Early Commencement and Long-Term Continuation of Tolvaptan Treatment Attenuate Functional Impairment of Renal Vasopressin V2 Receptors and Improve Clinical Outcomes in Patients with Heart Failure.

Preserved urinary excretion of aquaporin 2, an index for the function of vasopressin V2 receptor (V2-R), has been reported to predict a favorable response of heart failure patients to treatment with tolvaptan. In this study, we investigated the long-term effects of tolvaptan treatment on clinical outcomes and V2-R function in patients with acute decompensated heart failure (ADHF). We enrolled 90 consecutive patients who were hospitalized in Sapporo Medical University Hospital for ADHF and treated with tolvaptan in the BOREAS-ADHF registry and analyzed patients who continued taking tolvaptan after discharge. The effect of tolvaptan treatment on rehospitalization for HF or death was investigated according to whether the V2-R function was preserved (first morning urine osmolarity ≥ 352 mOsm/L, High-Uosm) or impaired (Uosm < 352 mOsm/L, Low-Uosm). During a median follow-up period of 443 days, significantly fewer patients in the High-Uosm group experienced adverse events than did patients in the Low-Uosm group (P < 0.001). Among the patients with High-Uosm, early commencement of tolvaptan administration (on or before day 7 of hospitalization, Early/High-Uosm) significantly reduced adverse events compared to late administration (after day 7 of hospitalization, Late/High-Uosm). Uosm measured during the long-term follow-up period after discharge was significantly reduced compared to that before commencement of tolvaptan administration in the Late/High-Uosm group (from 468 ± 88 to 395 ± 108 mOsm, -18.3 ± 19.6%, P < 0.05) but not in the Early/High-Uosm group (from 478 ± 115 to 455 ± 133 mOsm, -0.50 ± 35.3%, P = 0.66). These findings indicate that early commencement and long-term continuation of tolvaptan treatment attenuate functional impairment of V2-R and improve clinical outcomes in ADHF patients with preserved V2-R function.

Prognostic value of nutritional parameters in systolic heart failure with renal dysfunction.

Although it is known that assessment and management of the nutritional status of patients are important for treatment of patients with heart failure (HF), there are currently no established indicators. Therefore, we investigated the effects of nutritional parameters as well as conventional parameters on the prognosis of HF patients. A total of 1954 consecutive HF patients with left ventricular ejection fraction (LVEF) less than 50% were enrolled in this study. Transthoracic echocardiography was performed and conventional parameters for HF patients and parameters to assess nutritional status were measured in all patients. Patients were followed up with a primary endpoint of lethal cardiac events (CEs) for 30.2 months. During the follow-up period, cardiac events were documented in 619 HF patients. The CEs group had a lower level of cholinesterase (201.5U/L vs 265.2U/L, P <0.0001), lower estimated GFR (35.2 ml/min/1.73m2 vs 50.3ml/min/1.73m2, P< 0.0001), and lower Geriatric Nutritional Risk Index (GNRI) (91.9 vs 100.0, P< 0.0001) than those in the non-CEs group. Serum cholinesterase, estimated GFR, and GNRI were identified as significant prognostic determinants in multivariate analysis. ROC analyses revealed cut-off values of serum cholinesterase, estimated GFR, and GNRI of 229U/L, 34.2 ml/min/1.73m2, and 95.6, respectively, for identifying high-risk HF patients. HF patients with serum cholinesterase< 229U/L, estimated GFR<34.3 ml/min/1.73m2, and GNRI< 95.6 had a significantly greater rate of CEs than that in the other patients (P<0.0001). Low serum cholinesterase and low GNRI can predict cardiac mortality risk in systolic HF patients with renal dysfunction.

Impact of catheter contact angle on lesion formation and durability of pulmonary vein isolation.

