Lesion-Level Effects of LDL-C-Lowering Therapy in Patients With Acute Myocardial Infarction: A Post Hoc Analysis of the PACMAN-AMI Trial.

Importance: Previous studies investigated atherosclerotic changes induced by lipid-lowering therapy in extensive coronary segments irrespective of baseline disease burden (a vessel-level approach). Objective: To investigate the effects of lipid-lowering therapy on coronary lesions with advanced atherosclerotic plaque features and presumably higher risk for future events. Design, Setting, and Participants: The PACMAN-AMI randomized clinical trial (enrollment: May 2017 to October 2020; final follow-up: October 2021) randomized patients with acute myocardial infarction to receive alirocumab or placebo in addition to high-intensity statin therapy. In this post hoc lesion-level analysis, nonculprit lesions were identified as segments with plaque burden 40% or greater defined by intravascular ultrasound (IVUS). IVUS, near-infrared spectroscopy, and optical coherence tomography images at baseline and the 52-week follow-up were manually matched by readers blinded to treatment allocation. Data for this study were analyzed from October 2022 to November 2023. Interventions: Alirocumab or placebo in addition to high-intensity statin therapy. Main Outcomes and Measures: Lesion-level imaging outcome measures, including high-risk plaque characteristics and phenotypes. Results: Of the 245 patients in whom lesions were found, 118 were in the alirocumab group (mean [SD] age, 58.2 [10.0] years; 101 [85.6%] male and 17 [14.4%] female) and 127 in the placebo group (mean [SD] age, 57.7 [8.8] years; 104 [81.9%] male and 23 [18.1%] female). Overall, 591 lesions were included: 287 lesions (118 patients, 214 vessels) in the alirocumab group and 304 lesions (127 patients, 239 vessels) in the placebo group. Lesion-level mean change in percent atheroma volume (PAV) was -4.86% with alirocumab vs -2.78% with placebo (difference, -2.02; 95% CI, -3.00 to -1.05; P < .001). At the minimum lumen area (MLA) site, mean change in PAV was -10.14% with alirocumab vs -6.70% with placebo (difference, -3.36; 95% CI, -4.98 to -1.75; P < .001). MLA increased by 0.15 mm2 with alirocumab and decreased by 0.07 mm2 with placebo (difference, 0.21; 95% CI, 0.01 to 0.41; P = .04). Among 122 lipid-rich lesions, 34 of 55 (61.8%) in the alirocumab arm and 27 of 67 (41.8%) in the placebo arm showed a less lipid-rich plaque phenotype at follow-up (P = .03). Among 63 lesions with thin-cap fibroatheroma at baseline, 8 of 26 (30.8%) in the alirocumab arm and 3 of 37 (8.1%) in the placebo arm showed a fibrous/fibrocalcific plaque phenotype at follow-up (P = .02). Conclusions and Relevance: At the lesion level, very intensive lipid-lowering therapy induced substantially greater PAV regression than described in previous vessel-level analyses. Compared with statin therapy alone, alirocumab treatment was associated with greater enlargement of the lesion MLA and more frequent transition of presumably high-risk plaque phenotypes into more stable, less lipid-rich plaque phenotypes. Trial Registration: ClinicalTrials.gov Identifier: NCT03067844.

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.).

Prehospital Pulse-Dose Glucocorticoid in ST-Segment Elevation Myocardial Infarction: The PULSE-MI Randomized Clinical Trial.

