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Background Sudden cardiac death is prevalent in chronic hemodialysis (HD) patients while the dialysis process may have arrhythmogenic potential. We sought to examine the effect of HD on conventional electrocardiographic parameters as well as on novel indexes of repolarization, given that increased spatial dispersion of repolarization is related to ventricular arrhythmias. Methods We recorded clinical, echocardiographic, and laboratory parameters as well as electrocardiographic indexes before and after a single HD session. Specifically, we calculated the QTc interval, the QRS duration, the T peak-to-end (Tpe) interval, and the Tpe/QT ratio. Results The study population consisted of 66 chronic HD patients (mean age: 68.9 ± 11.8 years, 40 males). Heart rate, blood pressure, QRS duration, QTc interval, and QT dispersion did not change significantly after the HD session. However, the Tpe interval and the Tpe/QT ratio increased significantly (80 [65-90] ms vs 85 [77.5-100] ms; P = 0.04, and 0.21 [0.18-0.24] vs 0.25 [0.21-0.28]; P = 0.05, respectively). Correlation analysis and multiple regression analysis failed to show significant associations between the baseline parameters and the baseline values of Tpe and Tpe/QT or between the change of the laboratory parameters during HD and the corresponding change of the Tpe and the Tpe/QT values. No significant arrhythmias were observed during the HD sessions. Conclusions HD induces an increase in novel markers of spatial dispersion of ventricular repolarization. Whether the assessment of these indexes of heterogeneity of repolarization at baseline or their change during HD has a prognostic value with regard to future untoward events, remains to be elucidated. [ABSTRACT FROM AUTHOR]

Background: Cardiac resynchronization therapy (CRT) may be proarrhythmic in some patients. This may be due to the effect of left ventricular (LV) epicardial pacing on ventricular repolarization. The purpose of this study was to evaluate the effect of endocardial versus epicardial LV biventricular pacing on surface electrocardiogram (ECG) parameters that are known markers of arrhythmogenic repolarization. Methods: ECG markers of repolarization (QT dispersion, QTD; T peak to end, Tpeak-end; Tpeak-end dispersion, Tpeak-endD; QTc) were retrospectively measured before and after CRT in seven patients with transseptal LV endocardial leads (TS group), 28 matched patients with coronary sinus (CS) LV leads (CS group), and eight patients with surgical LV epicardial leads (SUR group). All ECGs were scanned and analyzed using digital callipers. Results: Compared to the CS group, the TS group CRT was associated with a significant postpacing reduction in QTD (−45.2 ± 35.6 vs −4.3 ± 43.6 ms, P = 0.03) and Tpeak-end (−24.2 ± 22.1 vs 3.4 ± 26.7 ms, P = 0.02). There was a nonsignificant post-CRT reduction in both Tpeak-endD (−11.3 ± 31.0 vs 2.4 ± 28.9 ms, P = 0.27) and QTc (−50.0 ± 46.4 vs 4.4 ± 70.2 ms, P = 0.06) in the TS versus the CS group. In contrast, there were no differences between the SUR and CS groups in terms of the effect of CRT on these repolarization parameters. Conclusions: CRT with (atrial transseptal) endocardial LV lead placement is associated with repolarization characteristics that are considered to be less arrhythmogenic than those generated by CS (epicardial) LV lead placement. Further work is needed to determine whether these changes translate to a reduction in proarrhythmia. (PACE 2011; 34:1258-1266) [ABSTRACT FROM AUTHOR]

