Sex-specific efficacy and safety of cryoballoon versus radiofrequency ablation for atrial fibrillation: An individual patient data meta-analysis

BACKGROUND: Atrial fibrillation (AF) is a growing health burden, and pulmonary vein isolation (PVI) using cryoballoon (CB) or radiofrequency (RF) represents an attractive therapeutic option. Sex-specific differences in the epidemiology, pathophysiology, and clinical presentation of AF and PVI are recognized. OBJECTIVE: We aimed at comparing the efficacy, safety, and procedural characteristics of CB and RF in women and men undergoing a first PVI procedure. METHODS: We searched for randomized controlled trials and prospective observational studies comparing CB and RF ablation with at least 1 year of follow-up. After merging individual patient data from 18 data sets, we investigated the sex-specific (procedure failure defined as recurrence of atrial arrhythmia, reablation, and reinitiation of antiarrhythmic medication), safety (periprocedural complications), and procedural characteristics of CB vs RF using Kaplan-Meier and multilevel models. RESULTS: From the 18 studies, 4840 men and 1979 women were analyzed. An analysis stratified by sex correcting for several covariates showed a better efficacy of CB in men (hazard ratio for recurrence 0.88; 95% confidence interval 0.78-0.98, P = .02) but not in women (hazard ratio 0.98; 95% confidence interval 0.83-1.16; P = .82). For women and men, the energy source had no influence on the occurrence of at least 1 complication. For both sexes, the procedure time was significantly shorter with CB (-22.5 minutes for women and -27.1 minutes for men). CONCLUSION: CB is associated with less long-term failures in men. A better understanding of AF-causal sex-specific mechanisms and refinements in CB technologies could lead to higher success rates in women

Circadian rhythm of cardiac troponin I and its clinical impact on the diagnostic accuracy for acute myocardial infarction

High-sensitivity cardiac troponin T (hs-cTnT) blood concentrations were shown to exhibit a diurnal rhythm, characterized by gradually decreasing concentrations throughout daytime, rising concentrations during nighttime and peak concentrations in the morning. We aimed to investigate whether this also applies to (h)s-cTnI assays and whether it would affect diagnostic accuracy for acute myocardial infarction (AMI).; Blood concentrations of cTnI were measured at presentation and after 1 h using four different cTnI assays: three commonly used sensitive (s-cTnI Architect, Ultra and Accu) and one experimental high-sensitivity assay (hs-cTnI Accu) in a prospective multicenter diagnostic study of patients presenting to the emergency department with suspected AMI. These concentrations and their diagnostic accuracy for AMI (quantified by the area under the curve (AUC)) were compared between morning (11 p.m. to 2 p.m.) and evening (2 p.m. to 11 p.m.) presenters.; Among 2601 patients, AMI was the final diagnosis in 17.6% of patients. Concentrations of (h)s-cTnI as measured using all four assays were comparable in patients presenting in the morning versus patients presenting in the evening. Diagnostic accuracy for AMI of all four (h)s-cTnI assays were high and comparable between patients presenting in the morning versus presenting in the evening (AUC at presentation: 0.90 vs 0.93 for s-cTnI Architect; 0.91 vs 0.94 for s-cTnI Ultra; 0.89 vs 0.94 for s-cTnI Accu; 0.91 vs 0.94 for hs-cTnI Accu).; Cardiac TnI does not seem to express a diurnal rhythm. Diagnostic accuracy for AMI is very high and does not differ with time of presentation.; NCT00470587, http://clinicaltrials.gov/show/NCT00470587

Automatically computed ECG algorithm for the quantification of myocardial scar and the prediction of mortality

Myocardial scar is associated with adverse cardiac outcomes. The Selvester QRS-score was developed to estimate myocardial scar from the 12-lead ECG, but its manual calculation is difficult. An automatically computed QRS-score would allow identification of patients with myocardial scar and an increased risk of mortality.; To assess the diagnostic and prognostic value of the automatically computed QRS-score.; The diagnostic value of the QRS-score computed automatically from a standard digital 12-lead was prospectively assessed in 2742 patients with suspected myocardial ischemia referred for myocardial perfusion imaging (MPI). The prognostic value of the QRS-score was then prospectively tested in 1151 consecutive patients presenting to the emergency department (ED) with suspected acute heart failure (AHF).; Overall, the QRS-score was significantly higher in patients with more extensive myocardial scar: the median QRS-score was 3 (IQR 2-5), 4 (IQR 2-6), and 7 (IQR 4-10) for patients with 0, 5-20 and > 20% myocardial scar as quantified by MPI (p < 0.001 for all pairwise comparisons). A QRS-score ≥ 9 (n = 284, 10%) predicted a large scar defined as > 20% of the LV with a specificity of 91% (95% CI 90-92%). Regarding clinical outcomes in patients presenting to the ED with symptoms suggestive of AHF, mortality after 1 year was 28% in patients with a QRS-score ≥ 3 as opposed to 20% in patients with a QRS-score < 3 (p = 0.001).; The QRS-score can be computed automatically from the 12-lead ECG for simple, non-invasive and inexpensive detection and quantification of myocardial scar and for the prediction of mortality. TRIAL-REGISTRATION: http://www.clinicaltrials.gov . Identifier, NCT01838148 and NCT01831115

