Optimal lesion preparation before implantation of a Magmaris bioresorbable scaffold in patients with coronary artery stenosis: Rationale, design and methodology of the OPTIMIS study.

Introduction: Percutaneous coronary intervention with implantation of a bioresorbable scaffold (BRS) provide the vessel support for a limited period allowing the vessel to restore normal vasomotion after degradation of the BRS, opposed to treatment with drug-eluting stents where the metal persist in the vessel wall. Late lumen loss and reduction in lumen area after implantation have been reported. The purpose of this study was to investigate whether intense pre-dilatation before BRS implantation resulted in less reduction of minimal lumen area at 6- and 12-month follow-up after implantation of a Magmaris BRS (MgBRS). Coronary imaging with optical coherence tomography (OCT) and intravascular ultrasound (IVUS) was assessed to track changes in lumen and vessel dimensions. Methods: The prospective Optimal lesion PreparaTion before Implantation of the Magmaris bioresorbable scaffold In patients with coronary artery Stenosis (OPTIMIS) study randomly assigned eighty-two patients with chronic coronary syndrome to two pre-dilatation treatment strategies. Patients were randomized in a 1:1 ratio to pre-dilatation with either a non-compliant scoring balloon or a standard non-compliant balloon prior to implantation of a MgBRS. The treated segment was evaluated with OCT and IVUS at baseline, after 6 and 12 months to assess changes in lumen and vessel dimensions. The hypothesis was that more intense pre-dilatation with a non-compliant scoring balloon before MgBRS implantation can reduce the risk of late lumen reduction compared to standard pre-dilatation. The power calculation used expected MLA after 6 months (6.22 mm2 for the scoring balloon and 5.01 mm2 for the standard non-compliant balloon), power of 80 %, significance level of 0.05 and expected drop-out rate of 15 %, requiring 82 patients to be enrolled. Results: Eighty-two patients were included in the study. Enrollment was from December 2020 to September 2023. Conclusion: The hypothesis was that more intense pre-dilatation with a non-compliant scoring balloon before MgBRS implantation can reduce the risk of late lumen reduction compared to standard pre-dilatation.

The Influence of Microcirculatory Dysfunction on the Resting Full Cycle Ratio Compared to Fractional Flow Reserve.

BACKGROUND: The relation between the resting full cycle ratio (RFR) and fractional flow reserve (FFR) is not fully understood. This study aims to investigate the influence of coronary microvascular dysfunction, assessed by the index of microvascular resistance (IMR), on RFR compared to FFR in patients undergoing functional assessment for coronary stenosis. MATERIALS AND METHODS: Two-hundred patients with borderline stenosis underwent functional assessment of RFR, FFR, coronary flow reserve (CFR) and IMR. Retriever operator curve analysis was performed to assess the diagnostic value of RFR in patients with (IMR ≥ 24) and (IMR < 24). RESULTS: Median RFR did not differ significantly in patients with IMR ≥ 24 compared to patients with IMR < 24: 0.89 (interquartile range (IQR) 0.84, 0.95) vs. 0.90 (IQR 0.84, 0.92), p = 0.29). FFR was significantly higher in patients with IMR ≥ 24 compared to patients with IMR < 24: median FFR 0.85 (IQR (0.76, 0.92)) vs. 0.82 (IQR 0.73, 0.86), p = 0.009, and median CFR was significantly lower 1.80 (IQR 1.40, 2.55) vs. 2.70 (IQR 1.80, 3.95), p < 0.001. The diagnostic value of RFR was high (Area under the curve (AUC) 0.89 95 % Confidence Interval: [0.85, 0.93]) and AUC did not differ between patients with IMR ≥ 24 compared to patients with IMR < 24: 0.89 vs. 0.90, p = 0.89. An overall optimal cut off of 0.88 was identified. The cut off did not differ significantly between patients with IMR ≥ 24 compared to patients with IMR < 24: 0.88 vs. 0.90, p = 0.397. CONCLUSION: In patients with coronary borderline stenosis, the coronary microvascular function did not influence on the cut off values or AUC of RFR compared to FFR.

Polymer-free biolimus-coated stents versus ultrathin-strut biodegradable polymer sirolimus-eluting stents: two-year outcomes of the randomised SORT OUT IX trial.

