doi:10.1002/ejhf.45 Online publish-ahead-of-print 14 December 2013
Microvolt T-wave alternans testing in patients recently hospitalized with decompensated heart failure: reply We appreciate the interest of DanilowiczSzymanowicz et al. in our study1 and are pleased to clarify the issues they raise. Our patients did not have acute heart failure (HF) and were stable at the time of microvolt T-wave alternans (MTWA) testing, having been discharged 4–6 weeks earlier. Only one patient eligible for MTWA testing was in NYHA class IV.2 Attributing cause of death in patients with HF is difficult, although contemporary studies in recently stabilized patients with HF and reduced LVEF suggest that around a third of deaths are sudden.3 This proportion is likely to be even higher in patients with preserved LVEF which were also included in our cohort. The frequency of indeterminate MTWA results in our study was not unusual and was similar to that (41%) in the MTWA substudy of the Sudden Cardiac Death in Heart Failure Trial (SCDHeFT).4 We did not withhold beta-blockers for a number of reasons. First, we wanted to evaluate the prognostic value of MTWA in patients taking evidence-based HF therapy, as any risk stratification test is only of clinical value if it is predictive in patients receiving optimal medical therapy. Secondly, while withholding beta-blockers may reduce the number of indeterminate tests due to failure to achieve the target heart rate, there is also a direct effect of beta-blockade on the magnitude of MTWA, potentially converting a positive to a negative result.5 Thirdly, and most importantly, interruption of beta-blocker therapy is potentially unsafe for patients with HF, and therefore unjustifiable.
We did not understand the point about the need for revascularization prior to MTWA testing, but none of our patients had HF secondary to an acute coronary syndrome and there was no other clinical indication for revascularization. Danilowicz-Szymanowicz and colleagues suggestion that the interpretation of indeterminate MTWA results depends on LVEF is based on a pooled analysis which included many patients that did not have HF.6 The finding from that analysis that indeterminate MTWA results are only associated with higher mortality rates when LVEF is ≤35% was not supported by our results. Although overall mortality rates were higher amongst patients with LVEF ≤35%, those with indeterminate results had proportionately more deaths than those with positive and negative results, across LVEF strata (50, 31, and 43% for LVEF ≤35%, and 36, 24 and 30% for LVEF >35%, for indeterminate, positive and negative results, respectively). Paradoxically, mortality rates were lowest for patients with positive MTWA results. Danilowicz-Szymanowicz et al. conclude that the patients we studied were not appropriate for MTWA-based risk stratification. We disagree—we aimed to assess the applicability and prognostic value of MTWA testing in a real-life unselected population of patients with HF, not investigated in previous studies. We acknowledged that not all our patients were candidates for a primary prevention implantable cardioverter defibrillator (ICD), but that specific population had been investigated in the MTWA substudy of SCDHeFT, which also found that MTWA testing failed to predict arrhythmic events or mortality. Our study provides clear evidence that in patients with HF, MTWA testing does not predict mortality and so cannot be recommended as a risk stratification tool.
Conlict of interest: none declared.
© 2013 The Authors European Journal of Heart Failure © 2013 European Society of Cardiology
................................................................................................................................................................
................................................................................................................................................................
CORRESPONDENCE
References 1. Jackson CE, Myles RC, Tsorlalis IK, Dalzell JR, Rocchiccioli JP, Rodgers JR, Spooner RJ, Greenlaw N, Ford I, Gardner RS, Cobbe SM, Petrie MC, McMurray JJ. Spectral microvolt T-wave alternans testing has no prognostic value in patients recently hospitalized with decompensated heart failure. Eur J Heart Fail 2013;15:1253–1261. 2. Jackson CE, Myles RC, Tsorlalis IK, Dalzell JR, Spooner RJ, Rodgers JR, Bezlyak V, Greenlaw N, Ford I, Cobbe SM, Petrie MC, McMurray JJ. Profile of microvolt T-wave alternans testing in 1003 patients hospitalized with heart failure. Eur J Heart Fail 2012;14:377–386. 3. Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, Vincent J, Pocock SJ, Pitt B, EMPHASIS-HF Study Group. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 2011;364:11–21. 4. Gold MR, Ip JH, Constantini O, Poole JE, McNulty S, Mark DB, Lee KL, Bardy GH. Role of microvolt Twave alternans in assessment of arrhythmia vulnerability among patients with heart failure and systolic dysfunction. Circulation 2008;118:2022–2028. 5. Klingenheben T, Gronefiled G, Li YG, Hohnloser SH. Effect of metoprolol and d,l-sotalol on microvolt T-wave alternans. Results of a prospective, double-blind, randomized study. J Am Coll Cardiol 2001;38:2013–2019. 6. Merchant FM, Ikeda T, Pedretti RF, Salerno-Uriarte JA, Chow T, Chan PS, Bartone C, Hohnloser SH, Cohen RJ, Armoundas AA. Clinical utility of microvolt T-wave alternans testing in identifying patients at high or low risk of sudden cardiac death. Heart Rhythm 2012;9:1256–1264.
