Left ventricular strain and untwist in hypertrophic cardiomyopathy: relation to exercise capacity.

BACKGROUND: Nonobstructive hypertrophic cardiomyopathy (nHCM) is often associated with reduced exercise capacity despite hyperdynamic systolic function as measured by left ventricular ejection fraction. We sought to examine the importance of left ventricular strain, twist, and untwist as predictors of exercise capacity in nHCM patients. METHODS: Fifty-six nHCM patients (31 male and mean age of 52 years) and 43 age- and gender-matched controls were enrolled. We measured peak oxygen consumption (peak Vo(2)) and acquired standard echocardiographic images in all participants. Two-dimensional speckle tracking was applied to measure rotation, twist, untwist rate, strain, and strain rate. RESULTS: The nHCM patients exhibited marked exercise limitation compared with controls (peak Vo(2) 23.28 +/- 6.31 vs 37.70 +/- 7.99 mL/[kg min], P < .0001). Left ventricular ejection fraction in nHCM patients and controls was similar (62.76% +/- 9.05% vs 62.48% +/- 5.82%, P = .86). Longitudinal, radial, and circumferential strain and strain rate were all significantly reduced in nHCM patients compared with controls. There was a significant delay in 25% of untwist in nHCM compared with controls. Both systolic and diastolic apical rotation rates were lower in nHCM patients. Longitudinal systolic and diastolic strain rate correlated significantly with peak Vo(2) (r = -0.34, P = .01 and r = 0.36, P = .006, respectively). Twenty-five percent untwist correlated significantly with peak Vo(2) (r = 0.36, P = .006). CONCLUSIONS: In nHCM patients, there are widespread abnormalities of both systolic and diastolic function. Reduced strain and delayed untwist contribute significantly to exercise limitation in nHCM patients.

Hypoxic modulation of exogenous nitrite-induced vasodilation in humans.

BACKGROUND: It has been proposed that under hypoxic conditions, nitrite may release nitric oxide, which causes potent vasodilation. We hypothesized that nitrite would have a greater dilator effect in capacitance than in resistance vessels because of lower oxygen tension and that resistance-vessel dilation should become more pronounced during hypoxemia. The effect of intra-arterial infusion of nitrite on forearm blood flow and forearm venous volumes was assessed during normoxia and hypoxia. METHODS AND RESULTS: Forty healthy volunteers were studied. After baseline infusion of 0.9% saline, sodium nitrite was infused at incremental doses from 40 nmol/min to 7.84 mumol/min. At each stage, forearm blood flow was measured by strain-gauge plethysmography. Forearm venous volume was assessed by radionuclide plethysmography. Changes in forearm blood flow and forearm venous volume in the infused arm were corrected for those in the control arm. The peak percentage of venodilation during normoxia was 35.8+/-3.4% (mean+/-SEM) at 7.84 micromol/min (P<0.001) and was similar during hypoxia. In normoxia, arterial blood flow, assessed by the forearm blood flow ratio, increased from 1.04+/-0.09 (baseline) to 1.62+/-0.18 (nitrite; P<0.05) versus 1.07+/-0.09 (baseline) to 2.37+/-0.15 (nitrite; P<0.005) during hypoxia. This result was recapitulated in vitro in vascular rings. CONCLUSIONS: Nitrite is a potent venodilator in normoxia and hypoxia. Arteries are modestly affected in normoxia but potently dilated in hypoxia, which suggests the important phenomenon of hypoxic augmentation of nitrite-mediated vasodilation in vivo. The use of nitrite as a selective arterial vasodilator in ischemic territories and as a potent venodilator in heart failure has therapeutic implications.

The safety and effects of bosentan in patients with a Fontan circulation.

