Leyla Elif Sade

Relation between epicardial fat thickness and coronary flow reserve in women with chest pain and angiographically normal coronary arteries

OBJECTIVE A significant proportion of women with angina-like chest pain and angiographically normal coronary arteries have microvascular dysfunction as detected by reduced coronary blood flow reserve (CFR). Classical clinical risk factors of atherosclerosis poorly predict this scenario. We sought to assess whether increased epicardial fat tissue, which is a metabolically active organ, could be associated with impaired CFR in these patients. METHODS We enrolled 68 women who underwent coronary angiography and had no obstructive coronary artery disease. Data about classical risk factors, insulin resistance and serum levels of C-reactive protein (CRP) and adiponectin were obtained. Stress tests were evaluated. Coronary flow velocities at baseline and under-induced hyperemia and epicardial fat thickness (EFT) were measured by transthoracic echocardiography within 48 h of angiography. CFR >or=2.0 was considered normal. RESULTS Forty percent of women had reduced CFR suggestive of microvascular dysfunction and 60% had normal CFR. Menopause, hypertension and abnormal stress tests were significantly more prevalent, adiponectin level was significantly decreased, CRP, insulin resistance, and EFT were significantly increased in women with microvascular dysfunction as compared with those without. On multivariate regression analysis EFT emerged as the only independent predictor of microvascular dysfunction (P<0.0001). EFT of >0.45 cm had 85% sensitivity and 75% specificity to detect CFR <2 (P<0.0001). Traditional risk factors for atherosclerosis did not predict women with abnormal microvascular function. CONCLUSIONS EFT has the potential to be an additional and easy diagnostic tool for risk stratification of women with chest pain and angiographically normal coronary arteries.

Effect of Mechanical Dyssynchrony and Cardiac Resynchronization Therapy on Left Ventricular Rotational Mechanics

Alterations in rotational mechanics can bring new aspects to the understanding of left ventricular (LV) dyssynchrony. The aims of this study were to investigate LV rotational mechanics in candidates for cardiac resynchronization therapy (CRT) and to assess the effect of CRT by speckle-tracking echocardiography. Fifty-four patients with heart failure and 33 healthy controls were studied. Thirty-three underwent CRT. Speckle tracking was applied to short- and long-axis views. Radial and longitudinal dyssynchrony were assessed as previously defined. Apical and basal rotations were measured as the average angular displacement about the LV central axis. LV twist and torsion were then calculated. Peak apical and basal rotation, peak LV twist and torsion, apical and basal rotation at aortic valve closure (AVC), and LV twist and torsion at AVC were significantly lower in patients than controls. Apical-basal rotation delay and AVC-to-peak LV twist interval were longer in patients and associated with decreased peak LV twist and LV twist at AVC, respectively. In patients, rotational indexes, particularly LV twist and torsion, were correlated strongly with radial dyssynchrony. LV torsion (cutoff 0.1 degrees /cm) and twist (cutoff 1 degrees ) at AVC had the highest sensitivity (90%) and specificity (77%) to predict CRT responders among all other parameters, including radial and longitudinal dyssynchrony. In conclusion, LV dyssynchrony is associated with discoordinate rotation of the apical and basal regions, which in turn significantly decreases peak LV twist and torsion and LV twist and torsion at AVC. CRT significantly restored the altered rotational mechanics in responders. These parameters have potential for predicting responders to CRT.

Tissue Doppler study of the right ventricle with a multisegmental approach: comparison with cardiac magnetic resonance imaging.

