International Journal of Cardiology 197 (2015) 312–314
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Simple stress echocardiography unmasks early pulmonary vascular disease in adult congenital heart disease Annelieke C.M.J. van Riel a,b, Rianne H.A.C.M. de Bruin-Bon a, Emma C. Gertsen a, Ilja M. Blok a,b, Barbara J.M. Mulder a,b, Berto J. Bouma a,⁎ a b
Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands ICIN — Netherlands Heart Institute, Utrecht, The Netherlands
a r t i c l e
i n f o
Article history: Received 18 May 2015 Accepted 18 June 2015 Available online 27 June 2015 Keywords: Adult congenital heart disease Exercise echocardiography Pulmonary arterial hypertension Pulmonary vascular disease
To the Editor, Pulmonary arterial hypertension (PAH) is a dramatic complication in patients with congenital shunts; even among adults in whom the shunts were successfully closed [1]. The pulmonary circulation is, however, a unique circuit that is able to compensate signs of early pulmonary vascular disease (PVD) for a long time. As a result, elevated resting pulmonary artery pressures during routine echocardiography screening are late markers of advanced PVD [2]. Exercise may, by increasing cardiac output, unmask early PVD and could facilitate timely diagnosis, early initiation of therapy and thereby improve patient quality of life and prevent premature death. Invasive measurement of pulmonary hemodynamics is considered to be the ‘gold standard’. However, exercise echocardiography is an easy applicable, physiological screening tool to detect early PVD. Moreover, it is non-invasive, less expensive, widely available and easily repeatable during follow-up. Already in several clusters of patients – like systemic sclerosis and idiopathic PAH – exercise echocardiography has been successfully used to identify early PVD [3]. However, it is currently unknown if exercise
⁎ Corresponding author at: Department of Cardiology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. E-mail address: [email protected] (B.J. Bouma).
http://dx.doi.org/10.1016/j.ijcard.2015.06.062 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
echocardiography is able to detect early PVD in congenital heart disease (CHD) patients. All consecutive adult patients with an open or closed systemic-topulmonary shunt visiting the outpatient clinic in a tertiary center between January 2013 and May 2015 were prospectively enrolled. Open shunts were only those considered too small for closure. Regular echocardiography at rest was performed, followed by a symptomlimited Master two-step test [4] and immediate (within 30 s) echocardiography afterwards, performed by experienced and European Society of Cardiology-certified sonographers. Suspected early PVD was defined as mean pulmonary arterial pressure (PAP) N 34 mm Hg with a cardiac output (CO) b10 L/min and a mean PAP–CO ratio of N3 mm Hg/L/min [5,6]. Patients without sufficient tricuspid regurgitation, significant left sided valvular disease, right ventricular (RV) outflow tract obstruction or left ventricular (LV) dysfunction (systolic or diastolic according to the recommendations of the American Society of Echocardiography [7]) were excluded. Systolic PAP was derived from continuous-wave Doppler interrogation of tricuspid regurgitation, with the addition of right atrial pressure estimated with measurement of inferior vena cava size and collapsibility. Mean PAP was calculated as 0.6× systolic PAP + 2 [8]. CO was calculated from the flow velocity time integral in the outflow tract of the LV. All measurements were made in triplicate, results are presented as means. Independent-sample t tests were used for comparisons of continuous variables between two groups. Categorical data were evaluated using the χ2-statistic. Optimal cut-off value was determined using receiver-operating characteristic (ROC) curve. All reported p-values are two sided, and p-values b0.05 were considered significant. Analyses were performed using SPSS version 20 (IBM, Armonk, New York). A total of 76 consecutive patients (mean age 43.2 ± 14.5, 66% female) fulfilled the inclusion criteria and underwent exercise echocardiographic screening with the Master 2-step test for early PVD. A group of 16 patients with suspected early PVD was identified, resulting in a prevalence of 21% in our cohort. Clinical and echocardiographic characteristics of the cohort are listed in Table 1. Both groups were comparable regarding gender, body mass index, underlying defect and age at closure. Most patients were in sinus rhythm (93%), 3 had atrial fibrillation and 2 had pacemaker rhythm. There were no significant differences in conduction time measured by electrocardiography. While the majority of patients with suspected early PVD were in New York Heart Association class I, 3 out of 16 patients did report signs of dyspnea.
