Ali Ergin

Effect of Diabetes Mellitus on Formation of Coronary Collateral Vessels

BACKGROUND Although myocardial ischemia is known to be significantly related to the development of coronary collateral vessels (CCVs), there is considerable variation between patients with ischemic heart disease in the presence of collateral development. The nature of this variability is not well known. Likewise, it remains unclear whether diabetes mellitus (DM) has any effect on CCVs. The aim of this study was to evaluate the effect of DM on CCVs. METHODS AND RESULTS Of the patients who underwent coronary angiography during the interval between March 1, 1993, and June 20, 1998, in our institution, 306 were diabetic. Those patients in whom coronary angiography is normal or severity of coronary artery stenosis is thought not to be sufficient for the development of CCVs (<75%) were excluded from the study. A total of 205 patients (mean age, 59+/-8 years) met the criteria for the DM group. For case-control matching, 205 consecutive nondiabetic patients (mean age, 58+/-9 years) who had >/=1 diseased vessel with >75% stenosis were included in the control group. The CCVs were graded according to the Rentrop scoring system, and the collateral score was calculated by summing the Rentrop numbers of every patient. There was no statistical difference between patients with and without DM in clinical baseline characteristics. The mean number of diseased vessels in the DM group (1.58+/-0.68) was higher than that in the nondiabetic group (1.42+/-0.65, P=0.005). The mean collateral score was 2.41+/-2.20 in the DM group and 2.60+/-2.39 in the control group. After confounding variables were controlled for, the collateral score in the diabetic group was significantly different from that in the nondiabetic group (P=0.034). CONCLUSIONS Our findings suggest that CCV development is poorer in patients with than in patients without DM. Thus, we can speculate that DM is an important factor affecting CCV development.

Protective effects of nebivolol against anthracycline-induced cardiomyopathy: A randomized control study

BACKGROUND We aimed to evaluate the effect of prophylactic nebivolol use on prevention of antracycline-induced cardiotoxicity in breast cancer patients. METHODS In this small, prospective, double-blind study, we randomly assigned 45 consecutive patients with breast cancer and planned chemotheraphy to receive nebivolol 5mg daily (n=27) or placebo (n=18). Echocardiographic measurements and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels were obtained at baseline and at 6-month of chemotherapy. RESULTS Both studied groups had comparable echocardiographic variables and NT-pro-BNP levels at baseline. At 6-month, the left ventricular (LV) end-systolic and end-diastolic diameters increased in the placebo group (LVESD: 29.7 ± 3.4 to 33.4 ± 4.5mm; LVEDD: 47.2 ± 3.8 to 52.0 ± 4.6mm, p=0.01 for both) but remained unchanged in the nebivolol group (LVESD: 30.4 ± 3.5 to 31.0 ± 3.6mm, p=0.20; LVEDD: 47.0 ± 4.4 to 47.1 ± 4.0mm, p=0.93). The placebo group also had lower LVEF than the nebivolol group (57.5 ± 5.6% vs. 63.8 ± 3.9%, p=0.01) at 6-month. NT-pro-BNP level remained static in the nebivolol group (147 ± 57 to 152 ± 69 pmol/l, p=0.77) while it increased in the placebo group (144 ± 66 to 204 ± 73 pmol/l, p=0.01). CONCLUSIONS Prophylactic use of nebivolol treatment may protect the myocardium against antracycline-induced cardiotoxicity in breast cancer patients.

