Design and Rationale of the COMMIT-LAD Registry: A Comprehensive Analysis of Medical and Invasive Treatment Strategies for Patients With Significant Left Anterior Descending Artery Disease (COMMIT-LAD).

The purpose of this three-dimensional intracoronary ultrasound (ICUS) study was to assess longitudinal plaque distribution patterns in patients with angiographically silent coronary artery disease (CAD) after heart transplantation (HTX). Out of 334 patients without diameter stenosis >/=25% determined by coronary angiography, 321 underwent successful three-dimensional ICUS (30 MHz) of the left main coronary artery (LMCA) and all segments of the left anterior descending coronary artery (LAD). Early plaque formation was found in 296 patients (92.2%). Single (focal CAD, n = 65) or multiple (polyfocal CAD, n = 77), discrete coronary lesions were found in 142 patients and continuous plaque formation of at least one entire coronary segment (diffuse CAD) in 154 patients. Using multivariate regression analysis, male sex (P = 0.01), increasing post-transplantation time (P = 0.003) and increasing donor age (P = 0.001) were independent clinical predictors for diffuse CAD. Both focal and diffuse CAD most frequently affected the proximal LAD (88% compared with 89.6%, NS). The mean intimal index of each LAD segment was significantly higher in patients with diffuse CAD (P < 0.001) and showed a proximal-to-distal decline in patients with focal/polyfocal (LMCA, 10.1 +/- 14.3, LAD-6, 30.1 +/- 17.4%, LAD-7, 16.3 +/- 14.1%, LAD-8, 4.6 +/- 11.1%; P < 0.001) and diffuse (LMCA, 27.0 +/- 16.0, LAD-6, 47.8 +/- 16.1%, LAD-7, 41.9 +/- 14.5%, LAD-8, 24.9 +/- 23.3%; P < 0.01) CAD. Evaluation of longitudinal plaque distribution after HTX by three-dimensional ICUS revealed a time-dependent increase in the incidence of diffuse CAD and a proximal-to-distal decline in frequency and magnitude of early plaque formation.

As stated in American College of Cardiology/American Heart Association Guidelines, randomized trials have not demonstrated that elective percutaneous coronary intervention (PCI) reduces myocardial infarction (MI) or mortality over medical treatment. Even the Fractional Flow Reserve Guided PCI Versus Medical Therapy in Stable Coronary Disease (FAME 2) trial showed no statistically significant benefit of PCI over the deferred group by traditional intention-to-treat, nonbenchmark analysis starting at randomization that includes procedure-related events. Benchmark analysis in FAME 2 beginning 1 week after PCI removed procedure-related events that counterbalanced subsequent reduced MI and mortality compared with the deferred group. Meta-analysis of the literature on risk of events related to fractional flow reserve (FFR), including FFR Versus Angiography in Multivessel Evaluation (FAME), and other physiological measures of severity reveal an underappreciated, powerful interdependence among physiological severity of stenosis, diffuse coronary artery disease (CAD), event rates, sample size, and statistical certainty of differences. This analytic review synthesizes an evidenced-based, quantitative hypothesis and potential solution to this issue based on hard data from the literature by coauthors of diverse cardiovascular disciplines in trial design, biostatistics, invasive procedures, coronary physiology, fluid dynamics, coronary pathology, and quantitative imaging. Our synthesis elucidates a dual hypothesis for failure of elective PCI in stable CAD to reduce MI or mortality and novel trial design for selecting patients for whom PCI will likely reduce these events. First, a large burden of global diffuse CAD carries a high risk of coronary events unmitigated by PCI of a focal stenosis. Second, focal stenosis severity in previous randomized revascularization trials has been too modest without objectively quantified sufficient severity to observe benefit of PCI. In previous trials, mixture of diffuse coronary disease and intermediate stenosis may not incur high enough risk for potential benefit by PCI for sample size of reported trials. Greater quantitative severity with …

ObjectivesErectile dysfunction (ED) and coronary artery disease (CAD) often share common risk factors and there is growing evidence that ED might serve as a clinical marker for cardiovascular disease. Despite...

