Atrial Fibrillation Occurring During Acute Hospitalization: A Scientific Statement From the American Heart Association.

Acute atrial fibrillation is defined as atrial fibrillation detected in the setting of acute care or acute illness; atrial fibrillation may be detected or managed for the first time during acute hospitalization for another condition. Atrial fibrillation after cardiothoracic surgery is a distinct type of acute atrial fibrillation. Acute atrial fibrillation is associated with high risk of long-term atrial fibrillation recurrence, warranting clinical attention during acute hospitalization and over long-term follow-up. A framework of substrates and triggers can be useful for evaluating and managing acute atrial fibrillation. Acute management requires a multipronged approach with interdisciplinary care collaboration, tailoring treatments to the patient's underlying substrate and acute condition. Key components of acute management include identification and treatment of triggers, selection and implementation of rate/rhythm control, and management of anticoagulation. Acute rate or rhythm control strategy should be individualized with consideration of the patient's capacity to tolerate rapid rates or atrioventricular dyssynchrony, and the patient's ability to tolerate the risk of the therapeutic strategy. Given the high risks of atrial fibrillation recurrence in patients with acute atrial fibrillation, clinical follow-up and heart rhythm monitoring are warranted. Long-term management is guided by patient substrate, with implications for intensity of heart rhythm monitoring, anticoagulation, and considerations for rhythm management strategies. Overall management of acute atrial fibrillation addresses substrates and triggers. The 3As of acute management are acute triggers, atrial fibrillation rate/rhythm management, and anticoagulation. The 2As and 2Ms of long-term management include monitoring of heart rhythm and modification of lifestyle and risk factors, in addition to considerations for atrial fibrillation rate/rhythm management and anticoagulation. Several gaps in knowledge related to acute atrial fibrillation exist and warrant future research.

Acute alcohol exposure and electrocardiographic changes: Finding from the HOLIDAY trial.

BACKGROUND: Alcohol consumption is associated with a higher increased risk of atrial fibrillation (AF), but the acute effects on cardiac electrophysiology in humans remain poorly understood. The HOw ALcohol InDuces Atrial TachYarrhythmias (HOLIDAY) Trial revealed that alcohol shortened pulmonary vein atrial effective refractory periods, but more global electrophysiologic changes gleaned from the surface ECG have not yet been reported. METHODS: This was a secondary analysis of the HOLIDAY Trial. During AF ablation procedures, 100 adults were randomized to intravenous alcohol titrated to 0.08% blood alcohol concentration versus a volume and osmolarity-matched, masked, placebo. Intervals measured from 12­lead ECGs were compared between pre infusion and at infusion steady state (20 min). RESULTS: The average age was 60 years and 11% were female. No significant differences in the P-wave duration, PR, QRS or QT intervals, were present between alcohol and placebo arms. However, infusion of alcohol was associated with a statistically significant relative shortening of the JT interval (r: -14.73, p = 0.048) after multivariable adjustment. CONCLUSION: Acute exposure to alcohol was associated with a relative reduction in the JT interval, reflecting shortening of ventricular repolarization. These acute changes may reflect a more global shortening of refractoriness, suggesting immediate proarrhythmic effects pertinent to the atria and ventricles.

Device Therapy and Arrhythmia Management in Left Ventricular Assist Device Recipients: A Scientific Statement From the American Heart Association.

Left ventricular assist devices (LVADs) are an increasingly used strategy for the management of patients with advanced heart failure with reduced ejection fraction. Although these devices effectively improve survival, atrial and ventricular arrhythmias are common, predispose these patients to additional risk, and complicate patient management. However, there is no consensus on best practices for the medical management of these arrhythmias or on the optimal timing for procedural interventions in patients with refractory arrhythmias. Although the vast majority of these patients have preexisting cardiovascular implantable electronic devices or cardiac resynchronization therapy, given the natural history of heart failure, it is common practice to maintain cardiovascular implantable electronic device detection and therapies after LVAD implantation. Available data, however, are conflicting on the efficacy of and optimal device programming after LVAD implantation. Therefore, the primary objective of this scientific statement is to review the available evidence and to provide guidance on the management of atrial and ventricular arrhythmias in this unique patient population, as well as procedural interventions and cardiovascular implantable electronic device and cardiac resynchronization therapy programming strategies, on the basis of a comprehensive literature review by electrophysiologists, heart failure cardiologists, cardiac surgeons, and cardiovascular nurse specialists with expertise in managing these patients. The structure and design of commercially available LVADs are briefly reviewed, as well as clinical indications for device implantation. The relevant physiological effects of long-term exposure to continuous-flow circulatory support are highlighted, as well as the mechanisms and clinical significance of arrhythmias in the setting of LVAD support.

