Last updated on November 2017

PARACHUTE IV Percutaneous Ventricular Restoration in Chronic Heart Failure Due to Ischemic Heart Disease


Brief description of study

PARACHUTE IV Percutaneous Ventricular Restoration in Chronic Heart Failure Due to Ischemic Heart Disease

Detailed Study Description

1.0 INTRODUCTION

CardioKinetix has developed a catheter-based treatment for patients with left ventricular dilation after an anterior MI. The implantable device, called the Parachute Implant, is a partitioning membrane deployed within the compromised ventricle. The Parachute Implant isolates the dysfunctional region of the ventricle and decreases functional chamber volume.

1.1 Myocardial Infarction and Heart Failure

In the majority of HF patients, the clinical syndrome of HF is a result of left ventricular systolic dysfunction (LVSD). Patients with predominant LVSD have a depressed ejection fraction (typically < 40%). The major cause of HF in patients with LVSD is coronary artery disease, which has been found as the underlying etiology in ~70% of the HF patients (1, 2). In large numbers of these patients, LVSD begins with an MI and progresses to HF (3). Presently, there is a known U.S. pool of 7.6 million post MI patients, annually increasing by 1,000,000 patients (4, 5). Despite the introduction of new pharmacological treatments and interventional procedures, the incidence and mortality for post-MI heart failure patients continues to be excessive (6, 7).

1.2 Ventricular Remodeling after Myocardial Infarction The major signs of HF progression after a MI are an increase in the LV volume (LV dilatation) and a change of the LV shape to a more spherical chamber – a process referred to as LV remodeling (8). The consequence of an MI is immediate ventricular dysfunction and the likelihood of rapid infarct expansion (9, 10). Soon after an infarction, the non-perfused myocardial cells stop contracting and many die. This leads to abnormal wall motion, myocardial thinning and an elongation of the affected region, i.e. structural changes in the myocardium (“structural myocardial dysfunction”). LV dilatation after an MI is an initially compensatory mechanism for the preservation of the LV stroke volume. Under these conditions, the LV increases in size while the ejection fraction decreases (11). LV dilatation also increases diastolic and systolic myocardial stress via the Law of Laplace and initiates detrimental remodeling. As a result of increased size and decreased ejection fraction of the LV, mean systolic stress and associated oxygen demand is augmented (8, 11). This self-perpetuating remodeling process results in dilated cardiomyopathy characterized with a large, spherical ventricle, increase in wall stress throughout the ventricle, decrease in ventricular pump function and an increase in filling pressures, all resulting in HF symptoms and ultimately contributing to HF morbidity and mortality.

Post MI remodeling and the symptoms of HF are more common in patients with an anterior infarction (12). The anterior-apical region is a particularly vulnerable region of the LV for dilatation because it is the thinnest and has the greatest curvature (13). When this region undergoes expansion and thinning, even small segmental elongation can greatly increase the radius of curvature resulting in a large stress increase.

In summary, in the U.S., more than 3.6 million patients have post-MI heart failure. In approximately 60% of these patients LV remodeling and HF symptoms occur after an anterior infarct. Therefore, a compelling need exists to provide therapeutic options for the treatment and prevention of LV remodeling and HF after anterior MIs.

1.3 Current Therapies for Heart Failure There are a number of treatment options available to minimize symptoms and somewhat slow disease progression. The combination of lifestyle changes and drug therapy—the foundation of almost all HF treatment regimens—can improve both survival rates and quality of life and is most often initiated in NYHA Class I and Class II patients. Each class of heart failure may warrant a different combination of medications. If drug therapy does not adequately enhance LV function, patients with advanced heart failure may become candidates for other interventions, including surgery and implantable devices.

Conventional Medical Therapies – Medication is the cornerstone of conventional treatment for HF. Studies show that early intervention with medication can slow the progression of HF and relieve symptoms. The mainstays of drug treatment for chronic heart failure are neurohormonal inhibitors and antagonists (angiotensin converting enzyme [ACE] inhibitors, beta-blockers, angiotensin receptor blockers, and aldosterone antagonists) to reduce morbidity and mortality and diuretics to control fluid volume (14).

Cardiac Resynchronization Therapy (CRT) – Approximately 25% of patients with advanced (ischemic) HF have ventricular dysynchrony resulting in a reduction of cardiac output. Patients with advanced HF and ventricular dysynchrony are most likely to benefit from the simultaneous pacing of both right and left ventricles (18, 19). Some CRT devices also provide defibrillation to protect against sudden cardiac death resulting from arrhythmias. In addition, some Implantable Cardiac Defibrillators (ICDs) have a CRT “capacity” and can be used in such patients to provide HF therapy combined with prophylactic treatment of ventricular fibrillation or sudden death.

