Differences in pharmacological property between combined therapy of the vasopressin V2-receptor antagonist tolvaptan plus furosemide and monotherapy of furosemide in patients with hospitalized heart failure.

BACKGROUND: Tolvaptan has been shown to improve congestion in heart failure patients. The purpose of this study was to evaluate the pharmacology and clinical efficacy of combined tolvaptan and furosemide therapy. METHODS: This study included 40 patients with systemic volume overload who were hospitalized for heart failure. Patients who showed no improvement in the condition after receiving 20 mg intravenous furosemide were included and were randomly selected to receive tolvaptan as an add-on to furosemide or to receive an increased dose of furosemide. We evaluated the bioelectrical impedance analyzer parameters, the parameters of the inferior vena cava using echocardiography, vital signs, body weight, urine output, and laboratory data for 5 days. RESULTS: In the changes from baseline between intracellular water volume (ICW) and extracellular water volume (ECW) after additional use of tolvaptan or furosemide from Day 1 to Day 5, there were no significant differences observed between ICW and ECW over 5 days in the tolvaptan + furosemide group, although differences were found in the furosemide group from Day 2 onward. Changes in the respiratory collapse of inferior vena cava increased significantly, and systolic blood pressure decreased significantly only in the furosemide group. CONCLUSIONS: The present study clearly demonstrates that combined therapy with tolvaptan and furosemide removed excess ICW and ECW to an equal extent, while furosemide alone primarily removed ECW, including intravascular water.

Clinical significance of arterial stiffness as a factor for hospitalization of heart failure with preserved left ventricular ejection fraction: a retrospective matched case-control study.

BACKGROUND: Previous studies have been conducted to identify characteristics of patients with heart failure with preserved ejection fraction (HFpEF), but the risk factors of HFpEF remain unclear. We investigated the associations between arterial stiffness and the risk of hospitalization for HFpEF patients. METHODS: For the case group, we enrolled patients with preserved EF who had been hospitalized for HF from April 2013 to March 2015 and examined the cardio-ankle vascular index (CAVI). For the control group, we enrolled outpatients with preserved EF and with hypertension, diabetes mellitus, dyslipidemia, and/or coronary artery disease but who did not present with HF symptoms and had never been diagnosed or treated for HF during the same period. The control group matched with the case group for age and sex. The association between hospitalized HFpEF and clinical variables was analyzed using conditional logistic regression models. RESULTS: The CAVI value was significantly higher in patients with hospitalized HFpEF compared with patients with the control [10.4 (9.8-11.0) vs. 9.2 (8.1-10.0), p < 0.001). On the multivariate conditional logistic regression analysis, high CAVI (OR 6.76, 95% CI 2.28-20.10, p < 0.001) and anemia (OR 3.91, 95% CI 1.47-10.40, p = 0.006) were independently associated with hospitalization of HFpEF patients. CONCLUSIONS: The present study has demonstrated that the high value of CAVI was independently associated with the hospitalization of HFpEF patients.

Effects of tolvaptan on urine output in hospitalized heart failure patients with hypoalbuminemia or proteinuria.

Hypoalbuminemia is an independent prognostic factor in hospitalization for heart failure (HHF). Hypoalbuminemia or proteinuria is related to resistance to loop diuretics. Tolvaptan is an oral non-peptide, competitive antagonist of vasopressin receptor-2. It has been used for the treatment of volume overload in HHF patients in several Asian countries. Several studies have demonstrated marked improvement in congestion in HHF patients. However, whether tolvaptan is useful for HHF patients with hypoalbuminemia or proteinuria (both of which are related to resistance to loop diuretics) has not been clarified. We examined the diuretic response to tolvaptan in HHF patients with hypoalbuminemia or proteinuria. We defined hypoalbuminemia as a serum level of albumin < 2.6 g/dl. Fifty-one HHF patients who received additional tolvaptan upon therapies with loop diuretics were divided into the hypoalbuminemia group (n = 24) or control group (n = 27). The changes in urine output per day were not different between the two groups [610 (range 100-1032); 742 (505-1247) ml, P = 0.313]. There was no difference in diuretic responses between patients with and without proteinuria. The serum level of albumin did not correlate with changes in urine output per day after tolvaptan treatment (P = 0.276, r = 0.156). Thus, additional administration of tolvaptan elicited a good diuretic response in HHF patients with hypoalbuminemia or proteinuria. These data suggest that tolvaptan might be beneficial for such HHF patients.

Long-term Hemodialysis Corrects Left Ventricular Dyssynchrony in End-stage Renal Disease: A Study with Gated Technetium-99m Sestamibi Myocardial Perfusion Single-photon Emission Computed Tomography.

