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.

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.

Comparison of infection and complication rates associated with transvenous vs. subcutaneous defibrillators in patients with stage 4 chronic kidney disease: a multicenter long-term retrospective follow-up.

Background: Patients with progressive chronic kidney disease (CKD) are at higher risk of infections and complications from cardiac implantable electronic devices (CIED). In patients with a primary or secondary prophylactic indication, implantable cardiac defibrillators (ICD) can prevent sudden cardiac deaths (SCD). We retrospectively compared transvenous-ICD (TV-ICD) and intermuscularly implanted subcutaneous-ICD (S-ICD) associated infections and complication rates together with hospitalizations in recipients with stage 4 kidney disease. Methods: We retrospectively analyzed 70 patients from six German centers with stage 4 CKD who received either a prophylactic TV-ICD with a single right ventricular lead, 49 patients, or a S-ICD, 21 patients. Follow-Ups (FU) were performed bi-annually. Results: The TV-ICD patients were significantly older. This group had more patients with a history of atrial arrhythmias and more were prescribed anti-arrhythmic medication compared with the S-ICD group. There were no significant differences for other baseline characteristics. The median and interquartile range of FU durations were 55.2 (57.6-69.3) months. During FU, patients with a TV-ICD system experienced significantly more device associated infections (n = 8, 16.3% vs. n = 0; p < 0.05), device-associated complications (n = 13, 26.5% vs. n = 1, 4.8%; p < 0.05) and device associated hospitalizations (n = 10, 20.4% vs. n = 1, 4.8%; p < 0.05). Conclusion: In this long-term FU of patients with stage 4 CKD and an indication for a prophylactic ICD, the S-ICD was associated with significantly fewer device associated infections, complications and hospitalizations compared with TV-ICDs.

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.

Analysis of the effectiveness of the latest 4th-generation cryoballoon catheters in pulmonary vein isolation using high-resolution mapping.

BACKGROUND: Long-term data showed that up to 27% of pulmonary veins are reconnected using cryoballoon ablation. This study aimed to evaluate the efficacy of the latest 4th-generation cryoballoon catheters using ultra high-resolution mapping. METHODS: In patients with atrial fibrillation, a standard pulmonary vein isolation (PVI) with the latest 4th-generation cryoballoon catheter (Arctic Front Advance PRO, Medtronic Minneapolis, USA) and the spiral mapping catheter (Achieve Advance, Medtronic, Minneapolis, MN, USA) was performed. Subsequently, high-resolution mapping was achieved using the novel multipolar grid mapping catheter (Advisor HD Grid SE, Abbott Laboratories, USA). Follow-up was obtained after 6 months by means of a 7-day Holter electrocardiogram. RESULTS: In our study, acute PVI was successfully achieved in all 31 patients. The latest 4th-generation cryoballoon catheter is safe in the acute phase of PVI. Additional high-resolution mapping (mean points per map 21,001 ± 4911) using the multipolar grid mapping catheter enabled us to identify residual gaps only in the carina pulmonary vein region; therefore, no additional ablation was performed. Three of 31 patients (10%) presented with atrial arrhythmia recurrence always related with pulmonary vein reconnection; using high-resolution mapping had no additional benefit in identifying pulmonary veins in which reconnection will occur. CONCLUSION: The utility of additional high-density mapping, facilitated by the HD Grid catheter after PVI with the 4th-generation cryoballoon catheter do not substantiate a discernible advantage over conventional mapping methodologies, particularly, the spiral mapping catheter. Residual carinal conduction was observed in a substantial cohort of patients (48%), highlighting a persistent challenge in achieving complete electrical isolation.

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.

Use of the Wearable Cardioverter-Defibrillator Among Patients With Myocarditis and Reduced Ejection Fraction or Ventricular Tachyarrhythmia: Data From a Multicenter Registry.

