Coronary artery disease among patients admitted with atrial fibrillation and chest pain.

INTRODUCTION: Patients who present to the emergency department with chest pain during an episode of atrial fibrillation (AF) impose a clinical challenge regarding the source of pain - being coronary artery disease (CAD) or AF in origin. The aim of this study was to identify clinical, imaging or laboratory markers which can predict significant CAD among patients with an AF episode and chest pain. METHODS: We included 57 consecutive patients admitted to our hospital with AF and chest pain. All patients underwent coronary evaluation. Significant CAD was defined as >50% stenosis in a major coronary artery by coronary angiography or cardiac CT. We compared CAD and non-CAD groups and analyzed risk factorsby regression analysis. RESULTS: Twenty-four patients (42%) were diagnosed with- and 33 patients (58%) without obstructive CAD. In a multivariate analysis of regional wall motion abnormality (RWMA), elevated troponin and hypertension were found to be predictors for CAD [odds ratio (OR), 22.4 (confidence interval (CI), 1.8-272.4; P = 0.02); OR, 5.6 (CI, 1-31.0; P = 0.05) and OR, 21.4 (CI, 1.6-284.6; P = 0.02), respectively]. There were no significant differences regarding the rate of typical chest pain at presentation in the CAD vs. the non-CAD group [13 (54%) vs. 20 (60%), P = 0.374], or in ECG ST-changes [12 (50%) vs.9 (27%), respectively; P = 0.08]. CONCLUSION: In patients who present acutely with chest pain and AF, troponin elevation and RWMA appear to be highly predictive of obstructive CAD, whereas clinical symptoms and ECG changes are not predictive. These findings may be helpful for guiding the management of patients admitted with AF and chest pain.

Inflammatory cytokines differ between patients with high versus low CHA2DS2-VASc scores in sinus rhythm-a possible mechanism for adverse cardiovascular events.

Background: The CHA2DS2-VASc score was shown to predict systemic thromboembolism and mortality in certain groups of patients in sinus rhythm (SR). Previous data showed that patients in SR with high CHA2DS2-VASc score have higher plasma levels of inflammatory markers such as sP-selectin and C-reactive protein. We further investigated this group. Methods: Blood samples were collected from consecutive patients in SR. Plasma was extracted and stored at -80 °C. Concentrations of a panel of soluble markers IL-1ß, IL-6, IL-8, IL-10, TNF-α and VEGF were measured by Magnetic Luminex Performance Assay. The PLF4 cytokine blood level was measured by ELISA. Results: 66 patients were enrolled (age 53 ± 18 years, 60% women). Patients with high CHA2DS2-VASc scores (n = 23) had significantly higher median IQR concentrations of TNF-α [10.34 (8.55,14.92) vs. 7.69 (6.06, 9.85) pg/ml, p = 0.009] and a trend towards higher levels of IL-1ß [0.59 (0.4,0.8) vs. 0.44 (0.31, 0.62) pg/ml, p = 0.07] and IL-8 [5.92 (4.5,9.4) vs. 5.04 (3.63, 6.04) pg/ml, p = 0.07], compared to the group with low scores (n = 43). Median IQR concentrations of VEGF, IL-6, IL-10 and PF4 did not significantly differ between the CHA2DS2-VASc score groups. Conclusion: Patients in SR with high versus low CHA2DS2-VASc scores have high plasma concentrations of systemic inflammation cytokines. The already proven high levels of sP-selectin, that promotes release of inflammatory cytokines from leukocytes, is in line with these results. This pro-inflammatory state in patients with high CHA2DS2-VASc scores, may explain the higher rate of adverse cardiovascular events associated with elevated CHA2DS2-VASc score even without atrial fibrillation.

Comparison of Factors Associated with Inflammation, Thrombosis, and Platelet Reactivity as well as Turnover between Patients with High versus Low CHA2DS2-VASc without Atrial Fibrillation.

