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Francois Haddad,
Shanon Peter,
Olivia Hulme,
David Liang,
Ingela Schnittger,
Josephine Puryear,
Fatemeh A Gomari,
Gherardo Finocchiaro,
Jonathan Myers,
Victor Froelicher,
Daniel Garza, Euan A Ashley
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ABSTRACT: Athletic training is associated with increases in ventricular mass and volume. Recent studies have shown that left ventricular mass increases proportionally in white athletes with a mass/volume ratio approaching unity. The objective of this study was to compare the proportionality in ventricular remodeling and ventricular function in black versus white National Collegiate Athletic Association Division I football players. From 2008 to 2011, football players at Stanford University underwent cardiovascular screening with a 12-point history and physical examination, electrocardiography, and focused echocardiography. Compared with white players, black players had on average higher left ventricular mass indexes (77 ± 11 vs 71 ± 11 g/m(2), p = 0.009), higher mass/volume ratios (1.18 ± 0.16 vs 1.06 ± 0.09 g/ml, p <0.001), and higher QRS vector magnitudes (3.2 ± 0.7 vs 2.7 ± 0.8, p = 0.002). Black race had an odds ratio of 14 (95% confidence interval 5 to 42, p <0.001) for a mass/volume ratio >1.2. Mass/volume ratio was inversely related to early diastolic tissue Doppler velocity e' (r = -0.50, p <0.001) but not to QRS vector magnitude (r = 0.065, p = 0.034). With regard to systolic indexes, there was no significant difference in the left ventricular ejection fraction, velocity of circumferential shortening, and isovolumic acceleration. In conclusion, black college football players exhibit more concentric ventricular remodeling, lower early diastolic annular velocities, and increased ventricular voltage compared with white players. Ventricular mass increases proportionally to volume in white players but not in black players.
The American journal of cardiology 04/2013; · 3.58 Impact Factor
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Rui Chen,
George I Mias,
Jennifer Li-Pook-Than,
Lihua Jiang,
Hugo Y K Lam,
Rong Chen,
Elana Miriami,
Konrad J Karczewski,
Manoj Hariharan,
Frederick E Dewey, [......],
Peter L Greenberg,
Phyllis Snyder,
Teri E Klein,
Russ B Altman,
Atul J Butte, Euan A Ashley,
Mark Gerstein,
Kari C Nadeau,
Hua Tang,
Michael Snyder
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ABSTRACT: Personalized medicine is expected to benefit from combining genomic information with regular monitoring of physiological states by multiple high-throughput methods. Here, we present an integrative personal omics profile (iPOP), an analysis that combines genomic, transcriptomic, proteomic, metabolomic, and autoantibody profiles from a single individual over a 14 month period. Our iPOP analysis revealed various medical risks, including type 2 diabetes. It also uncovered extensive, dynamic changes in diverse molecular components and biological pathways across healthy and diseased conditions. Extremely high-coverage genomic and transcriptomic data, which provide the basis of our iPOP, revealed extensive heteroallelic changes during healthy and diseased states and an unexpected RNA editing mechanism. This study demonstrates that longitudinal iPOP can be used to interpret healthy and diseased states by connecting genomic information with additional dynamic omics activity.
Cell 03/2012; 148(6):1293-307. · 32.40 Impact Factor
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Circulation 02/2012; 125(7):931-44. · 14.74 Impact Factor
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Hugo Y K Lam,
Michael J Clark,
Rui Chen,
Rong Chen,
Georges Natsoulis,
Maeve O'Huallachain,
Frederick E Dewey,
Lukas Habegger, Euan A Ashley,
Mark B Gerstein,
Atul J Butte,
Hanlee P Ji,
Michael Snyder
Nature Biotechnology 01/2012; 30(6):562. · 29.50 Impact Factor
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Hugo Y K Lam,
Michael J Clark,
Rui Chen,
Rong Chen,
Georges Natsoulis,
Maeve O'Huallachain,
Frederick E Dewey,
Lukas Habegger, Euan A Ashley,
Mark B Gerstein,
Atul J Butte,
Hanlee P Ji,
Michael Snyder
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ABSTRACT: Whole-genome sequencing is becoming commonplace, but the accuracy and completeness of variant calling by the most widely used platforms from Illumina and Complete Genomics have not been reported. Here we sequenced the genome of an individual with both technologies to a high average coverage of ∼76×, and compared their performance with respect to sequence coverage and calling of single-nucleotide variants (SNVs), insertions and deletions (indels). Although 88.1% of the ∼3.7 million unique SNVs were concordant between platforms, there were tens of thousands of platform-specific calls located in genes and other genomic regions. In contrast, 26.5% of indels were concordant between platforms. Target enrichment validated 92.7% of the concordant SNVs, whereas validation by genotyping array revealed a sensitivity of 99.3%. The validation experiments also suggested that >60% of the platform-specific variants were indeed present in the genome. Our results have important implications for understanding the accuracy and completeness of the genome sequencing platforms.
