Circulation: Clinical Summaries
Original Research Put Into Perspective for the Practicing Clinician
- Cardiac Resynchronization Therapy in Patients With Heart Failure and a QRS Complex <120 Milliseconds: The Evaluation of Resynchronization Therapy for Heart Failure (LESSER-EARTH) Trial
- Abnormal Lung Function in Adults With Congenital Heart Disease: Prevalence, Relation to Cardiac Anatomy, and Association With Survival
- Altered Activation of Endothelial Anti- and Proapoptotic Pathways by High-Density Lipoprotein from Patients with Coronary Artery Disease: Role of High-Density Lipoprotein-Proteome Remodeling
- A Prospective Study of Positive Early-Life Psychosocial Factors and Favorable Cardiovascular Risk in Adulthood
- Epac2 Mediates Cardiac β1-Adrenergic–Dependent Sarcoplasmic Reticulum Ca2+ Leak and Arrhythmia
- Variation Exists in Rates of Admission to Intensive Care Units for Heart Failure Patients Across Hospitals in the United States
- Stepwise Screening of Atrial Fibrillation in a 75-Year-Old Population: Implications for Stroke Prevention
- Info & Metrics
Cardiac Resynchronization Therapy in Patients With Heart Failure and a QRS Complex <120 Milliseconds: The Evaluation of Resynchronization Therapy for Heart Failure (LESSER-EARTH) Trial
The benefits of cardiac resynchronization therapy have been demonstrated in heart failure patients with systolic left ventricular dysfunction and prolonged QRS duration. Evaluation of Resynchronization Therapy for Heart Failure (LESSER-EARTH) studied the effects of cardiac resynchronization therapy in patients with QRS duration <120 milliseconds. The primary end point was exercise tolerance; secondary end points addressed left ventricular reverse remodeling. The trial was stopped prematurely (85 of 120 patients randomized) by the Data and Safety Monitoring Board because of futility reasons (no difference was observed in the major end points) and even a possible negative impact from cardiac resynchronization therapy on clinical adverse events. Our data do not support the use of cardiac resynchronization therapy in patients with narrow QRS. See p 873.
Abnormal Lung Function in Adults With Congenital Heart Disease: Prevalence, Relation to Cardiac Anatomy, and Association With Survival
Reduced forced vital capacity is prevalent among adult patients with congenital heart disease. Its severity relates to complexity of the underlying congenital heart defect and to past cardiac surgical history. Despite the heterogeneity of adult congenital heart disease, moderate to severe impairment of lung function was an independent predictor of mortality in our study, with a 1.6-fold increased risk of death in the medium term. We submit that lung function assessed by conventional spirometry, a simple and widely available test to measure lung flows, should be used as an adjunct to assess prognosis in this challenging patient population and that, when more than mild impairment of lung function is present, appropriate action should be taken. Whether a proactive treatment of lung disease and/or concomitant skeletal abnormalities alter prognosis remains speculative, but physicians need to be aware of respiratory and/or orthopedic complications and to be proactive in relevant aspects of care. See p 882.
Altered Activation of Endothelial Anti- and Proapoptotic Pathways by High-Density Lipoprotein from Patients with Coronary Artery Disease: Role of High-Density Lipoprotein-Proteome Remodeling
Reduced plasma levels of high-density lipoprotein (HDL) cholesterol are associated with an increased risk of coronary artery disease (CAD). Besides promoting reverse macrophage cholesterol transport, HDL from healthy subjects has been demonstrated to exert other potentially important antiatherogenic effects, such as inhibition of endothelial cell apoptosis. HDL-cholesterol–raising therapies are therefore currently examined as a potential novel strategy to reduce cardiovascular risk. Of note, endothelial dysfunction and injury are thought to play an important role in the progression of CAD. In the present study, however, we demonstrate for the first time that HDL from patients with CAD, in contrast to HDL from healthy subjects, does not activate endothelial antiapoptotic pathways, but rather stimulates potential endothelial proapoptotic signaling pathways. HDL-proteome remodeling, ie, changes in the clusterin and apolipoprotein C-III contents of HDL in patients with CAD, was identified as an important underlying mechanism leading to these altered functional properties of HDL, in particular, with respect to the effects of HDL on endothelial anti- and proapoptotic pathways in patients with coronary disease. These findings provide novel insights into mechanisms leading to altered vascular effects of HDL in coronary disease that at present may be of particular interest, given the interest in HDL-cholesterol raising as a potential therapeutic strategy in patients with CAD. See p 891.
A Prospective Study of Positive Early-Life Psychosocial Factors and Favorable Cardiovascular Risk in Adulthood
The American Heart Association’s national goals for cardiovascular health promotion emphasize that cardiovascular risk originates early in life, but little is known about childhood factors that may increase the likelihood of having favorable cardiovascular risk (eg, healthy blood pressure and lipid levels, no smoking, no diabetes mellitus, low body mass index, no antihypertensive or cholesterol medication use) in adulthood. We examined the prospective association of positive childhood factors assessed at age 7 years (attention regulation, cognitive ability, and home environment) and the likelihood of developing favorable cardiovascular risk in midlife. We demonstrate that positive childhood factors promote cardiovascular health in midlife, and the health benefit of having multiple childhood psychosocial assets is additive. We also demonstrate that positive childhood factors set up healthy lifestyle trajectories that cumulatively promote cardiovascular health over time. This study suggests that the capacity to attain, maintain, or regain a favorable cardiovascular health depends in part on life experience. Physician counseling in making lifestyle changes to reduce or prevent cardiovascular disease is a mainstay in clinical practice. This study suggests that the effectiveness of counseling may depend in part on psychosocial resources within the patient, including the capacity for attention and problem solving. These factors can be readily assessed in clinical practice and may influence a patient’s ability to engage in behavior change or understand the medical advice being given. From a primordial prevention perspective, this study suggests that pediatricians should evaluate the patient’s social, emotional, and physical environment and refer to services that build psychosocial resources. Doing so may support cardiovascular health for a lifetime. See p 905.
