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Background: Reperfusion of the infarct related artery (IRA) prior to PCI is prognostically important in patients with acute ST segment elevation myocardial infarction (STEMI). Reperfusion is either achieved spontaneously, facilitated by GP IIb/ IIIa inhibitors, or mechanically by crossing the guide wire beyond the lesion. In order to test the hypothesis that a visible coronary anatomy is independently associated with procedural and clinical outcomes, we evaluated the frequency and prognostic impact of guide wire facilitated reperfusion of the IRA before primary PCI., Methods and Results: We enrolled 311 consecutive patients with successful primary PCI for STEMI (TIMI grade > or =2 flow) within 12 h after onset of symptoms. Among these, 90 patients (28.9%) had a spontaneously reperfused IRA on initial angiogram, 56 patients (18.0%) achieved reperfusion after crossing of the guide wire, and 165 patients (53.1%) successful reperfusion only after PCI. Variables associated with successful guide wire facilitated reperfusion were younger age, no history of arterial hypertension, active smoking status, negative cardiac troponin T on admission, and an infarct in the territory of the right coronary artery. Patients with spontaneous reperfusion or reperfusion after crossing of the guide wire required less fluoroscopic time and less contrast material during angiography and had higher procedural success rates (TIMI grade 3 flow 91.1 vs 79.4%, p=0.048) than patients without initial reperfusion. In addition, patients with reperfusion after crossing the lesion with the guide wire had lower mortality rates at 30 days (3.6 vs 9.1%) and after a median of 16 months (3.6 vs 13.9%, p=0.03) than those with reperfusion after PCI., Conclusions: Reperfusion of an occluded IRA by crossing the guide wire is associated with higher procedural success rates and better outcomes. Better roadmapping and device selection represent potential reasons but the exact mechanism for these benefits is still illusive.

Background: Data from animal models suggest that inhibition of angiotensin converting enzymes result in an increased ventricular electrical stability after reperfusion in acute myocardial infarction (MI). As electrical stability is largely dependent on ventricular repolarization, we sought to determine the impact of low-dose intracoronary (i.c.) application of enalaprilat (EN) as an adjunct to direct primary coronary intervention (PCI) on QT dynamics in the acute phase of MI., Methods: Twenty-two consecutive patients with a first acute MI who underwent successful direct PCI (TIMI 3 flow) were randomized to i.c. EN (50 microg) or placebo/saline (PL), given immediately after reopening of the infarct vessel. On hospital admission, a 24-hour-Holter-electrocardiogram (ECG) was initiated. Slopes of the linear QT/RR regression were determined for the time intervals before reperfusion and after reperfusion., Results: A total of 7 patients in the EN group and 8 patients in the PL group had valid ECG recordings for beat-to-beat QT analysis. Mean RR interval and mean QT interval were not significantly different between the EN and the PL groups both before and after PCI. There were also no significant differences regarding QT/RR slopes between EN and PL groups before PCI. After PCI, QT/RR slopes significantly decreased in the EN group (0.169 +/- 0.04 to 0.121 +/- 0.03; P < 0.01), whereas there were no significant alterations in the PL group (0.175 +/- 0.04 to 0.171 +/- 0.03; P = ns)., Conclusions: Intracoronary EN therapy as an adjunct to direct PCI significantly decreases QT/RR slopes, suggesting a normalization of the coupling between heart rate and repolarization by improving electrical restitution. Thus, our findings offer new insights into possible beneficial effects of ACE inhibition on cardiac electrical stability in acute MI.

Dynamic parameters of ventricular repolarization as Holter derived parameters expressed as QT-interval adaptation to heart rate changes (QT/RR-slope) and QT-interval-variability are being more and more frequently used to identify patients with increased risk for ventricular arrhythmias. Steep QT-RR-slopes, reflecting inadequate adaptation of ventricular repolarization to heart rate changes, as well as increased QT-interval-variability, reflecting temporal inhomogeneity of ventricular repolarization duration, are frequently observed in patients at risk for sudden cardiac death. Additionally, there is strong evidence for significant alterations in the dynamics of action potential duration restitution in patients with structural heart disease. This review gives an up-to-date overview about the current research in methods of assessment and clinical relevance of dynamic parameters of ventricular repolarization.

Background: In the era of early reperfusion therapy, life-threatening ventricular arrhythmias (VA) remain common after recanalization of an occluded coronary artery. Experimental studies reported that angiotensin-converting (ACE) inhibitors suppress reperfusion-induced VA. However, whether ACE inhibitors lower the incidence of reperfusion clinical VA is unknown. We examined the effects of low doses of intracoronary (i.c.) enalaprilat (EN) as an adjunct to direct percutaneous coronary interventions (PCI) on reperfusion VA in the acute phase of myocardial infarction (MI)., Methods: We randomly assigned 22 patients with a first acute MI, who underwent successful direct PCI, to EN, 50 mug, i.c., or placebo (PL), administered immediately after reperfusion. VA were manually edited and counted from 24-hour Holter recordings begun upon hospital admission., Results: There were no significant between-groups differences in clinical characteristics. Mean RR interval before and after PCI, and the incidence of VA before PCI were similar in both groups. After PCI the incidence of reperfusion-induced VA was significantly lower in the EN-treated group (VPB/h: PL 29.9 +/- 12 vs EN 43.2 +/- 42, P < 0.05; couplets/h: EN 0.9 +/- 0.7 vs PL 4.1 +/- 5.0, P < 0.01; triplets/h: EN 0.3 +/- 0.2 vs PL 1.2 +/- 1.5, P < 0.05; ventricular tachycardia/h: EN 0.3 +/- 0.1 vs PL 0.8 +/- 0.5, P < 0.01)., Conclusions: Compared with PL, i.c. EN significantly lowered the incidence of reperfusion-associated VA. This previously unrecognized antiarrhythmic effect might be an important therapeutic benefit conferred by ACE inhibitors, beyond limitation of infarct size.

