Beat-to-beat QT interval variability associated with acute myocardial ischemia.

Beat-to-beat QT interval variability (QTV) quantifies lability in ventricular repolarization. We hypothesized that myocardial ischemia destabilizes ventricular repolarization and increases QTV. We analyzed 2-hour 2-lead digitized electrocardiogram records of 68 patients in the European ST-T Database. All patients had ischemic episodes during the 2-hour record, annotated by the developers of the database. We determined the normalized QTV (QTVnorm), QT variability index (QTVI), and normalized heart rate variability (HRVnorm) for each 5-minute epoch by automated analysis. QTVnorm was greater during ischemic episodes than during nonischemic episodes (1.41 +/- 0.77 vs. 0.88 +/- 0.23, P <.0001). There was no significant difference in HRVnorm between ischemic and nonischemic episodes (1.22 +/- 0.63 vs. 0.94 +/- 0.18, not significant). The QTVI was higher during ischemic episodes than during nonischemic episodes (0.14 +/- 0.31 vs. -0.051 +/- 0.12, P <.0001). Acute ischemia is associated with labile ventricular repolarization, which manifests as enhanced beat-to-beat QT interval variability. The association between ischemic repolarization liability and arrhythmic risk deserves further study.     

Use of magnesium sulfate in hypertrophic cardiomyopathy with stenosis of the outflow route

10 patients with hypertrophic cardiomyopathy with left ventricular outflow obstruction were intravenously given 100 mg/kg b.w. of magnesium sulphate. Significant decrease of repolarization disorders was observed in ecg recordings. Polycardiographically estimated prolonged A2-O interval significantly shortened from 188 +/- 49 to 168 +/- 45 ms. Echocardiographic examinations revealed increase of the left ventricular end-diastolic dimension from 43 +/- 6 to 45 +/- 6 mm (p less than 0.05), acceleration of the diastolic, posterior wall motion from 5.7 +/- 3 cm/s to 7.2 +/- 2 cm/s (p less than 0.01) and shortening of prolonged left ventricular isovolumetric relaxation interval from 108 +/- 15 to 94 +/- 14 ms (p less than 0.05). Intrasystolic anterior, mitral leaflet motion towards the intraventricular septum also significantly decreased. There were no changes of heart rate, blood pressure and left ventricular systolic parameters after MgSO4 administration. Obtained data indicate the dynamic nature of left ventricular diastolic function impairment and its positive modification by magnesium sulphate administration.     

Repolarization dynamics in patients with long QT syndrome

INTRODUCTION: Dynamics of ventricular repolarization may contribute to cardiac arrhythmias in subjects with the long QT syndrome (LQTS). The aim of the present study was to assess the dynamics of repolarization duration and the dynamics of repolarization complexity in LQTS patients and their unaffected family members. METHODS AND RESULTS: Twelve-lead 24-hour ambulatory ECG recordings were obtained from LQTS patients (n = 38) and unaffected family members (n = 20). The 24-hour dynamics of the QT interval, T wave complexity (TWC) index measured by principal component analysis, and the RR interval were analyzed using standard deviation (SD) and square root of the mean squared differences of successive values of the parameters (RMSSD). QT variability, mean TWC, and TWC variability were increased in the LQTS patients compared with unaffected family members (QT-SD: 38 +/- 20 msec vs 19 +/- 7 msec, P = 0.0001; QT-RMSSD: 36 +/- 20 msec vs 14 +/- 8 msec, P = 0.0001; TWC: 27.7% +/- 11.1% vs 20.4% +/- 6.7%, P = 0.003; TWC-SD: 6.7% +/- 2.8% vs 4.6% +/- 1.8%, P = 0.003; TWC-RMSSD: 5.3% +/- 2.8% vs 3.7% +/- 1.2%, P = 0.004, respectively). At the same time, the measures of heart rate variability were similar between the affected and unaffected LQTS subjects (SD of normal-to-normal RR intervals [SDNN]: 94 +/- 25 msec vs 89 +/- 37 ms, P = 0.56; RMSSD: 49 +/- 26 msec vs 49 +/- 34 ms, P = 0.97, respectively). CONCLUSION: Despite similar heart rate variability, QT variability and the variability of TWC are significantly increased in LQTS patients compared with unaffected family members, suggesting that disturbances in temporal dynamics of repolarization and repolarization complexity in LQTS patients possibly increase vulnerability to arrhythmias.     

