Fehmi Mercanoglu

The role of aspirin resistance on outcome in patients with acute coronary syndrome and the effect of clopidogrel therapy in the prevention of major cardiovascular events.

AbstractBackground: Aspirin resistance may increase up to more then threefold the risk of major cardiovascular events (MACE) in patients with stable coronary artery disease. Aim:The aim of our study was to determine; the prevalence of aspirin resistance in patients with acute coronary syndromes, the role of aspirin resistance on outcome in the follow-up and the effect of clopidogrel therapy in the prevention of MACE in aspirin resistant subjects. Material and methods: We detected the prevelance of aspirin resistance in 105 patients with acute coronary syndrome. Platelet functions were analyzed in Platelet Function Analyzer (PFA)-100 (Dade Behring, Germany) with collagen and/or epinephrine (Col/Epi) and collagen and/or ADP (Col/ADP) cartridges. Primary end points of the study were myocardial infarction, unstable angina, cardiac death. Results: 19% (n = 20) of patients were aspirin resistant by PFA-100. In the follow-up, MACE occured in 9 patients (45%) with aspirin resistance and in 10 patients (11.7%) with aspirin sensitive platelet aggregation (p = 0.001). Multivariate analysis showed that aspirin resistance was an independant predictor of MACE. The prevalence of MACE in patients who were on clopidogrel treatment for 12 months were lower compared to those who were on a clopidogrel treatment for the first six months (p = 0.040). Conclusions: We determined that the MACE risk in patients with acute coronary syndromes having detected aspirin resistance, was higher at statistically significant levels compared to patients having aspirin sensitive platelet aggregation. Our results showed that aspirin resistance, was an independant predictor of MACE in patients with acute coronary syndrome.

The effect of calcineurin inhibitors on endothelial function in renal transplant recipients.

Abstract:  Endothelial dysfunction is of vital importance, as it may cause ischemia and dysfunction in various organs. Despite, this problem has been well documented in patients with end‐stage renal disease (ESRD), there is not enough data considering this issue following renal transplantation. One of the potential causes of endothelial dysfunction in renal transplant recipients may be administration of calcineurin inhibitors. The aim of this study is to evaluate the effects of two different calcineurin inhibitors [cyclosporin A (CsA) and tacrolimus (FK506)] on endothelial function in renal transplant patients. Forty‐four renal transplant recipients [22 on FK506 (group I) and 22 on CsA (group II)] were studied. Endothelial functions of the brachial artery were evaluated by using high resolution vascular ultrasound. Endothelium‐dependent and ‐independent vasodilations were assessed by establishing reactive hyperemia and using sublingual nitroglycerine (NTG), respectively. Results are presented as percentage change from baseline values. Significant endothelial dysfunction was noted in renal transplant patients treated with CsA. While endothelium‐dependent vasodilation was 12.1 ± 5.1% in group I and it was 6.5 ± 3.7% in group II (p < 0.001). The increase in brachial artery diameter after sublingual NTG was 20.1 ± 6.3 and 12.7 ± 5.6% in groups I and II, respectively. This indicates that the endothelium‐dependent and ‐independent vasodilation of the patients on FK506 is better preserved than the patients on CsA therapy. Besides, blood flow volume (BFV) increase was 51.2 ± 39.4 and 43.9 ± 24.3%, in groups I and II, respectively, in reactive hyperemia period (p > 0.05). Post‐transplant course of renal transplant recipients is complicated by endothelial dysfunction. This problem is more prominent in patients on CsA therapy, which can predispose these patients to more frequent cardiac complications.

Association of haematological indices with the degree of microvascular injury in patients with acute anterior wall myocardial infarction treated with primary percutaneous coronary intervention

