High Incidence of Autonomic Dysfunction and Postural Orthostatic Tachycardia Syndrome in Patients with Long COVID: Implications for Management and Health Care Planning.

BACKGROUND: Autonomic dysfunction, including postural orthostatic tachycardia syndrome (POTS), has been reported in individuals with post-acute sequelae of COVID-19 (PASC). However, the degree of dysautonomia in PASC has not been compared to those with POTS and healthy controls. METHODS: All participants were prospectively enrolled between August 5, 2021 and October 31, 2022. Autonomic testing included beat-to-beat hemodynamic monitoring to assess respiratory sinus arrhythmia, Valsalva ratio, and orthostatic changes during a 10-minute active standing test, as well as sudomotor assessment. The Composite Autonomic Symptom Score (COMPASS-31) was used to assess symptoms and the EuroQuol 5-Dimension survey (EQ-5D-5L) was used to assess health-related quality of life (HrQoL) measures. RESULTS: A total of 99 participants (n = 33 PASC, n = 33 POTS, and n = 33 healthy controls; median age 32 years, 85.9% females) were included. Compared with healthy controls, the PASC and POTS cohorts demonstrated significantly reduced respiratory sinus arrhythmia (P < .001), greater heart rate increase during 10-minute active standing test (P < .001), greater burden of autonomic dysfunction evidenced by higher COMPASS-31 scores across all subdomains (all P < .001), and poor HrQoL across all EQ-5D-5L domains (all P < .001), lower median EuroQol-visual analogue scale (P < .001), and lower utility scores (P < .001). The majority (79%) of those with PASC met the internationally established criteria for POTS. CONCLUSION: The prevalence of autonomic symptomology for POTS was high in those with PASC, leading to poor HrQoL and high health disutility. Autonomic testing should be routinely undertaken in those with PASC to aid diagnosis and direct appropriate management to improve health outcomes.

Prevalence and Assessment of Sleep-Disordered Breathing in Patients With Atrial Fibrillation: A Systematic Review and Meta-analysis.

BACKGROUND: In this study, we sought to estimate the prevalence of concomitant sleep-disordered breathing (SDB) in patients with atrial fibrillation (AF) and to systematically evaluate how SDB is assessed in this population. METHODS: We searched Medline, Embase and Cinahl databases through August 2020 for studies reporting on SDB in a minimum 100 patients with AF. For quantitative analysis, studies were required to have systematically assessed for SDB in consecutive AF patients. Pooled prevalence estimates were calculated with the use of the random effects model. Weighted mean differences and odds ratios were calculated when possible to assess the strength of association between baseline characteristics and SDB. RESULTS: The search yielded 2758 records, of which 33 studies (n = 23,894 patients) met the inclusion criteria for qualitative synthesis and 13 studies (n = 2660 patients) met the meta-analysis criteria. The pooled SDB prevalence based on an SDB diagnosis cutoff of apnea-hypopnea index (AHI) ≥ 5/h was 78% (95% confidence interval [CI] 70%-86%; P < 0.001). For moderate-to-severe SDB (AHI ≥ 15/h), the pooled SDB prevalence was 40% (95% CI 32%-48%; P < 0.001). High degrees of heterogeneity were observed (I2 = 96% and 94%, respectively; P < 0.001). Sleep testing with the use of poly(somno)graphy or oximetry was the most common assessment tool used (in 22 studies, 66%) but inconsistent diagnostic thresholds were used. CONCLUSIONS: SDB is highly prevalent in patients with AF. Wide variation exists in the diagnostic tools and thresholds used to detect concomitant SDB in AF. Prospective systematic testing for SDB in unselected cohorts of AF patients may be required to define the true prevalence of SDB in this population.

Risk factor management and atrial fibrillation.

The management of atrial fibrillation (AF) is multifaceted and treatment paradigms have changed significantly in the last century. The treatment of AF requires a comprehensive approach which goes beyond the treatment of the arrhythmia alone. Risk factor management has been introduced as a crucial pillar of AF management. As a result, the landscape of care delivery is changing as well, and novel models of comprehensive care delivery for AF have been introduced. This article reviews the evidence for the role of risk factor management in AF, how this can be integrated and implemented in clinical practice by applying novel models of care delivery, and finally identifies areas for ongoing research and potential healthcare reform to comprehensively manage the burgeoning AF population.

