Electrocardiographic analysis of ectopic atrial activity obscured by ventricular repolarization: P wave isolation using an automatic 62-lead QRST subtraction algorithm

INTRODUCTION: Atrial activity on the surface ECG during premature beats and supraventricular arrhythmias frequently is obscured by the superimposed QRST complex of the previous cardiac cycle. This study examines the performance of a newly developed automatic QRST subtraction algorithm to isolate ectopic P waves from the preceding T-U wave. METHODS AND RESULTS: The 62-lead ECG recordings were obtained during (1) sinus rhythm and programmed right atrial stimulation in 12 patients (group A); and (2) sinus rhythm and atrial premature beats, atrial tachycardia, or paroxysmal atrial fibrillation in 5 patients (group B). Pacing in group A patients was conducted at a slow drive cycle length to generate an ectopic P wave not obscured by the previous QRST complex and by delivering single premature extrastimuli at progressively shorter coupling intervals to produce an ectopic P wave obscured by the upsloping (early T-U wave), peak (middle T-U wave), and downsloping component of the T-U wave (late T-U wave). All ectopic P waves in group B patients were concealed by the preceding T-U wave. Automatic QRST subtraction was attained using an adaptive template constructed from averaged QRST complexes (mean 83 +/- 25 complexes) obtained during sinus rhythm (groups A and B) or atrial overdrive pacing (group A). P wave integral maps subsequently were computed, visually compared, and mathematically correlated. A high correspondence in spatial map pattern was observed between integral maps of "nonobscured" and previously "obscured" paced P waves obtained in group A patients (mean r = 0.88 +/- 0.07) as well as between integral maps of two to three previously obscured P waves with the same atrial arrhythmia morphology obtained in group B patients (mean r = 0.94 +/- 0.05). Improved morphologic P wave replication in group A patients was acquired when concealment occurred in the early (mean r = 0.90 +/- 0.08) or late part of the T-U wave (mean r = 0.90 +/- 0.06) as opposed to the middle T-U wave (mean r = 0.85 +/- 0.07) (P = NS and P < 0.05 for early vs middle and late vs middle T-U wave, respectively). CONCLUSION: This novel automatic 62-lead QRST subtraction algorithm enables discrete isolation of T-U wave obscured ectopic atrial activity on the surface ECG while retaining the intricate spatial detail in P wave morphology. Future clinical application of the algorithm may enable improved ECG localization of focal triggers of paroxysmal atrial fibrillation, atrial tachycardia, and the atrial insertion of accessory pathways.     

T-U wave alternans. A case report and review of the literature.

A patient with severe hypertension, hypokalemia and marked T-U wave alternans on electrocardiogram is reported for its rarity. Relevant literature is reviewed. Recent data indicate that electric alternans is related to changes in action potential configuration, and that it may be a marker of cardiac electrical instability.     

Unique ECG presentations and clinical management of a symptomatic LQT2 female carrying a novel de novo KCNH2 mutation

A 26-year-old woman, 12 days in postpartum, developed recurrent syncope and cardiac arrest. Her ECG revealed QT-prolongation associated with LQT2-specific T-U wave patterns, T wave alternans, long QT-dependent torsade de pointes (TdP) and ventricular fibrillation (VF). She also had intermittent LBBB (80 bpm) on alternate beats and RBBB at sinus tachycardia (113 bpm). Family genotyping revealed a novel de novo missense mutation G604C of KCNH2. Propranolol slowed heart rate and further prolonged QT interval (610 ms) that caused TdP recurrence. Mexiletine combined with magnesium and potassium supplements prevented TdP/VF recurrence. This patient has remained event-free after 9-month follow-up.     

Right ventricular monophasic action potential during quinidine induce marked T and U waves abnormalities.

An unusual case with quinidine induced marked T and U waves abnormalities of giant size and alternans occuring in sinus rhythm is reported. Right ventricular monophasic action potential recorded during bizzare T and U waves abnormalities showed a marked prolongation of its duration and regressed after the drug was withdrawn.     

