Recognition and Initial Management of Fulminant Myocarditis: A Scientific Statement From the American Heart Association.

Fulminant myocarditis (FM) is an uncommon syndrome characterized by sudden and severe diffuse cardiac inflammation often leading to death resulting from cardiogenic shock, ventricular arrhythmias, or multiorgan system failure. Historically, FM was almost exclusively diagnosed at autopsy. By definition, all patients with FM will need some form of inotropic or mechanical circulatory support to maintain end-organ perfusion until transplantation or recovery. Specific subtypes of FM may respond to immunomodulatory therapy in addition to guideline-directed medical care. Despite the increasing availability of circulatory support, orthotopic heart transplantation, and disease-specific treatments, patients with FM experience significant morbidity and mortality as a result of a delay in diagnosis and initiation of circulatory support and lack of appropriately trained specialists to manage the condition. This scientific statement outlines the resources necessary to manage the spectrum of FM, including extracorporeal life support, percutaneous and durable ventricular assist devices, transplantation capabilities, and specialists in advanced heart failure, cardiothoracic surgery, cardiac pathology, immunology, and infectious disease. Education of frontline providers who are most likely to encounter FM first is essential to increase timely access to appropriately resourced facilities, to prevent multiorgan system failure, and to tailor disease-specific therapy as early as possible in the disease process.

Cardiac Transplantation Using Hearts With Transient Dysfunction: Role of Takotsubo-Like Phenotype.

BACKGROUND: The impact of different types of regional wall motion abnormalities (RWMAs), including the Takotsubo syndrome-like (TTS-like) phenotype, on posttransplant outcomes when using donor hearts with transient left ventricular systolic dysfunction (LVSD) is unknown. We evaluated the prevalence, clinical characteristics, and prognostic association of different RWMAs including TTS-like hypokinesis and posttransplant outcomes when using donor hearts with transient LVSD. METHODS: From all adult (≥18 years) heart transplants in United Network of Organ Sharing between January 2007 and September 2015, we identified 472 donor hearts with improving or transient LVSD, defined as left ventricular ejection fraction ≤ 40% on initial transthoracic echocardiogram (TTE) that improved to ≥50% on follow-up TTE during donor evaluation. These improved LVSD donors were then subdivided into 3 groups based on RWMAs on the initial TTE, TTS-like (49, 10.38%), non-TTS RWMAs (74, 15.68%), and diffuse global hypokinesis (349, 73.94%), and compared for baseline characteristics and posttransplant outcomes with follow up until June 2018. RESULTS: Donors with TTS-like LVSD were older and more likely to be female. The type of RWMA on initial TTE (including TTS-like) of transient LVSD donor hearts was not associated with 1-year or 5-year posttransplant mortality. Posttransplant functional status scores of recipients (at 1 year) and donor left ventricular ejection fraction (at median follow-up of 3.6 years) improved in all 3 subgroups. Rates of stroke or pacemaker predischarge were also similar. CONCLUSIONS: In the largest analysis of transplanted donor hearts with transient LVSD, 1 in 4 had RWMAs on the initial TTE, but this was not associated with adverse posttransplant outcomes. Donor hearts with initial LVSD should be pursued irrespective of TTS-like hypokinesis or other RWMAs.

Hemolysis and Nonhemorrhagic Stroke During Venoarterial Extracorporeal Membrane Oxygenation.

BACKGROUND: Hemolysis, even at low levels, activates platelets to create a prothrombotic state and is common during mechanical circulatory support. We examined the association of low-level hemolysis (LLH) and nonhemorrhagic stroke during venoarterial extracorporeal membrane oxygenation (VA ECMO) support. METHODS: A single-center retrospective review of all adult patients placed on VA ECMO from January 2012 to September 2017 was conducted. To determine the association between LLH and nonhemorrhagic stroke, patients were categorized as those with and without LLH. LLH was defined by 48-hour plasma free hemoglobin (PFHb) of 11 to 50 mg/dL after VA ECMO implantation. RESULTS: Of 201 patients who underwent VA ECMO placement, 150 (75%) met inclusion criteria and comprised the study population. They were 55 ± 14 years of age and 50 (33%) were women. Sixty-two (41%) patients had LLH. Patients with LLH had a higher likelihood of incident nonhemorrhagic stroke during VA ECMO support (20 [32%] versus 4 [5%]; adjusted hazard ratio [HR], 7.6; 95% confidence interval [CI], 2.2 to 25.9; p = 0.001). The severity of LLH was associated with an incrementally higher likelihood of a nonhemorrhagic stroke (PFHb 26 to 50 mg/dL: HR, 11.3; 95% CI, 3.6 to 35.1; p = 0.001; PFHb 11 to 25 mg/dL: HR, 4.4; 95% CI, 1.36 to 14.85; p = 0.014) in comparison with no LLH. Those with LLH had a 2-fold greater increase in mean platelet volume after VA ECMO placement (0.98 ± 1.1 fL versus 0.49 ± 0.96 fL; p = 0.03). Patients with a nonhemorrhagic stroke had a higher operative mortality (20 [83%] versus 57 [45%]; adjusted HR, 3.1; 95% CI, 1.8 to 5.3; p < 0.001). CONCLUSIONS: Hemolysis at low levels during VA ECMO support is associated with subsequent nonhemorrhagic stroke.

