Mechanical Circulatory Support During Surgical Revascularization for Ischemic Cardiomyopathy.

BACKGROUND: This study aimed to describe the use of perioperative mechanical circulatory support (MCS) and its impact on outcomes in patients with ischemic cardiomyopathy who were undergoing surgical revascularization. METHODS: Patients with an ejection fraction <35% who underwent isolated coronary artery bypass grafting (CABG) from 2015 to 2021 were identified (N = 378). Patients were divided into no MCS, preoperative MCS, and postoperative MCS groups on the basis of timing of MCS initiation, which included intraaortic balloon pump, extracorporeal membrane oxygenation, or Impella device (Abiomed) use. The primary outcome of interest was operative mortality. RESULTS: The median Society of Thoracic Surgeons Predicted Risk of Mortality was 2.4%. Sixty-six percent (n = 246) of patients had a previous myocardial infarction, and 61.8% of these patients were within 21 days of CABG. Twenty-one patients (5.6%) presented in cardiogenic shock. The preoperative MCS cohort consisted of 31 patients (8.2%) who underwent CABG a median of 2 days after MCS initiation. Thirty (7.9%) patients required postoperative MCS. Independent risk factors for requiring postoperative MCS included the preoperative ejection fraction (odds ratio, 0.93; P = .01 and the presence of preoperative MCS (odds ratio, 3.06; P = .02). Overall, operative mortality was 3.4%, and 3-year survival was 87.0%. Operative mortality in patients who did and did not receive preoperative MCS was 7.7% and 2.9% (P = .12) with no difference in long-term survival (P = .80), whereas patients requiring postoperative MCS had significantly increased operative (16.7%) and late mortality (63%; P <.01). CONCLUSIONS: CABG can be performed safely in patients with ischemic cardiomyopathy with selective use of perioperative MCS. Despite advanced disease severity, patients requiring preoperative MCS demonstrate acceptable short- and long-term survival. Patients requiring postoperative MCS have increased postoperative morbidity and mortality.

Monolithic silicon for high spatiotemporal translational photostimulation.

Electrode-based electrical stimulation underpins several clinical bioelectronic devices, including deep-brain stimulators1,2 and cardiac pacemakers3. However, leadless multisite stimulation is constrained by the technical difficulties and spatial-access limitations of electrode arrays. Optogenetics offers optically controlled random access with high spatiotemporal capabilities, but clinical translation poses challenges4-6. Here we show tunable spatiotemporal photostimulation of cardiac systems using a non-genetic platform based on semiconductor-enabled biomodulation interfaces. Through spatiotemporal profiling of photoelectrochemical currents, we assess the magnitude, precision, accuracy and resolution of photostimulation in four leadless silicon-based monolithic photoelectrochemical devices. We demonstrate the optoelectronic capabilities of the devices through optical overdrive pacing of cultured cardiomyocytes (CMs) targeting several regions and spatial extents, isolated rat hearts in a Langendorff apparatus, in vivo rat hearts in an ischaemia model and an in vivo mouse heart model with transthoracic optical pacing. We also perform the first, to our knowledge, optical override pacing and multisite pacing of a pig heart in vivo. Our systems are readily adaptable for minimally invasive clinical procedures using our custom endoscopic delivery device, with which we demonstrate closed-thoracic operations and endoscopic optical stimulation. Our results indicate the clinical potential of the leadless, lightweight and multisite photostimulation platform as a pacemaker in cardiac resynchronization therapy (CRT), in which lead-placement complications are common.

Long-term survival of ischemic cardiomyopathy patients with severe left ventricular dysfunction after CABG vs heart transplantation: A single center retrospective analysis.

BACKGROUND: There are no guidelines on the surgical management for ischemic cardiomyopathy (ICM) patients with severe left ventricular dysfunction. The present study aims to assess the long-term survival of these patients treated with two different surgical techniques, coronary artery bypass grafting (CABG) and heart transplantation (HTx). METHODS: This retrospective study included 218 ICM patients with left ventricular ejection fraction (LVEF) ≤35% who underwent CABG (n = 106) and HTx (n = 112) from 2011 to 2021 in a single center. After propensity adjustment analysis each group consisted of 51 patients. Clinical characteristics were evaluated for all-cause follow-up mortality by the Cox proportional hazards regression model. A risk prediction model was generated from multivariable-adjusted Cox regression analysis and applied to stratify patients with different clinical risks. The long-term survival was estimated by Kaplan-Meier analysis for different surgery groups. RESULTS: Long-term survival was comparable between CABG and HTx groups. After being stratified into different risk subgroups according to risk predictors, the HTx group exhibited superior survival outcomes compared to the CABG group among the high-risk patients (67.8% vs 44.4%, 64.1% vs 38.9%, and 64.1% vs 33.3%, p = 0.047) at 12, 36, and 60 months respectively, while the survival was comparable between HTx and CABG groups among low-risk patients (87.0% vs 97.0%, 82.4% vs 97.0%, and 70.2% vs 91.6%, p = 0.11) at 12, 36, and 60 months respectively in the PSM cohort. CONCLUSION: Long-term survival in ICM patients with severe left ventricular dysfunction who received CABG or HTx was comparable in general. Nonetheless, a favorable outcome of HTx surgery compared to CABG was observed among high-risk patients.

