Browsing by Subject "Electrocardiography"
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Item Open Access Acute Coronary Syndrome: Diagnosis and Initial Management.(American family physician, 2024-01) Nohria, Raman; Viera, Anthony JAcute coronary syndrome (ACS) is defined as reduced blood flow to the coronary myocardium manifesting as ST-segment elevation myocardial infarction or non-ST-segment elevation ACS, which includes unstable angina and non-ST-segment elevation myocardial infarction. Common risk factors include being at least 65 years of age or a current smoker or having hypertension, diabetes mellitus, hyperlipidemia, a body mass index greater than 25 kg per m2, or a family history of premature coronary artery disease. Symptoms most predictive of ACS include chest discomfort that is substernal or spreading to the arms or jaw. However, chest pain that can be reproduced with palpation or varies with breathing or position is less likely to signify ACS. Having a prior abnormal cardiac stress test result indicates increased risk. Electrocardiography changes that predict ACS include ST depression, ST elevation, T-wave inversion, or presence of Q waves. No validated clinical decision tool is available to rule out ACS in the outpatient setting. Elevated troponin levels without ST-segment elevation on electrocardiography suggest non-ST-segment elevation ACS. Patients with ACS should receive coronary angiography with percutaneous or surgical revascularization. Other important management considerations include initiation of dual antiplatelet therapy and parenteral anticoagulation, statin therapy, beta-blocker therapy, and sodium-glucose cotransporter-2 inhibitor therapy. Additional interventions shown to reduce mortality in patients who have had a recent myocardial infarction include smoking cessation, annual influenza vaccination, and cardiac rehabilitation.Item Open Access Adjunctive albuterol enhances the response to enzyme replacement therapy in late-onset Pompe disease.(FASEB J, 2014-05) Koeberl, Dwight D; Austin, Stephanie; Case, Laura E; Smith, Edward C; Buckley, Anne F; Young, Sarah P; Bali, Deeksha; Kishnani, Priya SEffective dosages for enzyme replacement therapy (ERT) in Pompe disease are much higher than for other lysosomal storage disorders, which has been attributed to low cation-independent mannose-6-phosphate receptor (CI-MPR) in skeletal muscle. We have previously demonstrated the benefit of increased CI-MPR-mediated uptake of recombinant human acid-α-glucosidase during ERT in mice with Pompe disease following addition of albuterol therapy. Currently we have completed a pilot study of albuterol in patients with late-onset Pompe disease already on ERT for >2 yr, who were not improving further. The 6-min walk test (6MWT) distance increased in all 7 subjects at wk 6 (30±13 m; P=0.002), wk 12 (34±14 m; P=0.004), and wk 24 (42±37 m; P=0.02), in comparison with baseline. Grip strength was improved significantly for both hands at wk 12. Furthermore, individual subjects reported benefits; e.g., a female patient could stand up from sitting on the floor much more easily (time for supine to standing position decreased from 30 to 11 s), and a male patient could readily swing his legs out of his van seat (hip abduction increased from 1 to 2+ on manual muscle testing). Finally, analysis of the quadriceps biopsies suggested increased CI-MPR at wk 12 (P=0.08), compared with baseline. With the exception of 1 patient who succumbed to respiratory complications of Pompe disease in the first week, only mild adverse events have been reported, including tremor, transient difficulty falling asleep, and mild urinary retention (requiring early morning voiding). Therefore, this pilot study revealed initial safety and efficacy in an open label study of adjunctive albuterol therapy in patients with late-onset Pompe disease who had been stable on ERT with no improvements noted over the previous several years.Item Open Access Comparison of long-term postoperative sequelae in patients with tetralogy of Fallot versus isolated pulmonic stenosis.(Am J Cardiol, 2014-07-15) Zdradzinski, Michael J; Qureshi, Athar M; Stewart, Robert; Pettersson, Gosta; Krasuski, Richard APatients with tetralogy of Fallot (TOF) after complete repair and pulmonic stenosis (PS) after surgical valvotomy often develop significant pulmonic regurgitation (PR) that eventually requires valve replacement. Although criteria exist for the timing of pulmonary valve replacement in TOF, it remains less clear when to intervene in valvotomy patients and whether TOF recommendations can be applied. Our aim was to compare the structural and functional sequelae of valvotomy for PS with complete repair for TOF. We compared the clinical characteristics, electrocardiograms, echocardiograms, cardiac magnetic resonance imaging (MRI), and invasive hemodynamics of 109 adults (34 PS and 75 TOF) newly referred to a congenital heart disease center for evaluation of PR between 2005 and 2012. Both cohorts were similar in terms of baseline demographics and presenting New York Heart Association function class. Valvotomy patients had a slightly greater degree of PR by echocardiogram, although it was similar by cardiac MRI. Electrocardiography QRS width was greater in patients with TOF (114±27 vs 150±28 ms, p<0.001). MRI right ventricular ejection fraction (49±8 vs 41±11%, p=0.001) and left ventricular ejection fraction (59±7 vs 52±10%, p=0.002) were lower in patients with TOF. Pacemaker or defibrillator implantation was significantly greater in patients with TOF (3% vs 23%, p=0.011). In conclusion, patients postvalvotomy and complete repair present with similar degrees of PR and severity of symptoms. Biventricular systolic function and electrocardiography QRS width appear less affected, suggesting morphologic changes in TOF and its repair that extend beyond the effects of PR. These findings suggest the need for developing disease-specific guidelines for patients with PR postvalvotomy.Item Open Access Differences between chest pain observation service patients and admitted "rule-out myocardial infarction" patients.(Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 1997-07) Dallara, J; Severance, HW; Davis, B; Schulz, GObjective
To compare and contrast the patient characteristics of ED patients at low risk for acute cardiac ischemia who were assigned to a chest pain observation service vs those admitted to a monitored inpatient bed for "rule-out acute myocardial infarction" (R/O MI).Methods
This was a retrospective, cross-sectional comparison of adult patients considered at relatively low risk for cardiac ischemia and who were evaluated in 1 of 2 settings: a short-term observation service and an inpatient monitored bed. All patients had an ED final diagnosis of "chest pain," "R/O MI," or "unstable angina" during the 7-month study period. Demographic features and presenting clinical features were examined as a function of site of patient evaluation.Results
Of 531 study patients, 265 (50%) were assigned to the observation service. Younger age (OR = 1.75, 95% CI 1.26, 2.44, for each decrement of 20 years), the complaint of "chest pain" (OR = 2.35, 95% CI 1.34, 4.12), and the absence of prior known coronary artery disease (OR = 1.64, 95% CI 1.13, 2.38) were the principal independent factors associated with assignment to a chest pain observation service bed.Conclusions
Patients evaluated in a chest pain observation service appear to have different clinical characteristics than other individuals admitted to a monitored inpatient bed for "R/O MI." Investigators should address differences in clinical characteristics when making outcome comparisons between these 2 patient groups.Item Open Access Economic Outcomes With Anatomical Versus Functional Diagnostic Testing for Coronary Artery Disease.(Annals of internal medicine, 2016-07) Mark, Daniel B; Federspiel, Jerome J; Cowper, Patricia A; Anstrom, Kevin J; Hoffmann, Udo; Patel, Manesh R; Davidson-Ray, Linda; Daniels, Melanie R; Cooper, Lawton S; Knight, J David; Lee, Kerry L; Douglas, Pamela S; PROMISE InvestigatorsBackground
PROMISE (PROspective Multicenter Imaging Study for Evaluation of Chest Pain) found that initial use of at least 64-slice multidetector computed tomography angiography (CTA) versus functional diagnostic testing strategies did not improve clinical outcomes in stable symptomatic patients with suspected coronary artery disease (CAD) requiring noninvasive testing.Objective
To conduct an economic analysis for PROMISE (a major secondary aim of the study).Design
Prospective economic study from the U.S. perspective. Comparisons were made according to the intention-to-treat principle, and CIs were calculated using bootstrap methods. (ClinicalTrials.gov: NCT01174550).Setting
190 U.S. centers.Patients
9649 U.S. patients enrolled in PROMISE between July 2010 and September 2013. Median follow-up was 25 months.Measurements
Technical costs of the initial (outpatient) testing strategy were estimated from Premier Research Database data. Hospital-based costs were estimated using hospital bills and Medicare cost-charge ratios. Physician fees were taken from the Medicare Physician Fee Schedule. Costs were expressed in 2014 U.S. dollars, discounted at 3% annually, and estimated out to 3 years using inverse probability weighting methods.Results
The mean initial testing costs were $174 for exercise electrocardiography; $404 for CTA; $501 to $514 for pharmacologic and exercise stress echocardiography, respectively; and $946 to $1132 for exercise and pharmacologic stress nuclear testing, respectively. Mean costs at 90 days were $2494 for the CTA strategy versus $2240 for the functional strategy (mean difference, $254 [95% CI, -$634 to $906]). The difference was associated with more revascularizations and catheterizations (4.25 per 100 patients) with CTA use. After 90 days, the mean cost difference between the groups out to 3 years remained small.Limitation
Cost weights for test strategies were obtained from sources outside PROMISE.Conclusion
Computed tomography angiography and functional diagnostic testing strategies in patients with suspected CAD have similar costs through 3 years of follow-up.Primary funding source
