Safety and efficacy of transcatheter mitral valve repair in patients with COPD; results from real-world cohort.

OBJECTIVE: To evaluate the safety and efficacy of transcatheter mitral valve repair (TMVR) in patients with chronic obstructive pulmonary disease (COPD). BACKGROUND: Heart failure and COPD share many clinical features and commonly coexist. Data about the safety and efficacy of TMVR in patients with COPD is not conclusive. METHODS: Three hundred and forty consecutive patients undergoing TMVR were retrospectively included. COPD diagnosis was based on pulmonary function tests (PFTs). Intra-hospital, 30-day- and 1-year outcomes were compared between both groups. RESULTS: Eighty-two patients had COPD (24%). There was no difference in intra-hospital mortality between patients with and without COPD (both 5%, p = 0.95). Among patients who had a successful procedure and survived to discharge there was a trend toward more rehospitalization due to decompensated heart failure at 30-day follow-up in patients with COPD (12.9% vs. 6.8%, p = 0.08) with no difference in mortality. At median follow-up of 1 year, New York heart association (NYHA) category was comparable among both groups and there was no significant difference in rehospitalization (COPD: 29.9% vs. non-COPD: 34%, p = 0.5). There was a trend toward increased 1-year mortality in COPD patients (31.2% vs. 20.6%, p = 0.06). However, a composite endpoint of rehospitalization or death at 1 year did not differ between both groups (48% vs. 42.5%, p = 0.4). Regression analysis showed no correlation between COPD severity and worse TMVR outcomes. CONCLUSIONS: COPD is highly prevalent among patients undergoing TMVR. However, TMVR seems to be safe and effective in COPD patients. COPD severity and PFT impairment alone should not be considered as a contraindication for TMVR.

Thin-cap fibroatheroma predicts clinical events in diabetic patients with normal fractional flow reserve: the COMBINE OCT-FFR trial.

AIMS: The aim of this study was to understand the impact of optical coherence tomography (OCT)-detected thin-cap fibroatheroma (TCFA) on clinical outcomes of diabetes mellitus (DM) patients with fractional flow reserve (FFR)-negative lesions. METHODS AND RESULTS: COMBINE OCT-FFR study was a prospective, double-blind, international, natural history study. After FFR assessment, and revascularization of FFR-positive lesions, patients with ≥1 FFR-negative lesions (target lesions) were classified in two groups based on the presence or absence of ≥1 TCFA lesion. The primary endpoint compared FFR-negative TCFA-positive patients with FFR-negative TCFA-negative patients for a composite of cardiac mortality, target vessel myocardial infarction, clinically driven target lesion revascularization or unstable angina requiring hospitalization at 18 months. Among 550 patients enrolled, 390 (81%) patients had ≥1 FFR-negative lesions. Among FFR-negative patients, 98 (25%) were TCFA positive and 292 (75%) were TCFA negative. The incidence of the primary endpoint was 13.3% and 3.1% in TCFA-positive vs. TCFA-negative groups, respectively (hazard ratio 4.65; 95% confidence interval, 1.99-10.89; P < 0.001). The Cox regression multivariable analysis identified TCFA as the strongest predictor of major adverse clinical events (MACE) (hazard ratio 5.12; 95% confidence interval 2.12-12.34; P < 0.001). CONCLUSIONS: Among DM patients with ≥1 FFR-negative lesions, TCFA-positive patients represented 25% of this population and were associated with a five-fold higher rate of MACE despite the absence of ischaemia. This discrepancy between the impact of vulnerable plaque and ischaemia on future adverse events may represent a paradigm shift for coronary artery disease risk stratification in DM patients.

Prognostic irrelevance of plaque vulnerability following plaque sealing in high-risk patients with type 2 diabetes: an optical coherence tomography study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with an increased cardiovascular risk related at least in part to a more vulnerable plaque phenotype. However, patients with T2DM exhibit also an increased risk following percutaneous coronary intervention (PCI). It is unknown if plaque vulnerability of a treated lesion influences cardiovascular outcomes in patients with T2DM. In this study, we aimed to assess the association of plaque morphology as determined by optical coherence tomography (OCT) with cardiovascular outcome following PCI in high-risk patients with T2DM. METHODS: 81 patients with T2DM and OCT-guided PCI were recruited. Pre-interventional OCT and systematic follow-up of median 66.0 (IQR = 8.0) months were performed. RESULTS: During follow-up, 24 patients (29.6%) died. The clinical parameters age (HR 1.16 per year, 95% CI 1.07-1.26, p < 0.001), diabetic polyneuropathy (HR 3.58, 95% CI 1.44-8.93, p = 0.006) and insulin therapy (HR 3.25, 95% CI 1.21-8.70, p = 0.019) predicted mortality in T2DM patients independently. Among OCT parameters only calcium-volume-index (HR 1.71 per 1000°*mm, 95% CI 1.21-2.41, p = 0.002) and lesion length (HR 1.93 per 10 mm, 95% CI 1.02-3.67, p = 0.044) as parameters describing atherosclerosis extent were significant independent predictors of mortality. However, classical features of plaque vulnerability, such as thickness of the fibrous cap, the extent of the necrotic lipid core and the presence of macrophages had no significant predictive value (all p = ns). CONCLUSION: Clinical parameters including those describing diabetes severity as well as OCT-parameters characterizing atherosclerotic extent but not classical features of plaque vulnerability predict mortality in T2DM patients following PCI. These data suggest that PCI may provide effective plaque sealing resulting in limited importance of local target lesion vulnerability for future cardiovascular events in high-risk patients with T2DM.