Relation of ventricular repolarization to cardiac cycle length in normal subjects, hypertrophic cardiomyopathy, and patients with myocardial infarction.

BACKGROUND: Prolonged QT interval and QT dispersion have been reported to reflect an increased inhomogeneity of ventricular repolarization, which is believed to be responsible for the development of arrhythmic events in patients with long QT syndrome, coronary heart disease, and myocardial infarction, congestive heart failure, and hypertrophic cardiomyopathy (HC). HYPOTHESIS: This study was undertaken to determine whether an abnormal QT/RR dynamicity may reflect autonomic imbalance and may contribute to arrhythmogenesis in patients with heart disease. METHODS: The relation between QT, QTpeak (QTp), Tpeak-Tend (TpTe) intervals and cardiac cycle length was assessed in 70 normal subjects, 37 patients with HC, and 48 survivors of myocardial infarction (MI). A set of 10 consecutive electrocardiograms was evaluated automatically in each subject using QT Guard software (Marquette Medical Systems, Milwaukee, Wisc.). RESULTS: In patients with HC, all intervals were significantly prolonged compared with normals (p < 0.001 for QT and QTp; p < 0.04 for TpTc); in survivors of MI, this was true for the maximum QT and QTp intervals (p < 0.05). A strong linear correlation between QT, QTp, and RR intervals was observed in normals and in patients with MI and HC (r = 0.65-0.59, 0.82-0.77, 0.79-0.74, respectively, p < 0.0001). TpTe interval only showed a weak correlation with heart rate in normals (r = 0.24, p < 0.05) and was rate-independent in both patient groups (p = NS). Compared with normals, the slopes of QT/RR and QTp/RR regression lines were significantly steeper in patients with MI and HC (0.0990-0.0883, 0.1597-0.1551, 0.1653-0.1486, respectively). Regression lines were neither parallel nor identical between normals and patients (T > 1.96, Z > 3.07). There was no difference in steepness for TpTeR/RR lines between groups (0.0110, 0.0076, 0.0163, respectively). TpTe/QTp ratio was similar in normals and in patients with MI and HC (0.30 +/- 0.03, 0.31 +/- 0.07, 0.30 +/- 0.04, respectively), in the absence of any correlation between QTp and TpTe intervals, suggesting disproportional prolongation of both components of QT interval. CONCLUSION: Compared with normals, a progressive increase in QT and QTp intervals at slower heart rates in patients with MI and HC may indicate an enhanced variability of the early ventricular repolarization and may be one of the mechanisms of arrhythmogenesis.     

Effects of acute alcohol infusion on duration and dispersion of QT interval in male patients with coronary artery disease and in healthy controls.

BACKGROUND AND HYPOTHESIS: Alcohol consumption may have advantageous epidemiologic effects but ethanol also increases the risk of sudden coronary death. Prolongation of QT interval has been reported in chronic alcoholics. Long QT period predisposes to serious arrhythmias, and therefore we studied whether acute alcohol intoxication prolongs repolarization in patients with stable coronary artery disease (CAD). METHODS: The effects of acute ethanol steady-state intravenous infusion (0.72 g/kg body weight within 60 min) on QT interval and QT dispersion, assessed by 12-lead electrocardiograms (ECG), were studied in 22 men with stable CAD and in 10 controls. Heart rate variability was measured by Holter recordings. RESULTS: Mean blood alcohol rose to 26.1 +/- 4.3 mmol/l(1.2 +/- 0.2/1000), and was maintained for 2 h. Heart rate was 56 +/- 7 beats/min before and 54 +/- 8 beats/min during ethanol infusion (NS). The heart rate-adjusted QT interval increased on the average 13-23 ms over the 12-lead ECG (p < 0.005). The QT dispersion remained unaltered. The was no difference in the repolarization response in the patients with CAD compared with the controls. The high- and low-frequency components of heart rate variability remained unaltered. CONCLUSIONS: In middle aged men, regardless of the presence of CAD, moderate amounts of alcohol cause prolongation of ventricular repolarization. Changes in the activity of the autonomic nervous system do not seem to explain the observed phenomenon.     