OBJECTIVE We investigated whether systolic right ventricular (RV) function and myocardial performance index (MPI) studied with a multisegmental approach improve the accuracy of RV function estimation based on tricuspid lateral annulus. METHODS Systolic and isovolumic contraction velocities, isovolumic acceleration, regional MPI from the tricuspid lateral and septal annulus, and basal and apical RV free wall and blood pool MPI were obtained in 69 patients and compared with RV ejection fraction (EF) by cardiac magnetic resonance. RESULTS Average systolic velocity from 2 annular sites had the highest correlation to the RVEF (r = 0.74; P < .001) and highest accuracy to estimate RVEF > 45% (cutoff = 7.0 cm/s; area under the curve 0.908; 95% confidence interval, 0.84-0.98; sensitivity 83%; specificity 86%; P < .0001). Average annular systolic velocity correlated with the RVEF more strongly than the lateral annular systolic velocity in patients with and without dilated RVs and in patients with and without pulmonary arterial hypertension. Four-region average MPI correlated with the RVEF (r = 0.70; P < .001) more strongly than regional MPI and blood pool MPI, with a higher accuracy to estimate RVEF > 45% (cutoff = 0.66; area under the curve 0.849; 95% CI, 0.76-0.94; sensitivity 86%; specificity 75%; P < .0001). Lateral annular measurements were mostly determined by the RVEF, whereas septal annular measurements were almost equally influenced by RVEF and left ventricular ejection fraction (LVEF). Consequently, when the RVEF and LVEF were discordant, only the lateral annular systolic velocity and MPI determined RVEF. CONCLUSION Average systolic velocity from 2 tricuspid annular sites provides the most accurate estimate of RVEF if the RVEF and LVEF are not discordant.

Serum gamma-glutamyl transferase activity: new high-risk criteria in acute coronary syndrome patients?

In acute coronary syndromes (ACS), oxidation and inflammation have very important roles and in-vitro studies have demonstrated that &ggr;-glutamyl transferase (GGT) participates in such oxidative and inflammatory reactions. We aimed to evaluate the prognostic value of baseline serum GGT activity on the development of major adverse cardiac event (MACE) in the follow-up of the patients with ACS in coronary care unit (CCU), after 1 and 6 month periods. We included 117 patients (mean age: 61.2±11.3 years, 93 males) hospitalized in CCU with the diagnosis of ACS. All had baseline serum GGT activity and were free of systemic and hepatobiliary disease. MACE was defined as the composite of mortality from cardiac causes, recurrent hospitalization with ACS and nonfatal recurrent myocardial infarction diagnoses, to need for coronary revascularization during CCU, over 1 and 6 month follow-up periods. During the follow-up of CCU, MACE occurred in 17 (14.5%) patients (two died). Serum GGT activity was significantly higher in the patients with MACE than those free of MACE (P=0.001) and GGT was found as the independent predictor of the development of MACE-CCU [relative hazard: 1.05, 95% confidence interval (CI): 1.01–1.09, P=0.007]. During the follow-up of 1 month, MACE occurred in 23 (20.0%) patients (five died). Serum GGT activity was significantly higher in patients with MACE than those free of MACE (P=0.021) and GGT was found as the independent predictor of the development of MACE-1 month (relative hazard: 1.04, 95% CI: 1.01–1.08, P=0.039). During the follow-up of 6 months, MACE occurred in 24 (21.8%) patients (two died). Again, GGT was significantly higher in patients who developed MACE than those free of MACE (P=0.001) and GGT was found as the independent predictor of the development of MACE-6 months (relative hazard 1.06, 95% CI: 1.03–1.10, P<0.001). Serum GGT activity was found to be an independent predictor of the development of MACE in the patients with ACS during CCU, over 1 and 6 month follow-up periods.

Right Ventricular Function Is a Determinant of Long-Term Survival after Cardiac Resynchronization Therapy

BACKGROUND Right ventricular (RV) dysfunction is a marker of poor prognosis in patients with heart failure. The aim of this study was to investigate the impact of RV function on the long-term outcomes of patients undergoing cardiac resynchronization therapy (CRT). METHODS A total of 120 consecutive patients treated with CRT according to guideline criteria were followed over 5 years. Comprehensive echocardiographic analyses of RV function and radial and longitudinal mechanical left ventricular dyssynchrony were performed at baseline and 6 months after implantation. RV function was evaluated by two-dimensional longitudinal strain of the free wall, fractional area change, tricuspid annular plane systolic excursion, and tricuspid annular systolic velocity. Long-term follow-up events were defined as all-cause mortality, heart transplantation, or assist device implantation. RESULTS Long-term events occurred in 38 patients. Among the studied variables for RV function, RV strain < 18% had the highest sensitivity (79%) and specificity (84%) to predict a poor outcome after CRT (area under curve, 0.821; P < .0001). When adjusted for confounding baseline variables of ischemic etiology, mechanical dyssynchrony, left ventricular end-systolic volume, mitral regurgitation, and medical therapy, RV dysfunction remained independently associated with outcomes, indicating a 5.7-fold increased risk for hard events (P < .0001). CONCLUSIONS Preserved RV function as assessed by speckle-tracking strain imaging appears to be an independent predictor of long-term event-free survival after CRT.

