FFR-Guided Complete or Culprit-Only PCI in Patients with Myocardial Infarction.

BACKGROUND: The benefit of fractional flow reserve (FFR)-guided complete revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease remains unclear. METHODS: In this multinational, registry-based, randomized trial, we assigned patients with STEMI or very-high-risk non-STEMI (NSTEMI) and multivessel disease who were undergoing primary percutaneous coronary intervention (PCI) of the culprit lesion to receive either FFR-guided complete revascularization of nonculprit lesions or no further revascularization. The primary outcome was a composite of death from any cause, myocardial infarction, or unplanned revascularization. The two key secondary outcomes were a composite of death from any cause or myocardial infarction and unplanned revascularization. RESULTS: A total of 1542 patients underwent randomization, with 764 assigned to receive FFR-guided complete revascularization and 778 assigned to receive culprit-lesion-only PCI. At a median follow-up of 4.8 years (interquartile range, 4.3 to 5.2), a primary-outcome event had occurred in 145 patients (19.0%) in the complete-revascularization group and in 159 patients (20.4%) in the culprit-lesion-only group (hazard ratio, 0.93; 95% confidence interval [CI], 0.74 to 1.17; P = 0.53). With respect to the secondary outcomes, no apparent between-group differences were observed in the composite of death from any cause or myocardial infarction (hazard ratio, 1.12; 95% CI, 0.87 to 1.44) or unplanned revascularization (hazard ratio, 0.76; 95% CI, 0.56 to 1.04). There were no apparent between-group differences in safety outcomes. CONCLUSIONS: Among patients with STEMI or very-high-risk NSTEMI and multivessel coronary artery disease, FFR-guided complete revascularization was not shown to result in a lower risk of a composite of death from any cause, myocardial infarction, or unplanned revascularization than culprit-lesion-only PCI at 4.8 years. (Funded by the Swedish Research Council and others; FULL REVASC ClinicalTrials.gov number, NCT02862119.).

International randomized trial on the effect of revascularization or optimal medical therapy of chronic total coronary occlusions with myocardial ischemia - ISCHEMIA-CTO trial - rationale and design.

BACKGROUND: Chronic total occlusions (CTO) are frequent among patients with coronary artery disease. Revascularization with percutaneous coronary intervention (PCI) is safe and feasible in experienced hands. However, randomized data are needed to demonstrate symptomatic as well as prognostic effect of CTO-PCI compared to optimal medical therapy alone. METHODS: This trial aims to evaluate the effect of CTO PCI in patients with a CTO lesion and target vessel diameter ≥ 2.5 mm, and myocardial ischemia in the relevant territory. First, all patients are subjected to optimal medical therapy (OMT) for at least for 3 months and non-CTO lesions are managed according to guidelines. Subsequently, prior to randomization myocardial ischemia and quality of life (Seattle Questionnaire (SAQ)) is assessed. Patients are divided into two cohorts based on their SAQ score and randomized to either OMT alone or OMT and CTO-PCI. Cohort A is defined as Low- or asymptomatic patients with a quality-of-life score > 60 and/or CCS class < 2, and more than 10 % ischemia in the left ventricle (LV). Cohort B is symptomatic patients with a quality-of-life score < 60 or CCS class angina > 1 and at least ischemia in 5% of the LV. The primary end-point in cohort A is a composite of major adverse cardiac and cerebral events, hospitalization for heart failure and malignant ventricular arrhythmias. The primary endpoint in cohort B is difference in quality of life 6 months after randomization. IMPLICATIONS: This trial is designed to investigate if CTO-PCI improves QoL and MACCE. Both positive and negative outcome of the trial will affect future guidelines and recommendations on how to treat patients with CTO.

In vivo morphologic comparison of saphenous vein grafts and native coronary arteries following non-ST elevation myocardial infarction.

OBJECTIVE: This study aimed to assess the pathophysiological differences between saphenous vein grafts (SVG) and native coronary arteries (NCA) following presentation with non-ST elevated myocardial infarction (NSTEMI). BACKGROUND: There is accelerated pathogenesis of de novo coronary disease in harvested SVG following coronary artery bypass (CABG) surgery, which contributes to both early and late graft failure, and is also causal in adverse outcomes following vein graft PCI. However in vivo assessment, with OCT imaging, comparing the differences between vein grafts and NCAs has not previously been performed. METHODS: We performed a retrospective, observational, analysis in patients who underwent PCI with adjunctive OCT imaging following presentation with NSTEMI, where the infarct-related artery (IRA) was either in an SVG or NCA. RESULTS: A total of 1550 OCT segments was analysed from thirty patients with a mean age of 66.3 (±9.0) years were included. The mean graft age of 13.9 (±5.6) years in the SVG group. OCT imaging showed that the SVG group had evidence of increased lipid pool burden (lipid pool quadrants, 2.1 vs 2.7; p = 0.021), with a reduced fibro-atheroma cap-thickness in the SVG group (45.0 µm vs 38.5 µm; p = 0.05) and increased burden of calcification (calcified lesion length = 0.4 mm vs 1.8 mm; p = 0.007; calcified quadrants = 0.2 vs 0.9; p = 0.001; arc of superficial calcium deposits = 11.6° vs 50.9°; p = 0.007) when compared to NCA. CONCLUSION: This OCT study has demonstrated that vein grafts have a uniquely atherogenic environment which leads to the development of calcified, lipogenic, thin-capped fibro-atheroma's, which may be pivotal in the increased, acute and chronic graft failure rate, and may underpin the increased adverse outcomes following vein graft PCI.

Permanent work disability in patients ≤50 years old after percutaneous coronary intervention and coronary artery bypass grafting (the CRAGS study).

