Prognostic Implications of Coronary Artery Sclerosis in Troponin-Positive Patients with Non-Obstructive Coronary Arteries.

INTRODUCTION: Coronary sclerosis is a risk factor for the progression to obstructive coronary artery disease (CAD). However, understanding its impact on the outcomes of patients with myocardial infarction and non-obstructive coronary arteries is limited. This study aimed to explore the prognostic influence of coronary sclerosis on in- and out-of-hospital events in troponin-positive patients with non-obstructive coronary arteries. METHODS: This study was a retrospective cohort analysis based on prospectively collected data. A total of 24,775 patients who underwent coronary angiography from 2010 to 2021 in a German university hospital were screened, resulting in a final study cohort of 373 troponin-positive patients with non-obstructive coronary arteries and a follow-up period of 6.2 ± 3.1 years. Coronary sclerosis was defined as coronary plaques without angiographically detectable stenotic lesions of 50% or more in the large epicardial coronary arteries. The primary study endpoint was the occurrence of in-hospital events. Secondary endpoints included events during follow-up. RESULTS: Patients with coronary sclerosis were significantly older (70 ± 12 vs. 58 ± 16 years, p < 0.001), had ST-segment elevation less frequently on electrocardiogram (9.4% vs. 18.7%, p = 0.013), and suffered more often from diabetes mellitus (23.3% vs. 13.1%, p = 0.009), arterial hypertension (79.6% vs. 59.8%, p < 0.001), chronic obstructive pulmonary disease (17.1% vs. 9.4%, p = 0.028), chronic kidney disease (22.2% vs. 8.4%, p < 0.001), atrial fibrillation (19.8% vs. 12.2%, p = 0.045), and valvular diseases than patients without CAD. Patients with coronary sclerosis were more likely to receive medication for primary/secondary prevention on admission and at discharge. The incidence of in- and out-of-hospital events was significantly higher in patients with coronary sclerosis (in-hospital: 42.8% vs. 29.9%, p = 0.010; out-of-hospital: 46.0% vs. 26.1%, p < 0.001). Mortality rates tended to be higher in the coronary sclerosis group (29.4% vs. 20.0%, p = 0.066). CONCLUSION: Patients diagnosed with coronary sclerosis presented a higher incidence of comorbidities and increased medication use, and experienced higher rates of both in-hospital and out-of-hospital events, primarily due to the clustering of cardiovascular risk factors.

Predictors of ventricular tachyarrhythmia in patients with a wearable cardioverter defibrillator: an international multicenter registry.

BACKGROUND AND AIMS: Wearable cardioverter defibrillator (WCD) can protect patients from sudden cardiac death due to ventricular tachyarrhythmias and serve as a bridge to decision of definite defibrillator implantation. The aim of this analysis from an international, multicenter WCD registry was to identify predictors of sustained ventricular tachycardia (VT) and/or ventricular fibrillation (VF) in this population. METHODS: One thousand six hundred seventy-five patients with WCD were included in a multicenter registry from 9 European centers, with a median follow-up of 440 days (IQR 120-893). The primary study end point was the occurrence of sustained VT/VF. RESULTS: Sustained VT was detected by WCD in 5.4% and VF in 0.9% of all patients. Of the 30.3% of patients receiving ICD implantation during follow-up, sustained VT was recorded in 9.3% and VF in 2.6%. Non-ischemic cardiomyopathy (HR 0.5, p < 0.001), and medication with angiotensin-converting enzyme inhibitors (HR 0.7, p = 0.027) and aldosterone antagonists (HR 0.7, p = 0.005) were associated with a significantly lower risk of VT/VF. CONCLUSIONS: Patients who received WCD due to a transient increased risk of sudden cardiac death have a comparatively lower risk of VT/VF in the presence of non-ischemic cardiomyopathy. Of note, optimal medical treatment for heart failure not only results in an improvement in left ventricular ejection fraction but also in a reduction in the risk for VT/VF.

Pacemaker-induced atrial fibrillation reconsidered-associations with different pacing sites and prevention approaches.

