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Objectives: This study sought to investigate the contribution of age-related microcirculatory dysfunction to abnormal coronary hemodynamics in patients with coronary atherosclerosis., Background: Impairment in myocardial blood supply in patients with coronary atherosclerosis can be accentuated due to age-related changes in microcirculatory function., Methods: Intracoronary pressure and flow were measured with the Doppler technique in 299 vessels (228 patients), and the thermodilution technique in 120 vessels (99 patients). In 172 patients, Doppler measurements were also performed in unobstructed vessels. Associations of coronary hemodynamics with aging were studied in both the stenosed and unobstructed arteries., Results: Aging was associated with a progressive increase in minimal microvascular resistance and a progressive decrease in hyperemic flow in both obstructed and nonobstructed coronary arteries. As such, coronary flow reserve decreased with advancing age. Epicardial stenosis severity assessed by resting Pd/Pa, basal stenosis resistance index, and hyperemic stenosis resistance index was equivalent across age groups. By contrast, fractional flow reserve increased with advancing age. Consequently, the adjusted risk of a fractional flow reserve/coronary flow reserve pattern reflective of concomitant focal epicardial and diffuse or microvascular disease (relative risk: 1.6; 95% confidence interval: 1.1 to 2.3; p = 0.017) increased with advancing age, whilst the adjusted risk of a fractional flow reserve/coronary flow reserve pattern reflective of non-flow-limiting stenosis with a healthy microcirculation decreased (relative risk: 0.7; 95% CI: 0.5 to 1.0; p = 0.022)., Conclusions: Aging is associated with progressive pan-myocardial impairment of coronary vasodilatory capacity due to an increase in minimal microvascular resistance. Concomitant aging-related impairment in microvascular function impacts the pathophysiology of ischemic heart disease in the individual patient and is not adequately identified by hyperemic coronary pressure measurements alone., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to assess the effectiveness, efficiency, and safety of a tiered, comprehensive cardiac computed tomography (CT) protocol in comparison with functional testing., Background: Although CT angiography accurately rules out coronary artery disease (CAD), incorporation of CT myocardial perfusion imaging as part of a tiered diagnostic approach could improve the clinical value and efficiency of cardiac CT in the diagnostic work-up of patients with angina pectoris., Methods: Between July 2013 and November 2015, 268 patients (mean age 58 years; 49% female) with stable angina (mean pre-test probability 54%) were prospectively randomized between cardiac CT and standard guideline-directed functional testing (95% exercise electrocardiography). The tiered cardiac CT protocol included a calcium scan, followed by CT angiography if calcium was detected. Patients with ≥50% stenosis on CT angiography underwent CT myocardial perfusion imaging., Results: By 6 months, the primary endpoint, the rate of invasive coronary angiograms without a European Society of Cardiology class I indication for revascularization, was lower in the CT group than in the functional testing group (2 of 130 [1.5%] vs. 10 of 138 [7.2%]; p = 0.035), whereas the proportion of invasive angiograms with a revascularization indication was higher (88% vs. 50%; p = 0.017). The median duration until the final diagnosis was 0 (0 of 0) days in the CT group and 0 (0 of 17) in the functional testing group (p < 0.001). Overall, 13% of patients randomized to CT required further testing, compared with 37% in the functional testing group (p < 0.001). The adverse event rate was similar (3% vs. 3%; p = 1.000), although the median cumulative radiation dose was higher for the CT group (3.1 mSv [interquartile range: 1.6 to 7.8] vs. 0 mSv [interquartile range: 0.0 to 7.1]; p < 0.001)., Conclusions: In patients with suspected stable CAD, a tiered cardiac CT protocol with dynamic perfusion imaging offers a fast and efficient alternative to functional testing. (Comprehensive Cardiac CT Versus Exercise Testing in Suspected Coronary Artery Disease 2 [CRESCENT2]; NCT02291484)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: To improve clinical outcomes after percutaneous coronary interventions of coronary bifurcation lesions, the Tryton Side Branch Stent™ (Tryton Medical, Durham) was developed. Registry studies evaluating the Tryton stent has shown promisingclinical results and the stent is currently compared with the provisional single stent strategy in a randomized trial. However, clinical results beyond one year are lacking, and therefore, we investigated the one- and two-year outcomes after Tryton stent placement in a single-center registry study., Methods and Results: All patients in our center in whom Tryton placement was attempted between October 2010 and December 2011 were included. Clinical outcomes were defined as cardiac death, any myocardial infarction (MI), target vessel revascularization (TVR), target lesion revascularization (TLR), stent thrombosis (ST), and target vessel failure (TVF; composite of cardiac death, MI, and TVR). Event rates were estimated using the Kaplan-Meier method. We included 91 patients. Almost half (42%) of the patients included had acute coronary syndrome (ACS) as indication for PCI (12% unstable angina, 14% NSTEMI, and 16% STEMI). Median follow-up duration was 713 days (IQR 617-840). TVF rates were 14.5% (one year) and 20.3% (two year). Two-year cardiac death, MI, TVR, TLR and ST rates were 4.4%, 10.2%, 12.7%, 9.2%, and 2.2%, respectively., Conclusions: In this single-center registry, use of the Tryton stent was associated with acceptable clinical outcomes at two-year follow-up.

