Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS): A Pilot Study

心肌病 (PAPS) 室性早搏抑制的前瞻性评估：初步研究

• 批准号: 9750791
• 负责人: Teresa De Marco
• 金额: $ 16.61万
• 依托单位: RICHMOND INSTITUTE FOR VETERANS RESEARCH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9750791
• 关键词: Ablation; Admission activity; Adverse event; Affect; Anti-Arrhythmia Agents; Arrhythmia; Blinded; Cardiac; Cardiomyopathies; Cessation of life; Cicatrix; Clinical; Clinical Research; Clinical Trials; Development; Diagnosis; Drops; Electrocardiogram; Enrollment; Functional disorder; Health; Health Care Costs; Healthcare; Heart failure; Holter Electrocardiography; Intention; Left Ventricular Ejection Fraction; Life Expectancy; Medical; Methods; Morbidity - disease rate; Multi-Institutional Clinical Trial; Multicenter Studies; Observational Study; Outcome; Participant; Patients; Pharmaceutical Preparations; Pharmacotherapy; Physicians; Pilot Projects; Population; Prevalence; Procedures; Prospective Studies; Quality of life; Radiofrequency Interstitial Ablation; Randomized; Randomized Clinical Trials; Research Design; Research Methodology; Resources; Rest; Retrospective Studies; Risk; Symptoms; Testing; Treatment Protocols; Treatment Side Effects; Ventricular Premature Complexes; active method; design; experience; follow-up; functional status; heart function; improved; improved functioning; interdisciplinary approach; mortality; multidisciplinary; outcome forecast; patient population; prospective; randomized trial; response; treatment group; treatment strategy; trial comparing

Premature ventricular contractions (PVCs) coexist in patients with heart failure (HF) and LV dysfunction. Frequent PVCs have shown to induce a reversible cardiomyopathy (PVC-CM). Yet, it is unclear why some patients develop PVC-CM, while others do not. Retrospective and observational studies have shown improvement of LV function after PVC suppression via radiofrequency ablation (RFA). Thus, appropriate diagnosis and treatment of patients with PVC-CM is believed to carry significant benefits, improving quality of life (QOL), HF symptoms / admissions and life expectancy. Currently, these patients are offered RFA, antiarrhythmic drugs (AADs) or no treatment depending on physician’s experience and resources. Thus, there is clear need for a large clinical trial comparing these treatment strategies. Yet, we need to better understand prevalence of PVC-CM, feasibility and limitations of such a trial. The long-term objectives of this study are to: 1) identify the best treatment strategy to suppress PVCs and improve PVC-CM, 2) compare the clinical benefits (quality of life, HF symptoms / admissions and adverse events) between RFA and AADs, and 3) identify patients and PVC features that predispose to the development of PVC- CM. The specific aims of the proposed pilot study include: 1) estimate the prevalence of PVC-CM in population receiving Holter monitors and 2) assess the feasibility and better design and power of a full scale large randomized study. We hypothesize that RFA has significant clinical benefits, besides improvement in CM with better outcomes and lower complications at 1 year when compared to AADs. Our pilot study hypothesizes that the prevalence of PVC-CM is underestimated and conducting a large randomized trial is feasible. Research Design and Methods. We propose to screen 20,000 consecutive ambulatory ECG Holter monitors of all participating centers to identify all patients with probable diagnosis of PVC-CM (PVC burden >10% and LVEF <45%). In addition, we will conduct a clinical pilot study, enrolling 30 patients with frequent PVCs (burden >10%) and CM (LVEF <45%) and randomize them to either: 1) RFA or 2) AADs. Prior to treatment, all patients will undergo a baseline cardiac MR and be allowed a 3-month observation period (optimal HF medical therapy). We plan to follow change in LV function/scar, PVC burden/arrhythmias and clinical/functional status (QOL, HF symptoms and admissions, NYHA class) and adverse events throughout the observation period and compare with PVC suppression strategies (RFA or AAD). Similar comparison will be made between RFA and AAD treatment groups during a 12-month follow up using a Prospective Randomized Open, Blinded End-point (PROBE) study design. The treatment regimens will be compared in an intention-to-treat analysis. This pilot study is intended to estimate the prevalence of this clinical entity and pave the way for a large full scale randomized trial to identify best treatment strategy for patients with PVC-CM. Treating and reversing this underestimated PVC-CM may improve patient’s health and subsequently decrease HF healthcare spending.

室性早搏（PVC）在心力衰竭（HF）和LV功能障碍患者中共存。 频繁的PVC已被证明可诱导可逆性心肌病（PVC-CM）。目前尚不清楚为什么有些人 患者发生PVC-CM，而其他人则不会。回顾性和观察性研究表明， 通过射频消融（RFA）抑制PVC后LV功能改善。因此，适当 PVC-CM患者的诊断和治疗被认为具有显著的益处， 寿命（QOL）、HF症状/入院和预期寿命。目前，这些患者被提供RFA， 抗抑郁药（AAD）或不治疗，这取决于医生的经验和资源。因此 显然需要进行一项大型临床试验来比较这些治疗策略。然而，我们需要更好地理解 PVC-CM的患病率，这种试验的可行性和局限性。 本研究的长期目标是：1）确定抑制PVC的最佳治疗策略， 改善PVC-CM，2）比较临床获益（生活质量、HF症状/入院和不良事件） RFA和AAD之间的差异，以及3）识别易发生PVC的患者和PVC特征- 厘米拟议的试点研究的具体目标包括：1）估计PVC-CM的患病率， 接受霍尔特监测的人群; 2）评估全量表的可行性、更好的设计和功效 大型随机研究。我们假设RFA除了改善CM外，还具有显著的临床获益 与AAD相比，1年时的结局更好，并发症更低。我们的初步研究假设 PVC-CM的患病率被低估，进行大型随机试验是可行的。 研究设计和方法。我们建议筛查20，000例连续动态心电图霍尔特 所有参与中心的监查员，以识别可能诊断为PVC-CM的所有患者（PVC负荷>10%） LVEF <45%）。此外，我们将开展一项临床试点研究，招募30名频繁发生PVC的患者 （负荷>10%）和CM（LVEF <45%），并将其随机分配至：1）RFA或2）AAD。治疗前，所有 患者将接受基线心脏MR，并允许3个月的观察期（最佳HF医疗 治疗）。我们计划随访LV功能/瘢痕、PVC负荷/心律失常和临床/功能状态的变化 (QOL，HF症状和入院，NYHA分级）和整个观察期内的不良事件， 与PVC抑制策略（RFA或AAD）进行比较。将在RFA和 使用前瞻性、随机、开放、设盲终点的12个月随访期间AAD治疗组 （PROBE）研究设计。将在意向治疗分析中比较治疗方案。 这项试点研究旨在估计这种临床实体的患病率，并为大规模的全面研究铺平道路。 规模随机试验，以确定PVC-CM患者的最佳治疗策略。治疗和逆转这一点 被低估的PVC-CM可以改善患者的健康，并随后降低HF医疗保健支出。