Percutaneous repair of moderate-to-severe or severe functional mitral regurgitation in patients with symptomatic heart failure: Baseline characteristics of patients in the RESHAPE-HF2 trial and comparison to COAPT and MITRA-FR trials.

AIM: The RESHAPE-HF2 trial is designed to assess the efficacy and safety of the MitraClip device system for the treatment of clinically important functional mitral regurgitation (FMR) in patients with heart failure (HF). This report describes the baseline characteristics of patients enrolled in the RESHAPE-HF2 trial compared to those enrolled in the COAPT and MITRA-FR trials. METHODS AND RESULTS: The RESHAPE-HF2 study is an investigator-initiated, prospective, randomized, multicentre trial including patients with symptomatic HF, a left ventricular ejection fraction (LVEF) between 20% and 50% with moderate-to-severe or severe FMR, for whom isolated mitral valve surgery was not recommended. Patients were randomized 1:1 to a strategy of delivering or withholding MitraClip. Of 506 patients randomized, the mean age of the patients was 70 ± 10 years, and 99 of them (20%) were women. The median EuroSCORE II was 5.3 (2.8-9.0) and median plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 2745 (1407-5385) pg/ml. Most patients were prescribed beta-blockers (96%), diuretics (96%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (82%) and mineralocorticoid receptor antagonists (82%). The use of sodium-glucose cotransporter 2 inhibitors was rare (7%). Cardiac resynchronization therapy (CRT) devices had been previously implanted in 29% of patients. Mean LVEF, left ventricular end-diastolic volume and effective regurgitant orifice area (EROA) were 31 ± 8%, 211 ± 76 ml and 0.25 ± 0.08 cm2, respectively, whereas 44% of patients had mitral regurgitation severity of grade 4+. Compared to patients enrolled in COAPT and MITRA-FR, those enrolled in RESHAPE-HF2 were less likely to have mitral regurgitation grade 4+ and, on average, HAD lower EROA, and plasma NT-proBNP and higher estimated glomerular filtration rate, but otherwise had similar age, comorbidities, CRT therapy and LVEF. CONCLUSION: Patients enrolled in RESHAPE-HF2 represent a third distinct population where MitraClip was tested in, that is one mainly comprising of patients with moderate-to-severe FMR instead of only severe FMR, as enrolled in the COAPT and MITRA-FR trials. The results of RESHAPE-HF2 will provide crucial insights regarding broader application of the transcatheter edge-to-edge repair procedure in clinical practice.

Preoperative and mid-term right ventricular systolic function assessment, at rest and during exercise, with speckle-tracking echocardiography after left ventricular assist device implantation.

OBJECTIVES: The study aimed to compare pre- and postoperative resting as well as postprocedural resting and exertional right ventricular speckle-tracking echocardiographic parameters at a mid-term follow-up after left ventricular assist device (LVAD) implantation. METHODS: Patients with implanted third-generation LVADs with hydrodynamic bearings were prospectively enrolled (NCT05063006). Myocardial deformation was evaluated before pump implantation and at least three months after the procedure, both at rest and during exercise. RESULTS: We included 22 patients, 7.3 months (IQR, 4.7-10.2) after the surgery. The mean age was 58.4 ± 7 years, 95.5% were men, and 45.5% had dilated cardiomyopathy. The RV strain analysis was feasible in all subjects both at rest and during exercise. The RV free wall strain (RVFWS) worsened from -13% (IQR, -17.3 to -10.9) to -11.3% (IQR, -12.9 to -6; p = 0.033) after LVAD implantation with a particular decline in the apical RV segment [-11.3% (IQR, -16.4 to -6.2) vs -7.8% (IQR, -11.7 to -3.9; p = 0.012)]. The RV four-chamber longitudinal strain (RV4CSL) remained unchanged [-8.5% (IQR, -10.8 to -6.9) vs -7.3% (IQR, -9.8 to -4.7; p = 0.184)]. Neither RVFWS (-11.3% (IQR, -12.9 to -6) vs -9.9% (IQR, -13.5 to -7.5; p = 0.077) nor RV4CSL [-7.3% (IQR, -9.8 to -4.7) vs -7.9% (IQR, -9.8 to -6.3; p = 0.548)] changed during the exercise test. CONCLUSIONS: In patients who are pump-supported, the right ventricular free wall strain tends to worsen after LVAD implantation and remains unchanged during a cycle ergometer stress test.

Computed tomography guided tailored approach to transfemoral access in patients undergoing transcatheter aortic valve implantation.

