Heart rate response and functional capacity in patients with chronic heart failure with preserved ejection fraction.

The mechanisms of exercise intolerance in heart failure with preserved ejection fraction (HFpEF) are not yet elucidated. Chronotropic incompetence has emerged as a potential mechanism. We aimed to evaluate whether heart rate (HR) response to exercise is associated to functional capacity in patients with symptomatic HFpEF. We prospectively studied 74 HFpEF patients [35.1% New York Heart Association Class III, 53% female, age (mean ± standard deviation) 72.5 ± 9.1 years, and 59.5% atrial fibrillation]. Functional performance was assessed by peak oxygen consumption (peak VO2 ). The mean (standard deviation) peak VO2 was 10 ± 2.8 mL/min/kg. The following chronotropic parameters were calculated: Delta-HR (HR at peak exercise - HR at rest), chronotropic index (CI) = (HR at peak exercise - resting HR)/[(220 - age) - resting HR], and CI according to the equation developed by Keteyian et al. (CIK) (HR at peak exercise - HR at rest)/[119 + (HR at rest/2) - (age/2) - 5 - HR at rest]. In a bivariate setting, peak VO2 was positively and significantly correlated with Delta-HR (r = 0.35, P = 0.003), CI (r = 0.27, P = 0.022), CIK (r = 0.28, P = 0.018), and borderline with HR at peak exercise (r = 0.22, P = 0.055). In a multivariable linear regression analysis that included clinical, analytical, echocardiographic, and functional capacity covariates, the chronotropic parameters were positively associated with peak VO2 . We found a linear relationship between Delta-HR and peak VO2 (β coefficient of 0.03; 95% confidence interval: 0.004-0.05; P = 0.030); conversely, the association among CIs and peak VO2 was exponentially shaped. In patients with chronic HFpEF, the HR response to exercise was positively associated to patient's functional capacity.

Domínguez E ，Palau P ，Núñez E ，Ramón JM ，López L ，Melero J ，Bellver A ，Santas E ，Chorro FJ ，Núñez J ... -  《ESC Heart Failure》

Inspiratory Muscle Function and Exercise Capacity in Patients With Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterized by impaired exercise capacity resulting from dyspnea and fatigue. The pathophysiological mechanisms underlying the exercise intolerance in HFpEF are not well established. We sought to evaluate the effects of inspiratory muscle function on exercise tolerance in symptomatic patients with HFpEF. A total of 74 stable symptomatic patients with HFpEF and New York Heart Association class II-III underwent a cardiopulmonary exercise test between June 2012 and May 2016. Inspiratory muscle weakness was defined as maximum inspiratory pressure (MIP)  <70% of normal predicted values. Pearson correlation coefficient and multivariate linear regression analysis were used to assess the association between percent of predicted MIP (pp-MIP) and maximal exercise capacity [measured by peak oxygen uptake (peak VO2) and percent of predicted peak VO2 (pp-peak VO2)]. Thirty-one patients (42%) displayed inspiratory muscle weakness. Mean (standard deviation) age was 72.5 ± 9.1 years, 53% were women, and 35.1% displayed New York Heart Association class III. Mean peak VO2 and pp-peak VO2 were 10 ± 2.8 mL•min•kg and 57.3 ± 13.8%, respectively. The median (interquartile range) of pp-MIP was 72% (58%-90%). pp-MIP was not correlated with peak VO2 (r = -0.047, P = .689) nor pp-peak VO2 (r = -0.078, P = .509). Furthermore, in multivariable analysis, pp-MIP showed no association with peak VO2 (β coefficient = 0.01, 95% confidence interval -0.01 to 0.03, P = .241) and pp-peak VO2 (β coefficient = -0.00, 95% confidence interval -0.10 to 0.10, P = .975). In symptomatic elderly patients with HFpEF, we found that pp-MIP was not associated with either peak VO2 or pp-peak VO2.

Palau P ，Domínguez E ，Núñez E ，Ramón JM ，López L ，Melero J ，Bellver A ，Chorro FJ ，Bodí V ，Bayés-Genis A ，Sanchis J ，Núñez J ... -  《-》

Importance of chronotropic response and left ventricular long-axis function for exercise performance in patients with heart failure and preserved ejection fraction.

We evaluated the relationship between the degree of chronotropic incompetence and left ventricular (LV) impairment during exercise with severity of exercise intolerance in patients with heart failure and preserved ejection fraction (HFPEF). All patients underwent exercise echocardiography during bicycle Ergometer exercise with the acquisition of long-axis tissue Doppler imaging (TDI). Peak heart rates during exercise were also recorded and the percentages of maximal age-predicted heart rate (%MPHR) and heart rate reserve (%HRR) were calculated thereby. Besides, cardiopulmonary exercise testing was performed with peak oxygen consumption (VO2) measuring averaged at the highest 30-second during exercise. Forty HFPEF patients (aged 65±9 years; 75% male) were divided into two groups according to the median of peak VO2: patients with peak VO2<16.5 and ≥16.5 ml/kg/min, respectively. Patients with lower peak VO2 had decreased peak heart rates, %MPHR, %HRR, stroke volume and cardiac indices (LVSI and LVCI) than those with higher peak VO2 (all p<0.05). The LV long-axis functions (TDI Sm, Em, s' and e') were reduced in patients with lower peak VO2 (all p<0.05). Moreover, peak VO2 correlated with the following parameters: peak heart rates, %MPHR, %HRR, LVSI, LVCI, TDI Sm, Em, s' and e'(all p<0.05). The degree of blunted chronotropic response and impaired LV long-axis function were more profound in HFPEF patients with poor exercise performance.

