microRNAs Associated with Carotid Plaque Development and Vulnerability: The Clinician's Perspective.

Ischemic stroke (IS) related to atherosclerosis of large arteries is one of the leading causes of mortality and disability in developed countries. Atherosclerotic internal carotid artery stenosis (ICAS) contributes to 20% of all cerebral ischemia cases. Nowadays, atherosclerosis prevention and treatment measures aim at controlling the atherosclerosis risk factors, or at the interventional (surgical or endovascular) management of mature occlusive lesions. There is a definite lack of the established circulating biomarkers which, once modulated, could prevent development of atherosclerosis, and consequently prevent the carotid-artery-related IS. Recent studies emphasize that microRNA (miRNA) are the emerging particles that could potentially play a pivotal role in this approach. There are some research studies on the association between the expression of small non-coding microRNAs with a carotid plaque development and vulnerability. However, the data remain inconsistent. In addition, all major studies on carotid atherosclerotic plaque were conducted on cell culture or animal models; very few were conducted on humans, whereas the accumulating evidence demonstrates that it cannot be automatically extrapolated to processes in humans. Therefore, this paper aims to review the current knowledge on how miRNA participate in the process of carotid plaque formation and rupture, as well as stroke occurrence. We discuss potential target miRNA that could be used as a prognostic or therapeutic tool.

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.

Profilin 1 and Mitochondria-Partners in the Pathogenesis of Coronary Artery Disease?

Atherosclerosis remains a large health and economic burden. Even though it has been studied for more than a century, its complex pathophysiology has not been elucidated. The relatively well-established contributors include: chronic inflammation in response to oxidized cholesterol, reactive oxygen species-induced damage and apoptosis. Recently, profilin 1, a regulator of actin dynamics emerged as a potential new player in the field. Profilin is abundant in stable atherosclerotic plaques and in thrombi extracted from infarct-related arteries in patients with acute myocardial infarction. The exact role of profilin in atherosclerosis and its complications, as well as its mechanisms of action, remain unknown. Here, we summarize several pathways in which profilin may act through mitochondria in a number of processes implicated in atherosclerosis.

NEUTROPHIL-LYMPHOCYTE RATIO AND PLATELET-LYMPHOCYTE RATIO AS PREDICTORS OF CORONARY MICROCIRCULATORY DISEASE OCCURRENCE AND OUTCOME IN PATIENTS WITH CHRONIC CORONARY SYNDROME AND NO SIGNIFICANT CORONARY ARTERY STENOSIS.

OBJECTIVE: Introduction: Index of microcirculatory resistance assessment is an invasive method of measuring coronary microcirculation function. Association between impaired microcirculatory function and higher rate of cardiovascular events was proven. Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio seem to be a promising parameters to predict coronary microcirculatory disease in patients with chronic coronary syndrome. The aim: To determine neutrophil-lymphocyte ratio and platelet-lymphocyte ratio levels in patients with coronary microcirculatory disease and potential association with clinical outcome. PATIENTS AND METHODS: Material and methods: 82 consecutive patients with mean age of 67 years, 67% male, were tested for presence of coronary microcirculatory disease using index of microcirculatory resistance. Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio were calculated based on admission full blood count. Follow-up with major adverse cardiac and cardiovascular events registration was performed (median 24 months). RESULTS: Results: The study showed significantly higher neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in patients with coronary microcirculatory disease compared to control group (3.58±2.61 vs 2.54±1.09 and 164±87.9 vs 124±36.6 respectively). Higher level of platelet-lymphocyte ratio in patients with coronary microcirculatory disease results in worse MACCE-free survival. Optimal cut-off values of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio to detect coronary microcirculatory disease were 3.2 and 181.3, respectively. CONCLUSION: Conclusions: Higher neutrophil-lymphocyte ratio and platelet-lymphocyte ratio are associated with increased index of microcirculatory resistance value. Platelet-lymphocyte ratio may be used as a predictor of worse outcome in patients with coronary microcirculatory disease.

Nitric oxide for inhalation in ST-elevation myocardial infarction (NOMI): a multicentre, double-blind, randomized controlled trial.

