The Take Home: SCAI
Cardiology Today’s Intervention was onsite at the Society for Cardiovascular Angiography and Interventions Scientific Sessions, held May 4-7, 2016, in Orlando, Florida, covering the latest clinical news and getting insights on the top issues in different disciplines in interventional cardiology.
Experts who offered their insight include Jeffrey W. Chambers, MD, of Metropolitan Heart and Vascular Institute, Mercy Hospital, Minneapolis; Jay Giri, MD, MPH, of Perelman School of Medicine, University of Pennsylvania; Timothy D. Henry, MD, from Cedars-Sinai Heart Institute; Cardiology Today’s Intervention Editorial Board member Sunil V. Rao, MD, of Duke University Medical Center and Durham VA Medical Center; John P. Reilly, MD, from Ochsner Heart and Vascular Institute, New Orleans; and George W. Vetrovec, MD, from Virginia Commonwealth University Pauley Heart Center.
ORBIT II STUDY
Chambers: I presented 3-year data from the single-arm, prospective ORBIT II study of 443 patients from 49 U.S. sites with severely calcified coronary arteries who were treated with an orbital atherectomy device (Diamondback 360 Coronary Atherectomy System Classic Crown, Cardiovascular Systems Inc.) prior to stent placement. These patients had lesions more severely calcified than seen in any study before. All had calcium on both sides of the arterial wall at least 15 mm long or 270° of calcium at one cross-section on IVUS.
The primary efficacy endpoint was stent delivery with residual stenosis 50% without in-hospital MACE. This was achieved in approximately 89% of patients, beating the performance goal by a significant margin. The primary safety endpoint was 30-day MACE, and the performance goal was also beat by a significant margin.
This presentation showed durable results at 3 years. The rate of cardiac death was 6.7% in a very sick, complicated patient population. The rate of target lesion revascularization was 7.8%, which is about what is expected from most trials at 1 year, much less 3 years. The rate of 3-year MACE was 23.5%, which is good for a population with such severe calcification.
The outcomes in these patients with severely calcified lesions were similar to those seen in patients from other cohorts with non-calcified lesions.
We also compared outcomes between men and women. Compared with men, women were older (P = .001) and had slightly worse renal function (P = .002). Compared with women, men had more prior CABG (P = .005) and a higher rate of smoking (P = .03). There were no differences in TLR, target vessel revascularization or MACE at 3 years. Men had a higher 3-year cardiac death rate (8.9% vs. 2.7%; P = .02) and women had a higher rate of severe dissection (6.4% vs. 1.7%; P = .01), which may be related to the size of the vessels, which were smaller in women. Despite slight differences, the outcomes in men and women were essentially equivalent.
QUALITY IMPROVEMENT INITIATIVE
Rao: The study of a quality improvement initiative across 11 regional health systems (8,713 PCI procedures, more than 200 operators, 21 hospitals) shows that you can implement evidence-based medicine at the bedside at a health-system level, and make real changes. Participating centers started using the National Cardiovascular Data Registry bleeding risk calculator at various points during the study period. The calculator stratified patients into high (score > 65), intermediate (score 25-65) or low (score < 25) risk for bleeding, and prompted clinicians to employ bleeding avoidance strategies, including not using bivalirudin (Angiomax, The Medicines Company) in low-risk patients and using bivalirudin and transradial access in high-risk patients. Bleeding incidence declined 40% during the study period, from 6.3% at baseline to 3.78% at 21 months. The reduction in bleeding events saved approximately $1 million across the health systems, and the reduction in use of bivalirudin saved another $1 million.
This is very exciting. It was not one doctor or one practice doing this — it was implemented across a health system in a way that we always talk about: bringing public evidence and risk scores that have been validated to the bedside and changing physician behavior. Other studies have shown that if you provide physicians with a calculated estimated risk of an event happening, it actually influences physician behavior. The system had an incentive to implement this program to reduce costs, but the change also improved outcomes, which ultimately is what patients care about. That kind of quality improvement research may not be as glamorous as some of the other things interventional cardiologists do, but it’s something that produces real change.
