Impact of atrial fibrillation phenotype and left atrial volume on outcome after pulmonary vein isolation.

AIMS: Pulmonary vein isolation (PVI) is increasingly performed in patients with atrial fibrillation (AF). Both AF phenotype and left atrial (LA) volume have been shown to influence ablation outcome. The inter-relationship of the two is incompletely understood. We aimed to investigate the impact of AF phenotype vs. LA volume on outcome after PVI. METHODS AND RESULTS: In a retrospective analysis of a prospective registry of patients undergoing a first PVI, the association of AF phenotype and LA volume index (LAVI) was assessed as well as their impact on AF recurrence during follow-up. Overall, 476 patients were enrolled (median age 63 years, 29% females, 65.8% paroxysmal AF). Obesity, hypertension, chronic kidney disease, and heart failure were all significantly more frequent in persistent AF. After 1 year, single-procedure, freedom from arrhythmia recurrence was 61.5%. Patients with paroxysmal AF had better outcomes compared with patients with persistent AF (65.6 vs. 52.7%, P = 0.003), as had patients with no/mild vs. moderate/severe LA dilation (LAVI <42 mL/m2 67.1% vs. LAVI ≥42 mL/m2 53%, P < 0.001). The combination of both parameters refined prediction of 1-year recurrence (P < 0.001). After adjustment for additional clinical risk factors in multivariable Cox proportional hazard analysis, both AF phenotype and LAVI ≥42 mL/m2 contributed significantly towards the prediction of 1-year recurrence. CONCLUSION: Atrial fibrillation phenotype and LA volume are independent predictors of outcome after PVI. Persistent AF with no/mild LA dilation has a similar risk of recurrence as paroxysmal AF with a moderate/severe LA dilation and should be given similar priority for ablation.

Procedural outcome and follow-up of stylet-driven leads compared with lumenless leads for left bundle branch area pacing.

AIMS: Left bundle branch area pacing (LBBAP) is most often delivered using lumenless leads (LLLs), but may also be performed using stylet-driven leads (SDLs). There are limited reports on the comparison of these tools, mainly limited to reports describing initial operator experience or without detailed procedural data. Our aim was to perform an in-depth comparison of SDLs and LLLs for LBBAP at implantation and follow-up in a larger cohort of patients with experience that extends beyond that of the initial learning curve. METHODS AND RESULTS: A total of 306 consecutive patients (age 77 ± 11 years, 183 males) undergoing LBBAP implantation at a single centre were prospectively included. The population was split into two groups of 153 patients based on the initial use of an SDL (from 4 manufacturers) or an LLL. After having discounted the initial learning curve of 50 patients, there was no difference in the success rate between the initial use of lead type (96.0% with SDL vs. 94.3% with LLL, P = 0.56). There were no significant differences in success between lead models. Electrocardiogram and electrical parameters were comparable between the groups. Post-operative macro-dislodgement occurred in 4.3% of patients (essentially within the first day following implantation) and presumed micro-dislodgement with loss of conduction system capture or rise in threshold (occurring mostly during the first month) was observed in 4.7% of patients, without differences between groups. CONCLUSION: Left bundle branch area pacing may be safely and effectively performed using either LLLs or SDLs, which provides implanters with alternatives for delivering this therapy.

Posterior wall ablation by pulsed-field ablation: procedural safety, efficacy, and findings on redo procedures.

AIMS: The left atrial posterior wall is a potential ablation target in patients with recurrent atrial fibrillation despite durable pulmonary vein isolation or in patients with roof-dependent atrial tachycardia (AT). Pulsed-field ablation (PFA) offers efficient and safe posterior wall ablation (PWA), but available data are scarce. METHODS AND RESULTS: Consecutive patients undergoing PWA using PFA were included. Posterior wall ablation was performed using a pentaspline PFA catheter and verified by 3D-electroanatomical mapping. Follow-up was performed using 7-day Holter ECGs 3, 6, and 12 months after ablation. Recurrence of any atrial arrhythmia lasting more than 30 s was defined as failure. Lesion durability was assessed during redo procedures. Posterior wall ablation was performed in 215 patients (70% males, median age 70 [IQR 61-75] years, 67% redo procedures) and was successful in all patients (100%) by applying a median of 36 (IQR 32-44) PFA lesions. Severe adverse events were cardiac tamponade and vascular access complication in one patient each (0.9%). Median follow-up was 7.3 (IQR 5.0-11.8) months. One-year arrhythmia-free outcome in Kaplan-Meier analysis was 53%. A redo procedure was performed in 26 patients (12%) after a median of 6.9 (IQR 2.4-11) months and showed durable PWA in 22 patients (85%) with only minor lesion regression. Among four patients with posterior wall reconnection, three (75%) presented with roof-dependent AT. CONCLUSION: Posterior wall ablation with this pentaspline PFA catheter can be safely and efficiently performed with a high durability observed during redo procedures. The added value of durable PWA for the treatment of atrial fibrillation remains to be evaluated.