Aims: Inhalation of nitric oxide (iNO) during myocardial ischaemia and after reperfusion confers cardioprotection in preclinical studies via enhanced cyclic guanosine monophosphate (cGMP) signalling. We tested whether iNO reduces reperfusion injury in patients with ST-elevation myocardial infarction (STEMI; NCT01398384). Methods and results: We randomized in a double-blind, placebo-controlled study 250 STEMI patients to inhale oxygen with (iNO) or without (CON) 80 parts-per-million NO for 4 h following percutaneous revascularization. Primary efficacy endpoint was infarct size as a fraction of left ventricular (LV) size (IS/LVmass), assessed by delayed enhancement contrast magnetic resonance imaging (MRI). Pre-specified subgroup analysis included thrombolysis-in-myocardial-infarction flow in the infarct-related artery, troponin T levels on admission, duration of symptoms, location of culprit lesion, and intra-arterial nitroglycerine (NTG) use. Secondary efficacy endpoints included IS relative to risk area (IS/AAR), myocardial salvage index, LV functional recovery, and clinical events at 4 and 12 months. In the overall population, IS/LVmass at 48-72 h was 18.0 ± 13.4% in iNO (n = 109) and 19.4 ± 15.4% in CON [n = 116, effect size -1.524%, 95% confidence interval (95% CI) -5.28, 2.24; P = 0.427]. Subgroup analysis indicated consistency across clinical confounders of IS but significant treatment interaction with NTG (P = 0.0093) resulting in smaller IS/LVmass after iNO in NTG-naïve patients (n = 140, P < 0.05). The secondary endpoint IS/AAR was 53 ± 26% with iNO vs. 60 ± 26% in CON (effect size -6.8%, 95% CI -14.8, 1.3, P = 0.09) corresponding to a myocardial salvage index of 47 ± 26% vs. 40 ± 26%, respectively, P = 0.09. Cine-MRI showed similar LV volumes at 48-72 h, with a tendency towards smaller increases in end-systolic and end-diastolic volumes at 4 months in iNO (P = 0.048 and P = 0.06, respectively, n = 197). Inhalation of nitric oxide was safe and significantly increased cGMP plasma levels during 4 h reperfusion. The Kaplan-Meier analysis for the composite of death, recurrent ischaemia, stroke, or rehospitalizations showed a tendency toward lower event rates with iNO at 4 months and 1 year (log-rank test P = 0.10 and P = 0.06, respectively). Conclusions: Inhalation of NO at 80 ppm for 4 h in STEMI was safe but did not reduce infarct size relative to absolute LVmass at 48-72h. The observed functional recovery and clinical event rates at follow-up and possible interaction with nitroglycerine warrant further studies of iNO in STEMI.

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.

Multiterritory Atherosclerosis and Carotid Intima-Media Thickness as Cardiovascular Risk Predictors After Percutaneous Angioplasty of Symptomatic Subclavian Artery Stenosis.

OBJECTIVES: To identify independent predictors of cardiovascular events among patients with subclavian artery stenosis. METHODS: Two hundred eighteen consecutive patients with subclavian artery stenosis referred to angioplasty were examined for coexistent coronary, renal, or lower extremity artery stenosis of 50% or greater. Initial carotid intima-media thickness and internal carotid artery (ICA) stenosis were assessed. Intima-media thickness was reassessed in 108 randomly chosen patients to evaluate the change over time. The incidence of cardiovascular death, myocardial infarction (MI), ischemic stroke, and symptomatic lesion progression was recorded. RESULTS: The patients included 116 men and 102 women (mean age ± SD, 62.1 ± 8.4 years). Isolated subclavian artery stenosis and involvement of 1, 2, and 3 or 4 other territories with stenosis of 50% or greater were found in 46 (21.1%), 83 (38.1%), 55 (25.2%), and 34 (15.6%) patients, respectively. Internal carotid artery stenosis of 50% or greater (relative risk [RR], 1.54; 95% confidence interval [CI], 1.39-1.70; P < .001) and initial intima-media thickness (RR, 1.16; 95% CI, 1.05-1.28; P = .005) were identified as independent markers of multiterritory atherosclerosis. The optimal intima-media thickness cutoff for atherosclerosis extent was 1.3 mm (sensitivity, 75.6%; specificity, 76.1%). During follow-up of 57 ± 35 months, cardiovascular death, MI, and ischemic stroke occurred in 29 patients (13.3%). Those patients had significantly higher intima-media thickness progression (+0.199 ± 0.57 versus +0.008 ± 0.26 mm; P = .039) and more widespread initial atherosclerosis (mean territories, 1.8 ± 1.1 versus 1.3 ± 1.1; P = .042). Independent predictors of cardiovascular death, MI, ischemic stroke, and lesion progression were coronary artery disease (RR, 1.32; 95% CI, 1.10-1.58; P = .003) and intima-media thickness progression (RR, 1.22; 95% CI, 1.02-1.46; P = .033; sensitivity, 75.0%; specificity, 61.8%). CONCLUSIONS: In patients with symptomatic subclavian artery stenosis, baseline carotid intima-media thickness and ICA stenosis of 50% or greater are associated with multiterritory atherosclerosis, whereas intima-media thickness progression is associated with the risk of cardiovascular events.

