Ajmaline‐Induced Abnormalities in Brugada Syndrome: Evaluation With ECG Imaging

Background The rate of sudden cardiac death (SCD) in Brugada syndrome (BrS) is ≈1%/y. Noninvasive electrocardiographic imaging is a noninvasive mapping system that has a role in assessing BrS depolarization and repolarization abnormalities. This study aimed to analyze electrocardiographic imaging parameters during ajmaline test (AJT). Methods and Results All consecutive epicardial maps of the right ventricle outflow tract (RVOT‐EPI) in BrS with CardioInsight were retrospectively analyzed. (1) RVOT‐EPI activation time (RVOT‐AT); (2) RVOT‐EPI recovery time, and (3) RVOT‐EPI activation‐recovery interval (RVOT‐ARI) were calculated. ∆RVOT‐AT, ∆RVOT‐EPI recovery time, and ∆RVOT‐ARI were defined as the difference in parameters before and after AJT. SCD‐BrS patients were defined as individuals presenting a history of aborted SCD. Thirty‐nine patients with BrS were retrospectively analyzed and 12 patients (30.8%) were SCD‐BrS. After AJT, an increase in both RVOT‐AT [105.9 milliseconds versus 65.8 milliseconds, P <0.001] and RVOT‐EPI recovery time [403.4 milliseconds versus 365.7 milliseconds, P <0.001] was observed. No changes occurred in RVOT‐ARI [297.5 milliseconds versus 299.9 milliseconds, P =0.7]. Before AJT no differences were observed between SCD‐BrS and non SCD‐BrS in RVOT‐AT, RVOT‐EPI recovery time, and RVOT‐ARI ( P =0.9, P =0.91, P =0.86, respectively). Following AJT, SCD‐BrS patients showed higher RVOT‐AT, higher ∆RVOT‐AT, lower RVOT‐ARI, and lower ∆RVOT‐ARI ( P <0.001, P <0.001, P =0.007, P =0.002, respectively). At the univariate logistic regression, predictors of SCD‐BrS were the following: RVOT‐AT after AJT (specificity: 0.74, sensitivity 1.00, area under the curve 0.92); ∆RVOT‐AT (specificity: 0.74, sensitivity 0.92, area under the curve 0.86); RVOT‐ARI after AJT (specificity 0.96, sensitivity 0.58, area under the curve 0.79), and ∆RVOT‐ARI (specificity 0.85, sensitivity 0.67, area under the curve 0.76). Conclusions Noninvasive electrocardiographic imaging can be useful in evaluating the results of AJT in BrS.

Assessing the Accuracy of Estimated Lipoprotein(a) Cholesterol and Lipoprotein(a)‐Free Low‐Density Lipoprotein Cholesterol

Background Accurate measurement of the cholesterol within lipoprotein(a) (Lp[a]‐C) and its contribution to low‐density lipoprotein cholesterol (LDL‐C) has important implications for risk assessment, diagnosis, and treatment of atherosclerotic cardiovascular disease, as well as in familial hypercholesterolemia. A method for estimating Lp(a)‐C from particle number using fixed conversion factors has been proposed (Lp[a]‐C from particle number divided by 2.4 for Lp(a) mass, multiplied by 30% for Lp[a]‐C). The accuracy of this method, which theoretically can isolate “Lp(a)‐free LDL‐C,” has not been validated. Methods and Results In 177 875 patients from the VLDbL (Very Large Database of Lipids), we compared estimated Lp(a)‐C and Lp(a)‐free LDL‐C with measured values and quantified absolute and percent error. We compared findings with an analogous data set from the Mayo Clinic Laboratory. Error in estimated Lp(a)‐C and Lp(a)‐free LDL‐C increased with higher Lp(a)‐C values. Median error for estimated Lp(a)‐C <10 mg/dL was −1.9 mg/dL (interquartile range, −4.0 to 0.2); this error increased linearly, overestimating by +30.8 mg/dL (interquartile range, 26.1–36.5) for estimated Lp(a)‐C ≥50 mg/dL. This error relationship persisted after stratification by overall high‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol subtypes. Similar findings were observed in the Mayo cohort. Absolute error for Lp(a)‐free LDL‐C was +2.4 (interquartile range, −0.6 to 5.3) for Lp(a)‐C<10 mg/dL and −31.8 (interquartile range, −37.8 to −26.5) mg/dL for Lp(a)‐C≥50 mg/dL. Conclusions Lp(a)‐C estimations using fixed conversion factors overestimated Lp(a)‐C and subsequently underestimated Lp(a)‐free LDL‐C, especially at clinically relevant Lp(a) values. Application of inaccurate Lp(a)‐C estimations to correct LDL‐C may lead to undertreatment of high‐risk patients.

