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.     

Changes in the occurrence of mechanical alternans after long-term beta-blocker therapy in patients with chronic heart failure

Mechanical alternans has been observed in patients with severe congestive heart failure, and the phenomenon is considered to be a terminal sign. Therapeutic strategies for chronic heart failure have significantly developed, but it is uncertain whether patients with mechanical alternans can be effectively treated or not. Seventeen consecutive patients with dilated cardiomyopathy were enrolled: 11 were treated with beta-blockers on conventional therapeutic regimens and 6 patients were not indicated for or were unable to continue beta-blockade. Mechanical alternans was detected during cardiac catheterization in the patients under physiologic tachycardia (110 beats/min) and stepwise dobutamine loading. In the initial study, mechanical alternans occurred in 70.6% of the patients: 8 of the 11 being treated with beta-blockers and 4 of the 6 without beta-blockade therapy. In the second study, none of the patients taking beta-blockers showed mechanical alternans under the same protocol; the occurrence of mechanical alternans did not change in the patients who were not being treated with beta-blockers. The left ventricular ejection fraction increased in patients whose mechanical alternans could not be induced during the follow up, but decreased in the patients in whom mechanical alternans was repeatedly inducible. It is concluded that mechanical alternans is associated with the failing myocardium and may be potentially correctable.     

Electromechanical concordance in alternans during sustained tachycardias.

Electrical alternans and mechanical alternans are intriguing phenomena that have been reported to occur during tachycardias. Their precise pathophysiologic mechanism and in particular their interrelation have not been well defined. This report documents an unusual electromechanical concordance in alternans during sustained supraventricular tachycardia and ventricular tachycardia in two patients, raising interesting possibilities on the underlying mechanism of the concordant phenomena. The findings highlight the principle of excitation--contraction coupling of the heart.     

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.     

微伏级T波电交替的研究进展

T波电交替是心肌电活动不稳定的标志,可作为室性心律失常高危患者的危险分层,是人类及动物缺血心肌发生室性心动过速、心室颤动的标志,是发生恶性室性心律失常及心性猝死的无创预测指标。现结合文献对T波电交替的机制、检测方法、研究现状、适应证、临床意义及优缺点作一综述。     

Electrophysiology of T-wave alternans: Mechanisms and pharmacologic influences

Extensive experimental evidence indicates a fundamental link between T-wave alternans (TWA) and arrhythmogenesis. Diverse physiologic and pathophysiologic influences alter TWA magnitude in parallel with their effects on vulnerability to ventricular tachyarrhythmias. Specifically, interventions that impede intracellular calcium handling, such as elevated heart rate, heightened adrenergic activity, myocardial ischemia, and heart failure, predispose to greater levels of TWA, reflecting heightened risk for arrhythmias. Conversely, vagus nerve stimulation, blockade of beta-adrenergic receptors and late sodium and L-type calcium channels, and sympathetic denervation decrease TWA magnitude, reflecting the potential of these interventions to reduce risk for ventricular tachycardia and fibrillation. TWA thus appears able to detect the influence of pathophysiologically relevant triggers as well as the efficacy of antiarrhythmic drugs without reducing the predictive capacity of the phenomenon.     

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.     

Predicting the Recurrence of Ventricular Tachyarrhythmias from T‐Wave Alternans Assessed on Antiarrhythmic Pharmacotherapy: A Prospective Study in Patients with Dilated Cardiomyopathy

Background: Microvolt T‐wave alternans (TWA) has been proposed as a useful index to identify patients at risk of ventricular tachyarrhythmias. Recent studies have demonstrated that antiarrhythmic drugs, such as amiodarone and procainamide, decrease the prevalence of TWA. In this study, we tested whether TWA in patients on antiarrhythmic pharmacotherapy significantly predicts the recurrence of ventricular tachyarrhythmias in patients with dilated cardiomyopathy. Methods: To evaluate the ability to predict the recurrence of ventricular tachyarrhythmias, determinate TWA and left ventricular ejection fraction (LVEF) were prospectively assessed in 49 patients with ischemic or nonischemic dilated cardiomyopathy on antiarrhythmic pharmacotherapy for sustained ventricular tachycardia (VT) or ventricular fibrillation (VF). The pharmacotherapy consisted of class I (17 patients), III (29 patients), and IV (3 patients) antiarrhythmic drugs. The study endpoint was the first recurrence of sustained VT or VF on treatment during the follow‐up period. Results: TWA was positive on antiarrhythmic pharmacotherapy in 30 patients (61%). During a follow‐up of 13 ±; 11 months, the sustained VT or VF recurred in 21 of the 41 patients (51%) with available follow‐up data. The sensitivity of TWA and LVEF for predicting recurrence of ventricular tachyarrhythmias was 76 and 38%, specificity was 60 and 70%, positive predictive value was 67 and 57%, and negative predictive value was 71 and 52%. Kaplan‐Meier event‐free analysis revealed that TWA was a significant risk stratifier (P = 0.02), whereas LVEF was not. Conclusions: This prospective study suggests that TWA significantly predicts the recurrence of ventricular tachyarrhythmias, even on antiarrhythmic pharmacotherapy, in patients with dilated cardiomyopathy. TWA may also be a useful marker for evaluating the efficacy of antiarrhythmic drugs for ventricular tachyarrhythmias. A.N.E. 2001; 6(3):203–208     