Borderline trend towards long-term mortality benefit from drug eluting stents implantation in ST-elevation myocardial infarction patients in Poland-data from NRDES registry.

OBJECTIVES: To analyze long-term outcome of ST-Elevation Myocardial Infarction (STEMI) and non-STEMI (NSTEMI) patients treated with Drug Eluting Stents (DES) stents with regard to mortality and stent thrombosis rates based on the national Polish PCI registry database. BACKGROUND: Only a few studies suggested potential trend towards lower mortality in STEMI patients treated with DES. Current European Society of Cardiology STEMI guidelines recommend DES use only with one restriction to suspected patient poor compliance or contraindication to dual antiplatelet therapy. METHODS: Thirteen high-volume interventional cardiology centers in Poland enrolled patients in National Registry of Drug Eluting Stents (NRDES) Registry from October 2010 till October 2011. RESULTS: There were 2686 patients enrolled in NRDES Registry. Eighty five patients (3%) had both DES and BMS implanted at index PCI procedure and were excluded from further analysis. A subpopulation of STEMI (1709; 66%) and NSTEMI (892; 34%) patients was selected for BMS vs DES comparison. A significant difference in favor of DES group for 1-year mortality was found in STEMI subgroup (P < 0.0001-unadjusted and P = 0.0497 after propensity score adjustment). No such differences were noticed for NSTEMI subgroup or stent thrombosis comparisons. CONCLUSIONS: A strong selection bias for DES stents was observed with regard to demographic and angiographic characteristics in both STEMI and NSTEMI. DES implantation was associated with similar ischemic outcome to BMS at 1-year follow-up. STEMI patients with DES presented a trend towards lower long-term mortality at 1 year in comparison to BMS.

Conduction abnormality and arrhythmia after transcatheter closure of atrial septal defect.

BACKGROUND: The aim of this study was to prospectively perform ambulatory 24-h ECG monitoring to assess the effects of transcatheter closure of atrial septal defect (ASD). METHODS AND RESULTS: A total of 235 consecutive subjects (female, n=163; male, n=72; age, 44.6±14.4 years) were enrolled in the study, who were due undergo ASD closure. Holter monitoring was performed before procedure and at 1, 6 and 12 months of follow-up. During the procedure transient supraventricular arrhythmia occurred in 8 patients (3.4%), and bradycardia in 3 (1.3%). In 3 patients (1.3%) an episode of atrial fibrillation occurred in the first hour after the procedure. In 8 patients (3.4%) transient first-degree atrioventricular block was noted. A significant increase in number of supraventricular extrasystoles (SVES)/24 h was noted 1 month after the procedure (P<0.001). On multiple forward stepwise regression analysis, device size and fluoroscopy time had an influence on increase in number of SVES seen 1 month after the procedure (P<0.001). CONCLUSIONS: Transcatheter closure of ASD is associated with a transient increase in supraventricular premature beats and a small risk of conduction abnormalities and paroxysmal atrial fibrillation in early follow-up. Transcatheter closure of ASD does not reduce arrhythmia that appears prior to ASD closure. Larger device size and longer procedure time are associated with increased risk of supraventricular arrhythmia on early follow-up.

Conduction Abnormality and Arrhythmia After Transcatheter Closure of Atrial Septal Defect.

Background:The aim of this study was to prospectively perform ambulatory 24-h ECG monitoring to assess the effects of transcatheter closure of atrial septal defect (ASD).Methods and Results:A total of 235 consecutive subjects (female, n=163; male, n=72; age, 44.6±14.4 years) were enrolled in the study, who were due undergo ASD closure. Holter monitoring was performed before procedure and at 1, 6 and 12 months of follow-up. During the procedure transient supraventricular arrhythmia occurred in 8 patients (3.4%), and bradycardia in 3 (1.3%). In 3 patients (1.3%) an episode of atrial fibrillation occurred in the first hour after the procedure. In 8 patients (3.4%) transient first-degree atrioventricular block was noted. A significant increase in number of supraventricular extrasystoles (SVES)/24 h was noted 1 month after the procedure (P<0.001). On multiple forward stepwise regression analysis, device size and fluoroscopy time had an influence on increase in number of SVES seen 1 month after the procedure (P<0.001).Conclusions:Transcatheter closure of ASD is associated with a transient increase in supraventricular premature beats and a small risk of conduction abnormalities and paroxysmal atrial fibrillation in early follow-up. Transcatheter closure of ASD does not reduce arrhythmia that appears prior to ASD closure. Larger device size and longer procedure time are associated with increased risk of supraventricular arrhythmia on early follow-up.

