Taysir S. Garadah

QTc Interval and QT Dispersion in patients with Thalassemia Major: electrocardiographic (eKG) and echocardiographic evaluation

Background Doppler echocardiographic studies in patients with β-Thalassemia Major (β-TM) had shown different patterns of left ventricle (LV) systolic and diastolic dysfunctions. Aim This cross-sectional study was designed to study the LV systolic and diastolic function in patients with β-TM using Pulsed Doppler (PD) Echocardiogram and assess the QTc interval and QT dispersion (QTd) on 12 leads ECG. Method All patients were evaluated clinically as well as by echocardiography and 12 leads ECG. The study included patients with β-TM (n = 38, age 15.7 ± 8.9 years), compared with an age-matched healthy control group (n = 38, age 15.9 ± 8.9 years). Results In 38 patients with β-TM Compared with healthy control group, The QTc interval and the QTd dispersion on ECG were increased with no significant difference mode echo showed that β-TM patients have thicker LV septal wall index (0.659 ± 0.23 vs. 0.446 ± 0.219 cm/M2, P < 0.001), posterior wall index (0.659 ± 0.235 vs. 0.437 ± 0.214 cm/M2, P < 0.01), and larger LVEDD index is (3.99 ± 0.48 vs. 2.170 ± 0.57 cm/M2. P < 0.05). Pulsed Doppler showed high LV trans-mitral E wave velocity index (70.818 ± 10.139 vs. 57.532 ± 10.139, P < 0.05) and E/A ratio (1.54 vs.1.23, P < 0.01). The duration of deceleration time index (DT) and isovolumic relaxation time index (IVRT) were significantly shorter in patients with β-TM (150.234 ± 20.0.23 vs. 167.123 ± 167.123 ± 19.143 msec/M2, P < 0.01) and (60.647 ± 6.77 vs. 75.474 ± 5.83 msec/M2, P < 0.001), respectively. The tricuspid valve velocity in patients with β-TM was significantly higher than controls (2.993 ± 0.569 vs. 1.93 ± 0.471 m/sec, respectively, P < 0.01), with calculated pulmonary artery pressure of 2.4 times the control (36.0 vs. 14.8 mmHg). However, the LVEF% or fractional shortening were not significantly different. Conclusion In this study, β-thalassemia major patients compared with controls have differences of QT dispersion and corrected QT interval that is of no statistical significance. A significantly thicker LV wall and LV diastolic filling indices are suggestive of restrictive diastolic pattern. These data indicate that LV diastolic abnormalities compromised initially in patients with β-thalassemia major.

Pulsed and Tissue Doppler Echocardiographic Changes in Patients with Thalassemia Major

