Changes In Ventricular Repolarization Research Articles

Electrocardiographic evidence of ventricular repolarization remodelling during atrial fibrillation

Some atrial fibrillation (AF) patients develop excessive QTc prolongation and torsade de pointes when they take QTc-prolonging antiarrhythmic drugs (class IA/III) immediately after termination of AF. We hypothesized that this is caused by changes in ventricular repolarization during AF. We aimed to establish whether such 'ventricular repolarization remodelling' occurs. We studied all patients who visited our cardiac emergency room with AF and converted to sinus rhythm (SR) in a 30 months' period. We defined four groups: (i) no antiarrhythmic drugs, electrical cardioversion (n = 30), (ii) no antiarrhythmic drugs, spontaneous AF termination (n = 19), (iii) antiarrhythmic drugs, electrical cardioversion (n = 29), and (iv) antiarrhythmic drugs, spontaneous AF termination (n = 9). We studied QTc duration at SR before AF (SR(baseline)), immediately after termination of AF (SR(postAF)), and at follow-up (SR(followup): > or =7 days after SR(postAF)). Moreover, we studied determinants of QTc prolongation at SR(postAF). We found that, in all groups, QTc at SR(postAF) was significantly and transiently prolonged compared with SR(baseline). Although of limited magnitude on average (approximately 5%), the increase was substantial (approximately 15%) in some individuals. The only independent predictor of the magnitude of QTc prolongation was QTc duration at SR(baseline); this relation had a negative correlation. AF causes ventricular repolarization remodelling, resulting in QTc prolongation. QTc prolongation is substantial in some patients and may render these patients vulnerable to pro-arrhythmia from class IA/III antiarrhythmic drugs immediately after termination of AF.

Investigation of pacing site-related changes in global restitution dynamics by non-contact mapping

The determination of dynamic changes in ventricular repolarization may provide insight into arrhythmogenic mechanisms as a consequence of pacing site. This study investigated acute pacing site effects on global characteristics of electrical restitution using high resolution, non-contact mapping (NCM). Activation-recovery intervals (ARIs) were determined from reconstructed left ventricular electrograms by the NCM system and were analysed during pacing from the right atrial appendage (RAA, intrinsic), right ventricular apex (RVA), and right ventricular septum (RVS) with extrasystoles delivered at intermediate and short coupling intervals in anesthetized swine (n = 5). Electrical restitution curves were determined by the S1-S2 pacing protocol. Activation-recovery interval restitution slopes were determined by the overlapping linear segments regression method. Global distribution of repolarization was defined as the coefficient of variation of the ARIs during restitution. The maximum ARI slopes yielded by RVA pacing were significantly greater than RAA pacing (0.44 vs. 0.32; P < 0.05) and RVS pacing (0.44 vs. 0.37; P = 0.05). There was no significant difference between RAA and RVS pacing (0.32 vs. 0.37). The global distribution of ARIs during restitution from RVA pacing was significantly greater than RAA pacing (12.0 vs. 8.1%; P < 0.05). Right ventricular apex pacing is associated with impaired global repolarization patterns compared to RAA and RVS. These observations support the hypothesis that RVA pacing may be associated with increased risk of ventricular arrhythmias compared to RVS pacing.

Abstract 3390: Marginal Overlap between Electrocardiographic Abnormalities in Patients with Hypertrophic Cardiomyopathy and Trained Athletes: Implications for Preparticipation Screening

