Systematic review and meta-analysis on the impact on outcomes of device algorithms for minimizing right ventricular pacing.

AIMS: Physiological activation of the heart using algorithms to minimize right ventricular pacing (RVPm) may be an effective strategy to reduce adverse events in patients requiring anti-bradycardia therapies. This systematic review and meta-analysis aimed to evaluate current evidence on clinical outcomes for patients treated with RVPm algorithms compared to dual-chamber pacing (DDD). METHODS AND RESULTS: We conducted a systematic search of the PubMed database. The predefined endpoints were the occurrence of persistent/permanent atrial fibrillation (PerAF), cardiovascular (CV) hospitalization, all-cause death, and adverse symptoms. We also aimed to explore the differential effects of algorithms in studies enrolling a high percentage of atrioventricular block (AVB) patients. Eight studies (7229 patients) were included in the analysis. Compared to DDD pacing, patients using RVPm algorithms showed a lower risk of PerAF [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.57-0.97] and CV hospitalization (OR 0.77, 95% CI 0.61-0.97). No significant difference was found for all-cause death (OR 1.01, 95% CI 0.78-1.30) or adverse symptoms (OR 1.03, 95% CI 0.81-1.29). No significant interaction was found between the use of the RVPm strategy and studies enrolling a high percentage of AVB patients. The pooled mean RVP percentage for RVPm algorithms was 7.96% (95% CI 3.13-20.25), as compared with 45.11% (95% CI 26.64-76.38) of DDD pacing. CONCLUSION: Algorithms for RVPm may be effective in reducing the risk of PerAF and CV hospitalization in patients requiring anti-bradycardia therapies, without an increased risk of adverse symptoms. These results are also consistent for studies enrolling a high percentage of AVB patients.

A systematic review and meta-analysis on oncological radiotherapy in patients with a cardiac implantable electronic device: Prevalence and predictors of device malfunction in 3121 patients.

BACKGROUND: The number of patients with cardiac implantable electronic devices (CIEDs) undergoing radiotherapy (RT) for cancer treatment is growing. At present, prevalence and predictors of RT-induced CIEDs malfunctions are not defined. METHODS: Systematic review and meta-analysis conducted following the PRISMA recommendations. PubMed, Scopus and Google Scholar were searched from inception to 31/01/2022 for studies reporting RT-induced malfunctions in CIEDs patients. Aim was to assess the prevalence of RT-induced CIEDs malfunctions and identify potential predictors. RESULTS: Thirty-two out of 3962 records matched the inclusion criteria and were included in the meta-analysis. A total of 135 CIEDs malfunctions were detected among 3121 patients (6.6%, 95% confidence interval [CI]: 5.1%-8.4%). The pooled prevalence increased moving from pacemaker (PM) to implantable cardioverter defibrillator (ICD), and cardiac resynchronization therapy and defibrillator (CRT-D) groups (4.1%, 95% CI: 2.9-5.8; 8.2% 95% CI: 5.9-11.3; and 19.8%, 95% CI: 11.4-32.2 respectively). A higher risk ratio (RR) of malfunctions was found when neutron-producing energies were used as compared to non-neutron-producing energies (RR 9.98, 95% CI: 5.09-19.60) and in patients with ICD/CRT-D as compared to patients with PM/CRT-P (RR 2.07, 95% CI: 1.40-3.06). On the contrary, no association was found between maximal radiation dose at CIED >2 Gy and CIEDs malfunctions (RR 0.93; 95% CI: 0.31-2.76). CONCLUSIONS: Radiotherapy related CIEDs malfunction had a prevalence ranging from 4% to 20%. The use of neutron-producing energies and more complex devices (ICD/CRT-D) were associated with higher risk of device malfunction, while the radiation dose at CIED did not significantly impact on the risk unless higher doses (>10 Gy) were used.

Atrial Fibrillation in the Setting of Acute Pneumonia: Not a Secondary Arrhythmia.

