Three-dimensional multidetector computed tomography versus conventional 2-dimensional transesophageal echocardiography for annular sizing in transcatheter aortic valve replacement: Influence on postprocedural paravalvular aortic regurgitation.

OBJECTIVES: In transcatheter aortic valve replacement (TAVR), the influence of aortic annular assessment with either multidetector computed tomography (MDCT) or conventional transesophageal echocardiography (TEE) on the incidence of postprocedural paravalvular aortic regurgitation (PAR) was evaluated. BACKGROUND: PAR remains a major limitation in TAVR. Appropriate selection of transcatheter heart valve (THV) size is crucial to prevent PAR. METHODS: Outcomes following TAVR with a balloon-expandable THV were compared in two retrospective cohorts identified according to whether THV size selection was based on TEE (study group 1, n = 80) or MDCT (study group 2, n = 58). RESULTS: The two study groups were comparable with regard to baseline clinical, risk score, and echocardiographic characteristics. The incidence of moderate/severe PAR was lower in study group 2 than in group 1, 8.6% versus 28.8% (P < 0.01). The difference between the THV nominal diameter and MDCT annular diameter was predictive of moderate/severe PAR (AUC 0.84; 95% CI: 0.72-0.92). Neither age, gender, body mass index, annular eccentricity index, aortic valve calcification nor the difference between the THV diameter and the TEE annular diameter predicted postprocedural PAR. Increased THV oversizing relative to the MDCT mean annular diameter was associated with reduced severity of PAR. No difference in perprocedural complications between two study groups was observed. CONCLUSION: MDCT-based annular sizing in TAVR significantly reduces postprocedural PAR, and THV oversizing appears pivotal in this aspect. Further delineation of the optimal degree of THV oversizing is needed.

Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial.

BACKGROUND: Remote ischaemic preconditioning attenuates cardiac injury at elective surgery and angioplasty. We tested the hypothesis that remote ischaemic conditioning during evolving ST-elevation myocardial infarction, and done before primary percutaneous coronary intervention, increases myocardial salvage. METHODS: 333 consecutive adult patients with a suspected first acute myocardial infarction were randomly assigned in a 1:1 ratio by computerised block randomisation to receive primary percutaneous coronary intervention with (n=166 patients) versus without (n=167) remote conditioning (intermittent arm ischaemia through four cycles of 5-min inflation and 5-min deflation of a blood-pressure cuff). Allocation was concealed with opaque sealed envelopes. Patients received remote conditioning during transport to hospital, and primary percutaneous coronary intervention in hospital. The primary endpoint was myocardial salvage index at 30 days after primary percutaneous coronary intervention, measured by myocardial perfusion imaging as the proportion of the area at risk salvaged by treatment; analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00435266. FINDINGS: 82 patients were excluded on arrival at hospital because they did not meet inclusion criteria, 32 were lost to follow-up, and 77 did not complete the follow-up with data for salvage index. Median salvage index was 0.75 (IQR 0.50-0.93, n=73) in the remote conditioning group versus 0.55 (0.35-0.88, n=69) in the control group, with median difference of 0.10 (95% CI 0.01-0.22; p=0.0333); mean salvage index was 0.69 (SD 0.27) versus 0.57 (0.26), with mean difference of 0.12 (95% CI 0.01-0.21; p=0.0333). Major adverse coronary events were death (n=3 per group), reinfarction (n=1 per group), and heart failure (n=3 per group). INTERPRETATION: Remote ischaemic conditioning before hospital admission increases myocardial salvage, and has a favourable safety profile. Our findings merit a larger trial to establish the effect of remote conditioning on clinical outcomes. FUNDING: Fondation Leducq.

Infarct size and myocardial salvage after primary angioplasty in patients presenting with symptoms for <12 h vs. 12-72 h.

AIMS: Primary angioplasty for ST-segment elevation myocardial infarction (STEMI) is recommended only if symptom duration is <12 h. We evaluated final infarct size (FIS) and myocardial salvage in early presenters (<12 h) vs. late presenters (12-72 h) undergoing primary angioplasty. METHODS AND RESULTS: Myocardial perfusion imaging (MPI) was performed acutely to assess area at risk (AAR) before angioplasty and repeated after 30 days to assess FIS (% of LV myocardium), salvage index (% non-infarcted AAR), and left ventricular ejection fraction (LVEF). Late presenters (n = 55) compared with early presenters (n = 341) had larger median FIS [14% (inter-quartile range 3-30) vs. 7% (2-18), P = 0.005], lower salvage index [53% (27-89) vs. 69% (45-91), P = 0.05], and lower LVEF [48% (44-58%) vs. 53% (47-59), P = 0.04]. However, FIS, salvage index, and LVEF correlated weakly with symptom duration (R(2)-values <0.10). In patients with TIMI-flow 0 (n = 247), late presenters had lower salvage index than early presenters [44% (23-73) vs. 57% (42-86), P = 0.03], but substantial salvage (>50% of AAR) was observed in 41% of late presenters despite total infarct-artery occlusion. CONCLUSION: FIS is larger in late presenters (>12 h) than early presenters after primary angioplasty for STEMI. However, substantial myocardial salvage can be obtained beyond the 12 h limit, even when the infarct-related artery is totally occluded.

