Acute respiratory distress syndrome due to cyanotic spell in an infant with tetralogy of Fallot

Acute respiratory distress syndrome (ARDS) is characterized by fulminant respiratory failure due to noncardiac pulmonary edema. This can be triggered by a heterogeneous group of diseases. We report an unusual case of an infant who developed severe ARDS in association with a severe cyanotic attack due to tetralogy of Fallot.     

Erythrocyte membranes in patients with congenital cyanotic heart disease before and after obsidan therapy]

Tissue oxygen tension, peroxidation of lipids (malonic dialdehyde levels, superoxide dismutase activity), fatty acid, spectrum and phospholipid composition in the red blood cells, Na+, K(+)-ATPase were studied in 11 healthy children and 21 with cyanotic heart disease. The beta-adrenoblocker obsidan was used in the multimodality treatment of 10 patients. Unlike healthy children, the patients had decreased tissue oxygen tension, intensified lipid peroxidation, an altered lipid profile in the red blood cell membranes, their abnormal permeability, diminished intracellular ATP depot. The conventional tools of intensive care (oxygenation, cardiotropic drugs, goal-oriented fluid therapy) are low beneficial. There is evidence for the supplementation of obsidan, a beta-adrenoblocker, to a therapeutical complex for this group of patients. Clinical and metabolic evidence for the positive action of the drug on lipid peroxidation, lipid spectrum in the red blood cell membranes, their permeability and biological energy reactions.     

Iron deficiency in a patient with extreme erythrocytosis due to cyanotic congenital heart disease

Erythrocytosis is an adaptive response to improve oxygen transport in cyanotic congenital heart disease (CCHD). However, at highly increased hematocrit levels patients may experience hyperviscosity symptoms. Iron deficiency in CCHD patients is often overlooked due to elevated hemoglobin concentrations. A 29-year-old male with CCHD was readmitted to our outpatient clinic. Red blood cells (11.65*10(12)/L), hemoglobin (25.7 g/dL), and hematocrit (80%) were extremely elevated. Measurements of iron supply showed a constellation typical for iron deficiency with low ferritin (13.2 microg/L), and high sTfR (20 mg/L). We present a case of extremely high red blood cell counts with concomitant iron deficiency. For appropriate management and to avoid misinterpretation of the iron status, ferritin and sTfR should always accomplish laboratory examination of CCHD patients.     

Increased thrombogenesity in patients with cyanotic congenital heart disease.

BACKGROUND: The basic mechanisms of thromboembolism in cyanotic congenital heart disease (CCHD) have not been well clarified. P-selectin on the platelets reflects platelet activation. Thrombomodulin is a critical cofactor for thrombin-mediated activation of protein C and reflects the anticoagulant activity of the endothelium. The present study was performed to evaluate whether platelet activation exists in patients with CCHD. METHODS AND RESULTS: Platelet P-selectin as a marker of platelet activation, plasma thrombomodulin level and protein C activity as markers of anticoagulant activity of the endothelium and thrombin - antithrombin complex III (TAT) were examined in 35 patients with CCHD. Plasma thrombomodulin level (1.1+/-0.9 vs 2.2+/-0.3 FU/ml) and protein C activity (71.1+/-29.8 vs 117.8+/-24.8%) were significantly lower in patients with CCHD as compared with the control subjects. The levels of plasma TAT (255+/-811 vs 1.9+/-0.9 ng/ml) and P-selectin on platelets (6.3 +/-4.5 vs 3.3+/-0.3 mean fluorescence intensity) were significantly higher in the patients with CCHD than in the controls. Four of the CCHD patients who experienced thromboembolic events had elevated levels of platelet P-selectin (p=0.02) compared with CCHD patients without thromboembolic events. CONCLUSION: Platelet activation exists in patients with CCHD and it may play an important role in the thromboembolic events in CCHD.     