Background: Hypertrophic cardiomyopathy (HCM) is usually associated with ECG abnormalities such as left ventricular hypertrophy (LVH), repolarization changes, and pathologic Q waves; instead, physiologic hypertrophy in trained athletes manifests as an isolated increase of QRS amplitude. We assessed whether the ECG pattern of pathologic hypertrophy of HCM overlaps with that of physiologic hypertrophy of athlete’s heart, particularly by evaluating what proportion of individuals from both groups had pure QRS voltage criteria (Sokolow-Lyon) for LVH. Methods: Using accepted diagnostic criteria, we examined and compared the ECG tracings of 260 consecutive patients with clinical and echocardiographic diagnosis of HCM and those of 1005 trained athletes undergoing preparticipation cardiovascular evaluation, including ECG and echocardiography. Results: An abnormal ECG was found in 246 of 260 (94.6%) patients with HCM and in 817 of 1005 athletes (81.3%). The majority of patients with HCM had one or more of the following ECG changes: repolarization ST/T abnormalities in 209 (80%), pathologic Q waves (Q waves ≥0.04 s in duration or ≥25% of the height of the ensuing R wave) in 103 (39.6%); left atrial enlargement in 75 (28.8%), intraventricular conduction abnormalities (QRS duration ≥90 ms) in 71 (27.3%) and left axis deviation in 9 (3.5%). ECG tracings showed isolated increase of QRS voltages in 5 HCM patients (1.9%) and were completely normal in 14 (5.4%). Compared with patients with HCM, trained athletes significantly more often had isolated voltage criteria for LVH (403, 40%; p&lt;0.0001), but less often showed negative T waves (27, 2.7%; p&lt;0.0001), pathologic Q waves (17, 1.7%; p&lt;0.0001), and nonvoltage criteria of LVH (13, 1.3%; p&lt;0.0001). No athletes with isolated voltage criteria had echocardiographic evidence of HCM. Conclusions: ECG in HCM overlaps marginally with ECG findings in trained athletes. An isolated increase of QRS voltage is an unusual pattern (1.9%) of LVH in patients with HCM, while is frequently observed in trained athletes. Systematic echocardiographic evaluation of athletes fulfilling isolated QRS voltage criteria at preparticipation screening is not justified, resulting in a considerable cost savings.

Study of ventricular repolarization changes after carnitine deprivation in rats by contactless magnetocardiography

Carnitine deficiency can be associated with cardiomyopathy and life-threatening arrhythmias. The aim of this study was to assess changes of ventricular repolarization (VR) intervals by contactless magnetocardiographic mapping (MCG), in a rat model of carnitine deficiency. 21 anesthetized Wistar rats (WR), 11 males and 10 females, were investigated, with an unshielded 36-channel MCG instrumentation. After a basal recording 10 animals were randomized to carnitine-deprivation induced by a 3-weeks diet containing N-trimethyl-hydrazine-3-propionate (THP). All WR were restudied 1 week after the end of THP treatment. RR, QRS, QT peak, QT end, JT peak, JT end and T peak-end intervals were measured from MCG waveforms. A prolongation of all HR-corrected VR intervals was observed in THP-treated animals (range 7.6–12.8%), as compared to their basal values. However, only the lengthening of QT end and T peak-end was statistically significant ( p < 0.05). Compared to untreated age-matched controls, the cardiac intervals of TPH-treated WR values were longer, but the differences were not significant. After 3 weeks of THP-induced reduction of cardiac and plasma levels of carnitine, abnormalities in myocardial function are expected. In this study we have found only a prolongation of HR-corrected QT end and T peak-end in THP-treated animals. The lack of significance versus age-matched controls could be either due to too early re-evaluation after deprivation, or to the effect of aging. In fact, age-related prolongation of VR intervals has been reported in WR at the age of 14 months.

Cardiac repolarization is prolonged in CD4C/HIV transgenic mice

Pharmacological agents used to treat patients with AIDS have been associated with QT prolongation and result in delayed repolarization. New evidence suggests that delayed repolarization can occur independently of pharmacological therapy. However, the effect of HIV on ventricular repolarization has not been investigated. Therefore, the objective of this study was to characterize cardiac repolarization in a mouse model of human HIV disease. All experiments were conducted on HIV transgenic mice (CD4C/HIV). These mice express the human HIV gene nef in cells of immune system and develop a severe AIDS-like disease that is similar to that observed in humans. ECG was recorded in conscious free moving mice and patch-clamp techniques were used to record action potentials and K + current densities in single ventricular myocytes. Results showed that the QT interval and action potential duration were significantly prolonged in CD4C/HIV mice compared to wild-type littermates. This delay in repolarization was associated with a significant reduction in outward K + currents. Echocardiography showed that cardiac structure and function were similar in CD4C/HIV and littermate control mice. This suggests that the changes in ventricular repolarization were not the result of heart failure or cardiac hypertrophy. Overall, this study shows that repolarization was delayed in CD4C/HIV mice and that this phenotype occurred in the absence of any pharmacological intervention. Thus, it appears that HIV may be responsible for the delayed ventricular repolarization phenotype observed in CD4C/HIV mice.

