Reduced peripheral arterial blood flow with preserved cardiac output during submaximal bicycle exercise in elderly heart failure.

BACKGROUND: Older heart failure (HF) patients exhibit exercise intolerance during activities of daily living. We hypothesized that reduced lower extremity blood flow (LBF) due to reduced forward cardiac output would contribute to submaximal exercise intolerance in older HF patients. METHODS AND RESULTS: Twelve HF patients both with preserved and reduced left ventricular ejection fraction (LVEF) (aged 68 +/- 10 years) without large (aorta) or medium sized (iliac or femoral artery) vessel atherosclerosis, and 13 age and gender matched healthy volunteers underwent a sophisticated battery of assessments including a) peak exercise oxygen consumption (peak VO2), b) physical function, c) cardiovascular magnetic resonance (CMR) submaximal exercise measures of aortic and femoral arterial blood flow, and d) determination of thigh muscle area. Peak VO2 was reduced in HF subjects (14 +/- 3 ml/kg/min) compared to healthy elderly subjects (20 +/- 6 ml/kg/min) (p = 0.01). Four-meter walk speed was 1.35 +/- 0.24 m/sec in healthy elderly verses 0.98 +/- 0.15 m/sec in HF subjects (p < 0.001). After submaximal exercise, the change in superficial femoral LBF was reduced in HF participants (79 +/- 92 ml/min) compared to healthy elderly (222 +/- 108 ml/min; p = 0.002). This occurred even though submaximal stress-induced measures of the flow in the descending aorta (5.0 +/- 1.2 vs. 5.1 +/- 1.3 L/min; p = 0.87), and the stress-resting baseline difference in aortic flow (1.6 +/- 0.8 vs. 1.7 +/- 0.8 L/min; p = 0.75) were similar between the 2 groups. Importantly, the difference in submaximal exercise induced superficial femoral LBF between the 2 groups persisted after accounting for age, gender, body surface area, LVEF, and thigh muscle area (p

Left ventricular infarct size assessed with 0.1 mmol/kg of gadobenate dimeglumine correlates with that assessed with 0.2 mmol/kg of gadopentetate dimeglumine.

OBJECTIVE: To determine myocardial infarct (MI) size during cardiovascular magnetic resonance at 1.5 Tesla using 0.1 mmol/kg body weight of gadobenate dimeglumine (Gd-BOPTA) and 0.2 mmol/kg body weight of gadopentetate dimeglumine (Gd-DTPA). METHODS: Twenty participants (16 men, 4 women), aged 58 +/- 12 years, with a prior chronic MI were imaged in a crossover design. Participants received 0.2 mmol/kg body weight of Gd-DTPA and 0.1 mmol/kg body weight of Gd-BOPTA on 2 occasions separated by 3 to 7 days. RESULTS: The correlations were high between Gd-DTPA and Gd-BOPTA measures of infarct volume (r = 0.93) and the percentage of infarct relative to left ventricular myocardial volume (r = 0.85). The size and location of the infarcts were similar (P = 0.9) for the 2 contrast agents. Interobserver correlation of infarct volume (r = 0.91) was high. CONCLUSIONS: In chronic MI, late gadolinium enhancement identified with a single 0.1 mmol/kg body weight dose of Gd-BOPTA is associated in volume and location to a double (0.2 mmol/kg body weight) dose of Gd-DTPA. Lower doses of higher relaxivity contrast agents should be considered for determining left ventricular myocardial infarct size.

Impact of mitral regurgitation on reverse remodeling and outcome in patients undergoing cardiac resynchronization therapy.

BACKGROUND: Mitral regurgitation (MR) is associated with reduced survival in patients with chronic heart failure, but may be improved with cardiac resynchronization therapy (CRT). We sought to evaluate the relationship between serial measurements of functional MR and reverse remodeling and outcomes in patients undergoing CRT. METHODS AND RESULTS: A total of 266 consecutive patients undergoing CRT with available baseline echocardiograms and subsequent clinical and echocardiographic follow-up were included in the analysis. Long-term follow-up included all-cause mortality, heart transplantation, and implantation of a left ventricular (LV) assist device. Temporal changes in MR severity and LV end-systolic volume index (LVESVi) were evaluated by linear mixed-model analysis. CRT led to an immediate sustained decrease in MR (P<0.0001), with no significant subsequent change. The amount of MR decrease correlated with a greater decrease in LVESVi late (P≤0.0001), but not early (P=0.14), after CRT began. Patients with severe MR before CRT experienced a larger LVESVi decrease (P=0.005). Although baseline MR severity was not associated with adverse events (P=0.13), a larger MR decrease (P=0.001) and a smaller residual MR after the initial 6 months of CRT (P=0.03) were predictive of better outcome in a multivariable model. CONCLUSIONS: Early reversal of functional MR was associated with reverse cardiac remodeling and improved outcomes. Patients with moderately severe to severe MR before CRT experienced relatively more reverse remodeling than patients with lesser degrees of MR.