Background Doppler echocardiographic studies of left ventricle (LV) systolic and diastolic function in patients with β-Thalassemia Major (β-TM) had shown different patterns of systolic and diastolic dysfunction. Aim This cross-sectional study was designed to study the LV systolic and diastolic function in patients with β-TM using Pulsed Doppler (PD) and Tissue Doppler (TD) echocardiography. Methods All patients were evaluated clinically and by echocardiography, The study included patients with β-TM (n = 38, age 15.7 ± 8.9 years) compared with an age-matched control group (n = 38, age 15.9 ± 8.9 years). The pulse Doppler indices were normalized for age and heart rate. Results Compared with control patients, M-Mode showed that patients with β-TM have thicker LV septal wall index (0.659 ± 0.23 vs. 0.446 ± 0.219 cm, P ≤ 0.001), posterior wall index (0.659 ± 0.235 vs. 0.437 ± 0.214 cm, P ≤ 0.01), and larger LVEDD index is (3.99 ± 0.48 vs. 2.170 ± 0.57 mm. P = 0.035). Pulsed Doppler showed high LV trans-mitral E wave velocity (70.818 ± 10.139 vs. 57.532 ± 10.139, p = 0.027) and E/A ratio (1.54 vs. 1.23, P ≤ 0.01). The duration of Deceleration time (DT) and isovolumic relaxation time (IVRT) were significantly shorter in patients with β-TM (150.234 ± 20.0.23 vs. 167.123 ± 19.143 msec, P ≤ 0.01) and (60.647 ± 6.77 vs. 75.474 ± 5.83 msec, P ≤ 0.001), respectively. The ratio of transmitral E wave velocity to the tissue Doppler E wave at the basal septal mitral annulus E/Em– was significantly higher in β-TM group (14.024 ± 2.29 vs. 12.132 ± 1.82, P ≤ 0.01). The Tissue Doppler systolic velocity (Sm) and the early diastolic velocity (Em) were significantly lower in β-TM group compared to control (4.31 ± 1.2 cm/s vs. 6.95 ± 2.1, P ≤ 0.01 and 4.31 ± 2.7 cm/s vs. 5.82 ± 2.5, P ≤ 0.01) respectively. The tricuspid valve velocity was significantly higher than controls (2.993 ± 0.569 vs. 1.93 ± 0.471 m/sec, respectively, P ≤ 0.01). However, the LVEF% and fractional shortening were normal with no significant difference in both groups. Conclusion In this study, patients with β-thalassemia major compared with controls, have significantly thicker LV wall, and larger LV cavity and LV diastolic filling indices suggestive of restrictive pattern with a higher tricuspid valve velocity. These data showed that left ventricle diastolic indices are compromised initially in patients with β-thalassemia major.

The pro-BNP Serum Level and Echocardiographic Tissue Doppler Abnormalities in Patients with Beta Thalassemia Major

Background Doppler echocardiographic studies of the left ventricle (LV) function in patients with β-Thalassemia Major (β-TM) had shown different patterns of systolic and diastolic dysfunctions associated with abnormal serum brain natriuretic peptide (BNP). Aim This cross-sectional study was designed to study the LV systolic and diastolic functions and correlate that with serum level of N-terminal pro brain natriuretic hormone (NT- pro BNP) in patients with β-TM using Pulsed Doppler (PD) and Tissue Doppler (TD) echocardiography. Methods The study was conducted on patients with β-TM (n = 38, age 15.7 ± 8.9 years) and compared with an age-matched controls (n = 38, age 15.9 ± 8.9 years). In all participants, PD and TD echocardiography were performed and blood samples were withdrawn for measuring the serum level of NT-pro BNP, ferritin, and alanine transaminase. Results Patients with β-TM compared with controls, have thicker LV septal wall index (0.65 ± 0.26 vs. 0.44 ± 0.21 cm, P < 0.001), posterior wall index (0.65 ± 0.23 vs. 0.43 ± 0.21 cm, P < 0.01), and larger LVEDD index (4.35 ± 0.69 vs.3.88 ± 0.153 mm, P < 0.001). In addition, β-TM patients have higher transmitral E wave velocity (E) (70.818 ± 10.139 vs. 57.532 ± 10.139, p = 0.027) and E/A ratio (1.54 ± 0.17 vs. 1.23 ± 0.19, P < 0.01) and shorter deceleration time (DT) (160.13 ± 13.3 vs. 170.50 ± 19.20 m sec, P < 0.01). Furthermore, the ratio of transmitral E wave velocity to the tissue Doppler E wave at the basal septal mitral annulus (E/Em–) was significantly higher in β-TM group (19.6 ± 2.81 vs. 13.868 ± 1.41, P < 0.05). The tissue doppler systolic wave (Sm) velocity and the early diastolic wave (Em) were significantly lower in β-TM group compared to controls (Sm: 4.82 ± 1.2 vs. 6.22 ± 2.1 mm/sec, P < 0.05; Em: 3.51 ± 2.7 vs. 4.12 ± 2.5 mm/sec P < 0.05, respectively). The tricuspid valve velocity was significantly higher in β-TM patients compared with controls (2.993 ± 0.569 vs. 1.93 ± 0.471 m/sec, respectively, P < 0.01). The mean serum NT pro-BNP in β-TM was significantly higher compared with controls (37.6 ± 14.73 vs. 5.5 ± 5.4pg/ml, P < 0.05). The left ventricle ejection fraction (EF%) and fractional shortening (FS%) were not significantly different between both groups. Conclusion We conclude that patients with β-TM had a significantly higher serum level of NT-pro BNP that is positively correlated with the E/Em ratio on tissue Doppler. Furthermore, we confirm our previous findings that patients with β-TM exhibit LV diastolic pattern on echocardiogram suggestive of restrictive type with well preserved left ventricle systolic function.