Cardiac Memory versus Likelihood of Ischemic Heart Disease in Hypertensive Patients with Ventricular Repolarization Abnormalities after Repetitive Uniform Ventricular Extrasystoles

Objectives: To investigate the value of T-wave inversion after premature ventricular complexes (PVCs) for the prediction of hypertensive patients with a likelihood of ischemic heart disease (IHD). Patients and Methods: Ambulatory 24-hour ECG, ambulatory 24-hour blood pressure (BP) recording, echocardiography, treadmill exercise ECG test and thallium-201 scintigraphy were performed for 210 hypertensive patients. Results: Predictive indices showed that persistent symmetrical T-wave inversion after repetitive uniform PVCs equaling 30 min can be considered an indicator for the prediction of IHD in hypertensive patients as sensitivity was 80%, specificity: 73%, accuracy: 78%, positive predictive value: 83%, and negative predictive value: 69%. kappa coefficient value (ĸ) indicated that there was good agreement between changes in ventricular repolarization after PVCs and stress thallium scintigraphy (ĸ = 0.897). Receiver-operating characteristic curve data showed that the ideal cutoff value of T-wave inversion voltage to predict IHD in hypertensive patients was 2.2 mV (sensitivity: 66% and false positive: 35%, and area under curve: 0.716), but the ideal cutoff value of time for resolution of T-wave inversion was 34 min (sensitivity: 83% and false positive: 18%, and area under curve: 0.873). Multivariate analysis revealed that T-wave inversion after repetitive uniform PVCs was significantly associated with non-sustained ventricular tachycardia, decreased parasympathetic activity, increased sympathetic activity, morning BP surge, systolic BP load >50% and left ventricular diastolic dysfunction status. Conclusion: The data show that persistent symmetrical T-wave changes following resumption of sinus rhythm after repetitive uniform PVCs are an independent variable for the prediction of IHD in hypertensive patients.

Early Changes in Ventricular Repolarization after Thrombolytic Therapy in Patients with Acute Myocardial Infarction as Indicators for Prediction of Epicardial Coronary Artery Reperfusion

Objectives: To investigate the relationship between early T-wave inversion after thrombolytic therapy and the likelihood of successful epicardial coronary reperfusion. Subjects and Methods: Thrombolytic therapy was given to 195 patients with ST segment elevation due to acute anterior myocardial infarction (AMI). Coronary angiography was performed. Receiver operating characteristic (ROC) curve (grade of sensitivity versus false positive) was calculated using likelihood ratio method to identify the ideal cut-off values of the ventricular repolarization variables. Results: Predictive indices showed 80% sensitivity, 83% specificity, 81% accuracy, 88% positive predictive value and 71% negative predictive value for early T-wave inversion after thrombolytic therapy. A good concordant agreement was noted between the data of coronary angiography and early T-wave inversion in the infarct-related ECG leads after thrombolysis (kappa coefficient ĸ= 0.876). Stepwise multivariate analysis revealed that early T-wave inversion after thrombolytic therapy of AMI was significantly associated with a history of preinfarction angina, residual infarct-related coronary artery stenosis >50%, short time to thrombolytic therapy <90 min, and evening time for occurrence of thrombolysis (p < 0.05). The ROC curve data analysis showed that early T-wave inversion amplitude after AMI had 87% sensitivity and 84% specificity for predicting successful reperfusion, with an ideal cut-off value of 7.2 mm, while time of T-wave inversion had 80% sensitivity and 79% specificity, with an ideal cut-off value of 120 min. Conclusion: The data indicate that early inversion of T wave after AMI is a statistically significant independent variable in predicting successful epicardial coronary thrombolysis status.