D-dimer levels predict ischemic and hemorrhagic outcomes after acute myocardial infarction: a HORIZONS-AMI biomarker substudy.

D-dimer is a product of cross linked fibrin degradation and is a measure of the amount of fibrin turnover. As such, D-dimer might be of utility in the prediction of both thrombotic and hemorrhagic events. Therefore, the aim of the present study was to evaluate whether elevated D-dimer levels on admission and at discharge could predict subsequent ischemic and hemorrhagic events in patients with acute myocardial infarction (AMI). D-dimer was measured on admission and at discharge in 461 out of a total of 3,602 patients in the HORIZONS-AMI trial, as part of the formal prespecified biomarker substudy. The predictive value for major adverse cardiovascular events (MACE) and non-CABG major bleeding after 3 year follow up was investigated by stratifying patients in groups of D-dimer level and comparing event rates using Kaplan-Meier and calculating hazard ratios using Cox proportional hazards models. D-dimer levels ≥ 0.71 µg/mL on admission were associated with an adjusted hazard ratio of 2.58 for MACE (p = 0.0014) and 4.61 for major bleeding (p = 0.0018). A discharge D-dimer level ≥ 1.26 µg/mL was associated with a higher risk for MACE by univariate analysis (HR 1.88, p = 0.037), but lost its significance after multivariate adjustment (HR 1.77, p = 0.070). High D-dimer levels on admission were associated with a higher risk of MACE and non-CABG major bleeding in STEMI patients undergoing pPCI.

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.

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.

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.

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.

Hemodynamic effects of larger volume intra-aortic balloon pump during high-risk percutaneous coronary interventions.

BACKGROUND: Percutaneous coronary intervention in high-risk patients (HRPCI) is associated with increased risk of complications. Mechanical circulatory support devices, including intra-aortic balloon pump (IABP) may bridge patient safely throughout the procedure. AIM: We aimed to describe hemodynamic effects of larger (MEGA) compared to standard (STRD) volume IABP or no balloon control group (CTRL) during HRPCI. METHODS: In this single-center, open-label randomized controlled trial HRPCI were randomly assigned to three groups according to planned hemodynamic support: MEGA, STDR and CTRL in a 1:1:1 scheme. Screening failure patients formed registry (REG). We analyzed data from pulmonary artery catheter especially cardiac output and cardiac power output (CPO) with Fick method and pulmonary artery wedge pressure (PCWP), as well as left ventricle systolic pressure (LVSP) with PIGTAIL catheter. We also calculated endocardial viability ratio (EVR) and analyzed pressure tracings from the IABP console. We compared baseline and on-support values. Final hemodynamic analysis was done on per-treatment basis, including REG patients. RESULTS: A total of 47 patients were analyzed (16 MEGA, 10 STRD and 21 CTRL). Compared to CTRL we found significant increase from baseline to on-support value for cardiac output and CPO in the MEGA, but not in the STRD group. The change in EVR (increase) and in LVSP (decrease) was significant equally in MEGA and STRD vs. CTRL group, but PCWP did not change significantly for both balloons vs. CTRL. Diastolic augmented pressure with IABP was higher in MEGA than STRD and was positively correlated with systolic unloading. CONCLUSIONS: We observed more favorable hemodynamic effects of larger compared to standard volume balloon.

Ticagrelor effectively inhibits platelet aggregation in comatose survivors of cardiac arrest undergoing primary percutaneous coronary intervention treated with mild therapeutic hypothermia.

