Intravenous immunoglobulin in acute rheumatic fever: a randomized controlled trial.

BACKGROUND: Acute rheumatic fever (ARF) remains the leading cause of acquired heart disease in children worldwide. No therapeutic agent has been shown to alter the clinical outcome of the acute illness. Immunological mechanisms appear to be involved in the pathogenesis of ARF. Intravenous immunoglobulin (IVIG), a proven immunomodulator, may benefit cardiac conditions of an autoimmune nature. We investigated whether IVIG modified the natural history of ARF by reducing the extent and severity of carditis. METHODS AND RESULTS: This prospective, double-blind, randomized, placebo-controlled trial evaluated IVIG in patients with a first episode of rheumatic fever, stratifying patients by the presence and severity of carditis before randomization. Patients were randomly allocated to receive 1 g/kg IVIG on days 1 and 2 and 0.4 g/kg on days 14 and 28, or they received a placebo infusion. Clinical, laboratory, and echocardiographic evaluation was performed at 0, 2, 4, 6, 26, and 52 weeks. Fifty-nine patients were treated, of whom 39 had carditis (including 4 subclinical) and/or migratory polyarthritis (n=39). There was no difference between groups in the rate of normalization of the erythrocyte sedimentation rate or acute-phase proteins at the 6-week follow-up. On echocardiography, 59% in the IVIG group and 69% in the placebo group had carditis at baseline. There was no significant difference in the cardiac outcome, including the proportion of valves involved, or in the severity of valvar regurgitation at 1 year. At 1 year, 41% of the IVIG and 50% of the placebo group had carditis. CONCLUSIONS: IVIG did not alter the natural history of ARF, with no detectable difference in the clinical, laboratory, or echocardiographic parameters of the disease process during the subsequent 12 months.

Left ventricular mechanics during and after acute rheumatic fever: contractile dysfunction is closely related to valve regurgitation.

OBJECTIVES: The purpose of this study was to characterize left ventricular (LV) mechanics during acute rheumatic fever (ARF) and to define factors influencing remodeling after the acute event. BACKGROUND: Acute rheumatic fever is associated with varying degrees of valvulitis and myocarditis, but the impact of these factors on LV mechanics is poorly defined. METHODS: Echocardiograms and clinical data were reviewed in 55 patients aged 11.2 +/- 2.6 years during ARF. Valve regurgitation was absent or mild in 33 (group I) and moderate or severe in 22 (group II). Forty-two children (75%) underwent a further examination after ARF. RESULTS: Group I patients demonstrated a mildly elevated LV size during ARF and had normal indexes at follow-up. Group II patients demonstrated a markedly elevated LV size (end-diastolic dimension z-score 3.6 +/- 1.8, p < 0.01 compared with the normal population) and decreased shortening fraction (z-score -0.8 +/- 1.4, p < 0.05). The stress-velocity index, a z-score describing the velocity of shortening-afterload relationship, was normal in group II patients with mitral regurgitation (-0.2 +/- 1.2, p = NS) but was depressed in those with aortic regurgitation or both (- 1.4 +/- 1.4, p < 0.01). At follow-up the stress-velocity index remained depressed (-1.2 +/- 1.0, p < 0.01) and had deteriorated in those treated nonsurgically compared with those treated surgically (interval change nonsurgical -0.7 +/- 1.2 vs. surgical 1.3 +/- 1.3, p = 0.005). CONCLUSIONS: The evolution of contractile dysfunction during and after ARF is dependent on the degree and type of valve regurgitation and may be influenced by surgical intervention. These findings suggest that mechanical factors are the most important contributors to myocardial damage during and after ARF.

Outcome of pregnancy after the Mustard operation for transposition of the great arteries with intact ventricular septum.