Submaximal exercise coronary artery flow increases in postmenopausal women without coronary artery disease after estrogen and atorvastatin.

OBJECTIVE: The aim of this study was to determine the effect of statins and hormone therapy on submaximal exercise-induced coronary artery blood flow in postmenopausal women without a history of coronary artery disease. Hormone therapy or statin therapy in early postmenopausal women without coronary artery disease has been shown to enhance arterial endothelial function; we hypothesized that these agents would improve submaximal exercise-induced coronary artery blood flow. METHODS: Sixty-four postmenopausal women, aged 50 to 65 years without documented coronary artery disease, were randomized in a double-blind, crossover fashion to receive 8 weeks of hormone therapy versus placebo, with or without 80 mg/day of atorvastatin. Before receipt of any therapy and after each treatment period, each woman underwent measures of coronary artery blood flow at rest and stress. RESULTS: The combination of hormone therapy and atorvastatin increased submaximal exercise-induced coronary artery blood flow (P = 0.04). In the subgroups of women compliant with treatment, resting coronary artery blood flow increased in those receiving hormone therapy (P = 0.03) or statin therapy (P = 0.02). CONCLUSIONS: In postmenopausal women aged 50 to 65 years without documented coronary artery disease, resting and submaximal exercise-induced coronary artery blood flow improves after receipt of high-dose atorvastatin and conjugated estrogens therapy.

Impact of longitudinal cardiac rotation on mitral and tricuspid atrioventricular annular diastolic motion.

BACKGROUND: It is unknown whether longitudinal rotation (LR), often seen in cardiac resynchronization therapy candidates, may affect mitral annular early diastolic (E') velocities and tricuspid annular motion. We assessed whether (1) LR affects the amplitude and timing of septal and lateral mitral annular E' velocities and tricuspid annular systolic and E' velocities and (2) if systolic strain heterogeneity seen in cardiac resynchronization therapy patients with LR extends into diastole. METHODS AND RESULTS: Ninety-nine cardiac resynchronization therapy candidates with suitable baseline echocardiograms were identified. Early diastolic (E') and systolic myocardial velocities of the tricuspid annulus and E' velocities of the septal and lateral part of the mitral annulus were analyzed from tissue Doppler images. Longitudinal rotation and basal systolic and diastolic strain rates were analyzed by speckle-tracking. LR correlated with lateral mitral annular E' (r= 0.45, P<0.001), tricuspid annular E' (r=-0.3, P=0.003), and with a difference between septal and lateral mitral annular E' velocities (r= -0.49, P<0.001) but not with septal mitral annular E' velocity. LR also correlated with tricuspid annular systolic velocity (r= 0.60, P<0.001). After categorizing the patients according to the quartiles of their LR, we showed that with decreasing quartile number, heterogeneity of systolic (P=0.003) but not diastolic (P>0.1) strain rates increased. CONCLUSIONS: LR direction and magnitude correlates with the amplitude of, and relative differences between, diastolic velocities of tricuspid, lateral mitral, and septal mitral annulus, which are a cornerstone of diastolic function assessment. LR is associated with systolic but not with diastolic regional heterogeneity.

Long-term reverse remodeling with cardiac resynchronization therapy: results of extended echocardiographic follow-up.

OBJECTIVES: The purpose of this study was to describe the long-term course of left ventricular remodeling induced by cardiac resynchronization therapy (CRT), adjusting for the confounding effect of patient loss due to disease. BACKGROUND: Reverse remodeling has been identified as the primary mechanism of improved symptoms and outcome in heart failure patients. METHODS: A total of 313 consecutive patients who underwent CRT with available baseline echocardiograms and subsequent clinical and echocardiographic follow-up were included in the analysis. Long-term follow-up included all-cause mortality, heart transplantation, and implantation of a left ventricular assist device. Longitudinal data analysis of left ventricular end-systolic volume index (LVESVi) was performed to adjust for the confounding effect of patient loss during follow-up. RESULTS: Patients with uneventful survival had a lower baseline LVESVi (Delta = 8.6 ml/m(2), SE = 4.6 ml/m(2), p < 0.0001) and a decreased LVESVi by -0.11 ml/m(2)/day during first 6 months, whereas the LVESVi remained unchanged in patients with adverse events (p < 0.0001). Beyond 6 months, the LVESVi remained unchanged in patients with uneventful survival, whereas the LVESVi continued to increase in those with adverse events at a rate of 0.01 ml/m(2)/day (p < 0.0001). Predictors of reverse remodeling were nonischemic etiology, female sex, and a wider QRS duration (p < 0.0001, p = 0.014, and p = 0.001, respectively). In the majority of patients, 6 months indicates a break point after which reverse remodeling becomes significantly less pronounced. CONCLUSIONS: CRT patients with uneventful survival show a significant decrease in the LVSVi at 6 months and generally maintain this response in the long term. Those with adverse outcomes are characterized by left ventricular dilation despite CRT.