Fonarow, Gregg C.

Importance Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with increased risk of diabetic retinopathy (DR) and nonarteritic anterior ischemic optic neuropathy (NAION). The risk of sight-threatening complications associated with GLP-1 RAs is underexamined. Objective To investigate whether the use of GLP-1 RAs in patients with T2D is associated with the development of DR, NAION, or DR complications. Design, Setting, and Participants This retrospective cohort study of adults (aged ≥18 years) with T2D and a recent hemoglobin A 1c level of 6.5% or higher was conducted between January 1, 2015, and September 30, 2022, using the TriNetX database. The cohort was divided into 2 groups, adjusted for baseline characteristics through propensity score matching (PSM), based on whether the individuals received prescriptions for a GLP-1 RA. The statistical analysis was conducted on October 10, 2024. Exposures At least 2 prescriptions of a GLP-1 RA given 6 months apart. Main Outcomes and Measures Cox proportional hazard regression models were used to evaluate the primary outcome: association between GLP-1 RAs and the risk of incident DR, NAION, or sight-threatening complications over a 2-year follow-up period. Results After PSM, 185 066 individuals (mean [SD] age, 59.0 [12.5] years; 93 389 females [50.5%]) were prescribed GLP-1 receptor agonists. Use of GLP-1 RAs was associated with an increased incidence of DR (hazard ratio [HR], 1.07; 95% CI, 1.03-1.11), while no statistically significant difference was observed in the risk of NAION (HR, 1.26; 95% CI, 0.94-1.70). In a subgroup analysis of 32 695 patients with preexisting DR, GLP-1 RAs were not associated with progression to proliferative DR (HR, 1.06; 95% CI, 0.97-1.15) or diabetic macular edema (HR, 0.98; 95% CI, 0.95-1.01) but were associated with a lower occurrence of vitreous hemorrhages (HR, 0.74; 95% CI, 0.68-0.80), neovascular glaucoma (HR, 0.78; 95% CI, 0.68-0.88), or blindness (HR, 0.77; 95% CI, 0.73-0.82). Conclusions and Relevance In this cohort study of individuals with T2D, GLP-1 RA use was associated with a modestly increased risk of incident DR; however, fewer patients experienced sight-threatening DR complications, including blindness, even among those with preexisting DR. These findings suggest that all patients with T2D treated with GLP-1 RAs, regardless of preexisting DR, should be regularly screened and monitored for potential complications of T2D.

Previous studies about the COVID-19 pandemic on STEMI patient outcomes have conflicting results. It remains unclear if this may be attributed to regional differences and/or differences during COVID-19 wave periods. Using the American Heart Association Get With The Guidelines–Coronary Artery Disease registry data, we evaluated (1) time metrics related to STEMI system goals and (2) regional variation in STEMI incidence and in-hospital mortality during pandemic wave time periods. The study included all patients 18–100 years old admitted with STEMI (n = 72,516) to 1 of 435 American Heart Association Get With The Guidelines–Coronary Artery Disease hospitals (1 October 2019–31 December 2021). Of these, 70.8% were male and 73.0% non-Hispanic White, with a median age of 63 (IQR 18) years. Compared to pre-pandemic time frames, patients with STEMI had a higher risk profile, delayed time to treatment, were treated with fibrinolytic therapy or primary PCI, and were transferred for primary PCI at similar rates, and had higher adjusted in-hospital mortality (during the second wave in the South and Midwest). Preservation of STEMI systems of care resulted in an overall lower in-hospital mortality rate than predicted, although opportunities exist to improve treatment delays. Regional differences in mortality rates require further study.