The purpose of this study was to evaluate the performance of 320-row computed tomography angiography (CTA) in the identification of significant coronary artery disease (CAD) in patients presenting with acute chest pain and to examine the relation to outcome during follow-up. A total of 106 patients with acute chest pain underwent CTA to evaluate presence of CAD. Each CTA was classified as: normal, non-significant CAD (<50% luminal narrowing) and significant CAD (≥50% luminal narrowing). CTA results were compared with quantitative coronary angiography. After discharge, the following cardiovascular events were recorded: cardiac death, non-fatal infarction, and unstable angina requiring revascularization. Among the 106 patients, 23 patients (22%) had a normal CTA, 19 patients (18%) had non-significant CAD on CTA, 59 patients (55%) had significant CAD on CTA, and 5 patients (5%) had non-diagnostic image quality. In total, 16 patients (15%) were immediately discharged after normal CTA and 90 patients (85%) underwent invasive coronary angiography. Sensitivity, specificity, and positive and negative predictive values to detect significant CAD on CTA were 100, 87, 93, and 100%, respectively. During mean follow-up of 13.7 months, no cardiovascular events occurred in patients with a normal CTA examination. In patients with non-significant CAD on CTA, no cardiac death or myocardial infarctions occurred and only 1 patient underwent revascularization due to unstable angina. In patients presenting with acute chest pain, an excellent clinical performance for the non-invasive assessment of significant CAD was demonstrated using CTA. Importantly, normal or non-significant CAD on CTA predicted a low rate of adverse cardiovascular events and favorable outcome during follow-up.

Aims: As the global population ages, elderly patients will form an increasing proportion of those undergoing percutaneous coronary intervention (PCI). We investigated the safety and efficacy of bare metal stents (BMS) and DES in all patients undergoing PCI at our institution, stratified by age., Methods and Results: We investigated three sequential groups of consecutive patients treated exclusively with BMS (n=2,194; January 2000 to April 2002), sirolimus-eluting stents (SES, n=834; April 2002 to February 2003) and paclitaxel-eluting stents (PES, n=2,841; February 2003 to December 2005). The primary endpoint was all-cause mortality. Secondary endpoints included target vessel revascularisation (TVR) and composite major adverse cardiac events (MACE, defined as all-cause death, any nonfatal myocardial infarction or TVR). Patients were followed up for a median of 1,366 days. Patients were stratified into equal quintiles based on age (<51.8, 51.8-58.4, 58.4-65.4, 65.4-73.0 and >73.0 years). All-cause mortality was significantly higher in the eldest two groups, while TVR rates were similar across all age groups. DES were associated with reductions in TVR and MACE and a trend towards reduced mortality in all age groups., Conclusions: DES are safe and effective when compared to BMS, irrespective of age.