Letter to the Editor
313
Table 1 Clinical and echocardiographic parameters of screened patients. n
Demographics Female sex BMI [kg/m2] BSA [m2] Age [years] Defect closed Age at closure [years] NYHA class 1 Type of defect ASD VSD PDA Other Electrocardiography Heart rate [bpm] PQ time [ms] QRS time [ms] Echocardiography Left atrial dilatation None/mild Moderate/severe Right atrial dilatation None/mild Moderate/severe Right ventricle function Good Moderate/poor Right ventricle dilatation None/mild Moderate/severe Right ventricle hypertrophy None/mild Moderate/severe Ejection fraction [%] sPAP [mmHg] mPAP [mmHg] Tapse [mm] RIMP TDI-S′ [cm/s] IVA [m/s2] E/A ratio E′ [cm/s] E/E′ HR [bpm] CO [L/min] CI [L/min/m2] Post-exercise echocardiography X-sPAP [mmHg] X-mPAP [mmHg] X-HR [bpm] X-CO [L/min] X-CI [L/min/m2] Delta HR [bpm] Delta mPAP [mmHg]
Normal exercise response
Suspected early PVD
60
16
38 (63) 24.5 ± 4.0 1.9 ± 0.2 42.3 ± 13.9 46 (77) 22.4 (3.4–45.8) 59 (98)
12 (75) 24.9 ± 3.1 1.8 ± 0.2 46.5 ± 16.5 14 (88) 26.0 (5.9–57.0) 13 (81)
35 (58) 20 (33) 1 (2) 4 (7)
10 (63) 2 (12) 2 (12) 2 (12)
76 71 76
69 ± 13 163 ± 35 106 ± 27
66 ± 10 168 ± 37 114 ± 29
0.50 0.64 0.30
72
50 (83) 7 (12)
11 (69) 4 (25)
0.17
72
50 (83) 7 (12)
13 (81) 2 (13)
0.91
75
50 (83) 9 (15)
13 (81) 3 (19)
0.74
75
45 (75) 14 (23)
14 (87) 2 (13)
0.33
75
15 (94) 1 (6) 59 ± 9 37.1 ± 7.9 24.2 ± 4.8 22.6 ± 6.3 0.50 ± 0.2 12.8 ± 3.9 2.185 ± 1.233 1.67 ± 0.6 9.7 ± 3.0 10.3 ± 2.9 64 ± 9 4.8 ± 1.0 2.7 ± 0.5
0.053
67 76 76 76 60 60 57 63 46 46 76 75 74
59 (98) 0 58 ± 9 27.5 ± 5.2 18.5 ± 3.1 22.1 ± 5.5 0.39 ± 0.1 11.9 ± 2.9 2.069 ± 0.907 1.78 ± 0.9 9.4 ± 2.6 9.9 ± 3.0 68 ± 10 5.4 ± 1.5 2.9 ± 0.8
0.55 b0.001 b0.001 0.76 0.012 0.37 0.72 0.71 0.81 0.72 0.18 0.21 0.39
76 76 76 67 66 76 76
40.2 ± 6.6 26.1 ± 4.0 90 ± 19 8.2 ± 3.2 4.3 ± 1.6 22 ± 17 7.6 ± 4.0
59.3 ± 8.5 37.6 ± 5.1 85 ± 16 7.0 ± 2.1 3.9 ± 1.1 21 ± 14 13.4 ± 4.6
b0.001 b0.001 0.33 0.20 0.36 0.74 b0.001
76 75 75 76 76 76 76
76
p value
0.38 0.68 0.21 0.30 0.35 0.52 0.007
0.10
Data are presented as mean ± sd, median (interquartile range) or as counts (percentages). BMI — body mass index; BSA — body surface area; ASD — atrial septal defect; VSD — ventricular septal defect; PDA — patent ductus arteriosus; sPAP — systolic pulmonary arterial pressure; mPAP — mean pulmonary arterial pressure; TAPSE — tricuspid annular plane systolic excursion; RIMP — right ventricular index of myocardial performance; TDI-S′ — peak systolic velocity of the lateral tricuspid valve annulus; IVA — isovolumic acceleration; E/A ratio — ratio of the early (E) to late (A) ventricular filling velocities; E′ — spectral tissue Doppler peak early diastolic velocity at the septal corner of mitral annulus; E/E′ — relationship between maximal values of passive mitral inflow (E, PW-Doppler) and lateral early diastolic mitral annular velocities (E′, TDI); HR — heart rate; CO — cardiac output; CI — cardiac index; X-*** — values during exercise.