Course and prognostic implications of QT interval and QT interval variability after primary coronary angioplasty in acute myocardial infarction

OBJECTIVES: The aim of this study was to determine the influence of early reperfusion on the course of QT interval and QT interval variability in patients undergoing primary percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction (AMI) and its prognostic implications on major arrhythmic events during one-year follow-up. BACKGROUND: Although early coronary artery recanalization by primary angioplasty is an established therapy in AMI, a substantial number of patients is still threatened by malignant arrhythmias even after early successful reperfusion, which may be caused by an inhomogeneity of ventricular repolarization despite reperfusion. METHOD: Temporal fluctuations of ventricular repolarization were studied prospectively in 97 consecutive patients with a first AMI by measurements of QT interval and QT interval variability during and after successful PTCA (Thrombolysis in Myocardial Infarction flow grades 2 and 3). Continuous beat-to-beat QT interval measurement was performed from 24-h Holter monitoring, which was initiated at admission before PTCA. RESULTS: Reperfusion caused a significant continuous increase of mean RR interval (738 +/- 98 to 808.5 +/- 121 ms; p < 0.001) and a significant decrease of parameters of QT interval (QTc: 440 +/- 32 to 416.5 +/- 37ms; p < 0.001) and QT interval variability (QTcSD: 27.5 +/- 3 to 24.9 +/- 6 ms; p < 0.001) in the majority of patients. However, in patients with major arrhythmic events at the one-year follow-up (sudden cardiac death, ventricular fibrillation or sustained ventricular tachycardia, n = 15), parameters of QT interval remained unaltered after successful reperfusion (QTc: 447.3 +/- 41 to 432.9 +/- 45 ms, p = NS; QTcSD: 35.1 +/- 13.4 to 29.0 +/- 9.1 ms, p = NS). CONCLUSIONS: Reduction of QT interval and QT interval variability after timely reperfusion of the infarct-related artery may be a previously unreported beneficial mechanism of primary PTCA in AMI, indicating successful reperfusion.     

Relation of QTc duration heterogeneity to mortality following orthotopic heart transplantation

Studies of heart failure patients have demonstrated that serial QT prolongation and abnormally prolonged QT intervals are associated with greater mortality. Serial QT interval measurements in patients who undergo orthotopic heart transplantation (OHT) may quantify the degree of myocardial repolarization heterogeneity and serve as a marker of arrhythmogenic substrate. In this study, the mean survival for those with "stable" QT(c) intervals (a change of -10 to 10 ms/year) was 124 +/- 8 months versus 63 +/- 25 months in those with annual QT(c) changes of >10 ms (p = 0.009). Ventricular repolarization heterogeneity may serve as a marker of identifying high-risk patients after OHT.     

Electrophysiologic effects of intravenous magnesium in patients with normal conduction systems and no clinical evidence of significant cardiac disease