Cardiac changes during arousals from non-REM sleep in healthy volunteers

Our aim was to evaluate cardiac changes evoked by spontaneous and sound-induced arousals from sleep. Cardiac responses to spontaneous and auditory-induced arousals were recorded during overnight sleep studies in 28 young healthy subjects (14 males, 14 females) during non-rapid eye movement sleep. Computerized analysis was applied to assess beat-to-beat changes in heart rate, atrio-ventricular conductance, and ventricular repolarization from 30 s before to 60 s after the auditory tone. During both types of arousals, the most consistent change was the increase in the heart rate (in 62% of spontaneous and in 89% of sound-induced arousals). This was accompanied by an increase or no change in PR interval and by a decrease or no change in QT interval. The magnitude of all cardiac changes was significantly higher for tone-induced vs. spontaneous arousals (mean +/- SD for heart rate: +9 +/- 8 vs. +13 +/- 9 beats per min; for PR prolongation: 14 +/- 16 vs. 24 +/- 22 ms; for QT shortening: -12 +/- 6 vs. -20 +/- 9 ms). The prevalence of transient tachycardia and PR prolongation was also significantly higher for tone-induced vs. spontaneous arousals (tachycardia: 85% vs. 57% of arousals, P < 0.001; PR prolongation: 51% vs. 25% of arousals, P < 0.001). All cardiac responses were short-lasting (10-15 s). We conclude that cardiac pacemaker region, conducting system, and ventricular myocardium may be under independent neural control. Prolongation of atrio-ventricular delay may serve to increase ventricular filling during arousal from sleep. Whether prolonged atrio-ventricular conductance associated with increased sympathetic outflow to the ventricular myocardium contributes to arrhythmogenesis during sudden arousal from sleep remains to be evaluated.

Dynamic Ventricular Repolarisation: From Physiology to Prognosis

Identification of high-risk patients for sudden cardiac death (SCD) remains difficult. Non-invasive markers evaluating changes in heart rate and ventricular repolarisation (VR) have been developed to stratify this risk. Most studies using VR analysis rely on static analysis of the QT interval which is poorly reproducible and heart rate dependent. Dynamic VR analysis assesses QT interval modification according to RR duration of the precedent heart cycle. This relation is characterized by the linear regression QT/RR (y = ax+b) thus defined by its slope (a) and the value of the QT for a virtual null RR cycle (b). Analysis can be made for QTa (apex) and QTe (end). In healthy subjects, the difference of QT/RR slopes observed between day and night highly suggest that the QT/RR slope is influenced by the autonomic tone. The QT/RR slope is also influenced by clinical, physiological, pharmacological and various diseases associated with an increased risk of SCD. The prognostic value of the QT/RR slope for SCD has been demonstrated after myocardial infarction and in chronic heart failure. These results suggest that QT dynamicity is a promising tool able to identify patients at risk of SCD.

Acute subendocardial ischaemia leads to homogenous prolongation in ventricular repolarization

Acute transmural ischaemia often shortens ventricular repolarization and increases repolarization dispersion, leading to life threatening ventricular arrhythmias in animal models and human subjects. Experimental studies and clinical observations have shown that acute subendocardial ischaemia rarely causes serious ventricular arrhythmia. We hypothesized that the different arrhythmia outcomes between transmural and subendocardial ischaemia are largely due to the homogenous prolongation in ventricular repolarization after acute subendocardial ischaemia. Further experimental studies on a subendocardial model are required to assess the changes in ventricular repolarization and its spatial dispersion, and to investigate the role of these changes in the pathogenesis of ventricular arrhythmias. These studies will facilitate our understanding on the mechanisms of life-threatening ventricular arrhythmias during acute myocardial ischaemia.