During resting echocardiography all cardiac chambers were evaluated and no differences were found in dilatation or hypertrophy. RV function as expressed by tricuspid annular plane systolic excursion, peak systolic velocity of the tricuspid annulus and isovolumic acceleration were not significantly different between patients with and without
Fig. 1. Change in mean pulmonary arterial pressure following Master two-step test. The dotted lines represent individual patients. The whisker plots display mean and standard deviation of mean pulmonary arterial pressure at rest and after the step test. mPAP — mean pulmonary arterial pressure; PVD — pulmonary vascular disease.
suspected early PVD. However, RV myocardial performance index (RIMP) was significantly higher in patients with signs of early PVD compared to patients with normal pulmonary vascular response during exercise (0.50 ± 0.2 versus 0.39 ± 0.2 respectively, p = 0.012). A RIMP value of 0.47 was determined as the optimal cut-off using ROC analysis (area under curve 0.70, 95% CI: 0.54–0.87, p = 0.03, sensitivity 62%, specificity 79%). Although both groups showed similar increase in heart rate and CO after the Master two-step test as listed in Table 1, patients with suspected early PVD had a markedly steeper increase in pulmonary pressures (Fig. 1). To confirm the values obtained during the simple Master twostep test, 10 out of 16 patients with suspected early PVD underwent subsequent exercise echocardiography on a semi-recumbent cycle ergometer with 20°–30° left lateral tilt (model 1200 EL; Ergoline, Bitz, Germany)
314
Letter to the Editor
during which all patients reached similar pulmonary pressures as during the Master two-step test. These results show the ease of the Master two-step test to detect an abnormal pulmonary vascular response among a significant number (21%) of CHD patients during routine follow-up. Furthermore, RV diastolic function as expressed by RIMP appeared to be significantly impaired in these patients. This might be explained by a decrease in RV compliance due to elevated afterload, similar to LV diastolic dysfunction in the presence of systemic hypertension. The use of exercise echocardiography provides a feasible and much more comprehensive assessment of the pulmonary circulation for routine screening purposes than invasive measurements. Although these techniques require further validation, many promising results have already accurately described early PVD as a clinically relevant stage of PAH development [3,5,9,10]. However, long term follow-up studies are needed to clarify the natural progression. Therefore noninvasive screening strategies are essential in these patients, where PAH can take many years to develop. Guidance is needed to provide optimal timing for further (invasive) testing or start of PAH specific therapy. Among patients with open and closed shunts a high prevalence of suspected early PVD can be identified by exercise echocardiography using the Master two-step test. Right ventricular diastolic function is significantly impaired in these patients and could further aid in identifying patients with early PVD (RIMP N 0.47). These patients require ongoing echocardiographic follow-up and specific therapies may be considered to prevent disease evolution. Conflict of interest None. Acknowlegdments This research was carried out in the context of the Parelsnoer Institute (PSI). PSI is part of and funded by the Dutch Federation of University Medical Centers.