Background: The impact of altered ventricular activation, including biventricular (BV) pacing, on T-wave alternans (TWA) and arrhythmic substrates is unclear. We studied how differing ventricular activation sequence alters TWA; the interval from peak-to-end of the T-wave (TpTe) and T-wave amplitude during right (RV), left (LV), and biventricular (BV) pacing; and right atrial (RA) pacing in patients with preexisting conduction delay. Methods and Results: We measured TWA during RA, RV, LV, and BV pacing in 33 patients receiving cardiac-resynchronization-therapy-defibrillators. TWA magnitude (Valt) was lower during BV than RV (P < 0.01), RA (P < 0.01), or LV pacing. As a result, BV-TWA was more often negative than RV-TWA (P < 0.01), LV-TWA, and RA-TWA, particularly when discordant between pacing modes (P < 0.01). Overall, 83% of TWA recordings were abnormal (25% indeterminate), and 17% negative. BV pacing reduced T-wave amplitude (P < 0.05) and TpTe (P < 0.005) compared to RV pacing and LV pacing (P < 0.05; P < 0.005 respectively). Notably, TWA magnitude varied linearly with T-wave amplitude for all pacing modes (P < 0.001). Over 410 ± 252 days' follow-up, RV-TWA predicted the combined endpoint of death and ICD therapy with 86% negative predictive value (P < 0.05). BV-TWA, RA-TWA, and other repolarization indices were not predictive. Conclusions: BV pacing attenuates TWA in tandem with reduced T-wave magnitude. In these patients with baseline QRS prolongation, RV-TWA predicted events more effectively than BV-TWA and RA-TWA. Further studies are required to understand how altered ventricular activation influences repolarization dynamics and arrhythmic tendency. [ABSTRACT FROM AUTHOR]

QT dispersion has been suggested and disputed as a risk marker for ventricular arrhythmias after myocardial infarction. Delayed ventricular activation after myocardial infarction may affect arrhythmic risk and QT intervals. This study determined if delayed activation as assessed by (1) QRS duration in the 12-lead ECG and by (2) late potentials in the signal-averaged ECG affects QT dispersion and its ability to assess arrhythmic risk after myocardial infarction. QT duration, JT duration, QT dispersion, and JT dispersion were compared to QHS duration in the 12-lead ECG and to late potentials in the signal-averaged ECG recorded in 724 patients 2-3 weeks after myocardial infarction. Prolonged QRS duration {> 110 ms) and high QRS dispersion increased QT and JT dispersion by 12%-15% (P < 0.05). Presence of late potentials, in contrast, did not change QT dispersion. Only the presence of late potentials (n = 113) was related to arrhythmic events during 6-month follow-up. QT dispersion, JT dispersion, QRS duration, and QRS dispersion were equal in patients with (n = 29) and without arrhythmic events (QT disp 80 ± 7 vs 78 ± 1 ms, JT disp 80 ± 6 vs 79 ± 2 ms, mean ± SEM, P > 0.2). In conclusion, prolonged QRS duration increases QT dispersion irrespective of arrhythmic events in survivors of myocardial infarction. Presence of late potentials, in contrast, relates to arrhythmic events but does not affect QT dispersion. Therefore, QT dispersion may not be an adequate parameter to assess arrhythmic risk in survivors of myocardial infarction. [ABSTRACT FROM AUTHOR]

QT interval dispersion may provide little information about repolarization dispersion. Some clinical measurements demonstrate an association bet ween high QT interval dispersion and high morbidity and mortality, but what is being measured is not clear. This study was designed to help resolve this dilemma. We compared the association between different clinical measures of QT interval dispersion and the £CG lead amplitudes derived from a heart vector model of repolarization with no repolarization dispersion whatsoever. We compared our clinical QT interval dispersion data obtained from 25 subjects without cardiac disease with similar data from published studies, and correlated these QT dispersion results with the distribution of lead amplitudes den vs from the projection of the heart vector onto the body surface during repolarization. Published results were available for mean relative QT intervals and mean differences from the maximum QT interval. The leads were derived from Uijen and Dower lead vector data. Using the Uijen lead vector data, the correlation between measurements of dispersion and derived lead amplitudes ranged from 0.78 to 0.99 for limb leads, and using the Dower values ranged from 0.81 to 0.94 for the precordial leads. These results show a clear association between the measured QT interval dispersion and the variation in ECG lead amplitudes derived from a simple heart vector model of repolarization with no regional information. Therefore, measured QT dispersion is related mostly to a projection effect and is not a true measure of repolarization dispersion. Our existing interpretation of QT dispersion must be reexamined, and other measurements that provide true repolarization dispersion data investigated. [ABSTRACT FROM AUTHOR]