Background: In acute myocardial infarction (AMI), increased neutrophil count has been associated with more severe coronary artery disease and larger infarct size. Increased mean platelet volume (MPV) is also associated with poor clinical outcome and impaired angiographic reperfusion in patients with AMI. However, the associations of neutrophil count and MPV with the indices of tissue level reperfusion were not fully elucidated. Aim: To elucidate the relationship between baseline neutrophil count and MPV on presentation and microvascular injury in patients with anterior AMI treated with primary percutaneous coronary intervention (pPCI). Methods: 41 patients with anterior wall AMI treated successfully with pPCI were included. The leucocyte count, neutrophil count and MPV were obtained on admission, and the percentage of neutrophils was calculated. After PCI thrombolysis in myocardial infarction, grade 3 flow was established in all patients. The coronary flow velocity pattern (diastolic deceleration time (DDT)) was examined with transthoracic echocardiography and measured intracoronary pressures with fibreoptic pressure–temperature sensor-tipped guidewire in the left anterior descending artery within 48 h after pPCI. Thermodilution-derived coronary flow reserve (CFR) was calculated. Index of microvascular resistance (IMR) was defined as simultaneously measured distal coronary pressure divided by the inverse of the thermodilution-derived hyperaemic mean transit time. Subsequently, a short compliant balloon was placed in the stented segment and inflated to measure coronary wedge pressure (CWP). Results: Higher neutrophil counts were strongly associated with higher IMR (r = 0.86, p<0.001), lower CFR (r = −0.60, p<0.001), shorter DDT (r = −0.73, p<0.001) and higher CWP (r = 0.73, p<0.001). Likewise, there were significant correlations among the percentage of neutrophils and CFR (r = −0.34, p = 0.02), IMR (r = 0.46, p = 0.002), DDT (r = −0.36, p = 0.01) and CWP (r = 0.49, p = 0.001). Relationships among leucocyte count and IMR (r = 0.38, p = 0.01), CFR (r = −0.33, p =  0.03), DDT (r = −0.36, p = 0.01) and CWP (r = 0.32, p = 0.026) were slightly significant. Higher neutrophil count remained independently associated with indices of microvascular perfusion in multivariable models controlling for age, smoking habits and time to treatment. Also, higher MPV on admission was strongly associated with higher IMR (r = 0.89, p<0.001), steeper DDT (r = −0.64, p<0.001), lower CFR (r = −0.43, p = 0.004) and higher CWP (r = 0.77, p<0.001). Conclusion: Absolute and relative neutrophilia and higher MPV on admission were independently associated with impaired microvascular perfusion in patients with anterior AMI treated with pPCI. It is possible that neutrophilia and high MPV are simple surrogate markers of worse microvascular injury in patients with AMI.

Clinical relevance of aspirin resistance in patients with stable coronary artery disease: a prospective follow-up study (PROSPECTAR).

Aspirin resistance may increase the risk of major adverse cardiac events (MACE) more than threefold in patients with stable coronary artery disease (CAD). This study aimed to determine the prevalence of aspirin resistance in patients with stable CAD, the role of aspirin resistance on outcome in the follow-up, and the effect of clopidogrel therapy in MACE prevention in aspirin-resistant individuals. We detected the prevalence of aspirin resistance in 234 patients with stable CAD. Platelet function was determined by PFA-100 with collagen and/or epinephrine and collagen and/or ADP cartridges. The mean follow-up time was 20.6 ± 6.9 months. The primary endpoints of the study were occurrence of myocardial infarction, unstable angina, stroke and cardiac death. Of patients, 22.2% (n = 52) were aspirin resistant by PFA-100. During follow-up, MACE occurred in eight patients (15.4%) with aspirin resistance and in 20 patients (11.0%) with aspirin-sensitive platelet aggregation (P = 0.269). MACE increased in aspirin-resistant patients after termination of clopidogrel therapy. Eleven patients experienced MACE after cessation of clopidogrel therapy (P < 0.001). The MACE risk in patients with stable CAD having detected aspirin resistance was similar compared with patients having aspirin-sensitive platelet aggregation by PFA-100. The MACE prevalence increased during follow-up, however, just after cessation of clopidogrel therapy.

Effect of carvedilol on silent anthracycline-induced cardiotoxicity assessed by strain imaging: A prospective randomized controlled study with six-month follow-up.

BACKGROUND The use of antracycline (ANT) in breast cancer has been associated with adverse cardiac events. Two-dimensional (2D) strain imaging (SI) can provide a more sensitive measure of altered left ventricular (LV) systolic function. We aimed to evaluate the preventive effect of carvedilol administration assessed by SI in a patient with breast cancer treated with ANT. METHODS Patients receiving ANT were randomly assigned to the carvedilol- or placebo-receiving group. Each received an echocardiographic examination with conventional 2D echocardiography, pulsed tissue Doppler, and 2D SI prior to and 6 months post ANT treatment. RESULTS During the 6-month follow-up period there were no patient deaths or interrupted chemotherapy treatments due to doxorubicin-induced cardiotoxicity. Both left ventricular ejection fraction (LVEF) and fractional shortening (FS) were within normal limits for all patients before and after ANT therapy. EF, FS and LV dimensions were measured using M-mode echocardiography and found to be similar in both groups before and after ANT therapy. The mean EF, FS, and LV echocardiograph baseline and control dimensions were similar in both groups after 6 months. Though baseline SI parameters were similar between the groups, there was a significant decrease in LV basal septal and basal lateral peak systolic strain in the control group compared to the carvedilol group. CONCLUSIONS These results indicate that carvedilol has a protective effect against the cardiotoxicity induced by ANT.

