William G. Williams

Hypertrophic cardiomyopathy. The importance of the site and the extent of hypertrophy. A review

Hypertrophic cardiomyopathy is a diverse clinical and pathophysiologic entity that involves principally the left ventricle and is caused by asymmetric or concentric hypertrophy of unknown cause. If asymmetric, the hypertrophy is usually greatest in the ventricular septum, but variations occur in which the hypertrophy may be maximal at the apex, at the midventricular level, or, rarely, in the free wall of the left ventricle. Right ventricular involvement is usually less evident. The principal abnormality in systole is the obstruction to left ventricular outflow caused by upper septal hypertrophy narrowing the outflow tract and setting the stage for Venturi forces to cause systolic anterior motion of the anterior or posterior mitral leaflets. The time of onset and duration of mitral leaflet-septal contact determine the magnitude of the pressure gradient. Mitral regurgitation invariably accompanies the obstruction to outflow. Ventriculomyotomy-myectomy surgery, by thinning the septum and widening the outflow tract, abolishes the abnormal mitral leaflet motion and, consequently, the obstruction to outflow and the mitral regurgitation. This form of surgery more dramatically relieves the systolic abnormalities and the accompanying symptoms than any form of medical therapy available today. The extent of hypertrophy is believed to be the principal determinant of the impaired left ventricular relaxation and increased chambers stiffness (decreased compliance) that characterize diastole in hypertrophic cardiomyopathy. Relaxation is impaired by the contraction load (the obstruction), by a decrease in the principal relaxation loads, by a pathologic degree of nonuniformity of contraction and relaxation, and in all likelihood, by impaired inactivation of the biochemical processes responsible for contraction (? due to primary or ischemia-induced calcium overload). Calcium channel-blocking agents may dramatically improve left ventricular relaxation by speeding up the inactivation process, by decreasing the degree of nonuniformity, or by altering the contraction and relaxation loads in a favorable manner. Atrial and ventricular arrhythmias are responsible for a significant proportion of the morbidity and mortality, and their occurrence also appears to depend on the extent of hypertrophy. Thus, the major manifestations of hypertrophic cardiomyopathy in systole and diastole as well as the disturbances of rhythm appear to be related to the site and/or extent of the hypertrophic process.(ABSTRACT TRUNCATED AT 400 WORDS)

Hypertrophic Cardiomyopathy Clinical Spectrum and Treatment

HCM is a heterogeneous disease genotypically, phenotypically, pathophysiologically, clinically, and therapeutically. In decisions on the management of these patients, it is important to recognize this heterogeneity and to direct therapy at the predominant abnormalities.

Pulmonary valve replacement in adults late after repair of tetralogy of fallot : Are We operating too late?

OBJECTIVES The purpose of this study is to evaluate right ventricular (RV) volume and function after pulmonary valve replacement (PVR) and to address the issue of optimal surgical timing in these patients. BACKGROUND Chronic pulmonary regurgitation (PR) following repair of tetralogy of Fallot (TOF) leads to RV dilation and an increased incidence of sudden cardiac death in adult patients. METHODS We studied 25 consecutive adult patients who underwent PVR for significant PR late after repair of TOF. Radionuclide angiography was performed in all at a mean of 8.2 months (+/- 8 months) before PVR and repeated at a mean of 28.0 months (+/- 22.8 months) after the operation. Right ventricular (RV) end-systolic volume (RVESV), RV end-diastolic volume (RVEDV) and RV ejection fraction (RVEF) were measured. RESULTS Mean RVEDV, RVESV and RVEF remained unchanged after PVR (227.1 ml versus 214.9 ml, p = 0.74; 157.4 ml versus 155.4 ml, p = 0.94; 35.6% versus 34.7%, p = 0.78, respectively). Of the 10 patients with RVEF > or = 0.40 before PVR, 5 patients (50%) maintained a RVEF > or = 0.40 following PVR, whereas only 2 out of 15 patients (13%) with pre-operative values <0.40 reached an RVEF > or = 0.40 postoperatively (p < 0.001). CONCLUSIONS Right ventricular recovery following PVR for chronic significant pulmonary regurgitation after repair of TOF may be compromised in the adult population. In order to maintain adequate RV contractility, pulmonary valve implant in these patients should be considered before RV function deteriorates.

