PCI in Patients Undergoing Transcatheter Aortic-Valve Implantation.

BACKGROUND: The benefit of percutaneous coronary intervention (PCI) in patients with stable coronary artery disease and severe aortic stenosis who are undergoing transcatheter aortic-valve implantation (TAVI) remains unclear. METHODS: In an international trial, we randomly assigned, in a 1:1 ratio, patients with severe symptomatic aortic stenosis and at least one coronary-artery stenosis with a fractional flow reserve of 0.80 or less or a diameter stenosis of at least 90% either to undergo PCI or to receive conservative treatment, with all patients also undergoing TAVI. The primary end point was a major adverse cardiac event, defined as a composite of death from any cause, myocardial infarction, or urgent revascularization. Safety, including bleeding events and procedural complications, was assessed. RESULTS: A total of 455 patients underwent randomization: 227 to the PCI group and 228 to the conservative-treatment group. The median age of the patients was 82 years (interquartile range, 78 to 85), and the median Society of Thoracic Surgeons-Procedural Risk of Mortality score (on a scale from 0 to 100%, with higher scores indicating a greater risk of death within 30 days after the procedure) was 3% (interquartile range, 2 to 4). At a median follow-up of 2 years (interquartile range, 1 to 4), a major adverse cardiac event (primary end point) had occurred in 60 patients (26%) in the PCI group and in 81 (36%) in the conservative-treatment group (hazard ratio, 0.71; 95% confidence interval [CI], 0.51 to 0.99; P = 0.04). A bleeding event occurred in 64 patients (28%) in the PCI group and in 45 (20%) in the conservative-treatment group (hazard ratio, 1.51; 95% CI, 1.03 to 2.22). In the PCI group, 7 patients (3%) had PCI procedure-related complications. CONCLUSIONS: Among patients with coronary artery disease who were undergoing TAVI, PCI was associated with a lower risk of a composite of death from any cause, myocardial infarction, or urgent revascularization at a median follow-up of 2 years than conservative treatment. (Funded by Boston Scientific and the Danish Heart Foundation; NOTION-3 ClinicalTrials.gov number, NCT03058627.).

Low body mass index and risk of mortality after mitral transcatheter edge-to-edge repair procedure: The "obesity paradox".

BACKGROUND: Most patients undergoing the mitral transcatheter edge-to-edge repair (TEER) technique are elderly comorbid patients. Low body mass index (BMI) < 23 kg/m2 has been identified in other elderly populations as a risk factor, but has not been studied sufficiently in mitral TEER. AIMS: We aimed to study the impact of low BMI (23 kg/m2) on the outcome after mitral TEER. METHODS: Patients undergoing first-time TEER for mitral regurgitation at a single tertiary center were included, with the exclusion of patients with preprocedural hemodynamic instability or missing BMI. The primary endpoint was all-cause mortality. Secondary endpoints were long-term major bleeding or admission with heart failure. RESULTS: A total of 120 patients (mean age 76 ± 10 years, 76% men) were included in the study. Thirty-nine (31%) had low BMI. Patients with low BMI had a similar symptomatic benefit as patients with BMI ≥ 23 kg/m2 at 1 year regarding decrease in diuretics dose and decrease in New York Heart Association (NYHA) class (p > 0.05). In a multivariable Cox regression analysis, BMI as a continuous variable (hazard ratio [HR]: 0.93 [95% confidence interval, CI: 0.87-0.99], p = 0.03) and low BMI (HR: 1.99 [95% CI: 1.12-3.52], p = 0.02) were associated with the primary outcome. Low BMI was not significantly associated with major bleeding (subdistribution hazard ratio [SHR]: 2.39 [95% CI: 0.96-5.97], p = 0.06) or admission with heart failure (SHR: 1.06 [95% CI: 0.61-1.88], p = 0.83) during follow-up with univariable competing risk regression analysis. CONCLUSION: Low BMI is a risk factor for mortality after mitral valve TEER, confirming the presence of an "obesity paradox" in this population and should receive attention in patient selection.

Impact of diabetes on long-term all-cause re-hospitalization after revascularization with percutaneous coronary intervention.