BACKGROUND: For patients with high bleeding risk, the BioFreedom stent is safer and more effective than a bare metal stent. However, at the one-year follow-up of the SORT OUT IX trial, the BioFreedom stent did not meet the criteria for non-inferiority for target lesion failure (TLF) when compared with the Orsiro stent and had a higher incidence of target lesion revascularisation (TLR). AIMS: The aim of the study was to compare the two-year outcomes following coronary implantation of the BioFreedom or the Orsiro stents in all-comer patients. METHODS: The Scandinavian Organization for Randomized Trials with Clinical Outcome (SORT OUT) IX trial is a prospective, multicentre, randomised clinical trial comparing the BioFreedom and the Orsiro stents. The primary endpoint, TLF, was a composite of cardiac death, myocardial infarction (MI; not related to other lesions) and TLR. RESULTS: A total of 1,572 patients were randomised to treatment with the BioFreedom stent and 1,579 patients with the Orsiro stent. At two-year follow-up, TLF was 7.8% in the BioFreedom and 6.3% in the Orsiro stent groups (rate ratio [RR] 1.23, 95% confidence interval [CI]: 0.94-1.61). Risks of cardiac death, MI and definite stent thrombosis did not differ significantly between the groups, whereas more patients in the BioFreedom group had TLR (5.1% vs 2.6%; RR 1.98, 95% CI: 1.26-2.89) attributable to a higher risk of TLR within the first year (3.5% vs 1.3%; RR 2.77, 95% CI: 1.66-4.62). CONCLUSIONS: At two years, there were no significant differences between the BioFreedom and Orsiro stents for TLF. TLR was significantly higher with the BioFreedom stent due to higher risk of TLR within the first year.

Optical Coherence Tomography- Versus Angiography-Guided Magnesium Bioresorbable Scaffold Implantation in NSTEMI Patients.

BACKGROUND: The purpose of a bioresorbable scaffold (BRS) is to provide radial support during coronary healing. In this study, coronary artery healing after optical coherence tomography (OCT)- versus angiography-guided magnesium BRS (MBRS) implantation in patients with non-ST-segment-elevation myocardial infarction (NSTEMI) is compared. METHODS: 75 patients were randomized 1:1 to OCT- or angiography-guided implantation of a MBRS with protocolled pre- and post-dilation. In the OCT-guided group, prespecified criteria indicating additional intervention were (1) scaffold under-expansion, (2) strut malapposition, (3) edge dissection, and (4) residual stenosis at distal or proximal reference segments. The primary endpoint was OCT-derived healing stage at 6 months. RESULTS: At 6 months, there was no difference in average healing stage between OCT- and angiography-guided intervention (4.6 [interquartile range (IQR): 4.5-4.7] versus 4.5 [IQR: 4.3-4.7]; p = 0.54). The MBRSs were completely resolved in 77.0% [IQR: 68.5-85.5] versus 76.5% [IQR: 67.9-85.5]; (p = 0.97). Minimal lumen area (MLA) was reduced at 6 months in both the OCT- (32.3%; p < 0.01) and the angiography-guided group (21.3%; p < 0.01), however OCT-guided implantation was associated with a greater reduction of total lumen volume (-27.1 ± 32.5 mm3 versus -5.0 ± 32.9 mm3; p < 0.01) and MLA (-2.3 ± 1.6 mm2 vs. -1.4 ± 1.4 mm2; p = 0.02). CONCLUSIONS: In NSTEMI patients, OCT-guidance with protocolled pre- and post-dilation of MBRS implantation showed similar healing pattern at 6 months compared to angiography-guidance alone. CLINICAL TRIAL REGISTRATION: The Coronary Artery Healing Process after Optical Coherence Tomography Guided Percutaneous Coronary Intervention with Magmaris Bioresorbable Scaffold in Patients with Non-ST-Segment-Elevation Myocardial Infarction: (HONEST) trial is registered with ClinicalTrials.gov, NCT03016624.

Coronary Artery Healing Process after Bioresorbable Scaffold in Patients with Non-ST-Segment Elevation Myocardial Infarction: Rationale, Design, and Methodology of the HONEST Study.

