Incidence and Risk Distribution of Heart Failure in Adolescents and Adults With Congenital Heart Disease After Cardiac Surgery
2006; Elsevier BV; Volume: 97; Issue: 8 Linguagem: Inglês
10.1016/j.amjcard.2005.10.065
ISSN1879-1913
AutoresKambiz Norozi, Armin Wessel, Valentin Alpers, Jan O. Arnhold, Siegfried Geyer, Monika Zoege, Reiner Buchhorn,
Tópico(s)Cardiac Structural Anomalies and Repair
ResumoHeart failure (HF) is a major problem in the long-term follow-up of adults with congenital heart disease (CHD) after cardiac surgery. The purpose of this study was to evaluate risk factors for HF in patients with CHD. N-terminal–pro-brain natriuretic peptide and maximal oxygen uptake (VO2max) were measured in 345 consecutive patients with CHD. HF was defined as an elevated N-terminal–pro-brain natriuretic peptide level (≥100 pg/ml) and reduced VO2max (≤25 ml/kg/min). The HF criteria were met by 89 patients. These patients were significantly older (mean ± SEM 30.8 ± 0.9 vs 24.8 ± 0.5 years), had significantly lower maximal heart rates (149 ± 3 vs 164 ± 1 beats/min), and had larger end-diastolic right ventricular diameters (36 ± 1 vs 27 ± 1 mm) and right ventricular pressure estimated by Doppler flow velocities of tricuspid valve regurgitation (2.9 ± 0.1 vs 2.3 ± 0.03 m/s). Mean fractional shortening of the left ventricle was within the normal range. To estimate risk stratification, odds ratios for HF were determined for the most frequently occurring types of congenital heart defects and surgical procedures. In conclusion, HF in adults with CHD predominately depends on diagnosis, age, the frequency of reoperation, and right ventricular function and may be related to chronotropic incompetence indicated by lower maximal heart rates. Heart failure (HF) is a major problem in the long-term follow-up of adults with congenital heart disease (CHD) after cardiac surgery. The purpose of this study was to evaluate risk factors for HF in patients with CHD. N-terminal–pro-brain natriuretic peptide and maximal oxygen uptake (VO2max) were measured in 345 consecutive patients with CHD. HF was defined as an elevated N-terminal–pro-brain natriuretic peptide level (≥100 pg/ml) and reduced VO2max (≤25 ml/kg/min). The HF criteria were met by 89 patients. These patients were significantly older (mean ± SEM 30.8 ± 0.9 vs 24.8 ± 0.5 years), had significantly lower maximal heart rates (149 ± 3 vs 164 ± 1 beats/min), and had larger end-diastolic right ventricular diameters (36 ± 1 vs 27 ± 1 mm) and right ventricular pressure estimated by Doppler flow velocities of tricuspid valve regurgitation (2.9 ± 0.1 vs 2.3 ± 0.03 m/s). Mean fractional shortening of the left ventricle was within the normal range. To estimate risk stratification, odds ratios for HF were determined for the most frequently occurring types of congenital heart defects and surgical procedures. In conclusion, HF in adults with CHD predominately depends on diagnosis, age, the frequency of reoperation, and right ventricular function and may be related to chronotropic incompetence indicated by lower maximal heart rates. The number of cases of adults with congenital heart disease (CHD) is steadily increasing because of the success of pediatric cardiology and heart surgery. Most of symptomatic cardiac malformations can now benefit from surgery or interventional catheterization. The results of this progress have been an extraordinary change in survival rates among patients with CHD.1Webb G.D. Challenges in the care of adult patients with congenital heart defects.Heart. 2003; 89: 465-469Crossref PubMed Scopus (24) Google Scholar However, late complications such as arrhythmias, endocarditis, and heart failure (HF) are common, so patients require medical treatment, reoperations, or catheter interventions for residual lesions.2Somerville J. Grown-up congenital heart disease—medical demands look back, look forward 2000.Thorac Cardiovasc Surg. 2001; 49: 21-26Crossref PubMed Scopus (69) Google Scholar It is axiomatic that symptoms of HF are manifested more during exertion than at rest. Conceptually, HF is primarily the failure of the cardiac pump to function adequately to support the more dynamic circulation required during exercise. Conversely, the extent of impairment in pump function is indirectly represented by a decrease in exercise capacity, best measured by maximal oxygen uptake (VO2max).3Cotter G. Williams S.G. Vered Z. Tan L.B. Role of cardiac power in heart failure.Curr Opin Cardiol. 