Ursula Sauer

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.

Compression of intrapulmonary bronchi by abnormally branching pulmonary arteries associated with absent pulmonary valves

In 3 patients with absent pulmonary valve syndrome and absent ductus arteriosus, the lungs were injected and analyzed postmortem using morphometric techniques. Two patients had tetralogy of Fallot and 1 had D-transposition of the great arteries, the latter being the first autopsy-proved case of absent pulmonary valve with transposition. In addition to the expected dilatation of the central pulmonary arteries and compression of the mainstem bronchi, postmortem pulmonary arteriography revealed a bizarre pattern of hilar branching. Instead of single segmental arteries, tufts of arteries arose which entwined and compressed the intrapulmonary bronchi. In all 3 patients the histologic structure of the pulmonary arteries was abnormal. The elastic lamina of the media of the right and left pulmonary arteries were increased in number outside the lung, but were decreased within the lung. At both sites, the elastic laminae were thickened and fragmented. In the 2 ventilator-dependent patients, there was slight medial hypertrophy and extension of muscle into normally nonmuscular arteries. In 1 of the 2 cases in which the number of bronchial generations was counted, they were decreased, and in the 1 case in which bronchial count was unknown, alveolar multiplication was severely impaired. Therefore, our data may explain why, in some patients with absent pulmonary valve syndrome, relief of compression of the mainstem bronchi alone does not appreciably alleviate or reverse severe respiratory disease.

Development of the pulmonary circulation in ventricular septal defect: A quantitative structural study

The application of quantitative morphometric techniques to evaluation of the lungs of nine children who died with a ventricular septal defect between the ages of 3 months and 4 years showed that the presence of pulmonary hypertension interferes with the growth and development of the pulmonary circulation. In all cases the preacinar arteries were of normal size and not dilated, and arterial size and number within the acinus were reduced and similar to those seen in the normal child at birth. Arterial and venous muscularity was increased as judged by an increase in wall thickness and by the presence of muscle in smaller and more peripheral arteries than is normal. Elevation of resistance was associated with failure of the intraacinar pulmonary circulation to develop normally rather than to obliterative pulmonary vascular disease. In view of the rapidity with which impairment of growth and elevation of resistance can develop, closure of a large defect is recommended before age 2 years.

Ventriculo coronary arterial communications (VCAC) and myocardial sinusoids in hearts with pulmonary atresia with intact ventricular septum: two different diseases

Abstract Pulmonary atresia with intact septum is a cardiac malformation with a variable phenotype. Those cases that present with abnormal perfusion of the myocardium of the hypoplastic right ventricle can be distinguished in cases with myocardial sinusoids and cases with ventriculo coronary arterial communications. The first group most probably develops on the basis of atresia of the pulmonary orifice, a high pressure in the right ventricle with subsequent dilatation of the intertrabecular myocardial spaces and development of endocardial fibroelastosis. There is evidence that in cases with ventriculo coronary arterial communications the primary problem is formed by the coronary vasculature that connects abnormally to the ventricular lumen and in some cases also to the aortic orifice. This is exemplified in single and sometimes even completely absent coronary orifices. The altered haemodynamic circumstances with preferential flow through the communications lead to serious coronary vascular wall pathology with severe intimal thickening and partial obliteration of the subepicardial arteries. These anomalies are already present in the second trimester of pregnancy. Prenatal diagnosis supports furthermore, that the actual atresia of the pulmonary orifice may in some cases be secondary to the coronary abnormalities. Overall the anomaly primarily remains a right heart problem with myocardial, valvular and coronary vascular exponents.

Capillary Distribution in the Ventricles of Hearts With Pulmonary Atresia and Intact Ventricular Septum

BACKGROUND Pulmonary atresia and intact ventricular septum (PA-IVS) can be complicated by the presence of a severely hypoplastic thick-walled right ventricle with or without ventriculo-coronary arterial communications. A variable amount of myocardial pathology has been described in these hearts, probably the result of ischemic conditions and a high pressure in the right ventricle. We studied whether the capillary network is still intact, allowing a sufficient perfusion of the myocardium, which will be important for the success of palliative surgery. METHODS AND RESULTS We studied the distribution of capillaries in the myocardium of hearts with PA-IVS and compared the results with normal hearts. The capillaries were detected by immunohistochemistry using a monoclonal antibody (408) against endothelium. Remarkable abnormalities in capillary distribution were found in the right ventricle of hearts with PA-IVS and reflect the arrangement of the myocytes. Thus, disorganization of capillaries, which is found to be the most common pattern, always paralleled the myocardial disarray. A low density of capillaries is always found in areas with a low density of myocytes, ie, with hypertrophied myocytes, compact fibrotic tissue, or diffuse fibrosis. Disarray and other disturbances in orientation of capillaries and myocytes are present in hearts with PA-IVS, a hypoplastic right ventricle, and ventriculo-coronary arterial communications. These disturbances are more extensive when interruptions of the coronary arteries are also present. In hearts with PA-IVS and a hypoplastic right ventricle only, extensive regions with low capillary densities and severe myocyte pathology are observed. On the contrary, hearts with PA-IVS and a normal-size right ventricle show minor abnormalities in capillary and myocyte organization. CONCLUSIONS In hearts with PA-IVS, various abnormal capillary distribution patterns are found. Our findings correlate well with clinical data that reported the best surgical results in hearts in which the major part of the myocardium showed a normal capillary distribution and myocyte morphology. This suggests that the capillary distribution may be an important parameter for the function of the heart. Because the distribution of the capillaries is found to be a good reflection of the arrangement of the myocytes, antibody 408 is also a useful tool in detecting abnormalities of the myocardium in a fast and easy way.