Intrinsic calcification angle: a novel feature of the vulnerable coronary plaque in patients with type 2 diabetes: an optical coherence tomography study.

BACKGROUND: Coronary calcification is associated with high risk for cardiovascular events. However, its impact on plaque vulnerability is incompletely understood. In the present study we defined the intrinsic calcification angle (ICA) as the angle externally projected by a vascular calcification and analyzed its role as novel feature of coronary plaque vulnerability in patients with type 2 diabetes. METHODS: Optical coherence tomography was used to determine ICA in 219 calcifications from 56 patients with stable coronary artery disease (CAD) and 143 calcifications from 36 patients with acute coronary syndrome (ACS). We then used finite elements analysis to gain mechanistic insight into the effects of ICA. RESULTS: Minimal (139.8 ± 32.8° vs. 165.6 ± 21.6°, p < 0.001) and mean ICA (164.1 ± 14.3° vs. 176.0 ± 8.4°, p < 0.001) were lower in ACS vs. stable CAD patients. Mean ICA predicted ACS with very good diagnostic efficiency (AUC = 0.840, 95% CI 0.797-0.882, p < 0.001, optimal cut-off 175.9°); younger age (OR 0.95 per year, 95% CI 0.92-0.98, p = 0.002), male sex (OR 2.18, 95% CI 1.41-3.38, p < 0.001), lower HDL-cholesterol (OR 0.82 per 10 mg/dl, 95% CI 0.68-0.98, p = 0.029) and ACS (OR 14.71, 95% CI 8.47-25.64, p < 0.001) were determinants of ICA < 175.9°. A lower ICA predicted ACS (OR for 10°-variation 0.25, 95% CI 0.13-0.52, p < 0.001) independently from fibrous cap thickness, presence of macrophages or extension of lipid core. In finite elements analysis we confirmed that lower ICA causes increased stress on a lesion's fibrous cap; this effect was potentiated in more superficial calcifications and adds to the destabilizing role of smaller calcifications. CONCLUSION: Our clinical and mechanistic data for the first time identify ICA as a novel feature of coronary plaque vulnerability.

Comparison of an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent for the treatment of coronary artery stenosis (ABSORB II): a 3 year, randomised, controlled, single-blind, multicentre clinical trial.

BACKGROUND: No medium-term data are available on the random comparison between everolimus-eluting bioresorbable vascular scaffolds and everolimus-eluting metallic stents. The study aims to demonstrate two mechanistic properties of the bioresorbable scaffold: increase in luminal dimensions as a result of recovered vasomotion of the scaffolded vessel. METHODS: The ABSORB II trial is a prospective, randomised, active-controlled, single-blind, parallel two-group, multicentre clinical trial. We enrolled eligible patients aged 18-85 years with evidence of myocardial ischaemia and one or two de-novo native lesions in different epicardial vessels. We randomly assigned patients (2:1) to receive treatment with an everolimus-eluting bioresorbable scaffold (Absorb; Abbott Vascular, Santa Clara, CA, USA) or treatment with an everolimus-eluting metallic stent (Xience; Abbott Vascular, Santa Clara, CA, USA). Randomisation was stratified by diabetes status and number of planned target lesions. At 3 year follow-up, the primary endpoint was superiority of the Absorb bioresorbable scaffold versus the Xience metallic stent in angiographic vasomotor reactivity after administration of intracoronary nitrate. The co-primary endpoint is the non-inferiority of angiographic late luminal loss. For the endpoint of vasomotion, the comparison was tested using a two-sided t test. For the endpoint of late luminal loss, non-inferiority was tested using a one-sided asymptotic test, against a non-inferiority margin of 0·14 mm. The trial is registered at ClinicalTrials.gov, number NCT01425281. FINDINGS: Between Nov 28, 2011, and June 4, 2013, we enrolled 501 patients and randomly assigned them to the Absorb group (335 patients, 364 lesions) or the Xience group (166 patients, 182 lesions). The vasomotor reactivity at 3 years was not statistically different (Absorb group 0·047 mm [SD 0·109] vs Xience group 0·056 mm [0·117]; psuperiority=0·49), whereas the late luminal loss was larger in the Absorb group than in the Xience group (0·37 mm [0·45] vs 0·25 mm [0·25]; pnon-inferiority=0·78). This difference in luminal dimension was confirmed by intravascular ultrasound assessment of the minimum lumen area (4·32 mm2 [SD 1·48] vs 5·38 mm2 [1·51]; p<0·0001). The secondary endpoints of patient-oriented composite endpoint, Seattle Angina Questionnaire score, and exercise testing were not statistically different in both groups. However, a device-oriented composite endpoint was significantly different between the Absorb group and the Xience group (10% vs 5%, hazard ratio 2·17 [95% CI 1·01-4·70]; log-rank test p=0·0425), mainly driven by target vessel myocardial infarction (6% vs 1%; p=0·0108), including peri-procedural myocardial infarction (4% vs 1%; p=0·16). INTERPRETATION: The trial did not meet its co-primary endpoints of superior vasomotor reactivity and non-inferior late luminal loss for the Absorb bioresorbable scaffold with respect to the metallic stent, which was found to have significantly lower late luminal loss than the Absorb scaffold. A higher rate of device-oriented composite endpoint due to target vessel myocardial infarction, including peri-procedural myocardial infarction, was observed in the Absorb group. The patient-oriented composite endpoint, anginal status, and exercise testing, were not statistically different between both devices at 3 years. Future studies should investigate the clinical impact of accurate intravascular imaging in sizing the device and in optimising the scaffold implantation. The benefit and need for prolonged dual antiplatelet therapy after bioresorbable scaffold implantation could also become a topic for future clinical research. FUNDING: Abbott Vascular.