Relation of Neutrophil/Lymphocyte Ratio to Coronary Flow to In-Hospital Major Adverse Cardiac Events in Patients With ST-Elevated Myocardial Infarction Undergoing Primary Coronary Intervention

With the growing understanding of the role of inflammation in patients with atherosclerotic disease, studies have focused on high-sensitivity C-reactive protein (hs-CRP) and other inflammatory markers in their association with outcomes in ST-segment elevation myocardial infarction. The goal of this study was to investigate the association of the neutrophil/lymphocyte (N/L) ratio and in-hospital major adverse cardiac events (MACEs) in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI). The association of hs-CRP and N/L ratio on admission with Thrombolysis In Myocardial Infarction (TIMI) flow grade after PCI was assessed in 418 consecutive primary patients with PCI. The N/L ratio was significantly higher in the no-reflow group (TIMI grade 0/1/2 flow, n = 158) compared to that of the normal-flow group (TIMI grade 3 flow, n = 260, 4.6 ± 1.7 vs 3.1 ± 1.9, p <0.001). In-hospital MACEs were significantly higher in patients with no reflow (23% vs 7%, p <0.001). There was a significant and positive correlation between hs-CRP and N/L ratio (r = 0.657, p <0.001). In receiver operating characteristic analysis, N/L ratio >3.3 predicted no reflow with 74% sensitivity and 83% specificity. In a multivariate regression model, N/L ratio remained an independent correlate of no reflow (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.34 to 1.76, p <0.001) and in-hospital MACEs (OR 1.14, 95% CI 0.98 to 1.32, p = 0.043). The N/L ratio, an inexpensive and easily measurable laboratory variable, is independently associated with the development of no reflow and in-hospital MACEs in patients with ST-segment elevation myocardial infarction undergoing primary PCI.

Hematologic Parameters and Angiographic Progression of Coronary Atherosclerosis

Hematologic parameters have prognostic importance in cardiovascular disease. However, the relation between atherosclerosis progression and hematologic parameters is not well defined. A total of 394 patients requiring repeat coronary angiography were included in the study. According to angiography, patients were divided into 2 groups, progressive (n = 196) and nonprogressive (n = 198) diseases. Hematologic parameters including mean platelet volume (MPV) and neutrophil/lymphocyte (N/L) ratio were measured. Glucose, creatinine, and cholesterol were significantly higher in the progressive group. Mean platelet volume count was similar in both groups. The N/L ratio was significantly higher in the progressive group (5.0 ± 5.1 vs 3.2 ± 3; P = .001). In multivariate analysis, the N/L ratio was significantly related with progression (relative risk [RR]: 2.267, 95% CI: 1.068-4.815, P = .03). Progression rate was significantly high in patients with high N/L ratio (39% vs 56%). Our results suggest that the N/L ratio is a predictor of progression of atherosclerosis.

Effect of Potential Confounding Factors on the Thrombolysis in Myocardial Infarction (TIMI) Trial Frame Count and Its Reproducibility

BACKGROUND The potential factors that introduce variability into TIMI frame count (TFC) have not been systematically investigated. The goal of this study was to determine if nitrate use, dye injection rate, catheter size, the phase of the cardiac cycle in which dye is injected, or heart rate affect the TFC and to investigate the reproducibility of the TFC. METHODS AND RESULTS The dye injection rate was increased 1 mL/s, and angiography was repeated. A coronary angiogram was taken first with an 8F catheter and then with a 6F catheter. After taking angiograms, intracoronary nitrate was given to the patient, and the second angiography was performed. Basal heart rate was increased 20 beats/min, and angiography was repeated. Dye injection was performed at the beginning of systole and diastole. The TFC was not significantly changed by increasing the dye injection rate (P=0.467) or by changing catheter size (P=0.693). Nitrate administration significantly increased the TFC from 26.4+/-11.9 to 32.8+/-13.3 frames (P<0.001). Dye injection at the beginning of diastole significantly decreased the TFC from 30.1+/-8.8 to 24.4+/-7.9 frames (P<0.001) for the left coronary artery and from 24.16+/-4.49 to 21. 24+/-4.45 frames (P<0.001) for the right coronary artery. Increasing heart rate significantly decreased the TFC from 30.4+/-6.1 to 25. 3+/-7.2 frames (P<0.001). Intraobserver and interobserver reproducibility of the TFC was good (mean difference, 1.33+/-1.24 and 2.57+/-1.72 frames, respectively). CONCLUSIONS Nitrate use, heart rate, and the phase of the cardiac cycle in which dye is injected had significant effects on the TFC. Therefore, studies comparing TFC need to consider these factors, and the use of nitrates should be either standardized or randomized.