BACKGROUND: Bioresorbable scaffolds (BRSs) is a relatively new approach in treating coronary artery stenosis. The initial results of the first commercially available scaffolds consisting of a backbone of poly-L-lactide raised safety concerns related to delayed resorption and healing. The magnesium alloy-based scaffold degrades via bio-corrosion within months, whereas it often takes several years for polymer scaffolds to degrade. The aim of the study was to assess the healing stage by optical coherence tomography (OCT) after 6 months in patients with non-ST-segment elevation myocardial infarct (NSTEMI) randomized to OCT or angiography-guided percutaneous coronary intervention with implantation of a magnesium sirolimus-eluting Magmaris scaffold (Magmaris; Biotronik, Bülach, Switzerland). METHODS: We analyzed the healing process by comparing OCT at baseline and after 6 months. Five stages of healing were defined with stage 1 being the least healed and stage 5 demonstrating complete resorption and healing with no visible scaffold/remnant. The primary end point is a calculated healing score that is based on 5 subtypes of healing stage: (1) malapposed, (2) uncovered with no detection of smooth surface tissue on top of struts or remnants, (3) covered protruding, (4) covered embedded, and (5) complete healing with a smooth neointimal surface and no sign of struts or visible remnants assessed by OCT 6 months after the index procedure. RESULTS: The impact of OCT-guided compared to angiography-guided scaffold implantation will be illuminated. CONCLUSION: The present study will provide new information on midterm healing properties of the magnesium BRS in patients with NSTEMI.

Randomized Comparison of the Polymer-Free Biolimus-Coated BioFreedom Stent With the Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Orsiro Stent in an All-Comers Population Treated With Percutaneous Coronary Intervention: The SORT OUT IX Trial.

BACKGROUND: In patients with increased bleeding risk, the biolimus A9-coated BioFreedom stent, a stainless steel drug-coated stent free from polymer, has shown superiority compared with a bare-metal stent. The aim of this study was to investigate whether the BioFreedom stent is noninferior to a modern ultrathin strut biodegradable polymer cobalt-chromium sirolimus-eluting Orsiro stent in an all-comers patient population treated with percutaneous coronary intervention. METHODS: The SORT OUT IX trial (Scandinavian Organization for Randomized Trials With Clinical Outcome IX), was a large-scale, registry-based, randomized, multicenter, single-blind, 2-arm, noninferiority trial. The primary end point, major adverse cardiovascular events, was defined as the composite of cardiac death, myocardial infarction not related to any segment other than the target lesion, or target lesion revascularization within 1 year, analyzed by intention-to-treat. The trial was powered to assess noninferiority for major adverse cardiovascular events of the BioFreedom stent compared with the Orsiro stent with a predetermined noninferiority margin of 0.021. RESULTS: Between December 14, 2015 and April 21, 2017, 3151 patients were assigned to treatment with the BioFreedom stent (1572 patients, 1966 lesions) or to the Orsiro stent (1579 patients, 1985 lesions). Five patients were lost to follow-up because of emigration (99.9% follow-up rate). Mean age was 66.3±10.9, diabetes mellitus was seen in 19.3% of patients, and 53% of the patients had acute coronary syndromes. At 1 year, intention-to-treat analysis showed that 79 (5.0%) patients, who were assigned the BioFreedom stent, and 59 (3.7%), who were assigned the Orsiro stent, met the primary end point (absolute risk difference 1.29% [upper limit of one-sided 95% CI 2.50%]; Pnoninferiority=0.14). Significantly more patients in the BioFreedom stent group had target lesion revascularization than those in the Orsiro stent group (55 [3.5%] vs 20 [1.3%], rate ratio 2.77 [95% CI, 1.66-4.62]; P<0.0001). CONCLUSIONS: The biolimus A9-coated BioFreedom polymer-free stent did not meet criteria for noninferiority for major adverse cardiovascular events at 12 months when compared with the ultrathin strut biodegradable polymer sirolimus-eluting Orsiro stent in an all-comers population Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02623140.

Clinical outcomes three-year after revascularization with biodegradable polymer stents: ultrathin-strut sirolimus-eluting stent versus biolimus-eluting stent: from the Scandinavian organization for randomized trials with clinical outcome VII trial.