References [1] A.C.M.J. Van Riel, M.J. Schuuring, I.D. van Hessen, A.H. Zwinderman, L. Cozijnsen, C.L.A. Reichert, et al., Contemporary prevalence of pulmonary arterial hypertension in adult congenital heart disease following the updated clinical classification, Int. J. Cardiol. 174 (2014) 299–305. [2] E.M.T. Lau, A. Manes, D.S. Celermajer, N. Galiè, Early detection of pulmonary vascular disease in pulmonary arterial hypertension: time to move forward, Eur. Heart J. 32 (2011) 2489–2498. [3] M. D'Alto, S. Ghio, A. D'Andrea, A.S. Pazzano, P. Argiento, R. Camporotondo, et al., Inappropriate exercise-induced increase in pulmonary artery pressure in patients with systemic sclerosis, Heart Br. Card. Soc. 97 (2011) 112–117. [4] A.M. Master, The Master two-step test, Am. Heart J. 75 (1968) 809–837. [5] P. Argiento, R.R. Vanderpool, M. Mulè, M.G. Russo, M. D'Alto, E. Bossone, et al., Exercise stress echocardiography of the pulmonary circulation: limits of normal and sex differences, Chest 142 (2012) 1158–1165. [6] G. Kovacs, A. Berghold, S. Scheidl, H. Olschewski, Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review, Eur. Respir. J. 34 (2009) 888–894. [7] R.M. Lang, L.P. Badano, V. Mor-Avi, J. Afilalo, A. Armstrong, L. Ernande, et al., Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging, Eur. Heart J. Cardiovasc. Imaging 16 (2015) 233–270. [8] D. Chemla, V. Castelain, M. Humbert, J.-L. Hébert, G. Simonneau, Y. Lecarpentier, et al., New formula for predicting mean pulmonary artery pressure using systolic pulmonary artery pressure, Chest 126 (2004) 1313–1317. [9] J.-W. Ha, D. Choi, S. Park, C.-Y. Shim, J.-M. Kim, S.-H. Moon, et al., Determinants of exercise-induced pulmonary hypertension in patients with normal left ventricular ejection fraction, Heart Br. Card. Soc. 95 (2009) 490–494. [10] J.J. Tolle, A.B. Waxman, T.L. Van Horn, P.P. Pappagianopoulos, D.M. Systrom, Exerciseinduced pulmonary arterial hypertension, Circulation 118 (2008) 2183–2189.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Simple stress echocardiography unmasks early pulmonary vascular disease in adult congenital heart disease Annelieke C.M.J. van Riel a,b, Rianne H.A.C.M. de Bruin-Bon a, Emma C. Gertsen a, Ilja M. Blok a,b, Barbara J.M. Mulder a,b, Berto J. Bouma a,⁎ a b
Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands ICIN — Netherlands Heart Institute, Utrecht, The Netherlands
a r t i c l e
i n f o
Article history: Received 18 May 2015 Accepted 18 June 2015 Available online 27 June 2015 Keywords: Adult congenital heart disease Exercise echocardiography Pulmonary arterial hypertension Pulmonary vascular disease
To the Editor, Pulmonary arterial hypertension (PAH) is a dramatic complication in patients with congenital shunts; even among adults in whom the shunts were successfully closed [1]. The pulmonary circulation is, however, a unique circuit that is able to compensate signs of early pulmonary vascular disease (PVD) for a long time. As a result, elevated resting pulmonary artery pressures during routine echocardiography screening are late markers of advanced PVD [2]. Exercise may, by increasing cardiac output, unmask early PVD and could facilitate timely diagnosis, early initiation of therapy and thereby improve patient quality of life and prevent premature death. Invasive measurement of pulmonary hemodynamics is considered to be the ‘gold standard’. However, exercise echocardiography is an easy applicable, physiological screening tool to detect early PVD. Moreover, it is non-invasive, less expensive, widely available and easily repeatable during follow-up. Already in several clusters of patients – like systemic sclerosis and idiopathic PAH – exercise echocardiography has been successfully used to identify early PVD [3]. However, it is currently unknown if exercise
⁎ Corresponding author at: Department of Cardiology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. E-mail address: [email protected] (B.J. Bouma).