The incidence of atrial fibrillation (AF) is significantly higher in patients with pacemakers than in the general population, which could be due to patient characteristics and the diagnostic tool of the pacemaker in detecting atrial high-rate episodes and subclinical AF, but also to the pacemaker itself providing AF-promoting conditions. It is well known that high ventricular pacemaker burden increases the likelihood of AF occurrence. However, the sites of atrial and ventricular pacing may also influence the risk for AF. The conventional sites for atrial and ventricular pacing are in the right atrial appendage and in the right ventricular apex. However, growing evidence suggests that alternative pacing sites may be superior for the prevention of AF. Bachmann bundle pacing, for example, promotes interatrial excitation conduction, resulting in atrial synchronicity and a shorter total atrial activation time, which may be preventive for the occurrence of AF. Moreover, in recent years, new ventricular pacing sites have come into focus with His bundle and left bundle branch pacing. In addition to the hemodynamic and electrophysiological cardiac benefits, these new options may also offer benefits in the prevention of AF. This review provides an overview of pacing-induced AF mechanisms and the association with different pacing sites, as well as approaches for prevention of pacing-induced AF, highlighting different sites and modes of atrial pacing and the newer sites of ventricular pacing.

Ejection Fraction-Related Differences of Baseline Characteristics and Outcomes in Troponin-Positive Patients without Obstructive Coronary Artery Disease.

Background: The development and course of myocardial infarction with non-obstructive coronary artery (MINOCA) disease is still not fully understood. In this study, we aimed to examine the baseline characteristics of in-hospital outcomes and long-term outcomes of a cohort of troponin-positive patients without obstructive coronary artery disease based on different left ventricular ejection fractions (LVEFs). Methods and results: We included a cohort of 254 patients (mean age: 64 (50.8-75.3) years, 120 females) with suspected myocardial infarction and no obstructive coronary artery disease (MINOCA) in our institutional database between 2010 and 2021. Among these patients, 170 had LVEF ≥ 50% (84 females, 49.4%), 31 patients had LVEF 40-49% (15 females, 48.4%), and 53 patients had LVEF < 40% (20 females, 37.7%). The mean age in the LVEF ≥ 50% group was 61.5 (48-73) years, in the LVEF 40-49% group was 67 (57-78) years, and in the LVEF < 40% group was 68 (56-75.5) years (p = 0.05). The mean troponin value was highest in the LVEF < 40% group, at 3.8 (1.7-4.6) µg/L, and lowest in the LVEF ≥ 50% group, at 1.1 (0.5-2.1) µg/L (p = 0.05). Creatine Phosphokinase (CK) levels were highest in the LVEF ≥ 50% group (156 (89.5-256)) and lowest in the LVEF 40-49% group (127 (73-256)) (p < 0.05), while the mean BNP value was lowest in the LVEF ≥ 50% group (98 (48-278) pg/mL) and highest in the <40% group (793 (238.3-2247.5) pg/mL) (p = 0.001). Adverse in-hospital cardiovascular events were highest in the LVEF < 40% group compared to the LVEF 40-49% group and the LVEF ≥ 50% group (56% vs. 55% vs. 27%; p < 0.001). Over a follow-up period of 6.2 ± 3.1 years, the all-cause mortality was higher in the LVEF < 40% group compared to the LVEF 40-49% group and the LVEF ≥ 50% group. Among the different factors, LVEF < 40% and LVEF 40-49% were associated with an increased risk of in-hospital cardiovascular events in the multivariable Cox regression analysis. Conclusions: LVEF has different impacts on in-hospital cardiovascular events in this cohort. Furthermore, LVEF influences long-term all-cause mortality.

Predictors of atrial fibrillation after embolic stroke of undetermined source in patients with implantable loop recorders.

