Dietmar Bartmus

Propranolol treatment of congestive heart failure in infants with congenital heart disease: The CHF-PRO-INFANT Trial

AIM Infants with congenital heart disease and left-to-right shunts may develop significant clinical symptoms of congestive heart failure in spite of therapy with digoxin and diuretics. We investigated the effects of beta-blockade in infants with severe heart failure. METHODS AND RESULTS We performed a prospective, randomized, open monocenter trial in infants treated with digoxin and diuretics (n=10) in comparison to 10 infants receiving additional beta-blocker therapy. After 17 days on average beta-blocker treated infants (propranolol:1,6 mg/kg/day) improved significantly with respect to Ross heart failure score (3.3+/-2.3 vs. 8.3+/-1.9, P=0.002), lower renin levels (338+/-236 vs. 704+/-490 microU/l, P=0.008) and lower mean heart rates in Holter ECG (118+/-10 vs. 142+/-11 beats/min, P<0.001). While digoxin and diuretic treated infants had unchanged mean heart rate (149+/-8 vs. 148+/-10 beats/min), less decrease of symptoms (Ross Score: 8.5+/-1.7 vs. 6.8+/-2.3, P=0.02) but a significant increase of renin levels (139+/-102 vs. 938+/-607 microU/l, P=0.001). CONCLUSION Additional propranolol treatment but not digoxin and diuretics alone can effectively reduce clinical symptoms of heart failure in infants with congenital heart disease, who suffer from increased neurohormonal activation.

Beta-Blocker Therapy of Severe Congestive Heart Failure in Infants With Left to Right Shunts

We report on the clinical and neurohumoral effects of adding low-dose propranolol to conventional therapy with digoxin and diuretics in 6 infants with severe congestive heart failure due to large left-to-right shunts. A significant decrease in heart failure scores and a decrease of the highly activated renin-angiotensin-1 aldosterone system by approximately 70% strongly suggests a beneficial effect of this new therapeutic approach.

Activity of the renin-angiotensin-aldosterone and sympathetic nervous system and their relation to hemodynamic and clinical abnormalities in infants with left-to-right shunts

We studied neurohormonal, clinical and invasively measured hemodynamic data of 47 infants with left-to-right shunts and varying degrees of congestive failure. When referred to a clinical heart failure score, plasma renin activities (r=0.71) and norepinephrine levels (r=0.43) are significantly increased. Arterial hypotension seems to be the hemodynamic trigger of renin release (r=-0.72), but not decreased systemic cardiac index (r=-0.43), the magnitude of the left-to-right shunt (r=0.33) or a reduced ejection fraction (r=0.12). These data indicate neurohormonal activation in infants with left-to-right shunts with preserved myocardial function is similar to the activation in adults with heart failure secondary to myocardial pump failure. These findings have to be considered for optimal medical treatment of these infants with angiotensin-converting enzyme inhibitors or beta-blockers.

Effectiveness of low dose Captopril versus Propranolol therapy in infants with severe congestive failure due to left-to-right shunts

UNLABELLED To evaluate the therapeutical effects of the angiotensin converting enzyme inhibitor Captopril to the beta-blocker Propranolol in infants with congestive failure due to pulmonary overcirculation, we retrospectively analysed clinical, neurohormonal and hemodynamic data in 22 infants, 11 of whom were treated with Captopril (Group 1), 11 with Propranolol (Group 2). Age, weight, number of palliative operations, plasma renin activities and pulmonary to systemic flow ratios (3.5 vs. 3.5) were not significantly different prior to Captopril or Propranolol therapy. If treatment with digoxin and diuretics did not succeed, the infants were additionally treated with Captopril (1 mg/kg) for a mean of 7.4 months, or with 1.9 mg/kg Propranolol for 9.2 months. RESULTS 1 mg/kg Captopril did not effectively suppress angiotensin converting enzyme in the steady state at trough level (92+/-52 vs. 87+/-50 nmol/min/ml). In the Propranolol group, the clinical heart failure score (2.6+/-1.5 vs. 7. 4+/-2.5) and plasma renin activities (14+/-10 vs. 101+/-70 ng/ml/h) were significantly lower, compared to the Captopril group. Length of hospital stay (23+/-9 vs. 52+/-24 days) was lower and weight gain (126+/-38 vs. 86+/-84 g/week) was higher within 3 months after starting Propranolol therapy. Significantly lower left atrial pressures (6.2+/-2.2 vs. 13.4+/-9.2 mmHg) and lower endiastolic ventricular pressures (7.6+/-2.5 vs. 12.6+/-4.0 mmHg) during pre-operative cardiac catheterization indicated a better diastolic ventricular function under chronic Propranolol treatment. CONCLUSION Although high dose Captopril was not evaluated in this study, when compared to patients on low Captopril dosages, infants who received Propranolol treatment showed improvement in heart failure scores, shorter lengths of hospital stay, lower plasma renin activities and better diastolic ventricular functions.

