Matsuo, Yoshiki

Objective— Endothelial dysfunction is an early manifestation of atherosclerosis. Inflammation and vasa vasorum play a pivotal role in the pathophysiology of plaque initiation, development, and complications. Optical coherence tomography allows high-resolution imaging of tissue microstructure. Therefore, the aim of this study was to test the hypothesis that segments with endothelial dysfunction show macrophages and vasa vasorum in patients with early coronary artery disease. Approach and Results— Optical coherence tomography images were obtained from 40 patients with mild coronary atherosclerosis who underwent coronary endothelial function assessment. Optical coherence tomography findings, including macrophages and microchannels, were evaluated in 76 coronary segments corresponding to those in endothelial response to acetylcholine. Coronary artery diameter change in response to acetylcholine was more severe in segments showing macrophages (−17.7±14.7% versus −6.3±13.9%; P <0.01) and microchannels (−15.9±15.9% versus −6.4±13.5%; P <0.01) than those without. There were increasing trends of the prevalence of macrophages and microchannels with endothelial dysfunction as stratified by quartiles of coronary artery diameter change ( P <0.01 and P =0.02 for trend, respectively). In particular, segments with both macrophages and microchannels (n=12) tended to have worse endothelial function than those with macrophages alone (n=15) and microchannels alone (n=15; −22.1±14.6% versus −10.9±15.6% and −10.9±15.6%; P =0.07 and P =0.06, respectively). Conclusions— Epicardial endothelial dysfunction was associated with optical coherence tomography –identified macrophages and microchannels in mild coronary atherosclerosis. The current study further supports the role of inflammation and vasa vasorum proliferation in the early stage of coronary atherosclerosis.

Background Cardiac allograft vasculopathy is the leading cause of graft failure and death in heart transplant ( HT x) recipients; however, the association between the etiology of heart failure (ischemic cardiomyopathy [ ICM ] or non‐ ICM ) that led to HT x and progression of c ardiac allograft vasculopathy , and adverse events after HT x has not been explored. Methods and Results We retrospectively included 165 HT x patients, who were followed‐up with at least 2 virtual histology–intravascular ultrasound examinations after HT x, and grouped them as ICM (n=46) or non‐ ICM (n=119). Coronary artery plaque volume was analyzed using virtual histology–intravascular ultrasound, and cardiovascular event data—a composite of myocardial infarction, hospitalization for heart failure and arrhythmia, revascularization, retransplantation, and death including cardiovascular death—were collected from the medical records of all study subjects. ICM patients had significantly higher plaque volume at both first ( P =0.040) and follow‐up ( P =0.015) intravascular ultrasound examinations. After multivariate adjustment for traditional coronary risk factors, ICM was significantly associated with plaque progression (odds ratio 3.10; CI 1.17 to 9.36; P =0.023). Ten‐year cardiovascular event‐free survival was 50% in ICM patients compared with 84% in non‐ ICM patients (log‐rank test P =0.003). In multivariate Cox proportional hazard analysis, ICM was significantly associated with a higher event rate after HT x (hazard ratio 2.02; 95% CI 1.01 to 4.00; P =0.048). Conclusion Our study demonstrates that ischemic etiology of cardiomyopathy prior to HT x may be independently associated with plaque progression and higher event rate after HT x.

Background— Sex-specific differences affect the evaluation, treatment, and prognosis of coronary artery disease. We tested the hypothesis that long-term outcomes of fractional flow reserve (FFR)–guided percutaneous coronary intervention (PCI) are different between women and men. Methods and Results— Consecutive 1090 patients, referred for PCI and undergoing FFR measurements at the Mayo Clinic between October 2002 and December 2009, were included in this registry study. Clinical events were compared between the sexes during a median follow-up of 50.9 months. Of all patients, women had higher FFR adjusted by visual coronary stenosis than men ( P =0.03). The Kaplan–Meier percent of major adverse cardiac events at 5 years was 35% in women and 38% in men ( P =0.54). Interestingly, in patients undergoing PCI with an FFR <0.75, the incidence of death or myocardial infarction was significantly higher in women than in men (hazard ratio, 2.16; 95% confidence interval, 1.04–4.51; P =0.04). Moreover, compared with patients with FFR >0.80, deferral of PCI for those with FFR between 0.75 and 0.80 was associated with an increased rate of major adverse cardiac events, particularly death or myocardial infarction in women (hazard ratio, 3.25; 95% confidence interval, 1.56–6.74; P =0.002) and revascularization in men (hazard ratio, 2.66; 95% confidence interval, 1.66–4.54; P <0.001). Conclusions— Long-term outcome differs between women and men undergoing FFR-guided PCI. Our data suggest that the sex-based treatment strategy is necessary to further optimize prognosis of patients with coronary artery disease.