Right ventricular contractile reserve in mitral stenosis: Implications on hemodynamic burden and clinical outcome

BACKGROUND We investigated whether isovolumic acceleration (IVA) under inotropic stimulation as a means of right ventricular (RV) contractile reserve, is a surrogate for hemodynamic burden and has prognostic value in patients with mitral stenosis (MS). METHODS Thirty-one pure MS patients and 20 controls underwent cardiac catheterization, exercise test, and dobutamine stress echocardiography. RV fractional area change (FAC), +dP/dt/P(max), RV tissue Doppler indices (isovolumic contraction [IVC] and systolic [S] velocity, and IVA) were measured. Patients were followed-up for the occurrence of cardiac adverse events. RESULTS Inotropic modulation unmasked statistically significant differences regarding magnitude of changes in IVA, IVC, S, and +dP/dt/P(max), but not RV FAC. Inability to increase IVA more than 6.5 m/s(2) was the only independent determinant of pulmonary capillary wedge pressure >or=18 mm Hg (P=.004). Although MS severity did not predict the RV contractile reserve and pulmonary artery pressure (PAP) behavior during inotropic stimulation, the RV contractile reserve was related to the degree of systolic PAP. IVA increases of <3.4 m/s(2) had 86% sensitivity and 75% specificity to predict unfavorable outcomes during long-term follow-up (20+/-8 months). CONCLUSION RV contractile reserve provides complementary data to the hemodynamic significance of MS severity, may contribute to clinical decision making, and be of prognostic value in these patients.

Follow-Up of Heart Transplant Recipients with Serial Echocardiographic Coronary Flow Reserve and Dobutamine Stress Echocardiography to Detect Cardiac Allograft Vasculopathy

BACKGROUND Implementation of reliable noninvasive testing for screening cardiac allograft vasculopathy (CAV) is of critical importance. The most widely used modality, dobutamine stress echocardiography (DSE), has moderate sensitivity and specificity. The aim of this study was to assess the potential role of serial coronary flow reserve (CFR) assessment together with DSE for predicting CAV. METHODS A total of 90 studies were performed prospectively over 5 years in 23 consecutive heart transplant recipients who survived >1 year after transplantation. Assessment of CFR with transthoracic Doppler echocardiography, DSE, coronary angiography, and endomyocardial biopsy was performed annually. Results of CFR assessment and DSE were compared with angiographic findings of CAV. RESULTS Acute cellular rejections were excluded by endomyocardial biopsies. CAV was detected in 17 of 90 angiograms. Mean CFR was similarly lower in both mild (CAV grade 1) and more severe (CAV grades 2 and 3) vasculopathy, but wall motion score index became higher in parallel with increasing grades of vasculopathy. Any CAV by angiography was detected either simultaneously with or later than CFR impairment, yielding 100% sensitivity for CFR. The combination of CFR and DSE increased the specificity of the latter from 64.3% to 87.2% without compromising sensitivity (77.8%). CONCLUSIONS CFR is very sensitive for detecting CAV and increases the diagnostic accuracy of DSE, raising the potential for patient management tailored to risk modification and to avoid unnecessary angiographic procedures.

Effect of right ventricular pacing lead on left ventricular dyssynchrony in patients receiving cardiac resynchronization therapy.