Ablation index-guided 50W radiofrequency ablation for left atrial posterior wall isolation in atrial fibrillation.

BACKGROUND: Ablation index (AI)-guided ablation for posterior wall isolation (PWI) using high-power, short-duration remains untested. We sought to evaluate the acute outcomes of AI-guided 50 W ablation vs. conventional ablation, and investigate the differences in relationship between contact force (CF), time and AI in both groups. METHODS: Consecutive patients undergoing first-time AI-guided ablation with PWI using either 50 W or 35-40 W ablation were enrolled. Acute procedural metrics and individual lesion level ablation data were compared between groups. RESULTS: 40 patients (50 W: n = 20, 35-40 W: n = 20) with atrial fibrillation were included. Total procedure time was significantly reduced with 50 W (120 vs. 143 mins, p = 0.004) and there was a trend toward decreased ablation time (22 vs. 28 mins, p = 0.052). First pass and acute success of PWI were comparable between the 50 W and 35-40 W groups (10 vs. 8 patients, p = 0.525 and 20 vs. 19 patients, p = 1.000, respectively). Individual lesion analysis of all 959 RF applications (50 W: n = 458, 35-40 W: n = 501) demonstrated that 50 W ablation led to lower ablation time per lesion (10.4 vs. 13.0s, p < 0.001), and increased AI (471 vs. 461, p < 0.001) and impedance drop (7.4 vs. 6.9ohms, p = 0.007). Excessive ablations (AI>600 for roof line; AI>500 elsewhere) were more frequently observed in the 50 W group (9.0% vs. 4.6%, p = 0.007). CF had very good discriminative capability for excessive ablation in both groups. At 50 W, limiting the CF to <10 g reduced the number of excessive ablations on the floor line and within the posterior box to 12% and 4%,respectively. Recurrence of atrial arrhythmias at 12 months were comparable between the groups. CONCLUSION: AI-guided 50 W RF ablation reduces the ablation time of individual lesions and total procedure time without compromising first pass and acute success rates of PWI or 12-month outcomes compared to conventional powers.

Procedural efficiencies, lesion metrics, and 12-month clinical outcomes for Ablation Index-guided 50 W ablation for atrial fibrillation.

AIMS: The safety of Ablation Index (AI)-guided 50 W ablation for atrial fibrillation (AF) remains uncertain, and mid-term clinical outcomes have not been described. The interplay between AI and its components at 50 W has not been reported. METHODS AND RESULTS: Eighty-eight consecutive AF patients (44% paroxysmal) underwent AI-guided 50 W ablation. Procedural and 12-month clinical outcomes were compared with 93 consecutive controls (65% paroxysmal) who underwent AI-guided ablation using 35-40 W. Posterior wall isolation (PWI) was performed in 44 (50%) and 23 (25%) patients in the 50 and 35-40 W groups, respectively, P < 0.001. The last 10 patients from each group underwent analysis of individual lesions (n = 1230) to explore relationships between different powers and the AI components. Pulmonary vein isolation was successful in all patients. Posterior wall isolation was successful in 41/44 (93.2%) and 22/23 (95.7%) in the 50 and 35-40 W groups, respectively (P = 0.685). Radiofrequency times (20 vs. 26 min, P < 0.001) and total procedure times (130 vs. 156 min, P = 0.002) were significantly lower in the 50 W group. No complication or steam pop was seen in either group. Twelve-month freedom from arrhythmia was similar (80.2% vs. 82.8%, P = 0.918). A higher proportion of lesions in the 50 W group were associated with impedance drop >7 Ω (54.6% vs. 45.5%, P < 0.001). Excessive ablation (AI >600 anteriorly, >500 posteriorly) was more frequent in the 50 W group (9.7% vs. 4.3%, P < 0.001). CONCLUSION: Ablation Index-guided 50 W AF ablation is as safe and effective as lower powers and results in reduced ablation and procedure times. Radiofrequency lesions are more likely to be therapeutic, but there is a higher risk of delivering excessive ablation.

