Exercise Training and Rehabilitation In Cardiac Amyloidosis
- Conditions
- Cardiac Amyloidosis
- Interventions
- Other: Exercise training (ET1+ET2)Behavioral: Optimal Medical Therapy (No-ET)
- Registration Number
- NCT06412432
- Lead Sponsor
- Federico II University
- Brief Summary
Notwithstanding the dramatic improvement associated with Tafamidis in Heart Failure (HF) due to wild-type transthyretin cardiac amyloidosis (ATTRwt-CA), remarkable morbidity and mortality still burden this disease. Exercise training (ET) is a first-line recommended treatment for unselected HF patients, whose effects on ATTRwt-CA form remain however unexplored. The investigators hereby present rationale and design of the Exercise training and Rehabilitation in Cardiac Amyloidosis (ERICA) study, whose aim is to determine whether a tailored, supervised ET program might improve exercise capacity in HF due to ATTRwt-CA. This interventional, controlled study will randomize ATTRwt-CA patients into a control group (C) and a primary training group (ET-1). After 12 weeks, patients in group C will be offered to undergo the same ET program (ET-2) for further 12 weeks, considering the last observation as baseline. Primary endpoint will be the distance obtained at the 6-minute walk test (6MWD) performed at baseline and after 12-weeks of treatment in pooled ET-1 and ET-2 groups compared to C. Quality of life, peak oxygen consumption, left and right heart architecture and function, natriuretic peptides will be secondary endpoints. This study will be the first testing the effects of ET in patients with ATTRwt-CA.
- Detailed Description
Among Systemic amyloidosis, the peculiar deposition of beta-amyloid fibrils agglomerates localized in the interstitial space between the cardiomyocytes characterizes the spectrum of cardiac amyloidosis (AC). All AC phenotypes culminate in a progressive deterioration of cardiac compliance up to a true infiltrative cardiomyopathy with restrictive physiology. Clinical presentation may vary from mildly symptomatic Heart Failure (HF), usually labeled, and mistakenly confused as a classic Heart Failure with preserved ejection fraction (HFpEF) up to a severe scenario of severe cardiac decompensation with fluid overload, marked shortness of breath, fatigue and orthostatic hypotension. Syncope may also appear due to infiltration in the conduction system leading to sinoatrial disease and atrioventricular block. To date, more than 30 proteins responsible for the deposition of fibrils have been identified and of these 9 have been identified as responsible for the cardiac involvement of the disease. AC is determined in 98% of cases by the accumulation of monoclonal light chains of immunoglobulins (AL) or transthyretin (ATTR); the latter can occur either in its hereditary form (ATTRv) or in the wild-type variant (ATTRwt). Although AC is perceived as a rare disease, standing a reported prevalence of around 1/100,000 inhabitants, a recent metanalysis reported AC as underlying HF cause in 13.7% of cases, varying from 15.1% of Heart Failure (HF) with preserved ejection fraction (HFpEF) and 11.3% in reduced fraction phenotype (HFrEF). This mismatch begets the hypothesis that AC is often underdiagnosed, probably due to its challenging diagnosis, the diverse spectrum of clinical presentation ranging from severely compromised clinical cases to rather silent manifestations, and the absence of specific therapies for this condition making until a few years ago AC a true orphan disease. This paradigm has been subverted in recent years, by the emergence of tafamidis, a targeted drug from amyloidosis that binds transthyretin, preventing tetramer dissociation and production of amyloid. Tafamidis has been successfully tested for ATTRwt-AC in a relatively large multicenter, international, double-blind, placebo-controlled, phase 3 trial, the Transthyretin Amyloidosis Cardiomyopathy Clinical Trial (ATTR-ACT), showing a remarkable improvement of the composite outcome of all-cause mortality and hospitalizations due to cardiovascular causes. Apart from Tafamidis, there are no evidence supporting the use of guideline-directed medical therapy (GDMT) used in classical forms of HF in ATTR-ACT. On top of GDMT, exercise training (ET) remains largely uninvestigated in AC. ET consists of a multidisciplinary approach, including a medical evaluation with modification of cardiovascular risk factors, prescription of a physical exercise program and psychosocial evaluation and is currently recommended with the highest degree of recommendation (in class I, type A level) in current guidelines on HF. To date, there are no data about the efficacy and safety of ET in AC, specifically in the ATTRwt-AC. We hereby present the outlines and the study protocol of the Exercise Rehabilitation and training in Cardiac Amyloidosis (ERICA) study, whose aim is to investigate and analyze the safety and the efficacy of cardiac rehabilitation on patients with AC, specifically those affected by the ATTR-wt form. The present study aims to investigate and analyze, through an interventional longitudinal, controlled, randomized, design, the effects of a structured program of Exercise training in patients with ATTRwt-AC.