Acute Carotid Artery Stenting Versus Balloon Angioplasty for Tandem Occlusions: A Systematic Review and Meta‐Analysis

Background Despite thrombectomy having become the standard of care for large‐vessel occlusion strokes, acute endovascular management in tandem occlusions, especially of the cervical internal carotid artery lesion, remains uncertain. We aimed to compare efficacy and safety of acute carotid artery stenting to balloon angioplasty alone on treating the cervical lesion in tandem occlusions. Similarly, we aimed to explore those outcomes’ associations with technique approaches and use of thrombolysis. Methods and Results We performed a systematic review and meta‐analysis to compare functional outcomes (modified Rankin Scale), reperfusion, and symptomatic intracranial hemorrhage and 3‐month mortality. We explored the association of first approach (anterograde/retrograde) and use of thrombolysis with those outcomes as well. Two independent reviewers performed the screening, data extraction, and quality assessment. A random‐effects model was used for analysis. Thirty‐four studies were included in our systematic review and 9 in the meta‐analysis. Acute carotid artery stenting was associated with higher odds of modified Rankin Scale score ≤2 (odds ratio [OR], 1.95 [95% CI, 1.24–3.05]) and successful reperfusion (OR, 1.89 [95% CI, 1.26–2.83]), with no differences in mortality or symptomatic intracranial hemorrhage rates. Moreover, a retrograde approach was significantly associated with modified Rankin Scale score ≤2 (OR, 1.72 [95% CI, 1.05–2.83]), and no differences were found on thrombolysis status. Conclusions Carotid artery stenting and a retrograde approach had higher odds of successful reperfusion and good functional outcomes at 3 months than balloon angioplasty and an anterograde approach, respectively, in patients with tandem occlusions. A randomized controlled trial comparing these techniques with structured antithrombotic regimens and safety outcomes will offer definitive guidance in the optimal management of this complex disease.

Novel Risk Model to Predict Emergency Department Associated Mortality for Patients Supported With a Ventricular Assist Device: The Emergency Department–Ventricular Assist Device Risk Score

Background The past decade has seen tremendous growth in patients with ambulatory ventricular assist devices. We sought to identify patients that present to the emergency department (ED) at the highest risk of death. Methods and Results This retrospective analysis of ED encounters from the Nationwide Emergency Department Sample includes 2010 to 2017. Using a random sampling of patient encounters, 80% were assigned to development and 20% to validation cohorts. A risk model was derived from independent predictors of mortality. Each patient encounter was assigned to 1 of 3 groups based on risk score. A total of 44 042 ED ventricular assist device patient encounters were included. The majority of patients were male (73.6%), <65 years old (60.1%), and 29% presented with bleeding, stroke, or device complication. Independent predictors of mortality during the ED visit or subsequent admission included age ≥65 years (odds ratio [OR], 1.8; 95% CI, 1.3–4.6), primary diagnoses (stroke [OR, 19.4; 95% CI, 13.1–28.8], device complication [OR, 10.1; 95% CI, 6.5–16.7], cardiac [OR, 4.0; 95% CI, 2.7–6.1], infection [OR, 5.8; 95% CI, 3.5–8.9]), and blood transfusion (OR, 2.6; 95% CI, 1.8–4.0), whereas history of hypertension was protective (OR, 0.69; 95% CI, 0.5–0.9). The risk score predicted mortality areas under the curve of 0.78 and 0.71 for development and validation. Encounters in the highest risk score strata had a 16‐fold higher mortality compared with the lowest risk group (15.8% versus 1.0%). Conclusions We present a novel risk score and its validation for predicting mortality of patients with ED ventricular assist devices, a high‐risk, and growing, population.