Predictors of abnormal bone mass density in adult patients with homozygous sickle-cell disease.

Background Adult patients with sickle-cell disease (SCD) often have multiple bone compactions causing tissue hypoxia and osteonecrosis. The impact on bone abnormalities lesion detected by bone mass density is not well defined. Aim The study is a cross sectional, perspective was designed to assess the prevalence of abnormal BMD in adult Bahraini patients with SCD and to assess the predictive risk of different metabolic variables such as serum level of vitamin D3, testosterone, and parathyroid hormone in addition to lactate dehydrogenase (LDH), hemoglobin (Hb), and reticulocyte count for the development of abnormal bone density on dual X-ray absorptiometry (DXA) scan. Method The study was conducted over the period of12 months from first of January 2012 to end of December 2012. All patients were evaluated clinically for severity of SCD and abnormal bone mass density (BMD) using DXA scan. Blood samples were withdrawn for measuring the serum level of vitamin D3, testosterone, and parathyroid hormone in addition to Hb, LDH, and reticulocyte count. Multiple logistic regression analysis was used to assess risk prediction of different variables for the development of abnormal BMD on DXA with T-score ≤–2.5 standard deviation (SD). Results The study included Bahraini patients with SCD (n = 55, age 29.24 ± 9.47 years, male 60% and female 40%) compared with an age-matched healthy control group (n = 55, age 28.82 ± 8.64 years, with 62% male and 38% female). Of the 55 patients with SCD compared with the control group, there were 33 (58%) patients with low BMD and 2 (3%) in the control. Among the 33 patients with SCD and with low BMD, there were 20 (36%) with osteoporosis (T-score of ≤–2.5 SD) and 13 (24%) with osteopenia (T-score of <–1 to −2.5 SD). The most affected site of low BMD was lumbar spine (55%), followed by the radius (30%) and neck of the femur (15%). SCD patients with osteoporosis compared with the healthy subjects had significantly lower body surface area (BSA, m2) of 1.4 ± 0.3 vs. 1.63 ± 0.5 BMI, low level of vitamin D3 of 21.11 ± 6.95 ng/mL vs. 46.2 ± 15.19 (P < 0.001), lower testosterone level of 1.34 ± 0.54 vs. 2.18 ± 0.56 ng/mL (P < 0.001), higher reticulocyte count (P < 0.001), and higher LDH level (P < 0.001). The low serum level of vitamin D3 (<20 ng/mL) and low testosterone of <0.9 ng/mL had risk prediction (odds ratio) of 1.14 and 1.2, respectively, for abnormal BMD in SCD. In the risk prediction of other variables of parathormone (PTH), LDH, and reticulocyte, were not significant. Conclusion The prevalence of abnormal bone mass density (BMD) is high (60%) in Bahraini patients with SCD. There is significant low serum level of vitamin D3 and low testosterone hormone in those with very low bone mass density (BMD) (osteoporosis and T-score <–2.5). The low serum level of vitamin D3 (<20 ng/mL) and low testosterone of <0.9 ng/mL had risk prediction (odds ratio) of 1.14 and 1.2, respectively, for abnormal BMD in SCD.