Effects of treatment with somatostatin analogues on QT interval duration in acromegalic patients

Cardiovascular disease is a major contributor to the increased mortality of acromegalic patients. Prolongation of the QT interval is considered an established risk factor for potentially fatal cardiac arrhythmias, an event frequently observed in acromegaly. Changes in ventricular repolarization have been observed with the use of octreotide, one of the somatostatin analogues (SSA) currently used for the medical treatment of this disease. Furthermore, octreotide is listed among the drugs able to prolong the QT interval. Thus, we elected to study the effects of long-term SSA administration on QT duration and left ventricular mass (LVM) in a group of acromegalic patients. In a retrospective study, 30 acromegalic patients (19 women and 11 men, aged 25-77 years) were studied under basal conditions; 24 of them (15 women and nine men, aged 25-77 years) were studied again after 3-63 months of treatment (median 18 months) with SSA. Twenty-four healthy volunteers served as controls. Patients and controls underwent electrocardiographic (ECG) analysis, and QT interval duration corrected for heart rate (QTc) was established according to the Bazett formula. In 17 of the SSA-treated patients, M- and B-mode echocardiography for the assessment of LVM index (LVMi) was performed. Baseline QTc was significantly longer in patients than in controls. SSA administration was followed by a significant decrease in QTc, which reached a mean value similar to that measured in the controls. In particular, treatment with SSA normalized QTc in three out of the six patients with abnormally elevated values at baseline. After treatment, a significant reduction in heart rate was recorded, while LVMi displayed a slight but not significant decrease. Acromegalic patients frequently display an abnormally prolonged QT interval, a known risk factor for potentially fatal arrhythmias. Treatment of these patients with SSA is able to improve and even normalize this alteration, probably contributing to the beneficial effects of these drugs on cardiac rhythm in this endocrine disorder. The inclusion of octreotide in the list of drugs that may increase QTc should be reconsidered as regards its indication in acromegaly.

Atrial-specific drug AVE0118 is free of torsades de pointes in anesthetized dogs with chronic complete atrioventricular block

The novel compound AVE0118 has been shown to prevent and terminate persistent atrial fibrillation. AVE0118 blocks I(Kur), I(KAch), and I(to), leading to prolongation of atrial repolarization with no change in ventricular repolarization. This finding suggests that AVE0118 may be devoid of proarrhythmic side effects. Experimentally, AVE0118 has been antiarrhythmic against some specific ventricular arrhythmias. The purpose of this study was to investigate the proarrhythmic and antiarrhythmic effects of AVE0118 in anesthetized dogs with chronic complete AV block, known for a high proclivity for torsades de pointes (TdP). AVE0118 was administered intravenously as a fast infusion (0.5 mg/kg/5 min) and a slow infusion (3 or 10 mg/kg/60 min). Dofetilide was given to induce TdP. ECG and monophasic action potentials were recorded. Short-term beat-to-beat variability (STV) of the left ventricular monophasic action potential duration (MAPD) was calculated. We examined whether AVE0118 (1) caused ventricular proarrhythmia (both infusions), (2) prevented dofetilide-induced TdP (slow infusion + dofetilide after 30 minutes), and (3) abolished TdP (fast infusion). At 0.55 +/- 0.10 microg/mL (fast infusion at 10 minutes), AVE0118 did not increase ventricular repolarization or induce TdP; however, right atrial MAPD(50) and MAPD(90) were significantly increased by 26% +/- 9% and 10% +/- 5%, respectively (P <.05 vs baseline). At 1.9 +/- 0.5 microg/mL and 6.1 +/- 1.2 microg/mL (30 minutes of 3 or 10 mg/kg/h), AVE0118 did not induce TdP (0/6 and 0/4) nor prevent dofetilide-induced TdP (6/6 and 2/2). Dofetilide significantly increased all repolarization parameters, including STV from 2.1 +/- 0.4 ms to 4.6 +/- 1.8 ms (P <.05 vs baseline), which were not changed by AVE0118 (to 2.1 +/- 0.3 ms after 30 minutes). Rapid infusion of AVE0118 did not suppress dofetilide-induced TdP. In the anesthetized chronic complete AV block dog, the atrial-specific drug AVE0118 is free of TdP and has no antiarrhythmic properties against dofetilide-induced torsades de pointes.