Background: Concerns exist regarding orthotropic heart transplantation (OHT) in hepatitis C (HCV) seropositive recipients. The UNOS national registry was accessed to evaluate HCV recipient sero-positivity and outcomes. Method: Retrospective analysis of the UNOS registry (2000-2014) to evaluate recipient profile and clinical outcome of HCV sero-positive (HCV+ve) and sero-negative (HCV -ve) pts. Early and late adjusted survival and adverse events at follow-up were compared. Results: From 23,507 patients (mean age 52 yrs; 75% male), 481 (2%) were HCV +ve (mean age 52 yrs; 77% male). Annual proportion of HCV +ve recipients was comparable over the study period (range 1.3-2.7%; p=0.2). The HCV +ve cohort had more African American (22% vs 17%; p=0.01), pts with a prior LVAD (21 vs 14%; p<0.01 and more hepatitis B core Ag+ve recipients (17% vs 5%; p<0.01). However, ECMO (p=0.7), inotropic (p=0.2), and intra-aortic balloon pump (p=0.7) support, serum creatinine (p=0.7) and serum bilirubin (p=0.7) were similar. Proportion of Status 1A pts was similar (24% HCV+ vs 21% HCV -); however wait-time for HCV + recipients was longer (mean 23 vs 19 days; p<0.01). Among donor variables, age (p=0.8), hepatitis B status (p=0.4) and CDC high risk status (p=0.9) were comparable. At a median follow up of 4 years, 67.1% patients were alive, 28.4% died and 1.1% were re-transplanted (3.4% missing). Overall survival was worse in the HCV+ cohort (64.3 vs 72.9 % and 43.2 vs 55% at five and ten years; p<0.01). Late renal [OR 1.2(1-1.6); p = 0.02] and liver dysfunction [OR 4.5 (1.2-15.7); p=0.01] occur in HCV +ve recipients. On adjusted analysis, HCV sero-positivity is associated with poorer survival [HR0.6 (0.5-0.8); p<0.01]. Conclusion: A small proportion of patients receiving a heart transplant in the United States have hepatitis C. In spite of comparable pre-operative hepatic function, hepatitis C sero-positive recipients develop late liver dysfunction and have poorer long-term survival.

Introduction: Limited data is available regarding the incidence of new-onset diabetes mellitus (NODM) after heart transplantation and it`s impact on patient survival. Hypothesis: Methods: From the United Network of Organ Sharing database (January 2004 to September 2014), we identified 13,353 patients without pre-operative diabetes mellitus undergoing heart transplantation. Multivariable Cox regression was implemented to determine predictors for the development of NODM. A matched cohort of New-onset Diabetes mellitus (NODM (+)) and NODM (-) was generated by 1:1 nearest neighbor propensity-matching. The association of NODM with long-term survival was then estimated with robust Cox regression. Results are presented at the 95% Confidence level; all tests are two-tailed. Results: During the study period, 1,921 of 13,353 (14%) developed NODM. Estimated freedom from NODM was 97% (96-98%) & 77% (76 - 78%) at the end of 1 and 5 years respectively. Predictors for the development of NODM were recipient age > 50 years (HR 1.2 95% CI1.05, 1.3; p < 0.01), recipient BMI > 30 (HR 1.4 95% CI1.2, 1.6; p < 0.01) and race (African American vs Caucasian (HR 1.3 95% CI1.2, 1.5; p < 0.01)). Cox-regression of a propensity-matched cohort of 1921 NODM+ve and NODM-ve recipient-pairs demonstrates that NODM is associated with poorer survival (HR for mortality: 1.3 95% CI 1.1, 1.5; p < 0.001). Conclusions: More than one in ten heart transplant recipients develop NODM post heart transplantation. Obesity, older age, and African American race patients to be at higher risk for NODM. New onset diabetes was independently associated with an almost 30% reduced long-term survival. More than one in ten heart transplant recipients develop NODM post heart transplantation. Obesity, older age, and African American race patients to be at higher risk for NODM. New onset diabetes was independently associated with an almost 30% reduced long-term survival.

AbstractBackgroundAn unmet need exists to reliably predict the risk of intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF) treated with oral anticoagulants (OACs).HypothesisAn externally validated model improves ICH risk stratification.MethodsIndependent factors associated with ICH were identified by Cox proportional hazard modeling, using pooled data from the GARFIELD‐AF (Global Anticoagulant Registry in the FIELD‐Atrial Fibrillation) and ORBIT‐AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registries. A predictive model was developed and validated by bootstrap sampling and by independent data from the Danish National Patient Register.ResultsIn the combined training data set, 284 of 53 878 anticoagulated patients had ICH over a 2‐year period (0.31 per 100 person‐years; 95% confidence interval [CI]: 0.28–0.35). Independent predictors of ICH included: older age, prior stroke or transient ischemic attack, concomitant antiplatelet (AP) use, and moderate‐to‐severe chronic kidney disease (CKD). Vitamin K antagonists (VKAs) were associated with a significantly higher risk of ICH compared with non‐VKA oral anticoagulants (NOACs) (adjusted hazard ratio: 1.61; 95% CI: 1.25–2.08; p = .0002). The ability of the model to discriminate individuals in the training set with and without ICH was fair (optimism‐corrected C‐statistic: 0.68; 95% CI: 0.65–0.71) and outperformed three previously published methods. Calibration between predicted and observed ICH probabilities was good in both training and validation data sets.ConclusionsAge, prior ischemic events, concomitant AP therapy, and CKD were important risk factors for ICH in anticoagulated AF patients. Moreover, ICH was more frequent in patients receiving VKA compared to NOAC. The new validated model is a step toward mitigating this potentially lethal complication.