Atrial fibrillation (AF) is the most common arrhythmia in the setting of critically ill patients. Pneumonia, and in particular community-acquired pneumonia, is one of the most common causes of illness and hospital admission worldwide. This article aims to review the association between AF and acute diseases, with specific attention to pneumonia, from the pathophysiology to its clinical significance. Even though the relationship between pneumonia and AF has been known for years, it was once considered a transient bystander. In recent years there has been growing knowledge on the clinical significance of this arrhythmia in acute clinical settings, in which it holds a prognostic role which is not so different as compared to that of the so-called "primary" AF. AF is a distinct entity even in the setting of pneumonia, and acute critical illnesses in general, and it should therefore be managed with a guidelines-oriented approach, including prescription of anticoagulants in patients at thromboembolic risk, always considering patients' individuality. More data on the significance of the arrhythmia in this setting will help clinicians to give patients the best possible care.

Current status of reimbursement practices for remote monitoring of cardiac implantable electrical devices across Europe.

Remote monitoring (RM) of cardiac implantable electrical devices (CIEDs) is currently proposed as a standard of care for CIEDs follow-up, as recommended by major cardiology societies worldwide. By detecting a series of relevant device and patient-related parameters, RM is a valuable option for early detection of CIEDs' technical issues, as well as changes in parameters related to cardio-respiratory functions. Moreover, RM may allow longer spacing between in-office follow-ups and better organization of in-hospital resources. Despite these potential advantages, resulting in improved patient safety, we are still far from a widespread diffusion of RM across Europe. Reimbursement policies across Europe still show an important heterogeneity and have been considered as an important barrier to full implementation of RM as a standard for the follow-up of all the patients with pacemakers, defibrillators, devices for cardiac resynchronization, or implantable loop recorders. Indeed, in many countries, there are still inertia and unresponsiveness to the request for widespread implementation of RM for CIEDs, although an improvement was found in some countries as compared to years ago, related to the provision of some form of reimbursement. As a matter of fact, the COVID-19 pandemic has promoted an increased use of digital health for connecting physicians to patients, even if digital literacy may be a limit for the widespread implementation of telemedicine. CIEDs have the advantage of making possible RM with an already defined organization and reliable systems for data transmissions that can be easily implemented as a standard of care for present and future cardiology practice.

Inhibition of lysyl oxidase stimulates TGF-ß signaling and metalloproteinases-2 and -9 expression and contributes to the disruption of ascending aorta in rats: protection by propylthiouracil.

Mutations in lysyl oxidase (LOX) genes cause severe vascular anomalies in mice and humans. LOX activity can be irreversibly inhibited by the administration of ß-aminoproprionitrile (BAPN). We investigated the mechanisms underlying the damage to the ascending thoracic aorta induced by LOX deficiency and evaluated whether 6-propylthiouracil (PTU) can afford protection in rats. BAPN administration caused disruption of the ascending aortic wall, increased the number of apoptotic cells, stimulated TGF-ß signaling (increase of nuclear p-SMAD2 staining), and up-regulated the expression of metalloproteinases-2 and -9. In BAPN-treated animals, PTU reduced apoptosis, p-SMAD2 staining, MMP-2, and -9 expression, and markedly decreased the damage to the aortic wall. Our results suggest that, as in some heritable vascular diseases, enhanced TGF-ß signaling and upregulation of MMP-2 and -9 can contribute to the pathogenesis of ascending aorta damage caused by LOX deficiency. We have also shown that PTU, a drug already in clinical use, protects against the effects of LOX inhibition. MMP-2 and -9 might be potential targets of new therapeutic strategies for the treatment of vascular diseases caused by LOX deficiency.

Remote monitoring and telemedicine in heart failure: implementation and benefits.

PURPOSE OF REVIEW: Remote monitoring (RM) of cardiac implantable electronic devices (CIEDs) is recommended as part of the individualized multidisciplinary follow-up of heart failure (HF) patients. Aim of this article is to critically review recent findings on RM, highlighting potential benefits and barriers to its implementation. RECENT FINDINGS: Device-based RM is useful in the early detection of CIEDs technical issues and cardiac arrhythmias. Moreover, RM allows the continuous monitoring of several patients' clinical parameters associated with impending HF decompensation, but there is still uncertainty regarding its effectiveness in reducing mortality and hospitalizations. Implementation of RM strategies, together with a proactive physicians' attitude towards clinical actions in response to RM data reception, will make RM a more valuable tool, potentially leading to better outcomes.

What do we do about atrial high rate episodes?