Objectives: This study sought to evaluate the long-term clinical outcome of patients with an angiographically intermediate left anterior descending coronary artery (LAD) stenosis in whom the revascularization strategy was based on fractional flow reserve (FFR)., Background: When revascularization is based mainly on angiographic guidance, a number of hemodynamically nonsignificant stenoses will be revascularized., Methods: In 730 patients with a 30% to 70% isolated stenosis in the proximal LAD and no significant valvular disease, FFR measurements were obtained to guide treatment strategy. When FFR was ≥ 0.80, the patients (n = 564) were treated medically (medical group); when FFR was <0.80, the patients (n = 166) underwent a revascularization procedure (revascularization group; 13% coronary artery bypass graft surgery and 87% percutaneous coronary intervention). A 100% long-term clinical follow-up (median follow-up: 40 months) was obtained. The 5-year survival of the medical group was compared with that of a reference population. For each patient, 4 controls were selected from an age- and sex-matched control population., Results: The 5-year survival estimate was 92.9% in the medical group versus 89.6% in the controls (p = 0.74). The mean diameter stenosis was significantly smaller in the medical than in the revascularization group (39 ± 14% vs. 54 ± 13%, p < 0.0001), but there was a large overlap between both groups. The 5-year event-free survival estimates (death, myocardial infarction, and target vessel revascularization) were 89.7% and 68.5%, respectively (p < 0.0001)., Conclusions: Medical treatment of patients with a hemodynamically nonsignificant stenosis (FFR ≥ 0.80) in the proximal LAD is associated with an excellent long-term clinical outcome with survival at 5 years similar to an age- and sex-matched control population., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: In the National Institute for Clinical Excellence (NICE) guidelines, lesions with a reference vessel diameter of less than 3.0 mm or lesions with a length of greater than 15 mm are considered carrying a high risk of restenosis. In contrast, lesions with a reference vessel diameter of at least 3.0 mm or a lesion length of 15 mm or less are considered at low risk of restenosis. We performed a retrospective analysis of consecutive patients undergoing nonurgent percutaneous coronary intervention (PCI) comparing bare metal stent (BMS) with drug-eluting stent (DES) using the NICE guidelines., Methods and Results: Between 2003 and 2007, a total of 3883 patients underwent a nonurgent PCI for a de-novo coronary lesion; 2050 patients were considered to be at low risk and 1833 patients were considered at high risk of restenosis according to the NICE criteria. In the low-risk group, the 1-year composite of cardiac death, myocardial infarction, and target vessel revascularization was 10.5% in the BMS group and 11.1% in the DES group (P=0.85). Target lesion revascularization (TLR) was 5.3% by PCI and 1.6% by coronary artery bypass grafting (CABG) in the BMS group and 4.0 and 3.0% in the DES group (P=0.59 and P=0.24). In the high-risk group, the composite of cardiac death, myocardial infarction, and target vessel revascularization was 12.1 and 11.0% in the BMS and DES groups (P=0.48). TLR was 6.7% by PCI and 1.3% by CABG in the BMS group and 3.9 and 2.8% in the DES group (P=0.01; P=0.02). Definite stent thrombosis (ST) was 0.8% in the BMS-treated patients and 1.7% in the DES-treated patients (P=0.09)., Conclusion: In patients with lesions carrying a low risk of restenosis, no differences were observed between BMS and DES in composite end points, TLR, or ST at 1-year follow-up. In patients with lesions carrying a high risk of restenosis, patients treated with BMS had a significantly higher rate of TLR by PCI, but a significantly lower rate of TLR by CABG compared with patients treated with DES. A nonsignificant lower rate of definite ST was observed in the BMS group compared with the DES group.

