Lymphocytic Myocarditis: A Genetically Predisposed Disease?

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New perspectives in diagnosis and risk stratification of non-ischaemic dilated cardiomyopathy

Dilated cardiomyopathy is a primitive heart muscle condition, characterized by structural and functional abnormalities, in the absence of a specific cause sufficient to determine the disease. It is, though, an 'umbrella' term that describes the final common pathway of different pathogenic processes and gene-environment interactions. Performing an accurate diagnostic workup and appropriate characterization of the patient has a direct impact on the patient's outcome. The physician should adapt a multiparametric approach, including a careful anamnesis and physical examination and integrating imaging data and genetic testing. Aetiological characterization should be pursued, and appropriate arrhythmic risk stratification should be performed. Evaluations should be repeated thoroughly at follow-up, as the disease is dynamical over time and individual risk might evolve. The goal is an all-around characterization of the patient, a personalized medicine approach, in order to establish a diagnosis and therapy tailored for the individual patient

Cardiology of the future: xenotransplantation with porcine heart

The reduced availability of human donor hearts compared with the needs of patients with advanced heart failure refractory to medical therapy has promoted the search for therapeutic alternatives to cardiac allografts. Porcine heart xenotransplantation represents one of the most promising frontiers in this field today. From the first researches in the 1960s to today, the numerous advances achieved in the field of surgical techniques, genetic engineering and immunosuppression have made it possible at the beginning of 2022 to carry out the first swine-to-human heart transplant, attaining a survival of 2 months after surgery. The main intellectual and experimental stages that have marked the history of xenotransplantation, the latest acquisitions in terms of genetic editing, as well as the improvement of immunosuppressive therapy are discussed analytically in this article in order to illustrate the underlying complexity of this therapeutic model

Prognostic Prediction of Genotype vs Phenotype in Genetic Cardiomyopathies

Background: Diverse genetic backgrounds often lead to phenotypic heterogeneity in cardiomyopathies (CMPs). Previous genotype-phenotype studies have primarily focused on the analysis of a single phenotype, and the diagnostic and prognostic features of the CMP genotype across different phenotypic expressions remain poorly understood. Objectives: We sought to define differences in outcome prediction when stratifying patients based on phenotype at presentation compared with genotype in a large cohort of patients with CMPs and positive genetic testing. Methods: Dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy, left-dominant arrhythmogenic cardiomyopathy, and biventricular arrhythmogenic cardiomyopathy were examined in this study. A total of 281 patients (80% DCM) with pathogenic or likely pathogenic variants were included. The primary and secondary outcomes were: 1) all-cause mortality (D)/heart transplant (HT); 2) sudden cardiac death/major ventricular arrhythmias (SCD/MVA); and 3) heart failure-related death (DHF)/HT/left ventricular assist device implantation (LVAD). Results: Survival analysis revealed that SCD/MVA events occurred more frequently in patients without a DCM phenotype and in carriers of DSP, PKP2, LMNA, and FLNC variants. However, after adjustment for age and sex, genotype-based classification, but not phenotype-based classification, was predictive of SCD/MVA. LMNA showed the worst trends in terms of D/HT and DHF/HT/LVAD. Conclusions: Genotypes were associated with significant phenotypic heterogeneity in genetic cardiomyopathies. Nevertheless, in our study, genotypic-based classification showed higher precision in predicting the outcome of patients with CMP than phenotype-based classification. These findings add to our current understanding of inherited CMPs and contribute to the risk stratification of patients with positive genetic testing

Towards standardization of echocardiography for the evaluation of left ventricular function in adult rodents : a position paper of the ESC Working Group on Myocardial Function

This work was supported by AIRC IG grant 2016 19032 to S.Z.; FEDER through Compete 2020 –Programa Operacional Competitividade E Internacionalização(POCI), the project DOCNET (norte-01-0145-feder-000003), supported by Norte Portugal regional operational programme (norte 2020), under the Portugal 2020 partnership agreement, through the European Regional Development Fund (ERDF), the project NETDIAMOND (POCI-01-0145-FEDER-016385), supported by European Structural And Investment Funds, Lisbon’s regional operational program 2020 to I.P.F.; grants from FSR-FNRS, FRC (Cliniques Universitaires Saint-Luc) and from Action de Recherche Concertée (UCLouvain) to C.B., E.P.D. and L.B; the ERA-Net-CVD project MacroERA,01KL1706, FP7-Homage N° 305507, and IMI2-CARDIATEAM (N° 821508)to S.H.,the DZHK (German Centre for Cardiovascular Research) and the German Ministry of Research and Education (BMBF)to F.W., T.E. and L.C., the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation, CVON2016-Early HFPEF, 2015-10, CVON She-PREDICTS, grant 2017-21, CVON Arena-PRIME, 2017-18, Flemish Research FoundationFWO G091018N and FWO G0B5930N to S.H.; Federico II University/Ricerca di Ateneo grant to C.G..T.; the European Research Area Networks on Cardiovascular Diseases (ERA-CVD) [LYMIT-DIS 2016, MacroERA], Fonds Wetenschappelijk Onderzoek [1160718N] to I.C; the Deutsche Forschungsgemeinschaft (DFG TH903/20-1, KFO311), the Transregio-SFB INST 95/15641 and the EU Horizon 2020 project Cardioregenix (GA 825670)to T.TPeer reviewedPostprin