Importance: In patients with ST-segment elevation myocardial infarction (STEMI), acute inflammation is related to the extent of myocardial damage and may increase infarct size. Thus, administration of pulse-dose glucocorticoid in the very early phase of infarction may reduce infarct size. Objective: To determine the cardioprotective effect of prehospital pulse-dose glucocorticoid in patients with STEMI. Design, Setting, and Participants: This was a 1:1 investigator-initiated, blinded, placebo-controlled, randomized clinical trial conducted between November 14, 2022, and October 17, 2023, with last follow-up on January 17, 2024. Patients 18 years and older with less than 12 hours of acute chest pain and STEMI were included in the prehospital setting throughout the Region Zealand and Capital Region of Denmark and transferred to Rigshospitalet, Denmark. Intervention: Patients were randomly allocated to intravenous glucocorticoid (methylprednisolone, 250 mg) or placebo in the prehospital setting. Main Outcomes and Measures: The primary outcome was final infarct size on cardiac magnetic resonance (CMR) at 3 months. The power calculation was based on an anticipated final infarct size of 13%. Secondary outcomes included CMR outcomes on acute scan and at 3 months, peak of cardiac biomarkers, clinical end points at 3 months, and adverse events. Results: Of 530 included patients (median [IQR] age, 65 [56-75] years; 418 male [78.9%]) with STEMI, 401 (76%) were assessed for the primary outcome, with 198 patients treated with glucocorticoid and 203 with placebo. Median final infarct size was similar in the treatment groups (glucocorticoid, 5%; IQR, 2%-11% vs placebo, 6%; IQR, 2%-13%; P = .24). Compared with placebo, the glucocorticoid group had smaller acute infarct size (odds ratio, 0.78; 95% CI, 0.61-1.00), less microvascular obstruction (relative risk ratio, 0.83; 95% CI, 0.71-0.99), and greater acute left ventricular ejection fraction (mean difference, 4.44%; 95% CI, 2.01%-6.87%). Other secondary outcomes were similar in both groups. Conclusions and Relevance: In patients with STEMI, treatment with prehospital pulse-dose glucocorticoid did not reduce final infarct size after 3 months. However, the trial was likely underpowered as the final infarct size was smaller than anticipated. The glucocorticoid group had improved acute parameters compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT05462730.

FFR-Guided Complete or Culprit-Only PCI in Patients with Myocardial Infarction.

BACKGROUND: The benefit of fractional flow reserve (FFR)-guided complete revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease remains unclear. METHODS: In this multinational, registry-based, randomized trial, we assigned patients with STEMI or very-high-risk non-STEMI (NSTEMI) and multivessel disease who were undergoing primary percutaneous coronary intervention (PCI) of the culprit lesion to receive either FFR-guided complete revascularization of nonculprit lesions or no further revascularization. The primary outcome was a composite of death from any cause, myocardial infarction, or unplanned revascularization. The two key secondary outcomes were a composite of death from any cause or myocardial infarction and unplanned revascularization. RESULTS: A total of 1542 patients underwent randomization, with 764 assigned to receive FFR-guided complete revascularization and 778 assigned to receive culprit-lesion-only PCI. At a median follow-up of 4.8 years (interquartile range, 4.3 to 5.2), a primary-outcome event had occurred in 145 patients (19.0%) in the complete-revascularization group and in 159 patients (20.4%) in the culprit-lesion-only group (hazard ratio, 0.93; 95% confidence interval [CI], 0.74 to 1.17; P = 0.53). With respect to the secondary outcomes, no apparent between-group differences were observed in the composite of death from any cause or myocardial infarction (hazard ratio, 1.12; 95% CI, 0.87 to 1.44) or unplanned revascularization (hazard ratio, 0.76; 95% CI, 0.56 to 1.04). There were no apparent between-group differences in safety outcomes. CONCLUSIONS: Among patients with STEMI or very-high-risk NSTEMI and multivessel coronary artery disease, FFR-guided complete revascularization was not shown to result in a lower risk of a composite of death from any cause, myocardial infarction, or unplanned revascularization than culprit-lesion-only PCI at 4.8 years. (Funded by the Swedish Research Council and others; FULL REVASC ClinicalTrials.gov number, NCT02862119.).

Microaxial Flow Pump or Standard Care in Infarct-Related Cardiogenic Shock.