Introduction: Patients with diabetes mellitus (DM) have an unfavorable prognosis after myocardial infarction (MI), partially due to a higher risk of sudden cardiac death (SCD). QT dynamicity is an independent predictor of SCD in post-MI patients. However, the effects of diabetes on QT dynamicity in patients with MI have not been described., Methods: We studied 468 survivors of MI (67 with DM) from the population-based MONICA registry (KORA Family Heart Study), Augsburg, Germany, by standardized questionnaire, anthropometry, electrocardiogram (ECG), 30-minute-Holter-ECG-recordings and echocardiography. In addition, 422 siblings without prior MI (22 with DM) were studied by the same protocol., Results: Among post-MI patients, the QT/RR slope was significantly steeper in diabetics than in nondiabetics (0.096 +/- 0.057 vs 0.077 +/- 0.045; P = 0.002). Likewise, among siblings without MI, the QT/RR slope was steeper in diabetics than in nondiabetics (0.104 +/- 0.053 vs 0.080 +/- 0.042; P = 0.008). The association of DM with steeper QT/RR slope remained significant in multivariate models in post-MI patients (beta: -0.14; P = 0.004) as well as in individuals without MI (beta: -0.10; P = 0.047)., Conclusions: In a large population of survivors of MI and unaffected siblings, patients and siblings presenting with DM exhibited an abnormal QT rate-dependence, compared with individuals without DM in both groups. Thus, diabetes itself may be a major determinant of ventricular arrhythmias, independently of a previous MI. These observations might in part explain the higher incidence of sudden cardiac death and ventricular arrhythmias in patients with DM.

Background: Baroreflex sensitivity (BRS), exercise pressor reflex (EPR), and aging influence the autonomic nervous response associated with orthostatic maneuvers. Standing significantly increases heart rate (HR), with an initial increase (1.deltaHR) due to EPR and a secondary, more gradual increase (2.deltaHR) due to BRS. HR then decreases (3.deltaHR), which is also attributable to BRS. Thus far, however, few data are available regarding the interdependence of these variables., Methods and Results: Ninety-five healthy volunteers (mean age 37 +/- 11 years, range 10-70 years; 50 women) underwent continuous noninvasive measurements of beat-to-beat blood pressure, HR, and spontaneous BRS in the supine (10 minutes) and upright (10 minutes) positions. After tilt, 1.deltaHR, 2.deltaHR, and 3.deltaHR were calculated from the HR recording. From the 1(st) to the 6(th) decade BRS, 2.deltaHR and 3.deltaHR decreased with normal aging ([BRS 11.88 +/- 7.97 ms/mmHg to 1.81 ms/mmHg, P = 0.006], 2.deltaHR [16.75 +/- 3.40 beats to 5.33 +/- 2.52 beats, P = 0.002], 3.deltaHR [52.25 +/- 5.91 beats to 11.33 +/- 4.04 beats, P < 0.001]). However, no such association was noted between 1.deltaHR and age (21.25 +/- 9.35 beats to 12.00 +/- 7.21 beats, ns). BRS while standing was correlated with 1.deltaHR (r = 0.432, P < 0.001)., Conclusions: EPR, in contrast to BRS, was not significantly influenced by normal aging. Furthermore, not only was BRS influenced by EPR, as is generally acknowledged, but EPR and BRS were interrelated. These observations offer new insights into the complex interactions of orthostasis-induced physiological autonomic reflexes associated with normal aging.

Background: Ventricular arrhythmias after myocardial infarction (MI) are often nocturnal. However, the arrhythmogenic effects of sleep after MI are unknown. We examined the effects of sleep stages on QT dynamicity and tested the hypothesis of a differential effect of sleep stage on the QT/RR relationship after recent MI, versus in healthy controls (HC)., Methods: Polysomnography and electrocardiograms were simultaneously recorded in 21 men in the subacute phase of a first uncomplicated MI, and in 10 age-matched, male HC. QT dynamicity (QT/RR slope) and parameters of QT interval were measured during wakefulness, stages 1-4 of nonrapid eye movement (non-REM) sleep, and REM sleep., Results: Mean QT and RR intervals increased through all sleep stages in both MI survivors and HC. The Bazett-corrected QT interval remained stable from wakefulness throughout all sleep stages. QT/RR slopes remained stable from wakefulness to stage 3 in both groups. However, unlike in MI survivors, the QT/RR slopes decreased and remained significantly lower during deep sleep and REM sleep in HC., Conclusion: An abnormal QT/RR relationship in deep sleep and REM sleep was observed after a recent MI, reflecting an insufficient shortening of ventricular repolarization with increasing heart rates, which might have important implications in the nocturnal distribution of ventricular arrhythmias after MI.