Atrial Fibrillation and Heart Failure: Epidemiology, Pathophysiology, Prognosis, and Management.

Atrial fibrillation (AF) and heart failure (HF) have similar risk factors, frequently coexist, and potentiate each other in a vicious cycle. Evidence suggests the presence of AF in both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) increases the risk of all-cause mortality and stroke, particularly when AF is incident. Catheter ablation may be an effective strategy in controlling symptoms and improving quality of life in AF-HFrEF. Strong data guiding management of AF-HFpEF are lacking largely due to its challenging diagnosis. Improving outcomes associated with these coexistent conditions requires further careful investigation.

Trends in the use, complications, and costs of permanent pacemakers in Australia: A nationwide study from 2008 to 2017.

OBJECTIVE: To characterize contemporary pacemaker procedure trends. METHODS: Nationwide analysis of pacemaker procedures and costs between 2008 and 2017 in Australia. The main outcome measures were total, age- and gender-specific implant, replacement, and complication rates, and costs. RESULTS: Pacemaker implants increased from 12,153 to 17,862. Implantation rates rose from 55.3 to 72.6 per 100,000, a 2.8% annual increase (incidence rate ratio [IRR] 1.028; 95% CI, 1.02-1.04; p < .001). Pacemaker implants in the 80+ age group were 17.37-times higher than the < 50 group (95% CI 16.24-18.59; p < .001), and in males were 1.48-times higher than in females (95% CI 1.42-1.55; p < .001). However, there were similar increases according to age (p = .10) and gender (p = .68) over the study period. Left ventricular lead rates were stable (IRR 0.995; 95% CI 0.98-1.01; p = .53). Generator replacements decreased from 20.5 to 18.3 per 100,000 (IRR 0.975; 95% CI 0.97-0.98; p < .001). Although procedures for generator-related complications were stable (IRR 0.995; 95% CI 0.98-1.01; p = .54), those for lead-related complications decreased (IRR 0.985; 95% CI 0.98-0.99; p < .001). Rates for all pacemaker procedures were consistently greater in males (p < .001). Although annual costs of all pacemaker procedures increased from $178 million to $329 million, inflation-adjusted costs were more stable, rising from $294 million to $329 million. CONCLUSIONS: Increasing demand for pacemaker implants is driven by the ageing population and rising rates across all ages, while replacement and complication procedure rates appeared more stable. Males have consistently greater pacemaker procedure rates than females. Our findings have significant clinical and public health implications for healthcare resource planning.

Ventricular arrhythmia burden during the coronavirus disease 2019 (COVID-19) pandemic.

AIMS: Our objective was to determine the ventricular arrhythmia burden in implantable cardioverter-defibrillator (ICD) patients during COVID-19. METHODS AND RESULTS: In this multicentre, observational, cohort study over a 100-day period during the COVID-19 pandemic in the USA, we assessed ventricular arrhythmias in ICD patients from 20 centres in 13 states, via remote monitoring. Comparison was via a 100-day control period (late 2019) and seasonal control period (early 2019). The primary outcome was the impact of COVID-19 on ventricular arrhythmia burden. The secondary outcome was correlation with COVID-19 incidence. During the COVID-19 period, 5963 ICD patients underwent remote monitoring, with 16 942 episodes of treated ventricular arrhythmias (2.8 events per 100 patient-days). Ventricular arrhythmia burden progressively declined during COVID-19 (P < 0.001). The proportion of patients with ventricular arrhythmias amongst the high COVID-19 incidence states was significantly reduced compared with those in low incidence states [odds ratio 0.61, 95% confidence interval (CI) 0.54-0.69, P < 0.001]. Comparing patients remotely monitored during both COVID-19 and control periods (n = 2458), significantly fewer ventricular arrhythmias occurred during COVID-19 [incident rate ratio (IRR) 0.68, 95% CI 0.58-0.79, P < 0.001]. This difference persisted when comparing the 1719 patients monitored during both the COVID-19 and seasonal control periods (IRR 0.69, 95% CI 0.56-0.85, P < 0.001). CONCLUSIONS: During COVID-19, there was a 32% reduction in ventricular arrhythmias needing device therapies, coinciding with measures of social isolation. There was a 39% reduction in the proportion of patients with ventricular arrhythmias in states with higher COVID-19 incidence. These findings highlight the potential role of real-life stressors in ventricular arrhythmia burden in individuals with ICDs. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry; URL: https://www.anzctr.org.au/; Unique Identifier: ACTRN12620000641998.