2003; 18: 215-222Crossref PubMed Scopus (144) Google Scholar These data as well as studies in adults with chronic HF clearly indicate that blood levels of N-terminal–pro-brain natriuretic peptide (NT–pro-BNP) and VO2max measured by cardiopulmonary exercise tests can be used for the objective assessment of HF and risk stratification. HF was assumed if the NT–pro-BNP plasma level was significantly elevated and maximal oxygen uptake was reduced.4de Groote P. Dagorn J. Soudan B. Lamblin N. McFadden E. Bauters C. B-type natriuretic peptide and peak exercise oxygen consumption provide independent information for risk stratification in patients with stable congestive heart failure.J Am Coll Cardiol. 2004; 43: 1584-1589Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar, 5Kruger S. Graf J. Kunz D. Stickel T. Hanrath P. Janssens U. Brain natriuretic peptide levels predict functional capacity in patients with chronic heart failure.J Am Coll Cardiol. 2002; 40: 718-722Abstract Full Text Full Text PDF PubMed Scopus (173) Google Scholar, 6Williams S.G. Ng L.L. O’Brien R.J. Taylor S. Li Y.F. Tan L.B. Comparison of plasma N-brain natriuretic peptide, peak oxygen consumption, and left ventricular ejection fraction for severity of chronic heart failure.Am J Cardiol. 2004; 93: 1560-1561Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar The purpose of our study was to evaluate the cardiocirculatory status of a large group of young adults with congenital heart defects operated in 1 institution using these parameters. From May 1, 2003, to May 31, 2004, we evaluated the cardiocirculatory status of 345 patients with CHD (141 female patients, 204 male patients). This group included adolescent and adult patients ranging in age from 14 to 50 years. On the basis of their original heart defects, patients were divided into 7 groups (Table 1). The left-to-right shunt (LRS) group included patients operated on to correct uncomplicated atrial or ventricular septal defects and patent ductus arteriosus Botalli. The miscellaneous group included 5 patients with hypertrophic cardiomyopathy, 3 patients with Ebstein’s malformation, 2 with double-outlet right ventricles with noncommitted ventricular septal defects, 3 with transposition of the great arteries (TGAs) 2 patients after arterial switch and 1 with Rastelli’s operation, and 2 with coronary fistulae. All patients had surgical or interventional therapy of their congenital heart defects at the University Hospital of Göttingen (Göttingen, Germany). Patients were consecutively recruited from our CHD outpatient clinic. We performed a prospectively designed protocol for exercise testing, echocardiography, and the assessment of clinical and neurohormonal variables. For each patient, the protocol took place over the course of 1 day. The study group was divided according to HF. HF was assumed if the NT–pro-BNP plasma level was significantly elevated (≥100 pg/ml)7Remme W.J. Swedberg K. Guidelines for the diagnosis and treatment of chronic heart failure.Eur Heart J. 2001; 22: 1527-1560Crossref PubMed Scopus (1538) Google Scholar, 8Scharhag J. Urhausen A. Herrmann M. Schneider G. Kramann B. Herrmann W. Kindermann W. No difference in N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations between endurance athletes with athlete’s heart and healthy untrained controls.Heart. 2004; 90: 1055-1056Crossref PubMed Scopus (34) Google Scholar, 9Maisel A. B-type natriuretic peptide levels a potential novel “white count” for congestive heart failure.J Card Fail. 2001; 7: 183-193Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar, 10Goetze J.P. Kastrup J. Pedersen F. Rehfeld J.F. Quantification of pro-B-type natriuretic peptide and its products in human plasma by use of an analysis independent of precursor processing.Clin Chem. 2002; 48: 1035-1042PubMed Google Scholar, 11Norozi K. Buchhorn R. Kaiser C. Hess G. Gruenewald R. Binder L. Wessel A. Plasma NT-proBNP as a marker of the right ventricular dysfunction in patients with tetralogy of Fallot after surgical repair.Chest. 