Markov Chain Models for Cardiac Rhythm Dynamics in Patients Undergoing Catheter Ablation of Atrial Fibrillation.

We have developed a novel Markov Chain modeling system that considers vectors of patients with atrial fibrillation (AF) by their AF status over a period of time. Our model examines the impact of catheter ablation of AF upon the dynamics of a patient's AF status and their potential return to sinus rhythm. We prove several theorems to determine the probabilities of patients achieving sinus rhythm or progressing to permanent AF. Additionally, we observed aggregation of patients within the paroxysmal AF state in simulation. The aggregating property of Markov chains illustrated the potential benefits of catheter ablation on healthcare resource allocation.

Global, Regional, and National Burden of Calcific Aortic Valve and Degenerative Mitral Valve Diseases, 1990-2017.

BACKGROUND: Nonrheumatic valvular diseases are common; however, no studies have estimated their global or national burden. As part of the Global Burden of Disease Study 2017, mortality, prevalence, and disability-adjusted life-years (DALYs) for calcific aortic valve disease (CAVD), degenerative mitral valve disease, and other nonrheumatic valvular diseases were estimated for 195 countries and territories from 1990 to 2017. METHODS: Vital registration data, epidemiologic survey data, and administrative hospital data were used to estimate disease burden using the Global Burden of Disease Study modeling framework, which ensures comparability across locations. Geospatial statistical methods were used to estimate disease for all countries, because data on nonrheumatic valvular diseases are extremely limited for some regions of the world, such as Sub-Saharan Africa and South Asia. Results accounted for estimated level of disease severity as well as the estimated availability of valve repair or replacement procedures. DALYs and other measures of health-related burden were generated for both sexes and each 5-year age group, location, and year from 1990 to 2017. RESULTS: Globally, CAVD and degenerative mitral valve disease caused 102 700 (95% uncertainty interval [UI], 82 700-107 900) and 35 700 (95% UI, 30 500-42 500) deaths, and 12.6 million (95% UI, 11.4 million-13.8 million) and 18.1 million (95% UI, 17.6 million-18.6 million) prevalent cases existed in 2017, respectively. A total of 2.5 million (95% UI, 2.3 million-2.8 million) DALYs were estimated as caused by nonrheumatic valvular diseases globally, representing 0.10% (95% UI, 0.09%-0.11%) of total lost health from all diseases in 2017. The number of DALYs increased for CAVD and degenerative mitral valve disease between 1990 and 2017 by 101% (95% UI, 79%-117%) and 35% (95% UI, 23%-47%), respectively. There is significant geographic variation in the prevalence, mortality rate, and overall burden of these diseases, with highest age-standardized DALY rates of CAVD estimated for high-income countries. CONCLUSIONS: These global and national estimates demonstrate that CAVD and degenerative mitral valve disease are important causes of disease burden among older adults. Efforts to clarify modifiable risk factors and improve access to valve interventions are necessary if progress is to be made toward reducing, and eventually eliminating, the burden of these highly treatable diseases.

Economic and Health Value of Delaying Atrial Fibrillation Progression Using Radiofrequency Catheter Ablation.

BACKGROUND: Radiofrequency catheter ablation (RFCA) is an established treatment for atrial fibrillation (AF) refractory to antiarrhythmic drugs. The economic value of RFCA in delaying disease progression has not been quantified. METHODS: An individual-level, state-transition health economic model estimated the impact of delayed AF progression using RFCA versus antiarrhythmic drug treatment for a hypothetical sample of patients with paroxysmal AF. The model incorporated the lifetime risk of progression from paroxysmal AF to persistent AF, informed by data from the ATTEST (Atrial Fibrillation Progression Trial). The incremental effect of RFCA on disease progression was modeled over a 5-year duration. Annual crossover rates were also included for patients in the antiarrhythmic drug group to mirror clinical practice. Estimates of discounted costs and quality-adjusted life years asssociated with health care utilization, clinical outcomes, and complications were projected over patients' lifetimes. RESULTS: From the payer's perspective, RFCA was superior to antiarrhythmic drug treatment with an estimated mean net monetary benefit per patient of $8516 ($148-$16 681), driven by reduced health care utilization, cost, and improved quality-adjusted life years. RFCA reduced mean (95% CI) per-patient costs by $73 (-$2700 to $2200), increased mean quality-adjusted life years by 0.084 (0.0-0.17) and decreased the mean number of cardiovascular-related health care encounters by 24%. CONCLUSIONS: RFCA is a dominant (less costly and more effective) treatment strategy for patients with AF, especially those with early AF for whom RFCA could delay progression to advanced AF. Increased utilization of RFCA-particularly among patients earlier in their disease progression-may provide clinical and economic benefits.