Drug-eluting versus bare metal stents in patients with st-segment-elevation myocardial infarction: eight-month follow-up in the Drug Elution and Distal Protection in Acute Myocardial Infarction (DEDICATION) trial.

BACKGROUND: Implantation of drug-eluting stents (DES) limits the rate of coronary restenosis in most patients with coronary artery disease, but data are scarce with regard to their use in patients with ST-segment-elevation myocardial infarction and in connection with distal protection of the microvascular perfusion during primary percutaneous coronary intervention. METHODS AND RESULTS: We randomly assigned 626 patients referred within 12 hours from symptom onset of an ST-elevation myocardial infarction to have a DES or a bare metal stent implanted in the infarct-related lesion with or without distal protection during primary percutaneous coronary intervention. Quantitative coronary angiography was performed during the index treatment and 8 months later. The primary end point was loss of the lumen diameter in the infarct-related lesion induced by neointimal proliferation. Patients were comparable with regard to baseline demographic and angiographic characteristics. The mean late lumen loss was significantly lower in patients treated with a DES (0.06 mm; SD, 0.66 mm) than in patients who had a bare metal stent implanted (0.47 mm; SD, 0.69 mm; P<0.001). The rate of the composite end point of cardiac death, recurrent myocardial infarction, and target lesion revascularization was 8.6% in the DES group versus 14.4% in the bare metal stent group (P=0.03). Cardiac death occurred in 4.2% and 1.6% of the patients (P=0.09) and stent thrombosis occurred in 2.0% and 2.6% (P=0.72), respectively. CONCLUSIONS: Implantation of DES improves the angiographic outcome and need for repeat revascularization without increasing the short-term risk of stent thrombosis but has a tendency to increase cardiac death in patients with ST-segment-elevation myocardial infarction.

Clinical reinfarction according to infarct location and reperfusion modality in patients with ST elevation myocardial infarction. A DANAMI-2 long-term follow-up substudy.

OBJECTIVES: To evaluate clinical reinfarction during a 3-year follow-up after randomization to primary angioplasty versus fibrinolysis in anterior and non-anterior ST elevation myocardial infarction (STEMI). METHODS: Clinical reinfarction was prospectively assessed by an endpoint committee blinded to the study treatment. RESULTS: At 30 days, primary angioplasty compared with fibrinolysis reduced the reinfarction rate both in anterior STEMI patients (n = 823; 2.5 vs. 5.6%, p = 0.02) and in non-anterior STEMI patients (n = 743; 0.8 vs. 7.4%, p < 0.001). After 3 years, the reduction in reinfarction rate was no longer present in anterior STEMI patients (11.2 vs. 11.2%, p = 0.86), but persisted in non-anterior STEMI patients (5.2 vs. 13.5%, p < 0.001). Reinfarction after anterior STEMI carried a higher mortality than reinfarction after non-anterior STEMI (37.6 vs. 15.3%, p = 0.01). Independent predictors of death were: age [hazard ratio (HR) per 1-year increase in age = 1.08 (1.07-1.09)], clinical reinfarction [HR = 5.15 (3.57-7.43)], anterior index STEMI [HR = 1.65 (1.24-2.19)], and Killip class > or =2 [HR = 1.42 (1.01-2.00)]. The additional late reinfarctions after angioplasty for anterior STEMI were located within the angioplasty-treated target segment. Anterior STEMI patients had smaller mean target vessel diameter, which was associated with reinfarction. CONCLUSIONS: Clinical reinfarction is an independent predictor of death. The early superiority of primary angioplasty over fibrinolysis on reinfarction rate after anterior STEMI diminished during long-term follow-up.

Comparison of stent thrombosis, myocardial infarction, and mortality following drug-eluting versus bare-metal stent coronary intervention in patients with diabetes mellitus.