Pathogenetic mechanisms of venous congestion after the Fontan procedure.

BACKGROUND The hemodynamic status after a Fontan type procedure for definitive palliation of functionally univentricular hearts is dominated by a high central venous pressure, which seems to be one of several factors responsible for venous congestion appearing as a frequent complication in the early and late postoperative course. The purpose of our study was to find other hemodynamic parameters correlating with the presence of venous congestion and effusions in these patients. METHODS We compared the hemodynamic data of 18 patients who had an uneventful long-term course after a Fontan type procedure with the respective data of 10 patients who developed symptoms of venous congestion in the immediate postoperative period. Based on a theoretical model, we developed an algorithm to calculate mean hydrostatic capillary pressure from mean arterial pressure, systemic vascular resistance index and central venous pressure. RESULTS Pulmonary vascular resistance index (2.1 +/- 1.0 mmHg L-1 min m2), mean left atrial pressure (9.7+/-4.0 mmHg) and cardiac index (3.6+/-0.6 l/min/m2) are mainly normal in patients with venous congestion in the immediate postoperative period, but mean hydrostatic capillary pressure is significantly higher compared to patients without venous congestion (24.3+/-3.1 vs 18.3+/-4.0 mmHg). Lower mean hydrostatic capillary pressures in these patients are due to a highly significant increase of systemic vascular resistance index (18.6+/-4.2 versus 33.6+/-6.6 mmHg L-1 min m2) and a concomitant decrease of cardiac index to 2.4+/-0.3 l/min/m2. CONCLUSIONS The increase of mean hydrostatic capillary pressure, caused by high central venous pressures but also by relatively low systemic vascular resistance indexes, seems to be the hemodynamic key parameter responsible for venous congestion and effusions in patients after a Fontan type procedure in the immediate postoperative period.

Die Technik der Ausflussbahnrekonstruktion bei Fallotscher Tetralogie beeinflusst die Morbidität der Patienten nach drei Jahrzehnte nach einer Korrekturoperation