Left ventricular remodeling and aortic distensibility in elite power athletes

The aim of this study was to determine left ventricular (LV) morphology and aortic function in power athletes and to compare them with normal subjects. Thirty-two elite male wrestlers and 15 age-matched healthy male controls were included. All subjects underwent echocardiographic examination. Measurements included LV cavity dimension at systole and diastole, wall thickness, diastolic parameters, and aortic diameter, 3 cm above aortic valve, at systole and diastole. Left ventricular mass and mass index were found to be higher in the athletes than in control subjects. The aortic distensibility index was found to be reduced in the athletes compared with controls (2.53 ± 0.91 vs 3.94 ± 1.77 cm2 dyne−1 10−6, P = 0.003), while the aortic stiffness index was significantly higher in the athletes than in controls (9.12 ± 3.23 vs 6.65 ± 2.35, P = 0.02). However, LV end-systolic wall stress was lower in the athletes than in controls. Furthermore, transmitral early (E) and late (A) peak velocity, peak velocity of the myocardial systolic wave (Sm), and early (Em) and atrial (Am) diastolic waves at the inferior wall were higher in the athletes than in controls. Reduced aortic distensibility in elite power athletes may be one of the cardiovascular adaptation factors which affect LV hypertrophy.

Improvement of Endothelial Dysfunction with Simvastatin in Patients with Autosomal Dominant Polycystic Kidney Disease

Cardiovascular problems are a major cause of morbidity and mortality in patients with autosomal dominant polycystic kidney disease (ADPKD). Endothelial dysfunction (ED), which is an early manifestation of vascular injury, has been shown in patients with ADPKD. Statins have a beneficial effect in the reversal of ED. The aim of this study was to investigate the effects of a statin, simvastatin, on ED in patients with ADPKD. Sixteen patients with ADPKD having well-preserved renal function were included in the study. Endothelial function of the brachial artery was evaluated by using high-resolution vascular ultrasound. Endothelial-dependent dilatation (EDD) was expressed as the percentage change in the brachial artery diameter from baseline to reactive hyperemia. After the baseline evaluations of EDDs, patients were started treatment with simvastatin at a dose of 40 mg/day and were treated for six months. EDDs were recalculated after one and six months of therapy. Interleukin-6 (IL-6) and high-sensitivity C-reactive protein were also measured as markers of inflammation. Baseline EDD was 11.3 ± 6.9% in patients with ADPKD. After one month of simvastatin treatment, EDD increased significantly to 14.6 ± 4.6 % (P = 0.016 versus baseline). Endothelial-dependent dilatation further increased significantly to 18.9 ± 7.5 % (P = 0.011 versus baseline, P = 0.048 versus first month) after six months of therapy. There was also a significant decrease in the level of IL-6 from 21.6 ± 21.7 pg/mL to 9.1 ± 3.5 pg/mL (P= 0.002). Six months of simvastatin therapy resulted in a significant improvement of ED in patients with ADPKD. This finding may be in part related to the pleiotropic effects of simvastatin.

Impact of vitamin D insufficiency on the epicardial coronary flow velocity and endothelial function.

ObjectiveIncreasing evidence suggests a relationship between vitamin D (VD) insufficiency and cardiovascular disease. The present study evaluated the effect of VD insufficiency on epicardial coronary flow rate, subclinical atherosclerosis, and endothelial function. MethodsThe present study was cross-sectional and observational. We enrolled 222 consecutive patients who had undergone coronary angiography for suspected ischemic heart disease and were found to have normal or near-normal coronary arteries. Thereafter, 25(OH)D3 levels were measured and the coronary flow rate was assessed using the thrombolysis in myocardial infarction frame count. Slow coronary flow (SCF) was defined as a thrombolysis in myocardial infarction frame count greater than 27/frame. Endothelial function was assessed by brachial artery flow-mediated dilatation. Carotid intima-media thickness, an indicator of subclinical atherosclerosis, was measured using B-mode ultrasonography. ResultsThe mean level of 25(OH)D3 was 31.8 ng/ml, and 47% (n=106) of the patients had insufficient 25(OH)D levels (<30 ng/ml). Baseline characteristics were similar between VD-insufficient and VD-sufficient groups. The incidence of SCF was significantly higher in the VD-insufficient group than in patients with sufficient VD (relative risk=3.5, 95% confidence interval=1.1–10.5, P=0.01). After adjusting for cardiovascular disease risk factors, VD insufficiency was independently associated with SCF. The linear regression analysis showed that VD insufficiency was correlated independently with % flow-mediated dilatation (&bgr;=0.424, P<0.001) and carotid intima-media thickness (&bgr;=0.43, P<0.001). ConclusionA strong association was found between VD insufficiency and the SCF phenomenon. In addition, VD insufficiency was associated with endothelial dysfunction and subclinical atherosclerosis. We believe that further studies are required to clarify the role of VD in patients with SCF.

