Accessory pathway properties are similar in symptomatic and asymptomatic preexcitation.

PURPOSE: Patients with WPW syndrome have an increased mortality rate compared to the general population. Although asymptomatic preexcitation has previously been considered benign, recent studies have found that also asymptomatic patients have clinical and electrophysiological factors associated with increased risk of sudden cardiac death. This study compares the baseline electrophysiological characteristics of accessory pathways in symptomatic and asymptomatic patients with preexcitation. We hypothesized that a significant proportion of asymptomatic patients has inducible orthodromic tachycardia during programmed electrical stimulation. METHODS: This retrospective study includes 1853 patients with preexcitation who underwent invasive electrophysiological testing in two Swedish University Hospitals between 1991 and 2018. The mean age was 36 ± 17 years with a range of 3-89 years. Thirty-nine percent was women. A total of 269 patients (15%) were children younger than 18 years. Electrophysiological data included effective refractory period of the accessory pathway (APERP, in 1069 patients), tachycardia cycle length, inducibility and type of tachycardia, and AP localization. RESULTS: A total of 1703 (93%) patients reported symptoms suggesting tachyarrhythmias before the study and 128 (7%) were asymptomatic. The proportion of potentially dangerous pathways with short APERP (≤ 250 ms) were similar in symptomatic and asymptomatic patients (187/949, 20% vs. 25/108, 23%) (P = 0.40) as was the mean APERP (303 ± 68 ms vs. 307 ± 75) (P = 0.61). The proportion of patients who had inducible arrhythmia was larger in the symptomatic group (64% vs. 31%) (P < 0.001). CONCLUSION: The results of this study strengthen the present guideline recommendation (IIA) to consider invasive risk assessment in patients with asymptomatic preexcitation.

Atrial fibrillation burden, episode duration and frequency in relation to quality of life in patients with implantable cardiac monitor.

AIMS: To assess the relation between atrial fibrillation (AF) characteristics and health-related quality of life (QoL), and which AF characteristic had the greatest impact. METHOD: The AF characteristics burden (percentage of time in AF), duration and number of AF episodes/month were obtained from implantable cardiac monitors during the 2-month run-in period in 150 patients included in the randomized CAPTAF trial comparing early ablation and antiarrhythmic drug therapy. The QoL was measured by the General Health and Vitality dimensions of the 36-Item Short-Form Health Survey. AF characteristics were analysed continuously and in quartiles (Q1-Q4). RESULTS: Greater AF burden (p = 0.003) and longer AF episodes (p = 0.013) were associated with impaired QoL (Vitality score only) in simple linear regression analyses. Greater AF burden was, however, the only AF characteristic associated with lower QoL, when adjusted for sex, type of AF, hypertension, heart rate above 110 beats per minute during AF, and beta-blocker use in multiple linear regression analyses. For every 10% increase in AF burden there was a 1.34-point decrease of Vitality score (95% confidence interval (CI) -2.67 to -0.02, p = 0.047). The Vitality score was 12 points lower (95% CI -22.73 to -1.27, p = 0.03) in patients with an AF burden > 33% (Q4) versus those with < 0.45% (Q1), but only in unadjusted analysis. CONCLUSION: AF burden had a greater impact on QoL (Vitality), than the duration and number of AF episodes, corroborating that AF burden may be the preferred outcome measure of rhythm control in trials including relatively healthy AF populations.

Effect of Catheter Ablation vs Antiarrhythmic Medication on Quality of Life in Patients With Atrial Fibrillation: The CAPTAF Randomized Clinical Trial.

