Authors:

Key Learning Points

1. Percutaneous ventricular assist device (VAD) therapies are essential and effective treatment modalities in cardiogenic shock and ST-segment elevation myocardial infarction (STEMI) patients.
2. Left ventricular (LV) unloading reduces infarct size when instituted within two hours of coronary occlusion and prior to reperfusion. Percutaneous VAD or intra-aortic balloon pump (IABP) should, therefore, be placed early since late placement (especially after shock develops post STEMI) has not shown to significantly improve outcomes.
3. Ventricular restoration therapies have had promising early results in studies showing improvements in New York Heart Association (NYHA) class, quality of life (QoL) and 6MWD in mostly ischemic cardiomyopathy patients with anterior/anteroseptal scars by reducing LV volume and improving LV geometry. More recently, however, the Algisyl injectable/implantable biopolymer also showed benefit in nonischemic cardiomyopathy patients.
4. Coronary sinus reducer device therapy improves functional class in refractory angina patients and offers a novel treatment option for these patients with limited options at the outset.
5. Adipose derived regenerative cell (ADRC)- and CD34+ve cell-based therapy have demonstrated significant improvement in angina class in refractory angina patients. CD34+ve cell therapy, although not commercially available yet, has also shown improvement in exercise time.
6. Chronic total occlusion therapies in high volume centers and with contemporary techniques and approaches can benefit patients with refractory angina offering them a >90% success rate and <3% complication rate. No randomized controlled trial data is available, but registry data is compelling.
7. Consider MitraClip device to improve severity of mitral regurgitation in advanced heart failure patients.

Hot Topics/New Knowledge

1. Ventricular restoration therapies: Parachute ventricular partitioning device; Revivent ventricular restoration system; Algisyl-LVR implantable/injectable biopolymer
2. A Prospective Comparison of Algisyl-LVR With Standard Medical Therapy to Determine Impact on Functional Capacity and Clinic Outcomes in Patients with Advanced Heart Failure (AUGMENT-HF) Trial
3. Coronary sinus reducer device
4. Coronary Sinus Reducer for Treatment of Refractory Angina (COSIRA) Trial
5. Hybrid chronic total occlusion (CTO) percutaneous coronary intervention (PCI)
6. MitraClip
7. Interventional Heart Failure

Overall Theme

This ACC.15 session highlighted the utility of device therapy in cardiogenic shock, decompensated heart failure, and refractory angina. In addition, cell therapy and CTO therapy were discussed as modalities of management of refractory angina.

Dr. Cohen introduced the session with an overview of percutaneous VAD (percutaneous VADs [pVADs], including IABP, Impella, TandemHeart and extracorporeal membrane oxygenation [ECMO]) and patient selection considerations for these devices. He introduced the concept of a "shock team," comprised of interventionalists, heart failure specialists, and cardiothoracic surgeons who collectively triage the patient and select appropriate therapy. The goal of pVADs is to improve survival and not prolong dying. If no quick turnaround is noted with an IABP (within hours), he stressed that physicians should proceed quickly to a pVAD. However, without an "exit strategy, withholding pVADs should also be strongly considered. In terms of devices, he demonstrated using pressure-volume loops that the TandemHeart offers the most LV unloading.

Dr. Smalling discussed the evolution of cardiogenic shock therapies from the Hemopump (developed in 1987; 21F transvalvular pump)¹ to the Impella and TandemHeart pumps of today. He showed that the latter two have, in fact, faired poorly in trials against the IABP. He also highlighted the lack of benefit of IABP in the Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) trial, noting, however, that the duration from onset of symptoms to IABP insertion/PCI in the trial was uncertain and likely greater than two hours, a significant timespan in terms of myocardial injury. In addition, he mentioned that only 13.4% of patients in IABP-SHOCK II had an IABP inserted prior to IABP, which he feels may also have been a significant factor for the overall negative result. From basic animal studies, he showed data supporting the concept that LV unloading prior to reperfusion prevents contraction band necrosis and pathologic myocardial thickening by reducing calcium overload and apoptosis. Clinically, this concept was tested in the Counterpulsation to Reduce Infarct Size Pre-PCI Acute Myocardial Infarction (CRISP AMI) trial,² in which IABP was inserted prior to PCI. There was no reduction in infarct size in this trial. However, since many patients in this trial were not reperfused within two hours of onset of symptoms, the efficacy may have been reduced. There was a trend towards decreased long-term mortality noted, which was also a significant finding of the trial.