There are many available risk scores. One reason why validated risk scores haven’t been adopted as much as they should be is because providers tend to think, “Oh, that’s one more thing I have to do.” I would like, in the era of smartphones and electronic medical records, to have them integrated into our normal workflow. We have the computing power to do it. We just have to be able to get to a system where, when I pull up a patient’s electronic health record, along with all their medications and lab results, there should be, based on a validated risk model, their estimated risks for bleeding, mortality, restenosis and acute kidney injury. I should be able to get those without having to calculate them. Then, based on that information, I may want to change the strategy I use in the cath lab. If we can integrate risk scores into our normal way of doing things, then they will be widely adopted.
Vetrovec: The presentation by Ehtisham Mahmud, MD, FACC, FSCAI, described the advancing opportunity to utilize robotic-assisted PCI (CorPath System, Corindus) in more complex coronary disease. The researchers analyzed 334 complex PCI procedures (108 with robotic assistance, 226 manual) performed in 315 patients. The primary endpoint of clinical success, defined as stent implantation with residual stenosis < 30%, TIMI 3 flow and without in-hospital MACE (death, urgent repeat revascularization and clinical MI), was 99.1% in the robotic PCI group vs. 99.6% in the manual PCI group (P = .64). Freedom from periprocedural MI (CK-MB more than three times the upper limit of normal) was 94.4% vs. 91.6%, respectively (P = .32).
The results are encouraging but somewhat limited by the fact that it is not randomized in a traditional fashion, is a single-center study and, importantly, a single, experienced-operator study. Despite these limitations, the study demonstrates no increased patient risk or adverse outcomes from the use of robotic-assisted PCI. Furthermore, when the robotic system was not capable, which was uncommon, there was no penalty to patient outcomes.
The advantage of the robotic system is lower operator radiation and back fatigue. While one would like to see less patient radiation, procedure time and reduced contrast use as a benefit of the robot, two factors may have played a significant role. First, this was the complete, initial experience of the operator and, thus, undoubtedly includes a significant learning curve. Second, the operator is an experienced and skilled interventionalist, increasing the challenge for robotic-assisted PCI to be better. One can speculate that one advantage of the robotic system may be making results more homogeneous among operators of variable skills. Thus, further studies are needed with multicenter and multi-operator experience to truly understand the overall effect of this exciting technology.
RENEW PIVOTAL STUDY
Reilly: The RENEW pivotal study of a cell therapy was designed to enroll 444 patients with refractory angina who were on maximal angina therapy, had evidence of ischemia and were not candidates for revascularization. The goal was to have approximately 200 evaluable patients randomly assigned granulocyte colony-stimulating factor (G-CSF) mobilized CD34+ cells, approximately 100 evaluable patients assigned placebo injection and approximately 100 evaluable patients assigned standard care. The trial was stopped after enrollment of 57 patients in the CD34+ group, 27 in the placebo group and 28 in the standard-care group as a result of financial and strategic decisions by the sponsor (Baxter). When the trial was stopped, exercise time improved approximately 1 minute more in the CD34+ group than in the placebo group at 6 months and in excess of 30 seconds more at 12 months. Angina frequency was decreased at 6 months in the CD34+ group compared with the placebo group (RR = 0.57; 95% CI, 0.36-0.92). At 2 years, the mortality rate was 3.7% in the CD34+ group, 7.1% in the standard-care group and 10% in the placebo group.
This is a frustrating patient population because we interventionalists feel that we can’t treat them. And the patients are very frustrated with their medical-treatment regimen, and many don’t want to have a surgical procedure for transmyocardial revascularization, for which efficacy in that group is inconclusive. I am hopeful that stem-cell or gene therapy will prove effective for these patients.
These do look like promising data, consistent with phase 2 studies that have been done. That was encouraging, and it’s unfortunate that the investigators did not get to complete the trial they had set out and designed. We will somehow have to get more data before we can know whether cell therapy benefits patients with refractory angina.
