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Background: Long-term hospital stay is associated with functional decline in patients with pneumonia, especially in the elderly. Among elderly patients with pneumonia, aspiration pneumonia is a major category. Clinical definition is usually used because it can occur without apparent aspiration episodes. It is still not clear whether a long-term hospital stay is due to aspiration pneumonia itself caused by underlying oropharyngeal dysfunction or simply due to functional decline in elderly patients with multiple comorbidities during acute infection. The aim of this study is to identify whether clinically defined aspiration pneumonia itself was associated with a long-term hospital stay., Methods: A prospective observational study on community-acquired (CAP) or healthcare-associated pneumonia (HCAP) was conducted from January 2012 through January 2014. Aspiration pneumonia was clinically defined as pneumonia not only occurring in patients after documented aspiration episodes, but also occurring in those with underlying oropharyngeal dysfunction: chronic disturbances of consciousness and/or chronic neuromuscular diseases. We defined thirty-day hospital stay as a long-term hospital stay and compared it with logistic regression analysis. Potential confounders included age, sex, HCAP, body mass index (BMI), long-term bed-ridden state, heart failure, cerebrovascular disorders, dementia, antipsychotics use, hypnotics use, and CURB score which is a clinical prediction tool used to assess the severity, standing for; C (presence of Confusion), U (high blood Urea nitrogen level), R (high Respiratory rate), and B (low Blood pressure). In a sub-analysis, we also explored factors associated with long-term hospital stay in patients with aspiration pneumonia., Results: Of 2,795 patients, 878 (31.4%) had aspiration pneumonia. After adjusting potential confounders, the aspiration pneumonia itself was significantly associated with long-term hospital stay (adjusted odds ratio 1.44; 95% confidence interval 1.09-1.89, p < 0.01), as were higher age, male sex, high CURB score, HCAP, low BMI, heart failure, cerebrovascular disease, and antipsychotics use. Sub-analysis revealed factors associated with long-term hospital stay in the aspiration pneumonia, which included male sex, and multi-lobar chest X-ray involvement., Conclusions: Clinically defined aspiration pneumonia itself was independently associated with long-term hospital stay. This result could potentially lead to specific rehabilitation strategies for pneumonia patients with underlying oropharyngeal dysfunction., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The day of the week of admission may influence the length of stay and in-hospital death. However, the association between the admission day of the week and in-hospital outcomes has been inconsistent in heart failure (HF) patients among studies reported from Western countries. We thus analyzed this association in HF patients encountered in routine clinical practice in Japan. We studied the characteristics and in-hospital treatment in 1620 patients hospitalized with worsening HF by using the database of the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD). Patients were divided into two groups according to weekday (n = 1355; 83.6%) or weekend admission (n = 265; 16.4%). The mean age was 70.7 years and 59.4% were male. Etiology was ischemic in 34.0%, and mean left ventricular ejection fraction was 42.5%. Patients admitted on the weekend were significantly older and had more comorbidities, and more severe symptoms and signs of HF on admission. Length of stay was comparable between weekend and weekday admission (35.2 ± 47.0 days vs 33.6 ± 32.0 days, P = 0.591). Crude in-hospital mortality did not differ between patients admitted on the weekend and weekdays (7.5% vs 5.2%, P = 0.136). Even after adjustment for covariates in multivariable modeling with patients admitted on weekday as the reference, in-hospital death was comparable between patients admitted on the weekend and weekdays (adjusted odds ratio 1.125, 95% confidence interval 0.631-2.004, P = 0.691). Among patients hospitalized for worsening HF, admission day of the week did not affect in-hospital death and length of stay.