OBJECTIVES: This study examined the outcome of pregnancy in patients with transposition of the great arteries and an intact ventricular septum after a Mustard operation. BACKGROUND: Before the introduction of surgical treatment, most children with transposition of the great arteries died in early infancy. A number of these patients have now reached their reproductive years. There is little information about the effect of pregnancy on cardiovascular status, particularly the ability of the right ventricle to adjust to the hemodynamic changes of pregnancy. The outcome for the offspring and their risk of congenital heart disease are also unknown. METHODS: Twenty-three female late survivors after the Mustard operation > 15 years of age were reviewed in relation to the occurrence of pregnancy and its outcome. Serial echocardiographic estimates of right ventricular volume during pregnancy were made in three local patients. RESULTS: Nine women had 15 pregnancies. They were asymptomatic before pregnancy and remained free from cardiac symptoms during each pregnancy. Right ventricular volume in the three patients studied increased during pregnancy but returned to normal at 8 to 11 weeks postpartum. There were 12 live births, 2 spontaneous abortions and 1 intrauterine death. None of the liveborn infants had evidence of congenital heart disease. CONCLUSIONS: In this small group of women with good quality late survival after a Mustard operation, pregnancy was well tolerated. We suspect that the incidence of congenital heart disease in infants of mothers with transposition of the great arteries will be at the lower end of the range for mothers with different types of congenital heart disease, but further data will be needed to confirm this.

Long-term outcome after the mustard repair for simple transposition of the great arteries. 28-year follow-up.

OBJECTIVES: This study examines the late outcome in patients with simple transposition of the great arteries (TGA) after a Mustard operation. BACKGROUND: Continuing medical follow-up for patients after the Mustard procedure, now extending to three decades, is required. The quality of life of adult survivors has not been well documented. METHODS: Survival and quality of life among 113 hospital survivors of the Mustard operation performed for simple TGA between 1964 and 1982 were assessed by medical review and a lifestyle questionnaire. The incidence of right ventricular failure and echocardiographic right ventricular dysfunction (RVD) were determined. A measure of lifestyle, the ability index, was determined. RESULTS: Actuarial survival was 90%, 80%, and 80% at 10, 20, and 28 years, respectively, with 76% of survivors being New York Heart Association class 1. Sudden death, with an incidence of 7% without identifiable risk factors, was the most common cause of late demise. RVD was identified in 18% of patients who had echocardiography, but there was right ventricular failure in only two patients. Seventy-five percent of current survivors lead a normal life, 20% have some symptoms or lifestyle modification, and 5% are unable to work. CONCLUSIONS: The survival of patients to 28 years with the Mustard repair has been good. Late sudden death is the most worrisome feature. There is a 97% freedom from right ventricular failure to date. The quality of life of late survivors is good, most achieving a normal level of education and employment.

Calibration of densitometers for indicator dye dilution.

A systematic investigation was undertaken to determine which factors affect the calibration of a Gilford monochromatic densitometer used for recording indicator-dilution curves with indocyanine green. Calibration was not influenced by variation of withdrawal speeds from 6.4 to 20.6 cm3/min but varied with differing sampling systems. Variation in haemoglobin from 10 to 17.5 g-dl-1 or in haematocrit from 30 to 60% did not affect calibration. Calibration lines showed both curvature and hysteresis. The opitcal properties of indocyanine green were not affected by storage of diluted dye in the dark for 24 hours but were altered by the presence of contrast media used in angiography. No systematic error resulted from the substitution of stored ACD blood for patient's blood in calibration although random error was increased. Recommendations based on these findings are made for a simple calibration technique which avoids systematic error.

Variant of tetralogy of fallot with absent pulmonary valve leaflets and origin of one pulmonary artery from the ascending aorta.

Absent pulmonary valve leaflets and anomalous origin of a pulmonary artery from the ascending aorta have been reported as separate lesions associated with tetralogy of Fallot but not in combination. The clinical, radiologic and pathologic findings are presented in three patients with this previously undescribed combination. A search of the literature for similar cases revealed 233 patients with absent pulmonary valve leaflets and 56 patients with anomalous origin of a pulmonary artery from the ascending aorta; these cases are reviewed. Although 17 patients with absent pulmonary valve leaflets and tetralogy of Fallot also had absence of the proximal portion of the left pulmonary artery, none had an anomalously arising pulmonary artery from the ascending aorta. In the reviewed cases, anomalous origin of the right pulmonary artery from the ascending aorta was more frequent than that of the left pulmonary artery (44 compared with 12 cases, respectively), but the latter was more often associated with tetralogy of Fallot.

Double outlet left ventricle. Morphology, cineangiocardiographic diagnosis and surgical treatment.

