Pericardiectomy to Treat Heart Failure With Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) is a major public health problem and a therapeutic conundrum—various pharmacological treatment strategies have failed to achieve substantial improvement in outcomes.1–4 Thus, novel approaches to its treatment are badly needed. There are many alterations in cardiac function in HFpEF that constitute potential therapeutic targets, the details of which are beyond the scope of this editorial. However, reduced passive or end-diastolic chamber compliance seems to be the norm and is almost certainly an important component of its pathophysiology.5–7 The mechanisms of reduced chamber compliance include both increased myocardial stiffness because of changes in titin phosphorylation7–9 and increased content and cross-linking of extracellular matrix collagen,7,10 as well as an increase in mass to volume ratio in the many HFpEF patients with concentric left ventricular (LV) remodeling.11 However, there is no clinical evidence that reversing this abnormality leads to improvement in HFpEF outcomes; indeed, improvement in chamber compliance has never actually been documented in HFpEF patients subjected to various treatment strategies. Such an approach was shown to be efficacious in a mouse model of HFpEF in which genetic manipulation was used to produce a greater proportion of large, highly compliant titin isoforms with resultant improvement in chamber compliance and marked amelioration of the HFpEF phenotype.12 Clearly, TAC in mice is far removed from patients with HFpEF, but this result at least offers the promise that a strategy directly targeted at chamber compliance might have benefit. See Article by Borlaug et al The notion that pericardiectomy might be beneficial in HFpEF has been bandied about informally for some time and is based on the idea that relief of the restraining effect of the pericardium on cardiac volume would be expected to improve diastolic …