Atrial high rate episodes (AHREs) are defined as asymptomatic atrial tachyarrhythmias detected by cardiac implantable electronic devices with atrial sensing, providing automated continuous monitoring and tracings storage, occurring in subjects with no previous clinical atrial fibrillation (AF) and with no AF detected at conventional electrocardiogram recordings. AHREs are associated with an increased thrombo-embolic risk, which is not negligible, although lower than that of clinical AF. The thrombo-embolic risk increases with increasing burden of AHREs, and moreover, AHREs burden shows a dynamic pattern, with tendency to progression along with time, with potential transition to clinical AF. The clinical management of AHREs, in particular with regard to prophylactic treatment with oral anticoagulants (OACs), remains uncertain and heterogeneous. At present, in patients with confirmed AHREs, as a result of device tracing analysis, an integrated, individual and clinically-guided assessment should be applied, taking into account the patients' risk of stroke (to be reassessed regularly) and the AHREs burden. The use of OACs, preferentially non-vitamin K antagonists OACs, may be justified in selected patients, such as those with longer AHREs durations (in the range of several hours or ≥24 h), with no doubts on AF diagnosis after device tracing analysis and with an estimated high/very high individual risk of stroke, accounting for the anticipated net clinical benefit, and informed patient's preferences. Two randomized clinical trials on this topic are currently ongoing and are likely to better define the role of anticoagulant therapy in patients with AHREs.

Performance of HAS-BLED and DOAC scores to predict major bleeding events in atrial fibrillation patients treated with direct oral anticoagulants: A report from a prospective European observational registry.

BACKGROUND: The DOAC score has been recently proposed for bleeding risk stratification of patients with atrial fibrillation treated with direct oral anticoagulants (DOAC). OBJECTIVE: To compare the performance of HAS-BLED and DOAC score in predicting major bleeding events in a contemporary cohort of European AF patients treated with DOAC. METHODS: We included patients derived from a prospective observational registry of European AF patients. HAS-BLED and DOAC scores were calculated as per the original schemes. Our primary endpoint was major bleeding events. Receiver operating characteristic (ROC) curves were used to compare the predictive ability of the scores. RESULTS: A total of 2834 AF patients (median age [IQR] 69 [62-77] years; 39.6 % female) treated with DOAC were included in the analysis. According to the HAS-BLED score, 577 patients (20.4 %) were categorized as very low risk of bleeding, as compared to 1276 (45.0 %) according to DOAC score. A total of 55 major bleeding events occurred with an overall incidence of 1.04 per 100 patient-years. Both scores showed only a modest ability for the prediction of bleeding events (HAS-BLED area under the curve [AUC], 0.65, 95 % confidence interval [CI] 0.55-0.70; DOAC score AUC 0.62, 95 % CI 0.59-0.71, p for difference = 0.332]. At calibration analysis, the DOAC score showed modest calibration, especially for patients at high risk, when compared to HAS-BLED. CONCLUSION: In a contemporary cohort of DOAC-treated AF patients, both HAS-BLED and DOAC scores only modestly predicted the occurrence of major bleeding events. Our results do not support the preferential use of DOAC score over HAS-BLED.

Cardiac resynchronization therapy (CRT) nonresponders in the contemporary era: A state-of-the-art review.

In the 2000s, cardiac resynchronization therapy (CRT) became a revolutionary treatment for heart failure with reduced left ventricular ejection fraction (HFrEF) and wide QRS. However, about one-third of CRT recipients do not show a favorable response. This review of the current literature aims to better define the concept of CRT response/nonresponse. The diagnosis of CRT nonresponder should be viewed as a continuum, and it cannot rely solely on a single parameter. Moreover, baseline features of some patients might predict an unfavorable response. A strong collaboration between heart failure specialists and electrophysiologists is key to overcoming this challenge with multiple strategies. In the contemporary era, new pacing modalities, such as His-bundle pacing and left bundle branch area pacing, represent a promising alternative to CRT. Observational studies have demonstrated their potential; however, several limitations should be addressed. Large randomized controlled trials are needed to prove their efficacy in HFrEF with electromechanical dyssynchrony.

New Perspectives on Risk Stratification and Treatment in Patients with Atrial Fibrillation: An Analysis of Recent Contributions on the Journal of Cardiovascular Disease and Development.

