Bryan Mist

Biventricular Response After Pulmonary Valve Replacement for Right Ventricular Outflow Tract Dysfunction Is Age a Predictor of Outcome

Background— The timing of pulmonary valve replacement (PVR) for free pulmonary incompetence in patients with congenital heart disease remains a dilemma for clinicians. We wanted to assess the determinants of improvement after PVR for pulmonary regurgitation over a wide range of patient ages and to use any identified predictors to compare clinical outcomes between patient groups. Methods and Results— Seventy-one patients (mean age 22±11 years; range, 8.5 to 64.9; 72% tetralogy of Fallot) underwent PVR for severe pulmonary regurgitation. New York Heart Association class improved after PVR (median of 2 to 1, P<0.0001). MRI and cardiopulmonary exercise testing were performed before and 1 year after intervention. After PVR, there was a significant reduction in right ventricular volumes (end diastolic volume 142±43 to 91±18, end systolic volume 73±33 to 43±14 mL/m2, P<0.0001), whereas left ventricular end diastolic volume increased (66±12 to 73±13 mL/m2, P<0.0001). Effective cardiac output significantly increased (right ventricular: 3.0±0.8 to 3.3±0.8 L/min, P=0.013 and left ventricular: 3.0±0.6 to 3.4±0.7 L/min, P<0.0001). On cardiopulmonary exercise testing, ventilatory response to carbon dioxide production at anaerobic threshold improved from 35.9±5.8 to 34.1±6.2 (P=0.008). Normalization of ventilatory response to carbon dioxide production was most likely to occur when PVR was performed at an age younger than 17.5 years (P=0.013). Conclusions— A relatively aggressive PVR policy (end diastolic volume <150 mL/m2) leads to normalization of right ventricular volumes, improvement in biventricular function, and submaximal exercise capacity. Normalization of ventilatory response to carbon dioxide production is most likely to occur when surgery is performed at an age ≤17.5 years. This is also associated with a better left ventricular filling and systolic function after surgery.

Prevalence of exercise-induced left ventricular outflow tract obstruction in symptomatic patients with non-obstructive hypertrophic cardiomyopathy

Background: Resting left ventricular outflow tract obstruction (LVOTO) occurs in 25% of patients with hypertrophic cardiomyopathy (HCM) and is an important cause of symptoms and disease progression. The prevalence and clinical significance of exercise induced LVOTO in patients with symptomatic non-obstructive HCM is uncertain. Methods and results: 87 symptomatic patients (43.3 (13.7) years, 67.8% males) with HCM and no previously documented LVOTO (defined as a gradient ⩾30 mm Hg) underwent echocardiography during upright cardiopulmonary exercise testing: 54 patients (62.1%; 95% CI 51.5 to 71.6) developed LVOTO during exercise (latent LVOTO); 33 (37.9%; 95% CI 28.4 to 48.5) had neither resting nor exercise LVOTO (non-obstructive). Patients with latent LVOTO were more likely to have systolic anterior motion of the mitral valve (SAM) at rest (relative risk 2.1, 95% CI 1.2 to 3.8; p = 0.01), and higher peak oxygen consumption (mean difference: 10.3%, 95% CI 2.1 to 18.5; p = 0.02) than patients with non-obstructive HCM. The only independent predictors of Δ gradient during exercise were a history of presyncope/syncope, incomplete/complete SAM at rest and Wigle score (all p<0.05). Subsequent invasive reduction of LVOTO in 10 patients with latent obstruction and drug refractory symptoms resulted in improved functional class and less syncope/presyncope (all p<0.05). Conclusions: Approximately two-thirds of patients with symptomatic non-obstructive HCM have latent LVOTO. This study suggests that all patients with symptomatic non-obstructive HCM should have exercise stress echocardiography.

Physiological and Clinical Consequences of Relief of Right Ventricular Outflow Tract Obstruction Late After Repair of Congenital Heart Defects

