Rare instances of concomitant acute myocardial infarction and stroke.

Cardio-cerebral infarction (CCI) is a term coined to describe concomitant myocardial infarction and acute ischemic stroke. Acute myocardial infarction and stroke, as separate events, constitute some of the most important causes for disability and mortality in aging societies. Stroke can either occur simultaneously with myocardial infarction or become a serious complication of myocardial infarction and/or its treatment. The frequency of CCI has been reported at a 0.009% incidence rate in stroke patients and is associated with an extremely high mortality. Because of the rare occurrence of CCI, there are currently no guidelines for assessing its diagnosis and optimal treatment. Therefore, currently, the management of CCI cases needs to be individualized. Hopefully, in the future, the results of large clinical trials or prospective registries are expected to enhance our understanding of managing concomitant acute MI and stroke. In this review we have focused on the current literacy in the diagnosis and treatment of CCIs. The paper illustrates potential distinct scenarios of CCI through the analysis of three patient cases (Fig. 5, Ref. 65). Text in PDF www.elis.sk Keywords: myocardial infarction, stroke, cardio-cerebral infarction, carotid artery stenting, cardiac surgery.

Long-term clinical outcomes from real-world experience of left atrial appendage exclusion with LARIAT device.

BACKGROUND: Left atrial appendage closure (LAAC) with LARIAT has emerged as one of the alternatives to oral anticoagulation (OAC) in patients with nonvalvular atrial fibrillation (AF). Our aim was to study long-term outcomes in patients undergoing LARIAT procedure. METHODS: We analyzed patients screened for LARIAT device in four centers between December 2009 and June 2012. Out of these, patients who didn't undergo LAAC with the LARIAT device due to unfavorable LAA morphology and other preprocedural contraindications were included in control group. We analyzed thromboembolism, bleeding events, and mortality between LAA and control group. RESULTS: About 153 patients were screened. Out of these, 108 (70.6%) patients underwent LARIAT placement (LAA arm) and 45 (29.4%) excluded patients were included in control arm. There were no differences in CHADS2 and CHA2 DS2 -VASc score. Mean HAS-BLED score was significantly higher in the LARIAT group (3.5 ± 1.06 vs 3.09 ± 1.22, P = .04). Mean follow-up time (in years) was 6.56 ± 0.84 in LAA and 6.5 ± 1.26 in control arm. During follow-up period, the LARIAT group was associated with significantly less thromboembolic events (1.9% vs 24%, P < .001), bleeding events (9.2% vs 24.4%, P = .03), and mortality (5.6% vs 20%, P = .01) as compared with the control group. CONCLUSIONS: Long-term data from routine clinical practice from our study suggests that LAA exclusion with LARIAT device is an effective treatment in management of nonvalvular AF patients with high risk of stroke, bleeding, and mortality. Further randomized trials, such as aMAZE, will provide more insight in this expanding field.

Role of chemokine RANTES in the regulation of perivascular inflammation, T-cell accumulation, and vascular dysfunction in hypertension.

Recent studies have emphasized the role of perivascular inflammation in cardiovascular disease. We studied mechanisms of perivascular leukocyte infiltration in angiotensin II (Ang II)-induced hypertension and their links to vascular dysfunction. Chronic Ang II infusion in mice increased immune cell content of T cells (255 ± 130 to 1664 ± 349 cells/mg; P < 0.01), M1 and M2 macrophages, and dendritic cells in perivascular adipose tissue. In particular, the content of T lymphocytes bearing CC chemokine receptor (CCR) 1, CCR3, and CCR5 receptors for RANTES chemokine was increased by Ang II (CCR1, 15.6 ± 1.5% vs. 31 ± 5%; P < 0.01). Hypertension was associated with an increase in perivascular adipose tissue expression of the chemokine RANTES (relative quantification, 1.2 ± 0.2 vs. 3.5 ± 1.1; P < 0.05), which induced T-cell chemotaxis and vascular accumulation of T cells expressing the chemokine receptors CCR1, CCR3, and CCR5. Mechanistically, RANTES(-/-) knockout protected against vascular leukocyte, and in particular T lymphocyte infiltration (26 ± 5% in wild type Ang II vs. 15 ± 4% in RANTES(-/-)), which was associated with protection from endothelial dysfunction induced by Ang II. This effect was linked with diminished infiltration of IFN-γ-producing CD8(+) and double-negative CD3(+)CD4(-)CD8(-) T cells in perivascular space and reduced vascular oxidative stress while FoxP3(+) T-regulatory cells were unaltered. IFN-γ ex vivo caused significant endothelial dysfunction, which was reduced by superoxide anion scavenging. In a human cohort, a significant inverse correlation was observed between circulating RANTES levels as a biomarker and vascular function measured as flow-mediated dilatation (R = -0.3, P < 0.01) or endothelial injury marker von Willebrand factor (R = +0.3; P < 0.01). Thus, chemokine RANTES is important in the regulation of vascular dysfunction through modulation of perivascular inflammation.-Mikolajczyk, T. P., Nosalski, R., Szczepaniak, P., Budzyn, K., Osmenda, G., Skiba, D., Sagan, A., Wu, J., Vinh, A., Marvar, P. J., Guzik, B., Podolec, J., Drummond, G., Lob, H. E., Harrison, D. G., Guzik, T. J. Role of chemokine RANTES in the regulation of perivascular inflammation, T-cell accumulation, and vascular dysfunction in hypertension.

