Detection of subclinical atrial fibrillation with cardiac implanted electronic devices: What decision making on anticoagulation after the NOAH and ARTESiA trials?

Atrial fibrillation (AF) may be asymptomatic and the extensive monitoring capabilities of cardiac implantable electronic devices (CIEDs) revealed asymptomatic atrial tachi-arrhythmias of short duration (minutes-hours) occurring in patients with no prior history of AF and without AF detection at a conventional surface ECG. Both the terms "AHRE" (Atrial High-Rate Episodes) and subclinical AF were used in a series of prior studies, that evidenced the association with an increased risk of stroke. Two randomized controlled studies were planned in order to assess the risk-benefit profile of anticoagulation in patients with AHRE/subclinical AF: the NOAH and ARTESiA trials. The results of these two trials (6548 patients enrolled, overall) show that the risk of stroke/systemic embolism associated with AHRE/subclinical AF is in the range of 1-1.2 % per patient-year, but with an important proportion of severe/fatal strokes occurring in non-anticoagulated patients. The apparent discordance between ARTESiA and NOAH results may be approached by considering the related study-level meta-analysis, which highlights a consistent reduction of ischemic stroke with oral anticoagulants vs. aspirin/placebo (relative risk [RR] 0.68, 95 % CI 0.50-0.92). Oral anticoagulation was found to increase major bleeding (RR 1.62, 95 % CI 1.05-2.5), but no difference was found in fatal bleeding (RR 0.79, 95 % CI 0.37-1.69). Additionally, no difference was found in cardiovascular death or all-cause mortality. Taking into account these results, clinical decision-making for patients with AHRE/subclinical AF at risk of stroke, according to CHA2DS2-VASc, can now be evidence-based, considering the benefits and related risks of oral anticoagulants, to be shared with appropriately informed patients.

Clinical decisions for appropriate management of patients with atrial fibrillation.

The management of patients with atrial fibrillation (AF) requires intricate clinical decision-making to optimize outcomes. In everyday clinical practice, physicians undergo difficult choices to better manage patients with AF. They need to balance thromboembolic and bleeding risk to focus on patients' symptoms and to manage a variety of multiple comorbidities. In this review, we aimed to explore the multifaceted dimensions of clinical decision-making in AF patients, encompassing the definition and diagnosis of clinical AF, stroke risk stratification, oral anticoagulant therapy selection, consideration of bleeding risk, and the ongoing debate between rhythm and rate control strategies. We will also focus on possible grey zones for the management of AF patients. In navigating this intricate landscape, clinicians must reconcile the dynamic interplay of patient-specific factors, evolving guidelines, and emerging therapies. The review underscores the need for personalized, evidence-based clinical decision-making to tailor interventions for optimal outcomes according to specific AF patient profiles.

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.

Asymptomatic vs. symptomatic atrial fibrillation: Clinical outcomes in heart failure patients.

BACKGROUND: The outcome implications of asymptomatic vs. symptomatic atrial fibrillation (AF) in specific groups of patients according to clinical heart failure (HF) and left ventricular ejection fraction (LVEF) need to be clarified. METHODS: In a prospective observational study, patients were categorized according to overt HF with LVEF≤40 %, or with LVEF>40 %, or without overt HF with LVEF40 %≤ or > 40 %, as well as according to the presence of asymptomatic or symptomatic AF. RESULTS: A total of 8096 patients, divided into 8 groups according to HF and LVEF, were included with similar proportions of asymptomatic AF (ranging from 43 to 48 %). After a median follow-up of 730 [699 -748] days, the composite outcome (all-cause death and MACE) was significantly worse for patients with asymptomatic AF associated with HF and reduced LVEF vs. symptomatic AF patients of the same group (p = 0.004). On adjusted Cox regression analysis, asymptomatic AF patients with HF and reduced LVEF were independently associated with a higher risk for the composite outcome (aHR 1.32, 95 % CI 1.04-1.69) and all-cause death (aHR 1.33, 95 % CI 1.02-1.73) compared to symptomatic AF patients with HF and reduced LVEF. Kaplan-Meier curves showed that HF-LVEF≤40 % asymptomatic patients had the highest cumulative incidence of all-cause death and MACE (p < 0.001 for both). CONCLUSIONS: In a large European cohort of AF patients, the risk of the composite outcome at 2 years was not different between asymptomatic and symptomatic AF in the whole cohort but adverse implications for poor outcomes were found for asymptomatic AF in HF with LVEF≤40 %.