A treatment algorithm for ischemic cardiomyopathy.

Treatment of ischemic cardiomyopathy has been the focus of increased attention by cardiologists due to recent evidence of an important outcome study comparing percutaneous coronary intervention (PCI) plus optimal medical treatment vs optimal medical treatment alone, concluding for the futility of myocardial revascularization by PCI. A relatively older trial of coronary artery bypass grafting (CABG) in the same condition, on the other hand, had concluded for some prognostic improvement at a long-term follow-up. This short manuscript addresses how to triage such patients, frequently encountered in medical practice and considering clinical presentation, imaging results, and surgical risk, to provide practical guidance to treatment.

Risk of Ischemic Heart Disease in Patients With Postpancreatectomy Diabetes and Pancreatic Cancer: A Population-Based Study.

BACKGROUND: Postpancreatectomy diabetes can be caused by resection of functioning pancreatic tissue and is associated with postoperative pancreatic islet cell mass loss and subsequent endocrine dysfunction. Diabetes is a well-known risk factor for ischemic heart disease. However, no previous studies have investigated ischemic heart disease in patients with postpancreatectomy diabetes and pancreatic cancer. METHODS AND RESULTS: Rates of patients with diabetes diagnosed with pancreatic cancer who underwent pancreatectomy between 2002 and 2019 in South Korea were obtained from the Korean National Health Insurance Service database. Patient-level propensity score matching was conducted to reduce the possibility of selection bias, and multivariate Cox proportional hazards models were used to determine the association between postpancreatectomy diabetes and ischemic heart disease. In total, 30 242 patients were initially enrolled in the study. After applying exclusion criteria and propensity score matching, 2952 patients were included in the comparative analysis between the postpancreatectomy group with diabetes and the group without diabetes. Patients in the postpancreatectomy group with diabetes had significantly higher rates of ischemic heart disease than those in the group without diabetes. In total, 3432 patients were included in the comparison between the postpancreatectomy and prepancreatectomy groups with diabetes. There was no significant difference in the risk of ischemic heart disease between the postpancreatectomy and prepancreatectomy groups with diabetes. CONCLUSIONS: Patients who developed diabetes after pancreatectomy had a higher risk of ischemic heart disease than patients who did not develop diabetes after pancreatectomy, and the rate of ischemic heart disease in these patients was similar to that in patients preoperatively diagnosed with diabetes.

Surgical Porcine Model of Chronic Myocardial Ischemia Treated by Exosome-laden Collagen Patch and Off-pump Coronary Artery Bypass Graft.

Chronic myocardial ischemia resulting from progressive coronary artery stenosis leads to hibernating myocardium (HIB), defined as myocardium that adapts to reduced oxygen availability by reducing metabolic activity, thereby preventing irreversible cardiomyocyte injury and infarction. This is distinct from myocardial infarction, as HIB has the potential for recovery with revascularization. Patients with significant coronary artery disease (CAD) experience chronic ischemia, which puts them at risk for heart failure and sudden death. The standard surgical intervention for severe CAD is coronary artery bypass graft surgery (CABG), but it has been shown to be an imperfect therapy, yet no adjunctive therapies exist to recover myocytes adapted to chronic ischemia. To address this gap, a surgical model of HIB using porcine that is amenable to CABG and mimics the clinical scenario was used. The model involves two surgeries. The first operation involves implanting a 1.5 mm rigid constrictor on the left anterior descending (LAD) artery. As the animal grows, the constrictor gradually causes significant stenosis resulting in reduced regional systolic function. Once the stenosis reaches 80%, the myocardial flow and function are impaired, creating HIB. An off-pump CABG is then performed with the left internal mammary artery (LIMA) to revascularize the ischemic region. The animal recovers for one month to allow for optimal myocardial improvement prior to sacrifice. This allows for physiologic and tissue studies of different treatment groups. This animal model demonstrates that cardiac function remains impaired despite CABG, suggesting the need for novel adjunctive interventions. In this study, a collagen patch embedded with mesenchymal stem cell (MSC)-derived exosomes was developed, which can be surgically applied to the epicardial surface distal to LIMA anastomosis. The material conforms to the epicardium, is absorbable, and provides the scaffold for the sustained release of signaling factors. This regenerative therapy can stimulate myocardial recovery that does not respond to revascularization alone. This model translates to the clinical arena by providing means of physiological and mechanistic explorations regarding recovery in HIB.