National Heart, Lung, and Blood Institute.Item Open Access Electrocardiographic J Wave and Cardiovascular Outcomes in the General Population (from the Atherosclerosis Risk In Communities Study).(Am J Cardiol, 2016-09-15) O'Neal, Wesley T; Wang, Yi Grace; Wu, Hau-Tieng; Zhang, Zhu-Ming; Li, Yabing; Tereshchenko, Larisa G; Estes, E Harvey; Daubechies, Ingrid; Soliman, Elsayed ZThe association between the J wave, a key component of the early repolarization pattern, and adverse cardiovascular outcomes remains unclear. Inconsistencies have stemmed from the different methods used to measure the J wave. We examined the association between the J wave, detected by an automated method, and adverse cardiovascular outcomes in 14,592 (mean age = 54 ± 5.8 years; 56% women; 26% black) participants from the Atherosclerosis Risk In Communities (ARIC) study. The J wave was detected at baseline (1987 to 1989) and during follow-up study visits (1990 to 1992, 1993 to 1995, and 1996 to 1998) using a fully automated method. Sudden cardiac death, coronary heart disease death, and cardiovascular mortality were ascertained from hospital discharge records, death certificates, and autopsy data through December 31, 2010. A total of 278 participants (1.9%) had evidence of a J wave. Over a median follow-up of 22 years, 4,376 of the participants (30%) died. In a multivariable Cox regression analysis adjusted for demographics, cardiovascular risk factors, and potential confounders, the J wave was not associated with an increased risk of sudden cardiac death (hazard ratio [HR] 0.74, 95% CI 0.36 to 1.50), coronary heart disease death (HR 0.72, 95% CI 0.40 to 1.32), or cardiovascular mortality (HR 1.16, 95% CI 0.87 to 1.56). An interaction was detected for cardiovascular mortality by gender with men (HR 1.54, 95% CI 1.09 to 2.19) having a stronger association than women (HR 0.74, 95% CI 0.43 to 1.25; P-interaction = 0.030). In conclusion, our findings suggest that the J wave is a benign entity that is not associated with an increased risk for sudden cardiac arrest in middle-aged adults in the United States.Item Open Access Emergency physician high pretest probability for acute coronary syndrome correlates with adverse cardiovascular outcomes.(Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 2009-08) Chandra, Abhinav; Lindsell, Christopher J; Limkakeng, Alexander; Diercks, Deborah B; Hoekstra, James W; Hollander, Judd E; Kirk, J Douglas; Peacock, W Frank; Gibler, W Brian; Pollack, Charles V; EMCREG i*trACS InvestigatorsOBJECTIVES: The value of unstructured physician estimate of risk for disease processes, other than acute coronary syndrome (ACS), has been demonstrated. The authors sought to evaluate the predictive value of unstructured physician estimate of risk for ACS in emergency department (ED) patients without obvious initial evidence of a cardiac event. METHODS: This was a post hoc secondary analysis of the Internet Tracking Registry for Acute Coronary Syndromes (i*trACS), a prospectively collected multicenter data registry of patients over the age of 18 years presenting to the ED with symptoms of ACS between 1999 and 2001. In this registry, following patient history, physical exam, and electrocardiogram (ECG), the unstructured treating physician estimate of risk was recorded. A 30-day follow-up and a medical record review were used to determine rates of adverse cardiac events, death, myocardial infarction (MI), or revascularization procedure. The analysis included all patients with nondiagnostic ECG changes, normal initial biomarkers, and a non-MI initial impression from the registry and excluded those without complete data or who were lost to follow-up. Data were stratified by unstructured physician risk estimate: noncardiac, low risk, high risk, or unstable angina. RESULTS: Of 15,608 unique patients in the registry, 10,145 met inclusion/exclusion criteria. Patients were defined as having unstable angina in 6.0% of cases; high risk, 23.5% of cases; low risk, 44.2%; and noncardiac, 26.3% of cases. Adverse cardiac event rates had an inverse relationship, decreasing from 22.0% (95% confidence interval [CI] = 18.8% to 25.6%) for unstable angina, 10.2% (95% CI = 9.0% to 11.5%) for those stratified as high risk, 2.2% (95% CI = 1.8% to 2.6%) for low risk, and to 1.8% (95% CI = 1.4% to 2.4%) for noncardiac. The relative risk (RR) of an adverse cardiac event for those with an initial label of unstable angina compared to those with a low-risk designation was 10.2 (95% CI = 8.0 to 13.0). The RR of an event for those with a high-risk initial impression compared to those with a low-risk initial impression was 4.7 (95% CI = 3.8 to 5.9). The risk of an event among those with a low-risk initial impression was the same as for those with a noncardiac initial impression (RR = 0.83, 95% CI = 0.6 to 1.2). CONCLUSIONS: In ED patients without obvious initial evidence of a cardiac event, unstructured emergency physician (EP) estimate of risk correlates with adverse cardiac outcomes.Item Open Access Evaluation of T-Wave Morphology in Patients With Left Bundle Branch Block and Suspected Acute Coronary Syndrome.