The aim of this study was to examine outcomes subsequent to implantation of drug-eluting stents (DESs) and bare-metal stents (BMSs) in patients with diabetes. From January 2002 to June 2005, data from all percutaneous coronary interventions performed in Western Denmark were prospectively recorded. A total of 1,423 consecutive diabetic patients treated with stent implantation (2,094 lesions) were followed up for 15 months. Of these, 871 patients (1,180 lesions) were treated with a BMS, and 552 patients (914 lesions) were treated with a DES. Dual antiplatelet therapy was recommended for 12 months in both treatment groups. Data for death and myocardial infarction (MI) were ascertained from national health care databases. Use of DESs was not associated with increased risk of definite stent thrombosis (adjusted relative risk [RR] 0.76, 95% confidence interval [CI] 0.10 to 3.26) or MI (adjusted RR 0.90, 95% CI 0.53 to 1.52). In the DES group compared with the BMS group, adjusted RRs of target-lesion revascularization (adjusted RR 0.48, 95% CI 0.33 to 0.71), total mortality (adjusted RR 0.66, 95% CI 0.44 to 0.99), and cardiac mortality (adjusted RR 0.53, 95% CI 0.31 to 0.90) decreased by 52%, 34%, and 47%, respectively. In conclusion, use of DESs reduced target-lesion revascularization in diabetic patients receiving routine clinical care. This result was obtained without increased risk of death, stent thrombosis, or MI.

Comparison of paclitaxel- and sirolimus-eluting stents in everyday clinical practice: the SORT OUT II randomized trial.

CONTEXT: Approval of drug-eluting coronary stents was based on results of relatively small trials of selected patients; however, in routine practice, stents are used in a broader spectrum of patients. OBJECTIVE: To compare the first 2 commercially available drug-eluting stents-sirolimus-eluting and paclitaxel-eluting-for prevention of symptom-driven clinical end points, using a study design reflecting everyday clinical practice. DESIGN, SETTING, AND PATIENTS: Randomized, blinded trial conducted August 2004 to January 2006 at 5 university hospitals in Denmark. Patients were 2098 men and women (mean [SD] age, 63.6 [10.8] years) treated with percutaneous coronary intervention (PCI) and randomized to receive either sirolimus-eluting (n = 1065) or paclitaxel-eluting (n = 1033) stents. Indications for PCI included ST-segment elevation myocardial infarction (STEMI), non-STEMI or unstable angina pectoris, and stable angina. MAIN OUTCOME MEASURES: The primary end point was a composite clinical end point of major adverse cardiac events, defined as either cardiac death, acute myocardial infarction, target lesion revascularization, or target vessel revascularization. Secondary end points included individual components of the composite end point, all-cause mortality, and stent thrombosis. RESULTS: The sirolimus- and the paclitaxel-eluting stent groups did not differ significantly in major adverse cardiac events (98 [9.3%] vs 114 [11.2%]; hazard ratio, 0.83 [95% confidence interval, 0.63-1.08]; P = .16) or in any of the secondary end points. The stent thrombosis rates were 27 (2.5%) and 30 (2.9%) (hazard ratio, 0.87 [95% confidence interval, 0.52-1.46]; P = .60), respectively. CONCLUSION: In this practical randomized trial, there were no significant differences in clinical outcomes between patients receiving sirolimus- and paclitaxel-eluting stents. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00388934.

Aortic valve and left ventricular outflow tract calcium volume and distribution in transcatheter aortic valve replacement: Influence on the risk of significant paravalvular regurgitation.

OBJECTIVES: We sought to determine the impact of aortic root calcium on the risk of significant paravalvular regurgitation (sPAR) in transcatheter aortic valve replacement (TAVR). METHODS: In 302 consecutive patients from 3 centers, aortic root calcium was quantified volumetrically on pre-TAVR multidetector computed tomography (MDCT) in three regions: 1) the aortic valve region, 2) the overall left ventricular outflow tract (LVOT) and 3) the upper LVOT. Transcathether heart valve (THV) oversizing was calculated as (THV nominal area/MDCT annular area-1) × 100. The study endpoint sPAR was a composite of post-dilatation (PD) and PAR > mild. RESULTS: sPAR occurred in 15% (46/302) of patients. Upper LVOT calcium volume was more predictive of sPAR than overall LVOT calcium volume, with an area under the receiver operating curve (AUC) (95% confidence interval [CI]) of 0.80 (0.67-0.89) vs. 0.60 (0.51-0.70); p = 0.0001. The optimal cut-off calcium volume thresholds determined from receiver operating curves were 21 mm3 and 30 mm3 for upper LVOT and overall LVOT calcium, respectively. Upper LVOT calcium ≥ 21 mm3, but not overall LVOT calcium ≥ 30 mm3, independently predicted sPAR, odds ratio (95%CI): 9.5 (4.1-22.3) vs 1.6 (0.6-2.7). Upper LVOT calcium was more predictive of sPAR in patients with THV oversizing ≥ 13% compared to patients with THV oversizing <13%, AUC (95% CI): 0.83 (0.72-0.93) vs. 0.67 (0.51-0.74); p < 0.0001. CONCLUSIONS: Upper LVOT calcium predicts more-than-mild paravalvular regurgitation following TAVR or the need for postdilatation. Upper LVOT calcium is most predictive of paravalvular regurgitation in the event of THV oversizing ≥ 13%.

