Diagnostic Yield and Clinical Implications of Implantable Loop Recorders in Patients with Syncope in Germany: A National Database Analysis.

In patients with unexplained syncope, implantable loop recorders (ILR) are used to detect arrhythmias as a cause of syncope. This study aimed to assess the diagnostic yield and clinical implications arising from ILR implantation in patients with syncope in Germany. Secondary longitudinal data were obtained from a large German research database including anonymized data from nationwide statutory health insurances, representative for the German population. Patients ≥ 18 years with a diagnosis of syncope and ILR implantation between 2017 and 2018 were analyzed, and cardiac diagnoses and therapies during a follow-up period of two years assessed. Of 2,403,301 continuously insured persons in 2017-2018, 1360 (0.1%) received an ILR and 675 patients (45.6% female) were included. During follow-up, arrhythmias were diagnosed in 65.0%. The following antiarrhythmic therapies were established: pacemaker and defibrillator implantations in 20% and 1.5%, respectively, ablation therapy in 3.0%, and antiarrhythmic drug therapy in 4.7%. Aside from the diagnoses typically associated with syncope, atrial fibrillation or flutter was diagnosed in 37.0%, and anticoagulation therapy was initiated in 21.5%. There was a high diagnostic yield of arrhythmias following ILR implantation, leading to a relevant number of syncope-specific treatment. Arrhythmias not necessarily related to syncope were also diagnosed, leading to a high rate of anticoagulation therapy.

Accuracy and comprehensibility of chat-based artificial intelligence for patient information on atrial fibrillation and cardiac implantable electronic devices.

AIMS: Natural language processing chatbots (NLPC) can be used to gather information for medical content. However, these tools contain a potential risk of misinformation. This study aims to evaluate different aspects of responses given by different NLPCs on questions about atrial fibrillation (AF) and clinical implantable electronic devices (CIED). METHODS AND RESULTS: Questions were entered into three different NLPC interfaces. Responses were evaluated with regard to appropriateness, comprehensibility, appearance of confabulation, absence of relevant content, and recommendations given for clinically relevant decisions. Moreover, readability was assessed by calculating word count and Flesch Reading Ease score. 52, 60, and 84% of responses on AF and 16, 72, and 88% on CIEDs were evaluated to be appropriate for all responses given by Google Bard, (GB) Bing Chat (BC) and ChatGPT Plus (CGP), respectively. Assessment of comprehensibility showed that 96, 88, and 92% of responses on AF and 92 and 88%, and 100% on CIEDs were comprehensible for all responses created by GB, BC, and CGP, respectively. Readability varied between different NLPCs. Relevant aspects were missing in 52% (GB), 60% (BC), and 24% (CGP) for AF, and in 92% (GB), 88% (BC), and 52% (CGP) for CIEDs. CONCLUSION: Responses generated by an NLPC are mostly easy to understand with varying readability between the different NLPCs. The appropriateness of responses is limited and varies between different NLPCs. Important aspects are often missed to be mentioned. Thus, chatbots should be used with caution to gather medical information about cardiac arrhythmias and devices.

Changes in eligibility for a subcutaneous cardioverter-defibrillator after implantation of a left ventricular assist device-A prospective analysis.

BACKGROUND: The number of left ventricular assist devices (LVADs) implanted in patients with end-stage heart failure is increasing. In this patient cohort, subcutaneous implantable cardioverter defibrillators (S-ICDs) could be a promising alternative to transvenous ICDs due to lower infection rates and avoidance of venous access. However, eligibility for the S-ICD depends on ECG features that may be influenced by an LVAD. The aim of the present study was a prospective evaluation of S-ICD eligibility before and after LVAD implantation. METHODS: The study recruited all patients presenting at Hannover Medical School for LVAD implantation between 2016 and 2020. S-ICD eligibility was evaluated using the ECG-based and the device-based S-ICD screening test before and after LVAD implantation. RESULTS: Twenty-two patients (57.3 ± 8.7 years of age, 95.5% male) were included in the analysis. The most common underlying diseases were dilated cardiomyopathy (n = 16, 72.7%) and ischemic cardiomyopathy (n = 5, 22.7%). Before LVAD implantation 16 patients were found eligible for the S-ICD according to both screening tests (72.7%), but only 7 patients were eligible after LVAD, 31.8%; p = 0.05). Oversensing due to electromagnetic interference was observed in 6 patients (66.6%) found ineligible for S-ICD after LVAD implantation. A lower S wave amplitude in leads I (p = 0.009), II (p = 0.006) and aVF (p = 0.006) before LVAD implantation was associated with higher rate of S-ICD ineligibility after LVAD implantation. CONCLUSION: LVAD implantation can impair S-ICD eligibility. Patients with lower S wave amplitude in leads I, II and aVF were more likely to be ineligible for S-ICD implantation after LVAD implantation. Thus, S-ICD therapy should be carefully considered in patients who are candidates for LVAD therapy.

