Signal averaging in Wolff-Parkinson-White syndrome: evidence that fractionated activation is not necessary for body surface high-frequency potentials.

It is commonly assumed that the presence of high frequency components in body surface potentials implies that fractionated activation fronts, caused by heterogeneously viable tissue, are present in the heart. However, it is possible that non-fractionated activation fronts can also give rise to high frequency surface potentials and that the relative amount of high frequency power is related to the complexity of the activation sequence. In a test of this idea, averaged body surface potentials were recorded during the entire QRS complex of nine Wolff-Parkinson-White (WPW) patients in situations in which fractionated activation fronts should not have been present, but which represent increasing degrees of complexity of ventricular activation: (1) postoperative ectopic pacing from subepicardial wires placed during surgery, when a single coherent activation front was present throughout most of the QRS; (2) Preoperative preexcited rhythm, when a single coherent activation front was present for one portion of the QRS (the delta wave); and (3) postoperative normal rhythm, when two or more activation fronts were present in the ventricles throughout most of the QRS. For comparison, averaged body surface potentials were also analyzed during the last 40 ms of the QRS complex and the ST segment of 14 postinfarction patients with chronic ventricular tachycardia. In the patients with WPW syndrome, relatively high frequency content increased (attenuation -36.7 vs -27.2 vs -18.3 dB) and QRS width decreased (160.7 vs 125.9 vs 94.1 ms) significantly from paced to preoperative to postoperative beats. Significant high frequency content was present in all cases, showing that coherent activation fronts can give rise to high frequencies. Interestingly, the postoperative QRS of WPW patients contained a larger proportion of high frequency power than did the late potentials of the patients with ventricular tachycardia. Thus, while the presence of late fractionated body surface potentials may be a marker for ventricular tachycardia, these potentials by themselves do not necessarily signify that the underlying cardiac activation giving rise to these signals is fractionated.

Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease.

BACKGROUND: Inherited mutations cause approximately 35 percent of cases of dilated cardiomyopathy; however, few genes associated with this disease have been identified. Previously, we located a gene defect that was responsible for autosomal dominant dilated cardiomyopathy and conduction-system disease on chromosome 1p1-q21, where nuclear-envelope proteins lamin A and lamin C are encoded by the LMNA (lamin A/C) gene. Mutations in the head or tail domain of this gene cause Emery-Dreifuss muscular dystrophy, a childhood-onset disease characterized by joint contractures and in some cases by abnormalities of cardiac conduction during adulthood. METHODS: We evaluated 11 families with autosomal dominant dilated cardiomyopathy and conduction-system disease. Sequences of the lamin A/C exons were determined in probands from each family, and variants were confirmed by restriction-enzyme digestion. The genotypes of the family members were ascertained. RESULTS: Five novel missense mutations were identified: four in the alpha-helical-rod domain of the lamin A/C gene, and one in the lamin C tail domain. Each mutation caused heritable, progressive conduction-system disease (sinus bradycardia, atrioventricular conduction block, or atrial arrhythmias) and dilated cardiomyopathy. Heart failure and sudden death occurred frequently within these families. No family members with mutations had either joint contractures or skeletal myopathy. Serum creatine kinase levels were normal in family members with mutations of the lamin rod but mildly elevated in some family members with a defect in the tail domain of lamin C. CONCLUSIONS: Genetic defects in distinct domains of the nuclear-envelope proteins lamin A and lamin C selectively cause dilated cardiomyopathy with conduction-system disease or autosomal dominant Emery-Dreifuss muscular dystrophy. Missense mutations in the rod domain of the lamin A/C gene provide a genetic cause for dilated cardiomyopathy and indicate that this intermediate filament protein has an important role in cardiac conduction and contractility.

Infections with nonthoracotomy implantable cardioverter defibrillators: can these be prevented? Endotak Lead Clinical Investigators.

Nonthoracotomy ICDs are believed to be the best therapeutic modality for treatment of life-threatening ventricular arrhythmias. Little is known about the risk of infection with initial implantation of these devices. We studied the incidence, clinical characteristics, and risk factors associated with infections in 1,831 patients with nonthoracotomy ICD from the Endotak-C nonthoracotomy lead registry of Cardiac Pacemakers, Inc. A transvenous lead was implanted in 950 patients (51.9%) and a combination transvenous plus subcutaneous patch was used in 881 patients (48.1%). Nine preselected data variables were studied, and all investigators identified as having patients with infections were personally contacted. Infections occurred in 22 (1.2%) of 1,831 patients receiving this nonthoracotomy ICD system. The mean time to infection was 5.7 +/- 6.5 months (range 1-25 months). Staphylococci were isolated in 58% of patients with reported infection. The presence of a subcutaneous defibrillator patch system was associated with the development of infection. Six of 950 patients (0.63%) with a totally transvenous lead system developed infection versus 16 of 838 (1.9%) patients with a transvenous lead plus subcutaneous patch system configuration (P = 0.015, Chi-square test), with an unadjusted estimated odds ratio of 3.06 (CI 1.19-7.86). The risk of infection encountered with the nonthoracotomy ICD is low, estimated from our data to be 1.2%. Placement of a subcutaneous defibrillator patch appears to be an independent risk factor for development of infection.

