Outcomes With Peripheral Venoarterial Extracorporeal Membrane Oxygenation for Suspected Acute Myocarditis: 10-Year Experience From the Extracorporeal Life Support Organization Registry.

BACKGROUND: Acute myocarditis can result in severe hemodynamic compromise requiring venoarterial extracorporeal membrane oxygenation (VA-ECMO). Outcomes and factors associated with mortality among myocarditis patients are not well described in the modern ECMO era. METHODS: We queried the Extracorporeal Life Support Organization registry from 2011 to 2020 for adults with suspected acute myocarditis undergoing peripheral VA-ECMO support. The primary outcome was in-hospital mortality and was compared to all-comers receiving VA-ECMO in the registry over the same period. Secondary outcomes were rates of bridging to advanced therapies and ECMO complications. We used multivariable logistic regression to examine factors associated with in-hospital mortality. RESULTS: Among 850 patients with suspected acute myocarditis receiving peripheral VA-ECMO, the mean age was 41 years, 52% were men, 39% Asian race, and 14.8% underwent extracorporeal cardiopulmonary resuscitation. During the study period, in-hospital mortality steadily declined and was 58.3% for all all-comers receiving VA-ECMO compared with 34.9% for patients with myocarditis (P<0.001). After multivariable modeling, risk factors for mortality were earlier year of support, older age, higher weight, Asian race, need for extracorporeal cardiopulmonary resuscitation, sepsis, and lower mean arterial pressure and pH prior to ECMO initiation. ECMO complications including bleeding, limb ischemia, infections and ischemic stroke were more common among nonsurvivors and significantly declined during the study period. CONCLUSIONS: Compared with all-comers supported with VA-ECMO, in-hospital mortality for patients with acute myocarditis is significantly lower, with nearly two-thirds of patients surviving to discharge. Major modifiable risk factors for mortality were ongoing cardiopulmonary resuscitation requiring ECMO and markers of illness severity prior to ECMO.

Cardiogenic shock related cardiovascular disease mortality trends in US population: Heart failure vs. acute myocardial infarction as contributing causes.

BACKGROUND: Observational and trial data have revealed significant improvement in cardiogenic shock (CS) mortality due to acute myocardial infarction (AMI) after introducing early coronary revascularization. Less is known about CS mortality due to heart failure (HF), which is increasingly recognized as a distinct entity from AMI-CS. METHODS AND RESULTS: In this nationwide observational study, the CDC WONDER database was used to identify national trends in age-adjusted mortality rates (AAMR) due to CS (HF vs. AMI related) per 100,000 people aged 35-84. AAMR from AMI-CS decreased significantly from 1999 to 2009 (AAPC: -6.9% [95%CI -7.7, -6.1]) then stabilized from 2009 to 2020. By contrast, HF-CS associated AAMR rose steadily from 2009 to 2020 (AAPC: 13.3% [95%CI 11.4,15.2]). The mortality rate was almost twice as high in males compared to females in both AMI-CS and HF-CS throughout the study period. HF-CS mortality in the non-Hispanic Black population is increasing more quickly than that of the non-Hispanic White population (AAMR in 2020: 4.40 vs. 1.97 in 100,000). The AMI-CS mortality rate has been consistently higher in rural than urban areas (30% higher in 1999 and 28% higher in 2020). CONCLUSIONS: These trends highlight the fact that HF-CS and AMI-CS represent distinct clinical entities. While mortality associated with AMI-CS has primarily declined over the last two decades, the mortality related to HF-CS has increased significantly, particularly over the last decade, and is increasing rapidly among individuals younger than 65. Accordingly, a dramatic change in the demographics of CS patients in modern intensive care units is expected.

Early Ambulation Among Hospitalized Heart Failure Patients Is Associated With Reduced Length of Stay and 30-Day Readmissions.

