Common genetic variation near the connexin-43 gene is associated with resting heart rate in African Americans: a genome-wide association study of 13,372 participants.

BACKGROUND: Genome-wide association studies have identified several genetic loci associated with variation in resting heart rate in European and Asian populations. No study has evaluated genetic variants associated with heart rate in African Americans. OBJECTIVE: To identify novel genetic variants associated with resting heart rate in African Americans. METHODS: Ten cohort studies participating in the Candidate-gene Association Resource and Continental Origins and Genetic Epidemiology Network consortia performed genome-wide genotyping of single nucleotide polymorphisms (SNPs) and imputed 2,954,965 SNPs using HapMap YRI and CEU panels in 13,372 participants of African ancestry. Each study measured the RR interval (ms) from 10-second resting 12-lead electrocardiograms and estimated RR-SNP associations using covariate-adjusted linear regression. Random-effects meta-analysis was used to combine cohort-specific measures of association and identify genome-wide significant loci (P≤2.5×10(-8)). RESULTS: Fourteen SNPs on chromosome 6q22 exceeded the genome-wide significance threshold. The most significant association was for rs9320841 (+13 ms per minor allele; P = 4.98×10(-15)). This SNP was approximately 350 kb downstream of GJA1, a locus previously identified as harboring SNPs associated with heart rate in Europeans. Adjustment for rs9320841 also attenuated the association between the remaining 13 SNPs in this region and heart rate. In addition, SNPs in MYH6, which have been identified in European genome-wide association study, were associated with similar changes in the resting heart rate as this population of African Americans. CONCLUSIONS: An intergenic region downstream of GJA1 (the gene encoding connexin 43, the major protein of the human myocardial gap junction) and an intragenic region within MYH6 are associated with variation in resting heart rate in African Americans as well as in populations of European and Asian origin.

Vegetation biopsy using transesophageal echocardiography guidance: a technique to aid in diagnosis of culture-negative endocarditis.

A method of obtaining a vegetation sample in a culture-negative endocarditis is described. A combination of fluoroscopy and transesophageal echocardiography was utilized to obtain the sample. The results positively influenced the diagnosis and treatment in this 16-yr-old male with complex congenital heart disease.

Fetal echocardiography in gravidas with historic risk factors for congenital heart disease.

All fetal echocardiograms performed at our institution between January 1, 1986, and June 1, 1991, were reviewed. The echocardiogram referral indication and results were verified for all women studied. Historic risk factors under consideration were pregestational diabetes, anticonvulsant or lithium ingestion in the first trimester, and a family history of congenital heart disease. Women with historic risk factors who had either a fetal abnormality on antenatal sonography or a known aneuploid fetus prior to the fetal echocardiograph were excluded. Of the 994 women who had a fetal echocardiogram performed during this study period, 486 (48.9%) were evaluated solely on the basis of a historic risk factor. Four of the 486 women (0.8%) were diagnosed as having a significant fetal structural cardiac malformation. Two of the four fetuses succumbed to obstetric complications. The remaining two infants were delivered at term and are doing well after postnatal cardiac surgery. In this select group of women with risk factors but no recognized fetal abnormality, the incidence of significant cardiac lesions was low. Although indications for fetal echocardiography must be evaluated on an individual basis, our data do not support a recommendation for the routine use of fetal echocardiography as a screening test in all women with historic risk factors.

Transesophageal echocardiographic diagnosis of multicentric left ventricular myxomas mimicking a left atrial tumor.

We report a case of multicentric left ventricular myxomas with prolapse of one myxoma into the left atrium during ventricular systole that mimicked a left atrial tumor. The transthoracic echocardiogram showed large masses in the region of the mitral valve leaflets consistent with vegetations or tumors. A computed tomographic scan of the chest demonstrated two distinct left atrial masses, one of which appeared to prolapse from the left atrium into the left ventricle. Intraoperative transesophageal echocardiography showed a large pedunculated mass moving between the two left-sided cardiac chambers with intermittent trapping of the mass in the left atrium. The mass was attached to the left ventricular posteromedial papillary muscle by a long stalk. Another adjacent large ventricular mass was also noted in the left ventricle. These findings were confirmed at operation, which also demonstrated a third small tumor arising from the atrial aspect of the posterior mitral leaflet.

Usefulness and limitations of transesophageal echocardiography in the assessment of proximal coronary artery stenosis.

To assess the usefulness of transesophageal echocardiography in the evaluation of proximal coronary artery stenosis, 111 consecutive patients (mean age 61 years) who had intraoperative transesophageal echocardiography and coronary angiography within 1 week of surgery were studied. Transesophageal echocardiography visualized the entire length of the left main artery (0.2 to 2.2 cm, mean 0.93), 0.2 to 2.2 cm of the proximal left anterior descending artery and 0.1 to 3.4 cm of the proximal left circumflex artery in 103 patients (93%) and 0.1 to 4.6 cm of the proximal right coronary artery in 55 patients (49%). In the coronary artery segments visualized by echocardiography and compared with the corresponding angiographic segments, transesophageal echocardiography correctly identified 23 (96%) of 24 left main stenoses, 11 (78%) of 14 stenoses involving the left anterior descending artery, 6 (75%) of 8 left circumflex stenoses and all 7 stenoses (100%) of the right coronary artery. In all seven patients with ostial stenosis (left main artery in five and right coronary artery in two), the condition was correctly diagnosed by this technique. The sensitivity and specificity of transesophageal echocardiography in the overall evaluation of proximal coronary artery stenosis as customarily defined by angiography were 96% and 99% for the left main artery, 48% and 99% for the left anterior descending artery, 67% and 100% for the left circumflex artery and 37% and 100% for the right coronary artery, respectively. The distance of the stenotic lesion from the origin of the vessel by transesophageal echocardiography also correlated well with that measured by angiography (r = 0.63 to 0.99).(ABSTRACT TRUNCATED AT 250 WORDS)