Isolated T wave alternans

Two patients with isolated T wave alternans are reported, with their vectocardiograms, their response to carotid sinus stimulation, and the response to calcium infusion in one of them with documented severe hypocalcemia. Eleven cases of the literature are briefly reviewed. The alternans of the T wave appears with severe QT prolongation, QT alternans, and an increased tendency to ventricular fibrillation. The findings are consistent with the hypothesis that T wave alternans may be the electrocardiographic manifestation of the transmembrane action potential alternans and could be related in some cases to hypocalcemia.     

Class I antiarrhythmic drug and coronary vasospasm-induced T wave alternans and ventricular tachyarrhythmia in a patient with Brugada syndrome and vasospastic angina

A 50-year-old man presented with a history of transient chest pain and palpitations. The 12-lead ECG at rest showed normal sinus rhythm. A slight ST segment elevation was observed in leads V1 to V3. During hospitalization, atrial fibrillation developed, and oral pilsicainide was administered. Thirty minutes after the drug was given, the ECG showed marked ST segment elevation in leads V1 to V3, and T wave alternans became visible in leads V2 and V3. Self-terminating ventricular tachycardia was initiated following frequent ventricular premature complexes, which showed a left bundle branch block pattern. The coronary angiogram was normal, but in the provocation test of vasospastic angina, acetylcholine administration into the left coronary artery resulted in complete occlusion of the left anterior descending and circumflex arteries. Marked ST segment elevation developed in leads I, aVL, and V3 to V6 concomitant with visible QT/T alternans in leads V4 and V5, and ventricular tachyarrhythmia was initiated. Brugada syndrome and vasospastic angina coexisted in this patient, and T wave alternans can be used as a predictor of ventricular tachyarrhythmias in such patients.     

Spatiotemporal transition to conduction block in canine ventricle

Interruption of periodic wave propagation by the nucleation and subsequent disintegration of spiral waves is thought to mediate the transition from normal sinus rhythm to ventricular fibrillation. This sequence of events may be precipitated by a period doubling bifurcation, manifest as a beat-to-beat alternation, or alternans, of cardiac action potential duration and conduction velocity. How alternans causes the local conduction block required for initiation of spiral wave reentry remains unclear, however. In the present study, a mechanism for conduction block was derived from experimental studies in linear strands of cardiac tissue and from computer simulations in ionic and coupled maps models of homogeneous one-dimensional fibers. In both the experiments and the computer models, rapid periodic pacing induced marked spatiotemporal heterogeneity of cellular electrical properties, culminating in paroxysmal conduction block. These behaviors resulted from a nonuniform distribution of action potential duration alternans, secondary to alternans of conduction velocity. This link between period doubling bifurcations of cellular electrical properties and conduction block may provide a generic mechanism for the onset of tachycardia and fibrillation.     

Linkage between mechanical and electrical alternans in patients with chronic heart failure

INTRODUCTION: Progressive heart failure and ventricular fibrillation are major causes of death in patients with chronic heart failure. Mechanical alternans (pulsus alternans) has been observed in patients with severe congestive heart failure. Visible T wave alternans occasionally is a precursor of ventricular fibrillation. We investigated the occurrence of both cardiac alternans in 94 patients with chronic heart failure. Methods AND RESULTS: Mean left ventricular ejection fraction (LVEF) of the study population was 35 +/- 10%. Mechanical alternans was detected in left ventricular pressure during diagnostic cardiac catheterization. Only sustained mechanical alternans was included in the study. Visible T wave alternans, not microvolt alternans, was noted on standard surface ECG. Cardiac alternans was examined at rest, during physiologic tachycardia, and during stepwise dobutamine loading (2-4-8 microg/kg/min). Prevalences of mechanical and electrical alternans were 19.1% and 4.4% at rest, 45.5% and 8.0% during physiologic tachycardia, and 62.1% and 9.5% under dobutamine loading. Overall, 70 patients (74.5%) showed mechanical alternans and 10 patients (10.6%) showed T wave alternans. T wave alternans always appeared with large mechanical alternans. Among patients with mechanical alternans, cases with T wave alternans showed lower LVEF than those without (27.5 +/- 4.4 and 35.1 +/- 10.2, P < 0.002). CONCLUSION: Visible T wave alternans was detectable in patients with chronic heart failure, especially under tachycardia or catecholamine exposure. Investigating mechanical and mechanoelectrical alternans may bring new insights into the management of patients with chronic heart failure.     