BACKGROUND: Transfemoral approach (TFA) is the most common access route for transcatheter aortic valve implantation (TAVI). Percutaneous femoral access (PA) is preferred over the surgical approach (SA), however, may be associated with a higher risk of access site complications. Thus, we aimed to assess outcomes of computed tomography-guided tailored approach to percutaneous and surgical TFA in patients undergoing TAVI. METHODS: We evaluated data of 158 patients, who underwent TAVI via femoral route between January 2017 and December 2018. In the PA group, vascular closure was performed with the use of two percutaneous suture devices and an additional mechanical seal device. We compared complications rate and outcomes. RESULTS: Of the 158 patients (92%; mean age 79.6 years, 60.8% female), in 92 (61%) patients PA was performed and in 66 (39%) patients SA was used. Median (interquartile range) radiation exposure as well as contrast volume dose was higher in the PA group compared to the SA group 614.0 (410.0; 1104.0) mGy vs. 405 (240.5; 658.0) mGy (p < 0.001) and 150.0 (120.0; 180.7) mL vs. 130.0 (100.0; 160.0) mL (p = 0.04), respectively. Bleeding complications were similar in the PA group 11 (12.2%) compared to 5 (8.62%) in the SA group (p = 0.48). Median length of hospital stay was also similar in the PA and the SA group 6.00 (5.00; 8.00) days vs. 6.00 (4.00; 8.00) days, respectively (p = 0.31). CONCLUSIONS: Computed tomography-guided PA in TAVI may provide comparable procedural outcomes compared to the SA, despite a higher radiation dose and the use of contrast dye, while being less invasive.

Clinical Characteristics Predicting Worse Long-Term Outcomes in Patients with Myocardial Infarction and Non-Obstructive Coronary Arteries (MINOCA).

Non-obstructive coronary artery disease occurs in 3.5-15% of patients presenting with acute myocardial infarction. This group of patients has a poor prognosis. Identification of factors that predict worse outcomes in myocardial infarction with non-obstructive coronary arteries (MINOCA) is therefore important. Patients with a diagnosis of MINOCA (n = 110) were enrolled in this single-center, retrospective registry. Follow-up was performed 12, 24 and 36 months after discharge. The primary composite endpoint was defined as myocardial infarction, coronary revascularization, stroke or TIA, all-cause death, or hospital readmission due to any cardiovascular event. The mean age of the study group was 64.9 (± 13.5) years and 38.2% of patients were male. The occurrence of the primary composite endpoint was 36.4%. In a COX proportional hazards model analysis, older age (p = 0.027), type 2 diabetes (p = 0.013), history of neoplasm (p = 0.004), ST-segment depression (p = 0.018) and left bundle branch block/right bundle branch block (p = 0.004) by ECG on discharge, higher Gensini score (p = 0.022), higher intraventricular septum (p = 0.007) and posterior wall thickness increases (p = 0.001) were shown to be risk factors for primary composite endpoint occurrence. Our study revealed that several factors such as older age, type 2 diabetes, ST-segment depression and LBBB/RBBB in ECG on discharge, higher Gensini score, and myocardial hypertrophy and history of neoplasm may contribute to worse clinical outcomes in MINOCA patients.

MicroRNA-134-5p and the Extent of Arterial Occlusive Disease Are Associated with Risk of Future Adverse Cardiac and Cerebral Events in Diabetic Patients Undergoing Carotid Artery Stenting for Symptomatic Carotid Artery Disease.

There is little known about the prognostic value of serum microRNAs (miRs) in diabetic patients with symptomatic internal carotid artery disease (ICAS) who underwent stent supported angioplasty (PTA) for ICAS. The present study aimed to investigate expression levels of selected miRs for future major adverse cardiac and cerebral events (MACCE) as a marker in diabetic patients following ICAS-PTA. The expression levels of 11 chosen circulating serum miRs were compared in 37 diabetic patients with symptomatic ICAS and 64 control group patients with symptomatic ICAS, but free of diabetes. The prospective median follow-up of 84 months was performed for cardiovascular outcomes. Diabetic patients, as compared to control subjects, did not differ with respect to age (p = 0.159), distribution of gender (p = 0.375), hypertension (p = 0.872), hyperlipidemia (p = 0.203), smoking (p = 0.115), coronary heart disease (p = 0.182), lower extremities arterial disease (LEAD, p = 0.731), and miRs expressions except from lower miR-16-5p (p < 0.001). During the follow-up period, MACCE occurred in 16 (43.2%) diabetic and 26 (40.6%) non-diabetic patients (p = 0.624). On multivariate Cox analysis, hazard ratio (HR) and 95% Confidence Intervals (95%CI) for diabetic patients associated with MACCE were miR-134-5p (1.12; 1.05−1.21, p < 0.001), miR-499-5p (0.16; 0.02−1.32, p = 0.089), hs-CRP (1.14; 1.02−1.28; p = 0.022), prior myocardial infarction (8.56, 1.91−38.3, p = 0.004), LEAD (11.9; 2.99−47.9, p = 0.005), and RAS (20.2; 2.4−167.5, p = 0.005), while in non-diabetic subjects, only miR-16-5p (1.0006; 1.0001−1.0012, p = 0.016), miR-208b-3p (2.82; 0.91−8.71, p = 0.071), and hypertension (0.27, 0.08−0.95, p = 0.042) were associated with MACCE. Our study demonstrated that different circulating miRs may be prognostic for MACCE in diabetic versus non-diabetic patients with symptomatic ICAS. Higher expression levels of miR-134 were prognostic for MACCE in diabetic patients, while higher expression levels of miR-16 were prognostic in non-diabetic patients.

