Hybrid extracorporeal cannulation for aortic root pseudoaneurysm re-operation: The role of a multidisciplinary team.

Introduction: Adequate cerebral protection for aortic reoperation is challenging and optimal technique is still controversial.Case Report: We report a hybrid cannulation approach to achieve safe cerebral protection during circulatory arrest to repair an aortic root pseudoaneurysm.Conclusion: A multidisciplinary approach combining conventional techniques and interventional expertise could be considered in complex aortic scenario.

Paracrine effect of regulatory T cells promotes cardiomyocyte proliferation during pregnancy and after myocardial infarction.

Cardiomyocyte proliferation stops at birth when the heart is no longer exposed to maternal blood and, likewise, to regulatory T cells (Tregs) that are expanded to promote maternal tolerance towards the fetus. Here, we report a role of Tregs in promoting cardiomyocyte proliferation. Treg-conditioned medium promotes cardiomyocyte proliferation, similar to the serum from pregnant animals. Proliferative cardiomyocytes are detected in the heart of pregnant mothers, and Treg depletion during pregnancy decreases both maternal and fetal cardiomyocyte proliferation. Treg depletion after myocardial infarction results in depressed cardiac function, massive inflammation, and scarce collagen deposition. In contrast, Treg injection reduces infarct size, preserves contractility, and increases the number of proliferating cardiomyocytes. The overexpression of six factors secreted by Tregs (Cst7, Tnfsf11, Il33, Fgl2, Matn2, and Igf2) reproduces the therapeutic effect. In conclusion, Tregs promote fetal and maternal cardiomyocyte proliferation in a paracrine manner and improve the outcome of myocardial infarction.

Myocarditis in Clinical Practice.

Myocarditis is a polymorphic disease characterized by great variability in clinical presentation and evolution. Patients presenting with severe left ventricular dysfunction and life-threatening arrhythmias represent a demanding challenge for the clinician. Modern techniques of cardiovascular imaging and the exhaustive molecular evaluation of the myocardium with endomyocardial biopsy have provided valuable insight into the pathophysiology of this disease, and several clinical registries have unraveled the disease's long-term evolution and prognosis. However, uncertainties persist in crucial practical issues in the management of patients. This article critically reviews current information for evidence-based management, offering a rational and practical approach to patients with myocarditis. For this review, we searched the PubMed and MEDLINE databases for articles published from January 1, 1980, through December 31, 2015, using the following terms: myocarditis, inflammatory cardiomyopathy, and endomyocardial biopsy. Articles were selected for inclusion if they represented primary data or were review articles published in high-impact journals. In particular, a risk-oriented approach is proposed. The different patterns of presentation of myocarditis are classified as low-, intermediate-, and high-risk syndromes according to the most recent evidence on prognosis, clinical findings, and both invasive and noninvasive testing, and appropriate management strategies are proposed for each risk class.

Characterization and Long-Term Prognosis of Postmyocarditic Dilated Cardiomyopathy Compared With Idiopathic Dilated Cardiomyopathy.

Dilated cardiomyopathy (DC) is the final common pathway of different pathogenetic processes and presents a significant prognostic heterogeneity, possibly related to its etiologic variety. The characterization and long-term prognosis of postmyocarditic dilated cardiomyopathy (PM-DC) remain unknown. This study assesses the clinical-instrumental evolution and long-term prognosis of a large cohort of patients with PM-DC. We analyzed 175 patients affected with DC consecutively enrolled from 1993 to 2008 with endomyocardial biopsy (EMB) data available. PM-DC was defined in the presence of borderline myocarditis at EMB or persistent left ventricular dysfunction 1 year after diagnosis of active myocarditis at EMB. Other patients were defined as affected by idiopathic dilated cardiomyopathy (IDC). Analysis of follow-up evaluations was performed at 24, 60, and 120 months. We found 72 PM-DC of 175 enrolled patients (41%). Compared with IDC, patients with PM-DC were more frequently females and less frequently presented a familial history of DC. No other baseline significant differences were found. During the long-term follow-up (median 154, first to third interquartile range 78 to 220 months), patients with PM-DC showed a trend toward slower disease progression. Globally, 18 patients with PM-DC (25%) versus 49 with IDC (48%) experienced death/heart transplantation (p = 0.045). The prognostic advantage for patients with PM-DC became significant beyond 40 months of follow-up. At multivariable time-dependent Cox analysis, PM-DC was confirmed to have a global independent protective role (hazard ratio 0.53, 95% confidence interval 0.28 to 0.97, p = 0.04). In conclusion, PM-DC is characterized by better long-term prognosis compared with IDC. An exhaustive etiologic characterization appears relevant in the prognostic assessment of DC.