Management of Tricuspid Valve Regurgitation During Surgical Ventricular Restoration for Ischemic Cardiomyopathy.

INTRODUCTION: We studied the effect of tricuspid valve (TV) surgery combined with surgical ventricular restoration (SVR) on operative outcomes, rehospitalization, recurrent tricuspid regurgitation, and survival of patients with ischemic cardiomyopathy. Additionally, surgery was compared to conservative management in patients with mild or moderate tricuspid regurgitation. To the best of our knowledge, the advantage of combining TV surgery with SVR in patients with ischemic cardiomyopathy had not been investigated before. METHODS: This retrospective cohort study included 137 SVR patients who were recruited from 2009 to 2020. Patients were divided into two groups - those with no concomitant TV surgery (n=74) and those with concomitant TV repair or replacement (n=63). RESULTS: Extracorporeal membrane oxygenation use was higher in SVR patients without TV surgery (P=0.015). Re-exploration and blood transfusion were significantly higher in those with TV surgery (P=0.048 and P=0.037, respectively). Hospital mortality occurred in eight (10.81%) patients with no TV surgery vs. five (7.94%) in the TV surgery group (P=0.771). Neither rehospitalization (log-rank P=0.749) nor survival (log-rank P=0.515) differed in patients with mild and moderate tricuspid regurgitation in both groups. Freedom from recurrent tricuspid regurgitation was non-significantly higher in mild and moderate tricuspid regurgitation patients with no TV surgery (P=0.059). Conservative management predicted the recurrence of tricuspid regurgitation. CONCLUSION: TV surgery concomitant with SVR could reduce the recurrence of tricuspid regurgitation; however, its effect on the clinical outcomes of rehospitalization and survival was not evident. The same effects were observed in patients with mild and moderate tricuspid regurgitation.

Cardiac magnetic resonance imaging for myocardial viability assessment: Optimizing surgical revascularization in ischemic heart disease.

BACKGROUND: Patients with poor ejection fraction undergoing coronary artery bypass grafting carry higher operative risk and have poor long-term survival. Cardiac magnetic resonance is a useful modality to assess viability which can identify patients likely to benefit most from revascularization. In this study, we aimed to assess the outcome in patients selected for surgical revascularization by cardiac magnetic resonance imaging and identify predictors associated with poor outcomes. METHODS: The study included patients with severely impaired left ventricular function but with at least six viable segments. Patients requiring emergency surgery, undergoing combined procedures, or where cardiopulmonary bypass was required were excluded. Cardiac magnetic resonance was carried out both preoperatively and at six months postoperatively by the same radiologist in all cases. Late gadolinium enhancement was used for the evaluation of myocardial viability. RESULTS: Amongst a total of 493 segments studied, there were 89 (18.1%) non-viable, 117 (23.7%) hibernating and 287 (58.2%) viable segments. At six months, the number of non-viable segments changed from 89 (18.1%) to 97 (19.7%), with an increase in viable segments from 287 (58.2%) to 374 (75.8%) and a corresponding reduction of hibernating segments from 117 (23.7%) to 22 (4.5%). There was improvement in ejection fraction from 28 ± 5.54 to 37 ± 5.86 (p < 0.0001) in the entire cohort at six months. Overall mortality was 1 (3.2%). Preoperative left ventricular end-systolic volume had the strongest negative correlation with post-operative ejection fraction. CONCLUSION: Cardiac magnetic resonance aided revascularization is associated with low mortality. Preoperative left ventricular end-systolic volume is an important determinant of postoperative ejection fraction.

Association of Sinus Wavefront Activation and Ventricular Extrastimuli Mapping With Ventricular Tachycardia Re-Entrant Circuits.