Coronary CT Angiographic and Flow Reserve-Guided Management of Patients With Stable Ischemic Heart Disease.

BACKGROUND: Clinical outcomes following coronary computed tomography-derived fractional flow reserve (FFRCT) testing in clinical practice are unknown. OBJECTIVES: This study sought to assess real-world clinical outcomes following a diagnostic strategy including first-line coronary computed tomography angiography (CTA) with selective FFRCT testing. METHODS: The study reviewed the results of 3,674 consecutive patients with stable chest pain evaluated with CTA and FFRCT testing to guide downstream management in patients with intermediate stenosis (30% to 70%). The composite endpoint (all-cause death, myocardial infarction, hospitalization for unstable angina, and unplanned revascularization) was determined in 4 patient groups: 1) CTA stenosis <30%, optimal medical treatment (OMT), and no additional testing; 2) FFRCT >0.80, OMT, no additional testing; 3) FFRCT ≤0.80, OMT, no additional testing; and 4) FFRCT ≤0.80, OMT, and referral to invasive coronary angiography. Patients were followed for a median of 24 (range 8 to 41) months. RESULTS: FFRCT was available in 677 patients, and the test result was negative (>0.80) in 410 (61%) patients. In 75% of the patients with FFRCT >0.80, maximum coronary stenosis was ≥50%. The cumulative incidence proportion (95% confidence interval [CI]) of the composite endpoint at the end of follow-up was comparable in groups 1 (2.8%; 95% CI: 1.4% to 4.9%) and 2 (3.9%; 95% CI: 2.0% to 6.9%) (p = 0.58) but was higher (when compared with group 1) in groups 3 (9.4%; p = 0.04) and 4 (6.6%; p = 0.08). Risk of myocardial infarction was lower in group 4 (1.3%) than in group 3 (8%; p < 0.001). CONCLUSIONS: In patients with intermediate-range coronary stenosis, FFRCT is effective in differentiating patients who do not require further diagnostic testing or intervention (FFRCT >0.80) from higher-risk patients (FFRCT ≤0.80) in whom further testing with invasive coronary angiography and possibly intervention may be needed. Further studies assessing the risk and optimal management strategy in patients undergoing first-line CTA with selective FFRCT testing are needed.

Randomized comparison of sirolimus eluting, and biolimus eluting bioresorbable polymer stents: the SORT-OUT VII optical coherence tomography study.

Aims: To show non-inferiority of the 67- or 87 µm thick, sirolimus-eluting Orsiro drug eluting stent (DES) to the 122 µm thick, biolimus-eluting Nobori DES regarding size of vessel lumen outside the stent at 13-month follow-up. Methods and results: This study was a substudy to the SORT-OUT VII trial, a prospective, 1:1-randomized, comparison of the two stents in patients with stable coronary artery disease or acute coronary syndrome. Optical coherence tomography was acquired after percutaneous coronary intervention and at 13-month follow-up. The substudy was powered to access non-inferiority (Δ = 0.60 mm2) of the Orsiro DES to the Nobori DES for the primary endpoint of mean extra stent lumen (ESL) i.e. vessel lumen outside the stent at 13-month follow-up. We randomized 124 patients to Orsiro (n = 60) or Nobori (n = 64). Due to a difference in the one-sided 95%-confidence interval of 0.26 mm2, but increased to 0.82 mm2 after appropriate log-transformation, it could not be rejected that Orsiro exceeded the non-inferiority limit. Testing for superiority, Orsiro had a significantly larger mean ESL at follow-up (Orsiro: 0.11 mm2 [0.02;0.30] mm2, Nobori: 0.03 mm2 [0.00;0.17] mm2, P = 0.04). Stent strut coverage was, Orsiro: 97.6 % [93.8;99.4]%, and Nobori: 96.3 % [90.5;98,6]% (P = 0.13). Conclusion: Orsiro DES had a significantly larger mean ESL at follow-up and it could not be excluded that Orsiro exceeded the limit for non-inferiority. Nobori DES had a more heterogeneous distribution of neointima but stent strut coverage did not differ significantly between the two stents.

A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction.