If medical therapy does not adequately enhance LV function, some patients may also be eligible for surgical therapy of heart failure, with 5 possibilities:

  • Coronary artery bypass surgery to supply more blood flow in ischemic zones when the coronary arterial network lends itself to bypass surgery.
  • Mitral surgery, by repair or replacement, can benefit patients with significant mitral regurgitation due to LV dilatation
  • Left Ventricular Assist Devices (LVADs) – The LVAD improves cardiac output by pumping blood in parallel with the weakened heart chamber. The new portable LVAD units enable some patients to resume some activities after discharge from the hospital (15). Recently, LVADs were approved for so called “destination therapy” as an alternative to heart transplantation in those patients not eligible for a heart transplant procedure (16, 17).
  • Transplant Surgery –For a small percentage of patients with HF, heart transplantation is employed as a lifesaving intervention in patients meeting specific criteria and who are in end-stage HF. These are patients with no other options who meet all of the criteria for transplant surgery. Less than 2,000 heart transplants are performed each year in the US, representing less than 1% of all patients with HF. Other surgeries may be considered if there is comorbidity amenable to concomitant surgical therapy such as Coronary Artery Bypass Grafting (CABG) or mitral valve repair or replacement.
  • Surgical Ventricular Restoration (SVR). Surgical remodeling of the enlarged, poorly functioning left ventricle to a more normal size and shape by inserting a patch into the ventricle and attaching it to the endocardium. This reshaping and reduction of the volume of the ventricle has two beneficial effects: (1) Wall stress is reduced decreasing overall myocardial consumption and (2) Enhanced efficiency of the pump. The long term results of this procedure indicate reduction in the expected mortality of the patients in NYHA Class III.

1.4 Need for Less Invasive Device-Based HF Therapies While the above therapies may represent the best treatment available today for the majority of HF patients, the medical community recognizes that pharmacologic therapy has been optimized to nearly the extent that is possible, and that any incremental improvements in the management of HF patients will now come from device based therapies. With this background, CardioKinetix has developed a catheter-based intravascular approach to ventricular partitioning using an implantable device. The purpose of this study is to assess the safety and feasibility of using the CardioKinetix Ventricular Partitioning Device to isolate the malfunctioning portion of the left ventricle in patients with symptoms of HF due to ischemic heart disease.

1.5 Summary of Clinical Trials CardioKinetix began clinical evaluations in Europe followed by U.S. studies. All studies were approved by local Ethics Committees or Institutional Review Boards besides appropriate country approvals. The first subject in the Cohort A trial in Europe was implanted with the PARACHUTE device in October 2005. Between October 2005 and June 2007, 16 subjects in Europe had the PARACHUTE placed in their left ventricle.

On June 7, 2007, CardioKinetix, Inc. received conditional approval (for 15 subjects at 5 institutions) for a U.S. feasibility study to assess the safety of implanting the CardioKinetix Parachute Implant into subjects experiencing chronic heart failure resulting from ischemic heart disease. The final condition free approval allowing an increase in subject sample size from 15 to 20 subjects at 5 institutions was received on October 4, 2007. The number of institutions was increased to 8 with the approval of G060130/S5 on May 14, 2008. In total, 10 centers were initiated and 8 centers enrolled/treated at least one subject which is within the allotted number of institutions approved by FDA.

The first subject in the U.S. was enrolled on March 11, 2008, at The Ohio State University and the 20th subject was enrolled on June 30, 2009 at Geisinger Clinic, Danville, PA. Enrollment has been completed and is in the follow-up phase. A total of 18 subjects in this trial had the PARACHUTE placed in their left ventricle.

The data generated from the studies provided evidence of effectiveness in terms of specific hemodynamic measurements that were sustained through 24-month follow-up. These improvements in the various hemodynamic measurements translated into functional improvements for many of these subjects; improved NYHA functional class ranking, improved quality of life, and improved exercise capacity. These benefits were all achieved within a risk profile comparable to other approved treatments for heart failure.

CE mark for the Parachute Implant device was obtained in Europe in June 2011. Currently, CardioKinetix is enrolling subjects in the Cohort B trial, a confirmatory cohort in the EU trial that was initiated in May 2011, and has initiated an EU post market surveillance study using the CE Mark device.

As of June 2013, over 140 subjects have been treated and discharged with the device in place. Analysis for these subjects is ongoing. However, two-year results from 31 treated U.S and European subjects from the EU Cohort A and the US feasibility trials demonstrated a near-full New York Heart Association (NYHA) class improvement at two years compared to baseline (2.6 vs. 1.9, p<0.01). In addition, reduction in left ventricular volume was maintained out to two years (p<0.001). Furthermore, the procedure stabilized the remodeling process as demonstrated by no statistical change in post-procedure functional volume over a two-year period (p=0.74). The combined rate of all-cause death and hospitalization due to worsening heart failure was 16.1 percent at one year and 32.3 percent at two years. The rate of cardiac death was 6.5 percent at two years. These outcomes compare favorably with current medical therapy in a similar high-risk subject population.

Clinical Study Identifier: TX8240

.

Contact Investigators or Research Sites near you

Start Over

Please choose location

View all locations

Feather Wafford

Baptist Health Clinical Research Center & Lexington Cardiac Research Foundation
Lexington, KY USA
  Connect »