In this study, we demonstrated that PARACHUTE therapy could be beneficial for maladaptive remodeling of patients with post-MI by restoring LV ejection and suppressing continuous and overwhelmed LV enlargement, thereby improving patients’ long-term prognosis especially in LVEF-sustained preserved subjects.
Typical LV dilation is common in patients with an anterior infarction(12). As a consequence of anterior MI, the LV continuously develops geometrically from ellipsoid to spherical(13), accompanied with chamber dilation and wall motion abnormalities. The dilation of the LV maintains cardiac output through inotropic and chronotropic effects by the Frank-Starling mechanism. However, according to the law of Laplace, increased LV volume elevates filling pressure, resulting in the enhanced burden of remaining myocytes, progressive subendocardial myocardial ischemia(14), a hemodynamic disorder such as functional mitral regurgitation(8), HF, and death(15). Many studies proved that LV remodeling is an independent clinical predictor of prognosis in patients with HF(16). The beneficial effects of drugs or medical devices on LV remodeling have also been associated with reduced long-term mortality(17). Therefore, effective and safe treatment strategies are urgently needed to restore LV function and improve outcomes of patients with HF.
PARACHUTE device has been investigated in several clinical trials, such as the Percutaneous Ventricular Restoration in Chronic Heart Failure due to Ischemic Heart Disease (PARACHUTE) Ι, II, III, and IV trials. The PARACHUTE First-In-Human trial simultaneously conducted in USA and Europe for 39 patients(8) demonstrated safety and feasibility for patients with HF (LV ejection fraction between 15% and 40%) and dilated LV. There was a stable and remarkable reduction in LV end-diastolic volume up to 3 years follow-up. Echocardiography revealed that stroke volume and LV ejection fraction were reduced as well. The PARACHUTE III(18) trial was a prospective, non-randomized observational study conducted in Europe. It included 100 subjects, with LV volumes significantly reduced and 6 minutes’ walk distance improved from 372 m to 397 m (p < 0.01). The following PARACHUTE IV(19) clinical trial was the first randomized controlled trial aiming to enroll 478 New York Heart Association (NYHA) classes III and IV, with LVEF of 15–40% and the use of optimal medical therapy. employed CT imaging was employed to assess optimal device implantation. The primary endpoint was death or hospitalization for worsening HF. Unfortunately, the study was terminated in June 2017 because of death or worsening HF (clinicaltrials.gov ≠ NCT01614652).
In this trial, 139 patients were diagnosed anterior myocardial infraction were informed this procedure (Fig. 1). However, this device is believed that could provide additional help to the patients with Left aneurysm. LVEF > 40% implies relative preserved LV function, and LVEF < 15% suggests end-stage heart failure. Therefore, these subjects were excluded. In order to exert the maximum benefit effect to heart failure patients restricted heart features were carefully evaluated, false tendons, ventricular thrombosis are contraindications of PARACHUTE procedure. At last 6 eligible subjects enrolled to the study, the cautiously HF patients selection also contribute to procedural safety eventually.
Despite the continuous improvement in the treatment of acute and long-term MI over recent decades, adverse LV remodeling is the principal reason for clinical HF. Both functional and structural measures of adverse LV remodeling, such as LVEF and LVEDD, are associated with mortality and cardiovascular events(20). The beneficial effect of drugs or medical devices on LV remodeling has been associated with reduced long-term mortality(21). The PARACHUTE device (Cardiokinetix, Redwood City, CA, USA) is designed to partition off the akinetic or aneurysmatic portion of the LV in patients with ischemic HF. The aforementioned studies(8, 18, 19, 22) suggested that the PARACHUTE device can reduce cardiac dimensions and end-diastolic wall stress and improve cardiac output. However, the 3 year results suggested a reduction of LVEF and stroke volume. The PARACHUTE IV trial was terminated because of death or rehospitalization for worsening HF.
Medication treatment such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and aldosterone antagonists remain the cornerstone of HF therapy, and these treatment agents were applied in our cohort. However, the six enrolled subjects eventually suffered from ventricular desynchrony. Surgical ventricular restoration (SVR) is an alternative for patients that require severe LV remodeling. Compared with the percutaneous delivery and insertion of the PARACHUTE device into the LV cavity, one might expect a lower rate of infectious complications associated with the use of PARACHUTE compared with the SVR(23). We carefully selected six of 139 patients with post-anterior MI. With TTE and CT evaluation, PARACHUTE implantation was performed successfully without acute device-related adverse events (Table 2, and Table 3).
