Elton Dudink

Vectorcardiographic QRS area as a novel predictor of response to cardiac resynchronization therapy

BACKGROUND QRS duration and left bundle branch block (LBBB) morphology are used to select patients for cardiac resynchronization therapy (CRT). We investigated whether the area of the QRS complex (QRSAREA) on the 3-dimensional vectorcardiogram (VCG) can improve patient selection. METHODS VCG (Frank orthogonal lead system) was recorded prior to CRT device implantation in 81 consecutive patients. VCG parameters, including QRSAREA, were assessed, and compared to QRS duration and morphology. Three LBBB definitions were used, differing in requirement of mid-QRS notching. Responders to CRT (CRT-R) were defined as patients with ≥15% reduction in left ventricular end systolic volume after 6months of CRT. RESULTS Fifty-seven patients (70%) were CRT-R. QRSAREA was larger in CRT-R than in CRT non-responders (140±42 vs 100±40 μVs, p<0.001) and predicted CRT response better than QRS duration (AUC 0.78 vs 0.62, p=0.030). With a 98μVs cutoff value, QRSAREA identified CRT-R with an odds ratio (OR) of 10.2 and a 95% confidence interval (CI) of 3.4 to 31.1. This OR was higher than that for QRS duration >156ms (OR=2.5; 95% CI 0.9 to 6.6), conventional LBBB classification (OR=5.5; 95% CI 0.9 to 32.4) or LBBB classification according to American guidelines (OR=4.5; 95% CI 1.6 to 12.6) or Strauss (OR=10.0; 95% CI 3.2 to 31.1). CONCLUSION QRSAREA is an objective electrophysiological predictor of CRT response that performs at least as good as the most refined definition of LBBB. CONDENSED ABSTRACT In 81 candidates for cardiac resynchronization therapy (CRT) we measured the area of the QRS complex (QRSAREA) using 3-dimensional vectorcardiography. QRSAREA was larger in echocardiographic responders than in non-responders and predicted CRT response better than QRS duration and than simple LBBB criteria. QRSAREA is a promising electrophysiological predictor of CRT response.

Systematic analysis of ECG predictors of sinus rhythm maintenance after electrical cardioversion for persistent atrial fibrillation

BACKGROUND Electrical cardioversion (ECV) is one of the rhythm control strategies in patients with persistent atrial fibrillation (AF). Unfortunately, recurrences of AF are common after ECV, which significantly limits the practical benefit of this treatment in patients with AF. OBJECTIVES The objectives of this study were to identify noninvasive complexity or frequency parameters obtained from the surface electrocardiogram (ECG) to predict sinus rhythm (SR) maintenance after ECV and to compare these ECG parameters with clinical predictors. METHODS We studied a wide variety of ECG-derived time- and frequency-domain AF complexity parameters in a prospective cohort of 502 patients with persistent AF referred for ECV. RESULTS During 1-year follow-up, 161 patients (32%) maintained SR. The best clinical predictor of SR maintenance was antiarrhythmic drug (AAD) treatment. A model including clinical parameters predicted SR maintenance with a mean cross-validated area under the receiver operating characteristic curve (AUC) of 0.62 ± 0.05. The best single ECG parameter was the dominant frequency (DF) on lead V6. Combining several ECG parameters predicted SR maintenance with a mean AUC of 0.64 ± 0.06. Combining clinical and ECG parameters improved prediction to a mean AUC of 0.67 ± 0.05. Although the DF was affected by AAD treatment, excluding patients taking AADs did not significantly lower the predictive performance captured by the ECG. CONCLUSION ECG-derived parameters predict SR maintenance during 1-year follow-up after ECV at least as good as known clinical predictors of rhythm outcome. The DF proved to be the most powerful ECG-derived predictor.

Acute cardioversion vs a wait-and-see approach for recent-onset symptomatic atrial fibrillation in the emergency department: Rationale and design of the randomized ACWAS trial