Type 2 diabetes mellitus is associated with a lower fibrous cap thickness but has no impact on calcification morphology: an intracoronary optical coherence tomography study.

BACKGROUND: Patients with type 2 diabetes (T2DM) are at high risk for cardiovascular events, which usually arise from the rupture of a vulnerable coronary plaque. The minimal fibrous cap thickness (FCT) overlying a necrotic lipid core is an established predictor for plaque rupture. Recently, coronary calcification has emerged as a relevant feature of plaque vulnerability. However, the impact of T2DM on these morphological plaque parameters is largely unexplored. Therefore, this study aimed to compare differences of coronary plaque morphology in patients with and without T2DM with a particular focus on coronary calcification. METHODS: In 91 patients (T2DM = 56, non-T2DM = 35) with 105 coronary de novo lesions (T2DM = 56, non-T2DM = 49) plaque morphology and calcification were analyzed using optical coherence tomography (OCT) prior to coronary intervention. RESULTS: Patients with T2DM had a lower minimal FCT (80.4 ± 27.0 µm vs. 106.8 ± 27.8 µm, p < 0.001) and a higher percent area stenosis (77.9 ± 8.1% vs. 71.7 ± 11.2%, p = 0.001) compared to non-diabetic subjects. However, patients with and without T2DM had a similar total number of calcifications (4.0 ± 2.6 vs. 4.2 ± 3.1, p = ns) and no significant difference was detected in the number of micro- (0.34 ± 0.79 vs. 0.31 ± 0.71), spotty (2.11 ± 1.77 vs. 2.37 ± 1.89) or macro-calcifications (1.55 ± 1.13 vs. 1.53 ± 0.71, all p = ns). The mean calcium arc (82.3 ± 44.8° vs. 73.7 ± 31.6), the mean thickness of calcification (0.54 ± 0.13 mm vs. 0.51 ± 0.15 mm), the mean calcified area (0.99 ± 0.72 mm2 vs. 0.78 ± 0.49 mm2), the mean depth of calcification (172 ± 192 µm vs. 160 ± 76 µm) and the cap thickness overlying the calcification (50 ± 71 µm vs. 62 ± 61 µm) did not differ between the diabetic and non-diabetic groups (all p = ns). CONCLUSION: T2DM has an impact on the minimal FCT of the coronary target lesion, but not on localization, size, shape or extent of calcification. Thus, the minimal FCT overlying the necrotic lipid core but not calcification is likely to contribute to the increased plaque vulnerability observed in patients with T2DM.

Combined optical coherence tomography morphologic and fractional flow reserve hemodynamic assessment of non- culprit lesions to better predict adverse event outcomes in diabetes mellitus patients: COMBINE (OCT-FFR) prospective study. Rationale and design.

