Survival and Left Ventricular Function Changes in Fulminant Versus Nonfulminant Acute Myocarditis.

BACKGROUND: Previous reports have suggested that despite their dramatic presentation, patients with fulminant myocarditis (FM) might have better outcome than those with acute nonfulminant myocarditis (NFM). In this retrospective study, we report outcome and changes in left ventricular ejection fraction (LVEF) in a large cohort of patients with FM compared with patients with NFM. METHODS: The study population consists of 187 consecutive patients admitted between May 2001 and November 2016 with a diagnosis of acute myocarditis (onset of symptoms <1 month) of whom 55 required inotropes and/or mechanical circulatory support (FM) and the remaining 132 were hemodynamically stable (NFM). We also performed a subanalysis in 130 adult patients with acute viral myocarditis and viral prodrome within 2 weeks from the onset, which includes 34 with FM and 96 with NFM. Patients with giant-cell myocarditis, eosinophilic myocarditis, or cardiac sarcoidosis and those <15 years of age were excluded from the subanalysis. RESULTS: In the whole population (n=187), the rate of in-hospital death or heart transplantation was 25.5% versus 0% in FM versus NFM, respectively (P<0.0001). Long-term heart transplantation-free survival at 9 years was lower in FM than NFM (64.5% versus 100%, log-rank P<0.0001). Despite greater improvement in LVEF during hospitalization in FM versus NFM forms (median, 32% [interquartile range, 20%-40%] versus 3% [0%-10%], respectively; P<0.0001), the proportion of patients with LVEF <55% at last follow-up was higher in FM versus NFM (29% versus 9%; relative risk, 3.32; 95% confidence interval, 1.45-7.64, P=0.003). Similar results for survival and changes in LVEF in FM versus NFM were observed in the subgroup (n=130) with viral myocarditis. None of the patients with NFM and LVEF ≥55% at discharge had a significant decrease in LVEF at follow-up. CONCLUSIONS: Patients with FM have an increased mortality and need for heart transplantation compared with those with NFM. From a functional viewpoint, patients with FM have a more severely impaired LVEF at admission that, despite steep improvement during hospitalization, remains lower than that in patients with NFM at long-term follow-up. These findings also hold true when only the viral forms are considered and are different from previous studies showing better prognosis in FM.

Report from the Cardio-Oncology Symposium at the Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) Annual Congress.

Overview of the meeting The Cardio-Oncology Symposium at the Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) Annual Meeting mainly focused on the diagnosis, management and prevention of cardiovascular toxicity of cancer drugs, in particular, cardiac dysfunction induced by anthracyclines. Although a variety of cardiac biomarkers and imaging modalities are available, there remains no consensus regarding their appropriate use to identify early and late cardiotoxicity and to guide preventive strategies. At the same time, the multitude of pharmacological trials, aimed at preventing cardiac damage through a neurohormonal blockade, provided conflicting results. Nevertheless, the advent of novel heart failure medications can change the decision-making of the cardio-oncologist. This symposium attempted to harmonize these issues.

[Ventricular aneurysm as a complication of giant cell myocarditis]. / Aneurisma ventricolare come complicanza successiva a miocardite giganto-cellulare.

Ventricular aneurysm as late complication has been described in cardiac sarcoidosis and occasionally in giant cell myocarditis. The images from the present case of ventricular aneurysm formation as a late complication of giant cell myocarditis underline a potential cause of sudden arrhythmic death in patients who survive this life-threatening condition in the absence of recurrent inflammation and with preserved left ventricular ejection fraction. Follow-up with cardiac magnetic resonance can detect small aneurysms, and an implantable cardioverter-defibrillator may be considered when this complication occurs.

Prevention and management of chronic heart failure in management of asymptomatic patients.

Symptomatic heart failure is preceded by a somewhat prolonged asymptomatic stage in many patients. The number of patients with asymptomatic heart dysfunction is about 4-fold greater than the number of patients with clinically overt heart failure. Pharmacologic treatment with angiotensin-converting enzyme inhibitors and beta-blockers (in particular carvedilol) of asymptomatic patients with systolic left ventricular (LV) dysfunction can prevent or delay the occurrence of symptoms and reduce mortality in the long term. Thus, it would be of utmost importance to recognize and appropriately treat these patients before they develop heart failure symptoms. The cost-effectiveness of screening for asymptomatic heart dysfunction in the general population and in cohorts at risk has not been extensively evaluated. A normal electrocardiogram has a high negative predictive value in patients at risk. Echocardiography is the best tool for diagnosis and characterization of heart dysfunction, but extensive use is limited by availability and cost. Natriuretic peptides (brain natriuretic peptide and N-terminal pro-brain natriuretic peptide) are very sensitive markers of heart dysfunction and volume overload, and their measurement has been proposed as a first-line test to select patients who need echocardiography. The definition of the etiology of LV dysfunction--in particular, of the ischemic etiology--has prognostic and therapeutic implications. In addition to revascularization, pharmacologic treatment with antiplatelets and statins is helpful in preventing new ischemic events and the development of heart failure. The prevention, or at least the delay, of clinical manifestations of heart failure is strongly related to an effective approach to the asymptomatic stage. Therefore, it is important to educate the entire medical community, particularly physicians in the primary care setting, about recognition and treatment of these patients.