Droplet digital PCR of serum miR-499, miR-21 and miR-208a for the detection of functionally relevant coronary artery disease

Background: microRNAs (miRNAs) have shown promise as potential new biomarkers for myocardial injury and myocardial ischemia. New digital polymerase chain reaction (PCR) techniques allow for highly precise and reliable absolute direct quantification. Methods: In this pilot study we used droplet digital PCR (ddPCR) to assess if miRNAs might be released into circulation in patients with functionally relevant coronary artery disease (CAD). Blood samples for measurement of high-sensitivity cardiac troponin I (hs-cTnI) and miRNAs were obtained before, immediately after peak stress, and 2 h after stress testing in a blinded manner in consecutive patients referred for rest/stress myocardial perfusion single-photon emission tomography/computer tomography (MPI-SPECT/CT). ddPCR was used to directly quantify the serum concentrations of miR-21, miR-208a, and miR-499 as potential markers of myocardial injury/ischemia. Functionally relevant CAD was determined by expert interpretation of MPI-SPECT/CT, coronary angiography and fractional flow reserve, if performed. Results: Overall, 200 patients were included and functionally relevant CAD was detected in 85 of them (42%). NeithermiR-21, miR-208a, nor miR-499 concentrations differed at rest, stress, or 2-h after stress when comparing patients with versus without functionally relevant CAD, while hs-cTnI concentrations were significantly higher in patients with functionally relevant CAD (P < 0.001). Exercise-induced changes in miRNA or hs-cTnI concentrations did not have diagnostic utility and were similar in patients with versus without functionally relevant CAD. Conclusion: miR-208a, miR-21 and miR-499 concentrations at rest, after exercise and exercise-induced changes do not provide additional clinical value regarding the detection of functionally relevant CAD. (c) 2018 Elsevier B.V. All rights reserved

Early standardized clinical judgement for syncope diagnosis in the emergency department

The diagnosis of cardiac syncope remains a challenge in the emergency department (ED).; Assessing the diagnostic accuracy of the early standardized clinical judgement (ESCJ) including a standardized syncope-specific case report form (CRF) in comparison with a recommended multivariable diagnostic score.; In a prospective international observational multicentre study, diagnostic accuracy for cardiac syncope of ESCJ by the ED physician amongst patients ≥ 40 years presenting with syncope to the ED was directly compared with that of the Evaluation of Guidelines in Syncope Study (EGSYS) diagnostic score. Cardiac syncope was centrally adjudicated independently of the ESCJ or conducted workup by two ED specialists based on all information available up to 1-year follow-up. Secondary aims included direct comparison with high-sensitivity cardiac troponin I (hs-cTnI) and B-type natriuretic peptide (BNP) concentrations and a Lasso regression to identify variables contributing most to ESCJ.; Cardiac syncope was adjudicated in 252/1494 patients (15.2%). The diagnostic accuracy of ESCJ for cardiac syncope as quantified by the area under the curve (AUC) was 0.87 (95% CI: 0.84-0.89), and higher compared with the EGSYS diagnostic score (0.73 (95% CI: 0.70-0.76)), hs-cTnI (0.77 (95% CI: 0.73-0.80)) and BNP (0.77 (95% CI: 0.74-0.80)), all P < 0.001. Both biomarkers (alone or in combination) on top of the ESCJ significantly improved diagnostic accuracy.; ESCJ including a standardized syncope-specific CRF has very high diagnostic accuracy and outperforms the EGSYS score, hs-cTnI and BNP

Impact of pre-existing heart failure on 60-day outcomes in patients hospitalized with COVID-19

