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Biventricular pacing results in left ventricular (LV) reverse remodeling in heart failure patients with wide QRS complexes. This study examines potential predictors of reverse remodeling. Echocardiography with tissue Doppler imaging was performed at baseline and 3 months after biventricular pacing in 30 patients (21 men and 9 women, mean age 62 +/- 14 years). There were 17 responders to reverse remodeling (defined as a reduction in LV end-systolic volume by >15%) and 13 nonresponders. Responders had significant improvement in 6-minute hall-walking distance (p = 0.006), metabolic equivalents (p = 0.02), peak oxygen uptake (p = 0.02), New York Heart Association functional class (p <0.001), and quality of life (p <0.001); an increase in the sphericity index (p = 0.007), ejection fraction (p <0.001), and diastolic filling time (p = 0.03); a decrease in myocardial performance index (p = 0.02), isovolumic relaxation time (p = 0.004), and mitral regurgitation (p = 0.007); and an improvement in systolic dyssynchrony (SD of the time to peak myocardial systolic contraction of the 12 LV segments as dyssynchrony index) (45.0 +/- 8.3 vs 32.5 +/- 14.5 ms, p = 0.003). In contrast, nonresponders only had a small degree of clinical improvement in New York Heart Association class (p = 0.03) and quality-of-life scores (p = 0.03), without any change in cardiac function, and worsening of systolic dyssynchrony (24.8 +/- 4.5 vs 34.1 +/- 13.5 ms, p = 0.02). When all the above factors were put into univariate and multivariate analyses models, systolic dyssynchrony was the only independent predictor of reverse remodeling (r = -0.76, p <0.001) (beta = -1.54, p = 0.007). A preimplant dyssynchrony index of 32.6 ms (+2 SDs from mean of 88 normal controls) was able to totally segregate responders from nonresponders of biventricular pacing. Thus, responders of LV reverse remodeling were associated with improvement in clinical status, cardiac function, and systolic synchronicity. Direct assessment of systolic synchronicity by tissue Doppler imaging is highly accurate in predicting responders to therapy.

Purpose: Hyperhomocysteinemia, a risk factor for atherosclerosis, is associated with endothelial dysfunction that can be improved with short-term folic acid supplementation. The current study aimed to assess whether folic acid supplementation could produce longer-term improvements in homocysteine levels and arterial endothelial function., Subjects and Methods: Twenty-nine healthy adults with hyperhomocysteinemia were selected from 89 volunteers enrolled in a community-based atherosclerosis screening project. All subjects were given folic acid (10 mg/d) for 1 year. Fasting plasma homocysteine levels were measured by high-performance liquid chromatography. Arterial endothelial function was measured as flow-mediated dilation of the brachial artery using high-resolution B-mode ultrasound., Results: Folic acid supplementation for 1 year was associated with a significant increase in mean (+/-SD) plasma folate levels (24 +/- 5 nmol/L to 40 +/- 5 nmol/L; P < 0.001) and a significant decline in homocysteine levels (9.0 +/- 1.7 micromol/L to 7.9 +/- 2.0 micromol/L; P < 0.001). Flow-mediated dilation also improved significantly, from 7.4% +/- 2.0% to 8.9% +/- 1.5% (P <0.0001), but there was no change in nitroglycerin-induced (endothelium-independent) responses., Conclusions: These results demonstrate that long-term folic acid improves arterial endothelial function and has potential implications for the prevention of atherosclerosis in adults with hyperhomocysteinemia.