In patients stabilized during hospitalization for acute decompensated heart failure (HF), initiation of sacubitril/valsartan compared with enalapril decreased the risk of cardiovascular death or ...rehospitalization for HF without increasing the risk of adverse events. It is unknown whether potentially high-risk subpopulations have a similar risk-benefit profile.
PIONEER-HF (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-proBNP N-terminal pro-B type natriuretic peptide in Patients Stabilized From an Acute HF Episode) was a multicenter, randomized, double-blind trial of in-hospital initiation of sacubitril/valsartan (n=440) versus enalapril (n=441) in patients stabilized during hospitalization for acute decompensated HF. The composite of cardiovascular death or rehospitalization for HF was adjudicated. Safety outcomes included worsening renal function, symptomatic hypotension, and hyperkalemia. We evaluated heterogeneity in the effect of sacubitril/valsartan on these efficacy and safety outcomes in selected subgroups of clinical concern: patients with baseline systolic blood pressure ≤118 mm Hg (median; n=448), baseline NT-proBNP >2701 pg/mL (median; n=395), estimated glomerular filtration rate <60 mL/minute per 1.73 m
(n=455), ≥1 additional hospitalization for HF within the prior year (n=343), admission to the ICU during the index hospitalization (n=96), inotrope use during the index hospitalization (n=68), and severe congestion (n=219).
The relative risk reduction in cardiovascular death or rehospitalization for HF with sacubitril/valsartan versus enalapril was consistent across all high-risk subgroups (
interaction=non-significant NS for each). The risks of worsening renal function, symptomatic hypotension, and hyperkalemia with sacubitril/valsartan versus enalapril were also consistent in each high- versus low-risk subgroup (
interaction=NS for each).
In high-risk subpopulations admitted for acute decompensated HF, treatment with sacubitril/valsartan after initial stabilization conferred a consistent reduction in cardiovascular death or rehospitalization for HF and was well tolerated.
Cardiogenic shock is a complex clinical syndrome of end-organ hypoperfusion due to impaired cardiac performance. Although cardiogenic shock has traditionally been viewed as a monolithic disorder ...predominantly caused by severe left ventricular dysfunction complicating acute myocardial infarction (AMI), there is increasing recognition of the diverse causes of cardiogenic shock and wide spectrum of clinical severity. The purpose of this review is to describe the contemporary epidemiology of cardiogenic shock, including trends in clinical outcomes and recent efforts to refine risk assessment.
The incidence of cardiogenic shock among patients with AMI has remained remarkably stable at 3-10%; however, the proportion of cardiogenic shock cases related to AMI has decreased over time to ∼30%, while the proportion of cardiogenic shock cases due to acute decompensated heart failure has steadily increased. Estimated in-hospital mortality from cardiogenic shock in contemporary registries is approximately 30-40%, suggesting modest improvement in cardiogenic shock outcomes over the last decade. There is a wide spectrum of clinical severity among patients presenting with cardiogenic shock, which is described by the Society for Cardiovascular Angiography and Interventions clinical staging criteria.
Improved clinical characterization and risk assessment of patients with cardiogenic shock may facilitate more effective clinical investigations of this morbid clinical syndrome.
Survival after nontraumatic out-of-hospital (OOH) cardiac arrest in Tucson, Arizona, has been flat at 6% (121/2177) for the decade 1992 to 2001. We hypothesized that interruptions of chest ...compressions occur commonly and for substantial periods during treatment of OOH cardiac arrest and could be contributing to the lack of improvement in resuscitation outcome.
Sixty-one adult OOH cardiac arrest patients treated by automated external defibrillator (AED)-equipped Tucson Fire Department first responders from November 2001 through November 2002 were retrospectively reviewed. Reviews were performed according to the code arrest record and verified with the AED printout. Validation of the methodology for determining the performance of chest compressions was done post hoc. The median time from "9-1-1" call receipt to arrival at the patient's side was 6 minutes, 27 seconds (interquartile range IQR, 25% to 75%, 5 minutes, 24 seconds, to 7 minutes, 34 seconds). An additional 54 seconds (IQR, 38 to 74 seconds) was noted between arrival and the first defibrillation attempt. Initial defibrillation shocks never restored a perfusing rhythm (0/21). Chest compressions were performed only 43% of the time during the resuscitation effort. Although attempting to follow the 2000 guidelines for cardiopulmonary resuscitation, chest compressions were delayed or interrupted repeatedly throughout the resuscitation effort. Survival to hospital discharge was 7%, not different from that of our historical control (4/61 versus 121/2177; P=0.74).
