ISE/ISHNE expert consensus statement on the ECG diagnosis of left ventricular hypertrophy: The change of the paradigm.

The ECG diagnosis of LVH is predominantly based on the QRS voltage criteria. The classical paradigm postulates that the increased left ventricular mass generates a stronger electrical field, increasing the leftward and posterior QRS forces, reflected in the augmented QRS amplitude. However, the low sensitivity of voltage criteria has been repeatedly documented. We discuss possible reasons for this shortcoming and proposal of a new paradigm. The theoretical background for voltage measured at the body surface is defined by the solid angle theorem, which relates the measured voltage to spatial and non-spatial determinants. The spatial determinants are represented by the extent of the activation front and the distance of the recording electrodes. The non-spatial determinants comprise electrical characteristics of the myocardium, which are comparatively neglected in the interpretation of the QRS patterns. Various clinical conditions are associated with LVH. These conditions produce considerable diversity of electrical properties alterations thereby modifying the resultant QRS patterns. The spectrum of QRS patterns observed in LVH patients is quite broad, including also left axis deviation, left anterior fascicular block, incomplete and complete left bundle branch blocks, Q waves, and fragmented QRS. Importantly, the QRS complex can be within normal limits. The new paradigm stresses the electrophysiological background in interpreting QRS changes, i.e., the effect of the non-spatial determinants. This postulates that the role of ECG is not to estimate LV size in LVH, but to understand and decode the underlying electrical processes, which are crucial in relation to cardiovascular risk assessment.

Left Atrial Mechanical Dysfunction and the Risk for Ischemic Stroke in People Without Prevalent Atrial Fibrillation or Stroke : A Prospective Cohort Study.

BACKGROUND: Atrial myopathy-characterized by changes in left atrial function and size-may precede and promote atrial fibrillation (AF) and cardiac thromboembolism. In people without prior AF or stroke, whether analysis of left atrial function and size can improve ischemic stroke prediction is unknown. OBJECTIVE: To evaluate the association of echocardiographic left atrial function (reservoir, conduit, and contractile strain) and left atrial size (left atrial volume index) with ischemic stroke and determine whether these measures can improve the stroke prediction achieved by CHA2DS2-VASc score variables. DESIGN: Prospective cohort study. SETTING: ARIC (Atherosclerosis Risk in Communities) study. PARTICIPANTS: 4917 ARIC participants without prevalent stroke or AF. MEASUREMENTS: Ischemic stroke events (2011 to 2019) were adjudicated by physicians. Left atrial strain was measured using speckle-tracking echocardiography. RESULTS: Over 5 years, the cumulative incidences of ischemic stroke in the lowest quintiles of left atrial reservoir, conduit, and contractile strain were 2.99% (95% CI, 1.89% to 4.09%), 3.18% (CI, 2.14% to 4.22%), and 2.15% (CI, 1.09% to 3.21%), respectively, and that of severe left atrial enlargement was 1.99% (CI, 0.23% to 3.75%). On the basis of the Akaike information criterion, left atrial reservoir strain plus CHA2DS2-VASc variables was the best predictive model. With the addition of left atrial reservoir strain to CHA2DS2-VASc variables, 11.6% of the 112 participants with stroke after 5 years were reclassified to higher risk categories and 1.8% to lower risk categories. Among the 4805 participants who did not develop stroke, 12.2% were reclassified to lower and 12.7% to higher risk categories. Decision curve analysis showed a predicted net benefit of 1.34 per 1000 people at a 5-year risk threshold of 5%. LIMITATION: Underascertainment of subclinical AF. CONCLUSION: In people without prior AF or stroke, when added to CHA2DS2-VASc variables, left atrial reservoir strain improves stroke prediction and yields a predicted net benefit, as shown by decision curve analysis. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute of the National Institutes of Health.

Electrocardiographic left atrial abnormality and risk of heart failure.