BACKGROUND: Drug-eluting stents with biodegradable polymers have been designed to improve safety and efficacy. However, drug-eluting stents with biodegradable polymers may not be a class effect, as stent strut thickness, polymer coating, and drug resorption differ between these groups of stents. Twelve months results of Scandinavian Organization for Randomized Trials With Clinical Outcome VII showed that ultrathin-strut sirolimus-eluting Orsiro stent was noninferior to the biolimus-eluting Nobori stent. The sirolimus-eluting Orsiro stent was associated with a reduced risk of definite stent thrombosis. METHODS: The Scandinavian Organization for Randomized Trials With Clinical Outcome VII trial is a prospective multicenter randomized clinical trial comparing sirolimus-eluting Orsiro stent and biolimus-eluting Nobori stent in all-comers patients. The endpoint target lesion failure was a composite of cardiac death, myocardial infarction (not related to other than index lesion) and target lesion revascularization. RESULTS: A total of 1261 patients were randomized to treatment with sirolimus-eluting Orsiro stent and 1264 patients to biolimus-eluting Nobori stent and followed for 3 years. At 3-year the target lesion failure was comparable for sirolimus-eluting Orsiro stent (9.0%) and the biolimus-eluting Nobori stent (9.1%), (rate ratio, 0.99; 95% confidence interval, 0.77-1.29). Cardiac death (sirolimus-eluting Orsiro stent 3.0% vs. biolimus-eluting Nobori stent 2.6% [rate ratio, 1.16; 95% confidence interval, 0.73-1.86]), target lesion revascularization (sirolimus-eluting Orsiro stent 5.2% vs. biolimus-eluting Nobori stent 5.9% [rate ratio, 0.90; 95% confidence interval, 0.64-1.25]), myocardial infarction (sirolimus-eluting Orsiro stent 4.7% vs. biolimus-eluting Nobori stent 4.5% [rate ratio, 1.04; 95% confidence interval, 0.72-1.50]), and definite stent thrombosis (sirolimus-eluting Orsiro stent 1.0% vs. biolimus-eluting Nobori stent 1.7% [rate ratio, 0.59; 95% confidence interval, 0.30-1.18]) did not differ significantly between the two groups. CONCLUSION: At 3-year follow-up, target lesion failure did not differ among ultrathin-strut sirolimus-eluting Orsiro stent and biolimus-eluting Nobori stent with biodegradable polymers.

Influence of Ezetimibe on Plaque Morphology in Patients with ST Elevation Myocardial Infarction Assessed by Optical Coherence Tomography: An OCTIVUS Sub-Study.

AIMS: The aim of the trial was to examine the influence of ezetimibe on plaque morphology in patients with ST-segment Elevation Myocardial Infarction (STEMI) with respect to fibrous cap thickness (FCT) and arcs of lipid plaque, calcific plaque, and macrophages using Optical Coherence Tomography (OCT). METHODS AND RESULTS: In 87 statin naïve patients with STEMI treated with primary percutaneous intervention, a non-culprit study plaque in a non-infarct related coronary artery was assessed with OCT at baseline and after 12 months. Patients were treated with atorvastatin 80 mg and randomized (1:1) to ezetimibe 10 mg (n = 43) or placebo (n = 44). An increase in median FCT (ezetimibe 200 (140-260) µm to 240 (190-305) µm (p = 0.002) vs. placebo 205 (135-260) µm to 230 (180-270) µm (p < 0.001), between groups p = ns), a reduction in lipid arc (ezetimibe 1728.5 (1022.5-3904.7)° to 1164.5 (736.6-2580.1)° (p = 0.001) vs. placebo 1671.6 (978.3-2868.7)° to 1373.7 (791.2-2267.3)° (p = 0.019), between groups p = ns), and macrophage arc (ezetimibe 1730.3 (965.7-2984.4)° to 1324.8 (819.0-2819.7)° (p < 0.05) vs. placebo 1570.5 (794.7-3016.8)° to 1418.9 (584.1-2501.1)° (p < 0.01), between groups p = ns) were observed. CONCLUSION: Aggressive LDL-lowering resulted in changes in OCT assessed plaque composition by increased FCT thickness and a reduction in lipid content and macrophage infiltration. Addition of ezetimibe 10 mg to atorvastatin 80 mg resulted in further LDL reduction, but no additional change in plaque composition was found.

Gender but not diabetes, hypertension or smoking affects infarct evolution in ST-elevation myocardial infarction patients - data from the CHILL-MI, MITOCARE and SOCCER trials.

