Gersh, Bernard J.

Background: Differences in the impact of comorbid conditions on outcomes in atrial fibrillation (AF) patients compared to population controls have not been well documented. Methods: The prevalence of 19 chronic conditions and smoking status was obtained in 1430 patients with incident AF from 2000-2010 and 1430 controls matched 1:1 on sex and age (within 5 years) from Olmsted County, MN. Andersen-Gill models determined associations of each condition with all-cause hospitalizations in AF cases and controls after adjusting for all other conditions and accounting for the matching. Cox regression determined associations of each condition with death. Results: Among 1430 matched pairs (median age 76 years, 48.6% men), the prevalence of chronic conditions was higher in AF cases compared to controls for all conditions except asthma, dementia, depression, hepatitis, and osteoporosis. Over a mean follow-up of 6.3 years, 2678 hospitalizations and 812 deaths occurred. The rates of hospitalization were 59 and 26 per 100 person-years and the rates of death were 10 and 5 per 100 person-years in AF cases and controls, respectively. After adjusting for all other conditions, the risk of hospitalization was lower in AF patients compared to controls for those with coronary artery disease, arthritis, cancer, chronic obstructive pulmonary disease, and osteoporosis (figure). In contrast, the risk of hospitalization was higher in AF cases for those with diabetes and substance abuse. For deaths, the only comorbidity with different associations between AF cases and controls was depression. The hazard ratios (95% CI) for death were 2.02 (1.26-3.24) in AF cases and 0.90 (0.58-1.38) in controls (p-value for interaction=0.008). Conclusions: AF patients have a higher prevalence of chronic conditions compared to population controls. The associations of comorbidities with hospitalizations differed between AF cases and controls, suggesting that management of comorbidities in patients with AF may need to be tailored to this specific patient population.

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice, causes substantial morbidity, and is associated with an excess risk of mortality. However, information on contemporary time trends in survival after AF is lacking. Thus, we aimed to determine whether survival after incident AF has changed over the last decade in a community-based cohort of 3413 individuals with incident AF between 2000 and 2010. Methods: Olmsted County, MN residents 18 years of age and older with a first-ever AF or atrial flutter event between 2000 and 2010 were identified using inpatient and outpatient diagnostic codes and electrocardiograms. Deaths from any cause were ascertained through August 31, 2012 and time trends in survival after AF were examined using Kaplan-Meier curves and Cox proportional hazards regression. Results: Among 3413 individuals with incident AF (52% men, age range 18-104) between 2000 and 2010, 1561 deaths were observed over a median follow-up of 3.4 years. Survival did not differ by year of AF diagnosis (figure). In addition, the proportion of cardiovascular disease-related deaths compared to non-cardiovascular deaths did not differ over time. After adjustment for age, sex, and Charlson comorbidity index, the hazard ratios for all-cause mortality were 1.09 (95% CI 0.97-1.23) for those diagnosed with AF in 2004-2007 vs. 2000-2003 and 1.04 (95% CI 0.90-1.12) for 2008-2010 vs. 2000-2003. Furthermore, the risk of death did not differ by sex after adjustment for age and comorbidity (HR 1.00, 95% CI 0.90-1.11 for men vs. women). Conclusions: In the community, survival after AF has remained constant over the last decade despite substantial changes in the recommendations for treatment of AF. This underscores the importance of identification of prognostic factors and continued surveillance of outcomes in AF, as well as a better understanding of how to optimize the management of AF to improve outcomes in these patients.