Acute echocardiographic and electrocardiographic effects of triggered left ventricular pacing.

Cardiac resynchronization therapy (CRT) is an essential pillar in the therapy of heart failure patients with reduced ejection fraction (HFrEF) presenting with broad left bundle branch block (LBBB) or pacemaker dependency. To achieve beneficial effects, CRT requires high bi-ventricular (BiV) pacing rates. Therefore, device-manufacturers designed pacing algorithms which maintain high BiV pacing rates by a left ventricular (LV) pacing stimulus immediately following a right ventricular sensed beat. However, data on clinical impact of these algorithms are sparse. We studied 17 patients implanted with a CRT device providing triggered left ventricular pacing (tLVp) in case of atrioventricular nodal conduction. Assessment of LV dyssynchrony was performed using echocardiographic and electrocardiographic examination while CRT-devices were set to three different settings: 1. Optimized bi-ventricular-stimulation (BiV); 2. Physiological AV nodal conduction (tLVp-off); 3. Physiological AV nodal conduction and tLVp-algorithm turned on (tLVp-on). QRS duration increased when the CRT-device was set to tLVp-off compared to BiV-Stim, while QRS duration was comparable to BiV-Stim with the tLVp-on setting. Echocardiographic analysis revealed higher dyssynchrony during tLVp-off compared to BiV-Stim. TLVp-on did not improve LV dyssynchrony compared to tLVp-off. QRS duration significantly decreased using tLVp-algorithms compared to physiological AV nodal conduction. However, echocardiographic examination could not show functional benefit from tLVp-algorithms, suggesting that these algorithms are inferior to regular biventricular pacing regarding cardiac resynchronization. Therefore, medical treatment and ablation procedures should be preferred, when biventricular pacing rates have to be increased. TLVp-algorithms can be used in addition to these treatment options.

Cardiac Rhythm Monitoring Using Wearables for Clinical Guidance before and after Catheter Ablation.

Mobile health technologies are gaining importance in clinical decision-making. With the capability to monitor the patient's heart rhythm, they have the potential to reduce the time to confirm a diagnosis and therefore are useful in patients eligible for screening of atrial fibrillation as well as in patients with symptoms without documented symptom rhythm correlation. Such is crucial to enable an adequate arrhythmia management including the possibility of a catheter ablation. After ablation, wearables can help to search for recurrences, in symptomatic as well as in asymptomatic patients. Furthermore, those devices can be used to search for concomitant arrhythmias and have the potential to help improving the short- and long-term patient management. The type of wearable as well as the adequate technology has to be chosen carefully for every situation and every individual patient, keeping different aspects in mind. This review aims to describe and to elaborate a potential workflow for the role of wearables for cardiac rhythm monitoring regarding detection and management of arrhythmias before and after cardiac electrophysiological procedures.

Delayed Improvement of Left Ventricular Function in Newly Diagnosed Heart Failure Depends on Etiology-A PROLONG-II Substudy.

