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EXPEDITED PUBLICATION

Prognostic Value of T-Wave Alternans in Patients With Heart Failure Due to Nonischemic Cardiomyopathy

Results of the ALPHA Study

Jorge A. Salerno-Uriarte, MD^_*,_*, Gaetano M. De Ferrari, MD, Catherine Klersy, MD, Roberto F.E. Pedretti, MD, Massimo Tritto, MD^||, Luciano Sallusti, BS^¶, Luigi Libero, MD^#, Giacinto Pettinati, MD^_**, Giulio Molon, MD, Antonio Curnis, MD, Eraldo Occhetta, MD, Fabrizio Morandi, MD^_*, Paolo Ferrero, MD^#, Francesco Accardi, BS^¶ for the ALPHA Study Group Investigators

^_* Dipartimento di Scienze Cardiovascolari, Università degli Studi dell’Insubria, Ospedale di Circolo e Fondazione Macchi, Varese, Italy
Dipartimento di Cardiologia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
Servizio di Biometria ed Epidemiologia Clinica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
Divisione di Cardiologia, IRCCS Fondazione Salvatore Maugeri, Istituto Scientifico, Tradate, Italy
^|| Laboratorio di Elettrofisiologia, Dipartimento di Cardiologia, Istituto Clinico Mater Domini, Castellanza, Italy
^¶ Dipartimento Clinico, Guidant Italia (Boston Scientific Corporation), Milano, Italy
^# Divisione Universitaria di Cardiologia, Università degli Studi di Torino, Azienda Ospedaliera San Giovanni Battista, Torino, Italy
^_** Divisione di Cardiologia, Presidio Ospedaliero F. Ferrari, Casarano, Italy
Divisione di Cardiologia, Ospedale Sacro Cuore, Negrar, Italy
Unità Operativa di Cardiologia, Università degli Studi di Brescia, Spedali Civili, Brescia, Italy
1° Divisione di Cardiologia, Università degli Studi del Piemonte Orientale, Ospedale Maggiore, Novara, Italy.

Manuscript received May 15, 2007; revised manuscript received August 9, 2007, accepted September 7, 2007.

^_* Reprint requests and correspondence: Prof. Jorge A. Salerno-Uriarte, Department of Cardiological Science, Ospedale di Circolo e Fondazione Macchi, Universitá dell’Insubria, Viale Borri 57, 21100 Varese, Italy. (Email: jorge.salerno{at}ospedale.varese.it).

The main data were presented at the Late-Breaking Clinical Trial Session I of the American College of Cardiology 56th Scientific Session, March 25, 2007, New Orleans, Louisiana.

Objectives: The aim of this study was to assess the prognostic value of T-wave alternans (TWA) in New York Heart Association (NYHA) functional class II/III patients with nonischemic cardiomyopathy and left ventricular ejection fraction (LVEF) 40%.

Background: There is a strong need to identify reliable risk stratifiers among heart failure candidates for implantable cardioverter-defibrillator (ICD) prophylaxis. T-wave alternans may identify low-risk subjects among post-myocardial infarction patients with depressed LVEF, but its predictive role in nonischemic cardiomyopathy is unclear.

Methods: Four hundred forty-six patients were enrolled and followed up for 18 to 24 months. The primary end point was the combination of cardiac death + life-threatening arrhythmias; secondary end points were total mortality and the combination of arrhythmic death + life-threatening arrhythmias.

Results: Patients with abnormal TWA (65%) compared with normal TWA (35%) tests were older (60 ± 13 years vs. 57 ± 12 years), were more frequently in NYHA functional class III (22% vs. 19%), and had a modestly lower LVEF (29 ± 7% vs. 31 ± 7%). Primary end point rates in patients with abnormal and normal TWA tests were 6.5% (95% confidence interval [CI] 4.5% to 9.4%) and 1.6% (95% CI 0.6% to 4.4%), respectively. Unadjusted and adjusted hazard ratios were 4.0 (95% CI 1.4% to 11.4%; p = 0.002) and 3.2 (95% CI 1.1% to 9.2%; p = 0.013), respectively. Hazard ratios for total mortality and for arrhythmic death + life-threatening arrhythmias were 4.6 (p = 0.002) and 5.5 (p = 0.004), respectively; 18-month negative predictive values for the 3 end points ranged between 97.3% and 98.6%.

Conclusions: Among NYHA functional class II/III nonischemic cardiomyopathy patients, an abnormal TWA test is associated with a 4-fold higher risk of cardiac death and life-threatening arrhythmias. Patients with normal TWA tests have a very good prognosis and are likely to benefit little from ICD therapy.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   CI = confidence interval   CRT = cardiac resynchronization therapy   HR = hazard ratio   ICD = implantable cardioverter-defibrillator   LVEF = left ventricular ejection fraction   NPV = negative predictive value   NYHA = New York Heart Association   PPV = positive predictive value   TWA = T-wave alternans   VF = ventricular fibrillation   VT = ventricular tachycardia

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