BACKGROUND: The effects of temporary mechanical circulatory support with a microaxial flow pump on mortality among patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock remains unclear. METHODS: In an international, multicenter, randomized trial, we assigned patients with STEMI and cardiogenic shock to receive a microaxial flow pump (Impella CP) plus standard care or standard care alone. The primary end point was death from any cause at 180 days. A composite safety end point was severe bleeding, limb ischemia, hemolysis, device failure, or worsening aortic regurgitation. RESULTS: A total of 360 patients underwent randomization, of whom 355 were included in the final analysis (179 in the microaxial-flow-pump group and 176 in the standard-care group). The median age of the patients was 67 years, and 79.2% were men. Death from any cause occurred in 82 of 179 patients (45.8%) in the microaxial-flow-pump group and in 103 of 176 patients (58.5%) in the standard-care group (hazard ratio, 0.74; 95% confidence interval [CI], 0.55 to 0.99; P = 0.04). A composite safety end-point event occurred in 43 patients (24.0%) in the microaxial-flow-pump group and in 11 (6.2%) in the standard-care group (relative risk, 4.74; 95% CI, 2.36 to 9.55). Renal-replacement therapy was administered to 75 patients (41.9%) in the microaxial-flow-pump group and to 47 patients (26.7%) in the standard-care group (relative risk, 1.98; 95% CI, 1.27 to 3.09). CONCLUSIONS: The routine use of a microaxial flow pump with standard care in the treatment of patients with STEMI-related cardiogenic shock led to a lower risk of death from any cause at 180 days than standard care alone. The incidence of a composite of adverse events was higher with the use of the microaxial flow pump. (Funded by the Danish Heart Foundation and Abiomed; DanGer Shock ClinicalTrials.gov number, NCT01633502.).

The role of remnant cholesterol in patients with ST-segment elevation myocardial infarction.

AIMS: Remnant cholesterol (RC) is the cholesterol content within triglyceride-rich lipoproteins. It promotes atherosclerotic cardiovascular disease beyond LDL cholesterol (LDL-C). The prognostic role of RC in patients with ST-segment elevation myocardial infarction (STEMI) is unknown. We aimed to estimate RC-related risk beyond LDL-C in patients with STEMI. METHODS AND RESULTS: A total of 6602 consecutive patients with STEMI treated with primary percutaneous coronary intervention (PCI) from 1999 to 2016 were included. Remnant cholesterol was calculated as total cholesterol minus LDL-C minus HDL cholesterol. Adjusted Cox models were used to estimate the association between continuous RC levels and all-cause mortality, cardiovascular death, ischaemic stroke, and recurrent myocardial infarction (MI) at long-term (median follow-up of 6.0 years). Besides, discordance analyses were applied to examine the risk of the discordantly high RC (RC percentile rank minus LDL-C percentile rank > 10 units) compared with the discordantly low RC (LDL-C percentile rank minus RC percentile rank > 10 units). The concordance was defined as the percentile rank difference between RC and LDL-C ≤ 10 units. The median age of patients was 63 years [interquartile range (IQR) 54-72] and 74.8% were men. There were 2441, 1651, and 2510 patients in the discordantly low RC group, concordant group, and discordantly high RC group, respectively. All outcomes in the discordantly high RC group were higher than the other groups, and the event rate of all-cause mortality in this group was 31.87%. In the unadjusted analysis, the discordantly high RC was associated with increased all-cause mortality [hazard ratio (HR) 1.82, 95% confidence interval (CI) 1.63-2.04] and increased cardiovascular death (HR 1.79, 95% CI 1.55-2.06) compared with the discordantly low RC. In an adjusted model, RC was associated with higher all-cause mortality (HR 1.14, 95% CI 1.07-1.22). The discordantly high RC was associated with increased all-cause mortality (adjusted HR 1.55, 95% CI 1.37-1.75) and increased cardiovascular death (adjusted HR 1.47, 95% CI 1.25-1.72) compared with the discordantly low RC. There were no associations between RC and ischaemic stroke or recurrent MI. CONCLUSION: In patients with STEMI treated with primary PCI, elevated RC levels beyond LDL-C and discordantly high RC were independently associated with increased all-cause mortality.

In patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI), elevated remnant cholesterol (RC) levels beyond LDL cholesterol were independently associated with increased all-cause mortality.About 38% of patients with STEMI present discordantly high RC, which is associated with elevated all-cause mortality and cardiovascular death.Remnant cholesterol as a continuous variable is associated with higher all-cause mortality.

Prognostic differences between physiology-guided percutaneous coronary intervention and optimal medical therapy in coronary artery disease: A systematic review and meta-analysis.