Dr. Abraham discussed ventricular restoration therapies to decrease LV volume and restore LV geometry (making it more elliptical). The first therapy was the Parachute ventricular partitioning device, a fluoropolymer membrane-based device mounted on a nitinol frame, introduced percutaneously into the LV apex. This device reduces wall stress in the upper LV chamber, provides more outward force ("trampoline effect"), and improves LV diastolic compliance (thus reducing LV filling pressures). Currently, it is for investigational use only in the U.S.; worldwide, about 300 patients have demonstrated improvement of NYHA class, QoL, and 6MWD in trials. A randomized, controlled, event-driven, outcomes trial for U.S. Food and Drug Administration (FDA) approval is ongoing and is currently half enrolled. The second device discussed was the Revivent ventricular restoration system, also CE mark approved in Europe. This has a surgical/hybrid implantation technique in which dysfunctional myocardial segments are "cinched up" using titanium anchors and tethers. Both of these devices are used for patients with anterior/anteroseptal scars. The third therapy discussed was the Algisyl-LVR surgically implantable/injectable biopolymer that was tested in the AUGMENT-HF trial. This showed improvement in NYHA class, QoL and 6MWD in both ischemic and nonischemic cardiomyopathies. This biopolymer has been approved in Europe recently and is currently undergoing randomized controlled trial in the U.S.

Dr. Jolicoeur presented the data from the Coronary Sinus Reducer for Treatment of Refractory Angina (COSIRA) trial that tested the coronary sinus reducer device for refractory angina. This device is an hour glass-shaped device introduced into the coronary sinus causing a controlled reduction in flow. This increases coronary sinus pressure that leads to redistribution of collateral blood flow and, thus, improves endocardial coronary perfusion by inverting the endocardial:epicardial perfusion ratio (back to around 1.2). The COSIRA trial was a prospective, sham-controlled, randomized, controlled trial in CCS III-IV, medically refractory angina patients unamenable to revascularization. Although there was notable placebo effect, the results were significantly in favor of the reducer device for both efficacy (decrease in CCS by ≥2 classes) and safety (cardiac death, myocardial infarction). A concordance domain analysis was also performed for secondary endpoints, and this also favored the device over medical therapy (from baseline to six months). A phase III trial is being planned currently.

Dr. Henry talked about the increasing burden of refractory angina as mortality from coronary artery disease continues to decline and the population continues ages. From the OPTIMIST Program at the Minneapolis Heart Institute where patients with refractory angina are followed, he cited the mortality of these patients to be about 3-4% at one year. As a result, he noted the issue with these patients is mostly QoL. He introduced cell therapy as a treatment modality for refractory angina beyond pre-existing therapies like enhanced external counterpulsation, neurostimulation, transmyocardial revascularization, and novel drugs and procedures. The first cell-based therapy using unselected bone marrow mononuclear cells for this indication demonstrated significant reduction in inducible ischemia on single-photon emission computed tomography (SPECT) imaging and mild improvement in angina class, QoL, LV ejection fraction (LVEF) in cell therapy arm versus placebo. More contemporary cell therapies include adipose-derived regenerative cells (ADRC) tested in the Prospective, Multi-Center Evaluation of the Accuracy of a Novel Continuous Implanted Glucose Sensor (PRECISE) trial in Europe leading to CE mark approval and the ongoing Effect of Dronedarone on Cardiovascular Outcomes in High-Risk Patients With Atrial Fibrillation or Atrial Flutter (ATHENA) trial in the U.S. Another cell-based therapy using CD34 +ve cells was tested in phase I trial in the U.S. (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation [ADVANCE] trial). The patients treated with CD34+ve cell therapy showed significant decrease in angina class and frequency and ischemic myocardial distribution (based on NOGA mapping and SPECT scans). The phase II ACT34 trial is the largest cell-based, placebo-controlled, blinded, randomized controlled trial that showed positive trends in major adverse cardiac events and a significant reduction in angina and exercise time. Meta-analysis of cell therapy trials have shown improvement in LVEF, LV volumes and mortality, and QoL, and have favored intra-myocardial injection over intra-coronary. The CD34+ve cell therapy is currently still not available commercially in the U.S.