Parenteral magnesium has been used for several decades in the empiric treatment of various arrhythmias, but the data on its electrophysiologic effects in man are limited. We evaluated the electrophysiologic effects of magnesium sulfate (MgSO4) administration in eight normomagnesemic patients with normal mononuclear cell magnesium content, who had no clinically significant heart disease and had normal baseline electrophysiologic properties. After administration of intravenous MgSO4, serum magnesium rose significantly from 1.9 +/- 0.1 to 4.4 +/- 1.7 mg/dl (p less than 0.02). During a maintenance magnesium infusion, we observed significant prolongation of the ECG PR interval (145 +/- 18 to 155 +/- 26 msec, p less than 0.05), AH interval (77 +/- 27 to 83 +/- 26 msec, p less than 0.002), antegrade atrioventricular (AV) nodal effective refractory period (278 +/- 67 to 293 +/- 67 msec, p less than 0.05), and sinoatrial conduction time (60 +/- 34 to 76 +/- 32 msec, p less than 0.02). No significant effect was observed on sinus cycle length, sinus node recovery time, intra-atrial or intraventricular conduction times, QRS duration (during both sinus rhythm and ventricular pacing), QT interval, HV interval, paced cycle length resulting in AV nodal Wenckebach block, AV nodal functional refractory period, retrograde ventriculoatrial (VA) effective refractory period, or atrial and ventricular refractory periods. These findings, in conjunction with the demonstrated ability of magnesium to block slow channels for sodium movement, may provide an explanation of the mechanism by which magnesium exerts its effect in the treatment of atrial and junctional arrhythmias.     

QT interval measurement: Q to TApex or Q to TEnd?

OBJECTIVE: To study QT interval. QT interval is frequently measured, though there is variation in the literature as to whether it is more appropriate to measure from the Q wave to the apex of the T wave, which is methodologically easy, or to measure to the end of the T wave. HYPOTHESIS: For Q-TApex interval to be used as a measure of repolarization, the variability of the Q-T interval should lie in this early phase. This should be true in health and in disease, at rest and with physiological interventions such as exercise. If there is variability in the TApex - TEnd interval, this should be reflected by the variability in the Q-TApex interval. METHODS: Fifty-six subjects were recruited: 24 with heart failure, 16 with left ventricular hypertrophy and 16 controls. Q-TApex, Q-TEnd and TApex-TEnd intervals were measured at rest and on exercise. RESULTS: Q-TApex intervals at rest were not different amongst the three groups studied, being 339 +/- 7 ms for controls, 341 +/- 6 ms in left ventricular hypertrophy and 351 +/- 6 ms in heart failure. The Q-TEnd interval at rest was 421 +/- 6 ms in controls, 420 +/- 6 ms in hypertrophy and 461 +/- 9 ms in failure (P < 0.05 for failure versus hypertrophy or control). Thus the TApex-TEnd interval was prolonged in heart failure at rest. However, at peak exercise there was no difference between the TApex-TEnd intervals in the different groups. Variability in the TApex-TEnd interval induced by disease or by exercise was not related to variability in the Q-TApex interval. CONCLUSION: Q-TEnd rather than Q-TApex should be used when Q-T interval measurement is required.     

Coronary artery bypass grafting is associated with a significant worsening of QT dynamicity and heart rate variability

BACKGROUND: Imbalance in autonomic nervous system and impaired myocardial repolarization has been shown to increase the risk for arrhythmias in patients with coronary artery disease. This study evaluated the effects of coronary artery bypass grafting (CABG) on heart rate variability and QT interval dynamicity in subjects with coronary artery disease undergoing elective CABG surgery. METHODS: The study group consisted of 68 consecutive patients (mean age +/-SD: 61 +/- 9 years) with coronary artery disease who underwent elective CABG. Twenty-four-hour Holter monitoring was performed 2-5 days before cardiac surgery and was repeated 10 days after CABG. ELATEC holter software was used to calculate heart rate variability and QT dynamicity parameters. All subjects had a complete history, laboratory examination and transthoracic echocardiography. RESULTS: All patients had beta-blocking agent medication pre- and postoperatively. Standard deviation of all NN intervals for a selected time period, square root of the mean of the sum of the squares of differences between adjacent RR intervals, the proportion of differences in successive NN intervals greater than 50 ms, normalized low-frequency power, and normalized high-frequency power were significantly decreased after CABG surgery, whereas low-frequency/high-frequency ratio was significantly increased after CABG. QT/RR slopes over 24 h were significantly increased after CABG surgery for QT end and QT apex (QTapex/RR: 0.16 +/- 0.13 vs. 0.28 +/- 0.19, p < 0.001; QTend/RR: 0.18 +/- 0.13 vs. 0.36 +/- 0.23, p < 0.001). CONCLUSION: This prospective study showed for the first time that CABG was associated with a significant worsening of heart rate variability and QT dynamicity parameters in the postoperative period.     