Background and Purpose: Hyponatremia is common and is associated with poor in-hospital outcomes in patients hospitalized with heart failure (HF). However, it is unknown whether hyponatremia is associated with long-term adverse outcomes. The purpose of this study was to clarify the characteristics, clinical status on admission, and management during hospitalization according to the serum sodium concentration on admission, and determine whether hyponatremia was associated with in-hospital as well as long-term outcomes in 1677 patients hospitalized with worsening HF on index hospitalization registered in the database of the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD)., Methods and Subjects: We studied the characteristics and in-hospital treatment in 1659 patients hospitalized with worsening HF by using the JCARE-CARD database. Patients were divided into 2 groups according to serum sodium concentration on admission <135mEq/mL (n=176; 10.6%) or ≥135mEq/mL (n=1483; 89.4%)., Results: The mean age was 70.7 years and 59.2% were male. Etiology was ischemic in 33.9% and mean left ventricular ejection fraction was 42.4%. After adjustment for covariates, hyponatremia was independently associated with in-hospital death [adjusted odds ratio (OR) 2.453, 95% confidence interval (CI) 1.265-4.755, p=0.008]. It was significantly associated also with adverse long-term (mean 2.1±0.8 years) outcomes including all-cause death (OR 1.952, 95% CI 1.433-2.657), cardiac death (OR 2.053, 95% CI 1.413-2.983), and rehospitalization due to worsening HF (OR 1.488, 95% CI 1.134-1.953)., Conclusions: Hyponatremia was independently associated with not only in-hospital but also long-term adverse outcomes in patients hospitalized with worsening HF., (Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: The characteristics, in-hospital management, and outcomes of patients hospitalized with worsening heart failure (HF) have been described by large-scale registries performed mainly in the USA and Europe. However, little information is available in Japan. We thus clarified the characteristics and clinical status as well as in-hospital management and outcomes among patients hospitalized with worsening HF in Japan and compared them with those reported in previous studies., Methods: The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) studied prospectively the characteristics and treatments in patients hospitalized with worsening HF. From the total cohort of JCARE-CARD, 1677 patients were randomly selected and their detailed data during acute phase were collected as another registry database in the present study. The characteristics, in-hospital management, and outcomes were analyzed., Results: The mean age was 70.7 years and 59.4% were male. Etiology was ischemic in 34.0% and mean left ventricular ejection fraction was 42.5%. Carperitide was highly used as in-hospital management in Japan (33.5%) compared to the use of nesiritide in the USA (8-11%). The use of angiotensin-converting enzyme inhibitors was lower and angiotensin II receptor blockers (ARB) were more commonly used in this study compared to other studies in the USA and Europe. In-hospital crude mortality rate was comparable among studies (4-8%), however, length of stay was longer in Japan (15-20 versus 4-9 days)., Conclusions: The characteristics, clinical status, and laboratory data on admission in patients hospitalized with worsening HF were similar between the present study and previous Japanese and western studies. Management was also similar except for higher use of carperitide and ARB. The most striking difference between Japanese registries and those from the USA and Europe was the longer length of stay., (Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: A subset of patients with hypertrophic cardiomyopathy (HCM) has been reported to progress into dilated-HCM (D-HCM), characterized by left ventricular (LV) systolic dysfunction and cavity dilatation, resembling idiopathic dilated cardiomyopathy (DCM). We compared the characteristics, treatments, and outcomes in patients with heart failure (HF) due to D-HCM vs. DCM by using national registry data in Japan., Methods and Results: The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) is a prospective observational study of patients hospitalized due to worsening HF with an average of 2.2 years of follow-up. Patients with D-HCM (n=41) were more likely to be male, have prior stroke, atrial fibrillation, and sustained ventricular tachycardia or ventricular fibrillation compared with DCM (n=486). Echocardiography demonstrated that D-HCM patients had smaller LV end-systolic diameter, higher ejection fraction, and greater wall thickness. Treatments for HF including angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, β-blocker, and spironolactone were similar between groups except for higher use of amiodarone, warfarin, and implantable cardioverter-defibrillator for D-HCM. Mortality was significantly higher in patients with D-HCM (29.7% vs. 14.4%; p<0.05). Sudden death tended to be higher also in D-HCM (8.1% vs. 2.6%; p=0.06), which, however, did not reach statistical significance., Conclusions: HF patients with D-HCM had higher mortality risk than those with DCM. Effective management strategies are critically needed to be established for D-HCM., (Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: The mode of death has not been investigated in the registry data of patients with heart failure and reduced ejection fraction (HFREF) vs. preserved ejection fraction (HFPEF). The aim of the present study was therefore to carry out this comparison., Methods and Results: The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) prospectively studied the characteristics and treatments in a broad sample of 2,675 patients hospitalized with worsening HF, and followed them for an average of 2.1 years. This study included 323 patients in whom information on both the mode of death and left ventricular EF on echocardiography could be obtained. The mode of death was cardiovascular (CV) in 63% (including 17% sudden, 36% HF, 3% myocardial infarction, and 3% stroke), non-CV in 23%, and unknown in 14%. The prevalence of CV death including sudden death was high in patients with HFREF compared to HFPEF (68% vs. 58%, P=0.020). HF death, the most common mode of death, was similar between groups (37% vs. 35%, P=0.694). In contrast, non-CV mortality was significantly higher in HFPEF than those with HFREF (28% vs. 18%, P=0.021)., Conclusions: In 60-70% of deaths the mode was CV, and HF death was the most common mode of death in either HFREF or HFPEF. The prevalence of sudden death was lower, and that of non-CV death higher, in HFPEF compared with HFREF.