Creation and Validation of an Algorithm for Predicting the Recurrence of Atrial Fibrillation Following Pulmonary Vein Isolation by Utilizing Real-World Data and Ensemble Modeling Techniques.

Introduction Catheter ablation (CA) of atrial fibrillation (AF) represents a mainstay in the treatment of this increasingly prevalent arrhythmia. Prospective clinical trials investigating the efficacy of CA may poorly represent real-world patient populations. However, many real-world clinical datasets possess missing data, which may impede their applicability in research. Thus, we sought to use ensemble modeling to address missing data and develop a model to estimate the probability of AF recurrence following CA. Methods We retrospectively analyzed clinical variables in 476 patients who underwent an initial CA of AF. Univariate and multivariate logistic regression was performed to determine those variables predictive of AF recurrence. A multivariate logistic model was created to estimate the probability of AF recurrence after CA. Missing data were addressed using ensemble modeling, and variable selection was performed using the aggregate of multiple models. Results After analysis, six variables remained in the model: AF during the post-procedural blanking period, coexistence of atrial flutter, end-stage renal disease, reduced left ventricular ejection fraction, prior failure of anti-arrhythmic drugs, and valvular heart disease. Predictive modeling was performed using these variables for 1000 randomly partitioned datasets (80% training, 20% testing) and 1000 random imputations for each partitioned dataset. The model predicted AF recurrence with an accuracy of 74.34 ± 3.99% (recall: 54.03 ± 8.15%; precision: 89.30 ± 4.21%; F1 score: 81.08 ± 3.65%).  Conclusion We successfully identified six clinical variables that, when modeled, predicted AF recurrence following CA with a high degree of classification accuracy. Application of this model to patients undergoing CA of AF may help identify those at risk of post-procedural AF recurrence.

Electrical Stimulation Increases the Secretion of Cardioprotective Extracellular Vesicles from Cardiac Mesenchymal Stem Cells.

Clinical trials have shown that electric stimulation (ELSM) using either cardiac resynchronization therapy (CRT) or cardiac contractility modulation (CCM) approaches is an effective treatment for patients with moderate to severe heart failure, but the mechanisms are incompletely understood. Extracellular vesicles (EV) produced by cardiac mesenchymal stem cells (C-MSC) have been reported to be cardioprotective through cell-to-cell communication. In this study, we investigated the effects of ELSM stimulation on EV secretion from C-MSCs (C-MSCELSM). We observed enhanced EV-dependent cardioprotection conferred by conditioned medium (CM) from C-MSCELSM compared to that from non-stimulated control C-MSC (C-MSCCtrl). To investigate the mechanisms of ELSM-stimulated EV secretion, we examined the protein levels of neutral sphingomyelinase 2 (nSMase2), a key enzyme of the endosomal sorting complex required for EV biosynthesis. We detected a time-dependent increase in nSMase2 protein levels in C-MSCELSM compared to C-MSCCtrl. Knockdown of nSMase2 in C-MSC by siRNA significantly reduced EV secretion in C-MSCELSM and attenuated the cardioprotective effect of CM from C-MSCELSM in HL-1 cells. Taken together, our results suggest that ELSM-mediated increases in EV secretion from C-MSC enhance the cardioprotective effects of C-MSC through an EV-dependent mechanism involving nSMase2.

Atrial fibrillation ablation with advanced radiofrequency catheter versus second-generation cryoballoon catheter.