(The Journal of emergency medicine, 2016-09) Meyers, H Pendell; Jaffa, Elias; Smith, Stephen W; Drake, Weiying; Limkakeng, Alexander TT-wave morphology in the setting of left bundle branch block (LBBB) has been proposed as an indicator of myocardial ischemia.We sought to identify T-wave morphology findings in patients with LBBB that predict non-ST-segment elevation myocardial infarction (NSTEMI). We hypothesized that two or more contiguous leads with concordant T waves would be predictive of NSTEMI.This was a retrospective cohort study performed by chart review in a tertiary care center emergency department. We identified a consecutive cohort who presented with LBBB and symptoms consistent with acute coronary syndrome. Exclusion criteria were diastolic blood pressure > 120 mm Hg, heart rate > 130 beats/min, positive pressure ventilation, potassium > 5.5 mEq/L, and cardiac arrest without prearrest electrocardiogram (ECG) available. We collected ECGs and classified T waves into five categories based on morphology, blinded to clinical outcome. Clinical outcome data were collected blinded to ECG findings. Those with ECG diagnostic of STEMI by modified Sgarbossa criteria were excluded from the primary analysis, which was sensitivity and specificity of two or more contiguous leads with concordant T waves for NSTEMI.There were 246 patients included. Mean age was 73 years; 160 (65%) were female, and 32 had myocardial infarction. Thirty percent had two or more contiguous precordial leads with partially or completely concordant T waves. For NSTEMI, the sensitivity and specificity of this finding were 19% (95% confidence interval [CI] 8-37) and 68% (95% CI 61-74).We found no clinically useful relationship between T-wave concordance and myocardial infarction in our patient population. Future investigation of LBBB T-wave morphology should focus on alternative populations and findings.Item Open Access Heart rate variability is associated with survival in patients with brain metastasis: a preliminary report.(Biomed Res Int, 2013) Wang, Yu-Ming; Wu, Hau-Tieng; Huang, Eng-Yen; Kou, Yu Ru; Hseu, Shu-ShyaImpaired heart rate variability (HRV) has been demonstrated as a negative survival prognosticator in various diseases. We conducted this prospective study to evaluate how HRV affects brain metastasis (BM) patients. Fifty-one BM patients who had not undergone previous brain operation or radiotherapy (RT) were recruited from January 2010 to July 2012, and 40 patients were included in the final analysis. A 5-minute electrocardiogram was obtained before whole brain radiotherapy. Time domain indices of HRV were compared with other clinical factors on overall survival (OS). In the univariate analysis, Karnofsky performance status (KPS) <70 (P = 0.002) and standard deviation of the normal-to-normal interval (SDNN) <10 ms (P = 0.004) significantly predict poor survival. The multivariate analysis revealed that KPS <70 and SDNN <10 ms were independent negative prognosticators for survival in BM patients with hazard ratios of 2.657 and 2.204, respectively. In conclusion, HRV is associated with survival and may be a novel prognostic factor for BM patients.Item Open Access Impact of beta-blockade premedication on image quality of ECG-gated thoracic aorta CT angiography.(Acta radiologica (Stockholm, Sweden : 1987), 2014-12) Entezari, Pegah; Collins, Jeremy; Chalian, Hamid; Tore, Huseyin Gurkan; Carr, James; Yaghmai, VahidBACKGROUND: Thoracic aortic aneurysm is one of the most common aorta pathologies worldwide, which is commonly evaluated by computed tomography angiography (CTA). One of the routine methods to improve the image quality of CTA is heart rate reduction prior to study by beta-blockade administration. PURPOSE: To assess the effect of beta-blockade on image quality of the ascending aorta in electrocardiography (ECG)-gated dual-source CTA (DSCTA) images. MATERIAL AND METHODS: In this retrospective study, ECG-gated thoracic aorta CTA images of 40 patients without beta-blocker administration were compared with ECG-gated images of 40 patients with beta-blockade. Images of the aorta were analyzed objectively and subjectively at three levels: sinus of Valsalva (sinus), sinotubular junction (STJ), and mid ascending aorta (MAA). Quantitative sharpness index (SI) and signal-to-noise ratio (SNR) were calculated and two radiologists evaluated the image quality using a 3-point scale. RESULTS: Mean heart rate in beta-blocker and non-beta-blocker groups was 61.7 beats per minute (bpm) (range, 58.1-63.9 bpm) and 72.9 bpm (range, 69.3-84.1 bpm), respectively (P < 0.05). Aorta wall SI, SNR, and subjective grading were comparable between the two groups at all three levels (P > 0.05). CONCLUSION: Beta-blocker premedication may not be necessary for imaging of ascending aorta with ECG-gated DSCTA.Item Open Access Interleukin-1β gene variants are associated with QTc interval prolongation following cardiac surgery: a prospective observational study.(Canadian journal of anaesthesia = Journal canadien d'anesthesie, 2016-04) Kertai, Miklos D; Ji, Yunqi; Li, Yi-Ju; Mathew, Joseph P; Daubert, James P; Podgoreanu, Mihai V; PEGASUS Investigative TeamBackground
We characterized cardiac surgery-induced dynamic changes of the corrected QT (QTc) interval and tested the hypothesis that genetic factors are associated with perioperative QTc prolongation independent of clinical and procedural factors.Methods
All study subjects were ascertained from a prospective study of patients who underwent elective cardiac surgery during August 1999 to April 2002. We defined a prolonged QTc interval as > 440 msec, measured from 24-hr pre- and postoperative 12-lead electrocardiograms. The association of 37 single nucleotide polymorphisms (SNPs) in 21 candidate genes -involved in modulating arrhythmia susceptibility pathways with postoperative QTc changes- was investigated in a two-stage design with a stage I cohort (n = 497) nested within a stage II cohort (n = 957). Empirical P values (Pemp) were obtained by permutation tests with 10,000 repeats.Results