Effectiveness of a School‐Based Educational Intervention to Improve Hypertension Control Among Schoolteachers: A Cluster‐Randomized Controlled Trial

Background The control of hypertension is low in low‐ and middle‐income countries like India. We evaluated the effects of a nurse‐facilitated educational intervention in improving the control rate of hypertension among school teachers in India. Methods and Results This was a cluster‐randomized controlled trial involving 92 schools in Kerala, which were randomly assigned equally into a usual care group and an intervention group. Participants were 402 school teachers (mean age, 47 years; men, 29%) identified with hypertension. Participants in both study groups received a leaflet containing details of a healthy lifestyle and the importance of regular intake of antihypertensive medication. In addition, the intervention participants received a nurse‐facilitated educational intervention on hypertension control for 3 months. The primary outcome was hypertension control. Key secondary outcomes included systolic blood pressure, diastolic blood pressure, and the proportion of participants taking antihypertensive medications. For the primary outcome, we used mixed‐effects logistic regression models. Two months after a 3‐month educational intervention, a greater proportion of intervention participants (49.0%) achieved hypertension control than the usual care participants (38.2%), with an odds ratio of 1.89 (95% CI, 1.06–3.35), after adjusting for baseline hypertension control. The odds of taking antihypertensive medications were 1.6 times higher in the intervention group compared with the usual care group (odds ratio, 1.62; 95% CI, 1.08–2.45). The reduction in mean systolic blood pressure was significantly greater in the intervention group by 4.2 mm Hg (95% CI, −7.2 to −1.1) than in the usual care group. Conclusions A nurse‐facilitated educational intervention was effective in improving the control and treatment rates of hypertension as well as reducing systolic blood pressure among schoolteachers with hypertension. Registration URL: https://www.ctri.nic.in ; Unique Identifier: CTRI/2018/01/011402.

Extremity Dysfunction After Large‐Bore Radial and Femoral Arterial Access

Background The use of large‐bore (LB) arterial access and guiding catheters has been advocated for complex percutaneous coronary intervention. However, the impact of LB transradial access (TRA) and transfemoral access (TFA) on extremity dysfunction is currently unknown. Methods and Results The predefined substudy of the COLOR (Complex Large‐Bore Radial PCI) trial aimed to assess upper and lower‐extremity dysfunction after LB radial and femoral access. Upper‐extremity function was assessed in LB TRA‐treated patients by the Quick Disabilities of the Arm, Shoulder, and Hand questionnaire and lower‐extremity function in LB TFA‐treated patients by the Lower Extremity Functional Scale questionnaire. Extremity pain and effect of access site complications and risk factors on extremity dysfunction was also analyzed. There were 343 patients who completed analyzable questionnaires. Overall, upper and lower‐extremity function did not decrease over time when LB TRA and TFA were used for complex percutaneous coronary intervention, as represented by the median Quick Disabilities of the Arm, Shoulder, and Hand score (6.8 at baseline and 2.1 at follow‐up, higher is worse) and Lower Extremity Functional Scale score (56 at baseline and 58 at follow‐up, lower is worse). Clinically relevant extremity dysfunction occurred in 6% after TRA and 9% after TFA. A trend for more pronounced upper‐limb dysfunction was present in female patients after LB TRA ( P =0.05). Lower‐extremity pain at discharge was significantly higher in patients with femoral access site complications ( P =0.02). Conclusions Following LB TRA and TFA, self‐reported upper and lower‐limb function did not decrease over time in the majority of patients. Clinically relevant limb dysfunction occurs in a small minority of patients regardless of radial or femoral access. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03846752.

Atrial Fibrillation and Stroke Symptoms in the REGARDS Study

Background It is unknown if stroke symptoms in the absence of a stroke diagnosis are a sign of subtle cardioembolic phenomena. The objective of this study was to examine associations between atrial fibrillation (AF) and stroke symptoms among adults with no clinical history of stroke or transient ischemic attack (TIA). Methods and Results We evaluated associations between AF and self‐reported stroke symptoms in the national, prospective REGARDS (Reasons for Geographic and Racial Differences in Stroke) cohort. We conducted cross‐sectional (n=27 135) and longitudinal (n=21 932) analyses over 8 years of follow‐up of REGARDS participants without stroke/transient ischemic attack and stratified by anticoagulant or antiplatelet agent use. The mean age was 64.4 (SD±9.4) years, 55.3% were women, and 40.8% were Black participants; 28.6% of participants with AF reported stroke symptoms. In the cross‐sectional analysis, comparing participants with and without AF, the risk of stroke symptoms was elevated for adults with AF taking neither anticoagulants nor antiplatelet agents (odds ratio [OR], 2.22; 95% CI, 1.89–2.59) or antiplatelet agents only (OR, 1.92; 95% CI, 1.61–2.29) but not for adults with AF taking anticoagulants (OR, 1.08; 95% CI, 0.71–1.65). In the longitudinal analysis, the risk of stroke symptoms was also elevated for adults with AF taking neither anticoagulants nor antiplatelet agents (hazard ratio [HR], 1.41; 95% CI, 1.21–1.66) or antiplatelet agents only (HR, 1.23; 95% CI, 1.04–1.46) but not for adults with AF taking anticoagulants (HR, 0.86; 95% CI, 0.62–1.18). Conclusions Stroke symptoms in the absence of a stroke diagnosis may represent subclinical cardioembolic phenomena or “whispering strokes.” Future studies examining the benefit of stroke symptom screening may be warranted.

