International Journal of Cardiology 176 (2014) 1294–1296
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Microvolt T-wave alternans profile in patients with pulmonary arterial hypertension Ewa Lewicka a,⁎, Ludmiła Daniłowicz-Szymanowicz a, Alicja Dąbrowska-Kugacka a, Bożena Zięba b, Paweł Zagożdżon c, Grzegorz Raczak a a b c
Department of Cardiology and Electrotherapy, Medical University of Gdańsk, Poland Department of Cardiology, Medical University of Gdańsk, Poland Department of Hygiene and Epidemiology, Medical University of Gdańsk, Poland
a r t i c l e
i n f o
Article history: Received 11 June 2014 Accepted 27 July 2014 Available online 5 August 2014 Keywords: Pulmonary arterial hypertension Heart failure Microvolt T-wave alternans Global longitudinal strain
Pulmonary arterial hypertension (PAH) is a devastating disease with poor prognosis. Despite novel medical therapies targeting PAH pathophysiology, right ventricular (RV) failure and sudden cardiac death account for the majority of deaths in these patients [1,2]. There are a number of indicators used for assessing the course of the disease and patient prognosis [3,4] but there is still a need for identification of non-invasive risk markers for predicting patient outcome. Microvolt Twave alternans (MTWA) is a well-known non-invasive predictor of ventricular arrhythmias in patients with cardiomyopathies of various etiologies [5,6]. Benoist et al. [7] reported on increased probability of alternans in experimental rat model of RV failure induced by pulmonary hypertension, but MTWA has not been explored in patients with RV failure, especially those with PAH. We aimed to investigate MTWA in an unselected population of PAH patients and evaluate the clinical characteristics associated with MTWA results. This was a prospective study enrolling consecutive patients treated in our center in whom a diagnosis of PAH had been established by echocardiography and right heart catheterization, after exclusion of pulmonary and thromboembolic diseases. In all patients 6-minute walk test, echocardiography, cardiopulmonary exercise test, laboratory tests and MTWA testing were obtained. The study protocol was ⁎ Corresponding author at: Department of Cardiology and Electrotherapy, Medical University of Gdansk, Debinki 7, 80-952 Gdańsk, Poland. Tel.: + 48 58 349 39 10; fax: +48 58 349 39 20. E-mail address: [email protected] (E. Lewicka).
http://dx.doi.org/10.1016/j.ijcard.2014.07.173 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
approved by the local ethical committee and all patients gave written informed consent to participation in the study. Echocardiography (Vivid E9, GE Healthcare, Horten, Norway) aimed to assess left ventricular (LV) and RV function. The LV ejection fraction (LVEF) was calculated using Simpson's biplane method. Depthadjusted two-dimensional (2D) LV images were acquired from the apical 2-, 3- and 4-chamber views for off-line (EchoPAC version BT12, GE Healthcare) measurement of LV global longitudinal strain (LV GLS) by means of 2D speckle-tracking. Cardiopulmonary exercise test was performed using cycloergometer (Lode Corival, Lode B.V. Netherlands) starting at 20 W with a constant (ramp) increment of 10 W/min. Oxygen uptake, carbon dioxide output, expiratory gas concentrations throughout the respiratory cycle, and minute ventilation were continuously measured on a breath-by-breath basis using Cortex equipment with Metasoft 