Assessment of Cardiac Autonomic Regulation and Ventricular Repolarization after Off-Pump Coronary Artery Bypass Grafting

Altered autonomic regulation precipitates cardiac arrhythmias and increases the risk of sudden cardiac death. This risk is further increased by changes in ventricular repolarization. Autonomic regulation is deranged in patients after myocardial on-pump revascularization. We aimed to clarify how off-pump coronary artery bypass grafting (CABG) affects postoperative cardiac autonomic regulation and ventricular repolarization within 4 weeks after CABG. Forty-two patients (mean age, 61.9 +/- 9.3 years; mean EURO score 2.6 +/- 1.9) were electively admitted for off-pump CABG. The electrocardiographic and respiratory waveform recordings were performed in the afternoon in the supine position for 10 minutes. Autonomic modulation was assessed using heart rate variability analysis. Power spectra were computed from 5-minute stable RR intervals using Fourier Transform analysis. Total power of spectra was defined in the range of 0.01 to 0.40 Hz, high-frequency power within 0.15 to 0.40 Hz, and low-frequency power within 0.04 to 0.15 Hz. Normalized power was defined as a ratio of power in each band/total power. The high- and low-frequency power as well as their normalized values indicated cardiac vagal and sympathetic modulation, respectively. Ventricular repolarization was assessed using QT interval, QT interval variability, and QT-RR interdependence analysis. QT intervals were determined from the beginning of the 5-minute segments. QT interval variability was evaluated by a T-wave template-matching algorithm. Pearson correlation between length of RR and QT interval was applied to study QT-RR characteristics. The results were tested for significance using the Fisher exact test, nonpaired t test, and analysis of variance; a P <.05 was considered significant. The frequency of arrhythmic events and heart rate increased from the fourth to the seventh postoperative day and returned to preoperative levels 4 weeks after CABG. Heart rate variability measures indicating autonomic modulation remained depressed even 4 weeks after the procedure. QT variability index increased from -1.2 +/- 0.5 to -0.8 +/- 0.4 on the fourth day after the operation (P <.05) and returned to -1.0 +/- 0.5 4 weeks after CABG (P = not significant). QT-RR correlation decreased from 0.41 to 0.23 (P <.05) and remained significantly impaired as long as 4 weeks after CABG. Observed faster heart rates until 1 week after off-pump CABG imply excessive adrenergic activation, which is comparable to on-pump CABG procedure rates. The results indicate profound autonomic derangement and loss of rate-dependent regulation after off-pump CABG even 4 weeks after operation. Restituted repolarization as assessed by QT variability index 4 weeks postoperatively corresponded with decreased frequency of rhythm disturbances 4 weeks after CABG. The loss of coupling between QT and RR intervals shows increased electrical instability postoperatively, which may serve as an additional promoter for postoperative arrhythmias, especially at higher heart rates.

AB38-6: Global changes of restitution dynamics during right ventricular apical and septal pacing

The ability to determine dynamic changes in ventricular repolarization may provide insight into possible arrhythmogenic mechanisms as a consequence of chronic pacing. The purpose of the study was to investigate the effect of pacing site on the global characteristics of electrical restitution using high-density, non-contact mapping (NCM).

Calcium gluconate and sodium succinate for therapy of sodium fluoroacetate experimental intoxication in cats: clinical and electrocardiographic evaluation

Sodium fluoroacetate (SFAC) or Compound 1080 is a potent rodenticide, largely used after 1946 for rodent and home pest control. The toxic effects of SFAC are caused by fluorocitrate action, a toxic metabolite, which has a competitive action with aconitase enzyme, leading to citrate accumulation and resulting in interference in energy production by Krebs cycle blockade. In the present study, domestic cats were intoxicated with oral doses of fluoroacetate (0.45 mg/kg). The intoxicated animals presented emesis, diarrhea with abdominal pain posture and an abdominal palpation, tachypnea, bilateral midriasis, hypothermia, hyperexcitability and convulsions. Blood gas analysis indicated decreased pH and bicarbonate levels. Serum ionized calcium was also decreased. ECG showed non-specific changes in ventricular repolarization and ventricular arrhythmias. The survival rate was 75% in the treated group with calcium gluconate and sodium succinate and 37.5% in the nontreated group.

