Seden Celik

A Comparison of Results of the US Food and Drug Administration’s Mini-Sentinel Program With Randomized Clinical Trials: The Case of Gastrointestinal Tract Bleeding With Dabigatran

A Comparison of Results of the US Food and Drug Administration’s Mini-Sentinel Program With Randomized Clinical Trials: The Case of Gastrointestinal Tract Bleeding With Dabigatran The US Food and Drug Administration (FDA) recently started an initiative called “Mini-Sentinel Program” to assess medical product safety using administrative-observational databases. One of the first utilizations of this program was to examine the bleeding risk of dabigatran in response to the unexpectedly high number of postmarketing reports of bleeding.1 However, there are major limitations of observational studies, and therefore the reliability of the Mini-Sentinel Program is unknown. Our objective was to compare the results of this program regarding the gastrointestinal (GI) tract bleeding risk of dabigatran vs warfarin with the results of randomized clinical trials (RCTs).

A case of coronary spasm induced by 5-fluorouracil.

Cardiotoxicity is an uncommon adverse effect of 5-fluorouracil (5-FU). Coronary artery spasm has been postulated to be involved in the mechanism of this incident. Patients may present with angina, myocardial infarction, arrhythmias and/or even sudden death.When the drug is readministered, there is a high risk of relapse. The underlying mechanisms of cardiotoxicity are not yet fully understood, although coronary vasospasm may be responsible.We report one woman receiving 5-fluorouracil therapy with typical chest pain and electrocardiographic changes consistent with acute coronary syndrome. A resolving pain and normalisation of ECG changes with nitrate therapy and normal coronary arteries indicate that this incident was about a coronary spasm caused by 5-FU.

The effects of hormonal therapy on aortic stiffness and left ventricular diastolic function.

Objective — The main objective of this study is to investigate the effects of oestrogen replacement therapy (ERT) and hormone replacement therapy (HRT) on aortic stiffness and on the left ventricular diastolic function, including tissue Doppler. Methods and results — The two study groups were composed of 20 postmenopausal women having HRT and 22 postmenopausal women having ERT. Each group was evaluated for aortic elasticity properties and the left ventricular diastolic function at both the pre-treatment stage and after 12 weeks of hormonal therapy.There was a significant improvement in beta index (5.2±2.5 vs. 3.2±2.2, p = 0.001), distensibility (5.2±3.7 vs. 6.1±4.1 cm2.dyn-1.10-3, p = 0.036) and mitral E/Em ratio (7.44±3.25 vs. 5.75±.2.34, p = 0.004) with ERT. HRT was observed to improve aortic elasticity properties (for strain 10.7±4.7 vs. 12.8±7.6%, for beta index 4.9±2.1 vs. 3.39±2.4 and for distensibility 4.6±2.1 vs. 5.69±4.1 cm2.dyn-1.10-3) and the mitral E/Em ratio (7.61±3.31 vs. 5.81±2.31, p = 0.003). Conclusion — Both ERT and HRT have an improving effect on aortic elasticity properties, as well as on the diastolic function.

Aortic stiffness in patients with cardiac syndrome X.

Aim — Recently, the close relationship between aortic stiffness and cardiovascular mortality has aroused the interest of investigators in carrying out studies related to aortic stiffness.This study aims to investigate the aortic stiffness parameters in patients with cardiac syndrome X, a disorder that is believed to be a generalized disturbance of the vasodilator function of small arteries. Material and methods — 18 patients with typical chest pain and angiographically normal coronary arteries associated with a positive exercise test were included in the study. The control group consisted of 27 patients with angiographically normal coronary arteries and no ischaemia on exercise testing. Antianginal medication was withheld 4 weeks before the study and transthoracic echocardiography was performed using a Hewlett-Packard Sonos 1500 instrument with a 2.5 MHz phased array transducer. Ascending aorta diameters were measured on the M-mode tracing at a level 3 cm above the aortic valve. Diameter change, pulse pressure, aortic strain and distensibility were measured as aortic stiffness parameters. Results —The aortic diameter change was less in the syndrome X group than in the control group (0.15±0.04 cm/m2 vs. 0.28±0.12 cm/m2, p<0.001). Likewise, aortic strain (9±3% vs. 18±8%, p<0.001) and distensibility (4.01±1.71 cm2.dyn-1.10-3 vs. 9.95±5.08 cm2.dyn-1.10-3, p<0.001) was significantly lower in the syndrome X group than in the control group. Conclusion—The deterioration in aortic elasticity properties in patients with cardiac syndrome X suggests that this disease may be a more generalized disturbance of the vasculature.

