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Cardiac involvement in systemic sclerosis (SSc) implies a worse prognosis. Little is known about the right atrial (RA) mechanics in this disease, but recent data suggest that it correlates well with the functional capacity of the patients in conditions with known right heart involvement. Thus we aimed to investigate the abnormalities of the RA function as compared with healthy subjects and to assess the potential correlations between RA mechanics and the functional capacity in SSc patients using 2D speckle tracking technique. A total of 70 SSc patients (age: 57 ± 12 years) were investigated. Functional capacity was measured with 6-minute walk test (6MWT). Echocardiographic parameters of the right ventricular (RV) systolic function (TAPSE, RVFAC), parameters of the tricuspid inflow (E, A), and tricuspid annular systolic (S), early- (e') and late- (a') diastolic myocardial velocities were measured. RV wall thickness was obtained. RA reservoir (ε R ), conduit (ε CD ), and contractile (ε CT ) strain were measured. RA stiffness was calculated as ratio of E/e' to ε R . Echocardiographic data were compared with an age- and gender-matched group of 25 healthy volunteers. RA ε R (49.3 ± 10.7 vs 59.6 ± 9.9%, p = 0.000) and ε CD (26.8 ± 8.1 vs 34.3 ± 7.3%, p = 0.000) were significantly lower in SSc patients. No significant difference was found in ε CT (22.9 ± 5.8 vs 25.3 ± 5.7%, p = 0.082). RA stiffness was significantly increased in SSc patients (0.11 ± 0.04 vs 0.08 ± 0.02, p = 0.001). 6MWT distance was 391 ± 95m. In stepwise multiple linear regression analysis RV wall thickness (r = -0.289, p = 0.030) and RA stiffness (r = -0.418, p = 0.002) became independent predictors of 6MWT distance. In conclusion, RA ε R and ε CD are impaired, while RA stiffness is increased in SSc compared with healthy subjects. Speckle tracking-derived RA stiffness is turned out to be one of the main determinants of the functional capacity in SSc patients., (Copyright © 2018. Published by Elsevier Inc.)

Evidence is conflicting regarding the clinical benefits of selecting P2Y 12 inhibitors based on platelet function testing (PFT). Between March 1, 2013 and March 1, 2014, we collected clinical characteristics and platelet function data in a nationwide acute myocardial infarction (AMI) registry from 15 interventional cardiology centers in Hungary. The risk of all-cause mortality at 1 year were compared after propensity score (PS) matching between patients receiving PFT-guided and unguided P2Y 12 -inhibitor therapies. High platelet reactivity on clopidogrel (HPRoC) was uniformly defined with the Multiplate assay. A total of 5,583 patients with AMI and coronary intervention were registered. After exclusion of cases with contraindication to prasugrel, propensity matching resulted in a sample of 2,104 patients with well-adjusted characteristics. Clopidogrel was the dominant P2Y 12 inhibitor in both groups (unguided: 96% vs PFT guided: 85%, p <0.001). In the PFT-guided group, 19% of patients had HPRoC and 77% of them were switched to prasugrel. According to the adjusted analysis, all-cause mortality at 1 year was significantly lower in the PFT-guided compared with the unguided group (hazard ratio 0.57 [95% confidence interval 0.43 to 0.77], p <0.001). Although prasugrel treatment was not associated with lower all-cause mortality in the overall cohort, patients with HPRoC who switched to prasugrel had significantly lower mortality when compared with those continuing clopidogrel (hazard ratio 0.33 [95% confidence interval 0.12 to 0.92], p <0.05). In conclusion, in patients with AMI, PFT-guided treatment with a high rate of switchover to prasugrel was associated with a lower risk of mortality. Prasugrel was a predictor of lower mortality in patients with HPRoC but not in the overall cohort of AMI., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Left ventricular (LV) diastolic dysfunction is common in systemic sclerosis (SSc). Less is known, however, about left atrial (LA) mechanics in this context. The aim of this study was to investigate the correlation between LV diastolic function and LA mechanics in SSc patients with the use of volumetric and 2-dimensional speckle tracking-derived strain techniques and to compare the results with those obtained in healthy