A case-control study of the risk factors for obstetric fistula in Tigray, Ethiopia.

INTRODUCTION AND HYPOTHESIS: We tested the null hypothesis that there were no differences between patients with obstetric fistula and parous controls without fistula. METHODS: A unmatched case-control study was carried out comparing 75 women with a history of obstetric fistula with 150 parous controls with no history of fistula. Height and weight were measured for each participant, along with basic socio-demographic and obstetric information. Descriptive statistics were calculated and differences between the groups were analyzed using Student's t test, Mann-Whitney U test where appropriate, and Chi-squared or Fisher's exact test, along with backward stepwise logistic regression analyses to detect predictors of obstetric fistula. Associations with a p value <0.05 were considered significant. RESULTS: Patients with fistulas married earlier and delivered their first pregnancies earlier than controls. They had significantly less education, a higher prevalence of divorce/separation, and lived in more impoverished circumstances than controls. Fistula patients had worse reproductive histories, with greater numbers of stillbirths/abortions and higher rates of assisted vaginal delivery and cesarean section. The final logistic regression model found four significant risk factors for developing an obstetric fistula: age at marriage (OR 1.23), history of assisted vaginal delivery (OR 3.44), lack of adequate antenatal care (OR 4.43), and a labor lasting longer than 1 day (OR 14.84). CONCLUSIONS: Our data indicate that obstetric fistula results from the lack of access to effective obstetrical services when labor is prolonged. Rural poverty and lack of adequate transportation infrastructure are probably important co-factors in inhibiting access to needed care.

The QT Interval as a Noninvasive Marker of Atrial Refractoriness.

BACKGROUND: Atrial refractoriness may be an important determinant of atrial fibrillation (AF) risk, but its measurement is not clinically accessible. Because the QT interval predicts incident AF and the atrium and ventricle share repolarizing ion currents, we investigated the association between an individual's QT interval and atrial effective refractory period (AERP). METHODS: In paroxysmal AF patients presenting for catheter ablation, the QT interval was measured from the surface 12-lead electrocardiogram. The AERP was defined as the longest S1-S2 coupling interval without atrial capture using a 600-ms drive cycle length. RESULTS: In 28 patients, there was a positive correlation between QTc and mean AERP. After multivariate adjustment, a 1-ms increase in QTc predicted a 0.70-ms increase in AERP. CONCLUSIONS: The QTc interval reflects the AERP, suggesting that the QTc interval may be used as a marker of atrial refractoriness relevant to assessing AF risk and mechanism-specific therapeutic strategies.

Work ability and labor supply after kidney transplantation.

BACKGROUND: The vocational rehabilitation after kidney transplantation (KTX) is suboptimal. We sought to evaluate correlates of occupational outcomes after KTX. METHODS: We included 336 working-age patients with at least one creatinine assessment in the 3-month screening period. We collected clinical information from medical records. All subjects answered a self-administered questionnaire, and a follow-up questionnaire was mailed to each participant after 6 months. Study outcomes were the Work Ability Index (WAI) and labor supply (the number of days each patient worked in the follow-up period). We estimated the glomerular filtration rate (eGFR) with the Modification of Diet in Renal Disease Study equation. RESULTS: The mean eGFR was 52.76 ± 23.68 ml/min/1.73 m(2). The age-standardized employment-to-population ratio was 62%. Comorbidities, self-reported work ability, gender, age, health insurance type, and time since transplant were associated with employment status at baseline. The WAI (38.79 ± 5.88) was associated with the severity of renal impairment, work attachment and comorbidities. After 6 months, labor supply (mean 19.4 ± 9.7 weeks) was associated with WAI item 1 (ρ = 0.22; p = 0.03); eGFR was significantly associated with labor supply, and this association was slightly stronger in patients with physically demanding jobs. CONCLUSIONS: We identified modifiable factors associated with poor occupational outcomes in kidney transplant recipients. Consistent with labor supply theory, our results suggest that health care coverage plays a key role in employment decisions after KTX independent of possible confounders. Additionally, our study provides the rationale to further evaluate the implications of renal function-preserving strategies for indirect cost savings and self-reported ability to work after transplant.