Dobutamine as bridge to angiotensin-converting enzyme inhibitor-nitrate therapy in endstage heart failure

BACKGROUND: Intravenous inotropic intervention in congestive heart failure is generally associated with a poor prognosis and is largely used as a "bridge" to mechanical support or heart transplantation. HYPOTHESIS: We hypothesized that the inotropic support afforded by dobutamine may serve as a bridge to the introduction and intensification of angiotensin-converting enzyme (ACE) inhibitor-nitrate therapy. METHODS: We studied the efficacy of transitioning inotrope-dependent patients in endstage heart failure from intravenous dobutamine to high-dose ACE inhibitor-nitrates, with 1-year follow-up. Forty-nine sequential dobutamine-dependent patients with left ventricular ejection fraction (LVEF) 17+/-17% were treated with increasing lisinopril (1.9+/-1.5 to 46+/-28 mg/day) and isosorbide dinitrate (7+/-6 to 229+/-161 mg/day). Outpatient dobutamine was continued or repeat infusions pursued, as indicated, and dobutamine was tapered when feasible. RESULTS: During the following year, 14 of 49 patients required repeat dobutamine, with home treatment with dobutamine for 6.3+/-3.7 months (n = 5). At 1 year, New York Heart Association (NYHA) classification improved from 3.6+/-0.5 to 1.9+/-1.0, p < 0.0001; yearly hospitalizations fell from 2.7+/-2.3 to 1.2+/-3.0, p = 0.02; and LVEF rose from 17+/-7% to 24+/-11%, p < 0.0001. At 1 year, 14 patients who remained dobutamine dependent had significantly more severe symptoms than dobutamine-independent patients (n = 35). Transplant or death occurred in 7 of 14 patients with follow-up dobutamine, and in 5 of 35 patients free of subsequent dobutamine, p = 0.03. Patients with poor outcome (transplant n = 10, death n = 12) continued to be more limited (NYHA 2.7+/-0.9 vs. 1.7+/-0.9, p = 0.0002), with more follow-up hospitalizations (3.6+/-5.4 vs. 0.6+/-0.8, p = 0.0004), and no improvement in LVEF (17+/-8vs. 28+/-11%, p = 0.003). CONCLUSIONS: Of the patients on dobutamine inotropic support, 70% were successfully transitioned to ACE inhibitor-nitrate therapy, with improved symptoms and LVEF, and with reduced hospitalizations and follow-up dobutamine or transplant. Thirty percent of patients with continued need for dobutamine had a significantly poorer 1-year clinical outcome.     

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.     

健康人微伏级T波电交替试验检测分析

微伏级T波电交替 (MTWA)与器质性心脏病恶性室性心律失常的发生密切相关。T波电交替偶见于正常人运动时。本研究的目的是探讨正常人静息和运动时MTWA的发生情况。用CambridgeHeart.HeartwaveTMsys tem心脏诊断系统 ,以频谱法检测 4 5例健康志愿者MTWA。结果 :所有受试者静息时MTWA阴性。运动负荷试验时 ,非持续性MTWA 5例 (11.11% ) ,持续性MTWA 2例 (4.4 4 % ) ,1例阈值心率 <110次 /分 ,另一例发作心率>110次 /分。 4 5例中 ,MTWA阳性 1例 (2 .2 2 % ) ,但持续时间短暂 (1min) ,不确定性 2例 (4.4 4 % ) ,阴性 4 2例(93.33% )。结论 :健康人MTWA阳性发生率低 (2 .2 2 % ) ,短暂的MTWA无恶性室性心律失常的临床意义。     