Aim: To compare cost and readmissions among atrial fibrillation (AF) patients undergoing ablation using the THERMOCOOL SMARTTOUCH™ SF (STSF) radiofrequency catheter versus the Arctic Front Advance™ (AFA) cryoballoon catheter. Patients & methods: The Premier Healthcare Database was used for the study purposes. Propensity score matching was used to match patients in the two groups. Costs and readmissions were assessed. A regression model was used for outcome assessment. Results: After propensity matching, 2767 patients were identified in each of the STSF and AFA cohorts. In the matched cohort, STSF patients had significantly lower supply costs than AFA patients. STSF patients had significantly lower 4-12-month AF-related inpatient readmissions compared with AFA patients (2.58% vs 3.99%; p = 0.0402). Costs of care summing index procedure and readmission costs were also lower for the STSF patients versus AFA patients. Conclusions: Patients who underwent AF ablation using the STSF catheter versus the AFA catheter had lower cost and AF-related readmissions.

Role of cardiac magnetic resonance imaging in the diagnosis and management of COVID-19 related myocarditis: Clinical and imaging considerations.

There is a growing evidence of cardiovascular complications in coronavirus disease 2019 (COVID-19) patients. As evidence accumulated of COVID-19 mediated inflammatory effects on the myocardium, substantial attention has been directed towards cardiovascular imaging modalities that facilitate this diagnosis. Cardiac magnetic resonance imaging (CMRI) is the gold standard for the detection of structural and functional myocardial alterations and its role in identifying patients with COVID-19 mediated cardiac injury is growing. Despite its utility in the diagnosis of myocardial injury in this population, CMRI's impact on patient management is still evolving. This review provides a framework for the use of CMRI in diagnosis and management of COVID-19 patients from the perspective of a cardiologist. We review the role of CMRI in the management of both the acutely and remotely COVID-19 infected patient. We discuss patient selection for this imaging modality; T1, T2, and late gadolinium enhancement imaging techniques; and previously described CMRI findings in other cardiomyopathies with potential implications in COVID-19 recovered patients.

Early detection of change patterns in COVID-19 incidence and the implementation of public health policies: A multi-national study.

OBJECTIVES: The COVID-19 pandemic caused by the novel SARS-CoV-2 coronavirus has drastically altered the global realities. Harnessing national scale data from the COVID-19 pandemic may better inform policy makers in decision making surrounding the reopening of society. We examined country-level, daily-confirmed, COVID-19 case data from the World Health Organization (WHO) to better understand the comparative dynamics associated with the ongoing global pandemic at a national scale. STUDY DESIGN: Observational study. METHODS: We included data from 20 countries in Europe, the Americas, Africa, Eastern Mediterranean and West Pacific regions, and obtained the aggregated daily new case data for the European Union including 27 countries. We utilized an innovative analytic approach by applying statistical change point models, which have been previously employed to model volatility in stock markets, changes in genomic data, and data dynamics in other scientific disciplines, to segment the transformed case data. This allowed us to identify possible change or turning points as indicated by the dynamics of daily COVID-19 incidences. We also employed B-spline regression models to express the estimated (predicted) trend of daily new incidences for each country's COVID-19 disease burden with the identified key change points in the model. RESULTS: We identified subtle, yet different change points (translated to actual calendar days) by either the mean and variance change point model with small p-values or by a Bayesian online change point algorithm with large posterior probability in the trend of COVID-19 incidences for different countries. We correlated these statistically identified change points with evidence from the literature surrounding these countries' policies regarding opening and closing of their societies in an effort to slow the spread of COVID-19. The days when change points were detected were ahead of the actual policy implementation days, and in most of the countries included in this study the decision lagged the change point days too long to prevent potential widespread extension of the pandemic. CONCLUSIONS: Our models describe the behavior of COVID-19 prevalence at a national scale and identify changes in national disease burden as relating to chronological changes in restrictive societal activity. Globally, social distancing measures may have been most effective in smaller countries with single governmental and public health organizational structures. Further research examining the impact of heterogeneous governmental responses to pandemic management appears warranted.

Potential Financial Impact of Incidental Cardiac Pathology Detected During Lung Cancer Screening.

