Publications

An 81-year-old female presented with chronic coronary disease (Canadian Cardiovascular Society angina severity grading III). The patient underwent coronary computed tomography angiography (CCTA) that revealed three-vessel coronary artery disease (3VD). This case illustrates that in a patient with 3VD, planning and execution of coronary artery bypass grafting (CABG) were successfully performed based solely on CCTA combined with fractional flow reserve derived from computed tomography angiography (FFRCT). Coronary artery bypass grafting (CABG) was planned and executed as follows: left internal mammary artery grafted to the left anterior descending artery (LAD), saphenous vein graft (SVG) to the right coronary artery (RCA), and SVG to the obtuse marginal artery (OM). Repeat imaging assessment with non-invasive CCTA and FFRCT at 30-day follow-up confirmed the safety of this approach. The FFRCT values of the RCA and LAD were normalized, whereas a borderline pressure drop was observed in the distal run-off of the OM (FFRCT=0.79). Notably, this is the first case in which post-CABG FFRCT assessment was performed. Post-CABG FFRCT is an investigational novel non-invasive tool for assessing the functional improvement of the epicardial conductance vessels following surgical revascularization.

The concentration of nitric oxide (NO) is increased in the exhaled air of patients with inflammatory lung diseases, including asthma, possibly reflecting cytokine-mediated chronic airway inflammation. Endogenous NO is generated from L-arginine by the action of several types of NO synthase (NOS). NOS have structural similarities with cytochrome P450 reductases. Alcohol decreases exhaled NO in animals, but this has not previously been investigated in man. We studied the effect of alcohol ingestion in nine asthmatic and 12 normal subjects, measuring the peak concentration of exhaled NO using a modified chemiluminescence analyser. A significant decrement in NO occurred in asthmatic patients (mean +/- SEM before ethanol 204 +/- 58 to 158 +/- 59 parts per billion (ppb) after ethanol; p < 0.02), without significant change in the normal subjects (122 +/- 14 to 114 +/- 15 ppb). Thus, in our study, alcohol decreased exhaled nitric oxide in asthmatic subjects but not in normal individuals. This may reflect preferential action on inducible nitric oxide synthase which is expressed in asthmatic airways. An inhibitory effect of ethanol on inducible nitric oxide synthase may contribute towards the effect of alcohol in asthma.

Background Use of everolimus-eluting stents (EES) has proven to be clinically effective and safe in patients with ST-segment elevation myocardial infarction but it remains unclear whether it is cost-effective compared to bare-metal stents (BMS) in the long-term. We sought to assess the cost-effectiveness of EES versus BMS based on the 5-year results of the EXAMINATION trial, from a Spanish health service perspective. Methods Decision analysis of the use of EES versus BMS was based on the patient-level clinical outcome data of the EXAMINATION trial. The analysis adopted a lifelong time horizon, assuming that long-term survival was independent of the initial treatment strategy after the end of follow-up. Life-expectancy, health-state utility scores and unit costs were extracted from published literature and publicly available sources. Non-parametric bootstrapping was combined with probabilistic sensitivity analysis to co-assess the impact of patient-level variation and parameter uncertainty. The main outcomes were total costs and quality-adjusted life-years. The incremental cost-effectiveness ratio was expressed as cost per quality-adjusted life-years gained. Costs and effects were discounted at 3%. Results The model predicted an average survival time in patients receiving EES and BMS of 10.52 and 10.38 undiscounted years, respectively. Over the life-long time horizon, the EES strategy was €430 more costly than BMS (€8,305 vs. €7,874), but went along with incremental gains of 0.10 quality-adjusted life-years. This resulted in an average incremental cost-effectiveness ratio over all simulations of €3,948 per quality-adjusted life-years gained and was below a willingness-to-pay threshold of €25,000 per quality-adjusted life-years gained in 86.9% of simulation runs. Conclusions Despite higher total costs relative to BMS, EES appeared to be a cost-effective therapy for ST-segment elevation myocardial infarction patients due to their incremental effectiveness. Predicted incremental cost-effectiveness ratios were below generally acceptable threshold values.

