Integration of genetics into a systems model of electrocardiographic traits using humanCVD BeadChip

<p>Background—Electrocardiographic traits are important, substantially heritable determinants of risk of arrhythmias and sudden cardiac death.</p> <p>Methods and Results—In this study, 3 population-based cohorts (n=10 526) genotyped with the Illumina HumanCVD Beadchip and 4 quantitative electrocardiographic traits (PR interval, QRS axis, QRS duration, and QTc interval) were evaluated for single-nucleotide polymorphism associations. Six gene regions contained single nucleotide polymorphisms associated with these traits at P<10−6, including SCN5A (PR interval and QRS duration), CAV1-CAV2 locus (PR interval), CDKN1A (QRS duration), NOS1AP, KCNH2, and KCNQ1 (QTc interval). Expression quantitative trait loci analyses of top associated single-nucleotide polymorphisms were undertaken in human heart and aortic tissues. NOS1AP, SCN5A, IGFBP3, CYP2C9, and CAV1 showed evidence of differential allelic expression. We modeled the effects of ion channel activity on electrocardiographic parameters, estimating the change in gene expression that would account for our observed associations, thus relating epidemiological observations and expression quantitative trait loci data to a systems model of the ECG.</p> <p>Conclusions—These association results replicate and refine the mapping of previous genome-wide association study findings for electrocardiographic traits, while the expression analysis and modeling approaches offer supporting evidence for a functional role of some of these loci in cardiac excitation/conduction.</p&gt

Prolonged PR interval, first-degree heart block and adverse cardiovascular outcomes: a systematic review and meta-analysis

Objective: First-degree atrioventricular block is frequently encountered in clinical practice and is generally considered a benign process. However, there is emerging evidence that prolonged PR interval may be associated with adverse outcomes. This study aims to determine if prolonged PR interval is associated with adverse cardiovascular outcomes and mortality. Methods: We searched MEDLINE and EMBASE for studies that evaluated clinical outcomes associated with prolonged and normal PR intervals. Relevant studies were pooled using random effects meta-analysis for risk of mortality, cardiovascular mortality, heart failure, coronary heart disease, atrial fibrillation and stroke or transient ischaemic attack (TIA). Sensitivity analyses were performed considering the population type and the use of adjustments. Results: Our search yielded 14 studies that were undertaken between 1972 and 2011 with 400 750 participants. Among the studies that adjusted for potential confounders, the pooled results suggest an increased risk of mortality with prolonged PR interval risk ratio (RR) 1.24 95% CI 1.02 to 1.51, five studies. Prolonged PR interval was associated with significant risk of heart failure or left ventricular dysfunction (RR 1.39 95% CI 1.18 to 1.65, three studies) and atrial fibrillation (RR 1.45 95% CI 1.23 to 1.71, eight studies) but not cardiovascular mortality, coronary heart disease or myocardial infarction or stroke or TIA. Similar observations were recorded when limited to studies of first-degree heart block. Conclusions: Data from observational studies suggests a possible association between prolonged PR interval and significant increases in atrial fibrillation, heart failure and mortality. Future prospective studies are needed to confirm the relationships reported, consider possible mechanisms and define the optimal monitoring strategy for such patients

Electrocardiographic repolarization-related variables as predictors of coronary heart disease death in the women's health initiative study.