Nature Biotechnology 12/2011; 30(1):78-82. · 29.50 Impact Factor
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Frederick E Dewey,
Rong Chen,
Sergio P Cordero,
Kelly E Ormond,
Colleen Caleshu,
Konrad J Karczewski,
Michelle Whirl-Carrillo,
Matthew T Wheeler,
Joel T Dudley,
Jake K Byrnes, [......],
Alexander W Zaranek,
Heidi L Rehm,
George M Church,
John S West,
Carlos D Bustamante,
Michael Snyder,
Russ B Altman,
Teri E Klein,
Atul J Butte, Euan A Ashley
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ABSTRACT: Whole-genome sequencing harbors unprecedented potential for characterization of individual and family genetic variation. Here, we develop a novel synthetic human reference sequence that is ethnically concordant and use it for the analysis of genomes from a nuclear family with history of familial thrombophilia. We demonstrate that the use of the major allele reference sequence results in improved genotype accuracy for disease-associated variant loci. We infer recombination sites to the lowest median resolution demonstrated to date (< 1,000 base pairs). We use family inheritance state analysis to control sequencing error and inform family-wide haplotype phasing, allowing quantification of genome-wide compound heterozygosity. We develop a sequence-based methodology for Human Leukocyte Antigen typing that contributes to disease risk prediction. Finally, we advance methods for analysis of disease and pharmacogenomic risk across the coding and non-coding genome that incorporate phased variant data. We show these methods are capable of identifying multigenic risk for inherited thrombophilia and informing the appropriate pharmacological therapy. These ethnicity-specific, family-based approaches to interpretation of genetic variation are emblematic of the next generation of genetic risk assessment using whole-genome sequencing.
PLoS Genetics 09/2011; 7(9):e1002280. · 8.69 Impact Factor
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ABSTRACT: Heart failure remains a leading cause of morbidity and mortality in developed nations. Our current understanding of molecular pathways involved in heart failure reveals little of the multiscale biological systems at work. Here we consider recent advances in understanding the integrative multiscale biology, or systems biology, of heart failure and present a framework for future work in the area.
Multiplexed assays of gene expression and the complex dynamics of protein-protein interactions in heart failure have illuminated key pathways important to myocardial adaptation. Modeling of complex systems has advanced to incorporate these dynamic data sources into networks that capture fundamental interactions on different biological scales. The complex syndrome of heart failure, like other complex disease syndromes, can be viewed as an emergent property of these multiscale systems.
A comprehensive understanding of adaptive mechanisms in heart failure requires integration of multiple data sources on several biological scales. A combination of holistic systems biology approaches and traditional reductionist experimentation will be required for a nuanced understanding of this multifaceted disease process.
Current opinion in cardiology 07/2011; 26(4):314-21. · 2.66 Impact Factor
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ABSTRACT: Ventricular reserve is emerging a strong predictor of outcome in heart failure and cardiovascular disease. Ventricular reserve is the term used to describe the extent of increase or change in ventricular function that occurs during exercise or pharmacological stress (typically with dobutamine).
The interest in ventricular reserve lies in its ability to assess viability in coronary artery disease, to predict clinical outcome and response to therapy in patients with heart failure and to screen patients for early cardiovascular disease.
In this paper, we will review the emerging role of ventricular reserve in heart failure and pulmonary hypertension. We will also explore the mechanisms involved in the pathophysiology of impaired ventricular reserve and discuss future directions of research in the field.
Current opinion in cardiology 03/2011; 26(2):123-31. · 2.66 Impact Factor
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ABSTRACT: Network analysis techniques allow a more accurate reflection of underlying systems biology to be realized than traditional unidimensional molecular biology approaches. Using gene coexpression network analysis, we define the gene expression network topology of cardiac hypertrophy and failure and the extent of recapitulation of fetal gene expression programs in failing and hypertrophied adult myocardium.
