Characterizing a Cohort of α-Thalassemia Couples Collected During Screening for Hemoglobinopathies: 14 Years of an Iranian Experience

Our study aimed to determine the number of couples with normal hemoglobin (Hb) electrophoresis and low-borderline hematological values, which may come up with a clinically critical status in their offspring. The number of couples at risk for severe α-thalassemia (α-thal) needed to be estimated before recommending genetic counseling and prenatal diagnosis (PND). During the past 14 years, from at least 7000 referrals, 754 couples were investigated for α-thal by direct mutation detection methods followed by reverse strip assay and α-globin gene sequencing for inconclusive cases. Detection of silent β-thalassemia (β-thal) mutations was done in suspected cases by complete β-globin gene sequencing. We were able to provide a molecular diagnosis in 87.3% (658/754) of couples. A total of 9.1% (60/658) may have a clinically significant hemoglobinopathy in their offspring. Significant conditions included hydrops fetalis (20.0%; 12/60), certain Hb H (β4) genotypes (78.3%; 47/60) and β-thal intermedia (β-TI) (1.7%; 1/60). The diagnostic flowchart for couples with microcytic hypochromic anemia in countries with a high prevalence of hemoglobinopathies should include α and β gene sequencing. As our results indicate, every nine out of 100 of these couples will face significant hemoglobinopathies and every two out of 100 can carry Hb Bart’s (γ4) hydrops fetalis in their pregnancies. For such cases, PND should be utilized to allow the carrier couples to decide whether or not to abort the fetus.     

Assessment of coronary bypass graft patency by electron-beam computed tomography

Twenty-one patients undergoing coronary artery bypass grafting were prospectively evaluated by conventional selective coronary angiography and electron-beam computed tomography. Eighty bypass grafts (60 saphenous vein and 20 left or right internal mammary artery) were evaluated for patency. The sensitivity and specificity of electron-beam computed tomography were 72% and 100%, respectively; positive and negative predictive values were 100% and 92.5%, respectively. Sensitivity and specificity according to coronary region were: left anterior descending artery, 33% and 100%; diagonal artery, 67% and 100%; circumflex artery, 75% and 100%; right coronary artery, 100% and 100%. Electron-beam computed tomography is relatively accurate and a promising tool for noninvasive evaluation of graft patency after coronary artery bypass graft surgery.     

Isfahan Healthy Heart Programme: a comprehensive integrated community-based programme for cardiovascular disease prevention and control. Design,methods and initial experience

The Isfahan Healthy Heart Programme (IHHP) is a five to six year comprehensive integrated community-based programme for cardiovascular diseases (CVD) prevention and control via reducing CVD risk factors and improvement of cardiovascular healthy behaviour in a target population. IHHP started late in 1999 and will be finished in 2005-2006. A primary survey was done to collect baseline data from interventional (Isfahan and Najaf-Abad) and reference (Arak) communities. In a two-stage sampling method, we randomly selected 5 to 10 percent of households from randomly selected clusters. Then individuals aged > or = 19 years were selected for the survey. This way, data from 12,600 individuals (6300 in interventional counties and 6300 in the reference county) was collected and stratified according to living area (urban vs. rural) and different age and sex groups. The samples underwent a 30-minute interview to complete validated questionnaires containing questions on demography, socioeconomic status, smoking behaviour, physical activity, nutritional habits and other behaviour regarding CVD. Blood pressure and body mass index (BMI) measurements were done and fasting blood samples were taken for two hours post load plasma glucose (2 hpp), serum (total, HDL and LDL) cholesterol and triglyceride levels. A twelve-lead electrocardiogram was recorded in all persons above 35 years of age. Community-wide surveillance of deaths, hospital discharges, myocardial infarction and stroke registry was carried out in the intervention and control areas. Four to five years of interventions based on different categories such as mass media, community partnerships, health system involvement and policy and legislation have started in the intervention area while Arak will be followed without intervention. Considering the results of the baseline surveys, (assessments needed, the objectives, existing resources and the possibility of national implementation) the interventions were planned. They were set based on specific target groups like school children, women, work-site, health personnel, high-risk persons, and community leaders were actively engaged as decision makers. A series of teams was arranged for planning and implementation of the intervention strategies. Monitoring will be done on small samples to assess the effect of different interventions in the intervention area. While four periodic surveys will be conducted on independent samples to assess health behaviours related to CVD risk factors in the intervention and reference areas, the original pre-intervention subjects aged more than 35 years will be followed in both areas to assess the individual effect of interventions and outcomes like sudden death, fatal and nonfatal MI and stroke. The whole baseline survey will be repeated on the original and an independent sample in both communities at the end of the study.     