subjects., Methods and Results: Seventy-two SSc patients and 30 healthy volunteers (H) were investigated. LV diastolic function was classified as normal (I), impaired relaxation (II), and pseudonormal pattern (III). LA reservoir (H: 51.8 ± 7.4%; I: 45.1 ± 8.1%; II: 42.2 ± 6.6%; III: 36.6 ± 7.3%; analysis of variance: P < .001) and contractile strain (H: 24.8 ± 4.9%; I: 18.2 ± 4.4%; II: 21.5 ± 2.8%; III: 16.8 ± 3.6%; P < .001) already showed significant worsening in SSc patients with preserved LV diastolic function compared with healthy subjects. LA conduit strain (H: 27.1 ± 4.6%; I: 26.9 ± 5.7%; II: 20.6 ± 6.1%; III: 19.5 ± 5.3%; P < .001) was preserved in this early phase. Further deterioration of reservoir strain was pronounced in the pseudonormal group only. LA contractile strain increased significantly in the impaired relaxation group and then decreased with the further worsening of the LV diastolic function. Regarding phasic volume indices, the differences between groups were not always statistically significant., Conclusion: LA mechanics strongly reflects the changes in LV diastolic function in SSc. On the other hand, strain parameters of the LA reservoir and contractile function already show significant worsening in SSc patients with preserved LV diastolic function, suggesting that impairment of the LA mechanics is an early sign of myocardial involvement in SSc., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aims to conduct a meta-analysis comparing efficacy and safety outcomes between subcutaneous implantable cardioverter-defibrillator (S-ICD) and transvenous implantable cardioverter-defibrillator (TV-ICD)., Background: The S-ICD was developed to minimize complications related to the conventional TV-ICD. Direct comparison of clinical outcomes between the 2 devices has been limited by varying patient characteristics and definitions of complications with no randomized trials completed comparing these systems., Methods: Studies in the PubMed and Embase databases and secondary referencing sources were systematically reviewed. Studies meeting criteria were included in the meta-analysis. Baseline characteristics and outcome data of the S-ICD and TV-ICD groups were appraised and analyzed. A random-effects model was used to derive odds ratio (OR) with 95% confidence interval (CI)., Results: Five studies met inclusion criteria. Baseline characteristics were similar between the S-ICD and TV-ICD groups. Fewer lead complications occurred in the S-ICD group compared to the TV-ICD group (OR: 0.13; 95% CI: 0.05 to 0.38). The infection rate was similar between the S-ICD and TV-ICD groups (OR: 0.75; 95% CI: 0.30 to 1.89). There were no differences in system or device failures between groups (OR: 1.13; 95% CI: 0.43 to 3.02). Overall, inappropriate therapy (T-wave oversensing, supraventricular tachycardia, episodes of inappropriate sensing) was similar between the 2 groups (OR: 0.87; 95% CI: 0.51 to 1.49). However, the nature of inappropriate therapy was different between the S-ICD and TV-ICD groups. Both devices appear to perform equally well with respect to appropriate shocks., Conclusions: S-ICD reduced lead-related complications but was similar to TV-ICD with regard to non-lead-related complications, including inappropriate therapy. These results support the concept that S-ICD is a safe and effective alternative to TV-ICD in appropriate patients., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Galectin-3 is a beta-galactoside-binding lectin that may be related to tissue sclerosis or aberrant activation of angiogenesis in systemic sclerosis (SSc). The aim of our study was to determine the associations between galectin-3 levels and patient characteristics, as well as to investigate the long term prognostic value of galectin-3 in a large cohort of SSc patients., Methods: 152 patients with SSc (55±11years, 138 female) were included in our follow-up study. Blood samples and clinical data were collected at baseline. Primary and secondary outcomes were all-cause and cardiovascular mortality, respectively., Resultss: Galectin-3 levels showed positive correlation with the grade of left ventricular diastolic function (r=0.193; p=0.026), erythrocyte sedimentation rate (r=0.172; p=0.036) and serum level of C-reactive protein (r=0.200; p=0.015) while negative correlation with diffusing