Colette E. Jackson BHF Cardiovascular Research Centre 126 University Place Glasgow G12 8TA UK Email: [email protected] Rachel C. Myles BHF Cardiovascular Research Centre 126 University Place Glasgow G12 8TA UK John J.V. McMurray BHF Cardiovascular Research Centre 126 University Place Glasgow G12 8TA UK
Microvolt T-wave alternans testing in patients recently hospitalized with decompensated heart failure: reply We appreciate the interest of DanilowiczSzymanowicz et al. in our study1 and are pleased to clarify the issues they raise. Our patients did not have acute heart failure (HF) and were stable at the time of microvolt T-wave alternans (MTWA) testing, having been discharged 4–6 weeks earlier. Only one patient eligible for MTWA testing was in NYHA class IV.2 Attributing cause of death in patients with HF is difficult, although contemporary studies in recently stabilized patients with HF and reduced LVEF suggest that around a third of deaths are sudden.3 This proportion is likely to be even higher in patients with preserved LVEF which were also included in our cohort. The frequency of indeterminate MTWA results in our study was not unusual and was similar to that (41%) in the MTWA substudy of the Sudden Cardiac Death in Heart Failure Trial (SCDHeFT).4 We did not withhold beta-blockers for a number of reasons. First, we wanted to evaluate the prognostic value of MTWA in patients taking evidence-based HF therapy, as any risk stratification test is only of clinical value if it is predictive in patients receiving optimal medical therapy. Secondly, while withholding beta-blockers may reduce the number of indeterminate tests due to failure to achieve the target heart rate, there is also a direct effect of beta-blockade on the magnitude of MTWA, potentially converting a positive to a negative result.5 Thirdly, and most importantly, interruption of beta-blocker therapy is potentially unsafe for patients with HF, and therefore unjustifiable.
We did not understand the point about the need for revascularization prior to MTWA testing, but none of our patients had HF secondary to an acute coronary syndrome and there was no other clinical indication for revascularization. Danilowicz-Szymanowicz and colleagues suggestion that the interpretation of indeterminate MTWA results depends on LVEF is based on a pooled analysis which included many patients that did not have HF.6 The finding from that analysis that indeterminate MTWA results are only associated with higher mortality rates when LVEF is ≤35% was not supported by our results. Although overall mortality rates were higher amongst patients with LVEF ≤35%, those with indeterminate results had proportionately more deaths than those with positive and negative results, across LVEF strata (50, 31, and 43% for LVEF ≤35%, and 36, 24 and 30% for LVEF >35%, for indeterminate, positive and negative results, respectively). Paradoxically, mortality rates were lowest for patients with positive MTWA results. Danilowicz-Szymanowicz et al. conclude that the patients we studied were not appropriate for MTWA-based risk stratification. We disagree—we aimed to assess the applicability and prognostic value of MTWA testing in a real-life unselected population of patients with HF, not investigated in previous studies. We acknowledged that not all our patients were candidates for a primary prevention implantable cardioverter defibrillator (ICD), but that specific population had been investigated in the MTWA substudy of SCDHeFT, which also found that MTWA testing failed to predict arrhythmic events or mortality. Our study provides clear evidence that in patients with HF, MTWA testing does not predict mortality and so cannot be recommended as a risk stratification tool.
Conlict of interest: none declared.
© 2013 The Authors European Journal of Heart Failure © 2013 European Society of Cardiology
................................................................................................................................................................
................................................................................................................................................................
CORRESPONDENCE
References 1. Jackson CE, Myles RC, Tsorlalis IK, Dalzell JR, Rocchiccioli JP, Rodgers JR, Spooner RJ, Greenlaw N, Ford I, Gardner RS, Cobbe SM, Petrie MC, McMurray JJ. Spectral microvolt T-wave alternans testing has no prognostic value in patients recently hospitalized with decompensated heart failure. Eur J Heart Fail 2013;15:1253–1261. 2. Jackson CE, Myles RC, Tsorlalis IK, Dalzell JR, Spooner RJ, Rodgers JR, Bezlyak V, Greenlaw N, Ford I, Cobbe SM, Petrie MC, McMurray JJ. Profile of microvolt T-wave alternans testing in 1003 patients hospitalized with heart failure. Eur J Heart Fail 2012;14:377–386. 3. Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, Vincent J, Pocock SJ, Pitt B, EMPHASIS-HF Study Group. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 2011;364:11–21. 4. Gold MR, Ip JH, Constantini O, Poole JE, McNulty S, Mark DB, Lee KL, Bardy GH. Role of microvolt Twave alternans in assessment of arrhythmia vulnerability among patients with heart failure and systolic dysfunction. Circulation 2008;118:2022–2028. 5. Klingenheben T, Gronefiled G, Li YG, Hohnloser SH. Effect of metoprolol and d,l-sotalol on microvolt T-wave alternans. Results of a prospective, double-blind, randomized study. J Am Coll Cardiol 2001;38:2013–2019. 6. Merchant FM, Ikeda T, Pedretti RF, Salerno-Uriarte JA, Chow T, Chan PS, Bartone C, Hohnloser SH, Cohen RJ, Armoundas AA. Clinical utility of microvolt T-wave alternans testing in identifying patients at high or low risk of sudden cardiac death. Heart Rhythm 2012;9:1256–1264.
Colette E. Jackson BHF Cardiovascular Research Centre 126 University Place Glasgow G12 8TA UK Email: [email protected] Rachel C. Myles BHF Cardiovascular Research Centre 126 University Place Glasgow G12 8TA UK John J.V. McMurray BHF Cardiovascular Research Centre 126 University Place Glasgow G12 8TA UK