The Prognostic Impact of the Evolution of RV Function in Idiopathic DCM.

OBJECTIVES: In this study, the authors analyzed the prognostic role of right ventricular systolic function (RVF) longitudinal trends in a large cohort of patients affected by dilated cardiomyopathy (DCM). BACKGROUND: RVF is a known prognostic predictor in DCM; however, whether RVF changes over time to better predict the long-term disease progression has not been investigated. METHODS: From 1993 to 2008, we analyzed 512 patients with DCM (46 years of age [36 to 55 years of age], left ventricular ejection fraction 32% [25% to 41%]) with a potential follow-up of ≥72 months and available data at baseline and at least 1 pre-specified follow-up evaluation (i.e., 6, 24, 48, or 72 months). RV dysfunction was defined as RV fractional area change <35% at 2-dimensional echocardiography. The primary outcome measure was a composite of death or heart transplantation. RESULTS: At enrollment, 103 (20%) patients had RV dysfunction. During follow-up, 89 of them (86%, 17% of the overall cohort) normalized RVF at a median time of 6 months, whereas 38 of the remaining 409 patients with normal baseline RVF (9%; 7% of the overall population) exhibited a new-onset RV dysfunction (median time: 36 months). RVF normalization was significantly associated with subsequent left ventricular reverse remodeling that was observed at a median time of 24 months (odds ratio: 2.49; 95% confidence interval [CI]: 1.17 to 5.3; p = 0.018). At baseline multivariate analysis, RV dysfunction was independently associated with the primary outcome measure (hazard ratio: 1.71; 95% CI: 1.02 to 2.85; p = 0.0413). At time-dependent model, RVF revaluation over time maintained an independent predictive value (hazard ratio: 2.83; 95% CI: 1.57 to 5.11; p = 0.0006). CONCLUSIONS: Patients with DCM frequently present RV dysfunction at first evaluation. However, a complete RVF recovery is largely observed early after optimization of medical therapy and predates subsequent left ventricular reverse remodeling. Systematic revaluation of patients including RVF throughout regular follow-up conferred additive long-term prognostic value to the baseline evaluation.

Persistent recovery of normal left ventricular function and dimension in idiopathic dilated cardiomyopathy during long­term follow­up: does real healing exist?

BACKGROUND: An important number of patients with idiopathic dilated cardiomyopathy have dramatically improved left ventricular function with optimal treatment; however, little is known about the evolution and long-term outcome of this subgroup, which shows apparent healing. This study assesses whether real healing actually exists in dilated cardiomyopathy. METHODS AND RESULTS: Persistent apparent healing was evaluated among 408 patients with dilated cardiomyopathy receiving tailored medical treatment and followed over the very long-term. Persistent apparent healing was defined as left ventricular ejection fraction ≥50% and indexed left ventricular end-diastolic diameter ≤33 mm/m(2) at both mid-term (19±4 months) and long-term (103±9 months) follow-up. At mid-term, 63 of 408 patients (15%) were apparently healed; 38 (60%; 9%of the whole population) showed persistent apparent healing at long-term evaluation. No predictors of persistent apparent healing were found. Patients with persistent apparent healing showed better heart transplant­free survival at very long-term follow-up (95% versus 71%; P=0.014) compared with nonpersistently normalized patients. Nevertheless, in the very longterm, 37% of this subgroup experienced deterioration of left ventricular systolic function, and 5% died or had heart transplantation. CONCLUSIONS: Persistent long-term apparent healing was evident in a remarkable proportion of dilated cardiomyopathy patients receiving optimal medical treatment and was associated with stable normalization of main clinical and laboratory features. This condition can be characterized by a decline of left ventricular function over the very long term, highlighting the relevance of serial nd individualized follow-up in all patients with dilated cardiomyopathy, especially considering the absence of predictors for longterm apparent healing.

Long-term evolution and prognostic stratification of biopsy-proven active myocarditis.