Importance: Quality of life is not a standard primary outcome in ablation trials, even though symptoms drive the indication. Objective: To assess quality of life with catheter ablation vs antiarrhythmic medication at 12 months in patients with atrial fibrillation. Design, Setting, and Participants: Randomized clinical trial at 4 university hospitals in Sweden and 1 in Finland of 155 patients aged 30-70 years with more than 6 months of atrial fibrillation and treatment failure with 1 antiarrhythmic drug or ß-blocker, with 4-year follow-up. Study dates were July 2008-September 2017. Major exclusions were ejection fraction <35%, left atrial diameter >60 mm, ventricular pacing dependency, and previous ablation. Interventions: Pulmonary vein isolation ablation (n = 79) or previously untested antiarrhythmic drugs (n = 76). Main Outcomes and Measures: Primary outcome was the General Health subscale score (Medical Outcomes Study 36-Item Short-Form Health Survey) at baseline and 12 months, assessed unblinded (range, 0 [worst] to 100 [best]). There were 26 secondary outcomes, including atrial fibrillation burden (% of time) from baseline to 12 months, measured by implantable cardiac monitors. The first 3 months were excluded from rhythm analysis. Results: Among 155 randomized patients (mean age, 56.1 years; 22.6% women), 97% completed the trial. Of 79 patients randomized to receive ablation, 75 underwent ablation, including 2 who crossed over to medication and 14 who underwent repeated ablation procedures. Of 76 patients randomized to receive antiarrhythmic medication, 74 received it, including 8 who crossed over to ablation and 43 for whom the first drug used failed. General Health score increased from 61.8 to 73.9 points in the ablation group vs 62.7 to 65.4 points in the medication group (between-group difference, 8.9 points; 95% CI, 3.1-14.7; P = .003). Of 26 secondary end points, 5 were analyzed; 2 were null and 2 were statistically significant, including decrease in atrial fibrillation burden (from 24.9% to 5.5% in the ablation group vs 23.3% to 11.5% in the medication group; difference -6.8% [95% CI, -12.9% to -0.7%]; P = .03). Of the Health Survey subscales, 5 of 7 improved significantly. Most common adverse events were urosepsis (5.1%) in the ablation group and atrial tachycardia (3.9%) in the medication group. Conclusions and Relevance: Among patients with symptomatic atrial fibrillation despite use of antiarrhythmic medication, the improvement in quality of life at 12 months was greater for those treated with catheter ablation compared with antiarrhythmic medication. Although the study was limited by absence of blinding, catheter ablation may offer an advantage for quality of life. Trial Registration: clinicaltrialsregister.eu Identifier: 2008-001384-11.

Value of the QRS-T area angle in improving the prediction of sudden cardiac death after acute coronary syndromes.

BACKGROUND: Prediction of sudden cardiac death (SCD) after acute coronary syndromes (ACS) remains a challenge. Although electrophysiology measures obtained by 3-D vectorcardiography (VCG) shortly after ACS may be useful predictors of SCD, they have not been adopted into clinical practice. The main objective of our study was to assess whether the VCG-derived QRS-T area angle (between area vectors) and the QRS-T angle (between maximum vectors) have additional value beyond standard risk factors in predicting SCD after ACS. METHODS AND RESULTS: We studied 643 consecutive ACS patients for whom data on VCG and echocardiography during the index hospitalization were available. Seventy-seven patients (12%) died, 37 (6%) from SCD and 21 (3%) from other cardiac causes during the 30-month follow-up. After adjusting for 9 standard risk factors (age, sex, diabetes, previous stroke, left ventricular ejection fraction; and estimated glomerular filtration rate, heart rate, systolic blood pressure<100mmHg, and Killip class>1 on admission), QRS-T area angle and QRS-T angle were shown to have independent predictive value for both SCD and all cardiac deaths. Reclassification analysis showed that both measures had additional predictive value beyond the 9 standard risk factors. For SCD, net reclassification improvements for QRS-T area angle and QRS-T angle were 46% and 45% and relative integrated discriminative improvements were 16% and 13% (vs the average~11% of the 9 standard risk factors). CONCLUSIONS: The VCG-derived QRS-T area angle and QRS-T angle improved prediction of SCD after ACS beyond standard risk factors. Further evaluation of their clinical utility and cost-effectiveness is therefore warranted.

Transient repolarization alterations dominate the initial phase of an acute anterior infarction--a vectorcardiography study.

OBJECTIVE: To study effects of ischemia-reperfusion on ventricular electrophysiology in humans by three-dimensional electrocardiography. METHODS: Fifty-seven patients with first-time acute anterior ST elevation myocardial infarction were monitored from admission and >24h after symptom onset with continuous vectorcardiography (VCG; modified Frank orthogonal leads). Global ventricular depolarization and repolarization (VR) measures were compared at maximum vs. minimum ST vector magnitude (STVM) (median 208; 111-303 vs. 362; 165-1359min after symptom onset). RESULTS: At maximum vs. minimum STVM the Tarea (overall VR dispersion) almost tripled (118 vs. 41µVs; p<0.0001), the T-loop bulginess was 90% greater (Tavplan 0.91 vs 0.48µV; p<0.0001), and Tpeak-end/QT was 39% larger (0.32 vs 0.23; p<0.0001). QRSarea (overall dispersion of depolarization) was 12% larger at maximum STVM, while QRS duration was 10% longer at minimum STVM. CONCLUSIONS: Ischemia-reperfusion was accompanied by profound and transient alterations of VR dispersion, while changes in depolarization were modest and delayed.