Background: The aim of this study was to investigate the incidence of permanent working disability (PWD) in young patients after percutaneous or surgical coronary revascularization. Methods and Results: The study included 1035 consecutive patients ≤50 years old who underwent coronary revascularization [910 and 125 patients in percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) groups, respectively] between 2002 and 2012 at 4 Finnish hospitals. The median follow-up time was 41 months. The overall incidence of PWD was higher after CABG compared to PCI (at 5 years, 34.8 vs. 14.7%, P < 0.001). Freedom from PWD in the general population aged 45 was 97.2% at 4 years follow-up. Median time to grant disability pension was 11.6 months after CABG and 24.4 months after PCI (P = 0.018). Reasons for PWD were classified as cardiac (35.3 vs. 36.9%), psychiatric (14.7 vs. 14.6%), and musculoskeletal (14.7 vs. 15.5%) in patients undergoing CABG vs. PCI. Overall freedom from PWD was higher in patients without major adverse cardiac and cerebrovascular event (MACCE) (at 5 years, 85.6 vs. 71.9%, P < 0.001). Nevertheless, rate of PWD was high also in patients without MACCE and patients with preserved ejection fraction during follow-up. Conclusions: Although coronary revascularization confers good overall survival in young patients, PWD is common especially after CABG and mostly for cardiac reasons even without occurrence of MACCE. Supportive measures to preserve occupational health are warranted concomitantly with coronary revascularization at all levels of health care.

Myeloperoxidase gene variation as a determinant of atherosclerosis progression in the abdominal and thoracic aorta: an autopsy study.

Myeloperoxidase (MPO) is an enzyme that transforms low-density lipoprotein into atherogenic particles. The MPO gene has a promoter polymorphism at position -463, which affects gene transcription and leads to high- (G/G) and low-expression (A/A, A/G) genotypes. To determine if these genotypes are associated with the severity of atherosclerosis, we performed an autopsy study of 300 men aged 33 to 69 years (Helsinki Sudden Death Study). We examined the percentage area of fatty streaks and fibrotic, calcified, and complicated lesions using computer-assisted planimetry. The MPO genotypes were determined by PCR. There were significant interactions of MPO genotype with the mean area of fibrotic (p < 0.01) and calcified (p < 0.05) lesions in the abdominal aorta and in fibrotic lesions in the thoracic aorta (p = 0.003). In the abdominal aorta, men < 53 years with low-expression genotypes had on average a 38.6% larger area of fibrotic lesions and a 43.8% larger area of calcified lesions than did the subjects with the G/G genotype. This association weakened with advancing age. Among men < 53 years, the MPO genotype was an independent predictor of fibrotic (p = 0.037) and calcified (p = 0.001) lesion area in the abdominal aorta after adjustment for age, body mass index, diabetes, hypertension, and smoking. MPO gene variation may modify the extent of advanced atherosclerotic lesions in the human aorta in early middle age.

Coronary artery calcification is related to functional polymorphism of matrix metalloproteinase 3: the Helsinki Sudden Death Study.

Matrix metalloproteinase 3 (MMP3) is expressed in human coronary atherosclerotic lesions and is known to be involved in degradation of the plaque and to be co-localized with calcium and fibrin deposits in advanced lesions, indicating a possible role of MMP3 in arterial calcification. The MMP3 gene promoter polymorphism leads to low promoter activity 6A6A, intermediate promoter activity 5A6A and high promoter activity 5A5A genotypes. To determine whether these genotypes predict the extent of atherosclerosis we investigated their association with different types of coronary lesions in an autopsy series of 300 middle-aged white Finnish men (aged 35-69 years) from the Helsinki Sudden Death Study (HSDS). Areas of the coronary wall covered with different atherosclerotic lesions were measured and MMP3 genotypes were determined by PCR and minisequencing. In men >/=53 years the mean area of calcified lesion in the most severely affected coronary artery was significantly associated with the MMP3 genotype (P=0.029). Subjects with high promoter activity genotypes had on average larger calcified lesion areas than those with the low-activity genotype. The MMP3 genotype (P=0.025) persisted as an independent predictor of mean calcified lesion area after stepwise adjustment for age, BMI, hypertension, diabetes, number of affected vessels and smoking. These data provide evidence that the proposed effect of MMP3 in the process of atherogenesis may be modified by the MMP3 genotype.

The relationship between somatic mtDNA rearrangements, human heart disease and aging.

The lifetime accumulation of low-abundance, somatic mtDNA re-arrangements (sublimons) has been proposed as a potential contributor to aging, and also to diseases such as cardiomyopathy or coronary heart disease. Tissue-specific sublimons, varying in abundance by three orders of magnitude between individuals, have recently been observed in myocardium of control subjects. To study the relationship between myocardial sublimon levels and various types of cardiac disease and aging, we applied a semi-quantitative fluorescent PCR assay on cellular DNA extracted from left ventricle in a series of 300 well characterized male victims of sudden death up to age 70 (Helsinki Sudden Death Study). The most prevalent classes of sublimons were present at <0.1 to 91 copies per cell, but their abundance did not correlate with any cardiac disease phenotype. In multiple regression analyses age (beta = 0.43, P < 0.0001) and smoking (bet = 0.25, P = 0.012) were the only independent factors found to correlate with sublimon levels. Thus, sublimons are inferred to accumulate with age in myocardium of a subset of individuals, but to levels where they do not appear to have any phenotypic effects during a typical life span. We propose that, instead of being a causal factor in cardiac aging, sublimons co-exist with wild-type mtDNA in an equilibrium which is regulated by as yet unknown mechanisms.