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).

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.

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.

How to facilitate seamless translation from basic concepts to new heart failure drugs. A scientific statement of the Heart Failure Association of the ESC.

A rift has opened and is widening between basic research (bench) and clinical research and patients (bed) who need their new treatments, diagnostics and preventive strategies. This problem involving the 'translation' of basic scientific findings into clinical applications and potential treatments or biomarkers for a condition like heart failure is widely recognized both in academia and industry. Despite the attempts that have been made by both sides to improve this situation, the high attrition rates of drug development and the problem with reproducibility and translatability of preclinical findings to human applications still persist.

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.

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.

High-Sensitivity Cardiac Troponin I for Risk Stratification in Wild-Type Transthyretin Amyloid Cardiomyopathy.

Background: Thresholds to define prognosis with hs-cTnI (high-sensitivity cardiac troponin I) have not been systematically addressed in wild-type transthyretin amyloid cardiomyopathy, in part because of the multiplicity of hs-cTnI assays. The aims of this study were: first, to assess the prognostic performance of hs-cTnI measured with different assays in patients with wild-type transthyretin amyloid cardiomyopathy and, second, to identify assay-specific hs-cTnI thresholds for prognosis that could be integrated into staging systems for risk stratification.

Methods: Observational multicenter study of stable wild-type transthyretin amyloid cardiomyopathy patients from different cohorts using the Abbott Architect Stat hs-cTnI assay and the Beckman Coulter Access hs-cTnI assay (testing cohorts) and the Siemens Centaur XPT hs-cTnI assay (validation cohort).

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.

Arrhythmic risk prediction in non-dilated left ventricular cardiomyopathy: The role of overlap with arrhythmogenic cardiomyopathy.

Background: Non-dilated left ventricular cardiomyopathy (NDLVC) has been defined as non-ischemic LV scarring or fatty replacement regardless of global or regional wall motion abnormalities, or isolated global LV hypokinesia without scarring. We evaluated the arrhythmic risk in NDLVC and assessed the prognostic value of overlapping features with arrhythmogenic cardiomyopathy (ACM).

Methods: All patients who underwent cardiovascular magnetic resonance (CMR) scan and genetic testing between 2012 and 2022 and met the diagnostic criteria for NDLVC were selected.

Arrhythmic Risk Stratification and Sudden Cardiac Death Prevention in Duchenne Muscular Dystrophy: A Critical Appraisal.

Duchenne muscular dystrophy (DMD) is a genetic progressive neuromuscular disorder characterized by early-onset proximal muscle weakness and significant long-term pulmonary and cardiac involvement. Due to the early pharmacological treatments and the wider adoption of non-invasive ventilation, life expectancy has significantly increased in recent years, highlighting the relevance of DMD-related cardiomyopathy and fatal arrhythmias, especially in the late stage of the disease. Current guideline-derived evaluation of sudden cardiac death (SCD) in DMD lacks accuracy, leading to inadequate arrhythmic risk stratification and jeopardized SCD prevention strategies.

Cardiac Amyloidosis: Role of the Endomyocardial Biopsy.

Amyloidosis is characterized by protein misfolding and extracellular deposition of insoluble beta-sheet fibrils. It represents a heterogeneous disease with different aetiologies and clinical manifestations. Cardiac involvement (ie, cardiac amyloidosis) has an adverse prognosis, early diagnosis and amyloid typing being crucial for treatment.

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.

Cardiac Amyloidosis: How Its Epidemiology is Changing.

Cardiac amyloidosis (CA) encompasses a group of disorders characterized by an abnormal accumulation of amyloid fibrils in the heart, leading to impaired cardiac function and ultimately heart failure. While the incidence of immunoglobulin light chains amyloidosis incidence seems stable at 8 to 15.2 cases per million persons (PMP)/year, the incidence and prevalence of wild type transthyretin-CA are steadily increasing, being currently estimated at 14 to 27 cases PMP/year and 30 to 170 cases PMP, respectively.

Cardiac amyloidosis: Innovations in diagnosis and treatment.

Cardiac amyloidosis (CA) is a progressive, underdiagnosed condition caused by the deposition of misfolded proteins in the myocardium, forming amyloid fibrils that impair cardiac structure and function. This review highlights recent advances in the diagnosis and treatment of amyloid light-chain (AL) and transthyretin (ATTR) CA, which globally account for most cases of CA. Novel diagnostic tools, including artificial intelligence-enhanced analysis and advanced imaging modalities like positron emission tomography with amyloid-specific tracers, might improve detection rates and diagnostic accuracy to enable non-invasive subtype differentiation.

Positron emission tomography in cardiac amyloidosis: current evidence and future directions.

The increasing recognition of cardiac amyloidosis (CA) as a cause of heart failure, coupled with advancements in therapeutic options, has underscored the need for early detection. Positron emission tomography (PET) imaging emerged as a promising non-invasive tool for diagnosing and managing CA. This review provides a comprehensive analysis of current PET imaging techniques, focusing on radiotracers, including [C]Pittsburgh Compound B, [F]Flutemetamol, [F]Florbetapir, [F]Florbetaben, [F]-sodium fluoride, and [I]Evuzamitide.

Cardiac amyloidosis: when to suspect and how to confirm.

Diagnosing cardiac amyloidosis (CA) is challenging because of its phenotypic heterogeneity, multiorgan involvement requiring interaction among experts in different specialties and subspecialties, lack of a single noninvasive diagnostic tool, and still limited awareness in the medical community. Missing or delaying the diagnosis of CA may profoundly impact on patients' outcomes, as potentially life-saving treatments may be omitted or delayed. The suspicion of CA should arise when "red flags" for this condition are present, together with increased left ventricular wall thickness.

Clinical Phenotype and Prognosis of Asymptomatic Patients With Transthyretin Cardiac Amyloid Infiltration.

Importance: Patients with transthyretin (ATTR) cardiac amyloid infiltration are increasingly diagnosed at earlier disease stages with no heart failure (HF) symptoms and a wide range of cardiac amyloid infiltration.

Objective: To characterize the clinical phenotype and natural history of asymptomatic patients with ATTR cardiac amyloid infiltration.

Design, Setting, And Participants: This cohort study analyzed data of all patients at 12 international centers for amyloidosis from January 1, 2008, through December 31, 2023.

Prevalence and functional impact of chronotropic incompetence in amyloid cardiomyopathy: a multicentre analysis.

Background: Little evidence is available about heart rate (HR) response to exercise as well as its relationship with functional capacity in amyloid cardiomyopathy. Then, in a multicentre cohort of patients with amyloid cardiomyopathy, we investigated the prevalence of chronotropic incompetence (CI) and its relationships with cardiopulmonary exercise testing (CPET) variables.

Methods: Data from 172 outpatients with amyloid cardiomyopathy who performed a maximal CPET and who had no significant rhythm disorders were analysed.