We assembled all myocardial transcript data in the Gene Expression Omnibus (n=1617). Because hierarchical analysis revealed species had primacy over disease clustering, we focused this analysis on the most complete (murine) dataset (n=478). Using gene coexpression network analysis, we derived functional modules, regulatory mediators, and higher-order topological relationships between genes and identified 50 gene coexpression modules in developing myocardium that were not present in normal adult tissue. We found that known gene expression markers of myocardial adaptation were members of upregulated modules but not hub genes. We identified ZIC2 as a novel transcription factor associated with coexpression modules common to developing and failing myocardium. Of 50 fetal gene coexpression modules, 3 (6%) were reproduced in hypertrophied myocardium and 7 (14%) were reproduced in failing myocardium. One fetal module was common to both failing and hypertrophied myocardium.
Network modeling allows systems analysis of cardiovascular development and disease. Although we did not find evidence for a global coordinated program of fetal gene expression in adult myocardial adaptation, our analysis revealed specific gene expression modules active during both development and disease and specific candidates for their regulation.
Circulation Cardiovascular Genetics 02/2011; 4(1):26-35. · 6.11 Impact Factor
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ABSTRACT: Background Broad criteria for classifying an electrocardiogram (ECG) as abnormal and requiring additional testing prior to participating in competitive athletics have been recommended for the preparticipation examination (PPE) of athletes. Because these criteria have not considered gender differences, we examined the effect of gender on the computerized ECG measurements obtained on Stanford student athletes. Currently available computer programs require a basis for "normal" in athletes of both genders to provide reliable interpretation. Methods During the 2007 PPE, computerized ECGs were recorded and analyzed on 658 athletes (54% male; mean age, 19 +/- 1 years) representing 22 sports. Electrocardiogram measurements included intervals and durations in all 12 leads to calculate 12-lead voltage sums, QRS amplitude and QRS area, spatial vector length (SVL), and the sum of the R wave in V5 and S wave in V2 (RSsum). Results By computer analysis, male athletes had significantly greater QRS duration, PR interval, Q-wave duration, J-point amplitude, and T-wave amplitude, and shorter QTc interval compared with female athletes (all P < 0.05). All ECG indicators of left ventricular electrical activity were significantly greater in males. Although gender was consistently associated with indices of atrial and ventricular electrical activity in multivariable analysis, ECG measurements correlated poorly with body dimensions. Conclusion Significant gender differences exist in ECG measurements of college athletes that are not explained by differences in body size. Our tables of "normal" computerized gender-specific measurements can facilitate the development of automated ECG interpretation for screening young athletes.
The Physician and sportsmedicine 06/2010; 38(2):156-64. · 1.02 Impact Factor
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The Lancet 05/2010; 375(9727):1749-51. · 38.28 Impact Factor
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Euan A Ashley,
Atul J Butte,
Matthew T Wheeler,
Rong Chen,
Teri E Klein,
Frederick E Dewey,
Joel T Dudley,
Kelly E Ormond,
Aleksandra Pavlovic,
Alexander A Morgan, [......],
Ryan Whaley,
Joshua W Knowles,
Michael F Chou,
Joseph V Thakuria,
Abraham M Rosenbaum,
Alexander Wait Zaranek,
George M Church,
Henry T Greely,
Stephen R Quake,
Russ B Altman
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ABSTRACT: The cost of genomic information has fallen steeply, but the clinical translation of genetic risk estimates remains unclear. We aimed to undertake an integrated analysis of a complete human genome in a clinical context.
We assessed a patient with a family history of vascular disease and early sudden death. Clinical assessment included analysis of this patient's full genome sequence, risk prediction for coronary artery disease, screening for causes of sudden cardiac death, and genetic counselling. Genetic analysis included the development of novel methods for the integration of whole genome and clinical risk. Disease and risk analysis focused on prediction of genetic risk of variants associated with mendelian disease, recognised drug responses, and pathogenicity for novel variants. We queried disease-specific mutation databases and pharmacogenomics databases to identify genes and mutations with known associations with disease and drug response. We estimated post-test probabilities of disease by applying likelihood ratios derived from integration of multiple common variants to age-appropriate and sex-appropriate pre-test probabilities. We also accounted for gene-environment interactions and conditionally dependent risks.
Analysis of 2.6 million single nucleotide polymorphisms and 752 copy number variations showed increased genetic risk for myocardial infarction, type 2 diabetes, and some cancers. We discovered rare variants in three genes that are clinically associated with sudden cardiac death-TMEM43, DSP, and MYBPC3. A variant in LPA was consistent with a family history of coronary artery disease. The patient had a heterozygous null mutation in CYP2C19 suggesting probable clopidogrel resistance, several variants associated with a positive response to lipid-lowering therapy, and variants in CYP4F2 and VKORC1 that suggest he might have a low initial dosing requirement for warfarin. Many variants of uncertain importance were reported.