Man vs machine: Performance of manual vs automated electrocardiogram analysis for predicting the chamber of origin of idiopathic ventricular arrhythmia.

BACKGROUND: Radiofrequency catheter ablation of idiopathic ventricular arrhythmias (VAs) is performed to eliminate symptoms and to prevent or reverse arrhythmia-induced cardiomyopathy. Preprocedural prediction of the chamber of VA origin is critical for patient counseling, procedure planning, and guidance of invasive mapping. OBJECTIVE: We aimed to assess the performance of manual expert versus automated 12-lead electrocardiogram (ECG) analysis in the prediction of VA origin. METHODS: Patients with ablation of idiopathic VA and sustained success were included. The VA origin was defined as the site where ablation caused arrhythmia suppression. Standard baseline 12-lead ECGs with documentation of the VA were analyzed manually in a blinded fashion by three electrophysiologists and three electrophysiology (EP) fellows. In addition, the same standard 12-lead ECG was analyzed by an automated computer algorithm using a vectorcardiographic approach. RESULTS: Thirty-eight patients (median age, 47 [interquartile range, 37-58]; 68% female) were enrolled. The VA originated from the right ventricle in 24 (63%) and the left ventricle in 14 (37%) patients. The electrophysiologists and EP fellows identified the VA chamber of origin with a similar accuracy of 73% and 72% (P = .72). The automated algorithm showed a higher accuracy of 89% (P = .03 compared with electrophysiologists and EP fellows). This resulted in a sensitivity of 95% and specificity of 86%. CONCLUSION: While the manual ECG analysis of the standard 12-lead ECG by both electrophysiologists and EP fellows correctly identified the chamber of VA origin in around 75% of cases, an automated vectorcardiographic computer algorithm achieved an accuracy of 89% with clinically acceptable diagnostic parameters.

Leadless pacemaker implantation quality: importance of the operator's experience.

AIMS: Leadless cardiac pacemaker (PM) implantation differs from conventional PM implantation. While the procedure has been considered safe, recent real-world data raised concerns about the learning curve of new operators and their implantation quality. The goal of this study was to investigate the influence of the first operator's experience on leadless PM implantation quality and procedural efficiency. METHODS AND RESULTS: We performed a bicentric analysis of all Micra TPS™ implantations in two large tertiary referral hospitals. We assessed both leadless PM implantation quality based on the absence of complications (requiring intervention or prolonged hospitalization), good electrical performance (pacing threshold ≤ 1.5 V/0.24 ms, R-wave amplitude > 5 mV), and acceptable fluoroscopy duration (<10 min) as well as procedural efficiency in relation to the operator's experience. Univariate and multivariate logistic regression analyses were performed to identify predictors for implantation quality and procedural efficiency. Leadless PM implantation was successful in 106/111 cases (95.5%). Three patients (2.7%) experienced acute complications (one cardiac tamponade, one femoral bleeding, one posture-related PM exit block). Multivariate analysis showed that implantation quality of more experienced first operators was higher [odds ratio 1.09 (95% confidence interval 1.00-1.19), P = 0.05]. Procedural efficiency increased with operator experience as evidenced by an inverse correlation of procedure time, time to the first deployment, fluoroscopy time, and the number of procedures performed (all P < 0.05). CONCLUSION: The operator's learning curve is a critical factor for leadless PM implantation quality and procedural efficiency.

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.

0/1-Hour Triage Algorithm for Myocardial Infarction in Patients With Renal Dysfunction.