capacity for carbon monoxide (r=-0.228; p=0.006), in age, gender and BSA adjusted analyses. During the follow-up of 7.2±2.3years, 35 SSc patients (23%) died. In multivariate Cox regression analyses adjusted for age, gender, BSA, creatinine and NT-proBNP levels, galectin-3 was an independent predictor both of the all-cause mortality (HR: 2.780, 95% CI: 1.320-5.858, p=0.007) and cardiovascular mortality (HR: 3.346, 95% CI: 1.118-10.012, p=0.031). Using receiver-operating characteristic analysis, galectin-3>10.25ng/ml was found to be the best predictor of the all-cause mortality., Conclusions: Our results suggest that galectin-3 is an independent predictor of all-cause and cardiovascular mortality in SSc. Validation studies are required to establish whether galectin-3 may be proposed as simple biomarker for identifying patients with high mortality risk in SSc., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Data are limited on the real-life use of coronary intervention (PCI) and on its long-term efficacy and safety in elderly patients with acute myocardial infarction (AMI)., Methods: Data from a nation-wide registry of patients treated due to an AMI event in centers of invasive cardiology were analyzed for the potential interaction of age on the utilization of invasive therapy and outcome. Follow-up data of consecutive patients between March 1, 2013, and March 1, 2014 were analyzed. Differences in the risk of all-cause death at 1year between patients undergoing PCI versus others receiving conservative treatment were determined from vital records and were compared with propensity score matching., Results: A total of 8485 consecutive patients were enrolled at 19 centers. Sixty-three percent of the patients were male; the mean age was 65.1±12.4years. The proportion of STEMI cases was 51%. STEMI cases were treated with primary PCI in 91.0% while patients with NSTEACS underwent PCI in 71.0%. The age of patients was a significant determinant of deferring coronary angiography (Hazard ratio (HR): 0.524 95% confidence interval (CI) 0.47-0.59, p<0.001) and PCI (HR: 0.76 95% CI 0.73-0.80, p<0.001). One-year survival after PCI was significantly better both in the overall and in the propensity matched cohort (HR: 0.44 [95% CI: 0.39-0.49] and HR: 0.59 [95% CI: 0.50-0.69], p<0.001, both). This benefit remained consistent in age-dependent subgroup analyses., Conclusion: Coronary intervention is underused among the elderly despite the mortality benefit of interventional therapy in myocardial infarction that is consistent in all age groups., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The coagulation system contributes greatly to the evolution of myocardial infarction (MI). Anticoagulation may reduce the occurrence of MI as monotherapy or with concomitant use of aspirin. Activated factor X antagonists (anti-Xa) and direct thrombin inhibitors have promising results in various indications in non-inferiority trials. However, results regarding their cardiovascular safety are heterogeneous. We systematically evaluated the risk of MI and mortality in patients receiving the new-generation oral anti-Xa agent apixaban. Electronic databases were searched to find prospective, randomized, controlled clinical trials (RCT) that evaluated the clinical impact of apixaban. Efficacy measures included frequency of MI, cardiovascular and overall mortality. Outcome parameters of RCTs were pooled with a random-effects model. Between January 2000 and December 2013, 12 RCTs comprising 54,054 patients were identified. Based on the pooled results, there was no increase in the risk of MI in patients treated with apixaban [odds ratio (OR) 0.90; 95 % confidence interval (CI) 0.77-1.05; p = 0.17] compared to different controls. Cardiovascular and overall mortality with apixaban was comparable to the control groups (OR 0.88; 95 % CI 0.72-1.06; p = 0.18, OR 0.89; 95 % CI 0.77-1.03; p = 0.11, respectively). The pooled risk of major bleeding was lower in the apixaban treated groups (OR 0.84; 95 % CI 0.62-1.12; p = 0.23) however this reached significant level only in subgroup analysis of trials with anticoagulant regimes in the control (OR 0.66; 95 % CI 0.51-0.87; p = 0.003). In a broad spectrum of patients and compared to different controls apixaban treatment was not associated with an increase in MI or mortality.