Contactless magnetocardiographic mapping in anesthetized Wistar rats: evidence of age-related changes of cardiac electrical activity

Magnetocardiography (MCG) is the recording of the magnetic field (MF) generated by cardiac electrophysiological activity. Because it is a contactless method, MCG is ideal for noninvasive cardiac mapping of small experimental animals. The aim of this study was to assess age-related changes of cardiac intervals and ventricular repolarization (VR) maps in intact rats by means of MCG mapping. Twenty-four adult Wistar rats (12 male and 12 female) were studied, under anesthesia, with the same unshielded 36-channel MCG instrumentation used for clinical recordings. Two sets of measurements were obtained from each animal: 1) at 5 mo of age (297.5 +/- 21 g body wt) and 2) at 14 mo of age (516.8 +/- 180 g body wt). RR and PR intervals, QRS segment, and QTpeak, QTend, JTpeak, JTend, and Tpeak-end were measured from MCG waveforms. MCG imaging was automatically obtained as MF maps and as inverse localization of cardiac sources with equivalent current dipole and effective magnetic dipole models. After 300 s of continuous recording were averaged, the signal-to-noise ratio was adequate for study of atrial and ventricular MF maps and for three-dimensional localization of the underlying cardiac sources. Clear-cut age-related differences in VR duration were demonstrated by significantly longer QTend, JTend, and Tpeak-end in older Wistar rats. Reproducible multisite noninvasive cardiac mapping of anesthetized rats is simpler with MCG methodology than with ECG recording. In addition, MCG mapping provides new information based on quantitative analysis of MF and equivalent sources. In this study, statistically significant age-dependent variations in VR intervals were found.

Global Dynamic Coupling of Activation and Repolarization in the Human Ventricle

The ability to determine spatial and dynamic changes in ventricular repolarization may help to understand arrhythmogenic mechanisms in humans. We hypothesized that noncontact mapping could be used to investigate global activation-repolarization coupling in the human ventricle during steady state and premature extrastimulation. Activation-recovery intervals (ARIs) determined from reconstructed unipolar electrograms by the Ensite system were analyzed during sinus rhythm, constant pacing, spontaneous ventricular ectopic beats, and premature stimulation at intermediate and short coupling intervals in the left or right ventricle of 13 patients (6 female; mean age, 48 years) without structural myocardial disease. ARIs were measured from 32 sites in each ventricle with the use of a method validated with monophasic action potential recordings and unipolar contact electrograms. Global T-wave distribution was displayed on a 3-dimensional geometry of the ventricle, with polarities opposite to the direction of activation during steady state and premature stimulation. There was a significant inverse correlation between activation times and ARIs during sinus rhythm, ventricular ectopy, and premature stimulation (r=0.72, slope=-0.76, P<0.001). Premature stimuli at short coupling intervals flattened the regression slope compared with sinus rhythm (-0.61 versus -0.81; P=0.05), but the global pattern of repolarization was preserved. In comparison to our method, the Wyatt method of ARI measurement failed to demonstrate significant coupling between activation and repolarization (r=0.34, slope=0.19). Global, dynamic repolarization mapping of the human ventricle is feasible. An inverse coupling of activation and repolarization during steady state and premature stimulation may preserve electric stability in the normal ventricle.

Estudo cardiológico longitudinal em crianças expostas ao vírus da imunodeficiência humana tipo 1 por via perinatal