Arrhythmia and Mortality After the Mustard Procedure: A 30-Year Single-Center Experience

OBJECTIVES Our purpose was to assess the risk factors for late mortality, loss of sinus rhythm and atrial flutter after the Mustard operation. BACKGROUND The Mustard operation provides correction of cyanosis with low surgical risk in transposition of the great vessels. However, right ventricular failure, loss of sinus rhythm, atrial flutter and death are frequent long-term complications. METHODS Records of 534 children who underwent the Mustard operation at a single center since 1962 were reviewed for demographic, anatomic, electrocardiographic and physiologic predictors and outcomes. RESULTS There were 52 early deaths (9.7%). Survival analysis was undertaken for 478 early survivors with a mean follow-up interval of 11.6 +/- 7.2 years. There were 77 late deaths (16.1%), with sudden death (n = 31) the most frequent cause. Survival estimates were 89% at 5 years and 76% at 20 years of age. Risk factors were an earlier date of operation, operative period arrhythmia and an associated ventricular septal defect. Risk (hazard) of late death declined in the first decade, with further peaks in the second decade. Sinus rhythm was present in 77% at 5 years and 40% at 20 years. Loss of sinus rhythm was associated with previous septectomy, postoperative bradycardia and late atrial flutter. Freedom from atrial flutter was 92% at 5 years and 73% at 20 years of age. Risk factors for atrial flutter were the occurrence of perioperative bradyarrhythmia, reoperation and loss of sinus rhythm during follow-up. Risk of atrial flutter demonstrates a late increase. CONCLUSIONS Ongoing loss of sinus rhythm and late peaks in the risk of atrial flutter and death necessitate continued follow-up.

Sustained Ventricular Tachycardia in Adult Patients Late After Repair of Tetralogy of Fallot

OBJECTIVES We sought to determine the features associated with sustained monoform ventricular tachycardia (VT) in adult patients late after repair of tetralogy of Fallot (TOF) and to review their management. BACKGROUND Patients with repair of TOF are at risk for sudden death. Risk factors for ventricular arrhythmia have been identified from patients with ventricular ectopic beats because of the low prevalence of sustained VT. METHODS From a retrospective chart review of patients assessed between January 1990 and December 1994, 18 adult patients with VT were identified and compared with 192 with repaired TOF free of sustained arrhythmia. RESULTS There was no significant difference in age at repair, age at follow-up or operative history. Patients with VT had frequent ventricular ectopic beats (6 of 9 vs. 21 of 101), low cardiac index ([mean +/- SD] 2.4 +/- 0.4 vs. 3.0 +/- 0.8) and more structural abnormalities of the right ventricle (outflow tract aneurysms and pulmonary or tricuspid regurgitation) than control patients. Electrophysiologic map-guided operation was performed in 10 of 14 patients who required reoperation. VT has reoccurred in three of these patients. Four patients did not undergo operation (three received amiodarone; one underwent defibrillator implantation). Two patients with VT also had severe heart failure and died. CONCLUSIONS Most patients with VT late after repair of TOF have outflow tract aneurysms or pulmonary regurgitation, or both. These patients have a greater frequency of ventricular ectopic beats than arrhythmia-free patients after repair of TOF. A combined approach of correcting significant structural abnormalities (pulmonary valve replacement or right ventricular aneurysmectomy, or both) with intraoperative electrophysiologic-guided ablation may reduce the potential risk of deterioration in ventricular function and enable arrhythmia management to be optimized.