INTRODUCTION: The association and the racial differences of the electrocardiographic markers of left atrial abnormality (ECG-LAA) with heart failure (HF) are unclear. METHODS: We examined the cross-sectional association of ECG-LAA, defined as deep terminal negativity of P wave in V1 (DTNPV1) with HF in 8460 participants (51.5% women, 60.3 ± 13.5 age and 49.8% Whites) from the US Third National Health and Nutrition Examination Survey. We excluded participants without P-wave in their ECG or with ECG findings that interfere with measurements of P-wave. DTNPV1 was automatically measured from ECGs processed at a central lab. Values of DTNPV1 ≥ 100 µV were considered abnormal. Past medical history of HF was identified through health interviews. Multivariable logistic regression analysis was used to examine the associations of DTNPV1 with HF. RESULTS: Abnormal DTNPV1 was detected in 3.2% (n = 271) of the participants. HF was significantly more common in individuals with abnormal, compared to those with normal, DTNPV1 (14.7% vs. 4.8%, respectively; p-value <0.001). In a model adjusted for socio-demographics and cardiovascular risk factors, ECG-LAA was associated with 98% increased odds of HF (OR (95% CI): 1.98 (1.30-3.01), p < 0.001). This association was stronger in non-White (vs. White) participants (OR (95% CI): 3.14 (1.82-5.43) vs. 1.01 (0.51-1.97), respectively; interaction p-value =0.01), but consistent in subgroups stratified by age and sex. CONCLUSIONS: ECG-LAA, defined as abnormal DTNPV1, is associated with an increased risk of HF, underscoring the role of atrial disease in developing HF. Racial differences in this association exist, possibly suggesting considering ECG-LAA in personalized assessments of HF risk.

Deep terminal negative of the P wave in V1 and incidence of ischemic stroke: The atherosclerosis risk in communities (ARIC) study.

BACKGROUND: Deep terminal negative of the P wave in V1 (DTNPV1) is a marker of left atrial remodeling. We aimed to evaluate the association of DTNPV1 with incident ischemic stroke. METHODS: The Atherosclerosis Risk in Communities study is a prospective community-based cohort study. All participants at visit 4 (1996-1998) except those with prevalent stroke, missing covariates, and missing or uninterpretable ECG were included. DTNPV1 was defined as the absolute value of the depth of the terminal negative phase >100 µV in the presence of biphasic P wave in V1. Association between DTNPV1 as a time-dependent exposure variable and incident ischemic stroke was evaluated. The accuracy of the prediction model consisting of DTNPV1 and CHA2DS2-VASc variables in predicting ischemic stroke was analyzed. RESULTS: Among 10,605 participants (63 ± 6 years, 56% women, 20% Black), 803 cases of ischemic stroke occurred over a median follow-up of 20.19 years. After adjusting for demographics, DTNPV1 was associated with an increased risk of stroke (HR 1.96, [95% CI 1.39-2.77]). After further adjusting for stroke risk factors, use of aspirin and anticoagulants, and time-dependent atrial fibrillation, DTNPV1 was associated with a 1.50-fold (95% CI 1.06-2.13) increased risk of stroke. When added to the CHA2DS2-VASc variables, DTNPV1 did not significantly improve stroke prediction as assessed by C-statistic. However, there was improvement in risk classification for participants who did not develop stroke. CONCLUSION: DTNPV1 is significantly associated with higher risk of ischemic stroke. Since DTNPV1 is a simplified electrocardiographic parameter, it may help stroke prediction, a subject for further research.

Lifestyle habits associated with cardiac conduction disease.

AIMS: Cardiac conduction disease can lead to syncope, heart failure, and death. The only available therapy is pacemaker implantation, with no established prevention strategies. Research to identify modifiable risk factors has been scant. METHODS AND RESULTS: Data from the Cardiovascular Health Study, a population-based cohort study of adults ≥ 65 years with annual 12-lead electrocardiograms obtained over 10 years, were utilized to examine relationships between baseline characteristics, including lifestyle habits, and conduction disease. Of 5050 participants (mean age 73 ± 6 years; 52% women), prevalent conduction disease included 257 with first-degree atrioventricular block, 99 with left anterior fascicular block, 9 with left posterior fascicular block, 193 with right bundle branch block (BBB), 76 with left BBB, and 102 with intraventricular block at baseline. After multivariable adjustment, older age, male sex, a larger body mass index, hypertension, and coronary heart disease were associated with a higher prevalence of conduction disease, whereas White race and more physical activity were associated with a lower prevalence. Over a median follow-up on 7 (interquartile range 1-9) years, 1036 developed incident conduction disease. Older age, male sex, a larger BMI, and diabetes were each associated with incident conduction disease. Of lifestyle habits, more physical activity (hazard ratio 0.91, 95% confidence interval 0.84-0.98, P = 0.017) was associated with a reduced risk, while smoking and alcohol did not exhibit a significant association. CONCLUSION: While some difficult to control comorbidities were associated with conduction disease as expected, a readily modifiable lifestyle factor, physical activity, was associated with a lower risk.