Background Current standard of care for patients with recent‐onset atrial fibrillation (AF) in the emergency department aims at urgent restoration of sinus rhythm, although paroxysmal AF is a condition that resolves spontaneously within 24 hours in more than 70% of the cases. A wait‐and‐see approach with rate‐control medication only and when needed cardioversion within 48 hours of onset of symptoms is hypothesized to be noninferior, safe, and cost‐effective as compared with current standard of care and to lead to a higher quality of life. Design The ACWAS trial (NCT02248753) is an investigator‐initiated, randomized, controlled, 2‐arm noninferiority trial that compares a wait‐and‐see approach to the standard of care. Consenting adults with recent‐onset symptomatic AF in the emergency department without urgent need for cardioversion are eligible for participation. A total of 437 patients will be randomized to either standard care (pharmacologic or electrical cardioversion) or the wait‐and‐see approach, consisting of symptom reduction through rate control medication until spontaneous conversion is achieved, with the possibility of cardioversion within 48 hours after onset of symptoms. Primary end point is the presence of sinus rhythm on 12‐lead electrocardiogram at 4 weeks; main secondary outcomes are adverse events, total medical and societal costs, quality of life, and cost‐effectiveness for 1 year. Conclusions The ACWAS trial aims at providing evidence for the use of a wait‐and‐see approach for patients with recent‐onset symptomatic AF in the emergency department.

Atherothrombosis and Thromboembolism : Position Paper from the Second Maastricht Consensus Conference on Thrombosis

Atherothrombosis is a leading cause of cardiovascular mortality and long-term morbidity. Platelets and coagulation proteases, interacting with circulating cells and in different vascular beds, modify several complex pathologies including atherosclerosis. In the second Maastricht Consensus Conference on Thrombosis, this theme was addressed by diverse scientists from bench to bedside. All presentations were discussed with audience members and the results of these discussions were incorporated in the final document that presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following five topics: 1. Risk factors, biomarkers and plaque instability: In atherothrombosis research, more focus on the contribution of specific risk factors like ectopic fat needs to be considered; definitions of atherothrombosis are important distinguishing different phases of disease, including plaque (in)stability; proteomic and metabolomics data are to be added to genetic information. 2. Circulating cells including platelets and atherothrombosis: Mechanisms of leukocyte and macrophage plasticity, migration, and transformation in murine atherosclerosis need to be considered; disease mechanism-based biomarkers need to be identified; experimental systems are needed that incorporate whole-blood flow to understand how red blood cells influence thrombus formation and stability; knowledge on platelet heterogeneity and priming conditions needs to be translated toward the in vivo situation. 3. Coagulation proteases, fibrin(ogen) and thrombus formation: The role of factor (F) XI in thrombosis including the lower margins of this factor related to safe and effective antithrombotic therapy needs to be established; FXI is a key regulator in linking platelets, thrombin generation, and inflammatory mechanisms in a renin-angiotensin dependent manner; however, the impact on thrombin-dependent PAR signaling needs further study; the fundamental mechanisms in FXIII biology and biochemistry and its impact on thrombus biophysical characteristics need to be explored; the interactions of red cells and fibrin formation and its consequences for thrombus formation and lysis need to be addressed. Platelet-fibrin interactions are pivotal determinants of clot formation and stability with potential therapeutic consequences. 4. Preventive and acute treatment of atherothrombosis and arterial embolism; novel ways and tailoring? The role of protease-activated receptor (PAR)-4 vis à vis PAR-1 as target for antithrombotic therapy merits study; ongoing trials on platelet function test-based antiplatelet therapy adjustment support development of practically feasible tests; risk scores for patients with atrial fibrillation need refinement, taking new biomarkers including coagulation into account; risk scores that consider organ system differences in bleeding may have added value; all forms of oral anticoagulant treatment require better organization, including education and emergency access; laboratory testing still needs rapidly available sensitive tests with short turnaround time. 5. Pleiotropy of coagulation proteases, thrombus resolution and ischaemia-reperfusion: Biobanks specifically for thrombus storage and analysis are needed; further studies on novel modified activated protein C-based agents are required including its cytoprotective properties; new avenues for optimizing treatment of patients with ischaemic stroke are needed, also including novel agents that modify fibrinolytic activity (aimed at plasminogen activator inhibitor-1 and thrombin activatable fibrinolysis inhibitor.

External electrical cardioversion in patients with cardiac implantable electronic devices: Is it safe and is immediate device interrogation necessary?

Atrial tachyarrhythmias are common in patients with cardiac implantable electronic devices (CIEDs). Restoration of sinus rhythm by external electrical cardioversion (eECV) is frequently used to alleviate symptoms and to ensure optimal device function.