Background: Imbalance of cardiac autonomic nervous modulation might prominently contribute to early relapses of atrial fibrillation (AF) after cardioversion (CV). The biphasic (Bi) waveform is more effective than the monophasic (Mo) waveform in CV of AF. Whether these waveforms have different effects on autonomic modulation early after CV is unknown., Methods: We investigated 171 consecutive patients after successful electrical CV (mean age 65.4 years, 82% male, 80% structural heart disease). Bi waveform was used in 89, Mo waveform in 82. Heart rate variability (HRV) was analyzed from 24-hour Holter recordings, started directly after CV., Results: Mean delivered total energy was significantly lower in the Bi group (Bi 223 +/- 163 W, Mo 355 +/- 211 W, P < 0.001). Mean RR interval decreased within 5 hours after CV and increased again within the remaining hours, without significant differences between Bi and Mo groups. Time courses of time domain parameters of HRV revealed Bi profiles with the lowest levels 6 hours after CV in both groups. However, the hourly values of HRV were significantly higher in the Bi subgroup., Conclusion: Our study indicates that waveform and total delivered energy significantly influence autonomic modulation of the sinus node in the early phase after CV of AF. In contrast to Bi CV, Mo CV is characterized by a significant decrease of cardiac vagal modulation, which may have an arrhythmic effect by increasing the degree of early electrical stunning after CV of AF.

Objective: Even though diffuse T wave inversion and prolongation of the QT interval in the surface electrocardiogram (ECG) have been consistently reported in patients with transient stress-induced left ventricular apical ballooning (AB), ventricular repolarization has not yet been systematically investigated in this clinical entity., Background: AB, an emerging syndrome that mimics acute ST-segment elevation myocardial infarction (MI), is characterized by reversible left ventricular wall motion abnormalities in the absence of obstructive coronary heart disease and significant QT interval prolongation., Methods: We prospectively enrolled 22 consecutive patients (21 women, median age 65 years) with transient left ventricular AB. A total of 22 age-, gender-, body-mass-index-, and left-ventricular-function-matched patients with acute anterior ST-segment elevation MI undergoing successful direct percutaneous coronary intervention for a proximal occlusion of the LAD, as well as 22 healthy volunteers served as control groups. Beat-to-beat QT interval and QT interval dynamicity were determined from 24-hour Holter ECGs, recorded on the third day after hospital admission., Results: There were no significant differences in baseline clinical characteristics, except higher peak enzyme release in MI patients. Compared with MI patients, AB patients exhibited significantly prolonged mean QT intervals and rate-corrected QT intervals (QT: 418 +/- 37 vs 384 +/- 33 msec, P < 0.01; QTcBazett: 446 +/- 40 vs 424 +/- 35 msec, P < 0.05; QTcFridericia: 437 +/- 35 vs 412 +/- 31 msec, P < 0.05). Mean RR intervals tended to be higher in AB patients, without reaching statistical significance (877 +/- 96 vs 831 +/- 102 msec, P = NS). The linear regression slope of QT intervals plotted against RR intervals was significantly flatter in AB patients at both day- and nighttime (QT/RR slopeday: 0.18 +/- 0.04 vs 0.22 +/- 0.06, P < 0.01; QT/RR slopenight: 0.12 +/- 0.03 vs 0.17 +/- 0.05, P < 0.01)., Conclusion: The present study is the first to demonstrate significant differences of QT interval modulation in patients with transient left ventricular AB and acute ST-segment elevation MI. Even though transient AB is associated with a significant QT interval prolongation, rate adaptation of ventricular repolarization (i.e., QT dynamicity) is not significantly altered, suggesting a differential effect of autonomic nervous activity on the ventricular myocardium in transient AB and in acute MI.

Right ventricular lead perforation, when acute, is a rare but potentially life-threatening complication of implantable cardioverter defibrillator (ICD) therapy. We report about a patient with early lead perforation presenting with repetitive ICD discharges due to oversensing of diaphragmatic electromyopotentials and describe the management of this complication.

Introduction: Nonpenetrating chest wall impact (commotio cordis) may lead to sudden cardiac death due to the acute initiation of ventricular fibrillation (VF). VF may result from sudden stretch during a vulnerable window, which is determined by repolarization inhomogeneity., Methods: We examined action potential morphologies and VF inducibility in response to sudden myocardial stretch in the left ventricle (LV). In six Langendorff perfused rabbit hearts, the LV was instrumented with a fluid-filled balloon. Increasing volume and pressure pulses were applied at different times of the cardiac cycle. Monophasic action potentials (MAPs) were recorded simultaneously from five LV epicardial sites. Inter-site dispersion of repolarization was calculated in the time and voltage domains., Results: Sudden balloon inflation induced VF when pressure pulses of 208-289 mmHg were applied within a window of 35-88 msec after MAP upstroke, a period of intrinsic increase in repolarization dispersion. During the pressure pulse, MAPs revealed an additional increase in repolarization dispersion (time domain) by 9 +/- 6 msec (P < 0.01). The maximal difference in repolarization levels (voltage domain) between sites increased from 19 +/- 3% to 26 +/- 3% (P < 0.05). Earliest stretch-induced activation was observed near a site with early repolarization, while sites with late repolarization showed delayed activation., Conclusions: Sudden myocardial stretch can elicit VF when it occurs during a vulnerable window that is based on repolarization inhomogeneity. Stretch pulses applied during this vulnerable window can lead to nonuniform activation. Repolarization dispersion might play a crucial role in the occurrence of fatal tachyarrhythmias during commotio cordis.