Noninvasive techniques for the diagnosis of anomalous origin of the left coronary artery from the pulmonary artery in adult patients.

Background Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital cardiac anomaly which requires surgical treatment, which improves left ventricular function and clinical outcomes. The definitive diagnosis of ALCAPA is based on coronary angiography, however, noninvasive visualization of the origin of the coronary artery is often helpful in the diagnosis of ALCAPA. Objectives The purpose of this study was to evaluate noninvasive techniques for the diagnosis of ALCAPA, and present the clinical outcomes in adults after surgical correction of ALCAPA. Methods Medical charts of five patients with ALCAPA treated at the John Paul II Hospital in Cracow between 2004 and 2012 were analyzed retrospectively. Noninvasive imaging techniques were used to visualize coronary vessels preoperatively. Patients were followed one year after the operation with echocardiograms and assessment of the New York Heart Association functional class. Results Computed tomography showed ALCAPA in four patients. Magnetic resonance imaging showed abnormal left ventricle remodeling suggestive of ischemia of the anterior cardiac wall. Myocardial perfusion imaging revealed ischemia of the middle and periapical segments of the anterior and anterolateral wall of the left ventricle in two patients. Postoperatively, patients had symptomatic improvement, but there was no statistically significant difference in mean ejection fraction. Conclusions Noninvasive techniques can be used to visualize the origin of the coronary arteries and characterize their morphology. Long-term follow-up of adult patients after surgical correction of ALCAPA is not well documented in the literature, but surgical treatment revealed beneficial short-term effects and symptoms relief.

Effect of Evolocumab on Progression of Coronary Disease in Statin-Treated Patients: The GLAGOV Randomized Clinical Trial.