In patients with newly diagnosed heart failure with reduced ejection fraction (HFrEF), three months of optimal therapy are recommended before considering a primary preventive implantable cardioverter-defibrillator (ICD). It is unclear which patients benefit from a prolonged waiting period under protection of the wearable cardioverter-defibrillator (WCD) to avoid unnecessary ICD implantations. This study included all patients receiving a WCD for newly diagnosed HFrEF (n = 353) at our center between 2012 and 2017. Median follow-up was 2.7 years. From baseline until three months, LVEF improved in patients with all peripartum cardiomyopathy (PPCM), myocarditis, dilated cardiomyopathy (DCM), or ischemic cardiomyopathy (ICM). Beyond this time, LVEF improved in PPCM and DCM only (10 ± 8% and 10 ± 12%, respectively), whereas patients with ICM showed no further improvement. The patients with newly diagnosed HFrEF were compared to 29 patients with a distinct WCD indication, which is an explantation of an infected ICD. This latter group had a higher incidence of WCD shocks and poorer overall survival. All-cause mortality should be considered when deciding on WCD prescription. In patients with newly diagnosed HFrEF, the potential for delayed LVEF recovery should be considered when timing ICD implantation, especially in patients with PPCM and DCM.

Feasibility and First Results of Heart Failure Monitoring Using the Wearable Cardioverter-Defibrillator in Newly Diagnosed Heart Failure with Reduced Ejection Fraction.

The wearable cardioverter-defibrillator (WCD) is used in patients with newly diagnosed heart failure and reduced ejection fraction (HFrEF). In addition to arrhythmic events, the WCD provides near-continuous telemetric heart failure monitoring. The purpose of this study was to evaluate the clinical relevance of additionally recorded parameters, such as heart rate or step count. We included patients with newly diagnosed HFrEF prescribed with a WCD. Via the WCD, step count and heart rate were acquired, and an approximate for heart rate variability (HRV5) was calculated. Multivariate analysis was performed to analyze predictors for an improvement in left ventricular ejection fraction (LVEF). Two hundred and seventy-six patients (31.9% female) were included. Mean LVEF was 25.3 ± 8.5%. Between the first and last seven days of usage, median heart rate fell significantly (p < 0.001), while median step count and HRV5 significantly increased (p < 0.001). In a multivariate analysis, a delta of HRV5 > 23 ms was an independent predictor for LVEF improvement of ≥10% between prescription and 3-month follow-up. Patients with newly diagnosed HFrEF showed significant changes in heart rate, step count, and HRV5 between the beginning and end of WCD prescription time. HRV5 was an independent predictor for LVEF improvement and could serve as an early indicator of treatment response.

Extended follow-up after wearable cardioverter-defibrillator period: the PROLONG-II study.

AIM: The wearable cardioverter-defibrillator (WCD) is used for temporary protection from sudden cardiac death (SCD) in patients with newly diagnosed heart failure with reduced ejection fraction before considering an implantable cardioverter-defibrillator (ICD). However, the prognostic significance of the WCD remains controversial due to conflicting evidence. The aim of the present study was to evaluate prognosis of patients receiving life-saving WCD shocks. METHODS AND RESULTS: All patients receiving a WCD at Hannover Medical School for heart failure with reduced ejection fraction between 2012 and 2017 were included. Data were acquired at baseline, at 3 months and at last available follow-up (FU). Three hundred and fifty-three patients were included (69% male; age 56 ± 15 years; left ventricular ejection fraction 25 ± 8%). FU after the WCD was 2.8 ± 1.5 years with a maximum of 6.8 years. Daily WCD wear time was 22 ± 4 h. Fourteen patients (4%) received appropriate WCD shocks. Two patients (0.6%) died during the WCD period. Thirty patients (9%) died during extended FU. Mean estimated survival after the WCD was similar between patients with and without WCD shocks. Patients without an ICD recommendation after WCD prescription did not experience SCD during FU. CONCLUSIONS: Patients with WCD shocks showed a favourable survival. Patients without an ICD recommendation after WCD prescription had no SCD during FU. These findings support the practice of careful risk stratification before considering an ICD and the use of the WCD for temporary protection from SCD.

A Novel SCN5A Variant Causes Temperature-Sensitive Loss Of Function in a Family with Symptomatic Brugada Syndrome, Cardiac Conduction Disease, and Sick Sinus Syndrome.

