Trastuzumab cardiotoxicity and drug cardioprotection in healthy and cardiac dysfunction mouse models.

Pre-existing cardiovascular disease is a recognised risk factor for cardiotoxicity in HER2-targeted therapies such as trastuzumab (TRZ), but few studies have addressed the impact of TRZ and the effects of cardioprotective drugs in pre-existing cardiac issues. This study examines the impact of TRZ-induced cardiotoxicity in pre-existing cardiac conditions and the effects of captopril and bisoprolol in mouse models with varying degrees of cardiac impairment. Adult mice models with and without baseline cardiac dysfunction ̶ healthy mice (WT), transgenic mice with cardiac hyperaldosteronism (AS) and mice with cardiac dysfunction (AS+ISO) ̶ were randomised to receive placebo, TRZ alone (6 mg/kg/week for 4 weeks), or TRZ administered concomitantly with a cardioprotective therapy based on captopril (ACEi, 20 mg/kg) and bisoprolol (BB, 5 mg/kg) (TRZ+ACEi/BB).

Impact of GFR Estimation Formulas on MECKI Score Performance and Prognostic Accuracy in Heart Failure: The MECKI-RENAL Study.

Background: Appropriate interpretation of kidney function is essential for clinical and therapeutic management of heart failure (HF). We evaluated the prognostic accuracy of 6 glomerular filtration rate estimation (eGFR) formulas in HF patients with reduced ejection fraction (HFrEF) and their impact on the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score prognostic accuracy.

Methods: We retrospectively analyzed 6,933 patients enrolled in the MECKI score database.

Characteristics of patients with suspected cardiac amyloidosis in Tuscany and Umbria: Insights from the cardiac amyloidosis RegistRY (CARRY).

Background: Cardiac amyloidosis (CA) involves the deposition of misfolded proteins in the heart, most commonly light-chains (AL) or transthyretin (ATTR). Advancements in non-invasive diagnostics have challenged the classification of CA as a rare disease. The Cardiac Amyloidosis RegistRY (CARRY) provides updated insights into CA's epidemiology, diagnosis, and clinical features.

Contemporary Oral Medication Use and Frequency in Patients with Transthyretin Amyloid Cardiomyopathy.

Introduction: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly recognized cause of heart failure (HF), with a higher prevalence in older patients with comorbidities requiring concomitant medical therapy. Acoramidis is a next-generation transthyretin stabilizer with near-complete protein stabilization (≥ 90%) administered orally twice daily (BID) for treatment of ATTR-CM. We report on oral medication use in patients with ATTR-CM using two complementary sources: the ATTRibute-CM trial and real-world claims data.

A prognostically meaningful definition of non-dilated left ventricular cardiomyopathy.

Non-dilated left ventricular cardiomyopathy (NDLVC) has been defined as non-ischemic LV scarring and/or fatty replacement and/or hypokinesia, without LV dilation. We tried to identify specific criteria for LV dilation and dysfunction to implement this definition. We identified all non-ischemic cardiomyopathy patients undergoing a cardiovascular magnetic resonance scan from 2012 to 2022 with LV ejection fraction (LVEF) < 55% and/or non-ischemic late gadolinium enhancement (LGE) and/or fatty replacement, and without specific etiologies.

Heart Failure Management in Cardiac Amyloidosis: Towards a Paradigm Shift.

Heart failure (HF) and cardiac amyloidosis (CA) are significant clinical challenges, with evolving epidemiological patterns reshaping the understanding of these conditions. Traditionally linked with HF with preserved ejection fraction, CA is increasingly recognised for its specific characteristics, including a considerable subset of patients presenting with reduced left ventricular ejection fraction. This review explores how the neurohormonal activation observed in CA impacts on disease progression and management strategies.

Advancing Cardiovascular Risk Stratification and Functional Assessment: A Narrative Review of CPET and ESE Applications.