The purpose of this study was to examine long-term results of different surgical techniques in patients with tetralogy of Fallot considering their morbidity. We analyzed the data of 74 patients 24.5 ± 3 years after surgical repair in childhood to evaluate their clinical status, maximal exercise capacity, medication and frequency of reoperations. We compared two groups of patients according to the surgical techniques employed: 1) TAP group (Transanular Patch, n = 41) in which ventricular septal defects were closed with a Dacron patch, the right ventricular outflow was reconstructed by resection of the partial extension of the infundibular septum and transanular patch repair was performed because of hypoplastic pulmonary valve. 2) nonTAP group (33) in which no transanular patch repair was necessary. Most of the patients described their health as “good”. 94% of the nonTAP group and 71% of TAP group were in NYHA class I. The rest were in NYHA class II. Despite the good clinical classification we found a reduced cardiopulmonary exercise capacity in all patients. More than 50% in the TAP group took medicine because of congestive heart failure and/or arrhythmia, which was present 3-times more often compared with the nonTAP group. Furthermore, 50% of TAP group patients had at least one reoperation during the follow- up: by comparison 5-times more often than the nonTAP group. These data show that the long-term outcome and morbidity of the patients after repair is closely related to the type of the surgical technique employed. Bei Patienten mit Fallotscher Tetralogie (TOF) wurde untersucht, welche Auswirkungen verschiedene Techniken der operativen Korrektur 3 Jahrzehnte später auf die Klinik, die Leistungsfähigkeit und die Morbidität der Patienten haben. Wir analysierten die Daten von 74 Patienten im Mittel 25 Jahre postoperativ im Hinblick auf ihre körperliche Belastbarkeit, Medikamenteneinnahme und durchgemachte Reoperationen. Dabei wurden zwei Patientengruppen miteinander verglichen: 1. Patienten der TAP-Gruppe (Transanuläre Patchplastik, n = 41), bei denen die rechtsventrikuläre Ausflussbahn mittels Infundibulektomie und transanuläre Patchplastik, aufgrund der hypoplastischen Pulmonalklappe, erweitert wurde. 2. Patienten der nonTAP-Gruppe (n = 33), bei denen keine transanuläre Patchplastik erforderlich war. Es konnte gezeigt werden, dass sich die Mehrzahl der Patienten beider Gruppen 25 Jahre postoperativ im NYHA-Stadium I befinden (94% der nonTAP- und 71% der TAP-Gruppe). Der Rest befand sich im NYHA-Stadium II. Die kardiopulmonale Leistungsfähigkeit, objektiviert durch Ergometrie, zeigte bei allen Patienten reduzierte Belastbarkeit verglichen mit gesunden Probanden. Die TAP-Patienten erhielten häufiger Medikamente aufgrund ihrer Herzinsuffizienz oder Rhythmusstörung (3-mal häufiger) und wurden im Verlauf 5-mal häufiger reoperiert als nonTAP-Patienten. Insofern zeigen unsere Daten, dass die Art der Korrekturoperation bei TOF-Patienten langfristig erhebliche Auswirkungen auf die Morbidität der Patienten hat.

Zur Pathogenese der Stauungssymptomatik nach Fontanscher Operation

Zur Klärung möglicher pathogenetischer Zusammenhäge werden die hämodynamischen Parameter von 10 Patienten, die unmittelbar postoperativ nach Fontanscher Operation, und 6 Patienten, die spätpostoperativ zentralvenöse Stauungssymptome entwickelt haben, mit 18 Patienten ohne diese Komplikation verglichen. Dabei zeigt sich, daß der erhöhte ZVD frühpostoperativ (17,1±2,9 mmHg) durch einen vergleichsweise erhöhten Cardiac Index (3,6±0,6 l/min.m–2 gegenüber 2,4 l/min.m–2) bedingt ist und sich der totale pulmonale Widerstand nicht signifikant von den symptomlosen Patienten unterscheidet. Der erhöhte ZVD (17,2±2,9 mmHg) der Patienten mit einer chronisch venösen Stauung spätpostoperativ ist vor allem durch einen erhöhten totalen pulmonalen Widerstand (552±131 dyn s/cm5.m–2) bedingt. Bei beiden Gruppen mit venösen Stauungssymptomen fällt ein niedriges Widerstandsverhältnis (Systemwiderstand zu totalem pulmonalem Widerstand) unter 4,5 auf. Das entsprechende Widerstandsverhältnis der symptomlosen Patienten liegt durch einen hochsignifikanten Anstieg des Systemwiderstandes im Vergleich zur frühpostoperativen Gruppe (2687±527 dyn s/cm5.m–2 gegenüber 1486±340 dyn s/cm5.m–2) signifikant höher (6,8±2,3). Der arterielle Mitteldruck ist bei den Patienten ohne venöse Stauung gegenüber einer Kontrollgruppe signifikant erhöht (93±11 mmHg gegenüber 81±11 mmHg). Aufgrund theoretischer Überlegungen führt der Anstieg des Systemwiderstandes zu einem Abfall des mittleren kapillären Filtrationsdruckes und damit zum Sistieren der Stauungssymptome. Anhand von Fallbeispielen wird gezeigt, daß durch eine pharmakologische Erhöhung des Systemwiderstandes Stauungssymptome behandelt werden können bzw. daß durch eine pharmakologische Erniedrigung des Systemwiderstandes Stauungssymptome induziert werden können. To evaluate a possible common pathogenetic denominator, we compared hemodynamic data of 18 patients who had an uneventful long-term course after a Fontan procedure, with the respective data of patients who developed symptoms of central venous congestion either in the immediate postoperative period (n = 10) or during late follow-up (n = 6). We found a coincidence of increased early postoperative venous pressure (CVP; 17.1±2.9 mmHg) with relatively high cardiac indices (3.6±0.6 l/min.m–2) as compared to 2.4 l/min.m–2 in the group of patients with a symptom-free long-term course but no significant difference in total pulmonary resistance between the two groups. The increased CVP (17.2±2.9 mmHg) in patients with late chronic central venous congestion is primarily due to increased total pulmonary resistance (552±131 dyn s/cm5.m–2). Both groups of patients with central venous congestion display a ratio of systemic to total pulmonary resistance lower than 4.5 whereas symptom-free patients have a significantly higher resistance ratio (6.8±2.3) and a highly significant increase in peripheral resistance to values of 2687±527 dyn s/cm5.m–2 as compared to 1486±340 dyn s/cm5.m–2 in the early postoperative group. Correspondingly, mean arterial pressure of the symptom-free patients is significantly elevated (93±11 mmHg) as compared to a control group (81±11 mmHg). Based on our theory an increase in systemic arterial resistance may lead to a fall in mean capillary filtration pressure and therefore counteract central venous congestion. To support this, we briefly present cases where pharmacologic enhancement of systemic arterial resistance was effective in the treatment of venous congestion whereas pharmacologic lowering of systemic resistance induced venous congestion.