Disparity in ST-segment elevation myocardial infarction practices and outcomes in Arabian Gulf Countries (Gulf COAST Registry)

Objectives: The objective of this study is to describe contemporary management and 1-year outcomes of patients hospitalized with ST-segment elevation myocardial infarction (STEMI) in Arabian Gulf countries. Methods: Data of patients admitted to 29 hospitals in four Gulf countries [Bahrain, Kuwait, Oman, United Arab Emirates (UAE)] with the diagnosis of STEMI were analyzed from Gulf locals with acute coronary syndrome (ACS) events (Gulf COAST) registry. This was a longitudinal, observational registry of consecutive citizens, admitted with ACS from January 2012 to January 2013. Patient management and outcomes were analyzed and compared between the four countries. Results: A total of 1039 STEMI patients were enrolled in Gulf COAST Registry. The mean age was 58 years, and there was a high prevalence of diabetes (47%). With respect to reperfusion, 10% were reperfused with primary percutaneous coronary intervention, 66% with fibrinolytic therapy and 24% were not reperfused. Only one-third of patients who received fibrinolytic therapy had a door-to-needle time of 30 min or less. The in-hospital mortality rate was 7.4%. However, we noted a significant regional variability in mortality rate (3.8%–11.9%). In adjusted analysis, patients from Oman were 4 times more likely to die in hospital as compared to patients from Kuwait. Conclusions: In the Gulf countries, fibrinolytic therapy is the main reperfusion strategy used in STEMI patients. Most patients do not receive this therapy according to timelines outlined in recent practice guidelines. There is a significant discrepancy in outcomes between the countries. Quality improvement initiatives are needed to achieve better adherence to management guidelines and close the gap in outcomes.

Pain frequency, severity and QT dispersion in adult patients with sickle cell anemia: correlation with inflammatory markers.

Background Inflammatory markers are increased during vaso-occlusive crisis (VOC) in adult patients with sickle cell anemia (SCA), but this is not clear in clinical steady state. Aim The present study aims to establish the frequency and intensity of bone pain episodes in adult patients with SCA in clinical steady state and to determine the correlation between different inflammatory markers, other variables including QT dispersion (QTd) and pain frequency and intensity in SCA. Patients and methods Patients were classified into two groups: group 1, those with more than three hospital admissions in the last 6 months, and group 2, those with no hospital admission. Pearson correlation between variables such as body mass index (BMI), level of tumor necrosis factor (TNF-α), interleukin-1 (IL-1), C-reactive protein (CRP), hemoglobin (Hb), reticulocyte count, white blood cell count (WBC), ferritin, lactate dehydrogenase (LDH), parathormone (PTH), vitamin D3 (25-OH cholecalciferol) and bone pain frequency with severity was evaluated. Results Forty-six patients were enrolled in this study with a mean age of 18.47±5.78 years, with 23 patients in each group. Vitamin D3 and Hb were lower (17.04±5.77 vs 37.59±4.83 ng/L, P<0.01 and 7.96±0.3 vs 8.44±0.27 g/dL, P<0.01, respectively); the inflammatory markers showed significantly higher level of TNF-α, IL-1 and CRP (56.52±5.43 pg/ml, 44.17±4.54 pg/ml and 3.20±0.72 mg/L, respectively, P<0.05); WBC, LDH and reticulocyte count were also significantly higher and the QTd was higher (45.0±2.22 vs 41.55±0.8 ms, P<0.05) in group 1 when compared with group 2. Pearson correlation coefficient showed significant positive correlation between serum level of TNF-α and bone pain frequency (r=0.414, P<0.005) and serum level of IL-1 (r=0.39, P<0.008). Conclusion There is a strong positive correlation between TNF-α, IL-1 and WBC and bone pain frequency in steady state in adult patients with SCA. CRP and low hemoglobin had weak positive correlation. QTd was significantly longer in patients who had hospitalizations with VOC.