BACKGROUND: In patients with embolic stroke of undetermined source (ESUS), underlying subclinical atrial fibrillation (AF) is often suspected. Previous studies identifying predictors of AF have been limited in their ability to diagnose episodes of AF. Implantable loop recorders enable prolonged, continuous, and therefore more reliable detection of AF. The aim of this study was to identify clinical and ECG parameters as predictors of AF in ESUS patients with implantable loop recorders. METHODS: 101 ESUS patients who received an implantable loop recorder between 2012 and 2020 were included in this study. Patients were followed up regularly on a three-monthly outpatient interval. RESULTS: During a mean follow-up of 647 ± 385 days, AF was detected in 26 patients (26%). Independent risk factors of AF were age ≥ 60 years (HR 2.753, CI 1.129-6.713, p = 0.026), P-wave amplitude in lead II ≤ 0.075 mV (HR 3.751, CI 1.606-8.761, p = 0.002), and P-wave duration ≥ 125 ms (HR 4.299, CI 1.844-10.021, p < 0.001). In patients without risk factors, the risk of developing AF was 16%. In the presence of one risk factor, the probability increased only slightly to 18%. With two or three risk factors, the risk of AF increased to 70%. CONCLUSION: AF was detected in about one in four patients after ESUS in this study. A comprehensive evaluation involving multiple parameters and the existence of multiple risk factors yields the highest predictive accuracy for detecting AF in patients with ESUS.

The impact of diabetes mellitus on the outcome of troponin-positive patients with non-obstructive coronary arteries.

Background: Diabetes mellitus is a major cardiovascular risk factor for the development of coronary artery disease, but knowledge about the impact of diabetes mellitus on the outcome of patients with myocardial infarction with non-obstructive coronary arteries is limited. The aim of this study was to investigate the prognostic impact of diabetes mellitus on in- and out-of-hospital adverse events in troponin-positive patients with non-obstructive coronary arteries. Methods and Results: A total of 373 troponin-positive patients with non-obstructive coronary arteries between 2010 and 2021 at Bergmannsheil University Hospital Bochum were enrolled, including 65 diabetics and 307 nondiabetics. The median follow-up was 6.2 years. The primary study end point was a composite of in-hospital major adverse cardiovascular events (MACE). Secondary endpoints covered MACE during follow-up.Mean age of the study cohort was 62.9 years and 49.3 % were male. Although the overall rate of in-hospital MACE was higher in diabetics (41.5 %) than in non-diabetics (33.9 %), this difference did not reach statistical significance (p = 0.240). The in-hospital mortality rate was low in both groups, 0 % of diabetes group versus 2.9 % of non-diabetic patients. During follow-up, diabetic patients had a significantly higher rate of MACE (51.9 % vs. 31.1 %, p = 0.004) and a significantly higher all-cause mortality rate than non-diabetic patients (42.3 % vs. 20.1 %, p < 0.001). Conclusion: Our study reveals that the impact of diabetes mellitus on cardiovascular outcomes in troponin-positive patients with non-obstructive coronary arteries intensifies over the long term, leading to increased rates of both cardiovascular adverse events and overall mortality.

Benefit of primary and secondary prophylactic implantable cardioverter defibrillator in elderly patients.

BACKGROUND: The benefit of implantable cardioverter-defibrillator (ICD) in elderly patients has been questioned. In the present study, we aimed to analyse the outcome of patients of different age groups with ICD implantation. METHODS: We included all patients who received an ICD in our hospital from 2011 to 2020. Primary endpoints were (1) death from any cause and (2) appropriate ICD therapy (antitachycardia pacing/shock). A "benefit of ICD implantation" was defined as appropriate ICD therapy before death from any cause/or survival. "No benefit of ICD implantation" was defined as death from any cause without prior appropriate ICD therapy. RESULTS: A total of 422 patients received an ICD (primary prophylaxis n = 323, secondary prophylaxis n = 99). At the time of implantation, 35 patients (8%) were >80 years and 106 patients were >75 years (25%). During the study period of 4.2 ± 3 years, benefit of ICD occurred in 89 patients (21%) and no benefit in 84 patients (20%). In primary prevention, the proportion of patients who had a benefit from ICD implantation decreased with increasing age, and there were no patients who benefited from ICD therapy in the group of patients >80 years. In secondary prophylaxis, the proportion of patients with a benefit from ICD implantation ranged from 20% to 30% in all age groups. CONCLUSION: Our study suggests that the indication of primary prophylactic ICD in elderly and very old patients should be critically assessed. On the other hand, no patient should be denied secondary prophylactic ICD implantation because of age.

Predicting risk of AF in ischaemic stroke using sinus rhythm ECG abnormalities: A meta-analysis.