INTRODUCTION: Left ventricular (LV) dyssynchrony is common in patients with end-stage renal disease (ESRD), and echocardiographic assessment has shown that it can be improved by a single session of hemodialysis (HD). The aim of this study was to assess the effects of chronic HD on LV dyssynchrony in patients ESRD by means of gated technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography (GSPECT) with phase analysis. MATERIALS AND METHODS: Twelve patients with ESRD underwent GSPECT and echocardiography before the start of long-term HD (baseline) and 3 months later. In addition, 7 control subjects matched for age and sex underwent GSPECT and echocardiography within a 2-month period. To evaluate LV dyssynchrony, both histogram bandwidth (HBW) and phase standard deviation (PSD) were determined with phase analysis of GSPECT images. The end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction were also measured with GSPECT, and the LV mass index (LVMI) was measured with echocardiography. The LV dyssynchrony, volume, function, and mass were compared among control subjects, patients with ESRD at baseline, and patients with ESRD after 3 months of chronic HD. RESULTS: The LV dyssynchrony, volume, and mass at baseline were significantly greater in patients with ESRD than in control subjects (HBW, 65.5°±54.4° vs. 22.3°±7.5°, P<0.05; PSD, 21.0°±15.5° vs. 7.6°±5.5°, P<0.05; EDV, 105.7±29.2 vs. 72.3±13.9 mL, P<0.05; ESV, 44.3±22.1 vs. 20.9±10.3 mL, P<0.05; LVMI, 136.5±48.3 vs. 65.4±5.6 g/m(2), P<0.01). From baseline to the third month of chronic HD, there were significant increases in EDV (78.6±25.4 vs. 105.7±29.2 mL, P<0.01) and ESV (27.6±16.2 vs. 44.3±22.1 mL, P<0.01) and significant decreases in HBW (65.5°±54.4° vs. 31.0°±15.7°, P<0.01) and PSD (21.0°±15.5° vs. 10.0°±8.2°, P<0.01). CONCLUSION: Chronic HD decreased LV dyssynchrony and volume in patients with ESRD. Serial phase analysis of GSPECT images is a useful method of assessing the effects of long-term HD on LV dyssynchrony and volume in patients with ESRD.

Clinical usefulness of gated technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography with phase analysis for the management of patients with isolated ventricular noncompaction.

Gated Tc-99m sestamibi myocardial perfusion single-photon emission computed tomography (GMPS) with phase analysis provides information on myocardial perfusion, left ventricular (LV) function, and LV dyssynchrony. We present a case of isolated left ventricular noncompaction (IVNC) cardiomyopathy in which GMPS with phase analysis proved to be beneficial and reliable to monitor the long-term response to cardiac resynchronization therapy with defibrillator (CRT-D). The patient was an 84-year-old man with shortness of breath on minimal exertion (New York Heart Association class III) who had severe drug-refractory heart failure with hypotension and ventricular tachycardia. He was diagnosed with IVNC using echocardiography. At baseline, GMPS with phase analysis revealed a reduced ejection fraction (EF, 21%), large perfusion defects in the inferior and inferolateral walls, and severe LV dyssynchrony [histogram bandwidth (HBW) 120°]. Combination therapy with CRT-D and a titrated beta-blocker was initiated to induce LV reverse remodeling and reduce LV dyssynchrony. Two years after CRT-D implantation, GMPS with phase analysis showed marked improvement in LV function and LV dyssynchrony (EF 28%, HBW 36°). This case demonstrates that GMPS with phase analysis is an important and useful modality to evaluate LV function and LV dyssynchrony in IVNC patients undergoing CRT-D. .

[QT dispersion increases during hemodialysis procedures in patients undergoing maintenance dialysis: association with an RA system and holter electrocardiogram].

BACKGROUND: Patients undergoing maintenance dialysis have been associated with a high incidence of arrhythmias, which increases with hemodialysis (HD) procedures. In recent years, QT dispersion (QT-d), which is defined as the difference between the maximum and minimum QT intervals (QTmax, QTmin) on an electrocardiogram (ECG), has attracted attention as a useful tool for predicting and evaluating ventricular arrhythmias. AIM: To determine the QT interval and QT-d before and after HD in stable subjects on maintenance dialysis. Further, to analyze the association of changes (Delta) in the QT interval and QT-d with the fluid removal ratio and changes in laboratory data. PATIENTS AND METHODS: We selected 82 patients undergoing maintenance dialysis who were less than 80 years of age. QT intervals before and after HD were obtained, and laboratory data including neurohumoral factors and the RA system were carried out. Of all the patients, 63 underwent a 24-hour holter-monitoring ECG. RESULTS: QTmax was significantly prolonged with QTmin remaining unchanged, and QT-d was significantly increased. DeltaQT-d demonstrated a significant correlation with DeltaQTmax, DeltaQTmin and Deltaaldosterone, but showed no correlation with the fluid removal ratio and changes in laboratory data. Results of the holter ECG revealed that in the grade 0 (Lown's classification) group, no change was obtained in DeltaQTmax, DeltaQTmin and DeltaQT-d, and in groups 1 to 5, significant increases were noted in DeltaQTmax and DeltaQT-d. CONCLUSIONS: The increase in QT-d has a possible link with arrhythmia inducibility during HD, and the results of the holter ECG suggest that an increase in QT-d may predict the frequency of arrhythmias. Change in the RA system appeared to have an impact on QT-d, but there was no impact of this parameter on the fluid removal ratio or changes in the laboratory data.

Assessment of left ventricular dyssynchrony during development of heart failure by a novel program using ECG-gated myocardial perfusion SPECT.

BACKGROUND: A novel program, "cardioGRAF", has been developed to analyze regional left ventricular (LV) systolic/diastolic function and dyssynchrony, so the present study aimed to use it confirm the presence of LV dyssynchrony, and to correlate LV function and dyssynchrony with plasma B-type natriuretic peptide (BNP) levels during the early to advanced stages of heart failure (HF). METHODS AND RESULTS: Fourteen control subjects (G-C) and 50 patients (New York Heart Association functional class I: G-1, 21 patients; class II: G-2, 15 patients; and class III: G-3, 14 patients) were examined by ECG-gated myocardial perfusion single-photon emission computed tomography, using the new index of dyssynchrony, maximal difference (MD), which is the difference between the earliest and latest temporal parameters among 17 segments. First-third filling rate (FR) and the MD of time to peak FR revealing diastolic dyssynchrony were significantly different between G-C subjects and G-1 patients. Ejection fraction, peak ejection rate, peak FR, MD of time to end-systole, and MD of time to peak ejection rate were significantly correlated with plasma BNP levels. CONCLUSION: Diastolic dyssynchrony was demonstrated even in the early stage of HF, but, although not correlated with the plasma BNP level, systolic dyssynchrony might affect it.