Comparison of the effects of trimetazidine and diltiazem on exercise performance in patients with coronary heart disease. The Turkish trimetazidine study (TTS).

Objective — A multicentre, double-blind comparative study was performed to compare the effects of trimetazidine with diltiazem on exercise performance in patients with stable angina pectoris. Methods and results — A total of 116 male patients with documented coronary artery disease at 11 centres were randomized into trimetazidine and diltiazem groups both including 58 men (mean age 55.1 ± 8.6 years and 54.9 ± 6.6 years, respectively) in a prospective, multicentre, double-blind active treatment trial.The study consisted of a two-week placebo washout period and a four-week active treatment phase. Clinical examinations and exercise tests were performed at the beginning (D0) and at the end (D28) of the active treatment. Laboratory investigations were also performed at the beginning of the washout period (D-14) and at D28. Holter recordings were done in the mid of the washout period (D-7) and D28. Both trimetazidine and diltiazem decreased the number of anginal attacks per week (p < 0.0001 for both drugs) and weekly nitrate consumption (p = 0.0008 and p < 0.0001, respectively). Both trimetazidine and diltiazem improved the recovery of anginal pain (p = 0.0188 and p = 0.0079, respectively) and maximal ST-segment depression (p = 0.0134 and p = 0.0214, respectively) but none of the drugs significantly changed the time to 1 mm ST-segment depression and ST recovery time on exercise test. Diltiazem caused a slight prolongation of PR and QRS durations (p = 0.039) on ambulatory ECG whereas trimetazidine did not change these parameters significantly. Conclusion — This study suggests that trimetazidine is an effective and safe alternative for diltiazem in the treatment of patients with stable angina pectoris. Although several other trials have shown that this drug can be used in combination with other antianginal drugs or instead of beta blockers or nifedipine in the symptomatic treatment of stable anginal syndromes, this study suggests that trimetazidine can be used instead of diltiazem, a well-known powerful antianginal drug.

GALECTIN-3: A NOVEL BIOMARKER PREDICTS SUDDEN CARDIAC DEATH IN HYPERTROPHIC CARDIOMYOPATHY

Background: Hypertrophic cardiomyopathy is a primary cardiac disease characterized by left ventricular hypertrophy, myocyte hypertrophy and irregularities and interstitial fibrosis in the absence of any cardiac or systemic diseases and may lead to sudden cardiac death (SCD). Galectin‐3 is a &bgr;‐galactoside‐binding lectin that has been associated with cardiac fibrosis and inflammation. In this study, we aimed to investigate the relationship between serum galectin‐3 levels and the criteria for 5‐year sudden death risk, recently defined in the European Society of Cardiology guidelines (2014), in patients with hypertrophic cardiomyopathy. Materials and Methods: A total of 52 hypertrophic cardiomyopathy patients were enrolled in the study. Patients were questioned for sudden death risk predictors as outlined in the 2014 European Society of Cardiology guideline. A standardized clinical evaluation was carried out on the basis of previously described prognostic variables to calculate the 5‐year risk of SCD. Blood samples were taken from all patients to measure serum galectin‐3 levels. A statistical significance level of P < 0.05 was accepted in all tests. Results: We found that there was a significant correlation between the estimated 5‐year risk of SCD and serum levels of galectin‐3. Conclusions: Galectin‐3 may be an inexpensive and easily accessible parameter to predict arrhythmia risk. In addition, it can be used to determine antiarrhythmic prophylaxis as a predictor of an arrhythmia storm in implantable cardioverter defibrillator‐implanted patients who are not available for magnetic resonance imaging.