The medical approach to atrial fibrillation (AF) underwent a paradigm shift over time, evolving from considering AF as a simple arrhythmic phenomenon to a complex nosological entity [...].

Single-lead VDD pacing: a literature review on short-term and long-term performance.

INTRODUCTION: VDD pacing system was introduced more than 30 years ago. Its use is considered by the 2021 European Society of Cardiology guidelines on cardiac pacing as a potential alternative to dual chambers system for patients with atrioventricular block and normal sinus node function. AREAS COVERED: In this article, we performed a narrative review of current literature in order to identify the strengths and weaknesses of this pacing system. VDD system allows the maintenance of AV synchronous pacing and its hemodynamic advantages. Some disadvantages may be related to the non-negligible incidence of atrial undersensing and the possible subsequent need for upgrade to DDD system. On the other hand, shorter implantation time and lower complications rate may be advantages. EXPERT OPINION: In the modern pacing era, VDD pacing system struggles to find its own space. However, it may still be considered as a valuable alternative to a dual-chamber pacemaker for selected patients, in specific clinical scenarios.

Low Occurrence of Infections and Death in a Real-World Cohort of Patients with Cardiac Implantable Electronic Devices.

BACKGROUND: The incidence of infections and death in patients implanted with cardiac implantable electronic devices (CIEDs) is not fully known yet. AIM: To describe the incidence of CIED-related infection and death, and their potential predictors in a contemporary cohort of CIED patients. METHODS: All consecutive patients implanted with a CIED at our institution were prospectively enrolled. Follow-up visits were performed 2 weeks after CIED implantation for all patients, and then every 6 months for implantable cardioverter defibrillator (ICD)/cardiac resynchronization therapy (CRT) patients and every 12 months for pacemaker (PM) patients. The adjudication of CIED-related infections was performed by two independent investigators and potential disagreement was resolved by a senior investigator. RESULTS: Between September 2016 and August 2020, a total of 838 patients were enrolled (34.6% female; median age 77 (69.6-83.6); median PADIT score 2 (2-4)). PMs were implanted in 569 (68%) patients and ICD/CRT in 269 (32%) patients. All patients had pre-implant antibiotic prophylaxis and 5.5% had an antibiotic-eluting envelope. Follow-up data were available for 832 (99.2%) patients. After a median follow-up of 42.3 (30.2-56.4) months, five (0.6%) patients had a CIED-related infection and 212 (25.5%) patients died. Using multivariate Cox regression analysis, end-stage chronic kidney disease (CKD) requiring dialysis and therapy with corticosteroids was independently associated with a higher risk of infection (hazard ratio (HR): 14.20; 95% confidence interval (CI) 1.48-136.62 and HR: 14.71; 95% CI 1.53-141.53, respectively). Age (HR: 1.07; 95% CI 1.05-1.09), end-stage CKD requiring dialysis (HR: 6.13; 95% CI 3.38-11.13) and history of atrial fibrillation (HR: 1.47; 95% CI 1.12-1.94) were independently associated with all-cause death. CONCLUSIONS: In a contemporary cohort of CIED patients, mortality was substantially high and associated with clinical factors depicting a population at risk. On the other hand, the incidence of CIED-related infections was low.

Drug management of atrial fibrillation in light of guidelines and current evidence: an Italian Survey on behalf of Italian Association of Arrhythmology and Cardiac Pacing.

AIM: Atrial fibrillation is a multifaceted disease requiring personalized treatment, in accordance with current ESC guidelines. Despite a wide range of literature, we still have various aspects dividing the opinion of the experts in rate control, rhythm control and thromboembolic prophylaxis. The aim of this survey was to provide a country-wide picture of current practice regarding atrial fibrillation pharmacological management according to a patient's characteristics. METHODS: Data were collected using an in-person survey that was administered to members of the Italian Association of Arrhythmology and Cardiac Pacing. RESULTS: We collected data from 106 physicians, working in 72 Italian hospitals from 15 of 21 regions. Our work evidenced a high inhomogeneity in atrial fibrillation management regarding rhythm control, rate control and thromboembolic prophylaxis in both acute and chronic patients. This element was more pronounced in settings in which literature shows a lack of evidence and, consequently, the indications provided by the guidelines are weak or absent. CONCLUSION: This National survey evidenced a high inhomogeneity in current approaches adopted for atrial fibrillation management by a sample of Italian cardiologist experts in arrhythmia management. Further studies are needed to explore if these divergences are associated with different long-term outcomes.