BACKGROUND: Fractional flow reserve (FFR) is a widely used tool for the identification of ischaemia-generating stenoses and to guide decisions on coronary revascularisation. However, the safety of FFR-based decisions in high-risk subsets, such as patients with Diabetes Mellitus (DM) or vulnerable stenoses presenting thin-cap fibro-atheroma (TCFA), is unknown. This study will examine the impact of optical coherence tomography (OCT) plaque morphological assessment and the identification of TCFA, in combination with FFR to better predict clinical outcomes in DM patients. METHODS: COMBINE (OCT-FFR) is a prospective, multi-centre study investigating the natural history of DM patients with ≥1 angiographically intermediate target lesion in three subgroups of patients; patients with FFR negative lesions without TCFA (group A) and patients with FFR negative lesions with TCFA (group B) as detected by OCT and to compare these two groups with each other, as well as to a third group with FFR-positive, PCI-treated intermediate lesions (group C). The study hypothesis is that DM patients with TCFA (group B) have a worse outcome than those without TCFA (group A) and also when compared to those patients with lesions FFR ≤0.80 who underwent complete revascularisation. The primary endpoint is the incidence of target lesion major adverse cardiac events (MACE); a composite of cardiac death, myocardial infarction or rehospitalisation for unstable/progressive angina in group B vs. group A. CONCLUSION: COMBINE (OCT-FFR) is the first prospective study to examine whether the addition of OCT plaque morphological evaluation to FFR haemodynamic assessment of intermediate lesions in DM patients will better predict MACE and possibly lead to new revascularisation strategies. Trial Registration Netherlands Trial Register: NTR5376.

Accuracy of intravascular ultrasound and optical coherence tomography in identifying functionally significant coronary stenosis according to vessel diameter: A meta-analysis of 2,581 patients and 2,807 lesions.

INTRODUCTION: Accuracy of intracoronary imaging to discriminate functionally significant coronary stenosis according to vessel diameter remains to be defined. METHODS: PubMed, Scopus, and Google Scholar were systematically searched for studies assessing diagnostic accuracy (area under the receiver operating characteristic curve [AUC], the primary end point) and sensitivity and specificity (the secondary end points) of minimal luminal area (MLA) or of minimal luminal diameter (MLD) derived from intravascular ultrasound (IVUS) or optical coherence tomography (OCT) to detect functionally significant stenosis as determined with fractional flow reserve (FFR). RESULTS: Fifteen studies were included, 2 with 110 patients analyzing only left main (LM), 5 with 224 patients and 306 lesions using OCT, and 9 with 1532 patients and 1681 lesions with IVUS. Median MLA for the OCT studies was 1.96 mm(2) (1.85-1.98 mm(2)), 2.9 mm(2) (2.7-3.1 mm(2)) for MLA of all lesions assessed with IVUS, 2.8 mm(2) (2.7-2.9 mm(2)) for lesions with an angiographic diameter >3 mm, 2.4 mm(2) (2.4-2.5 mm(2)) for lesions <3 mm, and 5.4 mm(2) (5.1-5.6 mm(2)) for LM lesions. For OCT-MLA, AUC was 0.80 (0.74-0.86), with a sensitivity of 0.81 (0.74-0.87) and specificity of 0.77 (0.71-0.83), whereas OCT-MLD had an AUC of 0.85 (0.79-0.91), sensitivity of 0.74 (0.69-0.78), and specificity of 0.70 (0.68-0.73). For IVUS-MLA, AUC was 0.78 (0.75-0.81) for all lesions, 0.78 (0.73-0.84) for vessels with a diameter >3 mm, and 0.79 (0.70-0.89) for those with a diameter <3 mm. Left main AUC was 0.97 (0.93-1). CONCLUSION: Intravascular ultrasound and OCT had modest diagnostic accuracy for identification hemodynamically significant lesions, also with specific cutoff for different diameters. Invasive imaging for assessment of LM severity demonstrated excellent correlation with FFR. What is already known about this subject? Fractional flow reserve represents the criterion standard to evaluate the prognostic value of coronary stenosis, whereas its relationship with IVUS and OCT remains to be assessed. What does this study add? Despite improvement, IVUS and OCT do not predict functional stenosis, even with dedicated cutoff, apart from LM disease. How might this impact on clinical practice? The recent guidelines of myocardial revascularization have stressed the crucial role of FFR before performing percutaneous coronary intervention on LM, whereas intravascular imaging is often exploited to drive revascularization. The present analysis stresses the point that LM percutaneous coronary intervention may be driven only by intravascular imaging, given the high accuracy for significant ischemic lesions, whereas for other vessels, these 2 techniques mirror 2 different aspects.

Serum levels of C-peptide are associated with coronary artery calcification in patients with rheumatoid arthritis.