2005; 128: 2563-2570Crossref PubMed Scopus (44) Google Scholar and VO2max was reduced (≤25 ml/kg/min).5Kruger S. Graf J. Kunz D. Stickel T. Hanrath P. Janssens U. Brain natriuretic peptide levels predict functional capacity in patients with chronic heart failure.J Am Coll Cardiol. 2002; 40: 718-722Abstract Full Text Full Text PDF PubMed Scopus (173) Google ScholarTable 1Diagnosis groupsCongenital Heart DefectnAge (yrs)Age at Operation (yrs)HFNYHA ClassYesNoIIIIIIIVLRS9323.3 ± 0.86.5 ± 0.61083692400TGA (atrial diversion procedure)3923.9 ± 1.12.4 ± 0.51227171750TOF9430.1 ± 0.97.3 ± 0.64450424750Single ventricle1726.1 ± 2.111.9 ± 2.0895930Aortic/pulmonary valve disease3927.6 ± 1.712.8 ± 1.7435191910Aortic coarctation4825.5 ± 1.13.0 ± 0.6147381000Miscellaneous1528.6 ± 1.813.9 ± 2.3786621All patients34526.4 ± 0.56.8 ± 0.486259196132161Values are expressed as mean ± SEM. Open table in a new tab Values are expressed as mean ± SEM. NT–pro-BNP is more useful than brain natriuretic peptide, atrial natriuretic peptide, endothelin, or norepinephrine as an independent predictor of morbidity and mortality in patients with chronic HF and is independent of other clinical, hemodynamic, and neurohumoral risk factors.12Tsutamoto T. Wada A. Maeda K. Hisanaga T. Mabuchi N. Hayashi M. Ohnishi M. Sawaki M. Fujii M. Horie H. et al.Plasma brain natriuretic peptide level as a biochemical marker of morbidity and mortality in patients with asymptomatic or minimally symptomatic left ventricular dysfunction Comparison with plasma angiotensin II and endothelin-1.Eur Heart J. 1999; 20: 1799-1807Crossref PubMed Scopus (232) Google Scholar, 13Hunt P.J. Richards A.M. Nicholls M.G. Yandle T.G. Doughty R.N. Espiner E.A. Immunoreactive amino-terminal pro-brain natriuretic peptide (NT-PROBNP) a new marker of cardiac impairment.Clin Endocrinol (Oxford). 1997; 47: 287-296Crossref PubMed Scopus (484) Google Scholar, 14Mueller T. Gegenhuber A. Poelz W. Haltmayer M. Head-to-head comparison of the diagnostic utility of BNP and NT-proBNP in symptomatic and asymptomatic structural heart disease.Clin Chim Acta. 2004; 341: 41-48Crossref PubMed Scopus (134) Google Scholar Endothelin and norepinephrine are closely correlated with exercise capacity in patients with chronic HF.15Krum H. Goldsmith R. Wilshire-Clement M. Miller M. Packer M. Role of endothelin in the exercise intolerance of chronic heart failure.Am J Cardiol. 1995; 75: 1282-1283Abstract Full Text PDF PubMed Scopus (87) Google Scholar, 16Kraemer M.D. Kubo S.H. Rector T.S. Brunsvold N. Bank A.J. Pulmonary and peripheral vascular factors are important determinants of peak exercise oxygen uptake in patients with heart failure.J Am Coll Cardiol. 1993; 21: 641-648Abstract Full Text PDF PubMed Scopus (139) Google Scholar However, the use of these markers, although they provide prognostic information, is difficult, impractical, and associated with long-lasting assays.17Francis G.S. Benedict C. Johnstone D.E. Kirlin P.C. Nicklas J. Liang C.S. Kubo S.H. Rudin-Toretsky E. Yusuf S. Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure. A substudy of the Studies of Left Ventricular Dysfunction (SOLVD).Circulation. 1990; 82: 1724-1729Crossref PubMed Scopus (1297) Google Scholar For this reason, NT–pro-BNP seems to be the most promising laboratory marker of cardiac dysfunction because of its simple and reliable assay. The exclusion criteria were acute infection and severe mental retardation. After adequate explanation of the purpose of the study, informed consent was obtained from all patients. The study protocol was approved by the local ethics committee. All patients underwent physical examinations and measurements of blood pressure, body weight, and height. Standard 12-lead electrocardiograms were recorded to analyze spontaneous rhythm and QRS complex duration. Exercise testing was