INTRODUCTION: Brugada syndrome (BrS) is an inherited arrhythmia syndrome associated with an increased risk of sudden cardiac death. SCN5A is the most important disease-modifying gene for BrS, but many SCN5A variants have not been functionally characterized. Furthermore, the temperature dependency of SCN5A is only rarely explored in in vitro analyses. METHODS: The clinical phenotype of the affected family was assessed by medical history, ECGs and ajmaline challenge. Whole-cell patch clamp recordings were performed on HEK 293T cells expressing Nav1.5-G1712S, a novel SCN5A variant found in the symptomatic family. RESULTS: Three male family members had experienced sudden cardiac death, sudden cardiac arrest, and rhythmogenic syncopes. Beside a positive ajmaline challenge with demarcation of a Brugada type 1 ECG, 1 patient also showed evidence of symptomatic cardiac conduction disease and sick sinus syndrome (SSS). In patch clamp analyses, Nav1.5-G1712S generated reduced peak currents as compared to the wild type. At body temperature, Nav1.5-G1712S additionally exhibited an enhanced slow inactivation and an impaired recovery from inactivation. CONCLUSION: We conclude that G1712S is a pathogenic SCN5A loss-of function mutation at physiological temperature associated with an overlapping presentation of BrS, SSS, and cardiac conduction disease.

Leadless pacemakers in critically ill patients requiring prolonged cardiac pacing: A multicenter international study.

BACKGROUND: Temporary transvenous pacing in critically ill patients requiring prolonged cardiac pacing is associated with a high risk of complications. We sought to evaluate the safety and efficacy of self-contained intracardiac leadless pacemaker (LPM) implantation in this population. METHODS AND RESULTS: Consecutive patients implanted with a Micra LPM during the hospitalization in an intensive care unit were retrospectively included. Inclusion criteria were: more than or equal to 1 supracaval central venous line, or a ventilation tube, or intravenous antibiotic therapy for ongoing sepsis or bacteremia. Patients with a history of the previous implantation of a pacemaker were excluded. Out of 1016 patients implanted with an LPM, 99 met the inclusion criteria. Mean age was 75 years and Charlson comorbidity index 7. LPM implantation was successfully performed in 98% of cases, with a perioperative complication rate of 5%, mainly cardiac injuries. In-hospital mortality rate was 6%. No late (>30 days) device-related complication occurred, especially no infection. CONCLUSIONS: LPM appears as an acceptable alternative to conventional temporary transvenous pacing in selected critically ill patients requiring prolonged cardiac pacing, especially regarding the risk of infection.

A Primary Prevention Clinical Risk Score Model for Patients With Brugada Syndrome (BRUGADA-RISK).

OBJECTIVES: The goal of this study was to develop a risk score model for patients with Brugada syndrome (BrS). BACKGROUND: Risk stratification in BrS is a significant challenge due to the low event rates and conflicting evidence. METHODS: A multicenter international cohort of patients with BrS and no previous cardiac arrest was used to evaluate the role of 16 proposed clinical or electrocardiogram (ECG) markers in predicting ventricular arrhythmias (VAs)/sudden cardiac death (SCD) during follow-up. Predictive markers were incorporated into a risk score model, and this model was validated by using out-of-sample cross-validation. RESULTS: A total of 1,110 patients with BrS from 16 centers in 8 countries were included (mean age 51.8 ± 13.6 years; 71.8% male). Median follow-up was 5.33 years; 114 patients had VA/SCD (10.3%) with an annual event rate of 1.5%. Of the 16 proposed risk factors, probable arrhythmia-related syncope (hazard ratio [HR]: 3.71; p < 0.001), spontaneous type 1 ECG (HR: 3.80; p < 0.001), early repolarization (HR: 3.42; p < 0.001), and a type 1 Brugada ECG pattern in peripheral leads (HR: 2.33; p < 0.001) were associated with a higher risk of VA/SCD. A risk score model incorporating these factors revealed a sensitivity of 71.2% (95% confidence interval: 61.5% to 84.6%) and a specificity of 80.2% (95% confidence interval: 75.7% to 82.3%) in predicting VA/SCD at 5 years. Calibration plots showed a mean prediction error of 1.2%. The model was effectively validated by using out-of-sample cross-validation according to country. CONCLUSIONS: This multicenter study identified 4 risk factors for VA/SCD in a primary prevention BrS population. A risk score model was generated to quantify risk of VA/SCD in BrS and inform implantable cardioverter-defibrillator prescription.