BACKGROUND: Active myocarditis is characterized by large heterogeneity of clinical presentation and evolution. This study describes the characteristics and the long-term evolution of a large sample of patients with biopsy-proven active myocarditis, looking for accessible and valid early predictors of long-term prognosis. METHODS AND RESULTS: From 1981 to 2009, 82 patients with biopsy-proven active myocarditis were consecutively enrolled and followed-up for 147±107 months. All patients underwent clinical and echocardiographic evaluation at baseline and at 6 months. At this time, improvement/normality of left ventricular ejection fraction (LVEF), defined as a LVEF increase > 20 percentage points or presence of LVEF≥50%, was assessed. At baseline, left ventricular dysfunction (LVEF<50%) and left atrium enlargement were independently associated with long-term heart transplantation-free survival, regardless of the clinical pattern of disease onset. At 6 months, improvement/normality of LVEF was observed in 53% of patients. Persistence of New York Heart Association III to IV classes, left atrium enlargement, and improvement/normality of LVEF at 6 months emerged as independent predictors of long-term outcome. Notably, the short-term reevaluation showed a significant incremental prognostic value in comparison with the baseline evaluation (baseline model versus 6 months model: area under the curve 0.79 versus 0.90, P=0.03). CONCLUSIONS: Baseline left ventricular function is a marker for prognosis regardless of the clinical pattern of disease onset, and its reassessment at 6 months appears useful for assessing longer-term outcome.

[Controversial issues and working practice in myocarditis: from scientific data to clinical grounds]. / Aspetti controversi e gestionali sulle miocarditi: dalla letteratura al paziente.

Although the cause of myocarditis often remains unknown, a large variety of infections, systemic diseases, drugs and toxins have been associated with this disease. In most cases, myocarditis is induced by cardiotropic viruses and often evolves silently without discernible prognostic impact. However, in some patients, the lack of complete viral clearance and/or the association of a heart-specific inflammation can cause persistent myocyte damage, ultimately leading to progressive myocardial dilation and dysfunction or life-threatening arrhythmias. Spontaneous improvement of left ventricular function is described for 40-50% of patients. The diagnostic work-up and prognostic assessment of myocarditis should be multiparametric and all available resources should be employed, i.e. biomarkers of myocardial damage and ventricular dysfunction (troponin I, brain natriuretic peptide), advanced echocardiography, cardiac magnetic resonance and, in selected cases, endomyocardial biopsy (with histopathologic, immunohistochemical and virological analyses). These are the necessary prerequisites for an evidence-based and personalized management of myocarditis, which may require in some cases specific immunoactive treatments. However, controversial issues regarding diagnosis (such as role and timing of cardiac magnetic resonance imaging, role of endomyocardial biopsy) and therapy of myocarditis still remain unsolved. The purpose of this review is to analyze these crucial features in order to provide useful instructions for clinical practice.

Idiopathic dilated cardiomyopathy and persistent viral infection: lack of association in a controlled study using a quantitative assay.

BACKGROUND: It remains unclear whether idiopathic dilated cardiomyopathy (DCM) might ensue as the consequence of viral myocarditis, due to viral persistence in cardiomyocytes. To address this issue, we quantified the levels of enterovirus, Epstein-Barr virus (EBV), Herpes Simplex Virus-1 (HSV-1), Herpes Simplex Virus-2 (HSV-2), adenovirus and parvovirus B19 genomes in endomyocardial biopsies (EMBs) from patients with DCM, active myocarditis and controls. METHODS: Real-time polymerase chain reaction (PCR)-based methods using TaqMan probes were developed for the quantitative detection of viral genomes in EMBs from 35 patients with DCM and 17 with active myocarditis. A control group included 20 surgical patients with valve or coronary artery disease. RESULTS: None of the 72 samples tested positive for enteroviruses, EBV, HSV-1 or -2. One DCM patient tested positive for adenovirus. Of notice, 20/52 (38%) of patients with cardiomyopathy and 8/20 (40%) of controls were positive for parvovirus B19; no significant differences in viral titre were detected between groups. CONCLUSIONS: Our preliminary results disfavour the hypothesis that persistent myocardial viral infection might be a frequent cause of DCM. The detection of parvovirus B19 from both cardiomyopathy and non-cardiomyopathy patients supports the notion that this virus is widely spread in the population.