performed in all patients on an upright bicycle ergometer beginning with a workload of 0.5 W/kg body weight. The load was increased by 0.5 W/kg every 2 minutes. Oxygen uptake was measured using breath-by-breath analysis (Oxycon pro, Jaeger Company, Hoechberg, Germany) throughout the exercise procedure. All patients exercised to maximum exercise capability. VO2max was determined as the largest value in the terminal phase of exercise. A 6-lead electrocardiogram and heart rate were recorded continuously during the test. Blood pressure was recorded every 2 minutes using a cuff sphygmomanometer. Peripheral venous blood samples were obtained from all participants after a rest of ≥15 minutes before exercise testing. The blood samples were immediately placed on ice and subsequently centrifuged at 5,000 rpm for 10 minutes. Plasma and serum aliquots were stored at −80°C until further analysis. NT–pro-BNP (Elecsys 2010, Roche Diagnostics GmbH, Mannheim, Germany) was determined using immunoassay. The mean value of the NT–pro-BNP from 100 age- and gender-matched healthy blood donors served as a reference for the patient data (mean ± SEM 36 ± 5 pg/ml, 99% confidence interval upper bound 43 pg/ml). We performed 2-dimensional and M-mode echocardiography using a transthoracic approach with a Hewlett-Packard Sonos 5500 (Hewlett-Packard Corporation, Palo Alto, California) echocardiograph interfaced with a multifrequency transducer. The end-systolic and end-diastolic diameters of the left ventricle were measured from the short-axis view by M-mode echocardiography, and fractional shortening ([end-diastolic diameter − end-systolic diameter]/end-diastolic diameter) was calculated as a parameter for systolic left ventricular function. For this analysis, we excluded 2 patient groups: those who had undergone the Mustard operation for TGAs and those with tetralogy of Fallot (TOF) with paradoxic movement of the ventricular septum identified by echocardiography and electrocardiography (complete right bundle branch block). Additionally, we measured right ventricular (RV) end-diastolic diameter from the short-axis view by M-mode echocardiography. The velocity of tricuspid valve regurgitation was measured by continuous-wave Doppler echocardiography and served to estimate RV systolic pressure. All results are reported as mean ± SEM. Because most clinical and echocardiographic variables were not normally distributed, nonparametric techniques were used. For all parameters, a value of p <0.01 was considered statistically significant. Odds ratios (ORs) for HF were computed using multivariate logistic regression. They were calculated for every type of cardiac defect compared with the 93 patients with LRS. Patients with aortic coarctation are normally the comparison group of choice because the corrective operation in these patients is performed without heart injury or cardiopulmonary bypass and hypothermia. However, in our case, this procedure was not appropriate for several reasons. Only 1 of 48 subjects with aortic coarctation had HF, so the statistical analyses were hampered by estimation problems in terms of unstable ORs and excessively wide confidence intervals. Additionally, about 20% of them were receiving β blockers for hypertension. We finally decided to choose patients with LRS as a comparison group. Their number in our study population was larger, and their surgery can be considered as curative, although their residual symptomatology is more pronounced than in the aforementioned group. The data analyses were performed using Excel 2000 (Microsoft Corporation, Redmond, Washington) and SPSS version 12.0 (SPSS, Inc., Chicago, Illinois). Of the enrolled patients, 196 were in New York Heart Association (NYHA) functional class I, 132 in NYHA class II, 16 in NYHA class III, and 1 in NYHA class IV. Eighty-nine of the 345 study patients (26%) fulfilled the HF criteria defined previously. As Table 2 demonstrates, patients with HF were significantly older (30.8 ± 0.9 vs 24.8 ± 0.5 years), their age at operation was on average 2.7 years greater, and their frequency of reoperations was significantly greater