BACKGROUND: The CHA2DS2-VASc score has been shown to predict systemic thromboembolism and mortality in certain groups in sinus rhythm (SR), similar to its predictive value with atrial fibrillation (AF). OBJECTIVES: To compare factors of inflammation, thrombosis, platelet reactivity, and turnover in patients with high versus low CHA2DS2-VASc score in SR. METHODS: We enrolled consecutive patients in SR and no history of AF. Blood samples were collected for neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), immature platelet fraction (IPF%) and count (IPC), CD40 ligand, soluble P-selectin (sP-selectin) and E-selectin. IPF was measured by autoanalyzer and the other factors by ELISA. RESULTS: The study comprised 108 patients (age 58 ± 18 years, 63 women (58%), 28 (26%) with diabetes), In addition, 52 had high CHA2DS2-VASc score (³ 2 for male and ³ 3 for female) and 56 had low score. Patients with low scores were younger, with fewer co-morbidities, and smaller left atrial size. sP-selectin was higher in the high CHA2DS2-VASc group (45, interquartile ratio [IQR] 36-49) vs. 37 (IQR 28-46) ng/ml, P = 0.041]. Inflammatory markers were also elevated, CRP 3.1 mg/L (IQR 1.7-9.3) vs. 1.6 (IQR 0.78-5.4), P < 0.001; NLR 2.7 (IQR 2.1-3.8) vs. 2.1 (IQR 1.6-2.5), P = 0.001, respectively. There was no difference in E-selectin, CD40 ligand, IPC, or IPF% between the groups. CONCLUSIONS: Patients in SR with high CHA2DS2-VASc score have higher inflammatory markers and sP-selectin. These findings may explain the higher rate of adverse cardiovascular events associated with elevated CHA2DS2-VASc score.

Echocardiography-guided Cardiac Implantable Electronic Device Implantation to Reduce Device Related Tricuspid Regurgitation: A Prospective Controlled Study.

BACKGROUND: Endocardial leads of permanent pacemakers (PPM) and implantable defibrillators (ICD) across the tricuspid valve (TV) can lead to tricuspid regurgitation (TR) or can worsen existing TR with subsequent severe morbidity and mortality. OBJECTIVES: To evaluate prospectively the efficacy of intraprocedural 2-dimentional-transthoracic echocardiography (2DTTE) in reducing/preventing lead-associated TR. METHODS: We conducted a prospective randomized controlled study comparing echocardiographic results in patients undergoing de-novo PPM/ICD implantation with intraprocedural echo-guided right ventricular (RV) lead placement (Group 1, n=56) versus non-echo guided implantation (Group 2, n=55). Lead position was changed if TR grade was more than baseline in Group 1. Cohort patients underwent 2DTTE at baseline and 3 and/or 6 months after implantation. Excluded were patients with baseline TR > moderate or baseline ≥ moderate RV dysfunction. RESULTS: The study comprised 111 patients (74.14 ± 11 years of age, 58.6% male, 19% ICD, 42% active leads). In 98 patients there was at least one follow-up echo. Two patients from Group 1 (3.6%) needed intraprocedural RV electrode repositioning. Four patients (3.5%, 2 from each group, all dual chamber PPM, 3 atrial fibrillation, 2 RV pacing > 40%, none with intraprocedural reposition) had TR deterioration during 6 months follow-up. One patient from Group 2 with baseline mild-moderate aortic regurgitation (AR) had worsening TR and AR within 3 months and underwent aortic valve replacement and TV repair. CONCLUSIONS: The rate of mechanically induced lead-associated TR is low; thus, a routine intraprocedural 2DTTE does not have a significant role in reducing/preventing it.

Evaluation of left atrial remodeling by 2D-speckle-tracking echocardiography versus by high-density voltage mapping in patients with atrial fibrillation.

BACKGROUND: Strain imaging during left atrial (LA) reservoir phase (LASr) is used as a surrogate for LA structural remodeling and fibrosis. Atrial fibrillation (AF) patients with >5% low-voltage zones (LVZs) obtained by 3D-electro-anatomical-mapping have higher recurrence rate post-ablation. We investigated the relationship between LA remodeling using two-dimensional-speckle-tracking echocardiography (2D-STE) and high-density voltage mapping in AF patients. METHODS: A prospective study of 42 consecutive patients undergoing AF ablation. 2D-echo, 2D-STE, and high-density contact LA bipolar voltage maps were constructed before ablation. LVZs were determined with different bipolar amplitudes and their ratio per patient's LA area were investigated for correlation with LASr. We compared 2D-LASr results in patients with LVZs ≥ 5% (LVZs group) versus those with LVZ < 5% (non-LVZs group). RESULTS: Compared with non-LVZs group (n = 15), LVZs group (n = 27) included significantly older patients, more women, more persistent AF, higher CHA2 DS2 -VASc score, higher E/A ratio and higher LA volume index (p < .05). LVZs group had lower %LASr values (12.4 ± 5.9% vs. 21.1 ± 6.3, respectively; p<.001). LVZs% in different amplitudes (<0.1 mV, <0.2 mV, and <0.5 mV) were negatively correlated with %LASr (r = -.63, r = -.68, and r = -.72, respectively; p< .001). Atrial strain thresholds for LVZs ≥ 5% in amplitudes <0.1 mV, <0.2 mV, and <0.5 mV were associated with %LASr 12.98, 16.16 and 19.55, respectively; p< .05). In a multivariate analysis, %LASr was the only independent indicator of LVZs (OR, 0.8; 95% CI, 0.6-0.9; p= .04). CONCLUSIONS: LVZs ≥ 5% has a negative association with atrial %LASr. Thus, a simple 2D-STE measurement of %LASr can be used as a noninvasive method to evaluate significant LA remodeling and fibrosis in AF patients.