OBJECTIVE: Adult patients with a Fontan circulation tend to have diminished exercise capacity. The principal objective of this study was to investigate the safety of the endothelin receptor antagonist bosentan in Fontan patients, and, secondarily, to assess effects on cardiovascular performance, New York Heart Association functional classification (NYHA FC), and ventricular function. DESIGN: A 6-month prospective, single-center, pilot, safety study of bosentan in Fontan patients. Setting. Adult Congenital Heart Disease referral center. PATIENTS: All patients ≥18 years old with a Fontan circulation and in NYHA FC ≥II were invited to enroll. Interventions. Patients started on 62.5 mg bid of bosentan, uptitrating to 125 mg bid after 2 weeks. OUTCOME MEASURES: Safety was assessed by the incidence of anticipated and unanticipated adverse events during the 6-month study period; specifically those relating to hepatic, renal, or hematological dysfunction as measured by monthly blood tests. Other outcome measures included cardiopulmonary exercise test, 6-minute walk distance test, Borg dyspnea index, NYHA FC, and ventricular function parameters using transthoracic echocardiography. RESULTS: Of the eight patients enrolled, six completed the study. Two patients withdrew from the study (one for non-trial related reasons, one due to adverse events). No clinically significant adverse events relating to bosentan therapy occurred during this study and, in particular, no significant abnormalities in hepatic function tests were observed. Three patients reported transient adverse events. Improvements in NYHA FC and systolic ventricular function were observed after 6 months of bosentan treatment. CONCLUSIONS: The small number of patients with a Fontan circulation in our study was able to tolerate bosentan for 6 months. The safety and tolerability of bosentan in a larger patient population remains unknown. The results presented here justify further investigation in larger studies.

Impaired heart rate recovery and chronotropic incompetence in patients with heart failure with preserved ejection fraction.

BACKGROUND: This study assessed the chronotropic response to exercise and heart rate (HR) recovery after exercise in a carefully phenotyped group of patients with heart failure with preserved left ventricular ejection fraction (HfpEF) and a control group of similar age and gender distribution. METHODS AND RESULTS: We studied 41 patients with HfpEF, 41 healthy controls, and 16 hypertensive controls. None were taking HR-limiting medications. All study participants had clinical examination, 12-lead ECG, pulmonary function test, echocardiogram, and metabolic exercise test with HR monitoring throughout exercise. Chronotropic response was measured by the percentage of the HR reserve used during maximal exercise and the peak exercise HR as a percentage of predicted maximal HR. Patients with HfpEF were generally women (70%), overweight, aged 69+/-8 years. Controls were of similar gender (63%) and age (67+/-6 years). Patients with HfpEF had significantly reduced peak VO(2) compared with controls (20+/-4 mL kg(-1) min(-1) versus 31+/-6 mL kg(-1) min(-1), P<0.001) and greater minute ventilation-carbon dioxide production relationship (V(E)/V(CO2)) slope) (33+/-6 versus 29+/-4, P<0.001). Chronotropic incompetence was significantly more common in patients with HfpEF compared with matched healthy controls as measured by the percentage of the HR reserve used during maximal exercise (63% versus 2%, <0.001) and percentage of predicted maximal HR (34% versus 2%, <0.001). In addition, abnormal HR recovery 1-minute after exercise (defined as the reduction in the HR from peak exercise 1-minute after exercise) was also significantly more common in patients with HfpEF compared with controls (23% versus 2%, P=0.01). Hypertensive controls showed similar chronotropic response to peak exercise and HR recovery after exercise as healthy controls. CONCLUSIONS: Patients with HfpEF have impaired chronotropic incompetence during maximal exercise and abnormal HR recovery after exercise.

Increased left ventricular torsion in uncomplicated type 1 diabetic patients: the role of coronary microvascular function.

OBJECTIVE: We used speckle tracking echocardiography to study the early changes in left ventricular (LV) torsion in young patients with uncomplicated type 1 diabetes and stress magnetic resonance imaging (MRI) to assess its interrelationships with coronary microangiopathy. RESEARCH DESIGN AND METHODS: We recruited 33 asymptomatic subjects with type 1 diabetes and 32 age-matched healthy control subjects. All subjects underwent echocardiograms. Stress MRIs were performed in 30 subjects (8 healthy control subjects) to compute myocardial perfusion reserve index (MPRI). RESULTS: A significant increase in LV torsion (2 +/- 0.7 vs. 1.4 +/- 0.7 degrees /cm, P < 0.05) was identified in longer-term and retinopathy-positive type 1 diabetic subjects (1.9 +/- 0.7 vs. 1.4 +/- 0.7 degrees /cm, P < 0.05) as compared with the healthy control subjects. The MPRI was independently associated with increased LV torsion. CONCLUSIONS: We demonstrate that LV torsion is increased in young patients with uncomplicated type 1 diabetes and that coronary microvascular disease may play a key pathophysiological role in the development of increased LV torsion.