Henry: I presented results from the ATHENA program of two parallel, randomized, prospective, double blind trials that assessed intramyocardial administration of adipose-derived regenerative cells in patients with symptoms of angina or HF, left ventricular ejection fraction 20% to 45%, multivessel CAD and inducible ischemia who were receiving maximal medical therapy.
Patients with class III HF or angina, despite medical and device therapy, have limited options. We randomly assigned them to receive adipose-derived cells or placebo. Adipose-derived stem cells are plentiful and can be removed via liposuction. Within 2 hours, they can be processed into a mixture of CD34+ cells, macrophages and monocytes (Cellution System, Cytori Therapeutics). In preclinical models, this mixture appeared to promote angiogenesis and decrease inflammation. Patients received intramyocardial injection of adipose-derived stem cells or placebo into the ischemic zone.
This was a high-risk, symptomatic population with a mean LVEF of 31%. Nearly one-third had a previous transient ischemic attack or stroke and were on chronic anticoagulation. During the trial, a patient had a possible TIA. One year later, there was a second potential TIA. Both patients had full recovery and both the FDA and the Data Safety and Monitoring Board recommended continuation, but the sponsor elected to stop the trial after the delay. Despite being underpowered for that reason, the results of the trial showed the cell-treated patients improved in the Minnesota Living With Heart Failure questionnaire (P = .038), improved in other quality-of-life measures and in symptoms of HF and angina. There were no differences in EF.
This trial was tantalizing because it showed the potential benefit of the cell therapy, but there were not enough patients to have a definitive answer. The results were similar to the PRECISE study of 27 patients in Europe. It appears adipose-derived cells are an excellent source of stem cells for these patients, but we need more data and larger trials.
MODERATE SEDATION in TAVR
Giri: This was a study on moderate sedation compared with general anesthesia in patients undergoing transcatheter aortic valve replacement conducted by myself and my colleagues. There has been a tremendous amount of interest in minimalist TAVR, which consists of fully percutaneous incision-less surgery without use of general anesthesia, which requires an endotracheal tube and a respirator. There has been interest in moving to moderate sedation, of which there are three general levels: local anesthesia; conscious sedation, involving use of medications from the cath lab; and moderate anesthesia care, which involves no endotracheal tube but the presence of an anesthesiologist.
We sought to define, at a U.S. level, the rates of performance of moderate sedation for TAVR. Additionally, we performed a comparative-effectiveness analysis of outcomes in patients with moderate sedation vs. those with general anesthesia. We analyzed 10,997 patients from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry who received percutaneous transfemoral TAVR between April 2014 and June 2015.
We saw that 16% of patients during that time period were treated with moderate sedation, and that the rates of moderate sedation are rising over time: less than 10% in April 2014, but up to 25% to 30% by the end of the study period.
The rates of procedural success were identical between moderate sedation and general anesthesia, approximately 98.5% in both arms. In an unadjusted analysis and a propensity-matched analysis adjusted for 51 clinical characteristics, we found 30-day mortality was slightly lower in the group treated with moderate sedation (unadjusted analysis: 2.9% vs. 4.1%; P = .029; propensity-matched analysis: 2.96% vs. 4.01%; P < .0001).
These are intriguing results which could have an impact on how the processes of care for TAVR proceed, in an era where more than 90% of TAVR cases are performed transfemorally, but only 30% are being treated with moderate sedation.
Disclosures: Chambers reports fee-for-service consulting for Cardiovascular Systems Inc. Giri reports serving as an investigator for a TAVR trial sponsored by St. Jude Medical. Henry reports serving as principal investigator for the ATHENA trials and receiving modest travel reimbursement from Cytori Therapeutics. Vetrovec reports being an investigator on the PRECISE study of robotic-assisted PCI and past consulting for Corindus. Rao and Reilly report no relevant financial disclosures.