Transient repolarization instability following the initiation of cardiac resynchronization therapy.

AIMS: Cardiac resynchronization therapy (CRT) may cause changes in ventricular repolarization (VR), particularly in the initial phase of treatment. This study investigated the effect of CRT cessation and re-initiation on parameters of VR duration and heterogeneity at different paced heart rates. METHODS: Cardiac resynchronization therapy was inactivated for 2 weeks in 16 treatment responders to CRT. QT and JT intervals were measured on the surface electrocardiogram at 60, 70, and 80 bpm (randomized order) and vectorcardiography (VCG) was performed with CRT 'on' (day 0), 'off' (day 0, 1, 7, and 14) and after CRT re-initiation (day 14, 15, 16, and 21). On day 0 ('on') and 14 ('off') echocardiography, the 6 min walking distance and brain natriuretic peptide were assessed. RESULTS: The QT interval at baseline (CRT 'on'), measured at 60, 70, and 80 bpm, was 482 ± 31, 468 ± 37, and 457 ± 39 ms, respectively, and decreased by 5, 5, and 6% during the first week following CRT cessation (all P< 0.05). Immediately after re-initiation on day 14, it increased again by 20 ± 18 (4%; P< 0.05), 34 ± 39 (8%; P< 0.01), and 16 ± 38 ms (4%, ns) followed by a gradual decrease towards previous 'off' levels. Similar changes were observed for the JT interval. Ventricular repolarization duration was significantly shortened by increasing the paced heart rate from 60 to 70 and 80 bpm. Vectorcardiography parameters reflecting VR gradients (ST-vector magnitude, Tarea, and Tavplan) increased significantly (by 31, 45, and 71%) after CRT cessation. A similar but non-significant pattern was observed after CRT re-initiation. CONCLUSION: The increase in repolarization duration and gradients observed after CRT initiation suggests a transient state of VR instability that can be attenuated by programming of higher paced heart rates during the initial phase of treatment.

Prediction of cardiovascular death and myocardial infarction by the QRS-T angle and T vector loop morphology after angioplasty in stable angina pectoris: an 8-year follow-up.

Reliable cardiovascular (CV) risk assessment by a noninvasive tool would be of great value for CV event prevention. The present study consists of 187 coronary artery disease patients with 8 years of follow-up. Eight vectorcardiographic parameters characterizing different aspects of ventricular repolarization were analyzed at baseline: (1) the ST-segment (ST-VM), (2) the T vector angles (QRS-T angle, Televation, and Tazimuth), (3) the T vector loop morphology (Tavplan and Teigenvalue), and (4) Tarea and Tpeak-end. Cardiovascular death, myocardial infarction (MI), and repeated revascularization were traced via national registries. There were 16 CV deaths and 19 MIs; 89 patients remained free from CV events and revascularization. Ventricular repolarization parameters independently predicted CV death (widened QRS-T angle) and new MI (increased Tavplan) during follow-up. CV mortality was associated with increased divergence between depolarization and repolarization waves (widened QRS-T angle). Increased Tavplan, presumably reflecting heterogeneous repolarization, predicted future MI, which is a novel finding.

Ischemia-induced repolarization response in relation to the size and location of the ischemic myocardium during short-lasting coronary occlusion in humans.

BACKGROUND: The ventricular repolarization (VR) response to short-lasting coronary occlusion has been characterized by 3-dimensional vectorcardiography (VCG) in humans; the T vector loop becomes distorted and more circular. The purpose of this study was to relate these changes to the size of the myocardium at risk (MAR) and its location. METHODS: Continuous VCG was applied during transient coronary occlusion in 35 elective angioplasty patients, and the size of the MAR was estimated by single-photon emission computed tomography. Three VR aspects were assessed at baseline vs maximum ischemia: the ST segment, the T vector angles, and the T vector loop morphology. RESULTS: The T loop morphology changes were significantly associated with MAR size, but also dependent of its location. In contrast, the early phase of VR reflected by the ST segment responded to acute ischemia in relation to the MAR size independent of location. CONCLUSION: The VR changes were related both to the size and the location of the MAR and most pronounced during occlusion of the left anterior descending artery.