Background: Intracoronary physiology, particularly fractional flow reserve (FFR), has been used as a guide for revascularization for patients with coronary artery disease (CAD). The optimal treatment in the physiological grey-zone area has been unclear and remains subject to ongoing debate. Methods: We conducted a systematic review of randomized controlled trials and observational studies comparing the prognostic effect of percutaneous coronary revascularization (PCI) and optimal medical therapy (OMT) in patients with CAD. Studies were identified by medical literature databases. The outcomes of interest were major adverse cardiac events (MACE) and its components, death, myocardial infarction (MI), and repeat revascularization. Results: A total of 16 studies with 27,451 patients were included. The pooled analysis demonstrated that PCI was associated with a prognostic advantage over OMT in patients with FFR value ≤0.80 (RR: 0.64, 95 % CI: 0.45-0.90, p < 0.01). Patients with an FFR value >0.80 were shown to benefit more from OMT (RR 1.38, 95 % CI 1.24-1.53, p < 0.01). The analysis also showed that there was no significant difference in MACE in the grey-zone area (FFR 0.75-0.80) (RR 0.64, 95 % CI: 0.35-1.16, p = 0.14), but a significant reduction in repeat revascularization (RR 0.54, 95 % CI, 0.31-0.91, p < 0.01) when patients were treated with PCI. Conclusions: Among patients with CAD and FFR values >0.80, OMT was associated with favorable outcomes over PCI in reducing the risk of MACE. However, among patients with FFR values ≤0.80, revascularization was superior in terms of reducing MACE. The available evidence supports the guideline-recommended use of an FFR cut-off of ≤0.80.

Organized thrombus is a frequent underlying feature in culprit lesion morphology in non-ST-elevation myocardial infarction. A study using optical coherence tomography and magnetic resonance imaging.

The concept that the culprit lesion in non-ST segment elevation myocardial infarction (NSTEMI) is caused by sudden plaque rupture with acute thrombus formation has recently been challenged. While angiography is an old gold-standard for culprit identification it merely visualizes the lumen contour. Optical coherence tomography (OCT) provides a detailed view of culprit features. Combined with myocardial edema on cardiac magnetic resonance (CMR), indicating acute ischemia and thus culprit location, we aimed to characterize culprit lesions using OCT. Patients with NSTEMI referred for angiography were prospectively enrolled. OCT was performed on angiographic stenoses ≥50% and on operator-suspected culprit lesions. Hierarchical OCT-culprit identifiers were defined in case of multiple unstable lesions, including OCT-defined thrombus age. An OCT-based definition of an organizing thrombus as corresponding to histological early healing stage was introduced. Lesions were classified as OCT-culprit or non-culprit, and characteristics compared. CMR was performed in a subset of patients. We included 65 patients with 97 lesions, of which 49 patients (75%) had 53 (54%) OCT-culprit lesions. The most common OCT-culprit identifiers were the presence of acute (66%) and organizing thrombus (19%). Plaque rupture was visible in 45% of OCT-culprit lesions. CMR performed in 38 patients revealed myocardial oedema in the corresponding territories of 67% of acute thrombi and 50% of organizing thrombi. A culprit lesion was identified by OCT in 75% patients with NSTEMI. Acute thrombus was the most frequent feature followed by organizing thrombus. Applying specific OCT-criteria to identify the culprit could prove valuable in ambiguous cases.

Pre-hospital pulse glucocorticoid therapy in patients with ST-segment elevation myocardial infarction transferred for primary percutaneous coronary intervention: a randomized controlled trial (PULSE-MI).

BACKGROUND: Inflammation in ST-segment elevation myocardial infarction (STEMI) is an important contributor to both acute myocardial ischemia and reperfusion injury after primary percutaneous coronary intervention (PCI). Methylprednisolone is a glucocorticoid with potent anti-inflammatory properties with an acute effect and is used as an effective and safe treatment of a wide range of acute diseases. The trial aims to investigate the cardioprotective effects of pulse-dose methylprednisolone administered in the pre-hospital setting in patients with STEMI transferred for primary PCI. METHODS: This trial is a randomized, blinded, placebo-controlled prospective clinical phase II trial. Inclusion will continue until 378 patients with STEMI have been evaluated for the primary endpoint. Patients will be randomized 1:1 to a bolus of 250 mg methylprednisolone intravenous or matching placebo over a period of 5 min in the pre-hospital setting. All patients with STEMI transferred for primary PCI at Rigshospitalet, Copenhagen University Hospital, Denmark, will be screened for eligibility. The main eligibility criteria are age ≥ 18 years, acute onset of chest pain with < 12 h duration, STEMI on electrocardiogram, no known allergy to glucocorticoids or no previous coronary artery bypass grafting, previous acute myocardial infarction in assumed culprit, or a history with previous maniac/psychotic episodes. Primary outcome is final infarct size measured by late gadolinium enhancement on cardiac magnetic resonance (CMR) 3 months after STEMI. Secondary outcomes comprise key CMR efficacy parameters, clinical endpoints at 3 months, the peak of cardiac biomarkers, and safety. DISCUSSION: We hypothesize that pulse-dose methylprednisolone administrated in the pre-hospital setting decreases inflammation and thus reduces final infarct size in patients with STEMI treated with primary PCI. TRIAL REGISTRATION: EU-CT number: 2022-500762-10-00; Submitted May 5, 2022. CLINICALTRIALS: gov Identifier: NCT05462730; Submitted July 7, 2022, first posted July 18, 2022.