PURPOSE: The purpose of the study was to investigate the incidence, cause and probability of re-hospitalization within 30 and 365 days after percutaneous coronary intervention (PCI) in patients with diabetes. METHOD: Between January 2010 and September 2014, 2763 patients with diabetes were treated with PCI at two Hospitals in Western Denmark. Reasons for readmission within 30 and 365 days were identified. RESULTS: Readmission risks for patients with diabetes were 58% within 365 days and 18% within 30 days. Reason for readmission was ischemic heart disease (IHD) in 725 patients (27%), and non-IHD-related reasons in 826 patients (31%). IHD-related readmission within 365 days was associated with female gender (OR 1.3, 95% CI: 1.1-1.5), and non-ST-segment elevation myocardial infarction, compared to stable angina at the index hospitalization (OR 1.3, 95% CI: 1.1-1.6). Among patients with diabetes, increased risk of readmission due to other reasons were age (OR 1.3, 95% CI: 1.2-1.5) and higher scores of modified Charlson Comorbidity index (CCI): CCI ≥3 (OR 3.6, 95% CI: 2.8-4.6). CONCLUSION: More than half of the patients with diabetes mellitus undergoing PCI were readmitted within 1 year. Comorbidities were the strongest predictor for non-IHD-related readmission, but did not increase the risk for IHD-related readmissions.

Diagnostic and Clinical Value of FFRCT in Stable Chest Pain Patients With Extensive Coronary Calcification: The FACC Study.

BACKGROUND: The influence of extensive coronary calcifications on the diagnostic and prognostic value of coronary computed tomography angiography-derived fractional flow reserve (FFRCT) has been scantily investigated. OBJECTIVES: The purpose of this study was to investigate the diagnostic and short-term role of FFRCT in chest pain patients with Agatston score (AS) >399. METHODS: This was a prospective multicenter study of 260 stable patients with suspected coronary artery disease (CAD) and AS >399. FFRCT was measured blinded by an independent core laboratory. All patients underwent invasive coronary angiography (ICA) and FFR if indicated. The agreement of FFRCT ≤0.80 with hemodynamically significant CAD on ICA/FFR (≥50% left main or ≥70% epicardial artery stenosis and/or FFR ≤0.80) was assessed. Patients undergoing FFR had colocation FFRCT measured, and the lowest per-patient FFRCT was registered in all patients. The association among per-patient FFRCT, coronary revascularization, and major clinical events (all-cause mortality, myocardial infarction, or unstable angina hospitalization) at 90-day follow-up was evaluated. RESULTS: Median age and AS were 68.5 years (IQR: 63-74 years) and 895 (IQR: 587-1,513), respectively. FFRCT was ≤0.80 in 204 patients (78%). Colocation FFRCT (n = 112) showed diagnostic accuracy, sensitivity, and specificity to identify hemodynamically significant CAD of 71%, 87%, and 54%. The area under the receiver-operating characteristics curve (AUC) was 0.75. When using the lowest FFRCT (n = 260), per-patient accuracy, sensitivity, and specificity were 57%, 95%, and 32%, respectively. The AUC was 0.84. A total of 85 patients underwent revascularization, and FFRCT was ≤0.80 in 96% of these. During follow-up, major clinical events occurred in 3 patients (1.2%), all with FFRCT ≤0.80. CONCLUSIONS: Most patients with AS >399 had FFRCT ≤0.80. Using ICA/FFR as the reference revealed a moderate diagnostic accuracy of colocation FFRCT. Compared with the lowest per-patient FFRCT, colocation FFRCT measurement improved diagnostic accuracy and specificity. The 90-day follow-up was favorable with few coronary revascularizations and no major clinical events occurring in patients with FFRCT >0.80. (Use of FFR-CT in Stable Intermediate Chest Pain Patients With Severe Coronary Calcium Score [FACC]; NCT03548753).

Early vascular healing after implantation of the polymer-free biolimus-eluting stent or the ultrathin strut biodegradable polymer sirolimus-eluting stent in patients with ST-segment elevation myocardial infarction.

OBJECTIVE: To evaluate the difference in early vascular healing between the ultrathin-strut biodegradable-polymer sirolimus-eluting Orsiro stent (O-SES) and the polymer-free biolimus-A9-eluting BioFreedom stent (BF-BES), assessed with optical coherence tomography (OCT) after primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarctions (STEMIs). METHODS: Eighty patients with STEMI who underwent primary PCI were randomly allocated 1:1 to treatment with BF-BES or O-SES. OCT was acquired after PCI and at 1-month follow-up. The primary endpoint was 1-month OCT-assessed vascular healing index based on the presence of uncovered and malapposed stent struts and intraluminal filling defects where low vascular healing index indicated favorable vascular healing. RESULTS: At 1-month, the vascular healing index was similar in O-SES 11.5 [interquartile range (IQR) 9.5-17.5], compared to BF-BES 11.5 (IQR 7.1-12.5; P = 0.14). Percentage of uncovered struts [O-SES 31.5% (IQR 20.7-41.9), P = 0.43] vs. BF-BES 27.8% (IQR 19.4-41.9; P = 0.44), and median volume of neointimal hyperplasia [O-SES 4.9 mm3 (IQR 1.4-13.1) vs. BF-BES 7.1 mm3 (IQR 2.8-17.0), P = 0.18] did not differ significantly between the two stent groups. Complete coverage was not observed in any of the stents. The percentages of stents with malapposition did not differ significantly (O-SES 87.1% vs. BF-BES 71.4%, P = 0.14) whereas percentage of malapposed struts [O-SES 3.5% (IQR 0.8-5.5) vs. BF-BES 0.8% (IQR 0.0-1.8), P = 0.003] was lower in the BF-BES group. CONCLUSION: In patients with STEMI, the drug-coated BF-BES and the thin strut O-SES had similar vascular healing index at 1-month. However, the thin O-SES struts were more often malapposed.

