Inflammatory cardiomyopathy, characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function, has a heterogeneous aetiology. Inflammatory cardiomyopathy is predominantly mediated by viral infection, but can also be induced by bacterial, protozoal or fungal infections as well as a wide variety of toxic substances and drugs and systemic immune-mediated diseases. Despite extensive research, inflammatory cardiomyopathy complicated by left ventricular dysfunction, heart failure or arrhythmia is associated with a poor prognosis. At present, the reason why some patients recover without residual myocardial injury whereas others develop dilated cardiomyopathy is unclear. The relative roles of the pathogen, host genomics and environmental factors in disease progression and healing are still under discussion, including which viruses are active inducers and which are only bystanders. As a consequence, treatment strategies are not well established. In this Review, we summarize and evaluate the available evidence on the pathogenesis, diagnosis and treatment of myocarditis and inflammatory cardiomyopathy, with a special focus on virus-induced and virus-associated myocarditis. Furthermore, we identify knowledge gaps, appraise the available experimental models and propose future directions for the field. The current knowledge and open questions regarding the cardiovascular effects associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are also discussed. This Review is the result of scientific cooperation of members of the Heart Failure Association of the ESC, the Heart Failure Society of America and the Japanese Heart Failure Society.

The authors sought to provide the pre-specified primary endpoint of the ROADMAP (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients) trial at 2 years. The ROADMAP trial was a prospective nonrandomized observational study of 200 patients (97 with a left ventricular assist device [LVAD], 103 on optimal medical management [OMM]) that showed that survival with improved functional status at 1 year was better with LVADs compared with OMM in a patient population of ambulatory New York Heart Association functional class IIIb/IV patients. The primary composite endpoint was survival on original therapy with improvement in 6-min walk distance ≥75 m. Patients receiving LVAD versus OMM had lower baseline health-related quality of life, reduced Seattle Heart Failure Model 1-year survival (78% vs. 84%; p = 0.012), and were predominantly INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profile 4 (65% vs. 34%; p < 0.001) versus profiles 5 to 7. More LVAD patients met the primary endpoint at 2 years: 30% LVAD versus 12% OMM (odds ratio: 3.2 [95% confidence interval: 1.3 to 7.7]; p = 0.012). Survival as treated on original therapy at 2 years was greater for LVAD versus OMM (70 ± 5% vs. 41 ± 5%; p < 0.001), but there was no difference in intent-to-treat survival (70 ± 5% vs. 63 ± 5%; p = 0.307). In the OMM arm, 23 of 103 (22%) received delayed LVADs (18 within 12 months; 5 from 12 to 24 months). LVAD adverse events declined after year 1 for bleeding (primarily gastrointestinal) and arrhythmias. Survival on original therapy with improvement in 6-min walk distance was superior with LVAD compared with OMM at 2 years. Reduction in key adverse events beyond 1 year was observed in the LVAD group. The ROADMAP trial provides risk-benefit information to guide patient- and physician-shared decision making for elective LVAD therapy as a treatment for heart failure. (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients [ROADMAP]; NCT01452802).

Red blood cell distribution width (RDW), an integral parameter of the complete blood count (CBC), has been traditionally used for the classification of several types of anemia. However, over the last decade RDW has been associated with outcome in patients with several cardiovascular diseases including heart failure. The role of RDW in acute, chronic and advanced heart failure is the focus of the present work. Several pathophysiological mechanisms of RDW’s increase in heart failure have been proposed (i.e., inflammation, oxidative stress, adrenergic stimulation, undernutrition, ineffective erythropoiesis, reduced iron mobilization, etc.); however, the exact mechanism remains unknown. Although high RDW values at admission and discharge have been associated with adverse prognosis in hospitalized heart failure patients, the prognostic role of in-hospital RDW changes (ΔRDW) remains debatable. RDW has been incorporated in recent heart failure prognostic models. Utilizing RDW as a treatment target in heart failure may be a promising area of research.

Background— We sought to assess the predictive value of the Seattle Heart Failure Model (SHFM) when applied to ambulatory patients with advanced heart failure (HF) presented to an advanced HF therapeutics committee at a tertiary care US institution. Methods and Results— We evaluated model discrimination and calibration in 215 consecutive ambulatory patients who were presented to the Cleveland Clinic advanced HF therapeutics committee between 2004 to 2007 for evaluation for advanced options including transplantation and ventricular assist device (VAD). Analyses were stratified by committee decision (not listed versus listed United Network of Organ Sharing [UNOS] Status 2). Eighty-five percent had 1 or no missing SHFM variables. The primary outcome was a composite of all-cause mortality, VAD, or urgent (UNOS Status 1) transplantation. During a median follow-up of 24 months, 68 died, 18 received VAD support, and 81 underwent heart transplantation. Discrimination was modest both for those not listed (c-index, 0.683 at 1 year and 0.648 at 2 years), and for those listed UNOS status 2 (c-index, 0.629 at 1 year and 0.628 at 2 years). Calibration was acceptable among those patients not listed for heart transplantation but with substantial underestimation of risk (ie, overestimation of survival free of VAD or urgent transplantation) among UNOS status 2 patients. Conclusions— In ambulatory patients presented to an advanced HF therapeutics committee for evaluation for heart transplantation, the SHFM offers modest discrimination of risk for the primary composite outcome of mortality, VAD, or urgent transplantation, with underestimation of risk in those patients listed for nonurgent transplantation. Interpretation of risk prediction by the SHFM in this patient population must be done with caution.