http://dx.doi.org/10.1016/j.ijcard.2015.06.062 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
echocardiography is able to detect early PVD in congenital heart disease (CHD) patients. All consecutive adult patients with an open or closed systemic-topulmonary shunt visiting the outpatient clinic in a tertiary center between January 2013 and May 2015 were prospectively enrolled. Open shunts were only those considered too small for closure. Regular echocardiography at rest was performed, followed by a symptomlimited Master two-step test [4] and immediate (within 30 s) echocardiography afterwards, performed by experienced and European Society of Cardiology-certified sonographers. Suspected early PVD was defined as mean pulmonary arterial pressure (PAP) N 34 mm Hg with a cardiac output (CO) b10 L/min and a mean PAP–CO ratio of N3 mm Hg/L/min [5,6]. Patients without sufficient tricuspid regurgitation, significant left sided valvular disease, right ventricular (RV) outflow tract obstruction or left ventricular (LV) dysfunction (systolic or diastolic according to the recommendations of the American Society of Echocardiography [7]) were excluded. Systolic PAP was derived from continuous-wave Doppler interrogation of tricuspid regurgitation, with the addition of right atrial pressure estimated with measurement of inferior vena cava size and collapsibility. Mean PAP was calculated as 0.6× systolic PAP + 2 [8]. CO was calculated from the flow velocity time integral in the outflow tract of the LV. All measurements were made in triplicate, results are presented as means. Independent-sample t tests were used for comparisons of continuous variables between two groups. Categorical data were evaluated using the χ2-statistic. Optimal cut-off value was determined using receiver-operating characteristic (ROC) curve. All reported p-values are two sided, and p-values b0.05 were considered significant. Analyses were performed using SPSS version 20 (IBM, Armonk, New York). A total of 76 consecutive patients (mean age 43.2 ± 14.5, 66% female) fulfilled the inclusion criteria and underwent exercise echocardiographic screening with the Master 2-step test for early PVD. A group of 16 patients with suspected early PVD was identified, resulting in a prevalence of 21% in our cohort. Clinical and echocardiographic characteristics of the cohort are listed in Table 1. Both groups were comparable regarding gender, body mass index, underlying defect and age at closure. Most patients were in sinus rhythm (93%), 3 had atrial fibrillation and 2 had pacemaker rhythm. There were no significant differences in conduction time measured by electrocardiography. While the majority of patients with suspected early PVD were in New York Heart Association class I, 3 out of 16 patients did report signs of dyspnea.
Letter to the Editor
313
Table 1 Clinical and echocardiographic parameters of screened patients. n