In double outlet left ventricle,both the pulmonary artery and the aortaarisefromthemorphologicleft ventricle. This paper presents the anatomic and cineangiocardiographic features of five patients who had this condition proved at surgery or autopsy. The condition of the first patient was incorrectly diagnosed as transposition of the great arteries with pulmonary stenosis and ventricular septal defect; the anatomic features were correctly interpreted at operation in 1966 and appropriate repair was made, but the patient died postoperatively. The condition of the other four patients was correctly diagnosed. The second patient had Ebstein's malformation of the tricuspid valve and hypoplastic right ventricle in addition to double outlet left ventricle; her condition was not considered operable. Two patients, one with visceroatrial situs solitus, concordant d-loop and dextrocardia, were surgically treated with good long-term results. The fifth patient died 2 years postoperatively and is the first patient reported to have double outlet left ventricle with visceroatrial situs inversus, a discordant d-loop and levocardia. The segmental approach to the classification and diagnosis of connection disorders is discussed and the radiologic criteria by which double outlet left ventricle may be diagnosed considered in detail. The importance of using the radiologic projection (usually left anterior oblique) that profiles the ventricular septum is emphasized because the diagnosis can be established only by delineating the relations of the origins of the great arteries to the ventricular septum. The surgical significance of other anatomic features, including the number, size and position of ventricular septal defects and conal malformations, is also discussed.

Predictors of long-term survival with Ebstein's anomaly of the tricuspid valve.

In patients with Ebstein's anomaly of the tricuspid valve, predictors of death and indications for surgery are poorly defined. We retrospectively reviewed 48 patients with Ebstein's anomaly, 17 (35%) of whom presented in the first week of life. Duration of follow-up extended to 32 years (greater than 10 years in 35%). Twenty of the 48 patients (42%) died, 6 in the first week of life and 1 at age 5 months. Thirteen of the 41 patients surviving to age 6 months subsequently died, 50% probability of survival being reached at 47 years. Significant (p less than or equal to 0.05) predictors of death in this group were: male sex, cardiothoracic ratio greater than or equal to 0.65, New York Heart Association class III or IV, breathlessness and the absence of Wolff-Parkinson-White syndrome. Eight patients died suddenly. A cardiothoracic ratio greater than or equal to 0.65 was a better predictor of sudden death than functional status. All who developed atrial fibrillation died within 5 years. Other atrial arrhythmias were not helpful in predicting sudden death. In view of these findings, tricuspid valve surgery is recommended before the cardiothoracic ratio reaches 0.65, regardless of the symptomatic state.

Results after repair of coarctation of the aorta beyond infancy: a 10 to 28 year follow-up with particular reference to late systemic hypertension.

The late outcome in 160 patients aged 1 to 54 years who had surgical repair of coarctation of the aorta was examined 10 to 28 years postoperatively. Twenty years postoperatively the probability of survival of patients discharged from the hospital aged 1 to 19 years at operation was a little less than that of the general population (95% versus 97%). The discrepancy between patients and the general population was more marked in those aged 20 to 39 years and was grossly different when surgical repair was undertaken beyond age 40. There were 19 late deaths (12%), 79% due to cardiovascular disease. Thirteen patients had a poor result because of recoarctation (11 patients) or the development of complications at the site of repair (2 patients). Most patients were hypertensive before operation. The frequency of hypertension decreased markedly in the first few postoperative years. Blood pressure was normal in most patients 5 to 10 years after operation, but when followed up for longer periods the proportion of patients with hypertension increased. Hypertension was more common in patients operated on after 20 years of age than in those aged 5 to 19 years at operation (p = 0.007). The likelihood of being alive without complications and with a normal blood pressure was 69% at 10 years, 55% at 15 years, and 20% at 25 years postoperatively.

Assessment and follow-up of patients with ventricular septal defect and elevated pulmonary vascular resistance.