BACKGROUND: Lung cancer screening (LCS) is broadly accepted. Screening also identifies incidental cardiac findings (S findings) that need follow-up. We report the magnitude of the potential downstream revenue generated by appropriate S finding management after 4 years of our free LCS program. MATERIALS AND METHODS: A retrospective database and chart review of a single-center free LCS program in the underserved southeast were performed. All patients who were enrolled in the screening required a primary care physician (PCP) as part of the decision-making model. Referrals to cardiac specialists for S findings found on LCS were recorded. Cost analysis was performed to track potential downstream revenue generated for the institution based upon Medicare allowable or Diagnosis-related group calculations. RESULTS: One thousand one hundred thirty-two scans were reviewed with 262 (23%) yielding positive S findings for 1 or more organ systems. 181/262 (69%) patients had cardiac findings, only 64/181 (35%) of these patients were referred to cardiology specialists by the PCP. The total Medicare billable amount for all cardiac referrals/interventions was $284 379, representing 35% of the potential billable amount of $804 260. Percutaneous coronary intervention (PCI) was the highest billable amount at $18 568. Eight percent of the patients undergoing appropriate cardiac evaluation required a PCI. If not for the screening and cardiac specialist referral, this patient group may not have received appropriate cardiovascular diagnosis and treatment. DISCUSSION: Lung cancer screening also identifies patients with significant cardiac disease, many of whom may not be appropriately referred. Identification and treatment of incidentally noted cardiovascular findings may both improve patient care and justify supporting free LCS programs.

A County-Level Analysis of Socioeconomic and Clinical Predictors of COVID-19 Incidence and Case-Fatality Rates in Georgia, March-September 2020.

OBJECTIVES: The global COVID-19 pandemic has affected various populations differently. We investigated the relationship between socioeconomic determinants of health obtained from the Robert Wood Johnson Foundation County Health Rankings and COVID-19 incidence and mortality at the county level in Georgia. METHODS: We analyzed data on COVID-19 incidence and case-fatality rates (CFRs) from the Georgia Department of Public Health from March 1 through August 31, 2020. We used repeated measures generalized linear mixed models to determine differences over time in Georgia counties among quartile health rankings of health outcomes, health behaviors, clinical care, social and economic factors, and physical environment. RESULTS: COVID-19 incidence per 100 000 population increased across all quartile county groups for all health rankings (range, 23.1-51.6 in May to 688.4-1062.0 in August). COVID-19 CFRs per 100 000 population peaked in April and May (range, 3312-6835) for all health rankings, declined in June and July (range, 827-5202), and increased again in August (range, 1877-3310). Peak CFRs occurred later in counties with low health rankings for health behavior and clinical care and in counties with high health rankings for social and economic factors and physical environment. All interactions between the health ranking quartile variables and month were significant (P < .001). County-level Gini indices were associated with significantly higher rates of COVID-19 incidence (P < .001) but not CFRs. CONCLUSIONS: From March through August 2020, COVID-19 incidence rose in Georgia's counties independent of health rankings categorization. Differences in time to peak CFRs differed at the county level based upon key health rankings. Public health interventions should incorporate unique strategies to improve COVID-19-related patient outcomes in these environments.

Percutaneous Ventricular Assist Device vs. Intra-Aortic Balloon Pump for Hemodynamic Support in Acute Myocardial Infarction-Related Cardiogenic Shock and Coexistent Atrial Fibrillation: A Nationwide Propensity-Matched Analysis'.

