Hemodynamic impact of pulmonary vasodilators on single ventricle physiology.

INTRODUCTION: The Fontan procedure is the palliative procedure for single ventricle physiology. Pulmonary resistance plays a key role in the success of this operation. There are conflicting data concerning the impact of pulmonary vasodilators on survival and functional capacity among Fontan patients. AIM: The aim of this retrospective, single-center, nonrandomized study was to investigate the potential effect of pulmonary vasodilators on pulmonary vasculature in Fontan patients. METHOD: Twenty-seven patients with single ventricle physiology were enrolled. Eighteen patients were treated with pulmonary vasodilators: 9 patients after Glenn procedure or just after the Fontan completion (Group A) and 9 patients >5 years after Fontan completion (Group B). Nine patients after Glenn procedure were enrolled as a control group (Group C). The primary endpoint was to assess changes in hemodynamic profile and pulmonary branches' diameter after 2 right heart catheterizations. Adverse events were recorded. RESULTS: Mean age ± SD was 3.2 ± 1.5 years (Group A), 26.8 ± 12.7 years (Group B), and 3.1 ± 1.0 years (Group C). Patients included in Group A had reduced arterial compliance (34.3 ± 15.4 vs 52.2 ± 24.2 mm2 /[m2 *mm Hg]; P = .03) at baseline compared with Group C. After treatment, Nakata index and pulmonary compliance increased in patients treated with pulmonary vasodilators (Group A), while remaining stable in the control group (Nakata index: +26 ± 24% vs -8 ± 17%, P = .003; pulmonary compliance +80 ± 49% vs -5 ± 30%, P = .001). Similar results were found in Group B (Nakata index: pre-168.6 ± 70.7 mm2 /m2 ; post-204.9 ± 97.5 mm2 /m2 ; P = .026). CONCLUSIONS: Pulmonary vasodilators reduce pulmonary artery resistance and increase vascular compliance, pulmonary artery diameter, and cardiac output in Fontan patients. Therefore, pulmonary vasodilators may be used before the Fontan procedure in patients at high risk of Fontan procedure failure.

Vitamin D versus placebo in improvement of endothelial dysfunction: a meta-analysis of randomized clinical trials.

AIMS: The possible effect of vitamin D administration in humans on endothelial dysfunction (ED) still remains undetermined. The current meta-analysis was performed to evaluate if vitamin D could improve ED. METHODS: Randomized, double-blind, and placebo-controlled clinical trials were identified by systematic search of the PubMed, the Cochrane Library, the Web of Science and the Scopus data bases, as well as different reviews and clinical trials articles. A random effects model was used to calculate the pooled overall effect on flow-mediated dilation (FMD) linked to the vitamin D administration. Meta-regression and subgroup analyses were performed to evaluate the impact of study characteristics on the effect of vitamin D administration on FMD. RESULTS: A total of eight studies with nine relevant study arms were identified. The obtained results of pooled analysis showed that vitamin D administration did not improve FMD (eight studies, 529 subjects; weighted mean difference (WMD): 0.96%, 95% CI: -1.24% to 2.06%; P = 0.09). This was probably due to significant heterogeneity in between included trials (I(2) = 84%, P < 0.00001). On the other hand, subgroup analysis demonstrated that vitamin D improved FMD in trials that lasted <16 weeks; if systolic blood pressure (SBP) was higher than 140 mmHg and in trials where diastolic blood pressure (DBP) was <80 mmHg. CONCLUSION: Although the current evidence clearly demonstrates that in certain conditions vitamin D can improve ED, a larger number of clinical trials are needed to confirm this assumption to confirm or reject the final statement on this topic.

Effect of nicorandil in patients with heart failure: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: It is unclear whether nicorandil, a metabolic therapeutic drug, can be applied clinically to therapy of heart failure (HF). This meta-analysis evaluated therapeutic effects of nicorandil on HF patients. EXPERIMENTAL APPROACH: We performed a systematic review and meta-analysis of published studies evaluating effect of nicorandil on HF patients. Studies were stratified according to controlled versus uncontrolled designs and analyzed using random-effects meta-analysis models. KEY RESULTS: We identified a total of 20 studies with a total of 1222 patients. In five randomized controlled studies, nicorandil treatment resulted in reduction in all-cause mortality and hospitalization for cardiac causes (HR: 0.35, P < 0.001) and improved cardiac pump function (SMD: 0.31, P = 0.02). In 15 observational studies, nicorandil therapy increases cardiac pump function (SMD: 0.75, P < 0.001), improves NYHA functional class (WMD: -1.33, P < 0.001), decreases PCWP (WMD: -6.86 mm Hg, P < 0.001), and pulmonary arterial pressure (SMD: -0.84, P < 0.001). CONCLUSIONS AND IMPLICATIONS: The use of nicorandil in HF patients exerts substantial beneficial effects, suggesting that it may be an additional therapeutic agent for HF.

eNOS overexpressing bone marrow cells are safe and effective in a porcine model of myocardial regeneration following acute myocardial infarction.

AIM: Cell therapy has been shown to be effective in improving LV function postmyocardial infarction (MI). We hypothesized that eNOS-transfected bone marrow cells (BMCs) are safe in a swine model of myocardial infarction (MI). We also hypothesized that endothelial nitric oxide synthase (eNOS) transfection would enhance cell function, as assessed by myocardial functional recovery post-MI. METHODS: Fifteen female Yorkshire pigs underwent bone marrow aspiration and creation of MI. Bone marrow cells were cultured for 7 days, and each pig received either autologous BMCs transiently transfected with eNOS plasmid (eNOS-BMC, n = 5), nontransfected BMCs (nt-BMC, n = 4), or phosphate-buffered saline (PBS) control (n = 6). Cardiac MRI was performed at baseline (1 week post-MI) and 6 weeks post-MI. RESULTS: There was no difference in safety outcomes between groups. Absolute left ventricular ejection fraction (LVEF) at 6 weeks showed a trend toward improvement in both cell therapy groups compared with baseline but worsened in the PBS control group. The absolute improvement in LVEF was significantly greater in both cell therapy groups compared with PBS control. Infarct mass was significantly lower in the eNOS-BMC group between baseline and 6 weeks, but the absolute change in infarct mass was not different between groups. Finally, there was a trend toward reduced LV mass in the eNOS-BMC group. CONCLUSIONS: Bone marrow cell delivery, with and without eNOS overexpression, is safe and leads to improvement in LVEF when administered in the coronary circulation 7 days following acute MI in swine. Transfection of healthy BMCs with eNOS resulted in some improvement in left ventricular remodeling. Further study is warranted in a preclinical model that approximates the impact of cardiovascular risk factors on BMC function.