Effect of Systemic Hypertension With Versus Without Left Ventricular Hypertrophy on the Progression of Atrial Fibrillation (from the Euro Heart Survey)

Hypertension is a risk factor for both progression of atrial fibrillation (AF) and development of AF-related complications, that is major adverse cardiac and cerebrovascular events (MACCE). It is unknown whether left ventricular hypertrophy (LVH) as a consequence of hypertension is also a risk factor for both these end points. We aimed to assess this in low-risk AF patients, also assessing gender-related differences. We included 799 patients from the Euro Heart Survey with nonvalvular AF and a baseline echocardiogram. Patients with and without hypertension were included. End points after 1 year were occurrence of AF progression, that is paroxysmal AF becoming persistent and/or permanent AF, and MACCE. Echocardiographic LVH was present in 33% of 379 hypertensive patients. AF progression after 1 year occurred in 10.2% of 373 patients with rhythm follow-up. In hypertensive patients with LVH, AF progression occurred more frequently as compared with hypertensive patients without LVH (23.3% vs 8.8%, p = 0.011). In hypertensive AF patients, LVH was the most important multivariably adjusted determinant of AF progression on multivariable logistic regression (odds ratio 4.84, 95% confidence interval 1.70 to 13.78, p = 0.003). This effect was only seen in male patients (27.5% vs 5.8%, p = 0.002), while in female hypertensive patients, no differences were found in AF progression rates regarding the presence or absence of LVH (15.2% vs 15.0%, p = 0.999). No differences were seen in MACCE for hypertensive patients with and without LVH. In conclusion, in men with hypertension, LVH is associated with AF progression. This association seems to be absent in hypertensive women.

The influence of progression of atrial fibrillation on quality of life: a report from the Euro Heart Survey

Aims Progression of atrial fibrillation (AF) from paroxysmal to persistent forms is an active field of research. The influence of AF progression on health related quality of life (HRQoL) is currently unknown. We aimed to assess the influence of AF progression on HRQoL, and whether this association is mediated through symptoms, treatment, and major adverse events. Methods and results In the Euro Heart Survey, 967 patients were included with paroxysmal AF who filled out EuroQoL-5D at baseline and at 1 year follow-up. Those who progressed (n = 132, 13.6%) developed more problems during follow-up than those who did not, on all EuroQoL-5D domains (increase in problems on mobility 20.5% vs. 11.4%; self-care 12.9% vs. 6.2%; usual activities 23.5% vs. 14.0%; pain/discomfort 20.5% vs. 13.7%; and anxiety/depression 22.7% vs. 15.7%; all P < 0.05), leading to a decrease in utility [baseline 0.744 ± 0.26, follow-up 0.674 ± 0.36; difference -0.07 (95% CI [-0.126,-0.013], P = 0.02)]. Multivariate analysis showed that the effect of progression on utility is mediated by a large effect of adverse events [stroke (-0.27 (95% CI [-0.43,-0.11]); P = 0.001], heart failure [-0.12 (95% CI [-0.20,-0.05]); P = 0.001], malignancy (-0.31 (95% CI [-0.56,-0.05]); P = 0.02] or implantation of an implantable cardiac defibrillator [-0.12 (95% CI [-0.23,-0.02]); P = 0.03)], as well as symptomatic AF [-0.04 (95% CI [-0.08,-0.01]); P = 0.008]. Conclusion AF progression is associated with a decrease in HRQoL. However, multivariate analysis revealed that AF progression itself does not have a negative effect on HRQoL, but that this effect can be attributed to a minor effect of the associated symptoms and a major effect of associated adverse events.

Symptomatic atrial fibrillation and risk of cardiovascular events: data from the Euro Heart Survey

Aims Atrial fibrillation (AF) is associated with a wide range of clinical presentations. Whether and how AF symptoms can affect prognosis is still unclear. Aims of the present analysis were to investigate potential predictors of symptomatic AF and to determine if symptoms are associated with higher incidence of cardiovascular (CV) events at 1-year follow-up. Methods and results The Euro Heart Survey on Atrial Fibrillation included 3607 consecutive patients with documented AF and available follow-up regarding symptoms status. Patients found symptomatic at baseline were classified into still symptomatic (SS group; n = 896) and asymptomatic (SA; n = 1556) at 1 year. Similarly, asymptomatic patients at baseline were classified into still asymptomatic (AA group; n = 903) and symptomatic (AS group; n = 252) at 1 year. Demographics, as well as clinical variables and medical treatments, were tested as potential predictors of symptoms persistence/development at 1-year. We also compared CV events between SS and SA groups, and AS and AA groups at 1-year follow-up. Both persistence and development of AF symptoms were associated with an increased risk of CV hospitalization, stroke, heart failure worsening, and thrombo-embolism. AF type, hypothyroidism, chronic heart failure, and chronic obstructive pulmonary disease (COPD), were independently associated with an increased risk of symptomatic status at 1-year follow-up between SS and SA groups. Conclusion Persistence or development of symptoms after medical treatment are associated with an increased risk of CV events during a 1-year follow-up. Type of AF, along with hypothyroidism, COPD and chronic heart failure are significantly associated with symptoms persistence despite medical treatment.