3.9 software (BiophisikGmbh, Germany). To be eligible for MTWA testing patients had to be in sinus rhythm, with no ventricular pacing. All prescribed medications were continued prior the testing. Treadmill exercise test was performed following the protocol for MTWA testing, and MTWA was analyzed using the analytic spectral method (CH2000 system, Cambridge Heart, Bedford MA, USA). Standard criteria were used in the interpretation of the tests [8]. Results were classified as positive, negative or indeterminate. Differences between the groups with positive and negative MTWA result were examined by the Kruskall–Wallis, one-way ANOVA or chisquare test. A ROC analysis and Cox proportional hazard models were used, but LVEF showing co-linearity with LV GLS was not taken into consideration in multivariate analysis. P b 0.05 was considered significant. STATA software (version 12.1, STATACorp) was used to calculate statistics. Clinical and echocardiographic characteristics of 33 patients enrolled to the study at the time of MTWA assessment are shown in Tables 1 and 2. All but 8 patients were on PAH-specific therapy (bosentan, sildenafil, iloprost or treprostinil). We found a significant amount of positive MTWA results — in 67% of patients. Moreover, the incidence of indeterminate MTWA results was low — in 9% of patients (due to limited physical capability or chronotropic incompetence preventing to obtain the target heart rate). MTWA test was negative in 24% of patients. Data according to MTWA results are presented in Tables 1 and 2. All patients showed symptoms of moderate-to-severe
E. Lewicka et al. / International Journal of Cardiology 176 (2014) 1294–1296
1295
Table 1 Clinical characteristics of patients with pulmonary arterial hypertension (PAH) according to a microvolt T-wave alternans (MTWA) result. MTWA negative (n = 8)
MTWA positive (n = 22)
MTWA indeterminate (n = 3)
Overall (n = 33)
pa
Age (years) Females (n) Idiopathic PAH (n) Connective tissue disease (n) Eisenmenger syndrome (n) History of syncope (n/%) WHO functional class BNP (pg/ml) 6 minute walk test (m)
36 ± 14 8 2 0 6 2(25) 2.6 ± 0.4 (2–3) 46 ± 40 385 ± 145
37 ± 16 11 9 2 11 6(27) 2.8 ± 0.4 (2–3.5) 222 ± 183 416 ± 100
56 ± 10 3 0 1 2 1(33) 3.2 ± 0.6 (2.5–3.5) 1675 ± 1712 220 ± 162
38 ± 16 22(67%) 11(33%) 3(9%) 19(58%) 9(27) 2.7 ± 0.5 (2–3.5) 314 ± 644 389 ± 128
0.9 0.7 0.7 1.0 0.4 1.0 0.9 0.01 0.5
Cardiopulmonary exercise test VO2peak (ml/kg/min) VO2AT (ml/kg/min) VE/VCO2 slope SBP max (mm Hg) PAH-specific treatment at time of MTWA test (n/%)
10.9 ± 3 7.8 ± 1.8 44 ± 8 125 ± 17 6(75)
11 ± 2.5 8 ± 2.7 46 ± 15 133 ± 23 17(77)
10 ± 1 9±1 39 ± 11 133 ± 38 2(67)
10.9 ± 2.5 8 ± 2.4 46 ± 13 131 ± 22 25(76)
0.9 0.8 0.8 0.4 1.0
3 1 1 1 0 3 17.7 ± 11 1.6 ± 0.8
12 0 1 4 2 8 7.4 ± 19.3 1.5 ± 0.7
3 0 1 3 1 3 2.4 ± 3.9 1.2 ± 0.5
18(54%) 1(3%) 3(9%) 8(24%) 3(9%) 14(42%) 9.5 ± 10 1.8 ± 0.8
0.7 0.3 0.5 1.0 1.0 1.0 0.008 0.7
Conventional therapy at time of MTWA test (n) Diuretics Calcium channel blocker Digitalis B-blocker ACEI/ARB Warfarin Time from RHC that revealed PAH (years) Follow-up (years)
VO2peak—peak O2 uptake, VO2AT—O2 uptake measured at anaerobic threshold, VE/VCO2—ventilatory equivalent for VCO2, O2Sat—oxygen saturation, SBP max—peak systolic arterial pressure, BNP—brain natriuretic peptide, ACEI—angiotensin-converting enzyme inhibitor, ARB—angiotensin receptor blocker, RHC—right heart catheterization. a MTWA positive vs. MTWA negative.