Associations of Physical Activity and Heart Rate Variability from a Two-Week ECG Monitor with Cognitive Function and Dementia: The ARIC Neurocognitive Study.

Low physical activity (PA) measured by accelerometers and low heart rate variability (HRV) measured from short-term ECG recordings are associated with worse cognitive function. Wearable long-term ECG monitors are now widely used, and some devices also include an accelerometer. The objective of this study was to evaluate whether PA or HRV measured from long-term ECG monitors was associated with cognitive function among older adults. A total of 1590 ARIC participants had free-living PA and HRV measured over 14 days using the Zio® XT Patch [aged 72-94 years, 58% female, 32% Black]. Cognitive function was measured by cognitive factor scores and adjudicated dementia or mild cognitive impairment (MCI) status. Adjusted linear or multinomial regression models examined whether higher PA or higher HRV was cross-sectionally associated with higher factor scores or lower odds of MCI/dementia. Each 1-unit increase in the total amount of PA was associated with higher global cognition (ß = 0.30, 95% CI: 0.16-0.44) and executive function scores (ß = 0.38, 95% CI: 0.22-0.53) and lower odds of MCI (OR = 0.38, 95% CI: 0.22-0.67) or dementia (OR = 0.25, 95% CI: 0.08-0.74). HRV (i.e., SDNN and rMSSD) was not associated with cognitive function. More research is needed to define the role of wearable ECG monitors as a tool for digital phenotyping of dementia.

Validation of a Zio XT Patch Accelerometer for the Objective Assessment of Physical Activity in the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Combination devices to monitor heart rate/rhythms and physical activity are becoming increasingly popular in research and clinical settings. The Zio XT Patch (iRhythm Technologies, San Francisco, CA, USA) is US Food and Drug Administration (FDA)-approved for monitoring heart rhythms, but the validity of its accelerometer for assessing physical activity is unknown. OBJECTIVE: To validate the accelerometer in the Zio XT Patch for measuring physical activity against the widely-used ActiGraph GT3X. METHODS: The Zio XT and ActiGraph wGT3X-BT (Actigraph, Pensacola, FL, USA) were worn simultaneously in two separately-funded ancillary studies to Visit 6 of the Atherosclerosis Risk in Communities (ARIC) Study (2016-2017). Zio XT was worn on the chest and ActiGraph was worn on the hip. Raw accelerometer data were summarized using mean absolute deviation (MAD) for six different epoch lengths (1-min, 5-min, 10-min, 30-min, 1-h, and 2-h). Participants who had ≥3 days of at least 10 h of valid data between 7 a.m-11 p.m were included. Agreement of epoch-level MAD between the two devices was evaluated using correlation and mean squared error (MSE). RESULTS: Among 257 participants (average age: 78.5 ± 4.7 years; 59.1% female), there were strong correlations between MAD values from Zio XT and ActiGraph (average r: 1-min: 0.66, 5-min: 0.90, 10-min: 0.93, 30-min: 0.93, 1-h: 0.89, 2-h: 0.82), with relatively low error values (Average MSE × 106: 1-min: 349.37 g, 5-min: 86.25 g, 10-min: 56.80 g, 30-min: 45.46 g, 1-h: 52.56 g, 2-h: 54.58 g). CONCLUSIONS: These findings suggest that Zio XT accelerometry is valid for measuring duration, frequency, and intensity of physical activity within time epochs of 5-min to 2-h.

Apixaban to Prevent Recurrence After Cryptogenic Stroke in Patients With Atrial Cardiopathy: The ARCADIA Randomized Clinical Trial.