Recruitment & Eligibility
- Status
- ENROLLING_BY_INVITATION
- Sex
- All
- Target Recruitment
- 34
- Patients aged 18 or older
- Established ATTRwt diagnosis
- Heart Failure diagnosis
- Informed consent according to Italian regulations
- Unstable Angina
- Acutely decompensated Heart Failure within 1 month before enrollment
- Occurrence of complex ventricular arrhythmias
- Presence of intracavitary thrombus
- recent (< 1 year) thrombophlebitis with or without pulmonary embolism
- Severe obstructive cardiomyopathies
- Severe or symptomatic aortic stenosis
- Uncontrolled inflammatory or infectious diseases
- Any musculoskeletal conditions preventing physical exercise
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Exercise training Exercise training (ET1+ET2) Patients will undergo exercise training, nutritional advice, smoking cessation, lipid profile evaluation, control and management of body weight and abdominal circumference; evaluation of the drug therapy in progress; psycho-social evaluation. Controls Optimal Medical Therapy (No-ET) control group who won't undergo exercise training and will be managed with optimal medical therapy
- Primary Outcome Measures
Name Time Method distance obtained at the 6-minute walk test (6MWD) Baseline and after 12-weeks of treatment distance (meters) obtained at the 6-minute walk test (6MWD) performed at baseline and after 12-weeks of treatment treatment in pooled ET-1 and ET-2 groups compared to No-ET.
- Secondary Outcome Measures
Name Time Method Transthyretin serum levels Baseline and after 12-weeks of treatment serum levels (ng/ml)
N terminal pro brain natriuretic peptide (NT-pro BNP) serum levels Baseline and after 12-weeks of treatment serum levels (ng/ml)
Troponin serum levels Baseline and after 12-weeks of treatment serum levels (ng/ml)
Work (Watt) Baseline and after 12-weeks of treatment assessed during Cardiopulmonary exercise test in watt
Adverse Events Baseline and after 12-weeks of treatment Any adverse Event with special focus on Serious Adverse event
Galectin-3 serum levels Baseline and after 12-weeks of treatment serum levels (ng/ml)
Quality of life assessment Baseline and after 12-weeks of treatment Kansas City Questionnaire (ranges 0 to 100 where 100 is the better quality of life score )
Left ventricular ejection fraction (LVEF) Baseline and after 12-weeks of treatment assessed at echocardiography (%)
Left atrial (LA,ml) volume Baseline and after 12-weeks of treatment assessed at echocardiography in ml
global longitudinal strain (GLS) Baseline and after 12-weeks of treatment assessed at echocardiography in %
Tricuspid Annular Plane Systolic Excursion (TAPSE) Baseline and after 12-weeks of treatment assessed at echocardiography in mm
Respiratory efficiency Baseline and after 12-weeks of treatment minute ventilation (VE)/ carbon dioxide (VCO2) slope assessed during Cardiopulmonary exercise test in watt
estimated systolic Pulmonary arterial pressure Baseline and after 12-weeks of treatment assessed at echocardiography in mmHg
Right Ventricular Free-wall Strain (RVFWS) Baseline and after 12-weeks of treatment assessed at echocardiography in %
Myocardial work Baseline and after 12-weeks of treatment assessed at echocardiography in mm Hg%
Peak oxygen consumption (VO2 peak) Baseline and after 12-weeks of treatment assessed during Cardiopulmonary exercise test in mL/(kg·min)
Trial Locations
- Locations (1)
Department of Translational Medical Sciences
🇮🇹Naples, Italy