Reduced Leaflet Motion after Transcatheter Aortic-Valve Replacement.

BACKGROUND: Subclinical leaflet thickening and reduced leaflet motion of bioprosthetic aortic valves have been documented by four-dimensional computed tomography (CT). Whether anticoagulation can reduce these phenomena after transcatheter aortic-valve replacement (TAVR) is not known. METHODS: In a substudy of a large randomized trial, we randomly assigned patients who had undergone successful TAVR and who did not have an indication for long-term anticoagulation to a rivaroxaban-based antithrombotic strategy (rivaroxaban [10 mg] plus aspirin [75 to 100 mg] once daily) or an antiplatelet-based strategy (clopidogrel [75 mg] plus aspirin [75 to 100 mg] once daily). Patients underwent evaluation by four-dimensional CT at a mean (±SD) of 90±15 days after randomization. The primary end point was the percentage of patients with at least one prosthetic valve leaflet with grade 3 or higher motion reduction (i.e., involving >50% of the leaflet). Leaflet thickening was also assessed. RESULTS: A total of 231 patients were enrolled. At least one prosthetic valve leaflet with grade 3 or higher motion reduction was found in 2 of 97 patients (2.1%) who had scans that could be evaluated in the rivaroxaban group, as compared with 11 of 101 (10.9%) in the antiplatelet group (difference, -8.8 percentage points; 95% confidence interval [CI], -16.5 to -1.9; P = 0.01). Thickening of at least one leaflet was observed in 12 of 97 patients (12.4%) in the rivaroxaban group and in 33 of 102 (32.4%) in the antiplatelet group (difference, -20.0 percentage points; 95% CI, -30.9 to -8.5). In the main trial, the risk of death or thromboembolic events and the risk of life-threatening, disabling, or major bleeding were higher with rivaroxaban (hazard ratios of 1.35 and 1.50, respectively). CONCLUSIONS: In a substudy of a trial involving patients without an indication for long-term anticoagulation who had undergone successful TAVR, a rivaroxaban-based antithrombotic strategy was more effective than an antiplatelet-based strategy in preventing subclinical leaflet-motion abnormalities. However, in the main trial, the rivaroxaban-based strategy was associated with a higher risk of death or thromboembolic complications and a higher risk of bleeding than the antiplatelet-based strategy. (Funded by Bayer; GALILEO-4D ClinicalTrials.gov number, NCT02833948.).

Everolimus-Eluting Versus Biolimus-Eluting Coronary Stent Implantation in Patients With and Without Diabetes Mellitus.

Diabetes mellitus is associated with a higher risk of target lesion revascularization after percutaneous coronary intervention. We compared clinical outcomes in patients with and without diabetes mellitus, treated with everolimus-eluting stents (EES; Synergy; Boston Scientific, Marlborough, Massachusetts) or biolimus-eluting stents (BES; BioMatrix NeoFlex; Biosensors Interventional Technologies Pte Ltd., Singapore). In total, 2,764 patients were randomized to stent implantation with EES (n = 1,385, diabetes: n = 250) or the BES (n = 1,379, diabetes: n = 262), stratified by gender and diabetes. The primary end point, target lesion failure (TLF), was a composite of cardiac death, target-lesion myocardial infarction, or target lesion revascularization at 12 months. Secondary end points included individual components of TLF, all-cause death, and stent thrombosis. TLF was 2.1% lower in the EES versus the BES groups in patients with diabetes (3.6% vs 5.7%; rate ratios 0.61, 95% confidence interval [CI] 0.27 to 1.41) and similar in patients without diabetes (4.1% vs 4.0%; rate ratios 0.99, 95% CI 0.66 to 1.51). In patients with diabetes, the point estimates of the individual components of TLF also favored the EES but CIs were wide. No interaction between stent type and presence of diabetes was found. The current subgroup analysis found that a thin-strut EES as compared with a thicker strut BES had a numerically lower TLF rate in patients with diabetes, but the subgroup analysis was underpowered for definite conclusions.

