Data Spotlight | Device-Based Approaches for Heart Failure: Updated Results from the PARACHUTE Pooled Analysis

Despite advances in optimal medical therapy for post-MI patients with ischemic heart disease, both left ventricular (LV) remodeling and heart failure (HF) continue to progress—resulting in poorer ventricular performance and poorer clinical outcomes for these patients. Current management strategies for ischemic LV dysfunction typically aim to reverse that remodeling process—with medications and sometimes surgery—but a novel heart catheter-based procedure via an alternative implantable device has recently been developed.

The Parachute® Ventricular Partitioning Device (CardioKinetix, Inc.; Menlo Park, CA) is the first minimally invasive treatment for patients with HF caused by damage to the heart muscle following an MI. Currently, the Parachute® system is CE-Mark approved in Europe, and is labeled as an investigational device and currently enrolling in a pivotal trial, PARACHUTE IV (clinicaltrials.gov identifier NCT01614652), in the United States.

Updated results from a PARACHUTE pooled analysis, presented at the recent ACC.14 Scientific Sessions, showed both hemodynamic and functional improvements in patients with ischemic disease who received the Parachute® implant, as well as a high procedural success rate. These results were presented by Phil Adamson, MD, the medical director at the Heart Failure Institute at Oklahoma Heart Hospital. Frank W. Smart, MD, principal investigator of the PARACHUTE trial and chief of the section of cardiology in the Department of Medicine and director of the Cardiovascular Center of Excellence at Louisiana State University School of Medicine, spoke with CSWN: Interventions about the role of the Parachute® system in the heart failure treatment landscape.

"We have a number of therapies for people with heart failure, and some of these individuals have been on medical therapy for a while but still continue to kind of limp along" Dr. Smart said. "If there was something that was easily delivered and safe that would make them have an improvement in their functional class, it would be extremely beneficial for a certain number of people."

Promising Results

Ultimately, the results from the data set showed that recipients experienced improved cardiac output and improved quality of life. As seen in TABLES 1 and 2, many of the 111 patients included in this analysis had significant functional impairment due to their cardiac disease (NYHA Class III) and increased left atrial volume (84.4±28.2 ml). All had ischemic heart disease, nearly one-third had a heart failure hospitalization prior to enrollment, and three-quarters had a prior PCI.

Functional and quality-of-life improvements were measured by changes in performance on the NYHA functional status and the 6-minute walk test (6MWT). Improvement in NYHA class was one of the most interesting findings, Dr. Smart said. "First off, patients showed improvement quickly and early post-implant, and they maintained this out to 12 months." While 29% of patients with NYHA functional class III maintained their status, 56% improved by one or more functional class (40% improved one class, 16% improved two classes), which represents a substantial difference in terms of lifestyle (FIGURE 1). Performance on 6MWT was also improved: from 365 meters at baseline to 390 at 12 months (p < 0.05), with 47% of patients improving by 20 meters or more and 28% maintaining. The functional and hemodynamic improvements support the relatively low rates of death (5.7%) and the combined endpoint of death and repeat hospitalization for heart failure (21.7%).

Procedural success reached 95.5%, with a relatively low rate of major and minor complications (7.2% and 8.2%, respectively).

A Unique Mechanism of Action

The Parachute® implant is comprised of a fluoropolymer (ePTFE) membrane stretched over a nitinol frame (FIGURE 2). The implant is delivered through a small catheter inserted in the femoral artery and deployed in the left ventricle to partition the damaged muscle—excluding the nonfunctional heart segment from the healthy, functional segment to decrease the overall volume of the left ventricle and restore its geometry and function (FIGURE 3).

"The Parachute® device is an interesting medical device" Dr. Smart said. "We've always thought that it reformed a failing heart or damaged heart—particularly ones with apical akinesis—into a more conical shape." The more conical shape, he explained, helps to reduce end-diastolic volume, and therefore the pressure that is applied to the heart at the end of diastole. "We all predicted that that was going to be one of the functions of the device, but the device actually also has properties of dynamic recoil."

In a sense, the nitinol actually allows for "a trampoline-like" effect. Typically, with an invasive strategy, Dr. Smart explained, the surgeon opens the ventricle and sews in a patch or ligated scar, essentially replacing a stiff portion with another stiff portion. This surgical remodeling does not allow for diastolic recoil or the rotational effects of the heart. Rather than hitting against a non-compliant, scarred wall as blood enters the ventricle, the ePTFE-coated nitinol frame absorbs some of that diastolic energy before recoiling that back into the ventricle.