OBJECTIVE: To identify ECG changes in sinus rhythm that may be used to predict subsequent development of new AF. METHOD: We identified prospective and retrospective cohort or case control studies evaluating ECG patterns from a 12-lead ECG in sinus rhythm taken in hospital or community predicting subsequent development of new AF. For each identified ECG predictor, we then identify absolute event rates and pooled risk ratios (RR) using an aggregate level random effects meta-analysis. RESULTS: We identified 609,496 patients from 22 studies. ECG patterns included P wave terminal force V1 (PTFV1), interatrial block (IAB) and advanced interatrial block (aIAB), abnormal P wave axis (aPWA), PR prolongation and atrial premature complexes (APCs). Pooled risk ratios reached significance for each of these; PTFV1 RR 1.48 (95% CI 1.04-2.10), IAB 2.54 (95% CI 1.64-3.93), aIAB 4.05 (95% CI 2.64-6.22), aPWA 1.89 (95% CI 1.25-2.85), PR prolongation 2.22 (95% CI 1.27-3.87) and APCs 3.71 (95% CI 2.23-6.16). Diabetes reduced the predictive value of PR prolongation. CONCLUSION: APC and aIAB were most predictive of AF, while IAB, PR prolongation, PTFV1 and aPWA were also significantly associated with development of AF. These support their use in a screening tool to identify at risk cohorts who may benefit from further investigation, or following stroke, with empirical anticoagulation.

P-wave parameters and their association with thrombi and spontaneous echo contrast in the left atrial appendage.

BACKGROUND: The aim of this study was to examine the prevalence of abnormal P-wave parameters in patients with thrombus and/or spontaneous echo contrast (SEC) in the left atrial appendage (LAA), and to identify P-wave parameters particularly associated with thrombus and SEC formation. HYPOTHESIS: We presume a significant relationship of P-wave parameters with thrombi and SEC. METHODS: All patients in whom a thrombus or SEC was detected in the LAA on transoesophageal echocardiography were included in this study. Patients at risk (CHA2DS2-VASc Score ≥3) and routine transoesophageal echocardiography to exclude thrombi served as the control group. A detailed ECG analysis was performed. RESULTS: Of a total of 4062 transoesophageal echocardiographies, thrombi and SEC were detected in 302 patients (7.4%). Of these patients, 27 (8.9%) presented with sinus rhythm. The control group included 79 patients. There was no difference in mean CHA2DS2-VASc score in the two groups (p = .182). A high prevalence of abnormal P-wave parameters was detected in patients with thrombus/SEC. Indicators for the presence of thrombi or SEC in the LAA were P-wave duration >118 ms (Odds ratio (OR) 3.418, Confidence interval (CI) 1.522-7.674, p < .001), P-wave dispersion >40 ms (OR 2.521, CI 1.390-4.571, p < .001) and advanced interatrial block (OR 1.431, CI 1.033-1.984, p = .005). CONCLUSION: Our study revealed that several P-wave parameters are associated with thrombi and SEC in the LAA. The results may help identify patients who are at particularly high risk for thromboembolic events (e.g., in patients with embolic stroke of undetermined source).

Left Atrial Cardiomyopathy - A Challenging Diagnosis.

Left atrial cardiomyopathy (LACM) has been an ongoing focus of research for several years. There is evidence that LACM is responsible for atrial fibrillation and embolic strokes of undetermined sources. Therefore, the correct diagnosis of LACM is of clinical importance. Various techniques, including electrocardiography, echocardiography, cardiac magnetic resonance imaging, computed tomography, electroanatomic mapping, genetic testing, and biomarkers, can both identify and quantify structural, mechanical as well as electrical dysfunction in the atria. However, the question arises whether these techniques can reliably diagnose LACM. Because of its heterogeneity, clinical diagnosis is challenging. To date, there are no recommendations for standardized diagnosis of suspected LACM. However, standardization could help to classify LACM more precisely and derive therapeutic directions to improve individual patient management. In addition, uniform diagnostic criteria for LACM could be important for future studies. Combining several parameters and relating them seems beneficial to approach the diagnosis of LACM. This review provides an overview of the current evidence regarding the diagnosis of LACM, in which several potential parameters are discussed and, consequently, a proposal for a diagnostic algorithm is presented.

