Irem Dincer

Assessment of left ventricular diastolic function with Doppler tissue imaging: Effects of preload and place of measurements

Mitral inflow velocities are widely used for the evaluation of left ventricular (LV) diastolic function. However, they are closely affected by other factors such as preload. The purpose of this study was to evaluate the usefulness of tissue Doppler velocities obtained from the mitral annulus for the evaluation of ventricular relaxation in patients under different loading conditions. We also evaluated the effect of preload at different sides on the mitral annulus. The study population consisted of 62 consecutive patients (38 male, 24 female with a mean age of 42 ± 13 years) who have undergone hemodialysis. Both mitral inflow velocities (E wave, A wave, E wave deceleration time and isovolumetric relaxation time) and mitral annulus tissue Doppler velocities (E′, A′) from the septal, lateral, anterior, posterolateral and inferior sides of the mitral annulus were measured immediately before and after hemodialysis. Mitral inflow E and A wave velocities and E/A ratio decreased significantly (p < 0.001, p = 0.007, p < 0.001, respectively) after hemodialysis. Mitral annulus E′ wave velocities and E′/A′ ratios obtained from five different sides of the annulus also changed significantly (p < 0.001 for all); however, there was no change in the A′ wave velocity (p > 0.05 for all) after hemodialysis. The decrease in E wave and E/A ratio in mitral inflow measurements and E′ velocities and E′/A′ ratios in tissue Doppler measurements were correlated with the amount of fluid extracted (for mitral inflow E wave, r = 0.392, p = 0.002 and E/A ratio, r = 0.280 and p = 0.027; for lateral side E′, r = 0.329, p = 0.009 and E′/A′ ratio, r = 0.286, p = 0.04; for septal side E′, r = 0.376, p = 0.003 and E′/A′ ratio, r = 0.297, p = 0.019; for anterior side E′, r = 0.342, p = 0.007 and E′/A′ ratio, r = 0.268, p = 0.035; for posterolateral side E′, r = 0.423, p = 0.001 and E′/A′ ratio, r = 0.343, p = 0.007; and for inferior side E′, r = 0.326, p = 0.01 and E′/A′ ratio, r = 0.278, p = 0.029). We conclude that mitral annular velocities obtained by tissue Doppler are preload dependent parameters for the evaluation of LV diastolic function.

Elevated levels of C-reactive protein are associated with impaired coronary collateral development.

Background  In vitro studies have shown that C‐reactive protein (CRP) attenuates nitric oxide production and inhibits angiogenesis, which may result in impaired collateral development. The aim of this study was to investigate the association between high sensitivity CRP (hsCRP) levels and the extent of coronary collaterals.

Effect of losartan on circulating Tnfα levels and left ventricular systolic performance in patients with heart failure

Background Tumor necrosis factor alpha (TNFα) plays an important role in the pathophysiology of heart failure. Recent studies have shown a beneficial effect of losartan in these patients. However, the effect of losartan on TNFα levels in heart failure has not yet been studied. We evaluated the effect of losartan on circulating TNFα levels and ejection fraction (EF) in patients with congestive heart failure. Methods Forty patients with heart failure and EF ≤ 40% were enrolled into the study. All of the patients have been given diuretic and digitalis therapy. Twenty patients were given losartan (50 mg/d) (Group I, 10 women, 10 men, 12 dilated cardiomyopathy, 8 ischemic heart disease, mean age 64.9 ± 8.9), and another 20 patients were not given losartan because of hypotension or renal dysfunction (Group II, 13 men, 7 women, 10 dilated cardiomyopathy, 10 ischemic heart disease, mean age 61.2 ±10.5). EF was measured at the initial evaluation and on the fifteenth day of the therapy by echocardiographic examination using an acoustic quantification method. Circulating TNFα levels were also measured at the initial evaluation and on the fifteenth day of therapy by the ELISA method. Results Losartan significantly increased EF and decreased TNFα (EF increased from 29.4 ± 7.3% to 36.0 ± 8.5%, P < 0.001, and TNFα decreased from 39.2 ± 37.4 pg/ml to 27.0 ± 30.0 pg/ml, P < 0.05). Changes in TNFα levels and EF were not found to be correlated (r=−0.28, P=0.24). However, in the control group, EF and TNFα levels were similar at baseline and at the fifteenth day (EF 31.4 ± 8.1% vs 31.7 ± 7.8%, P=0.1, and TNFα 91.5 ± 86.0 pg/ml vs 110.0 ± 80.7 pg/ml, P=0.1, respectively). Conclusions Losartan improves left ventricular systolic function and decreases TNFα level. The decreased TNFα level seems to be independent of EF.