compared with patients without HF (36% vs 24%). HF was associated with a lower maximal heart rate (149 ± 3 vs 164 ± 1 beats/min) and maximal systolic blood pressure (165 ± 4 vs 195 ± 2 mm Hg) during exercise, significantly increased RV end-diastolic diameter (36 ± 1 vs 27 ± 1 mm), increased tricuspid valve insufficiency velocity (2.9 ± 0.1 vs 2.3 ± 0.3 m/s), and prolonged QRS complex duration (136 ± 4 vs 106 ± 2 ms), which were evidence for a significant volume and/or pressure overload of the right ventricle in these patients. Prolonged QRS duration is a well-established surrogate index of RV dimension.18Frigiola A. Redington A.N. Cullen S. Vogel M. Pulmonary regurgitation is an important determinant of right ventricular contractile dysfunction in patients with surgically repaired tetralogy of Fallot.Circulation. 2004; 110: II153-II157Crossref PubMed Scopus (230) Google Scholar We also found a significant correlation between QRS duration and RV diastolic diameter (r = 0.50, p 100 pg/ml and VO2max <25 ml/kg/minCharacteristicHFp ValueYesNoNo.89256VO2max (ml/kg/min)19.9 ± 0.429.1 ± 0.4<0.0001†Selection criterion.NT–pro-BNP (pg/ml)336 ± 3797 ± 9<0.0001†Selection criterion.Age (yrs)30.8 ± 0.924.8 ± 0.5<0.0001Age at operation (yrs)8.9 ± 0.96.2 ± 0.4<0.005Reoperation (%)32 (36)61 (24)0.013NYHA class I/II/III/IV (%)28/48/12/1 (31/54/14/1)168/84/4 (66/32/2/0)<0.001QRS complex duration (ms)136 ± 4106 ± 2<0.0001Heart rate at rest (beats/min)77 ± 281 ± 1NSMaximal heart rate under exercise (beats/min)149 ± 3164 ± 1<0.0001SBP at rest (mm Hg)119 ± 2124 ± 1NSMaximal SBP under exercise (mm Hg)165 ± 4195 ± 2<0.0001Respiratory quotient at exercise1.09 ± 0.011.09 ± 0.01NSLeft ventricular FS (%)⁎Patients after Mustard operations for TGA and patients with TOF with paradoxical movement of the ventricular septum were excluded.34 ± 136 ± 0.4NSRight ventricular ED (mm)36 ± 127 ± 1<0.0001TV insufficiency velocity (m/s)2.9 ± 0.12.3 ± 0.03<0.0001Medicationβ blocker23 (26%)22 (9%)<0.001Digoxin18 (21%)7 (3%)<0.001ACE inhibitor9 (10%)8 (3%)<0.001Diuretic12 (14%)6 (2%)<0.001Values are expressed as mean ± SEM. Significant correlations are in bold face.ED = end-diastolic diameter; FS = fractional shortening; SBP = systolic blood pressure; TV = tricuspid valve. Patients after Mustard operations for TGA and patients with TOF with paradoxical movement of the ventricular septum were excluded.† Selection criterion. Open table in a new tab Values are expressed as mean ± SEM. Significant correlations are in bold face. ED = end-diastolic diameter; FS = fractional shortening; SBP = systolic blood pressure; TV = tricuspid valve. For the risk stratification of single cardiac defects, logistic regression was performed. We used the group of patients with LRS as a standard for comparison (Table 3). The risk for HF in patients with TOF was significantly greater than in the reference group (OR 4.65). For patients with TGA after the Mustard procedure, the OR was also significantly elevated (3.83). The highest risk for HF was found in patients with single ventricles after Fontan circulation (OR 7.21), but the confidence interval was wide (2.1 to 24.3). This was due to the small number of patients with single ventricles in our study population, especially in the older age group. The total number was 17, of whom 8 had HF. This applies also to the group with miscellaneous heart defects, with an OR of 5.7 (7 of 15 patients had HF). Patients with aortic coarctation and aortic valve and pulmonary valve disease had a low risk for HF.Table 3Odds ratios for heart failureVariableNHFOR95% CIp ValueLRS931TOF944.652.1–10.5<0.001TGA (atrial diversion procedure)393.831.4–10.20.007Single ventricle177.212.1–24.30.001Aortic and pulmonary valve disease390.660.2–2.40.53Aortic coarctation480.140.02–1.10.06Miscellaneous155.701.6–20.40.007Age1.081.05–1.13RVOT surgeryNo Transanular Patch312.050.68–6.130.2Transanular patch505.082.04–12.6<0.001Pulmonary valve replacement1318.484.46–76.7<0.001Significant correlation are in bold face.CI = confidence interval; RVOT = RV outflow tract. Open table in a new tab Significant correlation are