Impact of pulmonary vein isolation on obstructive sleep apnea in patients with atrial fibrillation

Background: Obstructive sleep apnea (OSA) has been identified as associated with the onset and propagation of atrial fibrillation (AF) and predicts recurrences of AF after pulmonary vein isolation (PVI). Vice versa, it has never been investigated whether PVI influences OSA. However, it has been controversial whether a restored atrial function can affect the course of OSA. There­fore, we have assessed whether PVI procedure modulates the prevalence and severity of OSA. Methods and Results: We included 23 individuals with AF that were assigned to undergo PVI into this study. Patients were 65 ± 7 years old, obese (BMI 29.9 ± 5.4 kg/m2), white (100%) and had a normal left ventricular function (LVEF 64 ± 9%). Polygraphic assessment was carried out before and 6 months after PVI. The prevalence of OSA, defined as an apnea-hypopnea index (AHI) ≥ 5 per hour of sleep, was 74% before PVI compared to 70% 6 months after the procedure (p > 0.05). Severity of OSA did not differ (AHI before vs. after: 18 ± 18/h vs. 15 ± 17/h, p > 0.05) as well as further polygraphic parameters did not differ before and after the procedure. Conclusions: Prevalence and severity of OSA are not affected by PVI in patients suffering from AF.

Impact of gender in patients with device-related thrombosis after left atrial appendage closure - A sub-analysis from the multicenter EUROC-DRT-registry.

BACKGROUND Device-related thrombosis (DRT) is a common finding after left atrial appendage closure (LAAC) and is associated with worse outcomes. As women are underrepresented in clinical studies, further understanding of sex differences in DRT patients is warranted. METHODS AND RESULTS This sub-analysis from the EUROC-DRT-registry compromises 176 patients with diagnosis of DRT after LAAC. Women, who accounted for 34.7% (61/176) of patients, were older (78.0 ± 6.7 vs. 74.9 ± 9.1 years, p = .06) with lower rates of comorbidities. While DRT was detected significantly later in women (173 ± 267 vs. 127 ± 192 days, p = .01), anticoagulation therapy was escalated similarly, mainly with initiation of novel oral anticoagulant (NOAC), vitamin K antagonist (VKA) or heparin. DRT resolution was achieved in 67.5% (27/40) of women and in 75.0% (54/72) of men (p = .40). In the remaining cases, an intensification/switch of anticoagulation was conducted in 50.% (9/18) of men and in 41.7% (5/12) of women. Final resolution was achieved in 72.5% (29/40) cases in women, and in 81.9% (59/72) cases in men (p = .24). Women were followed-up for a similar time as men (779 ± 520 vs. 908 ± 687 days, p = .51). Kaplan-Meier analysis revealed no difference in mortality rates in women (Hazard Ratio [HR]: 1.73, 95%-Confidence interval [95%-CI]: .68-4.37, p = .25) and no differences in stroke (HR: .83, 95%-CI: .30-2.32, p = .72) within 2 years after LAAC. CONCLUSION Evaluation of risk factors and outcome revealed no differences between men and women, with DRT in women being diagnosed significantly later. Women should be monitored closely to assess for DRT formation/resolution. Treatment strategies appear to be equally effective

Total beta-adrenoceptor knockout slows conduction and reduces inducible arrhythmias in the mouse heart.

INTRODUCTION: Beta-adrenoceptors (β-AR) play an important role in the neurohumoral regulation of cardiac function. Three β-AR subtypes (β(1), β(2), β(3)) have been described so far. Total deficiency of these adrenoceptors (TKO) results in cardiac hypotrophy and negative inotropy. TKO represents a unique mouse model mimicking total unselective medical β-blocker therapy in men. Electrophysiological characteristics of TKO have not yet been investigated in an animal model. METHODS: In vivo electrophysiological studies using right heart catheterisation were performed in 10 TKO mice and 10 129SV wild type control mice (WT) at the age of 15 weeks. Standard surface ECG, intracardiac and electrophysiological parameters, and arrhythmia inducibility were analyzed. RESULTS: The surface ECG of TKO mice revealed a reduced heart rate (359.2±20.9 bpm vs. 461.1±33.3 bpm; p<0.001), prolonged P wave (17.5±3.0 ms vs. 15.1±1.2 ms; p = 0.019) and PQ time (40.8±2.4 ms vs. 37.3±3.0 ms; p = 0.013) compared to WT. Intracardiac ECG showed a significantly prolonged infra-Hisian conductance (HV-interval: 12.9±1.4 ms vs. 6.8±1.0 ms; p<0.001). Functional testing showed prolonged atrial and ventricular refractory periods in TKO (40.5±15.5 ms vs. 21.3±5.8 ms; p = 0.004; and 41.0±9.7 ms vs. 28.3±6.6 ms; p = 0.004, respectively). In TKO both the probability of induction of atrial fibrillation (12% vs. 24%; p<0.001) and of ventricular tachycardias (0% vs. 26%; p<0.001) were significantly reduced. CONCLUSION: TKO results in significant prolongations of cardiac conduction times and refractory periods. This was accompanied by a highly significant reduction of atrial and ventricular arrhythmias. Our finding confirms the importance of β-AR in arrhythmogenesis and the potential role of unspecific beta-receptor-blockade as therapeutic target

