Unveiling the Future of Cardiac Care: A Review of Gene Therapy in Cardiomyopathies.

For years, the treatment of many cardiomyopathies has been solely focused on symptom management. However, cardiomyopathies have a genetic substrate, and directing therapy towards the pathophysiology rather than the epiphenomenon of the disease may be a winning strategy. Gene therapy involves the insertion of genes or the modification of existing ones and their regulatory elements through strategies like gene replacement and gene editing.

Update on the diagnosis and treatment of pericardial diseases: a position paper of the Italian Society of Cardiology in collaboration with the study group on cardiomyopathies and pericardial diseases.

The knowledge of pericardial diseases has now improved, including prospective and retrospective cohort studies focusing on the pathogenesis, diagnosis, treatment, and outcomes. The complex interplay between genetic predisposition (especially for autoinflammatory conditions), inflammation, and autoimmunity is now known to trigger recurrences of pericarditis. Moreover, diagnostic capabilities have improved with the implementation of multimodality imaging, particularly cardiac magnetic resonance (CMR), to detect and monitor pericardial inflammation, to allow diagnosis in more complicated cases, and tailor the duration of therapy based on objective parameters.

Exercise limitations in amyloid cardiomyopathy assessed by cardiopulmonary exercise testing-A multicentre study.

Aims: Amyloid cardiomyopathy is caused by the deposition of light chain (AL) or transthyretin amyloid (ATTR) fibrils, that leads to a restrictive cardiomyopathy, often resulting in heart failure (HF) with preserved or reduced ejection fraction. This study aimed to determine whether cardiac output reduction or ventilation inefficiency plays a predominant role in limiting exercise in patients with amyloid cardiomyopathy.

Methods: We conducted a multicentre prospective study in patients with AL or ATTR cardiomyopathy who underwent cardiopulmonary exercise testing across four centres.

Clinical characteristics and outcomes of Takotsubo syndrome in patients with chronic obstructive pulmonary disease.

Background: takotsubo syndrome (TTS) is an acute heart failure syndrome characterized by a relevant comorbid background, including chronic obstructive pulmonary disease (COPD). However, TTS patients with COPD are still not well characterized.

Aim: to describe the clinical characteristics and outcomes of patients with TTS and COPD.

Arrhythmic risk stratification in patients with left ventricular ring-like scar.

Aims: Left ventricular (LV) ring-like scar on cardiac magnetic resonance (CMR) has been linked to malignant arrhythmias in patients with non-ischemic cardiomyopathy. This study aimed to perform a comprehensive evaluation of this phenotype and to identify risk factors for life-threatening arrhythmic events (LAEs), a composite of sudden cardiac death (SCD), aborted SCD, and sustained ventricular tachycardia.

Methods And Results: One-hundred-fifteen patients (median age 39 [IQR 28-52], 42% females) were identified at 6 referral centres.

Management of overlapping immune-related myocarditis, myositis, and myasthenia in a young patient with advanced NSCLC: a case report.

Immunotherapy is increasingly used in advanced non-small-cell lung cancer (NSCLC), offering a significant anti-tumor response, as well as causing rising immune-related adverse effects. The incidence of immune checkpoint inhibitor-induced myocarditis-myositis-myasthenia gravis is increasing and particularly concerning due to its high mortality rate. Prompt recognition, diagnosis, and management are crucial.

Reanalysis of Next-generation Sequencing Data in Patients With Hypertrophic Cardiomyopathy: Contribution of Spliceogenic Variants in an Italian Cohort.

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac muscle disease characterized by clinical and genetic heterogeneity. Genetic testing can reveal the presence of disease-causing variants in genes encoding sarcomere proteins. However, it yields inconclusive or negative results in 40-60% of HCM cases, owing to, among other causes, technical limitations such as the inability to detect pathogenic intronic variants.

Impact of the Noninvasive Diagnostic Algorithm on Clinical Presentation and Prognosis in Cardiac Amyloidosis.

Background: The introduction of a noninvasive diagnostic algorithm in 2016 led to increased awareness and recognition of cardiac amyloidosis (CA).

Objectives: The purpose of this study was to analyze the impact of the introduction of the noninvasive diagnostic algorithm on diagnosis and prognosis in a multicenter Italian CA cohort.

Methods: This was a retrospective analysis of 887 CA patients from 5 Italian Cardiomyopathies Referral Centers: 311 light-chain CA, 87 variant transthyretin (TTR)-related CA, 489 wild-type TTR-related CA.

Accuracy of renovo predictions on variants reclassified over time.

Background: Interpreting the clinical consequences of genetic variants is the central problem in modern clinical genomics, for both hereditary diseases and oncology. However, clinical validation lags behind the pace of discovery, leading to distressing uncertainty for patients, physicians and researchers. This "interpretation gap" changes over time as evidence accumulates, and variants initially deemed of uncertain (VUS) significance may be subsequently reclassified in pathogenic/benign.

Guideline-Directed Medical Therapy in Patients With Heart Failure With Reduced Ejection Fraction and Incident Cancer.

Background: It has been postulated that cancer hampers the delivery of guideline-directed medical therapy (GDMT) for heart failure (HF). However, few data are available in this regard.