Background Data on the use of the wearable cardioverter-defibrillator (WCD) among patients with myocarditis remain sparse. Consequently, evidence for guideline recommendations in this patient population is lacking. Methods and Results In total, 1596 consecutive patients were included in a multicenter registry from 8 European centers, with 124 patients (8%) having received the WCD due to myocarditis and reduced left ventricular ejection fraction or prior ventricular tachyarrhythmia. The mean age was 51.6±16.3 years, with 74% being male. Patients were discharged after index hospitalization on heart failure medication: Angiotensin-converting enzyme inhibitors (62.5%), angiotensin-receptor-neprilysin inhibitor (22.9%), aldosterone-antagonists (51%), or beta blockers (91.4%). The initial median left ventricular ejection fraction was 30% (22%-45%) and increased to 48% (39%-55%) over long-term follow-up (P<0.001). The median BNP (brain natriuretic peptide) level at baseline was 1702 pg/mL (565-3748) and decreased to 188 pg/mL (26-348) over long-term follow-up (P=0.022). The mean wear time was 79.7±52.1 days and 21.0±4.9 hours per day. Arrhythmic event rates documented by the WCD were 9.7% for nonsustained ventricular tachycardia, 6.5% for sustained ventricular tachycardia, and 0% for ventricular fibrillation. Subsequently, 2.4% of patients experienced an appropriate WCD shock. The rate of inappropriate WCD shocks was 0.8%. All 3 patients with appropriate WCD shock had experienced ventricular tachycardia/ventricular fibrillation before WCD prescription, with only 1 patient showing a left ventricular ejection fraction <35%. Conclusions Patients with myocarditis and risk for occurrence of ventricular tachyarrhythmia may benefit from WCD use. Prior ventricular arrhythmia might appear as a better risk predictor than a reduced left ventricular ejection fraction <35% in this population.

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.

Empagliflozin Reduces Interleukin-6 Levels in Patients with Heart Failure.

Background: The inhibition of sodium-glucose co-transporter 2 (SGLT-2) has been shown to be beneficial in the treatment of diabetic and non-diabetic patients with heart failure. The underlying mechanisms are incompletely understood. The present prospective study investigates for the first time the effect of empagliflozin on various soluble markers of inflammation in patients with reduced ejection fraction (HFrEF). Methods: We included 50 inpatients with HFrEF and diabetes mellitus type 2. A total of 25 patients received a therapy with the SGLT-2-inhibitor empagliflozin in addition to standard medication; the other 25 patients did not receive empagliflozin and were considered the control group. Quality of life, functional status and soluble immunological parameters in serum were assessed at baseline and after 3 months. Results: The baseline characteristics of both groups revealed no significant differences. Patients on empagliflozin demonstrated a significant improvement in the Minnesota living with heart failure questionnaire (baseline 44.2 ± 20.2 vs. 24 ± 17.7; p < 0.001), in distance in the 6-min walk test (baseline 343 ± 145 m vs. 450 ± 115 m; p < 0.001) and in soluble interleukin-6 level (baseline 21.7 ± 21.8 pg/mL vs. 13.7 ± 15.8 pg/mL; p = 0.008). There was no significant change of these or other parameters in the control group (p > 0.05 each). Conclusions: The empagliflozin-induced improvement of quality of life and functional capacity in patients with HFrEF and type 2 diabetes mellitus is accompanied by a substantial reduction of interleukin-6 levels. Thus, anti-inflammatory effects may contribute to the benefits of SGLT-2-inhibitors in heart failure.

Urokinase versus Alteplase in Patients with Intermediate-High-Risk Pulmonary Embolism Treated with Ultrasound-Accelerated Endovascular Thrombolysis.