After adjusting for clinical and procedural risk factors, we selected four SNPs (P value range, 0.03-0.1) in stage I, which we then tested in the stage II cohort. Two functional SNPs in the pro-inflammatory cytokine interleukin-1β (IL1β), rs1143633 (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.53 to 0.95; Pemp = 0.02) and rs16944 (OR, 1.31; 95% CI, 1.01 to 1.70; Pemp = 0.04), remained independent predictors of postoperative QTc prolongation. The ability of a clinico-genetic model incorporating the two IL1B polymorphisms to classify patients at risk for developing prolonged postoperative QTc was superior to a clinical model alone, with a net reclassification improvement of 0.308 (P = 0.0003) and an integrated discrimination improvement of 0.02 (P = 0.000024).Conclusion
The results suggest a contribution of IL1β in modulating susceptibility to postoperative QTc prolongation after cardiac surgery.Item Open Access Large-Scale Assessment of a Smartwatch to Identify Atrial Fibrillation.(The New England journal of medicine, 2019-11) Perez, Marco V; Mahaffey, Kenneth W; Hedlin, Haley; Rumsfeld, John S; Garcia, Ariadna; Ferris, Todd; Balasubramanian, Vidhya; Russo, Andrea M; Rajmane, Amol; Cheung, Lauren; Hung, Grace; Lee, Justin; Kowey, Peter; Talati, Nisha; Nag, Divya; Gummidipundi, Santosh E; Beatty, Alexis; Hills, Mellanie True; Desai, Sumbul; Granger, Christopher B; Desai, Manisha; Turakhia, Mintu P; Apple Heart Study InvestigatorsBACKGROUND:Optical sensors on wearable devices can detect irregular pulses. The ability of a smartwatch application (app) to identify atrial fibrillation during typical use is unknown. METHODS:Participants without atrial fibrillation (as reported by the participants themselves) used a smartphone (Apple iPhone) app to consent to monitoring. If a smartwatch-based irregular pulse notification algorithm identified possible atrial fibrillation, a telemedicine visit was initiated and an electrocardiography (ECG) patch was mailed to the participant, to be worn for up to 7 days. Surveys were administered 90 days after notification of the irregular pulse and at the end of the study. The main objectives were to estimate the proportion of notified participants with atrial fibrillation shown on an ECG patch and the positive predictive value of irregular pulse intervals with a targeted confidence interval width of 0.10. RESULTS:We recruited 419,297 participants over 8 months. Over a median of 117 days of monitoring, 2161 participants (0.52%) received notifications of irregular pulse. Among the 450 participants who returned ECG patches containing data that could be analyzed - which had been applied, on average, 13 days after notification - atrial fibrillation was present in 34% (97.5% confidence interval [CI], 29 to 39) overall and in 35% (97.5% CI, 27 to 43) of participants 65 years of age or older. Among participants who were notified of an irregular pulse, the positive predictive value was 0.84 (95% CI, 0.76 to 0.92) for observing atrial fibrillation on the ECG simultaneously with a subsequent irregular pulse notification and 0.71 (97.5% CI, 0.69 to 0.74) for observing atrial fibrillation on the ECG simultaneously with a subsequent irregular tachogram. Of 1376 notified participants who returned a 90-day survey, 57% contacted health care providers outside the study. There were no reports of serious app-related adverse events. CONCLUSIONS:The probability of receiving an irregular pulse notification was low. Among participants who received notification of an irregular pulse, 34% had atrial fibrillation on subsequent ECG patch readings and 84% of notifications were concordant with atrial fibrillation. This siteless (no on-site visits were required for the participants), pragmatic study design provides a foundation for large-scale pragmatic studies in which outcomes or adherence can be reliably assessed with user-owned devices. (Funded by Apple; Apple Heart Study ClinicalTrials.gov number, NCT03335800.).Item Open Access Left ventricular dysfunction screening in hypertensive patients with N-terminal pro-B-type natriuretic peptide and electrocardiogram.(Am J Emerg Med, 2012-01) Limkakeng, Alexander T; Drake, Weiying; Mani, Giselle; Freeman, Debbie; Best, Randall; Newby, L Kristin; Chandra, AbhinavOBJECTIVE: Early recognition of left ventricular hypertrophy is important because antihypertensive treatment decreases morbidity and mortality. The ideal screening method for left ventricular hypertrophy in hypertensive emergency department (ED) patients has not been identified. Our objective was to determine the diagnostic accuracies of electrocardiogram (ECG) and N-terminal Pro-B-type natriuretic peptide (pro-BNP) for left ventricular hypertrophy individually and in combination in hypertensive ED patients. METHODS: Prospective diagnostic study in an academic urban tertiary care hospital ED with annual census of 65,000 visits. Inclusion criteria are as follows: adult ED patients with systolic blood pressure greater than or equal to 160 mm Hg or diastolic blood pressure greater than or equal to 100 mm Hg on 2 or more measurements taken 60 minutes apart. Exclusion criteria are as follows: patients with heart failure, renal insufficiency/failure, acute myocardial infarction, or