The LQTS is a prime example of bow molecular biology, ion channel, cellular, and organ physiology, coupled with clinical observations, promise to be the future paradigm for advancement of medical knowledge. Both the congenital and acquired LQTS are due to abnormalities (intrinsic and/or acquired) of the ionic currents underlying cardiac repolarization. In this review, the continually unraveling molecular biology of congenital LQTS is discussed. The various pharmacological agents associated with the acquired LQTS are listed. Although it is difficult to predict which patients are at risk for TdP, careful assessment of the risk-benefit ratio is important before prescribing drugs known to be able to cause QT prolongation. The in vivo electrophysiological mechanism of TdP in the LQTS is described using, as a paradigm, the anthopleurin-A canine model, a surrogate for LQT3. In the LQTS, prolonged repolarization is associated with increased spatial dispersion of repolarization. Prolongation of repolarization also acts as a primary step for the generation of EADs. The focal EAD induced triggered beat(s) can infringe on the underlying substrate of inhomogeneous repolarization to initiate polymorphic reentrant VT, sometimes having the characteristic twisting QHS configuration known as TdP. The review concludes by discussion of the clinical manifestations and current management of both the congenital and acquired LQTS. The initial therapy of choice for the large majority of patients with the congenital LQTS is a beta-blocking drug. This therapy seems to be effective in LQT1 and LQT2 patients, but may not be as effective in LQT3 patients. Other therapeutic options include pacemakers, cervicothoracic sympathectomy, and the implantable cardioverter defibrillator. Recent molecular genetic studies have suggested several genotype specific therapies; however, long-term efficacy data are not available. [ABSTRACT FROM AUTHOR]

QT dispersion has been adopted as a new index for the noninvasive assessment of the inhomogeneity of repolarization and has been evaluated in several clinical studies as an index of arrhythmia propensity. In most of these studies, indices of dispersion of repolarization were rate corrected by the Bazett formula calculating QT dispersion as QTcmax-QTcmin or JT dispersion as JTcmax-JTcmin, implying that dispersion of repolarization also changes with heart rate. This study aimed to determine in the electrically paced isolated heart whether dispersion of ventricular repolarization is rate dependent. Multiple (5–7) monophasic action potentials (MAPs) were recorded simultaneously from the epicardium and endocardium of both ventricles in 18 isolated Langendorff-perfused rabbit hearts. Hearts were paced from a right ventricular site at basic cycle lengths (CL) between 1,200 and 300 ms in 100-ms decrements. Action potential duration was measured at 90% repolarization (APD90), and recovery time (RT) was defined as the sum of APD90 and activation time in each of the simultaneous MAP recordings. The dispersion of APD90 and RT, respectively, were calculated as the maximal difference among all recordings. APD90 and RT shortened continuously throughout the range of paced steady-state CLs from 1,200 to 300 ms. APD90 was 197.6 ± 6.1 ms at a CL of 1,200 ms and decreased to 148.5 ± 2.5 ms at a CL of 300 ms (P < 0.0001). RT was 228.2 ± 6.2 ms at a CL of 1,000 ms and decreased to 175.9 ± 2.9 at a CL of 300 ms (P < 0.0001). In contrast, dispersion of APD90 and RT did not change significantly. Dispersion of APD90 was 24.8 ± 2.3 ms at a CL of 1,200 ms, 26.1 ± 1.9 msec at a CL of 1,000 ms, and 21.6 ± 2.1 at a CL of 300 ms (NS). Dispersion of RT was 29.7 ± 3.4 ms at a CL of 1,200 ms, 29.0 ± 3.0 ms at a CL of 1,000 ms, and 32.7 ± 3.2 ms at a CL of 300 ms (NS). In contrast to the duration of the QT interval, dispersion of ventricular repolarization does not change significantly with pacing induced changes in CL. Assuming that the rate-dependent behavior of action potential duration is similar between the rabbit and human heart, a rate correction of parameters of dispersion of repolarization is probably unnecessary. [ABSTRACT FROM AUTHOR]

The degree of temporo-spatial variation of repolarization during single (S2) and double (S3) premature stimulation was evaluated in five closed-chest anesthetized dogs. Monophasic action potentials (MAP) were simultaneously recorded with contact electrode and MAP duration (MAPD) restitution curves constructed from right ventricular (RVJ and left ventricular (LV) endocardial sites. At a given coupling interval, S3 was associated with significantly greater dispersion of MAPD then S2 (spatial dispersion, i.e., between RV and LV). Similarly, at a given diastolic interval, S3 at RV and LV sites, was associated with significantly greater dispersion of MAPD then S2 (temporal dispersion). It is concluded that S3 is associated with greater temporo-spatial dispersion of repolarization then S2. [ABSTRACT FROM AUTHOR]

