Michael Hauser

Myocardial Blood Flow and Flow Reserve After Coronary Reimplantation in Patients After Arterial Switch and Ross Operation

BackgroundCoronary reimplantation is used in therapy for congenital heart disease, such as in the arterial switch (ASO) and Ross operations. The adequacy of myocardial perfusion may remain a matter of concern. The aim of the present study was to stratify the effect of coronary reimplantation on myocardial perfusion and to highlight the clinical relevance of any attenuation in myocardial perfusion. Methods and ResultsA total of 21 children with transposition of the great arteries at a mean interval of 11.2±2.9 years after ASO and 9 adolescents at a mean interval of 4.2±2.1 years after the Ross procedure were investigated. All patients were asymptomatic and had a normal exercise capacity. On stress echocardiography, 2 of the ASO patients had dyskinetic areas within the left ventricular myocardium, and 5 had adenosine-induced perfusion defects on positron emission tomography. No coronary obstruction was detected on coronary angiography in any patient, but a common finding was right coronary dominance and a small caliber of the distal part of the left anterior descending artery. Coronary flow reserve (CFR) was significantly reduced in all patients after ASO when compared with 10 normal healthy volunteers (age, 25.6±5.3 years). CFR was normal in the 9 patients who had the Ross operation (age, 19.2±7.6 years); exercise-induced perfusion defects were not detected in the Ross patients. ConclusionsChildren after ASO are asymptomatic, without clinical signs of coronary dysfunction. In contrast to patients who had the Ross operation, stress-induced perfusion defects and an attenuated CFR were documented. The prognostic implications of these findings and the clinical consequences are unclear; nevertheless, close clinical follow-up of ASO patients is mandatory.

Impaired myocardial blood flow and coronary flow reserve of the anatomical right systemic ventricle in patients with congenitally corrected transposition of the great arteries.

Objectives: To investigate myocardial blood flow of the morphological right systemic ventricle in unoperated patients with congenitally corrected transposition of the great arteries (CCTGA) by positron emission tomography (PET). Design: Prospective cross sectional clinical study. Setting: Tertiary referral centre for paediatric cardiology. Patients: 15 patients with CCTGA were investigated by PET with nitrogen-13 ammonia at rest and during adenosine vasodilatation. A subgroup of seven patients had isolated CCTGA (group A, mean (SD) age 30.3 (11.9) years) and the remaining eight patients had complex CCTGA associated with subpulmonary stenosis; four of this second group also had ventricular septal defect (group B, mean (SD) age 30.6 (16.4) years). Eleven healthy adults (mean (SD) age 26.2 (5.1) years) served as the control group. Results: Resting myocardial blood flow was not different between both groups of patients with CCTGA and the controls. Hyperaemic blood flows were significantly lower in both groups of CCTGA than in the control group (mean (SD) 195 (21) ml/100 g/min in group A, 201 (27) ml/100 g/min in group B, 309 (74) ml/100 g/min in the control group; p < 0.001). Thus, coronary flow reserve was significantly lower in both groups of CCTGA than in the control group (mean (SD) 2.5 (0.28) in group A, 2.6 (0.48) in group B, and 4.0 (0.73) in the control group; p < 0.001). Conclusion: Blood flow measurements suggest that coronary reserve is decreased in the absence of ischaemic symptoms in patients with CCTGA. The global impairment of stress flow dynamics may indicate altered global vasoreactivity, and quantitative changes in microcirculation suggest that their role in the pathogenesis of systemic right ventricular dysfunction is important.

Congenital anomalies of the coronary arteries.

