Nobuyuki Kagiyama

Clinical Effectiveness of Tolvaptan in Patients With Acute Heart Failure and Renal Dysfunction

BACKGROUND More efficacious and/or safer decongestive therapy is clearly needed in acute heart failure (AHF) patients complicated by renal dysfunction. We tested the hypothesis that adding tolvaptan, an oral vasopressin-2 receptor antagonist, to conventional therapy with loop diuretics would be more effective treatment in this population. METHODS AND RESULTS A multicenter, open-label, randomized control trial was performed, and 217 AHF patients with renal dysfunction (estimated glomerular filtration rate 15-60 mL • min(-1) • 1.73 m(-2)) were randomized 1:1 to treatment with tolvaptan (n=108) or conventional treatment (n=109). The primary end point was 48-hour urine volume. The tolvaptan group showed more diuresis than the conventional treatment group (6464.4 vs 4999.2 mL; P <.001) despite significantly lower amounts of loop diuretic use (80 mg vs 120 mg; P <.001). Dyspnea relief was achieved significantly more frequently in the tolvaptan group at all time points within 48 hours except 6 hours after enrollment. The rate of worsening of renal function (≥0.3 mg/dL increase from baseline) was similar between the tolvaptan and conventional treatment groups (24.1% vs 27.8%, respectively; P =.642). CONCLUSIONS Adding tolvaptan to conventional treatment achieved more diuresis and relieved dyspnea symptoms in AHF patients with renal dysfunction. CLINICAL TRIAL REGISTRATION URL: http://www.umin.ac.jp/ctr/index/htm/ Unique identifier: UMIN000007109.

Carperitide Is Associated With Increased In-Hospital Mortality in Acute Heart Failure: A Propensity Score-Matched Analysis.

BACKGROUND Carperitide (α-human A-type natriuretic peptide) has been used for more than one-half of all acute heart failure (AHF) patients in Japan. However, its clinical effectiveness is not well documented. METHODS We retrospectively identified AHF patients presenting with acute onset or worsening of symptoms and admitted to 1 of the 3 participating hospitals. Propensity score-matched analysis was performed. The primary end point was in-hospital mortality. RESULTS Of all of the AHF patients included in this study, 402 (38.7%) were treated with carperitide, and in-hospital mortality rate for the total cohort was 7.6%. We matched 367 pairs of patients treated with and without carperitide according to propensity score. In this matched cohort, treatment with carperitide was associated with in-hospital mortality (odds ratio [OR] 2.13, 95% confidence interval [CI] 1.17-3.85; P = .013). Potentially more harmful effects were observed in elderly patients (OR 2.93, 95% CI 1.54-5.91). CONCLUSIONS Carperitide was significantly associated with increased in-hospital mortality rate in AHF patients. Our results strongly suggest the necessity for well designed randomized clinical trials of carperitide to determine its clinical safety and effectiveness.

Impact of right ventricular involvement on the prognosis of takotsubo cardiomyopathy

BACKGROUND Previous studies showed that patients with takotsubo cardiomyopathy had a higher long-term mortality rate than the general population and the incidence of in-hospital complications was higher in takotsubo cardiomyopathy with than without right ventricular (RV) involvement. This study was performed to investigate the long-term prognostic impact of RV involvement in takotsubo cardiomyopathy. METHODS AND RESULTS The clinical data of 113 patients (72.7 ± 11.4 years old, 84 females) with takotsubo cardiomyopathy were studied retrospectively. The patients were divided into two groups according to the presence (biventricular group, n = 21, 18.6%) or absence (classical group, n = 92, 81.4%) of RV involvement assessed by initial echocardiography. The end point was a composite of all-cause death, re-hospitalization due to heart failure, and recurrence of takotsubo cardiomyopathy. The in-hospital mortality rate was significantly higher in the biventricular group than the classical group (14.3 vs. 1.1%, respectively, P = 0.02). Kaplan-Meier analysis indicated a significantly lower event-free survival rate in the biventricular group than the classical group (log-rank, P < 0.001). On multivariate analysis, RV involvement was the only independent predictor of the end point (HR: 2.73, P = 0.026). CONCLUSION The rates of in-hospital and long-term events were significantly higher in takotsubo cardiomyopathy with than without RV involvement, and RV involvement was the independent predictor of the poor prognosis.

Prognostic impact of early treatment with tolvaptan in patients with acute heart failure and renal dysfunction.