Ticagrelor monotherapy beyond one month after PCI in ACS or stable CAD in elderly patients: a pre-specified analysis of the GLOBAL LEADERS trial.

AIMS: Antiplatelet treatment in the elderly post percutaneous coronary interventions (PCI) remains a complex issue. Here we report the results of the pre-specified subgroup analysis of the GLOBAL LEADERS trial evaluating the long-term safety and cardiovascular efficacy of ticagrelor monotherapy among patients categorised according to the pre-specified cut-off value of 75 years of age. METHODS AND RESULTS: This was a pre-specified analysis of the randomised GLOBAL LEADERS trial (n=15,991), comparing 23-month ticagrelor monotherapy (after one month of DAPT) with the reference treatment (12-month DAPT followed by 12 months of aspirin). Among elderly patients (>75 years; n=2,565), the primary endpoint (two-year all-cause mortality or new Q-wave core lab-adjudicated myocardial infarction [MI]) occurred in 7.2% and 9.4% of patients in the ticagrelor monotherapy and the reference group, respectively (hazard ratio [HR] 0.75, 95% confidence interval [CI]: 0.58-0.99, p=0.041; pint=0.23); BARC-defined bleeding type 3/5 occurred in 5.2% and 4.1%, respectively (HR 1.29, 95% CI: 0.89-1.86; p=0.180; pint=0.06). The elderly with stable CAD had a higher rate of BARC 3/5 type bleeding (HR 2.05, 95% CI: 1.18-3.55) with ticagrelor monotherapy versus the reference treatment (pint=0.02). Elderly patients had a lower rate of definite or probable stent thrombosis (ST) with ticagrelor monotherapy (0.4% vs 1.4%, p=0.015, pint=0.01), compared with the reference group. CONCLUSIONS: In this pre-specified, exploratory analysis of the overall neutral trial, there was no differential treatment effect of ticagrelor monotherapy (after one-month dual therapy with aspirin) found in elderly patients undergoing PCI with respect to the rate of the primary endpoint of all-cause death or new Q-wave MI. The lower rate of ST in the elderly with ticagrelor monotherapy is hypothesis-generating. ClinicalTrials.gov identifier: NCT01813435.

Prevalence and clinical presentation of myocardial bridge on the basis of the National Polish Percutaneous Interventions Registry and the Classification of Rare Cardiovascular Diseases.

BACKGROUND A myocardial bridge (MB) is defined as a congenital anomaly, in which a segment of an epicardial coronary artery takes an intramuscular course. AIMS The aim of the study was to evaluate the prevalence of MB in coronary arteries among patients who were diagnosed using coronary angiography. METHODS Data were obtained from the National Polish Percutaneous Interventions Registry for patients hospitalized between January 1, 2014, and December 31, 2016, in invasive cardiology departments in Poland and divided into groups with and without MB. RESULTS The study included 298 558 patients. The non­MB group comprised 296 133 patients (99.19%; women, 38.01%), while the MB group included 2425 patients (0.81%; women, 39.98%). The most frequent location of MB was the left anterior descending artery (n = 2355; 97.11% of patients). The MB group less often had diabetes (14.68% vs 21.63%), previous stroke (1.61% vs 2.96%), previous myocardial infarction (10.97% vs 21.97%), kidney disease (2.8% vs 5.04%), previous coronary artery bypass graft (1.03% vs 5.64%), previous percutaneous coronary intervention (13.20% vs 25.86%) than the non­MB group (P <0.0001). The incidence of acute coronary syndromes was lower in the MB group (P <0.0001), while smoking was more common (18.76% vs 16.87%, P <0.01). CONCLUSIONS Patients with MB were younger and had fewer comorbidities and risk factors for atherosclerosis than patients without MB. The condition was more common among patients with stable coronary artery disease. Smoking and female sex appeared to be associated with a more clinically symptomatic presentation of MB.

Reduced periprocedural mortality and bleeding rates of radial approach in ST-segment elevation myocardial infarction. Propensity score analysis of data from the ORPKI Polish National Registry.