The association of serum uric acid levels on coronary flow in patients with STEMI undergoing primary PCI

OBJECTIVE Uric acid has been shown as a predictor and an independent risk factor for coronary heart disease, but little is known regarding the association of uric acid levels with coronary blood flow in STEMI. We hypothesized that elevated uric acid levels would be associated with impaired flow and perfusion in the setting of STEMI treated with primary PCI. METHODS Two hundred and eighty nine patients with STEMI who treated primary PCI were enrolled to study. Patients were divided into two groups based upon the TIMI flow grade. No-reflow was defined as TIMI Grade 0, 1 and 2 flows (group 1). Angiographic success was defined as TIMI 3 flow (group 2). Uric acid, MPV and high sensitive CRP were measured. Major adverse cardiac events (MACE) were defined as in stent thrombosis, non-fatal myocardial infarction and in-hospital mortality. RESULTS There were 126 patients (mean age 63±11 and 71% male) in group 1 and 163 patients (mean age 58±12 and 80% male) in group 2. Uric acid, MPV, and hs-CRP levels on admission were higher in group 1 (p=0.0001 for each). A uric acid level ≥5.4 mg/dl measured on admission had a 77% sensitivity and 70% specificity in predicting no-reflow at ROC curve analysis. In-hospital MACE was significantly higher in group 1 (29% vs. 7%, p=0.0001). At multivariate analyses, high plasma uric acid (odds ratio (OR) 2.05, <95% confidence interval(CI) 1.49-2.81; p<0.0001), hs-CRP (OR 1.02, <95% CI 1.01-1.03; p=0.0007) and MPV (OR 3.09, <95% CI 1.95-4.89; p<0.0001) levels were independent predictors of no-reflow post primary PCI and uric acid (OR 2.75, <95% CI 1.93-3.94; p<0.0001), hs-CRP (OR 1.01, <95% CI 1-1.02; p=0.006) levels, but not MPV, were independent predictors of in-hospital MACE. CONCLUSION Plasma uric acid level on admission is a strong and independent predictor of poor coronary blood flow following primary PCI and in hospital MACE among patients with STEMI. Except for predictive value, uric acid levels may be a useful biomarker for stratification of risk in patients with STEMI and may also lead to carry further therapeutic implications.

Protective effects of spironolactone against anthracycline-induced cardiomyopathy

The protective effect of beta‐blockers, ACE inhibitors, and ARBs on anthracycline cardiotoxicity has already been demonstrated, but the effect of aldosterone antagonism, which inhibits the last step of the renin–angiotensin–aldosterone system (RAAS), was questioned. This study sought to investigate whether spironolactone protects the heart against anthracycline‐induced cardiotoxicity.

Preload Dependence of Doppler Tissue Imaging Derived Indexes of Left Ventricular Diastolic Function

Doppler tissue imaging (DTI) has been proposed as a tool for the evaluation of diastolic function. Controversy exists regarding whether DTI measurements are influenced by preload. Changes in the circulating volume associated with hemodialysis result in preload reduction. To determine the influence of preload reduction on DTI and standard pulsed‐Doppler transmitral diastolic velocities, 30 patients (mean age 41 ± 14) with chronic renal insufficiency without overt heart disease were studied by DTI and standard pulsed Doppler before and after hemodialysis. From the apical window, DTI sample volume was placed at the lateral and septal mitral annulus and at the midsegment of lateral and septal myocardial wall of the left ventricle. Peak early diastolic annular and myocardial, and peak late diastolic annular and myocardial velocities were measured. Transmitral peak early and late diastolic velocities were also recorded by standard pulsed Doppler. The peak velocity of early diastolic mitral flow decreased from 100 ± 30 to 85 ± 34 cm/s (P < 0.001) after hemodialysis. Hemodialysis elicited marked reduction in early diastolic lateral mitral annular and midlateral myocardial velocities (6.9 ± 3.2 to 6.3 ± 2.9 cm/s, P < 0.04 and 6.7 ± 0.3 to 5.5 ± 2 cm/s, P < 0.001, respectively). Early diastolic, septal mitral annular, and midseptal myocardial velocities were also significantly decreased (5.8 ± 2.8 to 4.6 ± 2 cm/s, P < 0.006 and 6.2 ± 2 to 5.1 ± 1 cm/s, P < 0.008, respectively). Late diastolic mitral annular and myocardial velocities did not change. It is concluded that early diastolic mitral annular and myocardial velocities are affected by acute preload reduction. It is necessary to consider preload when diastolic function is assessed by DTI.