Usefulness of transesophageal echocardiography in assessment of aortic dissection.

BACKGROUND: The value of transesophageal echocardiography in the assessment of patients with aortic dissection was studied. METHODS AND RESULTS: Group 1 (34 patients) represented all patients studied at our institution with this technique in whom aortic dissection was proven by aortography, surgery, or autopsy. Group 2 (27 patients) represented all patients studied with this technique at our institution in whom aortic dissection was excluded by aortography. Transesophageal echocardiography made a correct diagnosis of aortic dissection in 33 of 34 patients (sensitivity, 97%; specificity, 100%). It also correctly demonstrated the type of dissection in all 29 patients with aortographic or surgical proof. On the other hand, computed tomography scanning, performed in 24 of 34 patients in group 1, made a correct diagnosis in only 67% of patients and misclassified the type of dissection in 33%. Transesophageal echocardiography correctly identified involvement of the coronary arteries by aortic dissection in six of seven patients as well as absence of both left and right coronary artery involvement in 10 patients with aortic dissection. This technique was also useful in detecting communications between the true and false lumens, presence of thrombi in the false lumen, and, in two patients, localized dissection rupture with formation of a false aneurysm. In both groups 1 and 2, transesophageal echocardiography correctly identified patients with moderate to severe aortic regurgitation. CONCLUSIONS: Transesophageal echocardiography is very useful in the assessment of aortic dissection.

Transesophageal echocardiography in aortopulmonary communications.

The assessment of congenital aortopulmonary communications by transthoracic echocardiography may be suboptimal, particularly postoperatively, due to limited acoustic windows. We performed intraoperative transesophageal echocardiograms in six patients with eight proven systemic-pulmonary communications. Diagnosis included truncus arteriosus (1), aortopulmonary window (1), Waterston anastomosis (3), central Gore-Tex shunt (1), and modified left Blalock-Taussig shunt (2). All communications were accurately demonstrated by transesophageal echocardiography (TEE). The transesophageal technique also provided an assessment of the size of the aortopulmonary communications and the proximal pulmonary arteries. In addition, the gradient across some of the communications could be accurately estimated utilizing the high pulse repetition frequency Doppler. On the other hand, only two of the seven aortopulmonary communications were detected by transthoracic echocardiography. Postoperatively, transesophageal imaging demonstrated unobstructed conduit in five of five patients who underwent conduit repair, as well as intact closure of aortopulmonary communications and concomitant closure of ventricular septal defects.

Uses and limitations of transthoracic echocardiography in the assessment of atrial septal defect in the adult.

Two-dimensional and color Doppler echocardiography accurately detected the presence of an atrial septal defect (ASD) in 47 of 50 adults (mean age 40 years) confirmed by surgery or cardiac catheterization, or both. It correctly categorized all patients with ostium secundum and ostium primum ASD but misdiagnosed 3 of 5 patients with surgically proven sinus venosus ASD. The shunt flow volume across the ASD was calculated with the standard Doppler equation, and assuming the ASD to be circular correlated with shunt flow volume obtained by cardiac catheterization (r = 0.74). The maximum width of the color flow signals moving across the ASD was taken as its diameter. Mean flow velocity was determined either by placing a pulsed Doppler sample volume parallel to the flow across the ASD as visualized by color Doppler or by color M-mode examination, which allowed determination of flow velocities using a previously validated method that incorporates a computer analysis of pixel color intensity. The pulmonary to systemic blood flow ratio obtained by color-guided conventional Doppler interrogation of the left and right ventricular outflow tracts correlated poorly with cardiac catheterization results (r = 0.38). In patients with associated tricuspid regurgitation, the peak systolic pulmonary artery pressure obtained by color Doppler-guided continuous-wave Doppler correlated well with that obtained at cardiac catheterization (r = 0.89). The maximum color Doppler jet width of the flow across the ASD poorly correlated with ASD size estimated at surgery (r = 0.50).

Echocardiographic and electrocardiographic correlation in cases of congestive cardiomyopathy.

Echocardiographically diagnosed sixty cases of congestive cardiomyopathy were electrocardiographically analysed. None of the cases had normal electrocardiogram. The commonest rhythm disorder was premature ventricular contractions (P.V.C.-26.6%), and the commonest conduction disorder was left anterior hemi block (LAHB-17%). Nonspecific ST-T changes in the anterolateral leads was the most common electrocardiographic finding. No correlation was seen between electrocardiographic evidence of hypertrophy and echocardiographic evidence of cardiac enlargement.