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.

Impact of carfilzomib-based desensitization on heart transplantation of sensitized candidates.

BACKGROUND: Allosensitization in heart transplant candidates is associated with longer transplant wait times and post-transplant complications. We summarize our experience with desensitization using carfilzomib, an irreversible proteasome inhibitor that causes plasma cell apoptosis. METHODS: One cycle of desensitization consisted of plasmapheresis and carfilzomib 20 mg/m2 on days 1, 2, 8, 9, 15, and 16 with intravenous immune globulin 2 g/kg after carfilzomib on day 16. Patients underwent repeat cycles as indicated. We compare calculated panel-reactive antibody (cPRA) for neat combined Class I and II IgG and C1q pre- and post-treatment using a cutoff for cPRA entry of ≥ 4000 and 500 MFI, respectively. RESULTS: From June 2013 to October 2019, 9 patients underwent 20 cycles of carfilzomib-based desensitization. Each cycle resulted in an average cPRA decrease of 24% (95% CI: 6-42) for IgG and 36% (95% CI: 17-55) for C1q. From treatment start to finish, mean cPRA fell from 76% to 40% (p = 0.01) for IgG and 56% to 4% (p = 0.017) for C1q. Six of 9 patients have been transplanted with 5 of the transplanted hearts crossing preoperative donor-specific antibodies. During a median follow-up of 35.1 months, all transplanted patients have survived with only 1 occurrence of treated rejection. Side effects of desensitization included acute kidney injury (67%) and thrombocytopenia (33%) with all episodes self-resolving. CONCLUSIONS: A carfilzomib-based desensitization strategy among heart transplant candidates reduces the level of HLA antibodies and complement binding, facilitates successful transplantation, and is associated with excellent outcomes at 3 years.

A novel algorithm to predict the QT interval during intrinsic atrioventricular conduction from an electrocardiogram obtained during ventricular pacing.

BACKGROUND: QT interval prolongation is a major arrhythmia risk factor. Standard QT interval limits are defined for preserved intrinsic atrioventricular and interventricular conduction. However, ventricular pacing (VP) prolongs the QRS duration, induces electrical remodeling, and therefore obscures the intrinsic QT interval. No consensus exists on QT interval monitoring during VP. OBJECTIVE: The aim of this study was to develop an algorithm to predict the QT interval during intrinsic conduction (IC) from the VP electrocardiogram. METHODS: We measured electrocardiographic intervals QRS, QT, QTpeak, JTpeak, and TpeakTend in 38 participants with cardiac devices and preserved atrioventricular and interventricular conduction. We performed paired measurements in AAI (IC) and DDD (VP) pacing modes at equal heart rates at baseline and after 1 week of VP. We fit linear mixed models to predict IC QT intervals from VP intervals and compared their fit with other proposed methods of IC QT interval estimation. RESULTS: After 1 week of VP, the IC QT interval prolonged while the VP QT interval shortened from their respective baseline values. VP QT interval shortening was due to TpeakTend interval shortening. JTpeak and QTpeak intervals prolonged in both pacing modes at 1 week. A formula using VP QTpeak interval and heart rate closely predicted the IC QT interval (r = 0.94), outperforming other methods, including subtraction of "excess" QRS duration from the actual QT interval (r = 0.64) and subtraction of fixed values from heart rate-corrected QT interval (r = 0.58 and r = 0.69). Validation in 2000 bootstrapped data sets confirmed the model's performance (r = 0.93) compared to others (r = 0.43-0.58). CONCLUSION: In patients with VP, a formula using the QTpeak interval accurately predicts the intrinsic QT interval.

A comparison of the frequencies of risk factors for depression in older black and white participants in a study of indicated prevention.

BACKGROUND: To compare the frequencies of risk factors, we describe risks for depression as a function of race among consecutively admitted participants in a randomized clinical trial of indicated depression prevention in later life. METHODS: Seventy-two black and 143 white participants were screened for risk factors for depression. RESULTS: Black participants were more likely to have fewer years of education and lower household income. They were more likely to be obese, live alone, experience functional disability, have a history of alcohol and drug abuse, and have lower scores on the Mini-mental State Examination and the Executive Interview (EXIT). White participants were not found to have greater prevalence or higher mean score on any risk factor. On average, black participants experienced approximately one more risk factor than white participants (t(213) = 3.32, p = 0.0011). CONCLUSIONS: In our sample, black participants had higher frequencies of eight risk factors for depression and a greater mean number of risk factors compared to white participants.

Preventing depression in later life: translation from concept to experimental design and implementation.

OBJECTIVE: The authors detail the public health need for depression prevention research and the decisions made in designing an experiment testing problem solving therapy as "indicated" preventive intervention for high-risk older adults with subsyndromal depression. Special attention is given to the recruitment of African Americans because of well-documented inequalities in mental health services and depression treatment outcomes between races. METHODS: A total of 306 subjects (half white, half African American) with scores of 16 or higher on the Center for Epidemiological Studies of Depression Scale, but with no history of major depressive disorder in the past 12 months, are being recruited and randomly assigned to either problem solving therapy-primary care or to a dietary education control condition. Time to, and rate of, incident episodes of major depressive disorder are to be modeled using survival analysis. Level of depressive symptoms will be analyzed via a mixed models approach. RESULTS: Twenty-two subjects have been recruited into the study, and to date eight have completed the randomly assigned intervention and postintervention assessment. Four of 22 have exited after developing major depressive episodes. None have complained about study procedures or demands. Implementation in a variety of community settings is going well. CONCLUSION: The data collected to date support the feasibility of translating from epidemiology to RCT design and implementation of empirical depression prevention research in later life.