Meeting NewsPerspective

PARAGON HF Echo: RV enlargement among predictors of events in HFpEF

PHILADELPHIA — Right ventricular enlargement, left ventricular hypertrophy and elevated left- and right-sided pressures were among the predictors of HF hospitalization or CV death among patients with HF with preserved ejection fraction, according to data from the PARAGON-HF echocardiographic substudy.

Patients with multiple abnormalities of LV structure, diastolic function and indicators of pulmonary hypertension also had elevated risk for CV events, Amil M. Shah, MD, assistant professor of medicine at Harvard Medical School and co-director of the cardiac imaging core laboratory at Brigham and Women’s Hospital, said during a presentation at the Heart Failure Society of America Scientific Meeting.

“We wanted to characterize the cardiac structure and function in a subset of patients in PARAGON-HF, quantify their prognostic associations with heart failure hospitalization or cardiovascular mortality and contextualize these findings with other HFpEF studies,” Shah said during his presentation.

PARAGON-HF assigned patients with HFpEF to sacubitril/valsartan (Entresto, Novartis) or valsartan alone. As Healio previously reported, sacubitril/valsartan narrowly missed the primary endpoint of reduction of CV death or HF hospitalization.

Among the 1,097 patients from PARAGON-HF who had echocardiograms available for analysis, who were followed for a mean of 2.8 years, larger mean wall thickness (P = .03), greater LV mass index (P = .03), abnormal e’ based on tissue doppler imaging (P = .02), abnormal E/e’ ratio (P < .001), abnormal tricuspid regurgitation velocity (P < .001) and abnormal RV end-diastolic area (P = .007) were all associated with elevated risk for HF hospitalization or CV death, and there was a trend toward association between abnormal tricuspid annular plane systolic excursion, a measure of RV diameter, and poor outcomes (P = .06), Shah said.

Compared with patients who had none, patients who had all three of abnormal E/e’ ratio, tricuspid regurgitation velocity and LV hypertrophy had an eightfold higher risk for CV events (HR = 8.1; 95% CI, 3.6-18.2), whereas those who had two abnormal echo measures had a nearly threefold higher risk (HR = 2.9; 95% CI, 1.6-5.4), he said.

According to Shah, when the researchers compared this population with the imaging cohorts of TOPCAT Americas and iPRESERVE, they found event rates were similar, but echocardiographic characteristics were different.

“Differences in LV and left atrial structure between patients enrolled in PARAGON-HF, TOPCAT and iPRESERVE, despite similarly elevated E/e’ ratio and clinical event rates, highlight the phenotypic and pathophysiologic heterogeneity of the HFpEF syndrome,” he said.

Among the cohort (mean age, 74 years; 53% women), 8% had abnormal LV end-diastolic diameter, 62% had abnormal mean wall thickness, 45% had abnormal relative wall thickness, 21% had abnormal LV mass index, 68% had abnormal e’ based on tissue doppler imaging, 53% had abnormal E/e’ ratio, 59% had abnormal left atrial volume index, 83% had any left atrial enlargement, 31% had abnormal tricuspid regurgitation velocity, 39% had abnormal RV end-diastolic area and 31% had abnormal tricuspid annular plane systolic excursion.

Compared with the overall PARAGON-HF population, the substudy population was older (P < .001) and more likely to be from North America (30% vs. 6%; P < .001), Shah said.

“Future studies will explore differences in cardiac phenotype between subgroups demonstrating differential response to sacubitril/valsartan and will evaluate the prognostic relevance of newer parameters like myocardial mechanics in HFpEF,” he said. – by Erik Swain

Reference:

Shah AM, et al. Late-Breaking Clinical Trials and Insights with Angiotensin Receptor Neprilysin Inhibitors. Presented at: Heart Failure Society of America Scientific Meeting; Sept. 13-16, 2019; Philadelphia.

Disclosure: PARAGON-HF was funded by Novartis. Shah reports he received a research grant from Novartis.

PHILADELPHIA — Right ventricular enlargement, left ventricular hypertrophy and elevated left- and right-sided pressures were among the predictors of HF hospitalization or CV death among patients with HF with preserved ejection fraction, according to data from the PARAGON-HF echocardiographic substudy.