Demographics Female sex BMI [kg/m2] BSA [m2] Age [years] Defect closed Age at closure [years] NYHA class 1 Type of defect ASD VSD PDA Other Electrocardiography Heart rate [bpm] PQ time [ms] QRS time [ms] Echocardiography Left atrial dilatation None/mild Moderate/severe Right atrial dilatation None/mild Moderate/severe Right ventricle function Good Moderate/poor Right ventricle dilatation None/mild Moderate/severe Right ventricle hypertrophy None/mild Moderate/severe Ejection fraction [%] sPAP [mmHg] mPAP [mmHg] Tapse [mm] RIMP TDI-S′ [cm/s] IVA [m/s2] E/A ratio E′ [cm/s] E/E′ HR [bpm] CO [L/min] CI [L/min/m2] Post-exercise echocardiography X-sPAP [mmHg] X-mPAP [mmHg] X-HR [bpm] X-CO [L/min] X-CI [L/min/m2] Delta HR [bpm] Delta mPAP [mmHg]
Normal exercise response
Suspected early PVD
60
16
38 (63) 24.5 ± 4.0 1.9 ± 0.2 42.3 ± 13.9 46 (77) 22.4 (3.4–45.8) 59 (98)
12 (75) 24.9 ± 3.1 1.8 ± 0.2 46.5 ± 16.5 14 (88) 26.0 (5.9–57.0) 13 (81)
35 (58) 20 (33) 1 (2) 4 (7)
10 (63) 2 (12) 2 (12) 2 (12)
76 71 76
69 ± 13 163 ± 35 106 ± 27
66 ± 10 168 ± 37 114 ± 29
0.50 0.64 0.30
72
50 (83) 7 (12)
11 (69) 4 (25)
0.17
72
50 (83) 7 (12)
13 (81) 2 (13)
0.91
75
50 (83) 9 (15)
13 (81) 3 (19)
0.74
75
45 (75) 14 (23)
14 (87) 2 (13)
0.33
75
15 (94) 1 (6) 59 ± 9 37.1 ± 7.9 24.2 ± 4.8 22.6 ± 6.3 0.50 ± 0.2 12.8 ± 3.9 2.185 ± 1.233 1.67 ± 0.6 9.7 ± 3.0 10.3 ± 2.9 64 ± 9 4.8 ± 1.0 2.7 ± 0.5
0.053
67 76 76 76 60 60 57 63 46 46 76 75 74
59 (98) 0 58 ± 9 27.5 ± 5.2 18.5 ± 3.1 22.1 ± 5.5 0.39 ± 0.1 11.9 ± 2.9 2.069 ± 0.907 1.78 ± 0.9 9.4 ± 2.6 9.9 ± 3.0 68 ± 10 5.4 ± 1.5 2.9 ± 0.8
0.55 b0.001 b0.001 0.76 0.012 0.37 0.72 0.71 0.81 0.72 0.18 0.21 0.39
76 76 76 67 66 76 76
40.2 ± 6.6 26.1 ± 4.0 90 ± 19 8.2 ± 3.2 4.3 ± 1.6 22 ± 17 7.6 ± 4.0
59.3 ± 8.5 37.6 ± 5.1 85 ± 16 7.0 ± 2.1 3.9 ± 1.1 21 ± 14 13.4 ± 4.6
b0.001 b0.001 0.33 0.20 0.36 0.74 b0.001
76 75 75 76 76 76 76
76
p value
0.38 0.68 0.21 0.30 0.35 0.52 0.007
0.10
Data are presented as mean ± sd, median (interquartile range) or as counts (percentages). BMI — body mass index; BSA — body surface area; ASD — atrial septal defect; VSD — ventricular septal defect; PDA — patent ductus arteriosus; sPAP — systolic pulmonary arterial pressure; mPAP — mean pulmonary arterial pressure; TAPSE — tricuspid annular plane systolic excursion; RIMP — right ventricular index of myocardial performance; TDI-S′ — peak systolic velocity of the lateral tricuspid valve annulus; IVA — isovolumic acceleration; E/A ratio — ratio of the early (E) to late (A) ventricular filling velocities; E′ — spectral tissue Doppler peak early diastolic velocity at the septal corner of mitral annulus; E/E′ — relationship between maximal values of passive mitral inflow (E, PW-Doppler) and lateral early diastolic mitral annular velocities (E′, TDI); HR — heart rate; CO — cardiac output; CI — cardiac index; X-*** — values during exercise.
During resting echocardiography all cardiac chambers were evaluated and no differences were found in dilatation or hypertrophy. RV function as expressed by tricuspid annular plane systolic excursion, peak systolic velocity of the tricuspid annulus and isovolumic acceleration were not significantly different between patients with and without
Fig. 1. Change in mean pulmonary arterial pressure following Master two-step test. The dotted lines represent individual patients. The whisker plots display mean and standard deviation of mean pulmonary arterial pressure at rest and after the step test. mPAP — mean pulmonary arterial pressure; PVD — pulmonary vascular disease.