Prolongation of the QT interval in children with liver failure.

BACKGROUND: Alcoholic liver disease has been associated with QT prolongation and sudden cardiac death. HYPOTHESIS: We evaluated children with hepatic failure to determine whether they have abnormalities of ventricular repolarization. METHODS: Between October 1990 and January 1996, 38 pediatric patients (mean age 6.5 +/- 7.2 years) underwent evaluation for liver transplantation, including a 12-lead electrocardiogram and an echocardiogram. All patients had normal serum electrolytes, calcium, and magnesium at the time of cardiac evaluation and were not on any medications known to prolong repolarization. Follow-up electrocardiograms were performed on all survivors with QT prolongation following liver transplantation. RESULTS: Among those evaluated, seven (18%) were noted to have a prolonged QT interval corrected for rate (QTc > 450 ms; range 460-560 ms). All had a structurally normal heart, except one with an atrial and ventricular septal defect. When compared with patients with a normal QT interval, there was no significant difference in serum indices of liver function or indication for liver transplantation. None of the patients developed a ventricular arrhythmia. Two patients with a prolonged QTc died prior to transplant and another died immediately after surgery. All four survivors had normalization of the QTc following liver transplantation. CONCLUSION: QTc prolongation can be seen in a significant number of children with hepatic failure. While the mechanism is not known, it appears to be reversible following liver transplantation.     

24-Hour QT variability in heart failure

Background

Previous studies have shown that increased temporal variability of repolarization, as reflected by QT interval variability measured for 10 minutes, predicted spontaneous ventricular arrhythmias in implantable cardioverter defribrillator patients, but it is unclear how these measures perform in 24-hour recordings.

Methods

Twenty-four-hour digital Holter recordings from 372 subjects with chronic heart failure enrolled in Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza Cardiaca, (GISSI) Heart Failure study were analyzed using a template-matching, semiautomatic algorithm to measure QT and heart rate time series in sequential 5-minute epochs for 24 hours. QT variability was expressed as normalized QT variance (QTVN) or as the log ratio of the QTVN over normalized heart rate variance (QT variability index, or QTVI).

Results

A pronounced diurnal variation was seen in both QTVI and QTVN. Both were lowest in the midnight to 6 am time frame and increased throughout the day, peaking at noon to 6 pm, then decreasing 6 pm to midnight. For QTVI, all 4 time points were significantly different (P < .0001). QT variability index correlated with heart rate (r = 0.38, P < .0001) and was significantly higher for those in higher New York Heart Association (NYHA) classes (r = 0.22, P = .0003). Normalized QT variance did not correlate with heart rate or NYHA but correlated negatively with serum potassium (r = −0.22, P = .0002) and manifested the greatest increase during midmorning hours.

Conclusions

Repolarization lability as reflected in QT variability has a pronounced diurnal variation and increases significantly after 6 am, the time of greatest arrhythmic risk. QT variability for 24 hours might improve risk prediction in chronic heart failure patients and should be tested in appropriate trials.     

Increased beat-to-beat QT variability in patients with congestive cardiac failure

BACKGROUND: QT interval on the surface electrocardiogram reflects the time for repolarization of myocardium. Prolongation of rate-corrected QT interval, QTc is strongly associated with sudden cardiac death. Recent studies using novel techniques on beat-to-beat QT interval variability have shown that an increase in QT interval variability is associated with increased sympathetic activity and is a predictor of sudden cardiac death. We studied QT variability in patients with congestive cardiac failure, as it is associated with an increase in cardiac sympathetic activity and also sudden death. METHODS AND RESULTS: We compared beat-to-beat heart rate and QT interval data in 2 3 patients with congestive cardiac failure and 19 age-matched normal controls. The electrocardiographic data were acquired in lead II configuration at a sampling rate of 1000 Hz. Heart rate variability was found to be significantly lower while QT variability measures were significantly higher in patients compared to controls. QTvi (a common log ratio of QT variability normalized for mean QT interval squared divided by heart rate variability normalized for mean heart rate squared) was also significantly higher in patients compared to controls. Clinical improvement in some of these patients is associated with a decrease in QTvi, due mainly to an increase in cardiac vagal function. CONCLUSIONS: Our results suggest a decrease in cardiac vagal and an increase in cardiac sympathetic functions in patients with congestive cardiac failure. QTvi may prove to be a useful surrogate end point to evaluate treatment effect in these patients.     