BACKGROUND: Patients suffering an acute myocardial infarction complicated by cardiogenic shock (AMICS) may experience clinical deterioration with concomitant atrial fibrillation (AF). Recent data suggest that percutaneous ventricular assist devices (pVADs) provide superior hemodynamic support over intra-aortic balloon pump (IABP) in AMICS. In patients with AF+AMICS, however, outcomes data comparing these two devices remain limited. METHODS: Using the National Inpatient Sample datasets (2008-2014) and a propensity-score matched analysis, we compared the outcomes of AMICS+AF hospitalized patients undergoing PCI with pVAD vs. IABP support. RESULTS: A total of 12,842 AMICS+AF patients were identified (pVAD=468, IABP=12,374). The matched groups (pVAD=443, IABP=443) were comparable in terms of mean age (70.3 ± 12.0 vs. 70.4 ± 11.0yrs, p = 0.92). The utilization of pVAD was higher in whites but lower in Medicare/Medicaid beneficiaries as compared to IABP. The pVAD group demonstrated higher rates of obesity (13.6% vs. 7.8%, p = 0.006) and dyslipidemia (48.4% vs. 41.8%, p = 0.05). There was no difference in the in-hospital mortality (40.5% vs. 36.8%, p = 0.25); however, pVAD group had a lower incidence of post-procedural MI and higher incidences of stroke (7.8% vs. 4.4%, p = 0.03), hemorrhage (5.6% vs. 2.3%, p = 0.01), discharges to home health care (13.5% vs. 10.1%, p<0.001) and to other facilities (29.1% vs. 24.9%, p<0.001) as compared to IABP group. There was no difference between the groups in terms of mean length of stay or hospital charges. CONCLUSIONS: All-cause inpatient mortality was similar in AMICS+AF patients undergoing PCI who were treated with either pVAD or IABP. The pVAD group, however, experienced more complications while consuming greater healthcare resources.

Socioeconomic determinants of health and county-level variation in cardiovascular disease mortality: An exploratory analysis of Georgia during 2014-2016.

Since cardiovascular disease (CVD) represents the leading cause of death in the state of Georgia, we sought to describe the relationship between socioeconomic determinants of health (SDH) and CVD-related mortality in Georgia using publicly available population health and economic data. A multivariate regression model was estimated to examine physical inactivity, median household income, health insurance status, urban-rural status, and air quality on CVD mortality in Georgia between 2014 and 2016. We find that the median household income and annual average ambient concentrations of PM2.5 were the most significant factors in explaining CVD mortality. Lower levels of median household income and higher concentrations of PM2.5 were associated with higher CVD mortality rates. Leisure-time physical inactivity, health insurance status, and urban-rural status were not associated with worsened CVD-related mortality. As such, policies and interventions aimed at improving socioeconomic status in Georgia should be explored in an effort to positively impact CVD outcomes. Furthermore, this exploratory study could be extended for all counties in the U.S.

Elective cardiovascular care in the era of the COVID-19 pandemic: managing tragic choices.

The COVID-19 pandemic has led to significant morbidity and mortality globally. As health systems grapple with caring for patients affected with COVID-19, cardiovascular procedures that are deemed 'elective' have been postponed. Guidelines concerning which cardiac procedures should be performed during the pandemic vary by specialty and geography in the USA. We propose a clinical heuristic to guide individual physicians and governing bodies in their decision making regarding which cardiac procedures should be performed during the COVID-19 pandemic using the behavioural economics concept of heuristics and ecological rationality.

Successful Catheter Ablation of Two Macro-reentrant Atrial Tachycardias in a Patient with Congenitally Corrected Transposition of the Great Arteries: A Case Report.

Adults with congenital heart disease represent a complex and growing patient population. By virtue of their variant anatomy and the complex surgical repair often required in infancy, these patients are at risk of developing unique atrial and ventricular arrhythmias throughout their lifetimes. Electrophysiologists involved in the care of these patients should have a detailed understanding of their underlying anatomy and any prior surgical procedures to guide procedural planning and should have knowledge of the range of possible arrhythmia mechanisms that may differ from patients without structural heart disease. Despite this complexity, standard mapping techniques and electrophysiologic maneuvers may still be used to elucidate arrhythmia mechanisms, map tachycardia circuits, and guide catheter ablation. We report a case of two different macroreentrant right atrial tachycardias that were successfully ablated in a patient with congenitally-corrected transposition of the great arteries.

How to prevent and manage radiation-induced coronary artery disease.

Radiation-induced coronary heart disease (RICHD) is the second most common cause of morbidity and mortality in patients treated with radiotherapy for breast cancer, Hodgkin's lymphoma and other prevalent mediastinal malignancies. The risk of RICHD increases with radiation dose. Exposed patients may present decades after treatment with manifestations ranging from asymptomatic myocardial perfusion defects to ostial, triple-vessel disease and sudden cardiac death. RICHD is insidious, with a long latency and a tendency to remain silent late into the disease course. Vessel involvement is often diffuse and is preferentially proximal. The pathophysiology is similar to that of accelerated atherosclerosis, characterised by the formation of inflammatory plaque with high collagen and fibrin content. The presence of conventional risk factors potentiates RICHD, and aggressive risk factor management should ideally be initiated prior to radiation therapy. Stress echocardiography is more sensitive and specific than myocardial perfusion imaging in the detection of RICHD, and CT coronary angiography shows promise in risk stratification. Coronary artery bypass grafting is associated with higher risks of graft failure, perioperative complications and all-cause mortality in patients with RICHD. In most cases, the use of drug-eluting stents is preferable to surgical intervention, bare metal stenting or balloon-angioplasty alone.