OCT or Angiography Guidance for PCI in Complex Bifurcation Lesions.

BACKGROUND: Imaging-guided percutaneous coronary intervention (PCI) is associated with better clinical outcomes than angiography-guided PCI. Whether routine optical coherence tomography (OCT) guidance in PCI of lesions involving coronary-artery branch points (bifurcations) improves clinical outcomes as compared with angiographic guidance is uncertain. METHODS: We conducted a multicenter, randomized, open-label trial at 38 centers in Europe. Patients with a clinical indication for PCI and a complex bifurcation lesion identified by means of coronary angiography were randomly assigned in a 1:1 ratio to OCT-guided PCI or angiography-guided PCI. The primary end point was a composite of major adverse cardiac events (MACE), defined as death from a cardiac cause, target-lesion myocardial infarction, or ischemia-driven target-lesion revascularization at a median follow-up of 2 years. RESULTS: We assigned 1201 patients to OCT-guided PCI (600 patients) or angiography-guided PCI (601 patients). A total of 111 patients (18.5%) in the OCT-guided PCI group and 116 (19.3%) in the angiography-guided PCI group had a bifurcation lesion involving the left main coronary artery. At 2 years, a primary end-point event had occurred in 59 patients (10.1%) in the OCT-guided PCI group and in 83 patients (14.1%) in the angiography-guided PCI group (hazard ratio, 0.70; 95% confidence interval, 0.50 to 0.98; P = 0.035). Procedure-related complications occurred in 41 patients (6.8%) in the OCT-guided PCI group and 34 patients (5.7%) in the angiography-guided PCI group. CONCLUSIONS: Among patients with complex coronary-artery bifurcation lesions, OCT-guided PCI was associated with a lower incidence of MACE at 2 years than angiography-guided PCI. (Funded by Abbott Vascular and others; OCTOBER ClinicalTrials.gov number, NCT03171311.).

Concomitant Coronary Atheroma Regression and Stabilization in Response to Lipid-Lowering Therapy.

BACKGROUND: The frequency, characteristics, and outcomes of patients treated with high-intensity lipid-lowering therapy and showing concomitant atheroma volume reduction, lipid content reduction, and increase in fibrous cap thickness (ie, triple regression) are unknown. OBJECTIVES: This study was designed to investigate rates, determinants, and prognostic implications of triple regression in patients presenting with acute myocardial infarction and treated with high-intensity lipid-lowering therapy. METHODS: The PACMAN-AMI (Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients with Acute Myocardial Infarction) trial used serial intravascular ultrasound, near-infrared spectroscopy, and optical coherence tomography to compare the effects of alirocumab vs placebo in patients receiving high-intensity statin therapy. Triple regression was defined by the combined presence of percentage of atheroma volume reduction, maximum lipid core burden index within 4 mm reduction, and minimal fibrous cap thickness increase. Clinical outcomes at 1-year follow-up were assessed. RESULTS: Overall, 84 patients (31.7%) showed triple regression (40.8% in the alirocumab group vs 23.0% in the placebo group; P = 0.002). On-treatment low-density lipoprotein cholesterol levels were lower in patients with vs without triple regression (between-group difference: -27.1 mg/dL; 95% CI: -37.7 to -16.6 mg/dL; P < 0.001). Triple regression was independently predicted by alirocumab treatment (OR: 2.83; 95% CI: 1.57-5.16; P = 0.001) and a higher baseline maximum lipid core burden index within 4 mm (OR: 1.03; 95% CI: 1.01-1.06; P = 0.013). The composite clinical endpoint of death, myocardial infarction, and ischemia-driven revascularization occurred less frequently in patients with vs without triple regression (8.3% vs 18.2%; P = 0.04). CONCLUSIONS: Triple regression occurred in one-third of patients with acute myocardial infarction who were receiving high-intensity lipid-lowering therapy and was associated with alirocumab treatment, higher baseline lipid content, and reduced cardiovascular events. (Vascular Effects of Alirocumab in Acute MI-Patients [PACMAN-AMI]; NCT03067844).