Effect of the infusion of magnesium sulfate during atrial pacing on ECG intervals, serum electrolytes, and blood pressure

Magnesium salts have been used for decades for the empiric treatment of arrhythmias, particularly torsades de pointes, associated with long QT syndrome. The mechanism underlying this antiarrhythmic effect is still not clear. Therefore the effect of intravenous MgSO4 on serum electrolytes, blood pressure, and ECG variables was evaluated in nine patients with sick sinus syndrome, equipped with a DDD pulse generator, programmed in the atrial asynchronous mode. A total dose of 10 gm MgSO4 was given intravenously over 6 hours at a constant rate. Blood pressure and serum electrolytes were determined before (t0), 3 hours after (t3), and at the end of the magnesium infusion (t6). ECG variables were measured at t0, t3, and t6 at different pacing frequencies (60, 80, and 100 beats/min). Serum magnesium levels rose significantly from 0.88 mmol.l-1 at t0 to 1.91 mmol.l-1 at t6 (p less than 0.05). Magnesium infusion did not affect blood pressure, pulse rate, PR or QRS or QT interval. Increasing the pacing frequency resulted in a statistically significant QT shortening at each serum magnesium level. We conclude that intravenous magnesium administration does not influence the QT interval. Increasing atrial pacing rate shortens the QT interval and this QT shortening is not affected by magnesium. Sustained serum magnesium levels between 1.5 and 2 mmol.l-1 are hemodynamically well tolerated and do not give rise to the development of higher degree atrioventricular block.     

Prognostic significance of circadian variability of RR and QT intervals and QT dynamicity in patients with chronic heart failure

BACKGROUND: In patients with chronic heart failure (CHF), circadian variability of RR and QT intervals may be altered because of neurohumoral activation and functional and structural remodeling of the heart. OBJECTIVE: The aim of this study was to evaluate the prognostic significance of circadian variability of the RR and QT intervals and QT dynamicity (QT/RR slope) in CHF patients. METHODS: We prospectively enrolled 121 patients with stable CHF in sinus rhythm (age 67 +/- 14 years, mean +/- SD; range 34 to 87 years). The RR, QT, and rate-corrected QT (QTc) intervals and the QT/RR slope measured from 24-hour Holter electrocardiogram were fitted by cosine curves. RESULTS: During the follow-up period of 34 +/- 17 months, 40 (33%) patients died of cardiac causes, 10 of which were sudden. All patients showed significant circadian rhythms in the RR, QT, and QTc intervals and the QT/RR slope by cosine-curve fitting. In addition to the expected higher heart rate, longer QT interval, and steeper QT/RR slope, we found that patient who died of cardiac causes had reduced circadian variability of QT interval (10 +/- 10 ms vs 21 +/- 13 ms) and a later maximum RR interval (4.1 +/- 0.9 AM vs 2.3 +/- 2.1 AM) compared with survivors, among many other statistically significant circadian parameter differences. These 2 parameters were independent predictors of cardiac death in multivariate Cox proportional hazards regression analysis. CONCLUSION: Circadian variability analyses of Holter-derived RR and QT intervals may provide prognostic information beyond that provided by 24-hour averages of these parameters.     