Functional and Anatomical Testing in Intermediate Risk Chest Pain Patients with a High Coronary Calcium Score: Rationale and Design of the FACC Study.

Current guidelines do not recommend coronary computed tomography angiography (CCTA) in patients with high levels of coronary calcium, as severe calcification leads to difficulties in estimating stenosis severity due to blooming artifacts obscuring the vessel lumen. Whether the CCTA-derived fractional flow reserve (FFRCT) improves the diagnostic performance of CCTA in patients with high levels of coronary calcification has not been sufficiently evaluated. We hypothesize that a noninvasive diagnostic strategy using FFRCT will perform comparably to an invasive diagnostic strategy in the detection of hemodynamically significant coronary artery disease (CAD) in clinical stable chest pain patients with high levels of coronary calcium. In this prospective, blinded, multicenter study, patients with suspected stable CAD referred for CCTA and demonstrating an Agatston score >399 will be included. Patients accepting inclusion will, in addition to CCTA, undergo invasive coronary angiography (ICA) and invasive FFR measurement. FFRCT analyses are performed by an external core laboratory blinded to any patient data, and the FFRCT results are blinded to all participating study sites. The primary objective is to evaluate whether FFRCT can identify patients with and without hemodynamically significant CAD, when ICA with FFR is the reference standard. A negative study result would question the clinical usefulness of FFRCT in patients with high levels of coronary calcium. A positive study result, however, would imply a reduction in the number of patients referred for coronary catheterization and, at the same time, increase the proportion of patients with hemodynamically significant CAD at the subsequent invasive examination.

Angina Pectoris in Young Male due to Agenesis of Left Circumflex Artery.

BACKGROUND This case study demonstrated that although highly symptomatic, agenesis of the left circumflex artery was a benign finding. Anomalies of the coronary arteries were found to be the cause of sudden death in a young individual. Left circumflex anomalies were not associated with major cardiac events. CASE REPORT A 20-year-old male was admitted due to syncope preceded by chest pain. His electrocardiogram (ECG) showed global ST segment elevation as well as biphasic T waves in anterior precordial leads. Troponin T values were normal. Echocardiography was normal. Computerized axial tomography (CAT) scan showed agenesis of the circumflex artery with a super-dominant right coronary artery. Myocardial scintigraphy showed no perfusion defects. Exercise test did not present any arrhythmias. Tilt table test displayed stable blood pressure and pulse response. A reveal recorder registered no malignant arrhythmias. A coronary angiography confirmed the finding of the CAT scan and showed no collateral vessel development. CONCLUSIONS This case demonstrated that agenesis left circumflex artery although presenting with severe symptoms, such as chest pain, is a benign finding. Chest pain was not correlated to perfusion defects in this case. Although the patient experienced loss of consciousness, there was no objective support for cardiac origin as no malignant arrhythmias were found.

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.

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.

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.

High mortality among heart failure patients treated with antidepressants.

BACKGROUND: This study was designed to assess whether pharmacologically treated depression was associated with increased mortality risk in systolic heart failure (SHF) patients. METHODS: Patients (n=3346) with SHF (left ventricular ejection fraction ≤ 0.45) and primarily New York Heart Association (NYHA) classes II-III (78%) were recruited from a clinical database used in 20 heart failure clinics in Denmark. The association between pharmacologically treated depression identified by at least one prescription of an antidepressant and mortality risk was evaluated. RESULTS: Follow-up time was 540 days (range: 30-1600 days). 539 patients died. For 243 patients (7%) an antidepressant had been prescribed at least once. In a Cox Proportional Hazard Model, pharmacologically treated depression was associated with a 49% increased mortality risk (Hazard ratio: 1.49, 95% confidence interval: 1.03-2.16) after adjustment for traditional confounders. Three months after the baseline visit in the heart failure clinic, these patients received lower doses of beta-blockers than patients without antidepressant therapy (p=0.006). Female sex (p<0.001) and NYHA classes III-IV (p=0.007) were associated with the prescription of an antidepressant. CONCLUSIONS: Our analyses suggest that pharmacologically treated depression is associated with a 49% increased mortality risk, and that these high-risk patients receive lower doses of beta-blockers than patients with no antidepressant therapy.