Relation of Left Atrial Spontaneous Echocardiographic Contrast in Patients With Mitral Stenosis to Inflammatory Markers

Spontaneous echocardiographic contrast (SEC) is the presence of smoke-like echoes with a characteristic swirling motion of blood in echocardiography. Previous clinical studies have demonstrated that SEC is a risk factor for left atrial thrombus formation and an important indicator of potential systemic embolism originated from heart. An established relation exists between the inflammatory status and the prothrombotic state. Therefore, we investigated the role of inflammatory status on SEC in patients with mitral stenosis (MS). A total of 62 consecutive patients with MS who undergoing mitral balloon valvuloplasty were enrolled in the present study. The patients were divided into 2 groups according to the formation of SEC in the left atrium. Of the 62 patients, 32 (mean age 45 ± 12 years; 75% women) were in the SEC-negative group and 30 patients (mean age 45 ± 11 years; 63% women) were in the SEC-positive group. The high-sensitive C-reactive protein levels were significantly greater in the SEC-positive group than in the SEC-negative group (3.9 ± 2.2 vs 10.6 ± 6.3, p = 0.024). The neutrophil levels (64.6 ± 9.4 vs 72.6 ± 8.6) were significantly greater in the SEC-positive group, and the lymphocyte levels (24.4 ± 6.9 vs 18.3 ± 6.0) were significantly greater in the SEC-negative group (p = 0.001 for each). The neutrophil/lymphocyte (N/L) ratio was also significantly greater in the SEC-positive group (3.0 ± 1.8 vs 4.5 ± 1.8, p = 0.003). In the receiver operating characteristics curve analysis, a N/L ratio > 3.1 mg/dl had a 80% sensitivity and 72% specificity in predicting SEC in patients with MS. On multivariate analysis, high-sensitive C-reactive protein (odds ratio [OR] 1.235, 95% confidence interval [CI] 1.040 to 1.466; p = 0.016), N/L ratio (OR 1.461, 95% CI 0.977 to 2.184; p = 0.02), left atrial volume (OR 3.012, 95% CI 1.501 to 5.611; p = 0.001), and mitral valve area (OR 0.135, 95% CI 0.020 to 0.503; p = 0.017) were independent risk factors of SEC in patients with MS. In conclusion, the high-sensitive C-reactive protein and N/L ratio were independently associated with SEC in patients with MS.

Bilirubin levels and the burden of coronary atherosclerosis in patients with STEMI.

We investigated whether serum bilirubin level (a marker of heme oxygenase activity) is a predictor of high levels of SYNTAX score (SXscore) in patients with acute myocardial infarction. Patients (n = 281; male 77%; mean age 60 ± 12) who were admitted with ST-elevation myocardial infarctions (STEMIs) were enrolled. Patients were divided into 2 groups. Group 1 was defined as SXscore <22 and group 2 was defined as SXscore ≥22. Total bilirubin levels were significantly higher in the high-SXscore group than in the low-SXscore group (0.86 ± 0.42 vs 1.02 ± 0.51, P = .005). A significant correlation was detected between total bilirubin and SXscore (r = .42; P = .001). At multivariate analysis, total bilirubin (odds ratio: 1.86, 95% confidence interval 1.04-3.35; P = .038) was an independent risk factor for high SXscore in patients with STEMI. In conclusion, serum bilirubin level is independently associated with SXscore in patients with STEMI.