Cardiac involvement is among the leading causes of mortality in patients with systemic sclerosis (SSc). Previously, we demonstrated in a single-center, cross-sectional study the frequent coexistence of different forms of cardiac involvement in systemic sclerosis including pulmonary arterial hypertension (PAH), coronary artery disease (CAD), and microvascular dysfunction (MVD). The aim of the present study was to investigate the prognostic significance of cardiac involvement. One hundred twenty patients with SSc were enrolled. All cases underwent a non-invasive cardiovascular protocol. In 30 patients with suspected cardiac involvement, right heart catheterization and intra-coronary pressure-wire-supplemented coronary angiography were performed. Clinical follow-up was 5 years. Patients with CAD at the baseline showed a trend for higher cardiovascular mortality while in patients with MVD this difference was significant (26.7 % versus 9.5 %, p = 0.077 and 30 % versus 10.1 %, p < 0.05, respectively). Cardiovascular mortality of PAH cases was higher but, however, did not reach statistical significance 21.4 % versus 10.4 %, p = 0.261. Cardiovascular event-free survival was significantly lower among patients with combinations of two or three disorders (p < 0.05). Multivariate analysis of organ involvements and comorbidities showed that the diffuse cutaneous subset, the presence of kidney involvement, the velocity of the tricuspid regurgitation, as well as diabetes mellitus were independent predictors of overall mortality. MVD and CAD alone or in combination with PAH significantly affected the 5-year cardiovascular mortality. These findings highlight the prognostic importance of coronary disease in patients with SSc [ www.clinicaltrials.gov (Reg. Nr.: NCT00843102)].

A systematic review and meta-analysis was performed to evaluate the effects of carvedilol versus metoprolol on the incidence of postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting in randomized controlled trials. Ovid MEDLINE, PubMed, CENTRAL, and Excepta Medica (EMBASE) were searched up to March 2013 for suitable randomized controlled trials. Data were pooled using random-effects model for pairwise analyses. A total of 4 trials with 601 patients were included in this analysis. Pairwise analyses showed that compared with metoprolol, carvedilol significantly reduced the incidence of postoperative atrial fibrillation (odds ratio 0.50, 95% confidence interval 0.32 to 0.80). In conclusion, compared with metoprolol, carvedilol significantly reduces the incidence of postoperative atrial fibrillation in patients undergoing coronary artery bypass grafting., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Administration of a P2Y 12 -receptor antagonist in addition to aspirin is mandatory in patients with acute coronary syndromes (ACS) or undergoing percutaneous coronary intervention (PCI) to reduce the occurrence of thrombotic events; however, their impact on mortality and stroke is unclear. We aimed to evaluate the influence of moderate (clopidogrel) or potent (prasugrel/ticagrelor) P2Y 12 -receptor inhibition on major cardiovascular outcomes among patients with ACS or undergoing PCI. Systematic literature search was performed to find randomised, controlled clinical trials comparing the clinical impact of clopidogrel with placebo or prasugrel/ticagrelor versus clopidogrel. Outcome measures included cardiovascular death, myocardial infarction (MI), total stroke and intracranial haemorrhage (ICH). Random-effects model with Mantel-Heanszel weighting was used to pool outcomes into a meta-analysis. Four studies comparing clopidogrel with placebo and five trials comparing clopidogrel with new P2Y 12 -receptor inhibitors were identified including a total of 107,473 patients. Compared to placebo, clopidogrel reduced the risk of cardiovascular death (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.87-0.99, p=0.02), MI (OR 0.80; 95%CI 0.74-0.88, p<0.00001) and stroke (OR 0.84; 95%CI 0.72-0.97, p=0.02), without influencing risk for ICH (OR 0.96; 95%CI 0.69-1.33, p=0.79). Treatment with prasugrel/ticagrelor provided additional benefit over clopidogrel regarding cardiovascular mortality (OR 0.86; 95%CI 0.78-0.94, p=0.002) and MI (OR: 0.83; 95%CI 0.74-0.93, p<0.001), but no advantage in stroke (OR: 1.06; 95%CI 0.88-1.26, p=0.55) and in ICH (OR: 1.16; 95%CI 0.75-1.81; p=0.49) was observed. Increased potency of P2Y 12 -receptor inhibition is associated with decreased risk in cardiovascular death and MI; however, this association is not true in case of stroke, where potent P2Y 12 -receptor antagonists have no incremental benefit over clopidogrel.