Epac2 Mediates Cardiac β1-Adrenergic–Dependent Sarcoplasmic Reticulum Ca2+ Leak and Arrhythmia
In heart failure, β-adrenergic receptor (AR) activation can cause arrhythmias, mediated in part by abnormal diastolic Ca2+ release from the sarcoplasmic reticulum. This is generally attributed to the β-AR–induced increase in cAMP, which activates protein kinase A to phosphorylate key targets that increase Ca2+ current influx, sarcoplasmic reticulum Ca2+ uptake, and possibly the ryanodine receptor (RyR2). Recent studies have identified another direct cAMP target, an exchange protein directly activated by cAMP (Epac), that is upregulated in heart failure and can be activated in parallel to protein kinase A to regulate independent targets. Indeed, Epac activation by a cAMP analog (8-CPT) can recapitulate the heart failure–associated enhancement of proarrhythmic sarcoplasmic reticulum Ca2+ and the reduced sarcoplasmic reticulum Ca2+ load that cause systolic dysfunction. However, cardiac Epac signaling is incompletely understood. In this study, using genetic manipulation of Epac1, Epac2, RyR2, and Ca2+/calmodulin-dependent protein kinase II, we have clarified how Epac activation contributes to β-AR–induced arrhythmias. We show that Epac and protein kinase A activity may contribute nearly equally to β-AR–induced arrhythmias and diastolic sarcoplasmic reticulum Ca leak. Moreover, this Epac pathway specifically requires β1-AR–dependent activation of the Epac2 isoform, which activates the Ca2+/calmodulin-dependent protein kinase II δ isoform to phosphorylate the S2814 site on RyR2 to enhance arrhythmogenic Ca2+ release. These mechanistic findings clarify β-AR–mediated Ca2+ leak–induced arrhythmia signaling and highlight that Epac2 could be an important novel therapeutic target in the treatment of arrhythmias. See p 913.
Variation Exists in Rates of Admission to Intensive Care Units for Heart Failure Patients Across Hospitals in the United States
Increasing attention is being focused on identifying costly hospital practices that do not necessarily lead to improved patient outcomes. Intensive care units (ICUs) account for 20% to 35% of total hospital costs, yet few studies have examined hospital patterns of ICU use for patients admitted with heart failure (HF) and whether these rates are associated with improved patient outcomes. In the present observational study, we describe patterns of ICU use for patients admitted with HF among a diverse group of 341 US hospitals. Once we observed the variation in the use of ICUs, we compared groups of hospitals with distinct patterns of ICU use in terms of their management of HF within the ICU and in-hospital mortality rates. We found substantial variation in ICU admission rates across hospitals with the top quartile of hospitals admitting 32% of patients on average directly to the ICU compared with only 8% of patients at hospitals in the other quartiles (P<0.0001). In top-quartile hospitals, treatments requiring an ICU were used less often, including mechanical ventilation, noninvasive positive-pressure ventilation, vasopressors and/or inotropes, and vasodilators. Overall HF in-hospital risk-standardized mortality was similar (3.4% versus 3.5%; P=0.2). Our findings demonstrate that a substantial number of hospitals triage many more patients with HF to their ICUs relative to other hospitals without achieving better in-hospital mortality outcomes. Given the high price of ICU admission, it is plausible that some hospitals may be engaging in a low-value, high-cost behavior. Such findings indicate the potential positive impact of creating guidelines to aid practitioners in the decision of whether to use the ICU for patients admitted with HF. See p 923.
Stepwise Screening of Atrial Fibrillation in a 75-Year-Old Population: Implications for Stroke Prevention
Atrial Fibrillation (AF) is the most frequently encountered clinical arrhythmia and also a frequent source of cardiac emboli in stroke patients. AF will in some cases be present without any symptoms, often denoted “silent” AF. The prevalence of silent AF in the general population is not known. Silent AF seems to confer a stroke risk similar to symptomatic AF. Oral anticoagulation therapy (OAC) reduces the risk of stroke by 60-65% among patients with AF and thromboembolic risk factors. Unfortunately, approximately half of all patients with clinical apparent AF and risk factors are not treated with OAC, for various reasons. We conducted a screening study in which we invited all inhabitants 75 and 76 years old in the community of Halmstad, Sweden (n=1330). Of the 848 (64%) individuals who responded and recorded a 12-lead ECG, 1% was diagnosed with newly detected persistent or permanent AF. Among the 403 individuals with a CHADS2-score of at least 2 who made an additional intermittent ambulant ECG recording over two weeks, 7% were diagnosed with paroxysmal AF. Among patients with known AF, 35/81 were not on OAC treatment. After screening, 9% of the participants were new candidates for OAC treatment. As a result of the screening intervention, the frequency of OAC treatment more than doubled among the participants. See p 930.
- © 2013 American Heart Association, Inc.
- Epac2 Mediates Cardiac β1-Adrenergic–Dependent Sarcoplasmic Reticulum Ca2+ Leak and Arrhythmia
- Info & Metrics