AIMS: We sought to evaluate bleeding complications and periprocedural outcomes of the radial approach (RA) as compared to the femoral approach (FA) during percutaneous coronary intervention (PCI) in "real-world" patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: The study group consisted of 22,812 consecutive patients with STEMI treated with PCI and stent implantation between January 2014 and June 2015 in 151 tertiary invasive cardiology centres in Poland (the ORPKI Polish National Registry). Patients treated using the RA and FA were compared using a propensity score analysis to avoid possible selection bias. The analysis was carried out in an "as-treated" manner. The FA was used in 9,334 (40.9%) and the RA in 13,478 (59.1%) patients. After propensity score matching, a higher total amount of contrast (191.8±8.0 vs. 174.8±68.8 ml; p=0.001) and lower radiation doses (1,279.5±1,346.3 vs. 1,182.6±887 mGy; p=0.02) were reported in FA. More access-site-related bleeding complications after both angiography (0.17% vs. 0.02%; p=0.004) and PCI (0.23% vs. 0.09%; p=0.049) were reported in the FA group. Periprocedural death (1.94% vs. 0.93%; p=0.001) was more common after PCI performed with the FA. CONCLUSIONS: The radial approach was associated with a lower incidence of periprocedural death in STEMI patients as well as a significant reduction of bleeding complications at the access site.

Sex-Related Differences in Outcomes After Percutaneous Balloon Aortic Valvuloplasty.

OBJECTIVES: We aimed to evaluate sex-related differences in short-term and long-term outcomes of patients undergoing balloon aortic valvuloplasty (BAV) for severe aortic stenosis (AS). METHODS: A total of 112 patients with severe AS underwent 114 BAV procedures as palliative procedure, bridge to definitive treatment, or before urgent non-cardiac surgery. Patients were followed for 24 months. RESULTS: Of the 112 patients, 70 (62.5%) were women. Women were older, and had a higher STS score and higher prevalence of chronic kidney disease and arterial hypertension. Indications for BAV did not differ by gender. Women had a higher risk of vascular complications than men (15.7% vs 0.0%; P=.01), but with a similar rate of major periprocedural complications (17.1% vs 9.5%; P=.40). Transcatheter aortic valve implantation (TAVI) was performed in 22.8% of women and 26.2% of men (P=.61) and surgical aortic valve replacement in 10% of women and 11.9% of men (P=.70). Women and men treated finally with TAVI/aortic valve replacement had lower mortality as compared with conservative treatment (P<.01). No difference in in-hospital and 24-month mortality between women and men was observed (11.4% vs 4.9% [P=.26]; 63.3% vs 39.0% [P=.22], respectively). In a multivariable Cox model, STS score above 9.8% (hazard ratio, 2.29; 95% confidence interval, 1.09-4.83; P=.03) was an independent predictor of all-cause death only in women. CONCLUSION: Despite the presence of sex-related differences in baseline and procedural characteristics as well as in the risk of vascular complications, no difference in major procedural complications and long-term mortality was confirmed for patients with severe AS undergoing BAV.

Acute and long-term outcomes of percutaneous balloon aortic valvuloplasty for the treatment of severe aortic stenosis.

OBJECTIVES: This study aimed to evaluate the indications, short- and long-term outcomes of balloon aortic valvuloplasty (BAV) in patients with severe aortic stenosis (AS). METHODS: A cohort of 112 patients with AS underwent 114 BAV procedures between October 2012 and July 2015 in two Polish interventional cardiology centers. Clinical and echocardiographic data were prospectively collected within 1, 6, and 12 months follow-up. RESULTS: BAV was performed as a bridge to TAVI (51.8%), surgical aortic valve replacement (AVR, 5.4%), before urgent noncardiac surgery (8.0%), for symptom relief (33.0%) and cardiogenic shock (1.8%). Periprocedural, in-hospital, 1-, 6-, 12-month mortality were 2.7%; 8.9%; 8.9%; 16.9%; 22.3%, respectively. Serious periprocedural adverse events occurred in 18.8% of patients. After the procedure, mean aortic valve area (AVA) increased from 0.59 ± 0.18 to 0.82 ± 0.24 cm2 , mean peak aortic valve gradient (pAVG) decreased from 94.0 ± 27.6 to 65.4 ± 20.0 mm Hg, mean aortic gradient decreased from 58.0 ± 17.8 to 40.5 ± 14.6 mm Hg, P < 0.05 for all. Left ventricular ejection fraction (LVEF) increased from median (interquartile range) of 53.5 (30 - 64) to 60 (45 - 65)% after 1 month (P < 0.05). In patients with impaired left ventricle function (LVEF <40%), LVEF significantly improved (median increase of 16%) after 1 and 6 months (P < 0.05). At 12 months patients had higher AVA, pAVG, and LVEF as compared to baseline (P < 0.05). CONCLUSIONS: BAV is a useful procedure in high-risk AS patients, where achieved effects can be sufficient in bridging patients for TAVI/AVR. © 2016 Wiley Periodicals, Inc.