heart failure, and echocardiography revealed significant RV involvement in PAH, as our patients presented with severe RV hypertrophy and dilatation. Table 2 Echocardiographic data according to a microvolt T-wave alternans (MTWA) result. Variables
MTWA negative (n = 8)
MTWA positive (n = 22)
Overall MTWA indeterminate (n = 33) (n = 3)
pa
RVEDD (mm) RVWT (mm) RV:LV Right atrial area (cm2) Tricuspid regurgitant velocity (cm/s) RVSP (mm Hg) TAPSE (mm) S′ (cm/s) RVFAC (%) IVC Tacc (m/s2) LVEF (%) LVESD (mm) LVEDD (mm) LVESV (ml) LVEDV (ml) IVS (mm) PWD (mm) LV GLS (%) Pericardial effusion (n)
37 ± 4 9.8 ± 2 1.2 ± 0.2 16 ± 4
46 ± 13 10 ± 2 1.3 ± 0.5 22 ± 9
51 ± 4 10 ± 3 1.9 ± 0.5 32 ± 3
44 ± 12 10 ± 2 1.3 ± 0.4 22 ± 8
0.07 0.6 0.6 0.09
4.1 ± 0.7
4.5 ± 0.8
4.7 ± 0.6
4.4 ± 0.8
0.3
81 ± 24 18 ± 4 11.2 ± 2.3 40 ± 7 2.5 ± 1.5 65 ± 5 22 ± 5 38 ± 5 18 ± 12 51 ± 25 11 ± 2 9±1 −20 ± 2.1 3
92 ± 28 17 ± 7 11.2 ± 3.9 32 ± 10 2.6 ± 1.1 56 ± 9 29 ± 9 44 ± 4 34 ± 23 78 ± 43 11 ± 2 11 ± 2 −15 ± 3.4 6
99 ± 24 12 ± 3 10.4 ± 3.9 31 ± 13 2.6 ± 1.1 56 ± 4 17 ± 1 31 ± 3 14 ± 4 35 ± 12 12 ± 2 11 ± 1 −14 ± 1.4 1
90 ± 26 17 ± 6 11.1 ± 3.5 34 ± 10 2.6 ± 1.2 58 ± 8 26 ± 8 41 ± 8 28 ± 21 67 ± 39 11 ± 2 11 ± 2 −16 ± 3.6 10(30%)
0.3 0.6 1.0 0.06 0.9 0.007 0.06 0.04 0.08 0.1 0.7 0.04 0.003 0.7
RVEDD—right ventricular (RV) end-diastolic diameter in the apical 4-chamber view, RVWT—RV wall thickness, RV:LV—the ratio of RVEDD to LVEDD (measured in the 4chamber apical view), RVSP—RV systolic pressure, TAPSE—tricuspid annular plane systolic excursion, S′—tissue Doppler-derived tricuspid lateral annular systolic velocity, RVFAC— RV fractional area change, LVEF—left ventricular (LV) ejection fraction, LVESD—LV endsystolic diameter, LVEDD—LV end-diastolic diameter, IVS—interventricular septum thickness, PWD—posterior wall thickness, IVC Tacc—tissue Doppler-derived time of acceleration of isovolumic contraction, LV GLS—left ventricular global longitudinal strain. a MTWA positive vs. MTWA negative.
In patients with ischemic heart disease, heart failure or nonischemic cardiomyopathy MTWA reflects spatio-temporal heterogeneity of LV myocardium during repolarization, where the RV mass is small compared with the opposite ventricle and contributes little to the formation of T-wave. But in PAH patients, not only the LV, but also the RV must be concerned with the T-wave form because of the RV hypertrophy and thus possible MTWA phenomenon. Thus, one could expect that electrical instability, if recognized by MTWA, would represent heterogeneous repolarization of hypertrophied RV. But we found that mainly the poorer LV, and only to a lesser degree the poorer RV function, was associated with a positive MTWA result. By univariate logistic regression analysis LVEF and LV GLS showed a significant association with positive MTWA result, and LV GLS was an independent predictor by multivariate analysis. The area under the curve for LV GLS was 0.88 (95% confidence interval 0.74–1.00) and a cut-off value of ≥−17.6% showed a sensitivity and specificity of 81% and 86% to predict a positive MTWA result. This observation is in agreement with studies showing that changes in the RV structure and function affect also the LV. As the RV function deteriorates, it leads to increase in the RV contraction time and subsequently ventricular asynchrony, which together with a decline in the RV stroke volume impedes the LV diastolic filling [9,10]. Another important factor leading to the LV underfilling is the paradoxical movement of interventricular septum, when due to the RV pressure overload the septum flattens or even bulges to the LV in early diastole [9]. During the mean 1.8-year follow-up 3 patients died: 1 with MTWA positive (sudden cardiac death), and 2 patients with an indeterminate MTWA result (both due to right heart failure). However, as our population size was small and mortality rate was low we were unable to explore the prognostic significance of MTWA testing. This is the first study assessing factors that influence MTWA results in patients with PAH. We conclude that there is high incidence of positive MTWA tests in these patients. Despite normal LVEF, the LV GLS is significantly lower in patients with positive MTWA. The hypothesis, that positive MTWA test might indicate the presence of latent LV
1296
E. Lewicka et al. / International Journal of Cardiology 176 (2014) 1294–1296
dysfunction in PAH patients needs to be verified. Further research in larger populations is required to establish clinical implications of MTWA in PAH, and if its result predicts arrhythmic or cardiovascular mortality in these patients. Conflict of interest The authors declare no conflict of interests and report no relationships that could be construed as a conflict of interest. References [1] Tateno S, Niwa K, Nakazawa M, et al. Risk factors for arrhythmia and late death in patients with right ventricle to pulmonary artery conduit repair—Japanese multicenter study. Int J Cardiol 2006;106(3):373–81. [2] Humbert M. A critical analysis of survival in idiopathic pulmonary arterial hypertension. Presse Med 2010;39(Suppl. 1):IS41–5. [3] Humbert M, Sitbon O, Chaouat A, et al. Survival in patients with idiopathic, familial, anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation 2010;122(2):156–63.