Importance: Reducing levels of low-density lipoprotein cholesterol (LDL-C) with intensive statin therapy reduces progression of coronary atherosclerosis in proportion to achieved LDL-C levels. Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors produce incremental LDL-C lowering in statin-treated patients; however, the effects of these drugs on coronary atherosclerosis have not been evaluated. Objective: To determine the effects of PCSK9 inhibition with evolocumab on progression of coronary atherosclerosis in statin-treated patients. Design, Setting, and Participants: The GLAGOV multicenter, double-blind, placebo-controlled, randomized clinical trial (enrollment May 3, 2013, to January 12, 2015) conducted at 197 academic and community hospitals in North America, Europe, South America, Asia, Australia, and South Africa and enrolling 968 patients presenting for coronary angiography. Interventions: Participants with angiographic coronary disease were randomized to receive monthly evolocumab (420 mg) (n = 484) or placebo (n = 484) via subcutaneous injection for 76 weeks, in addition to statins. Main Outcomes and Measures: The primary efficacy measure was the nominal change in percent atheroma volume (PAV) from baseline to week 78, measured by serial intravascular ultrasonography (IVUS) imaging. Secondary efficacy measures were nominal change in normalized total atheroma volume (TAV) and percentage of patients demonstrating plaque regression. Safety and tolerability were also evaluated. Results: Among the 968 treated patients (mean age, 59.8 years [SD, 9.2]; 269 [27.8%] women; mean LDL-C level, 92.5 mg/dL [SD, 27.2]), 846 had evaluable imaging at follow-up. Compared with placebo, the evolocumab group achieved lower mean, time-weighted LDL-C levels (93.0 vs 36.6 mg/dL; difference, -56.5 mg/dL [95% CI, -59.7 to -53.4]; P < .001). The primary efficacy parameter, PAV, increased 0.05% with placebo and decreased 0.95% with evolocumab (difference, -1.0% [95% CI, -1.8% to -0.64%]; P < .001). The secondary efficacy parameter, normalized TAV, decreased 0.9 mm3 with placebo and 5.8 mm3 with evolocumab (difference, -4.9 mm3 [95% CI, -7.3 to -2.5]; P < .001). Evolocumab induced plaque regression in a greater percentage of patients than placebo (64.3% vs 47.3%; difference, 17.0% [95% CI, 10.4% to 23.6%]; P < .001 for PAV and 61.5% vs 48.9%; difference, 12.5% [95% CI, 5.9% to 19.2%]; P < .001 for TAV). Conclusions and Relevance: Among patients with angiographic coronary disease treated with statins, addition of evolocumab, compared with placebo, resulted in a greater decrease in PAV after 76 weeks of treatment. Further studies are needed to assess the effects of PCSK9 inhibition on clinical outcomes. Trial Registration: clinicaltrials.gov Identifier: NCT01813422.

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.

Elevated level of plasma endothelin-1 in patients with atrial septal defect.

BACKGROUND: The study aimed to assess the level of plasma Endothelin-1 (ET-1) in patients before and after transcatheter closure of atrial septal defect (ASD) and to evaluate the usefulness of measuring ET-1 levels for the diagnosis and selection of candidates for ASD closure. METHODS: 80 patients (55 F, 25 M), mean age 42,2 ± 11,5 years were enrolled for an attempt at ASD closure. A group of 19 healthy volunteers, (12 F, 7 M) mean age 39.2 ± 9.15 served as controls. All ASD patients underwent: clinical and echocardiographic study and cardiopulmonary exercise test. ET-1 levels were measured before and after closure. Whole blood was collected from femoral artery and vein and from pulmonary artery during cardiac catheterization. RESULTS: ET-1 levels at peripheral artery and vein in ASD patients were significantly higher than in the volunteers (p < 0.0001). The ASD subjects with highest ET-1 level presented the larger area of right ventricle and right atrium and higher pulmonary artery systolic pressure(p < 0.05). The ASD subjects with lower ET-1 level demonstrated longer time of exercise and higher peak oxygen consumption (p < 0.05). There was a decrease of ET-1 at peripheral artery (5.128 ± 8.8 vs. 2.22 ± 6.2; p < 0.001) and at peripheral vein (4.401 ± 3.33 vs. 2.05 ± 1.35; p < 0.001) within 48 hours after ASD closure, as compared to the baseline data. After 6 and 12 months farther drop in ET-1 level was observed. CONCLUSIONS: 1. The level of ET-1 in ASD patients is elevated in compare to healthy subject.2. The significant reduction of ET-1 level is observed after percutaneous closure of ASD.3. Elevated level of ET-1 in patients with ASD is associated with right heart enlargement.4. Measurements of ET-1 may be a supplemental diagnostic tool and may be helpful in establishing indications for defect closure.

Transcranial Doppler ultrasonography should it be the first choice for persistent foramen ovale screening?

BACKGROUND: Persistent foramen ovale (PFO) is considered a cause of cryptogenic stroke and a risk factor for neurological events in young patients. The reference standard for identifying a PFO is contrast-enhanced transesophageal echocardiography (TEE).The goal of this study was to evaluate the feasibility of transcranial color Doppler (TCD) and its diagnostic sensitivity compared with TEE. METHODS: We investigated 420 patients admitted to our department with cryptogenic stroke, transient ischemic attacks or other neurological symptoms. All patients underwent TCD and TEE evaluation. TCD and TEE examinations were performed according to a standardized procedure: air-mixed saline was injected into the right antecubital vein three times, while the Doppler signal was recorded during the Valsalva maneuver. During TCD the passage of contrast into the right-middle cerebral artery was recorded 25 seconds following the Valsalva maneuver. RESULTS: We detected a right-to-left shunt in 220 patients (52.3%) and no-shunts in 159 patients (37.9%) with both TCD and TEE. In 20 (4.8%) patients TEE did not reveal contrast passage which was then detected by TCD. In 21 (5.0%) patients only TEE revealed a PFO. The feasibility of both methods was 100%. TCD had a sensitivity of 95% and a specificity of 92% in the diagnosis of PFO. CONCLUSIONS: TCD has a relatively good sensitivity and specificity. TCD and TEE are complementary diagnostic tests for PFO, but TCD should be recommended as the first choice for screening because of its simplicity, non-invasive character, low cost and high feasibility.