BACKGROUND Renal dysfunction is a common comorbidity in acute heart failure (AHF) patients. The prognostic significance of early treatment with tolvaptan in AHF patients complicated with renal dysfunction has not been elucidated. METHODS Post hoc analysis was performed on a randomized clinical study for prespecified prognostic endpoints and prespecified subgroups. 217 AHF patients with renal dysfunction (eGFR 15 to 60mL/min/1.73m(2)) were randomized within 6h from hospitalization to either tolvaptan treatment for 2days or conventional treatment. The primary outcome was the combined endpoint of all-cause death and HF readmission. RESULTS During follow-up (636days, median) 99 patients experienced combined endpoint and 53 patients died. There was no significant difference in event-free survival rate for either the combined events (Log-rank: P=0.197) or all-cause death (Log-rank: P=0.894) between tolvaptan and conventional groups. In prespecified subgroup analysis, in patients whose BUN/creatinine ratio was above the median (>20), tolvaptan significantly reduced the risk of combined events (HR: 0.52, 95% CI: 0.30-0.91, P=0.021) with a significant interaction (P value for interaction=0.045). Likewise, in patients whose eGFR was 30mL/min/1.73m(2) or above, tolvaptan reduced the risk of combined events (HR: 0.54, 95% CI: 0.32-0.90, P=0.017) with a significant interaction (P value for interaction=0.015). CONCLUSION Short-term use of tolvaptan in acute-phase in AHF with renal dysfunction showed a neutral effect on prognosis. Patients with relatively preserved renal function and relatively high BUN/creatinine ratios are potentially favorable subgroups for treatment with tolvaptan.

Recovery from hyponatremia in acute phase is associated with better in-hospital mortality rate in acute heart failure syndrome

BACKGROUND Although hyponatremia on admission is a predictor of poor prognosis in acute heart failure (AHF) patients, little is known about the association between changes in sodium level in acute phase and in-hospital mortality. This study was performed to clarify the impact of sodium level improvement in the early phase on prognosis in AHF patients. METHODS A total of 882 consecutive hospitalized AHF patients were retrospectively enrolled in this study. Sodium levels were evaluated on days 1 and 3 of admission, and patients were classified into three groups: patients with hyponatremia on admission and day 3 (hypo-hypo group); patients with hyponatremia on admission and normonatremia on day 3 (hypo-normo group); and patients with normonatremia on admission (normo group). RESULTS Hyponatremia (sodium ≤135 mEq/L) was observed in 14.3% of cases. In multivariate linear regression analysis, age (standardized beta=0.084), male gender (standardized beta=-0.072), history of ischemic heart disease (standardized beta=-0.069), baseline sodium level (standardized beta=-0.435), and tolvaptan use (standardized beta=0.093) were independent determinants of changes in sodium level from day 1 to day 3. In-hospital mortality rates were significantly higher in the hypo-hypo group (23.7%) and hypo-normo group (9.7%) than the normo group (6.9%) (p<0.001). After adjustment for covariates, both hypo-normo (OR: 0.28, 95% CI: 0.08-0.93, p=0.038) and normo (OR: 0.42, 95% CI: 0.20-0.88, p=0.022) groups showed significantly lower in-hospital mortality rates than the hypo-hypo group. CONCLUSION Early recovery from hyponatremia in AHF patients is associated with lower in-hospital mortality rate.

Insufficient Leaflet Remodeling in Patients With Atrial FibrillationCLINICAL PERSPECTIVE: Association With the Severity of Mitral Regurgitation

Background— The relationship between annular dilatation caused by atrial fibrillation (AF) and mitral regurgitation (MR) remains controversial. We hypothesized that the small ratio of total leaflet area/annulus area (TLA/AA), reflecting insufficient leaflet remodeling to annular dilatation, is a main component of MR in patients with AF. Methods and Results— Three-dimensional transesophageal echocardiographic data of the mitral valve were analyzed in 28 AF patients with moderate or severe MR (MR group), age- and sex-matched 56 AF patients with mild or less MR (non-MR group), and 16 control subjects. AA was significantly greater in both the MR (645±126 mm2/m2, P<0.001) and non-MR groups (568±121 mm2/m2, P=0.001) compared with control subjects (444±108 mm2/m2). However, TLA/AA was significantly smaller in the MR (1.29±0.10, P<0.001), but not in the non-MR group (1.65±0.24, P>0.99), compared with control subjects (1.70±0.29). In linear regression analysis, TLA/AA was inversely associated with the effective regurgitant orifice (r=−0.73, P<0.001). The area under the receiver-operating-characteristics curve of TLA/AA was significantly greater than that of AA (0.95 versus 0.72, P<0.001). Multivariable analysis revealed that small TLA/AA (P<0.001) was independently associated with significant MR, while AA was not (P=0.26). Conclusions— In patients with AF, insufficient leaflet remodeling to annular dilatation, rather than crude annular dilatation, was strongly associated with the severity of MR.

