, the adjusted hazard ratio for incident heart failure over a median of 8.2 year of follow-up in the group with sarcoidosis was 1.65 (95% CI 1.43-1.91).

Risk for composites combining implantable cardioverter-defibrillator (ICD) implantation, ventricular arrhythmias, and cardiac arrest; pacemaker implantation, atrioventricular block, and sinoatrial dysfunction; and atrial fibrillation or flutter also were elevated in patients with sarcoidosis.

Sarcoidosis was also associated with an increased risk of all-cause mortality in heart failure patients compared with the non-sarcoidosis heart failure population (adjusted HR 1.35, 95% CI 1.10-1.64).

“This nationwide cohort study of the association between sarcoidosis and adverse cardiac outcomes yielded three major findings,” Yafasova and colleagues wrote.

“First, sarcoidosis was associated with a higher long-term risk of incident heart failure compared with the background population. Second, a history of sarcoidosis was associated with a higher mortality among patients who developed heart failure. Third, sarcoidosis was associated with a higher long-term risk of other adverse cardiac outcomes compared with the background population,” they pointed out.

In an accompanying editorial, Melissa Lyle, MD, and Leslie Cooper, Jr., MD, both of the Mayo Clinic in Jacksonville, Florida, said the findings were convincing. “These are important observations that should raise awareness of cardiovascular risk in patients with systemic sarcoidosis and promote debate regarding optimal screening and management strategies,” they wrote. “These findings support the need for monitoring for cardiac manifestations in patients with systemic sarcoidosis.”

“Future management guidelines for cardiac sarcoidosis should include these data for developing recommendations regarding the role of advanced imaging modalities and biopsy for diagnosis, prognosis, and treatment,” Lyle and Cooper added.

Systemic inflammation in sarcoidosis is characterized by noncaseating granulomas, most in the lungs, skin, and reticuloendothelial system, although they can involve any organ. As many as one-third of people with sarcoidosis have cardiac involvement at autopsy, though fewer than 10% have clinical manifestations during life. These include heart failure, asymptomatic left ventricular systolic dysfunction, arrhythmias, conduction abnormalities, and sudden cardiac death.

High grade atrioventricular block was the most common first sign of cardiac sarcoidosis in a recent study, and cardiac involvement portended a poorer prognosis compared with people who had sarcoidosis without cardiac involvement.

Yafasova and colleagues analyzed data from four relevant Danish health care registries, focusing on 11,834 adults diagnosed with sarcoidosis between January 1996 and December 2016. Patients were excluded if they had a history of heart failure, ventricular arrhythmias, cardiac arrest, atrioventricular block, sinoatrial dysfunction, atrial fibrillation or flutter, myocarditis, or pericarditis, or if they had an ICD or pacemaker implantation any time prior to sarcoidosis diagnosis.

Median age was about 43 and 54.3% were women. These were matched to 47,336 general population controls and follow-up was conducted for median 8.2 years.

Secondary outcomes included:

  • ICD implantation, ventricular arrhythmias, and cardiac arrest composite: HR 0.96% for sarcoidosis patients; 0.45% for the background population.
  • Pacemaker implantation, atrioventricular block, and sinoatrial dysfunction composite: HR 0.94% for sarcoidosis patients; 0.51% for the background population.
  • Atrial fibrillation or flutter composite: HR 3.44% for sarcoidosis patients; 2.66% for the background population.

Of 164 heart failure patients with sarcoidosis who died, causes of death included sarcoidosis (9.8%), cardiovascular diseases (35.4%), respiratory disease (14.6%), cancer (18.3%), and other causes (22.0%).

“It is possible that the development of heart failure in patients with sarcoidosis may be attributed to underlying atherosclerotic coronary artery disease or the treatment of sarcoidosis (e.g., steroid-induced hypertension or diabetes, which, in turn, increases the likelihood of heart failure) rather than the disease itself,” the authors observed, adding that data on heart failure etiology were not available in this study.

Analysis of prescription claims for heart failure or antiarrhythmic medications within 6 months of heart failure diagnosis showed no difference in the proportion of patients receiving antiarrhythmic medication. However, sarcoidosis patients with heart failure were less likely to receive beta-blockers and renin-angiotensin system inhibitors within 6 months after heart failure diagnosis compared with non-sarcoidosis patients with heart failure.

Noting that sarcoidosis patients with heart failure were less likely to receive guideline-recommended therapy for heart failure with reduced ejection fraction than patients with heart failure without a history of sarcoidosis, the authors wrote, “Although speculative, these findings suggest that sarcoidosis patients with heart failure to a greater degree develop heart failure with preserved ejection fraction, for which there is no guideline-recommended therapy at the moment.”

Limitations of this study include absence of heart failure etiology data. Also, cardiac sarcoidosis was not confirmed with imaging or biopsy, and specific treatment regimens were not determined. As an observational study, the research cannot determine cause-effect relationships.

  1. Patients with sarcoidosis had elevated long-term risk of adverse cardiac events, a retrospective analysis of national Danish health data showed.

  2. The findings may support the need for monitoring for cardiac manifestations in patients with systemic sarcoidosis.

Paul Smyth, MD, Contributing Writer, BreakingMED™

The researchers reported no disclosures. The editorialists reported no disclosures.

Cat ID: 3

Topic ID: 74,3,730,3,308,105,130,192,195,158,925