Long-term safety and efficacy of intramyocardial adenovirus-mediated VEGF-DΔNΔC gene therapy eight-year follow-up of phase I KAT301 study

In phase I KAT301 trial, intramyocardial adenovirus-mediated vascular endothelial growth factor -DΔNΔC (AdVEGF-D) gene therapy (GT) resulted in a significant improvement in myocardial perfusion reserve and relieved symptoms in refractory angina patients at 1-year follow-up without major safety concerns. We investigated the long-term safety and efficacy of AdVEGF-D GT. 30 patients (24 in VEGF-D group and 6 blinded, randomized controls) were followed for 8.2 years (range 6.3–10.4 years). Patients were interviewed for the current severity of symptoms (Canadian Cardiovascular Society class, CCS) and perceived benefit from GT. Medical records were reviewed to assess the incidence of major cardiovascular adverse event (MACE) and other predefined safety endpoints. MACE occurred in 15 patients in VEGF-D group and in five patients in control group (21.5 vs. 24.9 per 100 patient-years; hazard ratio 0.97; 95% confidence interval 0.36–2.63; P = 0.95). Mortality and new-onset comorbidity were similar between the groups. Angina symptoms (CCS) were less severe compared to baseline in VEGF-D group (1.9 vs. 2.9; P = 0.006) but not in control group (2.2 vs. 2.6; P = 0.414). Our study indicates that intramyocardial AdVEGF-D GT is safe in the long-term. In addition, the relief of symptoms remained significant during the follow-up.

The Impact of Cell Therapy on Cardiovascular Outcomes in Patients With Refractory Angina

Rationale: Cell-based therapies are a novel potential treatment for refractory angina and have been found to improve markers of angina. However, the effects on mortality and major adverse cardiac events (MACE) have not been definitively investigated. Objective: To investigate the efficacy and safety of stem cell treatment compared with optimal medical treatment for refractory angina by conducting an updated meta-analysis, looking at clinical outcomes. Methods and Results: We performed a systematic review and meta-analysis of randomized controlled trials using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A comprehensive search was performed of PubMed, EMBASE (Excerpta Medica database), Cochrane, ClinicalTrials.gov , Google Scholar databases of randomized controlled trials, and scientific session abstracts. Studies were deemed eligible if they met the following criteria: (1) full-length publications in peer-reviewed journals; (2) evaluated cell therapy use in patients with no further revascularisation options while on optimal medical treatment; (3) patients had ongoing angina, Canadian Cardiovascular Society class II—IV; and (4) included a placebo/control arm. We calculated risk ratios for all-cause mortality, combined MACE events. We assessed heterogeneity using χ 2 and I 2 tests. We identified 1191 citations with 8 randomized controlled trials meeting inclusion criteria involving 526 patients. Outcomes pooled were MACE, mortality, and indices of angina (angina episodes, Canadian Cardiovascular Society angina class, exercise tolerance, and antianginal medications). Our analysis showed a decreased risk of both MACE (odds ratio, 0.41; CI, 0.25−0.70) and mortality (odds ratio, 0.24; 95% CI, 0.10−0.60) in cell-treated patients compared with patients on maximal medical therapy. This was supported by improvements in surrogate end points of anginal episodes, use of antianginal medications, Canadian Cardiovascular Society class, and exercise tolerance. Conclusions: In addition to improvements in indices of angina, cell-based therapies improve cardiovascular outcomes (mortality/MACE) in patients with refractory angina. Given the premature termination of the phase III study, this supports the need for further definitive trials. Prospero Registration : URL: https://www.crd.york.ac.uk/prospero/ . Unique identifier: CRD42018084257.

Stabil coronariabetegség kezelésére alkalmazott trimetazidin prolong hatásosságának vizsgálata. Multicentrikus, prospektív, obszervációs, nyílt klinikai vizsgálat, ONECAPS-vizsgálat

Introduction: The effectiveness of the manegement of stable coronary artery disease among outpatients is not well known. Aim: The aim of the study was to evaluate the effect of daily once trimetazidine prolong 80 mg on the angina number and severity (Canadian Cardiovascular Society class). Method: This multicenter, prospective, observational, 3-month clinical study included 2160 patients, but only 1701 patients completed the study. The patients’ mean age was 68 years (17% under 60 years). The start of angina was 7.8 ± 6.7 years. Hypertension (93.4%) and hypercholesterolemia (81%) were very common. Results: The patients were well treated with beta-blocking agents (88%), calcium antagonists (49%), angiotensin-converting enzym inhibitors (90%) and statin (77%) but only 5% received ivabradine and 50.5% was treated with trimetazidine MR. The patients attended 3 visits (inclusion, 1 month, 3 month). During the 3-month period, the weekly angina number of all patients treated with trimetazidine prolong 80 mg decreased from 2.55 to 0.41 (p<0.0001). A favorable effect was observed in CCS grading: CCS I. from 40.37% to 66.81%, CCS II. from 49.89% to 30.59%, CCS III. from 9.17% to 2% and CCS IV. from 0.56% to 0%. The mean office measured blood pressure decreased from 137/83 mmHg to 130/80 mmHg and the heart rate from 74 bpm to 71 bpm. Conclusions: In the real-life, in the stable coronary artery disease the angina remains despite the medical treatment. Once a day administered trimetazidine prolong 80 mg significantly reduced the weekly number of angina and the severity, too. These beneficial effects mediated not only by antiischemic effect but also by increased medication adherence. Orv Hetil. 2018; 159(38): 1549–1555.