Methods: We performed a retrospective analysis from the HF Outpatient Clinic of the IRCCS Ospedale Policlinico San Martino in Genova, Italy.

A contemporary update on cancer and takotsubo syndrome.

Takotsubo syndrome (TTS) is characterized by a transient left ventricular systolic dysfunction, burdened by significant acute and long-term mortality and morbidity. The prognosis of TTS, especially in the long-term, is influenced by both non-cardiovascular (non-CV) and CV comorbidities, among which cancer is one of the most common. The presence of a malignancy is proven to be associated with higher mortality in TTS.

Clinical characteristics and outcome of end stage hypertrophic cardiomyopathy: Role of age and heart failure phenotypes.

Background: A minority of patients with hypertrophic cardiomyopathy (HCM) presents advanced heart failure (HF) during their clinical course, in the context of left ventricular (LV) remodeling with reduced LV ejection fraction (LVEF), or of severe diastolic dysfunction without impaired LVEF. Aim of this study was to describe a multicentric end stage (ES) HCM population and analyze clinical course and outcome among its different phenotypes.

Methods: Data of all HCM patients from 7 Italian referral centres were retrospectively evaluated.

Real-world candidacy to mavacamten in a contemporary hypertrophic obstructive cardiomyopathy population.

Aims: In the EXPLORER-HCM trial, mavacamten reduced left ventricular outflow tract obstruction (LVOTO) and improved functional capacity of symptomatic hypertrophic obstructive cardiomyopathy (HOCM) patients. We sought to define the potential use of mavacamten by comparing real-world HOCM patients with those enrolled in EXPLORER-HCM and assessing their eligibility to treatment.

Methods And Results: We collected information on HOCM patients followed up at 25 Italian HCM outpatient clinics and with significant LVOTO (i.

Benchmarking and improving the performance of variant-calling pipelines with RecallME.

Motivation: The steady increment of Whole Genome/Exome sequencing and the development of novel Next Generation Sequencing-based gene panels requires continuous testing and validation of variant calling (VC) pipelines and the detection of sequencing-related issues to be maintained up-to-date and feasible for the clinical settings. State of the art tools are reliable when used to compute standard performance metrics. However, the need for an automated software to discriminate between bioinformatic and sequencing issues and to optimize VC parameters remains unmet.

European Society of Cardiology Core Curriculum for cardio-oncology.

Cardio-oncology is a rapidly growing field of cardiovascular (CV) medicine that has resulted from the continuously increasing clinical demand for specialized CV evaluation, prevention and management of patients suffering or surviving from malignant diseases. Dealing with CV disease in patients with cancer requires special knowledge beyond that included in the general core curriculum for cardiology. Therefore, the European Society of Cardiology (ESC) has developed a special core curriculum for cardio-oncology, a consensus document that defines the level of experience and knowledge required for cardiologists in this particular field.

High-Fat Diet Promotes Acute Promyelocytic Leukemia through PPARδ-Enhanced Self-renewal of Preleukemic Progenitors.

Unlabelled: Risk and outcome of acute promyelocytic leukemia (APL) are particularly worsened in obese-overweight individuals, but the underlying molecular mechanism is unknown. In established mouse APL models (Ctsg-PML::RARA), we confirmed that obesity induced by high-fat diet (HFD) enhances leukemogenesis by increasing penetrance and shortening latency, providing an ideal model to investigate obesity-induced molecular events in the preleukemic phase. Surprisingly, despite increasing DNA damage in hematopoietic stem cells (HSC), HFD only minimally increased mutational load, with no relevant impact on known cancer-driving genes.

The Diagnostic Value of the 12-Lead ECG in Arrhythmogenic Left Ventricular Cardiomyopathy: Novel ECG Signs.

Background: Electrocardiographic (ECG) findings in arrhythmogenic left ventricular cardiomyopathy (ALVC) are limited to small case series.

Objectives: This study aimed to analyze the ECG characteristics of ALVC patients and to correlate ECG with cardiac magnetic resonance and genotype data.

Methods: We reviewed data of 54 consecutive ALVC patients (32 men, age 39 ± 15 years) and compared them with 84 healthy controls with normal cardiac magnetic resonance.

Immune-Related Adverse Event Likelihood Score Identifies "Pure" IRAEs Strongly Associated With Outcome in a Phase I-II Trial Population.

Background: Immune-related adverse events (IRAE) pose a significant diagnostic and therapeutic challenge in patients treated with immune-oncology (IO) drugs. IRAEs have been suggested to correlate with better outcome, but studies are conflicting. Estimating the true incidence of IRAEs is particularly difficult in the early phase I/II trial setting.

Electrocardiographic heterogeneity of patients with variant transthyretin amyloid cardiomyopathy: Genotype-phenotype correlations.

Backgorund: Hereditary transthyretin(vATTR) cardiac amyloidosis has extremely different features according to the type of transthyretin(TTR) mutation. Data about electrocardiographic findings(ECG) in vATTR are limited and not informative of genotype correlation. Aim of this study is to analyze ECG characteristics and their correlation to clinical and echocardiographic aspects in patients with vATTR, focusing on different TTR mutations.