Microelectrode arrays enable to map extracellular field potentials of excitable organs (eg, cardiac tissue) in an electrocardiogram-like manner: They allow to detect (a) rhythmicity, (b) the origin and route of excitation, (c) repolarization, and (d) conduction in heart tissue in short- and long-term experimental approaches. Using it as a screening tool for potential side effects of drugs, we here provide evidence for d-sotalol-induced delayed repolarization in human embryonic stem (hES) cell-derived cardiomyocytes. Thus, the combination of the microelectrode array system with cardiac clusters derived from hES cells heralds a paradigm shift toward improved pharmaceutical drug safety. However, the mixture of various cell types in hES cell cardiac clusters (eg, atrial, immature and mature ventricular cardiomyocytes) indicates the strong need for improved selectivity of cardiac differentiation protocols using hES cells.

Beta-adrenergic blockers exert significant antiarrhythmic activity during ischemia and reperfusion. To further explore the beneficial effects conferred by alpha-1-adrenoceptor blockade on ventricular repolarization dynamicity in the acute phase of myocardial infarction (AMI), we compared carvedilol with metoprolol in the setting of primary percutaneous coronary intervention (PCI). In a prospective study, 100 consecutive patients undergoing primary PCI for AMI were randomized to metoprolol 200 mg/day versus carvedilol 25 mg/day. The first oral dose of study drug was administered and a 24-hour ambulatory electrocardiogram recorded upon hospital admission. Slopes of the linear QT/RR regression were determined before and after reperfusion. A total of 38 recordings of patients treated with metoprolol and 34 recordings of patients with carvedilol were eligible for analysis of QT/RR slopes. The two study groups were similar with respect to age, gender, TIMI perfusion grades, ventricular function, duration of ischemia, and site and size of infarction. Mean RR- and QT-intervals were similar to the metoprolol and carvedilol groups, before and after PCI. Likewise, there was no significant difference in QT/RR slopes between the metoprolol and carvedilol groups before PCI. In contrast, after PCI, there was a trend toward lower QT/RR slopes in the metoprolol group (from 0.18 +/- 0.07 to 0.17 +/- 0.08), and a significant decrease in QT/RR slopes in the carvedilol group (from 0.17 +/- 0.07 to 0.14 +/- 0.09). In patients undergoing successful direct PCI for AMI, treatment with carvedilol, in contrast to metoprolol, was associated with a significant decrease in QT-RR slopes, suggesting greater cardiac electrical stability.

Beta-adrenergic blockers provide significant cardioprotection during acute ischemia and reperfusion. To further explore the effects of additional alpha-1-adrenoceptor blockade on autonomic modulation in acute myocardial infarction (AMI), carvedilol was compared with metoprolol in the setting of primary percutaneous coronary interventions (PCI). In a prospective study, 100 consecutive patients (61.1 +/- 11 years; 23 females) undergoing primary PCI for AMI were randomly assigned to metoprolol 200 mg/day vs carvedilol 25 mg/day. The first oral dose of study drug was administered upon hospital admission, and a 24-hour ambulatory electrocardiogram was recorded. A total of 40 recordings of patients assigned to metoprolol and 39 of patients assigned to carvedilol were eligible for analysis of heart rate turbulence. Turbulence onset (TO), turbulence slope (TS), and turbulence timing were measured after ventricular premature beats (VPBs). The mean value of the 10 preceding RR intervals (mean RR) before VPBs was also measured. There were no significant differences in mean age, gender distributions, TIMI perfusion grades, left ventricular ejection fraction, site and size of infarction, duration of ischemia, and mean 24-hour heart rate between the two groups. Though the mean RR were not significantly different (metoprolol 863.1 +/- 157 ms; carvedilol 839.6 +/- 151 ms), there was a trend toward lower values of TO in the carvedilol group (-0.015 +/- 0.016 vs -0.012 +/- 0.023%; P = NS) and significantly higher values for TS in the metoprolol group (6.96 +/- 5.8 vs 5.6 +/- 4.22; P < 0.05). Turbulence timing was similar in both groups (metoprolol 5.8 +/- 2.4 vs carvedilol 6.1 +/- 2.1). In patients undergoing direct PCI for AMI, treatment with carvedilol, in contrast to metoprolol, was associated with a higher early acceleration and a lower deceleration of heart rate after VPBs, indicating differing effects on baroreceptor response due to additional alpha-1-adrenoceptor blockade. These data offer new insights into effects of a broader antiadrenergic therapy on autonomic reflexes in the acute phase of AMI.

