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Background: Patients with long QT syndrome (LQTS) have inadequate shortening of the QT interval in response to the sudden heart rate accelerations provoked by standing-a phenomenon of diagnostic value. We now validate our original observations in a cohort twice as large. We also describe that this abnormal QT-interval response persists as the heart rate acceleration returns to baseline.Objectives: To describe a novel observation, termed "QT stunning" and to validate previous observations regarding the "QT-stretching" phenomenon in patients with LQTS by using our recently described "standing test."Methods: The electrocardiograms of 108 patients with LQTS and 112 healthy subjects were recorded in the supine position. Subjects were then instructed to stand up quickly and remain standing for 5 minutes during continuous electrocardiographic recording. The corrected QT interval was measured at baseline (QTc(base)), when heart rate acceleration without appropriate QT-interval shortening leads to maximal QT stretching (QTc(stretch)) and upon return of heart rate to baseline (QTc(return)).Results: QTc(stretch) lengthened significantly more in patients with LQTS (103 ± 80 ms vs 66 ± 40 ms in controls; P <.001) and so did QTc(return) (28 ± 48 ms for patients with LQTS vs -3 ± 32 ms for controls; P <.001). Using a sensitivity cutoff of 90%, the specificity for diagnosing LQTS was 74% for QTc(base), 84% for QTc(return), and 87% for QTc(stretch).Conclusions: The present study extends our previous findings on the abnormal response of the QT interval in response to standing in patients with LQTS. Our study also shows that this abnormal response persists even after the heart rate slows back to baseline. [ABSTRACT FROM AUTHOR]

Background: Although electrocardiographic (ECG) abnormalities are well known in ischemic stroke and subarachnoid hemorrhage, these changes have only rarely been investigated systematically in patients with intracerebral hemorrhage (ICH). The purpose of this study is to investigate the prevalence and type of ECG abnormalities in a consecutive series of ICH patients, and their possible association with pre-defined neurological and radiological parameters.Methods: The study population consisted of all consecutive patients with non-traumatic, intraparenchymal ICH admitted to the Academic Medical Center (AMC) between January 1, 2007 and October 1, 2007. Baseline information was prospectively registered in the AMC Stroke Register. ECGs obtained within 2 days after the initial hemorrhage were analyzed by one blinded observer. Admission cranial CT scans were re-analyzed by two blinded observers.Results: Thirty-one patients were included. Twenty-five patients (81%) had one or more ECG abnormalities. The most frequently observed ECG abnormality was QTc prolongation (36%), followed by ST-T morphologic changes (23%), sinus bradycardia (16%), and inverted T wave (16%). No patient was initially misdiagnosed for having myocardial ischemia. QTc prolongation was associated with ICH involvement of the insular cortex [OR 10.9 (95% CI 1.0-114.6)] and presence of intraventricular blood and hydrocephalus on admission CT scan [OR 10.8 (95% CI 1.6-70.9)].Conclusions: In ICH patients ECG abnormalities are common. QTc prolongation seems associated with insular cortex involvement, with the presence of intraventricular blood, and with hydrocephalus. A larger cohort of continuously monitored ICH patients is necessary to investigate whether these ECG abnormalities are associated with poor outcome or death. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To describe patients with a distinct electrocardiogram (ECG) pattern without ST-segment elevation in the presence of an acute occlusion of the proximal left anterior descending (LAD) artery. DESIGN: Single-centre observational study. PATIENTS: Patients with acute anterior wall myocardial infarction who were referred for primary percutaneous coronary intervention (PCI) between 1998 and 2008. RESULTS: We identified patients with a static, distinct ECG pattern without ST-segment elevation and an occlusion of the proximal LAD artery during urgent coronary angiography before PCI. Of 1890 patients who underwent primary PCI of the LAD artery, we could identify 35 patients (2%) with this distinct ECG pattern. The ECG showed ST-segment depression at the J-point of at least 1 mm in precordial leads with upsloping ST-segments continuing into tall, symmetrical T-waves. Patients with this distinct ECG pattern were younger, more often male and more often had hypercholesterolaemia compared to patients with anterior myocardial infarction and ST-segment elevation. CONCLUSIONS: In patients presenting with chest pain, ST-segment depression at the J-point with upsloping ST-segments and tall, symmetrical T-waves in the precordial leads of the 12-lead ECG signifies proximal LAD artery occlusion. It is important for cardiologists and emergency care physicians to recognise this distinct ECG pattern, so they can triage such patients for immediate reperfusion therapy. [ABSTRACT FROM AUTHOR]

