Dataset Information

Identifying a low-flow phenotype in heart failure with preserved ejection fraction: a secondary analysis of the RELAX trial.

ABSTRACT:

Aims

The relationship between resting stroke volume (SV) and prognostic markers in heart failure with preserved ejection fraction (HFpEF) is not well established. We evaluated the association of SV index (SVI) at rest with exercise capacity and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in stable patients with HFpEF.

Methods and results

Participants enrolled in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure (RELAX) trial with available data on SVI by the Doppler method were included in this analysis (n = 185). A low-flow state defined by resting SVI < 35 mL/m² was present in 37% of study participants. Multivariable adjusted linear regression analysis suggested that higher resting heart rate, higher body weight, prevalent atrial fibrillation, and smaller left ventricular (LV) end-diastolic dimension were each independently associated with lower SVI. Patients with low-flow HFpEF had lower systolic blood pressure and smaller LV end-diastolic dimension. In multivariable adjusted linear regression models, lower SVI was significantly associated with lower peak oxygen consumption (peak VO₂ ) and higher NT-proBNP levels at baseline, and greater decline in peak VO₂ at 6 month follow-up independent of other confounders. Resting LV ejection fraction was not associated with peak VO₂ and NT-proBNP levels.

Conclusions

There is heterogeneity in the resting SVI distribution among patients with stable HFpEF, with more than one-third of patients identified with the low-flow HFpEF phenotype (SVI < 35 mL/m² ). Lower SVI was independently associated with lower peak VO₂ , higher NT-proBNP levels, and greater decline in peak VO₂ . These findings highlight the potential prognostic utility of SVI assessment in the management of patients with HFpEF.

SUBMITTER: Patel KV

PROVIDER: S-EPMC6676300 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

Identifying a low-flow phenotype in heart failure with preserved ejection fraction: a secondary analysis of the RELAX trial.

Patel Kershaw V KV Mauricio Rina R Grodin Justin L JL Ayers Colby C Fonarow Gregg C GC Berry Jarett D JD Pandey Ambarish A

ESC heart failure 20190416 4

<h4>Aims</h4>The relationship between resting stroke volume (SV) and prognostic markers in heart failure with preserved ejection fraction (HFpEF) is not well established. We evaluated the association of SV index (SVI) at rest with exercise capacity and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in stable patients with HFpEF.<h4>Methods and results</h4>Participants enrolled in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure ...[more]

PMID: 30993916

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Project description:Phosphodiesterase-5 inhibition with sildenafil compared with a placebo had no effect on the exercise capacity or clinical status of patients with heart failure with preserved ejection fraction (HFpEF) in the PhosphodiesteRasE-5 Inhibition to Improve Clinical Status and Exercise Capacity in Diastolic Heart Failure with Preserved Ejection Fraction (RELAX) clinical trial. Metabolic impairments may explain the neutral results.To test the hypothesis that profiling metabolites in the RELAX trial would clarify the mechanisms of sildenafil effects and identify metabolites associated with clinical outcomes in HFpEF.Paired baseline and 24-week plasma samples of 160 stable outpatient individuals with HFpEF enrolled in the RELAX clinical trial were analyzed using flow injection tandem mass spectrometry (60 metabolites) and conventional assays (5 metabolites).Sildenafil (n?=?79) or a placebo (n?=?81) administered orally at 20 mg, 3 times daily for 12 weeks, followed by 60 mg, 3 times daily for 12 weeks.The primary measure was metabolite level changes between baseline and 24 weeks stratified by treatments. Secondary measures included correlations between metabolite level changes and clinical biomarkers and associations between baseline metabolite levels and the composite clinical score.No metabolites changed between baseline and 24 weeks in the group treated with a placebo; however, 7 metabolites changed in the group treated with sildenafil, including decreased amino acids (alanine and proline; median change [25th-75th], -38.26 [-100.3 to 28.19] and -28.24 [-56.29 to 12.08], respectively; false discovery rate-adjusted P?=?.01 and .03, respectively), and increased short-chain dicarboxylacylcarnitines glutaryl carnitine, octenedioyl carnitine, and adipoyl carnitine (median change, 6.19 [-3.37 to 14.18], 2.72 [-3 to 12.57], and 10.72 [-11.23 to 29.57], respectively; false discovery rate-adjusted P?=?.01, .04, and .05, respectively), and 1 long-chain acylcarnitine metabolite (palmitoyl carnitine; median change, 7.83 [-5.64 to 26.99]; false discovery rate-adjusted P?=?.03). The increases in long-chain acylarnitine metabolites and short-chain dicarboxylacylcarnitines correlated with increases in endothelin-1 and creatinine/cystatin C, respectively. Higher baseline levels of short-chain dicarboxylacylcarnitine metabolite 3-hydroxyisovalerylcarnitine/malonylcarnitine and asparagine/aspartic acid were associated with worse clinical rank scores in both treatment groups (?, -96.60, P?=?.001 and ?, -0.02, P?=?.01; after renal adjustment, P?=?.09 and .02, respectively).Our study provides a potential mechanism for the effects of sildenafil that, through adverse effects on mitochondrial function and endoplasmic reticulum stress, could have contributed to the neutral trial results in RELAX. Short-chain dicarboxylacylcarnitine metabolites and asparagine/aspartic acid could serve as biomarkers associated with adverse clinical outcomes in HFpEF.

Dataset Information

Identifying a low-flow phenotype in heart failure with preserved ejection fraction: a secondary analysis of the RELAX trial.

Aims

Methods and results

Conclusions

Publications

Identifying a low-flow phenotype in heart failure with preserved ejection fraction: a secondary analysis of the RELAX trial.

Similar Datasets

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