Introduction: Idiopathic Dilated (DCM) and hypertrophic cardiomyopathies (HCM) are leading causes of sudden cardiac death. The incidence and prevalence of both DCM and HCM were originally estimated in Olmsted County, MN over 1975-1984. Incidence was 6.0 and prevalence was 36.5 per 100,000 person-years, for DCM; with incidence and prevalence rates of 2.5 and 19.7 per 100,000 person-years for HCM. This study aims to determine the incidence and mortality rates of individuals diagnosed with HCM and DCM in Olmsted County, MN from 1984 to 2016. Methods: The Rochester Epidemiology Project is a validated long term medical record linkage system that collects and links medical information for the approximately 145000 residents of Olmsted County, Minnesota. Using this database and the Electronic Health Record systems at Mayo Clinic and Olmsted Medical Center in Rochester, MN, we manually reviewed and validated the medical records of 4440 patients. This cohort includes all patients with any mention of a cardiomyopathy based on ICD and HICDA codes during the period 1984 to 2016. Data were summarized with mean and standard deviation, frequency and percentage and compared between groups using two sample t-test for continuous data and chi-square for proportions. Survival was computed using Kaplan-Meier methods and compared to expected survival based on age and gender. Incidence was computed using Olmsted County population numbers during the time period and adjusted to the US 1980 white population to allow for comparison with the previous study. Results: The calculated crude incidence rate for DCM and HCM are 10.1 and 7.8 per 100,000 respectively. Incidence rates adjusted for comparison to US 1980 white population (age and sex adjusted) are 10.4 (95% CI: 9.3-11.4) and 8.0 (95% CI: 7.1-8.8) per 100,000 person-years, respectively. The observed number of deaths in this cohort (HCM and DCM) was 420 vs 194 expected. Conclusions: Calculated incidence, both crude and adjusted rates are higher than previously estimated rates. The crude incidence rate for HCM is almost 4-fold higher than that for DCM is 2.4 times higher than the original estimate by Codd et al. Individuals with cardiomyopathies were found to have a higher overall mortality rate than the general population with an observed to expected hazard ratio of 1.73 (95% CI 1.49-2.01, p<0.001) for DCM and 1.44 (95% CI 1.21-1.71, p<0.001) for HCM. Our findings suggest that previous studies may have underestimated the true burden of HCM and DCM in the population which has important implications for healthcare provision and cost.

Objective: Diabetes is a common among patients with atrial fibrillation (AF). However, little is known on the impact of diabetes on symptoms, health status, care and outcomes among AF patients. We assessed whether symptoms, health status, care and outcomes differ between AF patients with and without diabetes. Methods: This observational cohort study included 9,749 patients with AF from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation registry, a prospective, nationwide, multicenter outpatient registry of patients with incident and prevalent AF enrolled at 174 sites between June 2010 and August 2011. The outcomes were symptoms, health status, and AF treatment, as well as 2-year risks of death, readmission, thrombomebolic events, heart failure (HF) and AF progression. Results: Among AF patients; those with diabetes (29.5%) were younger and more likely to have hypertension, chronic kidney disease, HF, coronary heart disease, and stroke. Patients with diabetes had a lower Atrial Fibrillation Effects on Quality of Life score (80.6 [IQR: 62.5 - 92.6] vs. 82.4 [IQR: 67.6 -93.5]; P = 0.025), but a higher CHA 2 DS 2 -VASc score (5 [IQR: 4 - 6] vs. 4 [2 - 5]; P <0.0001) and were more likely to receive anticoagulation ( P <0.001). Diabetes was associated with higher mortality, with a greater overall (adjusted hazard ratio [aHR]: 1.63 [95% CI: 1.04-2.56] for age<70 vs. 1.25 [1.09-1.44] for age ≥70) and cardiovascular (2.20 [1.22-3.98] for age<70 vs. 1.24 [1.02-1.51] for age ≥70) mortality risks before age 70 years. Diabetes conferred a higher risk of non-cardiovascular (CV) death (1.29 [1.06-1.56]), sudden cardiac death (1.53 [1.04-2.26]), hospitalization (1.15 [1.09-1.22]), CV hospitalization (1.13 [1.05-1.22]) and non-CV and non-bleeding-related hospitalization (1.19 [1.10-1.30]); but no increase in risks of thromboembolic events, bleeding related hospitalization, new-onset HF, and AF progression. The use of oral anticoagulants (OAC) modifies the relation of diabetes and all-cause hospitalization, with a higher risk among those on OAC (1.21 [1.12-1.29]). Conclusions: Among patients with AF, diabetes was associated with worse AF symptoms and lower quality of life, as well an increased risk of death and hospitalizations, but not with the risk of thromboembolic or bleeding events.