Importance: Atrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. It is unknown whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation. Objective: To compare anticoagulation vs antiplatelet therapy for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy. Design, Setting, and Participants: Multicenter, double-blind, phase 3 randomized clinical trial of 1015 participants with cryptogenic stroke and evidence of atrial cardiopathy, defined as P-wave terminal force greater than 5000 µV × ms in electrocardiogram lead V1, serum N-terminal pro-B-type natriuretic peptide level greater than 250 pg/mL, or left atrial diameter index of 3 cm/m2 or greater on echocardiogram. Participants had no evidence of atrial fibrillation at the time of randomization. Enrollment and follow-up occurred from February 1, 2018, through February 28, 2023, at 185 sites in the National Institutes of Health StrokeNet and the Canadian Stroke Consortium. Interventions: Apixaban, 5 mg or 2.5 mg, twice daily (n = 507) vs aspirin, 81 mg, once daily (n = 508). Main Outcomes and Measures: The primary efficacy outcome in a time-to-event analysis was recurrent stroke. All participants, including those diagnosed with atrial fibrillation after randomization, were analyzed according to the groups to which they were randomized. The primary safety outcomes were symptomatic intracranial hemorrhage and other major hemorrhage. Results: With 1015 of the target 1100 participants enrolled and mean follow-up of 1.8 years, the trial was stopped for futility after a planned interim analysis. The mean (SD) age of participants was 68.0 (11.0) years, 54.3% were female, and 87.5% completed the full duration of follow-up. Recurrent stroke occurred in 40 patients in the apixaban group (annualized rate, 4.4%) and 40 patients in the aspirin group (annualized rate, 4.4%) (hazard ratio, 1.00 [95% CI, 0.64-1.55]). Symptomatic intracranial hemorrhage occurred in 0 patients taking apixaban and 7 patients taking aspirin (annualized rate, 1.1%). Other major hemorrhages occurred in 5 patients taking apixaban (annualized rate, 0.7%) and 5 patients taking aspirin (annualized rate, 0.8%) (hazard ratio, 1.02 [95% CI, 0.29-3.52]). Conclusions and Relevance: In patients with cryptogenic stroke and evidence of atrial cardiopathy without atrial fibrillation, apixaban did not significantly reduce recurrent stroke risk compared with aspirin. Trial Registration: ClinicalTrials.gov Identifier: NCT03192215.

Monogenic and Polygenic Contributions to QTc Prolongation in the Population.

BACKGROUND: Rare sequence variation in genes underlying cardiac repolarization and common polygenic variation influence QT interval duration. However, current clinical genetic testing of individuals with unexplained QT prolongation is restricted to examination of monogenic rare variants. The recent emergence of large-scale biorepositories with sequence data enables examination of the joint contribution of rare and common variations to the QT interval in the population. METHODS: We performed a genome-wide association study of the QTc in 84 630 UK Biobank participants and created a polygenic risk score (PRS). Among 26 976 participants with whole-genome sequencing and ECG data in the TOPMed (Trans-Omics for Precision Medicine) program, we identified 160 carriers of putative pathogenic rare variants in 10 genes known to be associated with the QT interval. We examined QTc associations with the PRS and with rare variants in TOPMed. RESULTS: Fifty-four independent loci were identified by genome-wide association study in the UK Biobank. Twenty-one loci were novel, of which 12 were replicated in TOPMed. The PRS composed of 1 110 494 common variants was significantly associated with the QTc in TOPMed (ΔQTc/decile of PRS=1.4 ms [95% CI, 1.3 to 1.5]; P=1.1×10-196). Carriers of putative pathogenic rare variants had longer QTc than noncarriers (ΔQTc=10.9 ms [95% CI, 7.4 to 14.4]). Of individuals with QTc>480 ms, 23.7% carried either a monogenic rare variant or had a PRS in the top decile (3.4% monogenic, 21% top decile of PRS). CONCLUSIONS: QTc duration in the population is influenced by both rare variants in genes underlying cardiac repolarization and polygenic risk, with a sizeable contribution from polygenic risk. Comprehensive assessment of the genetic determinants of QTc prolongation includes incorporation of both polygenic and monogenic risk.

Associations of dietary patterns with risk of incident atrial fibrillation in the REasons for Geographic And Racial Differences in Stroke (REGARDS).

BACKGROUND: We examined whether the risk of incident atrial fibrillation (AF) in a large, biracial, prospective cohort is lower in participants who adhere to heart-healthy dietary patterns and higher in participants who adhere to less heart-healthy diets. METHODS: Between 2003 and 2007, the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort study enrolled 30,239 Black and White Americans aged 45 years or older. Dietary patterns (convenience, plant-based, sweets, Southern, and alcohol and salads) and the Mediterranean diet score (MDS) were derived based on food frequency questionnaire data. The primary outcome was incident AF at the follow-up visit 2013-2016, defined by either electrocardiogram or self-reported medical history of a physician diagnosis. RESULTS: This study included 8977 participants (mean age 63 ± 8.3 years; 56% women; 30% Black) free of AF at baseline who completed the follow-up exam an average of 9.4 years later. A total of 782 incident AF cases were detected. In multivariable logistic regression analyses, neither the MDS score (odds ratio (OR) per SD increment = 1.03; 95% confidence interval (CI) 0.95-1.11) or the plant-based dietary pattern (OR per SD increment = 1.03; 95% CI 0.94-1.12) were associated with AF risk. Additionally, an increased AF risk was not associated with any of the less-healthy dietary patterns. CONCLUSIONS: While specific dietary patterns have been associated with AF risk factors, our findings fail to show an association between diet patterns and AF development.