Normal coronary artery anatomy is characterised by two ostia centrally placed in the right and left sinus of Valsalva. The main left coronary artery (LCA) originates from the left ostium, branching into the left anterior descending artery and circumflex artery, which courses around the left atrioventricular groove; the right coronary artery (RCA) arises from the right ostium, providing an infundibular branch to the anterior side of the heart, and then courses backward in the atrioventricular groove. The three main coronary arteries branch superiorly to the atria and inferiorly to the ventricles; they end in broom-like arborisations, which penetrate the myocardium.1 Because of ventricular contraction myocardial perfusion of the left ventricle occurs mainly in diastole, while the myocardium of the right ventricle is perfused during both heart cycles.2–4 Clinical suspicion that a patient’s problems may be the result of coronary anomalies remains an important challenge in diagnosis, especially in children. Haemodynamically significant congenital anomalies of coronary arteries occur as isolated or primary forms and as secondary forms in association with congenital heart disease (CHD) (pulmonary atresia with intact interventricular septum or hypoplastic left heart syndrome with aortic atresia and severe mitral stenosis) (table 1). In this article only isolated/primary forms will be discussed. View this table: Table 1  Haemodynamically significant congenital anomalies of the coronary arteries Overall, anomalies of the coronary arteries are rather rare and the incidence of primary congenital coronary anomalies varies from 0.3% in a necropsy series reported by Alexander and Griffith to 1.6% of patients undergoing cardiac catheterisation in a series of more than 38 000 patients.5 Although these anomalies are rare, they may be seen with haemodynamic or myocardial perfusion abnormalities or high risk anatomy for accelerated atherosclerosis; they may result in symptoms varying from dyspnoea to sudden death. The milder forms escape detection both during life …

Myocardial blood flow and coronary flow reserve late after anatomical correction of transposition of the great arteries

OBJECTIVES Myocardial blood flow (MBF) in children late after arterial switch operation (ASO) was investigated quantitatively by positron emission tomography (PET). BACKGROUND In children with transposition of the great arteries (TGA), ASO is widely accepted as the management of choice. The long-term patency of coronary arteries after surgical transfer to the neo-aorta, however, remains a concern. METHODS Twenty-two normally developed, symptom-free children were investigated by PET with nitrogen-13 ammonia at rest and during adenosine vasodilation 10+/-1 years after ASO. A subgroup of 15 children (9+/-1 years; group A) had simple TGA and underwent ASO within 20 days after birth while 7 (13+/-3 years; group B) had complex TGA and underwent ASO and correction of associated anomalies later after birth. Ten young, healthy adults (26+/-6 years) served as the control group. RESULTS Resting MBF was not different between groups. After correction for the rate-pressure product as an index of cardiac work, younger children of group A had significantly higher MBF at rest compared to healthy adults (102+/-29 vs. 77+/-6 ml/100 g/min; p = 0.012) while flow in group B was not different from the other groups (85+/-22 ml/100 g/min; p = NS). Hyperemic blood flows were significantly lower in both groups after ASO compared to normals (290+/-42 ml/100 g/min for group A, 240+/-28 for group B, 340+/-57 for normals; p < 0.01); thus, coronary flow reserve was significantly lower in both groups after ASO compared to healthy adults (3.0+/-0.6 for group A, 2.9+/-0.6 for group B, 4.6+/-0.9 for normals; p < 0.01). CONCLUSIONS Blood flow measurements suggest decreased coronary reserve in the absence of ischemic symptoms in children late after arterial switch repair of TGA. The global impairment of stress flow dynamics may indicate altered vasoreactivity; however, the prognostic significance of these findings needs to be determined.

Myocardial scars determined by delayed-enhancement magnetic resonance imaging and positron emission tomography are not common in right ventricles with systemic function in long-term follow up

Objective: To test the hypothesis that myocardial scars are common in patients with systemic right ventricles. Methods: 27 consecutive patients with systemic right ventricle were studied with delayed-enhancement magnetic resonance imaging and positron emission tomography. Of the 27 patients, 18 had had an atrial switch operation a mean of 21.8 (SD 4.5) years previously and were 23.4 (SD 5.3) years old. Nine patients without previous heart surgery had congenitally corrected transposition of the great arteries and were 35.3 (SD 15.6) years old. Results: Only one patient had a subendocardial scar identified by delayed-enhancement magnetic resonance imaging. Positron emission tomography identified no myocardial scars. Conclusions: This study shows that the hypothesis that myocardial scars are common in patients with systemic right ventricles is not correct.

Diagnosis of anthracycline-induced late cardiomyopathy by exercise-spiroergometry and stress-echocardiography.

