Williams, Bryan

Abstract Background Conflicting evidence exists regarding the functional and prognostic significance of hypertensive response to exercise (HRE), commonly defined as peak systolic blood pressure (SBP) >210 mmHg in males and >190 mmHg in females. No study yet has explored the impact of sex-specific, workload-indexed HRE in patients at different stages of the heart failure (HF) spectrum, as defined by the American College of Cardiology/American Heart Association HF staging system. Purpose We evaluated the SBP/Workload slope during exercise across the HF spectrum and investigated the hemodynamic, functional and prognostic correlates of HRE. Methods Fifty-eight healthy controls, 201 subjects at risk of developing HF (HF Stages A-B), and 369 patients with a definite diagnosis of HF (Stage C) were enrolled; among the latter, 143 had preserved (HFpEF) and 226 reduced (HFrEF) left ventricular ejection fraction. All patients underwent a combined cardiopulmonary-exercise stress echocardiography test. For each patient, we recorded at least two BP measurements during exercise: the first within the first minute of exercise and the last at peak effort. The SBP/Workload slope was calculated as the difference in SBP over the corresponding increment in watts (W): (SBPpeak – SBPfirst)/(Wpeak – Wfirst). In each ACC/AHA HF Stage, we divided patients according to SBP/Workload slope tertiles; HRE was defined as the highest sex-specific SBP/Workload slope tertile. A composite of all-cause mortality and hospitalization for cardiovascular reasons was chosen as the primary outcome. Results The median SBP/Workload slope was 0.53 (interquartile range 0.36-0.72) mmHg/W and was steeper in women than in men in all subgroups (p<0.0001). After adjusting for age and sex, SBP/Workload slope was significantly higher in Stages A-B (0.61, 0.47-0.75 mmHg/W) and HFpEF (0.63, 0.42-0.86 mmHg/W) compared to controls (0.43, 0.35-0.57 mmHg/W) and HFrEF (0.47, 0.30-0.63 mmHg/W, Figure 1). In all subgroups, patients with HRE showed significantly lower peak oxygen consumption and peripheral oxygen extraction (Table). After a median follow-up of 16 months, HRE was an independent predictor of adverse outcomes (Hazard Ratio 2.05, 95% confidence interval 1.81-5.18), while rest and peak absolute SBP values did not. Kaplan-Meier analysis confirmed a worse survival probability for patients with HRE in Stages A-B and HFpEF but not in HFrEF. After adjusting for confounding factors, the patients with the highest SBP/Workload slope had a 47% higher risk of the primary outcome than subjects in the lowest tertile (Figure 2). Conclusions Across the HF spectrum, patients with HRE, as evaluated by the SBP/Workload slope, present with peculiar pathophysiological features and impaired functional capacity. This is especially true for those in Stages A-B and patients with HFpEF. In these subgroups, HRE may portend an increased risk of adverse cardiovascular outcomes.SBP/workload slopesKaplan-Meier curves and Hazard Ratios

Objective: Limited evidence is available regarding the impact of workload-indexed hypertensive response to exercise (HRE) in patients at different stages of the heart failure (HF) spectrum. We evaluated the prevalence, pathophysiologic and prognostic correlates of HRE, evaluated by the systolic blood pressure (SBP)/Workload slope, across the HF spectrum as defined by the American College of Cardiology/American Heart Association. Design and method: We prospectively enrolled 58 healthy controls, 201 subjects at risk of developing HF (HF Stages A-B), and 369 patients with a definite diagnosis of HF (Stage C) and either preserved (HFpEF) or reduced (HFrEF) left ventricular ejection fraction. All patients underwent a combined cardiopulmonary-exercise stress echocardiography test. We recorded two SBP measurements for each patient: the first within the first minute of exercise and the last at peak effort. The SBP/Workload slope was calculated as the difference in SBP over the corresponding increment in watts (W): (SBPpeak – SBPfirst)/(Wpeak – Wfirst). In each subgroup, we divided patients according to SBP/Workload slope tertiles, using sex-specific cut-off values; HRE was defined as the highest SBP/Workload slope tertile in each HF stage. A composite of all-cause mortality and hospitalization for cardiovascular reasons was chosen as the primary outcome. Results: The median SBP/Workload slope was 0.53 (interquartile range 0.36 - 0.72) mmHg/W and was steeper in women than men in all subgroups. After adjusting for age and sex, SBP/Workload slope in controls was similar to HFrEF but significantly lower than Stages A-B and HFpEF. In all HF stages, 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 (Hazard Ratio 2.05, 95% confidence interval 1.81 - 5.18). Kaplan-Meier analysis confirmed a worse survival probability in Stages A-B and HFpEF, but not HFrEF. After adjusting for clinical and echocardiographic variables, patients in the highest SBP/Workload tertile had a 47% higher risk of the primary outcome than subjects in the lowest tertile. Conclusions: HRE is associated with peculiar pathophysiological features and possibly worse prognosis in patients in the earliest stages of cardiovascular disease and in those with HFpEF.

