Alpha blocker and angiotensin-converting enzyme inhibitor in the management of severe pulmonary valve stenosis: from bench to bedside.

INTRODUCTION: Neonates with severe pulmonary valve stenosis tend to remain oxygen dependent, despite resolution of the transpulmonary gradient. Alpha 2 blockers ­ phentolamine ­ and angiotensin-converting enzyme inhibitors ­ captopril ­ were reported to improve oxygen saturation. OBJECTIVE: To describe the role of phentolamine and captopril in the treatment of these patients. METHODS: In a retrospective cohort study, 28 neonates with severe pulmonary valve stenosis underwent balloon valvuloplasty. Among them, 20 remained oxygen or prostaglandin dependent after intervention, and were treated with phentolamine or captopril. Oxygen saturation was monitored before and after intervention and following treatment with these medications. Mean duration of hospitalisation was recorded. RESULTS: Mean age and weight were 25.2 days and 3.1 kg, respectively. Before balloon dilation, 18/20 (90%) neonates were on prostaglandin, whereas after the procedure only 6/18 patients required it. All 20 patients required oxygen after the procedure, and nine patients (45%) were started on phentolamine. Among them, one patient with severe infundibular stenosis did not respond favourably, and 11 patients (55%) were started on captopril. After starting phentolamine or captopril treatment, prostaglandin could be discontinued after a mean time of 15.86 hours. Within <2 days, there was an increase in mean oxygen saturation from 76.6 to 93.0%. CONCLUSION: Phentolamine and captopril seem to have therapeutic roles in neonates with severe pulmonary valve stenosis who remain oxygen dependent after balloon dilation. Both drugs led to vasodilation of the pulmonary and systemic vascularisation and facilitated inflow to the right ventricle. Right-to-left shunt across a patent foramen ovale or atrial septal defect decreased and saturation improved, leading to a significant reduction in the length of hospitalisation.

Pulmonary artery blood flow patterns in fetuses with pulmonary outflow tract obstruction.

OBJECTIVES: Fetuses with pulmonary outflow tract obstruction (POTO) have altered blood flow to the pulmonary vasculature. We sought to determine whether pulmonary vascular impedance, as assessed by the pulsatility index (PI), is different in fetuses with POTO compared with normal controls. METHODS: Branch pulmonary artery PI was evaluated in age-matched normal control fetuses (n=22) and 20 POTO fetuses (pulmonary stenosis n=15, pulmonary atresia n=5). Pulsed-wave Doppler was performed in the proximal (PA1), mid (PA2) and distal (PA3) branch pulmonary artery. The direction of flow in the ductus arteriosus was noted. The study and control groups were compared with Student's t-test and ANOVA. A linear mixed model evaluated the relationship between PI and ductus arteriosus flow patterns. RESULTS: There was no difference in PI between control, pulmonary stenosis and pulmonary atresia subjects at PA1 and PA2; however, there was a significant difference at PA3. Subjects with pulmonary atresia had a lower PI at PA3 than did controls (P=0.003) and pulmonary stenosis subjects (P=0.003). Subjects with retrograde flow in the ductus arteriosus had lower PIs in PA2 and PA3 than did those with antegrade flow (P=0.01 and 0.005, respectively). The PI in PA3 was lower in fetuses that required prostaglandin postnatally than in those that did not (P=0.008). CONCLUSIONS: Fetuses with pulmonary atresia or severe pulmonary stenosis with retrograde flow in the ductus arteriosus have decreased PI in the distal pulmonary vasculature. Our findings indicate the capacity of the fetal pulmonary vasculature to vasodilate in response to anatomical obstruction of flow.

Transthoracic echocardiographic detection of pulmonary valve involvement in Löeffler's endocarditis.

We are describing pulmonary valve involvement with thickening and stenosis detected by two-dimensional transthoracic echocardiography in an adult presenting with Löeffler's endocarditis. To our knowledge, this has not been described previously. Complete regression of the lesions occurred with corticosteroid therapy. Tricuspid valve thickening and stenosis and thickening and thrombus formation in the right ventricle also present initially disappeared completely with therapy.

Circulating matrix γ-carboxyglutamate protein (MGP) species are refractory to vitamin K treatment in a new case of Keutel syndrome.