The effects of L-carnitine treatment on left ventricular function and erythrocyte superoxide dismutase activity in patients with ischemic cardiomyopathy

We studied the effects of l‐carnitine on left ventricular systolic function and the erythrocyte superoxide dismutase activity in 51 patients with ischemic cardiomyopathy. They all previously were under the treatment of angiotensin‐converting enzyme inhibitor, digitalis and diuretics. Patients were randomized into two groups. In group I (n = 31), 2 g/day l‐carnitine was added to therapy. l‐Carnitine was not given to the other 20 patients (Group II). In group I (mean age 64.3 ± 7.8 years), 27 of the patients were men, and four were women. In group II (mean age 66.2 ± 8.7 years), 17 of the patients were men, and three were women. Twenty age‐matched healthy subjects (mean age: 60.1 ± 5.3 years) constituted the control group. In each group, left ventricular ejection fraction (LVEF) by echocardiography and red cell superoxide dismutase activity by spectrophotometric method were measured initially and after 1 month of randomisation. Compared with normal healthy subjects (n = 20), patients (n = 51) had significantly higher red cell SOD activity (5633 ± 1225 vs. 3202 ± 373 U/g Hb, P < 0.001). At the end of 1 month of l‐carnitine therapy, red cell SOD activity showed an increase in group I (5918 ± 1448 to 7218 ± 1917 U/g Hb, P < 0.05). In group II, red cell SOD activity showed no significant change after 1 month of randomisation (5190 ± 545 to 5234 ± 487 U/g Hb, P = 0.256). One month after randomisation there was a significant increase in LVEF in both groups I and II (37.8–42.3%, P < 0.001 in group I; 41.5–43.8%, P < 0.001 in group II). The improvement in LVEF was more significant in the l‐carnitine group (4.5% vs. 2.3%, P < 0.01). We conclude that, as a sign of increased free radical production, superoxide dismutase activity was further increased in patients with l‐carnitine treatment. l‐Carnitine treatment in combination with other traditional pharmacological therapy might have an additive effect for the improvement of left ventricular function in ischemic cardiomyopathy.

A Recurrent Right Heart Thrombus in a Patient with Behçet's Disease

We report the case of a patient who was admitted to the immunology unit of our medical facility. The patient had a history of recurrent oral ulcers, low‐grade fever, weight loss, and fatigue. Echocardiographic examination revealed a right ventricular mass that was initially thought to be a myxoma in an unusual location, and the patient was sent to surgery. Surgery revealed the mass to be a thrombus. After 5 months of anticoagulation therapy, the patient was readmitted to our institution with the same complaints, and a right atrial thrombus was found on echocardiographic examination. After a careful reevaluation of the patients history and episodes of recurrent oral and genital ulcers, as well as the papulopustular lesions found on his first admission to hospital, Behçets disease was diagnosed. The patient received thrombolytic therapy with a regression of thrombus, and continued with immunosuppressive and anticoagulation therapy. Five months later, echocardiographic examination showed complete disappearance of thrombus.