suspected early PVD. However, RV myocardial performance index (RIMP) was significantly higher in patients with signs of early PVD compared to patients with normal pulmonary vascular response during exercise (0.50 ± 0.2 versus 0.39 ± 0.2 respectively, p = 0.012). A RIMP value of 0.47 was determined as the optimal cut-off using ROC analysis (area under curve 0.70, 95% CI: 0.54–0.87, p = 0.03, sensitivity 62%, specificity 79%). Although both groups showed similar increase in heart rate and CO after the Master two-step test as listed in Table 1, patients with suspected early PVD had a markedly steeper increase in pulmonary pressures (Fig. 1). To confirm the values obtained during the simple Master twostep test, 10 out of 16 patients with suspected early PVD underwent subsequent exercise echocardiography on a semi-recumbent cycle ergometer with 20°–30° left lateral tilt (model 1200 EL; Ergoline, Bitz, Germany)
314
Letter to the Editor
during which all patients reached similar pulmonary pressures as during the Master two-step test. These results show the ease of the Master two-step test to detect an abnormal pulmonary vascular response among a significant number (21%) of CHD patients during routine follow-up. Furthermore, RV diastolic function as expressed by RIMP appeared to be significantly impaired in these patients. This might be explained by a decrease in RV compliance due to elevated afterload, similar to LV diastolic dysfunction in the presence of systemic hypertension. The use of exercise echocardiography provides a feasible and much more comprehensive assessment of the pulmonary circulation for routine screening purposes than invasive measurements. Although these techniques require further validation, many promising results have already accurately described early PVD as a clinically relevant stage of PAH development [3,5,9,10]. However, long term follow-up studies are needed to clarify the natural progression. Therefore noninvasive screening strategies are essential in these patients, where PAH can take many years to develop. Guidance is needed to provide optimal timing for further (invasive) testing or start of PAH specific therapy. Among patients with open and closed shunts a high prevalence of suspected early PVD can be identified by exercise echocardiography using the Master two-step test. Right ventricular diastolic function is significantly impaired in these patients and could further aid in identifying patients with early PVD (RIMP N 0.47). These patients require ongoing echocardiographic follow-up and specific therapies may be considered to prevent disease evolution. Conflict of interest None. Acknowlegdments This research was carried out in the context of the Parelsnoer Institute (PSI). PSI is part of and funded by the Dutch Federation of University Medical Centers.
References [1] A.C.M.J. Van Riel, M.J. Schuuring, I.D. van Hessen, A.H. Zwinderman, L. Cozijnsen, C.L.A. Reichert, et al., Contemporary prevalence of pulmonary arterial hypertension in adult congenital heart disease following the updated clinical classification, Int. J. Cardiol. 174 (2014) 299–305. [2] E.M.T. Lau, A. Manes, D.S. Celermajer, N. Galiè, Early detection of pulmonary vascular disease in pulmonary arterial hypertension: time to move forward, Eur. Heart J. 32 (2011) 2489–2498. [3] M. D'Alto, S. Ghio, A. D'Andrea, A.S. Pazzano, P. Argiento, R. Camporotondo, et al., Inappropriate exercise-induced increase in pulmonary artery pressure in patients with systemic sclerosis, Heart Br. Card. Soc. 97 (2011) 112–117. [4] A.M. Master, The Master two-step test, Am. Heart J. 75 (1968) 809–837. [5] P. Argiento, R.R. Vanderpool, M. Mulè, M.G. Russo, M. D'Alto, E. Bossone, et al., Exercise stress echocardiography of the pulmonary circulation: limits of normal and sex differences, Chest 142 (2012) 1158–1165. [6] G. Kovacs, A. Berghold, S. Scheidl, H. Olschewski, Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review, Eur. Respir. J. 34 (2009) 888–894. [7] R.M. Lang, L.P. Badano, V. Mor-Avi, J. Afilalo, A. Armstrong, L. Ernande, et al., Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging, Eur. Heart J. Cardiovasc. Imaging 16 (2015) 233–270. [8] D. Chemla, V. Castelain, M. Humbert, J.-L. Hébert, G. Simonneau, Y. Lecarpentier, et al., New formula for predicting mean pulmonary artery pressure using systolic pulmonary artery pressure, Chest 126 (2004) 1313–1317. [9] J.-W. Ha, D. Choi, S. Park, C.-Y. Shim, J.-M. Kim, S.-H. Moon, et al., Determinants of exercise-induced pulmonary hypertension in patients with normal left ventricular ejection fraction, Heart Br. Card. Soc. 95 (2009) 490–494. [10] J.J. Tolle, A.B. Waxman, T.L. Van Horn, P.P. Pappagianopoulos, D.M. Systrom, Exerciseinduced pulmonary arterial hypertension, Circulation 118 (2008) 2183–2189.
