Quality of Life and Exercise Capacity in Early Stage and Subclinical Hypertrophic Cardiomyopathy: A Secondary Analysis of the VANISH Trial.

BACKGROUND: The health-related quality of life (HRQOL) and cardiopulmonary exercise testing (CPET) performance of individuals with subclinical and early stage hypertrophic cardiomyopathy (HCM) have not been systematically studied. Improved understanding will inform the natural history of HCM and factors influencing well-being. METHODS: VANISH trial (Valsartan for Attenuating Disease Evolution in Early Sarcomeric HCM) participants with early stage sarcomeric HCM (primary analysis cohort) and subclinical HCM (sarcomere variant without left ventricular hypertrophy comprising the exploratory cohort) who completed baseline and year 2 HRQOL assessment via the pediatric quality of life inventory and CPET were studied. Metrics correlating with baseline HRQOL and CPET performance were identified. The impact of valsartan treatment on these measures was analyzed in the early stage cohort. RESULTS: Two hundred participants were included: 166 with early stage HCM (mean age, 23±10 years; 40% female; 97% White; and 92% New York Heart Association class I) and 34 subclinical sarcomere variant carriers (mean age, 16±5 years; 50% female; and 100% White). Baseline HRQOL was good in both cohorts, although slightly better in subclinical HCM (composite pediatric quality of life score 84.6±10.6 versus 90.2±9.8; P=0.005). Both cohorts demonstrated mildly reduced functional status (mean percent predicted peak oxygen uptake 73±16 versus 78±12 mL/kg per minute; P=0.18). Percent predicted peak oxygen uptake and peak oxygen pulse correlated with HRQOL. Valsartan improved physical HRQOL in early stage HCM (adjusted mean change in pediatric quality of life score +4.1 versus placebo; P=0.01) but did not significantly impact CPET performance. CONCLUSIONS: Functional capacity can be impaired in young, healthy people with early stage HCM, despite New York Heart Association class I status and good HRQOL. Peak oxygen uptake was similarly decreased in subclinical HCM despite normal left ventricular wall thickness and excellent HRQOL. Valsartan improved physical pediatric quality of life scores but did not significantly impact CPET performance. Further studies are needed for validation and to understand how to improve patient experience. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01912534.

Heart Failure With Preserved Ejection Fraction and Frailty: From Young to Superaged Coexisting HFpEF and Frailty.

Being commonly diagnosed in elderly women and associated with comorbidities as well as ageing-related cardio-vascular changes, heart failure with preserved ejection fraction (HFpEF) has been recently considered as a distinct cardiogeriatric syndrome. Frailty is another frequent geriatric syndrome. HFpEF and frailty share common underlying mechanisms, often co-exist, and represent each other's risk factors. A threshold of 65 years old is usually used to screen patients for both frailty and HFpEF in research and clinical settings. However, both HFpEF and frailty are very heterogenous conditions that may develop at younger ages. In this review we aim to provide a broader overview on the coexistence of HFpEF and frailty throughout the lifetime. We hypothesize that HFpEF and frailty patients' profiles (young, elderly, superaged) represent a continuum of the common ageing process modified by cumulative exposure to risk factors resulting to a presentation of HFpEF and frailty at different ages. We believe, that suggested approach might stimulate assessment of frailty in HFpEF assessment and vice versa regardless of age and early implementation of targeted interventions. Future studies of pathophysiology, clinical features, and outcomes of frailty in HFpEF by age are needed.

Cardiac Dysfunction and Exercise Tolerance in Patients after Complex Treatment for Cranial and Craniospinal Tumors in Childhood.

State-of-the-art therapy improves the five-year survival rate of patients under the age of 20 with cranial and craniospinal tumors by up to 74%. The urgency of dealing effectively with late treatment-associated cardiovascular complications is rising. Objective: We aimed to assess echocardiographic parameters and exercise performance in subjects with a history of complex treatment for cranial and craniospinal tumors in childhood. Methods: the study of 48 subjects who underwent cranial and craniospinal irradiation for CNS tumors in childhood and 20 healthy age- and sex-matched volunteers was conducted. The examination included hormone studies, cardiopulmonary exercise testing, and, in the main group, echocardiography (ECHO). Results: In five (10.4%) patients, ECHO changes were detected after complex anti-cancer treatment: thickening and calcification of the aortic valve leaflets (2%), and reduction in the systolic LV and RV function (8% and 6%, respectively). Irradiation of various areas was a significant predictor for reduced exercise tolerance, hyperventilation at rest and upon exertion, and an increased ventilatory equivalent for carbon dioxide. Low exercise tolerance was associated with a younger age at the time of treatment initiation. Significant differences were noted between the control group and the childhood cancer survivors with endocrine disorders. Conclusions: The obtained data confirm the importance of regular cardiovascular and endocrine monitoring of this group of cancer survivors.