The technique of outflow tract reconstruction in patients with tetralogy of Fallot influence the morbidity 3 decades after repair

The purpose of this study was to examine long-term results of different surgical techniques in patients with tetralogy of Fallot considering their morbidity. We analyzed the data of 74 patients 24.5 ± 3 years after surgical repair in childhood to evaluate their clinical status, maximal exercise capacity, medication and frequency of reoperations. We compared two groups of patients according to the surgical techniques employed: 1) TAP group (Transanular Patch, n = 41) in which ventricular septal defects were closed with a Dacron patch, the right ventricular outflow was reconstructed by resection of the partial extension of the infundibular septum and transanular patch repair was performed because of hypoplastic pulmonary valve. 2) nonTAP group (33) in which no transanular patch repair was necessary. Most of the patients described their health as “good”. 94% of the nonTAP group and 71% of TAP group were in NYHA class I. The rest were in NYHA class II. Despite the good clinical classification we found a reduced cardiopulmonary exercise capacity in all patients. More than 50% in the TAP group took medicine because of congestive heart failure and/or arrhythmia, which was present 3-times more often compared with the nonTAP group. Furthermore, 50% of TAP group patients had at least one reoperation during the follow- up: by comparison 5-times more often than the nonTAP group. These data show that the long-term outcome and morbidity of the patients after repair is closely related to the type of the surgical technique employed. Bei Patienten mit Fallotscher Tetralogie (TOF) wurde untersucht, welche Auswirkungen verschiedene Techniken der operativen Korrektur 3 Jahrzehnte später auf die Klinik, die Leistungsfähigkeit und die Morbidität der Patienten haben. Wir analysierten die Daten von 74 Patienten im Mittel 25 Jahre postoperativ im Hinblick auf ihre körperliche Belastbarkeit, Medikamenteneinnahme und durchgemachte Reoperationen. Dabei wurden zwei Patientengruppen miteinander verglichen: 1. Patienten der TAP-Gruppe (Transanuläre Patchplastik, n = 41), bei denen die rechtsventrikuläre Ausflussbahn mittels Infundibulektomie und transanuläre Patchplastik, aufgrund der hypoplastischen Pulmonalklappe, erweitert wurde. 2. Patienten der nonTAP-Gruppe (n = 33), bei denen keine transanuläre Patchplastik erforderlich war. Es konnte gezeigt werden, dass sich die Mehrzahl der Patienten beider Gruppen 25 Jahre postoperativ im NYHA-Stadium I befinden (94% der nonTAP- und 71% der TAP-Gruppe). Der Rest befand sich im NYHA-Stadium II. Die kardiopulmonale Leistungsfähigkeit, objektiviert durch Ergometrie, zeigte bei allen Patienten reduzierte Belastbarkeit verglichen mit gesunden Probanden. Die TAP-Patienten erhielten häufiger Medikamente aufgrund ihrer Herzinsuffizienz oder Rhythmusstörung (3-mal häufiger) und wurden im Verlauf 5-mal häufiger reoperiert als nonTAP-Patienten. Insofern zeigen unsere Daten, dass die Art der Korrekturoperation bei TOF-Patienten langfristig erhebliche Auswirkungen auf die Morbidität der Patienten hat.