Introduction: Higher body mass index (BMI) is an independent risk factor for incident atrial fibrillation (AF). However, its impact on management strategies and clinical outcomes among patients with prevalent AF is unclear. Methods: The study cohort included patients with AF enrolled in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry from June 2010 through August 2011. Participants with BMI > 18.5 kg/m2 were stratified into normal (18.5 - 25 kg/m2), overweight (25 - 30 kg/m2), Class I obese (30 - 35 kg/m2), Class II obese (35 - 40 kg/m2), and Class III obese (>40 kg/m2) categories. Unadjusted and adjusted Cox frailty models were constructed to assess the categorical and continuous association of BMI with AF progression, mortality, and incidence of thromboembolic events. Results: We evaluated 9,606 patients with AF (mean age: 74 + 11 years; 42% women) from 174 US ORBIT participating practices. Patients in the higher BMI categories were younger and had a higher prevalence of comorbidities such as diabetes, hypertension, and obstructive sleep apnea. AF symptom burden was greatest among patients in extreme BMI categories. Proportional use of anticoagulation, antiarrhythmic drugs, and invasive rhythm control strategies was significantly greater among patients in higher BMI categories. Rates for mortality and stroke/non-CNS embolism decreased in a near linear fashion across successively higher BMI categories (P<0.001; Table). After multivariable adjustment, higher BMI categories were associated with lower risk for mortality (p = 0.0002), with the lowest risk observed among overweight patients [Hazard Ratio (HR) (95% CI): 0.65 (0.54 - 0.79) ref. group: normal weight]. For every 5-kg/m2 increase in BMI, the odds of risk-adjusted mortality were 6% lower [HR (95% CI): 0.94 (0.89 - 0.98)]. In contrast, the association between BMI and risk for stroke/non-CNS embolism was significant on unadjusted analysis (P <0.001) but attenuated after adjustment for risk factors (P = 0.78; Table). No significant association was observed between BMI and AF progression rates in either unadjusted (P = 0.35) or adjusted analyses (P = 0.17). Conclusion: Among patients with AF, higher BMI was associated with a greater use of anticoagulation, rhythm control strategies, and lower mortality risk.

Background: Interruption of OAC is often required for invasive procedures, yet the frequency, management, and outcomes of temporary interruptions (TIs) in community practice are unknown. Methods: We assessed the frequency and reasons for TI in outpatients with AF enrolled in the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF). Patient characteristics and use of bridging anticoagulants were analyzed. Endpoints included periprocedural adverse events (bleeding, thrombotic, or other) and cause-specific hospitalization within 30 days after TI. Results: Overall 7,372 patients were treated with OAC at baseline; 30% (n=2200) required at least 1 TI during median follow-up of 1 year. Patients requiring TI were similar in age (mean age 74 for both) and CHADS2 scores (mean 2.4 for both) to those not requiring TI. Among 3104 interruptions, the most commonly-identified reasons were for non-cardiac surgery (n=827, 27%), followed by endoscopic procedures (n=551, 18%) and cardiac catheterization (n=308, 10%). Bridging anticoagulants were used in 23% (n=709) of interruptions, including low-molecular weight heparin (n=512) or unfractionated heparin (n=109). Rates of bridging were highest during cardiac surgery (44%), cardiac catheterization (32%), and catheter ablation (33%). Patients with a prior stroke or TIA were significantly more likely to receive bridging (35% vs. 25%, p=0.0003), however there was no difference between patients with CHADS2 score >=2 vs. 0-1 (27% vs. 25%, p=NS). Adverse events during interruption were more common in bridged patients (5.1% vs. 2.9%, p=0.02), including bleeding events (3.6% vs. 1.8%, p=0.02); thrombotic events were uncommon (0.7 [n=4] vs. 0.5% [n=10], p=NS). After interruption, adverse events occurred early in follow-up (Figure), and bridged patients were more likely to experience any adverse event (13% vs. 6.3%, p<0.0001), cardiovascular hospitalization (4.3% vs. 2.3%, p=0.02), and bleeding hospitalization (2.2% vs. 0.7%, p=0.002) within 30 days. Conclusions: Temporary interruptions are common in patients receiving OAC for AF, however, bridging anticoagulation is used in a minority. Bleeding events following TI occurred significantly more often in patients receiving bridging anticoagulation.

