Italian Registry on Cardiac Contractility Modulation Therapy
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Exercise tolerance
研究概览
简要总结
The Cardiac Contractility Modulation (CCM) system is a cardiac implantable device indicated for the treatment of patients with symptomatic heart failure with left ventricular systolic dysfunction despite optimal medical and electrical therapy. This system consists of a generator to which two stimulation leads are connected, which are fixed on the interventricular septum and deliver non-excitatory electrical signals during the absolute ventricular refractory period, with the aim of influencing the contractility properties of the myocardium in patients with chronic heart failure. Clinical data indicate that CCM therapy is safe and effective for the treatment of patients with symptomatic heart failure with reduced left ventricular systolic function, in which a significant improvement in quality of life and exercise tolerance has been shown, together with an impact on hospitalizations for heart failure.
This prospective registry includes patients undergoing CCM implantation for the above clinical indications. The inclusion criteria are age over 18; chronic heart failure with reduced left ventricular systolic function (FE ≤ 45%), symptomatic (class NYHA II or greater; class III or greater or II with episodes of acute decompensation for patients with FE 36-45%); presence of appropriate and optimized medical therapy (including beta-blockers and angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers or angiotensin-receptor neprylysin inhibitors and anti-aldosterone agents); narrow QRS (<120 msec) or cardiac resynchronization therapy non-responders; written informed consent for enrollment and participation in the prospective register; life expectancy> 1 year due to the absence of non-cardiac comorbidities that reduce its prognosis; availability of venous access that can be used for the implant. The exclusion criteria are the absence of venous access available for the implant; contraindication to the interventional CCM implant procedure; life expectancy of less than one year due to non-cardiovascular comorbidities.
The aim of this multicenter, prospective, observational registry is to investigate the impact of CCM on the medium and long-term on clinical and functional characteristics of the enrolled patients at the end of the follow-up, with respect to the baseline value: NYHA class, 6-minute walk test, ejection fraction and volumes of the left ventricle, quality of life expressed through a specific questionnaire (Minnesota Living With Heart Failure Questionnaire, MLWHF), hospitalizations for heart failure or progression of the underlying heart disease. In addition, the survival of patients undergoing CCM device implantation will be assessed in an observational manner at 24 months and then annually.
In addition, adverse events related to the device implantation procedure or to CCM therapy are collected in the registry as a safety parameter. In the case of patients undergoing heart transplantation or LVAD implantation, or in the event of interruption of therapy or explantation of a device, the information will be recorded with the motivation for discontinuing treatment.
Clinical follow-up includes follow-up assessments at 3 months, 6 months, 12 months and every 6 months thereafter. Each clinical follow-up visit includes objective examination, ECG, device function check, administration of an MLWHF quality of life questionnaire, a 6-minute walk test (or cardiopulmonary exercise test) and pharmacological therapy assessment and optimization. Furthermore, during the follow-up visits at 3 months, 12 months and every 12 months thereafter, a transthoracic echocardiogram and blood chemistry tests are scheduled.
This multicenter observational prospective registry therefore aims to assess the long-term clinical impact of CCM in patients suffering from symptomatic heart failure with moderately or severely impaired systolic function. In particular, it will allow to evaluate the impact on functional capacity, symptoms and quality of life, hospitalizations, survival and device-related complications, with the aim of defining the role of CCM therapy in management of patient with heart failure with reduced left ventricular systolic function.
详细描述
Introduction The Cardiac Contractility Modulation (CCM) system is a cardiac implantable device indicated for the treatment of patients with symptomatic heart failure with left ventricular systolic dysfunction despite optimal medical and electrical therapy.
This system consists of a generator to which two stimulation leads are connected, which are fixed on the interventricular septum and deliver non-excitatory electrical signals during the absolute ventricular refractory period, with the aim of influencing the contractility properties of the myocardium in patients with chronic heart failure. The generator of the device is rechargeable, and the patient is equipped with a special charger, while the device can be interrogated through a special programmer.
Currently available studies indicate that CCM therapy is safe and effective for the treatment of patients with symptomatic heart failure with reduced left ventricular systolic function despite appropriate and optimized medical therapy. Based on data available from clinical studies, the application of CCM signals to the heart during the absolute refractory period can increase the contraction force of the myocardium. In particular, a significant improvement in quality of life and exercise tolerance has been reported (highlighted by the improvements in the 6-minute walking test and in the peak of VO2 in the cardiopulmonary exercise test), together with a potential impact on hospitalizations for heart failure and survival. In addition, CCM therapy reverses the characteristics of left ventricular remodeling typical of decompensation and improves left ventricular contractile reserve. These effects are the result of a chain of intracellular molecular processes, some of which become evident within a few seconds after starting the CCM. For example, CCM signals have been shown to normalize the phosphorylation of regulatory proteins such as phospholamban in vitro within a few seconds of treatment. This rapid effect triggers a series of molecular events which result in the restoration of cellular function and in the acute improvement of contractile force. On the long term, there is a progressive normalization of the abnormal expression of the fetal gene program characteristic of heart failure and a progressive reduction of the end-diastolic volume with an increase in the ejection fraction of the left ventricle. These effects on intracellular signaling mechanisms also extend to regions of the ventricle far from the impulse delivery area.
The prospective register This prospective registry includes patients undergoing CCM implantation for the presence of heart failure with reduced left ventricular systolic function (EF < 45%) who are symptomatic despite optimal pharmacological and electrical therapy. The clinical trial study (prospective registry) will be conducted in accordance with this protocol, with the Helsinki Declaration and with the favorable opinion of the local Ethics Committee of the participating Centers Full detailed inclusion and exclusion criteria are reported in the specific section.
Aim of the study This prospective observational register is intended to collect data uniformly on patients treated with CCM. The data will be used to evaluate the medium and long-term clinical and instrumental effects on patients treated with CCM therapy and will have a purely scientific value.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •chronic heart failure with reduced left ventricular systolic function (EF ≤ 45%), symptomatic (class NYHA III or greater; or class II with previous episodes of acute decompensation for patients with FE 36-45%);
- •presence of appropriate and optimized medical therapy, including: beta-blocker and angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker or angiotensin-receptor neprylysin inhibitor and anti-aldosterone agent, titrated as tolerated by the patients;
- •narrow QRS (<120 msec) or cardiac resynchronization carriers with documented non-response to this treatment;
- •age above 18 years;
- •written informed consent for enrollment and participation in the prospective register.
排除标准
- •life expectancy < 1 year due to non-cardiac comorbidities that reduce the prognosis;
- •absence of vascular access that can be used for the implant;
- •other contraindications to the CCM implantation procedure (e.g. active infective processes, active severe coagulopathies);
- •refusal to be enrolled in the registry.
结局指标
主要结局
Exercise tolerance
时间窗: 24 months
6-minute walking test distance (meters)
Functional class
时间窗: 24 months
NYHA (New York Heart Association) class (range I-IV; IV means worse outcome)
Quality of life measured by Minnesota Living With Heart Failure questionnaire
时间窗: 24 months
Minnesota Living With Heart Failure questionnaire score (scale 0-105; high scorse mean worse outcome)
次要结局
- Hospitalizations(24 months)
- Left ventricular systolic function(24 months)
- Left ventricular volume(24 months)
研究者
Mario Matta
M.D.
S. Andrea Hospital