Myocardial Repolarization Research Articles

Электрокардиографические показатели электрической нестабильности миокарда у больных синдромом обструктивного апноэ-гипопноэ во время сна и впервые выявленной артериальной гипертензией

Objective. To study the rate of long QTc and JTc intervals in sleep-wakefulness cycle, and also their relationship with severity of obstructive sleep apnea-hypopnea syndrome (OSA) in patients with newly diagnosed hypertension (HTN). Design and methods. 24‑hour multifunctional monitoring was conducted in 59 male patients (age 38,0 ± 7,7 years old; body mass index 33,8 ± 5,4 kg/m 2) with elevated office blood pressure, who did not receive any medications. All patients had two or more risk factors of HTN. Organ damage was identified in 12 (20 %) patients. The long QTc interval was defined as 450 msec or more, automatic analysis was performed using 8‑lead dynamic ECG. Results. OSA was diagnosed in 40 (68 %) patients: 17 patients had mild sleep apnea (apneahypopnea index, AHI, from 5 to 14 episodes per hour), the rest of the patients had moderate and severe OSA (AHI from 18 to 97 episodes per hour). Nineteen (32 %) patients without OSA were included in the comparison group (AHI less than 5 episodes per hour). There was no differences in average heart rate during assessed time periods between the groups. There was a direct positive correlation between duration of QTc and JTc calculated separately for periods of wakefulness, sleep and AHI and hypoxemia index. Conclusions. More than 50 % of patients with newly diagnosed AH and OSA without associated cardiovascular diseases demonstrate changes in myocardial repolarization throughout sleep-wakefulness cycle. These changes are associated with the number of apneas/hypopneas and the severity of hypoxemia during sleep

Kcne4 deletion sex- and age-specifically impairs cardiac repolarization in mice.

Myocardial repolarization capacity varies with sex, age, and pathology; the molecular basis for this variation is incompletely understood. Here, we show that the transcript for KCNE4, a voltage-gated potassium (Kv) channel β subunit associated with human atrial fibrillation, was 8-fold more highly expressed in the male left ventricle compared with females in young adult C57BL/6 mice (P < 0.05). Similarly, Kv current density was 25% greater in ventricular myocytes from young adult males (P < 0.05). Germ-line Kcne4 deletion eliminated the sex-specific Kv current disparity by diminishing ventricular fast transient outward current (Ito,f) and slowly activating K(+) current (IK,slow1). Kcne4 deletion also reduced Kv currents in male mouse atrial myocytes, by >45% (P < 0.001). As we previously found for Kv4.2 (which generates mouse Ito,f), heterologously expressed KCNE4 functionally regulated Kv1.5 (the Kv α subunit that generates IKslow1 in mice). Of note, in postmenopausal female mice, ventricular repolarization was impaired by Kcne4 deletion, and ventricular Kcne4 expression increased to match that of males. Moreover, castration diminished male ventricular Kcne4 expression 2.8-fold, whereas 5α-dihydrotestosterone (DHT) implants in castrated mice increased Kcne4 expression >3-fold (P = 0.01) to match noncastrated levels. KCNE4 is thereby shown to be a DHT-regulated determinant of cardiac excitability and a molecular substrate for sex- and age-dependent cardiac arrhythmogenesis.

Salt Loading on QT Dispersion and the Protective Role of Potassium Supplement in Normotensive Adults