A Non-Coronary, Peripheral Arterial Atherosclerotic Disease (Carotid, Renal, Lower Limb) in Elderly Patients-A Review: Part I-Epidemiology, Risk Factors, and Atherosclerosis-Related Diversities in Elderly Patients.

Atherosclerosis is a generalized and progressive disease. Ageing is a key risk factor for atherosclerosis progression that is associated with the increased incidence of ischemic events in supplied organs, including stroke, coronary events, limb ischemia, or renal failure. Cardiovascular disease is the leading cause of death and major disability in adults ≥ 75 years of age. Atherosclerotic occlusive disease affects everyday activity and quality of life, and it is associated with reduced life expectancy. Although there is evidence on coronary artery disease management in the elderly, there is insufficient data on the management in older patients presented with atherosclerotic lesions outside the coronary territory. Despite this, trials and observational studies systematically exclude older patients, particularly those with severe comorbidities, physical or cognitive dysfunctions, frailty, or residence in a nursing home. This results in serious critical gaps in knowledge and a lack of guidance on the appropriate medical treatment and referral for endovascular or surgical interventions. Therefore, we attempted to gather data on the prevalence, risk factors, and management strategies in patients with extra-coronary atherosclerotic lesions.

A Non-Coronary, Peripheral Arterial Atherosclerotic Disease (Carotid, Renal, Lower Limb) in Elderly Patients-A Review PART II-Pharmacological Approach for Management of Elderly Patients with Peripheral Atherosclerotic Lesions outside Coronary Territory.

BACKGROUND: Aging is a key risk factor for atherosclerosis progression that is associated with increased incidence of ischemic events in supplied organs, including stroke, coronary events, limb ischemia, or renal failure. Cardiovascular disease is the leading cause of death and major disability in adults ≥ 75 years of age. Atherosclerotic occlusive disease affects everyday activity, quality of life, and it is associated with reduced life expectancy. As most multicenter randomized trials exclude elderly and very elderly patients, particularly those with severe comorbidities, physical or cognitive dysfunctions, frailty, or residence in a nursing home, there is insufficient data on the management of older patients presenting with atherosclerotic lesions outside coronary territory. This results in serious critical gaps in knowledge and a lack of guidance on the appropriate medical treatment. In addition, due to a variety of severe comorbidities in the elderly, the average daily number of pills taken by octogenarians exceeds nine. Polypharmacy frequently results in drug therapy problems related to interactions, drug toxicity, falls with injury, delirium, and non-adherence. Therefore, we have attempted to gather data on the medical treatment in patients with extra-cardiac atherosclerotic lesions indicating where there is some evidence of the management in elderly patients and where there are gaps in evidence-based medicine. Public PubMed databases were searched to review existing evidence on the effectiveness of lipid-lowering, antithrombotic, and new glucose-lowering medications in patients with extra-cardiac atherosclerotic occlusive disease.

Cardiac microRNAs: diagnostic and therapeutic potential.