Cardiopulmonary exercise testing combined with exercise stress Echocardiography (CPET-ESE) is an advanced diagnostic modality for evaluating cardiovascular disease and tailoring patient-specific treatment strategies. By integrating metabolic, ventilatory, and hemodynamic data with real-time imaging, CPET-ESE offers a comprehensive assessment of cardiovascular function under physiological stress. CPET provides detailed insights into metabolic and ventilatory performance, while ESE allows for the dynamic visualisation of cardiac structure and function during exercise.

Multimodality Imaging in a Patient With MINOCA and Anomalous Coronary Artery.

Background: Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a heterogeneous condition requiring multimodal imaging for accurate diagnosis and management. Identifying the underlying etiology is crucial for guiding treatment.

Case Summary: A 60-year-old man with hypertension and no prior coronary artery disease presented with angina.

A Novel Homozygous Mutation of the Desmoplakin Gene With Biventricular Arrhythmogenic Cardiomyopathy.

Background: A 23-year-old male with arrhythmic syncope and a presumed diagnosis of COVID-19 myocarditis was ultimately diagnosed with biventricular arrhythmogenic cardiomyopathy based on cardiac magnetic resonance imaging (MRI) and genetic testing (next-generation sequencing).

Case Summary: The patient presented with recurrent syncope, frequent ventricular ectopics, and reduced left ventricular ejection fraction. Cardiac MRI revealed biventricular dysfunction and nonischemic late gadolinium enhancement with ring-like pattern.

Gamma-glutamyltransferase independently predicts mortality and heart failure hospitalization in cardiac transthyretin amyloidosis.

Background: Transthyretin cardiac amyloidosis (ATTR-CA) is a leading cause of heart failure (HF). Although transthyretin is synthesized in the liver, overt liver disease is uncommon in ATTR-CA. We characterised hepatic involvement in patients with ATTR-CA, and identified the correlates and prognostic value of elevated gamma-glutamyl transferase (GGT), the most prominently deranged biomarker.

PET and Cardiac Amyloidosis: Which Possible Role?

PET has recently demonstrated promising capabilities in the diagnosis and differentiation of various forms of CA. Tracers labeled with 18F, such as 18F-flutemetamol, 18F-florbetapir, and 18F-florbetaben, are being increasingly researched due to their extended half-life, eliminating the requirement for on-site cyclotrons. Unlike bone tracers, PET amyloid-binding tracers exhibit a higher affinity for light-chain fibrils, potentially enabling accurate differentiation between various types of CA.

Current and emerging treatment options for transthyretin amyloid cardiomyopathy.

Transthyretin amyloidosis (ATTR) is a condition caused by TTR protein misfolding and amyloid deposition, particularly in the heart and nervous system, leading to organ dysfunction. Advances in therapeutic strategies have revolutionised the management of ATTR amyloidosis. Treatments available in clinical practice include TTR stabilisers (tafamidis and acoramidis), which prevent the dissociation of TTR tetramer into monomers and oligomers that subsequently form amyloid fibrils, and gene-silencing therapies (patisiran, inotersen and vutrisiran), which suppress the hepatic synthesis of TTR, which is the amyloid precursor protein.

Ischemic Heart Disease in Liver Transplant Candidates With High Bleeding Risk: Any Way Out?

Coronary artery disease in candidates for liver transplantation is a real challenge because of the need to balance the risks of bleeding and thrombosis. Antiplatelet therapy, essential to prevent thrombotic events, may increase the risk of hemorrhagic complications, especially in the context of hepatic surgery. A 71-year-old woman with end-stage liver disease (ESLD) presented for a pretransplantation evaluation.

Change in prevalence of ATTR variants in Italy - Results from a National Survey.

Introduction: Hereditary transthyretin amyloidosis (ATTRv) is a rare, heterogenous, inherited disorder caused by over 130 gene mutations. Its prevalence was estimated to 4.33/million in 2020 in Italy.

ANMCO position paper 'Hypertrophic cardiomyopathy: from diagnosis to treatment'.