The effects of antimalarial drugs on ventricular repolarization

Cardiotoxicity has become a major concern during treatment with antimalarial drugs. Lengthening of the QTc and severe cardiac arrhythmia have been observed, particularly after treatment with halofantrine for chloroquine-resistant Plasmodium falciparum malaria. The purpose of this prospective study was to evaluate whether antimalarial agents alter dispersion of the QTc and ventricular repolarization dynamicity. Sixty patients with uncomplicated falciparum malaria were randomly allocated in four groups of 15 patients and treated with quinine, mefloquine, artemether, or halofantrine at recommended doses. Patients in treatment groups were compared with a group including 15 healthy controls with no history of malaria and/or febrile illness within the last month. QTc dispersion was measured on surface electrocardiograms. Repolarization dynamicity was analyzed from Holter recordings, which allow automatic beat-to-beat measurement of QT and RR intervals. Plasma drug concentration was determined by reversed-phase high-performance liquid chromatography. No change in QTc dispersion was observed after treatment with quinine, mefloquine, or artemether. Treatment with halofantrine was followed by a significant increase in QTc dispersion at 9 hours (P < 0.0001) and 24 hours (P < 0.01). Assessment of QT heart rate variability by QT/RR nychtohemeral regression slope demonstrated no significant difference between the artemether (mean +/- SEM = 0.170 +/- 0.048), mefloquine (0.145 +/- 0.044), and the control groups (0.172 +/- 0.039). A significant decrease in the Q-eT/RR slope was observed in the quinine group compared with the control and artemether groups (0.135 +/- 0.057; P < 0.04). With halofantrine, a significant increase in the QT/RR regression slope (0.289 +/- 0.118) was observed (P < 0.0002). QTc interval, QT dispersion, and QT regression slope were significantly correlated with halofantrine and quinine plasma concentration. Mefloquine and artemether did not alter ventricular repolarization. Quinine induced a significant decrease in QT/RR slope of the same order of magnitude as those previously observed with quinidine. Both QTc dispersion and QT/RR slope were significantly modified by halofantrine. These repolarization changes were related to a class-III antiarrhythmic drug effect and may explain the occurrence of ventricular arrhythmia and/or sudden deaths reported after halofantrine intake.     

Dynamics of parameters of variability of processes of repolarization after transluminal balloon angioplasty in patients with ischemic heart disease

AIM: To study dynamics of processes of repolarization after transluminal balloon angioplasty in patients with ischemic heart disease. MATERIAL AND METHODS: ECG, Holter ECG monitoring, analysis of parameters of variability of processes of repolarization, echocardiography and treadmill stress echocardiography were carried out in 28 ischemic heart disease patients aged 51.3+/-8.1 years prior to percutaneous coronary intervention, before discharge and in 4.1+/-2.1 months after procedure. Coronary angiography was repeated after intervention when restenosis was suspected because of positive stress echo. RESULTS: Number of vessels with significant stenoses was 1.8+/-0.1, number of implanted stents - 2.0+/-0.2. Analysis of parameters of variability of processes of repolarization at rest and after exercise revealed significant increases of maximal value of QT (MQT(c)) and of its dispersion (QT(cd)). In 3-5 days after procedure significant lowering of these parameters occurred. Development of restenosis during follow-up (in 6 patients, 21.4%) was associated with repeated increases of MQT(c) and QT(cd). CONCLUSION: MQT(c) and QT(cd) are sensitive to myocardial ischemia and can be used as supplementary markers of myocardial ischemia during exercise tests in patients with ischemic heart disease.     

Relations among heart failure severity,left ventricular loading conditions,and repolarization length in advanced heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