Association of abnormal p-wave parameters with brain MRI morphology: The atherosclerosis risk in communities neurocognitive study (ARIC-NCS).

BACKGROUND: Recent evidence indicates that abnormal P-wave parameters (PWPs)-ECG markers of atrial myopathy-are associated with incident dementia, independent of atrial fibrillation (AF) and clinical ischemic stroke. However, the mechanisms remain unclear and may include subclinical vascular brain injury. Hence, we evaluated the association of abnormal PWPs with brain MRI correlates of vascular brain injury in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). METHODS: ARIC-NCS participants who underwent 3T brain MRI scans in 2011-2013 were included. PWPs were measured from standard 12-lead ECGs. Brain MRI outcomes included cortical infarcts, lacunar infarcts, cerebral microhemorrhages, brain volumes, and white matter disease (WMD) volume. We used weighted multivariable logistic and linear regression to evaluate the associations of abnormal PWPs with brain MRI outcomes. RESULTS: Among 1715 participants (mean age, 76.1 years; 61% women; 29% Black), 797 (46%) had ≥1 abnormal PWP. After multivariable adjustment, including adjusting for prevalent AF, abnormal P-wave terminal force in lead V1 (aPTFV1) and prolonged P-wave duration (PPWD) were associated with increased odds of both cortical (OR 1.41; 95% CI, 1.14 to 1.74 and OR 1.30; 95% CI, 1.04 to 1.63, respectively) and lacunar infarcts (OR 1.36; 95% CI, 1.15 to 1.63 and OR 1.37; 95% CI, 1.15 to 1.65, respectively). Advanced interatrial block (aIAB) was associated with higher odds of subcortical microhemorrhage (OR 2.04; 95% CI, 1.36 to 3.06). Other than a significant association between aPTFV1 with lower parietal lobe volume, there were no other significant associations with brain or WMD volume. CONCLUSION: In this exploratory analysis of a US community-based cohort, ECG surrogates of atrial myopathy are associated with a higher prevalence of brain infarcts and microhemorrhage, suggesting subclinical vascular brain injury as a possible mechanism underlying the association of atrial myopathy with dementia.

Association of silent myocardial infarction on electrocardiogram and coronary artery calcium: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Silent myocardial infarction (SMI) on electrocardiogram (ECG) is associated with atherosclerotic cardiovascular disease, but the relationship between SMI on ECG and coronary artery calcium (CAC) remains poorly understood. OBJECTIVE: Characterize the relationship between SMI on ECG and CAC. METHODS: Eligible participants from the Multi-Ethnic Study of Atherosclerosis study had ECG and CAC scoring at study enrollment (2000-2002). SMI was defined as ECG evidence of myocardial infarction in the absence of a history of clinical cardiovascular disease. CAC was modeled both continuously and categorically. The cross-sectional relationships between SMI on ECG and CAC were assessed using logistic regression and linear regression. RESULTS: Among 6705 eligible participants, 178 (2.7%) had baseline SMI. Compared to participants without SMI, those with SMI had higher CAC (median [IQR]: 61.2 [0-261.7] vs. 0 [0-81.5]; p < .0001). Participants with SMI were more likely to have non-zero CAC (74% vs. 49%) and were more likely to have CAC ≥ 100 (40% vs. 23%). In a multivariable-adjusted logistic model, SMI was associated with higher odds of non-zero CAC (odds ratio 2.17, 95% CI 1.48-3.20, p < .0001) and 51% higher odds of CAC ≥ 100 (odds ratio 1.51, 95% CI 1.06-2.16, p = .02). CONCLUSION: An incidental finding of SMI on ECG may serve to identify patients who have a higher odds of significant CAC and may benefit from additional risk stratification to further refine their cardiovascular risk. Further exploration of the utility of CAC assessment in this patient population is needed.

Relationship between premature ventricular complexes and stroke mortality in the general population.

