Developing therapies for heart failure with preserved ejection fraction: current state and future directions

Javed Butler, Gregg C Fonarow, Michael R Zile, Carolyn S Lam, Lothar Roessig, Erik B Schelbert, Sanjiv J Shah, Ali Ahmed, Robert O Bonow, John G F Cleland, Robert J Cody, Ovidiu Chioncel, Sean P Collins, Preston Dunnmon, Gerasimos Filippatos, Martin P Lefkowitz, Catherine N Marti, John J McMurray, Frank Misselwitz, Savina Nodari, Christopher O'Connor, Marc A Pfeffer, Burkert Pieske, Bertram Pitt, Giuseppe Rosano, Hani N Sabbah, Michele Senni, Scott D Solomon, Norman Stockbridge, John R Teerlink, Vasiliki V Georgiopoulou, Mihai Gheorghiade, Javed Butler, Gregg C Fonarow, Michael R Zile, Carolyn S Lam, Lothar Roessig, Erik B Schelbert, Sanjiv J Shah, Ali Ahmed, Robert O Bonow, John G F Cleland, Robert J Cody, Ovidiu Chioncel, Sean P Collins, Preston Dunnmon, Gerasimos Filippatos, Martin P Lefkowitz, Catherine N Marti, John J McMurray, Frank Misselwitz, Savina Nodari, Christopher O'Connor, Marc A Pfeffer, Burkert Pieske, Bertram Pitt, Giuseppe Rosano, Hani N Sabbah, Michele Senni, Scott D Solomon, Norman Stockbridge, John R Teerlink, Vasiliki V Georgiopoulou, Mihai Gheorghiade

Abstract

The burden of heart failure with preserved ejection fraction (HFpEF) is considerable and is projected to worsen. To date, there are no approved therapies available for reducing mortality or hospitalizations for these patients. The pathophysiology of HFpEF is complex and includes alterations in cardiac structure and function, systemic and pulmonary vascular abnormalities, end-organ involvement, and comorbidities. There remain major gaps in our understanding of HFpEF pathophysiology. To facilitate a discussion of how to proceed effectively in future with development of therapies for HFpEF, a meeting was facilitated by the Food and Drug Administration and included representatives from academia, industry, and regulatory agencies. This document summarizes the proceedings from this meeting.

Keywords: epidemiology; heart failure; preserved ejection fraction; prognosis; treatment.

Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
Potential Therapeutic Targets in Heart Failure with Preserved Ejection Fraction
Figure 2
Figure 2
Comprehensive Echocardiographic Phenotypic Analysis of Heart Failure with Preserved Ejection Fraction Comprehensive echocardiography, including two dimensional, Doppler, tissue Doppler, and speckle tracking, allows for detailed phenotypic analysis of cardiac structure, function, and mechanics in patients with heart failure with preserved ejection fraction. The figure shows examples of information that can be obtained from the apical 4-chamber view. Clockwise from the top: speckle-tracking echocardiography for assessment of LV regional and global longitudinal strain (early diastolic strain rate can also be obtained in this view). Mitral inflow and tissue Doppler imaging of the septal and lateral mitral annulus provide information on LV diastolic function grade and estimated LV filling pressure (E/e′ ratio), along with assessment of longitudinal systolic (s′) and atrial (a′) function. Speckle-tracking analysis of LA function provides peak LA contractile function (peak negative longitudinal LA strain) and LA reservoir function (peak positive longitudinal LA strain). Tricuspid annular plane systolic function (TAPSE) and basal RV free wall peak longitudinal tissue Doppler velocity (RV s′) provide information on longitudinal RV function, as does speckle tracking echocardiography of the RV (not shown). Finally, analysis of the tricuspid regurgitant jet Doppler profile, when added to the estimated RA pressure, provides an estimate of the PA systolic pressure. Additional data available from the apical 4-chamber view include assessment of LV volumes and ejection fraction, LA volume, and RV size and global systolic function (e.g., RV fractional area change). LV = left ventricular; LA = left atrial; PA = pulmonary artery; RV = right ventricular; RA = right atrial; A4C = apical 4-chamber Courtesy – Sanjiv J Shah, MD

Source: PubMed

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