Abstractβ-Arrestins, which were originally characterized as terminators of heterotrimeric guanine nucleotidebinding protein (G protein)-coupled receptor (GPCR) signaling, also act as important signal transducers. An emerging concept in GPCR signaling is β-arrestin-biased agonism, in which specific ligand-activated GPCR conformational states selectively signal through β-arrestins, rather than through G proteins. Here, we show that mechanical stretch induced β-arrestin-biased signaling downstream of angiotensin II type I receptors (AT1Rs) in the absence of ligand or G protein activation. Mechanical stretch triggered an AT1R-mediated conformational change in β-arrestin similar to that induced by a β-arrestin-biased ligand to selectively stimulate receptor signaling in the absence of detectable G protein activation. Hearts from mice lacking β-arrestin or AT1Rs failed to induce responses to mechanical stretch, as shown by blunted extra-cellular signal-regulated kinase and Akt activation, impaired transactivation of the epidermal growth factor receptor, and enhanced myocyte apoptosis. These data show that the heart responds to acute increases in mechanical stress by activating β-arrestin-mediated cell survival signals.

Background and ObjectivesThe burden of heart failure has increased in Korea. This registry aims to evaluate demographics, clinical characteristics, management, and long-term outcomes in patients hospitalized for acute heart failure (AHF).Subjects and MethodsWe prospectively enrolled a total of 5625 consecutive subjects hospitalized for AHF in one of 10 tertiary university hospitals from March 2011 to February 2014. Descriptive statistics were used to determine the baseline characteristics of the study population and to compare them with those from other registries.ResultsThe mean age was 68.5±14.5 years, 53.2% were male, and 52.2% had de novo heart failure. The mean systolic and diastolic blood pressures were 131.2±30.3 mmHg and 78.6±18.8 mmHg at admission, respectively. The left ventricular ejection fraction was ≤40% in 60.5% of patients. Ischemia was the most frequent etiology (37.6%) and aggravating factor (26.3%). Angiotensin converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and aldosterone antagonists were prescribed in 68.8%, 52.2%, and 46.6% of the patients at discharge, respectively. Compared with the previous registry performed in Korea a decade ago, extracorporeal membrane oxygenation (ECMO) and heart transplantation have been performed more frequently (ECMO 0.8% vs. 2.8%, heart transplantation 0.3% vs. 1.2%), and in-hospital mortality decreased from 7.6% to 4.8%. However, the total cost of hospital care increased by 40%, and one-year follow-up mortality remained high.ConclusionWhile the quality of acute clinical care and AHF-related outcomes have improved over the last decade, the long-term prognosis of heart failure is still poor in Korea. Therefore, additional research is needed to improve long-term outcomes and implement cost-effective care.

Aims The Korean Acute Heart Failure registry (KorAHF) aims to evaluate the clinical characteristics, management, hospital course, and long‐term outcomes of patients hospitalized for acute heart failure syndrome (AHFS) in Korea. Methods and results This is a prospective observational multicentre cohort study funded by the Korea National Institute of Health. Patients hospitalized for AHFS in 10 tertiary university hospitals across the country have been consecutively enrolled since March 2011. The study is expected to complete the scheduled enrolment of 5000 patients some time in 2014, and follow‐up is planned through 2016. As of April 2012, the interim analysis of 2066 consecutive subjects was performed to understand the baseline characteristics of the population. The mean age was 69 ± 14 years; 55% were male; and 50% were de novo heart failure. The mean left ventricular ejection fraction (LVEF) was 40 ± 18%. Ischaemia was both the leading cause (38%) and the most frequent aggravating factor (26%) of AHFS. ACE inhibitors/ARBs and beta‐blockers were prescribed at discharge in 65% and 51% of the patients, respectively. In‐hospital mortality was 5.2%, and 0.9% of patients received urgent heart transplantation. Low blood pressure and azotaemia were the most important predictors of in‐hospital mortality. The post‐discharge 30‐day and 180‐day all‐cause mortality were 1.2% and 9.2%, respectively. Conclusions Our analysis reveals that the prognosis of AHFS in Korea is poor and that there are specific features, including lower blood pressures at admission and lower rates of heart failure related to hypertension, compared with other registries. Adherence to current guidelines should be improved.

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Background and ObjectivesAcute heart failure (AHF) is associated with a poor prognosis and it requires repeated hospitalizations. However, there are few studies on the characteristics, treatment and prognostic factors of AHF. The aims of this study were to describe the clinical characteristics, management and outcomes of the patients hospitalized for AHF in Korea.Subjects and MethodsWe analyzed the clinical data of 3,200 hospitalization episodes that were recorded between June 2004 and April 2009 from the Korean Heart Failure (KorHF) Registry database. The mean age was 67.6±14.3 years and 50% of the patients were female.ResultsTwenty-nine point six percent (29.6%) of the patients had a history of previous HF and 52.3% of the patients had ischemic heart disease. Left ventricular ejection fraction (LVEF) was reported for 89% of the patients. The mean LVEF was 38.5±15.7% and 26.1% of the patients had preserved systolic function (LVEF ≥50%), which was more prevalent in the females (34.0% vs. 18.4%, respectively, p<0.001). At discharge, 58.6% of the patients received beta-blockers (BB), 53.7% received either angiotensin converting enzyme-inhibitors or angiotensin receptor blockers (ACEi/ARB), and 58.4% received both BB and ACEi/ARB. The 1-, 2-, 3- and 4-year mortality rates were 15%, 21%, 26% and 30%, respectively. Multivariate analysis revealed that advanced age {hazard ratio: 1.023 (95% confidence interval: 1.004-1.042); p=0.020}, a previous history of heart failure {1.735 (1.150-2.618); p=0.009}, anemia {1.973 (1.271-3.063); p=0.002}, hyponatremia {1.861 (1.184-2.926); p=0.007}, a high level of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) {3.152 (1.450-6.849); p=0.004} and the use of BB at discharge {0.599 (0.360-0.997); p=0.490} were significantly associated with total death.ConclusionWe present here the characteristics and prognosis of an unselected population of AHF patients in Korea. The long-term mortality rate was comparable to that reported in other countries. The independent clinical risk factors included age, a previous history of heart failure, anemia, hyponatremia, a high NT-proBNP level and taking BB at discharge.