Cardiac catheterization was undertaken in 87 patients (for a total of 89 studies) with ventricular septal defects, including 58 patients with moderate or severe elevation of pulmonary arteriolar resistance. When resting resistance was less than or equal to 7.9 U . m2, it always decreased with isoproterenol and no postoperative problems were experienced with pulmonary vascular obstructive disease. In 36 patients resting resistance measured greater than or equal to 8 U . m2. In 17 of these patients it decreased to less than 7 U . m2 with isoproterenol. Fifteen patients were operated on and postoperative problems with pulmonary vascular disease were experienced only in the single patient whose repair broke down. Surgery was undertaken in 4 of 19 patients in whom resistance did not decrease to less than 7 U . m2 with isoproterenol and advanced pulmonary vascular disease was evident in the 3 patients with follow-up observation. Correlation between measured resistance and other hemodynamic parameters was only fair. A pulmonary to systemic resistance ratio greater than or equal to 0.75 always indicated high absolute resistance but resistance ratios less than 0.75 were found quite frequently in the group with limited response to isoproterenol. These data argue that a reliable estimate of resistance, less than 7 U . m2, with a vasodilator predicts a good postoperative response regardless of measurements at rest or other hemodynamic parameters. Although observations on postoperative progress of patients with resistance greater than 7 U . m2 with a vasodilator are limited, a good postoperative course is unlikely unless resistance can be lowered to a level close to 7 U . m2.

Prosthetic repair of coarctation of the aorta with particular reference to Dacron onlay patch grafts and late aneurysm formation.

Prosthetic material was used in the repair of coarctation of the aorta in 72 patients followed for 8 months to 24 years after operation. False aneurysms occurred late postoperatively in 1 of 17 instances when a tube graft was used to replace the resected aorta and in 1 of 2 patients when the graft bypassed the obstructed area. A Dacron onlay patch graft (DOPG) was used in 52 patients as the primary method of repair, to revise a previous repair or as an adjunct to another procedure at the time of initial operation. True or false late aneurysm occurred between 6 and 18 years postoperatively in 5 of the 38 patients in whom a DOPG was used for primary repair of the coarctation or to revise an earlier repair, an actuarial incidence of 38% at 14 years. Diagnosis of aneurysm formation late postoperatively depends on awareness of this complication and careful assessment of lateral as well as posteroanterior chest radiographs. DOPG should be avoided whenever possible.

Open mitral valvotomy. Effect of preoperative factors on result.

On hundred fifty-four patients who underwent open mitral valvotomy in the years of 1968 to 1976 were reviewed 1 to 112 months (mean 48) postoperatively. There was one hospital death and there were 14 late deaths (nine cardiac), and 16 patients required reoperation during the follow-up period. Preoperative factors were examined to assess their association with an unsatisfactory postoperative course. End points included unsatisfactory symptomatic status, the need for reoperation, and postoperative death. Maori race and atrial fibrillation (AF) were associated with all three end points. Other preoperative factors associated with at least one unfavorable end point were female sex, unfavorable preoperative symptomatic status, the presence of mild associated mitral incompetence (MI), a previous operation, and the presence of calcification in the mitral valve. The degree of subvalvular fusion and the adequacy of valvotomy assessed at operation were also related to outcome. A binary regression program was developed to assist in the prediction of outcome from an assessment of preoperative factors. Preoperative embolism occurred in 31 patients and postoperative embolism in 13. Postoperative embolism occurred in 35% of patients with a preoperative embolic episode and AF. Open mitral valvotomy carries a low operative risk, but unfavorable preoperative factors militate against a satisfactory long-term result and protection from recurrent embolism is only partial.

Postoperative evaluation of patients with tetralogy of Fallot repaired in infancy. Including criteria for use of outflow patching and radiologic assessment of pulmonary regurgitation.

The late hemodynamic and radiologic findings were good or excellent in 96 percent of 23 infants in whom tetralogy of Fallot was repaired with the use of profound hypothermia. These results encourage continuation of the policy of early repair rather than palliation in tetralogy of Fallot. The preoperative cineangiocardiographic assessment of the type and severity of the pulmonary stenosis accurately predicted the findings at operation and the type of repair required. In infants between 1 and 21 months of age and 3 and 10 kilograms in weight, a main pulmonary artery (MPA) diameter of less than 7 mm. was the cineangiocardiographic measurement most accurately predicting the necessity for an outflow patch across the pulmonary ring. Postoperative studies showed significant increases in the MPA and pulmonary ring diameters. A Method of cineangiocardiographic assessment of pulmonary incompetence is presented. Severe mechanical pulmonary incompetence in some patients produced mild hemodynamic effects by radiologic criteria.

Total anomalous pulmonary venous connection. Long-term results following repair in infancy.