Abstract 15337: The Prevalence of Clinically Significant Ischemia in Patients Undergoing Percutaneous Coronary Intervention, a Report From the Multicenter Registry

Background: Myocardial perfusion scintigraphy (MPS) plays an important role in the evaluation and quantification of myocardial ischemia, and those with significant ischemia (SI) benefit most from revascularization procedures. This study aimed to identify the clinical factors and anatomical features associated with SI in patients with stable ischemic heart disease (SIHD). Methods and Results: Data were analyzed from 4197 SIHD patients undergoing PCI in The Japan Cardiovascular Database (N = 11,258) between September 2008 and April 2013. MPS was used to evaluate 1070 (25.5%) patients. Significant ischemia (SI) was defined as more than 10% ischemic region. Logistic regression analysis was performed to identify any clinical factors associated with SI. Patients with a history of heart failure, stroke, or anginal symptoms with Canadian Cardiovascular Society class 2 or more were more likely to have SI (odds ratio [OR] 1.63, p = 0.025, OR: 1.85, p = 0.009, and OR: 1.49, p = 0.003, respectively). When angiographic variables were considered, a proximal left anterior descending artery (pLAD) lesion was the sole factor associated with SI (OR: 1.46, p = 0.012) (Table). Importantly, those with SI had more complications (p = 0.006), most notably post-PCI infarcts (p = 0.008) (Figure). Conclusions: Patients’ background data, such as stronger anginal symptoms or a pLAD lesion, were associated with SI. Since patients with SI are necessary to be treated with PCI to improve long-term prognosis, however procedure-related complications happen more frequently than non-SI patients. Physicians must give their full attention to the PCI procedure in SI patients to minimize their complication rate.

Anomalous Origin of the Left Main Coronary Artery from the Right Coronary Artery with a Preaortic Course

We report the case of a 51-year-old woman who presented with stable angina pectoris and Canadian Cardiovascular Society class II functional capacity. An electrocardiogram during a treadmill exercise test showed substantial ST-segment depression in the inferolateral leads. Coronary angiograms revealed an anomalous origin of the left main coronary artery from the opposite sinus of Valsalva and an interarterial course between the ascending aorta and pulmonary artery. Although this phenomenon is dangerous, the patient refused further examination. We discuss the diagnosis and treatment of patients who have an anomalous origin of a coronary artery from the opposite sinus of Valsalva.

Neoangiogenesis after direct intramyocardial implantation of bone marrow-derived stem cells in a patient with severe coronary artery disease ineligible for percutaneous or surgical revascularization

Bone marrow-derived stem cells (BMSC) may be an alternative for the treatment of patients with severe coronary artery disease ineligible for either percutaneous or surgical revascularization. This case report presents a 65-year-old male patient with untreatable angina pectoris (Canadian Cardiovascular Society Class III) and severe coronary artery disease. A mixture of BMSC containing approximately 3×106 CD34+ cells was directly injected into preoperatively determined ischemic regions of the myocardium by median sternotomy. At baseline, at 3 months, and at 1 year of follow-up, echocardiography (demonstrating wall motions of 16 segments), single-photon emission computed tomography, and coronary angiography (at baseline and at 1 year) were performed to assess myocardial perfusion, left ventricular (LV) function and coronary anatomy. The patient reached Canadian Cardiovascular Society Class I after 6 months of cell implantation. The ejection fraction increased from 34% to 37% at the third month and 40% at 1 year of follow-up. At 1 year of follow-up, preoperatively akinetic mid-base septum and anteroseptal regions progressed to mild hipokinesia and severe hypokinetic mid-base-apical anterior regions and apical lateral-inferior regions became normokinesia. Single-photon emission computed tomography revealed a visible improvement in anterior and lateral segments at 1 year of follow-up. Coronary angiography showed newly developed collateral arteries at 1 year of follow-up. BMSC transplantation in a patient with severe coronary artery disease resulted in increase of LV ejection fraction, an increase of the perfusion of ischemic myocardial regions, and improvement in wall motion defects without any adverse events.