BACKGROUND: Infarct evolution rate and response to acute reperfusion therapy may differ between patients, which is important to consider for accurate management and treatment of patients with ST-elevation myocardial infarction (STEMI). The aim of this study was therefore to investigate the association of infarct size and myocardial salvage with gender, smoking status, presence of diabetes or history of hypertension in a cohort of STEMI-patients. METHODS: Patients (n = 301) with first-time STEMI from the three recent multi-center trials (CHILL-MI, MITOCARE and SOCCER) underwent cardiac magnetic resonance (CMR) imaging to determine myocardium at risk (MaR) and infarct size (IS). Myocardial salvage index (MSI) was calculated as MSI = 1-IS/MaR. Pain to balloon time, culprit vessel, trial treatments, age, TIMI grade flow and collateral flow by Rentrop grading were included as explanatory variables in the statistical model. RESULTS: Women (n = 66) had significantly smaller MaR (mean difference: 5.0 ± 1.5% of left ventricle (LV), p < 0.01), smaller IS (mean difference: 5.1 ± 1.4% of LV, p = 0.03), and larger MSI (mean difference: 9.6 ± 2.8% of LV, p < 0.01) compared to men (n = 238). These differences remained significant when adjusting for other explanatory variables. There were no significant effects on MaR, IS or MSI for diabetes, hypertension or smoking. CONCLUSIONS: Female gender is associated with higher myocardial salvage and smaller infarct size suggesting a pathophysiological difference in infarct evolution between men and women.

Comparison of the polymer-free biolimus-coated BioFreedom stent with the thin-strut biodegradable polymer sirolimus-eluting Orsiro stent in an all-comers population treated with percutaneous coronary intervention: Rationale and design of the randomized SORT OUT IX trial.

BACKGROUND: In patients with increased bleeding risk during dual antiplatelet therapy, the biolimus A9-coated BioFreedom, a stainless steel drug-coated stent devoid of polymer, has shown superiority compared to a bare-metal stent. The aim of this study was to investigate whether the polymer-free biolimus A9-coated BioFreedom is noninferior to a modern thin-strut biodegradable polymer cobalt-chromium sirolimus-eluting Orsiro stent in an all-comers patient population treated with percutaneous coronary intervention. METHODS: The multicenter SORT OUT IX trial (NCT02623140) randomly assigned all-comers patients to treatment with the BioFreedom drug-coated stent or the biodegradable polymer Orsiro stent in 4 Danish University Hospitals. The primary end point target lesion failure is a composite of cardiac death, myocardial infarction (not related to other than index lesion), or target lesion revascularization within 12 months. Clinically driven event detection based on Danish registries will be used and continue through 5 years. Assuming an event rate of 4.2% in each stent group, 1,563 patients in each treatment arm will provide 90% power to detect noninferiority of the drug-coated BioFreedom stent with a noninferiority margin of 2.1%. RESULTS: A total of 3,150 patients have been randomized and enrolled in the study. CONCLUSIONS: The SORT OUT IX trial will determine whether the drug-coated BioFreedom stent is noninferior to a modern biodegradable polymer Orsiro stent.

Overlap between angina without obstructive coronary artery disease and left ventricular diastolic dysfunction with preserved ejection fraction.

BACKGROUND: A link between angina with no obstructive coronary artery disease (CAD) and heart failure with preserved left ventricular ejection fraction has been proposed, but evidence in support of this is lacking. In a cross-sectional study, we investigated whether left ventricular diastolic function in women with angina pectoris and no obstructive CAD differed from a reference population. METHODS: We included 956 women with angina and <50% coronary artery stenosis at invasive coronary angiography. Women with cardiovascular risk factors, but no history of chest pain or cardiac disease served as controls (n = 214). Left ventricular diastolic function was assessed by transthoracic echocardiography. RESULTS: The women with angina were slightly older, had higher body mass index, higher heart rate, and more had diabetes compared with controls while systolic blood pressure was lower. In age-adjusted analyses, angina patients had significantly lower E/A (Estimated difference -0.13, 95% CI: -0.17; -0.08), higher left ventricular mass index (5.73 g/m2, 95% CI: 3.71; 7.75), left atrial volume index (2.34 ml/m2, 95% CI: 1.23; 3.45) and E/e' (0.68, 95% CI: 0.30; 1.05) and a larger proportion had higher estimated left ventricular filling pressure (17% versus 6%, p = 0.001). No between group differences were seen for e' or deceleration time. After adjustment for known cardiovascular risk factors, between group differences for echocardiographic parameters remained statistically significant. CONCLUSIONS: Patients with angina and no obstructive CAD had a more impaired left ventricular diastolic function compared with an asymptomatic reference population. This suggests some common pathophysiological pathway between the two syndromes.