Resolution of ischemic symptoms after percutaneous angioplasty for a symptomatic subclavian artery stenosis.

OBJECTIVE: A minor part of patients with subclavian or innominate artery occlusive disease (subclavian artery stenosis [SAS]) experience symptoms of vertebrobasilar insufficiency, upper extremity exertional ischemia (UEEI), or cardiac ischemia owing to subclavian-coronary steal (SCS) in some instances. The study aimed to assess the impact of percutaneous transluminal angioplasty (PTA) of symptomatic SAS on symptom resolution and to determine factors related with SAS recurrence. METHODS: Symptom resolution and incidence of restenosis (RS) were evaluated for up to 15 years in patients who had undergone successful PTA of SAS. RESULTS: The study group comprised 232 consecutive subjects after successful PTA of SAS (61.9 ± 8.4 years old 53.4% men). The mean follow-up time was 101 ± 40 months (range, 5-188 months). One month after PTA, 85.4% of the study participants were free from dizziness, 94.4% from imbalance, 97.1% from visual disturbances, 97.8% from syncope, 98.7% from UEEI, and 100% from SCS. RS was found in 37 patients (15.9%) in long-term observation. UEEI, dizziness, imbalance, and SCS were significantly more frequent in patients with SAS recurrence, as compared with patients with patent artery (65.9% vs 3.1% [P < .001] 63.4% vs 19.4% [P < .001]; 26.8% vs 9.4% [P = .005]; and 100% vs 15.4% [P = .018], respectively). Smaller stent diameter (odds ratio [OR], 0.87; 95% confidence interval [CI], 0.79-0.96; P = .004), implantation of ≥2 stents for a lesion (OR, 1.15; 95% CI, 1.05-1.26; P = .003), concomitant stenosis in the carotid or vertebral artery (OR, 1.10; 95% CI, 1.01-1.21; P = .036), high-sensitivity C-reactive protein level (OR, 1.20; 95% CI, 1.09-1.31; P < .001), and high-density lipoprotein level (OR, 0.91; 95% CI, 0.82-0.98; P = .021) were associated independently with risk of RS, whereas recurrence of UEEI (relative risk, 1.71; 95% CI, 1.55-1.90; P < .001), dizziness (OR, 1.26; 95% CI, 1.14-1.39; P < .001), limb paresthesia (OR, 1.14; 95% CI, 1.04-1.25; P = .005), and angina in subjects after coronary artery bypass grafting (OR, 1.11; 95% CI, 1.01-1.21; P = .024) were associated with RS/SAS progression after PTA. CONCLUSIONS: Angioplasty of SAS leads to symptom resolution in most patients. UEEI, dizziness, and angina recurrence are predictors of RS or SAS progression; high-sensitivity C-reactive protein, smaller stent diameter, and number of implanted stents predict RS.

Invasive treatment for carotid fibromuscular dysplasia.

INTRODUCTION: Fibromuscular dysplasia (FMD) is an infrequent non-inflamatory disease of unknown etiology that affects mainly medium-size arteries. The prevalence of FMD among patients scheduled for endovascular treatment of carotid artery stenosis is unknown. AIM: To evaluate the prevalence and treatment options of carotid FMD in patients scheduled for carotid artery stenting (CAS). MATERIAL AND METHODS: Between Jan 2001 and Dec 2013, 2012 CAS procedures were performed in 1809 patients (66.1% men; age 65.3 ±8.4 years, 49.2% symptomatic). In case of FMD suspicion in Doppler-duplex ultrasound (DUS), computed tomography angiography was performed for aortic arch and extracranial and intracranial artery imaging. For invasive treatment of FMD carotid stenosis, balloon angioplasty was considered first. If the result of balloon angioplasty was not satisfactory (> 30% residual stenosis, dissection), stent placement was scheduled. All patients underwent follow-up DUS and neurological examination 3, 6 and 12 months after angioplasty, then annually. RESULTS: There were 7 (0.4%) (4 symptomatic) cases of FMD. The FMD group was younger (47.9 ±7.5 years vs. 67.2 ±8.9 years, p = 0.0001), with higher prevalence of women (71.4% vs. 32.7%, p = 0.0422), a higher rate of dissected lesions (57.1% vs. 4.6%, p = 0.0002) and less severe stenosis (73.4% vs. 83.9%, p = 0.0070) as compared to the non-FMD group. In the non-FMD group the prevalence of coronary artery disease was higher (65.1% vs. 14.3% in FMD group, p = 0.009). All FMD patients underwent successful carotid artery angioplasty with the use of neuroprotection devices. In 4 cases angioplasty was supported by stent implantation. CONCLUSIONS: Fibromuscular dysplasia is rare among patients referred for CAS. In case of significant FMD carotid stenosis, it may be treated with balloon angioplasty (stent supported if necessary) with optimal immediate and long-term results.