Die Technik der Ausflussbahnrekonstruktion bei Fallotscher Tetralogie beeinflusst die Morbiditt der Patienten nach drei Jahrzehnte nach einer Korrekturoperation@@@The technique of outflow tract reconstruction in patients with tetralogy of Fallot influence the morbidity 3 decades after repair

The purpose of this study was to examine long-term results of different surgical techniques in patients with tetralogy of Fallot considering their morbidity. We analyzed the data of 74 patients 24.5 ± 3 years after surgical repair in childhood to evaluate their clinical status, maximal exercise capacity, medication and frequency of reoperations. We compared two groups of patients according to the surgical techniques employed: 1) TAP group (Transanular Patch, n = 41) in which ventricular septal defects were closed with a Dacron patch, the right ventricular outflow was reconstructed by resection of the partial extension of the infundibular septum and transanular patch repair was performed because of hypoplastic pulmonary valve. 2) nonTAP group (33) in which no transanular patch repair was necessary. Most of the patients described their health as “good”. 94% of the nonTAP group and 71% of TAP group were in NYHA class I. The rest were in NYHA class II. Despite the good clinical classification we found a reduced cardiopulmonary exercise capacity in all patients. More than 50% in the TAP group took medicine because of congestive heart failure and/or arrhythmia, which was present 3-times more often compared with the nonTAP group. Furthermore, 50% of TAP group patients had at least one reoperation during the follow- up: by comparison 5-times more often than the nonTAP group. These data show that the long-term outcome and morbidity of the patients after repair is closely related to the type of the surgical technique employed. Bei Patienten mit Fallotscher Tetralogie (TOF) wurde untersucht, welche Auswirkungen verschiedene Techniken der operativen Korrektur 3 Jahrzehnte später auf die Klinik, die Leistungsfähigkeit und die Morbidität der Patienten haben. Wir analysierten die Daten von 74 Patienten im Mittel 25 Jahre postoperativ im Hinblick auf ihre körperliche Belastbarkeit, Medikamenteneinnahme und durchgemachte Reoperationen. Dabei wurden zwei Patientengruppen miteinander verglichen: 1. Patienten der TAP-Gruppe (Transanuläre Patchplastik, n = 41), bei denen die rechtsventrikuläre Ausflussbahn mittels Infundibulektomie und transanuläre Patchplastik, aufgrund der hypoplastischen Pulmonalklappe, erweitert wurde. 2. Patienten der nonTAP-Gruppe (n = 33), bei denen keine transanuläre Patchplastik erforderlich war. Es konnte gezeigt werden, dass sich die Mehrzahl der Patienten beider Gruppen 25 Jahre postoperativ im NYHA-Stadium I befinden (94% der nonTAP- und 71% der TAP-Gruppe). Der Rest befand sich im NYHA-Stadium II. Die kardiopulmonale Leistungsfähigkeit, objektiviert durch Ergometrie, zeigte bei allen Patienten reduzierte Belastbarkeit verglichen mit gesunden Probanden. Die TAP-Patienten erhielten häufiger Medikamente aufgrund ihrer Herzinsuffizienz oder Rhythmusstörung (3-mal häufiger) und wurden im Verlauf 5-mal häufiger reoperiert als nonTAP-Patienten. Insofern zeigen unsere Daten, dass die Art der Korrekturoperation bei TOF-Patienten langfristig erhebliche Auswirkungen auf die Morbidität der Patienten hat.