In patients with heart failure (HF), low peak oxygen consumption (VO(2)) and prolonged QT interval or enhanced QT variability are associated with poor prognosis. Whether HF severity or left ventricular (LV) loading conditions can influence repolarization length is unknown. Survival, QTc interval, peak VO(2), clinical, laboratory, echocardiographic, and invasive hemodynamic data were analyzed in 154 transplant candidates; mortality was examined after a mean follow-up of 4.3 +/- 1.8 years. The relation between the QTc interval and other variables was examined using multivariate analysis and multiple correlation coefficients. Patients were stratified by peak VO(2) to study its relation with peak VO(2), mortality, loading conditions, and QTc intervals. Mean ejection fraction was 10 +/- 9%; mean cardiac index was 2.06 +/- 0.7 L/min/m(2). Seventy-one patients (47%) were dead at the end of study. Mortality and nonfatal ventricular arrythmias were higher (p <0.01) in patients with lower peak VO(2) and longer QTc intervals (p <0.001). An inverse correlation was found between QTc interval length and peak VO(2) (r = -0.790, p <0.0001). No correlation was found between QTc interval and LV loading conditions or the other analyzed variables. Thus, repolarization length measured by the QTc interval is inversely correlated with HF severity measured by peak VO(2) and is independent of LV loading conditions in patients with severe HF.     

QT dispersion, T-wave projection, and heterogeneity of repolarization in patients with coronary artery disease

The clinically useful prognostic value of precordial QT dispersion in patients with heart disease is generally attributed to its measurement of regional heterogeneity of ventricular repolarization. However, when repolarization is abnormal, differences in measured QT intervals might result simply from variation in projection of the T-wave loop. To provide insight into the mechanism of QT dispersion, we used an analog device to transform conventional 12-lead electrocardiograms (ECGs) of 78 patients to derived 12-lead ECGs based on the heart vector. Because the electrical activity of the heart is represented by a single dipole, all QT dispersion in the transformed ECGs results from variation in projection of the T-wave loop and cannot be due to local heterogeneity of repolarization. Measured as the difference between the longest and shortest precordial QT intervals, QT dispersion in the derived ECGs, with no local heterogeneity of repolarization, was 53 +/- 49 ms (mean +/- SD). QT dispersion in these derived ECGs was similar in magnitude to that measured from the original standard 12-lead ECGs in these patients (49 +/- 23 ms, p = NS). Therefore, the precordial QT dispersion measured from standard ECGs of patients with coronary artery disease can be explained by interlead variation in precordial projection of the T-wave loop. Although regional heterogeneity might still contribute to precordial repolarization findings and to prognosis, this is not required to explain the QT dispersion observed in patients with coronary artery disease. Therefore, QT interval dispersion is not equivalent to heterogeneity of repolarization.     

Spironolactone has antiarrhythmic activity in ischaemic cardiac patients without cardiac failure

OBJECTIVES: To examine whether endogenous aldosterone can cause either arrhythmias (and some of their underlying mechanisms) or endothelial dysfunction in patients with coronary artery disease (CAD) but without heart failure. BACKGROUND: Aldosterone blockade has been shown to reduce the incidence of sudden death in patients with heart failure. This could be caused by a reduction in arrhythmias or in coronary events. Whether either effect also occurs in other cardiac patients without heart failure is currently unknown. METHOD: We performed a randomized, placebo-controlled, double-blind crossover study on 98 patients with CAD but without heart failure on standard therapy, comparing 12.5-50 mg/day spironolactone (3 months) with placebo. Endothelial function was assessed by bilateral forearm venous occlusion plethysmography. Ventricular extrasystoles, procollagen III N-terminal peptide (PIIINP) and QT interval length were used to represent arrhythmias and their determinants. RESULTS: Spironolactone produced a highly significant 75% reduction in ventricular extrasystoles (median 192, range 48-744) on placebo compared with spironolactone (median 48, range 19.2-288, P < 0.003). Spironolactone also decreased the QT interval from a mean of 440 +/- 28 to a mean of 425 +/- 25 (P < 0.001) and a collagen marker (PIIINP) from a mean of 3.6 +/- 0.9 to a mean of 3.0 +/- 0.8 (P < 0.001), but did not significantly change endothelial dysfunction or heart rate variability. CONCLUSION: These results suggest that despite conventional therapy, endogenous aldosterone can be an arrhythmogenic influence in patients with CAD, but without heart failure. The possible mechanisms are that aldosterone promotes myocardial fibrosis and lengthens the QTc interval as well as decreasing potassium in CAD patients without heart failure.