Background: Loop diuretics are commonly used in patients with heart failure (HF) to remove retained fluid and improve symptoms. However, they may potentially worsen outcomes in HF. It remains unknown whether the use of loop diuretics is associated with adverse HF outcomes in routine clinical practice. We thus determined the effects of loop diuretic use at discharge on long-term mortality and rehospitalization among patients hospitalized with HF., Methods and Results: The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) prospectively studied the characteristics and treatments of a broad sample of patients hospitalized with worsening HF and followed for 2.1 years. Among a total of 2,549 HF patients, loop diuretics were used by 2,015 patients (79%), but not 534 patients (21%). The mean age was 70.7 years and 60% were male. Etiology was ischemic in 32% and mean left ventricular ejection fraction was 42%. After adjustment for covariates, discharge use of loop diuretics was associated with significant adverse risks of cardiac death (adjusted hazard ratio [HR] 2.348, 95% confidence interval [CI] 1.246-4.423, P=0.008) and rehospitalization (adjusted HR 1.427, 95% CI 1.040-1.959, P=0.027)., Conclusions: Among patients hospitalized with worsening HF, loop diuretic use at discharge was associated with long-term adverse outcomes, which suggests that routine chronic use of loop diuretics may be harmful for patients with HF.

Background: Hyperuricemia is associated with worse outcomes of patients with chronic heart failure (HF). However, it is unknown in an unselected HF patients encountered in routine clinical practice. We thus assessed the impact of hyperuricemia on long-term outcomes including mortality and rehospitalization among patients hospitalized with worsening HF., Methods: The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) studied prospectively the characteristics and treatments in a broad sample of hospitalized HF patients and the outcomes were followed for 2.1 years after discharge. Study cohorts (n=1869) were divided into 2 groups according to serum uric acid (UA) at discharge; ≥ 7.4 mg/dL (n=908) and <7.4 mg/dL (n=961)., Results: Of the total cohort of HF patients, 56% had hyperuricemia defined as UA ≥ 7.0mg/dl. Patients with UA ≥ 7.4 mg/dL had higher rates of all-cause death, cardiac death, rehospitalization, and all-cause death or rehospitalization due to worsening HF. After multivariable adjustment, higher UA levels were a significant and independent predictor for all-cause death (adjusted hazard ratio [HR] 1.413, 95% confidence interval [CI] 1.094-1.824, P=0.008) and cardiac death (adjusted HR 1.399, 95% CI 1.020-1.920, P=0.037)., Conclusions: Hyperuricemia was common in patients with HF encountered in clinical practice and higher UA was independently associated with long-term adverse outcomes in these patients., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Aging is associated with adverse outcomes in patients with cardiac diseases. Whether elderly patients hospitalized with heart failure (HF) had increased risks for mortality and rehospitalization compared with younger patients during the long-term follow-up was examined. The predictors of these adverse outcomes were also identified., Methods and Results: The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) studied prospectively the characteristics and treatments in a broad sample of 2,675 patients hospitalized with worsening HF and the outcomes were followed up. The majority of elderly patients were female, had lower body mass index (BMI), a higher rate of ischemic, valvular, and hypertensive heart disease as etiologies of HF, a lower estimated glomerular filtration rate (eGFR), lower hemoglobin, and higher left ventricular ejection fraction values. Even after adjustment for covariates, the elderly patients were associated with higher risks of adverse outcomes. The predictors for all-cause death were: lower eGFR, lower BMI, male sex, sustained ventricular tachycardia or fibrillation (VT/VF), and the use of diuretics at discharge., Conclusions: Among patients hospitalized with HF, elderly patients had a worse prognosis than younger patients. Lower eGFR, lower BMI, male sex, sustained VT/VF, and diuretic use were independent predictors for all-cause death in these patients with higher risk.