without recent or scheduled echocardiograms. All patients received echocardiograms and had pro-BNP levels measured using a RAMP point-of-care device (Response Biomedical, Vancouver, BC, Canada). We calculated diagnostic test characteristics with 95% confidence intervals (CIs). RESULTS: A total of 49 patients were enrolled. The average age was 57.9 years, 26.5% were male, and 63.3% were African American. Thirty-two patients (65%) had left ventricular hypertrophy by echocardiogram. Twenty-one (43%) had ECG evidence of left ventricular hypertrophy. Median pro-BNP level was 268 pg/mL. The combination of the 2 tests provided the greatest specificity (94%; 95% CI, 69%-99.7%) and positive predictive value (94%; 95% CI, (68%-99.7%). CONCLUSIONS: The combination of ECG and pro-BNP is a promising screening algorithm for identification of hypertensive ED patients with left ventricular hypertrophy.Item Open Access Novel long QT syndrome-associated missense mutation, L762F, in CACNA1C-encoded L-type calcium channel imparts a slower inactivation tau and increased sustained and window current.(International journal of cardiology, 2016-10) Landstrom, AP; Boczek, NJ; Ye, D; Miyake, CY; De la Uz, CM; Allen, HD; Ackerman, MJ; Kim, JJBACKGROUND:Mutations in the CACNA1C-encoded L-type calcium channel have been associated with Timothy syndrome (TS) with severe QT prolongation, syndactyly, facial dysmorphisms, developmental delay, and sudden death. Recently, patients hosting CACNA1C mutations with only long QT syndrome (LQTS) have been described. We sought to identify novel variants in CACNA1C associated with either TS or LQTS, and to determine the impact of the mutation on channel function. METHODS/RESULTS:Two probands were identified with mutations in CACNA1C, one with a TS-associated mutation, G406R, and a second with genotype-negative LQTS. Illumina HiSeq 2000 whole exome sequencing on the genotype-negative LQTS proband revealed a novel variant, CACNA1C-L762F, that co-segregated within a multi-generational family. The missense mutation localized to the DII/DIII intracellular interlinker segment of the channel in a highly conserved region in close proximity to the 6th transmembrane segment of domain II (DIIS6). Whole cell patch clamp of heterologously expressed CACNA1C-L762F in TSA201 cells demonstrated slower inactivation tau and increased sustained and window current. Comprehensive review and topological mapping of all described CACNA1C mutations revealed TS-specific hotspots localizing to the cytoplasmic aspect of 6th transmembrane segment of respective domains. Probands hosting TS mutations were associated with elevated QTc, higher prevalence of 2:1 AV block, and a younger age at presentation compared to LQTS. CONCLUSIONS:The CACNA1C-L762F mutation is associated with development of LQTS through slower channel inactivation and increased sustained and window current. TS-associated mutations localize to specific areas of CACNA1C and are associated with a younger age at presentation, higher QTc, and 2:1 AV block than isolated LQTS-associated mutations.Item Open Access Outpatient versus observation/inpatient management of emergency department patients rapidly ruled-out for acute myocardial infarction: Findings from the HIGH-US study.(American heart journal, 2021-01) Nowak, Richard M; Jacobsen, Gordon; Limkakeng, Alexander; Peacock, William F; Christenson, Robert H; McCord, James; Apple, Fred S; Singer, Adam J; deFilippi, Christopher RBackground
The actual Emergency Department (ED) dispositions of patients enrolled in observational studies and meeting criteria for rapid acute myocardial infarction (AMI) rule-out are unknown. Additionally, their presenting clinical profiles, cardiac testing/treatments received, and outcomes have not been reported.Methods
Patients in the HIGH-US study (29 sites) that ruled-out for AMI using a high-sensitivity cardiac troponin I 0/1-hour algorithm were evaluated. Clinical characteristics of patients having ED discharge were compared to patients placed in observation or hospital admitted (OBS/ADM). Reports of any OBS/ADM cardiac stress test (CST), cardiac catheterization (Cath) and coronary revascularization were reviewed. One year AMI/death and major adverse cardiovascular event rates were determined.Results
Of the 1,020 ruled-out AMI patients 584 (57.3%) had ED discharge. The remaining 436 (42.7%) were placed in OBS/ADM. Patients with risk factors for AMI, including personal or family history of coronary artery disease, hypertension, previous stroke or abnormal ECG were more often placed in OBS/ADM. 175 (40.1%) had a CST. Of these 32 (18.3%) were abnormal and 143 (81.7%) normal. Cath was done in 11 (34.3%) of those with abnormal and 13 (9.1%) with normal CST. Of those without an initial CST 85 (32.6%) had Cath. Overall, revascularizations were performed in 26 (6.0%) patients. One-year AMI/death rates were low/similar (P = .553) for the groups studied.Conclusions