Background— Right ventricular outflow tract obstruction (RVOTO) is a common problem after repair of congenital heart disease. Percutaneous pulmonary valve implantation (PPVI) can treat this condition without consequent pulmonary regurgitation or cardiopulmonary bypass. Our aim was to investigate the clinical and physiological response to relieving RVOTO. Methods and Results— We studied 18 patients who underwent PPVI for RVOTO (72% male, median age 20 years) from a total of 93 who had this procedure for various indications. All had a right ventricular outflow tract (RVOT) gradient >50 mm Hg on echocardiography without important pulmonary regurgitation (less than mild or regurgitant fraction <10% on magnetic resonance imaging [MRI]). Cardiopulmonary exercise testing, tissue Doppler echocardiography, and MRI were performed before and within 50 days of PPVI. PPVI reduced RVOT gradient (51.4 to 21.7 mm Hg, P<0.001) and right ventricular systolic pressure (72.8 to 47.3 mm Hg, P<0.001) at catheterization. Symptoms and aerobic (25.7 to 28.9 mL · kg−1 · min−1, P=0.002) and anaerobic (14.4 to 16.2 mL · kg−1 · min−1, P=0.002) exercise capacity improved. Myocardial systolic velocity improved acutely (tricuspid 4.8 to 5.3 cm/s, P=0.05; mitral 4.7 to 5.5 cm/s, P=0.01), whereas isovolumic acceleration was unchanged. The tricuspid annular velocity was not maintained on intermediate follow-up. Right ventricular end-diastolic volume (99.9 to 89.7 mL/m2, P<0.001) fell, whereas effective stroke volume (43.7 to 48.3 mL/m2, P=0.06) and ejection fraction (48.0% to 56.8%, P=0.01) increased. Left ventricular end-diastolic volume (72.5 to 77.4 mL/m2, P=0.145), stroke volume (45.3 to 50.6 mL/m2, P=0.02), and ejection fraction (62.6% to 65.8%, P=0.03) increased. Conclusions— PPVI relieves RVOTO, which leads to an early improvement in biventricular performance. Furthermore, it reduces symptoms and improves exercise tolerance. These findings have important implications for the management of this increasingly common condition.

Exercise-induced ventricular arrhythmias and risk of sudden cardiac death in patients with hypertrophic cardiomyopathy

BACKGROUND Non-sustained ventricular tachycardia (NSVT) during ambulatory electrocardiographic monitoring (typically occurring at rest or during sleep) is associated with an increased risk of sudden cardiac death in patients with hypertrophic cardiomyopathy. The prevalence and prognostic significance of ventricular arrhythmias during exercise is unknown. METHODS AND RESULTS This was a cohort study, with prospective data collection. We studied 1380 patients, referred to a cardiomyopathy clinic in London, UK [mean age 42 years (SD 15); 62% male; mean follow-up 54 (SD 49) months]. Patients underwent two-dimensional and Doppler echocardiography, upright exercise testing, and Holter monitoring. Twenty-seven patients [mean age 40 (SD 14) years (18-64); 22 (81.5%) male] had NSVT (24) or ventricular fibrillation (VF) (3) during exercise. During exercise, 13 (54.2%) had more than one run of NSVT (maximum 5) with a mean heart rate of 221 (SD 48) b.p.m. Patients with exercise NSVT/VF had more severe hypertrophy (22.6 vs. 19.5 mm, P = 0.009) and larger left atria (47.3 vs. 43.7 mm, P = 0.03). Male gender was significantly associated with exercise NSVT/VF [22 (81.5%) vs. 832 (61.5%), P = 0.03]. Eight (29.6%) of the exercise NSVT/VF patients died or had a cardiac event (SD/ICD discharge/transplant) compared with 150 (11.1%) patients without exercise NSVT/VF, P = 0.008. Patients with NSVT/VF had a 3.73-fold increase in risk of SD/ICD discharge (HR 95% CI: 1.61-8.63, P = 0.002). Exercise NSVT alone was associated with a 2.82-fold increased risk (HR 95% CI: 1.02-7.75, P = 0.049). In multivariable analysis with other risk markers, exercise NSVT/VF (but not NSVT alone) was independently associated with an increased risk of SD/ICD [HR 3.14 (95% CI: 1.29-7.61, P = 0.01)]. CONCLUSION Ventricular arrhythmia during symptom limited exercise is rare in patients with hypertrophic cardiomyopathy, but is associated with an increased risk of sudden cardiac death.

Cardiopulmonary Exercise Testing and Prognosis in Hypertrophic Cardiomyopathy

Background—Exercise testing is performed in patients with hypertrophic cardiomyopathy to evaluate blood pressure response, a risk factor for sudden cardiac death. The prognostic role of exercise gas exchange variables is unknown. Methods and Results—Between 1998 and 2010, 1898 patients (age 47±15 years, range 16–86 years; 67% male) with hypertrophic cardiomyopathy underwent cardiopulmonary exercise testing. A total of 178 (9.4%) patients reached the primary end point of all-cause mortality or heart transplant (death/transplant) during a median follow-up of 5.6 years (interquartile range 2.6–8.9), giving an annual event rate of 1.6% per person year. Peak oxygen consumption (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.77–0.88, P<0.001), ventilatory efficiency (adjusted HR 1.10, 95% CI 1.00–1.22, P=0.049), and ventilatory anaerobic threshold (adjusted HR 0.82, 95% CI 0.70–0.96, P=0.016) were predictors of the primary outcome after correction for age, sex, left atrial size, nonsustained ventricular tachycardia, and ejection fraction. The overall adjusted death/transplant estimates for patients in the lowest quartile with peak oxygen consumption ⩽15.3 mL/kg/min were 14% at 5 years and 31% at 10 years. Peak oxygen consumption (HR 0.81, 95% CI 0.77–0.86, P<0.01) and ventilation to carbon dioxide production (HR 1.10, 95% CI 1.08–1.13, P<0.001) were predictors of death because of heart failure or transplantation but not sudden cardiac death or implantable cardioverter defibrillator shocks. Conclusions—Cardiopulmonary exercise testing provides prognostic information in patients with hypertrophic cardiomyopathy. Submaximal exercise parameters, such as ventilatory efficiency and anaerobic threshold, measured alone or in combination with peak oxygen consumption, predict death from heart failure.