Poor anticoagulation relates to extended access times for cardioversion and is associated with long-term major cardiac and cerebrovascular events

BACKGROUND Patients undergoing elective electrical cardioversion (ECV) for atrial fibrillation have a temporarily increased risk of thromboembolism. Current guidelines recommend adequate anticoagulation for ≥3 consecutive weeks precardioversion, i.e. consecutive INR values 2.0-3.0 in patients with vitamin K antagonists (VKA). We aimed to evaluate the occurrence and impact of subtherapeutic INRs precardioversion and to study factors associated with these unwanted fluctuations. METHODS We recruited 346 consecutive patients undergoing elective ECV in the Maastricht University Medical Centre between 2008 and 2013. Predictors of subtherapeutic INR values were identified and incorporated into a logistic regression model. RESULTS A subtherapeutic INR precardioversion occurred in 55.2% of patients. The only statistically significant predictor was VKA-naivety (Odds Ratio (OR) 4.78, 95% Confidence Interval (CI) 2.67-8.58, p<0.001). In patients with ≥1 subtherapeutic INR precardioversion, time from referral until cardioversion was 91.1±42.8days, compared to 41.7±26.6days (p<0.001) in patients without subtherapeutic INRs. No thromboembolic events occurred <30days after the ECV. Independent predictors for the combined endpoint of cardiovascular death, ischemic stroke and the need of blood transfusion (n=30, median follow-up of 374days) were coronary artery disease in the history (OR 3.35, 95%CI 1.54-7.25, p=0.002) and subtherapeutic INR precardioversion (OR 3.64, 95%CI 1.43-9.24, p=0.007). CONCLUSIONS The use of VKA often results in subtherapeutic INRs precardioversion and is associated with a significant delay until cardioversion, especially in patients with recent initiation of VKA therapy. Furthermore, subtherapeutic INR levels prior to ECV are associated with the combined endpoint of cardiovascular death, ischemic stroke and the need of blood transfusion.

217 Differences in Blood Biomarker Composition Between Paroxysmal AF and Sinus Rhythm Patients, Without Heart Failure

Introduction Atrial fibrillation (AF) affects 2% of the population and is associated with cardiovascular disease and increased stroke and mortality rates. The myocardium releases proteins (SCF, VEGF-D and BNPs). Detection of such markers in blood could be used to differentiate specific types of AF, or to guide screening for silent, undiagnosed AF. Aim To identify plasma proteins discerning between patients with and without AF. Methods We studied blood from consecutive patients undergoing CT coronary angiography at Maastricht Medical center. We only enrolled patients without a history of stroke, hypertension, diabetes or heart failure. Using unique DNA-coupled paired antibodies and qPCR, we simultaneously analysed 92 plasma proteins. CCL21 protein was measured by ELISA (n = 240). Stats: Mann-Whitney test, mean normalized protein expression (NPX) +/-SEM. Results 176 patients (paroxysmal AF=50, sinus rhythm (SR) controls=126) were analysed. Mean age was 54 years in both groups. N— terminal fragment proB-type natriuretic peptide (NT-proBNP) protein was higher in patients with than in those without AF (6.23 ± 0.62 vs 4.72 ± 0.33, p = 0.012, n = 176). We also performed an exploratory analysis only in patients without signs of coronary artery disease on CTCA (AF=27, SR=80). In this subgroup, NT-proBNP (6.478 ± 0.8442 vs 4.554 ± 0.4122, p = 0.023*), BNP (1.111 ± 0.083 vs 0.9713 ± 0.029, p = 0.0175*), Stem Cell Factor (SCF, 162.8 ± 7.860 vs 140.4 ± 5.127 p = 0.0097**) and VEGF-D (47.44 ± 2.708 vs 41.38 ± 1.694 p = 0.0389*) were higher in the 27 patients with AF. Conclusion While NT-proBNP is mostly known as a marker for heart failure, NT-proBNP appears as a potential blood marker for AF in patients without history of stroke, hypertension, diabetes or heart failure. Further validation of these initial, hypothesis-generating results seems warranted.Abstract 217 Figure 1 Plasma NT-pro-BNP