Predictors for the detection of arrhythmia requiring pacemaker/ICD implantation-Results from a loop recorder study.

BACKGROUND: There are few large studies on which factors are associated with the occurrence of arrhythmias. Implantable loop recorders (ILR) are useful in detecting arrhythmia due to prolonged and continuous ECG monitoring. Therefore, the aim of this study is to identify and evaluate clinical characteristics and ECG parameters for predicting arrhythmias requiring pacemaker/ICD implantation by analyzing a study cohort with ILR. METHODS: This bicentric study comprised a study cohort of 451 patients (mean age 64 ± 16 years, 209 women) receiving ILR implantation between 2011 and 2021. Patients were followed up on a 3 monthly outpatient interval. All arrhythmias with a pacemaker or ICD indication were considered clinically relevant. The primary study endpoint was the detection of clinically relevant arrhythmia. RESULTS: During a follow up of 678 ± 392 days, a clinically relevant arrhythmia was detected in 81 of 451 patients (18%). Multivariate analysis revealed five independent risk factors: coronary artery disease (HR 1.954, CI 1.077-3.546, p = .028), atrial fibrillation (HR 2.253, CI 1.201-4.228, p = .011), previous syncope (HR 6.404, CI 3.202-12.808, p < .001), right bundle branch block (HR 4.370, CI 2.215-8.621, p < .001) and left bundle branch block (HR 2.685, CI 1.116-6.461, p = .028). Our risk model, based on these independent predictors, divided the study cohort into patients with low (2%), intermediate (18%), medium (34%), and high (45%) risk for clinically relevant arrhythmia. CONCLUSION: By the use of ILR, a clinically relevant arrhythmia has been detected in almost one fifth of the study cohort. In addition, clinical and electrocardiographic parameters were shown to be suitable predictors of clinically relevant arrhythmia.

How should I treat patients with subclinical atrial fibrillation and atrial high-rate episodes? Current evidence and clinical importance.

Long-term and continuous ECG monitoring using cardiac implantable electronic devices and insertable cardiac monitors has improved the capability of detecting subclinical atrial fibrillation (AF) and atrial high-rate episodes. Previous studies demonstrated a high prevalence (more than 20%) in patients with cardiac implantable electronic devices or insertable cardiac monitors. Subclinical AF and atrial high-rate episodes are often suspected as the cause of prior or potential future ischemic stroke. However, the clinical significance is still uncertain, and the evidence is limited. This review aims to present and discuss the current evidence on the clinical impact of subclinical AF and atrial high-rate episodes. It focuses particularly on the association between the duration of the episodes and major clinical outcomes like thromboembolic events. As subclinical AF and atrial high-rate episodes are presumed to be associated with ischemic strokes, detection will be particularly important in patients with cryptogenic stroke and in high-risk patients for thromboembolism. In this context, it is also interesting whether there is a temporal relationship between the detection of subclinical AF and atrial high-rate episodes and the occurrence of thromboembolic events. In addition, the review will examine the question whether there is a need for a therapy with oral anticoagulation.

Rate of atrial fibrillation and flutter induced tachycardiomyopathy in a cohort of hospitalized patients with heart failure and detection of indicators for improved diagnosis.

Background: Atrial fibrillation (AF) and atrial flutter (AFL) induced tachycardiomyopathy (TCM) has been known to cause reversible heart failure (HF) for many years. However, the prevalence of the disease is unknown, and diagnosis is challenging. Therefore, the aim of the present study was (1) to assess the rate of AF/AFL induced TCM and (2) to identify indicators for diagnosis. Methods: Consecutively, all patients with a diagnosis of HF who were hospitalized in our department within 12 months were reviewed. For the main analysis, all patients with HF with reduced ejection fraction (HFrEF) and AF or AFL were included. AF/AFL induced TCM was diagnosed when there was at least a 10% improvement in left ventricular ejection fraction under rhythm or rate control within 3 months. Patients with HFrEF with AF/AFL but without TCM served as control group. Results: A total of 480 patients were included. AF/AFL induced TCM occurred in 26 patients (5.4%) and HFrEF with AF/AFL in 53 patients (11%). Independent indicators of AF/AFL induced TCM were age<79 years [Odds ratio 5.887, confidence interval (CI) 1.999-17.339, p < 0.001], NT-pro-BNP <5,419 pg/mL (Odds ratio 2.327, CI 1.141-4.746, p = 0.004), and a resting heart rate >112 bpm (Odds ratio 2.503, CI 1.288-4.864, p = 0.001). Conclusion: Approximately 5% of all patients hospitalized for HF suffer from AF/AFL induced TCM. Improved discrimination of AF/AFL induced TCM to HFrEF with AF/AFL is possible considering age, NT-pro-BNP level, and resting heart rate >112 beats/minute. Based on these parameters, an earlier diagnosis and improved therapy might be possible.