Dr. Samady began his discussion of CTO by stating that there is no randomized controlled trial demonstrating benefit of CTO therapy over conventional management of refractory angina. He showed registry data showing that incompletely revascularized patients and CTOs have a higher mortality and MI rate. In addition, in STEMI and cardiogenic shock patients, those with more than one occluded artery had worse outcomes than those with only culprit artery occlusion. He stressed that the benefit of CTO revascularization will be highest in those patients with the highest ischemic burden (at least ≥ moderate). He also highlighted that even collateralized vessels can remain ischemic (demonstrated by fractional flow reserve) and can benefit from CTO therapy. CTO meta-analysis data have shown a trend towards mortality benefit with CTO therapy. Success rates in high volume centers is about 90% or higher with low complication rates (<3%). He mentioned the concept of Hybrid CTO PCI with rapid escalation strategies as being a more successful contemporary model used at most dedicated CTO centers.

Dr. Naidu presented a case of an 81-year-old man with advanced ischemic cardiomyopathy on inotropes with severe mitral regurgitation and angina who was treated with graft and native vessel PCI followed by a deployment of a Mitraclip device subsequently resulting in him being coming off inotropes and getting discharged with only mild mitral regurgitation and in NYHA class II functional status. He highlighted the usefulness of the Mitraclip in this scenario and of significant potential benefit in advanced heart failure patients. In addition, Dr. Naidu stressed that "interventional heart failure" is an evolving subspecialty already recognized by The Society for Cardiovascular Angiography and Interventions (SCAI) with its own working committee.

References

1. Smalling RW, Sweeney M, Lachterman B, et al. Transvalvular left ventricular assistance in cardiogenic shock secondary to acute myocardial infarction: evidence for recovery from near fatal myocardial stunning. J Am Coll Cardiol 1994;23:637-644.
2. Patel MR, Smalling RW, Thiele H, et al. Intra-aortic balloon counterpulsation and infarct size in patients with acute anterior myocardial infarction without shock: the CRISP AMI randomized trial. JAMA 2011;306:1329-37.

Keywords: Alloys, Amiodarone, Angina Pectoris, Angiography, Apoptosis, Arteries, Atrial Fibrillation, Atrial Flutter, Biopolymers, Bone Marrow, Calcium, Cardiomyopathies, Cell- and Tissue-Based Therapy, Cicatrix, Coronary Artery Disease, Coronary Occlusion, Coronary Sinus, Cost of Illness, Counterpulsation, Diabetes Mellitus, Drug Combinations, Extracorporeal Membrane Oxygenation, Gliclazide, Glucose, Goals, Heart Failure, Heart-Assist Devices, Indapamide, Intra-Aortic Balloon Pumping, Mitral Valve Insufficiency, Myocardial Infarction, Patient Selection, Percutaneous Coronary Intervention, Perindopril, Pharmaceutical Preparations, Placebo Effect, Prospective Studies, Quality of Life, Registries, Shock, Cardiogenic, Specialization, Surgeons, Titanium, Tomography, Emission-Computed, Single-Photon, Triage, United States Food and Drug Administration

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