T wave alternans after sotalol: evidence for increased sensitivity to sotalol after conversion from atrial fibrillation to sinus rhythm

A 64 year old woman with an 11 year history of paroxysmal atrial fibrillation presented to the emergency room because of palpitations that had started two weeks previously. She had used sotalol 80 mg once daily for three years without any episodes of proarrhythmia or other adverse effects. However, she developed pronounced T wave alternans with giant inverted T waves and excessive QT prolongation following sotalol administration one day after conversion from atrial fibrillation to sinus rhythm. This case demonstrates bizarre T wave changes, T wave alternans, and extreme QT prolongation following sotalol administration shortly after conversion from atrial fibrillation to sinus rhythm. In this situation, sotalol administration may be proarrhythmic, because it enhances repolarisation inhomogeneities based on a spatially inhomogeneous distribution of repolarisation controlling ion channels to induce repolarisation abnormalities that may lead to torsade de pointes.

Keywords: T wave alternans; long QT syndrome; torsade de pointes; sotalol; atrial fibrillation     

Mechanical alternans in patients with chronic heart failure.

BACKGROUND: Clinical implications of mechanical alternans in patients with chronic heart failure have remained uncertain. In this study, prevalence, characteristics, and prognostic implications of mechanical alternans were investigated. METHODS AND RESULTS: Consecutive 51 patients with dilated cardiomyopathy underwent diagnostic cardiac catheterization using a micromanometer-tipped catheter. Under basal conditions, 7 of 35 patients with sinus rhythm showed mechanical alternans. Physiologic tachycardia (110 bpm) induced mechanical alternans in another 15 patients with sinus rhythm and in another 10 of 16 patients with atrial fibrillation. Low doses of dobutamine also induced mechanical alternans in another 8 patients, but a high dose of dobutamine eliminated mechanical alternans. Consequently, 40 patients (78%) showed mechanical alternans. Mechanical alternans was always accompanied by alternating changes of positive dP/dt, a parameter of contractility during isovolumetric contraction time, but negative dP/dt was occasionally constant. Concordant mechanical alternans between both ventricles was more prevalent than discordant alternans. The left ventricular end-diastolic volume indices and end-systolic volume indices of patients with mechanical alternans were larger than those of patients without. The left ventricular ejection fraction of patients with alternans was significantly lower than that of patients without. CONCLUSIONS: Mechanical alternans was highly prevalent in patients with chronic heart failure. The origin of mechanical alternans seems to exist before or at the isovolumetric contraction time.     

Alternating atrial electromechanical dissociation as contributing factor for pulsus alternans.

Ten patients with mechanical pulsus alternans were studied by echocardiography and mechanocardiography. All had been or were in congestive heart failure. An atrial mechanism for pulsus alternans could be identified in two patients: one with primary congestive cardiomyopathy and one after aortic valve replacement for calcific aortic stenosis. Each strong systole was preceded by an "a" wave, while each weak systole was not. This was documented on both the apexcardiogram and the M-mode echocardiogram. Since both patients were in normal sinus rhythm with regular PP intervals, it was concluded that alternating atrial electromechanical dissociation was either the underlying mechanism or contributed to the pulsus alternans. Thus, alternating atrial electromechanical dissociation exists and may cause pulsus alternans. Pulsus alternans is not necessarily the result of left ventricular myocardial dysfunction alone.     

Microvolt level T wave alternans: a new marker for noninvasive risk stratification

Prospective identification of patients with structural heart disease who could profit from prophylactic ICD therapy is hampered by the low predictive power of the currently available risk stratification parameters. Microvolt T wave alternans measured noninvasively is a new promising parameter to assess impaired ventricular repolarization which has been associated with an increased incidence of ventricular tachyarrhythmias. T wave alternans is rate-dependent; to induce alternans, heart rate may be increased by atrial stimulation during invasive EP testing or noninvasively by exercise stress testing. The first clinical validation with respect to prediction of inducibility of ventricular tachyarrhythmias and of arrhythmic events during follow-up in patients undergoing invasive EP testing was reported in 1994. Subsequently, a good concordance between the results of invasive and noninvasive assessment of T wave alternans was demonstrated by our group. The first prospective evaluation of the noninvasive alternans measurement using submaximal exercise testing was performed in patients surviving prehospital ventricular fibrillation or sustained ventricular tachycardia referred to our institution. The occurrence of T wave alternans in this patient population was predictive of future tachyarrhythmic events with subsequent appropriate ICD therapy. The results of the currently performed prospective trials in various patient populations will help to establish the utility of T wave alternans assessment as a risk stratifier in clinical practice.     