BACKGROUND: The European Society of Cardiology recommends a 0/1-hour algorithm for rapid rule-out and rule-in of non-ST-segment elevation myocardial infarction using high-sensitivity cardiac troponin (hs-cTn) concentrations irrespective of renal function. Because patients with renal dysfunction (RD) frequently present with increased hs-cTn concentrations even in the absence of non-ST-segment elevation myocardial infarction, concern has been raised regarding the performance of the 0/1-hour algorithm in RD. METHODS: In a prospective multicenter diagnostic study enrolling unselected patients presenting with suspected non-ST-segment elevation myocardial infarction to the emergency department, we assessed the diagnostic performance of the European Society of Cardiology 0/1-hour algorithm using hs-cTnT and hs-cTnI in patients with RD, defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2, and compared it to patients with normal renal function. The final diagnosis was centrally adjudicated by 2 independent cardiologists using all available information, including cardiac imaging. Safety was quantified as sensitivity in the rule-out zone, accuracy as the specificity in the rule-in zone, and efficacy as the proportion of the overall cohort assigned to either rule-out or rule-in based on the 0- and 1-hour sample. RESULTS: Among 3254 patients, RD was present in 487 patients (15%). The prevalence of non-ST-segment elevation myocardial infarction was substantially higher in patients with RD compared with patients with normal renal function (31% versus 13%, P<0.001). Using hs-cTnT, patients with RD had comparable sensitivity of rule-out (100.0% [95% confidence interval {CI}, 97.6-100.0] versus 99.2% [95% CI, 97.6-99.8]; P=0.559), lower specificity of rule-in (88.7% [95% CI, 84.8-91.9] versus 96.5% [95% CI, 95.7-97.2]; P<0.001), and lower overall efficacy (51% versus 81%, P<0.001), mainly driven by a much lower percentage of patients eligible for rule-out (18% versus 68%, P<0.001) compared with patients with normal renal function. Using hs-cTnI, patients with RD had comparable sensitivity of rule-out (98.6% [95% CI, 95.0-99.8] versus 98.5% [95% CI, 96.5-99.5]; P=1.0), lower specificity of rule-in (84.4% [95% CI, 79.9-88.3] versus 91.7% [95% CI, 90.5-92.9]; P<0.001), and lower overall efficacy (54% versus 76%, P<0.001; proportion ruled out, 18% versus 58%, P<0.001) compared with patients with normal renal function. CONCLUSIONS: In patients with RD, the safety of the European Society of Cardiology 0/1-hour algorithm is high, but specificity of rule-in and overall efficacy are decreased. Modifications of the rule-in and rule-out thresholds did not improve the safety or overall efficacy of the 0/1-hour algorithm. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00470587.

Combining High-Sensitivity Cardiac Troponin I and Cardiac Troponin T in the Early Diagnosis of Acute Myocardial Infarction.

BACKGROUND: Combining 2 signals of cardiomyocyte injury, cardiac troponin I (cTnI) and T (cTnT), might overcome some individual pathophysiological and analytical limitations and thereby increase diagnostic accuracy for acute myocardial infarction with a single blood draw. We aimed to evaluate the diagnostic performance of combinations of high-sensitivity (hs) cTnI and hs-cTnT for the early diagnosis of acute myocardial infarction. METHODS: The diagnostic performance of combining hs-cTnI (Architect, Abbott) and hs-cTnT (Elecsys, Roche) concentrations (sum, product, ratio, and a combination algorithm) obtained at the time of presentation was evaluated in a large multicenter diagnostic study of patients with suspected acute myocardial infarction. The optimal rule-out and rule-in thresholds were externally validated in a second large multicenter diagnostic study. The proportion of patients eligible for early rule-out was compared with the European Society of Cardiology 0/1 and 0/3 hour algorithms. RESULTS: Combining hs-cTnI and hs-cTnT concentrations did not consistently increase overall diagnostic accuracy as compared with the individual isoforms. However, the combination improved the proportion of patients meeting criteria for very early rule-out. With the European Society of Cardiology 2015 guideline recommended algorithms and cut-offs, the proportion meeting rule-out criteria after the baseline blood sampling was limited (6% to 24%) and assay dependent. Application of optimized cut-off values using the sum (9 ng/L) and product (18 ng2/L2) of hs-cTnI and hs-cTnT concentrations led to an increase in the proportion ruled-out after a single blood draw to 34% to 41% in the original (sum: negative predictive value [NPV] 100% [95% confidence interval (CI), 99.5% to 100%]; product: NPV 100% [95% CI, 99.5% to 100%]) and in the validation cohort (sum: NPV 99.6% [95% CI, 99.0-99.9%]; product: NPV 99.4% [95% CI, 98.8-99.8%]). The use of a combination algorithm (hs-cTnI <4 ng/L and hs-cTnT <9 ng/L) showed comparable results for rule-out (40% to 43% ruled out; NPV original cohort 99.9% [95% CI, 99.2-100%]; NPV validation cohort 99.5% [95% CI, 98.9-99.8%]) and rule-in (positive predictive value [PPV] original cohort 74.4% [95% Cl, 69.6-78.8%]; PPV validation cohort 84.0% [95% Cl, 79.7-87.6%]). CONCLUSIONS: New strategies combining hs-cTnI and hs-cTnT concentrations may significantly increase the number of patients eligible for very early and safe rule-out, but do not seem helpful for the rule-in of acute myocardial infarction. CLINICAL TRIAL REGISTRATION: URL (APACE): https://www.clinicaltrial.gov . Unique identifier: NCT00470587. URL (ADAPT): www.anzctr.org.au . Unique identifier: ACTRN12611001069943.