BACKGROUND: Substrate-based ablation targets areas of delayed and fractionated electrograms during sinus rhythm, which are sensitive for identifying the ventricular tachycardia (VT) isthmus but is influenced by the activation wavefront direction and decremental pacing. OBJECTIVES: The aim of this study was to correlate the areas of latest activation during varying wavefront activation mapping and decremental pacing mapping with sites critical to the VT isthmus. METHODS: Three high-density electroanatomical substrate maps were created in patients presenting for ablation of monomorphic VT: 1) native sinus rhythm; 2) right ventricular (RV) apical pacing; and 3) an RV apical S2 map following the S1 drive train at 20 ms above the ventricular effective refractory period. Areas corresponding to the latest activation were compared with the VT isthmus identified by conventional mapping. RESULTS: Twenty patients with structural heart disease with a mean age of 55.6 ± 16.9 years were included. The majority of the cohort consisted of patients with ischemic heart disease (50%) and arrhythmogenic RV cardiomyopathy (35%). Epicardial ablation was performed in 45% of patients. The concordance of the site of latest activation in sinus rhythm with the VT isthmus was 75%. The location of the latest activation during RV apical pacing corresponded with the VT isthmus in 85% of cases. However, in 95% of cases, the site of the latest activation following the S2 stimulus colocalized to the VT isthmus. CONCLUSIONS: In a mix of underlying myocardial substrates, regions of conduction slowing during decremental pacing colocalize with the VT isthmus more frequently than sinus rhythm activation mapping and may have a role in substrate-based ablation where VT induction is undesirable.

[Myocardial revascularization in chronic coronary artery disease. State of art].

The review addresses debatable issues of myocardial revascularization in chronic forms of ischemic heart disease, shows major differences between percutaneous coronary intervention and coronary artery bypass grafting in terms of long-term prognosis, and the dependence of the results on the clinical profile of the disease. The review of current publications demonstrates advantages of open surgery in long-term survival and prevention of adverse outcomes in target groups of patients.

Evolution, coronary artery bypass surgery and outcomes of right ventricular dysfunction in ischaemic cardiomyopathy.

OBJECTIVES: Whether the presence or evolution of right ventricular dysfunction (RVD) affects the prognosis and the therapeutic choice between coronary artery bypass grafting (CABG) or medical therapy alone in patients with ischaemic cardiomyopathy (ICM) remains unclear. We investigate the prognostic and therapeutic implications of RVD in patients with ICM. METHODS: Patients with baseline echocardiographic right ventricular (RV) assessment were included from the Surgical Treatment of Ischaemic Heart Failure trial. The primary outcome was all-cause mortality. RESULTS: Of 1212 patients enrolled in the Surgical Treatment of Ischaemic Heart Failure trial, 1042 patients were included, with 143 (13.7%) mild RVD and 142 (13.6%) moderate-to-severe RVD. After a median follow-up of 9.8 years, compared with patients with normal RV function, patients with RVD had a higher risk of mortality [mild RVD: adjusted hazard ratio (aHR) 1.32; 95% confidence interval (CI) 1.06-1.65; moderate-to-severe RVD: aHR, 1.75; 95% CI 1.40-2.19]. Among patients with moderate-to-severe RVD, CABG provided no additional survival benefits compared to medical therapy alone (aHR: 0.98; 95% CI: 0.67-1.43). Among 746 patients with pre- and post-therapeutic RV assessment, a gradient risk for death increased from patients with consistent normal RV function, to patients with recovery from RVD, new-onset RVD and persistent RVD. CONCLUSIONS: RVD was associated with a worse prognosis in patients with ICM, and CABG provided no additional survival benefits to patients with moderate-to-severe RVD. The evolution of RV function had important prognostic implications, which emphasized the importance of both pre- and post-therapeutic RV assessment.

Revascularization in Ischemic Heart Failure with Reduced Left Ventricular Ejection Fraction.