Background: Dabigatran is a novel oral anticoagulant approved in October 2010 for thromboprophylaxis in atrial fibrillation (AF), yet patterns of adoption of this novel agent in clinical practice are unknown. Methods: Using the ORBIT-AF Registry, a national outpatient prospective AF registry involving 170 sites, we examined patterns of those switching to dabigatran from warfarin from 2010 to 2012. Results: Of 7,066 patients with AF receiving warfarin at baseline, 511 (7%) were switched to dabigatran during follow-up. Patients switched to dabigatran were younger (median age 73 vs. 76, p<0.0001), more likely to be White (94% vs. 89%, p=0.001), and had better kidney function (median creatinine clearance (CrCl) 77 mL/min vs. 69 mL/min, p<0.0001), but less likely to have a history of anemia, (14% vs. 18%, p=0.009) or history of any cerebrovascular disease (14% vs. 17%, p=0.04) or CAD (22% vs. 34%, p<0.0001) or be followed in an anticoagulation clinic (36% vs. 45%, p<0.0001). Patients switched to dabigatran were more likely to have been recently diagnosed with AF (5.3% vs. 3.0%, p=0.03), and their CHADS 2 scores were significantly lower (p<0.0001). Conclusions: Patients receiving warfarin who were switched to dabigatran were younger, with lower CHADS 2 scores, better kidney function, and less concomitant cardiovascular disease than those not switched. This conservative transition pattern suggests greater physician emphasis on bleeding avoidance than on stroke risk reduction.

Background. Oral anticoagulation therapy (OAC) reduces the risk of thromboembolic events associated with atrial fibrillation (AF), yet a substantial proportion of patients with AF are not prescribed OAC. The frequencies of and factors associated with contraindications to OAC therapy in clinical practice are not well-described. Methods. We used data from the ORBIT-AF study, a national, prospective, outpatient registry of incident and prevalent AF. OAC contraindications were uniformly collected at study enrollment by site personnel. Patient and provider characteristics were compared between participants with documented OAC contraindications at baseline and those without OAC contraindications. Results. From June 2010 to August 2011, 10124 patients ≥18 years old with electrocardiographically documented AF were enrolled at 176 practices. Of these, 1409 (13.9%) had OAC contraindications documented at the baseline visit: prior bleed (26.2%), patient refusal/preference (26.0%), high bleeding risk (22.6%), frequent falls/frailty (16.6%), other (11.9%), need for dual antiplatelet therapy (9.8%), unable to adhere/monitor warfarin (5.7%), comorbid illness (5.0%), prior intracranial hemorrhage (4.7%), allergy (2.3%), occupational risk (0.8%), and pregnancy (0.2%). Compared to patients without contraindications, those with contraindications had higher stroke risk (CHADS2>2) and were older, more likely to be female, more likely to be seen by a cardiologist and less likely to be seen by an electrophysiologist (Table 1). Among those patients with reported contraindications, 28.4% were taking warfarin. Conclusions. Contraindications to OAC therapy among AF patients are common and often due to high bleeding risk. Furthermore, many patients with reported contraindications are taking warfarin, suggesting that many contraindications to warfarin therapy are minor, relative, or temporary.

Introduction: Randomized trials have not demonstrated significant differences in stroke, heart failure or mortality between rhythm and rate control strategies for management of atrial fibrillation (AF). The comparative outcomes in contemporary clinical practice are not well described. The objective of this study was to evaluate outcomes in clinical practice with rhythm control versus rate control strategy. Methods: Patients managed with a rhythm control strategy targeting maintenance of sinus rhythm were retrospectively compared with a strategy of rate control alone in a AF registry across various US practice settings. Unadjusted and adjusted (inverse-propensity weighted) outcomes were estimated. Results: The overall study population (n=6988) had a median age of 74 (25th, 75th percentile 65, 81) years, 56% were males, 77% had first detected or paroxysmal AF and 89% had CHA2DS2-VASc score ≥2. In unadjusted analyses, rhythm control was associated with lower all-cause death, cardiovascular death, first stroke/non-central nervous system systemic embolization/transient ischemic attack, or first major bleeding event (all p<0.05); however, rhythm control was associated with more cardiovascular hospitalizations (HR 1.24, 95% CI 1.10-1.39, p=0.0003; Figure). Conclusion: Among patients with AF in clinical practice, rhythm control was not superior to rate control strategy for outcomes of stroke, heart failure, or mortality, but was associated with more cardiovascular hospitalizations.