Clinical Utility of Procalcitonin in the Diagnosis of Pneumonia.

BACKGROUND: The clinical utility of procalcitonin in the diagnosis and management of pneumonia remains controversial. METHODS: We assessed the clinical utility of procalcitonin in 2 prospective studies: first, a multicenter diagnostic study in patients presenting to the emergency department with acute dyspnea to directly compare the diagnostic accuracy of procalcitonin with that of interleukin 6 and C-reactive protein (CRP) in the diagnosis of pneumonia; second, a randomized management study of procalcitonin guidance in patients with acute heart failure and suspected pneumonia. Diagnostic accuracy for pneumonia as centrally adjudicated by 2 independent experts was quantified with the area under the ROC curve (AUC). RESULTS: Among 690 patients in the diagnostic study, 178 (25.8%) had an adjudicated final diagnosis of pneumonia. Procalcitonin, interleukin 6, and CRP were significantly higher in patients with pneumonia than in those without. When compared to procalcitonin (AUC = 0.75; 95% CI, 0.71-0.78), interleukin 6 (AUC = 0.80; 95% CI, 0.77-0.83) and CRP (AUC = 0.82; 95% CI, 0.79-0.85) had significantly higher diagnostic accuracy (P = 0.010 and P < 0.001, respectively). The management study was stopped early owing to the unexpectedly low AUC of procalcitonin in the diagnostic study. Among 45 randomized patients, the number of days on antibiotic therapy and the length of hospital stay were similar (both P = 0.39) in patients randomized to the procalcitonin-guided group (n = 25) and usual-care group (n = 20). CONCLUSIONS: In patients presenting with dyspnea, diagnostic accuracy of procalcitonin for pneumonia is only moderate and lower than that of interleukin 6 and CRP. The clinical utility of procalcitonin was lower than expected. SUMMARY: Pneumonia has diverse and often unspecific symptoms. As the role of biomarkers in the diagnosis of pneumonia remains controversial, it is often difficult to distinguish pneumonia from other illnesses causing shortness of breath. The current study prospectively enrolled unselected patients presenting with acute dyspnea and directly compared the diagnostic accuracy of procalcitonin, interleukin 6, and CRP for the diagnosis of pneumonia. In this setting, diagnostic accuracy of procalcitonin for pneumonia was lower as compared to interleukin 6 and CRP. The clinical utility of procalcitonin was lower than expected. CLINICALTRIALSGOV IDENTIFIER: NCT01831115.

Impact of age on the performance of the ESC 0/1h-algorithms for early diagnosis of myocardial infarction.

Aims: We aimed to evaluate the impact of age on the performance of the European Society of Cardiology (ESC) 0/1h-algorithms and to derive and externally validate alternative cut-offs specific to older patients. Methods and results: We prospectively enrolled patients presenting to the emergency department (ED) with symptoms suggestive of acute myocardial infarction in three large diagnostic studies. Final diagnoses were adjudicated by two independent cardiologists. High-sensitivity cardiac troponin (hs-cTn) T and I concentrations were measured at presentation and after 1 h. Patients were stratified according to age [<55 years (young), ≥55 to <70 years (middle-age), ≥70 years (old)]. Rule-out safety of the ESC hs-cTnT 0/1h-algorithm was very high in all age-strata: sensitivity 100% [95% confidence interval (95% CI) 94.9-100] in young, 99.3% (95% CI 96.0-99.9) in middle-age, and 99.3% (95% CI 97.5-99.8) in old patients. Accuracy of rule-in decreased with age: specificity 97.0% (95% CI 95.8-97.9) in young, 96.1% (95% CI 94.5-97.2) in middle-age, and 92.7% (95% CI 90.7-94.3) in older patients. Triage efficacy decreased with increasing age (young 93%, middle-age 80%, old 55%, P < 0.001). Similar results were found for the ESC hs-cTnT 0/1h-algorithm. Alternative, slightly higher cut-off concentrations optimized for older patients maintained very high safety of rule-out, increased specificity of rule-in (P < 0.01), reduced overall efficacy for hs-cTnT (P < 0.01), while maintaining efficacy for hs-cTnI. Findings were confirmed in two validation cohorts (n = 2767). Conclusion: While safety of the ESC 0/1h-algorithms remained very high, increasing age significantly reduced overall efficacy and the accuracy of rule-in. Alternative slightly higher cut-off concentrations may be considered for older patients, particularly if using hs-cTnI. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT00470587, number NCT00470587 and NCT02355457 (BACC).