PURPOSE OF REVIEW: Coronary artery disease (CAD) is estimated to account for over 60% of heart failure (HF) patients and is associated with worse outcomes than a non-ischemic etiology. In patients with ischemic HF, myocardial revascularization has multiple mechanisms of action based on the concept that blood flow restoration of viable but underperfused myocardium might reverse the hibernation of the left ventricle and prevent future spontaneous myocardial infarction, which could potentially improve patients' outcomes. Here, we aim to elaborate on indications, timing, type, and impact of completeness of revascularization in patients with heart failure with reduced ejection fraction (HFrEF) and ischemic etiology. RECENT FINDINGS: For decades, coronary artery bypass graft surgery has been the pilar of revascularization in patents with multivessel CAD and reduced EF. Recent development in the interventional field led to overall increase of percutaneous coronary intervention (PCI) adoption in treatment of ischemic HFrEF. However, recently published randomized study demonstrated no added benefit of PCI over optimal medical therapy in patients with severe ischemic cardiomyopathy challenging the beneficial role of revascularization in this setting. Since the decision on revascularization in ischemic cardiomyopathy frequently cannot be made based strictly on guidelines, tailored treatment strategy should be mandated with the essential role of multidisciplinary approach. These decisions should be based on capability to achieve complete revascularization, with the consideration that in certain situations it may not be accomplished.

Myocardial Revascularization in Patients With Ischemic Cardiomyopathy: For Whom and How.

Background Myocardial revascularization has been advocated to improve myocardial function and prognosis in ischemic cardiomyopathy (ICM). We discuss the evidence for revascularization in patients with ICM and the role of ischemia and viability detection in guiding treatment. Methods and Results We searched for randomized controlled trials evaluating the prognostic impact of revascularization in ICM and the value of viability imaging for patient management. Out of 1397 publications, 4 randomized controlled trials were included, enrolling 2480 patients. Three trials (HEART [Heart Failure Revascularisation Trial], STICH [Surgical Treatment for Ischemic Heart Failure], and REVIVED [REVascularization for Ischemic VEntricular Dysfunction]-BCIS2) randomized patients to revascularization or optimal medical therapy. HEART was stopped prematurely without showing any significant difference between treatment strategies. STICH showed a 16% lower mortality with bypass surgery compared with optimal medical therapy at a median follow-up of 9.8 years. However, neither the presence/extent of left ventricle viability nor ischemia interacted with treatment outcomes. REVIVED-BCIS2 showed no difference in the primary end point between percutaneous revascularization or optimal medical therapy. PARR-2 (Positron Emission Tomography and Recovery Following Revascularization) randomized patients to imaging-guided revascularization versus standard care, with neutral results overall. Information regarding the consistency of patient management with viability testing results was available in ≈65% of patients (n=1623). No difference in survival was revealed according to adherence or no adherence to viability imaging. Conclusions In ICM, the largest randomized controlled trial, STICH, suggests that surgical revascularization improves patients' prognosis at long-term follow-up, whereas evidence supports no benefit of percutaneous coronary intervention. Data from randomized controlled trials do not support myocardial ischemia or viability testing for treatment guidance. We propose an algorithm for the workup of patients with ICM considering clinical presentation, imaging results, and surgical risk.

Systolic blood pressure time in target range and long-term outcomes in patients with ischemic cardiomyopathy.

BACKGROUND: The relationship between the degree of systolic blood pressure (SBP) control and outcomes remains unclear in patients with ischemic cardiomyopathy (ICM). Current control metrics may not take into account the potential effects of SBP fluctuations over time on patients. METHODS: This study was a post-hoc analysis of the surgical treatment of ischemic heart failure trial which enrolled 2,136 participants with ICM. Our SBP target range was defined as 110 to 130 mm Hg and the time in target range (TTR) was calculated by linear interpolation. RESULTS: A total of 1,194 patients were included. Compared with the quartile 4 group (TTR 77.87%-100%), the adjusted hazard ratios and 95% confidence intervals of all-cause mortality were 1.32 (0.98-1.78) for quartile 3 group (TTR 54.81%-77.63%), 1.40 (1.03-1.90) for quartile 2 group (TTR 32.59%-54.67%), and 1.53 (1.14-2.04) for quartile 1 group (TTR 0%-32.56%). Per 29.28% (1-SD) decrement in TTR significantly increased the risk of all-cause mortality (1.15 [1.04-1.26]). Similar results were observed in the cardiovascular (CV) mortality and the composite outcome of all-cause mortality plus CV rehospitalization, and in the subgroup analyses of either coronary artery bypass grafting or medical therapy, and different baseline SBP. CONCLUSIONS: In patients with ICM, the higher TTR was significantly associated with decreased risk of all-cause mortality, CV mortality and the composite outcome of all-cause mortality plus CV rehospitalization, regardless of whether the patient received coronary artery bypass grafting or medical therapy, and the level of baseline SBP. TTR may be a surrogate metric of long-term SBP control in patients with ICM.

Differences in diagnostication, and revascularisation of ischaemic heart disease in Western Denmark.