BACKGROUND: Early ambulation (EA) is associated with improved outcomes for mechanically ventilated and stroke patients. Whether the same association exists for patients hospitalized with acute heart failure is unknown. We sought to determine whether EA among patients hospitalized with heart failure is associated with length of stay, discharge disposition, 30-day post discharge readmissions, and mortality. METHODS AND RESULTS: The study population included 369 hospitals and 285 653 patients with heart failure enrolled in the Get With The Guidelines-Heart Failure registry. We used multivariate logistic regression with generalized estimating equations at the hospital level to identify predictors of EA and determine the association between EA and outcomes. Sixty-five percent of patients ambulated by day 2 of the hospital admission. Patient-level predictors of EA included younger age, male sex, and hospitalization outside of the Northeast (P<0.01 for all). Hospital size and academic status were not predictive. Hospital-level analysis revealed that those hospitals with EA rates in the top 25% were less likely to have a long length of stay (defined as >4 days) compared with those in the bottom 25% (odds ratio, 0.83; confidence interval, 0.73-0.94; P=0.004). Among a subgroup of fee-for-service Medicare beneficiaries, we found that hospitals in the highest quartile of rates of EA demonstrated a statistically significant 24% lower 30-day readmission rates (P<0.0001). Both end points demonstrated a dose-response association and statistically significant P for trend test. CONCLUSIONS: Multivariable-adjusted hospital-level analysis suggests an association between EA and both shorter length of stay and lower 30-day readmissions. Further prospective studies are needed to validate these findings.

Relationship of Provider and Practice Volume to Performance Measure Adherence for Coronary Artery Disease, Heart Failure, and Atrial Fibrillation: Results From the National Cardiovascular Data Registry.

BACKGROUND: There is a reported association between high clinical volume and improved outcomes. Whether this relationship is true for outpatients with coronary artery disease (CAD), heart failure (HF), and atrial fibrillation (AF) remains unknown. METHODS AND RESULTS: Using the PINNACLE Registry (2009-2012), average monthly provider and practice volumes were calculated for CAD, HF, and AF. Adherence with 4 American Heart Association CAD, 2 HF, and 1 AF performance measure were assessed at the most recent encounter for each patient. Hierarchical logistic regression models were used to assess the relationship between provider and practice volume and performance on eligible quality measures. Data incorporated patients from 1094 providers at 71 practices (practice level analyses n=654 535; provider level analyses n=529 938). Median monthly provider volumes were 79 (interquartile range [IQR], 51-117) for CAD, 27 (16-45) for HF, and 37 (24-54) for AF. Median monthly practice volumes were 923 (IQR, 476-1455) for CAD, 311 (145-657) for HF, and 459 (185-720) for AF. Overall, 55% of patients met all CAD measures, 72% met all HF measures, and 58% met the AF measure. There was no definite relationship between practice volume and concordance for CAD, AF, or HF (P=0.56, 0.52, and 0.79, respectively). In contrast, higher provider volume was associated with increased concordance for CAD and AF performance measures (P<0.001 for both), but not for HF (P=0.36). CONCLUSIONS: In the PINNACLE registry, performance was modest and variable. Higher provider volume was positively associated with quality, whereas practice volume was not.

Derivation and validation of a 30-day heart failure readmission model.

In 2006, there were >1 million hospital admissions for heart failure (HF), and the estimated cost to the United States in 2009 was >$37.2 billion. Better models to target aggressive therapy to patients at the highest risk for readmission are clearly needed. We studied 3,413 consecutive admissions for HF based on discharge diagnosis codes from October 2007 to August 2011 from a single academic center. We randomly generated derivation and validation sets in a 3:1 ratio. We used generalized estimating equations to develop our models, accounting for repeated hospitalizations and the Hosmer-Lemeshow test to examine model calibration. The 30-day readmission rate was 24.2% in the derivation set. Of 25 candidate variables, the best fitting model included creatinine, troponin, hematocrit, and hyponatremia at discharge; race; zip code of residence; discharge hour; and number of hospitalizations in the previous year. Insignificant variables included intravenous diuretic use on day of discharge, discharge service, diabetes, atrial fibrillation, age, and gender. The risk of 30-day readmission increased with increasing decile of predicted risk in both the validation and derivation cohorts. The area under the receiver operating characteristic curve for the model was 0.69 in the derivation set and 0.66 in the validation set. In conclusion, we derived and validated a simple model relating discharge-specific characteristics at risk of 30-day readmission. Application of this approach may facilitate targeted intervention to reduce the burden of rehospitalization in patients with HF, but our results suggest that the best readmission models may require incorporation of both clinical and local system factors for optimal prediction.