OBJECTIVES: Predictors for increased stroke mortality identify those who may need closer monitoring and better hospital care. While the link between premature ventricular complexes (PVCs) and incident ischemic stroke has been reported, studies on the association with fatal stroke are non-existent. MATERIALS AND METHODS: We examined the association of PVCs with stroke mortality in 8047 participants (56.5 ± 0.39 years, 53% women, 80.9% Non-Hispanic Whites) without prior history of stroke from the Third National Health and Nutrition Examination Survey. National Death Index was used to identify the date and cause of death. PVCs were detected from 12­lead standard electrocardiograms. Cox proportional hazard analysis was used to examine the association between any PVC with stroke mortality. RESULTS: Approximately 2.1% (n = 134) participants had PVCs at baseline. Over a median follow-up of 22 years, 337 fatal strokes occurred. More strokes occurred in participants with baseline PVCs compared to those without (unadjusted cumulative incidence of stroke 9.5% vs. 2.5% respectively, p-value 0.001). In a multivariable-adjusted model, the presence of PVC was associated with an increased risk of stroke mortality (HR (95%CI): 2.50 (1.15-5.43). This association was stronger in participants with coronary heart disease (CHD) than those without it (HR (95%CI): 5.98 (2.2-16.2) vs. 1.97 (0.75-5.1) respectively; interaction-p = 0.008). CONCLUSIONS: PVCs are associated with an increased risk of stroke mortality, especially among individuals with CHD. Whether improved hospital care or modifying PVCs could change outcomes should be examined in prospective studies.

Relationship between abnormal P-wave axis, chronic obstructive pulmonary disease and mortality in the general population.

BACKGROUND: It is unclear whether the presence of a vertical P-wave axis on electrocardiogram modifies the association of COPD with mortality. OBJECTIVE: To examine the association and interaction of abnormal P-wave axis and COPD with mortality. STUDY DESIGN AND METHODS: The analysis included 7359 with ECG data from the Third National Health and Nutrition Examination Survey (NHANES-III) who were free of cardiovascular disease (CVD) at enrollment. Abnormal P-wave axis (aPWA) was defined as values above 75°. COPD was self-reported as either a diagnosis of emphysema or chronic bronchitis. National Death Index was used to identify the date of death and cause of death. Using multivariable Cox proportional hazard analysis, we examined the association of COPD with all-cause mortality by aPWA status. RESULTS: Over a median follow-up of 14 years, 2435 deaths occurred. Participants with concomitant presence of aPWA and COPD experienced higher death rates (73.9 per 1000 person-years (PY)) compared to either COPD or aPWA alone (36.4 per 1000 PY and 31.1 per 1000 PY), respectively. In multivariable-adjusted models, a stronger association between COPD and mortality was noted in the presence compared to the absence of aPWA (HR 95% CI): 1.71 (1.37-2.13) vs. 1.22(1.00-1.49), respectively (interaction P-value = 0.02). Similarly, a stronger association between aPWA and mortality was observed in the presence compared to the absence of COPD (HR 95% CI): 1.66(1.26-2.19) vs. 1.18(1.06-1.31), respectively (interaction P-value = 0.02). Similar higher death rates and mortality risk was observed when spirometry-confirmed COPD and aPWA were present together than in isolation. CONCLUSION: The concomitant presence of aPWA and COPD leads to a significantly higher mortality rate compared to the presence either COPD or aPWA alone as a clinical variable. P-wave axis, reported routinely on ECG printout, can potentially identify patients with COPD who need intensive control of risk factors and disease management.

ISE/ISHNE Expert Consensus Statement on ECG Diagnosis of Left Ventricular Hypertrophy: The Change of the Paradigm. The joint paper of the International Society of Electrocardiology and the International Society for Holter Monitoring and Noninvasive Electrocardiology.

The ECG diagnosis of LVH is predominantly based on the QRS voltage criteria, i.e. the increased QRS complex amplitude in defined leads. The classical ECG diagnostic paradigm postulates that the increased left ventricular mass generates a stronger electrical field, increasing the leftward and posterior QRS forces. These increased forces are reflected in the augmented QRS amplitude in the corresponding leads. However, the clinical observations document increased QRS amplitude only in the minority of patients with LVH. The low sensitivity of voltage criteria has been repeatedly documented. We discuss possible reasons for this shortcoming and proposal of a new paradigm.

Association of physical activity with the incidence of atrial fibrillation in persons > 65 years old: the Atherosclerosis Risk in Communities (ARIC) study.