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.

Atrial fibrillation in vascular surgery: a systematic review and meta-analysis on prevalence, incidence and outcome implications.

AIMS: To know the prevalence of atrial fibrillation (AF), as well as the incidence of postoperative AF (POAF) in vascular surgery for arterial diseases and its outcome implications. METHODS: We performed a systematic review and meta-analysis following the PRISMA statement. RESULTS: After the selection process, we analyzed 44 records (30 for the prevalence of AF history and 14 for the incidence of POAF).The prevalence of history of AF was 11.5% [95% confidence interval (CI) 1-13.3] with high heterogeneity (I2 = 100%). Prevalence was higher in the case of endovascular procedures. History of AF was associated with a worse outcome in terms of in-hospital death [odds ratio (OR) 3.29; 95% CI 2.66-4.06; P < 0.0001; I2 94%] or stroke (OR 1.61; 95% CI 1.39-1.86; P < 0.0001; I2 91%).The pooled incidence of POAF was 3.6% (95% CI 2-6.4) with high heterogeneity (I2 = 100%). POAF risk was associated with older age (mean difference 4.67 years, 95% CI 2.38-6.96; P = 0.00007). The risk of POAF was lower in patients treated with endovascular procedures as compared with an open surgical procedure (OR 0.35; 95% CI 0.13-0.91; P = 0.03; I2 = 61%). CONCLUSIONS: In the setting of vascular surgery for arterial diseases a history of AF is found overall in 11.5% of patients, more frequently in the case of endovascular procedures, and is associated with worse outcomes in terms of short-term mortality and stroke.The incidence of POAF is overall 3.6%, and is lower in patients treated with an endovascular procedure as compared with open surgery procedures. The need for oral anticoagulants for preventing AF-related stroke should be evaluated with randomized clinical trials.

Quantification of Myocardial Contraction Fraction with Three-Dimensional Automated, Machine-Learning-Based Left-Heart-Chamber Metrics: Diagnostic Utility in Hypertrophic Phenotypes and Normal Ejection Fraction.

Aims: The differentiation of left ventricular (LV) hypertrophic phenotypes is challenging in patients with normal ejection fraction (EF). The myocardial contraction fraction (MCF) is a simple dimensionless index useful for specifically identifying cardiac amyloidosis (CA) and hypertrophic cardiomyopathy (HCM) when calculated by cardiac magnetic resonance. The purpose of this study was to evaluate the value of MCF measured by three-dimensional automated, machine-learning-based LV chamber metrics (dynamic heart model [DHM]) for the discrimination of different forms of hypertrophic phenotypes. Methods and Results: We analyzed the DHM LV metrics of patients with CA (n = 10), hypertrophic cardiomyopathy (HCM, n = 36), isolated hypertension (IH, n = 87), and 54 healthy controls. MCF was calculated by dividing LV stroke volume by LV myocardial volume. Compared with controls (median 61.95%, interquartile range 55.43-67.79%), mean values for MCF were significantly reduced in HCM-48.55% (43.46-54.86% p < 0.001)-and CA-40.92% (36.68-46.84% p < 0.002)-but not in IH-59.35% (53.22-64.93% p < 0.7). MCF showed a weak correlation with EF in the overall cohort (R2 = 0.136) and the four study subgroups (healthy adults, R2 = 0.039 IH, R2 = 0.089; HCM, R2 = 0.225; CA, R2 = 0.102). ROC analyses showed that MCF could differentiate between healthy adults and HCM (sensitivity 75.9%, specificity 77.8%, AUC 0.814) and between healthy adults and CA (sensitivity 87.0%, specificity 100%, AUC 0.959). The best cut-off values were 55.3% and 52.8%. Conclusions: The easily derived quantification of MCF by DHM can refine our echocardiographic discrimination capacity in patients with hypertrophic phenotype and normal EF. It should be added to the diagnostic workup of these patients.