Routine revascularization with percutaneous coronary intervention in patients with coronary artery disease undergoing transcatheter aortic valve implantation - the third nordic aortic valve intervention trial - NOTION-3.

BACKGROUND: Coronary artery disease (CAD) frequently coexists with severe aortic valve stenosis (AS) in patients planned for transcatheter aortic valve implantation (TAVI). How to manage CAD in this patient population is still an unresolved question. In particular, it is still not known whether fractional flow reserve (FFR) guided revascularization with percutaneous coronary intervention (PCI) is superior to medical treatment for CAD in terms of clinical outcomes. STUDY DESIGN: The third Nordic Aortic Valve Intervention (NOTION-3) Trial is an open-label investigator-initiated, multicenter multinational trial planned to randomize 452 patients with severe AS and significant CAD to either FFR-guided PCI or medical treatment, in addition to TAVI. Patients are eligible for the study in the presence of at least 1 significant PCI-eligible coronary stenosis. A significant stenosis is defined as either FFR ≤0.80 and/or diameter stenosis >90%. The primary end point is a composite of first occurring all-cause mortality, myocardial infarction, or urgent revascularization (PCI or coronary artery bypass graft performed during unplanned hospital admission) until the last included patient have been followed for 1 year after the TAVI. SUMMARY: NOTION-3 is a multicenter, multinational randomized trial aiming at comparing FFR-guided revascularization vs medical treatment of CAD in patients with severe AS planned for TAVI.

Long-term changes in coronary physiology after aortic valve replacement.

BACKGROUND: The detrimental effects of long-standing severe aortic stenosis (AS) often include left ventricular hypertrophy (LVH) and exhaustion of coronary flow reserve (CFR), the reversibility of which is unclear after valve replacement. AIMS: Our aims were to 1) investigate whether CFR in the left anterior descending artery (LAD) would improve following valve replacement, and if the change was related to changes in hyperaemic coronary flow (QLAD) and minimal microvascular resistance (Rµ,LAD); and 2) investigate the relationship between changes in CFR and changes in left ventricular mass (LVM) and stroke work (LVSW). METHODS: We measured intracoronary bolus thermodilution-derived CFR, and continuous thermodilution-derived QLAD and Rµ,LAD before and 6 months after aortic valve replacement. Cardiac magnetic resonance imaging was used to quantify left ventricular anatomy and function for the calculation of LVM and LVSW.  Results: Thirty-four patients were included (17 patients had transcatheter aortic valve implantation; 14 had surgical valve replacement with a bioprosthesis and 3 with a mechanical prosthesis) who underwent invasive assessment in the LAD. CFR increased from 2.5 (interquartile range [IQR] 1.5-3.3) at baseline to 3.1 (IQR 2.2-5.1) at follow-up (p=0.005), despite no significant change in QLAD (230±106 mL/min to 250±101 mL/min; p=0.26) or Rµ,LAD (347 [IQR 247-463] to 287 [IQR 230-456]; p=0.20). When indexed for LVM, QLAD was 39% (IQR 8-98%) higher at follow-up compared with baseline (p<0.001). The improvement in CFR was correlated with ΔLVSW, r= -0.39; p=0.047.   Conclusions: CFR in the LAD increased significantly at follow-up although global hyperaemic flow and minimal microvascular resistance remained unchanged. Thus, a decrease in resting flow was the cause of CFR improvement. CFR improvement was associated with reduction in LVSW.

Scar border zone mass and presence of border zone channels assessed with cardiac magnetic resonance imaging are associated with ventricular arrhythmia in patients with ST-segment elevation myocardial infarction.