BACKGROUND: Mild therapeutic hypothermia (MTH) is believed to reduce the effectiveness of antiplatelet drugs. Effective dual-antiplatelet therapy after percutaneous coronary intervention (PCI) is mandatory to avoid acute stent thrombosis. The effectiveness of ticagrelor in MTH-treated out-of-hospital cardiac arrest (OHCA) survivors is still a matter of debate. The aim of the study was to evaluate the impact of MTH on the platelet-inhibitory effect of ticagrelor in comatose survivors of OHCA treated with primary PCI. METHODS: Eighteen comatose survivors of OHCA with acute coronary syndrome undergoing immediate PCI treated with MTH were compared with 14 patients with uncomplicated primary myocardial infarction after PCI, matched for gender and age, in a prospective, single-center, observational study. Platelet aggregation was evaluated using VerifyNow P2Y12 point-of-care testing at 3 time points: admission (T0), during MTH (T1), and 48-72 h after rewarming (T2). RESULTS: Ticagrelor effectively inhibits platelet aggregation in OHCA patients subjected to MTH and in all patients in the control group. The effectiveness of ticagrelor did not differ between the MTH group and the control group (p = 0.581). In 2 cases in the MTH population, the platelet response to ticagrelor was inadequate, and in one of them it remained insufficient during the re-warming phase. There was no stent thrombosis in these patients. CONCLUSIONS: The present study confirmed the effectiveness of ticagrelor to inhibit platelets in myocardial infarction patients after OHCA treated with primary PCI undergoing hypothermia. The use of cooling was not associated with an increased risk of stent thrombosis.

Right ventricular-pulmonary arterial coupling in patients with implanted left ventricular assist devices.

OBJECTIVE: Both the right ventricular (RV) contractile function and pulmonary arterial (PA) pressure influence clinical outcomes in patients supported with left ventricular assist devices (LVADs), but the impact of RV-PA coupling is unknown. This study aimed to determine the prognostic impact of RV-PA coupling in patients with implanted LVADs. METHODS: Patients with implanted third-generation LVADs were retrospectively enrolled. The RV-PA coupling was assessed preoperatively by the ratio of RV free wall strain (RVFWS) derived from speckle-tracking echocardiography and noninvasively measured peak RV systolic pressure (RVSP). The primary end point was a composite of all-cause mortality or right heart failure (RHF) hospitalization. Secondary end points consisted of all-cause mortality at a 12-month follow-up and RHF hospitalization. RESULTS: A total of 103 patients were screened, and 72 with good RV myocardial imaging were included. The median age was 57 years; 67 patients (93.1%) were men, and 41 (56,9%) had dilated cardiomyopathy. A receiver-operating characteristic analysis (AUC 0.703, 51.5% sensitivity, 94.9% specificity) was used to identify the optimal cutoff point (0.28%/mmHg) for the RVFWS/TAPSE threshold. Nineteen subjects (26.4%) had advanced RV-PA uncoupling. Event rates were estimated using the Kaplan-Meier method showing a strong association with an increased risk for the primary end point of death or RHF hospitalization (89.47% vs. 30.19%, p < 0.001). A similar observation applied to all-cause mortality (47.37% vs. 13.21%, p = 0.003) and RHF hospitalization (80.43% vs. 20%, p < 0.001). CONCLUSIONS: An advanced RV dysfunction assessed by RV-PA coupling may serve as a predictor of adverse outcomes in patients with implanted LVADs.

The change of angina levels in patients with chronic coronary syndromes and coronary microcirculatory dysfunction - a prospective study with 24 months follow-up.

Introduction: A substantial proportion of patients with chronic coronary syndromes suffer from angina even after medical treatment and revascularization. Coronary microvascular dysfunction (CMD) is discussed as a potential mechanism. Aim: To assess angina status in patients with chronic coronary syndromes undergoing functional assessment of coronary circulation regarding the presence of coronary microcirculatory dysfunction. Material and methods: The study included 101 consecutive patients referred for coronary angiography requiring functional stenosis assessment, with median age of 66 years, 74% male, diagnosed or treated for dyslipidemia (91%) and diabetes type 2 (42%), 20% with a history of prior non-ST myocardial infarction. Fractional flow reserve (FFR), coronary flow reserve (CFR), resistive reserve ratio (RRR), and index of microcirculatory resistance (IMR) were measured. The diagnosis of CMD was defined by either IMR ≥ 25 units or CFR ≤ 2.0 in case of no significant stenosis. A change of one CCS class over 24 months follow-up was considered clinically significant. Results: In patients without CMD diagnosis, there was a significant decrease in angina intensity (p < 0.001). Lack of angina improvement was associated with lower median RRR (2.30 (1.70, 3.30) vs. 3.05 (2.08, 4.10), p = 0.004) and lower median CFR (1.90 (1.40, 2.50) vs. 2.30 (IQR: 1.60, 3.00), p = 0.021), as compared to patients with angina improvement. Conclusions: The presence of CMD is a risk factor for no angina improvement. Impaired coronary resistive reserve ratio and lower microvascular reactivity may be one of the pathomechanisms leading to the lack of angina improvement in patients with chronic coronary syndromes.