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Aim: Brugada syndrome is an inherited cardiac disease with an increased risk of sudden cardiac death. Thus far Brugada syndrome has been linked only to mutations in SCN5A, the gene encoding the a-subunit of cardiac Na + channel. In this study, a novel SCN5A gene mutation (D1714G) is reported, which has been found in a 57-year-old male patient. Since the mutation is located in a segment of the ion-conducting pore of the cardiac Na + channel, which putatively determines ion selectivity, it may affect ion selectivity properties. Methods: HEK-293 cells were transfected with wild-type (WT) or D1714G a-subunit and b-subunit cDNA. Whole-cell configuration of the patch-clamp technique was used to study biophysical properties at room temperature (21°C) and physiological temperature (36°C). This study represents the first measurements of human Na + channel kinetics at 36°C. Ion selectivity, current density, and gating properties of WT and D1714G channel were studied. Results: D1714G channel yielded nearly 80% reduction of Na + current density at 21 and 36°C. At both temperatures, no significant changes were observed in V 1/2 values and slope factors for voltage-dependent activation and inactivation. At 36°C, but not at 21°C, D1714G channel exhibited more slow inactivation compared with WT channel. Ion selectivity properties were not affected by the mutation at both temperatures, as assessed by either current or permeability ratio. Conclusion: This study shows no changes in ion selectivity properties of D1714G channel. However, the profoundly decreased current density associated with the D1714G mutation may explain the Brugada syndrome phenotype in our patient.

Objective: There is conflicting data regarding the tricuspid annular velocities and their relation to right ventricular filling pressures. We aimed to assess if the time interval between the onset of Tricuspid E wave and annular Ea wave has any correlation with right sided filling pressure in patients with heart failure. Methods: Thirty heart failure patients (left ventricular ejection fraction≤35%) were enrolled. Echocardiography was performed to obtain tricuspid inflow and tissue Doppler annular velocities just before a standard right heart catheterization. The right atrial pressure was obtained from right heart catheterization. The E/Ea [the ratio of peak velocity of early tricuspid inflow wave (E) to peak velocity of early diastolic wave of the lateral tricuspid annulus (Ea)] and the time intervals between the beginning of R wave of electrocardiogram and onset of E (TE) as well as between the beginning of R wave and onset of Et (T Ea ) were measured, T E-Ea was calculated as T E-TEa . Results: The mean right atrial pressure (RAP) was 8.8 (SD=4.7) mm Hg. The mean T E-Ea was + 8.61 milliseconds. There was no significant correlation between RAP and E/Ea (r=0.08, p>0.05) but the correlation between T E-Ea and RAP was significant (r=0.5, p=0.01). Conclusion: According to our results and in contrary to some prior studies, we showed for the first time that right side T E-Ea stands as a better surrogate of right atrial pressure than E/Ea in heart failure patients. This finding needs more accurate studies and could present T E-Ea as a feasible tool to look into hemodynamics of heart failure patients. (Anadolu Kardiyol Derg 2014; 14(0): 000-000)

Background: Beta-thalassemia major is one of the major health problems in our country. Many studies have confirmed the fact that, these patients have an increased susceptibility to bacterial infections. Objective: In this study, we have assessed the ...

Noncompaction of ventricular myocardium (NCVM) is a rare cardiomyopathy characterized by numerous prominent trabeculations in the ventricular wall and deep intertrabecular recesses communicating with the ventricular cavity. This article reports a 33-year-old female with a familial history of cardiovascular disease, who presented with shortness of breath and palpitations. Transesophageal echocardiography and cardiac magnetic resonance imaging (MRI) were consistent with the diagnosis of NCVM. The advantages of MRI in depicting both the morphological features and pathological characteristics of NCVM were presented.