PURPOSE: This study is aimed to evaluate the impact of catheter contact angle on lesion formation and durability of pulmonary vein isolation (PVI). METHODS: Both in vitro experiment and retrospective observational study were conducted. For in vitro experiment, radiofrequency lesions were created on explanted swine hearts in three different catheter contact angles (0°, 45°, and 90°). In the retrospective observational study, we assessed patients who had undergone repeat catheter ablation due to atrial fibrillation recurrence after initial PVI. When pulmonary vein (PV) reconnection was observed, we analyzed the previous ablation points within and without the gap area. The gap areas were where ablation had changed the PV activation sequence or eliminated the PV potential in the repeat session. RESULTS: In the in vitro experiment, lesion width was the smallest (5.3 ± 0.4 mm) in perpendicular contact compared to 0° (vs 5.8 ± 0.5 mm, p = 0.040) and 45° (vs 6.4 ± 0.4 mm, p < 0.001). In the retrospective observational study, we assessed 666 tags of 16 patients with PV reconnections, and 60 tags were in the gap area. Tags in the gap area had longer interlesion distance (odds ratio [OR] 1.49, p < 0.001), greater contact force variability (OR 1.03, p = 0.008), and higher rate of perpendicular contact (OR 3.26, p < 0.001) on multivariate analysis. CONCLUSIONS: Perpendicular contact was associated with a smaller lesion and higher rate of PV reconnection.

Improved risk-stratification in heart failure patients with mid-range to severe abnormalities of QRS duration and systolic function using mechanical dyssynchrony assessed by myocardial perfusion-gated SPECT.

BACKGROUND: The use of left ventricular mechanical dyssynchrony (LVMD), which has been reported to be responsible for unfavorable outcomes, might improve conventional risk-stratification by clinical indices including QRS duration (QRSd) and systolic dysfunction in patients with heart failure (HF). METHODS AND RESULTS: Following measurements of 12-lead QRSd and left ventricular ejection fraction (LVEF), three-dimensional (3-D) LVMD was evaluated as a standard deviation (phase SD) of regional mechanical systolic phase angles by gated myocardial perfusion imaging in 829 HF patients. Patients were followed up for a mean period of 37 months with a primary endpoint of lethal cardiac events (CEs). In an overall multivariate Cox proportional hazards model, phase SDs were identified as significant prognostic determinants independently. The patients were divided into 4 groups by combining with the cut-off values of LVEF (35% and 50%) and QRSd (130 ms and 150 ms). The groups with lower LVEF and prolonged QRSd more frequently had CEs than did the other groups. Patient groups with LVEF < 35% and with 35% ≦ LVEF < 50% were differentiated into low-risk and high-risk categories by using an optimal phase SD cut-off value of both QRSd thresholds. CONCLUSIONS: 3-D LVMD can risk-stratify HF patients with mid-range as well as severe abnormalities of QRSd and systolic dysfunction.

Impaired Cardiac Sympathetic Innervation Increases the Risk of Cardiac Events in Heart Failure Patients with Left Ventricular Hypertrophy and Mechanical Dyssynchrony.

BACKGROUND: Left ventricular mechanical dyssynchrony (LVMD), left ventricular hypertrophy, and impaired cardiac sympathetic innervation are closely related to the development of heart failure (HF) and unfavorable outcomes. METHODS AND RESULTS: A total of 705 consecutive HF patients with reduced left ventricular ejection fraction (EF) < 50% were registered in our hospital HF database. LVMD and left ventricular mass index (LVMI) were evaluated three-dimensionally by gated myocardial perfusion SPECT. LVMD was measured as a heterogeneity index (phase SD) of the regional contraction phase angles calculated by Fourier analysis. Cardiac sympathetic innervation was quantified as a normalized heart-to-mediastinum ratio (HMR) of the 123I-metaiodobenzylguanidine (MIBG) activity. The patients were followed up with a primary end point of lethal cardiac events (CEs) for 42 months. CEs were documented in 246 of the HF patients who had a greater phase SD, greater LVMI, and lower MIBG HMR than those in HF patients without CEs. In the overall multivariate analysis, phase SD, LVMI, and MIBG HMR were identified as significant CE determinants. The three biomarkers were incrementally related to increases in CE risks. CONCLUSIONS: Assessment of cardiac sympathetic innervation can further stratify patients with systolic heart failure at increased cardiac risk identified by left ventricular hypertrophy and mechanical dyssynchrony.

