Efficacy of Add-on Therapy with Carvedilol and the Direct Renin Inhibitor Aliskiren for Improving Cardiac Sympathetic Nerve Activity, Cardiac Function, Symptoms, Exercise Capacity and Brain Natriuretic Peptide in Patients with Dilated Cardiomyopathy.

Purpose/Method: Aliskiren is a direct renin inhibitor that has been reported to be effective for CHF, but the usefulness of combined therapy with carvedilol and aliskiren has not been reported. Forty-four patients with dilated cardiomyopathy (DCM) were randomized into a group receiving add-on therapy with carvedilol plus aliskiren and another group receiving carvedilol alone for 6 months. Nuclear imagings with 123I-Metaiodobenzylguanidine (MIBG) and 99mTc-Sestamibi were performed. Exercise capacity using a specific activity scale (SAS) and the New York Heart Association (NYHA) class were evaluated. Cardiac sympathetic nerve activity was evaluated by 123I-MIBG imaging, with the delayed heart-to-mediastinum activity ratio (H/M), delayed total defect score (TDS), and washout rate (WR). Results: Combined add-on therapy with carvedilol and aliskiren improved several parameters much more than carvedilol alone (p<0.05) with respect to TDS, ejection fraction (EF), NYHA, SAS on 6 months and the changes in TDS, EF, end-diastolic volume and brain natriuretic peptide (BNP). Conclusion: Add-on therapy with carvedilol and aliskiren is more effective than carvedilol alone for improving cardiac sympathetic nerve activity, cardiac function, symptoms, exercise capacity, and brain natriuretic peptide in patients with DCM.

Ventilatory Efficacy After Transcatheter Aortic Valve Replacement Predicts Mortality and Heart Failure Events in Elderly Patients.

BACKGROUND: We aimed to clarify the predictors of death or heart failure (HF) in elderly patients who undergo transcatheter aortic valve replacement (TAVR).Methods and Results:We prospectively enrolled 83 patients (age, 83±5 years) who underwent transthoracic echocardiography (TTE) and cardiopulmonary exercise testing (CPET) with impedance cardiography post-TAVR. We investigated the association of TTE and CPET parameters with death and the combined outcome of death and HF hospitalization. Over a follow-up of 19±9 months, peak oxygen uptake (V̇O2) was not associated with death or the combined outcome. The minimum ratio of minute ventilation (V̇E) to carbon dioxide production (V̇CO2) and the V̇E vs. V̇CO2slope were higher in patients with the combined outcome. After adjusting for age, sex, Society of Thoracic Surgeons score and peak V̇O2, ventilatory efficacy parameters remained independent predictors of the combined outcome (minimum V̇E/V̇O2: hazard ratio, 1.108; 95% confidence interval, 1.010-1.215; P=0.031; V̇E vs. V̇CO2slope: hazard ratio, 1.035; 95% confidence interval, 1.001-1.071; P=0.044), and had a greater area under the receiver-operating characteristic curve. The V̇E vs. V̇CO2slope ≥34.6 was associated with higher rates of the combined outcome, as well as lower cardiac output at peak work rate during CPET. CONCLUSIONS: In elderly patients, lower ventilatory efficacy post-TAVR is a predictor of death and HF hospitalization, reflecting lower cardiac output at peak exercise.

Adaptive servo-ventilation therapy improves cardiac sympathetic nerve activity, cardiac function, exercise capacity, and symptom in patients with chronic heart failure and Cheyne-Stokes respiration.

PURPOSE: Adaptive servo-ventilation (ASV) therapy has been reported to be effective for improving central sleep apnea (CSA) and chronic heart failure (CHF). The purpose of this study was to clarify whether ASV is effective for CSA, cardiac sympathetic nerve activity (CSNA), cardiac symptoms/function, and exercise capacity in CHF patients with CSA and Cheyne-Stokes respiration (CSR-CSA). METHODS: In this study, 31 CHF patients with CSR-CSA and a left ventricular ejection fraction (LVEF) ≤ 40% were randomized into an ASV group and a conservative therapy (non-ASV) group for 6 month. Nuclear imagings with 123I-Metaiodobenzylguanidine (MIBG) and 99mTc-Sestamibi were performed. Exercise capacity using a specific activity scale (SAS) and the New York Heart Association (NYHA) class were evaluated. CSNA was evaluated by 123I-MIBG imaging, with the delayed heart/mediastinum activity ratio (H/M), delayed total defect score (TDS), and washout rate (WR). RESULTS: The ASV group had significantly better (P < .05) results than the non-ASV group with respect to the changes of AHI (-20.8 ± 14.6 vs -0.5 ± 8.1), TDS (-7.9 ± 4.3 vs 1.4 ± 6.0), and H/M(0.16 ± 0.16 vs -0.04 ± 0.10) on 123I-MIBG imaging, as well as the changes of LVEF (5.3 ± 3.9% vs 0.7 ± 32.6%), SAS (1.6 ± 1.4 vs 0.3 ± 0.7), and NYHA class (2.2 ± 0.4 vs 2.7 ± 0.5) after 6-month therapy. CONCLUSIONS: Performing ASV for 6 months achieved improvement of CSR-CSA, CSNA, cardiac symptoms/function, and exercise capacity in CHF patients with CSR-CSA.