[4] Howard L. Prognostic factors in pulmonary arterial hypertension: assessing the course of the disease. Eur Respir Rev 2011;20(122):236–42. [5] Chow T, Kereiakes DJ, Bartone C, et al. Prognostic utility of microvolt T-wave alternans in risk stratification of patients with ischemic cardiomyopathy. J Am Coll Cardiol 2006;47(9):1820–7. [6] Gupta A, Hoang D, Karliner L, et al. Ability of microvolt T-wave alternans to modify risk assessment of ventricular tachyarrhythmic events: a meta-analysis. Am Heart J 2012;163(3):354–64. [7] Benoist D, Stones R, Drinkhill M, et al. Cardiac arrhythmia mechanisms in rats with heart failure induced by pulmonary hypertension. Am J Physiol Heart Circ Physiol 2012;302(11):H2381–95. [8] Bloomfield DM, Hohnloser SH, Cohen RJ. Interpretation and classification of microvolt T wave alternans tests. J Cardiovasc Electrophysiol 2002;13(5):502–12. [9] Marcus J, Gan C, Zwanenburg J, et al. Interventricular mechanical asynchrony in pulmonary arterial hypertension: left-to-right delay in peak shortening is related to right ventricular overload and left ventricular underfilling. J Am Coll Cardiol 2008;51(7):750–7. [10] Mauritz G, Marcus J, Westerhof N, Postmus P, Vonk-Noordegraaf A. Prolonged right ventricular post-systolic isovolumic period in pulmonary arterial hypertension is not a reflection of diastolic dysfunction. Heart 2011;97(6):473–8.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Microvolt T-wave alternans profile in patients with pulmonary arterial hypertension Ewa Lewicka a,⁎, Ludmiła Daniłowicz-Szymanowicz a, Alicja Dąbrowska-Kugacka a, Bożena Zięba b, Paweł Zagożdżon c, Grzegorz Raczak a a b c
Department of Cardiology and Electrotherapy, Medical University of Gdańsk, Poland Department of Cardiology, Medical University of Gdańsk, Poland Department of Hygiene and Epidemiology, Medical University of Gdańsk, Poland
a r t i c l e
i n f o
Article history: Received 11 June 2014 Accepted 27 July 2014 Available online 5 August 2014 Keywords: Pulmonary arterial hypertension Heart failure Microvolt T-wave alternans Global longitudinal strain
Pulmonary arterial hypertension (PAH) is a devastating disease with poor prognosis. Despite novel medical therapies targeting PAH pathophysiology, right ventricular (RV) failure and sudden cardiac death account for the majority of deaths in these patients [1,2]. There are a number of indicators used for assessing the course of the disease and patient prognosis [3,4] but there is still a need for identification of non-invasive risk markers for predicting patient outcome. Microvolt Twave alternans (MTWA) is a well-known non-invasive predictor of ventricular arrhythmias in patients with cardiomyopathies of various etiologies [5,6]. Benoist et al. [7] reported on increased probability of alternans in experimental rat model of RV failure induced by pulmonary hypertension, but MTWA has not been explored in patients with RV failure, especially those with PAH. We aimed to investigate MTWA in an unselected population of PAH patients and evaluate the clinical characteristics associated with MTWA results. This was a prospective study enrolling consecutive patients treated in our center in whom a diagnosis of PAH had been established by echocardiography and right heart catheterization, after exclusion of pulmonary and thromboembolic diseases. In all patients 6-minute walk test, echocardiography, cardiopulmonary exercise test, laboratory tests and MTWA testing were obtained. The study protocol was ⁎ Corresponding author at: Department of Cardiology and Electrotherapy, Medical University of Gdansk, Debinki 7, 80-952 Gdańsk, Poland. Tel.: + 48 58 349 39 10; fax: +48 58 349 39 20. E-mail address: [email protected] (E. Lewicka).