Double-orifice mitral valve associated with nonisolated left ventricular noncompaction: A case report

Double-orifice mitral valve is a rare congenital anomaly. Although it is more frequently associated with other cardiac abnormalities, it may occur as an isolated lesion. There are 2 forms of myocardial noncompaction: isolated and nonisolated myocardial noncompaction. Nonisolated myocardial noncompactions are occasionally reported postnatally in association with congenital heart anomalies such as ventricular septal defect, pulmonic stenosis, and atrial septal defect. To our knowledge, this is the first case presentation reporting a double-orifice mitral valve associated with nonisolated myocardial noncompaction.

Assessment of the effects of various maneuvers on both atrial pressure changes

The aim of the present study was to determine which maneuver causes the greatest pressure difference between both atria by measuring right and left atrial pressures simultaneously after certain maneuvers. Thirty-two coronary care unit patients, whom a Swan-Ganz catheter was inserted because of acute left ventricular dysfunction, hypotension, sinus tachycardia with unknown cause, were included in this study. The basal values of peak right atrium (RA) pressure and corresponding pulmonary capillary wedge pressure (PCWP) were measured via two separated transducers. Patients were tutored with several trials to perform breath holding, successive three strong coughs, Valsalva maneuver, 20 degrees head down, respectively. In the end of these maneuvers, the peak RA pressure and corresponding PCWP were measured simultaneously. All maneuvers caused an increase in RA pressure. The highest peak RA pressure was obtained by means of the Valsalva maneuver (7.6 +/- 5 versus 20.4 +/- 7.6 mmHg before and after Valsalva, respectively; P<0.001). PCWP (18.8 +/- 5.9 mmHg) increased only with coughing (21.2 +/- 6.7 mmHg, P<0.01) and 20 degrees head down maneuver (20 +/- 5.7 mmHg, P<0.05). The highest increase in pressure gradient between peak RA pressure and corresponding PCWP was observed during Valsalva maneuver (-11 +/- 6.6 vs. 2.3 +/- 5.9 mmHg, P<0.001). The lowest increase was obtained in 20 degrees head down maneuver (-11 +/- 6.6 vs. -8.5 +/- 5.8 mmHg, P<0.001). When measuring the pressure of both atria invasively and simultaneously, Valsalva maneuver was the most effective maneuver consistent with pressure difference in favour of RA among all the other maneuvers.

Transthoracic Doppler echocardiographic coronary flow imaging in identification of left anterior descending coronary artery stenosis in patients with left bundle branch block.

Background: Conventional noninvasive methods have well‐known limitations for the detection of coronary artery disease (CAD) in patients with left bundle branch block (LBBB). However, advancements in Doppler echocardiography permit transthoracic imaging of coronary flow velocities (CFV) and measurement of coronary flow reserve (CFR). Our aim was to evaluate the diagnostic value of transthoracic CFR measurements for detection of significant left anterior descending (LAD) stenosis in patients with LBBB and compare it to that of myocardial perfusion scintigraphy (MPS). Methods: Simultaneous transthoracic CFR measurements and MPS were analyzed in 44 consecutive patients with suspected CAD and permanent LBBB. Typical diastolic predominant phasic CFV Doppler spectra of distal LAD were obtained at rest and during a two‐step (0.56–0.84 mg/kg) dipyridamole infusion protocol. CFR was defined as the ratio of peak hyperemic velocities to the baseline values. A reversible perfusion defect at LAD territory was accepted as a positive scintigraphy finding for significant LAD stenosis. A coronary angiography was performed within 5 days of the CFR studies. Results: The hyperemic diastolic peak velocity (44 ± 9 cm/sec vs 62 ± 2 cm/sec; P=0.01) and diastolic CFR (1.38 ± 0.17 vs 1.93 ± 0.3; P=0.001) were significantly lower in patients with LAD stenosis compared to those without LAD stenosis. The diastolic CFR values of <1.6 yielded a sensitivity of 100% and a specificity of 94% in the identification of significant LAD stenosis. In comparison, MPS detected LAD stenosis with a sensitivity of 100% and a specificity of 29%. Conclusions: CFR measurement by transthoracic Doppler echocardiography is an accurate method that may improve noninvasive identification of LAD stenosis in patients with LBBB.