Coronary microvascular dysfunction is associated with cardiac time intervals in women with angina and no obstructive coronary artery disease: An iPOWER substudy.

BACKGROUND: Coronary microvascular dysfunction (CMD) may cause angina in the absence of obstructive coronary artery disease (CAD) and increases the risk of future adverse cardiovascular events. Transthoracic Doppler echocardiography (TTDE) with pharmacological stress can assess coronary flow velocity reserve (CFVR), a measure of coronary microvascular function. However, simpler methods would be preferable for diagnosing CMD. Therefore, we examined the relationship between CFVR and cardiac time intervals measured by TTDE in a cohort of women with angina and no obstructive CAD. METHODS: In a prospective cohort study, we included 389 women with angina, left ventricular ejection fraction > 45%, and no obstructive CAD. CMD was defined as CFVR < 2.0. The study population was divided into three groups according to cutoff values of CFVR < 2, 2 ≤ CFVR ≤ 2.5, and CFVR > 2.5. Isovolumic contraction time (IVCT), ejection time (ET), and isovolumic relaxation time (IVRT) were measured by tissue Doppler M-mode, and the myocardial performance index (MPI = (IVCT + IVRT)/ET) was calculated. RESULTS: Coronary microvascular dysfunction was associated with increasing age, hypertension, higher resting heart rate, and lower diastolic blood pressure. Moreover, CMD was associated with higher E/e' ratio (P = 0.002) and longer IVCT (P < 0.001), higher MPI (P < 0.001) and shorter ET (P = 0.002), but not with IVRT or conventional measures of left ventricular geometry, mass, and function. In multivariable analysis, longer IVCT (P < 0.001) and higher MPI (P = 0.002) remained associated with CMD. CONCLUSION: In women with angina and no obstructive CAD, CMD is associated with longer IVCT and higher MPI indicating a link between CMD and subtle alternations of systolic and combined measures of cardiac time intervals.

Randomized clinical comparison of the dual-therapy CD34 antibody-covered sirolimus-eluting Combo stent with the sirolimus-eluting Orsiro stent in patients treated with percutaneous coronary intervention: Rationale and study design of the Scandinavian Organization for Randomized Trials with Clinical Outcome (SORT OUT) X trial.

BACKGROUND: The Combo stent (OrbusNeich, Hoevelaken, the Netherlands) combining an abluminal, bioabsorbable polymer eluting sirolimus with a luminal CD34+ antibody to capture endothelial progenitor cells has been developed to further improve safety and efficacy of coronary interventions. We have designed a large-scale registry-based randomized clinical trial to compare the Combo stent to the Orsiro stent (Biotronik, Bülach, Switzerland) in patients undergoing percutaneous coronary intervention. METHODS: The SORT OUT X study will randomly assign 3,140 patients to treatment with Combo or Orsiro stents at 3 sites in Western Denmark. Patients are eligible if they are ≥18 years old, have chronic stable coronary artery disease or acute coronary syndromes, and have ≥1 coronary lesion with >50% diameter stenosis requiring treatment with a drug-eluting stent. The primary end point target lesion failure is a composite of cardiac death, myocardial infarction (not related to other than index lesion), or target lesion revascularization within 12 months. Clinically driven event detection will be derived from validated Danish registries. An event rate of 4.2% is assumed in each stent group. With a sample size of 1,570 patients in each treatment arm, a 2-group large-sample normal approximation test of proportions with a 1-sided 5% significance level will have 90% power to detect noninferiority of the Combo stent compared with the Orsiro stent with a predetermined noninferiority margin of 2.1%. CONCLUSION: The SORT OUT X trial will determine whether the dual-therapy Combo stent is noninferior to the Orsiro stent with respect to clinically driven events (ClinicalTrials.govNCT03216733).

Longitudinal left ventricular function is globally depressed within a week of STEMI.