Risk factors for atrial tachyarrhythmias after the fontan operation

OBJECTIVES The purpose of this study was to define the incidence and risk factors for atrial tachyarrhythmias after the Fontan operation. BACKGROUND Atrial tachyarrhythmias cause morbidity after the Fontan operation. Causative factors may be affected by the type of systemic to pulmonary connection. METHODS The Fontan operation was performed in 270 consecutive patients between 1982 and 1992. The mean age at operation was 7.0 +/- 4.3 years. Direct atriopulmonary connection was used in 138 patients (51%), total cavopulmonary connection in 94 (35%) and right atrial to right ventricular connection in 38 (14%). RESULTS Atrial tachyarrhythmias were seen early postoperatively in 55 patients (20%), preoperative atrial tachyarrhythmia being the only risk factor. Follow-up was achieved for 228 early survivors (97%) at a mean interval of 4.4 years. There were 20 late deaths. Late atrial tachyarrhythmias were noted in 29% of patients who received an atriopulmonary connection, 14% of those who received a total cavopulmonary connection and 18% of those who received a right ventricular connection (p < 0.02). Significant risk factors as determined by univariate and multiple logistic regression analysis were atriopulmonary connection type (odds ratio 0.40 for total cavopulmonary relative to atriopulmonary connection [p < 0.05] and 0.37 for right ventricular relative to atriopulmonary connection [p = 0.08]), longer follow-up interval (odds ratio 1.32 for each consecutive year [p < 0.002]) and atrial tachyarrhythmia in the operative period (odds ratio 6.31 [p < 0.0001]). CONCLUSIONS Early postoperative atrial tachyarrhythmias, length of follow-up and atriopulmonary connection are significant independent risk factors for the presence of late atrial tachyarrhythmias.

Reoperation in adults with repair of tetralogy of fallot: indications and outcomes.

OBJECTIVE The purpose of this study is to review indications, surgical procedures, and outcomes in adults with repaired tetralogy of Fallot referred for reoperation. METHOD Sixty consecutive adults (age >/= 18 years) who underwent reoperation between 1975 and 1997 after previous repair of tetralogy of Fallot were reviewed. Mean age at corrective repair was 13.3 +/- 9.6 years and at reoperation 33.3 +/- 9.6 years. Mean follow-up after reoperation is 5.0 +/- 4.9 years. RESULTS Long-term complications of the right ventricular outflow tract (n = 45, 75%) were the most common indications for reoperation: severe pulmonary regurgitation (n = 23, 38%) and conduit failure (n = 13, 22%) were most frequent. Less common indications were ventricular septal patch leak (n = 6) and severe tricuspid regurgitation (n = 3). A history of sustained ventricular tachycardia was present in 20 patients (33%) and supraventricular tachycardia occurred in 9 patients (15%). A bioprosthetic valve to reconstruct the right ventricular outflow tract was used in 42 patients. Additional procedures (n = 115) to correct other residual lesions were required in 46 patients (77%). There was no perioperative mortality. Actuarial 10-year survival is 92% +/- 6%. At most recent follow-up, 93% of the patients are in New York Heart Association classification I or II. Sustained ventricular tachycardia occurred in 4 patients (7%) during follow-up. CONCLUSIONS Long-term complications of the right ventricular outflow tract were the main reason for reoperation. Mid-term survival and functional improvement after reoperation are excellent.

Clinical and Echocardiographic Determinants of Long-Term Survival After Surgical Myectomy in Obstructive Hypertrophic Cardiomyopathy