BACKGROUND: For the treatment of myocardial infarction with ST-segment elevation, primary angioplasty is considered superior to fibrinolysis for patients who are admitted to hospitals with angioplasty facilities. Whether this benefit is maintained for patients who require transportation from a community hospital to a center where invasive treatment is available is uncertain. METHODS: We randomly assigned 1572 patients with acute myocardial infarction to treatment with angioplasty or accelerated treatment with intravenous alteplase; 1129 patients were enrolled at 24 referral hospitals and 443 patients at 5 invasive-treatment centers. The primary study end point was a composite of death, clinical evidence of reinfarction, or disabling stroke at 30 days. RESULTS: Among patients who underwent randomization at referral hospitals, the primary end point was reached in 8.5 percent of the patients in the angioplasty group, as compared with 14.2 percent of those in the fibrinolysis group (P=0.002). The results were similar among patients who were enrolled at invasive-treatment centers: 6.7 percent of the patients in the angioplasty group reached the primary end point, as compared with 12.3 percent in the fibrinolysis group (P=0.05). Among all patients, the better outcome after angioplasty was driven primarily by a reduction in the rate of reinfarction (1.6 percent in the angioplasty group vs. 6.3 percent in the fibrinolysis group, P<0.001); no significant differences were observed in the rate of death (6.6 percent vs. 7.8 percent, P=0.35) or the rate of stroke (1.1 percent vs. 2.0 percent, P=0.15). Ninety-six percent of patients were transferred from referral hospitals to an invasive-treatment center within two hours. CONCLUSIONS: A strategy for reperfusion involving the transfer of patients to an invasive-treatment center for primary angioplasty is superior to on-site fibrinolysis, provided that the transfer takes two hours or less.

Clinical Use of Coronary CTA-Derived FFR for Decision-Making in Stable CAD.

OBJECTIVES: The goal of this study was to assess the real-world clinical utility of fractional flow reserve (FFR) derived from coronary computed tomography angiography (FFRCT) for decision-making in patients with stable coronary artery disease (CAD). BACKGROUND: FFRCT has shown promising results in identifying lesion-specific ischemia. The real-world feasibility and influence on the diagnostic work-up of FFRCT testing in patients suspected of having CAD are unknown. METHODS: We reviewed the complete diagnostic work-up of nonemergent patients referred for coronary computed tomography angiography over a 12-month period at Aarhus University Hospital, Denmark, including all patients with new-onset chest pain with no known CAD and with intermediate-range coronary lesions (lumen reduction, 30% to 70%) referred for FFRCT. The study evaluated the consequences on downstream diagnostic testing, the agreement between FFRCT and invasively measured FFR or instantaneous wave-free ratio (iFR), and the short-term clinical outcome after FFRCT testing. RESULTS: Among 1,248 patients referred for computed tomography angiography, 189 patients (mean age 59 years; 59% male) were referred for FFRCT, with a conclusive FFRCT result obtained in 185 (98%). FFRCT was ≤0.80 in 31% of patients and 10% of vessels. After FFRCT testing, invasive angiography was performed in 29%, with FFR measured in 19% and iFR in 1% of patients (with a tendency toward declining FFR-iFR guidance during the study period). FFRCT ≤0.80 correctly classified 73% (27 of 37) of patients and 70% (37 of 53) of vessels using FFR ≤0.80 or iFR ≤0.90 as the reference standard. In patients with FFRCT >0.80 being deferred from invasive coronary angiography, no adverse cardiac events occurred during a median follow-up period of 12 (range 6 to 18 months) months. CONCLUSIONS: FFRCT testing is feasible in real-world symptomatic patients with intermediate-range stenosis determined by coronary computed tomography angiography. Implementation of FFRCT for clinical decision-making may influence the downstream diagnostic workflow of patients. Patients with an FFRCT value >0.80 being deferred from invasive coronary angiography have a favorable short-term prognosis.

Comparison of Durable-Polymer Zotarolimus-Eluting and Biodegradable-Polymer Biolimus-Eluting Coronary Stents in Patients With Coronary Artery Disease: 3-Year Clinical Outcomes in the Randomized SORT OUT VI Trial.