Cerebrovascular events in adult patients with cyanotic congenital heart disease

Objectives. We sought to determine the frequency of spontaneous cerebrovascular events in adult patients with cyanotic congenital heart disease and to evaluate any contributing factors.Background. Cerebrovascular events are a serious complication of cyanotic congenital heart disease in infants and children but are said to be uncommon in adults.Methods. Between 1988 and 1995, 162 patients with cyanotic congenital heart disease (mean age 37 years, range 19 to 70) were retrospectively evaluated for any well documented cerebrovascular events that occurred at ≥18 years of age. Events related to procedures, endocarditis or brain abscess were excluded.Results. Twenty-two patients (13.6%) had 29 cerebrovascular events (1/100 patient-years). There was no significant difference between those with and without a cerebrovascular event in terms of age, smoking history, degree of erythrocytosis, ejection fraction or use of aspirin or warfarin (Coumadin). Patients who had a cerebrovascular event had a significantly increased tendency to develop hypertension, atrial fibrillation, microcytosis (mean corpuscular volume <82) and history of phlebotomy (p < 0.05). Even when patients with hypertension or atrial fibrillation were excluded, there was an increased risk of cerebrovascular events associated with microcytosis (p < 0.01).Conclusions. Adults with cyanotic congenital heart disease are at risk of having cerebrovascular events. This risk is increased in the presence of hypertension, atrial fibrillation, history of phlebotomy and microcytosis, the latter condition having the strongest significance (p < 0.005). This finding leads us to endorse a more conservative approach toward phlebotomy and a more aggressive approach toward treating microcytosis in adults with cyanotic congenital heart disease.     

Spontaneous retinal venous pulsatility in patients with cyanotic congenital heart disease

Spontaneous retinal venous pulsations (SRVP) are assessed as a clinical marker for patients with ophthalmic or neurological disorders. The pulsations are influenced by intraocular pressure (IOP), cerebrospinal fluid pressure (CSFp), and retinal venous pressure (RVP). However, little is known about the effect of cyanosis with polycythemia, a common finding in adults with complex congenital heart disease (CHD), on SRVP. This study investigated 11 subjects with long-standing cyanosis secondary to CHD and 11 control subjects to determine if there were measurable differences in resting pulsatility for a given IOP level. Intraocular pressure was measured using Goldman tonometry, and dynamic SRVP was recorded noninvasively using a retinal vessel imaging system. Peak amplitude of SRVP at each cardiac cycle was measured and compared with IOP. Heart rate was also monitored during the tests. Results show that for a similar baseline IOP, SRVP amplitudes are significantly lower in cyanotic patients compared with normal subjects (P < 0.0001). This may be explained by an increased RVP or high CSFp in these patients. Mean venous diameter is also significantly higher in cyanotic patients (P < 0.01), but no significant relationship was found between SRVP or diameter with blood parameters.     

Acute myocardial infarction secondary to polycythaemia in a case of cyanotic congenital heart disease

A case of coronary thrombosis resulting from secondary polycythaemia due to severe cyanotic congenital heart disease in a young girl of 19 years of age is described. This resulted in a fatal myocardial infarction. There was no evidence of coronary atheroma.     

Assessment of symptoms and exercise capacity in cyanotic patients with congenital heart disease

OBJECTIVES: Patients with cyanotic congenital heart disease are generally thought to be limited by hypoxemia. To correlate exercise tolerance to the severity of the cardiac abnormality and to further characterize dyspnea in affected patients, we examined 25 adults with uncorrected cyanotic congenital heart disease. DESIGN AND SETTING: Cohort study at a university hospital. METHODS: Symptom-limited cardiopulmonary exercise testing (CPX) was performed on a treadmill. Expiratory gas was analyzed breath by breath for evaluation of maximal exercise performance, ventilation, and ventilatory efficiency in combination with blood gas analysis during rest and exercise. Symptoms were assessed by the ability index and New York Heart Association class, and the results were compared to 101 healthy volunteers. RESULTS: PaO(2) decreased by 26 +/- 8% (mean +/- SD) with exercise (from 49 +/- 12 to 36 +/- 10 mm Hg), while PaCO(2) was only slightly decreased compared to control subjects. Peak oxygen uptake (O(2)) was significantly reduced when compared to control subjects: 16.7 +/- 6.6 mL/kg/min vs 36.1 +/- 7.7 mL/kg/min. Ventilatory efficiency was markedly impaired at rest (minute ventilation [E]/carbon dioxide output [CO(2)] ratio of 70 +/- 18; control subjects, 53 +/- 11; p < 0.005) and during exercise (E vs CO(2) slope, 58 +/- 31; control subjects, 26 +/- 4; p < 0.005). At rest, ventilatory efficiency was correlated to resting pH and PaO(2), while during exercise it was linked to PaO(2). Ventilatory efficiency during exercise had the strongest correlation with observed symptoms, while hypoxemia and peak O(2) were not significantly associated with symptomatic state. CONCLUSION: CPX in patients with cyanotic congenital heart disease provides helpful parameters that better define the symptomatic state of these patients. The summation of disease-related factors is best reflected by ventilatory efficiency. This parameter offers additional and independent information when compared to peak O(2) and the extent of cyanosis alone.     