QT interval dispersion (QTd) has been suggested to reflect the heterogeneity of myocardial repolarization and widely used in hypertension, coronary heart disease, arrhythmia, evaluation of a drug and so on. The aim of this study was to investigate the effects of dietary sodium intake on QTd and T peak -T end interval (Tp-Te) in normotensive healthy adults and the protective effect of dietary potassium. Sixty-four normotensive subjects aged 20~60 were selected and involved in a 3-week test in chronic salt loading and potassium supplementation, including baseline survey (baseline phase) for 3 d, low-salt diet (3g/day, NaCl, low-salt phase), high-salt diet (18g/day, salt loading phase) and high-salt with potassium supplementation diet (4.5g/day, KCl, salt and potassium supplement phase) each for 7 d. Blood pressure was measured and ECG was recorded at the last day of each phase, QT interval, QTd, corrected QTd (QTcd) and Tp-Te were measured and calculated. QTd, QTcd and Tp-Te at low-salt phase were less than those at baseline phase (QTd, 45.6±7.6ms vs. 52.1±9.4ms; QTcd, 53.4±8.4ms vs. 62.9±10.1ms; Tp-Te, 75.2±8.2ms vs. 85.0±9.6ms, P±0.05); QTcd and Tp-Te after salt loading were greater than those at low-salt phase (QTcd, 62.3±7.9ms vs. 53.4±8.4ms; Tp-Te, 84.7±10.0ms vs. 75.2±8.2ms, P<0.05); compared with those at salt loading phase, QTd, QTcd and Tp-Te were all reduced by large doses of oral potassium supplementation(QTd, 42.6±8.3ms vs. 53.4±9.1ms; QTcd, 52.2±6.2ms vs. 62.3±7.9ms; Tp-Te, 75.1± 8.5ms vs. 84.7±10.0ms, P±0.05). Salt loading increases blood pressure and prolongs QTd, QTcd and Tp-Te, while potassium supplementation reduces the influences of high salt on QTd, QTcd and Tp-Te, suggesting that high potassium intake may decrease the heterogeneity of cardiac repolarization and prevent arrhythmia by shortening repolarization time.

Predictors of Short- and Long-Term Outcomes of Takotsubo Cardiomyopathy

Takotsubo cardiomyopathy (TC) is a reversible cardiomyopathy with a benign short-term prognosis but is associated with recurrence rate of 10%. Clinical variables that predict long-term mortality and recurrence are unknown; 56 consecutive patients presenting to a single urban medical center who fulfilled the Mayo Clinic criteria for the diagnosis of TC were included. Patients were followed with 100% completeness; >60 clinical factors were analyzed, including presentation, treatment, electrocardiogram, and echocardiographic, angiographic, and demographic variables. Survival analysis was performed using the Kaplan-Meier function and Cox proportional hazards regression models. There were 15 deaths during follow-up: 5 in-hospital, 4 before 90days, and 6 after 90days. Mean survival was 4.47years (95% confidence interval 3.81 to 5.13). All short-term survivors had repeat ejection fraction evaluation demonstrating improvement; 45 of 56 patients were women and 96% were postmenopausal. The nonfatal recurrence rate was 1.8%. QTc interval at presentation was the factor most strongly predictive of overall outcome, after intubation. All patients with mortality had QTc intervals between 400 and 550 ms. In conclusion, this study demonstrates the prognostic significance of QTc prolongation at presentation in TC. Because the cause of TC involves intense catecholamine release and hyperadrenergic tone, the QTc may reflect the individual impact on myocardial repolarization and the balance between sympathetic innervation and parasympathetic compensation. In conclusion, in thisseries, TC was associated with an 8.9% in-hospital mortality, an additional 17.9% mortality after discharge, and a nonfatal recurrence rate of 1.8%. Moreover, the QTc on presentation with TC was predictive of outcome.

Prognostic value of Tpeak-Tend interval in patients with acute pulmonary embolism.

BackgroundThe aim of this study was to examine the Tpeak-Tend (Tpe/corrected Tpe) interval, which is an indicator of transmural myocardial repolarization, measured non-invasively via electrocardiogram in patients with acute pulmonary embolism (PE), and to investigate the relationship with 30-day mortality and morbidity.MethodsThe study included 272 patients diagnosed with acute PE, comprising 154 females and 118 males, with a mean age of 63.1 ± 16.8 years. Tpe/cTpe intervals were calculated from the electrocardiograms with a computer program after using a ruler or vernier caliper manual measuring tool to obtain highly sensitive measurements. The relationship between the electrocardiogram values and 30-days mortality and morbidity were measured.ResultsThe study group was divided into three groups according to cTpe intervals: Group 1, < 113 ms; Group 2, 113–133 ms; and Group 3, > 133 ms. White blood cell count and troponin T levels, corrected QT intervals with QRS complex durations, percentage of right ventricle dilatation with right/left-ventricular ratio, 30-day death, and combinations of these values were seen at a higher rate in Group 3 patients compared to the other groups. Kaplan–Meier analysis showed that the cTpe interval measured at > 126 ms could be used as a cut-off value in the prediction of mortality and morbidity. The cTpe cut-off values of 126 ms had sensivity, specificity, negative predictive value, and positive predictive value of 80.56 %, 59.32 %, 95.2 %, and 23.2 %, respectively.ConclusionscTpe interval could be a useful method in early risk stratification in patients with acute PE.