Background: Obesity is a risk factor for cardiovascular disease (CVD) and is also associated with an increased risk of death in subjects without CVD. However, in heart failure (HF), elevated body mass index (BMI) has been shown to be associated with better prognosis, but it is unknown whether this is the case in unselected HF patients encountered in routine clinical practice in Japan., Methods and Results: The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) studied prospectively the characteristics and treatments in a broad sample of patients hospitalized with worsening HF and the outcomes were followed for 2.1 years. Study cohort (n=2,488) was classified into 3 groups according to baseline BMI: <20.3kg/m(2) (n=829), 20.3-23.49kg/m(2) (n=832), and ≥23.5kg/m(2) (n=827). The mean BMI was 22.3±4.1kg/m(2). Patients with higher BMI had lower rates of all-cause death, cardiac death, and rehospitalization because of worsening HF. After multivariable adjustment, the risk for all-cause death and cardiac death significantly increased with decreased BMI levels compared with patients with BMI ≥23.5kg/m(2). However, BMI levels were not associated with rehospitalization for worsening HF., Conclusions: Lower BMI was independently associated with increased long-term all-cause, as well as cardiac, mortality in patients with HF encountered in routine clinical practice in Japan.

Background: Previous studies demonstrated that beta-blocker use at the time of hospital discharge significantly increased postdischarge treatment rates, associated with an early (60- to 90-day) survival benefit in patients with heart failure (HF). However, it is unknown whether this therapeutic approach can also improve the long-term survival. We thus examined the long-term effects of beta-blocker use at discharge on outcomes in patients hospitalized for HF and left ventricular systolic dysfunction (LVSD) (ejection fraction <40%)., Methods and Results: The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) enrolled HF patients hospitalized with worsening symptoms and they were followed during an average of 2.2 years. A total of 947 patients had LVSD, among whom 624 (66%) were eligible to receive a beta-blocker at discharge. After adjustment for covariate and propensity score, discharge use of beta-blocker, when compared to no beta-blocker use, was associated with a significant reduced risk of all-cause mortality (hazard ratio (HR) 0.564, 95% confidence interval (CI) 0.358-0.889, P=0.014) and cardiac mortality (HR 0.489, 95%CI 0.279-0.859, P=0.013) after hospital discharge., Conclusions: Beta-blocker use at the time of discharge was associated with a long-term survival benefit in a diverse cohort of patients hospitalized with HF.

Large-scale, placebo-controlled, randomized clinical trials have shown that angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) reduce mortality and hospitalization in patients with heart failure (HF) caused by left ventricular systolic dysfunction (LVSD). However, it is unknown whether ACE inhibitors and ARBs have similar effects on the long-term outcomes in HF patients encountered in routine clinical practice. The Japanese Cardiac Registry of Heart Failure in Cardiology enrolled HF patients hospitalized with worsening symptoms and they were followed during an average of 2.2 years. The outcome data were compared in patients with LVSD by echocardiography (ejection fraction, EF <40%) according to the predischarge use of ACE inhibitors (n=356) or ARBs (n=372). The clinical characteristics were similar between patients with ACE inhibitor and ARB use, except for higher prevalence of hypertensive etiology and diabetes mellitus. There was no significant difference between ACE inhibitor and ARB use in all-cause death (adjusted hazard ratio 0.958, 95% confidence interval 0.601-1.527, P=0.858) and rehospitalization (adjusted hazard ratio 0.964, 95% confidence interval 0.683-1.362, P=0.836). The effects of ACE inhibitor and ARB use on the outcomes were generally consistent across all clinically relevant subgroups examined, including age, sex, etiology, EF, hypertension, diabetes mellitus, and beta-blocker use. Discharge use of ARBs provided comparable effects with ACE inhibitors on outcomes in patients hospitalized for HF. These findings provide further support for guideline recommendations that ARBs can be used in patients with HF and LVSD as an alternative of ACE inhibitors.