Abrupt Onset of Cardiac Tamponade in Sarcoidosis.

Sarcoidosis is a systemic inflammatory disease characterized by the formation of noncaseating epithelioid granulomas. Multiple organs, including the lung, eyes, and skin, are involved in this disorder, and cardiac involvement is a major cause of morbidity and mortality in patients with this disorder. We present the case history of a 22-year-old man with neurosarcoidosis complicated by abrupt onset of cardiac tamponade. Cardiac tamponade is a rare but potentially fatal manifestation of sarcoidosis, which is treatable with glucocorticoid therapy. Including the present case, previously reported cases of sarcoidosis with cardiac tamponade are reviewed to delineate its clinical characteristics.

Impact of Frailty on Bleeding Events Related to Anticoagulation Therapy in Patients With Atrial Fibrillation.

BACKGROUND: Although anticoagulation is the key treatment to prevent stroke in patients with atrial fibrillation (AF), including elderly patients, anticoagulation is sometimes withheld for elderly people because of concerns about frailty. However, it remains unknown whether frailty increases bleeding events.Methods and Results:A total of 120 consecutive non-valvular AF patients admitted with symptoms of AF or congestive heart failure were included in this study. Frailty was assessed using the Cardiovascular Health Study (CHS) frailty index. We performed a retrospective analysis of the risk factors associated with major bleeding events. After a median follow-up of 518 days, major bleeding events occurred in 17 (14.2%) patients. Patients with major bleeding events had a higher CHS frailty index (P=0.015). The cutoff value for high-risk CHS frailty index was 2 (area under the ROC curve: 0.68 [95% confidence interval (CI): 0.57-0.78]). The event-free rates at 2 years were 97.6% (95% CI: 83.9-99.7) in patients with a CHS frailty index <2 and 59.6% (95% CI: 27.9-81.0) for those with a CHS frailty index ≥2 (P<0.001). CONCLUSIONS: Frailty is associated with increased bleeding events related to anticoagulant therapy in patients previously hospitalized with AF. Greater care should be taken with patients with a CHS frailty index ≥2.

Paradoxical Prognostic Implications of Visceral Adiposity for Lethal Cardiac Events in Association with Impaired Cardiac Sympathetic Innervation in Chronic Heart Failure.

Background: Obesity increases the risk for development of heart failure (HF) but, when present is likely to be related to better outcomes in patients with HF. This study aimed to clarify the paradoxical prognostic values of visceral obesity in association with cardiac sympathetic function in HF patients. Methods and Results: A total of 653 consecutive patients with systolic HF who underwent visceral adiposity area (VAA) measurements using a computed tomographic technique were divided into 3 groups: VAA 1, area <80 cm2; VAA 2, area 80-140 cm2; VAA 3, area >140 cm2. Sympathetic innervation was quantified by 123I-MIBG cardiac activity. Patients were followed up for an average of 22 months with a primary endpoint of lethal cardiac events (CE). The CE group (n=200) had a lower late heart-to mediastinum ratio (HMR) and a smaller VAA than those in the non-CE group. Rates of overall CE/HF death were inversely correlated with VAA: 39.2% ± 6.2% for VAA 1, 27.4% ± 19.9% for VAA 2 and 24.1% ± 15.3% for VAA 3. In addition to sudden cardiac death rate, lethal arrhythmic event rate increased in association with visceral fat obesity: 3.0% for VAA 1, 7.5% for VAA 2 and 8.8% for VAA 3. Late HMR identified high-risk sub-populations in each group. Conclusion: Visceral obesity has paradoxical prognostic implications in terms of HF mortality and lethal arrhythmic/sudden cardiac death events. Cardiac sympathetic denervation and quantitative visceral adiposity are synergistically associated with overall cardiac mortality, contributing to better risk stratification of HF patients.