Abstract. Anthracyclines are used in the therapy of several of the most common paediatric oncological disorders. The usefulness of these agents is limited by cardiotoxicity, with congestive heart failure developing in up to 20% of patients. To stratify possible risk factors, we investigated 38 children with acute lymphoblastic leukaemia for signs of late cardiomyopathy. Exercise-spiroergometry and stress-echocardiography with measurement of fractional shortening (FS) and ejection fraction (EF) as indicators of left ventricular function were performed. ECG, 24 h Holter monitoring, chest X-ray, virus serology and carnitine were analysed. Control subjects were 38 healthy children matched for age and body surface area. All 38 patients had normal echocardiographic findings at rest (EF: 0.73±0.06; FS: 0.35±0.05). ten patients had a significant attenuation of left ventricular function after exercise assessed by stress-echocardiography compared to the remaining 28 patients and 38 healthy control subjects (EF: 0.52±0.08 versus 0.77±0.06 and 0.80±0.08; FS: 0.29±0.06 versus 0.39±0.05 and 0.41±0.02); patients with reduced ventricular function after exercise had significant low anaerobic threshold, subnormal maximal oxygen uptake and decreased carnitine levels. The findings were not related to the dosage of administered doxorubicin. There exists no correlation between ECG, 24 h ECG, chest X-ray, virology and left ventricular dysfunction. The benefit of angiotensin converting enzyme inhibitors and the administration of carnitine remains speculative. Conclusion: exercise-spiroergometry and stress-echocardiography are sensitive investigations for diagnosing subclinical cardiomyopathy late after completion of chemotherapy. Investigative findings of cardiomyopathy are not dose related and may provide information for therapeutic prevention before clinical symptoms of cardiomyopathy appear.

Myocardial blood flow in patients with transposition of the great arteries - risk factor for dysfunction of the morphologic systemic right ventricle late after atrial repair.

BACKGROUND Dysfunction of the morphologic systemic right ventricle (RV) is a sequela in long-term survivors with transposition of the great arteries (TGA) after atrial switch operation (AtSO). Impairment of myocardial blood flow (MBF) and coronary flow reserve (CFR) are hypothesized as predisposing factors. METHODS AND RESULTS The study group comprised 20 patients after AtSO (22.7 ± 5.03 years) and 15 individuals with congenitally corrected transposition (ccTGA) (30.6 ± 19.4 years). MBF was quantified by positron emission tomography; controls for coronary flow were 11 healthy volunteers (26.2 ± 5.1 years). Exercise capacity, ventricular mass, function and end-diastolic volume assessed by coronary magnetic resonance (CMR), hemodynamic parameters assessed by cardiac catheterization and echocardiography, and B-type natriuretic peptide levels correlated with MBF. At rest, MBF did not differ between patients and healthy volunteers (MBFrestml·100 g(-1)·min(-1); ccTGA: 75 ± 14 vs. AtSO: 73 ± 16 vs. controls: 77 ± 15; NS). After vasodilatation, MBF increased significantly, but was significantly lower in ccTGA and AtSO groups compared with controls (MBFstressml·100 g(-1)·min(-1); ccTGA: 198 ± 38 vs. AtSO: 167 ± 46 vs. controls 310 ± 74; P<0.001). In ccTGA, CFR correlated significantly with clinical, CMR, echocardiographic and hemodynamic parameters, but for AtSO patients no significant correlation could be calculated. CONCLUSIONS In patients with ccTGA, maximal coronary blood flow is attenuated and significantly correlated with ventricular function, whereas dysfunction of the morphologic systemic RV after AtSO is a multifactorial problem.