Increased susceptibility of spontaneously hypertensive rats to ventricular tachyarrhythmias in early hypertension

Key points

• Hypertension is a risk factor for sudden cardiac death caused by ventricular tachycardia and fibrillation.
• Whether hypertension in its early stage is associated with an increased risk of ventricular tachyarrhythmias is not known.
• Based on experiments performed at the cellular and whole heart levels, we show that, even early in chronic hypertension, the hypertrophied and fibrotic ventricles of spontaneously hypertensive rats aged 5 to 6 months have already developed increased stress‐induced arrhythmogenicity, and this increased susceptibility to ventricular arrhythmias is primarily a result of tissue remodelling rather than cellular electrophysiological changes.
• Our findings highlight the need for early hypertension treatment to minimize myocardial fibrosis, ventricular hypertrophy, and arrhythmias.

Abstract

Hypertension is a risk factor for sudden cardiac death caused by ventricular tachycardia and fibrillation (VT/VF). We hypothesized that, in early hypertension, the susceptibility to stress‐induced VT/VF increases. We compared the susceptibility of 5‐ to 6‐month‐old male spontaneously hypertensive rats (SHR) and age/sex‐matched normotensive rats (NR) to VT/VF during challenge with oxidative stress (H₂O₂; 0.15 mmol l⁻¹). We found that only SHR hearts exhibited left ventricular fibrosis and hypertrophy. H₂O₂ promoted VT in all 30 SHR but none of the NR hearts. In 33% of SHR cases, focal VT degenerated to VF within 3 s. Simultaneous voltage‐calcium optical mapping of Langendorff‐perfused SHR hearts revealed that H₂O₂‐induced VT/VF arose spontaneously from focal activations at the base and mid left ventricular epicardium. Microelectrode recording of SHR hearts showed that VT was initiated by early afterdepolarization (EAD)‐mediated triggered activity. However, despite the increased susceptibility of SHR hearts to VT/VF, patch clamped isolated SHR ventricular myocytes developed EADs and triggered activity to the same extent as NR ventricular myocytes, except with larger EAD amplitude. During the early stages of hypertension, when challenged with oxidative stress, SHR hearts showed an increased ventricular arrhythmogenicity that stems primarily from tissue remodelling (hypertrophy, fibrosis) rather than cellular electrophysiological changes. Our findings highlight the need for early hypertension treatment to minimize myocardial fibrosis, ventricular hypertrophy, and arrhythmias.

Abbreviations

AP

action potential

APD

action potential duration

APD₉₀

action potential at 90% duration

CaMKII

calcium/calmodulin‐dependent protein kinase II

CaT

calcium transient

CaTD₉₀

calcium transient at 90% duration

CI

confidence interval

DBP

diastolic blood pressure

EAD/DAD

early/delayed after‐depolarization

HR

heart rate

ICC

interclass correlation

I_Ca,L

L‐type calcium current

I_Ks

slow delayed rectifier potassium current

I_Na

sodium current

I_to

transient outward potassium current

IVS(d,s) interventricular septum thickness (during diastole

during systole)

LV

left ventricle

LVEF

left ventricular ejection fraction

LVFS

left ventricular fractional shortening

LVH

left ventricular hypertrophy

LVID(d,s) left ventricular internal diameter (during diastole

during systole)

MV

mitral valve

NR

normotensive rats

PA peak vel

pulmonary artery peak velocity

(P)CL

(pacing) cycle length

PW

posterior wall

P‐ECG

pseudo‐electrocardiogram

RV

right ventricle

RWT

relative wall thickness

SHR

spontaneously hypertensive rats

SHHF

spontaneously hypertensive heart failure

SBP

systolic blood pressure

VT/VF

ventricular tachycardia and fibrillation