Obstructive sleep apnea and increased QT dispersion

Exaggerated dispersion of repolarization is likely to play a role in both the initiation and the maintenance of malignant ventricular arrhythmias. Interlead QT interval differences within a 12-lead electrocardiogram (ECG), termed “QT dispersion”, may reflect regional differences in myocardial refractoriness. Presumably, abnormal QT dispersion may be related to obstructive sleep apnea (OSA). This work aimed to provide a meta-analysis of the relevant available publications. A MEDLINE search was performed in PubMed (National Library of Medicine, NLM) from 2000 through to 2014. An all-fields search for index terms “QT” AND “dispersion” was conducted. Case–control studies and surveys were included into analysis, provided they encompassed healthy controls and subjects with diagnosed OSA, without other major health problems. Outcome measures were either crude (QTd) or heart rate-corrected (QTcd) dispersions. Four studies met the inclusion criteria. Overall, the analysis encompassed 222 patients with diagnosed OSA and 182 control subjects. Mean calculated age of the OSA patients was 37.7 years (standard error, SE: 11.5 years). Aggregate standardized difference in the means of QTd was 0.571 (95 % confidence interval, CI: 0.354–0.789; SE = 0.111, p < 0.001); for QTcd the difference was 0.859 (95 % CI: 0.142–1.577; SE = 0.366, p = 0.019). Meta-regression analysis found a statistically significant negative correlation between the effect sizes and the proportion of males in the OSA group. OSA is associated with increased QT dispersion. This may reflect disturbed myocardial repolarization in patients with OSA and predispose them to cardiac arrhythmias.

Early Myocardial Repolarization Heterogeneity Is Detected by Magnetocardiography in Diabetic Patients with Cardiovascular Risk Factors.

Multi-channel magnetocardiography (MCG) is a sensitive technique to map spatial ventricular repolarization with high resolution and reproducibility. Spatial ventricular repolarization heterogeneity measured by MCG has been shown to accurately detect and localize myocardial ischemia. Here, we explored whether these measurements correlated with cardiovascular risk factors in patients with type 2 diabetes. Two hundreds and seventy-seven type 2 diabetic patients without known coronary artery disease (CAD) and arrhythmia were recruited consecutively from the outpatient clinic of National Taiwan University Hospital. The spatially distributed QTc contour maps were constructed with 64-channel MCG using the superconducting quantum interference device (SQUID) system. Indices of myocardial repolarization heterogeneity including the smoothness index of QTc (SI-QTc) and QTc dispersion were derived and analyzed for association with conventional cardiovascular risk factors. SI-QTc correlated strongly with the QTc dispersion (r = 0.70, p <0.0001). SI-QTc was significantly higher in patients with presence of metabolic syndrome in comparison to those without metabolic syndrome (8.56 vs. 7.96 ms, p = 0.02). In univariate correlation analyses, QTc dispersion was associated with smoking status (average 79.90, 83.83, 86.51, and 86.00 ms for never smokers, ex-smokers, current smokers reporting less than 10 cigarettes daily, and current smoker reporting more than 10 cigarettes daily, respectively, p = 0.03), body weight (r = 0.15, p = 0.01), and hemoglobin A1c (r = 0.12, p = 0.04). In stepwise multivariate regression analyses, QTc dispersion was associated with smoking (p = 0.02), body weight (p = 0.04), total cholesterol levels (p = 0.05), and possibly estimated glomerular filtration rate (p = 0.07). In summary, spatial heterogeneity of myocardial repolarization measured by MCG is positively associated cardiovascular risk factors including adiposity, smoking, and total cholesterol levels.

Device therapy in the setting of long QT syndrome.

Congenital long QT syndrome (LQTS) is an inherited disorder of myocardial repolarization characterized by prolongation of the QT interval associated with life-threatening polymorphic ventricular tachycardia. The treatment of congenital LQTS involves antiadrenergic therapies: β-blockers and surgical left cardiac sympathetic denervation (LCSD) to decrease sympathetic input to the heart, cardiac pacing, and implantable cardioverter-defibrillator (ICDs). Although this article focuses on the role of device therapy for the treatment of LQTS, it also discusses the role of β-blockers and LCSD because they are concomitant with device therapy. After implantation, programming should be optimized to minimize the risk for inappropriate ICD therapies.

Long QT Syndrome: An Emerging Role for Inflammation and Immunity.