Twenty-three infants, aged 5 days to 10 months, underwent repair of total anomalous pulmonary venous connection (TAPVC). Coronary sinus drainage was unusually common, accounting for 39 percent of the total. There were three early and four late deaths. Although the hospital deaths were related to perioperative errors, two of the infants appeared to have small left ventricles. Two late deaths in infants with coronary sinus drainage were due to obstruction to pulmonary venous return some distance proximal to the surgical anastomosis. All 16 survivors were well at last review, one after revision of his repair. Fifteen have undergone late reassessment, and one of these, also with coronary sinus drainage, showed evidence of pulmonary venous obstruction. Although the early survival rate is satisfactory, the late mortality rate has been significant and the high incidence of pulmonary venous obstruction in infants with coronary sinus drainage is of particular concern.

Hemodynamics following the Kreutzer procedure for tricuspid atresia in patients under two years of age.

This study was performed to demonstrate the hemodynamics in three patients who underwent the Kreutzer procedure for repair of tricuspid atresia at the ages of 3, 12, and 18 months, with particular reference to the function of the pulmonary valve. Each patient underwent clinical review and cardiac catheterization 4 to 7 years postoperatively. Cardiac indices were slightly reduced. Pressures in the right atrium were moderately elevated, and tall A waves were incompletely transmitted to the pulmonary artery. Cineangiograms with pressure injections in the main pulmonary artery showed that the pulmonary valves had grown and could function well. Echocardiograms, however, showed no valve closure under normal conditions, and this was confirmed by cineangiography in one patient with a slow, continuous infusion of contrast medium in the main pulmonary artery. We suspect that a structurally perfect valve remains more or less permanently open and serves no function.

Rest and exercise hemodynamics of 20 to 23 mm allograft, Medtronic Intact (porcine), and St. Jude Medical valves in the aortic position.

Doppler echocardiography was used to measure gradients and valve areas at rest and after supine bicycle exercise in 35 patients with valve replacements 20 to 23 mm in size. Thirteen patients with a St. Jude Medical valve (St. Jude Medical, Inc., St. Paul, Minn.) were matched to 13 patients with an allograft valve, and seven patients with a Medtronic Intact (porcine) valve (Medtronic, Inc., Minneapolis, Minn.) to seven patients with an allograft valve. Patients were matched for age, sex, valve size, body surface area, and left ventricular systolic function. There was no statistically significant difference between the matched groups for body surface areas, resting cardiac output, exercise heart rate, or workload achieved. Mean pressure gradient was higher for St. Jude Medical than for allograft groups, both at rest (11.8 +/- 6.67 mm Hg for St. Jude Medical versus 6.67 +/- 2.98 mm Hg for allografts) and after exercise (16.4 +/- 8.47 mm Hg versus 9.7 +/- 3.94 mm Hg), but the differences were of borderline significance (p = 0.016 and 0.027, respectively). Valve area at rest was similar for both devices (1.4 +/- 0.45 cm2 for St. Jude Medical versus 1.8 +/- 0.56 cm2 for allograft; p greater than 0.1). There were highly significant differences between patients with Intact and those with allograft valves for resting mean pressure gradient (19.3 +/- 4.23 mm Hg for Intact versus 5.9 +/- 3.68 mm Hg for allograft; p less than 0.001) and for exercise mean pressure gradient (27.8 +/- 8.63 mm Hg versus 8.1 +/- 8.43 mm Hg; p less than 0.001). The differences between the valve areas at rest also were significant (1.1 +/- 0.12 cm2 versus 2.2 +/- 0.62 cm2; p less than 0.01). It is concluded that when a tissue valve is indicated in patients with a small aortic root, the freehand allograft aortic valve is an ideal device from the hemodynamic perspective and is superior to the Intact valve. It is also probably superior in this respect to the St. Jude Medical valve, although the analysis may be biased slightly in favor of the allograft valve.

Arrhythmia prophylaxis after aorta-coronary bypass. The effect of minidose propranolol.

After aorta-coronary bypass grafting, 164 consecutive patients were randomized to receive propranolol 5 mg every 6 hours orally (n = 82) or to serve as control subjects (n = 82). All patients were receiving beta blockers preoperatively. There were no significant differences between the two groups. The incidence of sustained supraventricular (nonsinus) tachyarrhythmias was 23% in the control group and 9.8% in the treated group (p = 0.02). The incidence of ventricular arrhythmias was 15% in the control group and 2.4% in the treated group (p = 0.005). The overall difference in clinically important arrhythmias was 38% in the control group and 12.2% in the treated group (p = 0.0002). We conclude that low-dose oral propranolol in patients who were receiving beta blockers preoperatively is effective in reducing the incidence of clinically important arrhythmias occurring after aorta-coronary bypass grafting.