Frequent interruption of chest compressions results in no circulatory support during more than half of resuscitation efforts. Such interruptions could be a major contributing factor to the continued poor outcome seen with OOH cardiac arrest.
Abstract
Background
Atrial fibrillation (AF) is associated with an increased risk of thromboembolism, which can be significantly reduced with anticoagulant treatment. Key goals in the clinical ...management of AF are the identification of patients at high risk for developing AF and accurate stratification of the risk of stroke and systemic embolic events (S/SEE) as well as treatment-related major bleeding.
Content
In this review, we describe the expanding evidence regarding the use of circulating biomarkers for predicting the risks of both incident AF and its clinically important complications of S/SEE and treatment-related major bleeding. We also review emerging biomarker-based scores for assessing these risks.
Summary
Patients with AF undergo progressive cardiac structural remodeling, which may precede the onset of the arrhythmia. Abnormal concentrations of circulating biomarkers reflecting the underlying pathophysiologic mechanisms of hemodynamic stress (i.e., natriuretic peptides), inflammation (i.e., C-reactive protein), and myocardial fibrosis identify patients at higher risk of developing AF. Circulating biomarkers can also be used to identify patients with AF who are at greatest risk for developing S/SEE or major bleeding. In particular, biomarkers of hemodynamic stress, myocardial injury (i.e., cardiac troponin), and coagulation activity (i.e., D-dimer) are key indicators of thromboembolic risk, and cardiac troponin and growth-differentiation factor-15 are strongly associated with risk of anticoagulant-related major bleeding. The biomarker-based age, biomarker, clinical history (ABC)-stroke and ABC-bleeding risk scores improve risk stratification for S/SEE and major bleeding, respectively, when compared with traditional clinical risk scores like the CHA2DS2-VASc and HAS-BLED scores.
BACKGROUND:The ABC (age, biomarker, clinical history)-stroke and ABC-bleeding risk scores incorporate clinical variables and cardiovascular biomarkers to estimate risk of stroke or systemic embolic ...events and bleeding, respectively, in patients with atrial fibrillation. These scores have been proposed for routine clinical use, but their performance in external cohorts remains uncertain.
METHODS:ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation—Thrombolysis in Myocardial Infarction 48) was a multinational randomized trial of the oral factor Xa inhibitor edoxaban in patients with atrial fibrillation and a CHADS2 score ≥2. We performed a nested prospective biomarker study in 8705 patients, analyzing baseline high-sensitivity troponin T (hsTnT), NT-proBNP (N-terminal B-type natriuretic peptide), and growth differentiation factor-15 (GDF-15), as well as in serial samples after 12 months. The ABC-stroke (age, prior stroke/transient ischemic attack, hsTnT, NT-proBNP) and ABC-bleeding (age, prior bleeding, hemoglobin, hsTnT, and GDF-15) scores were tested. Hazard ratios were adjusted for estimated glomerular filtration rate and the components of the CHA2DS2-VASc and HAS-BLED scores, respectively. Discrimination and reclassification were compared with these established scores.
RESULTS:Median baseline hsTnT, NT-proBNP, and GDF-15 levels were 13.7 ng/L (25th–75th percentiles, 9.6–20.4 ng/L), 811 pg/mL (386–1436 pg/mL), and 1661 pg/mL (1179–2427 pg/mL), respectively. Elevated hsTnT, NT-proBNP, and GDF-15 were independently associated with higher rates of stroke or systemic embolic events, and elevated hsTnT and GDF-15 were independently associated with higher rates of major bleeding (P<0.001 for each). The ABC-stroke and ABC-bleeding scores were well calibrated and yielded higher c indexes than the CHA2DS2-VASc score for stroke or systemic embolic events (0.67 95% CI, 0.65–0.70 versus 0.59 95% CI, 0.57–0.62; P<0.001) and HAS-BLED score for major bleeding (0.69 95% CI, 0.66–0.71 versus 0.62 95% CI, 0.60–0.64; P<0.001), respectively. The ABC-stroke and ABC-bleeding scores stratified patients within CHA2DS2-VASc and HAS-BLED risk categories (P<0.001 for both). Patients with ABC-bleeding scores predicting a high 1-year risk of bleeding (>2%) derived greater benefit from treatment with edoxaban compared with warfarin.
CONCLUSIONS:The ABC-stroke and ABC-bleeding scores evaluated in this anticoagulated clinical trial cohort were well calibrated and outperformed the CHA2DS2-VASc and HAS-BLED scores, respectively. These scores may help identify patients most likely to derive a benefit from treatment with non–vitamin K antagonist oral anticoagulants.
CLINICAL TRIAL REGISTRATION:URLhttps://www.clinicaltrials.gov. Unique identifierNCT00781391.
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