Deep phenotype characterization of hypertensive response to exercise: implications on functional capacity and prognosis across the heart failure spectrum

Abstract

Aims Limited evidence is available regarding the role of hypertensive response to exercise (HRE) in heart failure (HF). We evaluated the systolic blood pressure (SBP) to workload slope during exercise across the HF spectrum, investigating haemodynamic and prognostic correlates of HRE. Methods and results We prospectively enrolled 369 patients with HF Stage C (143 had preserved [HFpEF], and 226 reduced [HFrEF] ejection fraction), 201 subjects at risk of developing HF (HF Stages A–B), and 58 healthy controls. We performed a combined cardiopulmonary exercise stress echocardiography testing. We defined HRE as the highest sex‐specific SBP/workload slope tertile in each HF stage. Median SBP/workload slope was 0.53 mmHg/W (interquartile range 0.36–0.72); the slope was 39% steeper in women than men (p < 0.0001). After adjusting for age and sex, SBP/workload slope in HFrEF (0.47, 0.30–0.63) was similar to controls (0.43, 0.35–0.57) but significantly lower than Stages A–B (0.61, 0.47–0.75) and HFpEF (0.63, 0.42–0.86). Patients with HRE showed significantly lower peak oxygen consumption and peripheral oxygen extraction. After a median follow‐up of 16 months, HRE was independently associated with adverse outcomes (all‐cause mortality and hospitalization for cardiovascular reasons: hazard ratio 2.05, 95% confidence interval 1.81–5.18), while rest and peak SBP were not. Kaplan–Meier analysis confirmed a worse survival probability in Stages A–B (p = 0.005) and HFpEF (p < 0.001), but not HFrEF. Conclusion A steeper SBP/workload slope is associated with impaired functional capacity across the HF spectrum and could be a more sensitive predictor of adverse events than absolute SBP values, mainly in patients in Stages A–B and HFpEF.

Haemodynamic and metabolic phenotyping of patients with aortic stenosis and preserved ejection fraction: A specific phenotype of heart failure with preserved ejection fraction?

“…We used stepwise multivariable linear regression models with peak VO 2 as the dependent variable while using baseline exercise parameters selected on prior knowledge and pathophysiology as independent variables. 13,17,28,29 Variance inflation factor >5 was used to exclude multi-collinearity between selected variables. We tested the assumptions of regression analyses demonstrating linearity of residuals, independence of residuals, normal distribution of residuals and equal variance of residuals.…”

“…However, the present approach has been previously validated and used in multiple different settings. 13,26,27,29,35,52,53 The V D /V T (physiologic dead space/tidal volume) ratio requires the measurement of partial pressure of CO 2 in the arterial blood (PaCO 2 ); for practical reasons, we estimated PaCO 2 during exertion non-invasively from P ET CO 2 . 54 Finally, we evaluated EAT thickness by two-dimensional echocardiography; while alternative imaging methods such as cardiac magnetic resonance or CT may allow for more accurate, three-dimensional EAT quantification, echocardiography grants a widespread, fast and reliable evaluation.…”

Bio-Humoral and Non-Invasive Haemodynamic Correlates of Renal Venous Flow Patterns across the Heart Failure Spectrum

“…After adjusting for covariates including hypertension, diabetes mellitus, HF Stage C and serum creatinine, worsening of RVF remained associated with worse ultrasound and bio-humoral indexes of congestion, worse non-invasive haemodynamic variables and reduced RV-arterial coupling. Elevated levels of natriuretic peptides (i.e., NT-proBNP) [30], the presence of echocardiographic signs of EVLW (i.e., B-lines) [31][32][33][34], systemic venous congestion (i.e., IVC diameter) [35] and RV-arterial uncoupling (i.e., TAPSE/sPAP) [20,36,37] have well-known prognostic value in patients with definite HF diagnosis, regardless of LVEF. Accordingly, in the report by Iida et al, RVF patterns strongly correlated with clinical outcomes, independent of right atrial pressure and other risk factors, with pattern D displaying the worst prognosis [9].…”

April 2023 at a glance: focus on diagnosis and comorbidities

“…Hypertension is a major cause of HF 11,12 . Pugliese et al 13 . analysed the hypertensive response to exercise (HRE) in 369 patients with HF, 201 subjects at risk of HF and 58 healthy controls using cardiopulmonary exercise testing and echocardiography.…”

“…8,9 Zannad et al 10 suggest standardization and implementation of PROs not only for clinical trials but also in clinical practice, involving patients, as well as their families and caregivers.Hypertension is a major cause of HF. 11,12 Pugliese et al 13 analysed the hypertensive response to exercise (HRE) in 369 patients with HF, 201 subjects at risk of HF and 58 healthy controls using cardiopulmonary exercise testing and echocardiography. After adjusting for age and sex, the systolic blood pressure/workload slope was similar in patients with HF and reduced ejection fraction (HFrEF) vs. control subjects.…”