Sixty percent of stroke volume (SV) is generated by atrioventricular plane displacement (AVPD) in a healthy left ventricle (LV). The aims were to determine the effect of ST-elevation myocardial infarction (STEMI) on AVPD and contribution of AVPD to SV and to study the relationship between AVPD and infarct size (IS) and location. Patients from CHILL-MI and MITOCARE studies with cardiovascular magnetic resonance within a week of STEMI (n = 177, 59 ± 11 years) and healthy controls (n = 20, 62 ± 11 years) were included. Left ventricular volumes were quantified in short-axis images. AVPD was measured in six locations in long-axis images. Longitudinal contribution to SV was calculated as AVPD multiplied by the short-axis epicardial area. Patients (IS 17 ± 10% of LV) had decreased ejection fraction (48 ± 8%) compared to controls (60 ± 5%, P<0·001). Global AVPD was decreased in patients (11 ± 2 mm versus 15 ± 2 mm in controls, P<0·001) and this held true for both infarcted and remote segments. AVPD contribution to SV was lower in patients (58 ± 9%) than in controls (64 ± 8%) (P<0·001). There was a weak negative correlation between IS and AVPD (r2 =0·06) but no differences in global AVPD linked to infarct location. Decrease in global and regional AVPD occur even in remote myocardium within 1 week of STEMI. Global AVPD decrease is independent of MI location, and MI size has only minor effect. Longitudinal pumping is slightly lower compared to controls but remains to be the main component to SV even after STEMI. These results highlight the difficulty in determining infarct location and size from longitudinal measures of LV function.

Electrocardiographic scores of severity and acuteness of myocardial ischemia predict myocardial salvage in patients with anterior ST-segment elevation myocardial infarction.

BACKGROUND: Terminal "QRS distortion" on the electrocardiogram (ECG) (based on Sclarovsky-Birnbaum's Grades of Ischemia Score) is a sign of severe ischemia, associated with adverse cardiovascular outcome in ST-segment elevation myocardial infarction (STEMI). In addition, ECG indices of the acuteness of ischemia (based on Anderson-Wilkins Acuteness Score) indicate myocardial salvage potential. We assessed whether severe ischemia with or without acute ischemia is predictive of infarct size (IS), myocardial salvage index (MSI) and left ventricular ejection fraction (LVEF) in anterior versus inferior infarct locations. METHODS: In STEMI patients, the severity and acuteness scores were obtained from the admission ECG. Based on the ECG patients were assigned with severe or non-severe ischemia and acute or non-acute ischemia. Cardiac magnetic resonance (CMR) was performed 2-6days after primary percutaneous coronary intervention (pPCI). LVEF was measured by echocardiography 30days after pPCI. RESULTS: ECG analysis of 85 patients with available CMR resulted in 20 (23%) cases with severe and non-acute ischemia, 43 (51%) with non-severe and non-acute ischemia, 17 (20%) with non-severe and acute ischemia, and 5 (6%) patients with severe and acute ischemia. In patients with anterior STEMI (n=35), ECG measures of severity and acuteness of ischemia identified significant and stepwise differences in myocardial damage and function. Patients with severe and non-acute ischemia had the largest IS, smallest MSI and lowest LVEF. In contrast, no difference was observed in patients with inferior STEMI (n=50). CONCLUSIONS: The applicability of ECG indices of severity and acuteness of myocardial ischemia to estimate myocardial damage and salvage potential in STEMI patients treated with pPCI, is confined to anterior myocardial infarction.

Uncovered Culprit Plaque Ruptures in Patients With ST-Segment Elevation Myocardial Infarction Assessed by Optical Coherence Tomography and Intravascular Ultrasound With iMap.