The long QT syndrome (LQTS), classified as congenital or acquired, is a multi-factorial disorder of myocardial repolarization predisposing to life-threatening ventricular arrhythmias, particularly torsades de pointes. In the latest years, inflammation and immunity have been increasingly recognized as novel factors crucially involved in modulating ventricular repolarization. In the present paper, we critically review the available information on this topic, also analyzing putative mechanisms and potential interplays with the other etiologic factors, either acquired or inherited. Accumulating data indicate inflammatory activation as a potential cause of acquired LQTS. The putative underlying mechanisms are complex but essentially cytokine-mediated, including both direct actions on cardiomyocyte ion channels expression and function, and indirect effects resulting from an increased central nervous system sympathetic drive on the heart. Autoimmunity represents another recently arising cause of acquired LQTS. Indeed, increasing evidence demonstrates that autoantibodies may affect myocardial electric properties by directly cross-reacting with the cardiomyocyte and interfering with specific ion currents as a result of molecular mimicry mechanisms. Intriguingly, recent data suggest that inflammation and immunity may be also involved in modulating the clinical expression of congenital forms of LQTS, possibly triggering or enhancing electrical instability in patients who already are genetically predisposed to arrhythmias. In this view, targeting immuno-inflammatory pathways may in the future represent an attractive therapeutic approach in a number of LQTS patients, thus opening new exciting avenues in antiarrhythmic therapy.

A step forward parameter for the effects of transcatheter aortic valve implantation: transmural dispersion of repolarization.

We have recently reported a potential beneficial effect of transcatheter aortic valve implantation (TAVI) on reducing ventricular arrhytmias beyond relieving symptoms in patients with symptomatic severe aortic stenosis.[1] Basically, we showed a reduction in myocardial repolarization dispersion evaluated by QT dispersion (QTd) after TAVI in this population. QTd is the most frequently used non-invasive method to assess the myocardial repolarization abnormalities in many diseases in literature. It has been well known that QTd may provide prognostic data for future ventricular tachyarrhythmias and sudden death.[2]–[4] However, ‘achilles heel’ of this method is the reproducibility of QTd measurements. In general, it is low in both manual and automatic measurement techniques and inter- and intraobserver variability is especially high in manual measurements of QTd.[5],[6] This situation was chiefly caused by using insufficient quality of electrocardiography (ECG) samples to measurement of QTd. Such ECG's do not reflect the end of T wave with sufficient certainty. Therefore, using the appropriate ECG samples is essential to obtain the reliable data on myocardial dispersion abnormalities by QTd. In our study, we used only ECG samples which have high quality. And, we believe that our results are reliable and have future perspectives on the effects of TAVI beyond relieving symptoms in patients with symptomatic severe aortic stenosis. On the other hand, the notion of ‘transmural dispersion’ has emerged in early last decade and has led to a new perception on the understanding of myocardial repolarization. According to this model, it has been accepted that three layer of myocardium including endocardium, epicardium and mid myocardial M cells have different electrophysiological features which represents a repolarization heterogenity in basal situation.[7] Conditions affecting the myocardial repolarization such as heart rate, blood electrolyte status and drugs have a different effects on these myocardial layers which can increase the basal repolarization heterogenity and can cause ventricular arrhytmia. On ECG, the peak of T-wave represents the epicardial repolarization while the end of T-wave suggests the repolarization of midmyocardial M-cells. The time between the peak and end of the T wave is called ‘Tp-e interval’ and its ratio with QTd (Tp-e/QTd) were defined as indexes of transmural dispersion of repolarization which can predict life treating arrhytmias in different populations.[8],[9] We evaluated the Tp-e interval and Tp-e/QTd ratio on ECG of patients in our study group to comply with the author's suggestions. Both Tp-e interval and Tp-e/QTd ratio were significantly reduced after TAVI procedure in patients with severe aortic stenosis (80.1 ± 3.5 vs. 78.5 ± 2.6 ms; P = 0.008 and 0.20 ± 0.1 vs. 0.19 ± 0.1; P = 0.001, respectively). We agree with the authors that the results might be useful to completely reveal of effect of TAVI procedure on electrical heterogeneity of the myocardium.