Right ventricular (RV) pacing-induced left ventricular (LV) dyssynchrony can be 1 reason of nonresponse to cardiac resynchronization therapy (CRT) by potentially interfering with spontaneous dyssynchrony. We investigated the effect of the RV pacing lead on LV dyssynchrony in patients receiving CRT. LV radial dyssynchrony was assessed in a 16-segment model by using the novel speckle-tracking imaging before CRT and after the procedure, when the device was randomized to biventricular and RV pacing with crossover after 48 hours. LV lead tip was localized under fluoroscopic guidance. Of 43 patients, 30 (70%) acutely responded to CRT by a decrease in end-systolic volume >10%. RV pacing did not significantly increase the magnitude but altered the pattern of intraventricular dyssynchrony in the overall study group. During RV pacing, major shifts in the latest activated region occurred in 20 patients. However, LV radial dyssynchrony during spontaneous rhythm, but not the 1 induced by RV pacing, predicted response to CRT. When lead localization was optimal according to spontaneous dyssynchrony, response rate was 89% compared with 50% when lead localization was not optimal (p = 0.01). In contrast, when lead localization was optimal according to RV pacing-induced dyssynchrony, response rate was 81% compared with 67% when lead localization was not optimal (p = NS). In conclusion, RV apical pacing can alter the pattern of spontaneous LV dyssynchrony in patients receiving CRT. However, this alteration does not detract from the value of assessing LV dyssynchrony during spontaneous rhythm to predict responders to CRT.

Assessment of Subclinical Atherosclerosis by Carotid Intima-Media Thickness and Epicardial Adipose Tissue Thickness in Prediabetes.

Impaired fasting glucose (IFG) and impaired glucose intolerance (IGT) are predictors of cardiovascular disease (CVD). We tested the hypothesis that epicardial fat thickness (EFT) and carotid intima–media thickness (cIMT), as markers of early atherosclerosis, are increased in patients with prediabetes. We prospectively enrolled 246 patients (162 with prediabetes and 84 controls). Prediabetes was defined according to American Diabetes Association criteria, and patients were divided into 3 groups: group 1—IFG, group 2—IGT, and group 3—IFG + IGT. Both cIMT and EFT were significantly greater in patients with prediabetes compared with controls (0.81 ± 0.20 mm vs 0.68 ± 0.16 mm, P < .001 and 7.0 ± 2.0 mm vs 5.6 ± 1.6 mm, P < .001, respectively). This difference was mainly attributed to patients with IGT. Age, waist circumference, and 2-hour glucose independently predicted cIMT, while 2-hour glucose was the only independent predictor of EFT in multivariate analysis among other relevant parameters for cIMT and EFT. The cIMT and EFT (measured noninvasively) could be useful indicators of CVD risk in these patients. In order to prove this hypothesis, long-term prospective studies with greater patient numbers are required.

[Serum gamma-glutamyltransferase activity: a new marker for coronary artery bypass graft disease].

OBJECTIVES Serum gamma-glutamyltransferase (GGT) activity has been shown to be related to the development of atherosclerosis and cardiovascular events. We evaluated the association between GGT and severe graft disease in patients undergoing coronary artery bypass graft (CABG) surgery. STUDY DESIGN We evaluated 113 patients (mean age 62±9 years; range 21 to 81 years) who underwent control coronary angiography after a mean of 39 months (range 18 to 84 months) following CABG surgery. A graft was considered patent if there was <70% stenosis or severely diseased if there was ≥70% stenosis on coronary angiography. Preoperative serum GGT levels were measured in all the patients and none had severe systemic or hepatobiliary disease. The association between serum GGT level and severe graft disease was investigated. The grafts were also evaluated separately. RESULTS Coronary angiography showed severe graft disease involving at least one graft in 65 patients (57.5%). Serum GGT level was significantly higher in patients with severe graft disease (p=0.001). ROC curve analysis yielded a cut-off value of 29.5 U/l for serum GGT level to predict severe graft disease (area under the curve: 0.69) with 48% sensitivity and 82% specificity. While GGT levels were similar for internal mammary artery grafts (p>0.05), radial artery grafts and saphenous vein grafts (SVG) with severe graft disease were associated with significantly higher GGT levels (p=0.003 and p<0.001, respectively). In multivariate analysis, family history of coronary artery disease at a young age (OR 2.46, 95% CI 1.08-5.61, p=0.03) and serum GGT (OR 1.03, 95% CI 1.00-1.07, p=0.05) were independent predictors of severe graft disease. Separate analysis based on the graft types showed that GGT was an independent predictor of severe graft disease for only SVG (OR 1.02, 95% CI 1.00-1.04, p=0.03). CONCLUSION Serum GGT level may be an independent marker for the development of severe SVG disease in patients undergoing CABG surgery.