Risk Stratification and in Hospital Morality in Patients Presenting with Acute Coronary Syndrome (ACS) in Bahrain

Background: Risk factors and short-term mortality in patients presented with Acute Coronary Syndrome (ACS) in Bahrain has not been evaluated before. Aim: In this prospective observational study, we aim to determine the clinical risk profiles of patients with ACS in Bahrain and describe the incidence, pattern of presentation and predictors of in-hospital clinical outcomes after admission. Methods: Patients with ACS were prospectively enrolled over a 12 month period. The rate of incidence of risk factors in patients was compared with 635 non-cardiac patient admissions that matched for age and gender. Multiple logistic regression analysis was used to predict poor outcomes in patients with ACS. The variables were ages >65 years, body mass index (BMI) >28 kg/m2, GRACE (Global Registry of Acute Coronary Events) score >170, history of diabetes mellitus (DM), systolic hypertension >180 mmHg, level of creatinine >160 μmol/l and Heart Rate (HR) on admission >90 bpm, serum troponin rise and ST segment elevation on the ECG. Results: Patients with ACS (n=635) were enrolled consecutively. Mean age was 61.3 ± 13.2 years, with 417 (65.6%) male. Mean age for patients with ST-segment elevation myocardial infarction (STEMI, n=156) compared with non-STEMI (NSTEMI, n=158) and unstable angina (UA, n=321) was 56.5± 12.8 vs 62.5±14.0 years respectively. In-hospital mortality was 5.1%, 3.1% and 2.5% for patients with STEMI, NSTEMI, and UA, respectively. In STEMI patients, thrombolytic therapy was performed in 88 (56.5%) patients and 68 (43.5%) had primary coronary angioplasty (PCI). The predictive value of different clinical variables for in-hospital mortality and cardiac events in the study were: 2.8 for GRACE score >170, 3.1 for DM, 2.2 for SBP >180 mmHg, 1.4 for age >65 years, 1.8 for BMI >28, 1.7 for creatinine >160 μmol/L, 2.1 for HR >90 bpm, 2.2 for positive serum troponin and 2.3 for ST elevation. Conclusion: Patients with STEMI compared with NSTEMI and UA were of younger age. There was higher in-hospital mortality in STEMI compared with NSTEMI and UA patients. The most significant predictors of death or cardiac events on admission in ACS were DM, GRACE Score >170, systolic hypertension >180 mmHg, positive serum troponin and HR >90 bpm.

Hormonal and echocardiographic abnormalities in adult patients with sickle-cell anemia in Bahrain

Background Adrenal, thyroid, and parathyroid gland hormonal changes are recognized in children with homozygous (HbSS) sickle-cell anemia (SCA), but are not clear in adult patients with SCA. Aim To assess the metabolic and endocrine abnormalities in adult patients with SCA and evaluate left ventricular (LV) systolic and diastolic functions compared with patients with no SCA and further study the relationship between serum levels of cortisol, free thyroxine (T4), and testosterone with serum ferritin. Materials and methods The study was conducted on 82 patients with adult HbSS SCA compared with a sex- and age-matched control group. The serum levels of cortisol, parathyroid hormone (PTH), testosterone, thyroid-stimulating hormone (TSH), and free T4 were compared. Blood levels of hemoglobin, reticulocyte count, lactate dehydrogenase (LDH), calcium, alkaline phosphatase (ALP), vitamin D3, and ferritin were also compared. Pulsed Doppler echo was performed to evaluate the LV mass, wall thickness, and cavity dimensions with diastolic filling velocities of early (E) and atria (A) waves. Biometric data were analyzed as mean ± standard deviation between the two groups. Multiple regression analysis was performed between serum levels of ferritin as independent variable and testosterone, cortisol, and thyroid hormones. Results A total of 82 adult patients with HbSS SCA were enrolled who had a mean age of 21±5.7 years, with 51 males (62%). Patients with SCA compared with the control group had significantly lower hemoglobin, body mass index, cortisol, vitamin D3, testosterone, and T4. Furthermore, there were significantly high levels of reticulocyte count, PTH, TSH, ferritin, LDH, ALP, and uric acid. The incidence of subclinical hypothyroidism and adrenal insufficiency was 7% and 4.8%, respectively, with hypogonadism 9.8% and vitamin D3 deficiency 61%. There were inverse relationships between ferritin as independent variable and serum levels of testosterone, T4, and cortisol, with regression coefficients of −0.49 (P<0.001), −0.33 (P<0.001), and −0.11 (P<0.92), respectively. Conclusion Patients with adult SCA had a high prevalence of in vivo hypoadrenialism (4.8%), hypogonadism (9.8%), and hypothyroidism (7%). There were significant inverse relationships between serum ferritin as independent variable and cortisol, testosterone, and T4. Pulsed Doppler echocardiography showed increased LV mass, with a restrictive LV diastolic pattern suggestive of diastolic dysfunction.