T or U wave alternans in association with long QTU and torsade de pointes (TdP) is uncommon and its mechanism(s) is unknown. We studied three patients with TU alternans, long QTU, and TdP: patient 1 was a newborn with congenital long QTU; patient 2 had marked hypokalemia and hypomagnesemia; and patient 3 was receiving procainamide. In the three patients, TU alternans was tachycardia dependent and preceded the onset of TdP. In the patient on procainamide, TU alternans and TdP occurred at long cardiac cycles. In this patient, endocardial monophasic action potential (MAP) recordings showed that TU alternans was associated with alternation of the duration of the plateau. A deflection consistent with early afterdepolarization (EAD) arose at a constant time interval from phase 0 but alternated from high and low levels of phase 3. The first ectopic heat of TdP arose on the descending limb of the EAD. TU alternans was investigated by MAP recordings in six normal dogs, following the administration of anthopleurin-A (AP-A), a drug shown to delay sodium inactivation and to induce bradycardia dependent long QTU, EADs, and TdP. In two dogs TU alternans was associated with 2:1 recordings of EAD and nearly constant plateau duration. In three dogs, TU alternans was associated with EAD that occurred in consecutive beats at constant time intervals from phase 0, but alternated from high and low phase 3 because of alternation of the duration of the plateau. In one dog, alternation of EAD and plateau duration occurred. In 36 separate episodes of TdP that were analyzed in the six dogs, 32 were bradycardia dependent but four developed on abrupt shortening of the cardiac cycle associated with alternation of action potential duration. Our results suggest: (1) TU alternans may be due to 2:1 propagation of an EAD or to alternation of the recovery kinetics of u repolarization current; (2) The constant occurrence of EAD in relation to phase 0 in spite of alternation of plateau duration suggests an ionic mechanism synchronized to depolarization; (3) Tachycardia dependent TdP in clinical and experimental examples of long QTU seems to be characteristically associated with TU alternans. Dispersion of repolarization may underlie the increased ventricular electrical instability in these cases. [ABSTRACT FROM AUTHOR]

Rate-dependent bifurcations and aperiodic changes in action potential duration and amplitude were observed in periodically stimulated cardiac Purkinje and ventricular muscle cells isolated from dogs with quinidine-induced ventricular fibrillation and ventricular tachycardia. The slope of the action potential duration restitution curve was higher in the quinidine intoxicated fibers than in normal untreated fibers. Aperiodicity and bifurcations in action potential duration (APD) could not be observed in normal untreated cardiac fibers. The data suggest that induction of reentrant ventricular fibrillation and ventricular tachycardia could be brought about not by fixed but rather by changing alterations in cellular electrical activity. Theory based on nonlinear dynamics seems to provide a quantitative basis for such on analysis. This could have important implications in the issue of sudden cardiac death, a major problem in cardiology. [ABSTRACT FROM AUTHOR]

Experimental studies have shown that transmural dispersion of repolarization (DoR), defined as the difference in action potential duration between mid-myocardial M-cells, epicardial, and endocardial cells is reflected in the duration of the terminal portion of the T wave (TpTe) on the surface ECG. Since DoR is an important factor associated with the propensity for reentrant arrhythmias, this study examined if TpTe may serve as a marker of risk of ventricular arrhythmias. Data from 18 patients with coronary artery disease and inducible sustained ventricular tachycardia (VT group) were compared with those of 16 survivors of myocardial infarction with out inducible VT (control group). TpTe was automatically measured in each beat of 24-hour ECG recordings, and programmed ventricular stimulation was performed in the antiarrhythmic drug-free state. TpTe was expressed as the absolute interval in milliseconds, and relative to the duration of QTe (TpTe/QTe X 100%). TpTe duration was 74 ± 14 ms in the VT group versus 63 ± 16 ms in the control group (P < 0.004). The TpTe interval expressed as a percent of the QT interval was 21 ± 4% in the VT group versus 17 ± 3% in the control group (P = 0.02). In patients with coronary artery disease, TpTe was longer in patients with, versus without, inducible VT. The results of this study support the hypothesis that TpTe reflects transmural dispersion of repolarization. [ABSTRACT FROM AUTHOR]