C-peptide has pro-atherogenic effects in animal models, and elevated C-peptide levels are associated with cardiovascular and all-cause mortality in patients undergoing coronary angiography. This cross-sectional study investigated the association between C-peptide serum levels and coronary artery calcification (CAC) in patients with rheumatoid arthritis (RA), a high-risk group for cardiovascular events. Fifty-four patients with RA were recruited from an arthritis outpatient department at the University Hospital in Aachen, Germany. CAC was measured by multi-slice CT scan, and blood samples were drawn from all patients for the analysis of C-peptide and other cardiovascular biomarkers. Mean serum levels of C-peptide (1.187 ± 0.771 vs 0.745 ± 0.481 nmol/L, p = 0.02), YKL-40, LDL cholesterol, and triglycerides were significantly higher in patients with CAC (n = 32, 59 %) compared to those without CAC (n = 22, 41 %). Univariate analysis revealed a significant association of C-peptide [OR 4.7, 95 % CI (1.1, 20.2)], YKL-40, triglycerides, hypertension, smoking, age, and male sex with the presence of CAC. After adjustment for body mass index, cholesterol, diabetes, adiponectin, calcium, and phosphate, C-peptide was still significantly associated with CAC in a multivariate logistic regression model. In conclusion, C-peptide serum levels are independently associated with the presence of CAC in patients with RA. These data suggest a potential role of C-peptide in cardiovascular disease in patients with RA.

A score to quantify coronary plaque vulnerability in high-risk patients with type 2 diabetes: an optical coherence tomography study.

BACKGROUND: Patients with type 2 diabetes are at a high risk for acute cardiovascular events, which usually arise from the rupture of a vulnerable coronary lesion characterized by specific morphological plaque features. Thus, the identification of vulnerable plaques is of utmost clinical importance in patients with type 2 diabetes. However, there is currently no scoring system available to identify vulnerable lesions based on plaque characteristics. Thus, we aimed to characterize the diagnostic value of optical coherence tomography (OCT) - derived lesion characteristics to quantify plaque vulnerability both as individual parameters and when combined to a score in patients with type 2 diabetes. METHODS: OCT was performed in the coronary culprit lesions of 112 patients with type 2 diabetes. The score, which quantifies plaque vulnerability, was defined as the predicted probability that a lesion is the cause for an acute coronary syndrome (ACS) (vs. stable angina (SAP)) based on its specific plaque morphology. RESULTS: Multivariable logistic regression analysis demonstrated that plaque vulnerability was independently predicted by the minimal fibrous cap thickness overlying a lesion's lipid core (odds ratio (OR) per 10 µm 0.478, p = 0.002), the medium lipid arc (OR per 90° 13.997, p < 0.001), the presence of macrophages (OR 4.797, p = 0.015) and the lipid plaque length (OR 1.290, p = 0.098). CONCLUSION: This is the first study to present a score to quantify lesion vulnerability in patients with type 2 diabetes. This score may be a valuable adjunct in decision-making and useful in guiding coronary interventions.

Optical coherence tomography derived differences of plaque characteristics in coronary culprit lesions between type 2 diabetic patients with and without acute coronary syndrome.

OBJECTIVE: To compare optical coherence tomography (OCT)-derived plaque characteristics of coronary target lesions between diabetic patients with acute coronary syndrome (ACS) versus stable angina pectoris (SAP). BACKGROUND: In vivo assessment of plaque composition of coronary culprit lesions in a cardiovascular high-risk population with diabetes mellitus is incompletely elucidated. METHODS: 102 diabetic patients with coronary de novo lesions were enrolled and categorized into an ACS-group (40 patients) and a SAP-group (62 patients) according to their clinical presentation. Assessment of clinical data, angiographic, and OCT imaging including the analysis of plaque composition and lipid content of the target lesions were performed prior to percutaneous coronary intervention and compared between the two groups. RESULTS: Plaque characteristics of patients in the ACS-group compared with the SAP-group showed a higher incidence of lipid-rich plaque [33 (82.5%) vs. 25 (40.3%)], thin-capped fibroatheroma [29 (72.5%) vs. 10 (16.1%)], macrophage infiltration [32 (80.0%) vs. 21 (33.9%)], thrombus [23 (57.5%) vs. 2 (3.2%)], and plaque rupture [27 (67.5%) vs. 2 (3.2%)] (all P < 0.001). Moreover, there was a wider lipid arc (174.5 ± 33.8° vs. 122.9 ± 43.9°), a longer lipid plaque length (6.52 ± 2.04 mm vs. 3.73 ± 2.16 mm), a greater lipid volume index (1117.2 ± 349.9 vs. 504.8 ± 379.3), and a smaller minimal fibrous cap thickness (51.52 ± 9.14 µm vs. 80.33 ± 26.71 µm) within lipid-rich lesions of ACS patients (all P < 0.001). CONCLUSION: Diabetic patients with ACS exhibit more vulnerable plaque features in coronary culprit lesions compared with diabetic patients with SAP. This may provide rationale for a specific therapeutic strategy either by pharmacological plaque stabilization or coronary intervention in any lesion with vulnerable plaque morphology in patients with diabetes.

