Jackson, Colette Elizabeth
Microvolt T-wave alternans in chronic heart failure: a study of prevalence and incremental prognostic value.
PhD thesis, University of Glasgow.
Patients with heart failure (HF) are at risk of sudden cardiac death (SCD). Most SCD is caused by ventricular tachyarrhythmias events (VTE) that can be treated with an implantable cardioverter-defibrillator (ICD). Identifying patients at risk of VTE remains a clinical challenge. The microvolt T-wave alternans (MTWA) test examines beat-to-beat fluctuations in the morphology of the electrocardiographic T-wave. The presence of significant alternans is thought to reflect dynamic instability of repolarisation and be mechanistically linked to VTE. Observational studies in highly selected populations have suggested that MTWA testing may be used as a non-invasive tool for identifying patients at risk of VTE who, by implication, may benefit from primary prevention ICD therapy. However, to date, no study has investigated the use of MTWA testing in a real-life population of patients with HF. The main aims of this study were to evaluate the applicability of MTWA testing in an unselected cohort of patients with HF receiving contemporary pharmacological therapy and determine the prevalence and incremental prognostic value of this test. Between 1st December 2006 and 12th January 2009, 1003 patients hospitalised with decompensated HF were recruited. 648 patients returned for MTWA testing one month following hospital discharge. The mean age of those returning for MTWA testing was 70.8 years (SD 10.6) and 58% were male. 318 patients (49%) were ineligible for MTWA testing due to atrial fibrillation (AF), pacemaker-dependency or physical inability to undertake the treadmill test. Of 330 patients who underwent MTWA treadmill testing, 100 (30%) were positive, 78 (24%) were negative and 152 (46%) were indeterminate. The majority of indeterminate tests (75%) occurred because of failure to achieve the target heart rate due to chronotropic incompetence, secondary to beta-blocker therapy or physical limitations. There were more abnormal clinical characteristics associated with an indeterminate result, than a positive or negative result. There was no significant difference in crude all-cause mortality rates between the three MTWA groups. MTWA was analysed in the accepted way of non-negative (positive and indeterminate) and negative, but this did not alter the results. MTWA had no incremental prognostic value when added to a multivariable model containing the strongest predictors of mortality in this study. The independent predictors of all-cause mortality following stepwise multivariable modelling were; lower body mass index, New York Heart Association class III-IV, previous myocardial infarction, elevated B-type natriuretic peptide concentration and elevated troponin levels. In summary, MTWA treadmill-testing was not widely applicable in typical patients with HF and failed to predict mortality risk. At present MTWA cannot be endorsed as a tool for improving risk stratification in HF.