Objectives The aim of this study was to investigate the impact of post–percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) on clinical outcomes in patients with de novo 3-vessel disease (3VD) treated with contemporary PCI. Background The clinical impact of post-PCI QFR in patients treated with state-of-the-art PCI for de novo 3VD is undetermined. Methods All vessels treated in the SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) II trial were retrospectively screened and analyzed for post-PCI QFR. The primary endpoint of this substudy was vessel-oriented composite endpoint (VOCE) at 2 years, defined as the composite of vessel-related cardiac death, vessel-related myocardial infarction, and target vessel revascularization. The receiver-operating characteristic curve was used to calculate the optimal cutoff value of post-PCI QFR for predicting 2-year VOCE. All the analyzable vessels were stratified on the basis of the optimal cutoff value. Results A total of 968 vessels treated with PCI were screened. Post-PCI QFR was analyzable in 771 (79.6%) vessels. A total of 52 (6.7%) VOCEs occurred at 2 years. The mean value of post-PCI QFR was 0.91 ± 0.07. The diagnostic performance of post-PCI QFR to predict 2-year VOCE was moderate (area under the curve: 0.702; 95% confidence interval: 0.633 to 0.772), with the optimal cutoff value of post-PCI QFR for predicting 2-year VOCE 0.91 (sensitivity 0.652, specificity 0.635). The incidence of 2-year VOCE in the vessels with post-PCI QFR <0.91 (n = 284) was significantly higher compared with vessels with post-PCI QFR ≥0.91 (n = 487) (12.0% vs. 3.7%; hazard ratio: 3.37; 95% confidence interval: 1.91 to 5.97; p < 0.001). Conclusions A higher post-PCI QFR value is associated with improved vessel-related clinical outcomes in state-of-the art PCI practice for de novo 3VD. Achieving a post-PCI QFR value ≥0.91 in all treated vessels should be a target when treating de novo 3VD. These findings require confirmation in future prospective trials.

Sirolimus-eluting stents (SES) have recently been proven to reduce restenosis and reintervention compared with bare stents. Safety and effectiveness of SES in acute myocardial infarction remain unknown.Since April 16, 2002, a policy of routine SES implantation has been instituted in our hospital, with no clinical or anatomic restrictions, as part of the RESEARCH (Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital) registry. During 6 months of enrollment, 96 patients with ST-elevation acute myocardial infarction underwent percutaneous recanalization and SES implantation; these patients comprise the study population. The incidence of major adverse cardiac events (death, nonfatal myocardial infarction, reintervention) was evaluated. Six-month angiographic follow-up was scheduled per protocol. At baseline, diabetes mellitus was present in 12.5% and multivessel disease in 46.9%. Primary angioplasty was performed in 89 patients (92.7%). Infarct location was anterior in 41 (42.7%) of the cases, and 12 patients (12.5%) had cardiogenic shock. Postprocedural TIMI-3 flow was achieved in 93.3% of the cases. In-hospital mortality was 6.2%. One patient (1.1%) had reinfarction and target lesion reintervention the first day as a result of distal dissection and acute vessel occlusion. During follow-up (mean follow-up of 218+/-75 days), 1 patient died (1.1%), no patient had recurrent myocardial infarction, and there were no additional reinterventions. No early or late stent thromboses were documented. At angiographic follow-up (70%), late loss was -0.04+/-0.25, and no patient presented angiographic restenosis.In this study, sirolimus-eluting stent implantation for patients with ST-elevation acute myocardial infarction was safe without documented angiographic restenosis at 6 months.