Background: A growing number of observational studies suggest that high on-clopidogrel platelet reactivity (HPR) is associated with recurrent thrombotic events after percutaneous coronary intervention. We aimed to perform an updated systematic review and meta-analysis on the clinical relevance of HPR to summarize the available evidence and to define more precise effect estimates., Methods: Relevant observational studies published between January 2003 and February 2010 were searched that presented intent-to-treat analyses on the clinical relevance of HPR measured with an adenosine diphosphate (ADP)-specific platelet function assay. The main outcome measures were cardiovascular (CV) death, definite/probable stent thrombosis (ST), nonfatal myocardial infarction (MI), and a composite end point of reported ischemic events. The outcome parameters were pooled with the random-effect model via generic inverse variance weighting., Results: Twenty studies comprising a total number of 9,187 patients qualified. High on-clopidogrel platelet reactivity appeared to be a strong predictor of MI, ST, and the composite end point of reported ischemic events (odds ratios [95% CI]: 3.00 [2.26-3.99], 4.14 [2.74-6.25], and 4.95 [3.34-7.34], respectively; P < .00001 for all cases). According to the meta-analysis, patients with HPR had a 3.4-fold higher risk for CV death compared with patients with normal ADP reactivity (odds ratio 3.35, 95% CI 2.39-4.70, P < .00001). Although there were large differences in the methodology as well as in the definition of HPR between studies, the predicted risk for CV death, MI, or ST was not heterogeneous (I(2): 0%, 0%, and 12%, respectively; P = not significant for all cases)., Conclusions: High on-clopidogrel platelet reactivity, measured by an ADP-specific platelet function assay, is a strong predictor of CV death, MI, and ST in patients after percutaneous coronary intervention., (2010 Mosby, Inc. All rights reserved.)

Background: Although transradial percutaneous coronary intervention (TRPCI) is widely applied for percutaneous procedures, its safety in the setting of ST-segment elevation (STEMI) is controversial. Our aim was to assess the safety and efficacy of TRPCI versus transfemoral PCI in the context of treating patients suffering acute myocardial infarction with STEMI., Methods: Randomized, case-control, and cohort studies comparing access-related complications were analyzed. Our objective was to determine if radial access reduces major bleeding and thereby reduces death and ischemic events compared to femoral access in this setting. A fixed-effects model was used with random effects for sensitivity analysis., Results: Twelve studies involving 3324 patients were identified. Transradial PCI reduced major bleeding compared to transfemoral PCI (P = .0001), and significant reductions were found in the composite of death, myocardial infarction, or stroke (P = .001). Mortality reduction showed a significant toward benefit in the case of TRPCI (2.04% vs 3.06%, OR 0.54 [95% CI 0.33-0.86], P = .01). The fluoroscopic time was longer, and access site crossover was more frequent for TRPCI (P = .001, P < .00001, respectively)., Conclusions: Transradial PCI reduces the risk of periprocedural major bleeding and major adverse events in the STEMI setting.