Plaque vulnerability of coronary artery lesions is related to left ventricular dilatation as determined by optical coherence tomography and cardiac magnetic resonance imaging in patients with type 2 diabetes.

BACKGROUND: Patients with type 2 diabetes are at increased risk for both, left ventricular (LV)-dilatation and myocardial infarction (MI) following the rupture of a vulnerable plaque. This study investigated the to date incompletely understood relationship between plaque vulnerability and LV-dilatation using optical coherence tomography (OCT) and cardiac magnetic resonance imaging (CMR) in patients with type 2 diabetes and stable coronary artery disease. METHODS: CMR was performed in 58 patients with type 2 diabetes, in which 81 coronary lesions were investigated using OCT. RESULTS: A decreased minimal fibrous cap thickness (FCT) of coronary lesions was associated with an increase of several CMR-derived parameters including LV-end diastolic volume (LVEDV, r = 0.521, p < 0.001), LV-end diastolic diameter (r = 0.502, p < 0.001) and LV-end systolic volume (r = 0.467, p = 0.001). Similar results were obtained for mean FCT. CONCLUSION: These data suggest that vulnerability of coronary lesions is associated with LV-dilatation in high risk patients with type 2 diabetes. CMR may be a useful adjunct to the risk-stratification in this population. Future studies are warranted to investigate potential mechanisms linking plaque vulnerability and LV-dilatation.

Whole-heart dynamic three-dimensional magnetic resonance perfusion imaging for the detection of coronary artery disease defined by fractional flow reserve: determination of volumetric myocardial ischaemic burden and coronary lesion location.

AIMS: Dynamic three-dimensional-cardiac magnetic resonance (3D-CMR) perfusion proved highly diagnostic for the detection of angiographically defined coronary artery disease (CAD) and has been used to assess the efficacy of coronary stenting procedures. The present study aimed to relate significant coronary lesions as assessed by fractional flow reserve (FFR) to the volume of myocardial hypoenhancement on 3D-CMR adenosine stress perfusion imaging and to define the inter-study reproducibility of stress inducible 3D-CMR hypoperfusion. METHODS AND RESULTS: A total of 120 patients with known or suspected CAD were examined in two CMR centres using 1.5 T systems. The protocol included cine imaging, 3D-CMR perfusion during adenosine infusion, and at rest followed by delayed enhancement (DE) imaging. Fractional flow reserve was recorded in epicardial coronary arteries and side branches with ≥2 mm luminal diameter and >40% severity stenosis (pathologic FFR < 0.75). Twenty-five patients underwent an identical repeat CMR examination for the determination of inter-study reproducibility of 3D-CMR perfusion deficits induced by adenosine. Three-dimensional CMR perfusion scans were visually classified as pathologic if one or more segments showed an inducible perfusion deficit in the absence of DE. Myocardial ischaemic burden (MIB) was measured by segmentation of the area of inducible hypoenhancement and normalized to left ventricular myocardial volume (MIB, %). Three-dimensional CMR perfusion resulted in a sensitivity, specificity, and diagnostic accuracy of 90, 82, and 87%, respectively. Substantial concordance was found for inter-study reproducibility [Lin's correlation coefficient: 0.98 (95% confidence interval: 0.96-0.99)]. CONCLUSION: Three-dimensional CMR stress perfusion provided high diagnostic accuracy for the detection of functionally significant CAD. Myocardial ischaemic burden measurements were highly reproducible and allowed the assessment of CAD severity.

Chronic kidney disease is related to impaired left ventricular strain as assessed by cardiac magnetic resonance imaging in patients with ischemic cardiomyopathy.

INTRODUCTION: Chronic kidney disease (CKD) is an important cardiovascular risk factor. However, the relationship between CKD and myocardial strain as a parameter of myocardial function is still incompletely understood, particularly in patients with ischemic cardiomyopathy (ICM). Cardiac magnetic resonance imaging (CMR) feature tracking allows to analyze myocardial strain with high reproducibility. Therefore, the aim of the present study was to assess the relationship between CKD and myocardial strain as described by CMR in patients with ICM. METHODS: We retrospectively performed CMR-based myocardial strain analysis in 89 patients with ICM and different stages of CKD, classified according to the KDIGO stages. In all patients, global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS) analysis of left ventricular myocardium were performed. Furthermore, segmental longitudinal (SLS), circumferential (SCS) and radial strain (SRS) according to the AHA 16/17-segment model was determined. RESULTS: Creatinine levels (GLS: r = 0.46, p < 0.001; GCS: r = 0.34, p = 0.001; GRS: r = - 0.4, p < 0.001), urea levels (GLS: r = 0.34, p = 0.001; GCS: r = 0.30, p = 0.005; GRS: r = - 0.31, p = 0.003) as well as estimated glomerular filtration rate (GLS: r = -0.40, p < 0.001; GCS: r = - 0.27, p = 0.012; GRS r = 0.34, p < 0.001) were significantly associated with global strains as determined by CMR. To further investigate the relationship between CKD and myocardial dysfunction, segmental strain analysis was performed: SLS was progressively impaired with increasing severity of CKD (KDIGO-1: - 11.93 ± 0.34; KDIGO-5: - 7.99 ± 0.38; p < 0.001 for KDIGO-5 vs. KDIGO-1; similar data for SCS and SRS). Interestingly, myocardial strain was impaired with CKD in both segments with and without scarring. Furthermore, in a multivariable analysis, eGFR was independently associated with GLS following adjustment for LV-EF, scar burden, diabetes, hypertension, age, gender, LV mass or LV mass index. CONCLUSION: CKD is related to impaired LV strain as assessed by CMR in patients with ICM. In our cohort, this relationship is independent of LV-EF, the extent of myocardial scarring, diabetes, hypertension, age, gender, LV mass or LV mass index.

