Toshiaki Isogai

Out-of-hospital versus in-hospital Takotsubo cardiomyopathy: Analysis of 3719 patients in the Diagnosis Procedure Combination database in Japan

BACKGROUND Although Takotsubo cardiomyopathy (TC) generally occurs after a stressful event out-of-hospital, it occasionally occurs secondary to acute medical illness after hospital admission. No study has examined and compared patient backgrounds and in-hospital outcomes between patients with out-of-hospital TC and those with in-hospital TC. METHODS AND RESULTS Using the Diagnosis Procedure Combination inpatient database in Japan, we identified 3719 eligible patients with a diagnosis of TC who underwent coronary angiography without any revascularization procedure between 2010 and 2013, including 419 patients with in-hospital TC and 3300 patients with out-of-hospital TC. There was no significant difference in age between those with in-hospital TC and those with out-of-hospital TC (74.2 ± 10.9 years versus 73.4 ± 11.3 years, p=0.211). Patients with in-hospital TC had a higher proportion of males than out-of-hospital TC patients (31.3% versus 21.3%, p<0.001). Patients with in-hospital TC had significantly higher proportions of several chronic comorbidities and acute medical illnesses. In-hospital mortality was significantly higher in patients with in-hospital TC than in patients with out-of-hospital TC (17.9% versus 5.4%, p<0.001). In the multivariable logistic regression analysis, in-hospital TC was significantly associated with higher in-hospital mortality (adjusted odds ratio 2.02; 95% confidence interval, 1.43 to 2.85; p<0.001), even after adjustment for patient backgrounds. Malignancy, chronic liver disease, rheumatic disease, sepsis, pneumonia, cerebrovascular diseases, acute renal failure, and acute gastrointestinal diseases were also significantly associated with higher in-hospital mortality. CONCLUSIONS In-hospital TC was associated with more severe clinical background and poorer short-term prognosis than out-of-hospital TC.

Characterization of predictors of in-hospital cardiac complications of takotsubo cardiomyopathy: Multi-center registry from Tokyo CCU Network

BACKGROUND Takotsubo cardiomyopathy (TC) is an acute cardiac syndrome characterized by transient left ventricular dysfunction and relatively good prognosis after discharge. However, cardiac complications during hospitalization remain to be fully determined. We attempted to determine features characterizing patients with adverse clinical outcome by comparing those with cardiac complication and without cardiac complication during hospitalization. METHODS AND RESULTS We investigated 107 patients with TC from the Tokyo CCU Network database, comprising 67 cardiovascular centers in the metropolitan area during January 1 to December 31, 2010. Cardiac complications were defined as cardiac death, pump failure (Killip grade≥II), sustained ventricular tachycardia or fibrillation (SVT/VF), and advanced atrioventricular block (AVB). Cardiac complications were observed in 41 patients (37 pump failure complicated by 3 cardiac deaths and 2 SVT/VF and 2 AVB without pump failure), and there was no cardiac complication in the remaining 66 patients. There was no difference in age, peak creatinine kinase level, C-reactive protein level and ST elevation on electrocardiogram. Multiple logistic regression analysis showed that white blood cell count (p=0.039) and brain natriuretic peptide (p=0.001) were independent predictors of in-hospital adverse cardiac complications. CONCLUSIONS Cardiac complications are relatively high in patients with TC during hospitalization. High white blood cell count and brain natriuretic peptide level are associated with poor clinical outcome in patients with TC.

Early β-blocker use and in-hospital mortality in patients with Takotsubo cardiomyopathy

Objective A catecholamine-mediated mechanism has been implicated in the pathogenesis of Takotsubo cardiomyopathy (TC). However, the impact of β-blockers in acute-phase management of TC remains uncertain. This study aimed to examine whether early β-blocker use in TC was associated with lower in-hospital mortality. Methods This was a retrospective cohort study using the Diagnosis Procedure Combination nationwide inpatient database in Japan. Patients with TC aged ≥20 years who were admitted to acute-care hospitals between 2010 and 2014 were identified. Thirty-day in-hospital mortality was compared between patients who started β-blocker therapy on hospitalisation day 1 or 2 (early β-blocker group) and those who did not receive a β-blocker during hospitalisation (control group) using propensity score-matching and instrumental variable analyses. Results Of 2672 eligible patients (female, 81.5%; 423 early β-blocker therapy, 2249 controls) from 615 hospitals, 1:4 propensity score-matching created a cohort of 2110 patients (422 early β-blocker therapy, 1688 controls). There was no significant difference in 30-day in-hospital mortality between the early β-blocker group and control group (2.4% vs 2.0%, p=0.703; risk difference, 0.4%; 95% CI, −1.2% to 2.0%). Logistic regression analysis did not show a significant association between early β-blocker use and 30-day in-hospital mortality (OR, 1.17; 95% CI 0.58 to 2.37). Instrumental variable analysis also found that early β-blocker use was not associated with lower 30-day in-hospital mortality (risk difference, 1.2%; 95% CI −3.1% to 5.5%). Conclusions This study found no significant association between early β-blocker use and in-hospital mortality in patients with TC.