Although challenges remain, our results suggest that whole-genome sequencing can yield useful and clinically relevant information for individual patients.
National Institute of General Medical Sciences; National Heart, Lung And Blood Institute; National Human Genome Research Institute; Howard Hughes Medical Institute; National Library of Medicine, Lucile Packard Foundation for Children's Health; Hewlett Packard Foundation; Breetwor Family Foundation.
The Lancet 05/2010; 375(9725):1525-35. · 38.28 Impact Factor
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ABSTRACT: Inclusion of 12-lead electrocardiography (ECG) in preparticipation screening of young athletes is controversial because of concerns about cost-effectiveness.
To evaluate the cost-effectiveness of ECG plus cardiovascular-focused history and physical examination compared with cardiovascular-focused history and physical examination alone for preparticipation screening.
Decision-analysis, cost-effectiveness model.
Published epidemiologic and preparticipation screening data, vital statistics, and other publicly available data.
Competitive athletes in high school and college aged 14 to 22 years.
Lifetime.
Societal.
Nonparticipation in competitive athletic activity and disease-specific treatment for identified athletes with heart disease.
Incremental health care cost per life-year gained.
Addition of ECG to preparticipation screening saves 2.06 life-years per 1000 athletes at an incremental total cost of $89 per athlete and yields a cost-effectiveness ratio of $42 900 per life-year saved (95% CI, $21 200 to $71 300 per life-year saved) compared with cardiovascular-focused history and physical examination alone. Compared with no screening, ECG plus cardiovascular-focused history and physical examination saves 2.6 life-years per 1000 athletes screened and costs $199 per athlete, yielding a cost-effectiveness ratio of $76 100 per life-year saved ($62 400 to $130 000).
Results are sensitive to the relative risk reduction associated with nonparticipation and the cost of initial screening.
Effectiveness data are derived from 1 major European study. Patterns of causes of sudden death may vary among countries.
Screening young athletes with 12-lead ECG plus cardiovascular-focused history and physical examination may be cost-effective.
Stanford Cardiovascular Institute and the Breetwor Foundation.
Annals of internal medicine 03/2010; 152(5):276-86. · 16.73 Impact Factor
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Vy-Van Le,
Matthew T Wheeler,
Sandra Mandic,
Frederick Dewey,
Holly Fonda,
Marco Perez,
Gannon Sungar,
Daniel Garza, Euan A Ashley,
Gordon Matheson,
Victor Froelicher
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ABSTRACT: Although the use of standardized cardiovascular (CV) system-focused history and physical examination is recommended for the preparticipation examination (PPE) of athletes, the addition of the electrocardiogram (ECG) has been controversial. Because the impact of ECG screening on college athletes has rarely been reported, we analyzed the findings of adding the ECG to the PPE of Stanford athletes.
For the past 15 years, the Stanford Sports Medicine program has mandated a PPE questionnaire and physical examination by Stanford physicians for participation in intercollegiate athletics. In 2007, computerized ECGs with digital measurements were recorded on athletes and entered into a database.
Although the use of standardized CV-focused history and physical examination are recommended for the PPE of athletes, the addition of the ECG has been controversial. Because the feasibility and outcomes of ECG screening on college athletes have rarely been reported, we present findings derived from the addition of the ECG to the PPE of Stanford athletes. For the past 15 years, the Stanford Sports Medicine program has mandated a PPE questionnaire and physical examination by Stanford physicians for participation in intercollegiate athletics. In 2007, computerized ECGs with digital measurements were recorded on athletes and entered into a database.
Six hundred fifty-eight recordings were obtained (54% men, 10% African-American, mean age 20 years) representing 24 sports. Although 68% of the women had normal ECGs, only 38% of the men did so. Incomplete right bundle branch block (RBBB) (13%), right axis deviation (RAD) (10%), and atrial abnormalities (3%) were the 3 most common minor abnormalities. Sokolow-Lyon criteria for left ventricular hypertrophy (LVH) were found in 49%; however, only 27% had a Romhilt-Estes score of >or=4. T-wave inversion in V2 to V3 occurred in 7%, and only 5 men had abnormal Q-waves. Sixty-three athletes (10%) were judged to have distinctly abnormal ECG findings possibly associated with conditions including hypertrophic cardiomyopathy or arrhythmogenic right ventricular dysplasia/cardiomyopathy. These athletes were offered further testing but this was not mandated according to the research protocol.