Comparison of Coronary Flow Velocities Between Patients with Obstructive and Nonobstructive Type Hypertrophic Cardiomyopathy: Noninvasive Assessment by Transthoracic Doppler Echocardiography

Background: We aimed to compare coronary flow velocity (CFV) measurements of patients with nonobstructive (NHCM) and obstructive hypertrophic cardiomyopathy (HOCM) by using transthoracic Doppler echocardiography (TTDE). Methods and Results: In 11 patients with NHCM and 26 with HOCM, CFV in the distal left anterior descending (LAD) coronary was measured by TTDE (3.5 MHz) under the guidance of color Doppler flow mapping in addition to standard 2D and Doppler echocardiography. The results were compared with 24 normal participants who had no evidence of cardiac disease. Peak diastolic velocity of LAD was also higher in NHCM and HOCM than controls (52 ± 14 cm/sec and 54 ± 20 cm/sec vs 41 ± 11 cm/sec, respectively, P < 0.01). The analysis of systolic velocities revealed abnormal flow patterns in 16 (61%) patients with HOCM (12 systolic‐reversal flow and 4 no systolic flow) and 6 (54%) (5 reversal flow and 1 zero flow) patients with NHCM (−11 ± 30 cm/sec and −13 ± 38 cm/sec, vs 24 ± 9 cm/sec, respectively, P < 0.001). Linear regression analysis demonstrated no correlation between intraventricular pressure gradient and coronary flow velocities in HOCM patients. However, there were significant positive and negative correlations between septal thickness and diastolic and systolic velocities, respectively (r = 0.50, P < 0.002, and r =−0.43, P < 0.005). Conclusion: We conclude that the coronary flow velocity abnormalities are independent from the type of hypertrophic cardiomyopathy.

Hydatid Cyst in the Wall of the Ascending Aorta

Hydatid disease rarely involves the aortic wall. We report a case of hydatidosis involving the ascending aorta and the left atrium. The patient underwent replacement of the ascending aorta with a prosthetic Dacron graft and left atrial cystectomy. At the 6-month follow-up, she was leading a normal life.

Evaluation of Enalapril+Losartan Treatment with Cardiopulmonary Exercise Test in Patients with Left Ventricular Dysfunction

The aim of this study was to evaluate the effects of the combination of enalapril and losartan in patients with left ventricular systolic dysfunction by means of cardiopulmonary exercise test (CPET). Patients with left-ventricular systolic dysfunction and ejection fractions of 40% or less were included to the study. All patients were under the treatment of enalapril 20 mg once daily. The study group consisted of 20 patients (18 men, 2 women; mean age ± standard deviation: 62.4 ±6.5 years) and the comparison group consisted of 10 (8 men, 2 women; mean age 59.3 ±11.9 years). The dose of 50 mg of losartan once daily was given additionally to the study patients. Breath-by-breath CPET was performed before administration of losartan and then 6-8 weeks later in the study group and 2 times with an interval of 6-8 weeks in the control group without any change in the treatment protocol. In the study group the average exercise times were 361 ±192 and 454 ±205 seconds (p=0.001) before and after the study. Peak oxygen consumption (V̇O2) values were 1,209 ±366 and 1,284 ±398 mL/minute before and after the study (p=0.01). Anaerobic threshold V̇O2 values were 785 ±187 and 855 ±217 mL/minute before and after the study, respectively (p=0.01). Peak heart rates (HR) were 141 ±28 and 143 ±22/minute (p=0.35); peak V̇O2/HR values were 9.02 ±3.1 and 9.3 ±3 mL/minute (p=0.4) before and after the study, respectively. On the other hand, in the control group, average exercise times were 556 ±250 and 528 ±251 seconds (p=0.8); peak V̇O2 values were 1,502 ±537 and 1,450 ±501 mL/minute (p=0.2); and anaerobic threshold V̇O2 values were 1,005 ±338 and 975 ±319 mL/min (p=0.7), before and after the study respectively. At the highest comparable exercise stage for both tests in the study group the expired volume/oxygen consumption (V̇E/V̇O2) ratio declined from 35.1 ±6.2 to 32.4 ±5.6 (p=0.007). V V̇E values declined from 37.5 ±10.9 to 33.9 ±10.1 L (p=0.02); heart rate declined from 140 ±27 to 132 ±21/minute (p=0.02). No significant change was observed in the mentioned values for the control group. Addition of losartan to the standard therapy in patients with left ventricular systolic dysfunction improved exercise capacity and caused lower heart rate and ventilation requirements for the same exercise level.