Spatial QT Dispersion Predicts Nonsustained Ventricular Tachycardia and Correlates with Confined Systodiastolic Dysfunction in Hypertrophic Cardiomyopathy

Objectives: An increased dispersion of myocardial repolarization represents one of the mechanisms underlying the arrhythmic risk in hypertrophic cardiomyopathy (HCM). We investigated spatial myocardial repolarization dispersion indices in HCM patients with nonsustained ventricular tachycardia (NSVT) and, contextually, their main clinical determinants. Methods: Fifty-two well-matched HCM outpatients were categorized into two groups according to the presence or the absence of NSVT at 24-hour Holter electrocardiogram (ECG) monitoring. Each patient underwent a clinical examination, including Doppler echocardiogram integrated with tissue Doppler imaging, cardiac magnetic resonance, and 12-lead surface ECG to calculate the dispersion for the following intervals: QRS, Q-T_end (QT_e), Q-T_peak, T_peak-T_end (T_pT_e), J-T_peak, and J-T_end. Results: The NSVT group showed only QT_e dispersion and T_pT_e dispersion values to be significantly higher than their counterparts. NSVT occurrence was independently predicted by late gadolinium enhancement presence (p = 0.021) and QT_e Bazett dispersion (p = 0.030), the latter strongly associated with the myocardial performance index (MPI) obtained at the basal segment of the interventricular septum (p = 0.0004). Conclusion: Our data support QT_e dispersion as an easy and noninvasive tool for identifying HCM patients with NSVT propensity. The strong relationship between QT_e dispersion and MPI allows us to hypothesize an intriguing link between electrical instability and confined myocardial areas of systodiastolic dysfunction.

Effects of hypothermia combined with dexmedetomidine on myocardial monophasic action potentials in isolated rabbit hearts

Objective To investigate the effects of hypothermia combined with dexmedetomidine on myocardial monophasic action potentials(MAPs)in isolated rabbit hearts. Methods Adult rabbits, weighing 2.0-2.5 kg, were heparinized and anesthetized with pentobarbital sodium 30 mg/kg.Their hearts were rapidly removed and retrogradely perfused in a Langendorff apparatus at 37 ℃.Eighteen hearts were randomly divided into 3 groups(n=6 each)using a random number table: control group(group C), hypothermia group(group H), and hypothermia+ dexmedetomidine group(group HD). The hearts were continuously perfused for 60 min with 37 ℃ K-H solution in group C, with 32 ℃ K-H solution in group H, or with 32 ℃ K-H solution containing dexmedetomidine 25 ng/ml in group HD.At the end of equilibration(T0)and at 15, 30 and 60 min of perfusion with K-H solution, HR and MAPs of left ventricular epicardium, mid-myocardium and endocardium were recorded.MAP duration at 50% repolarization(MAPD50)and at 90% repolarization(MAPD90), monophasic action potential amplitude(MAPA)and maximal velocity(Vmax)were calculated. Results Compared with group C, HR was significantly decreased, and MAPD50 and MAPD90 were prolonged at each time of perfusion with K-H solution in H and HD groups.There was no significant difference in HR, MAPD50 and MAPD90 between H group and HD group.There was no significant difference in MAPA and Vmax between the three groups. Conclusion Hypothermia combined with dexmedetomidine can lead to prolongation of myocardial repolarization, and dexmedetomidine exerts no effect on hypothermia-induced change in MAPs in isolated rabbit hearts. Key words: Hypothermia, induced; Dexmedetomidine; Action potentials; Intraoperative complications

Modulation of the QT interval duration in hypertension with antihypertensive treatment.

The duration of the QT interval as measured by 12-lead electrocardiography is a measure of myocardial repolarization and is widely used to describe cardiac abnormalities, to determine the presence of cardiac toxicity and to evaluate drug safety. In hypertension, the QT interval is a predictor of the risk of both coronary events and cardiovascular death, after adjusting for the effects of additional risk factors. The mechanism of QT interval prolongation is multifactorial and includes cardiomyocyte hypertrophy and increased left ventricular mass, with accompanying changes in left ventricular transmural dispersion of repolarization, as well as changes in the tone of the autonomic nervous system of some patients with hypertension and mechano-electrical feedback, although this mechanism is less likely. Antihypertensive drugs vary in their effect on QT interval duration. The mechanisms underlying their effect depend on changes in left ventricular mass and autonomic nervous system tone, as well as changes in the activity of cardiac ion channels. Although blood pressure reduction is the primary goal of antihypertensive drug therapy and although the choice of antihypertensive drug treatment regimens varies among different individuals, the data regarding the disparate effects of antihypertensive drugs on the duration of the QT interval warrant consideration when implementing long-term pharmacotherapy for hypertension.