Hyperhomocysteinemia and Restenosis

Objective This study was undertaken to assess the effect of plasma homocysteine level on angiographic restenosis 6 months after coronary angioplasty. Methods The plasma homocysteine level was measured in 100 consecutive patients at the time of coronary angioplasty, 56 patients who attended a 6-month follow-up angiogram being enrolled to the study; the 44 patients without a control coronary angiogram were not enrolled. Patients with and without angiographic restenosis were designated as groups A (n = 34) and B (n = 22) respectively. Results The baseline demographic (groups A and B), angiographic (groups A and B) and procedural characteristics were similar in both groups. The mean plasma homocysteine level (SD) was 15.2 (7.7) and 11.1 (2.5) μmol/l in groups A and B respectively (P = 0.007; 95% CI −6.9 to −1.1). With respect to the plasma homocysteine level, the upper and the lower thirds were compared by binary logistic regression (the lower third homocysteine level being < 10.6 μmol/l and the upper third homocysteine level > 14.1 μmol/l). The angiographic restenosis rate for the lower and upper tertiles was 47.4% and 89.5% respectively (P = 0.01; OR = 9.4; 95% CI 1.6−52.7). After adjustment for age and sex, the statistical significance did not change (P = 0.013; OR = 9.43; 95% CI 1.6-54.9). Even after adjustment for age, sex, smoking, hypertension, hypercholesterolemia, and diabetes mellitus, there was a statistically significant difference between the upper and lower tertiles (P = 0.008; OR = 41.3; 95% CI 2.6-635). Conclusion Increased plasma homocysteine level and diabetes mellitus were independent risk factors for angiographic restenosis after percutaneous transluminal coronary angioplasty and coronary stenting.

Association between the severity of heart failure and the susceptibility of myocytes to apoptosis in patients with idiopathic dilated cardiomyopathy

BACKGROUND Bcl-2 proto-oncogene, an inhibitor of apoptosis and Bax proto-oncogene, an inducer of apoptosis play critical roles in the molecular circuit controlling apoptosis in cardiac muscle. The ratio of Bax to Bcl-2 proto-oncogene determines survival or death after an apoptotic stimulus. We speculated that susceptibility of myocytes to apoptosis determined as the Bax/Bcl-2 ratio might vary with the severity of heart failure. METHODS AND RESULTS We studied immunohistochemically 108 endomyocardial biopsy specimens from 30 patients with idiopathic dilated cardiomyopathy (mild heart failure, n=14; moderate or severe heart failure, n=16) with the use of Bcl-2 and Bax monoclonal antibodies. The expression of each protein was determined semiquantitatively as the fraction of myocytes labeled with specific monoclonal antibodies using a digital morphometric analysis system. Patients with mild heart failure showed significantly increased Bax/Bcl-2 ratio than the patients with advanced heart failure (1.59+/-1.26 vs. 0.34+/-0.43, P=0.002). The expression of Bcl-2 was found to be independent of the severity of heart failure whereas the expression of Bax was significantly higher in patients with mild heart failure compared to the patients with moderate or severe heart failure (52.1+/-29.3 vs. 21.6+/-22.4%, P=0.005). Additionally, Bax/Bac-2 ratio was inversely correlated with the mitral E-interventricular septum distance, left ventricular end-systolic and end-diastolic diameter. CONCLUSION The susceptibility of myocytes to apoptosis is significantly increased in the early phase of heart failure but it decreases with worsening of the disease due to depressed expression of Bax onco-protein. Increased myocyte susceptibility to apoptosis may have a role in the transition from mild heart failure to severe in patients with idiopathic dilated cardiomyopathy.