Coronary microvascular dysfunction is a hallmark of all subtypes of MINOCA.

INTRODUCTION: Myocardial infarction without obstructive coronary artery disease (MINOCA) is a heterogeneous clinical condition presenting with myocardial necrosis not due to an obstruction of a major coronary artery. Recently, a relevant role of coronary microvascular dysfunction (CMD) in the pathogenesis of MINOCA has been suggested; however, data on this are scarce. Particularly, it is unclear if CMD is equally present in all subtypes of MINOCA or differentially identifies one or more of these conditions. Therefore, the aim of this study was to assess CMD in all three coronary vessels of MINOCA patients, relating it with the clinical subtype. METHODS: We retrospectively assessed coronary microvascular function in all three coronary territories by means of angiography-based index of microvascular resistance (aIMR) in 92 patients (64 with working diagnosis of MINOCA, 28 control patients). To further assess the association of CMD with MINOCA subtypes, MINOCA patients were subdivided according to clinical data in coronary cause (n = 13), takotsubo (n = 13), infiltrative or inflammatory cardiomyopathy (n = 9) or unclear (n = 29). RESULTS: Patients with working diagnosis of MINOCA showed a significantly elevated average aIMR compared to control patients (30.5 ± 7.6 vs. 22.1 ± 5.9, p < 0.001) as a marker of a relevant CMD; these data were consistent in all vessels. Among MINOCA subtypes, no significant difference in average aIMR could be detected between patients with coronary cause (33.2 ± 6.6), takotsubo cardiomyopathy (29.2 ± 6.9), infiltrative or inflammatory cardiomyopathy (28.1 ± 6.8) or unclear cause (30.6 ± 8.5; p = 0.412). Interestingly, aIMR was significantly elevated in the coronary vessel supplying the diseased myocardium compared with other vessels (31.9 ± 11.4 vs. 27.8 ± 8.2, p = 0.049). CONCLUSION: Coronary microvascular dysfunction is a hallmark of all MINOCA subtypes. This study adds to the pathophysiological understanding of MINOCA and sheds light into the role of CMD in MINOCA.

Morphological characteristics of lesions with thin cap fibroatheroma-a substudy from the COMBINE (OCT-FFR) trial.

AIMS: To study if any qualitative or quantitative optical coherence tomography (OCT) variables in combination with thin cap fibroatheroma (TCFA) patients could improve the identification of lesions at risk for future major adverse cardiac events (MACEs). METHODS AND RESULTS: From the combined optical coherence tomography morphologic and fractional flow reserve hemodynamic assessment of non- culprit lesions to better predict adverse event outcomes in diabetes mellitus patients: COMBINE (OCT-FFR) trial database (NCT02989740), we performed a detailed assessment OCT qualitative and quantitative variables in TCFA carrying diabetes mellitus (DM) patients with vs. without MACE during follow-up. MACEs were defined as a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, and hospitalization for unstable angina. From the 390 fractional flow reserve (FFR)-negative DM patients, 98 (25.2%) had ≥1 OCT-detected TCFA, of which 13 (13.3%) had MACE and 85 (86.7%) were event-free (non-MACE). The baseline characteristics were similar between both groups; however, a smaller minimal lumen area (MLA) and lower mean FFR value were observed in MACE group (1.80 vs. 2.50 mm2, P = 0.01, and 0.85 vs. 0.89, P = 0.02, respectively). Prevalence of healed plaque (HP) was higher in the MACE group (53.85 vs. 21.18%, P = 0.01). TCFA were predominantly located proximal to the MLA. TCFA area was smaller in the MACE group, while no difference was observed regarding the lesion area. CONCLUSION: Within TCFA carrying patients, a smaller MLA, lower FFR values, and TCFA location adjacent to a HP were associated with future MACE. Carpet-like measured lesion area surface was similar, while the TCFA area was smaller in the MACE arm, and predominantly located proximal to the MLA.