Introduction: Patient understanding of available therapies for atrial fibrillation (AF) is foundational to shared medical decision making and long term medication adherence. Yet, there is a paucity of data regarding the extent to which patients newly diagnosed with AF in routine community practice understand their options. Hypotheses: 1) Understanding of warfarin, novel oral anticoagulants (NOAC), rhythm control therapy, cardioversion and radio frequency ablation changes little from baseline to 6 months and 2) treatment rates at 6 months are associated with patient understanding of therapies at baseline. Methods: We analyzed survey data from SATELLITE, a substudy of new-onset AF patients enrolled at 56 US sites participating in the ORBIT-AF registry. Patients were surveyed at the baseline and 6 month follow up clinic visit using Likert scales. Agreement between time points was assessed with the McNemar test, and the relationship between understanding and treatment was assessed only for the subset not on treatment at baseline. Results: Of 1000 patients enrolled in SATELLITE, 506 had 6-month survey data (data collection is continuing). Among these, the median age was 69.0 years (IQR 63.0 - 76.0) and 93.7% (474 of 506) were white. There was evidence of improvement in the self-reported understanding of warfarin and NOACs from baseline to 6 months, but not for rhythm control, ablation or cardioversion. The proportion reporting high understanding improved significantly for warfarin (p<.0001) and NOACs (p<.0001) from 47% (223 of 474) and 51% (245 of 481) at baseline to 60% (284 of 474) and 69% (332 of 481) at 6 months respectively (Figure 1). Patients with high understanding of the benefits of ablation (p=0.0005) and options for ablation (p=0.0093) at baseline were more likely to have this therapy at the 6 month follow up (N=590), but improved understanding was not associated with increased use of warfarin/NOACs (N=83) or rhythm control (N=444). Conclusions: Patients with new-onset AF had improved self-reported understanding of some treatment options over the first 6-months from diagnosis; however, factors other than patient understanding may influence AF treatments received at 6 months. Patient understanding of AF treatments remains suboptimal at 6 months, and our results suggest a need for ongoing patient education.

Background Aortic stenosis (AS) affects, and is associated with significant comorbidity and mortality, including sudden cardiac death (SCD) from unknown mechanisms. However, it is difficult to predict which patients with AS will suffer a SCD event. Anemia and low iron are known risk factors for mortality in heart failure populations and AS. We hypothesized that anemia in patients with AS is associated with increased risk of SCD. Purpose Understand the relationship and prognostic implications between anemia and SCD in patients with severe AS. Methods and Results We selected 8,144 of 10,850 patients with severe AS (mean transvalvular gradient ≥40 mmHg or peak velocity ≥4 m/s or calculated valve area < 1 cm 2 ) from the Mayo Clinic Aortic Stenosis Registry, which includes all consecutive patients with severe AS over the time period January 1 st , 1983 to September 30 th , 2015. Subjects in this analysis (median age 76 years and 57% male) were diagnosed starting in 1995 and had hemoglobin (Hb) measurements within one year of diagnosis and prior to intervention. The mean Hb level was 12.8 (± 1.9) g/dL. The prevalence of anemia (Hb<13.0g/dL for men, <12.0g/dL for women) was 40%, 14% microcytic, 20% macrocytic, with the remainder normocytic. Of the 8,144 patients, a total of 4,440 died (10‐year survival 39%; and 240 were confirmed as SCD events [10 year cumulative incidence 4%]). Anemia was associated with increased all‐cause mortality (HR 1.87, 95% CI 1.76–1.99, P=<0.001) and increased SCD events (HR 1.58, 95% CI 1.22–2.06, P=<0.001) in patients with severe AS. Every SD decrease in Hb (1.9 g/dL) was associated with an increased risk of SCD (HR 1.42, 95% CI 1.24–1.62, P<0.001). Conclusions Anemia is highly prevalent in patients with severe aortic stenosis and is independently associated with increased all‐cause mortality, and more specifically with increased SCD risk. Possible mechanisms include anemia aggrevating myocardial hypoxia, increasing propensity for arrhythmia and abnormal Bezold‐Jarisch reflex mismatch. Anemia may be a useful prognostic marker and a potential therapeutic target in patients with severe AS. Support or Funding Information CAAC is supported by AHA17POST33400211 and NIH HL134885. This study was supported by a grant from the Department of Cardiovascular Medicine, Mayo Clinic Rochester. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Introduction: Cardiovascular disease remains the leading cause of morbidity and mortality in patients with amyloid light chain (AL) amyloidosis. Current prognostic evaluation in AL cardiomyopathy (AL-CM) largely relies upon disparate proxy measurements to assess mortality. With respect to observed myocardial volume changes between systole and diastole, we describe a single measurement derived from cardiac MRI (CMR) to assess mortality of AL-CM. Methods: A cohort of 129 consecutive patients with AL-CM undergoing CMR with amyloid protocol from the years 2001 - 1997 was reviewed. Myocardial volume change at end systole and end diastole was assessed by disc summation with CMR. The myocardial function index (MFI) was calculated by consolidating blood pool and myocardial volume measures as confluent components of myocardial function utilizing operator tracings. The association of MFI and death was assessed with adjusted hazard ratios (HR) derived by a Cox model. Results: Data at time of CMR was reviewed. The mean age was 60 ±10; 68% subjects were female. Median survival from CMR was 47 months. Mean LVEF was assessed by echocardiography to be 55% ± 12. Mean calculated MFI was 19.8% ±7. Univariate analysis suggested MFI is strongly associated with death (HR 0.004; 95%CI 0.00002-0.0838; p = 0.0003). A multivariate analysis re-demonstrated the strong predictive value of MFI when controlled for age (HR 0.006; 95%CI 0.00003 - 0.1156; p = 0.0006). Conclusion: MFI strongly correlates with mortality in AL-CM. In contrast to previously described assessments of ventricular function (extracellular volume imaging, myocardial perfusion imaging, and myocardial contraction fraction), MFI is easily derived from CMR and considers blood pool and myocardial volumes as confluent components of myocardial function. Further studies are needed to assess MFI amongst patients with varying etiologies of heart failure.