Background: In the coronavirus disease 2019 (COVID-19) global pandemic, patients with cardiovascular disease represent a vulnerable population with higher risk for contracting COVID-19 and worse prognosis with higher case fatality rates. However, the relationship between COVID-19 and heart failure (HF) is unclear, specifically whether HF is an independent risk factor for severe infection or if other accompanying comorbidities are responsible for the increased risk. Methods: This is a retrospective analysis of 1331 adult patients diagnosed with COVID-19 infection between March and June 2020 admitted at Rush University System for Health (RUSH) in metropolitan Chicago, Illinois, USA. Patients with history of HF were identified by International Classification of Disease, Tenth Revision (ICD-10) code assignments extracted from the electronic medical record. Propensity score matching was utilized to control for the numerous confounders, and univariable logistic regression was performed to assess the relationship between HF and 60-day morbidity and mortality outcomes. Results: The propensity score matched cohort consisted of 188 patients in both the HF and no HF groups. HF patients did not have lower 60-day mortality (OR 0.81; Conclusions: This study highlights the complex network of confounders present between HF and COVID-19. When balanced for these numerous factors, those with HF appear to be at no higher risk of 60-day mortality from COVID-19 but are at increased risk for morbidity

Combining high-sensitivity cardiac troponin and B-type natriuretic peptide in the detection of inducible myocardial ischemia.

BACKGROUND Single biomarker approaches provide only moderate accuracy in the non-invasive detection of exercise-induced myocardial ischemia. We therefore assessed the combination of the two most promising single biomarkers: high-sensitivity cardiac troponin I (hs-cTnI) and B-type natriuretic peptide (BNP). METHODS Consecutive patients with suspected myocardial ischemia referred to stress myocardial perfusion single-photon emission tomography imaging (MPI) were enrolled. Clinical judgment (CJ) of the treating cardiologist regarding myocardial ischemia, quantified using a visual analogue scale, and blood concentrations of hs-cTnI and BNP were determined before and after stress. The presence of myocardial ischemia was adjudicated by independent cardiologists using MPI, blinded to biomarker measurements. Death and acute myocardial infarction (AMI) during follow-up were the prognostic endpoints. RESULTS Among 1142 consecutive patients inducible myocardial ischemia was found in 456 (40%) of all patients. For the detection of inducible myocardial ischemia, CJ before exercise stress testing (CJb) showed an area under the receiver-operating-characteristics curve (AUC) of 0.66 (95%CI 0.63-0.69), hs-cTnI 0.70 (95%CI 0.67-0.73, p=0.07 vs CJb), and BNP 0.66 (95%CI 0.62-0.69, p=0.98). The use of a dual-biomarker strategy combining hs-cTnI and BNP with CJb did not provide a significant advantage over the combination of hs-cTnI alone and CJb (AUC 0.74, 95%CI 0.72-0.77 vs AUC 0.74, 95%CI 0.71-0.77, p=0.16). Hs-cTnI showed good prognostic value for AMI (HR 1.6, 95%CI 1.3-1.9), and BNP for death (HR 1.6, 95%CI 1.3-2.1). CONCLUSION A dual-biomarker strategy combing BNP and hs-cTnI does not further increase diagnostic accuracy on top of clinical judgment and hs-cTnI alone. SUMMARY AND HIGHLIGHTS We included 1142 consecutive patients with suspected inducible ischemia, and evaluated the added value of the biomarkers high-sensitivity cardiac troponin (hs-cTn) and B-type natriuretic peptide (BNP), alone and in combination, on top of clinical judgment. CLINICAL TRIAL REGISTRATION Biochemical and Electrocardiographic Signatures in the Detection of Exercise-induced Myocardial Ischemia (BASEL VIII), NCT01838148, https://clinicaltrials.gov/ct2/show/NCT01838148

Incremental value of high-frequency QRS analysis for diagnosis and prognosis in suspected exercise-induced myocardial ischaemia.