Miniaturized implantable cardiac monitor with a long sensing vector (BIOMONITOR III): Insertion procedure assessment, sensing performance, and home monitoring transmission success.

BACKGROUND: Implantable Cardiac Monitors (ICMs) are used for long-term monitoring of arrhythmias. BIOMONITOR III is a novel ICM with a miniaturized profile, long sensing vector due to a flexible antenna, simplified implantation with a dedicated insertion tool for pocket formation and ICM placement in a single step, and daily automatic Home Monitoring (HM) function. METHODS: In 47 patients undergoing BIOMONITOR III insertion for any ICM indication, 16 investigators at 10 Australian sites assessed handling characteristics of the insertion tool, R-wave amplitudes, noise burden, P-wave visibility, and HM transmission success. Patients were followed for 1 month. RESULTS: All 47 attempted insertions were successful. Median time from skin incision to removal of the insertion tool after ICM insertion was 39 s (IQR 19-65) and to wound closure and cleaning was 4.7 min (IQR 3.5-7.8). All aspects of the insertion tool were rated as "good" or "excellent" in ≥97.9% and "fair" in ≤2.1% of patients, except for "force needed for tunnelling" (91.5% good/excellent, 8.5% fair). Based on HM data, R-waves in the first month were stable at 0.70 ± 0.37 mV. Median noise burden (disabling automatic rhythm evaluation) was 0.19% (IQR 0.00-0.93), equivalent to 2.7 min (IQR 0.0-13.4) per day. In HM-transmitted ECG strips with regular sinus rhythm, P-waves were visible in 89 ± 24% of heart cycles. Patient-individual automatic Home Monitoring transmission success was 98.0% ± 5.5%. CONCLUSIONS: The novel ICM performed well in all aspects studied, including fast insertion, reliable R-wave sensing, good P-wave visibility, and highly successful HM transmissions.

Home-Based Education and Learning Program for Atrial Fibrillation: Rationale and Design of the HELP-AF Study.

BACKGROUND: Atrial fibrillation (AF) is a growing global epidemic, with its prevalence expected to significantly rise over coming decades. AF poses a substantial burden on health care systems, largely due to hospitalizations. Home-based clinical characterization has demonstrated improved outcomes in cardiac populations, but its impact on AF remains poorly defined. To test this hypothesis in AF, we developed the Home-Based Education and Learning Program for Patients With Atrial Fibrillation (HELP-AF) study. METHODS: The HELP-AF study is a prospective multicentre randomized controlled trial that will recruit 620 patients presenting to hospital emergency departments (EDs) with symptomatic AF (ANZCTR Registration: ACTRN12611000607976). Patients will be randomized to either the HELP-AF intervention or usual care. The intervention consists of 2 home visits by a nurse or pharmacist trained in the structured educational visiting (SEV) method. Patients in the control group will receive usual discharge follow-up care. RESULTS: The primary endpoints are total unplanned hospital admissions and quality of life. Secondary endpoints include AF symptom severity and burden score; time to first hospital admission; total unplanned days in hospital; total AF-related hospital admissions (including atrial flutter); total cardiac and noncardiac hospital admissions; total AF- or atrial flutter-related; cardiac- and noncardiac-related ED presentations; and all-cause mortality. An economic evaluation will also be performed. Clinical endpoints will be adjudicated by independent blinded assessors. Follow-up will be at 24 months. CONCLUSIONS: This study will assess the efficacy of a home-based structured patient-centred educational intervention in patients with AF.