The Effect of Procainamide on T Wave Alternans

INTRODUCTION: The measurement of microvolt level T wave alternans (TWA) is a technique for detecting arrhythmia vulnerability. Previous studies demonstrated that the magnitude of TWA is dependent on heart rate. However, the effects of antiarrhythmic drugs on TWA are unknown. METHODS AND RESULTS: This was a prospective evaluation of intravenous procainamide on TWA in 24 subjects with inducible sustained ventricular tachycardia (VT). Measurements of TWA were performed at baseline in the drug-free state and after procainamide loading (1,204+/-278 mg). Recordings were made in normal sinus rhythm, and during atrial pacing at 100 beats/min and 120 beats/min. The magnitude of TWA in the vector magnitude lead was decreased by procainamide at all heart rates: 0.6+/-0.8 to 0.3+/-0.4 microV in sinus rhythm, 2.0+/-1.6 to 0.7+/-0.7 microV at 100 beats/min, and 3.0+/-2.0 to 1.7+/-1.8 microV at 120 beats/min (P<0.001 by analysis of variance). The sensitivity of TWA for the induction of VT at baseline was 5% in sinus, 60% at 100 beats/min, and 87% at 120 beats/min, while it decreased with procainamide to 5%, 19%, and 60%, respectively. Decreases in TWA in response to procainamide were independent of the antiarrhythmic effects on VT inducibility. CONCLUSIONS: These results indicate that the magnitude of TWA decreases with acute procainamide loading and this effect decreases the sensitivity of TWA for the induction of sustained VT.     

Left ventricular inotropic reserve and right ventricular function predict increase of left ventricular ejection fraction after beta-blocker therapy in nonischemic cardiomyopathy.

OBJECTIVES: The purpose of this study was to determine whether higher left ventricular inotropic reserve, defined as the increase in left ventricular ejection fraction (LVEF) in response to intravenous dobutamine infusion, or other ventriculographic variables predict the increase in LVEF after beta-blocker therapy in patients with nonischemic cardiomyopathy (NICM). BACKGROUND: Long-term beta-blocker therapy increases LVEF in some patients with NICM. Other than dose, there are no definite predictors of LVEF increase. METHODS: Thirty patients with LVEF < or = 0.35 and NICM underwent assessment of LVEF at rest and after a 10-min intravenous infusion of dobutamine at 10 microg/kg/min, using equilibrium radionuclide ventriculography. Age was 49 +/- 11 years, 33% women, functional class 2.6 +/- 0.5, duration of chronic heart failure 3.2 +/- 2.9 years, LVEF 0.21 +/- 0.07, left ventricular end-diastolic volume index 180 +/- 64 ml/m2. Right ventricular ejection fraction (RVEF) was abnormal in 37%. Mean dobutamine-induced augmentation of LVEF (DoALVEF) was 0.12 +/- 0.08. Patients were started on one of three beta-blockers (carvedilol, bucindolol or metoprolol) and the dose was advanced to the maximum tolerated. RESULTS: Left ventricular ejection fraction, reassessed 7.4 +/- 5.9 months after maximum beta-blocker dose was reached, increased to 0.34 +/- 0.13 (p = 0.0006). The following baseline variables correlated with improvement of LVEF: DoALVEF (p = 0.001), RVEF (p = 0.005), systolic blood pressure at end of dobutamine infusion (p = 0.02) and dose of beta-blocker (p = 0.07). In a multivariate analysis, only DoALVEF (p = 0.0003) and RVEF (p = 0.002) were predictive of the increase in LVEF. CONCLUSIONS: Patients with nonischemic cardiomyopathy who have higher left ventricular inotropic reserve and normal RVEF derive higher increase in LVEF from beta-blocker therapy.     

Sleep disorders in systolic heart failure: a prospective study of 100 male patients. The final report

BACKGROUND: Heart failure is a highly prevalent disorder. The main aims of this study were to determine the prevalence, consequences and markers of sleep apnea and the periodic limb movements (PLMS) in heart failure. METHODS AND RESULTS: This is a prospective study of 100 of 114 consecutive eligible patients with heart failure and LVEF <45%. Forty-nine percent of patients had sleep apnea with an average index of 49 per hour. Thirty-seven percent of patients had CSA and 12% had OSA. Comparing patients with CSA to those without sleep apnea, the markers associated with CSA were poorer functional classification, atrial fibrillation, PaCO2 <36 mm Hg, LVEF <20%, and nocturnal ventricular arrhythmias including >30 PVC's, >1 couplets and >1 episodes of ventricular tachycardia/hour. In contrast, comparing heart failure patients with CSA to OSA, OSA patients were significantly obese (mean body weight 109+/-27 vs 78+/-18 kg) and had habitual snoring (83% vs 38%). Twenty percent of patient with heart failure had PLMS with an average index of 35 per hour. PLMS resulted in a mildly increased number of arousals (3.4+/-2 per hour). CONCLUSIONS: 49% of male patients with systolic heart failure suffer from sleep apnea and 20% have PLMS. CSA occurs in about 37%, and OSA in 12% of patients. Habitual snoring and obesity are the hallmarks of OSA. In contrast, heart failure patients with CSA are commonly thin and mostly do not snore. Hallmarks of CSA are Class III New York Heart, artrial fibrillation, frequent nocturnal ventricular arrhythmias, low arterial PCO2 and LVEF <20%.     

