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.

Differences in Intravascular Ultrasound Measurement Values Between Treatment Modalities for Restenosis in Femoropopliteal Lesions.

BACKGROUND: The risk of restenosis after intervention is higher in femoropopliteal than in aortoiliac lesions. However, the appropriate endovascular therapy (EVT) for preventing restenosis after intervention for femoropopliteal lesions remains unknown. This study aimed to elucidate the relationship between lesion characteristics and patency after EVT using intravascular ultrasound (IVUS) measurement and to determine the predictors of restenosis on IVUS.Methods and Results:This prospective observational study was performed at 18 Japanese centers. We evaluated the lesion characteristics before and after EVT for femoropopliteal lesion using IVUS. Angiographic or duplex ultrasound follow-up was performed at 1 year after EVT. A total of 263 lesions underwent EVT between December 2016 and December 2017. In total, 20 lesions (8 cases of isolated common femoral artery lesion and 12 cases of restenosis lesion) were excluded, and 243 lesions were enrolled in this study. A total of 181 lesions were treated with stent placement, and 62 lesions were treated only with balloon angioplasty. In the case of stent use, a larger distal plaque burden was associated with restenosis, while a lower calcification angle was associated with higher patency in the case of balloon angioplasty alone. CONCLUSIONS: The factors related to patency differed depending on the treating modality. The findings suggest that IVUS is a useful tool for predicting patency because it can provide a more accurate evaluation after EVT for femoropopliteal lesions.

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. .

Usefulness of rosuvastatin to prevent periprocedural myocardial injury in patients undergoing elective coronary intervention.

The aim of the present study was to investigate whether percutaneous coronary intervention-related periprocedural myocardial infarction (MI) can be suppressed more significantly with high- compared with low-dose rosuvastatin. A total of 232 patients scheduled to undergo elective percutaneous coronary intervention within 5 to 7 days were assigned to groups that would receive either 2.5 or 20 mg/day of rosuvastatin (n = 116 each). The incidence of periprocedural MI did not significantly differ between the high and low-dose groups (8.7% vs 18.7%, p = 0.052). In patients who were not taking statins at the time of enrollment, high-dose rosuvastatin significantly suppressed periprocedural MI compared with the low dose (10.5% vs 30.0%, p = 0.037). The difference was not significant in patients who were already taking statins (high vs low dose 7.6% vs 10.6%, p = 0.582). In conclusion, the incidence of percutaneous coronary intervention-related periprocedural MI was reduced more effectively by high-dose than by low-dose rosuvastatin in statin-naive patients. However, low-dose rosuvastatin is sufficient for patients who are already taking statins.

Cytokine levels in pleural effusions of patients under intensive care.

BACKGROUND: Pleural effusions develop for various reasons in patients admitted to intensive care units (ICUs). To understand why this occurs is important, yet cytokine levels in pleural effusions have rarely been measured from a cardiovascular viewpoint. OBJECTIVE: To understand the characteristics of pleural cytokines in patients admitted to the ICU. METHODS: The subjects were 43 patients with pleural effusion who were admitted to the ICU from June 2001 through March 2006. We divided the patients into transudate (n=23) and exudate (n=20) groups. We measured levels of interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-alpha in pleural effusions and peripheral blood and evaluated their relationships with body temperature, C-reactive protein (CRP) level, and the peripheral white blood cell (WBC) count. RESULTS: Levels of pleural IL-6 were significantly higher and levels of TNF-alpha tended to be higher in pleural effusions from the exudate than in those from the transudate group (3,350+/-3,627 vs. 1,677+/-1,086 pg/m and 6.6+/-3.4 vs. 4.8+/-2.6 pg/mL, respectively). However, in both groups levels of IL-10 in pleural effusions were similar to those in serum and levels of IL-6 were significantly higher in pleural effusion than in serum. Serum IL-6 levels correlated with inflammatory markers (CRP and body temperature), whereas cytokines in pleural effusion did not correlate with any of these markers (body temperature, CRP, and WBC). CONCLUSION: Pleural levels of IL-6 were significantly higher in the exudate group than in the transudate group but did not correlate with serum levels of IL-6 or with systemic inflammatory markers. These findings suggest that pleural IL-6 levels correlate with local lung or pleural inflammation in patients admitted to the ICU.

Diagnostic score to differentiate acute aortic dissection in the emergency room.

BACKGROUND: Acute aortic dissection (AAD) is a life-threatening cardiovascular disorder that is similar to acute coronary syndrome (ACS), which means differentiating AAD and ACS is sometimes difficult in an emergency. METHODS AND RESULTS: Specific information from 131 patients with AAD or ACS was analyzed between April 2001 and March 2002. The emergency room AAD (ERAAD) score was defined as the total number of specific indexes for AAD among 15 indexes that were obtainable in the emergency room (Study 1). The clinical applicability of the ERAAD score was also investigated in another 711 patients with AAD or ACS between April 2002 and March 2006 (Study 2). The ERAAD score was based on (1) presence of back pain, (2) mediastinal thoracic ratio >30%, (3) aortic regurgitation and (4) aortic diameter >30 mm on ultrasonography in Study 1. The ERAAD score was significantly higher in patients with AAD than with ACS (3.19+/-0.83 vs 1.17+/-0.99) in Study 2. The sensitivity and specificity for AAD were 93.1% and 77.6%, respectively, when the ERAAD score was >or=3. CONCLUSION: The ERAAD score enables clinical diagnosis of AAD and correct treatment.

Coronary perforation during percutaneous coronary intervention.

Coronary perforation is an undesirable complication during percutaneous coronary intervention (PCI). We reviewed the cases of overt coronary perforation in our institute and analyzed their clinical backgrounds, the characteristics of the target lesion, management, and clinical outcomes. Between 1991 and 2005, we experienced 12 cases (0.35%) of coronary perforation in a total of 3415 PCI procedures. The perforation occurred during the use of debulking devices in 3 cases, immediately after stenting in 2, immediately after postdilatation of the stent in 2, and during wiring in 3 cases. Restoration was attempted by long inflation of a balloon in 7 cases, implantation of a covered stent graft in 1, and emergency surgical repair in 1 case. Subsequent cardiac tamponade occurred in 3 patients who required pericardiocentesis, and 1 patient died due to congestive heart failure. Administration of protamine was effective in stopping the bleeding in 6 patients, whereas continuation of antiplatelet therapy resulted in no overt rebleeding. Coronary perforation during PCI is a rare complication but is associated with significant morbidity and mortality. Intravenous administration of protamine is effective when it is used in conjunction with nonsurgical devices for initial management of perforation.