Six hundred fifty-three recordings were obtained (54% men, 7% African American, mean age 20 years), representing 24 sports. Although 68% of the women had normal ECGs, only 38% of the men did so. Incomplete RBBB (13%), RAD (10%), and atrial abnormalities (3%) were the 3 most common minor abnormalities. Sokolow-Lyon criteria for LVH were found in 49%; however, only 27% had a Romhilt-Estes score of >or=4. T-wave inversion in V2 to V3 occurred in 7% and only 5 men had abnormal Q-waves. Sixty-five athletes (10%) were judged to have distinctly abnormal ECG findings suggestive of arrhythmogenic right ventricular dysplasia, hypertrophic cardiomyopathy, and/or biventricular hypertrophy. These athletes will be submitted to further testing.
Mass ECG screening is achievable within the collegiate setting by using volunteers when the appropriate equipment is available. However, the rate of secondary testing suggests the need for an evaluation of cost-effectiveness for mass screening and the development of new athlete-specific ECG interpretation algorithms.
Clinical journal of sport medicine: official journal of the Canadian Academy of Sport Medicine 03/2010; 20(2):98-105. · 1.50 Impact Factor
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ABSTRACT: Cardiac resynchronization therapy improves morbidity and mortality in appropriately selected patients. Whether atrioventricular (AV) and interventricular (VV) pacing interval optimization confers further clinical improvement remains unclear. A variety of techniques are used to estimate optimum AV/VV intervals; however, the precision of their estimates and the ramifications of an imprecise estimate have not been characterized previously.
An objective methodology for quantifying the precision of estimated optimum AV/VV intervals was developed, allowing physiologic effects to be distinguished from measurement variability. Optimization using multiple conventional techniques was conducted in individual sessions with 20 patients. Measures of stroke volume and dyssynchrony were obtained using impedance cardiography and echocardiographic methods, specifically, aortic velocity-time integral, mitral velocity-time integral, A-wave truncation, and septal-posterior wall motion delay. Echocardiographic methods yielded statistically insignificant data in the majority of patients (62%-82%). In contrast, impedance cardiography yielded statistically significant results in 84% and 75% of patients for AV and VV interval optimization, respectively. Individual cases demonstrated that accepting a plausible but statistically insignificant estimated optimum AV or VV interval can result in worse cardiac function than default values.
Consideration of statistical significance is critical for validating clinical optimization data in individual patients and for comparing competing optimization techniques. Accepting an estimated optimum without knowledge of its precision can result in worse cardiac function than default settings and a misinterpretation of observed changes over time. In this study, only impedance cardiography yielded statistically significant AV and VV interval optimization data in the majority of patients.
Circulation Heart Failure 02/2010; 3(3):395-404. · 6.29 Impact Factor
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ABSTRACT: To investigate apelin-APJ (angiotensin receptor-like 1) signalling in vascular remodelling, we have examined the pathophysiological response to carotid ligation in apelin knockout mice.
Apelin null animals compared with wild-type mice had significantly decreased neointimal lesion area (1.17 +/- 0.17 vs. 3.33 +/- 1.04 x 10(4) microm(2), P < 0.05) and intima/media ratio (0.81 +/- 0.23 vs. 1.49 +/- 0.44, P < 0.05), averaged over four sites 0.5-2 mm from the ligation. Exogenous apelin infusion rescued the apelin-KO phenotype, promoting neointima formation in the null animals. Apelin null animals showed decreased smooth muscle positive area in the neointima (82.3 +/- 2.4 vs. 63.9 +/- 8.4, P < 0.05), and a smaller percentage BrdU positive cells in the neointima and media (11.06 +/- 1.00 vs. 6.53 +/- 0.86, P < 0.05). Apelin mRNA expression increased initially (5.2-fold, P < 0.01) followed by increased apelin receptor expression (10.1-fold, P < 0.05) in the ligated artery. Cytochemistry studies localized apelin expression to luminal endothelial cells and apelin receptor upregulation to smooth muscle cells (SMC) in the media and neointima. In vitro experiments with cultured rat aortic SMC revealed that apelin stimulation increased migration. In contrast to the increased expression of apelin and apelin receptor in carotid remodelling, expression was not upregulated in the apoE high fat model, and correlated with the known disease-inhibitory effect in this model.
These data suggest that increased apelin receptor expression by SMC provides a paracrine pathway in injured vessels that allows endothelial-derived apelin to stimulate their division and migration into the neointima.