Depressed cardiac parasympathetic activity is associated with electrical instability and adverse outcomes after myocardial infarction (MI). Heart rate turbulence (HRT), reflecting reflex vagal activity, and heart rate variability (HRV), reflecting tonic autonomic variations are both reduced in the subacute phase of MI. However, the evolution of these components of cardiac autonomic control between subacute and chronic phase of MI has not been defined. We prospectively studied 100 consecutive patients with a recent first MI with ST-segment elevation, who underwent successful direct percutaneous coronary interventions. Beta-adrenergic blockers and angiotensin-converting enzyme (ACE) inhibitors were administered according to the state-of-the-art medical practice guidelines. HRT and HRV were measured from 24-hour ambulatory electrocardiographic recordings 10 days and 12 months after the index MI. There was no significant difference in mean RR interval between the subacute and chronic phase of MI (875 +/- 145 versus 859 +/- 122 ms). Indices of HRV increased significantly during the observation period (SDNN: from 88.8 +/- 26.8 to 116.0 +/- 35.7 ms, P < 0.001; SDNNi: from 37.9 +/- 15.9 to 46.0 +/- 16.3 ms, P < 0.001; SDANN: from 79.6 +/- 34.7 to 105.6 +/- 35.4 ms, P < 0.001). In contrast, there were no significant changes in indices of HRT (turbulence onset: from -0.008 +/- 0.022 to -0.012 +/- 0.025%; turbulence slope: from 7.78 +/- 5.9 to 8.06 +/- 6.8 ms/beat). In contrast to reflex autonomic activity, there was a significant recovery of tonic autonomic activity within 12 months after MI. These different patterns of recovery of reflex versus tonic cardiac autonomic control after MI need to be considered when risk stratifying post-MI patients.

Background: Complete coronary artery reperfusion in acute myocardial infarction (AMI) has been shown to significantly improve survival. Electrical stability may be the decisive mechanism for this beneficial effect. Because electrical stability is largely dependent on ventricular repolarization, we sought to determine the impact of a modern reperfusion strategy (ie, direct percutaneous coronary intervention [PCI]) on QT dynamicity in AMI and examined its association with infarct-related artery flow., Methods and Results: We prospectively investigated QT dynamicity in 128 patients undergoing direct PCI for a first AMI. Slopes and correlation coefficients of the linear QT/RR regression were determined in the time interval before reperfusion, within the initial hour after reperfusion, and within the remaining recording period from Holter ECG recordings, which were initiated on admission. Subgroup analysis based on TIMI 3 (n=100) and TIMI 2 (n=28) flow after PCI revealed no significant differences in QT/RR slope before PCI (0.145+/-0.12 versus 0.160+/-0.19,P=NS). After PCI, QT/RR slopes increased only in the TIMI 2 subgroup (P<0.05). In TIMI 2 patients, QT/RR slopes were significantly steeper in the hour after PCI and in the remaining recording period, respectively (0.155+/-0.12 versus 0.192+/-0.15,P<0.05, and 0.159+/-0.10 versus 0.210+/-0.17,P<0.01)., Conclusions: Alterations of QT dynamicity in patients with incomplete reperfusion may suggest an altered electrical restitution, potentially providing a substrate for serious ventricular arrhythmias. Thus, our findings offer new insights into mechanisms by which complete reperfusion may affect electrical stability.

A higher incidence of pacemaker related complications has been reported in DDD systems as compared to VVI devices. The implantation of single lead VDD pacemakers might reduce the complication rate of physiological pacing in patients with AV block. In a retrospective study, the data records of 1,214 consecutive patients with pacemaker implantation for AV block between 1990 and 2001 (VVI 36.5%, DDD 32.9%, VDD 30.6%) were analyzed. Complications requiring surgical interventions were compared during a follow-up period of 64 +/- 31 months. Operation and fluoroscopic times were longer in DDD pacemaker implantation compared to VDD and VVI devices:58 +/- 23 versus 39 +/- 10 and 37 +/- 13 minutes (P<0.001), 9.2 +/- 5.2 versus 4.1 +/- 2.4 and 3.5 +/- 2.3 minutes, respectively. Differences remained significant after correction for covariates. In a multivariate Cox regression model, the corrected complication hazard of a DDD pacemaker implantation was increased by 3.9 (1.4-11.3) compared to VVI and increased by 2.3 (1.1-4.5) compared to VDD pacing. Higher complication rates in DDD pacing were mainly due to a higher incidence of early reoperation for atrial lead dysfunction, whereas the long-term complication rate was not different from VDD or VVI pacing. Early and long-term complication rates did not differ between VDD and VVI pacemaker systems. In conclusion, operation time and complication rates of physiological pacing are reduced by VDD pacemaker implantation achieving values comparable to VVI pacing. Thus, single lead VDD pacing can be recommended for patients with AV block.