Similar outcome of ST-elevation myocardial infarction patients treated with primary percutaneous coronary intervention regardless of presence of cardiac surgery on-site.

BACKGROUND: The growing penetration of mechanical reperfusion in ST-elevation myocardial infarction (STEMI) has been achieved by the creation of new percutaneous coronary intervention (PCI) centres which have helped to shorten delays but have compromised PCI volumes. AIM: To compare the outcomes in STEMI patients treated in PCI centres with or without surgical back-up. METHODS: Data concerning 1,650 registry patients was analysed. The analysis was based on cathlab classification with cardiac surgery on site (n = 996) and without (n = 654). RESULTS: There was a 0.3% rate of transfer (two patients out of 654) for urgent coronary artery bypass grafting from PCI centres without cardiac surgery on site. There were no differences in in-hospital and long-term mortality in patients in both studied groups. CONCLUSIONS: No differences in short and long-term outcomes were noticed for STEMI patients treated in centres with or without cardiac surgery on-site.

Impact of percutaneous coronary intervention on biomarker levels in patients in the subacute phase following myocardial infarction: the Occluded Artery Trial (OAT) biomarker ancillary study.

BACKGROUND: The purpose of the Occluded Artery Trial (OAT) Biomarker substudy was to evaluate the impact of infarct related artery (IRA) revascularization on serial levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and dynamics of other biomarkers related to left ventricular remodeling, fibrosis and angiogenesis. METHODS: Patients were eligible for OAT-Biomarker based on the main OAT criteria. Of 70 patients (age 60.8 ± 8.8, 25% women) enrolled in the substudy, 37 were randomized to percutaneous coronary intervention (PCI) and 33 to optimal medical therapy alone. Baseline serum samples were obtained prior to OAT randomization with follow up samples taken at one year. The primary outcome was percent change of NT-proBNP from baseline to 1 year. The secondary outcomes were respective changes of matrix metalloproteinases (MMP) 2 and 9, tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), Vascular Endothelial Growth Factor (VEGF), and Galectin-3. RESULTS: Paired (baseline and one-year) serum samples were obtained in 62 subjects. Baseline median NT-proBNP level was 944.8 (455.3, 1533) ng/L and decreased by 69% during follow-up (p < 0.0001). Baseline MMP-2 and TIMP-2 levels increased significantly from baseline to follow-up (p = 0.034, and p = 0.027 respectively), while MMP-9 level decreased from baseline (p = 0.038). Levels of VEGF and Galectin-3 remained stable at one year (p = NS for both). No impact of IRA revascularization on any biomarker dynamics were noted. CONCLUSIONS: There were significant changes in measured biomarkers related to LV remodeling, stress, and fibrosis following MI between 0 and 12 month. Establishing infarct vessel patency utilizing stenting 24 hours-28 days post MI did not however influence the biomarkers' release.

Mechanisms of oxidative stress in human aortic aneurysms--association with clinical risk factors for atherosclerosis and disease severity.

UNLABELLED: Aortic abdominal aneurysms (AAA) are important causes of cardiovascular morbidity and mortality. Oxidative stress may link multiple mechanisms of AAA including vascular inflammation and increased metalloproteinase activity. However, the mechanisms of vascular free radical production remain unknown. Accordingly, we aimed to determine sources and molecular regulation of vascular superoxide (O2(-)) production in human AAA. METHODS AND RESULTS: AAA segments and matched non-dilated aortic samples were obtained from 40 subjects undergoing AAA repair. MDA levels (determined by HPLC/MS) were greater in plasma of AAA subjects (n=16) than in risk factor matched controls (n=16). Similarly, superoxide production, measured by lucigenin chemiluminescence and dihydroethidium fluorescence, was increased in aneurysmatic segments compared to non-dilated aortic specimens. NADPH oxidases and iNOS are the primary sources of O2(-) in AAA. Xanthine oxidase, mitochondrial oxidases and cyclooxygenase inhibition had minor or no effect. Protein kinase C inhibition had no effect on superoxide production in AAA. NADPH oxidase subunit mRNA levels for p22phox, nox2 and nox5 were significantly increased in AAAs while nox4 mRNA expression was lower. Superoxide production was higher in subjects with increased AAA repair risk Vanzetto score and was significantly associated with smoking, hypercholesterolemia and presence of CAD in AAA cohort. Basal superoxide production and NADPH oxidase activity were correlated to aneurysm size. CONCLUSIONS: Increased expression and activity of NADPH oxidases are important mechanisms underlying oxidative stress in human aortic abdominal aneurysm. Uncoupled iNOS may link oxidative stress to inflammation in AAA. Oxidative stress is related to aneurysm size and major clinical risk factors in AAA patients.

