Efficacy of Tafamidis in Transthyretin Amyloid Cardiomyopathy in the ATTR-ACT Trial
Publication date: September–October 2019Source: Heart &Lung, Volume 48, Issue 5Author(s): BackgroundTransthyretin cardiomyopathy (ATTR-CM) is an underdiagnosed, fatal disease caused by the deposition of transthyretin amyloid fibrils in the heart leading to heart failure (HF). It can be hereditary due to mutations in the TTR gene (ATTRm) or acquired (wild-type [ATTRwt]). Tafamidis is a selective transthyretin stabilizer which prevents tetramer dissociation and amyloidogenesis. The Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) was an international, multicenter, double-blind, placebo-controlled, randomized trial of Tafamidis in patients with ATTR-CM.ObjectivesGiven the limited number of patients with ATTR-CM, a novel study design was utilized to enable rigorous testing of the efficacy of tafamidis on hard cardiovascular (CV) endpoints in a study of relatively modest size compared with traditional CV trials. The primary results of this trial were further supported through the application of pre-specified sensitivity analyses.MethodsPatients with ATTR-CM were randomized (2:1:2) to tafamidis (80 mg or 20 mg of tafamidis meglumine), or placebo (orally, once daily), for 30 months. Enrollment was stratified by NYHA class and genotype. The primary efficacy analysis was a hierarchical combination of all-cause mortality and frequency of CV-related hospitalizations comparing the pooled tafamidis groups (20 mg and 80 mg) vs. the placebo group using the Finke...
ConclusionsBy utilizing and inclusion/exclusion criteria, setting limits on the frequency a patient is allowed to ambulate and creating a protocol to ensure a controlled setting, patients with PACs can safely ambulate without monitoring the PA waveforms. The use of a standard dressing and immobilization technique prevents catheter dislodgement during ambulation. By increasing physical activity, patients will gain strength to help prevent deconditioning during prolonged hospitalizations
CONCLUSIONS: These results demonstrate that patients with LMNA-related cardiomyopathy are characterized by VTs refractory to RFCA probably because of the deep intramural focus at the basal ventricular septum, resulting in poor prognosis with progressive severe heart failure despite all available optimized therapies. Thus, we should consider heart transplantation in their early 50s when several VT events begin to occur. PMID: 31060954 [PubMed - as supplied by publisher]
Systolic heart failure (HF) is a progressive disease characterized by adverse remodeling from ischemia (ischemic cardiomyopathy, ICM) or a multitude of other causes termed non-ischemic cardiomyopathy (NICM). To accurately characterize the myocardial transcriptome in advanced HF using RNA-sequencing (RNAseq) and identify gene signatures that predict HF phenotypes.
Occasionally new onset cardiomyopathy patients (pts) present late, in such advanced disease stage that they cannot tolerate heart failure (HF) drug therapy. We investigated the cardiac recovery (CR) potential following a combination of left ventricular assist device (LVAD) and guideline-directed HF drug therapy in this medication-naive population.
Noncompaction cardiomyopathy (NCC) results as an arrest of the myocardial compaction process in the embryonic period, leading to the impaired formation of the microvasculature. Myocardial perfusion abnormalities have already been described, however, the functional impact in NCC patients remains undefined. We sought to analyze a potential correlation between myocardial ischemia and heart failure progression in patients with NCC.
Transthyretin amyloid cardiomyopathy (ATTR-CM), an underdiagnosed, fatal disease caused by the deposition of transthyretin amyloid fibrils in the heart leading to heart failure, can be hereditary, due to mutations in the transthyretin gene, or wild-type. Tafamidis, a selective transthyretin stabilizer which prevents tetramer dissociation and amyloidogenesis, was recently shown to be an effective treatment for ATTR-CM patients in the international, multicenter, double-blind, placebo-controlled, randomized, Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT).
In this study, we tested the hypothesis that children and adults with DCM and heart failure (DCM/HF) display different plasma peptide biomarker profiles.
Cardiac amyloidosis causes significant morbidity and mortality, leading to restrictive cardiomyopathy, heart failure, and death. Many patients are diagnosed late when irreversible amyloid fibril deposition has occurred. Heart transplantation may be considered in such patients. Historically, heart transplant outcomes were worse in cardiac amyloid patients compared with other types of heart failure, in part due to the systemic nature of the disease. However, effective therapies, particularly for light chain (AL) amyloidosis, have emerged, and disease remission is now possible.
Patients with muscular dystrophy may have an associated cardiomyopathy, resulting in advanced heart failure requiring transplantation. However, the skeletal muscle dysfunction can result in respiratory impairment, dysphagia, and inability to participate in rehabilitation after heart transplantation. The purpose of this study was to describe the characteristics and outcomes of muscular dystrophy patients undergoing heart transplantation at our center.
Peripartum cardiomyopathy (PPCM) is a rare, but serious and potentially life-threatening condition. The nursing hormone Prolactin has been hypothesized as potential pathogenic factor of PPCM. Positive family history could be a reason for genetically caused peripartum heart failure that has possibly been demasked by the physiological pregnancy stress in a subset of patients. From animal models mutations in STAT3 may be involved in these genetic forms of PPCM.