Wang J ，Fang F ，Yip GW ，Sanderson JE ，Feng W ，Xie JM ，Luo XX ，Lee AP ，Lam YY ... -  《-》

Effect of β-Blocker Withdrawal on Functional Capacity in Heart Failure and Preserved Ejection Fraction.

Chronotropic incompetence has shown to be associated with a decrease in exercise capacity in heart failure with preserved ejection fraction (HFpEF), yet β-blockers are commonly used in HFpEF despite the lack of robust evidence. This study aimed to evaluate the effect of β-blocker withdrawal on peak oxygen consumption (peak Vo2) in patients with HFpEF and chronotropic incompetence. This is a multicenter, randomized, investigator-blinded, crossover clinical trial consisting of 2 treatment periods of 2 weeks separated by a washout period of 2 weeks. Patients with stable HFpEF, New York Heart Association functional classes II and III, previous treatment with β-blockers, and chronotropic incompetence were first randomized to withdrawing from (arm A: n = 26) versus continuing (arm B: n = 26) β-blocker treatment and were then crossed over to receive the opposite intervention. Changes in peak Vo2 and percentage of predicted peak Vo2 (peak Vo2%) measured at the end of the trial were the primary outcome measures. To account for the paired-data nature of this crossover trial, linear mixed regression analysis was used. The mean age was 72.6 ± 13.1 years, and most of the patients were women (59.6%) in New York Heart Association functional class II (66.7%). The mean peakVo2 and peak Vo2% were 12.4 ± 2.9 mL/kg/min, and 72.4 ± 17.8%, respectively. No significant baseline differences were found across treatment arms. Peak Vo2 and peak Vo2% increased significantly after β-blocker withdrawal (14.3 vs 12.2 mL/kg/min [Δ +2.1 mL/kg/min]; P < 0.001 and 81.1 vs 69.4% [Δ +11.7%]; P < 0.001, respectively). β-blocker withdrawal improved maximal functional capacity in patients with HFpEF and chronotropic incompetence. β-blocker use in HFpEF deserves profound re-evaluation. (β-blockers Withdrawal in Patients With HFpEF and Chronotropic Incompetence: Effect on Functional Capacity [PRESERVE-HR]; NCT03871803; 2017-005077-39).

Palau P ，Seller J ，Domínguez E ，Sastre C ，Ramón JM ，de La Espriella R ，Santas E ，Miñana G ，Bodí V ，Sanchis J ，Valle A ，Chorro FJ ，Llácer P ，Bayés-Genís A ，Núñez J ... -  《-》

Contributions of Nondiastolic Factors to Exercise Intolerance in Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) has a complex etiology. Factors responsible for development of impaired exercise tolerance and disease progression are incompletely defined. The authors sought to define the contributions of contractile reserve, ventriculo-arterial coupling (VAC) reserve, and chronotropic response to the progression of HFpEF. We performed echocardiography at rest and immediately post-cardiopulmonary exercise test in 207 patients (63 ± 8 years of age) with stage C heart failure (HF) (exertional dyspnea, New York Heart Association functional class II to III, exercise capacity <80% of normal, left ventricular ejection fraction >50%, and diastolic dysfunction) and 60 patients with stage B HF (normal exercise tolerance with left ventricular hypertrophy, and/or reduced global longitudinal strain, with diastolic dysfunction). Symptomatic patients were grouped as stage C1 (ratio of peak early diastolic mitral flow velocity to peak early diastolic mitral annular velocity [E/e'] <13 both at rest and exercise; n = 63), C2 (E/e' >13 only at exercise; n = 118), and C3 (E/e' >13 both at rest and exercise; n = 26) HF. Exercise capacity and cardiovascular functional reserve were less impaired in stage C1 than in stages C2 and C3. Chronotropic response was more disturbed in stage C3 than C1 and C2. Changes from rest to exercise in E/e' (-0.6 ± 1.7 vs. 3.7 ± 2.8; p < 0.0001), global longitudinal strain (2.9 ± 2.0 vs. 1.6 ± 2.8; p < 0.002), VAC (-0.21 ± 0.17 vs. -0.09 ± 0.15; p < 0.0001), and in VO2-HR gradient (0.30 ± 0.07 vs. 0.26 ± 0.11; p < 0.01) were significantly different in stages B and C. Normal E/e' response to exertion in symptomatic HFpEF is associated with less profound impairment of exercise capacity and is accompanied by derangements of contractile state and VAC. The transition from asymptomatic to overt HFpEF is linked to diastolic, systolic, and chronotropic deficits and an increasing degree of hemodynamic disturbances in stage C HF.

Kosmala W ，Rojek A ，Przewlocka-Kosmala M ，Mysiak A ，Karolko B ，Marwick TH ... -  《-》