A comparative analysis of clinical outcomes and disposable costs of different catheter ablation methods for the treatment of atrioventricular nodal reentrant tachycardia.

BACKGROUND: Catheter ablation of atrioventricular nodal reentrant tachycardia (AVNRT) is a commonly performed electrophysiology (EP) procedure. Few data exist comparing conventional (CONV) versus novel ablation strategies from both clinical and direct cost perspectives. We sought to investigate the disposable costs and clinical outcomes associated with three different ablation methodologies used in the ablation of AVNRT. METHODS: We performed a retrospective review of AVNRT ablations performed at Augusta University Medical Center from 2006 to 2014. A total of 183 patients were identified. Three different ablation techniques were compared: CONV manual radiofrequency (RF) (n=60), remote magnetic navigation (RMN)-guided RF (n=67), and cryoablation (CRYO) (n=56). RESULTS: Baseline demographics did not differ between the three groups except for a higher prevalence of cardiomyopathy in the RMN group (p<0.01). The clinical end point of interest was recurrent AVNRT following the index ablation procedure. A significantly higher number of recurrent AVNRT cases occurred in the CRYO group as compared to CONV and RMN (p=0.003; OR =7.75) groups. Cost-benefit analysis showed both CONV and RMN to be dominant compared to CRYO. Cost-minimization analysis demonstrated the least expensive ablation method to be CONV (mean disposable catheter cost = CONV US$2340; CRYO US$3515; RMN US$5190). Despite comparable clinical outcomes, the incremental cost of RMN over CONV averaged US$3094 per procedure. CONCLUSION: AVNRT ablation using either CONV or RMN techniques is equally effective and associated with lower AVNRT recurrence rates than CRYO. CONV ablation carries significant disposable cost savings as compared to RMN, despite similar efficacy.

MAGNETIC VT study: a prospective, multicenter, post-market randomized controlled trial comparing VT ablation outcomes using remote magnetic navigation-guided substrate mapping and ablation versus manual approach in a low LVEF population.

PURPOSE: Patients with ischemic cardiomyopathy (ICM) are prone to scar-related ventricular tachycardia (VT). The success of VT ablation depends on accurate arrhythmogenic substrate localization, followed by optimal delivery of energy provided by constant electrode-tissue contact. Current manual and remote magnetic navigation (RMN)-guided ablation strategies aim to identify a reentry circuit and to target a critical isthmus through activation and entrainment mapping during ongoing tachycardia. The MAGNETIC VT trial will assess if VT ablation using the Niobe™ ES magnetic navigation system results in superior outcomes compared to a manual approach in subjects with ischemic scar VT and low ejection fraction. METHODS AND RESULTS: This is a randomized, single-blind, prospective, multicenter post-market study. A total of 386 subjects (193 per group) will be enrolled and randomized 1:1 between treatment with the Niobe ES system and treatment via a manual procedure at up to 20 sites. The study population will consist of patients with ischemic cardiomyopathy with left ventricular ejection fraction (LVEF) of ≤35% and implantable cardioverter defibrillator (ICD) who have sustained monomorphic VT. The primary study endpoint is freedom from any recurrence of VT through 12 months. The secondary endpoints are acute success; freedom from any VT at 1 year in a large-scar subpopulation; procedure-related major adverse events; and mortality rate through 12-month follow-up. Follow-up will consist of visits at 3, 6, 9, and 12 months, all of which will include ICD interrogation. CONCLUSIONS: The MAGNETIC VT trial will help determine whether substrate-based ablation of VT with RMN has clinical advantages over manual catheter manipulation. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02637947.