Effect of a Strategy of Comprehensive Vasodilation vs Usual Care on Mortality and Heart Failure Rehospitalization Among Patients With Acute Heart Failure: The GALACTIC Randomized Clinical Trial.

Importance: Short-term infusions of single vasodilators, usually given in a fixed dose, have not improved outcomes in patients with acute heart failure (AHF). Objective: To evaluate the effect of a strategy that emphasized early intensive and sustained vasodilation using individualized up-titrated doses of established vasodilators in patients with AHF. Design, Setting, and Participants: Randomized, open-label blinded-end-point trial enrolling 788 patients hospitalized for AHF with dyspnea, increased plasma concentrations of natriuretic peptides, systolic blood pressure of at least 100 mm Hg, and plan for treatment in a general ward in 10 tertiary and secondary hospitals in Switzerland, Bulgaria, Germany, Brazil, and Spain. Enrollment began in December 2007 and follow-up was completed in February 2019. Interventions: Patients were randomized 1:1 to a strategy of early intensive and sustained vasodilation throughout the hospitalization (n = 386) or usual care (n = 402). Early intensive and sustained vasodilation was a comprehensive pragmatic approach of maximal and sustained vasodilation combining individualized doses of sublingual and transdermal nitrates, low-dose oral hydralazine for 48 hours, and rapid up-titration of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or sacubitril-valsartan. Main Outcomes and Measures: The primary end point was a composite of all-cause mortality or rehospitalization for AHF at 180 days. Results: Among 788 patients randomized, 781 (99.1%; median age, 78 years; 36.9% women) completed the trial and were eligible for primary end point analysis. Follow-up at 180 days was completed for 779 patients (99.7%). The primary end point, a composite of all-cause mortality or rehospitalization for AHF at 180 days, occurred in 117 patients (30.6%) in the intervention group (including 55 deaths [14.4%]) and in 111 patients (27.8%) in the usual care group (including 61 deaths [15.3%]) (absolute difference for the primary end point, 2.8% [95% CI, -3.7% to 9.3%]; adjusted hazard ratio, 1.07 [95% CI, 0.83-1.39]; P = .59). The most common clinically significant adverse events with early intensive and sustained vasodilation vs usual care were hypokalemia (23% vs 25%), worsening renal function (21% vs 20%), headache (26% vs 10%), dizziness (15% vs 10%), and hypotension (8% vs 2%). Conclusions and Relevance: Among patients with AHF, a strategy of early intensive and sustained vasodilation, compared with usual care, did not significantly improve a composite outcome of all-cause mortality and AHF rehospitalization at 180 days. Trial Registration: ClinicalTrials.gov Identifier: NCT00512759.

Direct Comparison of Cardiac Myosin-Binding Protein C With Cardiac Troponins for the Early Diagnosis of Acute Myocardial Infarction.