Cardiovascular research 02/2010; 87(1):156-65. · 5.80 Impact Factor
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Circulation 02/2010; 121(9):1066-8. · 14.74 Impact Factor
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ABSTRACT: Building on seminal studies of the last 20 years, genetic testing for hypertrophic cardiomyopathy (HCM) has become a clinical reality in the form of targeted exonic sequencing of known disease-causing genes. This has been driven primarily by the decreasing cost of sequencing, but the high profile of genome-wide association studies, the launch of direct-to-consumer genetic testing, and new legislative protection have also played important roles. In the clinical management of hypertrophic cardiomyopathy, genetic testing is primarily used for family screening. An increasing role is recognized, however, in diagnostic settings: in the differential diagnosis of HCM; in the differentiation of HCM from hypertensive or athlete's heart; and more rarely in preimplantation genetic diagnosis. Aside from diagnostic clarification and family screening, use of the genetic test for guiding therapy remains controversial, with data currently too limited to derive a reliable mutation risk prediction from within the phenotypic noise of different modifying genomes. Meanwhile, the power of genetic testing derives from the confidence with which a mutation can be called present or absent in a given individual. This confidence contrasts with our more limited ability to judge the significance of mutations for which co-segregation has not been demonstrated. These variants of "unknown" significance represent the greatest challenge to the wider adoption of genetic testing in HCM. Looking forward, next-generation sequencing technologies promise to revolutionize the current approach as whole genome sequencing will soon be available for the cost of today's targeted panel. In summary, our future will be characterized not by lack of genetic information but by our ability to effectively parse it.
Journal of Cardiovascular Translational Research 12/2009; 2(4):381-91. · 2.61 Impact Factor
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ABSTRACT: To determine the relation between echocardiogram findings and exercise capacity in hypertrophic cardiomyopathy (HCM).
Sixty-three patients (48 +/- 15 years) were referred for cardiopulmonary testing and exercise echocardiography. They were classified by morphology: proximal (n = 11), reverse curvature (n = 32), apical (n = 7), and concentric HCM (n = 13). There were more women in proximal and reverse curvature groups. Proximal HCM patients were older. Maximal left ventricular thickness was highest in reverse curvature group. At peak exercise, concentric HCM achieved the lowest percent predicted maximal Vo2. Excluding apical group, no significant differences in gradient were noted between groups. Overall, no statistically significant correlation was found between peak Vo2, wall thickness, and gradient. Significant correlations were noted between peak Vo2 and indexed left atrial (LA) volume (r = -0.52), lateral E' (r = 0.50), and lateral E/E' ratio (r = -0.46). A multivariate model including age, lateral E', indexed LA volume, and mitral A wave explained 46% of the variance in peak Vo2 (P = .01).
Lateral E' and indexed LA volume are negatively correlated with functional capacity. Although patients with concentric morphology achieved the lowest peak Vo2, wall thickness and gradient did not predict exercise capacity.
American heart journal 10/2009; 158(3):e27-34. · 4.65 Impact Factor
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ABSTRACT: Atrial fibrillation (AF) is the most prevalent arrhythmia in the United States and accounts for more than 750,000 strokes per year. Noninvasive predictors of AF may help identify patients at risk of developing AF. Our objective was to identify the electrocardiographic characteristics associated with onset of AF.
This was a retrospective cohort analysis of 42,751 patients with electrocardiograms (ECGs) ordered by physician's discretion and analyzed using a computerized system. The population was followed for detection of AF on subsequent ECGs. Cox proportional hazard regression analysis was performed to test the association between these ECG characteristics and development of AF.
For a mean follow-up of 5.3 years, 1,050 (2.4%) patients were found to have AF on subsequent ECG recordings. Several ECG characteristics, such as P-wave dispersion (the difference between the widest and narrowest P waves), premature atrial contractions, and an abnormal P axis, were predictive of AF with hazard ratio of approximately 2 after correcting for age and sex. P-wave index, the SD of P-wave duration across all leads, was one of the strongest predictors of AF with a concordance index of 0.62 and a hazard ratio of 2.7 (95% CI 2.1-3.3) for a P-wave index >35. These were among the several independently predictive markers identified on multivariate analysis.
Several ECG markers are independently predictive of future onset of AF. The P index, a measurement of disorganized atrial depolarization, is one of the strongest predictors of AF. The ECG contains valuable prognostic information that can identify patients at risk of AF.
American heart journal 10/2009; 158(4):622-8. · 4.65 Impact Factor