Yield of diagnosis and risk of stroke with screening strategies for atrial fibrillation: a comprehensive review of current evidence.

Atrial fibrillation (AF) is the most prevalent arrhythmia worldwide. The presence of AF is associated with increased risk of systemic thromboembolism, but with the uptake of oral anticoagulant (OAC) and implementation of a holistic and integrated care management, this risk is substantially reduced. The diagnosis of AF requires a 30-s-long electrocardiographic (ECG) trace, irrespective of the presence of symptoms, which may represent the main indication for an ECG tracing. However, almost half patients are asymptomatic at the time of incidental AF diagnosis, with similar risk of stroke of those with clinical AF. This has led to a crucial role of screening for AF, to increase the diagnosis of population at risk of clinical events. The aim of this review is to give a comprehensive overview about the epidemiology of asymptomatic AF, the different screening technologies, the yield of diagnosis in asymptomatic population, and the benefit derived from screening in terms of reduction of clinical adverse events, such as stroke, cardiovascular, and all-cause death. We aim to underline the importance of implementing AF screening programmes and reporting about the debate between scientific societies' clinical guidelines recommendations and the concerns expressed by the regulatory authorities, which still do not recommend population-wide screening. This review summarizes data on the ongoing trials specifically designed to investigate the benefit of screening in terms of risk of adverse events which will further elucidate the importance of screening in reducing risk of outcomes and influence and inform clinical practice in the next future.

The search for a gold standard to clinically diagnose and monitor atrial cardiomyopathy.

INVITED EDITORIAL COMMENTING ON: Tufano A, Lancellotti P. "Atrial cardiomyopathy: Pathophysiology and clinical implications". Eur J Intern Med. 2022 Mar 11:S0953-6205(22)00097-8. doi: 10.1016/j.ejim.2022.03.007. Epub ahead of print. PMID: 35288030.

Comparing atrial fibrillation guidelines: Focus on stroke prevention, bleeding risk assessment and oral anticoagulant recommendations.

Clinical practice in atrial fibrillation (AF) patient management is constantly evolving. In the past 3 years, various new AF guidelines or focused updates have been published, given this rapidly evolving field. In 2019, the American College of Cardiology/American Heart Association published a focused update of the 2014 guidelines. In 2020, both the European Society of Cardiology and the Canadian Cardiovascular Society released their new guidelines. Finally, the most recent guidelines were those published in 2021 by the Asian Pacific Heart Rhythm Society, which updates their 2017 version and the 2021 National Institute for Health and Care Excellence (NICE) guidelines. In the present narrative review, we compare these guidelines, emphasizing similarities and differences in the following mainstay elements of patient care: thromboembolic risk assessment, oral anticoagulants (OACs) prescription, bleeding risk evaluation, and integrated patient management. A formal evaluation of baseline thromboembolic and bleeding risks and their reassessment during follow-up is evenly recommended, although some differences in using risk stratification scores. OACs prescription is highly encouraged where appropriate, and prescription algorithms are broadly similar. The importance of an integrated and multidisciplinary approach to patient care is emerging, aiming to address several different aspects of a multifaceted disease.

Clinical Profile, Arrhythmias, and Adverse Cardiac Outcomes in Emery-Dreifuss Muscular Dystrophies: A Systematic Review of the Literature.