in bold face. CI = confidence interval; RVOT = RV outflow tract. The impact of the surgical technique could be demonstrated by 3 different types of RV outflow tract reconstruction in patients with TOF (Table 3). Compared with patients who initially had pulmonary valve replacements or conduits (OR 18.48) or needed transannular patches (OR 5.08), the risk for HF in patients without transannular patches was significantly less (OR 2.05). According to age at follow-up and age at operation, there were no significant differences between the groups (data not shown). In our study group, 89 patients (26%) had significantly elevated NT–pro-BNP plasma levels and reduced VO2max. If NT–pro-BNP plasma levels can differentiate between cardiac and pulmonary causes of exercise intolerance,19McCullough P.A. Nowak R.M. McCord J. Hollander J.E. Herrmann H.C. Steg P.G. Duc P. Westheim A. Omland T. Knudsen C.W. et al.B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure analysis from Breathing Not Properly (BNP) Multinational Study.Circulation. 2002; 106: 416-422Crossref PubMed Scopus (793) Google Scholar, 20Maisel A.S. Krishnaswamy P. Nowak R.M. McCord J. Hollander J.E. Duc P. Omland T. Storrow A.B. Abraham W.T. Wu A.H. et al.Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure.N Engl J Med. 2002; 347: 161-167Crossref PubMed Scopus (2844) Google Scholar, 21Hobbs F.D. Davis R.C. Roalfe A.K. Hare R. Davies M.K. Kenkre J.E. Reliability of N-terminal pro-brain natriuretic peptide assay in diagnosis of heart failure cohort study in representative and high risk community populations.BMJ. 2002; 324: 1498Crossref PubMed Google Scholar reduced VO2max in these patients may be predominantly caused by HF. Compared with patients with LRS, the calculated ORs (Table 3) show that HF in adults with CHD predominantly occurred in patients with TOF, single ventricles, and after the Mustard operation for TGA. The risk for HF in patients with aortic coarctation and aortic and pulmonary valve disease was small. According to this risk profile, HF in adults with CHD is predominantly caused by right-sided HF, indicated by significantly increased RV end-diastolic diameters and RV systolic pressures. Fractional shortening of the left ventricle was normal in the 2 groups of adults with CHD with and without HF. Longer QRS complex durations in patients with HF was not only related to a greater incidence of complete right bundle branch block after surgery but also was a surrogate index of RV dimension. The significant correlation between QRS complex duration and RV diastolic diameter in our study clearly confirms previous data.18Frigiola A. Redington A.N. Cullen S. Vogel M. Pulmonary regurgitation is an important determinant of right ventricular contractile dysfunction in patients with surgically repaired tetralogy of Fallot.Circulation. 2004; 110: II153-II157Crossref PubMed Scopus (230) Google Scholar, 22Neffke J.G. Tulevski I.I. van der Wall E.E. Wilde A.A. van Veldhuisen D.J. Dodge-Khatami A. Mulder B.J. ECG determinants in adult patients with chronic right ventricular pressure overload caused by congenital heart disease relation with plasma neurohormones and MRI parameters.Heart. 2002; 88: 266-270Crossref PubMed Scopus (50) Google Scholar Because patients with HF were on average 6 years older than those without HF, our data may indicate that the development of HF in adults with CHD is age dependent. Figure 1 shows that the probability of having HF is not the same over all age groups and all types of heart defects. The probability monoexponentially increases, and the greatest risk occurs in patients who were operated on for single ventricles, TOF, and TGA (atrial diversion procedures). There is a clear division into 3 groups: (1) a high-risk group; (2) those with less severe defects, whose risk for HF is small over the whole time span considered; and (3) those with aortic coarctation with the smallest risk for HF. The influence of surgical technique on developing HF is indicated in Table 3 by means of RV outflow tract reconstruction in patients with TOF. Despite a higher OR for HF in patients with pulmonary