BackgroundWe evaluated 25 repolarization-related ECG variables for the risk of coronary heart disease (CHD) death in 52 994 postmenopausal women from the Women's Health Initiative study.Methods and resultsHazard ratios from Cox regression were computed for subgroups of women with and without cardiovascular disease (CVD). During the average follow-up of 16.9 years, 941 CHD deaths occurred. Based on electrophysiological considerations, 2 sets of ECG variables with low correlations were considered as candidates for independent predictors of CHD death: Set 1, Ѳ(Tp|Tref), the spatial angle between T peak (Tp) and normal T reference (Tref) vectors; Ѳ(Tinit|Tterm), the angle between the initial and terminal T vectors; STJ depression in V6 and rate-adjusted QTp interval (QTpa); and Set 2, TaVR and TV1 amplitudes, heart rate, and QRS duration. Strong independent predictors with over 2-fold increased risk for CHD death in women with and without CVD were Ѳ(Tp|Tref) >42° from Set 1 and TaVR amplitude >-100 μV from Set 2. The risk for these CHD death predictors remained significant after multivariable adjustment for demographic/clinical factors. Other significant predictors for CHD death in fully adjusted risk models were Ѳ(Tinit|Tterm) >30°, TV1 >175 μV, and QRS duration >100 ms.ConclusionsѲ(Tp|Tref) angle and TaVR amplitude are associated with CHD mortality in postmenopausal women. The use of these measures to identify high-risk women for further diagnostic evaluation or more intense preventive intervention warrants further study.Clinical trial registration urlhttp://www.clinicaltrials.gov. Unique identifier: NCT00000611

Electrocardiographic patch devices and contemporary wireless cardiac monitoring.

Cardiac electrophysiologic derangements often coexist with disorders of the circulatory system. Capturing and diagnosing arrhythmias and conduction system disease may lead to a change in diagnosis, clinical management and patient outcomes. Standard 12-lead electrocardiogram (ECG), Holter monitors and event recorders have served as useful diagnostic tools over the last few decades. However, their shortcomings are only recently being addressed by emerging technologies. With advances in device miniaturization and wireless technologies, and changing consumer expectations, wearable “on-body” ECG patch devices have evolved to meet contemporary needs. These devices are unobtrusive and easy to use, leading to increased device wear time and diagnostic yield. While becoming the standard for detecting arrhythmias and conduction system disorders in the outpatient setting where continuous ECG monitoring in the short to medium term (days to weeks) is indicated, these cardiac devices and related digital mobile health technologies are reshaping the clinician-patient interface with important implications for future healthcare delivery

Pattern of Cardiovascular Diseases Among Elderly Patients Admitted in Medical Wards at Muhimbili National Hospital Dar es salaam Tanzania

Cardiovascular disease is the most frequent cause of death in persons over the age 50 years and most importantly it is responsible for considerable morbidity and large burden of disability in the community. Cardiovascular diseases are an increasing cause of admissions among elderly in Africa, yet little research is available on pattern and magnitude of the problem. To determine the pattern of cardiovascular disease in elderly patients admitted in medical wards at Muhimbili National Hospital Dar es Salaam Tanzania. This was a descriptive cross sectional study that was carried our between September 2008 and September 2009. Social demographic information; medical history physical examination; electrocardiographic and echocardiography examination; biochemical and haematological parameters were collected from study patients One hundred eighty five elderly patients admitted at MNH, medical department, were enrolled into the study, all were of African black race. Majority, 116 (62.7%), were male. Their mean age was 66.1 (SD, 9.3; range, 50-87) years. The mean body mass index\ud (BMI) was 23.9 (SD, 3.9; range, 16.6-40.1) kg/m2. Hypertension was the most frequent condition encountered affecting both males (67.2%)and females (68.1%). Congestive heart failure was second common condition affecting 37% elderly patients. According to the echocardiogram findings, among 185 elderly patients 68.6% were diagnosed to have cardiovascular disease. There were no significant sex differences in the prevalence of cardiac disease (p>005). The commonest echocardiographic diagnosis were left ventricular hypertrophy (LVH) secondary to hypertension found in 45%, diastolic dysfunction found in 31% and systolic dysfunction 25%.The least common types were septal defect, pulmonary hypertension and calcified mitral valve found in one percent each. The commonest clinical presentations were palpitations, dyspnoea, orthopnoea, pedal oedema and right upper quadrant abdominal pain. Obese patients presenting with cardiovascular abnormalities were 9 (7.1%). Anaemia was the leading co- morbidity affecting 90.3% of the patients Hypertension, congestive heart failure and left ventricular hypertrophy were the commonest cardiovascular diseases among elderly patients at MNH. Coexistence of anaemia, stroke, renal impairment and diabetes was also frequent. Elderly patients should be screened for cardiovascular diseases especially hypertension whenever they are admitted to the hospital even if the reasons for admission are not cardiovascular problems.\u