Coronary artery calcification as a new predictor of non-target lesion revascularization during the chronic phase after successful percutaneous coronary intervention.

In the drug-eluting stent era, the outcome of patients undergoing percutaneous coronary intervention (PCI) has remarkably improved. Nevertheless, non-target lesion revascularization (non-TLR) is often performed even after successful PCI and optimized medical therapy. This study aimed to determine the predictor of non-TLR. In all, 125 consecutive patients with stable angina pectoris underwent intravascular ultrasound (IVUS)-guided PCI and were followed up for 3.3 ± 0.5 years. We performed oral glucose-tolerance tests in patients with no history of known diabetes mellitus (DM) to investigate glucose tolerance. To evaluate the severity of coronary artery calcification (CAC), we calculated CAC score by multiplying the arc (degree) with the length (mm) of the superficial calcium deposit detected by IVUS. Fourteen patients underwent non-TLR (non-TLR group); the remaining 111 did not (reference group). Glycosylated hemoglobin (HbA1c; %) and prevalence of known DM were similar in both groups, but the non-TLR group had higher fasting blood glucose (103 ± 16 vs. 94 ± 11 mg/dl, p = 0.04) and blood glucose (196 ± 60 vs. 149 ± 48 µU/ml, p = 0.01) and insulin at 2 h (184 ± 241 vs. 67 ± 49 µU/ml, p < 0.01) than did the reference group. CAC score was significantly higher in the non-TLR group (788 ± 585 vs. 403 ± 466, p = 0.01). Multiple logistic analysis indicated that CAC score is an independent predictor of non-TLR (p = 0.008). Non-TLR-free rate was significantly higher for patients with CAC score ≥400 than for those with CAC score <400 (p = 0.01). Non-TLR is associated with abnormal glucose tolerance and CAC score; CAC score is an independent predictor of non-TLR. Secondary prevention is especially important in patients with high CAC scores.

Combination of ¹²³I-metaiodobenzylguanidine scintigraphy and flow-mediated dilation for the detection of patients with coronary spastic angina.

BACKGROUND: This study evaluated the usefulness of cardiac sympathetic nerve activity, estimated by (123)I-MIBG scintigraphy, and endothelial function, estimated by flow-mediated dilation (FMD), in the detection of coronary spastic angina (CSA). METHODS AND RESULTS: We compared 78 consecutive patients suspected of CSA with ten age-matched controls. On the basis of a spasm provocation test with acetylcholine, 53 patients were diagnosed as CSA and 25 patients were considered to have chest-pain syndrome (CPS). The total defect score (TDS) by delayed (123)I-MIBG scintigraphy was significantly higher in both patient groups than in controls (P < 0.05), and was significantly higher in CSA than in CPS patients (P = 0.02). The heart/mediastinum activity (H/M) ratio by delayed (123)I-MIBG scintigraphy and FMD were significantly lower in both patient groups than in controls (P < 0.05), and were lower in CSA than in CPS patients (P = 0.04). In receiver-operating curve analysis, the areas under the curve for TDS, H/M, and FMD were 0.78, 0.72, and 0.70, respectively. The combination of delayed (123)I-MIBG scintigraphy and FMD showed a higher diagnostic value than either method alone. CONCLUSIONS: (123)I-MIBG scintigraphy and FMD can distinguish CSA patients among patients complaining of chest pain at rest, with good sensitivity and specificity.

Impact of angiographic peri-stent contrast staining (PSS) on late adverse events after sirolimus-eluting stent implantation: an observation from the multicenter j-Cypher registry PSS substudy.

This study sought to assess clinical significance of angiographic peri-stent contrast staining (PSS) after sirolimus-eluting stent (SES) implantation in a large multicenter study with 5-year follow-up. The j-Cypher PSS substudy is a multicenter study including 5712 patients (7838 lesions) who underwent follow-up angiographic study within 12 months after SES implantation. Late acquired PSS was observed in 184 patients (3.2 %) or 194 lesions (2.5 %). Independent risk factors of PSS were chronic total occlusion and left anterior descending artery lesion, while negative risk factors were in-stent restenosis, diabetes mellitus, ≥70 years of age, and left circumflex coronary artery lesion. Cumulative incidence of definite very late stent thrombosis (VLST) at 4 years after the index follow-up angiography in lesions with PSS was significantly higher than that in lesions without PSS (5.3 versus 0.7 %, P < 0.0001). Late target-lesion revascularization (TLR) was also more frequently observed in the PSS group (13 versus 6.9 %, P = 0.01), while late TLR for restenosis excluding those TLR procedures for VLST tended to be higher in the PSS group (9.9 versus 6.3 %; P = 0.15). PSS found in 2.5 % of lesions within 12 months after SES implantation was associated with higher risk for subsequent VLST.