Hypertrophic cardiomyopathy (HCM) is a non-rare genetic cardiomyopathy, with an estimated prevalence of 1:500, characterized by an increase in the left ventricular wall thickness in the absence of increased loading conditions. The hypertrophy is mostly asymmetric and predominantly affects the basal septum and anterior wall. Left ventricular outflow tract obstruction, at rest or after provocative tests, is detected in many patients and represents the primary cause of reduced functional capacity, as well as an independent predictor of sudden cardiac death and advanced heart failure.

[ANMCO Position paper: Hypertrophic cardiomyopathy: from diagnosis to treatment].

Hypertrophic cardiomyopathy (HCM) is a non-rare genetic cardiomyopathy, with an estimated prevalence of 1:500, characterized by an increase in the left ventricular wall thickness in absence of increased loading conditions. The hypertrophy is mostly asymmetric and predominantly affects the basal septum and anterior wall. Left ventricular outflow tract obstruction, at rest or after provocative tests, is detected in many patients and represents the primary cause of reduced functional capacity, as well as an independent predictor of sudden cardiac death and advanced heart failure.

[Management of cardiac amyloidosis in Italy: a national survey of the Italian Cardiac Amyloidosis Network (RIAC)].

Background: The national survey of the SIC-ANMCO Amyloidosis Centers was designed to create a geographical mapping of the centers that identify and follow patients with cardiac amyloidosis in Italy and to describe their diagnostic capabilities and multidisciplinary organization.

Methods: The survey was administered to 212 centers in Italy. Among them, 153 centers responded (72%), 31/35 (89%) of which were academic medical centers and 122/177 (69%) hospitals.

Late gadolinium enhancement dispersion for predicting malignant arrhythmic events in patient with non-ischaemic dilated cardiomyopathy.

Aims: Arrhythmic risk stratification in patients with non-ischaemic dilated cardiomyopathy (DCM) remains challenging. The LGE-dispersion mapping is a novel method for the quantification of tissue heterogeneity through the Global Dispersion Score (GDS). We sought to evaluate the usefulness of GDS in arrhythmic risk stratification of DCM patients.

Right ventricular strain predicts outcome in patients receiving sacubitril/valsartan: A sub-analysis of DISCOVER-ARNI.

Aims: Angiotensin receptor/neprilysin inhibitors (ARNI) have emerged as a pivotal medical treatment considerably improving the clinical outcome of patients with heart failure and reduced ejection fraction (HFrEF). Identifying individuals who stand to benefit the most from ARNI could markedly enhance patient management strategies. The aim of this sub-analysis of DISCOVER-ARNI register was to evaluate the prospective prognostic significance of speckle tracking echocardiography (STE) parameters in patients undergoing ARNI therapy.

Etiological Treatment of Cardiac Amyloidosis: Standard of Care and Future Directions.

Purpose Of Review: Cardiac amyloidosis (CA) is a condition caused by interstitial infiltration of misfolded proteins structured into amyloid fibrils. Transthyretin (ATTR) and immunoglobulin light chain (AL) amyloidosis represent the most common forms of CA. CA was traditionally perceived as a rare and incurable disease, but diagnostic and therapeutic advances have undermined the conventional paradigm.

Echocardiographic Estimate of Pulmonary Capillary Wedge Pressure Improves Outcome Prediction in Heart Failure Patients With Reduced and Mildly Reduced Ejection Fraction.

Background: An echocardiographic algorithm to estimate pulmonary capillary wedge pressure (ePCWP) and pulmonary vascular resistance (ePVR) has been recently validated versus right heart catheterization.

Objective: To assess the prognostic significance of these measures in heart failure (HF) patients with reduced and mildly reduced ejection fraction.

Methods: Consecutive outpatients with HF and left ventricular ejection fraction (LVEF) <50% undergoing echocardiography were selected and followed up for the composite end point of all-cause death or HF hospitalization.