Cardiac output response and peripheral oxygen extraction during exercise among symptomatic hypertrophic cardiomyopathy patients with and without left ventricular outflow tract obstruction

Objective Reduction of left ventricular outflow tract obstruction (LVOTO) often improves symptoms in hypertrophic cardiomyopathy (HCM), but the correlation between exercise performance and measured LVOT gradients is weak. We investigated the relationship between LVOTO and cardiorespiratory responses during exercise. Methods The study cohort included 70 patients with HCM (32 with LVOTO, 55 male, age 47±13) attending a dedicated cardiomyopathy clinic and 28 normal volunteers. All underwent cardiopulmonary exercise testing with simultaneous non-invasive haemodynamic assessment using finger plethysmography. Main outcome measures were peak oxygen consumption, cardiac index and arteriovenous oxygen difference. Results When compared with controls, patients had reduced peak exercise oxygen consumption (22.4±6.1 vs 34.7±7.7 mL/kg/min, p<0.0001) and cardiac index (5.5±1.9 vs 9.4±2.9 L/min/m2, p<0.0001). At all workloads, stroke volume index (SVI) was lower and arteriovenous oxygen difference greater in patients. During all stages of exercise, LVOTO in patients was associated with failure to augment SVI and higher oxygen consumption; cardiac reserve (4.4±2.7 vs 6.3±3.6 L/min, p=0.025) and peak mean arterial pressure (104±16 vs 112±16 mm Hg, p=0.033) were lower. Multivariable predictors of cardiac output response were age (β: −0.11; CI −0.162 to −0.057; p<0.0001), peak LVOT gradient (β: −0.018; CI −0.034 to −0.002; p=0.031) and gender (β: −2.286; CI −0.162 to −0.577; p=0.01). Within the obstructive cohort, different patterns of SV response were elicited in patients with similar clinical features. Conclusions Cardiac reserve is reduced in HCM because of failure of SV augmentation. LVOTO exacerbates this abnormal response, but haemodynamic responses vary significantly. Non-invasive exercise haemodynamic assessment may improve understanding of symptoms and help tailor therapy.

Non-invasive assessment of cardiac output at rest and during exercise by finger plethysmography

We sought to determine the accuracy of finger plethysmography using pulse waveform analysis with brachial calibration for measurement of cardiac output during submaximal exercise by comparing it against an acetylene (C2H2) uptake technique.

88 Cardiopulmonary Exercise Testing and Prognosis in Hypertrophic Cardiomyopathy

Background Exercise testing is commonly performed in patients with hypertrophic cardiomyopathy (HCM) to evaluate blood pressure response, a conventional risk factor for sudden cardiac death. The 2011 ACCF/AHA guidelines state “the role of metabolic stress testing in the evaluation of patients with HCM remains to be decided, particularly with regard to clinical outcome. Methods and results Between 1998 and 2010, 1,898 patients (age 47 ± 15 years, 67% male) with HCM underwent cardiopulmonary exercise testing (CPX). During a mean follow-up of 5.8 ± 4 years, 178 (9.4%) patients reached the primary endpoint of all-cause mortality or orthotropic heart transplant. Peak oxygen consumption, V˙O2 (HR 0.91 95% CI 0.89–0.93, p < 0.001), ventilatory efficiency, V˙EV˙CO2 (HR 1.08 95% CI 1.06–1.09), and ventilatory anaerobic threshold V˙AT (HR 0.88 95% CI 0.84–0.92) were predictors of the primary outcome. A progressively worse prognosis was associated with higher ventilatory class (Figure 1). V˙EV˙CO2 was a good predictor of heart failure death or transplantation (HR 1.1 95% CI 1.07–1.14 p < 0.001) outcome but not sudden cardiac death (HR 1.01 95% CI 0.97–0.96 p = 0.54). Abstract 88 Figure 1 Kaplan Kaplan Meier plot showing survival rates in 1898 patients with HCM stratified by ventilatory class. Table shows population at risk at 5 year time points Conclusions CPX provides important prognostic information in patients with HCM. Sub-maximal exercise parameters are potentially more useful than peak VO2 alone. Patients with an enhanced ventilatory response have a substantially higher risk of death or transplantation. Reference 1 Gersh, et al. JACC 2011;58(25):212–60