OBJECTIVES: The authors sought to compare the safety and efficacy of the biocompatible durable-polymer zotarolimus-eluting stent with the biodegradable-polymer biolimus-eluting stent in unselected coronary patients. BACKGROUND: Biodegradable-polymer biolimus-eluting stents are superior to first-generation durable-polymer drug-eluting stents in long-term randomized all-comer trials. Long-term data comparing them to second-generation durable-polymer drug-eluting stents are lacking. METHODS: The study was a randomized, multicenter, all-comer, noninferiority trial in patients with chronic stable coronary artery disease or acute coronary syndromes and at least 1 coronary artery lesion requiring treatment with a drug-eluting stent. Endpoints included major adverse cardiac events (MACE), a composite of safety (cardiac death and myocardial infarction not clearly attributable to a non-target lesion) and efficacy (target lesion revascularization); the individual endpoints of MACE; all-cause mortality; any myocardial infarction; target vessel revascularization; and definite or probable stent thrombosis at 36 months. RESULTS: From March 2011 to August 2012, 2,999 patients were randomly assigned (1:1) to receive either the zotarolimus-eluting (1,502 patients) or the biolimus-eluting (1,497 patients) stent. At 3-year follow-up, MACE occurred in 128 (8.6%) patients assigned to the durable-polymer zotarolimus-eluting stent and in 144 (9.6%) assigned to the biodegradable-polymer biolimus-eluting stent (p = 0.36). Occurrence of cardiac death (2.7% vs. 3.4%), myocardial infarction not clearly attributable to a non-target lesion (2.7% vs. 2.5%), and target lesion revascularization (5.4% vs. 5.5%) did not differ significantly between the 2 groups. Definite very late stent thrombosis occurred in 6 (0.4%) patients assigned to the durable-polymer zotarolimus-eluting stent and in 10 (0.7%) assigned to the biodegradable-polymer biolimus-eluting stent (p = 0.33). CONCLUSIONS: At 3-year follow-up, the durable-polymer zotarolimus-eluting stent and the biodegradable-polymer biolimus-eluting stent were similar in clinical outcome, with no significant difference in safety and efficacy outcomes, including stent thrombosis.

Myocardial Perfusion Imaging Versus Computed Tomography Angiography-Derived Fractional Flow Reserve Testing in Stable Patients With Intermediate-Range Coronary Lesions: Influence on Downstream Diagnostic Workflows and Invasive Angiography Findings.

BACKGROUND: Data on the clinical utility of coronary computed tomography angiography-derived fractional flow reserve (FFRCT) are sparse. In patients with intermediate (40-70%) coronary stenosis determined by coronary computed tomography angiography, we investigated the association of replacing standard myocardial perfusion imaging with FFRCT testing with downstream utilization of invasive coronary angiography (ICA) and the diagnostic yield of ICA (rate of no obstructive disease, and rate of revascularization). METHODS AND RESULTS: This was a single-center observational study of symptomatic patients with suspected coronary artery disease referred to coronary computed tomography angiography between 2013 and 2015. Patients were divided into 3 historical groups based on the adjunctive functional testing approach: myocardial perfusion imaging (n=1332) or FFRCT "implementation" (n=800) or "clinical use" (n=1391). Propensity score matching was used to estimate the average period effect on outcomes. Patients in the FFRCT clinical use group versus the myocardial perfusion imaging group were older and had higher pretest probability of obstructive disease. After adjusting for baseline risk characteristics, there was a reduction in downstream ICA utilization (absolute risk difference: -4.2; 95% CI, -6.9 to -1.6; P=0.002). In patients referred to ICA, findings of no obstructive coronary artery disease decreased (-12.8%; 95% CI, -22.2 to -3.4; P=0.008) and rate of coronary revascularization increased (14.1%; 95% CI, 3.3-24.9; P=0.01), as did availability of functional information for guidance of revascularization (27.8%; 95% CI, 11.3-44.4; P<0.001) after clinical adoption of FFRCT. CONCLUSIONS: Replacing adjunctive myocardial perfusion imaging with FFRCT testing for functional assessment of intermediate stenosis determined by coronary computed tomography angiography in stable coronary artery disease was associated with less ICA utilization, and a higher ICA diagnostic yield. The findings in this observational study needs confirmation in prospective, randomized trials.

Effect of Ischemic Postconditioning During Primary Percutaneous Coronary Intervention for Patients With ST-Segment Elevation Myocardial Infarction: A Randomized Clinical Trial.

Importance: Ischemic postconditioning of the heart during primary percutaneous coronary intervention (PCI) induced by repetitive interruptions of blood flow to the ischemic myocardial region immediately after reopening of the infarct-related artery may limit myocardial damage. Objective: To determine whether ischemic postconditioning can improve the clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Design, Setting, And Participants: In this multicenter, randomized clinical trial, patients with onset of symptoms within 12 hours, STEMI, and thrombolysis in myocardial infarction (TIMI) grade 0-1 flow in the infarct-related artery at arrival were randomized to conventional PCI or postconditioning. Inclusion began on March 21, 2011, through February 2, 2014, and follow-up was completed on February 2, 2016. Analysis was based on intention to treat. Interventions: Patients were randomly allocated 1:1 to conventional primary PCI, including stent implantation, or postconditioning performed as 4 repeated 30-second balloon occlusions followed by 30 seconds of reperfusion immediately after opening of the infarct-related artery and before stent implantation. Main Outcome and Measures: A combination of all-cause death and hospitalization for heart failure. Results: During the inclusion period, 1234 patients (975 men [79.0%] and 259 women [21.0%]; mean [SD] age, 62 [11] years) underwent randomization in the trial. Median follow-up was 38 months (interquartile range, 24-58 months). The primary outcome occurred in 69 patients (11.2%) who underwent conventional primary PCI and in 65 (10.5%) who underwent postconditioning (hazard ratio, 0.93; 95% CI, 0.66-1.30; P = .66). The hazard ratios were 0.75 (95% CI, 0.49-1.14; P = .18) for all-cause death and 0.99 (95% CI, 0.60-1.64; P = .96) for heart failure. Conclusions and Relevance: Routine ischemic postconditioning during primary PCI failed to reduce the composite outcome of death from any cause and hospitalization for heart failure in patients with STEMI and TIMI grade 0-1 flow at arrival. Trial Registration: clinicaltrials.gov Identifier: NCT01435408.