Background: Atrial fibrillation (AF) is a common arrhythmia in patients with heart failure (HF), but its prognostic importance is controversial. The effect of AF on long-term outcomes, including mortality and rehospitalization, among unselected HF patients hospitalized with HF in routine clinical practice in Japan was assessed in the present study., Methods and Results: The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) prospectively studied the characteristics and treatment strategies of a broad sample of patients hospitalized with worsening HF and the outcomes were followed with an average of 2.4 years of follow-up. The study cohort (n=2,659) was grouped according to the presence (n=937; 35.2%) or absence (n=1,722; 64.8%) of AF at baseline. After multivariable adjustment, patients with and without AF had a comparable risk for all-cause death (adjusted hazard ratio (HR) 0.931, 95% confidence interval (CI) 0.690-1.258, P=0.643), cardiac death (adjusted HR 0.949, 95%CI 0.655-1.377, P=0.784), rehospitalization because of the worsening HF (adjusted HR 1.028, 95%CI 0.816-1.295, P=0.816), and all-cause death or rehospitalization (adjusted HR 1.039, 95%CI 0.842-1.281, P=0.722)., Conclusions: Among patients hospitalized for HF in Japan, AF was common, but was not an independent risk for long-term adverse outcomes, including death or rehospitalization, in routine clinical practice.

Background: Heart failure (HF) with preserved ejection fraction (EF) is common. We compared the characteristics, treatments, and outcomes in HF patients with reduced vs preserved EF by using the national registry database in Japan., Methods and Results: The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) is a prospective observational study in a broad sample of patients hospitalized with worsening HF. The study enrolled 2,675 patients from 164 hospitals with an average of 2.4 years of follow-up. Patients with preserved EF (EF >or=50% by echocardiography; n=429) were more likely to be older, female, have hypertension and atrial fibrillation, and less likely to have ischemic etiology compared with those with reduced EF (EF <40%; n=985). Unadjusted risk of in-hospital mortality (6.5% vs 3.9%; P=0.03) and post-discharge mortality (22.7% vs 17.8%; P=0.058) was slightly higher in patients with preserved EF, which, however, were not different after multivariable adjustment. Patients with preserved EF had similar rehospitalization rates (36.2% vs 33.4%; P=0.515) compared with patients with reduced EF., Conclusions: HF patients with preserved EF had a similar mortality risk and equally high rates of rehospitalization as those with reduced EF. Effective management strategies are critically needed to be established for this type of HF.

Background: Anemia is common in patients with heart failure (HF) and is associated with worse outcomes. However, the effects of anemia are unknown in an unselected group of HF patients encountered in routine clinical practice in Japan. The impact of anemia on long-term outcomes including mortality and rehospitalization among patients hospitalized with HF was thus assessed., Methods and Results: The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) prospectively studied the characteristics and treatments in a broad sample of patients hospitalized with worsening HF and the outcomes were followed. Study cohorts (n=1,960) were classified into 4 groups by discharge hemoglobin quartiles: <10.1 g/dl (n=482), 10.1-11.9 g/dl (n=479), 12.0-13.6 g/dl (n=487), and >or=13.7 g/dl (n=512). Of the total cohort of HF patients, 57% had anemia, defined by using the World Health Organization definition. Patients with lower hemoglobin quartiles had higher rates of all-cause death, cardiac death, and rehospitalization due to worsening HF. After multivariable adjustment, the risk for all-cause death, cardiac death, and rehospitalization significantly increased with low hemoglobin concentrations., Conclusions: Anemia was quite common especially in patients with HF encountered in routine clinical practice in Japan, and lower hemoglobin was independently associated with long-term adverse outcomes in these patients.