The Late Effects of Pregnancy on Aortic Dimensions in Patients with Marfan Syndrome.

While the immediate effects of pregnancy on aortic dimension in patients with Marfan syndrome (MFS) have been evaluated, the late effects of subsequent pregnancies in these patients are less known. For this purpose, we evaluated 2 groups of women with MFS who were under specialized care in our institution. Group A included 23 women with MFS who experienced 55 pregnancies; group B included 12 nulliparous MFS patients. Patients in group A were similar in age (36.13 ± 5.6 years vs. 34.25 ± 6.54 years, p = 0.41) and follow-up time (group A 6.05 ± 3.56 years and group B 4.92 ± 3.37 years, p = 0.37). Baseline aortic root diameters as well as the aortic root diameters at follow-up visits were similar between groups (35.60 ± 4.42 vs. 35.08 ± 3.82 mm, p = 0.73, and 37.57 ± 4.66 vs. 37.33 ± 4.83 mm, p = 0.89, respectively). The aortic root diameter increased by 0.5 (0, 2) mm in group A and 1 (0, 4.5) mm in group B (p = 0.54). The rate of aortic dilation per year of follow-up was similar between the groups (0.34 ± 0.52 mm/year in group A vs. 0.55 ± 0.75 mm/year in group B [p = 0.52]). Chronic medical treatment was similar in both groups. Patients in both groups were treated similarly with ß-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers. In summary, subsequent pregnancies in patients with MFS were not associated with an increase in the rate of aortic root dilation in these patients.

Measurements of immature platelet fraction and inflammatory markers in atrial fibrillation patients - Does persistency or ablation affect results?

PURPOSE: Atrial fibrillation (AF) is associated with platelet hyperactivity and a higher proportion of immature platelets. We aimed to examine whether immature platelet fraction (IPF) and inflammatory markers differ between AF types and whether they are affected by ablation. METHODS: A prospective study included patients with atrial fibrillation/flutter (AFL). We excluded patients with hematologic, inflammatory, or acute coronary states. Blood samples for IPF, white blood cells (WBC), neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP) were collected at baseline, within one-hour postablation in those undergoing ablations, and the day after ablation. IPF was measured by an autoanalyzer (Sysmex 2100 XE). RESULTS: One hundred and four patients were included (paroxysmal AF-63, persistent AF-36, AF and AFL-7, AFL alone-5), (Mean age 67.7 ± 12.8 years, 54.8% male, CHA2 D2 -VASC2 3.2 ± 1.8). Seventy-two patients underwent ablation (cryoballoon AF ablation-60, AFL radiofrequency ablation-5, both-7). There was no difference between paroxysmal and persistent AF regarding baseline markers. There was a significant change in the following parameters after ablation: WBC (baseline 6.9 ± 2.0, 1-h post 8.0 ± 2.4, and 1-day post 9.0 ± 2.8 ×109 /L), NLR (2.9 ± 2.2, 3.0 ± 2.4, 4.2 ± 2.9, respectively), and CRP (3.6 ± 3.7, 3.6 ± 3.5, 12.4 ± 9.0 mg/L, respectively) (P < .05 for all). However, there were no differences in immature platelet count (8.6 ± 4.8, 8.5 ± 4.9, 8.4 ± 5.2 ×109 /L) or IPF (4.6 ± 3.2, 4.7 ± 3.3, 4.9 ± 3.6%) from baseline to postablation (p = NS). CONCLUSIONS: AF persistency does not affect IPF and inflammation. In patients undergoing cryoablation of AF, there is a postablation inflammatory process; however, platelet activation is probably not affected.

Maternal and Neonatal Complications of Pregnant Women with Mitral Stenosis.