http://dx.doi.org/10.1016/j.ijcard.2014.07.173 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
approved by the local ethical committee and all patients gave written informed consent to participation in the study. Echocardiography (Vivid E9, GE Healthcare, Horten, Norway) aimed to assess left ventricular (LV) and RV function. The LV ejection fraction (LVEF) was calculated using Simpson's biplane method. Depthadjusted two-dimensional (2D) LV images were acquired from the apical 2-, 3- and 4-chamber views for off-line (EchoPAC version BT12, GE Healthcare) measurement of LV global longitudinal strain (LV GLS) by means of 2D speckle-tracking. Cardiopulmonary exercise test was performed using cycloergometer (Lode Corival, Lode B.V. Netherlands) starting at 20 W with a constant (ramp) increment of 10 W/min. Oxygen uptake, carbon dioxide output, expiratory gas concentrations throughout the respiratory cycle, and minute ventilation were continuously measured on a breath-by-breath basis using Cortex equipment with Metasoft 3.9 software (BiophisikGmbh, Germany). To be eligible for MTWA testing patients had to be in sinus rhythm, with no ventricular pacing. All prescribed medications were continued prior the testing. Treadmill exercise test was performed following the protocol for MTWA testing, and MTWA was analyzed using the analytic spectral method (CH2000 system, Cambridge Heart, Bedford MA, USA). Standard criteria were used in the interpretation of the tests [8]. Results were classified as positive, negative or indeterminate. Differences between the groups with positive and negative MTWA result were examined by the Kruskall–Wallis, one-way ANOVA or chisquare test. A ROC analysis and Cox proportional hazard models were used, but LVEF showing co-linearity with LV GLS was not taken into consideration in multivariate analysis. P b 0.05 was considered significant. STATA software (version 12.1, STATACorp) was used to calculate statistics. Clinical and echocardiographic characteristics of 33 patients enrolled to the study at the time of MTWA assessment are shown in Tables 1 and 2. All but 8 patients were on PAH-specific therapy (bosentan, sildenafil, iloprost or treprostinil). We found a significant amount of positive MTWA results — in 67% of patients. Moreover, the incidence of indeterminate MTWA results was low — in 9% of patients (due to limited physical capability or chronotropic incompetence preventing to obtain the target heart rate). MTWA test was negative in 24% of patients. Data according to MTWA results are presented in Tables 1 and 2. All patients showed symptoms of moderate-to-severe
E. Lewicka et al. / International Journal of Cardiology 176 (2014) 1294–1296
1295
Table 1 Clinical characteristics of patients with pulmonary arterial hypertension (PAH) according to a microvolt T-wave alternans (MTWA) result. MTWA negative (n = 8)
MTWA positive (n = 22)
MTWA indeterminate (n = 3)
Overall (n = 33)
pa
Age (years) Females (n) Idiopathic PAH (n) Connective tissue disease (n) Eisenmenger syndrome (n) History of syncope (n/%) WHO functional class BNP (pg/ml) 6 minute walk test (m)
36 ± 14 8 2 0 6 2(25) 2.6 ± 0.4 (2–3) 46 ± 40 385 ± 145
37 ± 16 11 9 2 11 6(27) 2.8 ± 0.4 (2–3.5) 222 ± 183 416 ± 100
56 ± 10 3 0 1 2 1(33) 3.2 ± 0.6 (2.5–3.5) 1675 ± 1712 220 ± 162
38 ± 16 22(67%) 11(33%) 3(9%) 19(58%) 9(27) 2.7 ± 0.5 (2–3.5) 314 ± 644 389 ± 128
0.9 0.7 0.7 1.0 0.4 1.0 0.9 0.01 0.5
Cardiopulmonary exercise test VO2peak (ml/kg/min) VO2AT (ml/kg/min) VE/VCO2 slope SBP max (mm Hg) PAH-specific treatment at time of MTWA test (n/%)
10.9 ± 3 7.8 ± 1.8 44 ± 8 125 ± 17 6(75)
11 ± 2.5 8 ± 2.7 46 ± 15 133 ± 23 17(77)
10 ± 1 9±1 39 ± 11 133 ± 38 2(67)
10.9 ± 2.5 8 ± 2.4 46 ± 13 131 ± 22 25(76)
0.9 0.8 0.8 0.4 1.0
3 1 1 1 0 3 17.7 ± 11 1.6 ± 0.8
12 0 1 4 2 8 7.4 ± 19.3 1.5 ± 0.7
3 0 1 3 1 3 2.4 ± 3.9 1.2 ± 0.5
18(54%) 1(3%) 3(9%) 8(24%) 3(9%) 14(42%) 9.5 ± 10 1.8 ± 0.8
0.7 0.3 0.5 1.0 1.0 1.0 0.008 0.7
Conventional therapy at time of MTWA test (n) Diuretics Calcium channel blocker Digitalis B-blocker ACEI/ARB Warfarin Time from RHC that revealed PAH (years) Follow-up (years)
VO2peak—peak O2 uptake, VO2AT—O2 uptake measured at anaerobic threshold, VE/VCO2—ventilatory equivalent for VCO2, O2Sat—oxygen saturation, SBP max—peak systolic arterial pressure, BNP—brain natriuretic peptide, ACEI—angiotensin-converting enzyme inhibitor, ARB—angiotensin receptor blocker, RHC—right heart catheterization. a MTWA positive vs. MTWA negative.