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.

Case Report: Irreversible Watery Diarrhea, Severe Metabolic Acidosis, Hypokalemia and Achloridria Syndrome Related to Vasoactive Intestinal Peptide Secreting Malignant Pheochromocytoma.

Background: Pheochromocytoma (PHEO) clinical manifestations generally mirror excessive catecholamines secretion; rarely the clinical picture may reflect secretion of other hormones. Watery diarrhea, hypokalemia and achlorhydria (WDHA) is a rare syndrome related to excessive secretion of vasoactive intestinal peptide (VIP). Clinical Case: A 73-year-old hypotensive man affected by adrenal PHEO presented with weight loss and watery diarrhea associated with hypokalemia, hyperchloremic metabolic acidosis (anion gap 15 mmol/l) and a negative urinary anion gap. Abdominal computed tomography scan showed a right adrenal PHEO, 8.1 cm in maximum diameter, with tracer uptake on 68GaDOTA-octreotate positron emission tomography. Metastasis in lumbar region and lung were present. Both chromogranin A and VIP levels were high (more than10 times the normal value) with slightly elevated urine normetanephrine and metanephrine excretion. Right adrenalectomy was performed and a somatostatin analogue therapy with lanreotide started. Immunostaining showed chromogranin A and VIP co-expression, with weak somatostatin-receptor-2A positivity. In two months, patient clinical conditions deteriorated with severe WDHA and multiple liver and lung metastasis. Metabolic acidosis and hypokalemia worsened, leading to hemodynamic shock and exitus. Conclusions: A rare case of WDHA syndrome caused by malignant VIP-secreting PHEO was diagnosed. High levels of circulating VIP were responsible of the rapidly evolving clinical picture with massive dehydration and weight loss along with severe hyperchloremic metabolic acidosis and hypokalemia due to the profuse untreatable diarrhea. The rescue treatment with lanreotide was unsuccessful because of the paucity of somatostatin-receptor-2A on VIP-secreting PHEO chromaffin cells.

[Acute kidney injury as a risk marker for hospital readmission: a single-center pilot study in the general population of the Parma area].

Acute Kidney Injury (AKI) is an important issue for the healthcare system, as it is associated with high mortality and increased risk of readmission, with consequent elevated healthcare resource utilization. We investigated the incidence of AKI based on the examination of the discharge cards of all patients admitted between January 1 2011 and December 31 2015 at the Parma University Hospital, as well as the frequency and type of 30-day hospital readmission in the patients discharged with a first AKI diagnosis (index admission). The mean pooled 5-year incidence of AKI was 2.4%. The mean frequency of 30-day readmission for any disease in patients discharged with a first AKI diagnosis in the selected time interval was 23.1%/year. The main four disease categories, as assessed by the Diagnosis Related Group (DRG) classification, responsible for patient 30-day readmission were a new AKI episode, heart failure, respiratory failure requiring or not requiring mechanical ventilation, and sepsis. The mean lenght of hospital stay of patients discharged with AKI as a principal or secondary diagnosis was 14.4 and 21.8 days, respectively. Based on the evaluation of administrative data from all hospital admissions at the Parma University Hospital in the 2011-2015 5-year period, we conclude that AKI represents a serious challenge for the healthcare system, with high short-term morbidity and increased resource utilization due to frequent hospital readmissions.