Rapidly ruled-out for AMI ED patients having a higher clinician perceived risk for new or worsening coronary artery disease and placed in OBS/ADM underwent many diagnostic tests, were infrequently revascularized and had excellent outcomes. Alternate efficient strategies for these patients are needed.Item Open Access Performance of Novel High-Sensitivity Cardiac Troponin I Assays for 0/1-Hour and 0/2- to 3-Hour Evaluations for Acute Myocardial Infarction: Results From the HIGH-US Study.(Annals of emergency medicine, 2020-07) Nowak, Richard M; Christenson, Robert H; Jacobsen, Gordon; McCord, James; Apple, Fred S; Singer, Adam J; Limkakeng, Alexander; Peacock, William F; deFilippi, Christopher RSTUDY OBJECTIVE:We determine the accuracy of high-sensitivity cardiac troponin I (hs-cTnI), European-derived, rapid, acute myocardial infarction, rule-out/rule-in algorithms applied to a US emergency department (ED) population. METHODS:Adults presenting to the ED with suspected acute myocardial infarction were included. Plasma samples collected at baseline and between 40 and 90 minutes and 2 and 3 hours later were analyzed in core laboratories using the Siemens Healthineers hs-cTnI assays. Acute myocardial infarction diagnosis was independently adjudicated. The sensitivity, specificity, and negative and positive predictive values for rapid acute myocardial infarction rule-out/rule-in using European algorithms and 30-day outcomes are reported. RESULTS:From 29 US medical centers, 2,113 subjects had complete data for the 0/1-hour algorithm analyses. With the Siemens Atellica Immunoassay hs-cTnI values, 1,065 patients (50.4%) were ruled out, with a negative predictive value of 99.7% and sensitivity of 98.7% (95% confidence interval 99.2% to 99.9% and 96.3% to 99.6%, respectively), whereas 265 patients (12.6%) were ruled in, having a positive predictive value of 69.4% and specificity of 95.7% (95% confidence interval 63.6% to 74.7% and 94.7% to 96.5%, respectively). The remaining 783 patients (37.1%) were classified as having continued evaluations, with an acute myocardial infarction incidence of 5.6% (95% confidence interval 4.2% to 7.5%). The overall 30-day risk of death or postdischarge acute myocardial infarction was very low in the ruled-out patients but was incrementally increased in the other groups (rule-out 0.2%; continued evaluations 2.1%; rule-in 4.8%). Equivalent results were observed in the 0/2- to 3-hour analyses and when both algorithms were applied to the hs-cTnI ADVIA Centaur measurements. CONCLUSION:The European rapid rule-out/rule-in acute myocardial infarction algorithm hs-cTnI cut points can be harmonized with a demographically and risk-factor diverse US ED population.Item Open Access Platelet aggregation and mental stress induced myocardial ischemia: Results from the Responses of Myocardial Ischemia to Escitalopram Treatment (REMIT) study.(Am Heart J, 2015-04) Jiang, Wei; Boyle, Stephen H; Ortel, Thomas L; Samad, Zainab; Velazquez, Eric J; Harrison, Robert W; Wilson, Jennifer; Kuhn, Cynthia; Williams, Redford B; O'Connor, Christopher M; Becker, Richard CBACKGROUND: Mental stress-induced myocardial ischemia (MSIMI) is common in patients with ischemic heart disease (IHD) and associated with a poorer cardiovascular prognosis. Platelet hyperactivity is an important factor in acute coronary syndrome. This study examined associations between MSIMI and resting and mental stress-induced platelet activity. METHODS: Eligible patients with clinically stable IHD underwent a battery of 3 mental stress tests during the recruitment phase of REMIT study. MSIMI was assessed by echocardiography and electrocardiography. Ex vivo platelet aggregation in response to ADP, epinephrine, collagen, serotonin, and combinations of serotonin plus ADP, epinephrine, and collagen were evaluated as was platelet serotonin transporter expression. RESULTS: Of the 270 participants who completed mental stress testing, and had both resting and post-stress platelet aggregation evaluation , 43.33% (n=117) met criteria for MSIMI and 18.15% (n=49) had normal left ventricular response to stress (NLVR). The MSIMI group, relative to the NLVR groups, demonstrated heightened mental stress-induced aggregation responses, as measured by area under the curve, to collagen 10μM (6.95[5.54] vs. -14.23[8.75].; P=0.045), epinephrine 10μM (12.84[4.84] vs. -6.40[7.61].; P=0.037) and to serotonin 10 μM plus ADP 1 μM (6.64[5.29] vs. -27.34[8.34]; P<.001). The resting platelet aggregation and serotonin transporter expression, however, were not different between the two groups. CONCLUSIONS: These findings suggest that the dynamic change of platelet aggregation caused by mental stress may underlie MSIMI. While the importance of these findings requires additional investigation, they raise concern given the recognized relationship between mental stress-induced platelet hyperactivity and cardiovascular events in patients with IHD.Item Open Access PLN-encoded phospholamban mutation in a large cohort of hypertrophic cardiomyopathy cases: summary of the literature and implications for genetic testing.