As indicated in Fig. 2, except for a premature death that occurred in 1.8 years post-implantation due to worsening HF, no other mortality occurred at an average of 4.6 years follow-up, the survival rate was 83.3%. With current aggressive invasive strategies and advanced pharmacotherapy, acute MI survival rates have increased but may have led to a group of patients with a high risk of developing HF. Survival after HF diagnosis has improved over time, as shown by data from the Framingham Heart Study(24) and the Olmsted County Study(25). However, the death rate remains high: about 50% of people diagnosed with HF will die within 5 years. To this extent, the PARACHUTE implantation improved patients’ prognosis. In addition, subjects enrolled in our trial suffered from severe LV maladaptive remodeling with cardiac output reduction. Even with the assistance of PARACHUTE, half of them demonstrated worsening HF during follow-up. On the basis of pooled data from the National Heart, Lung, and Blood Institute (NHLBI), after the first MI, 20% of men and 23% of women will die within 5 years(26). In terms of the HF hospitalization data, the PARACHUTE device seems to increase the HF ratio, which is consistent with the PARACHUTE IV(27) trial. However, we believe that this finding was not completely attributed to the side effect of the device but partially because the selected patients suffered from serious MI and remodeling. Because no severe ventricular arrhythmia was observed, we have no patient implanted ICD in this cohort.
The device restored enrolled patients’ LV systolic function, and this result was consistent with findings of former studies(8, 9, 18). LVEF significantly improved from preimplantation to 7 days after deployment (35.83% ± 1.47% vs. 46.00% ± 6.00%, P = 0.009). Besides, the LVEDD and estimated PAP were relatively stable, which suggested that this therapy was effective and safe for patients. The improvement in NYHA functional class was also observed in other patients (shown in Fig. 3).
Patients with prior MI have a much higher risk to develop HF and multivessel coronary artery disease than their counterparts(28). The device is designed to prevent maladaptive LV remodeling, which is helpless to inhibit recurrent coronary attack. Therefore, personalized treatment should be sought to decrease coronary risks. The HF that occurred in half of our enrolled patients may be partly because the patients we selected suffered from severe cardiac remodeling, thereby enhancing the ratio of cardiac adverse events. However, the device-related MACEs also contribute to the poor prognosis.
As this clinical trial previously designed, all patients received low‑dose aspirin and anticoagulation with warfarin for at least 12 months post-device implantation. Drug-eluting stents (DESs) improved the efficacy of percutaneous coronary intervention by modulating vascular inflammation and preventing neointimal proliferation and restenosis. DES effectively reduced neointimal proliferation but also slowed reendothelialization and the healing process. Dual antiplatelet therapy is recommended under delayed reendothelialization to prevent stent-related thrombosis(29). For patients with atrial fibrillation (AF), who have elevated stroke risk, and require percutaneous approaches to occlusion of the left atrial appendage (LAA), the device is an option for patients who are suitable for short-term warfarin treatment but unable to undergo long-term oral anticoagulation. Patients who received LAA occlusion by WATCHMAN device are only recommended to undergo 3 months of anticoagulation treatment, followed by long-term antiplatelet therapy(30). DES and WATCHMAN device are prevalent in coronary atherosclerosis and AF treatment, respectively. With proper antiplatelet or anticoagulation, device-related embolization rarely occurs. The duration of antiplatelet or anticoagulation is based on the spontaneous reendothelialization time. Extra anticoagulation is unnecessary when the implants are completely reendothelialized. The concept is also applicable to the PARACHUTE device. In color doppler flow imaging, we observed that blood flow crossed the device, suggesting it was not entirely reendothelialized even after 3 years, so thrombosis may be promoted. The evidence implies that the PARACHUTE device may need to be refined to fit the geometry of the dilated ventricle.
Despite this small number of patients in our center, we have the longest clinical observation of the PARACHUTE cohort in China. In this trial, the efficiency and safety of the PARACHUTE procedure were investigated, and long-term MACE and cardiac function were evaluated as well. These data add additional evidence to PARACHUTE studies and prove that the ventricular partition device is relatively safe and may reduce long-term death. However, the PARACHUTE device could increase the HF ratio.