CD34+ cell therapy significantly reduces adverse cardiac events, health care expenditures, and mortality in patients with refractory angina.

Patients with refractory angina who are suboptimal candidates for further revascularization have improved exercise time, decreased angina frequency, and reduced major adverse cardiac events with intramyocardial delivery of CD34+ cells. However, the effect of CD34+ cell therapy on health care expenditures before and after treatment is unknown. We determined the effect of CD34+ cell therapy on cardiac-related hospital visits and costs during the 12 months following stem cell injection compared with the 12 months prior to injection. Cardiac-related hospital admissions and procedures were retrospectively tabulated for patients enrolled at one site in one of three double-blinded, placebo-controlled CD34+ trials in the 12 months before and after intramyocardial injections of CD34+ cells vs placebo. Fifty-six patients were randomized to CD34+ cell therapy (n = 37) vs placebo (n = 19). Patients randomized to cell therapy experienced 1.57 ± 1.39 cardiac-related hospital visits 12 months before injection, compared with 0.78 ± 1.90 hospital visits 12 months after injection, which was associated with a 62% cost reduction translating to an average savings of $5500 per cell therapy patient. Patients in the placebo group also demonstrated a reduction in cardiac-related hospital events and costs, although to a lesser degree than the CD34+ group. Through 1 January 2019, 24% of CD34+ subjects died at an average of 6.5 ± 2.4 years after enrollment, whereas 47% of placebo patients died at an average of 3.7 ± 1.9 years after enrollment. In conclusion, CD34+ cell therapy for subjects with refractory angina is associated with improved mortality and a reduction in hospital visits and expenditures for cardiac procedures in the year following treatment.

Long-Term (3 Years) Outcomes of Ranolazine Therapy for Refractory Angina Pectoris (from the Ranolazine Refractory Registry).

Ranolazine is approved for patients with chronic stable angina but has not been formally studied in patients with refractory angina pectoris (RAP). Patients with RAP have limited therapeutic options and significant limitations in their quality of life. The Ranolazine Refractory Angina Registry was designed to evaluate the safety, tolerability, and effectiveness of ranolazine in RAP patients in order to expand treatment options for this challenging patient population. Using an extensive prospective database, we enrolled 158 consecutive patients evaluated in a dedicated RAP clinic. Angina class, medications, major adverse cardiac events including death, myocardial infarction, and revascularization were obtained at 12, 24, and 36 months. At 3 years, 95 (60%) patients remained on ranolazine. A ≥2 class improvement in angina was seen in 48% (38 of 80 patients with known Canadian Cardiovascular Society class) of those who remained on ranolazine. Discontinuation due to side effects, ineffectiveness, cost, and progression of disease were the principle reasons for discontinuation, but primarily occurred within the first year. In conclusion, ranolazine is an effective antianginal therapy at 3-year follow-up in patients with RAP and may reduce cardiac readmission.

Incidence, predictors, management and outcomes of coronary perforations.

OBJECTIVES: We examined the contemporary incidence, types, predictors, angiographic characteristics, management and outcomes of coronary perforation. BACKGROUND: Coronary perforation is a rare, but important, complication of percutaneous coronary intervention (PCI). There is lack of data on perforations stratified as large and distal vessel perforations. METHODS: Retrospective, observational cohort study of all patients who underwent PCI at a high volume, tertiary hospital between the years 2009 and 2016. Angiograms of all coronary perforation cases were reviewed to determine the mechanism, type, and management of perforation. Risk-adjusted periprocedural complication rates were compared between patients with and without coronary perforation. One-year mortality outcomes of patients with large vessel vs. distal vessel perforation were also examined. RESULTS: Coronary perforation occurred in 68 of 13,339 PCIs (0.51%) performed during the study period: 51 (75%) were large vessel perforations and 17 (25%) distal vessel perforations. Most (67%) large vessel perforations were due to balloon/stent inflation, whereas most (94%) distal vessel perforations were due to guidewire exit. Patients with coronary perforations had significantly higher risk for periprocedural complications (adjusted odds ratio 7.57; 95% CI: 4.22-13.50; P < 0.001). Only one patient with large vessel perforation required emergency cardiac surgery, yet in-hospital mortality was high with both large vessel (7.8%) and distal vessel (11.8%) perforations. CONCLUSIONS: Coronary perforation is an infrequent, but potentially severe PCI complication. Most coronary perforations are large vessel perforations. Although coronary perforations rarely lead to emergency cardiac surgery, both distal vessel and large vessel perforations are associated with high in-hospital mortality, highlighting the importance of prevention.

Long-term survival in patients with refractory angina.

AIMS: An increasing number of patients with severe coronary artery disease (CAD) are not candidates for traditional revascularization and experience angina in spite of excellent medical therapy. Despite limited data regarding the natural history and predictors of adverse outcome, these patients have been considered at high risk for early mortality. METHODS AND RESULTS: The OPtions In Myocardial Ischemic Syndrome Therapy (OPTIMIST) program at the Minneapolis Heart Institute offers traditional and investigational therapies for patients with refractory angina. A prospective clinical database includes detailed baseline and yearly follow-up information. Death status and cause were determined using the Social Security Death Index, clinical data, and death certificates. Time to death was analysed using survival analysis methods. For 1200 patients, the mean age was 63.5 years (77.5% male) with 72.4% having prior coronary artery bypass grafting, 74.4% prior percutaneous coronary intervention, 72.6% prior myocardial infarction, 78.3% 3-vessel CAD, 23.0% moderate-to-severe left-ventricular (LV) dysfunction, and 32.6% congestive heart failure (CHF). Overall, 241 patients died (20.1%: 71.8% cardiovascular) during a median follow-up 5.1 years (range 0-16, 14.7% over 9). By Kaplan-Meier analysis, mortality was 3.9% (95% CI 2.8-5.0) at 1 year and 28.4% (95% CI 24.9-32.0) at 9 years. Multivariate predictors of all-cause mortality were baseline age, diabetes, angina class, chronic kidney disease, LV dysfunction, and CHF. CONCLUSION: Long-term mortality in patients with refractory angina is lower than previously reported. Therapeutic options for this distinct and growing group of patients should focus on angina relief and improved quality of life.

Multicenter cell processing for cardiovascular regenerative medicine applications: the Cardiovascular Cell Therapy Research Network (CCTRN) experience.

Abstract Background aims. Multicenter cellular therapy clinical trials require the establishment and implementation of standardized cell-processing protocols and associated quality control (QC) mechanisms. The aims here were to develop such an infrastructure in support of the Cardiovascular Cell Therapy Research Network (CCTRN) and to report on the results of processing for the first 60 patients. Methods. Standardized cell preparations, consisting of autologous bone marrow (BM) mononuclear cells, prepared using a Sepax device, were manufactured at each of the five processing facilities that supported the clinical treatment centers. Processing staff underwent centralized training that included proficiency evaluation. Quality was subsequently monitored by a central QC program that included product evaluation by the CCTRN biorepositories. Results. Data from the first 60 procedures demonstrated that uniform products, that met all release criteria, could be manufactured at all five sites within 7 h of receipt of BM. Uniformity was facilitated by use of automated systems (the Sepax for processing and the Endosafe device for endotoxin testing), standardized procedures and centralized QC. Conclusions. Complex multicenter cell therapy and regenerative medicine protocols can, where necessary, successfully utilize local processing facilities once an effective infrastructure is in place to provide training and QC.