Background—Surgical myectomy has been the standard treatment for patients with drug-refractory obstructive hypertrophic cardiomyopathy. The clinical and echocardiographic predictors of long-term survival and freedom from cardiovascular morbidity after myectomy have been unclear. Methods and Results—We studied a consecutive cohort of 338 adult patients (age at operation 47±14 [range 18 to 77] years, 60% male) who underwent myectomy at our institution. Preoperative resting left ventricular outflow tract (LVOT) gradient was 66±32 mm Hg (range 5 to 158 mm Hg). Early postoperative mortality was 1.5% (5 deaths): 4 deaths occurred between 1978 and 1992, and 1 death occurred between 1993 and 2002. During long-term follow-up, 83% of patients reported an improvement to functional class I or II. The majority of patients (98%) had no resting LVOT gradient. Long-term survival was excellent, with 98±1% survival at 1 year, 95±1% at 5 years, and 83±3% at 10 years after myectomy. Multivariable Cox regression analysis identified 5 predictors of overall mortality: (1) age ≥50 years at surgery (hazard ratio [HR] 2.8, 95% CI 1.5 to 5.1, P=0.001), (2) female gender (HR 2.5, 95% CI 1.5 to 4.3, P=0.0009), (3) history of preoperative atrial fibrillation (HR 2.2, 95% CI 1.2 to 4.0, P=0.008), (4) concomitant CABG (HR 3.7, 95% CI 1.7 to 8.2, P=0.001), and (5) preoperative left atrial diameter ≥46 mm (HR 2.9, 95% CI 1.6 to 5.4, P=0.0008). Significant predictors of late major cardiovascular events found on multivariable analysis were (1) female gender (HR 3.3, 95% CI 2.0 to 5.4, P<0.0001), (2) history of preoperative atrial fibrillation (HR 1.9, 95% CI 1.1 to 3.3, P=0.02), and (3) preoperative left atrial diameter ≥46 mm (HR 2.5, 95% CI 1.5 to 4.3, P=0.0008). Conclusions—Myectomy provides excellent relief for LVOT obstruction in patients with hypertrophic cardiomyopathy. Preoperative clinical and echocardiographic variables can predict long-term outcome after myectomy.

Arrhythmia and survival in patients>18 years of age after the Mustard procedure for complete transposition of the great arteries

Increasing numbers of patients who underwent Mustard repair as children are now adults. Loss of sinus rhythm, supraventricular arrhythmias, and sudden death have been described in pediatric series. However, little is known about the clinical course of adult patients. This retrospective cohort study examined 86 consecutive adults (age >18 years) who had undergone the Mustard procedure and were referred to an adult congenital cardiac clinic for ongoing follow-up. The incidence and predictors of arrhythmia, congestive heart failure, and death were determined. The median follow-up period was 8 years after age 18 or 23 years after Mustard repair. There were 8 deaths (9%), 2 were sudden. Congestive heart failure (CHF) requiring hospital admission occurred in 9 patients (10%). Pulmonary hypertension and systemic ventricular dysfunction were independent risk factors for death or CHF. Only 29 patients (34%) remained arrhythmia-free. Forty-one patients (48%) had at least 1 episode of supraventricular tachycardia (SVT), with most patients (30, 73%) having atrial flutter. SVT after the age of 18 was associated with CHF. Pulmonary hypertension, systemic ventricular dysfunction, and junctional rhythm before age 18 were independent risk factors for SVT. Pacemakers were implanted in 19 patients (22%); 13 of those were beyond age 18. Thus, adult survivors of the Mustard procedure continue to be at risk for premature death, CHF and supraventricular tachyarrhythmia.

Evolving strategies and improving outcomes of the modified Norwood procedure: a 10-year single-institution experience

BACKGROUND This study reviews our 10-year experience with the modified Norwood procedure to determine its early and midterm outcomes. The focus is on the impact of evolving management strategies and accumulated institutional experience. METHODS A modified Norwood operation was performed in 171 infants over a 10-year period. Sixty-eight percent of the infants were male, the median age at operation was 6 days (range 1 to 175 days), and the median weight was 3.3 kg (range 1.7 to 4.8 kg). The 10-year period was divided into three eras: era I; 1990 through 1993; era II; 1994 through 1997; and era III; 1998 into 2000. Outcomes and risk factors for mortality were sought. RESULTS Hypoplastic left heart syndrome or a variant was the primary diagnosis in 118 infants (69%). The overall 5-year survival rate was 43%. Multivariate analysis revealed that only need of preoperative ventilatory support, earlier date of operation, and lower weight at operation were significant independent predictors of increased time-related mortality. Morphologic features such as a diagnosis other than hypoplastic left heart syndrome, ascending aortic size, and noncardiac anomalies were not significantly associated with an increased risk of death. The hospital survival rate for stage-one palliation in era III was 82%, significantly better than that in the preceding eras (p < 0.001). Attrition between stages one and two accounted for a 15% mortality rate among hospital survivors. CONCLUSIONS With increasing experience and improvements in perioperative care and surgical technique, good outcomes can be expected for the first-stage modified Norwood procedure. Greater monitoring of patients in the interstage period may reduce interval mortality and improve overall survival.