heart failure, and echocardiography revealed significant RV involvement in PAH, as our patients presented with severe RV hypertrophy and dilatation. Table 2 Echocardiographic data according to a microvolt T-wave alternans (MTWA) result. Variables
MTWA negative (n = 8)
MTWA positive (n = 22)
Overall MTWA indeterminate (n = 33) (n = 3)
pa
RVEDD (mm) RVWT (mm) RV:LV Right atrial area (cm2) Tricuspid regurgitant velocity (cm/s) RVSP (mm Hg) TAPSE (mm) S′ (cm/s) RVFAC (%) IVC Tacc (m/s2) LVEF (%) LVESD (mm) LVEDD (mm) LVESV (ml) LVEDV (ml) IVS (mm) PWD (mm) LV GLS (%) Pericardial effusion (n)
37 ± 4 9.8 ± 2 1.2 ± 0.2 16 ± 4
46 ± 13 10 ± 2 1.3 ± 0.5 22 ± 9
51 ± 4 10 ± 3 1.9 ± 0.5 32 ± 3
44 ± 12 10 ± 2 1.3 ± 0.4 22 ± 8
0.07 0.6 0.6 0.09
4.1 ± 0.7
4.5 ± 0.8
4.7 ± 0.6
4.4 ± 0.8
0.3
81 ± 24 18 ± 4 11.2 ± 2.3 40 ± 7 2.5 ± 1.5 65 ± 5 22 ± 5 38 ± 5 18 ± 12 51 ± 25 11 ± 2 9±1 −20 ± 2.1 3
92 ± 28 17 ± 7 11.2 ± 3.9 32 ± 10 2.6 ± 1.1 56 ± 9 29 ± 9 44 ± 4 34 ± 23 78 ± 43 11 ± 2 11 ± 2 −15 ± 3.4 6
99 ± 24 12 ± 3 10.4 ± 3.9 31 ± 13 2.6 ± 1.1 56 ± 4 17 ± 1 31 ± 3 14 ± 4 35 ± 12 12 ± 2 11 ± 1 −14 ± 1.4 1
90 ± 26 17 ± 6 11.1 ± 3.5 34 ± 10 2.6 ± 1.2 58 ± 8 26 ± 8 41 ± 8 28 ± 21 67 ± 39 11 ± 2 11 ± 2 −16 ± 3.6 10(30%)
0.3 0.6 1.0 0.06 0.9 0.007 0.06 0.04 0.08 0.1 0.7 0.04 0.003 0.7
RVEDD—right ventricular (RV) end-diastolic diameter in the apical 4-chamber view, RVWT—RV wall thickness, RV:LV—the ratio of RVEDD to LVEDD (measured in the 4chamber apical view), RVSP—RV systolic pressure, TAPSE—tricuspid annular plane systolic excursion, S′—tissue Doppler-derived tricuspid lateral annular systolic velocity, RVFAC— RV fractional area change, LVEF—left ventricular (LV) ejection fraction, LVESD—LV endsystolic diameter, LVEDD—LV end-diastolic diameter, IVS—interventricular septum thickness, PWD—posterior wall thickness, IVC Tacc—tissue Doppler-derived time of acceleration of isovolumic contraction, LV GLS—left ventricular global longitudinal strain. a MTWA positive vs. MTWA negative.
