Could Modification of Titin Contribute to an Answer for Heart Failure With Preserved Ejection Fraction?
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Article, see p 1085
In 2016, treatment of heart failure with preserved ejection fraction (HFpEF) remains a critical unmet need. A recent guideline publication1 stated: “No treatment has yet been shown, convincingly, to reduce morbidity or mortality in patients with HFpEF.” This fact stands in stark contrast with the disease burden borne by HFpEF patients2: It is estimated that >50% of all patients with heart failure have HFpEF; 5-year mortality is >60%; the 6-month rehospitalization rate for decompensated HFpEF is >50%; and many patients have profound disability, often comparable to patients with reduced ejection fraction who are candidates for transplantation. A recent opinion article by Shah et al3 discussed phenotypic diversity in the HFpEF population and proposed an approach to treatment on the basis of specific aspects of pathophysiology present in individual patients. The accompanying article in this issue of Circulation by Methawasin et al,4 with its focus on titin, is an example of how such an approach might ultimately work.
Seven large randomized clinical trials of pharmacological approaches have failed to demonstrate a reduction in morbidity and mortality.1,2 Why? Were the studies designed or conducted poorly? Did they include the wrong groups of patients? Did they test the wrong end points? It is certainly possible that each of these factors contributed to the neutral results. However, lack of demonstrated efficacy may be based on the possibility that the underlying mechanisms specific to the syndrome of HFpEF were not the target of the treatments tested or the treatment targets were too narrow. In large part, treatment for heart failure with reduced ejection fraction targets left ventricular remodeling characterized by increased chamber volume and marked neurohumoral activation.1 As shown in the Table, these are either not present or present to a …