OBJECTIVES: This study assessed the incidence and course of healing of uncovered plaque ruptures (PR) following primary percutaneous coronary intervention. BACKGROUND: The infarct-related occlusion is frequently located at the lesion site with maximum thrombus burden, whereas the culprit PR may be situated more proximally or distally. METHODS: Uncovered PR in segments adjacent to the stent were identified by optical coherence tomography and intravascular ultrasound using iMap (Boston Scientific, Marlborough, Massachusetts) within 48 h and after 12 months. The percentages of necrotic core, fibrotic tissue, lipid tissue, and calcific tissue were determined. RESULTS: Eleven uncovered PR were found in 10 of 77 patients (13.0%). Eight of these ruptures (10.4%) were identified as culprit and were located proximal to the stent. Two patients were treated before follow-up due to recurrent symptoms. After 12 months, 3 PR had healed incompletely without causing symptoms. The lumen area at the PR site was reduced (7.5 mm2 [interquartile range (IQR): 4.8 to 9.3 mm2] to 3.6 mm2 [IQR: 2.8 to 8.0 mm2]; p = 0.012). Proximal segments with uncovered PR had greater plaque volumes (62.1 mm3 [IQR: 50.2 to 83.6 mm3] vs. 38.7 mm3 [IQR: 29.6 to 47.6 mm3], respectively; p < 0.001), vessel volumes (110.7 mm3 [IQR: 92.3 to 128.1 mm3] vs. 76.0 mm3 [IQR: 63.8 to 100.3 mm3], respectively; p < 0.001), and greater percentages of necrotic core (34.0% [IQR: 29.0% to 44.5%] vs. 20.5% (IQR: 10.0% to 29.0%]; p < 0.001). Conversely, percentages of fibrotic tissue were lower (44.0% [IQR: 32.0% to 47.0%] vs. 56.0% [IQR: 46.0% to 66.0%]; p = 0.001), whereas no differences were found for lipid tissue and calcific tissue. CONCLUSIONS: Uncovered culprit ruptures detected by optical coherence tomography were common following primary percutaneous coronary intervention and were found to be associated with significant lumen reduction during the healing process.

Ventricular repolarization alterations in women with angina pectoris and suspected coronary microvascular dysfunction.

OBJECTIVES: CMD could be the explanation of angina pectoris with no obstructive CAD and may cause ventricular repolarization changes. We compared T-wave morphology and QTc interval in women with angina pectoris with a control group as well as the associations with CMD. METHODS: Women with angina pectoris and no obstructive coronary artery disease (n=138) and age-matched controls were compared in regard to QTc interval and morphology combination score (MCS) based on T-wave asymmetry, flatness and presence of T-wave notch. CMD was assessed as a coronary flow velocity reserve (CFVR) by transthoracic echocardiography. RESULTS: Women with angina pectoris had significantly longer QTc intervals (429±20ms) and increased MCS (IQR) (0.73 [0.64-0.80]) compared with the controls (419±20ms) and (0.63 [(0.53-0.73]), respectively (both p<0.001). CFVR was associated with longer QTc interval (p=0.02), but the association was attenuated after multivariable adjustment (p=0.08). CONCLUSION: This study suggests that women with angina pectoris have alterations in T-wave morphology as well as longer QTc interval compared with a reference population. CMD might be an explanation.

Sex-Related Differences in Vasomotor Function in Patients With Angina and Unobstructed Coronary Arteries.

BACKGROUND: Coronary vasomotor dysfunction is an important mechanism for angina in patients with unobstructed coronary arteries. OBJECTIVES: The purpose of this study was to determine sex differences in the prevalence and clinical presentation of vasomotor dysfunction in a European population and to examine sex differences in the dose of acetylcholine leading to a positive acetylcholine provocation test (ACH test). METHODS: Between 2007 and 2014, we included 1,379 consecutive patients with stable angina, unobstructed coronaries and ACH test performed for epicardial vasospasm or coronary microvascular dysfunction (CMD) due to microvascular spasm. The predictive value of sex, risk factors, symptoms, and noninvasive test results was analyzed by means of logistic regression. RESULTS: The mean patient age was 62 years, and 42% were male. There were 813 patients (59%) with a pathological ACH test, 33% for CMD and 26% for epicardial vasospasm. A pathological test was more common in females (70% vs. 43%; p < 0.001). In a multivariable logistic regression model the sex difference was statistically significant with a female-male odds ratio for CMD and epicardial vasospasm of 4.2 (95% confidence interval: 3.1 to 5.5; p < 0.001) and 2.3 (95% confidence interval: 1.7 to 3.1; p < 0.001), respectively. Effort-related symptoms, but neither risk factors nor noninvasive stress tests, contributed to predicting a pathological test. Female patients were more sensitive to acetylcholine with vasomotor dysfunction occurring at lower ACH doses compared with male patients. CONCLUSIONS: Vasomotor dysfunction is frequent in patients with angina and unobstructed coronaries in a European population. Female patients have a higher prevalence of vasomotor dysfunction (especially CMD) compared with male patients. A pathological ACH test was observed at lower ACH doses in women compared with men.