H eart failure (HF) is considered a growing health problem and requires an individualized approach to therapeutic strategy for each patient. In systolic HF, increased load to right ventricular (RV) function, which is the result of secondary changes in pulmonary vasculature and hemodynamics (such as secondary pulmonary hypertension [PH]), leads to RV hypertrophy, decreased RV ejection fraction (EF), depressed stroke volume, low cardiac output (CO), and eventually progressive RV failure. 1,2 The importance of RV structure and function in PH is supported by data showing that baseline RVEF, right atrial pressure, RV end-diastolic volume, stroke volume index, and cardiac index (CI) predict survival in patients with PH, 3,4 whereas pulmonary artery pressure does not, in the current era. 5 Furthermore, RV function per se predicts outcome in congestive HF. RV afterload and vascular reactivity are currently evaluated through measurement of pulmonary vascular resistance (PVR), which is the ratio of mean pressure drop across the pulmonary vasculature to mean pulmonary flow and is based on the assumption of steady hemodynamics. 7 This technique can be problematic, since RV afterload and consequently pulmonary hemodynamics can change because of the acute and chronic variations in proximal artery compliance and pressure and flow pulse reflections. However, none of these is considered in current measurements. Concerning the low resistance ⁄ high compliance nature of pulmonary circulation, the pulsatile component of hydraulic load is also important to consider. The pulmonary arterial impedance spectrum provides a much more precise and complete description of the pulmo-nary vascular load. 11 However, because of its complexity, this approach is difficult to use in clinical practice. Sunagawa and colleagues introduced the concept of the effective arterial elastance (Ea), which is the slope of the arterial end-systolic pressure-stroke volume relationship. In the systemic circulation, both normal and hypertensive human subjects have shown good congruence between the calculated Ea using the left ventricular pressure-volume loop and the one resulted from Windkessel model recorded in the aorta. In the pulmonary circulation, effective Ea of pulmonary vasculature [Ea(PV)] can be used as a substitute of Ea(WK) (WK denotes Ea derivation from Windkessel model). On the other hand, one of the main predictors of HF prognosis is heart rate. 15 Cardiac output is the product of heart rate and stroke volume. Failing hearts try to maintain the needed output at the expense of increasing heart rate, which by all means is detrimental to cardiovascular system. Pulmonary vascular resistance, which is routinely calculated by transpulmonary gradient divided by CO, might not be capable of showing the hemodynamic status between different levels of stroke volume. In this regard, Ea*(PV), defined as Assessment of right ventricular afterload in systolic heart failure seems mandatory as it plays an important role in predicting outcome. The purpose of this study is to estimate pulmonary vascular elastance as a reliable surrogate for right ventricular afterload in systolic heart failure. Forty-two patients with systolic heart failure (ejection fraction <35%) were studied by right heart catheterization. Pulmonary arterial elastance was calculated with three methods: Ea(PV) = (end-systolic pulmonary arterial pressure) ⁄ stroke volume; Ea*(PV) = (mean pulmonary arterial pressure ) pulmonary capillary wedge pressure) ⁄ stroke volume; and PPSV = pulmonary arterial pulse pressure (systolic ) diastolic) ⁄ stroke volume. These measures were compared with pulmonary vascular resistance ([mean pulmonary arterial pressure ) pulmonary capillary wedge pressure] ⁄ CO). All estimates of pulmonary vascular elastance were significantly correlated with pulmonary vascular resistance (r=0.772, 0.569, and 0.935 for Ea(PV), Ea*(PV), and PPSV, respectively; P<.001). Pulmonary vascular elastance can easily be estimated by routine right heart catheterization in systolic heart failure and seems promising in assessment of right ventricular afterload.

Brugada syndrome (BrS) is associated with increased risk for atrial fibrillation (AFib). However, the role of SCN5A mutations in the occurrence of AFib remains unclear. Cardiac sodium current reduction caused by SCN5A mutations may facilitate AFib by slowing intra-atrial conduction and inducing structural changes, but also prevent it by suppressing atrial ectopic activity. Here, we examined the relation between SCN5A mutations, atrial conduction velocity, atrial structural changes, and atrial ectopic activity in BrS.

Although obesity, dyslipidemia, and insulin resistance (IR) are well known risk factors for systemic cardiovascular disease, their impact on pulmonary arterial hypertension (PAH) is unknown. Our previous studies indicate that IR may be a risk factor for PAH. We now investigate the prevalence of IR in PAH and explore its relationship to disease severity.

Atrial fibrillation, characterized by rapid and irregular atrial firing, is the most prevalent clinically relevant arrhythmia. It is a major cause of morbidity and mortality because it increases the risk for stroke and heart failure and compels the use of drugs that not only affect atrial electrophysiology but also exert proarrhythmic effects on ventricular electrical activity. 1-3 Atrial fibrillation also can occur in individuals with no risk factors ("lone atrial fibrillation"). Mutations in genes encoding cardiac sodium or potassium channels recently have been linked to lone atrial fibrillation. 4 Virtually all mutations in genes encoding cardiac potassium channels increase the outward potassium currents and thereby promote atrial fibrillation by shortening the effective refractory period (ERP) and facilitating the maintenance of reentrant circuits. In contrast, mutations in SCN5A, the gene encoding the pore-forming ion-conducting ␣-subunit of the cardiac sodium channel Na v 1.5, may promote atrial fibrillation by different mechanisms.