Exercise-Induced Repolarization Changes in Patients with Isolated Myocardial Bridging.

BackgroundAlthough myocardial bridging (MB) is defined as an angiographic phenomenon with a benign course, it has also been associated with adverse cardiovascular events. The effects of exercise on myocardial repolarization in patients with MB were tested in this study, with Tp-e and Tp-e/QT repolarization indexes.Material/MethodsA total of 50 patients in whom isolated MB was diagnosed at coronary angiography (CAG) (Group I) and 48 patients with normal CAG results (Group II) were included in this study. The participants underwent treadmill exercise stress testing according to the Bruce protocol. QT dispersion (QTd) was defined as the minimum QT interval subtracted from the maximum. The Tp-e interval was defined as the difference between the QT and the QT peak time period. QTd and Tp-e intervals were calculated for all patients before and after exercise testing and differences between groups were compared.ResultsAt peak exercise, QTd and cQTd showed a significant increase in comparison to baseline values in the group of patients with myocardial bridges. Significant increases were also found with exercise in the Tp-e, cTp-e durations and Tp-e/QT ratio of the MB patient group in comparison to the baseline values. On the other hand, significant differences in QTd, cQTd, Tp-e, cTp-e intervals, and Tp-e/QT ratio during peak exercise in comparison with baseline values were not detected in the control group (p>0.05).ConclusionsSignificant increases in QTd, cQTd, Tp-e and cTp-e intervals and Tp-e/QT ratio were detected in the MB patients during exercise testing.

Chronic Hyperglycemia and Inhomogenous Ventricular Repolarisation - an Electrophysiological Approach

The QT interval expresses the myocardial depolarization and repolarisation time. QTd is regarded as an index of myocardial electrical activity. Present study was done to investigate the differences in QTd between non-diabetics, well controlled diabetes patients and poorly controlled diabetics. The study group comprised of 60 type 2 diabetes patients within the age group of 40–60 years coming to diabetic clinic and those hospitalized in medicine wards, They were further classified in to two sub-groups(n = 30 in each group), Type2 diabetes patients with good glycemic control (HbA1c 7). Glycosylated hemoglobin level was detected by calorimetric method (spectronic -2). The control group consisted of 30 age matched healthy subjects (volunteers). After thorough examination of the subjects as per the proforma, 12 lead ECG was taken with (Montara instrument ELI 250), QT interval was measured on the 12 lead resting ECG. QTd was calculated manually. The value of QT dispersion was significantly high (p < 0.01) in Type2 Diabetes mellitus patients with poor glycemic control compared to well controlled diabetics and healthy subjects. Chronic hyperglycemia is associated with high QT dispersion which suggests that such patients have a greater inhomogeneity of repolarization and therefore they are more prone for adverse cardiovascular events.

Coronary Fistulas in a Patient with a Novel Long QT Syndrome Mutation

The congenital long QT syndrome (LQTS) is a genetic cardiac channelophathy with variable penetrance characterized by corrected QT (QTc) interval prolongation and predisposition to polymorphic ventricular tachycardia (PVT), which normally presents with syncope or sudden death. It can be caused by mutations in different ion channels, resulting in prolongation of the myocardial repolarization1. The clinical course of LQTS throughout a patient’s lifetime is significantly influenced by the genotype and acquired factors that additionally compromise myocardial repolarization, including drug use, serum electrolyte abnormalities, autoimmune diseases, severe bradycardia, acute heart failure decompensation and myocardial ischemia2. This report presents the first description of PVT precipitated by myocardial ischemia secondary to multiple coronary fistulas in a patient with a novel LQTS-causing mutation.

Contributions of the Mexican electrovectorcardiography

We narrate the main stages of the long journey that led to the structuring of modern electrovectorcardiography based on the fundamentals established by Willem Einthoven (1860-1927), who held the physiology chair of the Leyden University (The Netherlands), and presented his string electrocardiograph in 1901. The Mexican electrovectorcardiography became strong thanks to the endeavor of Dr. Demetrio Sodi Pallares, a disciple of F.N. Wilson of Ann Arbor. Dr. Sodi Pallares founded the Mexican School of Electrovectorcardiography, which was a cornerstone in the field and was widely recognized internationally for several decades. This fact is due to the rational and not empirical approach to the electrical exploration of the heart, thanks to the application of the inductive-deductive Galilean procedure. It was then possible to obtain these results, through the study of myocardial depolarization and repolarization processes, under normal conditions and with bundle branch block, performed by Dr. Gustavo A. Medrano and collaborators, in the 1950 decade. The electrovectorcardiographic manifestations of the non complicated myocardial infarct were the object of studies, as well as those of the infarction complicated with rhythm and conduction disorders. Likewise, proximal and distal or peripheral blocks were studied. The current disciples of that School are now studying of cardiac arrhythmias with promising results.