Surrogates of poor prognostic signs in adult patients with homozygous sickle cell disease: an echocardiographic study.

Background: Pulmonary Arterialhypertension (PAH) is a late complication in adult patients with homozygous sickle cell Anaemia (SCA). The ear ly identification of PAH may be of paramount importance. Aim: This study is aimed at evaluating the usefulness of NT pro BNP in the assessment of diastolic function of RV in adult patients with sickle cell disease. It is also aimed at the assessment of thepredictive risk of serum level of NT pro BNP hormone and ferritin with other pulsed and tissue Doppler indices for the development of pulmonary hypertension in patients with SCA. In addition, we measured the usefulness of tissue Doppler velocity of lateral annulus of tricuspid valve in the assessment of diastolic function of RV in adult patients with SCD. Method: In this cross sectional prospective study, 103 patients with homozygous SCD were studied and compared with age andgender matched healthy control.Every patient had a clinical assessment, pulsed and tissue Doppler evaluation. Blood samples were withdrawn for the level of haemoglobin, ferritin and NT pro BNP hormone. The mean

The Pulsed Doppler Predictors of Intra Dialysis Hypotension and Relationship between Doppler Indices and Net Fluid Loss after Dialysis in Patients with End Stage Renal Disease: Pulsed Doppler Study

Background In patients with end stage renal disease (ESRD) on regular haemodialysis (HD), fluid status in the body has an important impact on the left ventricular (LV) filling and it can lead to intra-dialysis hypotension. The aim of the study is to study the pattern of diastolic pulsed Doppler filling in patients who had hypotension during HD and to correlate that with the net fluid loss at end of dialysis session. Material Fifty two patients with (ESRD) on regular HD, 34 male, with mean age of 45.5 ± 13 year were studied. Each patient had pulsed Doppler study before and immediately after HD. Each patient was observed for the development of acute clinical events and hypotension defined as systolic blood pressure of less than 90 mmHg. Patients were divided into two groups according to the amount of net ultra filtrate loss after HD, group I (n = 25) with fluid loss of <2 litres, and group II (n = 27) with ≥2 litres. Results The mean age was 45 ± 12 year for group I and 46 ± 11 year for group II. In the study group, 11 out of 52 (21%) patients developed systolic hypotension less than 90 mmHg during HD compared to those without, no patient necessitate HD discontinuation. The mean pre dialysis pulsed Doppler Early filling to late filling wave (E/A ratio) of those who developed hypotension was (0.7 ± 0.2 vs. 1.1 ± 0.2.1, p < 0.001) and the mean of Deceleration time of E wave (DT) (246 ± 40 vs. 224 ± 34 m.sec, p < 0.05) respectively. The mean difference between pre and post HD pulsed Doppler indices in group II compared with group I were as follow: the mean reduction of E wave velocity (32 ± 17 vs. 12 ± 15 m.sec, p < 0.01), the mean reduction of A wave velocity (13 ± 17 vs. 11 ± 16 m.sec, p = NS), E/A ratio reduced to 0.14 ± 0.03 vs. 0.01 ± 0.04, p < 0.05), the mean DT of E wave increase from (43 ± 51 vs. 16 ± 64 m.sec, p < 0.05). Conclusion In patient ESRD on regular hemodialysis, the prolonged DT >246 m.sec of E wave and E/A ratio less than 0.7 both may be used as a predictors of asymptomatic hypotension during HD. The net fluid loss during HD is directly proportional to the reduction of left ventricle Doppler diastolic indices.