Cardiac fatigue in long-distance runners is associated with ventricular repolarization abnormalities.

BACKGROUND: Prolonged exercise can induce cardiac fatigue, which is characterized by biomarker release and impaired myocardial function. The impact on ventricular electrophysiology is largely unknown. OBJECTIVE: The objective of this study was to examine changes in ventricular repolarization after a 30-km cross-country race in runners aged >or=55 years. METHODS: Fifteen healthy participants (62 +/- 5 years) were assessed using biomarkers (N-terminal pro-brain natriuretic peptide [NT-proBNP], troponin T [TnT]), tissue Doppler echocardiography, and vectorcardiography at baseline, within 1 hour postrace and on days 1 and 6 postrace. RESULTS: During the race, NT-proBNP increased from 42 ng/L (interquartile range 25-117) to 187 ng/L (113-464), and TnT increased from undetectable levels to 0.03 microg/L (0.015-0.05). Global strain (19.1% +/- 2.2%) decreased on day 1 (17.2% +/- 1.8%) and day 6 (17.9% +/- 1.5%; P <.01). QT(c) increased from 431 +/- 15 ms prerace to 445 +/- 22 ms postrace and 445 +/- 15 ms on day 1 (P <.05), mainly because of an increased T(peak-end) interval (prerace 108 +/- 13 ms, postrace 127 +/- 43 ms, day 1 127 +/- 43 ms; P <.05). Postrace, T(area) (baseline 75 +/- 26 microVs) peaked on day 1 (105 +/- 42 microVs) and remained high on day 6 (89 +/- 37 microVs; P <.05). Runners with higher baseline NT-proBNP developed greater impairment of myocardial velocities (rho = -0.68 to -0.54; P <.05) and a larger increase in T(area) (rho = 0.73; P <.01). CONCLUSION: Cardiac fatigue induced by prolonged exertion is associated with sustained abnormalities in ventricular repolarization. Runners with higher baseline NT-proBNP are especially liable to such alterations of cardiac function.

Distorted T-vector loop and increased heart rate are associated with ventricular fibrillation in a porcine ischemia-reperfusion model.

BACKGROUND: The ventricular repolarization (VR) response to short-lasting coronary occlusion has been characterized by 3-dimensional vectorcardiography during angioplasty in humans; the T-vector loop becomes distorted (increased T(avplan)) and more circular (decreased T(eigenvalue)), but these changes have not been related to ventricular arrhythmias. PURPOSE: The VR response was therefore explored in a porcine ischemia-reperfusion model and compared in pigs with (n = 16) vs without (n = 17) ventricular fibrillation (VF). METHODS: Different aspects of VR were evaluated at baseline, at maximum ischemia, before reperfusion and at the subsequent ST maximum, after 1 hour of reperfusion, and before VF. Three aspects of the VR response were assessed: the ST-segment, the T-vector angles, and the T-vector loop morphology. RESULTS: All parameters changed significantly from baseline during ischemia and/or reperfusion. The early changes were similar to those previously observed in humans during angioplasty. The VF episodes were preceded by a significantly exaggerated T-loop distortion (increased T(avplan)) and increased heart rate. CONCLUSION: Aggravated T-loop distortion might, in this porcine ischemia-reperfusion model, reflect aspects of VR relevant to arrhythmogenesis.

Right ventricular pacing-induced electrophysiological remodeling in the human heart and its relationship to cardiac memory.