Diagnosing cachexia

Cachexia is a clinically relevant factor, and its presence should be proactively investigated in hospitalized patients and outpatients. Unfortunately, a unifying definition and generally accepted diagnostic criteria do not yet exist, contributing to the skepticism of many doctors toward nutrition diagnosis in patients. However, the key features of cachexia are the presence of weight loss, increased inflammatory response and muscle wasting. It is now also accepted that the cachexia syndrome progresses from the stage of precachexia to overt cachexia to refractory cachexia. Direct measurement of muscle mass is still not routinely considered in daily clinical practice, owing to a number of reasons. However, the functional assessment of muscle strength may provide relevant insights into the deterioration of muscle mass during cachexia. © 2014 Future Medicine Ltd

Cardiac Biomarkers in the Emergency Department: The Role of Soluble ST2 (sST2) in Acute Heart Failure and Acute Coronary Syndrome—There is Meat on the Bone

Soluble ST2 (sST2) has recently emerged as a promising biomarker in the field of acute cardiovascular diseases. Several clinical studies have demonstrated a significant link between sST2 values and patients’ outcome. Further, it has been found that higher levels of sST2 are associated with an increased risk of adverse left ventricular remodeling. Therefore, sST2 could represent a useful tool that could help the risk stratification and diagnostic and therapeutic work-up of patients admitted to an emergency department. With this review, based on recent literature, we have built sST2-assisted flowcharts applicable to three very common clinical scenarios of the emergency department: Acute heart failure, type 1, and type 2 acute myocardial infarction. In particular, we combined sST2 levels together with clinical and instrumental evaluation in order to offer a practical tool for emergency medicine physicians

Whole‐exome sequencing: Clinical characterization of pediatric and adult Italian patients affected by different forms of hereditary cardiovascular diseases

Abstract Background Hereditary cardiovascular diseases comprise several different entities. In this study, we focused on cardiomyopathies (i.e., hypertrophic, dilated, arrhythmogenic, and left ventricular non‐compaction), channelopathies (i.e., Brugada syndrome and long QT syndrome), and aortopathies and pulmonary arterial hypertension (i.e., thoracic/abdominal aortic aneurysm and pulmonary arterial hypertension), and genetically characterized 200 Italian patients affected by these diseases. Methods We employed whole‐exome sequencing (WES), focused on four in silico gene panels, and the MLPA method for hypertrophic and arrhythmogenic right ventricular cardiomyopathy cases. Results Cardiomyopathies affected 87.5% of analyzed patients, channelopathies 7%, and aortopathies and pulmonary arterial hypertension 5.5%. The molecular diagnosis was confirmed for 21.5% of cases with a higher detection rate in familial forms (34%) than sporadic ones (14%). We highlighted the importance of family segregation to better understand the pathogenic role of the identified variants and their involvement in the clinical phenotype. Negative results could be ascribed to the high genetic and clinical heterogeneity of hereditary cardiovascular diseases; clinical follow‐up and revaluation of WES data will be essential. Conclusion This study highlights the importance of a multi‐step approach (WES and MLPA) to characterize hereditary cardiovascular diseases, provides crucial information for clinical management and recurrence risk estimation, and lays the foundation for future personalized therapies

Current diagnostic strategies for dilated cardiomyopathy: a comparison of imaging techniques

Dilated cardiomyopathy (DCM) is generally thought as a final common pathway of several conditions leading to the same clinical phenotype. Multiple imaging modalities play a fundamental role in recognizing the underlying pathological substrate in DCM. Areas covered: Echocardiography represents the first reliable and easily accessible diagnostic tool, allowing the identification of associated cardiac abnormalities, such as valve disease and highlighting features associated with an adverse prognosis. Recent advances in technology such as strain analysis and 3D-echocardiography have improved the diagnostic and prognostic capabilities of this technique. Cardiac magnetic resonance (CMR) is considered the gold standard for an accurate and reproducible assessment of ventricular volumes and ejection fraction. In addition, CMR allows us to perform tissue characterization that, through new sophisticated sequences, could be obtained even without gadolinium. Nuclear images could be useful to identify specific causes of left ventricular dysfunction, such as cardiac sarcoidosis and amyloidosis. Finally, endomyocardial biopsy is generally performed if acute myocarditis is suspected in high-risk patients. Expert commentary: Strengths and limitations are different for every method, but multiparametric evaluation of patients and family members could progressively improve current understanding of the disease. This is fundamental to specifically target therapy, allowing us to improve patients' prognosis

Prognostic value of echocardiographic evaluation of cardiac mechanics in patients with aortic stenosis and preserved left ventricular ejection fraction

Left ventricular ejection function (LVEF) is not reliable in identifying subtle systolic dysfunction. Speckle Tracking (ST) plays a promising role and hemodynamic forces (HDFs) are emerging as marker of LV function. The role of LV myocardial deformation and HDFs was investigated in a cohort of patients with aortic stenosis (AS) and normal LVEF. Two hundred fifty three patients (median age 79 years, IQR 73 - 83 years) with mild (n = 87), moderate (n =77) and severe AS (n =89) were retrospectively enrolled. 2D echocardiographic global longitudinal strain (GLS), circumferential strain (GCS) and HDFs were determined. The worsening of AS was associated with raising inappropriate LV mass (p -19,9%) and LV systolic longitudinal force (LVsysLF) value (< 12,49), patients with impaired ST and lower HDFs components had increased incidence of aortic valve replacement (AVR) and worse survival (p <0.024 and p <0.037, respectively). Among ST and HDFs parameters, only LVsysLF was independently associated with AVR and all causes mortality on multivariable Cox regression analysis (HR 0.94; 95% CI 0.89-0.99; p= 0.012). Reduced values of LVsysLF were associated with AVR and reduced survival in AS patients. LVsysLF could provide useful information in the stratification of patients with AS and possibly in the choice of timing for AVR