Introduction: Recent studies showed post-operative atrial fibrillation (POAF) is associated with increased stroke risk - even approaching that of unprovoked AF. This raises the question of whether patients with POAF should receive anticoagulation. We aim to compare different anticoagulation strategies in patients with POAF after cardiac and non-cardiac surgeries. Methods: Using a large national administrative database (OptumLabs Data Warehouse), we identified 33,981 patients with POAF between 1/1/2013-9/30/2019. Patients were divided to four groups based on the initial treatment within 30 days of POAF: (1) no anticoagulation (N=28,807) (2) apixaban (N=2178) (3) rivaroxaban (N=1320) (4) warfarin (N=1676). Follow up started at the 30 th day after POAF to exclude patients who died shortly after surgery and minimize immortal time bias. The follow up continued until patients changed treatment strategies, insurance, or died. 1:1 propensity score matching was performed between each anticoagulant to no treatment to balance on 86 baseline characteristics. Results: The mean age was 71.1±11.2 yr; mean CHA 2 DS 2 -VASc was 4.1±1.8; 29.1% received cardiac surgeries; 15.2% received anticoagulation within 30 days of POAF. The event rate per 100 person years was 1.58 for stroke in no-anticoagulation group, and 1.29 for anticoagulation group; 2.86 for major bleeding in no-anticoagulation group and 4.50 for anticoagulation group. After matching, apixaban and rivaroxaban were associated with a lower risk of stroke, but a higher risk of major bleeding; warfarin was not associated with a lower risk of stroke, but a higher risk of major bleeding (Figure). The effect was consistent across subgroups, e.g., age and surgery type. Conclusions: In patients with POAF, the stroke rate was lower than what was typically observed in clinical AF. Treatment with apixaban and rivaroxaban immediately after POAF was associated with a reduced risk of stroke but an increased risk of major bleeding.

Introduction: Watchman has been increasingly used in AF patients who have difficulties taking anticoagulation, but the RCTs only compared Watchman to warfarin. There was also a signal of increased ischemic stroke with Watchman in comparison to warfarin in RCTs, which made some clinicians question the fundamental premise that Watchman can reduce stroke. We aimed to compare Watchman to no anticoagulation in a large national cohort of patients in the US. Methods: We identified AF patients treated with Watchman (N=7,309) or no anticoagulation (N=1,234,543) between 2015-2017 from the OptumLabs Data Warehouse, which is the first to link private insurance, Medicare Advantage, and Medicare Fee-for-Service records at patient level longitudinally. One-to-one propensity score matching was used to balance patients on demographics and medical history. The primary outcomes were ischemic stroke or systemic embolism (hereafter referred to as stroke) and major bleeding. Secondary outcomes included all-cause mortality and intracranial bleeding. Results: In the unmatched cohort, the mean age was 76.6±6.4 yr in the Watchman group and 76.6 ±8.5 yr in the no anticoagulation group, but Watchman patients were more likely to have a history of bleeding (44.9% vs 13.7%) and intracranial bleeding (9.5% vs 2.6%). After matching, the two groups were similar on 18 baseline characteristics. Watchman was associated with a lower risk of stroke and mortality, but a higher risk of major bleeding and a similar risk of intracranial bleeding. The associations were largely consistent across subgroups, including those with relative contraindications to anticoagulation (Figure). Conclusions: In AF patients who had difficulties taking anticoagulation, Watchman offers an alternative approach to reduce stroke and mortality. The results provide important evidence to inform clinical decision making in the absence of RCTs, since 40% of AF patients in routine practice are not on anticoagulation.