Increasing trends in hospitalisations due to atrial fibrillation in Australia from 1993 to 2013.

OBJECTIVE: The aim of this study is to characterise hospitalisations due to atrial fibrillation (AF) compared with two other common cardiovascular conditions, myocardial infarction (MI) and heart failure (HF), in addition to the associated economic burden of these hospitalisations and contribution of AF-related procedures. METHODS: The primary outcome measure was the rate of increase of AF, MI and HF hospitalisations from 1993 to 2013. The rate of increase of AF-related procedures including cardioversion and ablation were also collected, in addition to direct costs associated with hospitalisations for each of these three conditions. RESULTS: AF hospitalisations increased 295% over the 21-year period to a total of 61 424 in 2013. In comparison, MI and HF hospitalisations increased by only 73% and 39%, respectively, over the same period. Considering population changes, there was an annual increase in AF hospitalisations of 5.2% (incidence rate ratio [IRR] 1.052; 95% CI 1.046 to 1.059; p<0.001). In contrast, there was a 2.2% increase per annum for MI (IRR 1.022; 95% CI 1.017 to 1.027; p<0.001) and negligible annual change for HF hospitalisations (IRR 1.000; 95% CI 0.997 to 1.002; p=0.78). Cardioversion and AF ablation increased by 10% and 26% annually, respectively. AF hospitalisation costs rose by 479% over the 21-year period, an increase that was more than double that of MI and HF. CONCLUSIONS: The burden of AF hospitalisations continues to rise unabated. AF has now surpassed both MI and HF hospitalisations and represents a growing cost burden. New models of healthcare delivery are required to stem this growing healthcare burden.

Contact force and ablation assessment of surgical bipolar radiofrequency clamps in the treatment of atrial fibrillation.

OBJECTIVES: Atrial fibrillation is treated surgically by creating conduction block lesions. Radiofrequency (RF) lesions have reduced efficacy compared to 'cut-and-sew'. Catheter ablation studies demonstrate a relationship between lesion depth and contact force. We hypothesized that contact force and lesion depth are dependent on design of the bipolar surgical RF clamps. METHODS: Hinged and parallel jaw style RF clamps were studied. Muscle samples were clamped with pressure-sensitive film at increasing tissue thicknesses. Films were analysed determining clamp pressure profiles. A sheep model was utilized for ablation testing using each clamp style until the device indicated transmurality. Separate muscle areas had 1, 2 or 3 burns applied. The muscle was excised, sectioned every 1 cm and stained for lesion depth and fat thickness analysis. RESULTS: Pressure profiling comparing the proximal and distal segments of each clamp style demonstrated only one statistically significant difference in the parallel clamp; the hinged clamp had statistically significant differences (P ≤ 0.03) for all tissue thicknesses. There was no evidence for differences in the proximal lesion depth of both clamps (P = 0.13) but deeper distally in the parallel clamp (10.17 mm vs 8.02 mm, P = 0.003). The logistic regression analysis demonstrated increased odds of transmurality with parallel clamps at 1, 2 or 3 burns (P = 0.03, P = 0.003 and P = 0.002). Every 1 mm increase in overlying fat decreased likelihood of transmurality by 11% (P < 0.05). CONCLUSIONS: The parallel and hinged clamps have different pressure profiles with higher likelihood of transmurality using the parallel clamp. Fat reduces the ability of RF to deliver a transmural lesion. These findings have implications for optimal surgical RF ablation technique.

Predicted longevity of contemporary cardiac implantable electronic devices: A call for industry-wide "standardized" reporting.