Sirolimus versus bare metal stent implantation in patients with total coronary occlusions: subgroup analysis of the Stenting Coronary Arteries in Non-Stress/Benestent Disease (SCANDSTENT) trial.

BACKGROUND: Coronary restenosis is more common in a total coronary occlusion (TCO) than other lesion types after implantation of bare metal stents (BMS). But whereas sirolimus-eluting stents (SES) have been shown to improve the outcomes in simple coronary artery lesions, data on their efficacy in complex coronary lesions are scarce. METHODS: We enrolled 127 patients with coronary artery disease and a TCO > or = 15 mm in length to have either SES or BMS implanted after successful recanalization. Outcome measures included the minimal lumen diameter, the late lumen loss, and angiographic restenosis (> 50% diameter stenosis) at 6 months follow-up and the occurrence of target vessel failure during a 7-month period. RESULTS: The patients were well matched in demographic and angiographic baseline characteristics, and 20% had diabetes. The reference vessel was 2.92 mm in mean, and the lesion length was 25.2 mm. At follow-up, patients who received SES had a minimal lumen diameter of 2.49 mm compared with 1.46 mm in those who received BMS (P = .015), 0% versus 38% developed restenosis (P < .001), lumen loss was -0.05 versus 0.99 mm (P < .001), and the target vessel failure rate 5% with SES versus 35% with BMS (P < .001). Stent thrombosis occurred in 1 patient in the BMS group. CONCLUSIONS: Implantation of SES is safe, and it markedly reduces angiographic restenosis and the occurrence of adverse events in patients with a TCO.

Comparison of sirolimus-eluting and bare metal stents in coronary bifurcation lesions: subgroup analysis of the Stenting Coronary Arteries in Non-Stress/Benestent Disease Trial (SCANDSTENT).

BACKGROUND: Sirolimus-eluting stent implantation improves the outcome in simple coronary artery lesions compared with bare metal stents, but there is limited evidence of their safety and efficacy when implanted in complex lesions like coronary bifurcations. METHODS: SCANDSTENT was a randomized controlled study comparing implantation of sirolimus-eluting stents with bare-metal stents in patients with complex coronary artery disease. This substudy evaluates the angiographic and clinical outcome of 126 patients with lesions located in a coronary bifurcation. RESULTS: The baseline characteristics of the patients were comparable: 15% had diabetes, and 1.7 stents were implanted per lesion. At follow-up, the minimum lumen diameter of the main branch was 2.35 mm in patients who received sirolimus-eluting stents compared with 1.68 mm in those who received bare-metal stents, and that of the side branch was 1.70 versus 1.19 mm (both P < .001). The late lumen loss in the main branch was 0.12 mm in the sirolimus-eluting stent group versus 0.99 mm in the bare-metal stent group and 0.03 versus 0.56 mm in the side branch (both P < .001). Thus, sirolimus-eluting stents reduced the restenosis rate from 28.3% to 4.9% in the main branch and from 43.4% to 14.8% in the side branches (both P < .001). Major adverse cardiac events occurred in 9% with sirolimus-eluting stents versus 28% with bare-metal stents (P = .01), and stent thrombosis was observed in 0% versus 9% (P = .02). CONCLUSION: Sirolimus-eluting stent implantation improves both the angiographic and clinical outcomes considerably compared with that of bare-metal stents in patients with stenoses located in coronary bifurcations.

Transcatheter Aortic Valve Thrombosis: Incidence, Predisposing Factors, and Clinical Implications.