To determine the frequency of cardiac abnormalities and its natural history in children perinatally exposed to HIV-1. Eighty-four children exposed to HIV-1 were evaluated by serial clinical, electrocardiographic (ECG), and Doppler-echocardiographic (ECHO) examinations. Group I--(seroreversion)--43 children (51.2%). Absence of clinical abnormalities. ECG: incomplete right bundle branch block (RBBB) 5 cases. ECHO: atrial septal defect (ASD) and ventricular septal defect (VSD)--1 case each. Group II--41 HIV-infected children (48.8%), of whom 51.2% were found to have cardiac abnormalities. Asymptomatic or mildly symptomatic children without immunosuppression: no clinical and echocardiographic abnormalities; ECG: incomplete right bundle branch block (RBBB)--(2 cases). Children with moderate and severe symptoms and immunological impairment: the following abnormalities were found: 1) clinical (31.7%)-isolated tachycardia (1 case), congestive heart failure (12 cases). 2) electrocardiographic (43.9%)- sinus tachycardia associated with other abnormalities (10 cases), incomplete right bundle branch block (5 cases), left anterior hemiblock (1 case), right anterior hemiblock (1 case), changes in ventricular repolarization (11 cases), right ventricular overload (2 cases), left ventricular overload (1 case), right QRS axis deviation (1 case), and arrhythmias (3 cases). 3) echocardiographic (26.8%)- dilated cardiomyopathy (5 cases), pericardial effusion with tamponade (2 cases), pulmonary hypertension (2 cases), and mitral valve prolapse (1 case). Cardiac involvement was a characteristic of the HIV-infected group. Higher prevalence of abnormalities was found among children belonging to the most advanced clinical and immunological category. The most commonly observed clinical, electrocardiographic and echocardiographic findings were congestive heart failure (CHF), changes in ventricular repolarization, and dilated cardiomyopathy, respectively. The latter was reversible in one case. Electrocardiogram changes were significantly more frequent than clinical and echocardiographic changes.

Prolonged Repolarization After Ventricular Assist Device Support Is Associated With Arrhythmias in Humans With Congestive Heart Failure

Background Recent observations indicate that the QTc interval often increases in the early postoperative period (<1 week) after mechanical unloading of severely failing hearts with a left ventricular assist device (LVAD). The present study examined whether early changes in ventricular repolarization after LVAD placement are associated with ventricular arrhythmias. Methods and Results An electrocardiogram was obtained within 4 days before LVAD placement, <12 hours after LVAD placement, and weekly thereafter. Patient records were reviewed for documented ventricular tachycardia (VT) or ventricular fibrillation (VF) for 1 week preoperatively and the first 2 weeks postoperatively. Differences in QTc interval between patients with and without VT were evaluated. Ten of 17 patients enrolled (59%) had VT or VF after LVAD placement. Of these, 4 required therapeutic intervention because of clinical instability or symptoms. The change in the QTc (ΔQTc) between the preoperative and immediate postoperative period was significantly different among patients with VT/VF compared with patients without VT/VF (+23 ms vs. −68 ms, P < .001). Conclusion The early period after initiation of LVAD support of the failing human heart is associated with a relatively high incidence of significant ventricular arrhythmias after LVAD placement. Beyond the impact of myocardial inflammation and wound healing occurring after all LVAD implants, early postoperative increases in the QTc interval after cardiac unloading appear to predispose to ventricular arrhythmias.

Coronary Artery Disease Alters Ventricular Repolarization Dynamics in Type 2 Diabetes

Ventricular repolarization dynamics (VRD) is an important predictor of outcome in diabetes. We examined the potential impact of coronary artery disease (CAD) on VRD in type 2 diabetic patients. We recorded 5-minute high-resolution resting electrocardiograms in 38 diabetic patients undergoing elective coronary angiography, and in 38 age- and gender-matched apparently healthy subjects (controls). Using leads-I and -II, time-domain indices of VRD were calculated. Coronary angiography was regarded as positive if >/= 50% stenosis was found. Angiography was positive in 21 diabetic patients (55%). Patients with CAD had a significantly higher degree of VRD than controls (SDNN(QT): 15.81 +/- 7.22 ms versus 8.94 +/- 6.04 ms; P < 0.001, rMSSD(QT): 21.02 +/- 7.07 ms versus 11.18 +/- 7.45 ms; P < 0.001). Ventricular repolarization dynamics in diabetic patients with negative angiograms did not differ from VRD in controls (SDNN(QT): 8.94 +/- 6.04 ms versus 7.44 +/- 5.72 ms; P = 0.67, rMSSD(QT): 11.18 +/- 7.45 ms versus 10.22 +/- 5.35 ms; P = 0.82). CAD increases VRD in patients with type 2 diabetes. Therefore, changes in ventricular repolarization in diabetic patients may be due to silent CAD rather than due to diabetes per se.