Cardiac myxoma characterized by clonal telomeric association.

We report on the cytogenetic analysis of a case of cardiac myxoma of the "syndrome myxoma" type, in which clonal telomeric associations between chromosomes 13 and 15, as well as nonclonal telomeric associations between chromosomes 12 and 17 and between chromosome 2 and an unidentified chromosome were observed. Nonclonal structural abnormalities were also present. This is the second reported case of cytogenetic abnormalities of syndrome cardiac myxoma, and the fourth case in which telomeric associations have been described.

Familial congenital sinus rhythm anomalies: clinical and pathological correlations.

We describe pathological abnormalities in a 72-year-old male member of a family with a congenital absence of sinus rhythm and a tendency to develop atrial fibrillation at an early age, and in a 54-year-old female member of a family with cardiomyopathy and progressive conduction system disease manifested by first-degree atrioventricular (AV) block, left bundle branch block, and atrial arrhythmias. Both patients died suddenly. The absence of sinus rhythm in case 1 could be explained by marked atrophy, degeneration, and isolation of the sinoatrial (SA) node. The SA node was also diseased in the member of the other family with atrial arrhythmias. Additional common features in both cases included: fatty metamorphosis and degenerative changes of the approaches to the SA node, the atrial preferential fibers, and the approaches to the AV node, a small AV node, degenerative changes of the bundle branches, and floppy AV valves. These findings show that the pathological substrate of familial supraventricular arrhythmias consists of a diffuse involvement of the entire conduction system, bearing resemblance to pathological findings in elderly subjects with acquired sick sinus syndrome.

Familial occurrence of accessory atrioventricular pathways (preexcitation syndrome).

Accessory atrioventricular pathways, the anatomical structures responsible for the preexcitation syndromes, may result from a developmental failure to eradicate the remnants of the atrioventricular connections present during cardiogenesis. To study whether preexcitation syndromes could also be transmitted genetically, we determined the prevalence of preexcitation in the first-degree relatives of 383 of 456 consecutive patients (84 percent) with electrophysiologically proved accessory pathways. We compared the observed prevalence of preexcitation among the 2343 first-degree relatives with the frequency reported in the general population (0.15 percent). For 13 of the 383 index patients (3.4 percent), accessory pathways were documented in one or more first-degree relatives. At least 13 of the 2343 relatives identified (0.55 percent) had preexcitation; this prevalence was significantly higher than that in the general population (P less than 0.0001). Identification of affected relatives may have been incomplete because clinical information was obtained only about symptomatic relatives. Patients with familial preexcitation have a higher incidence of multiple accessory pathways and possibly an increased risk of sudden cardiac death. Our data suggest a hereditary contribution to the development of accessory pathways in humans. The pattern of inheritance appears to be autosomal dominant.

Acute myocardial infarction associated with initial cocaine use.

We have described a young man who had acute myocardial infarction after his first use of cocaine. This case demonstrates that potentially lethal myocardial infarctions may be associated with such initial "experimentation" with cocaine even in relatively small doses. Cocaine intoxication should be considered in young patients with acute myocardial ischemia or necrosis. We recommend that cocaine metabolites be checked in the urine if a drug history is unreliable in such patients.

"Syndrome myxoma": a subset of patients with cardiac myxoma associated with pigmented skin lesions and peripheral and endocrine neoplasms.

From January 1954 to December 1985 cardiac myxoma was diagnosed in 75 patients at the Mayo Clinic. The clinical presentation was typical in 70 cases and was referred to as "sporadic myxoma". Forty four other cases of cardiac myxomas (five from the Mayo Clinic) presented with a combination of distinctive clinical features and these cases are described as "syndrome myxoma". The patients with syndrome myxoma were younger (mean age, 25 vs 56 years) and had unusual skin freckling (68%), associated benign non-cardiac myxomatous tumours (57%), endocrine neoplasms (30%), and a high frequency of familial cardiac myxoma (25%) and familial endocrine tumours (14%). The two types of cardiac tumour were different (syndrome vs sporadic): atrial location, 87% vs 100%; ventricular location, 13% vs 0%; single tumour, 50% vs 99%; multiple tumours, 50% vs 1%; and recurrent tumour, 18% vs 0%. It is concluded that patients with syndrome myxoma represent a distinctive subgroup in which there are important clinical, surgical, and genetic implications. More importantly, syndrome myxoma appears to be only one expression of a much larger disease entity.