Effectiveness of Inferior Vena Cava Filters on Mortality as an Adjuvant to Antithrombotic Therapy

BACKGROUND Despite growing evidence of complications, inferior vena cava filters are being used increasingly in patients with venous thromboembolism based on limited efficacy data. In such a controversial situation, the effectiveness of filter use on mortality as an adjuvant to antithrombotic therapy for pulmonary embolism remains uncertain. METHODS Using the Diagnosis Procedure Combination database in Japan, we identified patients hospitalized with pulmonary embolism who received anticoagulation or thrombolytic therapy from the day of admission. We compared the in-hospital mortality between patients who received a filter and patients who did not, using propensity score and instrumental variable methods. RESULTS Of 13,125 eligible patients, 3948 received a filter, and 9177 did not receive a filter. The propensity score-matched analysis showed that filter use was significantly associated with lower in-hospital mortality than nonuse (2.6% vs 4.7%, P < .001; risk ratio 0.55; 95% confidence interval [CI], 0.43-0.71; risk difference -2.1%; 95% CI, -3.0% to -1.2%; number needed to treat, 48; 95% CI, 34-82). We obtained similar results in the inverse probability of treatment-weighting analysis. The instrumental variable analysis confirmed that filter use was associated with a decreased risk of in-hospital mortality with adjustment for all measured variables (risk difference -2.5%, 95% CI, -4.6% to -0.4%). CONCLUSIONS This study suggested that filter use was potentially effective for reducing in-hospital mortality in patients with pulmonary embolism. Prospective studies are needed to confirm the effectiveness observed in our results and to define which subpopulations of patients would benefit most from filters.

Gender Differences in Patients with Takotsubo Cardiomyopathy: Multi-Center Registry from Tokyo CCU Network

Background The clinical features of gender differences in takotsubo cardiomyopathy (TC) remain to be determined. The aim of this study was to evaluate the differences in clinical characteristics of male and female patients with TC. Methods We obtained the clinical information of 368 patients diagnosed with TC (84 male, 284 female) from the Tokyo CCU Network database collected from 1 January 2010 to 31 December 2012; the Network is comprised of 71 cardiovascular centers in the Tokyo (Japan) metropolitan area. We attempted to characterize clinical differences during hospitalization, comparing male and female patients with TC. Results There were no significant differences in apical ballooning type, median echocardiography ejection fraction, serious ventricular arrhythmias (such as ventricular tachycardia or fibrillation), or cardiovascular death between male and female patients. Male patients were younger than female patients (median age at hospitalization for male patients was 72 years vs. 76 years for female patients; p = 0.040). Prior physical stress was more common in male than female patients (50.0% vs.31.3%; p = 0.002), while emotional stress was more common in female patients (19.0% vs. 31.0%; p = 0.039). Severe pump failure (defined as Killip Class > III) (20.2% vs. 10.6%; p = 0.020) and cardiopulmonary supportive therapies (28.6% vs. 12.7%, p < 0.001) were more common in male than female patients. Multivariate analysis revealed that male gender (odds ratio = 4.32, 95% CI = 1.41–13.6, p = 0.011) was an independent predictor of adverse composite cardiac events, including cardiovascular death, severe pump failure, and serious ventricular arrhythmia. Conclusions Cardiac complications in our dataset appeared to be more common in male than female patients with TC during their hospitalization. Further investigation is required to clarify the underlying mechanisms responsible for the observed gender differences.

Hospital Volume and Cardiac Complications of Endomyocardial Biopsy: A Retrospective Cohort Study of 9508 Adult Patients Using a Nationwide Inpatient Database in Japan

Recent research on complications with endomyocardial biopsy (EMB) has been based on single‐center or 2‐center studies in high‐volume cardiovascular centers. No study has examined the association between hospital volume and the complication rate after EMB.

Serious Cardiac Complications in Coronary Spasm Provocation Tests Using Acetylcholine or Ergonovine: Analysis of 21 512 Patients From the Diagnosis Procedure Combination Database in Japan

Previous studies on complications with coronary spasm provocation tests were based on small sample sizes or were limited to high‐volume centers. The risk of provocation tests using acetylcholine (ACH) or ergonovine (ER) remains to be fully examined by a large‐scale multicenter study.

Factors affecting in-hospital mortality and likelihood of undergoing surgical resection in patients with primary cardiac tumors.