Differential Improvement in Angina and Health-Related Quality of Life After PCI in Focal and Diffuse Coronary Artery Disease

Objective To investigate the effect of PCI on patient-reported outcomes in focal and diffuse coronary artery disease (CAD) as defined by the pullback pressure gradient (PPG). Background Improvements in fractional flow reserve (FFR) following PCI are associated with freedom from angina. CAD patterns influence the FFR change after stenting. Therefore, CAD patterns might be essential to assess the likelihood of PCI success in terms of angina relief. Methods This is a sub-analysis of the TARGET-FFR randomized clinical trial (NCT03259815). The 7-item Seattle Angina Questionnaire (SAQ-7) and EuroQol five-level EQ-5D questionnaire (EQ-5D-5L) were administered at baseline and three months after PCI. The PPG index was calculated from manual pre-PCI FFR pullbacks and the median PPG value was used to define focal and diffuse CAD. Results 103 patients (51 with focal and 52 with diffuse disease) were analyzed. There were no differences in baseline characteristics between patients with focal and diffuse CAD. Patients with focal disease had larger increases in FFR with PCI than those with diffuse disease (0.30±0.14 units vs 0.19±0.12 units, p&amp;lt;0.001). Patients who underwent PCI to focal CAD had significantly higher SAQ-7 summary scores at follow-up compared to those with diffuse CAD (87.1±20.3 vs. 75.6±24.4, mean difference 11.5 [95% CI 2.8 to 20.3], p=0.01). Following PCI, residual angina was present in 39.8% of all patients but was significantly lower among those with treated focal CAD (27.5% vs 51.9%, p-value=0.020). Conclusion Persistent angina after PCI was almost twice as common in patients with diffuse CAD as defined by the pre-PCI PPG. Patients with focal disease reported greater improvement in angina and quality of life with PCI. The likelihood of successful angina relief from PCI can be predicted by the baseline pattern of CAD. Funding Acknowledgement Type of funding sources: None.

Coronary Atherosclerosis Phenotypes in Focal and Diffuse Disease

Aims The pattern of CAD predicts angina relief after PCI. Our aim was to evaluate the cost-effectiveness of PCI in diffuse coronary artery disease (CAD) to deferral from PCI in these patients. Methods This is a sub-analysis of the TARGET-FFR randomized clinical trial (NCT03259815). The pullback pressure gradient (PPG) was calculated to differentiate focal from diffuse CAD. Healthcare resource use associated with the index hospitalization and with follow-up outpatient visits, medications, was recorded prospectively. We did not discount costs because of the limited follow-up period. Costs of procedures and follow-up consultations were derived from Healthcare Resource Group reference costs and drug costs from the National Health Service (NHS). Quality-adjusted life-years (QALYs) were derived from health-related quality of life and survival during the 3-month time horizon of the trial. Quality-of-life indexes (utilities) were evaluated at baseline and 3 months with the European Quality of Life–5 Dimensions (EQ-5D) instrument with UK weights scaled from 0 (death) to 1 (perfect health). The overall QALYs for each patient were estimated as the area under the curve determined by the utility values at baseline and 3 months. We computed confidence intervals for differences in costs and QALYs and in the incremental cost-effectiveness rate (ICER) using the bootstrap technique with the percentile method with 10 000 replications. A Markov model was used to simulate deferral of diffuse disease from PCI and not using PPG to select treatment. Probabilistic sensitivity analysis was undertaken to test the robustness of results to parameter uncertainty. Results Patients who underwent PCI for focal CAD had higher EQ-5D index values at follow-up (0.89 ± 0.18 vs 0.76 ± 0.28, p=0.004) and higher QALYs after 3 months follow-up (0.19 ± 0.06 vs 0.21 ± 0.04, p=0.022). Mean cumulative costs were £1574.3 ± 230.5 and significantly higher in patients treated for diffuse CAD as compared to patients treated for focal CAD (£1697 ± 293.4 vs £1393 ± 264.3; p&amp;lt;0.001). The ICER was £7746/QALY (95% CI 5024 – 11007). PCI in focal CAD saved £1522.2/QALY when compared to PCI in diffuse CAD (£7009.2 ± 1919.4 /QALY vs. £8531.4±2753.4 /QALY, p&amp;lt; 0.001). Deferring 30% of the diffuse CAD patients from PCI to optimized medical therapy would save £673.8/QALY (£7072.2 ± 1730.147 /QALY vs. £7746 ± 1943.5/QALY, p&amp;lt; 0.001). Conclusion PCI is more cost-effective in focal than diffuse CAD. Treatment of diffuse CAD results in worst QALYs and costlier procedures. Every 5% of the diffuse CAD patients that were deferred from PCI saved aproximately £100/QALY. Further trials are needed to determine if the cost-effectiveness of PCI can be improved by deferring patients with diffuse CAD.Quality of life in focal and diffuse CADCost-effectiveness focal vs diffuse CAD