valve replacement and patients with transannular patches compared with those without transannular patches, we must take into account that the decision for the surgical technique applied to individual patients depends on the morphology of the underlying heart defect. The greater incidence of HF in these patients may depend on the severity of their underlying heart defects, not on the operative techniques alone. Additionally, our data show the effect of reoperations on the development of HF. Patients with HF underwent more frequent reoperations (Table 2). Our and other recently published papers23Ohuchi H. Takasugi H. Ohashi H. Okada Y. Yamada O. Ono Y. Yagihara T. Echigo S. Stratification of pediatric heart failure on the basis of neurohormonal and cardiac autonomic nervous activities in patients with congenital heart disease.Circulation. 2003; 108: 2368-2376Crossref PubMed Scopus (108) Google Scholar, 24Tulevski I.I. Groenink M. Der Wall E.E. van Veldhuisen D.J. Boomsma F. Stoker J. Hirsch A. Lemkes J.S. Mulder B.J. Increased brain and atrial natriuretic peptides in patients with chronic right ventricular pressure overload correlation between plasma neurohormones and right ventricular dysfunction.Heart. 2001; 86: 27-30Crossref PubMed Scopus (185) Google Scholar indicate that patients with HF due to CHD also manifest all the pathophysiologic criteria that constitute the so-called chronic HF syndrome. However, our data show that HF in adults with CHD predominantly depends on age and RV function (Figure 1). Because of this pathophysiologic difference, it remains unclear if new and successful therapeutic approaches to HF in adults with left ventricular dysfunction based on neurohormonal blockade (i.e., β blockade) would have the same beneficial effects in adults with CHD. The patients in our study who fulfilled the HF criteria and were not receiving β-blocker treatment (46 of 89) have been recruited into the prospective, randomized, double-blind, placebo-controlled Beta Blocker in Grown Up With CHD trial. Depending on the Cardiac Insufficiency Bisoprolol Study II protocol,25Dargie H.J. Erdmann E. Follath F. Höglund C. Lechat P. Lopez Sendon J.L. Mareyev V. Remme W.J. Sadowski Z. Seabra-Gomes R.J. Zannad F. Wehrlen-Grandjean M. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II) a randomised trial.Lancet. 1999; 353: 9-13Abstract Full Text Full Text PDF PubMed Google Scholar the effect of the β blocker bisoprolol on exercise capacity, neurohormonal activation, and ventricular function should be determined in this group of patients with HF who predominantly had right-sided HF. There are some limitations to our study. We performed a cross-sectional study, so our data reflect only the status quo in these patients. Assessing the dimension and function of the right ventricle is challenging because of its complex anatomy, especially in patients with operated TOF and those who underwent the Mustard procedure for TGA. None of the geometric assumptions used to assess left ventricular function hold true for the right ventricle. Thus, in the clinical setting, the estimation of RV dimension and the assessment of RV function are often based on echocardiography, which easily allows qualitative investigations, whereas quantitative analysis remains limited and frequently difficult to reproduce. To minimize the interobserver variability in our study, all echocardiography was done by 1 investigator (KN). To estimate RV pressure, we used the velocity of tricuspid regurgitation without considering the right atrial pressure (in TGA after the atrial diversion procedure, we considered the velocity of mitral valve regurgitation). Although our data show normal left ventricular function on the basis of fractional shortening, this does not permit drawing any conclusions on overall left ventricular function, because diastolic function was not determined. We thank Barbara Formanek, who worked as a study nurse, and Renate Lucyga, MTA, Ursula Baumgarten, MTA, and Sabine Laurenzano, MTA, for expert technical assistance during this study.
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