AIMS: To evaluate the association of physical activity (PA) with atrial fibrillation (AF) incidence in an elderly population. METHODS: We studied 5166 participants of the Atherosclerosis Risk in Communities cohort examined in 2011-2013 free of AF. Self-reported PA was evaluated with a validated questionnaire. Weekly minutes of leisure-time moderate to vigorous physical activity (MVPA) were calculated and categorized using the 2018 Physical Activity Guidelines for Americans (no activity [0 min/week], low [> 0- < 150 min/week], adequate [150- < 300 min/week], high [≥ 300 min/week]). Incident AF through 2019 was ascertained from hospital discharges and death certificates. Cox models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for AF by levels of physical activity adjusting for potential confounders. RESULTS: The mean (SD) age for the sample was 75 (5) years (59% female, 22% Black). During a mean (SD) follow-up time of 6.3 (2.0) years, 703 AF events were identified. The association of MVPA with AF incidence showed a U-shaped relationship. Compared to those not engaging in MVPA, individuals with low MVPA had a 23% lower hazard of AF (HR = 0.77; 95% CI 0.61, 0.96), while those with adequate MVPA had a 14% lower hazard (HR 0.86; 95% CI 0.69, 1.06). High levels of MVPA were not associated with AF risk (HR 0.97; 95% CI 0.78, 1.20). CONCLUSION: This study suggests that being involved in low to moderate levels of MVPA is associated with lower AF risk, with no evidence of increased risk of AF in those with higher levels of MVPA.

Multiple SCN5A variant enhancers modulate its cardiac gene expression and the QT interval.

The rationale for genome-wide association study (GWAS) results is sequence variation in cis-regulatory elements (CREs) modulating a target gene's expression as the major cause of trait variation. To understand the complete molecular landscape of one of these GWAS loci, we performed in vitro reporter screens in cardiomyocyte cell lines for CREs overlapping nearly all common variants associated with any of five independent QT interval (QTi)-associated GWAS hits at the SCN5A-SCN10A locus. We identified 13 causal CRE variants using allelic reporter activity, cardiomyocyte nuclear extract-based binding assays, overlap with human cardiac tissue DNaseI hypersensitive regions, and predicted impact of sequence variants on DNaseI sensitivity. Our analyses identified at least one high-confidence causal CRE variant for each of the five sentinel hits that could collectively predict SCN5A cardiac gene expression and QTi association. Although all 13 variants could explain SCN5A gene expression, the highest statistical significance was obtained with seven variants (inclusive of the five above). Thus, multiple, causal, mutually associated CRE variants can underlie GWAS signals.

Two-Week Burden of Arrhythmias across CKD Severity in a Large Community-Based Cohort: The ARIC Study.

BACKGROUND: CKD is associated with sudden cardiac death and atrial fibrillation (AF). However, other types of arrhythmia and different measures of the burden of arrhythmias, such as presence and frequency, have not been well characterized in CKD. METHODS: To quantify the burden of arrhythmias across CKD severity in 2257 community-dwelling adults aged 71-94 years, we examined associations of major arrhythmias with CKD measures (eGFR and albuminuria) among individuals in the Atherosclerosis Risk in Communities study. Participants underwent 2 weeks of noninvasive, single-lead electrocardiogram monitoring. We examined types of arrhythmia burden: presence and frequency of arrhythmias and percent time in arrhythmias. RESULTS: Of major arrhythmias, there was a higher prevalence of AF and nonsustained ventricular tachycardia among those with more severe CKD, followed by long pause (>30 seconds) and atrioventricular block. Nonsustained ventricular tachycardia was the most frequent major arrhythmia (with 4.2 episodes per person-month). Most participants had ventricular ectopy, supraventricular tachycardia, and supraventricular ectopy. Albuminuria consistently associated with higher AF prevalence and percent time in AF, and higher prevalence of nonsustained ventricular tachycardia. When other types of arrhythmic burden were examined, lower eGFR was associated with a lower frequency of atrioventricular block. Although CKD measures were not strongly associated with minor arrhythmias, higher albuminuria was associated with a higher frequency of ventricular ectopy. CONCLUSIONS: CKD, especially as measured by albuminuria, is associated with a higher burden of AF and nonsustained ventricular tachycardia. Additionally, eGFR is associated with less frequent atrioventricular block, whereas albuminuria is associated with more frequent ventricular ectopy. Use of a novel, 2-week monitoring approach demonstrated a broader range of arrhythmias associated with CKD than previously reported.

Association of Echocardiographic Measures of Left Atrial Function and Size With Incident Dementia.