In patients with ischemic heart disease, heart failure or nonischemic cardiomyopathy MTWA reflects spatio-temporal heterogeneity of LV myocardium during repolarization, where the RV mass is small compared with the opposite ventricle and contributes little to the formation of T-wave. But in PAH patients, not only the LV, but also the RV must be concerned with the T-wave form because of the RV hypertrophy and thus possible MTWA phenomenon. Thus, one could expect that electrical instability, if recognized by MTWA, would represent heterogeneous repolarization of hypertrophied RV. But we found that mainly the poorer LV, and only to a lesser degree the poorer RV function, was associated with a positive MTWA result. By univariate logistic regression analysis LVEF and LV GLS showed a significant association with positive MTWA result, and LV GLS was an independent predictor by multivariate analysis. The area under the curve for LV GLS was 0.88 (95% confidence interval 0.74–1.00) and a cut-off value of ≥−17.6% showed a sensitivity and specificity of 81% and 86% to predict a positive MTWA result. This observation is in agreement with studies showing that changes in the RV structure and function affect also the LV. As the RV function deteriorates, it leads to increase in the RV contraction time and subsequently ventricular asynchrony, which together with a decline in the RV stroke volume impedes the LV diastolic filling [9,10]. Another important factor leading to the LV underfilling is the paradoxical movement of interventricular septum, when due to the RV pressure overload the septum flattens or even bulges to the LV in early diastole [9]. During the mean 1.8-year follow-up 3 patients died: 1 with MTWA positive (sudden cardiac death), and 2 patients with an indeterminate MTWA result (both due to right heart failure). However, as our population size was small and mortality rate was low we were unable to explore the prognostic significance of MTWA testing. This is the first study assessing factors that influence MTWA results in patients with PAH. We conclude that there is high incidence of positive MTWA tests in these patients. Despite normal LVEF, the LV GLS is significantly lower in patients with positive MTWA. The hypothesis, that positive MTWA test might indicate the presence of latent LV
1296
E. Lewicka et al. / International Journal of Cardiology 176 (2014) 1294–1296
dysfunction in PAH patients needs to be verified. Further research in larger populations is required to establish clinical implications of MTWA in PAH, and if its result predicts arrhythmic or cardiovascular mortality in these patients. Conflict of interest The authors declare no conflict of interests and report no relationships that could be construed as a conflict of interest. References [1] Tateno S, Niwa K, Nakazawa M, et al. Risk factors for arrhythmia and late death in patients with right ventricle to pulmonary artery conduit repair—Japanese multicenter study. Int J Cardiol 2006;106(3):373–81. [2] Humbert M. A critical analysis of survival in idiopathic pulmonary arterial hypertension. Presse Med 2010;39(Suppl. 1):IS41–5. [3] Humbert M, Sitbon O, Chaouat A, et al. Survival in patients with idiopathic, familial, anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation 2010;122(2):156–63.
[4] Howard L. Prognostic factors in pulmonary arterial hypertension: assessing the course of the disease. Eur Respir Rev 2011;20(122):236–42. [5] Chow T, Kereiakes DJ, Bartone C, et al. Prognostic utility of microvolt T-wave alternans in risk stratification of patients with ischemic cardiomyopathy. J Am Coll Cardiol 2006;47(9):1820–7. [6] Gupta A, Hoang D, Karliner L, et al. Ability of microvolt T-wave alternans to modify risk assessment of ventricular tachyarrhythmic events: a meta-analysis. Am Heart J 2012;163(3):354–64. [7] Benoist D, Stones R, Drinkhill M, et al. Cardiac arrhythmia mechanisms in rats with heart failure induced by pulmonary hypertension. Am J Physiol Heart Circ Physiol 2012;302(11):H2381–95. [8] Bloomfield DM, Hohnloser SH, Cohen RJ. Interpretation and classification of microvolt T wave alternans tests. J Cardiovasc Electrophysiol 2002;13(5):502–12. [9] Marcus J, Gan C, Zwanenburg J, et al. Interventricular mechanical asynchrony in pulmonary arterial hypertension: left-to-right delay in peak shortening is related to right ventricular overload and left ventricular underfilling. J Am Coll Cardiol 2008;51(7):750–7. [10] Mauritz G, Marcus J, Westerhof N, Postmus P, Vonk-Noordegraaf A. Prolonged right ventricular post-systolic isovolumic period in pulmonary arterial hypertension is not a reflection of diastolic dysfunction. Heart 2011;97(6):473–8.