Background The SYNTAX score II 2020 (SSII-2020), which was derived and externally validated from randomized trials, was designed to predict death following percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with three-vessel disease and/or left main disease. We aimed to investigate its value in identifying the safest modality of revascularization in a non-randomized setting. Methods Five-year mortality was assessed in 7362 patients with three-vessel disease and/or left main disease enrolled in a Japanese PCI/CABG registry. New-generation drug eluting stents and imaging guidance became the default PCI strategy during enrolment of the last cohort. The discriminative ability of the SSII-2020 for 5-year mortality was assessed using Harrell's C statistic (C-index). Agreement between observed and predicted rates of all-cause mortality following either PCI or CABG and treatment benefit (absolute risk difference) for this outcome were assessed by calibration plots. Results The SSII-2020 had helpful discrimination (C-index = 0.72) and good calibration (intercept = −0.11, slope = 0.92) for 5-year mortality. The absolute risk difference in mortality between CABG and PCI (treatment benefit) was well calibrated when the whole population was grouped into quarters according to the predicted absolute risk difference of 5-year mortality. The observed differences in survival in favor of CABG were 4.2% (0.1 to 8.2%, log-rank p=0.05) and 8.5% (3.8 to 13.2%, log-rank p&amp;lt;0.01) in the respective third and fourth quarters. In contrast, the observed differences in survival were not significantly different in either the first (3.0% [−0.8 to 6.8%, log-rank p=0.12]) or the second quarter (1.3% [−2.4 to 5.1%, log-rank p=0.39]). Conclusions The SSII-2020 is well able to predict death at 5 years – and the mortality difference between PCI and CABG, and therefore has the potential to support decision making on revascularization in patients with three-vessel disease and/or left main coronary artery disease. Funding Acknowledgement Type of funding sources: None.

Background Coronary microvascular dysfunction (CMD) after ST-Elevation Myocardial Infarction (STEMI) is associated with persistent symptoms and poor outcomes. Microvascular Resistance Reserve (MRR) is an innovative metric for evaluating coronary microvasculature that is unaffected by epicardial stenoses or the hemodynamic impact of vasodilators. While MRR's prognostic ability is recognized in chronic coronary syndrome, its application in ACS remains unestablished. Purpose We sought to investigate the prognostic value of MRR in STEMI patients. Methods This is a prospective study of 210 STEMI patients with multivessel disease who had undergone successful primary percutaneous coronary intervention (PCI). At 3 months follow-up, they returned for complete revascularization and coronary physiology evaluations, including coronary flow reserve (CFR), fractional flow reserve (FFR), and index of microcirculatory resistance (IMR), using bolus thermodilution. MRR was calculated using the formula: MRR = (CFR/FFR) × (Pa rest/Pa hyper), where Pa rest and Pa hyper represent resting and hyperemic aortic pressure, respectively1. We utilized an MRR cutoff of 3.0 based on Boerhour et al. The association between MRR and major adverse cerebrocardiovascular events (MACCE) at 12-month follow-up, defined as the composite of stroke, revascularization, myocardial infarction (MI), heart failure hospitalization, and death, was investigated. Results The median age was 65 years, and 40.48% were female. At a 3-month follow-up, 27% (56 patients) exhibited MRR &amp;lt;3.0, who were predominantly female (62.50% vs 32.47%, p&amp;lt;0.001) with a higher incidence of diabetes (39.29% vs 18.83%, p = 0.004). No significant differences were observed in age, body mass index, or STEMI location (anterior or inferior) when comparing between MRR groups. The MACCE-free survival at 12 months was significantly lower in patients with an MRR &amp;lt; 3.0 (48.2%) compared to those with an MRR ≥ 3.0 (11.0%; log-rank p &amp;lt; 0.001, Fig1A). The MRR &amp;lt; 3.0 group showed higher rates of ischemic stroke (8.93% vs. 1.30%, p = 0.022) and hospitalization for heart failure (21.43% vs. 2.60%, p &amp;lt; 0.001), while the incidence of nonfatal myocardial infarction (MI) and cardiovascular death were similar between the two MRR groups (Figu1B). In multivariable Cox regression analysis, MRR was an independent predictor for 12-month MACCE (Hazard Ratio 0.45 per unit increase, 95% Confidence Interval 0.31-0.67, p&amp;lt;0.001). The areas under the receiver operating characteristic curves for predicting 12-month MACCE using FFR, CFR, IMR, and MRR yielded values of 0.609, 0.762, 0.781, and 0.743, respectively (Fig2). The prognostic performances of CFR, IMR, and MRR were similar and superior to that of FFR. Conclusion This study establishes the novel parameter MRR as a superior prognostic indicator in STEMI patients compared to FFR, and on par with CFR and IMR. MRR is a reliable predictor of MACCE, and various clinical incidents post-STEMI.