Importance: Atrial myopathy-characterized by alterations in left atrial (LA) function and size-is associated with ischemic stroke, independent of atrial fibrillation (AF). Electrocardiographic markers of atrial myopathy are associated with dementia, but it is unclear whether 2-dimensional echocardiographic (2DE)-defined LA function and size are associated with dementia. Objective: To examine the association of LA function and size with incident dementia. Design, Setting, and Participants: The Atherosclerosis Risk in Communities (ARIC) study is a community-based prospective cohort. An exploratory, retrospective analysis was conducted. ARIC centers are located in Forsyth County, North Carolina; Jackson, Mississippi; Washington County, Maryland; and suburban Minneapolis, Minnesota. For this analysis, visit 5 (2011-2013) served as the baseline. Participants without prevalent AF and stroke and who had 2DEs in 2011-2013 were included and surveilled through December 31, 2019. Exposures: LA function (reservoir strain, conduit strain, contractile strain, emptying fraction, passive emptying fraction, and active emptying fraction), and LA size (maximal and minimal volume index) as evaluated by 2DE. Main Outcomes and Measures: Dementia cases were identified using in-person and phone cognitive assessments, hospitalization codes, and death certificates. Cox proportional hazards models were used. Results: Among 4096 participants (mean [SD] age, 75 [5] years; 60% women; 22% Black individuals), 531 dementia cases were ascertained over a median follow-up of 6 years. Dementia incidence for the lowest LA quintile was 4.80 for reservoir strain, 3.94 for conduit strain, 3.29 for contractile strain, 4.20 for emptying fraction, 3.67 for passive emptying fraction, and 3.27 for active emptying fraction per 100 person-years. After full-model adjustments, there were statistically significant associations between measures of LA function and dementia; the hazard ratios (HRs) from the lowest vs highest quintile for reservoir strain were 1.98 (95% CI, 1.42-2.75); for conduit strain, 1.50 (95% CI, 1.09-2.06); for contractile strain, 1.57 (95% CI, 1.16-2.14); for emptying fraction, 1.87 (95% CI, 1.31-2.65); and for active emptying fraction, 1.43 (95% CI, 1.04-1.96). LA passive emptying fraction was not significantly associated with dementia (HR, 1.26 [95% CI, 0.93-1.71]). Dementia incidence for the highest LA maximal volume index quintile was 3.18 per 100 person-years (HR for highest vs lowest quintile, 0.77 [95% CI, 0.58-1.02]) and for the highest minimal volume index quintile was 3.50 per 100 person-years (HR for the highest vs lowest quintile, 0.95 [95% CI, 0.71-1.28]). Both measures were not significantly associated with dementia. These findings were robust to sensitivity analyses that excluded participants with incident AF or stroke. Conclusions and Relevance: In this exploratory analysis of a US community-based cohort, several echocardiographic measures of lower LA function were significantly associated with an increased risk of subsequent dementia. Measures of LA size were not significantly associated with dementia risk. These findings suggest that impaired LA function may be a risk factor associated with dementia.

Continuous cardiac rhythm monitoring post-stroke: A feasibility study in REGARDS.

OBJECTIVES: Cardiac rhythm monitoring is increasingly used after stroke. We studied feasibility of telephone guided, mail-in ambulatory long-term cardiac rhythm monitoring in Black and White stroke survivors. MATERIALS AND METHODS;: We contacted 28 participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study who had an ischemic stroke during follow-up. After obtaining informed consent by telephone, a noninvasive 14-day cardiac rhythm monitoring device (ZIO® XT patch; iRhythm Technologies, San Francisco, CA) was mailed to each participant. We evaluated the results of telephone consent, follow-up calls, compliance and wear time as the primary objective. Secondarily, we reported prevalence of atrial and ventricular arrhythmias. RESULTS: The majority of those contacted (20/28 = 71%) agreed to enroll in the monitoring study. Non-participation was nominally more common in Black than White participants; 6/16 (37.5%) vs. 2/12 (17%). Of those who agreed, 15 participants (75%, 6 Black, 9 White) completed ambulatory monitoring with mean wear time 12.9 ± 2.5 days. Arrhythmias were observed in two-thirds of the 15 participants: AF in 2, brief atrial tachycardia in 12, NSVT in 2, premature ventricular contractions in 3, and pause or atrioventricular block in 2. CONCLUSIONS: Non-invasive rhythm monitoring was feasible in this pilot from a large, national cohort study of stroke survivors that employed a telephone guided, mail-in monitoring system, and these preliminary results suggest a high prevalence of arrhythmias. Increased emphasis on recruitment strategies for Black stroke survivors may be required. We demonstrated a high yield of significant cardiac arrhythmias among post-stroke participants who completed monitoring.