Electrical and mechanical alternans during ventricular tachycardia with moderate chronic heart failure

A chronic heart failure (CHF) rat underwent epicardial programmed electrical stimulation (PES). Ventricular tachycardia (VT) developed during PES. Mechanical alternans was noted despite fixed tachycardia cycle length. Anti-tachycardia pacing attempts initiated a second VT that generated pulse intermittently and then degenerated into pulseless VT with electrical alternans.To our knowledge electrical and mechanical alternans have not been recorded in animal models of CHF during VT. The distinct events of mechanical alternans and electrical alternans may be indicative of progressively worsened calcium handling in the compromised cardiomyocytes.Although ion channel differences between rodents and humans exist, this work attempts to demonstrate this rat model's usefulness in understanding cardiac electrophysiology in CHF.     

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.     

The Prevalence and the Prognostic Value of Microvolt T‐Wave Alternans in Patients with Hypertrophic Cardiomyopathy

Background: Nonsustained ventricular tachycardia (nVT) may have ominous implications for patients with hypertrophic cardiomyopathy (HCM). The microvolt T‐wave alternans (TWA) has been proposed as a noninvasive tool‐identifying patients at risk of sudden cardiac death and ventricular tachycardia/fibrillation (VT/VF). The aim of the study was to determine the significance of TWA in predicting nVT episodes and compare how other electrocardiographic parameters can predict the occurrence of nVT. Methods: The study group consisted of 88 patients with HCM. TWA was assessed during exercise test using the CH2000 system. All patients underwent Holter monitoring (HM) within 2–4 weeks before TWA test (preexercise HM1) and immediately after (postexercise HM2). During HM, we analyzed: arrhythmias, QT intervals, the presence of late ventricular potentials (LP), heart rate variability, heart rate turbulence. Results: Depending on TWA results, the patients were divided into two groups: TWA+; 46 patients (52.3%) with positive/indeterminate results, and TWA–; 42 patients (47.7%) with negative results. The nVT episodes were more frequent among TWA(+) both in HM1 and HM2. The presence of TWA increases the risk of postexercise nVT over twenty times (OR = 21.03). Moreover, in HM1, QTc and LP, and in HM2, again QTc and N‐terminal precursor of brain natriuretic peptide proved to be significant predictors of nVT. The addition of TWA to the models did not improve the arrhythmia risk assessment. Conclusions: Repolarization abnormality plays an important role in generating nVT in patients with HCM, but TWA does not specifically predict the risk of arrhythmic end point. Ann Noninvasive Electrocardiol 2011;16(3):276–286     

Detection of T-wave alternans using an implantable cardioverter-defibrillator

BACKGROUND: Microvolt T-wave alternans (TWA) increases acutely prior to ventricular tachycardia (VT) or ventricular fibrillation (VF) in computer simulations and animal models, suggesting that TWA may provide a warning for VT/VF in patients with an implantable cardioverter-defibrillator (ICD). OBJECTIVES: The purposes of this study were to develop a method for analyzing TWA recorded from ICD electrograms (EGMs) and to evaluate the degree of concordance between EGM TWA and TWA recorded from the surface ECG. METHODS: We developed a software program to measure EGM TWA in the frequency domain and then used simulated EGMs to determine the effects of ICD signal processing, electrical noise, and variation in the EGM fiducial point on the recorded amplitude and K score (signal-to-noise ratio) of TWA. We then applied this method to analyze TWA simultaneously using both surface ECGs and ICD EGMs during incremental pacing in 25 ICD patients. Pacing modes and EGM sources were varied in repeated trials. EGMs with dynamic range adjusted to achieve a large T wave were telemetered to a digital Holter recorder and measured offline. ECG TWA was analyzed using a commercial system. A positive (+) ECG test had sustained alternans >or=1.9 microV with K score >or=3. Stored EGMs were reviewed for VT/VF during a 6-month follow-up period. RESULTS: Simulations demonstrated that the EGM method accurately identified TWA >or=10 microV. Overall, 10 (40%) patients had at least one ECG TWA+ test and 15 patients (60%) had no ECG TWA+ tests. The maximum value of TWA was greater in EGMs than in ECGs (median 64 microV vs 2.2 microV, P <.0001). EGM TWA was greater in ECG TWA+ tests than in ECG TWA- tests (169 +/- 175 microV vs 71 +/- 61 microV, P <.001). Using a sustained EGM TWA threshold of 30 microV, EGM TWA was concordant with ECG TWA in 63 (84%) of 75 analyzed tests (P <.0001) and predicted ECG TWA results with 85% sensitivity and 84% specificity. Both ECG and EGM TWA predicted VT/VF during follow-up (ECG: P = .006; EGM: P = .035). CONCLUSION: The amplitude of TWA is at least 10 times greater on ICD EGMs than on surface ECGs. EGM and ECG TWA have substantial concordance and comparable predictive value for spontaneous VT/VF. These observations support the hypothesis that ECG and EGM TWA detect the same electrical alternans phenomenon.     