Aim. The article evaluates 30-day results of percutaneous coronary intervention (PCI) with ABSORB biodegradable vascular scaffold (BVS) implanted in the case of stenosis of the left anterior descending (LAD) coronary artery in patients with stable angina.Methods. 64 patients with significant (≥ 70%) LAD disease were included in the study. At 30 days, scaffold thrombosis and major adverse cardiovascular events (all-cause mortality, myocardial infarction, stroke, target vessel revascularization) were evaluated. The indicator of successful percutaneous coronary intervention (residual stenosis ≤20% in the presence of counterpulsation corresponding to TIMI 3rd Grade and in the absence of significant in-patient clinical complications) and successful intervention assessed by clinical criteria (successful percutaneous coronary intervention alongside with a decrease in objective and subjective symptoms of myocardial ischemia, or their complete disappearance) were also analyzed. Results. Mean age of patients was 61.6±8.5 years, with males accounting for 64%; 33% had earlier MI, 14% – diabetes mellitus. Mean left ventricular ejection fraction was 61.3±6.8%. Left anterior descending artery disease was presented in 89% of patients with SYNTAX Score 6.6±2.2. Mean number of implanted stents was 1.2±0.4, with mean length of the stented segment equal to18.7±1.8 mm and mean diameter 3.2±0.3 mm. At 30-day follow-up, the success of intervention assessed by clinical criteria amounted to 96.9% (n=62); that of myocardial infarction 3.1% (n=2); stent thrombosis 1.56% (n=1); repeated revascularization 1.56% (n=1); major adverse cardiovascular events (MACE) 3.1%.Conclusion. The implantation of everolimus-eluting BVS for LAD stenosis demonstrates satisfactory results at 30-day follow-up.Received 16 January 2017. Accepted 21 March 2017.Financing: The study did not have sponsorship.Conflict of interest: The authors declare no conflict of interest.

Background Intracoronary pressure measurements, including fractional flow reserve (FFR) and resting full-cycle ratio (RFR), are valuable for assessing lesion severity and guiding treatment decisions. However, the impact of pullback measurements on treatment decision-making remains unclear in clinical practice. Purpose This study assessed the influence of pullback measurements on the allocation of pharmacological, percutaneous, and surgical interventions for stable coronary artery disease (CAD). Methods This single-centre, retrospective cohort study identified patients with stable CAD and a positive FFR (≤0.80) or RFR (≤0.90) in the Left Anterior Descending (LAD) artery in 2022 and 2023. Patients were stratified and compared based on whether a pullback measurement was performed. Focal CAD was defined by a &amp;gt;75% pressure drop at ≤2 locations on pullback measurement. All other cases were classified as diffuse CAD. An additional analysis was conducted to identify patient differences across treatment strategies (conservative management (OMT), percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG)). Finally, multinomial logistic regression was performed to identify independent predictors of treatment decisions, incorporating clinically relevant variables and those selected based on baseline characteristics (BMI, hypercholesterolemia, smoking, triple vessel disease, symptom burden, pullback measurements and FFR value). Results Among 422 patients, 303 (72%) underwent a pullback measurement. Patients in the non-pullback group were older, while other baseline characteristics were similar (Table 1). OMT patients had higher FFR values compared to those treated with PCI or CABG (0.78 [IQR 0.74-0.79] vs 0.72 [IQR 0.68-0.76], p&amp;lt;0.001). Using receiver operating characteristic (ROC) analysis, an FFR threshold of 0.75 was identified as the optimal cut-off for differentiating between conservative management and revascularization (AUC: 0.766, sensitivity: 0.729, specificity: 0.665), matching older guidelines. In the subset of patients with an FFR ≤0.75, OMT was significantly more prevalent among those with diffuse disease (52%) compared to those with focal disease (14%) (p&amp;lt;0.001). PCI was more frequently performed in cases of focal disease (55% for focal vs 24% for diffuse disease, p&amp;lt;0.001). Pullback measurements, FFR &amp;gt;0.75, age and symptom burden were all independent predictors of treatment choice (Table 2). Conclusions Despite current guidelines, conservative treatment is common for borderline significant CAD (FFR 0.75-0.80). In significant CAD (FFR ≤0.75), pullback measurements guide treatment decisions: PCI for focal, OMT for diffuse disease. Physiological and clinical factors, rather than solely anatomical severity, appear to be the primary determinants of treatment selection.