Continuous-Flow Left Ventricular Assist Device Survival Improves With Multidisciplinary Approach.

BACKGROUND: Continuous-flow left ventricular assist devices have revolutionized the management of advanced heart failure. Device complications continue to limit survival, but enhanced management strategies have shown promise. This study compared outcomes for HeartMate II recipients before and after implementation of a multidisciplinary continuous support heart team (HTMCS) strategy. METHODS: Between January 2012 and December 2016, 124 consecutive patients underwent primary HeartMate II implantation at our institution. In January 2015, we instituted a HTMCS approach consisting of (1) daily simultaneous cardiology/cardiac surgery/critical care/pharmacy/coordinator rounds, (2) pharmacist-directed anticoagulation, (3) speed optimization echocardiogram before discharge, (4) comprehensive device thrombosis screening and early intervention, (5) blood pressure clinic with pulsatility-adjusted goals, (6) early follow-up after discharge and individual long-term coordinator/cardiologist assignment, and (7) systematic basic/advanced/expert training and credentialing of ancillary in-hospital providers. All patients completed 1-year of follow-up. RESULTS: Demographic characteristics for pre-HTMCS (n = 71) and HTMCS (n = 53) groups, including age (55.8 ± 12.1 versus 52.5 ± 14.1 years, p = not significant), percentage of men (77.5% versus 71.7%, p = not significant), and Interagency Registry for Mechanically Assisted Circulatory Support class 3 (84.5% versus 83.0%, p = not significant), were comparable. One-year survival was 74.6% versus 100% for the pre-HTMCS and HTMCS groups, respectively (p = 0.0002). One-year survival free of serious adverse events (reoperation to replace device or disabling stroke) was 70.4% versus 84.9% for the pre-HTMCS and HTMCS groups, respectively (p = 0.059). Event per patient-year rates for disabling stroke (0.15 versus 0, p = 0.019), gastrointestinal bleeding (0.87 versus 0.51, p = 0.11), and driveline infection (0.24 versus 0.10, p = 0.18) were lower for the HTMCS group, whereas pump thrombosis requiring device exchange was higher (0.09 versus 0.18, p = 0.14). CONCLUSIONS: Implementing a comprehensive multidisciplinary approach substantially improved outcomes for recipients of continuous-flow left ventricular assist devices.

Outcomes of heart transplantation in patients with human immunodeficiency virus.

Human immunodeficiency virus-positive (HIV+) patients are not routinely offered heart transplantation (HT) due to lack of adequate outcomes data. Between January 2004 and March 2017, we identified 41 adult (≥18 years) HT recipients with known HIV+ serostatus at the time of transplant in UNOS and evaluated post-HT outcomes. Overall, Kaplan-Meier (KM) estimates of survival at 1 and 5 years were 85.9% and 77.3%, respectively, with no significant difference in bridge-to-transplant ventricular-assist device (BTT-VAD, n = 22) and no-BTT-VAD (n = 19). KM estimates of cardiac allograft vasculopathy (CAV) and malignancy at 5 years were 32% and 19%, respectively. Using propensity scores, 41 HIV+ HT recipients were matched to 41 HIV- HT recipients for idiopathic dilated-cardiomyopathy; and there was no significant difference in post-HT survival up to 5 years. Furthermore, only 24 centers in the United States had performed HIV+ HT during the study period, indicating that >80% of HT centers in the United States had not performed any HIV+ HT. In a cohort representative of the current status of HIV+ HTs in the United States, we found that the posttransplant survival was excellent and rates of CAV and malignancy were comparable to the overall HT population. These results should encourage greater number of centers to offer HT to suitable HIV+ candidates and help reduce unequal access to HT for HIV+ patients.