Background: The presence of admission cardiac troponin-T (cTnT) is a means of identifying a high-risk subgroup in patients with acute ST-segment elevation myocardial infarction (AMI). Because a substantial number of these patients has malignant ventricular arrhythmias, we hypothesized that there is a relation between cTnT status on admission and inhomogeneity of ventricular repolarization, and we tested this assumption in the setting of primary percutaneous coronary intervention (PCI)., Methods: Temporal fluctuations of ventricular repolarization were studied during and after primary PCI (Thrombolysis In Myocardial Infarction [TIMI] 2 and 3) in 94 consecutive patients with a first AMI by continuous beat-to-beat QT-interval measurement, performed with Holter monitoring initiated on admission. Troponin-T levels on admission were >0.1 ng/mL in 53 patients (cTnT+) and <0.1 ng/mL in 41 patients (cTnT-). There were no significant differences in baseline clinical characteristics between the groups., Results: The incidence of severe reperfusion arrhythmias (RAs) was significantly higher in patients in the cTnT+ group within the first 2 hours after recanalization. The course of the QT interval revealed a significant decline (P <.001) after recanalization of the infarcted vessel within 10 hours in both groups; however, hourly values were significantly lower and normalization of the QT parameters was more rapid in patients in the cTnT- group than patients in the cTnT+ in this period (QTc, 438.5 +/- 28.3 ms vs 449.3 +/- 35.3 ms [hour 1, P <.01]; 413.6 +/- 35.8 ms vs 420.1 +/- 39.2 ms [hour 10, P <.05]). QT-interval variability also significantly declined within 4 hours after PCI (P <.001), and likewise, patients in the cTnT- group exhibited lower values in this period (QTSD, 29.7 +/- 6.8 ms vs 33.5 +/- 10.5 ms [hour 1, P <.01]; 23.0 +/- 6.1 ms vs 25.9 +/- 7.5 ms [hour 4, P <.01])., Conclusions: Positivity of cTnT on admission is associated with a significantly higher temporal inhomogeneity of ventricular repolarization and a higher incidence of malignant RAs, which suggests more advanced microvascular injury. Early successful primary PCI ultimately results in a significant recovery of parameters of QT interval and mean RR interval in all patients, although it was significantly delayed in patients in the cTnT+ group.

The limited prognostic value of QT dispersion has been demonstrated in recent studies. However, longitudinal data on physiological variations of QT interval and the influence of aging and sex are few. This analysis included 172 healthy subjects (89 women, 83 men; mean age 38.7 +/- 15 years). Beat-to-beat QT interval duration (QT, QTapex [QTa], Tend [Te]), variability (QTSD, QTaSD), and the mean R-R interval were determined from 24-hour ambulatory electrocardiograms after exclusion of artifacts and premature beats. All volunteers were fully active, awoke at approximately 7:00 AM, and had 6-8 hours of sleep. QT and R-R intervals revealed a characteristic day-night-pattern. Diurnal profiles of QT interval variability exhibited a significant increase in the morning hours (6-9 AM; P < 0.01) and a consecutive decline to baseline levels. In female subjects the R-R and Tend intervals were significantly lower at day- and nighttime. Aging was associated with an increase of QT interval mainly at daytime and a significant shift of the T wave apex towards the end of the T wave. The circadian profile of ventricular repolarization is strongly related to the mean R-R interval, however, there are significant alterations mainly at daytime with normal aging. Furthermore, the diurnal course of the QT interval variability strongly suggests that it is related to cardiac sympathetic activity and to the reported diurnal pattern of malignant ventricular arrhythmias.

The impact of continuous telemetry of atrial electrogram and marker annotations on Holter ECG interpretation was assessed in 98 patients with bipolar dual chamber pacemakers (VDD pacemakers n = 29, DDD(R) systems n = 69). Atrial electrogram and marker annotations were continuously sampled by a telemetry coil that was externally positioned on the pacemaker pocket, amplified, and transduced to a three-channel Holter ECG recorder in addition to an ECG recording. Holter tapes were analyzed by two experienced investigators for quality of P wave recognition and episodes suspicious of pacemaker dysfunction. Initially, only the ECG channel was analyzed. Thereafter, results were compared to those achieved on the basis of the complete recording including atrial electrogram and marker annotations. Recognition of atrial rhythm was markedly improved by Holter telemetry. During 99.3% of recording time telemetry showed a satisfying quality, whereas ECG alone allowed a reliable P wave recognition only during 84.4% of recording time (P < 0.001). One hundred twenty-nine episodes suspicious of pacemaker malfunction occurred in 17 of 98 patients. By analysis of ECG, only 78.3% of episodes were concordantly classified by the investigators. However, 98.4% of all episodes were properly identified when atrial electrogram and marker annotations were added to the analysis (P < 0.001). In particular, discrimination between atrial undersensing, sinus bradycardia, and atrial sensed events within the refractory periods was facilitated. Holter telemetry of atrial electrogram and marker annotations facilitates the analysis of Holter ECGs in pacemaker recipients and improves the detection of pacemaker dysfunctions.

Unipolar ventricular leads were implanted in a considerable percentage of pacemaker recipients. There is little information on incidence and risk factors for unipolar pacemaker dysfunction using modern lead designs. Included in a cross-sectional analysis were 682 patients who fulfilled the following criteria: chronically implanted bipolar ventricular leads (> 1 year), intraoperative stimulation threshold < 1.0 V/0.5 ms, and potential amplitude > 6 mV. Incidences of chest wall stimulation (CWS) at an output of twice the amplitude threshold and of myopotential oversensing (MPO) at a sensitivity of half the sensing threshold were assessed. Energy (0.60 [0.72] vs 0.63 [0.81] microJ) and sensing thresholds (8.31 [3.18] mV vs 8.47 [3.47] mV) did not differ between uni- and bipolar modes. While all pacemakers worked properly during bipolar configuration, malfunctions were observed in 5.9% of patients during unipolar configuration (CWS = 1.9%, MPO = 4.2%). Patient age > 76 years (hazard ratio HR 8.2; P < 0.001), heart failure > or = NYHA Class II (HR 3.8; P < 0.001), and an antiarrhythmic therapy with Class I or III drugs (HR 3.3; P = 0.002) were independently associated with the occurrence of unipolar pacemaker dysfunction. Use of steroid-eluting leads reduced the probability of pacemaker dysfunction (HR 0.45; P = 0.03). Risk factors for unipolar ventricular pacemaker malfunction were higher age, heart failure, and antiarrhythmic drug therapy. Particularly in these patients, use of bipolar ventricular leads is beneficial.