Deficiency of cyclase-associated protein 2 promotes arrhythmias associated with connexin43 maldistribution and fibrosis

Introduction: Cyclase-associated protein 2 (CAP2) plays a major role in regulating the actin cytoskeleton. Since inactivation of CAP2 in a mouse model by a gene trap approach (Cap2(gt/gt)) results in cardiomyopathy and increased mortality, we hypothesized that CAP2 has a major impact on arrhythmias and electrophysiological parameters. Material and methods: We performed long-term-ECG recordings in transgenic CAP2 deficient mice (C57BL/6) to detect spontaneous arrhythmias. In vivo electrophysiological studies by right heart catheterization and ex vivo epicardial mapping were used to analyze electrophysiological parameters, the inducibility of arrhythmias, and conduction velocities. Expression and distribution of cardiac connexins and the amount of cardiac fibrosis were evaluated. Results: Spontaneous ventricular arrhythmias could be detected in Cap2(gt/gt) during the long-term-ECG recording. Cap2(gt/gt) showed marked conduction delays at atrial and ventricular levels, including a reduced heart rate (421.0 +/- 40.6 bpm vs. 450.8 +/- 27.9 bpm; p < 0.01), and prolongations of PQ (46.3 +/- 4.1 ms vs. 38.6 +/- 6.5 ms; p < 0.01), QRS (16.2 +/- 2.6 ms vs. 12.6 +/- 1.4 ms; p < 0.01), and QTc interval (55.8 +/- 6.0 ms vs. 45.2 +/- 3.3 ms; p = 0.02) in comparison to wild type mice. The PQ prolongation was due to an infra-Hisian conduction delay (HV: 9.7 +/- 2.1 ms vs. 6.5 +/- 3.1 ms; p = 0.02). The inducibility of ventricular tachycardias during the electrophysiological studies was significantly elevated in the mutant mice (inducible animals: 88% vs. 33%; p = 0.04). Cap2(gt/gt) showed more abnormal distribution of connexin43 compared to WT (23.0 +/- 4.7% vs. 2.9 +/- 0.8%; p < 0.01). Myocardial fibrosis was elevated in Cap2(gt/gt) hearts (9.1 +/- 6.7% vs. 5.5 +/- 3.3%; p < 0.01). Conclusions: Loss of CAP2 results in marked electrophysiological disturbances including impaired sinus node function, conduction delays, and susceptibility to malignant arrhythmias. Structural changes in Cap2(gt/gt) are associated with alterations in myocardial connexins and fibrosis

Experimental research Deficiency of cyclase-associated protein 2 promotes arrhythmias associated with connexin43 maldistribution and fibrosis