BACKGROUND: Battery longevity is an important factor that may influence the selection of cardiac implantable electronic devices (CIEDs). However, there remains a lack of industry-wide standardized reporting of predicted CIED longevity to facilitate informed decision-making for implanting physicians and payers. OBJECTIVE: The purpose of this study was to compare the predicted longevity of current generation CIEDs using best-matched CIEDs settings to assess differences between brands and models. METHODS: Data were extracted for current model pacemakers, implantable cardioverter-defibrillators (ICDs), and cardiac resynchronization therapy-defibrillators (CRT-Ds) from product manuals and, where absent, by communication with the manufacturers. Pacemaker longevity estimations were based on standardized pacing outputs (2.5V, 0.40-ms pulse width, 500-Ω impedance) and pacing loads of 50% or 100% at 60 bpm. ICD and CRT-D longevity were estimated at 0% pacing and 15% atrial plus 100% biventricular pacing, with essential capacitor reforms and zero clinical shocks. RESULTS: Mean maximum predicted longevity of single- and dual-chamber pacemakers was 12.0 ± 2.1 and 9.8 ± 1.9 years, respectively. Use of advanced features such as remote monitoring, prearrhythmia electrogram storage, and rate response can result in ∼1.4 years of reduction in longevity. Mean maximum predicted longevity of ICDs and CRT-Ds was 12.4 ± 3.0 and 8.8 ± 2.1 years, respectively. Of note, there were significant variations in predicted CIED longevity according to device manufacturers, with up to 44%, 42%, and 44% difference for pacemakers, ICDs, and CRT-Ds, respectively. CONCLUSION: Contemporary CIEDs demonstrate highly variable predicted longevity according to device manufacturers. This may impact on health care costs and long-term clinical outcomes.

Risk Factor Management and Atrial Fibrillation Clinics: Saving the Best for Last?

Atrial fibrillation (AF) is a leading cause of cardiovascular morbidity and mortality worldwide. Management of AF is a complex process involving: 1) the prevention of thromboembolic complications with anticoagulation; 2) rhythm control; and 3) the detection and treatment of underlying heart disease. However, cardiometabolic risk factors, such as obesity, hypertension, diabetes mellitus, and obstructive sleep apnoea, have been proposed as contributors to the expanding epidemic of atrial fibrillation (AF). Thus, a fourth pillar of AF care would include aggressive targeting of interdependent, modifiable cardiovascular risk factors as part of an integrated care model. Such risk factor management could retard and reverse the pathological processes underlying AF and reduce AF burden.

Cost-Effectiveness and Clinical Effectiveness of the Risk Factor Management Clinic in Atrial Fibrillation: The CENT Study.

BACKGROUND: Atrial fibrillation (AF) imposes a substantial cost burden on the healthcare system. Weight and risk factor management (RFM) reduces AF burden and improves the outcomes of AF ablation. OBJECTIVES: This study sought to evaluate the cost and clinical effectiveness of integrating RFM into the overall management of AF. METHODS: Of 1,415 consecutive patients with symptomatic AF, 825 patients had body mass index ≥27 kg/m2. After screening for exclusion criteria, the final cohort comprised 355 patients: 208 patients who opted for RFM and 147 control subjects and were followed by 3 to 6 monthly clinic review, 7-day Holter monitoring, and AF Symptom Score. A decision analytical model calculated the incremental cost-effectiveness ratios of cost per unit of global well-being gained and unit of AF burden reduced. RESULTS: There were no differences in baseline characteristics or follow-up duration (p = NS). Arrhythmia-free survival was better in the RFM compared with control subjects (Kaplan-Meier: 79% vs. 44%; p < 0.001). At follow-up, RFM group had less unplanned specialist visits (0.19 ± 0.40 vs. 1.94 ± 2.00; p < 0.001), hospitalizations (0.74 ± 1.3 vs. 1.05 ± 1.60; p = 0.03), cardioversions (0.89 ± 1.50 vs. 1.51 ± 2.30; p = 0.002), emergency presentations (0.18 ± 0.50 vs. 0.76 ± 1.20; p < 0.001), and ablation procedures (0.60 ± 0.69 vs. 0.72 ± 0.86; p = 0.03). Antihypertensive (0.53 ± 0.70 vs. 0.78 ± 0.60; p = 0.04) and antiarrhythmic (0.26 ± 0.50 vs. 0.91 ± 0.60; p = 0.003) use declined in RFM. The RFM group had an increase of 0.1930 quality-adjusted life years and a cost saving of $12,094 (incremental cost-effectiveness ratios of $62,653 saved per quality-adjusted life years gained). CONCLUSIONS: A structured physician-directed RFM program is clinically effective and cost saving.