Infarct size determines myocardial uptake of CD34+ cells in the peri-infarct zone: results from a study of (99m)Tc-extametazime-labeled cell visualization integrated with cardiac magnetic resonance infarct imaging.

BACKGROUND: Effective progenitor cell recruitment to the ischemic injury zone is a prerequisite for any potential therapeutic effect. Cell uptake determinants in humans with recent myocardial infarction are not defined. We tested the hypothesis that myocardial uptake of autologous CD34(+) cells delivered via an intracoronary route after recent myocardial infarction is related to left ventricular (LV) ejection fraction (LVEF) and infarct size. METHODS AND RESULTS: Thirty-one subjects (age, 36-69 years; 28 men) with primary percutaneous coronary intervention-treated anterior ST-segment-elevation myocardial infarction and significant myocardial injury (median peak troponin I, 138 ng/dL [limits, 58-356 ng/dL]) and sustained LVEF depression at ≤45% were recruited. On day 10 (days 7-12), 4.3×10(6) (0.7-9.9×10(6)) (99m)Tc-extametazime-labeled autologous bone marrow CD34(+) cells (activity, 77 MBq [45.9-86.7 MBq]) were administered transcoronarily (left anterior descending coronary artery). (99m)Tc-methoxyisobutyl isonitrile (99(m)Tc-MIBI) single-photon emission computed tomography before cell delivery showed 7 (2-11) (of 17) segments with definitely abnormal/absent perfusion. Late gadolinium-enhanced infarct core mass was 21.7 g (4.4-45.9 g), and infarct border zone mass was 29.8 g (3.9-60.2 g) (full-width at half-maximum, signal intensity thresholding algorithm). One hour after administration, 5.2% (1.7%-9.9%) of labeled cell activity localized in the myocardium (whole-body planar γ scan). Image fusion of labeled cell single-photon emission computed tomography with LV perfusion single-photon emission computed tomography or with cardiac magnetic resonance infarct imaging indicated cell uptake in the peri-infarct zone. Myocardial uptake of labeled cells activity correlated in particular with late gadolinium-enhanced infarct border zone mass (r=0.84, P<0.0001) and with peak troponin I (r=0.76, P<0.001); it also correlated with severely abnormal/absent perfusion segment number (r=0.45, P=0.008) and late gadolinium-enhanced infarct core (r=0.58 and r=0.84, P<0.0001) but not with echocardiography LVEF (r=-0.07, P=0.68) or gated single-photon emission computed tomography LVEF (r=-0.28, P=0.16). The correlation with cardiac magnetic resonance imaging-LVEF was weak (r=-0.38; P=0.04). CONCLUSIONS: This largest human study with labeled bone marrow CD34(+) cell transcoronary transplantation after recent ST-segment-elevation myocardial infarction found that myocardial cell uptake is determined by infarct size rather than LVEF and occurs preferentially in the peri-infarct zone.

Relationship between biomarkers and subsequent bleeding risk in ST-segment elevation myocardial infarction patients treated with paclitaxel-eluting stents: a HORIZONS-AMI substudy.

Major bleeding complications in STEMI patients result in significant mortality, morbidity and healthcare cost. Identification of patients at increased risk of bleeding is therefore essential. New biomarkers might be of incremental value to identify patients at risk for bleeding after primary PCI. A total of 26 biomarkers were measured at enrolment and analyzed at a central core laboratory in 464 STEMI patients in the HORIZONS-AMI trial. We investigated the relationship between tertiles of biomarker and in hospital non-CABG major bleeding. In hospital non-CABG major bleeding occurred in 3.7% of patients (n = 17). Increasing levels of cystatin C and D-dimer at admission were associated with higher rates of in hospital major bleeding. After adjustment for a risk score for bleeding, the odds ratio for in hospital major bleeding was 3.13 for cystatin C > 2.04 mg/L (p = 0.046) and 3.28 for ESAM > 34 ng/mL (p = 0.037). In this exploratory analysis of the HORIZONS-AMI biomarker substudy, high cystatin C and ESAM levels were associated with a higher risk of major bleeding. Larger studies are warranted to confirm the prognostic value of cystatin C and ESAM for major bleeding in STEMI patients.