Abstract Funding Acknowledgements Type of funding sources: None. Background Conflicting data exist regarding the prognostic significance of hypertensive response to exercise (HRE), commonly defined according to absolute peak systolic blood pressure (SBP) values. Limited evidence is available regarding the impact of workload-indexed HRE in patients at different stages of the heart failure (HF) spectrum as defined by the American College of Cardiology/American Heart Association HF staging system. Purpose We evaluated the SBP/Workload slope during exercise across the HF spectrum and investigated the haemodynamic, functional and prognostic correlates of HRE. Methods We prospectively enrolled 58 healthy controls, 201 subjects at risk of developing HF (HF Stages A-B), and 369 patients with a definite diagnosis of HF (Stage C); among the latter, 143 had preserved (HFpEF) and 226 reduced (HFrEF) left ventricular ejection fraction. All patients underwent a combined cardiopulmonary-exercise stress echocardiography test. For each patient, we recorded the first (i.e., within the first minute of exercise) and last (i.e., at peak effort) BP measurement during the ramp protocol. The SBP/Workload slope (Figure 1) was calculated as the ratio of the difference in SBP over the corresponding increment in watts (W): (SBPpeak – SBPfirst)/(Wpeak – Wfirst). In each subgroup, we divided patients according to SBP/Workload slope tertiles; HRE was defined as the highest sex-specific SBP/Workload slope tertile in each HF stage. The primary outcome was a composite of all-cause mortality and hospitalization for cardiovascular reasons. Results Median SBP/Workload slope was 0.53 mmHg/W, interquartile range 0.36-0.72 mmHg/W; the slope was 39% steeper in women than in men (p<0.0001). After adjusting for age and sex, SBP/Workload slope in controls (0.43, 0.35-0.57 mmHg/W) was similar to HFrEF (0.47, 0.30-0.63 mmHg/W) but significantly lower than Stages A-B (0.61, 0.47-0.75 mmHg/W) and HFpEF (0.63, 0.42-0.86 mmHg/W). In all HF stages, 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 (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. After adjusting for age, sex, body mass index, rest and peak SBP, rest and peak cardiac output, and rest and peak left ventricular ejection fraction, patients with the highest SBP/Workload slope had a 47% higher risk of the primary outcome than subjects in the lowest tertile (Figure 2). Conclusion HRE, as evaluated by the SBP/Workload slope, is associated with distinct pathophysiological features and impaired functional capacity across the HF spectrum, especially in Stages A-B and in patients with HFpEF. Patients with HRE in these subgroups may be at increased risk of adverse cardiovascular outcomes.

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.

Even though it has been more than a decade since renal denervation (RDN) was first used to treat hypertension and an intense effort on researching this therapy has been made, it is still not clear how RDN fits into the antihypertensive arsenal. There is no question that RDN lowers blood pressure (BP), it does so to an extent at best corresponding to one antihypertensive drug. The procedure has an excellent safety record. However, it remains clinically impossible to predict whose BP responds to RDN and whose does not. Long-term efficacy data on BP reduction are still unconvincing despite the recent results in the SPYRAL HTN-ON MED trial; experimental studies indicate that reinnervation is occurring after RDN. Although BP is an acceptable surrogate endpoint, there is complete lack of outcome data with RDN. Clear indications for RDN are lacking although patients with resistant hypertension, those with documented increase in activity of the sympathetic system and perhaps those who desire to take fewest medication may be considered.