When two hearts do not beat as one - An unusual cause of pacemaker related tachycardia.

We describe an unusual cause of intermittent rapid ventricular paced rhythm in a patient implanted with a dual chamber pacemaker due to sinus node dysfunction after heart transplantation. During implantation of the pacemaker lead measurements were reported normal, atrial sensing was not documented because of sinus arrest. After implantation the patient complained about intermittent palpitations. Via pacemaker interrogation we could demonstrate electrical isolation of the atrial lead, which was implanted in the donor's atrial myocardium. This led to intermittent pacemaker related tachycardia and AV-dissociation. This case report highlights the difficulty of atrial lead placement in heart transplanted patients using the biatrial surgical technique.

Electrocardiographic changes after implantation of a left ventricular assist device - Potential implications for subcutaneous defibrillator therapy.

BACKGROUND: Implantation of a left ventricular assist device (LVAD) leads to a diverse spectrum of changes on the twelve-lead surface electrocardiogram (ECG). We aimed to elucidate the changes of the surface ECG in patients after LVAD implantation potentially impacting ECG based screening tests of subcutaneous implantable cardioverter-defibrillators (S-ICD). METHODS: Patients from 2005 until 2017 with a documented twelve-lead ECG before and after LVAD implantation were included. Baseline parameters were obtained through hospital records. The twelve-lead ECGs registered before and after LVAD implantation were analyzed. RESULTS: From 415 patients undergoing an LVAD implantation, complete datasets were available for 253 patients. 216 patients (85%) were male. Mean age at time of LVAD implantation was 54.7 ±â€¯12.4 years. The underlying etiology was ischemic cardiomyopathy in 119 (47%), dilated cardiomyopathy in 112 (44%), myocarditis in 8 (3%) and other in 14 (6%). We observed a reduction in the amplitude of the R wave in lead I (p < 0.0001), lead II (p < 0.0001), lead III (p < 0.004), lead aVL (p < 0.001) and lead aVF (p < 0.0001) as well as of the S wave in lead III (p < 0.001) and lead aVR (p < 0.0001) after LVAD implantation. We also noticed a reduction of the R:T ratio in lead I (p < 0.0001) as well as in lead II (p = 0.100) and lead aVF (p = 0.292) although statistically non-significant. CONCLUSION: LVAD implantation leads to significant alterations of the surface ECG, especially the R:T ratio in leads I, II and aVF. These leads correlate with the vectors of the ECG based S-ICD screening test. Thus, these ECG changes may impact the continuous eligibility for subcutaneous ICD therapy in patients after LVAD implantation.

Polymorphonuclear neutrophils and granulocytic myeloid-derived suppressor cells inhibit natural killer cell activity toward Aspergillus fumigatus.

Invasive aspergillosis is a devastating infectious disease in immunocompromised patients. Besides neutrophils and macrophages, natural killer (NK) cells have recently emerged as important players in immunity to this infection. It was shown that NK cells comprise an essential role in the clearance of Aspergillus fumigatus (A. fumigatus) in neutropenic but not in nonneutropenic mice. However, the antifungal activity of NK cells and their regulation have not been fully characterized. In this study, we investigated the interplay between polymorphonuclear neutrophils (PMNs) or granulocyte myeloid-derived suppressor cells (Gr-MDSCs) with NK cells. Both cell types exhibited an equal inhibitory effect on NK cell activation through downregulation of NKp30 expression on the cell surface and cytotoxicity towards the cell line K562. Furthermore, we showed that NK cell activation and antifungal cytotoxicity were impaired when NK cells had been cultured in the presence of PMNs or Gr-MDSCs before fungal stimulation. Besides the reduced cytotoxicity a decreased release of interferon gamma (IFNγ), a key player in the clearance of an A. fumigatus infection, was observed. Thus, inhibition of NK cell activity by PMNs or Gr-MDSCs might impair an effective anti-fungal immune response during recovery from conditions such as hematopoietic stem cell transplantation.