INTRODUCTION: In Denmark, the incidence of and mortality from ischaemic heart disease (IHD) has been declining. In this context, it is of interest to assess any regional differences in diagnostication and invasive treatment of IHD. METHODS: We intended to describe the diagnostication and invasive treatment of IHD in Western Denmark at the regional/municipal level using the Western Denmark Heart Registry. Coronary angiography (CAG), percutaneous coronary intervention (PCI) and coronary arterial bypass grafting were registered from 2000 through 2019; cardiac multislice computed tomography (CMCT), from 2015 through 2019. RESULTS: Concerning the use of revascularisation for acute coronary syndrome (ACS), we found comparable regional activity levels but significant differences between individual municipalities. Furthermore, the use of CAG for chronic coronary syndrome (CCS) was significantly higher and the use of CMCT significantly lower in the North Denmark Region than in the Central and South Denmark Regions. CONCLUSION: We found differences in the rates of PCI for ACS at the municipal level but not between the Western Denmark regions. Furthermore, at the regional level, evaluation of chronic IHD differed regarding use of elective CAG and CMCT, and use of CMCT was not paralleled by a reduction in the number of CAG procedures. This may possibly prompt discussions on the strategy for invasive and non-invasive diagnosis of CCS and on targeted preventive measures. FUNDING: none TRIAL REGISTRATION. not relevant.

Morphological and immunological markers of repeated heart remodeling after surgical reconstruction of the left ventricle in ischemic cardiomyopathy.

INTRODUCTION: Effective treatment of patients with ischemic cardiomyopathy (ICM) is one of the most challenging issues in modern cardiac surgery. The aim of this study was to assess the state of cardiomyocytes and myocardial extracellular matrix, as well as to identify informative markers of an unfavorable prognosis for surgical treatment of ICM. MATERIALS AND METHODS: We retrospectively reviewed patients who underwent surgical treatment of ICM between 2011 and 2018 at a single center. Patients were divided into groups depending on the presence of repeated left ventricle (LV) remodeling in one-year follow-up after surgical reconstruction of the LV in ICM patients. RESULTS: A total of 45 patients with ICM were reviewed. The mean age of the patients was 57.9 ± 7.8 years. According to the results of the study, the area of cardiomyocyte nuclei differed statistically significantly among the regions with varying degrees of impaired local contractility (p = 0.042). According to the results of the pairwise comparison in dyskinetic areas of the myocardium, the area of cardiomyocyte nuclei was higher than in normokinetic areas (p = 0.042). A moderate positive correlation was found between the LV ejection fraction measured in one-year follow-up period after surgery and the number of CD163-positive cells (p = 0.012). CONCLUSION: In the myocardium of patients with LV reverse remodeling in the long-term postoperative period, perivascular fibrosis occurs more frequently than in patients with progressive LV remodeling. The number of M2-anti-inflammatory macrophages prevails in the myocardium of the patients with reverse remodeling compared with patients with progressive remodeling.

Autologous CD133 + Cells and Laser Revascularization in patients with severe Ischemic Cardiomyopathy.

OBJECTIVE: We tested the hypothesis that targeted TMLR combined with intramyocardial injection of autologous CD 133+ progenitor cells is safe and feasible in patients with chronic ischemic cardiomyopathy (ICM) and no revascularization options. METHODS: Eight male patients (age 62 ± 2.4 years) with multivessel severe ischemic heart disease and no revascularization options were enrolled. Autologous CD 133 + endothelial progenitor cells were derived and purified from the bone marrow on the day of surgery using the clinical-grade closed CliniMACS system. Using a lateral thoracotomy approach, TMLR was performed, followed by transmyocardial transplantation of purified CD133 + cells (mean number of transplanted cells: 12.5 × 106) in the region surrounding the TMLR sites. These sites were selected based on ischemia on pre-procedure perfusion imaging. We performed clinical and myocardial perfusion imaging pre-procedure and then at 6- and 12-month follow-up. RESULTS: No major complications or death occurred during the procedure or during the peri-operative hospital stay. One patient died of cardiac cause 6 months post-procedure. There was a reported short-term improvement in anginal and heart failure symptoms and a modest reduction in the ischemic score as assessed by perfusion imaging. CONCLUSIONS: Our phase 1 clinical study examining the combination therapy of targeted transmyocardial laser revascularization therapy and autologous CD133 + endothelial progenitor cells in patients with chronic ICM and no revascularization options demonstrates the feasibility and short-term safety of this combined approach and warrants future larger phase 2 randomized clinical studies.