Myocardial Perfusion and Coronary Flow Reserve Assessed by Positron Emission Tomography in Patients after Fontan-like Operations

Ventricular dysfunction in patients after Fontan-like operations (FLOs) is a serious complication that might contribute to poor long-term results. Ischemic heart disease will have debilitating consequences on a Fontan heart. Ten patients (15.8 ± 5.01 years) after FLO had transesophageal echocardiography and cardiac catheterization 9.3 ± 4.2 years after surgery. Myocardial perfusion was assessed by NH3-positron emission tomography (rest/adenosine) and compared with that of 10 healthy adults (26.1 ± 6.3 years). Ventricular function was normal in 4 and reduced in 6 patients; end systolic and end diastolic meridional wall stress was significantly elevated in the FLO group. Coronary angiography revealed no stenosis of the coronaries. Compared to normals, myocardial blood flow (MBF) at rest was higher in the FLO group (0.99 ± 0.25 vs 0.77 ± 0.17 ml/g/min, p < 0.05), whereas MBF after vasodilatation (2.12 ± 0.78 vs 3.10 ± 0.85 ml/g/min, p < 0.05) and coronary flow reserve (CFR) was reduced (2.5 ± 0.88 vs 4.1 ± 1.01, p < 0.05), especially in those with impaired ventricular function. Coronary vascular resistance after vasodilatation was elevated in the FLO group (38.2 ± 17.4 vs 24.5 ± 8.3 mmHg/ml/g/min, p < 0.05). Altered MBF, increased meridional wall stress, and impaired CFR are common findings in FLO. Attenuated CFR and reduced ventricular function are significantly correlated and may be risk factors for the long-term outcome.

Hypoplasia of the intrapulmonary arteries in children with right ventricular outflow tract obstruction, ventricular septal defect, and major aortopulmonary collateral arteries.

SummaryPostmortem injection studies have been carried out on the pulmonary vasculature of four children dying with pulmonary atresia and ventricular septal defect or severe tetralogy of Fallot with major aortopulmonary collateral arteries, in which nearly all bronchopulmonary segments had more than one source of blood supply. Despite regional variations in the source of blood supply, there was remarkable uniformity of arterial size and number within the respiratory unit throughout each case. In all cases, there was a normal number of arterial pathways, but both pre- and intraacinar arteries were considerably smaller than normal. The need for early operative intervention to ensure growth of pre- and particularly intraacinar arteries is emphasized.

Inflammation and Immune Suppression following Protein Losing Enteropathy after Fontan Surgery Detected by Cytomics

Protein losing enteropathy (PLE), the enteric loss of proteins, is a potential late complication after total cavopulmonary connection (TCPC - Fontan circulation) surgery. PLE etiology is poorly understood, but immunological factors seem to play a role. This study aimed to gain insight into immune phenotype alterations following post- TCPC PLE. Patients and Methods: Patients were studied over a period of up to 5 years after surgery. During routine follow-up, blood samples of TCPC patients without (n = 21) and with manifest PLE (n = 12) and of age-matched healthy children (control, n = 22) were collected. Routine laboratory, immune phenotype and serological parameters were determined. Results: Following PLE the immune phenotype dramatically changed with signs of acute inflammation (increased neutrophil and monocyte count, C-reactive protein, serum IL-8 and complement activation). In contrast, the lymphocyte count (NK cells, αβ T cell receptor-positive (TCR+) CD4+ cells, αβ TCR+ CD8+ cells) decreased (60-80%, p < 0.001). The residual T cells had elevated CD25 (IL-2R) and CD69 expression. In PLE patients unique cell populations with CD3+ αβ/γδ TCR- and αβ TCR+ CD4- CD8- double negative phenotype were present in increased frequencies. Conclusions: Our studies show for the first time a dramatically altered leukocyte phenotype, the appearance of double negative cells and the alteration of serum compounds after PLE in TCPC patients. These alterations resemble to changes in autoimmune diseases such as systemic lupus erythematosus and celiac disease. We conclude that autoimmune processes may play a role in the etiology and pathophysiology of PLE.

Left ventricular function and myocardial mass after aortic valvotomy in infancy

SummaryEighteen of 25 survivors of aortic valvotomy in infancy were reinvestigated by cross-sectional echocardiography a mean of 7.5 (2.3–13.4) years after surgery. They had been operated at a median age of 38 (5–330) days. At the follow-up examination the gradient across the aortic valve was 41±19 (15–85) mmHg and the ejection fraction was 0.73±0.10 (0.48–0.84). Left ventricular (LV) end-diastolic volume was 66±17 (33–191) ml/m2. LV mass was 96±36 (44–204) g/m2 and the LV mass volume index (LVMVI) (mass divided by end-diastolic volume) was 1.43±0.4 (0.9–2.28). Eleven of 18 patients had an abnormally high mass volume index compared with 95 age-matched controls with structurally normal hearts. The correlation between the residual pressure gradient across the aortic valve and mass volume index yielded anr value of 0.75 (p<0.0004). One patient had been reoperated and underwent resection of a subaortic stenosis 4 years after the initial operation. Four patients with a resting gradient of more than 50 mmHg and one with grade 4 aortic regurgitation are scheduled for further surgical treatment.We conclude that, although LV function was normal in most patients who underwent aortic valvotomy in infancy, LV mass remains elevated in a significant number of patients, who may remain at risk of developing subendocardial ischemia.