This diastolic dynamic recoil was an unexpected finding from Dr. Smart's experiences implanting the Parachute® device, but one that improved patients' diastolic pressure: "We knew people were getting better, and we couldn't explain how much better they were getting based solely on reduction in ventricular volumes, so that's when we started looking at the reduction in diastolic pressures indicated by the remodeling of the left atrium closer to normal ranges. Reductions of this magnitude have only been observed post-placement of active devices such as cardiac resynchronization therapies."

Another benefit of the minimally-invasive LV partitioning approach: restoring the conical shape of the heart. "The conical shape is also really important for the heart's performance, and the Parachute is better at restoring that because it really does not affect the healthy, functioning part of the heart" Dr. Smart added. "Not only is it a percutaneous approach that is less invasive and less fraught with problems than a surgical ventricular restoration procedure, but the device offers LV remodeling with minimal time and recovery."

Next Steps

"We're learning more and more from the human anatomy—watching the end-diastolic volume fall, the end-systolic volume fall—and because of those changes, ejection fraction changes, although very minimally" Dr. Smart said. Other areas of improvement: the contractility index and the stroke work index. "What we're hoping to see is that there is a durable effect on all of the parameters, including 6-minute walk, in larger trials."

In terms of the optimal patient population for the device, Dr. Smart said that the patients who are likely to respond best to the minimally invasive Parachute procedure are those with anteroapical hypokinesis or akinesis, abnormal wall motion in the LV apex, and a prior MI. However, he noted, larger clinical trials may show that there are broader applications for the device. "The more we learn about it and the more we understand this dynamic recoil, as well as some of the systolic wall tension reduction, I think we're going to see more and more people who could potentially benefit."

Speaking about his personal experience with implanting the Parachute® device, Dr. Smart described the dramatic improvement in functional capacity that patients have experienced: "With the first procedure I ever performed, I was routinely shocked by how well she was doing. Being born a skeptic anyway, I was always trying to look for other reasons."

As always, the issue will be finding a balance between safety and efficacy, but recent trials are encouraging, added Dr. Smart: "The device appears to be very safe and pretty efficacious in the short run. If that efficacy is held up in the longer term, and if the safety is maintained, I think this will be a big deal for a certain number of people."

Sponsored by CardioKinetix

TABLE 1. Patient Baseline Characteristics
Demographics
Age 60.7±10.6 years
Male 93/111 (83.8%)
BMI 28.5±5.1
Ischemic heart disease 111/111 (100%)
NYHA I* 1/111 (0.9%)
NYHA II* 45/111 (40.6%)
NYHA III 65/111 (58.5%)
Medical History
Smoking 78/105 (74.3%)
Hypertension 76/111 (68.5%)
Prior ICD 39/111 (37.8%)
Prior CRT 20/111 (18.0%)
Prior PCI 84/111 (75.7%)
Prior CABG 19/111 (17.1%)
HF hospitalization (12 months prior to enrollment) 30/95 (31.6%)
*NYHA III or IV in the last 3 months

 

TABLE 2. Hemodynamic Data
  N Baseline 12 Months p Value
Heart Rate 95 67.5±13.1 67.9±10.5 NS
Blood Pressure        
Systolic, mmHg 95 118.6±17.2 117.3±14.6 NS
Diastolic, mmHg 95 71.7±10.0 71.6±10.1 NS
LV volume        
ESVi, ml/m2 81 87.6±24.6 73.2±22.7 <0.0001
EDVi, ml/m2 81 120.8±26.2 103.8±25.9 <0.0001
Systolic improvement        
Ejection fraction, % 81 28.4±8.0 30.4±8.1 <0.05
Fractional shortening, % 72 18.5±9.8 20.3±8.6 0.14
Contractility index, mmHg-m2/ml 81 1.3±0.5 1.6±0.6 <0.0001
Stroke work / EDVi, mmHg 81 26.8±8.7 29.0±8.2 <0.05
Diastolic improvement        
LAVi, ml/m2 43 43.6±15.1 37.8±10.9 <0.05

 

FIGURE 1. Improvement in NYHA Functional Class
Figure Graphic
Click Image to Enlarge.

 

FIGURE 2. The Parachute® Implant
Figure Graphic
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FIGURE 3. Angiographic Sequence of Implantation in the Left Ventricle
Figure Graphic
Click Image to Enlarge.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Implantable Devices, Acute Heart Failure

Keywords: Myocardial Ischemia, Life Style, Heart Atria, Reference Values, Cardiac Output, Femoral Artery, Blood Pressure, Cardiac Catheters, Cardiac Resynchronization Therapy, Cicatrix, Quality of Life, Ventricular Remodeling, Heart Failure, Physician Executives, Heart Ventricles, Hospitalization


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