Two Cases of Acute Bioprosthetic Mitral Valve Thrombosis Immediately After Mitral Valve Replacement

Prosthetic valve thrombosis (PVT) is a rare complication, and most of PVT occurs in patients with mechanical valves. We present 2 extremely rare cases of acute bioprosthetic mitral valve thrombosis immediately after mitral valve replacement under veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and anticoagulant therapy. In Case 1, a 75-year-old woman underwent aortic valve replacement and mitral valve replacement with 23- and 29-mm bioprosthetic valves, respectively. On postoperative day 2, VA-ECMO was started because of hemodynamic compromise. At the initiation of VA-ECMO, transthoracic echocardiography indicated normal bioprosthesis function (Figure 1; see Movie I in the online-only Data Supplement). On postoperative day 9, transesophageal echocardiography revealed severely stenotic bioprosthetic mitral valve, but the bioprosthetic aortic valve was normal (Figure 2; see Movies II and III in the online-only Data Supplement). Emergent percutaneous mitral valvuloplasty was performed, resulting in partial improvement of hemodynamic state. On postoperative day 17, re-mitral valve replacement was performed. The left atrial side of the retrieved bioprosthetic valve leaflet was covered with thrombus, …

Infective endocarditis with negative blood culture and negative echocardiographic findings.

A 61-year-old male presented with fever. He had a history of aortic valve replacement, and infective endocarditis was suspected. The transthoracic and transesophageal echocardiography on admission could not detect vegetation, and all blood cultures obtained were negative. We concluded that infective endocarditis was not likely. However, repeated echocardiography revealed paravalvular regurgitation and paravalvular abscess. Serum antibody testing for Bartonella henselae was positive, leading to the diagnosis of blood culture-negative endocarditis. Even when blood cultures and echocardiography were negative on initial examination, careful history-taking, blood tests accounting for these pathogens, and repeated echocardiography are crucial for diagnosis.

Multimodality Imaging in Aortic Arch Aneurysm Ruptured into Pulmonary Artery

Fig 3. Aacute heart failure. He had a medical history of thoracic aortic aneurysm (TAA), which was 5.0 cm at the last follow-up 5 years earlier. Echocardiography showed severe tricuspid and pulmonary regurgitation with an enlarged right side of the heart. Further examination revealed a mass on the bifurcation of the pulmonary artery (PA) and a great amount of continuous inflow coming from the mass into the main PA (Fig 1 [Ao 1⁄4 aorta; Lt 1⁄4 left; Rt 1⁄4 right], Video 1). To assess the patient’s hemodynamic condition, catheter examination was performed. The ratio of pulmonary blood flow to systemic blood flow (Qp/Qs) was 3.15. Aortography revealed a large fistula from aortic arch into the PA (Fig 2 [Ao 1⁄4 aorta; AP 1⁄4 anteroposterior; LAO 1⁄4 left anterior oblique; lt 1⁄4 left], Video 2), and computed tomographic angiography confirmed that a TAA at the arch had ruptured into the PA (Fig 3, arrow). Surgical treatment was refused by his family, and he died 8 days later. TAA rupture is a life-threatening disease, and prompt diagnosis and treatment are essential to save a patient’s life. Treatment options can be open operation, endovascular occlusion or replacement, or a staged combination of these procedures. Although postmortem studies

Preoperative Simulation Using CT Virtual Endoscopy for Minimally Invasive Surgery of Hypertrophic Obstructive Cardiomyopathy

Transaortic septal myectomy is a procedure that involves a learning curve for surgeons because the bulging interventricular septum usually interferes with the visualization of the deep parts of the left ventricular chamber. In this case report, we demonstrate computed tomography virtual endoscopy for preoperative simulation, which enabled us to clearly image the relationship among the bulging septum, the expected myectomy area, and the structures deep in the left ventricle, such as the papillary muscle and abnormal muscular bundles, which are hidden by the hypertrophic septum, thus preventing visualization. This approach could make minimally invasive transaortic septal myectomy safe and easy.