Relationship between anthropometric measures and early electrocardiographic changes in obese rats.

BackgroundThe degree of cardiovascular function impairment parallels the degree of obesity and obese subjects have abnormal changes on the electrocardiogram (ECG). Early ECG changes in obesity have not been previously studied. The objective of the present study was to determine the early ECG changes in obese rats and their relationship with anthropometric measurements.ResultsAt seven weeks all rats in the experiment were obese and in sinus rhythm. In the experiment resting heart rate was increased (364 ± 13 vs. 313 ± 12 bpm, P <0.01). In contrast, the following parameters were shortened: QRS duration (77 ± 3.6 vs. 65 ± 2.6 ms, P < 0.01); QT interval (102 ± 5.2 vs. 88 ± 3.7 ms, P < 0.05); Q wave amplitude (−12.8 ± 1.0 vs. -5.1 ± 0.9 μv, P <0.01); and T wave amplitude (18.8 ± 1.4 vs. 5.8 ± 0.6, P <0.01). All other ECG parameters remained unchanged. With increased weight the resting heart rate (r =0.46, P < 0.01) and R wave amplitude (r = 0.60, P < 0.01) increased.ConclusionEarly in obesity there are no rhythm disturbances, but resting heart rate is increased. The QRS duration is shortened and Q and T-wave amplitudes reduced signifying ventricular changes related to impaired myocardial depolarization and repolarization. Furthermore, weight gain is correlated with an increase in heart rate and accentuation of the R wave amplitude.

EP News: Basic and Translational

The QT interval is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death and could indicate the presence of the potentially lethal Mendelian long QT syndrome (LQTS). By using a genome-wide association and replication study in up to 100,000 individuals, Arking et al (Nat Genet 2014;46:826, PMID 24952745) identified 35 common variant loci (eg, ATP2A2 and PLN) that collectively explain 8%–10% of the variation in the QT interval, highlighting calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval–associated loci in 298 probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Newly identified loci encode proteins that physically interact with other recognized repolarization proteins. The authors conclude that their integration of common variant association, expression, and orthogonal protein-protein interaction screens provides new insights into new candidate genes for ventricular arrhythmias, LQTS, and sudden cardiac death.

Vernakalant in an Experimental Model of Pacing-Induced Heart Failure: Lack of Proarrhythmia Despite Prolongation of Repolarization

BackgroundThe present ESC guidelines on atrial fibrillation have introduced vernakalant (VER) for pharmacologic cardioversion of atrial fibrillation. The aim of the present study was to investigate possible proarrhythmic effects of vernakalant in an experimental model of heart failure (HF). Methods and ResultsIn 12 female rabbits, HF was induced with the use of 4 weeks of rapid ventricular pacing. Twelve rabbits were sham operated. Isolated hearts demonstrated a significant prolongation of myocardial repolarization after induction of HF. Vernakalant caused a concentration-dependent (10 μmol/L and 30 μmol/L) increase of action potential duration (APD90) and QT interval without affecting spatial and temporal dispersion of repolarization. The increase in APD90 was accompanied by a greater increase in refractory period resulting in a significant increase in post-repolarization refractoriness. In control conditions, programmed ventricular stimulation and burst pacing led to ventricular fibrillation (VF) in 2 of the 12 sham (4 episodes) and in 3 of the 12 HF (24 episodes) subjects. In the presence of 30 μmol/L vernakalant, VF was no longer inducible in both groups (0 episodes). In the presence of low K+ concentration, neither sham nor HF vernakalant-treated subjects developed early after-depolarizations or ventricular tachyarrhythmias. ConclusionIn the present study, application of vernakalant led to a significant prolongation of myocardial repolarization and increased post-repolarization refractoriness but did not induce early after-depolarization and therefore did not cause proarrhythmia in failing hearts.