Diastolic Dysfunction With Preserved Ejection Fraction After the Fontan Procedure

Background Heart failure phenotyping in single‐ventricle Fontan patients is challenging, particularly in patients with normal ejection fraction (EF). The objective of this study was to identify Fontan patients with abnormal diastolic function, who are high risk for heart failure with preserved ejection fraction (HFpEF), and characterize their cardiac mechanics, exercise function, and functional health status. Methods and Results Data were obtained from the Pediatric Heart Network Fontan Cross‐sectional Study database. EF was considered abnormal if <50%. Diastolic function was defined as abnormal if the diastolic pressure:volume quotient (lateral E:e’/end‐diastolic volume) was >90th percentile (≥0.26 mL ‐1 ). Patients were divided into: controls=normal EF and diastolic function; systolic dysfunction (SD) = abnormal EF with normal diastolic function; diastolic dysfunction (DD) = normal EF with abnormal diastolic pressure:volume quotient. Exercise function was quantified as percent predicted peak VO 2 . Physical Functioning Summary Score (FSS) was reported from the Child Health Questionnaire. A total of 239 patients were included, 177 (74%) control, 36 (15%) SD, and 26 (11%) DD. Median age was 12.2 (5.4) years. Arterial elastance, a measure of arterial stiffness, was higher in DD (3.6±1.1 mm Hg/mL) compared with controls (2.5±0.8 mm Hg/mL), P <0.01. DD patients had lower predicted peak VO 2 compared with controls (52% [20] versus 67% [23], P <0.01). Physical FSS was lower in DD (45±13) and SD (44±13) compared with controls (50±7), P <0.01. Conclusions Fontan patients with abnormal diastolic function and normal EF have decreased exercise tolerance, decreased functional health status, and elevated arterial stiffness. Identification of patients at high risk for HFpEF is feasible and should be considered when evaluating Fontan patients.

Effect of Shared Decision‐Making for Stroke Prevention on Treatment Adherence and Safety Outcomes in Patients With Atrial Fibrillation: A Randomized Clinical Trial

Background Guidelines promote shared decision‐making (SDM) for anticoagulation in patients with atrial fibrillation. We recently showed that adding a within‐encounter SDM tool to usual care (UC) increases patient involvement in decision‐making and clinician satisfaction, without affecting encounter length. We aimed to estimate the extent to which use of an SDM tool changed adherence to the decided care plan and clinical safety end points. Methods and Results We conducted a multicenter, encounter‐level, randomized trial assessing the efficacy of UC with versus without an SDM conversation tool for use during the clinical encounter (Anticoagulation Choice) in patients with nonvalvular atrial fibrillation considering starting or reviewing anticoagulation treatment. We conducted a chart and pharmacy review, blinded to randomization status, at 10 months after enrollment to assess primary adherence (proportion of patients who were prescribed an anticoagulant who filled their first prescription) and secondary adherence (estimated using the proportion of days for which treatment was supplied and filled for direct oral anticoagulant, and as time in therapeutic range for warfarin). We also noted any strokes, transient ischemic attacks, major bleeding, or deaths as safety end points. We enrolled 922 evaluable patient encounters (Anticoagulation Choice=463, and UC=459), of which 814 (88%) had pharmacy and clinical follow‐up. We found no differences between arms in either primary adherence (78% of patients in the SDM arm filled their first prescription versus 81% in UC arm) or secondary adherence to anticoagulation (percentage days covered of the direct oral anticoagulant was 74.1% in SDM versus 71.6% in UC; time in therapeutic range for warfarin was 66.6% in SDM versus 64.4% in UC). Safety outcomes, mostly bleeds, occurred in 13% of participants in the SDM arm and 14% in the UC arm. Conclusions In this large, randomized trial comparing UC with a tool to promote SDM against UC alone, we found no significant differences between arms in primary or secondary adherence to anticoagulation or in clinical safety outcomes. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: clinicaltrials.gov. Identifier: NCT02905032.