Computed tomography coronary angiography and invasive coronary angiography demonstrate high correlation for area stenosis quantification in noncalcified and mixed plaques.

We compared the variance of area and diameter significant stenosis measurement between quantitative computed tomography coronary angiography (QCTA) and quantitative invasive coronary angiography (QCA). Fifty patients presenting 65 significant coronary artery stenoses (≥70% area stenosis) in QCTA and QCA were included. Spearman's rank correlation revealed that area stenosis measurement by QCTA and QCA yields higher correlation than diameter stenosis and is highest for noncalcified and mixed lesions.

Platelet activation and microvascular injury in patients with ST-segment elevation myocardial infarction.

BACKGROUND: Dual antiplatelet therapy reduces the risk of thrombotic complications after primary percutaneous coronary intervention (PCI). AIM: To assess whether inhibition of platelet function attenuates microvascular damage in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: We studied 83 STEMI patients treated with primary PCI. Platelet aggregation was measured on admission (ADM) and 4 days later (D4) by light transmission aggregometry after stimulation with 0.5 mM of arachidonic acid and after stimulation with 5 and 20 µM of adenosine diphosphate (ADP) on treatment with dual antiplatelet therapy with aspirin and clopidogrel. Platelet-neutrophil aggregate (PNA) and platelet-monocyte aggregate (PMA) were analysed by flow cytometry. Contrast-enhanced magnetic resonance imaging was performed 2-4 days after STEMI to detect the area of perfusion defect at rest and to determine the size of microvascular obstruction. Microvascular obstruction was expressed as a percentage of infarct area. RESULTS: Perfusion defect at rest was found in 56 (67.5%) patients whereas microvascular obstruction in 63 (75.9%) patients. Patients with perfusion defect at rest had on admission a significantly higher level of both PMA (7.0 vs. 4.5%, p = 0.004) and PNA (4.1 vs. 2.2%, p = 0.016), however there were no significant differences at D4. Platelet aggregation after stimulation with 5 µM of ADP on ADM was correlated (r = 0.37, p = 0.004) with microvascular obstruction area. Moreover, the higher the concentration of PMA(ADM) (r = 0.31, p = 0.016), PNA(ADM) (r = 0.34, p = 0.006) and PM(AD4) (r = 0.35, p = 0.005) the larger the size of microvascular obstruction. Infarct size (ß = 0.43, 95% CI 0.19 to 0.67, p 〈 0.0001), TIMI < 3 after PCI (ß = -0.27, 95% CI -1.90 to -0.11, p = 0.015) and PMA(D4) (ß = 0.21, 95% CI 0.13 to 1.86, p = 0.032) independently influenced the size of microvascular obstruction (R2 = 0.60, p 〈 0.0001). CONCLUSIONS: Excessive platelet activation during reperfusion in STEMI patients despite dual antiplatelet therapy is associated with greater microvascular impairment.

Relationship between biomarkers and subsequent clinical and angiographic restenosis after paclitaxel-eluting stents for treatment of STEMI: a HORIZONS-AMI substudy.

Drug-eluting stents (DES) reduce the incidence of in-stent restenosis (ISR) after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). Whether the use of biomarkers might be of utility to identify patients who remain at risk for DES ISR after primary PCI has never been examined. A total of 26 biomarkers were measured at enrollment and 30 days and analyzed at a central core laboratory in 501 STEMI patients from the HORIZONS-AMI trial. All patients underwent primary PCI with the TAXUS paclitaxel-eluting stent (PES), were scheduled for routine angiographic follow-up at 13 months, and were followed for 3 years. Mean in-stent late-loss was 0.28 ± 0.57 mm, and target lesion revascularization (TLR) at 3 years occurred in 9.1 % of patients. Low levels of interleukin-6 (IL-6) and placental growth factor (PLGF) at admission were associated with both higher in-stent late loss and ischemia-driven TLR. Additionally, low admission levels of cardiotrophin-1 (CT-1) were associated with higher rates of ischemia-driven TLR. At 30-day follow-up lower values of IL-1ra (IL-1ra), matrix metalloproteinase 9 (MMP9), and myeloperoxidase (MPO), and a decline relative to admission in IL-1ra, monocyte chemotactic protein-1 (MCP-1), and MMP9 were associated with higher in-stent late loss. Low values of IL-6 at 30 days were also associated with ischemia-driven TLR. After multivariate adjustment, only MPO at 30 days and a decline of MCP-1 between admission and 30 days were associated with in-stent late loss, and only CT-1 was associated with TLR. MPO at 30 days and a decline of MCP-1 between admission and 30 days were independently associated with in-stent late loss, and CT-1 was associated with TLR. Additional studies to confirm and validate the utility of these biomarkers are warranted.