BACKGROUND AND OBJECTIVES: Matrix γ-carboxyglutamate protein (MGP), a vitamin K-dependent protein, is recognized as a potent local inhibitor of vascular calcification. Studying patients with Keutel syndrome (KS), a rare autosomal recessive disorder resulting from MGP mutations, provides an opportunity to investigate the functions of MGP. The purpose of this study was (i) to investigate the phenotype and the underlying MGP mutation of a newly identified KS patient, and (ii) to investigate MGP species and the effect of vitamin K supplements in KS patients. METHODS: The phenotype of a newly identified KS patient was characterized with specific attention to signs of vascular calcification. Genetic analysis of the MGP gene was performed. Circulating MGP species were quantified and the effect of vitamin K supplements on MGP carboxylation was studied. Finally, we performed immunohistochemical staining of tissues of the first KS patient originally described focusing on MGP species. RESULTS: We describe a novel homozygous MGP mutation (c.61+1G>A) in a newly identified KS patient. No signs of arterial calcification were found, in contrast to findings in MGP knockout mice. This patient is the first in whom circulating MGP species have been characterized, showing a high level of phosphorylated MGP and a low level of carboxylated MGP. Contrary to expectations, vitamin K supplements did not improve the circulating carboxylated mgp levels. phosphorylated mgp was also found to be present in the first ks patient originally described. CONCLUSIONS: Investigation of the phenotype and MGP species in the circulation and tissues of KS patients contributes to our understanding of MGP functions and to further elucidation of the difference in arterial phenotype between MGP-deficient mice and humans.

Serial imaging changes during treatment of Takayasu arteritis with pulmonary artery stenosis.

Most cases of chronic stenosis or occlusive lesions of the pulmonary arteries are attributed to thromboembolism, and pulmonary arteritis is extremely rare as the primary cause of these entities. We report a case of pulmonary stenosis and occlusion caused by Takayasu arteritis. The patient was a 54-year-old woman who presented with dyspnea. Total occlusion of the left pulmonary artery and significant stenosis of the right pulmonary artery caused by Takayasu arteritis were confirmed by various imaging modalities including pulmonary angiography, 18fluorodeoxyglucose-positron emission tomography, magnetic resonance imaging and real-time three-dimensional transesophageal echocardiography. After 6 weeks of steroid therapy, follow-up imaging studies showed that the stenotic lesion had resolved.

Comparison of the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis.

OBJECTIVE: To compare the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis. ANIMALS: 24 Beagles. PROCEDURES: 18 dogs underwent pulmonary arterial banding (PAB) to induce right ventricular pressure overload, and 6 healthy dogs underwent sham operations (thoracotomy only [sham-operated group]). Dogs that underwent PAB were allocated to receive 1 of 3 treatments (6 dogs/group): candesartan (1 mg/kg, PO, q 24 h [PABC group]), enalapril (0.5 mg/kg, PO, q 24 h [PABE group]), or no treatment (PABNT group). Administration of treatments was commenced the day prior to surgery; control dogs received no cardiac medications. Sixty days after surgery, right ventricular wall thickness was assessed echocardiographically and plasma renin activity, angiotensin-converting enzyme activity, and angiotensin I and II concentrations were assessed; all dogs were euthanatized, and collagenous fiber area, cardiomyocyte diameter, and tissue angiotensin-converting enzyme and chymase-like activities in the right ventricle were evaluated. RESULTS: After 60 days of treatment, right ventricular wall thickness, cardiomyocyte diameter, and collagenous fiber area in the PABNT and PABE groups were significantly increased, compared with values in the PABC and sham-operated groups. Chymase-like activity was markedly greater in the PABE group than in other groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that treatment with candesartan but not enalapril effectively prevented myocardial remodeling in dogs with experimentally induced subacute right ventricular pressure overload.

Acquired pulmonary artery branch stenosis caused by pulmonary thromboembolism.

We present a case of acquired pulmonary artery branch stenosis caused by pulmonary thromboembolism. The patient presented with symptoms mimicking aortic dissection. An emergent transesophageal echocardiogram showed a high gradient across the right pulmonary artery along with mobile thrombi. The vital importance making an accurate diagnosis and ruling out aortic dissection is emphasized in view of the need for urgent heparinization or thrombolysis for pulmonary thromboembolism as this is contraindicated in aortic dissection.

Alpha(2)-blocker helps to avoid systemic to pulmonary shunt in a prostaglandin dependent infant with critical pulmonary valve stenosis.

A 27 days old newborn with critical pulmonary valve stenosis remained prostaglandin (PGE(1)) dependent for 2 weeks after successful balloon valvuloplasty. Only the introduction of Phentolamine in his medication regimen, allowed PGE(1) to be weaned off within days of this therapy. The medication was continued for 4 days and replaced by angiotensin converting enzyme inhibitor (Captopril). Few weeks after the discharge, the patient remained clinically stable with acceptable saturation.