BACKGROUND: There are limited data on the incidence, clinical implications, and predisposing factors of transcatheter heart valve (THV) thrombosis following transcatheter aortic valve replacement (TAVR). OBJECTIVES: The authors assessed the incidence, potential predictors, and clinical implications of THV thrombosis as determined by contrast-enhanced multidetector computed tomography (MDCT) after TAVR. METHODS: Among 460 consecutive patients who underwent TAVR with the Edwards Sapien XT or Sapien 3 (Edwards Lifesciences, Irvine, California) THV, 405 (88%) underwent MDCT in addition to transthoracic and transesophageal echocardiography 1 to 3 months post-TAVR. MDCT scans were evaluated for hypoattenuated leaflet thickening that indicated THV thrombosis. RESULTS: MDCT verified THV thrombosis in 28 of 405 (7%) patients. A total of 23 patients had subclinical THV thrombosis, whereas 5 (18%) patients experienced clinically overt obstructive THV thrombosis. THV thrombosis risk did not differ among different generations of THVs (8% vs. 6%; p = 0.42). The risk of THV thrombosis in patients who did not receive warfarin was higher compared with patients who received warfarin (10.7% vs. 1.8%; risk ratio [RR]: 6.09; 95% confidence interval [CI]: 1.86 to 19.84). A larger THV was associated with an increased risk of THV thrombosis (p = 0.03). In multivariable analysis, a 29-mm THV (RR: 2.89; 95% CI: 1.44 to 5.80) and no post-TAVR warfarin treatment (RR: 5.46; 95% CI: 1.68 to 17.7) independently predicted THV thrombosis. Treatment with warfarin effectively reverted THV thrombosis and normalized THV function in 85% of patients as documented by follow-up transesophageal echocardiography and MDCT. CONCLUSIONS: Incidence of THV thrombosis in this large study was 7%. A larger THV size may predispose to THV thrombosis, whereas treatment with warfarin appears to have a protective effect. Although often subclinical, THV thrombosis may have important clinical implications.

Long-term outcome of sirolimus-eluting and zotarolimus-eluting coronary stent implantation in patients with and without diabetes mellitus (a Danish organization for randomized trials on clinical outcome III substudy).

We compared 5-year clinical outcomes in diabetic and nondiabetic patients treated with Endeavor zotarolimus-eluting stents (ZESs; Endeavor Sprint, Medtronic, Santa Rosa, California) or Cypher sirolimus-eluting stents (SESs; Cordis, Johnson & Johnson, Warren, New Jersey) coronary implantation. We randomized 2,332 patients to either ZESs (n = 1,162, n = 169 diabetic patients) or SESs (n = 1,170, n = 168 diabetic patients) stratified according to presence or absence of diabetes mellitus. End points included major adverse cardiac event (MACE), a composite of cardiac death, myocardial infarction, target vessel revascularization (TVR), and definite stent thrombosis. Among diabetic patients, MACE occurred more frequently in patients treated with ZESs than SESs (48 [28.4%] vs 31 [18.5%]; odds ratio [OR] 1.75, 95% confidence interval [CI] 1.05 to 2.93, p = 0.032) because of a higher rate of TVR (32 [18.9%] vs 14 [8.3%]; OR 2.57, 95% CI 1.32 to 5.02, p = 0.006). Among nondiabetic patients, ZES and SES had similar MACE rates at 5-year follow-up but SES was associated with a significantly higher risk of definite stent thrombosis (10 [1.0%] vs 23 [2.3%]; OR 0.43, 95% CI 0.20 to 0.91, p = 0.028). Moreover, during the last 4 years, ZES had fewer MACE, TVR, and stent thrombosis events among nondiabetic patients. In conclusion, SES remains superior to ZES in patients with diabetes throughout the 5-year follow-up, however, among nondiabetic patients, SES demonstrated a highly dynamic performance with favorable initial results followed by a late catch-up that included an overall higher risk of stent thrombosis.

Feasibility and early safety of hybrid coronary revascularisation combining off-pump coronary surgery through J-hemisternotomy with percutaneous coronary intervention.

AIMS: To assess the procedural feasibility and early safety of hybrid coronary revascularisation, combining off-pump left internal mammary artery grafting to the left descending coronary artery (LAD) through an inferior J-hemisternotomy (JOPCAB) with percutaneous coronary intervention (PCI) of non-LAD lesions. METHODS AND RESULTS: A total of 100 patients with multivessel coronary artery disease involving LAD were included in this prospective registry. Hybrid revascularisation was performed by JOPCAB, either prior to PCI (89%) or following PCI (11%). In 96% of the cases, the procedure was carried out according to the preoperative strategy and without perioperative (24 hours) major adverse cardiac or cerebral events. At one month, we observed no deaths, one stroke and two procedure-related myocardial infarctions. Five patients underwent reoperation for graft dysfunction, four of whom were identified by angiography without prior signs of ischaemia. Reoperation due to bleeding was necessary in six patients, and nine patients received red blood cell transfusion. CONCLUSIONS: Our prospective registry documented promising procedural feasibility and early safety of coronary hybrid revascularisation combining JOPCAB with PCI. ClinicalTrials.gov identifier: NCT01496664.