The incidence, recurrence rate, and prognostic significance of atrial fibrillation or flutter (AF) following hospital discharge after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for left main coronary artery disease (LMCAD) are unknown. We sought to determine the 3-year incidence and clinical impact of postdischarge AF in patients with LMCAD treated with PCI or CABG. In the EXCEL trial, 1,905 patients with LMCAD were randomized to PCI versus CABG. We analyzed the occurrence of postdischarge AF through 3 years and its time-adjusted association with adverse outcomes. A total of 1,802 patients without AF at baseline comprised the study cohort. Within 3 years, 227 episodes of AF occurred (29 [12.8%] in the PCI arm and 198 [87.2%] in the CABG arm, p <0.0001); of those, 63 (27.7%) occurred following discharge from the index hospitalization in 57 patients. In-hospital AF predicted postdischarge AF (hazard ratio [HR] 2.94, 95% confidence interval [CI] 1.42 to 6.10, p = 0.004). By multivariable analysis, time-updated postdischarge AF was an independent predictor of 3-year cardiovascular death (HR 4.91, 95% CI 1.92 to 12.60, p = 0.0009), stroke (HR 4.87, 95% CI 1.12 to 21.12, p = 0.035), and the composite outcome of death, stroke or myocardial infarction (HR 3.09, 95% CI 1.56 to 3.6-6.11, p = 0.001). Among patients with postdischarge AF, the rate of the primary composite outcome did not vary according to presence or absence of in-hospital AF (21.0% vs 23.8%, p = 0.78). In conclusion, postdischarge AF following CABG or PCI for LMCAD is associated with increased mortality and stroke. In-hospital atrial fibrillation is an independent predictor of AF following discharge.

Once plaques intrude into the lumen, the shear stress they are exposed to alters with hitherto unknown consequences for plaque composition. We investigated the relationship between shear stress and strain, a marker for plaque composition, in human coronary arteries. We imaged 31 plaques in coronary arteries with angiography and intravascular ultrasound. Computational fluid dynamics was used to obtain shear stress. Palpography was applied to measure strain. Each plaque was divided into four regions: upstream, throat, shoulder, and downstream. Average shear stress and strain were determined in each region. Shear stress in the upstream, shoulder, throat, and downstream region was 2.55+/-0.89, 2.07+/-0.98, 2.32+/-1.11, and 0.67+/-0.35 Pa, respectively. Shear stress in the downstream region was significantly lower. Strain in the downstream region was also significantly lower than the values in the other regions (0.23+/-0.08% vs. 0.48+/-0.15%, 0.43+/-0.17%, and 0.47+/-0.12%, for the upstream, shoulder, and throat regions, respectively). Pooling all regions, dividing shear stress per plaque into tertiles, and computing average strain showed a positive correlation; for low, medium, and high shear stress, strain was 0.23+/-0.10%, 0.40+/-0.15%, and 0.60+/-0.18%, respectively. Low strain colocalizes with low shear stress downstream of plaques. Higher strain can be found in all other plaque regions, with the highest strain found in regions exposed to the highest shear stresses. This indicates that high shear stress might destabilize plaques, which could lead to plaque rupture.