Background: Previous studies have demonstrated that renal dysfunction is common in patients with heart failure (HF), but it is not known whether chronic kidney disease (CKD) is associated with increased risks of long-term adverse outcomes in unselected HF patients encountered in current routine clinical practice in Japan., Methods and Results: The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) prospectively studied a broad sample of patients hospitalized with worsening HF and their outcomes with an average of 2.4 years of follow-up. The study cohort (n=2,013) were classified into 3 groups by estimated glomerular filtration rate (eGFR): > or =60 (n=579), 30-59 (n=1,025), and <30 ml x min(-1) x 1.73 m(-2) or patients with dialysis (n=409); 1,372 patients (70.3%) had an eGFR <60 ml x min(-1) x 1.73 m(-2) and 62 patients were treated with dialysis. The multivariable adjusted risk for all-cause death or rehospitalization increased with reduced eGFR; an adjusted hazard ratio (HR) 1.520 (95% confidence interval (CI) 1.186-1.949) for eGFR 30-59 ml x min(-1) x 1.73 m(-2) (P=0.001) and HR 2.566 (95%CI 1.885-3.492) for eGFR <30 ml x min(-1) x 1.73 m(-2) or patients with dialysis (P<0.001)., Conclusions: CKD is common in HF and was independently associated with long-term adverse outcomes in a broad cohort of Japanese patients.

Type 2 diabetes adversely affects the outcomes in patients with myocardial infarction (MI), which is associated with the development of left ventricular (LV) failure. NAD(P)H oxidase-derived superoxide (O(2)(-)) production is increased in type 2 diabetes. However, its pathophysiological significance in advanced post-MI LV failure associated with type 2 diabetes remains unestablished. We thus hypothesized that an inhibitor of NAD(P)H oxidase activation, apocynin, could attenuate the exacerbated LV failure after MI in high-fat diet (HFD)-induced obese mice with type 2 diabetes. Male C57BL/6J mice were fed on either HFD or normal diet (ND) for 8 wk. At 4 wk of feeding, MI was created in mice by ligating the left coronary artery. HFD-fed MI mice were treated with either 10 mmol/l apocynin or vehicle. HFD + MI had significantly greater LV end-diastolic diameter (LVEDD; 5.7 +/- 0.1 vs. 5.3 +/- 0.2 mm), end-diastolic pressure (12 +/- 2 vs. 8 +/- 1 mmHg), and lung weight/tibial length (10.1 +/- 0.3 vs. 8.7 +/- 0.7 mg/mm) than ND + MI, which was accompanied by an increased interstitial fibrosis of noninfarcted LV. Treatment of HFD + MI with apocynin significantly decreased LVEDD (5.4 +/- 0.1 mm), LV end-diastolic pressure (9.7 +/- 0.8 mmHg), lung weight/tibial length (9.0 +/- 0.3 mg/mm), and concomitantly interstitial fibrosis of noninfarcted LV to the ND + MI level without affecting body weight, glucose metabolism, and infarct size. NAD(P)H oxidase activity and O(2)(-) production were increased in noninfarcted LV tissues from HFD + MI, both of which were attenuated by apocynin to the ND + MI level. Type 2 diabetes was associated with the exacerbation of LV failure after MI via increasing NAD(P)H oxidase-derived O(2)(-), which may be a novel important therapeutic target in advanced heart failure with diabetes.

Blockade of the renin-angiotensin system reduces cardiovascular morbidity and mortality in diabetic patients. Angiotensin II (Ang II) plays an important role in the structural and functional abnormalities of the diabetic heart. We investigated whether or not Ang II type 1 receptor blocker (ARB) could attenuate left ventricular (LV) remodeling in male mice with diabetes mellitus (DM) induced by the injection of streptozotocin (200 mg/kg, i.p.). Diabetic mice were treated with candesartan (1 mg/kg/day; DM+Candesartan, n=7) or vehicle (DM+Vehicle, n=7) for 8 weeks. Heart rate and aortic blood pressure were comparable between the groups. Normal systolic function was preserved in diabetic mice. In contrast, diastolic function was impaired in DM+Vehicle and was improved in DM+Candesartan, as assessed by the deceleration time of the peak velocity of transmitral diastolic flow (40.3+/-0.3 vs. 37.3+/-0.5 ms, p<0.01) and the time needed for relaxation of 50% maximal LV pressure to baseline value (tau; 10.6+/-0.7 vs. 8.7+/-0.6 ms, p<0.05) without significant changes in heart rate and aortic blood pressure. Improvement of LV diastolic function was accompanied by the attenuation of myocyte hypertrophy, interstitial fibrosis and apoptosis in association with the expression of connective tissue growth factor (CTGF) and myocardial oxidative stress. Moreover, candesartan directly inhibited Ang II-mediated induction of CTGF in cultured cardiac fibroblasts. ARB might be beneficial to prevent cardiac abnormalities in DM.