BACKGROUND: Ultrasound-accelerated thrombolysis (USAT) is a safe and effective treatment for patients with intermediate-high-risk pulmonary embolism (PE). In all studies investigating USAT in the setting of PE, the recombinant tissue-plasminogen activator (rt-PA) alteplase or actilyse was used. Currently, there is a shortage of alteplase (Alteplase, Boehringer Ingelheim) in Europe. It is unknown whether the efficacy of urokinase (UK) is comparable with alteplase for USAT in patients with PE. METHODS: Patients with intermediate-high-risk PE undergoing USAT with urokinase and alteplase were included in this study. One-to-one nearest neighbour matching was performed to account for baseline differences. We identified one patient treated with USAT and UK (n = 9) for each patient treated with USAT and alteplase (n = 9). RESULTS: A total of 56 patients underwent USAT. The treatment was successful in all patients. The propensity score matched the identified nine pairs of patients. There were no statistically significant differences in the change in right ventricle-to-left ventricle (RV/LV) ratio (0.4 ± 0.3 versus 0.5 ± 0.4, p = 0.54), systolic pulmonary artery pressure (17.3 ± 8.0 versus 18.1 ± 8.1, p = 0.17), or improvement of RV function (5.8 ± 3.8 versus 5.1 ± 2.6, p = 1.0). The complication rates were comparable (11% in both groups, p = 0.55). There were no deaths in hospital or during 90 days in either group. CONCLUSIONS: In this case-matched comparison, the short-term clinical and echocardiographic outcomes showed comparable results between USAT-UK and USAT-rt-PA.

The Safety and Efficacy of Ultrasound-Accelerated Catheter-Directed Thrombolysis in Patients with Intermediate-High-Risk Pulmonary Embolism: Bo-NE-Experience.

Ultrasound-accelerated thrombolysis (USAT) is an advanced interventional therapy for patients with intermediate-high-risk pulmonary embolism (PE) who deteriorated on anticoagulation or for high-risk patients for whom systemic thrombolysis is contraindicated. The aim of this study is to investigate the safety and efficacy of this therapy with a focus on the improvement of vital signs and laboratory parameters. Seventy-nine patients with intermediate-high-risk PE were treated with USAT from August 2020 to November 2022. The therapy significantly decreased the mean RV/LV ratio from 1.2 ± 0.22 to 0.9 ± 0.2 (p < 0.001) as well as the mean PAPs from 48.6 ± 11 to 30.1 ± 9.0 mmHg (p < 0.001). The respiratory and heart rate decreased significantly (p < 0.001). Serum creatinine decreased significantly from 1.0 ± 0.35 to 0.9 ± 0.3 (p < 0.001). There were 12 access-associated complications, which could be treated conservatively. One patient had haemothorax after the therapy and had to be operated on. USAT is an effective therapy for patients with intermediate-high-risk PE, with favourable hemodynamic, clinical, and laboratory outcomes.

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).

Infective endocarditis of a left atrial appendage closure device: a case report and literature review.

Background: Due to advances in interventional cardiology in recent years, more and more patients are currently receiving cardiac devices, with a subsequent increase in the number of patients with device-associated endocarditis. Device-associated endocarditis is a life-threatening disease with special diagnostic and therapeutic challenges. Interventional devices for left atrial appendage (LAA) closure have been available for several years. However, there have been very few case reports of LAA closure device-associated endocarditis. Case summary: An 83-year-old woman presented with fever and fatigue. She had a history of permanent atrial fibrillation and recurrent bleeding on oral anticoagulation. Consequently, the patient underwent interventional LAA closure ∼20 months earlier. Blood cultures grew Staphylococcus aureus. Transoesophageal echocardiography revealed an LAA closure device-associated mobile, echo-dense mass that was consistent with infectious vegetation in this clinical context. Intravenous antibiotic therapy was started, and our heart team recommended complete removal of the device, which the patient refused. The patient subsequently died as a result of progressive endocarditis and multiple pre-existing co-morbidities. Discussion: Left atrial appendage occlusion device-associated endocarditis has rarely been reported. Due to the increase in LAA closure device implantation, device-associated endocarditis is expected to increase in the future. Transoesophageal echocardiography is required for correct diagnosis. Our case report suggests that an infection can occur long after implantation.