Risk stratification for sudden cardiac death in dilated cardiomyopathy using microvolt-level T-wave alternans

Predicting sudden cardiac death (SCD) in patients with dilated cardiomyopathy (DCM) is difficult, so the present study evaluated the efficacy of microvolt-level T-wave alternans (TWA) and compared it with conventional parameters for prospective risk stratification of SCD in patients with DCM. Eighty-two patients with DCM (53+/-15 years old, 67M/15F) underwent assessment of TWA, left ventricular end-diastolic diameter (LVDd), left ventricular ejection fraction (LVEF), signal-averaged ECG, and analysis of 24-h Holter monitoring and QT dispersion (QTd). The endpoint of the study was defined as either SCD or documented sustained ventricular tachycardia/ventricular fibrillation (SVT/VF) during the follow-up period. During an average follow-up period of 24 months, 1 patient died suddenly and 9 patients had SVT/VF. Kaplan-Meier survival analysis showed that TWA, LVEF (< or =35%), nonsustained ventricular tachycardia, and QTd (>90ms) were significant univariate risk stratifiers (p<0.005, p<0.005, p<0.005, and p<0.05, respectively). Multivariate Cox regression analysis showed that TWA and the LVEF were statistically significant independent risk stratifiers (p<0.05 and p<0.01, respectively). A combination of TWA and LVEF identified high risk DCM patients (p<0.01); TWA for the electrical substrate and the LVEF for the hemodynamic function.     

Role of structural barriers in the mechanism of alternans-induced reentry

Previously, using an animal model of T-wave alternans in structurally normal myocardium, we demonstrated that repolarization can alternate with opposite phase between neighboring myocytes (ie, discordant alternans), causing spatial dispersions of repolarization that form the substrate for functional block and reentrant ventricular fibrillation (VF). However, the mechanisms responsible for cellular discordant alternans and its electrocardiographic manifestation (ie, T-wave alternans) in patients with structural heart disease are unknown. We hypothesize that electrotonic uncoupling between neighboring regions of cells by a structural barrier (SB) is a mechanism for discordant alternans. Using voltage-sensitive dyes, ventricular action potentials were recorded from 26 Langendorff-perfused guinea pig hearts in the absence (ie, control) and presence of an insulating SB produced by an epicardial laser lesion. Quantitative analysis of magnitude and phase of cellular alternans revealed that in controls, action potential duration alternated in phase at all ventricular sites above a critical heart rate (269+/-17 bpm), ie, concordant alternans. Also, above a faster critical heart rate threshold (335+/-24 bpm), action potential duration alternated with opposite phase between sites, ie, discordant alternans. In contrast, only discordant but not concordant alternans was observed in 80% of hearts with the SB, and discordant alternans always occurred at a significantly slower heart rate (by 68+/-28 bpm) compared with controls. Therefore, the SB had a major effect on the alternans-heart rate relation, which served to facilitate the development of discordant alternans. Whether a SB was present or not, discordant alternans produced considerable increases (by approximately 170%) in the maximum spatial gradient of repolarization, which in turn formed the substrate for unidirectional block and reentry. However, by providing a structural anchor for stable reentry, discordant alternans in the presence of a SB led most often to sustained monomorphic ventricular tachycardia rather than to VF, whereas in the absence of a SB discordant alternans caused VF. SBs facilitate development of discordant alternans between cells with different ionic properties by electrotonically uncoupling neighboring regions of myocardium. This may explain why arrhythmia-prone patients with structural heart disease exhibit T-wave alternans at lower heart rates. These data also suggest a singular mechanism by which T-wave alternans forms a substrate for initiation of both VF and sustained monomorphic ventricular tachycardia.