A b s t r a c t Introduction: Cyclase-associated protein 2 (CAP2) plays a major role in regulating the actin cytoskeleton. Since inactivation of CAP2 in a mouse model by a gene trap approach (Cap2 gt/gt ) results in cardiomyopathy and increased mortality, we hypothesized that CAP2 has a major impact on arrhythmias and electrophysiological parameters. Material and methods: We performed long-term-ECG recordings in transgenic CAP2 deficient mice (C57BL/6) to detect spontaneous arrhythmias. In vivo electrophysiological studies by right heart catheterization and ex vivo epicardial mapping were used to analyze electrophysiological parameters, the inducibility of arrhythmias, and conduction velocities. Expression and distribution of cardiac connexins and the amount of cardiac fibrosis were evaluated. Results: Spontaneous ventricular arrhythmias could be detected in Cap2 gt/gt during the long-term-ECG recording. Cap2 gt/gt showed marked conduction delays at atrial and ventricular levels, including a reduced heart rate (421.0 ±40.6 bpm vs. 450.8 ±27.9 bpm; p &lt; 0.01), and prolongations of PQ (46.3 ±4.1 ms vs. 38.6 ±6.5 ms; p &lt; 0.01), QRS (16.2 ±2.6 ms vs. 12.6 ±1.4 ms; p &lt; 0.01), and QTc interval (55.8 ±6.0 ms vs. 45.2 ±3.3 ms; p = 0.02) in comparison to wild type mice. The PQ prolongation was due to an infra-Hisian conduction delay (HV: 9.7 ±2.1 ms vs. 6.5 ±3.1 ms; p = 0.02). The inducibility of ventricular tachycardias during the electrophysiological studies was significantly elevated in the mutant mice (inducible animals: 88% vs. 33%; p = 0.04). Cap2 gt/gt showed more abnormal distribution of connexin43 compared to WT (23.0 ±4.7% vs. 2.9 ±0.8%; p &lt; 0.01). Myocardial fibrosis was elevated in Cap2 gt/gt hearts (9.1 ±6.7% vs. 5.5 ±3.3%; p &lt; 0.01). Conclusions: Loss of CAP2 results in marked electrophysiological disturbances including impaired sinus node function, conduction delays, and susceptibility to malignant arrhythmias. Structural changes in Cap2 gt/gt are associated with alterations in myocardial connexins and fibrosis

CHA2DS2-VASC score predicts coronary artery disease progression and mortality after ventricular arrhythmia in patients with implantable cardioverter-defibrillator

Aim: The CHA2DS2-VASC score has expanded its use beyond the initial purpose of predicting the risk of stroke in patients with atrial fibrillation. We aimed to investigate the value of the CHA2DS2-VASC score as a risk assessment tool to predict relevant coronary artery disease (CAD) leading to percutaneous coronary intervention (PCI), and all-cause mortality after detected ventricular arrhythmia (VA) in patients with an Implantable Cardioverter-Defibrillator (ICD). Methods: A total of 183 ICD-patients who underwent coronary angiography after VA were included and classified according to their CHA2DS2-VASC score in a low(1-3), intermediate(4-5) and high(6-8) score group. We evaluated the predictive value of CHA2DS2-VASC score for the presence of relevant CAD leading to percutaneous coronary intervention (PCI), as well as late all-cause mortality. Results: A total of 60 patients (32.8%) had significant CAD and underwent successful PCI. After adjustment for relevant parameters such as ischemic cardiomyopathy, angina pectoris, left ventricular ejection fraction, CHA2DS2-VASC score remained the only independent predictor of CAD leading to PCI [HR 1.73 (1.07–2.80)]. The Area under curve was 0.64 (0.56–72, p = 0.002). Kaplan-Meier analysis and log-rank showed an increased three-year mortality of ICD-patients with an intermediate or high score after VA (p = 0.003). Multivariate cox-regression analysis revealed that CHA2DS2-VASC score was also independently associated with all-cause mortality following adjustment for clinically relevant variables (HR 2.20, 1.17–4.14). Conclusions: CHA2DS2-VASC score can be a predictor of CAD leading to PCI in ICD-patients after VA. ICD-Patients with a high score have an increased risk for reduced three-year all-cause mortality after VA

