Ovid Technologies (Wolters Kluwer Health)

Although coronary thrombosis plays a critical role in the pathogenesis of unstable angina and non-Q-wave myocardial infarction (NQMI), the effects of thrombolytic therapy in these disorders is not clear. Also, the role of routine early coronary arteriography followed by revascularization has not been established.

Patients (n = 1473) seen within 24 hours of ischemic chest discomfort at rest, considered to represent unstable angina or NQMI, were randomized using a 2 x 2 factorial design to compare (1) TPA versus placebo as initial therapy and (2) an early invasive strategy (early coronary arteriography followed by revascularization when the anatomy was suitable) versus an early conservative strategy (coronary arteriography followed by revascularization if initial medical therapy failed). All patients were treated with bed rest, anti-ischemic medications, aspirin, and heparin. The primary end point for the TPA-placebo comparison (death, myocardial infarction, or failure of initial therapy at 6 weeks) occurred in 54.2% of the TPA-treated patients and 55.5% of the placebo-treated patients (P = NS). Fatal and nonfatal myocardial infarction after randomization (reinfarction in NQMI patients) occurred more frequently in TPA-treated patients (7.4%) than in placebo-treated patients (4.9%, P = .04, Kaplan-Meier estimate). Four intracranial hemorrhages occurred in the TPA-treated group versus none in the placebo-treated group (P = .06). The end point for the comparison of the two strategies (death, myocardial infarction, or an unsatisfactory symptom-limited exercise stress test at 6 weeks) occurred in 18.1% of patients assigned to the early conservative strategy and 16.2% of patients assigned to the early invasive strategy (P = NS). In the latter, the average length of initial hospitalization, incidence of rehospitalization within 6 weeks, and days of rehospitalization all were significantly lower.

In the overall trial, patients with unstable angina and NQMI were managed with low rates of mortality (2.4%) and myocardial infarction or reinfarction (6.3%) at the time of the 6-week visit. These results can be achieved using either an early conservative or early invasive strategy, the latter resulting in a reduced incidence of days of hospitalization and of rehospitalization and in the use of antianginal drugs. The addition of a thrombolytic agent is not beneficial and may be harmful.

Out-of-hospital cardiac arrest (OHCA) is a significant global health problem. There has been considerable investment in improving the emergency medical response to OHCA, with associated improvements in survival. However, concern remains that survivors have a poor quality of life. This study describes the quality of life of OHCA survivors at 1-year postarrest in Victoria, Australia.

Adult OHCA patients who arrested between 2010 and 2012 were identified from the Victorian Ambulance Cardiac Arrest Registry. Paramedics attended 15 113 OHCA patients of which 46.3% received an attempted resuscitation. Nine hundred and twenty-seven (13.2%) survived to hospital discharge of which 76 (8.2%) died within 12 months. Interviews were conducted with 697 (80.7%) patients or proxies, who were followed-up via telephone interview, including the Glasgow Outcome Scale–Extended, the 12-item short form health survey, and the EuroQol. The majority (55.6%) of respondents had a good recovery via the Glasgow Outcome Scale–Extended≥7 (41.1% if patients who died postdischarge were included and nonrespondents were assumed to have poor recovery). The mean EuroQol index score for respondents was 0.82 (standard deviation, 0.19), which compared favorably with an adjusted population norm of 0.81 (standard deviation, 0.34). The mean 12-item short form Mental Component Summary score for patients was 53.0 (standard deviation, 10.2), whereas the mean Physical Component Summary score was 46.1 (standard deviation, 11.2).

This is the largest published study assessing the quality of life of OHCA survivors. It provides good evidence that many survivors have an acceptable quality of life 12 months postarrest, particularly in comparison with population norms.

Despite recent advances, the average survival after out-of-hospital cardiac arrest (OHCA) remains <10%. Early defibrillation by an automated external defibrillator is the most important intervention for patients with OHCA, showing survival proportions >50%. Accordingly, placement of automated external defibrillators in the community as part of a public access defibrillation program (PAD) is recommended by international guidelines. However, different strategies have been proposed on how exactly to increase and make use of publicly available automated external defibrillators. This systematic review aimed to evaluate the effect of PAD and the different PAD strategies on survival after OHCA.

PubMed, Embase, and the Cochrane Library were systematically searched on August 31, 2015 for observational studies reporting survival to hospital discharge in OHCA patients where an automated external defibrillator had been used by nonemergency medical services. PAD was divided into 3 groups according to who applied the defibrillator: nondispatched lay first responders, professional first responders (firefighters/police) dispatched by the Emergency Medical Dispatch Center (EMDC), or lay first responders dispatched by the EMDC.