(American heart journal, 2011-01) Landstrom, AP; Adekola, BA; Bos, JM; Ommen, SR; Ackerman, MJBACKGROUND:hypertrophic cardiomyopathy (HCM) is a major cause of sudden death in young athletes and one of the most common inherited cardiovascular diseases, affecting 1 in 500 individuals. Often viewed as a disease of the cardiac sarcomere, mutations in genes encoding myofilament proteins are associated with disease pathogenesis. Despite a clinically available genetic test, a significant portion of HCM patients remain genetically unexplained. We sought to determine the spectrum and prevalence of mutations in PLN-encoded phospholamban in a large cohort of HCM cases as a potential cause of mutation-negative HCM. METHODS:comprehensive genetic interrogation of the promoter and coding region of PLN was conducted using polymerase chain reaction, denaturing high-performance liquid chromatography, and direct DNA sequencing. RESULTS:one L39X nonsense mutation was identified in 1 of 1,064 HCM proband cases with a family history of HCM, previously found to be negative for the current HCM genetic test panel. This mutation cosegregated with incidence of HCM in a multigenerational family. Compared with similar studies, we identified an overall yield of PLN-HCM mutations of 0.65%, similar to 3 genes that are part of current HCM genetic test panels. We did not observe any PLN coding sequence genetic variation in 600 reference alleles. CONCLUSIONS:overall, mutations in PLN are rare in frequency, yet the small size of the genetic locus may make it amenable to inclusion on HCM gene test panels, especially because the frequency of background genetic variation among otherwise healthy subjects appears negligible. The exact role of mutations in PLN and other calcium-handling proteins in the development of HCM warrants further investigation.Item Open Access Role of ST2 in non-ST-elevation acute coronary syndrome in the MERLIN-TIMI 36 trial.(Clinical chemistry, 2012-01) Kohli, Payal; Bonaca, Marc P; Kakkar, Rahul; Kudinova, Anastacia Y; Scirica, Benjamin M; Sabatine, Marc S; Murphy, Sabina A; Braunwald, Eugene; Lee, Richard T; Morrow, David AObjective
We investigated the prognostic performance of ST2 with respect to cardiovascular death (CVD) and heart failure (HF) in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) in a large multinational trial.Background
Myocytes that are subjected to mechanical stress secrete ST2, a soluble interleukin-1 receptor family member that is associated with HF after STE-ACS.Methods
We measured ST2 with a high-sensitivity assay in all available baseline samples (N=4426) in patients enrolled in the Metabolic Efficiency With Ranolazine for Less Ischemia in the Non-ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36), a placebo-controlled trial of ranolazine in NSTE-ACS. All events, including cardiovascular death and new or worsening HF, were adjudicated by an independent events committee.Results
Patients with ST2 concentrations in the top quartile (>35 μg/L) were more likely to be older and male and have diabetes and renal dysfunction. ST2 was only weakly correlated with troponin and B-type natriuretic peptide. High ST2 was associated with increased risk for CVD/HF at 30 days (6.6% vs 1.6%, P<0.0001) and 1 year (12.2% vs 5.2%, P<0.0001). The risk associated with ST2 was significant after adjustment for clinical covariates and biomarkers (adjusted hazard ratio CVD/HF 1.90, 95% CI 1.15-3.13 at 30 days, P=0.012; 1.51, 95% CI 1.15-1.98 at 1 year, P=0.003), with a significant integrated discrimination improvement (P<0.0001). No significant interaction was found between ST2 and ranolazine (Pinteraction=0.15).Conclusions
ST2 correlates weakly with biomarkers of acute injury and hemodynamic stress but is strongly associated with the risk of HF after NSTE-ACS. This biomarker and related pathway merit further investigation as potential therapeutic targets for patients with ACS at risk for cardiac remodeling.Item Open Access Simplified Predictive Instrument to Rule Out Acute Coronary Syndromes in a High-Risk Population.(J Am Heart Assoc, 2015-12-14) Fanaroff, Alexander C; Schulteis, Ryan D; Pieper, Karen S; Rao, Sunil V; Newby, L KristinBACKGROUND: It is unclear whether diagnostic protocols based on cardiac markers to identify low-risk chest pain patients suitable for early release from the emergency department can be applied to patients older than 65 years or with traditional cardiac risk factors. METHODS AND RESULTS: In a single-center retrospective study of 231 consecutive patients with high-risk factor burden in which a first cardiac troponin (cTn) level was measured in the emergency department and a second cTn sample was drawn 4 to 14 hours later, we compared the performance of a modified 2-Hour Accelerated Diagnostic Protocol to Assess Patients with Chest Pain Using Contemporary Troponins as the Only Biomarker (ADAPT) rule to a new risk classification scheme that identifies patients as low risk if they have no known coronary artery disease, a nonischemic electrocardiogram, and 2 cTn levels below the assay's limit of detection. Demographic and outcome data were abstracted through chart review. The median age of our population was 64 years, and 75% had Thrombosis In Myocardial Infarction risk score ≥2. Using our risk classification rule, 53 (23%) patients were low risk with a negative predictive value for 30-day cardiac events of 98%. Applying a modified ADAPT rule to our cohort, 18 (8%) patients were identified as low risk with a negative predictive value of 100%. In a sensitivity analysis, the negative predictive value of our risk algorithm did not change when we relied only on undetectable baseline cTn and eliminated the second cTn assessment. CONCLUSIONS: If confirmed in prospective studies, this less-restrictive risk classification strategy could be used to safely identify chest pain patients with more traditional cardiac risk factors for early emergency department release.