Aims: Evidence regarding the optimal treatment of non-culprit lesions detected during primary PCI is lacking. Our aim was to investigate whether early invasive treatment improves left ventricular ejection fraction (EF) and prevents major adverse cardiac events (MACE)., Methods and Results: Of 121 patients with at least one non-culprit lesion, 80 were randomised to early FFRguided PCI (invasive group), and 41 to medical treatment (conservative group). Primary endpoint was EF at six months, secondary endpoints included MACE. In the invasive group, early angiography was performed 7.5 days (5-20) after primary PCI. Forty percent of the non-culprit lesions did not show haemodynamic significance (FFR > 0.75). Subsequent PCI of at least one non-culprit lesion was performed in 52%, PCI without preceding FFR was performed in 8% and elective CABG was done in 4%. No in-hospital events occurred in the conservative group. After six months, EF was comparable (59+/-9% vs. 57+/-9%, p=0.362), and there was no difference in MACE between invasively and conservatively treated patients (21 vs. 22%, p=0.929)., Conclusions: An invasive strategy towards non-culprit lesions does not lead to an increase in EF or a reduction in MACE. The functional stenosis severity of non-culprit lesions is frequently overestimated.

Although the safety of drug-eluting stents has been under considerable scrutiny, limited real-world follow-up data extending up to 4 years are available. The randomized clinical trials carefully selected patients and are not reflective of everyday practice. From April to October 2002, 508 consecutive patients treated with sirolimus-eluting stents (SES) were enrolled. The control group consisted of 450 patients treated with bare-metal stents during the preceding 6 months. After 4 years of follow-up, the incidence of composite major adverse clinical events (all-cause death, myocardial infarction, or target vessel revascularization) was found to be significantly lower in the SES group (23.0% vs 28.7%, adjusted hazard ratio 0.66, 95% confidence interval 0.51 to 0.86), as were rates of target vessel revascularization (12.2% vs 17.8%, adjusted hazard ratio 0.57, 95% confidence interval 0.39 to 0.83). There were no differences in all-cause mortality (10.5% for SES vs 10.6% for bare-metal stents, p = 0.9) or in the rates of cardiac death (4.5% vs 6.9%, p = 0.1). Although there was no difference in overall stent thrombosis (2.3% vs 2.2%, p = 1.0), SES had a higher rate of very late stent thrombosis (1.4% vs 0%, p = 0.02), balanced by a lower rate of early stent thrombosis (0.4% vs 1.8%, p = 0.05). In conclusion, after 4 years, SES were found to remain safe and effective compared with bare-metal stents. Nevertheless, the higher rate of very late stent thrombosis remains a concern. Longer term follow-up will be required to determine the extent of this problem.

Since activation of the haemostatic system is an important feature of the wound healing response triggered by arterial injury, variations in genes involved in thrombus formation may play a role in restenosis after percutaneous coronary interventions (PCI). Therefore, our aim was to examine the relationship between polymorphisms that are known to play a role in the haemostatic system and the risk of clinical restenosis in the GENetic DEterminants of Restenosis (GENDER) study, a multicenter prospective study design that enrolled 3,104 consecutive patients after successful PCI. Target vessel revascularization (TVR) was the primary endpoint. All patients were genotyped for six polymorphisms in the Factor II, Factor V, Factor VII and PAI-1 genes. The PAI-1 4G variant was associated with an increased risk of TVR. When compared to 5G/5G homozygotes, heterozygous patients were at higher risk for TVR (HR: 1.46, 95% CI: 1.05-2.03), whereas patients with the 4G/4G genotype had an even further increased risk (HR: 1.69, 95% CI: 1.19-2.41). In contrast, the factor V 506Gln (factor V Leiden) amino acid substitution was associated with a decreased risk of TVR (HR: 0.41, 95% CI: 0.19-0.86). Our findings indicate that polymorphisms in the factorV and PAI-1 genes may play a role in the process of restenosis.