MicroRNAs are small non-coding post-translational biomolecules which, when expressed, modify their target genes. It is estimated that microRNAs regulate production of approximately 60% of all human proteins and enzymes that are responsible for major physiological processes. In cardiovascular disease pathophysiology, there are several cells that produce microRNAs, including endothelial cells, vascular smooth muscle cells, macrophages, platelets, and cardiomyocytes. There is a constant crosstalk between microRNAs derived from various cell sources. Atherosclerosis initiation and progression are driven by many pro-inflammatory and pro-thrombotic microRNAs. Atherosclerotic plaque rupture is the leading cause of cardiovascular death resulting from acute coronary syndrome (ACS) and leads to cardiac remodeling and fibrosis following ACS. MicroRNAs are powerful modulators of plaque progression and transformation into a vulnerable state, which can eventually lead to plaque rupture. There is a growing body of evidence which demonstrates that following ACS, microRNAs might inhibit fibroblast proliferation and scarring, as well as harmful apoptosis of cardiomyocytes, and stimulate fibroblast reprogramming into induced cardiac progenitor cells. In this review, we focus on the role of cardiomyocyte-derived and cardiac fibroblast-derived microRNAs that are involved in the regulation of genes associated with cardiomyocyte and fibroblast function and in atherosclerosis-related cardiac ischemia. Understanding their mechanisms may lead to the development of microRNA cocktails that can potentially be used in regenerative cardiology.

Association of Increased Vascular Stiffness with Cardiovascular Death and Heart Failure Episodes Following Intervention on Symptomatic Degenerative Aortic Stenosis.

BACKGROUND: The resistive (RI) and pulsatile (PI) indices are markers of vascular stiffness (VS) which are associated with outcomes in patients with cardiovascular disease. We aimed to assess whether VS might predict incidence of cardiovascular death (CVD) and heart failure (HF) episodes following intervention on degenerative aortic valve stenosis (DAS). METHODS: The distribution of increased VS (RI ≥ 0.7 and PI ≥ 1.3) from supra-aortic arteries was assessed in patients with symptomatic DAS who underwent aortic valve replacement (AVR, n = 127) or transcatheter aortic valve implantation (TAVI, n = 119). During a 3-year follow-up period (FU), incidences of composite endpoint (CVD and HF) were recorded. RESULTS: Increased VS was found in 100% of TAVI patients with adverse event vs. 88.9% event-free TAVI patients (p = 0.116), and in 93.3% of AVR patients with event vs. 70.5% event-free (p = 0.061). Kaplan-Mayer free-survival curves at 1-year and 3-year FU were 90.5% vs. 97.1 % and 78% vs. 97.1% for patients with increased vs. lower VS. (p = 0.014). In univariate Cox analysis, elevated VS (HR 7.97, p = 0.04) and age (HR 1.05, p = 0.024) were associated with risk of adverse outcomes; however, both failed in Cox multivariable analysis. CONCLUSIONS: Vascular stiffness is associated with outcome after DAS intervention. However, it cannot be used as an independent outcome predictor.

The impact of coronary microvascular dysfunction on the discordance between fractional flow reserve and resting full-cycle ratio in patients with chronic coronary syndromes.

Background: Resting full-cycle ratio (RFR) is an alternative to fractional flow reserve (FFR) for the evaluation of borderline coronary artery lesions. Although FFR and RFR results are discordant in some cases, factors associated with the discordance remain unclear. The role of coronary microvascular dysfunction (CMD) is discussed as a potential mechanism to explain these discrepancies. Aim: The study aimed to assess concordance between RFR and FFR in a real-life cohort from a high-volume center regarding the role of CMD. Methods: Consecutive patients with borderline coronary lesions undergoing coronary functional testing for chronic coronary syndromes were included in the study. Measurements of RFR and FFR were performed alongside additional coronary flow reserve (CFR), resistance reserve ratio (RRR), and an index of microcirculatory resistance (IMR) measurements. CMD was defined according to the current guideline by either IMR ≥25 or CFR ≤2.0 in vessels with no significant stenosis. Results: Measurements were performed in 157 coronary arteries, in 101 patients, with a median age of 66 y., 74% male, with prior history of arterial hypertension (96%), dyslipidaemia (91%), and diabetes (40%). The median value of vessel diameter stenosis was 45% according to QCA.Overall, FFR and RFR values were significantly correlated (r = 0.66, p < 0.001), where positive FFR/negative RFR and negative FFR/positive RFR were observed in 6 (3.8%) and 38 (24.2%) of 157 vessels. The RFR/FFR discrepancy was present in 44 (28%) of measurements. CMD was confirmed in 28 (64%) of vessels with discrepant RFR/FFR and in 46 (41%) of vessels with concordant results (p = 0.01). In discordant RFR/FFR vessels, as compared to concordant ones, significantly lower values of CFR [median 1.95 (IQR: 1.37, 2.30) vs. 2.10 (IQR: 1.50, 3.00), p = 0.030] and RRR [median 2.50 (IQR: 1.60, 3.10) vs. 2.90 IQR (1.90, 3.90), p = 0.048] were observed.Main predictors of RFR/FFR discrepancy in a univariate regression analysis were: higher age of patients [OR = 1.06 (1.01; 1.10), p = 0.010], presence of CMD [OR = 2.51 (1.23; 5.25), p = 0.012], lower CFR [OR = 1.64 (1.12; 2.56), p = 0.018], and lower RRR values [OR = 1.35 (95% CI: 1.03; 1.83), p = 0.038]. Conclusion: In discrepant RFR/FFR vessels, CMD is more prevalent than in concordant RFR/FFR measurements, which can be driven by lower CFR or RRR values. Further research is needed to confirm this observation.