Interventions for heart failure readmissions: successes and failures.

Heart failure readmissions result in significant costs to the health care system and to patients' quality of life, but programs to reduce readmissions have met with mixed success. Successful strategies have included multidisciplinary hospital-based quality initiatives, disease management programs, and care transition interventions. Devices like telemonitors and indwelling catheters, however, have met with mixed success. Research is still needed to elucidate the most effective interventions for readmission reduction in the HF population.

Frequency and impact of bleeding in elective coronary stent clinical trials--utility of three commonly used definitions.

BACKGROUND: Bleeding events are common after percutaneous coronary intervention (PCI) and have been shown to increase mortality in studies of acute coronary syndrome (ACS) and anti-thrombotic therapy. Despite this evidence, bleeding has not been included as a traditional major endpoint in clinical trials of low-risk populations enrolled in PCI clinical trials. Thus, the impact of specific bleeding definitions has not been evaluated fully among these patients. METHODS AND RESULTS: Using patient-level pooled data from sirolimus and zotarolimus drug-eluting stent clinical trials, we identified bleeding events using three common definitions of bleeding, ACUITY, TIMI, and GUSTO, and assessed the impact on mortality and MI at 12 months after PCI. The GUSTO, ACUITY, and TIMI classifications identified bleeding rates of 2.3%, 1.9%, and 2.1%, respectively. The GUSTO criteria classified all 118 suspected bleeding events. There were 22 (18.6%) and 8 (6.8%) suspected bleeding events that did not meet ACUITY and TIMI criteria, respectively. The combined endpoint of all-cause death or myocardial infarction (MI) at 12 months was significantly higher for patients with a bleeding event compared with those who did not bleed [hazard ratio 1.95 (95% CI 1.06-3.60)]. CONCLUSION: There is a substantial variability in the utility and inclusiveness of three widely used bleeding definitions in identifying clinically significant bleeding events in clinical trials of low risk patients undergoing PCI with DES. Patients with bleeding after elective PCI have an increased one-year risk of death or MI compared to those patients who do not bleed.

AG-013736, a novel inhibitor of VEGF receptor tyrosine kinases, inhibits breast cancer growth and decreases vascular permeability as detected by dynamic contrast-enhanced magnetic resonance imaging.

Dynamic contrast-enhanced MRI (DCE-MRI) was used to noninvasively evaluate the effects of AG-03736, a novel inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, on tumor microvasculature in a breast cancer model. First, a dose response study was undertaken to determine the responsiveness of the BT474 human breast cancer xenograft to AG-013736. Then, DCE-MRI was used to study the effects of a 7-day treatment regimen on tumor growth and microvasculature. Two DCE-MRI protocols were evaluated: (1) a high molecular weight (MW) contrast agent (albumin-(GdDTPA)(30)) with pharmacokinetic analysis of the contrast uptake curve and (2) a low MW contrast agent (GdDTPA) with a clinically utilized empirical parametric analysis of the contrast uptake curve, the signal enhancement ratio (SER). AG-013736 significantly inhibited growth of breast tumors in vivo at all doses studied (10-100 mg/kg) and disrupted tumor microvasculature as assessed by DCE-MRI. Tumor endothelial transfer constant (K(ps)) measured with albumin-(GdDTPA)(30) decreased from 0.034+/-0.005 to 0.003+/-0.001 ml min(-1) 100 ml(-1) tissue (P<.0022) posttreatment. No treatment-related change in tumor fractional plasma volume (fPV) was detected. Similarly, in the group of mice studied with GdDTPA DCE-MRI, AG-013736-induced decreases in tumor SER measures were observed. Additionally, our data suggest that 3D MRI-based volume measurements are more sensitive than caliper measurements for detecting small changes in tumor volume. Histological staining revealed decreases in tumor cellularity and microvessel density with treatment. These data demonstrate that both high and low MW DCE-MRI protocols can detect AG-013736-induced changes in tumor microvasculature. Furthermore, the correlative relationship between microvasculature changes and tumor growth inhibition supports DCE-MRI methods as a biomarker of VEGF receptor target inhibition with potential clinical utility.