Background: Long QT syndrome (LQTS) is a potentially lethal, highly treatable cardiac channelopathy for which genetic testing has matured from discovery to translation and now clinical implementation.Objectives: Here we examine the spectrum and prevalence of mutations found in the first 2,500 unrelated cases referred for the FAMILION LQTS clinical genetic test.Methods: Retrospective analysis of the first 2,500 cases (1,515 female patients, average age at testing 23 +/- 17 years, range 0 to 90 years) scanned for mutations in 5 of the LQTS-susceptibility genes: KCNQ1 (LQT1), KCNH2 (LQT2), SCN5A (LQT3), KCNE1 (LQT5), and KCNE2 (LQT6).Results: Overall, 903 referral cases (36%) hosted a possible LQTS-causing mutation that was absent in >2,600 reference alleles; 821 (91%) of the mutation-positive cases had single genotypes, whereas the remaining 82 patients (9%) had >1 mutation in > or =1 gene, including 52 cases that were compound heterozygous with mutations in >1 gene. Of the 562 distinct mutations, 394 (70%) were missense, 428 (76%) were seen once, and 336 (60%) are novel, including 92 of 199 in KCNQ1, 159 of 226 in KCNH2, and 70 of 110 in SCN5A.Conclusion: This cohort increases the publicly available compendium of putative LQTS-associated mutations by >50%, and approximately one-third of the most recently detected mutations continue to be novel. Although control population data suggest that the great majority of these mutations are pathogenic, expert interpretation of genetic test results will remain critical for effective clinical use of LQTS genetic test results. [ABSTRACT FROM AUTHOR]

BACKGROUND: Transient loss of consciousness (TLOC) is a common clinical problem. OBJECTIVE: The aim of this study was to assess the yield and accuracy of the initial evaluation, consisting of standardized history, physical examination, and ECG performed by attending physicians in patients with TLOC. METHODS AND RESULTS: Five hundred and three adult patients (mean age 53 +/- 19; 56% male) presenting with TLOC to the Academic Medical Center Amsterdam between February 2000 and May 2002 were included in this study. After initial evaluation, the physician made a certain, a highly likely (>80% certain), or no initial diagnosis. Initially undiagnosed patients received additional cardiological testing, additional history taking, and autonomic function tests. After 2 years of follow-up, an expert committee determined the final diagnoses. Two-year follow-up was obtained in 99% of the patients. The yield of certain diagnoses after the initial evaluation was 24%, increasing to 63% after including the highly likely diagnoses. The diagnostic accuracy of the initial certain diagnoses was 93% (95% CI 87-97%), decreasing to 88% (95% CI 84-91%) after inclusion of the initial highly likely diagnoses. CONCLUSION: Attending physicians can make a diagnosis based on initial evaluation in 63% of patients with TLOC, with an overall diagnostic accuracy of 88%. The use of additional testing, beyond history, physical examination, and ECG can be avoided in many patients with TLOC. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to identify the genetic defect underlying the combined clinical presentation of bradycardia and left ventricular noncompaction cardiomyopathy (LVNC), hypothesizing that these two clinical abnormalities have a common genetic cause.Background: Familial forms of primary sinus bradycardia have in some cases been attributed to mutations in HCN4, SCN5A and ANK2. In these studies no structural cardiac alterations were reported in mutation carriers. However a cluster of reports in the literature describe patients presenting with sinus bradycardia in association with LVNC pointing to a shared genetic cause.Methods: Exome sequencing was carried out in two cousins from the index family that were affected by the combined bradycardia-LVNC phenotype; shared variants thus identified were subsequently overlaid with the chromosomal regions shared among five affected family members that were identified using SNP-array analysis.Results: The combined linkage analysis and exome sequencing in the index family identified 11 novel variants shared among the two affected cousins. One of these, p.G482R in HCN4, segregated with the combined bradycardia and LVNC phenotype in the entire family. Subsequent screening of HCN4 in three additional families, with the same clinical combination of bradycardia and LVNC, identified HCN4 mutations in all three. In electrophysiological studies, all found HCN4 mutations showed a more negative voltage-dependency of activation, consistent with the observed bradycardia.Conclusions: While mutations in HCN4 have been previously linked to bradycardia, our study provides the first evidence that mutations in this ion channel gene may also associate with structural abnormalities of the myocardium. [ABSTRACT FROM PUBLISHER]

Objectives: The aims of this study were to determine the spectrum and prevalence of "background genetic noise" in the arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC) genetic test and to determine genetic associations that can guide the interpretation of a positive test result.Background: ARVC is a potentially lethal genetic cardiovascular disorder characterized by myocyte loss and fibrofatty tissue replacement of the right ventricle. Genetic variation among the ARVC susceptibility genes has not been systematically examined, and little is known about the background noise associated with the ARVC genetic test.Methods: Using direct deoxyribonucleic acid sequencing, the coding exons/splice junctions of PKP2, DSP, DSG2, DSC2, and TMEM43 were genotyped for 93 probands diagnosed with ARVC from the Netherlands and 427 ostensibly healthy controls of various ethnicities. Eighty-two additional ARVC cases were obtained from published reports, and additional mutations were included from the ARVD/C Genetic Variants Database.Results: The overall yield of mutations among ARVC cases was 58% versus 16% in controls. Radical mutations were hosted by 0.5% of control individuals versus 43% of ARVC cases, while 16% of controls hosted missense mutations versus a similar 21% of ARVC cases. Relative to controls, mutations in cases occurred more frequently in non-Caucasians, localized to the N-terminal regions of DSP and DSG2, and localized to highly conserved residues within PKP2 and DSG2.Conclusions: This study is the first to comprehensively evaluate genetic variation in healthy controls for the ARVC susceptibility genes. Radical mutations are high-probability ARVC-associated mutations, whereas rare missense mutations should be interpreted in the context of race and ethnicity, mutation location, and sequence conservation. [ABSTRACT FROM AUTHOR]