Spontaneous T wave alternans and premature ventricular contractions during febrile illness in a patient with Brugada syndrome

A 69-year-old man who had experienced syncope and ventricular fibrillation was referred to our hospital. ECG showed a right bundle branch block pattern with ST segment elevation in the right precordial leads. When the patient presented to the hospital with febrile illness, spontaneous T wave alternans and premature ventricular contractions were observed. When the patient became afebrile, ST segment elevation improved, and T wave alternans and premature ventricular contractions disappeared.     

Intravenous administration of class I antiarrhythmic drugs induced T wave alternans in a patient with Brugada syndrome

A 71-year-old man who experienced aborted sudden death was referred to our hospital. Coronary artery disease and cerebral accident were ruled out by conventional tests. The 12-lead ECG obtained at rest showed a right bundle branch block pattern and ST segment elevation in leads V1 to V3. Double ventricular extrastimuli at coupling intervals >180 msec induced ventricular fibrillation (VF) twice during electrophysiologic study. Intravenous administration of procainamide accentuated ST segment elevation in leads V1 to V3, and visible T wave alternans was induced in leads V2 and V3 at a dose of 450 mg. Initiation of T wave alternans was not associated with changes of the cardiac cycle or development of premature beats. When procainamide infusion was discontinued, T wave alternans disappeared before the elevated ST segment returned to the control level. Pilsicainide also accentuated ST segment elevation and induced similar T wave alternans in leads V2 and V3. Class I antiarrhythmic drug-related T wave alternans has been reported rarely in Brugada syndrome, but it may represent enhanced arrhythmogenicity of VF. We need to monitor closely and study the clinical implications of T wave alternans in Brugada syndrome.     

Sarcoplasmic reticulum calcium content fluctuation is the key to cardiac alternans

The aim of this work was to investigate whether beat-to-beat alternation in the amplitude of the systolic Ca(2+) transient (Ca(2+) alternans) is due to changes of sarcoplasmic reticulum (SR) Ca(2+) content, and if so, whether the alternans arises due to a change in the gain of the feedback controlling SR Ca(2+) content. We found that, in rat ventricular myocytes, stimulating with small (20 mV) depolarizing pulses produced alternans of the amplitude of the Ca(2+) transient. Confocal measurements showed that the larger transients resulted from propagation of Ca(2+) waves. SR Ca(2+) content (measured from caffeine-evoked membrane currents) alternated in phase with the alternans of Ca(2+) transient amplitude. After a large transient, if SR Ca(2+) content was elevated by brief exposure of the cell to a Na(+)-free solution, then the alternans was interrupted and the next transient was also large. This shows that changes of SR Ca(2+) content are sufficient to produce alternans. The dependence of Ca(2+) transient amplitude on SR content was steeper under alternating than under control conditions. During alternation, the Ca(2+) efflux from the cell was also a steeper function of SR Ca(2+) content than under control. We attribute these steeper relationships to the fact that the larger responses in alternans depend on wave propagation and that wave propagation is a steep function of SR Ca(2+) content. In conclusion, alternans of systolic Ca(2+) appears to depend on alternation of SR Ca(2+) content. This, in turn results from the steep dependence on SR Ca(2+) content of Ca(2+) release and therefore Ca(2+) efflux from the cell as a consequence of wave propagation.     

Torsade de Pointes with T wave alternans in a patient receiving moderate dose of chlorpromazine: report of a case