Coronary Extramural Haematoma Caused by Perforation during Left Main Coronary Artery Intervention

Aim. Evaluates 3-year clinical outcomes of percutaneous coronary intervention (PCI) with bioresorbable vascular scaffold (BVS) versus minimally invasive direct coronary artery bypass (MIDCAB) surgery for the treatment of left anterior descending (LAD) lesions.Methods. In this single-center study were included 130 patients with stable angina and significant (≥70%) LAD disease. Patients were randomly assigned in a 1:1 ratio to PCI with everolimus-eluting bioresorbable vascular scaffold (Absorb) (n = 65) or MIDCAB (n = 65). The primary end-point was major adverse cerebrocardiovascular events (MACCE) and secondary was. Primary and secondary endpoints were, respectively, major adverse cerebro-cardiovascular events (MACCE) and target vessel failure at 3-year.Results.The groups of patients were comparable for all baseline demographic, clinical and angiographic parameters. The primary composite endpoint of MACCE through 3 years occurred in 16.9% of BVS patients and 9.2% of MIDCAB patients (p = 0.19). But 3-year any revascularization rates were higher with BVS (13.8% vs. 3.1%; p = 0.027). TVF was favor of the MIDCAB group (12,3% vs. 3,1%, p = 0.04), mainly triggered by high subsequent need for revascularization of the targeted vessel in the BVS group (9.2% vs. 1.5%; p = 0.05).Conclusion. At 3-year follow-up, PCI by BVS and MIDCAB in in patients with isolated LAD lesions yielded similar long-term outcomes regarding the primary composite clinical endpoint. The bioresorbable scaffold was associated with a higher incidence of reinterventions, TVF and TVR than the MIDCAB through 3 years of follow-up.

Introduction The pathophysiological interplay between coronary physiology and plaque characteristics remains poorly understood. Pullback pressure gradient (PPG) is a novel physiological index that discriminates focal from diffuse coronary artery disease (CAD) based on coronary physiology. We aimed to compare plaque characteristics using between atherosclerotic patterns defined by coronary physiology. Methods Multicenter, prospective, controlled, single-arm study conducted in five countries (NCT03782688). Patients with functionally significant lesions based on invasive fractional flow reserve (FFR&amp;lt;0.80) were included. Subjects underwent coronary computed tomography angiography (CCTA) with quantitative plaque analysis followed by an invasive procedure with optical coherence tomography (OCT) and motorized intracoronary pressure recordings. Fractional flow reserve (FFR) pullback curves were processed to calculate the PPG. The PPG ranges from 0, indicating diffuse disease, to 1, pointing to focal CAD. Focal and diffuse CAD were defined according to the median PPG value. Results Overall, 117 patients (120 vessels) were included. The mean age was 64±9, 80% were male, and 22% had diabetes (no difference between focal vs. diffuse). Median PPG was 0.66 [0.54, 0.75]. In CCTA analysis, the plaque burden at minimum lumen area was higher in patients with focal CAD (87±8% focal vs. 82±10% diffuse, p=0.003). Calcifications were significantly more prevalent in patients with diffuse CAD (Agatston score per vessel 50 [9, 166] focal vs. 151 [46, 360] diffuse, p=0.019). In OCT plaque analysis, patients with focal CAD had a significantly higher prevalence of circumferential lipid-rich plaque (37% focal vs. 4% diffuse, p=0.001) and thin-cap fibroatheroma (TCFA 47% focal vs. 10% diffuse, p=0.002). High PPG predicted the presence of TCFA with an AUC of 0.73 (95% CI 0.58 to 0.87). PPG and fibrous cap thickness were negatively correlated (r=-0.55, 95% CI -0.74 to -0.28) independently of FFR. Conclusions Atherosclerotic plaque phenotypes associate with intracoronary hemodynamics. Vessels with focal disease (high PPG) had a higher plaque burden and predominantly lipid-rich plaque with a high prevalence of TCFA, whereas calcifications were the hallmark of vessels with diffuse pressure loss.