Impaired coronary flow reserve in patients with poor type 2 diabetes control: Preliminary results from prospective microvascular dysfunction registry.

BACKGROUND: Type 2 diabetes (DM) is a common comorbidity associated with cardiovascular disease, especially when poor glucose control is present. Extracardiac microcirculatory complications prevalence is well documented, however coronary microcirculatory dysfunction (CMD) seem to be underreported in this group. METHODS: The present study analyzed coronary physiology measurements (coronary flow reserve [CFR], index of microcirculatory resistance [IMR], resistance reserve ratio [RRR]) in 47 diabetic patients (21 subjects with poor glycemia control defined as fasting glucose levels > 7.2 mmol/L and 26 with normal fasting glucose), and compared to 54 non-diabetic controls, who had undergone coronary angiography due to symptoms of chronic coronary syndrome. The median age of patients was 65.5 [59.0; 73.0] years old, 74% male, similar in terms of cardiovascular risk factors and prior myocardial infarction. Insulin was used by 19% of diabetic patients with poor glucose control and by 15% of those with DM and low fasting glucose. RESULTS: Prevalence of CMD was 38% in poor glycemia control patients, 27% in DM-patients with proper glucose control and 31% of non-diabetics. Median CFR values were the lowest in poor DM control patients compared to both, normal fasting glucose (1.75 [1.37; 2.32] vs. 2.30 [1.75; 2.85], p = 0.026) and to non-diabetics (1.75 [1.37; 2.32] vs. 2.15 [1.50; 2.95], p = 0.045). Levels of IMR, RRR and MRR did not differ significantly between compared groups (p > 0.05 for all comparisons). CONCLUSIONS: Poor glycemia control in type 2 DM might be associated with a higher prevalence of CMD driven by decreased coronary flow reserve, however, further research in larger groups of patients should be performed to confirm this observation.

Serum and Vascular Stiffness Biomarkers Associated with the Severity of Degenerative Aortic Valve Stenosis and Cardiovascular Outcomes.

Background: Although degenerative aortic valve stenosis (DAS) is the most prevalent growth-up congestive heart valve disease, still little known about relationships between DAS severity, vascular stiffness (VS), echocardiographic parameters, and serum biomarkers in patients undergoing transcatheter (TAVR) or surgical aortic valve replacement (SAVR). The objective of this study was to identify biomarkers associated with DAS severity, and those that are associated with cardiovascular death (CVD) and episodes of chronic heart failure (CHF) exacerbation. Methods: A total of 137 patients with initially moderate-to-severe DAS were prospectively evaluated for the relationship between DAS severity, baseline VS, and serum biomarkers (uPAR, GDF-15, Gal-3, IL-6Rα, ET-1, PCSK9, RANTES/CCL5, NT-proBNP, and hs-TnT), and were followed-up for 48 months. The prognostic significance of each variable for CVD and CHF risk was measured by hazard ratio of risk (HR), which was calculated by Cox's proportional hazard model. Results: DAS severity showed correlations with IL-6Rα (r = 0.306, p < 0.001), uPAR (r = 0.184, p = 0.032), and NT-proBNP (r = −0.389, p < 0.001). Levels of ET-1 and Gal-3 were strongly correlated with VS parameters (r = 0.674, p < 0.001; r = 0.724, p < 0.001). Out of 137 patients, 20 were referred to TAVR, 88 to SAVR, and 29 to OMT. In TAVR patients, the highest levels of ET-1, Gal-3, and VS were found as compared to other patients. The highest incidence of CVD was observed in patients who underwent TAVR (35%), compared to SAVR (8%) and OMT (10.3%) (p = 0.004). In a multivariate analysis, ET-1 occurred predictive of CVD risk (HR 25.1, p = 0.047), while Gal-3 > 11.5 ng/mL increased the risk of CHF exacerbation episodes requiring hospital admission by 12%. Conclusions: Our study indicated that ET-1 and Gal-3 levels may be associated with the outcomes in patients with DAS.