BACKGROUND: Right ventricular apical (RVA) pacing induces electrophysiological and structural remodeling. Cardiac memory (CM) evolves during the course of pacing and is readily apparent on electrocardiography (ECG) or vectorcardiography (VCG) when normal ventricular activation resumes. OBJECTIVE: This study sought to assess ventricular repolarization (VR) changes during pacing and intermittent normal ventricular conduction by ECG and VCG and to determine the temporal and conformational evolution of CM. METHODS: Twenty sick sinus patients received a dual-chamber rate-adaptive (DDD-R) pacemaker and were paced from the RVA endocardium. The pacemakers were programmed to a short AV delay to maximize ventricular preexcitation. The ECG and VCG were recorded before and 1 day after implantation, and then daily for the first week (n=6) or weekly for 5 to 8 weeks (n=14), with the pacemakers temporarily programmed to AAI (normal ventricular activation). RESULTS: The first parameters to change were T-vector amplitude, T(area), and T(peak)-T(end) (T(p-e)), which decreased within 1 day after initiating pacing. CM became apparent between day 1 and day 3, was fully established after 1 week, and then remained stable. Signs of increased VR heterogeneity were observed as the T loop became more circular (decreased T(egenv)) and distorted (increased T(avplan)), which have previously been observed in conditions with increased risk for arrhythmias. Over weeks, VR duration was prolonged (increased QTc). In contrast, during ventricular pacing, a gradual shortening of the repolarization time was observed, suggesting a stabilizing adaptive process. CONCLUSION: In sick sinus syndrome patients in whom ventricular pacing is indicated, switching between normal AV conduction and ventricular pacing should be minimized to avoid periods of repolarization instability.

Ischemia induces aggravation of baseline repolarization abnormalities in left ventricular hypertrophy: a deleterious interaction.

Epidemiological studies show that left ventricular hypertrophy (LVH) and hypertension (HT) in coronary artery disease increases the risk for cardiovascular events including sudden cardiac death (SCD). According to experimental studies, myocardial hypertrophy is associated both with altered electrophysiological properties (including prolonged repolarization) and increased vulnerability to ischemia. However, human data to support a repolarization-related mechanism for the increased SCD risk has not been provided. We therefore studied 187 patients undergoing three-dimensional vectorcardiographic monitoring during coronary angioplasty. Eight parameters reflecting different aspects of ventricular repolarization were used: 1) the ST segment (ST-VM and STC-VM), 2) the T vector (QRS-T angle, Televation, and Tazimuth), and 3) the T vector loop (Tavplan, Teigenv, and Tarea). Data collection was performed at rest and at the time of maximum ischemia during coronary occlusion. The patients were divided into three groups: 33 patients with ECG signs of LVH (18 with HT), 54 with HT but without LVH signs, and 100 patients with neither. Coronary artery disease patients with LVH not only had the most abnormal baseline repolarization (as expected) but also a significantly more pronounced repolarization response during coronary occlusion, whereas HT patients had mean parameter values between LVH patients and those without neither HT nor LVH signs. Because there is a relation between increased SCD risk and repolarization disturbances in various clinical settings, the results of the present study are in agreement with animal data and epidemiological observations, although other factors than disturbed repolarization might be of importance.

T vector and loop characteristics in coronary artery disease and during acute ischemia.

OBJECTIVE: Three-dimensional characterization of the ventricular repolarization by the T vector and T vector loop morphology in coronary artery disease (CAD), and their response to short-term (no flow) ischemia induced by coronary occlusion during a percutaneous intervention (PCI). BACKGROUND: The risk for sudden cardiac death is increased in conditions of acute or permanently heterogeneous ventricular repolarization, for which ischemia is a risk factor. METHODS: Fifty-six CAD patients without visible collateral circulation were studied during an elective single-vessel PCI, and 10 healthy controls twice at rest. T vector parameters (Televation, Tazimuth, and QRS-T angle), and T loop parameters (Tarea, Tavplan, and Teigenv) were measured by vectorcardiography. ST vector magnitude (ST-VM) and its change (STC-VM) were used for reference. RESULTS: At rest, T vector loop morphology (Tarea, Teigenv) was significantly different in CAD patients and controls, while T vector angles did not separate the groups. Ischemia induced significant changes in T loop parameters in the entire CAD group, whereas in the LAD subgroup significant changes were seen also in T vector angle. The T loop morphology was significantly different at baseline and a more pronounced response to ischemia (Tarea) was seen in patients with, than in those without, a history of hypertension. CONCLUSION: T loop morphology, rather than the T vector angle, separated CAD patients from healthy controls. Coronary occlusion had significant impact on ventricular repolarization, as assessed by T vector and morphology analysis, and most prominently in the LAD group. Hypertensive patients appeared especially vulnerable to ischemia.