A total of 41 studies were included; 18 reported PAD by nondispatched lay first responders, 20 reported PAD by EMDC-dispatched professional first responders (firefighters/police), and 3 reported both. We identified no qualified studies reporting survival after PAD by EMDC-dispatched lay first responders. The overall survival to hospital discharge after OHCA treated with PAD showed a median survival of 40.0% (range, 9.1–83.3). Defibrillation by nondispatched lay first responders was associated with the highest survival with a median survival of 53.0% (range, 26.0–72.0), whereas defibrillation by EMDC-dispatched professional first responders (firefighters/police) was associated with a median survival of 28.6% (range, 9.0–76.0). A meta-analysis of the different survival outcomes could not be performed because of the large heterogeneity of the included studies.

This systematic review showed a median overall survival of 40% for patients with OHCA treated by PAD. Defibrillation by nondispatched lay first responders was found to correlate with the highest impact on survival in comparison with EMDC-dispatched professional first responders. PAD by EMDC-dispatched lay first responders could be a promising strategy, but evidence is lacking.

Despite intensive efforts over many years, the United States has made limited progress in improving rates of survival from out-of-hospital cardiac arrest. Recently, national organizations, such as the American Heart Association, have focused on promoting bystander cardiopulmonary resuscitation, use of automated external defibrillators, and other performance improvement efforts.

Using the Cardiac Arrest Registry to Enhance Survival (CARES), a prospective clinical registry, we identified 70 027 U.S. patients who experienced an out-of-hospital cardiac arrest between October 2005 and December 2012. Using multilevel Poisson regression, we examined temporal trends in risk-adjusted survival. After adjusting for patient and cardiac arrest characteristics, risk-adjusted rates of out-of-hospital cardiac arrest survival increased from 5.7% in the reference period of 2005 to 2006 to 7.2% in 2008 (adjusted risk ratio, 1.27; 95% confidence interval, 1.12–1.43; P <0.001). Survival improved more modestly to 8.3% in 2012 (adjusted risk ratio, 1.47; 95% confidence interval, 1.26–1.70; P <0.001). This improvement in survival occurred in both shockable and nonshockable arrest rhythms ( P for interaction=0.22) and was also accompanied by better neurological outcomes among survivors ( P for trend=0.01). Improved survival was attributable to both higher rates of prehospital survival, where risk-adjusted rates increased from 14.3% in 2005 to 2006 to 20.8% in 2012 ( P for trend<0.001), and in-hospital survival ( P for trend=0.015). Rates of bystander cardiopulmonary resuscitation and automated external defibrillator use modestly increased during the study period and partly accounted for prehospital survival trends.

Data drawn from a large subset of U.S communities suggest that rates of survival from out-of-hospital cardiac arrest have improved among sites participating in a performance improvement registry.

G-protein–coupled receptor kinase 2 (GRK2) is a primary regulator of β-adrenergic signaling in the heart. G-protein–coupled receptor kinase 2 ablation impedes heart failure development, but elucidation of the cellular mechanisms has not been achieved, and such elucidation is the aim of this study.

Myocyte contractility, Ca ²⁺ handling and excitation-contraction coupling were studied in isolated cardiomyocytes from wild-type and GRK2 knockout (GRK2KO) mice without (sham) or with myocardial infarction (MI). In cardiac myocytes isolated from unstressed wild-type and GRK2KO hearts, myocyte contractions and Ca ²⁺ transients were similar, but GRK2KO myocytes had lower sarcoplasmic reticulum (SR) Ca ²⁺ content because of increased sodium-Ca ²⁺ exchanger activity and inhibited SR Ca ²⁺ ATPase by local protein kinase A–mediated activation of phosphodiesterase 4 resulting in hypophosphorylated phospholamban. This Ca ²⁺ handling phenotype is explained by a higher fractional SR Ca ²⁺ release induced by increased L-type Ca ²⁺ channel currents. After β-adrenergic stimulation, GRK2KO myocytes revealed significant increases in contractility and Ca ²⁺ transients, which were not mediated through cardiac L-type Ca ²⁺ channels but through an increased SR Ca ²⁺ . Interestingly, post-MI GRK2KO mice showed better cardiac function than post-MI control mice, which is explained by an improved Ca ²⁺ handling phenotype. The SR Ca ²⁺ content was better maintained in post-MI GRK2KO myocytes than in post-MI control myocytes because of better-maintained L-type Ca ²⁺ channel current density and no increase in sodium-Ca ²⁺ exchanger in GRK2KO myocytes. An L-type Ca ²⁺ channel blocker, verapamil, reversed some beneficial effects of GRK2KO.

These data argue for novel differential regulation of L-type Ca ²⁺ channel currents and SR load by GRK2. G-protein–coupled receptor kinase 2 ablation represents a novel beneficial Ca ²⁺ handling phenotype resisting adverse remodeling after MI.