Impact of Medication Nonadherence in a Clinical Trial of Dual Antiplatelet Therapy.

BACKGROUND: Nonadherence to antiplatelet therapy after percutaneous coronary intervention (PCI) is common, even in clinical trials. OBJECTIVES: The purpose of this study was to investigate the impact of nonadherence to study protocol regimens in the MASTER DAPT (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen) trial. METHODS: At 1-month after PCI, 4,579 high bleeding risk patients were randomized to single antiplatelet therapy (SAPT) for 11 months (or 5 months in patients on oral anticoagulation [OAC]) or dual antiplatelet therapy (DAPT) for ≥2 months followed by SAPT. Coprimary outcomes included net adverse clinical events (NACE), major adverse cardiac and cerebral events (MACE), and major or clinically relevant nonmajor bleeding (MCB) at 335 days. Inverse probability-of-censoring weights were used to correct for nonadherence Academic Research Consortium type 2 or 3. RESULTS: In total, 464 (20.2%) patients in the abbreviated-treatment and 214 (9.4%) in the standard-treatment groups incurred nonadherence Academic Research Consortium type 2 or 3. At inverse probability-of-censoring weights analyses, NACE (HR: 1.01; 95% CI: 0.88-1.27) or MACE (HR: 1.07; 95% CI: 0.83-1.40) did not differ, and MCB was lower with abbreviated compared with standard treatment (HR: 0.51; 95% CI: 0.60-0.73) consistently across OAC subgroups; among OAC patients, SAPT discontinuation 6 months after PCI was associated with similar MACE and lower MCB (HR: 0.47; 95% CI: 0.22-0.99) compared with SAPT continuation. CONCLUSIONS: In the MASTER DAPT adherent population, 1-month compared with ≥3-month DAPT was associated with similar NACE or MACE and lower MCB. Among OAC patients, SAPT discontinuation after 6 months was associated with similar MACE and lower MCB than SAPT continuation (Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen [MASTER DAPT]; NCT03023020).

Influence of chronic inflammation and autoimmunity on coronary calcifications and myocardial perfusion defects in systemic lupus erythematosus patients.

OBJECTIVE: Conventional risk factors for coronary artery disease fail to explain the increased frequency or cardiovascular morbidity in systemic lupus erythematosus (SLE) patients. This study was conducted to determine the possible influence of autoimmune and inflammatory phenomena markers on coronary artery calcifications and myocardial perfusion abnormalities in SLE patients. MATERIALS AND METHODS: Multi-detector computed tomography (MDCT)-based coronary calcium scoring and single photon emission computerized tomography (SPECT) studies (Tc-99m sestamibi) were performed in 60 SLE patients in stable clinical condition, without a prior history of coronary artery disease. Laboratory evaluation included serum C-reactive protein (CRP), complement C3c and C4 components and antiphospholipid antibodies (aPL). The latter included anticardiolipin (aCL) and anti-ß2-glycoprotein I (aß2GPI) antibodies, of both IgG and IgM classes, and lupus anticoagulant (LA) in plasma. RESULTS: SPECT revealed persistent perfusion defects in 22 (36.7%) patients and exercise-induced defects in eight (13.3%), while MDCT revealed coronary calcifications in 15 (25%). Calcium scores ranged from 1 to 843.2 (mean 113.5 ± 259.7). No association was found between conventional coronary artery disease risk factors (obesity, hypertension, tobacco use, hyperlipidaemia, diabetes) nor CRP, C3c or C4 levels and coronary calcifications or myocardial perfusion defects. On the contrary, in patients with these pathologies, augmented autoimmunization was found, reflected by increased aCL IgG and antiß2GPI IgG levels. In patients with aCL IgG >20 RU/ml or antiß2GPI IgG >3 RU/ml, the relative risk of coronary calcification formation was 4.1 compared to patients with normal values. Accordingly, in LA-positive patients the relative risk of coronary calcification formation was 4.4 compared to LA-negative patients. CONCLUSIONS: Conventional risk factors for coronary artery disease as well as markers of an ongoing inflammation did not show any association with perfusion defects and/or coronary artery calcifications in SLE patients. On the contrary, calcified atherosclerotic plaques and myocardial perfusion defects were observed mainly in patients with elevated levels of anticardiolipin and aß2GPI antibodies of the IgG class. It might be speculated that coronary artery calcifications and perfusion defects are a result of antiphospholipid antibodies-induced coronary artery microthrombosis.