Assessment of myocardial fibrosis by endoventricular electromechanical mapping in experimental nonischemic cardiomyopathy.

Cardiac fibrosis plays an important prognostic role in nonischemic cardiomyopathy (NICM), making it a potential therapeutic target. Although electromechanical mapping has been used to identify myocardial scar and facilitate intramyocardial intervention in the setting of ischemic heart disease, its application has not been described in NICM. We assessed the detection of myocardial fibrosis by endoventricular electromechanical mapping in an experimental model of NICM. The NOGA® XP system was used to perform left ventricular mapping in twelve sheep that had undergone intracoronary doxorubicin dosing to induce NICM and in six healthy control animals. Results for endocardial voltage and mechanical shortening were evaluated against myocardial fibrosis burden, as determined by delayed-enhancement cardiac magnetic resonance and quantitative histomorphometry. Doxorubicin treatment resulted in dilated cardiomyopathy with moderate-severe impairment of left ventricular ejection fraction. Late gadolinium uptake was present in 9/12 doxorubicin animals, while histological fibrosis was approximately doubled compared to controls and was distributed multisegmentally throughout the left ventricle. Cardiomyopathy was associated with widespread reductions in unipolar and bipolar voltage amplitude and endocardial shortening. Each parameter showed an inverse relationship with the burden of fibrosis. Moreover, unipolar voltage and linear local shortening ratio displayed moderate accuracy for identifying myocardial segments with delayed contrast enhancement or increased fibrosis content, with optimal discriminatory thresholds of 7.5 mV and 11.5%, respectively. In this model of NICM, electromechanical mapping shows potential for delineating segmental differences in fibrosis. Pending clinical evaluation, it may therefore have applicability for directing targeted intramyocardial interventions in nonischemic heart disease.

Validation of cardiovascular magnetic resonance assessment of pericardial adipose tissue volume.

BACKGROUND: Pericardial adipose tissue (PAT) has been shown to be an independent predictor of coronary artery disease. To date its assessment has been restricted to the use of surrogate echocardiographic indices such as measurement of epicardial fat thickness over the right ventricular free wall, which have limitations. Cardiovascular magnetic resonance (CMR) offers the potential to non-invasively assess total PAT, however like other imaging modalities, CMR has not yet been validated for this purpose. Thus, we sought to describe a novel technique for assessing total PAT with validation in an ovine model. METHODS: 11 merino sheep were studied. A standard clinical series of ventricular short axis CMR images (1.5T Siemens Sonata) were obtained during mechanical ventilation breath-holds. Beginning at the mitral annulus, consecutive end-diastolic ventricular images were used to determine the area and volume of epicardial, paracardial and pericardial adipose tissue. In addition adipose thickness was measured at the right ventricular free wall. Following euthanasia, the paracardial adipose tissue was removed from the ventricle and weighed to allow comparison with corresponding CMR measurements. RESULTS: There was a strong correlation between CMR-derived paracardial adipose tissue volume and ex vivo paracardial mass (R2 = 0.89, p < 0.001). In contrast, CMR measurements of corresponding RV free wall paracardial adipose thickness did not correlate with ex vivo paracardial mass (R2 = 0.003, p = 0.878). CONCLUSION: In this ovine model, CMR-derived paracardial adipose tissue volume, but not the corresponding and conventional measure of paracardial adipose thickness over the RV free wall, accurately reflected paracardial adipose tissue mass. This study validates for the first time, the use of clinically utilised CMR sequences for the accurate and reproducible assessment of pericardial adiposity. Furthermore this non-invasive modality does not use ionising radiation and therefore is ideally suited for future studies of PAT and its role in cardiovascular risk prediction and disease in clinical practice.