BACKGROUND: Cardiac myosin-binding protein C (cMyC) is a cardiac-restricted protein that is more abundant than cardiac troponins (cTn) and is released more rapidly after acute myocardial infarction (AMI). We evaluated cMyC as an adjunct or alternative to cTn in the early diagnosis of AMI. METHODS: Unselected patients (N=1954) presenting to the emergency department with symptoms suggestive of AMI, concentrations of cMyC, and high-sensitivity (hs) and standard-sensitivity cTn were measured at presentation. The final diagnosis of AMI was independently adjudicated using all available clinical and biochemical information without knowledge of cMyC. The prognostic end point was long-term mortality. RESULTS: Final diagnosis was AMI in 340 patients (17%). Concentrations of cMyC at presentation were significantly higher in those with versus without AMI (median, 237 ng/L versus 13 ng/L, P<0.001). Discriminatory power for AMI, as quantified by the area under the receiver-operating characteristic curve (AUC), was comparable for cMyC (AUC, 0.924), hs-cTnT (AUC, 0.927), and hs-cTnI (AUC, 0.922) and superior to cTnI measured by a contemporary sensitivity assay (AUC, 0.909). The combination of cMyC with hs-cTnT or standard-sensitivity cTnI (but not hs-cTnI) led to an increase in AUC to 0.931 (P<0.0001) and 0.926 (P=0.003), respectively. Use of cMyC more accurately classified patients with a single blood test into rule-out or rule-in categories: Net Reclassification Improvement +0.149 versus hs-cTnT, +0.235 versus hs-cTnI (P<0.001). In early presenters (chest pain <3 h), the improvement in rule-in/rule-out classification with cMyC was larger compared with hs-cTnT (Net Reclassification Improvement +0.256) and hs-cTnI (Net Reclassification Improvement +0.308; both P<0.001). Comparing the C statistics, cMyC was superior to hs-cTnI and standard sensitivity cTnI (P<0.05 for both) and similar to hs-cTnT at predicting death at 3 years. CONCLUSIONS: cMyC at presentation provides discriminatory power comparable to hs-cTnT and hs-cTnI in the diagnosis of AMI and may perform favorably in patients presenting early after symptom onset. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00470587.

Direct Comparison of 4 Very Early Rule-Out Strategies for Acute Myocardial Infarction Using High-Sensitivity Cardiac Troponin I.

BACKGROUND: Four strategies for very early rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I (hs-cTnI) have been identified. It remains unclear which strategy is most attractive for clinical application. METHODS: We prospectively enrolled unselected patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction. The final diagnosis was adjudicated by 2 independent cardiologists. Hs-cTnI levels were measured at presentation and after 1 hour in a blinded fashion. We directly compared all 4 hs-cTnI-based rule-out strategies: limit of detection (LOD, hs-cTnI<2 ng/L), single cutoff (hs-cTnI<5 ng/L), 1-hour algorithm (hs-cTnI<5 ng/L and 1-hour change<2 ng/L), and the 0/1-hour algorithm recommended in the European Society of Cardiology guideline combining LOD and 1-hour algorithm. RESULTS: Among 2828 enrolled patients, acute myocardial infarction was the final diagnosis in 451 (16%) patients. The LOD approach ruled out 453 patients (16%) with a sensitivity of 100% (95% confidence interval [CI], 99.2%-100%), the single cutoff 1516 patients (54%) with a sensitivity of 97.1% (95% CI, 95.1%-98.3%), the 1-hour algorithm 1459 patients (52%) with a sensitivity of 98.4% (95% CI, 96.8%-99.2%), and the 0/1-hour algorithm 1463 patients (52%) with a sensitivity of 98.4% (95% CI, 96.8%-99.2%). Predefined subgroup analysis in early presenters (≤2 hours) revealed significantly lower sensitivity (94.2%, interaction P=0.03) of the single cutoff, but not the other strategies. Two-year survival was 100% with LOD and 98.1% with the other strategies (P<0.01 for LOD versus each of the other strategies). CONCLUSIONS: All 4 rule-out strategies balance effectiveness and safety equally well. The single cutoff should not be applied in early presenters, whereas the 3 other strategies seem to perform well in this challenging subgroup. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00470587.

Clinical Validation of a Novel High-Sensitivity Cardiac Troponin I Assay for Early Diagnosis of Acute Myocardial Infarction.