Background: The occurrence of paroxysmal atrial fibrillation is related to changes in autonomic tone. Vagally mediated atrial fibrillation predominantly occurs at night in young male patients without history of structural heart disease. In contrast, sympathetically mediated atrial fibrillation is typically triggered by stress., Analysis of Heart Rate Variability: Heart rate variability usually measured by Holter monitoring can determine changes in autonomic tone immediately preceding the onset of atrial fibrillation. Studies on this topic found divergent results on the incidence of atrial fibrillation mediated by changes in autonomic tone. Dependent on the results of different studies, night-time episodes of idiopathic atrial fibrillation either are vagally or sympathetically mediated. A sympathetic predominance is found in patients after coronary bypass surgery, concordantly. The inconsistency of these findings points to the fact that not only one mechanism, but more complex changes in autonomic tone are responsible for the occurrence of atrial fibrillation in many cases. In modern pacemakers and implantable cardioverter-defibrillators, PP or RR intervals can be stored automatically before the onset of an arrhythmia. By use of these stored intervals, time-domain parameters of heart rate variability can be calculated. We determined changes in short-term heart rate variability (10-second intervals) by analyzing 26 episodes of PP intervals sampled over the last 2 minutes before onset of atrial fibrillation by a modern dual chamber pacemaker. We observed a significant increase of the standard deviation of PP intervals (SDNN10s) as well as of the mean square route of the squared PP intervals (rMSSD10s) within the last 10-second interval before onset of atrial fibrillation (p < 0.05). This finding points to changes in autonomic tone-immediately preceding the onset of atrial fibrillation., Conclusion: The preliminarity of these findings and the use of yet not validated short intervals for determination of heart rate variability does not allow to draw pathogenetic or even therapeutic conclusions from these findings.

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.

Unexpected atrial fibrillation (AF) during implantation of an atrial pacemaker lead is sometimes encountered. Intraoperative cardioversion may lengthen and complicate the implantation process. This study prospectively investigates the performance of atrial leads implanted during AF (group A) and compares atrial sensing and pacing properties to an age- and sex-matched control group in which sinus rhythm had been restored before atrial lead placement (group B). Patient groups consisted of 32 patients each. All patients received DDDR pacemakers and bipolar, steroid-eluting, active fixation atrial leads. In patients with AF at the time of implantation (group A), a minimal intracardiac fibrillatory amplitude of at least 1.0 mV was required for acceptable atrial lead placement. In patients with restored sinus rhythm (group B), a voltage threshold < 1.5 V at 0.5 ms and a minimal atrial potential amplitude > 1.5 mV was required. Patients of group A in whom spontaneous conversion to sinus rhythm did not occur within 4 weeks after implantation underwent electrical cardioversion to sinus rhythm. Pacemaker interrogations were performed 3, 6, and 12 months after implantation. In group A, implantation time was significantly shorter as compared to group B (58.7 +/- 8.6 minutes vs 73.0 +/- 17.3 minutes, P < 0.001). Mean atrial potential amplitude during AF was correlated with the telemetered atrial potential during sinus rhythm (r = 0.49, P < 0.001), but not with the atrial stimulation threshold. Twelve months after implantation, sensing thresholds (1.74 +/- 0.52 mV vs 1.78 +/- 0.69 mV, P = 0.98) and stimulation thresholds (1.09 +/- 0.42 V vs 1.01 +/- 0.31 V, P = 0.66) did not differ between groups A and B. However, in three patients of group A, chronic atrial sensing threshold was < or = 1 mV requiring atrial sensitivities of at least 0.35 mV to achieve reliable atrial sensing. Atrial lead placement during AF is feasible and reduces implantation time. However, bipolar atrial leads and the option to program high atrial sensitivities are required.