Systemic Arterial Oxygen Levels Differentiate Pre- and Post-capillary Predominant Hemodynamic Abnormalities During Exercise in Undifferentiated Dyspnea on Exertion.

BACKGROUND: Whether systemic oxygen levels (SaO2) during exercise can provide a window into invasively derived exercise hemodynamic profiles in patients with undifferentiated dyspnea on exertion is unknown. METHODS: We performed cardiopulmonary exercise testing with invasive hemodynamic monitoring and arterial blood gas sampling in individuals referred for dyspnea on exertion. Receiver operator analysis was performed to distinguish heart failure with preserved ejection fraction from pulmonary arterial hypertension. RESULTS: Among 253 patients (mean ± SD, age 63 ± 14 years, 55% female, arterial O2 [PaO2] 87 ± 14 mmHg, SaO2 96% ± 4%, resting pulmonary capillary wedge pressure [PCWP] 18 ± 4mmHg, and pulmonary vascular resistance [PVR] 2.7 ± 1.2 Wood units), there was no exercise PCWP threshold, measured up to 49 mmHg, above which hypoxemia was consistently observed. Exercise PaO2 was not correlated with exercise PCWP (rho = 0.04; P = 0.51) but did relate to exercise PVR (rho = -0.46; P < 0.001). Exercise PaO2 and SaO2 levels distinguished left-heart-predominant dysfunction from pulmonary-vascular-predominant dysfunction with an area under the curve of 0.89 and 0.89, respectively. CONCLUSION: Systemic O2 levels during exercise distinguish relative pre- and post-capillary pulmonary hemodynamic abnormalities in patients with undifferentiated dyspnea. Hypoxemia during upright exercise should not be attributed to isolated elevation in left heart filling pressures and should prompt consideration of pulmonary vascular dysfunction.

Sequencing and titrating approach of therapy in heart failure with reduced ejection fraction following the 2021 European Society of Cardiology guidelines: an international cardiology survey.

AIMS: In symptomatic patients with heart failure and reduced ejection fraction (HFrEF), recent international guidelines recommend initiating four major therapeutic classes rather than sequential initiation. It remains unclear how this change in guidelines is perceived by practicing cardiologists versus heart failure (HF) specialists. METHODS AND RESULTS: An independent academic web-based survey was designed by a group of HF specialists and posted by email and through various social networks to a broad community of cardiologists worldwide 1 year after the publication of the latest European HF guidelines. Overall, 615 cardiologists (38 [32-47] years old, 63% male) completed the survey, of which 58% were working in a university hospital and 26% were HF specialists. The threshold to define HFrEF was ≤40% for 61% of the physicians. Preferred drug prescription for the sequential approach was angiotensin-converting enzyme inhibitors or angiotensin receptor-neprilysin inhibitors first (74%), beta-blockers second (55%), mineralocorticoid receptor antagonists third (52%), and sodium-glucose cotransporter 2 inhibitors (53%) fourth. Eighty-four percent of participants felt that starting all four classes was feasible within the initial hospitalization, and 58% felt that titration is less important than introducing a new class. Age, status in training, and specialization in HF field were the principal characteristics that significantly impacted the answers. CONCLUSION: In a broad international cardiology community, the 'historical approach' to HFrEF therapies remains the preferred sequencing approach. However, accelerated introduction and uptitration are also major treatment goals. Strategy trials in treatment guidance are needed to further change practices.

In-hospital electrical muscle stimulation for patients early after heart failure decompensation: results from a prospective randomised controlled pilot trial.