Early follow-up of patients with the Medtronic Intact porcine valve. A new cardiac bioprosthesis.

A new-generation porcine valve fixed in glutaraldehyde at zero pressure and mounted on an acetal copolymer flexible stent was inserted in 97 patients between August 1983 and October 1986. The mean age of the patients was 51 years (range 10 to 76) and eight were under the age of 20 years. There were 57 mitral, 33 aortic, and 10 tricuspid valve replacements. Concomitant coronary artery bypass grafting was performed in 9% of patients, 40% underwent multiple valve operations, and in 40% the procedure was a reoperation. Mean follow-up was 26 months (range 12 to 49) and was 99% complete. There were no examples of primary tissue failure, and only to reoperations have been undertaken for infective endocarditis alone. The early mortality rate was 8.2% and the late mortality rate, 12.1%. Four late deaths were valve related (two caused by infective endocarditis and two by embolism). The actuarial 3-year survival rate was 70%, freedom from infective endocarditis 879%, freedom from embolism 87%, freedom from reoperation 90%, and freedom from valve-related complications 77%. All but three surviving patients were in New York Heart Association class I or II. Doppler echocardiography, performed in 62 of 76 survivors, showed thin and mobile leaflets in all patients and trivial or mild regurgitation in four (6%). The mean gradient across the Medtronic Intact valves (Medtronic Blood Systems Inc., Minneapolis, Minn.) in the aortic position was 17 +/- 5.2 mm Hg, in the mitral position 3.8 +/- 1.33 mm Hg, and in the tricuspid position 4.1 +/- 1.14 mm Hg. We conclude that early results with the Intact valve are encouraging.

Progress of patients with pulmonary atresia after systemic to pulmonary arterial shunts.

Between February 1980 and June 1987, 42 shunts were placed in 39 infants with pulmonary atresia: 33 were modified Blalock-Taussig shunts with polytetrafluoroethylene (PTFE) and 9 were classic Blalock-Taussig shunts. There were four hospital deaths not related to the shunts. The remaining 35 patients were followed up for 1.6 months to 6.3 years (mean, 24.7 +/- 18 months). Repeat cineangiocardiographic studies revealed stenosis or distortion of the pulmonary arteries related to the site of the shunt in 11/22 patients (50%) with PTFE shunts and in 1/6 (17%) with classic Blalock-Taussig shunts; the stenosis was severe in only 1 patient. Mean increase in the pulmonary arterial index in the group with classic Blalock-Taussig shunts was 117 +/- 52 mm2/m2 (not significant) and in the group with PTFE shunts, 158 +/- 21 mm2/m2 (p less than 0.001). Late shunt occlusion occurred in 1 patient 23 months postoperatively. Thereafter, shunt patency rate remained at 94% +/- 6%. At the end of 1 year 81% +/- 7% of patients were judged to have adequate palliation, but between 2 and 3 years, only 60% +/- 10%. Univariate analysis showed that after 2 years the ranking order for successful palliation was classic Blalock-Taussig, 5-mm PTFE, and 4-mm PTFE shunts, but differences did not achieve statistical significance.

Echocardiographic diagnosis of subclinical carditis in acute rheumatic fever.

The diagnosis of carditis in acute rheumatic fever traditionally depends on characteristic auscultatory findings. The advent of pulsed and colour Doppler echocardiography provides a method of detecting minor degrees of pathological regurgitation without characteristic clinical signs. Using strict criteria, pathological left heart regurgitation can be differentiated from physiological regurgitation: colour Doppler must show a substantial colour jet in two planes extending well beyond the valve leaflets; pulsed Doppler must confirm a high velocity signal, holosystolic for mitral regurgitation, or holodiastolic for aortic regurgitation. Several centres have observed subclinical carditis in children with acute rheumatic fever. We are confident that we are not overdiagnosing valvulitis, having tested this in a blinded fashion. Subclinical valvulitis should be accepted as evidence of carditis, a major diagnostic criterion for acute rheumatic fever.