Assessment of the Willis circle flow changes and the severity of degenerative aortic stenosis and cognitive impairment.

BACKGROUND: Degenerative aortic stenosis (DAS) and cognitive function deterioration frequently coexist in elderly patients, which affects the prognosis. AIMS: We aimed to evaluate the Willis circle intracranial blood flow parameters and cognitive status in patients with DAS. METHODS: Ultrasonography of the Willis circle and the assessment of cerebral blood flow (CBF) volume, acceleration time (AT), pulsatile and resistive indexes (PI, RI), as well as cognition tests (Mini­Mental Status Examination [MMSE] and Montreal Cognitive Assessment [MoCA]) were performed in group 1-41 patients with severe DAS (aortic valve area indexed to the body surface area [AVAi] <0.5 cm2/m2) and group 2-41 patients with moderate DAS (AVAi [range], 0.51-0.99 cm2/m2). The control group comprised 52 patients without DAS. RESULTS: Compared with controls, mean (SD) CBF volume ingroups 1 and 2 was lower (1.37 [0.32] l/min vs 1.5 [0.44] l/min vs 1.71 [0.21] l/min, respectively; P <0.001), while AT (212 [20] ms vs 161 [33] ms vs 86 [21] ms, respectively; P <0.001), RI (0.64 [0.07] vs 0.65 [0.06] vs 0.59 [0.05], respectively; P <0.001), and PI (1.13 [0.21] vs 1.16 [0.17] vs 0.99 [0.12]; P <0.001) were higher. Both MMSE and MoCA scores did not differ according to CBF, RI, PI, and AT. In multivariable regression analysis, age, renal failure, left ventricular ejection fraction, and diabetes, yet not CBF parameters, were independently associated with cognitive function. CONCLUSIONS: Patients with DAS had significantly reduced CBF volume and increased arterial stiffness. However, cognitive impairment may be attributed to concomitant comorbidities rather than CBF parameters.

Importance of Increased Arterial Resistance in Risk Prediction in Patients with Cardiovascular Risk Factors and Degenerative Aortic Stenosis.

BACKGROUND: Cardiovascular disease is a leading cause of heart failure (HF) and major adverse cardiac and cerebral events (MACCE). OBJECTIVE: To evaluate impact of vascular resistance on HF and MACCE incidence in subjects with cardiovascular risk factors (CRF) and degenerative aortic valve stenosis (DAS). METHODS: From January 2016 to December 2018, in 404 patients with cardiovascular disease, including 267 patients with moderate-to-severe DAS and 137 patients with CRF, mean values of resistive index (RI) and pulsatile index (PI) were obtained from carotid and vertebral arteries. Patients were followed-up for 2.5 years, for primary outcome of HF and MACCE episodes. RESULTS: RI and PI values in patients with DAS compared to CRF were significantly higher, with optimal cut-offs discriminating arterial resistance of ≥0.7 for RI (sensitivity: 80.5%, specificity: 78.8%) and ≥1.3 for PI (sensitivity: 81.3%, specificity: 79.6%). Age, female gender, diabetes, and DAS were all independently associated with increased resistance. During the follow-up period, 68 (16.8%) episodes of HF-MACCE occurred. High RI (odds ratio 1.25, 95% CI 1.13-1.37) and PI (odds ratio 1.21, 95% CI 1.10-1.34) were associated with risk of HF-MACCE. CONCLUSIONS: An accurate assessment of vascular resistance may be used for HF-MACCE risk stratification in patients with DAS.