Everolimus immunosuppression in de novo heart transplant recipients: what does the evidence tell us now?

The efficacy of everolimus with reduced cyclosporine in de novo heart transplant patients has been demonstrated convincingly in randomized studies. Moreover, everolimus-based immunosuppression in de novo heart transplant recipients has been shown in two randomized trials to reduce the increase in maximal intimal thickness based on intravascular ultrasound, indicating attenuation of cardiac allograft vasculopathy (CAV). Randomized trials of everolimus in de novo heart transplantation have also consistently shown reduced cytomegalovirus infection versus antimetabolite therapy. In maintenance heart transplantation, conversion from calcineurin inhibitors to everolimus has demonstrated a sustained improvement in renal function. In de novo patients, a renal benefit may only be achieved if there is an adequate reduction in exposure to calcineurin inhibitor therapy. Delayed introduction of everolimus may be appropriate in patients at high risk of wound healing complications, e.g. diabetic patients or patients with ventricular assist device. The current evidence base suggests that the most convincing reasons for use of everolimus from the time of heart transplantation are to slow the progression of CAV and to lower the risk of cytomegalovirus infection. A regimen of everolimus with reduced-exposure calcineurin inhibitor and steroids in de novo heart transplant patients represents a welcome addition to the therapeutic armamentarium.

[Proposal for updated listing criteria for heart transplantation and indications to implant of left ventricular assist devices]. / Evoluzione delle indicazioni al trapianto cardiaco e all'impianto di dispositivi di assistenza ventricolare sinistra.

Heart transplantation (HTx) is considered to be the gold standard treatment for advanced heart failure (HF) but it is available only for a minority of patients, due to paucity of donor hearts (278 HTx were performed in 2011 in Italy). Patients listed for HTx have a prolonged waiting time (that is about 2.3 years in the 2006-2010 time period in Italy) that is superior compared with patients who receive HTx (median time around 6 months), to underline the presence of an allocation system that prioritizes candidates in critical conditions. Patients listed for HTx have a poor quality of life and their annual mortality is around 8-10%. Another 10-15% of HTx candidates are removed from the waiting list each year because they are no longer suitable for transplantation. On the other hand, continuous-flow left ventricular assist devices (LVADs) have been demonstrated to improve survival and quality of life of patients with advanced/refractory HF. LVAD therapy can represent a valid alternative to HTx, and it is recommended for patients with advanced HF in the recent edition of the European Society of Cardiology guidelines on HF management. In the United States, a larger number of centers compared with European ones started to apply a strategy of LVAD implant for many patients who meet clinical criteria for listing for HTx. Data from our center concerning the last 6 years of LVAD implant (51 implants since 2006) reported a 75.5% survival rate at 1 year. In Italian series, as in our center, current HTx survival is only slightly superior (83% survival rate at 1 year), based on data from the Italian National Transplant Center. We report a proposal for updated listing criteria for HTx and indications for LVAD implant in patients with advanced acute and chronic HF. Criteria for identifying suitable patients for HTx and/or LVAD considering the shortage of donors are discussed.

[Changes in patient survival and quality of life after heart transplantation]. / Come sono cambiate la sopravvivenza e la qualità di vita del paziente trapiantato?

Heart transplantation was performed firstly in 1967, but it became a valuable option in the 1980s, due to the availability of cyclosporine and of the technique for rejection monitoring by means of serial endomyocardial biopsies. Post-transplant survival improved over the years, mainly due to a reduction in early mortality for infection or acute rejection. Expected 1-year and 5-year survivals are around 85% and 70%, respectively. During the past 20-30 years, better therapies for heart failure have been developed, leading to restriction of heart transplant candidacy to truly refractory heart failure. On the contrary, the criteria for donor acceptance have been liberalized, due to the discrepancy between heart transplant candidates and available organs. It must be kept in mind that renal and/or hepatic insufficiency that may be a consequence of heart failure, pulmonary hypertension, and donor age, all remain risk factors for mortality after transplantation. In order to maintain and possibly improve the results of heart transplantation, effective strategies to increase safely the donor pool are of utmost importance. Moreover, long-term post-transplant recipients present new challenges to research and clinical practice. Mechanical circulatory support devices represent a surgical bridge or an alternative to transplantation; their expansion is limited by costs, organizational burden, and by patient difficulties in accepting this therapy.