Quadravalvular Noninfectious Endocarditis.

Nonbacterial thrombotic endocarditis is characterized by sterile thrombi on cardiac valves. This report describes the case of nonbacterial endocarditis without pathologic findings of fibrin or platelet deposition. Quadrivalvular endocarditis was found to be due to immunoglobulin M heavy chain deposition. This was a case of nonbacterial, nonthrombotic quadrivalvular endocarditis, which was termed noninfective endocarditis. (Level of Difficulty: Intermediate.).

Digoxin Is Associated With a Decreased Incidence of Angiodysplasia-Related Gastrointestinal Bleeding in Patients With Continuous-Flow Left Ventricular Assist Devices.

BACKGROUND: Gastrointestinal bleeding (GIB) is one of the principal adverse events affecting patients with continuous-flow left ventricular assist devices (CF-LVADs). Despite the early recognition that GIB is commonly because of gastrointestinal angiodysplasia (GIAD), the exact pathophysiology of this process remains elusive. It has been postulated that the abnormal hemodynamic profile in CF-LVAD patients may activate the angiogenesis signaling cascade via the HIF (hypoxia-inducible factor)-1α/angiopoietin-2 pathway leading to formation of GIADs. Digoxin is a potent inhibitor of HIF-1α synthesis, and we hypothesized that its use reduces the incidence of GIAD and GIB in patients with CF-LVAD. METHODS AND RESULTS: Charts of all adult patients implanted with CF-LVAD between February 2006 and February 2017 were reviewed with particular emphasis on occurrence and cause of GIB. Fifty-four of 199 patients (27%) experienced a GIB. Overall frequency of GIB was lower in the 64 patients receiving digoxin compared with the 135 patients not receiving digoxin (16% versus 33%, P=0.01). Multivariable-adjusted Cox regression analysis confirmed that digoxin use was independently associated with a reduced risk for overall GIB (hazard ratio, 0.49; 95% CI, 0.24-0.98; P=0.045). GIBs were then categorized as non-GIAD, GIAD, or likely GIAD. Although the incidence of non-GIAD was similar in both groups (11% versus 7%, P=0.41), the frequency of GIAD/likely GIAD bleeding was significantly reduced in the digoxin group (5% versus 25%, P=0.0003). Multivariable-adjusted analysis confirmed that digoxin use was independently associated with a reduced risk for GIAD/likely GIAD bleeding (hazard ratio, 0.18; 95% CI, 0.06-0.6; P=0.005). However, digoxin use was not associated with reduced risk for non-GIAD GIB (hazard ratio, 1.54; 95% CI, 0.58-4.08; P=0.39). CONCLUSIONS: Use of digoxin was associated with a significant reduction in GIAD-related GIB in patients with CF-LVAD.

Ventricular assist device support as a bridge to heart transplantation in patients with giant cell myocarditis.

AIMS: Giant cell myocarditis (GCM) carries a poor prognosis and many patients require end-stage therapies. This study sought to determine the outcome of patients bridged with ventricular assist devices (VAD) to orthotopic heart transplantation (OHT). METHODS AND RESULTS: A retrospective data collection of all patients with GCM was performed. Diagnosis was determined by endomyocardial or explanted heart biopsy. Eight patients were found, but two of those patients went directly to OHT and were excluded. The remaining six patients received VADs, and these patients, aged 44 ± 18 years, were included. Five of the six patients were bridged with biventricular support and one patient was supported by left ventricular assist device (LVAD) alone. Two patients died on device support. Four patients were bridged to OHT 77 ± 42 days after device implantation. All four patients bridged with a VAD are alive, with a mean follow-up of 5.7 ± 4.1 years. Two patients were found to have recurrent GCM in the transplanted heart and were treated successfully with immunosuppression. Three patients had high grade (2R) rejection at 66 ± 52 days post-OHT. Cardiac function was preserved in all patients, and only one patient had cardiac allograft vasculopathy. CONCLUSION: Patients with end-stage GCM can be successfully bridged with VADs to OHT with very good post-OHT survival. The proper immunosuppressive regimen for this group needs further investigation given the frequency of rejection and GCM recurrence.