BACKGROUND: Rheumatic mitral stenosis (MS) is a relatively rare diagnosis in the developed countries and its treatment during pregnancy is challenging due to hemodynamic changes. With the demographic changes due to recent waves of immigration an increase in the prevalence of rheumatic heart disease is expected. OBJECTIVES: To evaluate maternal and neonatal complications in patients with mitral stenosis. METHODS: During the years 2006-2017, 22 women who underwent 31 pregnancies were followed at the Sheba Medical Center in Israel. We collected on regarding hemodynamic changes and their clinical course. MS was classified as mild, moderate, or severe according to mitral valve area by echocardiography. Maternal and fetal adverse events were evaluated according to severity of MS and compared by Poisson regression modeling. RESULTS: MS was severe in 7 pregnancies (22.6%), moderate in 9 (29%), and mild in 15 (48.4%). Twenty patients were managed conservatively and 2 underwent a successful percutaneous mitral balloon valvuloplasty (PBMVP) during pregnancy. All pregnancies ended with a liveborn neonate and with no maternal mortality. Peak and mean mitral pressure gradients increased during pregnancy from 13.3 ± 5.3 to 18.6 ± 5.1 mmHg and from 5.9 ± 2.3 to 9.6 ± 3.4 mmHg respectively (P < 0.05). Eight pregnancies (25.8%) were complicated by pulmonary congestion, 2/15 (13.3%) with mild MS, 2/9 (22.2%) with moderate, and 4/7 (57.1%) with severe MS. The adverse event rate was higher among patients with severe MS compared with moderate and mild MS [hazard ratio (HR) 3.15, 95% confidence interval (95%CA) 1.04-9.52 and HR 4.06, 95%CI 1.4-11.19 respectively, P < 0.05]. Nine of 31 deliveries were vaginal; 6 of 22 cesarean sections (27.3%) were performed for cardiac indications. CONCLUSIONS: The number of total adverse events were higher among patients with severe MS. Patients with moderate and mild MS should be treated attentively, but good obstetric and maternal outcome can be expected.

Prognostic value of ejection fraction in patients admitted with acute coronary syndrome: A real world study.

There are limited data regarding factors affecting outcomes among acute coronary syndrome (ACS) patients presenting with varying degrees of left ventricle (LV) dysfunction. We aimed to identify factors associated with mortality according to LV ejection fraction (LVEF) at 1st admission in ACS patients.A total of 8983 ACS patients prospectively enrolled in the Acute Coronary Syndrome Israeli Survey (2000-2010) were categorized according to their LVEF at admission: severe LV dysfunction (LVEF < 30% [n = 845]), mild-moderate LV dysfunction (LVEF 30%-49% [n = 4470]); preserved LV function (LVEF ≥ 50% [n = 3659]). Multivariable Cox proportional hazards regression modeling was used to assess the risk factors for 1-year mortality according to LVEF on admission.Over the past decade there was a gradual decline in the proportion of patients admitted with low LVEF. Mortality rates were highest among patients with severe LV dysfunction (36%), intermediate among those with mild-moderate LV dysfunction (10%), and lowest among those with preserved LV function (4%, P < 0.001). We recognized different risk factors for mortality according to LVEF at admission. Admission clinical features (syncope, anterior myocardial infarction, and ST elevation myocardial infarction [STEMI]) predicted mortality risk in patients with severe LV dysfunction (all P < 0.05), whereas the presence of comorbidities (hypertension, diabetes mellitus, chronic renal failure, and peripheral arterial disease) predicted mortality risk in patients with more preserved LV function. Age and admission Killip class ≥II were consistent predictors in all LVEF subsets.LVEF at admission is a strong predictor of mortality in ACS, and prognostic factors differ according to LVEF during admission. In patients with severe LV dysfunction signs of clinical instability are related to 1-year mortality; in patients with a more preserved LV function the prognosis is related to the presence of co-morbidities.

Gender-Related Cardiovascular Risk in Healthy Middle-Aged Adults.

Men tend to develop cardiovascular disease (CVD) earlier in life than women. Whether this difference is attributable only to gender is a matter of debate. The purpose of this study was to evaluate gender differences in cardiovascular risk in a large cohort of asymptomatic men and women and explore gender-related risk in prespecified risk factor subgroups. We investigated 14,966 asymptomatic men and women free of diabetes, hypertension, or ischemic heart disease who were annually screened. The primary end point of the present study was the occurrence of ischemic or cerebrovascular disease as composite end point. Multivariate Cox proportional hazards regression modeling was used to assess the gender difference regarding CVD and to examine the association between CVD risk factors and gender. Mean age of the study population was 47 ± 10 years and 30% were women. Kaplan-Meier survival analysis showed that at 6.2 ± 3.9 years' follow-up, the rate of CVD events was 6.1% among men compared with 1.8% among women (log-rank p <0.001). Consistently, multivariate analysis demonstrated that male gender was independently associated with a significant threefold increased risk for development of CVD events (hazard ratio 3.05, CI 2.25 to 4.14). The CVD risk associated with male gender was consistent in each risk subset analyzed, including older age, low high-density lipoprotein, impaired fasting glucose, and positive family history for ischemic heart disease (all p values for gender-by-risk factor interactions <0.05). Higher performance on treadmill test had a protective effect regarding CVD development in both men and women. In conclusions, healthy middle-aged men experienced increased risk for the development of CVD events compared with women independently of traditional CVD risk factors. However, better exercise capacity is associated with a protective effect.