Cardiac Contractility Modulation Therapy in Amyloid Cardiomyopathy Patients With Heart Failure With Mid-range Ejection Fraction: a Multicentre Registry
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Composite of occurrence of hospitalizations due to worsening of heart failure and/or acute intravenous administrations of diuretics or inotropic drugs over the 12 months after entry into the registry.
研究概览
简要总结
The primary aim of this observational registry is to evaluate the efficacy of CCM in patients with heart failure with mid-range or reduced EF and diagnosis of TTR amyloidosis. The efficacy will be evaluated in terms of composite of occurrence of heart failure-related hospitalizations and/or acute intravenous interventions (IVI) at 12-month follow up compared to those reported 12 months before CCM implantation. Among the secondary endpoints, clinical functional status, quality of life, drug changes and Echocardiographic parameters will be evaluated and compared from baseline to follow up.
详细描述
Amyloidosis represents a group of human degenerative diseases characterized by the deposition of aggregates of abnormally folded proteins in single or multi-organs. Cardiac amyloidosis is primarily associated with the systemic production and release of a number of amyloidogenic proteins, notably immunoglobulin light chain proteins (also known as amyloid light chain or AL) or transthyretin proteins (TTR). Notably, although myocardial dysfunction is generally understood as a result of infiltration by extracellular amyloid deposits, there is experimental evidence of direct cytotoxic effect, possibly due to oxidative stress.
Since neither HF optimal medical therapy nor HF devices seems to have a clear benefit in amyloid cardiomyopathy, this clinical setting needs to test other therapeutic options.
Randomized clinical trials have shown that Cardiac contractility modulation (CCM) may be considered as a concrete therapeutic option in patients with symptomatic Heart Failure (HF) despite optimal medical therapy (OMT), with Left Ventricular Ejection Fraction (LVEF) between 25% and 45%, with narrow QRS complex (<130ms).
CCM signal treatment reverses the cardiac maladaptive fetal gene program and normalizes expression of key sarcoplasmic reticulum Ca2+ cycling and stretch response genes. Specifically, 3-month on CCM therapy resulted in decreased expression of A- and B-type natriuretic peptides, p38 mitogen activated protein kinase (MAPK) and p21 Ras and increased expression of α-MHC, SERCA-2a, phospholamban, and ryanodine receptors. Notably, pre-clinical data suggest that triggering p38α MAPK autophosphorylation plays a crucial role in amyloidogenic light-chain mediated cellular oxidative stress, dysfunction and ultimately cell death in cardiomyocytes. Therefore CCM mechanism of action could be beneficial in cardiac amyloidosis but there are no data in this specific clinical setting.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years or older
- •Male or a nonpregnant female
- •All of the following: Established diagnosis of amyloid TTR Cardiomyopathy; baseline ejection fraction ≥25% and ≤45%; at least one hospitalization due to worsening heart failure over the year before entry into the registry.
- •ICD if indicated
- •PM if indicated
- •Willing and able to return for all follow-up visits
排除标准
- •AL amyloid cardiomyopathy
- •Subjects who have a potentially correctible cause of heart failure (eg, Ischemic or valvular or congenital heart disease).
- •Scheduled for CABG or PCI or has undergone a CABG within 90 d or PCI within 30 d.
- •Myocardial infarction within 90 days
- •Mechanical tricuspid valve
- •Prior heart transplant
- •Chronic haemodialysis
- •Familial TTR amyloidotic cardiomyopathy with significant polyneuropathy potentially eligible for Patirisan or Inotersen17
- •Unable to provide informed consent
结局指标
主要结局
Composite of occurrence of hospitalizations due to worsening of heart failure and/or acute intravenous administrations of diuretics or inotropic drugs over the 12 months after entry into the registry.
时间窗: 12-month
The occurrence of any of the events mentioned (worsening of heart failure or intravenous intervention) involves reaching the endpoint
次要结局
- NYHA class(12-month)
- Echocardiographic parameters (Ejection Fraction)(12-month)
- Echocardiographic parameters (End diastolic volume and End systolic volume)(12-month)
- Distance walked at the 6-minute walking test(12-month)
- Biomarker (HS-Troponin)(12-month)
- Occurrence of clinical need to increase oral dose of diuretic drug and/or to add another diuretic drug class(12-month)
- Occurrence of oral dose diuretic drug reduction(12-month)
- Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score(12-month)
- Biomarker (NT-proBNP)(12-month)
研究者
Procolo Marchese
Principal Investigator
Ospedale C & G Mazzoni