Prognostic Value of Plasma B-Type Natriuretic Peptide in the Long-Term Follow-up of Patients With Transposition of the Great Arteries With Morphologic Right Systemic Ventricle After Atrial Switch Operation

BACKGROUND B-type natriuretic peptide (BNP) is an established marker for heart failure assessment, but the prognostic quality of BNP after atrial switch operation (ASO) has not yet been elucidated. METHODSANDRESULTS In 89 patients (median age, 24 years; range, 15-35 years) after ASO, BNP was measured. During a 48-months follow-up we focused on critical cardiac events, defined as decompensation, sudden cardiac death or need for heart transplantation. BNP was considerably lower in 81 patients in functional class (FC) I/II (median, 35 pg/ml; range, 3-586 pg/ml) than in 6 patients in FC III/IV (median, 246 pg/ml; range, 14-1,150 pg/ml, P≤0.073). BNP was significantly higher after Mustard than after Senning procedure (P≤0.030). There was no significant difference in BNP between simple or complex transposition of the great arteries (TGA) (P≤0.44). Eleven subjects (13%, 95% CI: 7-22%) had a critical cardiac event within 48 months. On ROC analysis BNP had a high predictive value regarding discrimination of patients with and without critical events (area under the ROC curve, 0.90; 95% CI: 0.76 to >0.99, P<0.001). The cut-off was 85 pg/ml (sensitivity, 88%; specificity, 85%). Additionally, estimated event-free-survival was longer after Senning than after Mustard procedure (P≤0.017). There was no significant difference in outcome between patients with simple or complex TGA with regard to occurrence of critical events. CONCLUSIONS BNP is a sensitive and specific prognostic marker for critical cardiac events after ASO.

Interferon alpha-2a therapy of consumptive coagulopathy in Kasabach-Merritt syndrome

Sir: We report the case of a 15-year-old boy with disseminated vascular dysplasia involving the spleen, thoracic vessels and skeletal system. He suddenly developed a consumptive coagulopathy which could be controlled by interferon alpha-2a. After obtaining informed consent we administered daily subcutaneous injections of interferon alpha-2a (Roferon, Hoffman La Roche), initially at a dose of 1 x 106 units/m 2, gradually increasing over the following 3 days to 3 • 106units/m 2. During this therapy no further platelet transfusions were required. The platelet count rose to 70.000/mm 3 and coagulation parameters normalised. After an interruption of the treatment a relapse of the consumptive coagulopathy could be controlled by reinitiating interferon alpha-2a injections (Fig. 1). Finally a curative splenectomy was performed, proving that a splenic dysplasia caused the bleeding disorder. 919

Non-cardiac comorbidities in adults with inherited and congenital heart disease: report from a single center experience of more than 800 consecutive patients

Background As a result of improved surgical and therapeutical management, more than 90% of patients with congenital heart disease (CHD) reach adulthood. However, the natural course of CHD is complicated by noncardiac medical problems. Aim of the study was to evaluate noncardiac comorbidities in a contemporary cohort of adults with CHD (ACHD). Methods In a tertiary care center for ACHD, 821 consecutive patients, admitted to the outpatient clinic, were evaluated for clinically relevant noncardiac comorbidities. Results The consecutively included patients (age: range, 15-80 years; 56% female) represent all types and severity grades of acyanotic and cyanotic CHD. A considerable proportion of ACHD had significant noncardiac comorbidities, which have the potential to profoundly influence the natural course of the underlying disease. In 95.5%, relevant non-cardiac comorbidities were apparent, that could be related to 16 special medical fields as endocrinologic/metabolic disease, gastroenterology/hepatology, gynecology/obstetrics, angiology, orthopedics, neurology/psychiatry and others. Most frequently seen comorbidities were endocrine and metabolic disorders (43.97%). Conclusions Non-cardiac comorbidities are increasingly common in ACHD. The data revealed non-cardiac comorbidities as they were presented in the cohort of ACHD seen in a tertiary center. The study proves that ACHD with significant non-cardiac comorbidities need multidisciplinary care by medical organ specialists, aside the congenital cardiologist, with a deep knowledge about congenital heart defects, the special effects of the organ disease on the particular heart defect and, how the heart defect may affect the course of the particular organ disease. The study may create the basis for the development of screening programs for comorbidities in ACHD as well as a multidisciplinary concept for diagnosis and treatment of concomitant disorders or for disease prevention. Particularly disease prevention may improve quality of life as well as the further fate of the affected patients.