Background Monocytes play an integral role in the development of atherosclerosis. Specific monocyte subsets have been associated with excess cardiovascular events in different patient populations and highlighted as a potential therapeutic target. Objective To compare blood monocyte subsets in patients with focal coronary artery disease (CAD) and diffuse CAD. Methods Three monocyte subsets (CD14 + +CD16-CCR2+ [classical, Mon 1], CD14 + +CD16 + CCR2+ [intermediate, Mon 2] and CD14 + CD16 + +CCR2- [non-classical, Mon 3]) and their aggregates with platelets (monocyte-platelet aggregates, MPAs) were quantified by flow cytometry in 71 CAD patients (subdivided into a group with diffuse CAD [n = 50] and a group with focal CAD [n = 21] based on angiographic coronary artery morphology) and 39 age, sex and risk factor matched controls with normal coronary arteries assessed either invasively or non-invasively using computed tomography coronary angiography (CTCA). Results The clinical characteristics of each group are shown in Table 1. Patients with diffuse CAD had a significantly higher proportion of Mon 2 than patients with focal disease (p = 0.02) or normal coronary arteries (p = 0.03) (Table 2). MPA associated with Mon 2 was also significantly higher in the diffuse CAD group (p Conclusion Patients with diffuse CAD have higher peripheral blood levels of Mon 2 and MPA associated with Mon 2 than patients with focal CAD. Our data support the notion that Mon 2 is related to worse CAD morphology.

Comparison of exercise electrocardiography and quantitative thallium imaging for one-vessel coronary artery disease

Erectile dysfunction (ED) and coronary artery disease (CAD) often share common risk factors, and there is growing evidence that ED might serve as a clinical marker for cardiovascular disease. Despite rising trends of CAD in Asian Indians, limited data are available on the prevalence of ED and its correlation with CAD severity in such patients. To study the prevalence of ED in Asian Indian patients undergoing coronary angiography and to assess if the severity of ED correlates with angiographic severity of CAD. In all patients undergoing coronary angiography, ED was assessed using the International Index of Erectile Function-5 questionnaire. Among 175 male patients, ED was present in 70%; patients with ED had a higher incidence of multivessel CAD (80% vs. 36%, P 0.001), diffuse CAD (81% vs. 34%, P 0.001), and higher number of mean coronary vessels involved compared with those without ED. Those with severe ED had higher prevalence of multivessel CAD and higher number of mean coronary vessels involved compared with those with milder grades of ED. Onset of symptoms of ED preceded symptoms of CAD by a mean of 24.6 months in 84% of patients. The presence of severe ED was associated with a 21-fold higher risk of having triple-vessel disease (odds ratio [OR] 21.94, 95% confidence interval [CI] 3.41-141.09, P = 0.001) and an 18-fold higher risk of having diffuse angiographic CAD (OR 17.91, 95% CI 3.11-111.09, P = 0.001). Asian Indians with angiographic CAD frequently have ED; symptoms of ED precede that of CAD in most patients. Incidence of multivessel and diffuse CAD is significantly more common in patients with ED. It is important for physicians to be aware of the close relationship between the two conditions so that patients with ED can have optimal risk stratification for concomitant CAD whenever required.