BACKGROUND Previous studies on primary cardiac tumors were mainly based on small case series collected from a limited number of institutions. Contemporary data of patients with primary cardiac tumors treated with or without surgery in a nationwide clinical setting are limited. METHODS Using the Diagnosis Procedure Combination database, we retrospectively identified 1317 patients hospitalized with a primary cardiac tumor (1023 myxomas, 63 non-myxomas, 72 sarcomas, 41 malignant lymphoma, 118 unspecified tumors) at 486 hospitals in Japan from July 2010 to March 2013. The outcome was overall in-hospital mortality, defined as in-hospital death occurring during the initial hospitalization or during rehospitalization. We examined the associations of baseline factors with overall in-hospital mortality and undergoing surgical resection using multivariable logistic regression analyses. RESULTS Overall, 914 (69.4%) patients underwent surgery and 403 (30.6%) did not. The surgery group was younger (median age, 67 years vs. 71 years, p<0.001) and was more likely to be treated at an academic hospital (38.9% vs. 27.8%, p<0.001) than the no-surgery group. The surgery group also had a higher Barthel index and a higher conscious level and showed a lower frequency of extracardiac malignancies than the no-surgery group. The likelihood of undergoing surgery was associated with coexisting cerebral infarction [adjusted odds ratio (95% confidence interval), 1.96 (1.23-3.12)] and academic hospital [1.58 (1.20-2.09)]. Patients with lower Barthel index and coexisting extracardiac malignancies were less likely to undergo surgery. Overall in-hospital mortality was 2.1% and 13.4% in the surgery and non-surgery groups, respectively. Older age, lower Barthel index, lower consciousness level, coexisting metastatic extracardiac malignancy [2.95 (1.24-7.01)], and sarcoma [21.04 (8.28-53.42)] were associated with higher overall in-hospital mortality, while academic hospital [0.41 (0.20-0.84)] and surgical resection [0.39 (0.20-0.74)] were associated with lower mortality. CONCLUSIONS Several background factors were associated with prognosis and surgery in patients hospitalized with primary cardiac tumors.

Safety and efficacy of direct oral anticoagulants over warfarin in Japanese patients with acute venous thromboembolism: A meta-analysis

BACKGROUND Direct oral anticoagulants (DOACs) have been developed as alternatives to conventional therapy with warfarin for the treatment of acute venous thromboembolism (VTE) events. The safety and efficacy of DOACs in Japanese patients with acute VTE has been investigated in small trials or subgroups from global randomized controlled trials (RCTs). METHODS AND RESULTS We conducted a systematic review and meta-analysis of RCTs, to compare the safety and efficacy of DOACs to those of conventional therapy in Japanese patients with acute VTE. Published research was systematically searched for RCTs that compared DOAC to conventional therapy in Japanese patients with acute VTE. Random-effects models were used to pool safety and efficacy data across RCTs. Three studies, including 386 patients, were identified. Patients randomized to DOAC had a decreased risk for all bleeding [risk ratio (RR) 0.69, 95% confidential interval (CI) 0.50-0.95], without any significant differences in recurrent VTE (RR 0.84, 95% CI 0.29-2.43) and recurrent VTE/all-cause death (RR 0.60, 95% CI 0.23-1.56). CONCLUSION DOACs offer clinical benefit over conventional therapy in Japanese patients with acute VTE, showing a significant difference in their bleeding profile.

Predictive Value of QRS Duration at Admission for In-Hospital Clinical Outcome of Takotsubo Cardiomyopathy

BACKGROUND Prolonged QRS duration (pQRSd) on electrocardiogram (ECG) is a strong predictor of poor outcome in heart failure, myocardial infarction, and myocarditis, but it is unclear whether pQRSd also predicts poor outcomes of takotsubo cardiomyopathy (TC).Methods and Results:Between 1 January 2010 and 31 December 2012, we retrospectively enrolled 299 patients with TC (mean age, 73.5±11.7 years; 21.4% male) from the Tokyo CCU Network database, which consists of 71 cardiovascular centers in the metropolitan area. In-hospital clinical outcomes were compared between patients with pQRSd on admission ECG (QRS ≥120 ms; n=34) and those with normal QRS duration (<120 ms; n=265). The in-hospital mortality rate for pQRSd was significantly higher than that for normal QRS duration (23.5% vs. 3.8%, P<0.001). Similarly, prevalence of ventilator use (38.2% vs. 11.4%, P<0.001), ventricular tachycardia or fibrillation (14.7% vs. 1.5%, P<0.001), and circulatory failure requiring catecholamine or cardiopulmonary supportive devices (41.2% vs. 14.0%, P<0.001) was significantly higher in the pQRSd group. On multivariate logistic regression analysis, pQRSd was an independent predictor for both in-hospital mortality (OR, 5.06; 95% CI: 1.79-14.30, P=0.002) and cardiac death (OR, 7.34; 95% CI: 1.33-40.51, P=0.02). CONCLUSIONS TC with pQRSd is associated with poor in-hospital clinical outcome. Aggressive intervention may be required to prevent severe complications in these patients.