Cardiac autonomic dysfunction in adult congenital heart disease

Abstract Purpose Due to recent advances in diagnosis and treatment, the number of adults with congenital heart disease (ACHD) has substantially increased. This achievement is mitigated by rhythm disorders. Here, we sought to determine alterations in heart rate variability (HRV) and their prognostic value in ACHD. Methods Ninety seven ACHD patients (39.2 ± 14.1 years, 51.5% female) and 19 controls (39.7 ± 15.0 years, 47.4% female) underwent 24-h Holter monitoring. Results As compared to controls, ACHD patients offered a significantly higher burden of premature ventricular contractions (p = 0.02) and decreased HRV indices (natural logarithmic transformation of very low frequency (lnVLF): 7.46 ± 0.76 ms2 vs. 7.91 ± 0.92ms2, p = 0.03; natural logarithmic transformation of low frequency (lnLF): 6.39 ± 0.95ms2 vs. 7.01 ± 1.07ms2, p = 0.01; natural logarithmic transformation of the ratio of low to high frequency spectra (lnLF/HF): 0.81 ± 0.74 vs. 1.17 ± 0.51, p = 0.04). No differences in HRV measures were observed across ACHD lesion groups. NT-proBNP levels were significantly related to both time and frequency domain indices (natural logarithmic transformation of the standard deviation of NN intervals (lnSDNN): Spearman´s rho = -0.32, p = 0.001; natural logarithmic transformation of the standard deviation of the average NN intervals for each 5-min segment of a 24-h Holter monitoring (lnSDANN): Spearman´s rho: -0.33, p = 0.001; natural logarithmic transformation of the total power (lnTP): Spearman´s rho: -0.25, p = 0.01; lnVLF: Spearman´s rho: -0.33, p = 0.001; lnLF: Spearman´s rho: -0.35, p < 0.001; lnLF/HF: Spearman´s rho: -0.34, p = 0.001). After a mean follow-up of 3.9 ± 0.7 years, 8 patients died and 3 patients survived sudden cardiac death (SCD). Several HRV parameters were significantly higher in event-free ACHD patients than in those who died or survived SCD (natural logarithmic transformation of the average of the standard deviations of NN intervals for each 5-min segment of a 24-h Holter monitoring (lnASDNN): p = 0.04; lnPNN30: p = 0.04; lnVFL: p = 0.03; lnLF: p < 0.01). On univariate Cox regression analysis, the time domain indices lnSDNN, lnASDNN and lnPNN30, as well as the frequency domain parameters lnTP, lnVLF and lnLF were associated with death and survived cardiac arrest. Conclusion ACHD is accompanied by HRV impairment that carries prognostic implications on ACHD mortality and survived SCD

Assessment of LAA Strain and Thrombus Mobility and Its Impact on Thrombus Resolution—Added-Value of a Novel Echocardiographic Thrombus Tracking Method

Purpose—The mobility of left atrial appendage (LAA) thrombi and changes hereof under anticoagulation may serve as a marker of both risk of embolism and efficacy of treatment. In this study, we sought to evaluate thrombus mobility and hypothesized that LAA dynamics and thrombus mobility could serve as a baseline marker of thrombus dissolvability. Methods—Patients with two-dimensional transesophageal echocardiographic images of the LAA, and with evidence of LAA thrombus were included in this study. Using a speckle tracking algorithm, functional information from the LAA and thrombi of different patients was computed. While the LAA motion was quantified through the longitudinal strain, thrombus mobility was evaluated using a novel method by directly tracking the thrombus, isolated from the global cardiac motion. Baseline characteristics and echocardiographic parameters were compared between responders (thrombus resolution) and non-responders (thrombus persistence) to anticoagulation. Results—We included 35 patients with atrial fibrillation with evidence of LAA thrombi. Patients had a mean age of 72.9 ± 14.1 years, exhibited a high risk for thromboembolism (CHA2DS2-VASc-Score 4.1 ± 1.5) and had moderately reduced LVEF (41.7 ± 14.4%) and signs of diastolic dysfunction (E/E¢ = 19.7 ± 8.5). While anticoagulation was initiated in all patients, resolution was achieved in 51.4% of patients. Significantly higher LAA peak strain ( 3.0 ± 1.3 vs. 1.6 ± 1.5%, p < 0.01) and thrombus mobility (0.33 ± 0.13 mm vs. 0.18 ± 0.08 mm, p < 0.01) were observed in patients in whom thrombi resolved (i.e. responders against non-responders). Receiver operating characteristic (ROC) analysis revealed a high discriminatory ability for thrombus mobility with regards to thrombus resolution (AUC 0.89). Conclusion—Isolated tracking of thrombus mobility from echocardiographic images is feasible. In patients with LAA thrombus, higher thrombus mobility appeared to be associated with thrombus resolution. Future studies should be conducted to evaluate the role of the described technique to predict LAA thrombus resolution or persistence

Probability of induction of arrhythmias.

<p>The probability of induction of AF was significantly lower in TKO compared to WT. The probability of induction of VTs was highly significant lower in TKO as in this group not any VTs could be induced during the electrophysiological study. n = 10 for TKO and n = 10 for WT.</p

Representative ECG recordings of TKO and WT mice.

<p>A: Surface ECG. B: Intracardiac ECG at His–bundle level (A: first intracardiac atrial signal. H: His signal. V: first intracardiac ventricular signal).</p