AIMS: Late gadolinium enhancement cardiac magnetic resonance (CMR) permits characterization of left ventricular ischaemic scars. We aimed to evaluate if scar core mass, border zone (BZ) mass, and BZ channels are risk markers for subsequent ventricular arrhythmia (VA) in ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: A sub-study of the DANish Acute Myocardial Infarction-3 multi-centre trial and Danegaptide phase II proof-of-concept clinical trial in which a total of 843 STEMI patients had a 3-month follow-up CMR. Of these, 21 patients subsequently experienced VA during 100 months of follow-up and were randomly matched 1:5 with 105 controls. A VA event was defined as: ventricular tachycardia, ventricular fibrillation, or sudden cardiac death. Ischaemic scar characteristics were automatically detected by specialized software. We included 126 patients with a median left ventricular ejection fraction of 51.0 ± 11.6% in cases with VA vs. 55.5 ± 8.5% in controls (P = 0.10). Cases had a larger mean BZ mass and more often BZ channels compared to controls [BZ mass: 17.2 ± 10.3 g vs. 10.3 ± 6.0 g; P = 0.0002; BZ channels: 17 (80%) vs. 44 (42%); P = 0.001]. A combination of ≥17.2 g BZ mass and the presence of BZ channels was five times more prevalent in cases vs. controls (P ≤ 0.00001) with an odds ratio of 9.40 (95% confidence interval 3.26-27.13; P ≤ 0.0001) for VA. This identified cases with 52% sensitivity and 90% specificity. CONCLUSION(S): Scar characterization with CMR indicates that a combination of ≥17.2 g BZ mass and the presence of BZ channels had the strongest association with subsequent VA in STEMI patients. CLINICALTRIALS.GOV: Unique identifier: NCT01435408 (DANAMI 3-iPOST and DANAMI 3-DEFER), NCT01960933 (DANAMI 3-PRIMULTI), and NCT01977755 (Danegaptide).

The Incidence and Impact of Permanent Right Ventricular Infarction on Left Ventricular Infarct Size in Patients With Inferior ST-Segment Elevation Myocardial Infarction.

Mounting evidence shows that right ventricle (RV) function carries independent prognostic influence in various disease states. This study aimed to investigate the incidence and impact of permanent RV infarction in patients with inferior ST-segment elevation myocardial infarction (STEMI) and culprit lesion in the right coronary artery (RCA). In this substudy of the DANAMI-3 (DANish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction) trial, cardiac magnetic resonance was performed in 291 patients at day 1 and follow-up 3 months after primary percutaneous coronary intervention of 674 patients with STEMI with the culprit lesion in the RCA. Final infarct was assessed using late gadolinium enhancement on cardiac magnetic resonance at 3 months. Patients with permanent RV infarction (20%) had lower ventricular function at follow-up; RV ejection fraction (EF) 47% ±6 versus 50% ± 5 (p <0.005) and left ventricular (LV) EF 56% ± 8 versus 60% ± 9 (p <0.006). Furthermore, patients with permanent RV infarction had a higher incidence of microvascular obstruction 39 (67%) versus 81 (39%) (p <0.001), larger final LV infarct size 16% ±8 versus 10% ± 8 (p <0.001) and larger LV area at risk 33% ± 10 versus 29% ± 9 (p <0.001). Permanent RV infarction was an independent predictor of final LV infarct size (p <0.001) but was not associated with LVEF (ß = -0.0; p = 0.13) in multivariable analyses. In conclusion, permanent RV infarction was seen in 20% of patients with inferior STEMI and culprit lesion in RCA and independently predicted final LV infarct size. However, permanent RV infarction did not predict overall LV function. LGE was used to detect infarct location and quantify infarct size.17 LGE in RV free wall on follow-up CMR was considered as permanent infarction. LGE images were obtained 10 minutes after intravenous injection of 0.1-mmol/kg body weight of gadolinium-based contrast (Gadovist; Bayer Schering, Berlin, Germany) using an electrocardiogram (ECG)-triggered inversion-recovery sequence. The inversion time was adjusted to null the signal from the normal myocardium. Short-axis images were acquired from the atrioventricular plane to the apex with adjacent 8-mm slices. The remaining protocol has been described previously.16.