Heart failure (HF) is a chronic, progressive illness that is highly prevalent in the United States and worldwide. This morbid illness carries a very poor prognosis, and leads to frequent hospitalizations. Repeat hospi...Heart failure (HF) is a chronic, progressive illness that is highly prevalent in the United States and worldwide. This morbid illness carries a very poor prognosis, and leads to frequent hospitalizations. Repeat hospitalization in HF is both largely burdensome to the patient and the healthcare system, as it is one of the most costly medical diagnoses among Medicare recipients. For years, investigators have strived to determine methods to reduce hospitalization rates of HF patients. Despite such efforts, recent reports indicate that rehospitalization rates remain persistently high, without any improvement over the past several years and thus, this topic clearly needs aggressive attention. We performed a key-word search of the literature for relevant citations. Published articles, limited to English abstracts indexed primarily in the PubMed database through the year 2011, were reviewed. This article discusses various clinical parameters, serum biomarkers, hemodynamic parameters, and psychosocial factors that have been reviewed in the literature as predictors of re-hospitalization of HF patients. With this information, ourhope is that the future holds better risk-stratification models that will allow providers to identify high-risk patients, and better customize effective interventions according to the needs of each individual HF patient.展开更多
In recent decades,a cardiomyocyte membrane scaffolding protein bridging integrator 1(BIN1) has emerged as a critical multifunctional regulator of transverse-tubule(t-tubule) function and calcium signaling in cardiomyo...In recent decades,a cardiomyocyte membrane scaffolding protein bridging integrator 1(BIN1) has emerged as a critical multifunctional regulator of transverse-tubule(t-tubule) function and calcium signaling in cardiomyocytes.Encoded by a single gene with 20 exons that are alternatively spliced,more than ten BIN1 protein isoforms are expressed with tissue and disease specificity.The recently discovered cardiac alternatively spliced isoform BIN1(cBIN1 or BIN1 +13 + 17)plays a crucial role in organizing membrane microfolds within cardiac t-tubules.These cBIN1-induced microfolds form functional dyad microdomains by trafficking L-type calcium channels(LTCC) to t-tubule membrane and recruiting ryanodine receptors(RyR) to junctional sarcoplasmic reticulum membrane.When cBIN1 is transcriptionally reduced as occurs in heart failure,cBIN1-microfolds are disrupted and fail to form LTCC and RyR couplons.As a result,impaired dyad formation limits excitation-contraction coupling thus cardiac contractility,and accumulation of orphaned leaky RyRs outside of dyads increases ventricular arrhythmias.Reduced myocardial BIN1 in heart failure is also detectable at the blood level,and plasma BIN1 level predicts heart failure progression and future arrhythmias in cardiomyopathy patients.Here we will review the recent progress in BIN1-related cardiomyocyte biology studies and discuss the diagnostic and predictive values of cBIN1 in future clinical use.展开更多
文摘Heart failure (HF) is a chronic, progressive illness that is highly prevalent in the United States and worldwide. This morbid illness carries a very poor prognosis, and leads to frequent hospitalizations. Repeat hospitalization in HF is both largely burdensome to the patient and the healthcare system, as it is one of the most costly medical diagnoses among Medicare recipients. For years, investigators have strived to determine methods to reduce hospitalization rates of HF patients. Despite such efforts, recent reports indicate that rehospitalization rates remain persistently high, without any improvement over the past several years and thus, this topic clearly needs aggressive attention. We performed a key-word search of the literature for relevant citations. Published articles, limited to English abstracts indexed primarily in the PubMed database through the year 2011, were reviewed. This article discusses various clinical parameters, serum biomarkers, hemodynamic parameters, and psychosocial factors that have been reviewed in the literature as predictors of re-hospitalization of HF patients. With this information, ourhope is that the future holds better risk-stratification models that will allow providers to identify high-risk patients, and better customize effective interventions according to the needs of each individual HF patient.
基金supported by the United States National Institute of Health/National Heart,Lung,and Blood Institute (NIH/NHLBI,Hong R01 HL133286)American Heart Association (AHA)(IRG27780031,BGIA27770151)
文摘In recent decades,a cardiomyocyte membrane scaffolding protein bridging integrator 1(BIN1) has emerged as a critical multifunctional regulator of transverse-tubule(t-tubule) function and calcium signaling in cardiomyocytes.Encoded by a single gene with 20 exons that are alternatively spliced,more than ten BIN1 protein isoforms are expressed with tissue and disease specificity.The recently discovered cardiac alternatively spliced isoform BIN1(cBIN1 or BIN1 +13 + 17)plays a crucial role in organizing membrane microfolds within cardiac t-tubules.These cBIN1-induced microfolds form functional dyad microdomains by trafficking L-type calcium channels(LTCC) to t-tubule membrane and recruiting ryanodine receptors(RyR) to junctional sarcoplasmic reticulum membrane.When cBIN1 is transcriptionally reduced as occurs in heart failure,cBIN1-microfolds are disrupted and fail to form LTCC and RyR couplons.As a result,impaired dyad formation limits excitation-contraction coupling thus cardiac contractility,and accumulation of orphaned leaky RyRs outside of dyads increases ventricular arrhythmias.Reduced myocardial BIN1 in heart failure is also detectable at the blood level,and plasma BIN1 level predicts heart failure progression and future arrhythmias in cardiomyopathy patients.Here we will review the recent progress in BIN1-related cardiomyocyte biology studies and discuss the diagnostic and predictive values of cBIN1 in future clinical use.