Cardiolaminopathies are a heterogeneous group of disorders which are due to mutations in the genes encoding for nuclear lamins or their binding proteins. The whole spectrum of cardiac manifestations encompasses atrial arrhythmias, conduction disturbances, progressive systolic dysfunction, and malignant ventricular arrhythmias. Despite the prognostic significance of cardiac involvement in this setting, the current recommendations lack strong evidence. The aim of our work was to systematically review the current data on the main cardiovascular outcomes in cardiolaminopathies. We searched PubMed/Embase for studies focusing on cardiovascular outcomes in LMNA mutation carriers (atrial arrhythmias, ventricular arrhythmias, sudden cardiac death, conduction disturbances, thromboembolic events, systolic dysfunction, heart transplantation, and all-cause and cardiovascular mortality). In total, 11 studies were included (1070 patients, mean age between 26-45 years, with follow-up periods ranging from 2.5 years up to 45 ± 12). When available, data on the EMD-mutated population were separately reported (40 patients). The incidence rates (IR) were individually assessed for the outcomes of interest. The IR for atrial fibrillation/atrial flutter/atrial tachycardia ranged between 6.1 and 13.9 events/100 pts-year. The IR of atrial standstill ranged between 0 and 2 events/100 pts-year. The IR for malignant ventricular arrhythmias reached 10.2 events/100 pts-year and 15.6 events/100 pts-year for appropriate implantable cardioverter-defibrillator (ICD) interventions. The IR for advanced conduction disturbances ranged between 3.2 and 7.7 events/100 pts-year. The IR of thromboembolic events reached up to 8.9 events/100 pts-year. Our results strengthen the need for periodic cardiological evaluation focusing on the early recognition of atrial arrhythmias, and possibly for the choice of preventive strategies for thromboembolic events. The frequent need for cardiac pacing due to advanced conduction disturbances should be counterbalanced with the high risk of malignant ventricular arrhythmias that would justify ICD over pacemaker implantation.

Mobile health technology in atrial fibrillation.

INTRODUCTION: Mobile health (mHealth) solutions in atrial fibrillation (AF) are becoming widespread, thanks to everyday life devices, such as smartphones. Their use is validated both in monitoring and in screening scenarios. In the published literature, the diagnostic accuracy of mHealth solutions wide differs, and their current clinical use is not well established in principal guidelines. AREAS COVERED: mHealth solutions have progressively built an AF-detection chain to guide patients from the device's alert signal to the health-care practitioners' (HCPs) attention. This review aims to critically evaluate the latest evidence regarding mHealth devices and the future possible patient's uses in everyday life. EXPERT OPINION: The patients are the first to be informed of the rhythm anomaly, leading to the urgency of increasing the patients' AF self-management. Furthermore, HCPs need to update themselves about mHealth devices use in clinical practice. Nevertheless, these are promising instruments in specific populations, such as post-stroke patients, to promote an early arrhythmia diagnosis in the post-ablation/cardioversion period, allowing checks on the efficacy of the treatment or intervention.

Atrial High-Rate Episodes Detected by Cardiac Implantable Electronic Devices: Dynamic Changes in Episodes and Predictors of Incident Atrial Fibrillation.

BACKGROUND: Atrial high rate episodes (AHRE) detected by cardiac implantable electronic devices (CIEDs) may be associated with a risk of progression towards long-lasting episodes (≥24 h) and clinical atrial fibrillation (AF). METHODS: Consecutive CIED patients presenting AHRE (with confirmation of an arrhythmia lasting 5 min-23 h 59 min, atrial rate ≥175/min, with no AF at 12-lead ECG and no prior clinical AF) were retrospectively enrolled. The aims of this study were to describe patients' characteristics and the incidence of adverse events, and second, to identify potential predictors of the composite outcome of clinical AF and/or AHRE episodes lasting ≥24 h. RESULTS: 104/107 (97.2%) patients (median age 79.7 (74.0-84.2), 33.7% female) had available follow-up data. Over a median follow-up of 24.3 (10.6-40.3) months, 31/104 (29.8%) patients experienced the composite outcome of clinical AF or AHRE episodes lasting ≥24 h. Baseline CHA2DS2-VASc score and the longest AHRE episode at enrollment lasting 12 h-23 h 59 min were independently associated with the composite outcome (Hazard ratio (HR); 95% CI: 1.40; 1.07-1.83 and HR: 8.15; 95% CI 2.32-28.65, respectively). Baseline CHA2DS2-VASc score and the longest AHRE episode at enrollment lasting 12 h-23 h 59 min were the only independent predictors of incident clinical AF (HR: 1.45; 95% CI 1.06-2.00 and HR: 4.25; 95% CI 1.05-17.20, respectively). CONCLUSIONS: In patients with AHRE, the incidence of clinical AF or AHRE episodes lasting ≥24 h is high in a two-year follow-up. Baseline patients' characteristics (CHA2DS2-VASc score) and AHRE duration may help to intensify monitoring and decision-making, being independently associated with clinical AF at follow-up.