Steroid elution reduces the acute increase in stimulation threshold particularly in active fixation leads. The aim of this study was to investigate the long-term efficacy of steroid elution in atrial screw-in leads compared to conventional lead design. Two different bipolar active fixation platinum lead designs were implanted. Leads were similar except for the presence (group S, n = 66) or absence (group N, n = 68) of steroid elution. Patients received dual chamber pacemakers with the following atrial leads in consecutive order: Medtronic 4058 M (group N, n = 30), Medtronic 4068 (group S, n = 40), Vitatron IMS 13 (identical to 4058 M, group N, n = 38), and Vitatron IMX 13 (identical to 4068, group S, n = 26). The mean follow-up period was 40.7 +/- 16.1 months (range 10 to 84 months). Stimulation thresholds, pacing impedances, P wave potentials, and sensing threshold were assessed for both groups immediately, 10 days, 6 weeks, and 3 months after implantation followed by 6-months intervals. Energy thresholds, chronaxie-rheobase products, and energy consumption of atrial pacing were calculated. Chronic values were deduced from the most recent measurement performed in an individual patient. Within the first 10 days after implantation, atrial voltage threshold at pulse duration of 0.4 ms increased from 0.91 +/- 0.42 to 2.06 +/- 0.45 V in group N (P < 0.001). Less increase was observed in group S (0.83 +/- 0.39 to 1.08 +/- 0.53 V, P = 0.003). Atrial voltage thresholds remained markedly lower in steroid-eluting leads during whole follow-up (1.12 +/- 0.49 V in group S vs 1.58 +/- 0.71 V in group N, P < 0.001). Chronic energy consumption was markedly reduced in group S (4.0 +/- 2.7 microJ) compared to group N (9.8 +/- 7.5 microJ, P < 0.001). An atrial voltage threshold below 1.25 V at 0.4 ms was achieved in 92.3% of patients of group S allowing programming of an output of 2.5 V. Such low outputs were feasible in only 49.3% of patients in group N (P < 0.001). Chronic P wave amplitudes did not differ significantly between groups (3.27 +/- 1.81 mV in group N vs 3.24 +/- 1.18 mV in group S, P = 0.91). Steroid elution diminishes the increase of stimulation thresholds of nonsteroid atrial active fixation platinum leads resulting in a long-term reduction of energy consumption. Thus, use of steroids can be recommended for general use in atrial active fixation lead designs.

Implantation of single lead VDD pacemakers is an established therapeutic option in patients with AV block and normal sinus node function. However, related to occurrence of sinus node disease and atrial undersensing, there is concern whether VDD devices are appropriate in physically active young patients. Two hundred thirty-two consecutive patients with isolated AV block and VDD pacemakers were investigated. This population was subdivided into quartiles of 58 patients according to age at time of inclusion: 26.2-59.4 years (group A), 59.5-70.1 years (group B), 70.2-81.0 years (group C), and 81.1-92.5 years (group D). Follow-up visits included pacemaker telemetry, Holter monitoring, and exercise testing. Patients were visited at 2 and 12 weeks after implantation thereafter followed by 6-month intervals. Mean follow-up period was 35 +/- 14 months. Three months after implantation, atrial sensing threshold was significantly higher in young patients: 1.18 +/- 0.58 mV (group A) versus 0.79 +/- 0.35 mV (group B), 0.68 +/- 0.33 mV (group C), and 0.60 +/- 0.25 mV (group D), P < 0.001 for comparison of group A to all other groups. Atrial undersensing was observed less frequently in young patients: 6.9% (group A) versus 17.2% (group B), 24.1% (group C), and 27.6% (group D), P = 0.025 for intergroup comparisons. Sinus node dysfunction did not occur in group A. Atrial arrhythmias and loss of AV synchronized pacing mode occurred rarely in young patients: 0.6% (0.4%) per year in group A versus 1.3% (1.3%) in group B, 3.9% (3.4%) in group C, and 5.7% (7.4%) per year in group D, P < 0.01 for intergroup comparisons. Our data show good atrial sensing performance, low incidence of sinus node dysfunction, and few atrial arrhythmias in young patients with VDD pacing for AV block. Thus, single lead VDD pacing can be recommended particularly for young patients with AV block.

In dual chamber pacemakers, atrial sensing performance is decisive for maintenance of AV synchrony. Particularly, the efficacy of mode switching algorithms during intermittent atrial tachyarrhythmias depends on the sensitive detection of low potential amplitudes. Therefore, a high atrial sensitivity of 0.18 mV, commonly used in single lead VDD pacemakers, was investigated for its efficacy and safety in DDD pacing. Thirty patients received dual chamber pacemakers and bipolar atrial screw-in leads for sinus node syndrome or AV block; 15 patients suffered from intermittent atrial fibrillation. Pace makers were programmed to an atrial sensitivity of 0.18 mV. Two weeks, 3, 9, and 15 months after implantation, P wave sensing threshold and T wave oversensing thresholds for the native and paced T wave were determined. The myopotential oversensing thresholds were evaluated by isometric contraction of the pectoral muscles. Automatic mode switch to DDIR pacing was activated when the mean atrial rate exceeded 180 beats/min. The patients were followed by 24-hour Holter monitoring. Two weeks after implantation, mean atrial sensing threshold was 1.81 +/- 0.85 mV (range 0.25-2.8 mV) without significant differences during further follow-up. Native T wave sensing threshold was < 0.18 mV in all patients. In 13% of patients, paced T waves were perceived in the atrial channel at the highest sensitivity. This T wave sensing could easily be avoided by programming a postventricular atrial refractory period exceeding 300 ms. Myopotential oversensing could not be provoked and Holter records showed no signs of sensing dysfunction. During a 15-month follow-up, 1,191 mode switch events were counted by autodiagnostic pacemaker function. Forty-two of these events occurred during Holter monitoring. Unjustified mode switch was not observed. In DDD pacemakers, bipolar atrial sensing with a very high sensitivity is efficient and safe. Using these sensitivity settings, activation of the mode switch algorithm almost completely avoids fast transmission of atrial rate to the ventricle during atrial fibrillation.