BACKGROUND: Electrical muscle stimulation (EMS) is being evaluated as a possible alternative to exercise training to improve functional capacity in severely deconditioned patients with heart failure (HF). However, there is insufficient data on delayed effects of EMS starting early after decompensation. The aim of this study was to determine the impact of a short inpatient EMS intervention in severely deconditioned patients with HF on functional capacity and quality of life (QoL) over a follow-up period of 1 month. METHODS: This is a prospective randomised sham-controlled pilot study. 45 patients hospitalised for decompensated systolic HF (58% men, mean age 66.4±10.2 years) were randomised to EMS (n=22) or sham stimulation (n=23) of lower limbs starting within 3 days after admission. The intervention included 7-10 sessions lasting from 30 to 90 min. The 6-minute walking test distance (6-MWTD), Duke Activity Status Index (DASI) and Minnesota Living with Heart Failure Questionnaire (MLHFQ) were evaluated at baseline, discharge and after 1 month. RESULTS: All patients completed the programme with good EMS tolerance. 37 patients were included in the final analysis. At discharge, 6-MWTD improved from 206,1±61,3 to 299.5±91 m, DASI from 12.1±5.6 to 18.3±7.2 and MLHFQ from 55.6±8.5 to 34.2±9 with EMS compared with smaller improvements in the sham group (p<0.05 for all). One month after discharge, improvements in the EMS group remained significant for MLHFQ (p=0.004) and DASI (p=0.042) and statistically non-significant for 6-MWTD compared with the sham group. CONCLUSIONS: Short-term in-hospital EMS leads to improvements in functional capacity and QoL in selected patients early after HF decompensation that are retained over 1 month after discharge and therefore may serve as initial intervention to improve physical capacity or as a bridge to further conventional exercise training. Larger studies are required to evaluate individual responses to an early initiation of EMS in decompensated HF as well as long-term effects.

A new algorithm for optimization of rate-adaptive pacing improves exercise tolerance in patients with HFpEF.

AIM: To develop an algorithm for optimization of rate-adaptive pacing settings in heart failure patients with preserved ejection fraction (HFpEF) and permanent cardiac pacing. METHODS: This is a prospective randomized controlled study. A total of 54 patients with HFpEF, permanent atrial fibrillation (AF), and VVIR pacing were randomized to an intervention group with optimization of rate-adaptation parameters by using cardiopulmonary exercise testing (CPET) and pacemaker stress echocardiography (PASE), and to a control group with conventional programming. CPET, 6-min walk test (6-mwt), echocardiography (echo), Duke Activity Status Index (DASI), and Minnesota questionnaire (MLHFQ) were performed at baseline and after 3 months. PASE was used to exclude exercise-induced ischemia and to determine safe upper sensor rate. Pacing parameters were corrected to achieve optimal heart rate increments of 3-6 bpm for 1 mL/min/kg of VO2 (oxygen uptake). RESULTS: After 3 months, the intervention group demonstrated significant improvement of VO2 peak by 1.64 ± 1.6 mL/min/kg, anaerobic threshold by 1.33 ± 1.3 mL/min/kg, exercise time by 170 ± 98 s, 6-mwt distance by 75 ± 63 m (P < .0001 for all), DASI by 5.23 points (P = .009), MLHFQ-score (reduction by 9 points, P < .0001), and echo parameters (decrease in LA volume from 108 (84; 132) to 95 (85; 130) mL, P = .026; E/e' from 11.7 ± 3.2 to 10.4 ± 2.9, P = .025; systolic pulmonary artery pressure (SPAP) from 44 ± 14 to 39 ± 12 mm Hg, P = .001) compared to the control group. CONCLUSION: An algorithm incorporating CPET and PASE for optimal programming of rate-adaptation parameters is a valuable tool to improve exercise capacity in HFpEF patients with permanent AF and VVIR pacing who remain exercise intolerant after conventional programming.

Interval training early after heart failure decompensation is safe and improves exercise tolerance and quality of life in selected patients.

Aims To evaluate safety and efficacy of moderate intensity interval exercise training early after heart failure decompensation on exercise tolerance and health-related quality of life (HRQoL). Methods and results This is a prospective randomized controlled study. We screened 234 consecutive patients admitted with decompensated heart failure; 46 patients (42 men/4 women; 61 ± 12 years of age) were randomized to a moderate intensity aerobic interval training ( n = 24) or to a control group ( n = 22). Patients underwent cardiopulmonary exercise testing, echocardiography and Minnesota Living with Heart Failure questionnaire (MLHFQ) at baseline, after three weeks and after three months. After three weeks, peak-VO2 increased by 17% in the training group ( p = 0.003) with further increase by 10% after three months ( p < 0.001) but did not change significantly in controls. MLHFQ score improved after three weeks, with better results in the training group (from 64.6 ± 15.6 to 30.8 ± 12.9, p < 0.001). After three months, MLHFQ further improved in the exercise training group, but not in controls. Left ventricular ejection fraction was not significantly different between the two groups at baseline and after three months. No serious adverse events related to exercise testing or training were observed. Conclusions Interval exercise training early after an episode of heart failure decompensation is safe and effective in improving exercise tolerance and health-related quality of life in selected patients after achievement of clinical stability. Positive effects remained sustained after three months. Further studies are needed to define role and indications for interval exercise training early after heart failure decompensation.