Impaired longitudinal systolic-diastolic coupling and cardiac response to exercise in patients with hypertrophic cardiomyopathy.

BACKGROUND: In patients with hypertrophic cardiomyopathy (HCM), impaired augmentation of stroke volume and diastolic dysfunction contribute to exercise intolerance. Systolic-diastolic (S-D) coupling characterizes how systolic contraction of the left ventricle (LV) primes efficient elastic recoil during early diastole. Impaired S-D coupling may contribute to the impaired cardiac response to exercise in patients with HCM. METHODS: Patients with HCM (n = 25, age = 47 ± 9 years) and healthy adults (n = 115, age = 49 ± 10 years) underwent a cardiopulmonary exercise testing (CPET) and echocardiogram. S-D coupling was defined as the ratio of LV longitudinal excursion of the mitral annulus during early diastole (EDexc) and systole (Sexc) and compared between groups. Peak oxygen uptake (peak V̇O2) (Douglas bags), cardiac index (C2H2 rebreathe), and stroke volume index (SVi) were assessed during CPET. Linear regression was performed between S-D coupling and peak V̇O2, peak cardiac index, and peak SVi. RESULTS: S-D coupling was lower in HCM (Controls: 0.63 ± 0.08, HCM: 0.56 ± 0.10, p < 0.001). Peak V̇O2 and stroke volume reserve were lower in patients with HCM (Peak VO2 Controls: 28.5 ± 5.5, HCM: 23.7 ± 7.2 mL/kg/min, p < 0.001, SV reserve: Controls 39 ± 16, HCM 30 ± 18 mL, p = 0.008). In patients with HCM, S-D coupling was associated with peak V̇O2 (r = 0.47, p = 0.018), peak cardiac index (r = 0.60, p = 0.002), and peak SVi (r = 0.63, p < 0.001). CONCLUSION: Systolic-diastolic coupling was impaired in patients with HCM and was associated with fitness and the cardiac response to exercise. Inefficient S-D coupling may link insufficient stroke volume generation, diastolic dysfunction, and exercise intolerance in HCM.

Randomized Controlled Trial of Moderate- and High-Intensity Exercise Training in Patients With Hypertrophic Cardiomyopathy: Effects on Fitness and Cardiovascular Response to Exercise.

Background Moderate intensity exercise training (MIT) is safe and effective for patients with hypertrophic cardiomyopathy, yet the efficacy of high intensity training (HIT) remains unknown. This study aimed to compare the efficacy of HIT compared with MIT in patients with hypertrophic cardiomyopathy. Methods and Results Patients with hypertrophic cardiomyopathy were randomized to either 5 months of MIT, or 1 month of MIT followed by 4 months of progressive HIT. Peak oxygen uptake (V˙O2; Douglas bags), cardiac output (acetylene rebreathing), and arteriovenous oxygen difference (Fick equation) were measured before and after training. Left ventricular outflow gradient and volumes were measured by echocardiography. Fifteen patients completed training (MIT, n=8, age 52±7 years; HIT, n=7, age 42±8 years). Both HIT and MIT improved peak V˙O2 by 1.3 mL/kg per min (P=0.009). HIT (+1.5 mL/kg per min) had a slightly greater effect than MIT (+1.1 mL/kg per min) but with no statistical difference (group×exercise P=0.628). A greater augmentation of arteriovenous oxygen difference occurred with exercise (Δ1.6 mL/100 mL P=0.005). HIT increased left ventricular end-diastolic volume (+17 mL, group×exercise P=0.015) compared with MIT. No serious arrhythmias or adverse cardiac events occurred. Conclusions This randomized trial of exercise training in patients with hypertrophic cardiomyopathy demonstrated that both HIT and MIT improved fitness without clear superiority of either. Although the study was underpowered for safety outcomes, no serious adverse events occurred. Exercise training resulted in salutary peripheral and cardiac adaptations. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03335332.

Retractable foreskin reduces urinary tract infections in infant boys with vesicoureteral reflux.

BACKGROUND: Uncircumcised males are at higher risk of urinary tract infection (UTI) in the first year of life and circumcision is recommended as an option for males with vesicoureteral reflux (VUR). Uncircumcised males treated successfully with topical corticosteroid cream have decreased risk of UTI but the role of preputial management has not been explored previously in males with VUR. OBJECTIVE: We hypothesized that among uncircumcised boys with VUR, those with retractable foreskin would be at reduced risk of UTI compared to those with non-retractable foreskin. STUDY DESIGN: Males less than one year of age with primary VUR were prospectively enrolled. Patients with concomitant urologic diagnoses or less than one month of follow-up were excluded. Phimosis severity was graded on a 0-5 scale. Primary outcome was UTI during follow-up. Patients were divided into three groups for analysis: circumcised, low grade phimosis (grades 0-3) and high grade phimosis (grades 4-5). Multivariable Cox proportional hazards regression was used to estimate UTI risk adjusting for risk factors. RESULTS: One-hundred and five boys (24 circumcised and 81 uncircumcised) with VUR were included. Median age at enrollment was 4.4 months (IQR 2.2-6.6) and median follow-up was 1.1 years (IQR 0.53-2.9). Males with phimosis grades 4-5 had a higher UTI rate (29%) compared to phimosis grade 0-3 (4%). Based on Kaplan-Meier curves, boys with initial phimosis grades 4-5 were significantly more likely to develop a UTI than boys who were circumcised or had phimosis grades 0-3 (p = 0.005). On multivariable analysis, boys with phimosis grades 4-5 were significantly more likely to develop UTI when compared to boys with grades 0-3 phimosis (HR = 8.4, 95% CI: 1.1-64, p = 0.04). DISCUSSION: Males with a retractable prepuce had a lower UTI risk compared to males with non-retractable prepuce (high grade phimosis) and this remained significant on multivariable analysis. This is concordant with prior studies demonstrating that a retractable prepuce is associated with decreased UTI risk. Limitations of our study include using phimosis grade at time of study enrollment and heterogenous prophylactic antibiotic use in our population. CONCLUSIONS: Retractable foreskin reduces UTI risk in uncircumcised boys less than one year of age with VUR. Medical phimosis treatment to achieve a retractable prepuce offers an alternative and less invasive modality to reduce UTI risk in males with VUR.