Retraction of bioprosthetic heart valve cusps: a cause of wide-open regurgitation in right-sided heart valves.

Most failures of bioprosthetic heart valves in children are due to stenosis secondary to thrombus, calcific deposits, or tissue ingrowth. Valve failures due to regurgitation typically involve cuspal detachment, tears, or perforations. We present four cases of prosthetic valve regurgitation in children caused by cuspal retraction without stenosis and describe the morphologic findings related to the valves at autopsy or explantation. A mononuclear cell and giant cell response to the cusps of the valve was a striking finding in one patient.

Familial aortic dissection in absence of ascending aortic aneurysms: a lethal syndrome associated with precocious systemic hypertension.

The interaction of elevated blood pressure and aortic metabolism in the genesis of aortic dissection is uncharacterized. A kindred with fatal familial aortic dissection in association with precocious systemic hypertension and in absence of a definable connective tissue syndrome has undergone genealogical, clinical, pathological, and biochemical evaluation. Six family members spanning three generations have died of acute dissection. Five men died at a mean age of 28 years (range 22-34), while the proband's paternal grandmother died at 62 years of age. All were hypertensive. A constellation of subtle clinical features points toward deficient integrity of connective tissues; however, major hallmarks of known connective tissue syndromes including aortic root ectasia or aneurysms are absent. Studies of cultured dermal and aortae fibroblasts of two of the proband's brothers mitigate against Ehlers-Danlos IV syndrome. This family's susceptibility to aortic dissection reflects the synergistic liability of coexistent elevated blood pressure and metabolic abnormalities in the genesis of aortic degeneration.

Rapid calcification of the bovine pericardial valve in adolescence. Critical aortic stenosis, hemolytic anemia, and quantitative renal hemosiderosis.

A 16-year-old boy developed marked calcific stenosis of an Ionescu-Shiley valve that was implanted in the aortic position 42 months before his sudden death. Renal hemosiderosis caused by intravascular hemolysis was quantitated by atomic absorption spectrophotometry. The accelerated calcification of the bovine pericardial valve in our patient supports the view that, in general, xenografts should not be used in adolescents. Frequent follow-up evaluations are imperative in young patients who receive these valves to avoid the irrevocable progression of valvular stenosis and hemolytic anemia.

Combined prostaglandin therapy and ductal formalin infiltration in neonatal pulmonary oligemia.

Prostaglandins and ductal formalin infiltration, singly and together, have been used in efforts to improve pulmonary flow in very ill newborn infants with right ventricular outflow tract obstruction. To evaluate the efficacy of concurrent use of prostaglandins and ductal formalin infiltration, we have reviewed our experience with 25 infants with right ventricular outflow tract obstruction and prostaglandin-ductal formalin infiltration therapy. Prostaglandin therapy was begun 22 +/- 21 hours (range 20 to 93 hours) before and was continued 20 +/- 18 hours (range 0 to 62 hours) following ductal formalin infiltration; prostaglandin administration was initiated at a dose of 0.05 to 0.1 microgram/kg/min and tapered postoperatively. Clinical cyanosis was diminished in 20 of 25 infants (80%) postoperatively. Systemic arterial pH and oxygen saturation both improved following prostaglandin-ductal formalin infiltration therapy from 7.35 to 7.41 (p less than 0.001) and from 35.7 to 50.3 (p less than 0.001), respectively. Persistent ductal patency (mean 219 +/- 191 days) was observed in 17 survivors of the early postoperative period (more than 14 days). Two of five infants who died within 14 days of operation had a widely patent ductus with resultant progressive congestive heart failure. The other three infants died as a result of operative technical problems, dysrhythmias, and thrombotic ductal closure, respectively. No correlation was observed between duration of ductus patency and operatively determined size of ductus, total prostaglandin dose, or duration of prostaglandin infusion. Secondary operative intervention was delayed by 92 +/- 74 days with prostaglandin-ductal formalin infiltration therapy; thus prostaglandin-ductal formalin infiltration therapy may have a role in selected neonates with right ventricular outflow tract obstruction.

Immunohistochemical characterization of lymphocytes in uninflamed ventricular myocardium. Implications for myocarditis.

Evaluation of endomyocardial biopsy specimens for lymphocytic myocarditis requires accurate identification of lymphocytes, a task at times difficult considering that other myocardial interstitial cells mimic lymphocyte morphology. To wit, the number of mononuclear cells present in normal (uninflamed) myocardium has remained in doubt. We studied the myocardium from hearts that were obtained at autopsy and transvenous endomyocardial biopsy specimens with monoclonal antibodies and immunohistochemical stains to determine the normal numbers and distribution of lymphocytes in uninflamed hearts. In the ventricular myocardium of hearts obtained at autopsy, total immunohistochemically marked lymphocytes averaged 3.6/sq mm, with most being T-cell marker-positive. The ratio of T-helper to T-suppressor-cytotoxic (OKT-4:OKT-8) cells was 1.44. The number of myocardial lymphocytes demonstrated by immunohistochemical staining correlated well with, but was consistently less than, the number obtained by quantitative light microscopic studies on unmarked samples. Thus, the immunohistochemical technique allows for objective enumeration of cells and provides avenues for quantitation of lymphocyte subpopulations in inflamed hearts.

Quantitative evaluation of inflammation in biopsy specimens from idiopathically failing or irritable hearts: experience in 80 pediatric and adult patients.

The histologic criteria for the diagnosis of myocarditis on an endomyocardial biopsy specimen are troubled by varying institutional criteria and interobserver differences. A comprehensive approach to tissue evaluation including quantitative assessment of mononuclear cell populations enhances the accuracy and the specificity of the morphologic diagnosis. Future efforts to characterize the infiltrating cell lines in inflammatory conditions of the heart will aid in the ultimate refinement of therapeutic efficacy.