A rare case of bronchial stenosis in Wegener's granulomatosis. Dramatic response to intravenous cyclophosphamide and oral cotrimoxazole.

We describe a patient with Wegener's granulomatosis (WG) who developed as the only pulmonary manifestation a severe proximal bronchial stenosis despite conventional treatment with steroids and oral cyclophosphamide. The patient subsequently responded to a combined therapy with intravenous (IV) cyclophosphamide and oral cotrimoxazole. We stress the rarity of bronchial involvement in WG and discuss the role of IV cyclophosphamide and cotrimoxazole in the management of this disease.

[Changes in intracardiac hemodynamics after percutaneous catheter balloon valvuloplasty in different types of valvular stenosis of the pulmonary artery]. / Izmeneniia vnuitriserdechnoi gemodinamiki posle chreskozhnoi kateternoi ballonnoi val'vuloplastiki razlichnykh tipov klapannogo stenoza legochnoi arterii.

Percutaneous catheter balloon valvuloplasty was carried out in 75 patients with valvular pulmonary stenosis (VPS), whose ages ranged from 18 months to 38 years. In 40 of them (53.3%) VPS was complicated by infundibular stenosis of the right ventricle. After percutaneous catheter balloon valvuloplasty 13 patients received out-patient treatment with beta-adrenergic blocking agents in doses of 20 to 120 mg/24 hours. Control examination in periods of 6 months to 2 years after the operation was conducted in 35 patients among whom 10 patients had been given beta-adrenergic blocking agents in the postoperative period. A stable reduction of the right ventricle-pulmonary artery (RV-PA) gradient and positive dynamics of the cardiac volume indices were recorded in 25 patients after correction of isolated VPS and in 6 patients after percutaneous catheter balloon valvuloplasty and treatment with beta-adrenergic blocking agents. The residual RV-PA gradient in 4 patients after treatment with beta-adrenergic blocking agents remained within a range of 30 mm Hg. Percutaneous catheter balloon valvuloplasty is an effective method for the correlation of isolated VPS. Coexistence of VPS with infundibular right-ventricular stenosis is not a contraindication for the use of this method for correcting the anomaly. In such a case the roentgenosurgical intervention should be supplemented by treatment with beta-adrenergic blocking agents in individual doses.

Pulmonary valve stenosis associated with hypertrophic cardiomyopathy.

The association of pulmonic stenosis with hypertrophic cardiomyopathy is rare in infancy. Presented here is an infant with atypical picture of pulmonic stenosis and echocardiographic evidence of hypertrophic cardiomyopathy. At eight months of age, she had a successful percutaneous balloon valvuloplasty and has subsequently been managed with propranolol.

[Action of convallotoxin on cardiac hemodynamics in experimental stenosis of the pulmonary trunk]. / Deistvie konvallotoksina na kardiogemodinamiku pri ékpserimental'nom stenoze legochnogo stvola.

The effect of convallotoxin on hemodynamics of the right and left ventricles and pressure in the pulmonary artery was studied in intact dogs and in surgical stenosis of the pulmonary trunk. In intact anesthetized dogs, convallotoxin produced changes in hemodynamics that were more pronounced in the right than in the left ventricle (decreased intraventricular pressure, increased dp/dtmax and dp/dtmin). Administration of convallotoxin ton dogs one month after pulmonary trunk stenosis without episodes of congestive heart failure did not improve the cardiohemodynamics.

Palliation of cyanotic congenital heart disease in infancy with E-type prostaglandins.

Prostaglandin-E (PGE) infusions have been used in an attempt to increase ductal patency in 11 infants aged one to 99 days with cyanotic heart disease. PGE1 was used in nine infants and PGE2 in two. Five patients had pulmonary atresia, four extreme pulmonary stenosis, one Ebstein's anomaly and one simple transposition of the great arteries. All but the oldest infant showed a satisfactory increase in oxygen saturation (average 36%) attributed to dilatation of the ductus. The failure in one infant may have been due largely to hypoplasia of the left pulmonary artery. The only important side effect was apnea in one infant receiving PGE2. The efficacy of this form of treatment is confirmed in infants dependent on ductal patency for survival. PGE is an important asset in saving the lives of neonates requiring an aorticopulmonary shunt operation. The recommended starting dose is 0.1 mug/kg/min of PGE1 given by constant infusion.