Long-term outcomes of patients with normal fractional flow reserve and thin-cap fibroatheroma.

BACKGROUND: The long-term prognostic implications of fractional flow reserve (FFR)-negative lesions hosting vulnerable plaques remain unsettled. AIMS: The aim of this study was to evaluate the association of non-ischaemic lesions hosting optical coherence tomography (OCT)-detected thin-cap fibroatheromas (TCFA) with first and recurrent cardiovascular events during follow-up up to 5 years in a diabetes mellitus (DM) patient population. METHODS: COMBINE OCT-FFR is a prospective, international, double-blind, natural history study. Patients with DM and with ≥1 FFR-negative lesion were classified into 2 groups based on the presence or absence of ≥1 TCFA lesion. The primary endpoint (PE) is a composite of cardiac mortality, target vessel-related myocardial infarction (TV-MI), clinically driven target lesion revascularisation (TLR), or unstable angina (UA) requiring hospitalisation during follow-up up to 5 years. RESULTS: Among 390 DM patients (age 67.5±9 years; 37% female) with ≥1 FFR-negative lesion, 292 (74.9%) were TCFA-negative while 98 (25.1%) were TCFA-positive. The PE occurred more frequently in TCFA-positive than in TCFA-negative patients (21.4% vs 8.2%, hazard ratio [HR] 2.89, 95% confidence interval [CI]: 1.61-5.20; p<0.001; 6.42 vs 2.46 events per 100 patient-years, rate ratio [RR] 2.61, 95% CI: 1.38-4.90; p=0.002). Furthermore, when TV-MI, TLR, and UA were treated as recurrent components of the PE, TCFA-positive patients experienced a higher risk of recurrent events (HR 2.89, 95% CI; 1.74-4.80; p<0.001; 13.45 vs 2.87 events per 100 patient-years, RR 4.69, 95% CI: 2.86-7.83; p<0.001). A multivariable analysis identified the presence of TCFA as an independent predictor of the PE (HR 2.76, 95% CI: 1.53-4.97; p<0.001). CONCLUSIONS: OCT-detected TCFA-positive lesions, although not ischaemia-generating, are associated with an increased risk of adverse events during long-term follow-up. CLINICALTRIALS: gov: NCT02989740.

Coronary CT angiography: right atrial and ventricular muscle bridges of the right coronary artery.

Using cardiac computed tomography we examined a 72-year-old woman before surgery because of constrictive pericarditis after radiation therapy. Incidentally we discovered an anatomic variation of the right coronary artery with both atrial and ventricular muscle bridges. According to the patient's anamnesis and the characteristics of the courses the findings can be classified as not being harmful to the patient.

[Mitral valve: When conservative, when surgical, when interventional therapy?] / Mitralklappe: wann konservativ, wann operativ, wann interventionell?

The management of severe symptomatic mitral regurgitation is in contrast to the aortic-valve-intervention more challenging due to the complex mitral-valve anatomy. In primary mitral regurgitation surgical therapy is recommended, whereas there are various therapeutic options in secondary mitral regurgitation. Besides the established mitral-valve Transcatheter Edge-to-Edge-Repair (M-TEER) and the interventional annuloplasty - devices dynamic developments have recently been made in the field of Transcatheter Mitral Valve Replacement-therapy (TMVR). This article surveys the current recommendations and available therapeutic options in mitral regurgitation.

Quantitative Flow Ratio Is Related to Anatomic Left Main Stem Lesion Parameters as Assessed by Intravascular Imaging.

Introduction: Previously, an association between anatomic left main stem (LMS) lesion parameters, as described by intravascular ultrasound (IVUS) and fractional flow reserve (FFR), was shown. Quantitative flow ratio (QFR) is a novel, promising technique which can assess functional stenosis relevance based only on angiography. However, as little is known about the relationship between anatomic LMS parameters and QFR, it was thus investigated in this study. Methods: In 53 patients with LMS disease, we tested the association between anatomic assessment using OCT (n = 28) or IVUS (n = 25) on the one hand and functional assessment as determined by QFR on the other hand. LMS-QFR was measured using a dedicated approach, averaging QFR over left anterior descending (LAD) and circumflex (LCX) and manually limiting segment of interest to LMS. Results: The minimal luminal area of the LMS (LMS-MLA) as measured by intravascular imaging showed a consistent correlation with QFR (R = 0.61, p < 0.001). QFR could predict a LMS-MLA < 6 mm2 with very good diagnostic accuracy (AUC 0.919) and a LMS-MLA < 4.5 mm2 with good accuracy (AUC 0.798). Similar results were obtained for other stenosis parameters. Conclusions: QFR might be a valuable tool to assess LMS disease. Further studies focusing on patient outcomes are needed to further validate the effectiveness of this approach.