BACKGROUND: Clinical performance of the novel high-sensitivity cardiac troponin I (Siemens-hs-cTnI-Centaur) assay is unknown. We aimed to clinically validate the Siemens-hs-cTnI-Centaur assay and develop 0/1-h and 0/2-h algorithms. METHODS: We enrolled patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction (AMI). Final diagnoses were centrally adjudicated by 2 independent cardiologists including all clinical information twice: first, using serial hs-cTnT (Roche-Elecsys, primary analysis); second, using hs-cTnI (Abbott-Architect, secondary analysis) measurements in addition to the clinically applied (hs)-cTn. Siemens-hs-cTnI-Centaur was measured at presentation, 1 h, and 2 h. The primary objective was a direct comparison of diagnostic accuracy, quantified by the area under the ROC curve (AUC), of Siemens-hs-cTnI-Centaur vs the 2 established hs-cTn assays (Roche-hs-cTnT-Elecsys, Abbott-hs-cTnI-Architect). Secondary objectives included the development of Siemens-hs-cTnI-Centaur-specific 0/1-h and 0/2-h algorithms. RESULTS: AMI was the final diagnosis in 318 of 1755 (18%) patients (using Roche-hs-cTnT-Elecsys for adjudication). The AUC at presentation for Siemens-hs-cTnI-Centaur was 0.94 (95% CI, 0.92-0.96) and comparable with 0.95 (95% CI, 0.93-0.97) for Roche-hs-cTnT-Elecsys and 0.93 (95% CI, 0.90-0.96) for Abbott-hs-cTnI-Architect. Applying the derived Siemens-hs-cTnI-Centaur 0/1-h algorithm to the validation cohort, 46% of patients were ruled out (sensitivity, 99.1%; 95% CI, 95.3-100), and 18% of patients were ruled in (specificity, 94.1%; 95% CI, 91.8-95.9). The Siemens-hs-cTnI-Centaur 0/2-h algorithm ruled out 55% of patients (sensitivity, 100%; 95% CI, 94.1-100), and ruled in 18% of patients (specificity, 96.0%; 95% CI, 93.1-97.9). Findings were confirmed in the secondary analyses using serial measurements of Abbott-hs-cTnI-Architect for adjudication. CONCLUSIONS: Diagnostic accuracy and clinical utility of the novel Siemens-hs-cTnI-Centaur assay are high and comparable with the established hs-cTn assays. ClinicalTrials.gov Identifier: NCT00470587.

[Device therapy in heart failure]. / Device-Therapie bei Herzinsuffizienz.

Device therapy in heart failure Abstract. Despite advances in medical therapy, heart failure remains a disease with very high mortality and morbidity. In carefully selected patients, cardiac resynchronisation therapy and implantable cardioverter defibrillators are an important treatment option, thus, giving a chance to improve survival and quality of life in this vulnerable patient population.

Direct Comparison of 2 Rule-Out Strategies for Acute Myocardial Infarction: 2-h Accelerated Diagnostic Protocol vs 2-h Algorithm.

BACKGROUND: We compared 2 high-sensitivity cardiac troponin (hs-cTn)-based 2-h strategies in patients presenting with suspected acute myocardial infarction (AMI) to the emergency department (ED): the 2-h accelerated diagnostic protocol (2h-ADP) combining hs-cTn, electrocardiogram, and a risk score, and the 2-h algorithm exclusively based on hs-cTn concentrations and their absolute changes. METHODS: Analyses were performed in 2 independent diagnostic cohorts [European Advantageous Predictors of Acute Coronary Syndrome Evaluation (APACE) study, Australian-New Zealand 2-h Accelerated Diagnostic Protocol to Assess patients with chest Pain symptoms using contemporary Troponins as the only biomarker (ADAPT) study] employing hs-cTnT (Elecsys) and hs-cTnI (Architect). The final diagnosis was adjudicated by 2 independent cardiologists. RESULTS: AMI was the final diagnosis in 16.5% (95% CI, 14.6%-18.6%) of the 1372 patients in APACE, and 12.6% (95% CI, 10.7%-14.7%) of 1153 patients in ADAPT. The negative predictive value (NPV) and sensitivity for AMI were very high and comparable with both strategies using either hs-cTnT or hs-cTnI in both cohorts (all statistical comparisons nonsignificant). The percentage of patients triaged toward rule-out was significantly lower with the 2h-ADP (36%-43%) vs the 2-h algorithm (55%-68%) with both assays and in both cohorts (P < 0.001). The sensitivity of the 2h-ADP was higher for 30-day major adverse cardiovascular events. CONCLUSIONS: Both algorithms provided very high and comparable safety as quantified by the NPV and sensitivity for AMI and major adverse cardiac events (MACE) at 30 days in patients triaged toward rule-out, although sensitivity for MACE at 30 days was lower with both algorithms in cohort 2. Although the 2-h algorithm was more efficacious, not all patients ruled out for AMI by this algorithm were appropriate candidates for early discharge. The 2h-ADP seems superior in the selection of patients for early discharge from the ED. CLINICAL TRIAL REGISTRATION: APACE: http://clinicaltrials.gov/show/NCT00470587ADAPT: Australia-New Zealand Clinical Trials Registry ACTRN12611001069943.