Objectives: To evaluate long-term outcomes after drug-eluting stents (DES) implantation in small coronary vessels., Background: Sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) have been reported to improve both the angiographic and clinical outcomes compared with bare metal stents even in 'real world' settings. Currently, no data is available on long-term outcomes after DES implantation in small vessels., Methods: Since April 2002, our institution has implanted DES, either SES or PES, as a default strategy in all patients irrespective of their clinical presentation. Between October 2002 and September 2003, 197 consecutive patients were enrolled: 107 consecutive patients received at least one 2.25-mm SES (SES group) and 90 consecutive patients received at least one 2.25-mm PES (PES group)., Results: The two cohorts presented with high-risk characteristics. At 2 years, the cumulative incidence of major adverse cardiac events (MACE) in the SES group was significantly lower than that in the PES group (10.3% vs. 23.3%, P=0.02). There were two subacute angiographic stent thromboses in the PES group and none in the SES group. By multivariate analysis, PES utilization (HR 2.37, 95% CI 1.07-5.26), presentation with acute coronary syndromes (ACS) (HR 3.34, 95% CI 1.44-7.70) and multi-vessel disease (MVD) (HR 3.91, 95% CI 1.27-12.0) were identified as independent predictors of MACE., Conclusions: In an unselected population treated for small vessel disease, SES were associated with significantly better 2-year clinical outcomes than PES. The use of PES and the presentation with ACS and MVD were identified as independent predictors of MACE., (Copyright (c) 2006 Wiley-Liss, Inc.)

In acute ST-elevation myocardial infarction (STEMI), patients with multivessel disease (MVD) are considered to be a subgroup with an increased risk of mortality compared with patients with single-vessel disease (SVD). To evaluate the effect of MVD on 1-year mortality in patients with STEMI, we studied 1,417 consecutive patients with STEMI who were admitted between 1997 and 2002 and treated with primary percutaneous coronary intervention. Further, we hypothesized that the effect of MVD on mortality is due to the presence of a chronic total occlusion in a noninfarct-related artery. Patients with MVD and/or a chronic total occlusion had multiple differences in baseline and angiographic characteristics that were associated with worse outcome. Mortalities in patients with SVD, MVD, and a chronic total occlusion were 8%, 16%, and 35%, respectively. After correction for the baseline differences, MVD was an independent predictor of mortality (odds ratio 1.5, 95% confidence interval 1.1 to 2.1). However, when chronic total occlusion was included in the model, MVD was no longer an independent predictor for mortality, whereas chronic total occlusion was a strong and independent predictor for 1-year mortality in patients with STEMI treated with percutaneous coronary intervention (odds ratio 3.8, 95% confidence interval 2.5 to 5.8). In conclusion, patients with STEMI and MVD have a higher 1-year mortality rate compared with patients with SVD, which is mainly determined by the presence of a chronic total occlusion in a noninfarct-related artery. In the setting of primary percutaneous coronary intervention, the presence of a chronic total occlusion, and not the mere presence of MVD, is an independent predictor of mortality.

Objective: Percutaneous coronary intervention in patients with a history of previous coronary artery bypass grafting (CABG) is associated with an increased rate of subsequent adverse events compared to those without prior CABG. We evaluated the impact of utilizing the sirolimus-eluting stent (SES) in this high-risk population., Methods: Since April 2002, SES implantation was utilized as the default strategy for all percutaneous procedures in our hospital. Consecutive patients with a history of previous CABG and de novo lesions (n=47) treated exclusively with SES, were compared to 66 patients who received bare stents in the 6-month period just before SES introduction., Results: There were no significant differences between the groups (SES and bare stent) with respect to baseline clinical or lesion characteristics. The only difference between the groups related to the nominal diameter of stent utilized, which was smaller in the SES group than the bare stent group. (The maximum diameter of SES available was 3.0 mm). At 1 year, the cumulative incidence of major adverse events (defined as death, myocardial infarction, or target vessel revascularization) was significantly lower in the SES group than the bare stent group [8.5 versus 30.3%, hazard ratio 0.37 (95% confidence interval 0.15-0.91); P=0.03]., Conclusions: The utilization of the sirolimus-eluting stent for percutaneous intervention in a high-risk population with a history of previous CABG surgery is associated with a significant reduction in the rate of major adverse cardiac events at 1 year.