AIM Exercise stress testing is used to detect myocardial ischaemia, but is limited by low sensitivity and specificity. The authors investigated the value of the analysis of high-frequency QRS components as a marker of abnormal depolarization in addition to standard ST-deviations as a marker of abnormal repolarization to improve the diagnostic accuracy. METHODS AND RESULTS Consecutive patients undergoing bicycle exercise stress nuclear myocardial perfusion imaging were prospectively enrolled. Presence of myocardial ischaemia, the primary diagnostic endpoint, was adjudicated using MPI and coronary angiography. Automated high-frequency QRS analysis was performed in a blinded fashion. The prognostic endpoint was major adverse cardiac events (MACEs) during two years of follow-up. Exercise-induced ischaemia was detected in 147/662 patients (22%). The sensitivity of high-frequency QRS was similar to ST-deviations (46% vs. 43%, p=0.59), while the specificity was lower (75% vs. 87%, p<0.001). The combined use of high-frequency QRS and ST-deviations classified 59% of patients as 'rule-out' (both negative), 9% as 'rule-in' (both positive) and 32% in an intermediate zone (one test positive). The sensitivity for 'rule-out' and the specificity for 'rule-in' improved to 63% and 97% compared with ST-deviation analysis alone (both p<0.001). MACE-free survival was 90%, 80% and 42% in patients in the 'rule-out', intermediate and 'rule-in' groups ( p<0.001). After adjustment for age, gender, ST-deviations and clinical post-test probability of ischaemia, high-frequency QRS remained an independent predictor for the occurrence of MACEs. CONCLUSION The use of high-frequency QRS analysis in addition to ST-deviation analysis improves the diagnostic accuracy during exercise stress testing and adds independent prognostic information

Sex-specific efficacy and safety of cryoballoon versus radiofrequency ablation for atrial fibrillation: An individual patient data meta-analysis

Atrial fibrillation (AF) is a growing health burden, and pulmonary vein isolation (PVI) using cryoballoon (CB) or radiofrequency (RF) represents an attractive therapeutic option. Sex-specific differences in the epidemiology, pathophysiology, and clinical presentation of AF and PVI are recognized.; We aimed at comparing the efficacy, safety, and procedural characteristics of CB and RF in women and men undergoing a first PVI procedure.; We searched for randomized controlled trials and prospective observational studies comparing CB and RF ablation with at least 1 year of follow-up. After merging individual patient data from 18 data sets, we investigated the sex-specific (procedure failure defined as recurrence of atrial arrhythmia, reablation, and reinitiation of antiarrhythmic medication), safety (periprocedural complications), and procedural characteristics of CB vs RF using Kaplan-Meier and multilevel models.; From the 18 studies, 4840 men and 1979 women were analyzed. An analysis stratified by sex correcting for several covariates showed a better efficacy of CB in men (hazard ratio for recurrence 0.88; 95% confidence interval 0.78-0.98, P = .02) but not in women (hazard ratio 0.98; 95% confidence interval 0.83-1.16; P = .82). For women and men, the energy source had no influence on the occurrence of at least 1 complication. For both sexes, the procedure time was significantly shorter with CB (-22.5 minutes for women and -27.1 minutes for men).; CB is associated with less long-term failures in men. A better understanding of AF-causal sex-specific mechanisms and refinements in CB technologies could lead to higher success rates in women

External Validation of the MEESSI Acute Heart Failure Risk Score: A Cohort Study

Background The MEESSI-AHF (Multiple Estimation of risk based on the Emergency department Spanish Score In patients with AHF) score was developed to predict 30-day mortality in patients presenting with acute heart failure (AHF) to emergency departments (EDs) in Spain. Whether it performs well in other countries is unknown. Objective To externally validate the MEESSI-AHF score in another country. Design Prospective cohort study. (ClinicalTrials.gov: NCT01831115). Setting Multicenter recruitment of dyspneic patients presenting to the ED. Participants The external validation cohort included 1572 patients with AHF. Measurements Calculation of the MEESSI-AHF score using an established model containing 12 independent risk factors. Results Among 1572 patients with adjudicated AHF, 1247 had complete data that allowed calculation of the MEESSI-AHF score. Of these, 102 (8.2%) died within 30 days. The score predicted 30-day mortality with excellent discrimination (c-statistic, 0.80). Assessment of cumulative mortality showed a steep gradient in 30-day mortality over 6 predefined risk groups (0 patients in the lowest-risk group vs. 35 [28.5%] in the highest-risk group). Risk was overestimated in the high-risk groups, resulting in a Hosmer-Lemeshow P value of 0.022. However, after adjustment of the intercept, the model showed good concordance between predicted risks and observed outcomes (P = 0.23). Findings were confirmed in sensitivity analyses that used multiple imputation for missing values in the overall cohort of 1572 patients. Limitations External validation was done using a reduced model. Findings are specific to patients with AHF who present to the ED and are clinically stable enough to provide informed consent. Performance in patients with terminal kidney failure who are receiving long-term dialysis cannot be commented on. Conclusion External validation of the MEESSI-AHF risk score showed excellent discrimination. Recalibration may be needed when the score is introduced to new populations. Primary Funding Source The European Union, the Swiss National Science Foundation, the Swiss Heart Foundation, the Cardiovascular Research Foundation Basel, the University of Basel, and University Hospital Basel