Background: Mutations in KCNQ1 cause type 1 long QT syndrome (LQT1), a heritable disease characterized by prolonged QT interval, increased risk of fatal arrhythmias, and marked variability in disease severity. Recently, the minor alleles of SNPs rs2519184 (A) and rs8234 (G) in the 3= untranslated region (3=UTR) of KCNQ1 were shown to function as allele-specific modifiers of LQT1 disease severity via the microRNAmediated reduction of Kv7.1 expression. Here, we hypothesized that the disease modifying effect of the minor AG 3=UTR haplotype might be strongest in patients who harbor dominant-negative mutations whereby the alteration of the balance between normal and mutated Kv7.1 subunits may have the greatest clinical significance. Methods: In this study, 180 LQT1 cases (98 females, mean age 37 Ϯ 20 yrs, mean QTc 450 Ϯ 35 ms) were genotyped for SNPs in the 3=UTR of KCNQ1 using DNA sequencing. LQT1-causative mutations were classified as higher risk (dominant-negative, DN-LQT1) or lower risk (haploinsufficient, HI-LQT1) based on location and cellular electrophysiological phenotype. Results: In comparison to DN-LQT1 cases homozygous for the major GA 3=UTR haplotype (n ϭ 30, mean QTc 449 Ϯ 26 ms, 13% symptomatic), DN-LQT1 cases with the minor AG 3=UTR suppressive haplotype on their mutant KCNQ1 allele had a 25 Ϯ 29 ms shorter QTc (n ϭ 15, P Ͻ.01) and tended to experience less symptoms (7%), while DN-LQT1 cases with the minor AG 3=UTR haplotype on their normal KCNQ1 allele had a 74 Ϯ 32 ms longer QTc (n ϭ 6, P Ͻ.001) and experienced more symptoms (50%, P Ͻ.05). Interestingly, compared to HI-LQT1 cases homozygous for the major GA 3=UTR haplotype (n ϭ 15, mean QTc 432 Ϯ 26 ms, 7% symptomatic), HI-LQT1 cases with the minor AG 3=UTR haplotype on their normal allele had a 24 Ϯ 8 ms longer QTc (n ϭ 3, P Ͻ.01) and tended to experience more symptoms (33%), while the modifying effect of the minor AG 3=UTR haplotype on the mutant allele was absent in HI-LQT1 cases.

a 40-year-old medical doctor from Sri Lanka was referred to our hospital for repeated typical chest pain after exertion. He had left Sri Lanka in 2010, and, after a short stay in Thailand, migrated to the Netherlands. Till 2010, he had no medical history and no risk factors for atherosclerosis. In August 2010, in Bangkok, he had experienced an acute transmural myocardial infarction of the inferior wall ( , for which he was treated with streptokinase. Oral therapy with aspirin, metoprolol, enalapril and simvastatin was initiated. Coronary angiography was not performed. At referral to our hospital in March 2012, physical examination, blood tests, and ECG at rest and during exercise were normal. Echocardiography showed hypokinesia of the inferior septal wall. The diagnosis stable angina pectoris was made and the drug regimen was continued. In November 2012, he was admitted to the Cardiac Care Unit of our hospital after experiencing acute typical chest pain in rest. Physical examination was normal. Baseline ECG showed slight ST segment elevation in the inferior leads . The diagnosis acute coronary syndrome was made, aspirin was continued and initial loading doses of clopidogrel and fondaparinux were given. Serial blood tests revealed elevated cardiac enzymes (highly sensitive troponine-T peak of 160 ng/L). Echocardiography showed no novel abnormalities. Coronary angiography was performed and showed up to 10 mm diameter aneu-rysms in the proximal segments of the left anterior descending coronary artery and the circumflex coronary artery ) and through the entire length of the right coronary artery ( , with decreased blood flow in the coronary arteries and possible signs of thrombosis in the distal segments of the right coronary artery ( . Dual antiplatelet therapy with aspirin (100 mg daily) and clopidogrel (75 mg daily) was continued and acenocoumarol was initiated. The patient made a full recovery without recurrence of severe symptoms of angina when seen at the last follow-up in September 2013. A control coronary angiography showed no more signs of thrombosis in the coronary arteries.