Patients with multiple abnormalities of LV structure, diastolic function and indicators of pulmonary hypertension also had elevated risk for CV events, Amil M. Shah, MD, assistant professor of medicine at Harvard Medical School and co-director of the cardiac imaging core laboratory at Brigham and Women’s Hospital, said during a presentation at the Heart Failure Society of America Scientific Meeting.

“We wanted to characterize the cardiac structure and function in a subset of patients in PARAGON-HF, quantify their prognostic associations with heart failure hospitalization or cardiovascular mortality and contextualize these findings with other HFpEF studies,” Shah said during his presentation.

PARAGON-HF assigned patients with HFpEF to sacubitril/valsartan (Entresto, Novartis) or valsartan alone. As Healio previously reported, sacubitril/valsartan narrowly missed the primary endpoint of reduction of CV death or HF hospitalization.

Among the 1,097 patients from PARAGON-HF who had echocardiograms available for analysis, who were followed for a mean of 2.8 years, larger mean wall thickness (P = .03), greater LV mass index (P = .03), abnormal e’ based on tissue doppler imaging (P = .02), abnormal E/e’ ratio (P < .001), abnormal tricuspid regurgitation velocity (P < .001) and abnormal RV end-diastolic area (P = .007) were all associated with elevated risk for HF hospitalization or CV death, and there was a trend toward association between abnormal tricuspid annular plane systolic excursion, a measure of RV diameter, and poor outcomes (P = .06), Shah said.

Compared with patients who had none, patients who had all three of abnormal E/e’ ratio, tricuspid regurgitation velocity and LV hypertrophy had an eightfold higher risk for CV events (HR = 8.1; 95% CI, 3.6-18.2), whereas those who had two abnormal echo measures had a nearly threefold higher risk (HR = 2.9; 95% CI, 1.6-5.4), he said.

According to Shah, when the researchers compared this population with the imaging cohorts of TOPCAT Americas and iPRESERVE, they found event rates were similar, but echocardiographic characteristics were different.

“Differences in LV and left atrial structure between patients enrolled in PARAGON-HF, TOPCAT and iPRESERVE, despite similarly elevated E/e’ ratio and clinical event rates, highlight the phenotypic and pathophysiologic heterogeneity of the HFpEF syndrome,” he said.

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Among the cohort (mean age, 74 years; 53% women), 8% had abnormal LV end-diastolic diameter, 62% had abnormal mean wall thickness, 45% had abnormal relative wall thickness, 21% had abnormal LV mass index, 68% had abnormal e’ based on tissue doppler imaging, 53% had abnormal E/e’ ratio, 59% had abnormal left atrial volume index, 83% had any left atrial enlargement, 31% had abnormal tricuspid regurgitation velocity, 39% had abnormal RV end-diastolic area and 31% had abnormal tricuspid annular plane systolic excursion.

Compared with the overall PARAGON-HF population, the substudy population was older (P < .001) and more likely to be from North America (30% vs. 6%; P < .001), Shah said.

“Future studies will explore differences in cardiac phenotype between subgroups demonstrating differential response to sacubitril/valsartan and will evaluate the prognostic relevance of newer parameters like myocardial mechanics in HFpEF,” he said. – by Erik Swain

Reference:

Shah AM, et al. Late-Breaking Clinical Trials and Insights with Angiotensin Receptor Neprilysin Inhibitors. Presented at: Heart Failure Society of America Scientific Meeting; Sept. 13-16, 2019; Philadelphia.

Disclosure: PARAGON-HF was funded by Novartis. Shah reports he received a research grant from Novartis.

    Perspective
    Mary Norine Walsh

    Mary Norine Walsh

    The importance of a study like this is that it gives us more information on the pathophysiology and the changes that this agent brings to our patients. This study is one of the first to show mechanistic evidence that we did not have before.

    • Mary Norine Walsh, MD, MACC
    • Cardiology Today Editorial Board Member
      St. Vincent Heart Center, Indianapolis
      Past President, American College of Cardiology

    Disclosures: Walsh reports no relevant financial disclosures.

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