A case is presented of Torsade de Pointes (TDP) with T wave alternans in a 31-year-old female receiving a moderate dose of chlorpromazine. She was treated in an another hospital for schizophrenia with chlorpromazine (100 mg daily) for several years and admitted to Fujisawa city hospital for numerous episodes of syncope. The electrocardiogram immediately after admission revealed a marked QTc prolongation to 0.81 seconds, T wave alternation without any obvious change in morphology of the QRS complex, and recurrent ventricular tachycardia called TDP. The T wave alternans and TDP were easily abolished by intravenous administration of a bolus of 50 mg lidocaine infusion. The QT interval however, remained prolonged. Physical examination, including cardiac examination, was normal. Serum potassium was 3.6/mEq. Chlorpromazine was discontinued immediately after admission and no further episodes of TDP were seen after the first day. After the QT interval returned to almost normal, chlorpromazine (50 mg daily) was re-administered. Two days after the re-administration, the electrocardiogram revealed marked QT interval prolongation with prominent T waves. Psychotropic drugs, such as chlorpromazine, prolong the QT interval and cause TDP. Chlorpromazine appears to have been responsible for TDP and the T wave alternans in this case. TDP caused by a moderate dose of chlorpromazine has not been previously reported. Lone T wave alternans unaccompanied by changes in the QRS complex is a rare phenomenon and the mechanism underlying T wave alternans remains unknown.     

P-wave locking in the postventricular atrial refractory period of cardiac resynchronization devices

Electrical desynchronization in cardiac resynchronization therapy (CRT) occurs when sinus P waves are continually locked in the postventricular atrial refractory period (PVARP). This process is characterized by sequences of a P wave as an atrial event in the PVARP followed by a conducted and sensed ventricular event. Such sequences are more common in patients with a prolonged PR interval, often initiated by premature ventricular complexes (PVC) and terminated by PVCs or slowing of the sinus rate. Specific algorithms automatically identify a recurring pattern of P wave locking in the PVARP, whereupon they shorten the PVARP temporarily until atrial tracking is restored with the programmed sensed AV interval. The Biotronik family of Lumax CRT devices use an AV control window which is not an algorithm that "unlocks" P waves trapped in the PVARP. Rather, it prevents P waves from becoming trapped in the PVARP. A ventricular sensed event occurring within the AV control interval does not start a PVARP so that P wave locking cannot occur when the AV conduction time is shorter than the AV control interval.     

起源于主动脉窦频发室性期前收缩的心电生理特征及射频消融治疗

目的报道11例起源于主动脉窦的频发室性期前收缩（premature ventricular contraction,PVC）患者的心电生理特征、射频消融（radiofrequency catheter ablation,RFCA）方法及疗效。方法分析患者术前体表心电图和动态心电图PVC的特点,测量V1或V2导联r波时限和振幅,计算r波与QRS波时限的比值及r波于S波振幅的比值。术中行主动脉窦内激动标测和起搏标测确定PVC起源部位,并行冠状动脉造影辅助定位后行RFCA。结果11例均有频发PVC,5例有反复短阵室性心动过速。下壁导联QRS波呈R形且高大直立,V1导联呈rS型,胸前导联多移行于V3以前,V6导联多呈Rs型或无S波。V1导联r波时限（84.6±9.8）ms,占QRS波时限的50%以上;r/S振幅比值0.72±0.31。有效消融靶点局部电图V波较体表心电图的QRS波明显提前（35.6±8.9）ms,有效靶点放电2～8 s见PVC减少至消失。结论起源于主动脉窦的PVC其下壁导联QRS波呈R形且高大直立,V1或V2导联r波时限宽（〉50%同导联QRS波）,r波振幅高（〉30%同导联S波）;主动脉窦内PVC的射频消融治疗是安全、有效的。     

心腔内单极电图旁道定位和消融靶点的图形特征

采用冠状窦和二尖瓣环单极记录标测左侧显性旁道和确定消融靶点指导射频消融治疗20例预激综合征。同步记录多部位冠状窦单极电图均清楚显示房波(UP)和室波(UR),其旁道定位点表现为 UP 降支和 UR 起始几乎融合构成特征性的复合波——PQS 波,而远离旁道的单极电图显示 UP 和 UR 分离构成 P—QS 或 P—rS 波。二尖瓣环单极记录时其图形变化类同冠状窦。比较冠状窦标测点和二尖瓣环单极电图的图形特征能迅速、直观地确定消融靶点。     

U wave alternans: an electrocardiographic sign of left ventricular failure

All postextrasystolic complexes seen over a twelve year period were carefully analyzed. Normally only the first complex is different, showing a slightly altered T and a larger U wave. Ten patients with left ventricular failure and postextrasystolic pulsus alternans consistently showed postextrasystolic U wave alternans. Besides introducing an electrocardiographic sign of heart failure, this provides some insight into the underlying etiology of the U wave.