Short- and long-term outcome of patients with spontaneous echo contrast or thrombus in the left atrial appendage in the era of the direct acting anticoagulants.

BACKGROUND: Thrombi and spontaneous echo contrast (SEC) in the left atrial appendage (LAA) are associated with thromboembolic events and poor prognosis. There are very few data on long-term outcome, especially with the use of direct acting anticoagulants (DOAC). METHODS: In this retrospective study, all transoesophageal echocardiographies performed at a tertiary care university hospital from 2015 to 2020 were analyzed. All patients with thrombus or SEC in the LAA were included. Medical history, laboratory, echocardiographic parameters and medication at discharge were documented. The primary endpoint of the study was a composite endpoint (all-cause mortality, non-fatal stroke or transient ischaemic attack [TIA], non-fatal systemic embolization, non-fatal major bleeding and non-fatal myocardial infarction). RESULTS: Of a total of 4062 transoesophageal echocardiographies, thrombi were detected in 51 patients (1.2%) and SEC in 251 patients (6.2%). These patients formed the final study cohort (n = 302). During a mean follow-up period of 956 ± 663 days, 87 patients (29%) suffered the primary point. The following baseline characteristics predicted the primary endpoint: age, haemoglobin, a previous coronary artery bypass grafting, dialysis and choice of anticoagulation. Prescription of apixaban at discharge was associated with lower rate of adverse events (hazard ratio 0.564, confidence interval 0.331-0.960; p = 0.035) while prescription of dabigatran was associated with higher rate of adverse events (hazard ratio 3.091, confidence interval 1.506-6.347; p = 0.002). CONCLUSION: Even in the DOAC era, the occurrence of thrombus or SEC in the LAA is associated with a high rate of MACCE. Our study suggests that the choice of DOAC therapy may have an impact on long-term survival.

Impact of P-wave indices in prediction of atrial fibrillation-Insight from loop recorder analysis.

BACKGROUND: Several P-wave indices are associated with the development of atrial fibrillation (AF). However, previous studies have been limited in their ability to reliably diagnose episodes of AF. Implantable loop recorders allow long-term, continuous, and therefore more reliable detection of AF. HYPOTHESIS: The aim of this study is to identify and evaluate ECG parameters for predicting AF by analyzing patients with loop recorders. METHODS: This study included 366 patients (mean age 62 ± 16 years, mean LVEF 61 ± 6%, 175 women) without AF who underwent loop recorder implantation between 2010-2020. Patients were followed up on a 3 monthly outpatient interval. RESULTS: During a follow-up of 627 ± 409 days, 75 patients (20%) reached the primary study end point (first detection of AF). Independent predictors of AF were as follows: age ≥68 years (hazard risk [HR], 2.66; 95% confidence interval [CI], 1.668-4.235; p < .001), P-wave amplitude in II <0.1 mV (HR, 2.11; 95% CI, 1.298-3.441; p = .003), P-wave terminal force in V1  ≤ -4000 µV × ms (HR, 5.3; 95% CI, 3.249-8.636; p < .001, and advanced interatrial block (HR, 5.01; 95% CI, 2.638-9.528; p < .001). Our risk stratification model based on these independent predictors separated patients into 4 groups with high (70%), intermediate high (41%), intermediate low (18%), and low (4%) rates of AF. CONCLUSIONS: Our study indicated that P-wave indices are suitable for predicting AF episodes. Furthermore, it is possible to stratify patients into risk groups for AF using simple ECG parameters, which is particularly important for patients with cryptogenic stroke.