The incidence and risk factors for new onset atrial fibrillation in the PROSPER study

Aims Atrial fibrillation/flutter (AF) is the most common arrhythmia in older people. It associates with reduced exercise capacity, increased risk of stroke, and mortality. We aimed to determine retrospectively whether pravastatin reduces the incidence of AF and whether any electrocardiographic measures or clinical conditions might be risk factors for its development. Methods and results The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) was a randomized, double-blind controlled trial that recruited 5804 individuals aged 70-82 years with a history of, or risk factors for, vascular disease. A total of 2891 were allocated to pravastatin and 2913 to placebo; mean follow-up was 3.2 years. Electrocardiograms (ECGs), which were recorded at baseline, annually thereafter, and at run-out, were processed by computer and reviewed manually. In all, 264 of 2912 (9.1%) of the placebo group and 283 of 2888 (9.8%) of the pravastatin-treated group developed AF [hazard ratio 1.08 (0.92,1.28), P = 0.35)]. Multivariate analysis showed that PR and QTc intervals, age, left ventricular hypertrophy, and ST-T abnormalities were related to development of AF after adjustment for many variables including alcohol consumption, which itself was univariately predictive of developing AF. Previous myocardial infarction on the ECG was not a risk factor. A history of vascular disease was strongly linked with developing AF but not diabetes and hypertension. Conclusion Pravastatin does not reduce the incidence of AF in older people at risk of vascular disease, at least in the short-medium term. Risk factors for AF include older age, prolongation of PR or QTc intervals, left ventricular hypertrophy, and ST-T abnormalities on the EC

High School and College Athletes Should Be Required to Undergo Pre-Participation Cardiac Screening Prior to Participation in Competitive Sports

Sudden Cardiac Arrest (SCA) is the leading cause of death in young athletes. Most of these athletes are unaware they have a condition that puts them at risk. In addition it is estimated that approximately 1 in 220,000 young athletes experience Sudden Cardiac Death (SCD) each year, although, these numbers are not truly reliable because there is no national mandatory reporting system in the United States. My paper argues that all high school and college athletes should be required to undergo pre-participation cardiac screening (i.e. an ECG and extensive family health history) as a part of a required physical exam to identify student-athletes at risk of SCD. Studies in Italy, where pre-participation screening is mandatory, and at some US universities in the US where collegiate athletes received cardiovascular screening prior to sports participation suggest that including ECG improved overall sensitivity, mass ECG screening is achievable and cost-effective, and that screening lowered the death rates in the population screened. Some critics believe that the cost of the screening is not cost-effective, but others believe the costs are reasonable; some hospitals in the US now provide student athletes with free ECG screening, or at reduced cost. ECG screening will save lives, and should not be discounted as being too costly. Every parent who has a child participating in school athletics should be informed of the risks, and be given the opportunity to have their child tested. Saving someone’s child is worth the cost of testing. My interest in this topic comes from my family’s personal experience with a student athlete who experienced a cardiac event characterized by shortness of breath and dizziness while playing in a collegiate baseball game. Our son, Neil, was a healthy 21-year-old student athlete who had participated in organized sports since he was seven years old. His event was initially diagnosed as a panic attack, but after he underwent a series of cardiac testing, including an ECG that showed an abnormality, he was diagnosed with Arrhythmogenic Right Ventricular Dysplasia (ARVD), a progressive heart disease. We have no family history to link to Neil’s disease, and we had no idea he was at risk. Today Neil lives with an implantable cardioverter defibrillator (ICD), takes anti-arrhythmic medication, and no longer participates in team sports. Neil is one of the lucky ones who survived, and his survival impelled me to get involved in my community to promote awareness about sudden cardiac arrest, and the importance of CPR training and the availability of automated external defibrillators (AEDs). Our experience also inspired me to research adding pre-participation cardiac screening for young athletes. If such a program had been instituted at his high school or college, Neil’s disease would have been diagnosed and treated, keeping him from being at risk during athletics