Drug treatment effects on outcomes in heart failure with preserved ejection fraction: a systematic review and meta-analysis.

BACKGROUND: Clinical drug trials in patients with heart failure and preserved ejection fraction have failed to demonstrate improvements in mortality. METHODS: We systematically searched Medline, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCT) assessing pharmacological treatments in patients with heart failure with left ventricular (LV) ejection fraction≥40% from January 1996 to May 2016. The primary efficacy outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, heart failure hospitalisation, exercise capacity (6-min walk distance, exercise duration, VO2 max), quality of life and biomarkers (B-type natriuretic peptide, N-terminal pro-B-type natriuretic peptide). Random-effects models were used to estimate pooled relative risks (RR) for the binary outcomes, and weighted mean differences for continuous outcomes, with 95% CI. RESULTS: We included data from 25 RCTs comprising data for 18101 patients. All-cause mortality was reduced with beta-blocker therapy compared with placebo (RR: 0.78, 95%CI 0.65 to 0.94, p=0.008). There was no effect seen with ACE inhibitors, aldosterone receptor blockers, mineralocorticoid receptor antagonists and other drug classes, compared with placebo. Similar results were observed for cardiovascular mortality. No single drug class reduced heart failure hospitalisation compared with placebo. CONCLUSION: The efficacy of treatments in patients with heart failure and an LV ejection fraction≥40% differ depending on the type of therapy, with beta-blockers demonstrating reductions in all-cause and cardiovascular mortality. Further trials are warranted to confirm treatment effects of beta-blockers in this patient group.

Genetic disorders of surfactant protein dysfunction: when to consider and how to investigate.

Genetic mutations affecting proteins required for normal surfactant protein function are a rare cause of respiratory disease. The genes identified that cause respiratory disease are surfactant protein B, surfactant protein C, ATP binding cassette number A3 and thyroid transcription factor-1. Surfactant protein dysfunction syndromes are highly variable in their onset and presentation, and are dependent on the genes involved and environmental factors. This heterogeneous group of conditions can be associated with significant morbidity and mortality. Presentation may be in a full-term neonate with acute and progressive respiratory distress with a high mortality or later in childhood or adulthood with signs and symptoms of interstitial lung disease. Genetic testing for these disorders is now available, providing a non-invasive diagnostic test. Other useful investigations include radiological imaging and lung biopsy. This review will provide an overview of the genetic and clinical features of surfactant protein dysfunction syndromes, and discuss when to suspect this diagnosis, how to investigate it and current treatment options.