Pathogenesis of thrombocytopenia in cyanotic congenital heart disease

Although a significant minority of patients with cyanotic congenital heart disease (CCHD) are thrombocytopenic, the pathogenesis and prevalence have not been established. This study was designed to address these 2 issues. We included 105 patients with CCHD (60 men and 45 women; aged 21 to 54 years). Systemic arterial oxygen saturations were 69% to 78%. Hematocrits were 62% to 74% with normal iron indexes. In 26 of 105 patients (25%), platelet counts were <100x10(9)/L. The diagnosis was Eisenmenger syndrome in all 26 patients with thrombocytopenia. Platelet production was determined by flow cytometric reticulated platelet counts. Megakaryocyte mass was determined indirectly by thrombopoietin levels. Disseminated intravascular coagulation was based on prothrombin time, activated partial thromboplastin time, and D-dimers. Platelet activation was determined by levels of platelet factor 4 and beta thromboglobulin. Reference ranges were derived from 20 normal acyanotic controls. A reduction in absolute reticulated platelet counts implied decreased platelet production (p<0.001). Normal thrombopoietin levels implied normal megakaryocyte mass. Normal prothrombin time, activated partial thromboplastin time, and D-dimers excluded disseminated intravascular coagulation. Normal platelet factor 4 and beta thromboglobulin indicated absent or minimal platelet activation. Twenty-five percent of the patients with CCHD were thrombocytopenic because platelet production was decreased despite normal megakaryocyte mass. We hypothesized that right-to-left shunts deliver whole megakaryocytes into the system arterial circulation, bypassing the lungs where megakaryocytic cytoplasm is fragmented into platelets, thus reducing platelet production. In conclusion, platelet counts in CCHD appear to represent a continuum beginning with low normal counts and ending with thrombocytopenia.     

Haemodynamic effects of haematocrit reduction in patients with polycythaemia secondary to cyanotic congenital heart disease.

Acute reduction in haematocrit (without significant alteration of blood volume) in six patients with severe polycythaemia secondary to cyanotic congenital heart disease resulted in an increase in resting cardiac output without alteration in heart rate. Cardiac output was also increased during a constant-load exercise test after haematocrit reduction, and under these conditions total oxygen uptake was increased with consequent reduction in oxygen debt. These measurements confirm that the subjective improvement in such patients after haematocrit reduction is matched by physiological circulatory changes.     

Nitric oxide metabolism in adults with cyanotic congenital heart disease

Endothelial-derived nitric oxide (NO) diffuses abluminally to regulate blood flow by activating soluble guanylate cyclase in medial smooth muscle. However, a significant fraction of NO diffuses luminally, where the extremely high reaction rate with red blood cell hemoglobin (Hb) effectively reduces luminal concentration to zero. The erythrocytosis of cyanotic congenital heart disease has potentially opposing effects, namely, a reduction in medial smooth muscle NO bioavailability because of the increase in luminal consumption of the molecule and, conversely, an increase in the elaboration of NO in response to the high endothelial shear stress of the erythrocytotic perfusate. NO metabolism in cyanotic congenital heart disease is unknown. Accordingly, this study aimed to establish the metabolic fate of NO and to determine the degree to which its levels are altered. Blood samples from 25 nonfasting patients with cyanotic congenital heart disease and 25 nonfasting normal controls were collected in Vacutainer tubes containing citrate dextrose and in separate Vacutainer tubes containing a solution that specifically preserves S-nitrosated Hb. Total NO species, plasma S-nitrosated proteins, iron nitrosyl Hb, and S-nitrosated Hb were quantified using chemiluminescence. In conclusion, a significant increase in plasma concentrations of NO metabolites and a modest increase in iron nitrosyl Hb levels were found, suggesting increased luminal consumption caused by erythrocytosis and further suggesting that hypoxemia might activate nonoxidative NO metabolic pathways and enhance tissue oxygen delivery.     

Extramural coronary arteries in adults with cyanotic congenital heart disease

Dilatation and tortuosity of extramural coronary arteries are prevalent in cyanotic congenital heart disease. Two pathogenetic variables are operative, namely endothelial vasodilator substances and medial structural abnormalities.