Good Collaterals Predict Viable Myocardium

The authors undertook this study to see whether highly developed coronary collaterals at an area shed by a totally occluded coronary artery predicts myocardial viability. Percutaneous coronary intervention (PCI) of a totally occluded coronary artery has been debated since its introduction. It is recommended to search for viable myocardium before opening a totally occluded coronary artery; however, there is no practical yet sensitive method of assessing myocardial viability in the catheterization laboratory. Forty-seven consecutive patients (12 women, 25.5%; 35 men, 74.5%), each with 1 totally occluded coronary artery, were prospectively enrolled to the study. After the diagnostic coronary angiography, all patients underwent dobutamine stress echocardiography to determine viable myocardium at the territory of the totally occluded coronary artery, and the status of angiographic coronary collaterals was assessed. Patients were then divided into 2 groups according to the presence (Group A) or absence (Group B) of viable myocardium by stress echocardiography. Eighteen patients (38.3%) had viable myocardium (Group A) in the area shed by the totally occluded coronary artery and 29 patients (61.7%) had nonviable myocardium (Group B). The incidences of significant coronary collateral circulation to the viable (Group A) and nonviable (Group B) areas were 66.7% (12 patients) and 20.7% (6 patients), respectively (p = 0.002). Logistic regression analysis was used to evaluate the independent factors for viable myocardium, and only significant coronary collateral circulation was found to be an independent factor for the detection of viable myocardium (p = 0.006, OR 16.7, 95% CI 2.25 to 124.4). The sensitivity and specificity of good collateral circulation for the detection of viable myocardium were 75% and 65.7%, respectively. The positive predictive and negative predictive values of the good coronary collateral circulation in detecting viable myocardium were 75% and 79%, respectively. The authors conclude that good coronary collaterals have a high sensitivity and positive predictive value for the prediction of viability as shown by dobutamine echocardiography, and only by assessing the coronary collateral circulation can one decide for percutaneous coronary revascularization, if not for coronary artery bypass surgery.

Second recurrence of familial cardiac myxomas in atypical locations

Recurrence rates reported for cardiac myxomas are 4% to 7% for sporadic cases and 10% to 21% for familial cases. Although recurrence rates are high, second recurrences are rare. Familial cardiac myxomas in a mother and daughter are reported, both of whom had their second recurrences within six years. Both had recurrences in uncommon places, such as the left atrial posterior wall, between the left atrial appendage and the pulmonary vein, and the anterior mitral leaflet.

Association between the dosage and duration of statin treatment with coronary collateral development.

BackgroundThe coronary collateral circulation is an alternative source of blood supply to myocardium in the presence of advanced coronary artery disease and the therapeutic promotion of collateral growth appears to be a valuable treatment strategy in these patients. Although it has been shown in in-vivo studies that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) promote vasculogenesis and accelerate coronary collateral development in ischemic tissues, there are discordant results in clinical studies. Our aim was to investigate the effect of statin therapy, including dosage and duration of treatment, on coronary collateral growth in patients with advanced coronary artery disease. MethodsStudy population consisted of 400 (306 men, with the mean age of 62±10 years) consecutive patients who have undergone clinically indicated coronary angiography and had at least one major coronary artery stenosis of ≥95%. Coronary collaterals were graded from 0 to 3 according to the Cohen–Rentrop method and patients with grade 0–1 collateral development were regarded as having poor collateral and patients with grade 2–3 collateral development were regarded as having good collateral. ResultsAmong 400 patients, 196 (48%) were on statin therapy. Patients with good collateral score were more likely to have stable angina pectoris as clinical presentation (P<0.001), and were on statin therapy (P=0.001), and have multivessel disease (P=0.003). Statin therapy for less than 3 months had no effect on collateral development (P=0.19); however, patients who were on statin therapy for more than 3 months had significantly better collateral development (P=0.002). Statin therapy had no effect on coronary collateral development in patients having <10 mg atorvastatin-equivalent dose (P=0.13); however, patients having ≥10 mg atorvastatin-equivalent dose had better collateral development (P<0.001). Diabetes mellitus was the only negative predictor for coronary collateral formation (P=0.03). On multivariate analysis, stable angina pectoris [odds ratio 2.88, 95% confidence interval (1.8–4.7), P<0.001], statin therapy with ≥10 mg atorvastatin-equivalent dose [odds ratio 2.06, 95% confidence interval (1.3–2.6), P<0.001] and having multivessel disease [odds ratio 1.86, 95% confidence interval (1.16–3), P=0.01] were found to be associated with rich collateralization. ConclusionStatin therapy (≥10 mg atorvastatin-equivalent dose), stable angina pectoris and having multivessel disease are associated with enhanced coronary collateral development in patients with advanced coronary artery disease.