Feeling a Little Blue After Ablation: Iatrogenic Atrial Septal Defect With Right-to-Left Shunt Following Atrial Fibrillation Ablation.

Atrial fibrillation is the most common cardiac arrhythmia. Cardiac ablation is indicated for patients refractory to medical management. During the ablation process, a transseptal puncture is utilized to access and isolate the pulmonary veins, which results in a temporary iatrogenic atrial septal defect (iASD). Generation of an iASD is considered unavoidable and is a generally accepted risk due to high rates of spontaneous closure. Studies have shown that persisting iASD may occur in 5%-20% of patients for up to nine to 12 months after undergoing radiofrequency ablation and that spontaneous rates of closure are high in patients with normal intracardiac pressures. Patients with preexisting elevated right intracardiac pressures from pulmonary hypertension or other right-sided cardiac pathology are at an increased risk of complications from iASD. These increased pressures can lead to clinically significant hypoxemia from right-to-left shunting following a transseptal puncture. Intervention with closure is considered in high-risk settings such as right atrial or ventricular enlargement, right-to-left shunting with hypoxemia, and intraseptal defect greater than 8 mm. This case vignette describes a 67-year-old female who developed clinically significant right-to-left shunting intraoperatively from iASD with ongoing hypoxemia for several months but with spontaneous closure. We highlight this case as it demonstrates spontaneous closure in a high-risk iASD. We also provide a review of the literature on iASD after cardiac ablations.

Real-world data of radiofrequency catheter ablation in paroxysmal atrial fibrillation: Short- and long-term clinical outcomes from the prospective multicenter REAL-AF Registry.

BACKGROUND: The safety and long-term efficacy of radiofrequency (RF) catheter ablation (CA) of paroxysmal atrial fibrillation (PAF) has been well established. Contemporary techniques to optimize ablation delivery, reduce fluoroscopy use, and improve clinical outcomes have been developed. OBJECTIVE: The purpose of this study was to assess the contemporary real-world practice approach and short and long-term outcomes of RF CA for PAF through a prospective multicenter registry. METHODS: Using the REAL-AF (Real-world Experience of Catheter Ablation for the Treatment of Symptomatic Paroxysmal and Persistent Atrial Fibrillation; ClincalTrials.gov Identifier: NCT04088071) Registry, patients undergoing RF CA to treat PAF across 42 high-volume institutions and 79 experienced operators were evaluated. The procedures were performed using zero or reduced fluoroscopy, contact force sensing catheters, wide area circumferential ablation, and ablation index as a guide with a target of 380-420 for posterior and 500-550 for anterior lesions. The primary efficacy outcome was freedom from all-atrial arrhythmia recurrence at 12 months. RESULTS: A total of 2470 patients undergoing CA from January 2018 to December 2022 were included. Mean age was 65.2 ±11.14 years, and 44% were female. Most procedures were performed without fluoroscopy (71.5%), with average procedural and total RF times of 95.4 ± 41.7 minutes and 22.1±11.8 minutes, respectively. At 1-year follow-up, freedom from all-atrial arrhythmias was 81.6% with 89.7% of these patients off antiarrhythmic drugs. No significant difference was identified comparing pulmonary vein isolation vs pulmonary vein isolation plus ablation approaches. The complication rate was 1.9%. CONCLUSION: Refinement of RF CA to treat PAF using contemporary tools, standardized protocols, and electrophysiology laboratory workflows resulted in excellent short- and long-term clinical outcomes.

The effect of antiarrhythmic medication management on atrial fibrillation ablation outcomes.

BACKGROUND: Patients commonly present for atrial fibrillation (AF) ablation while taking antiarrhythmic (AA) medications. It is unknown if AA use at the time of ablation affects procedural outcome. This study compares the AF ablation outcomes of patients who underwent ablation while on AA medications to those who were not on AA medications. METHODS AND RESULTS: A total of 180 consecutive patients who underwent their first catheter ablation of AF were identified from the Johns Hopkins Hospital AF registry and divided into 2 cohorts: those On AA at the time of ablation (127 patients, mean follow-up 24.6 months) and those Off AA at the time of ablation (53 patients, mean follow-up 20.3 months). Follow-up was performed to identify recurrent AF. There was no statistically significant difference in the percentage of patients without a recurrence of symptomatic AF (single procedure success rate) in the On and Off AA groups at 6 months postablation (53.5% vs 50.1%, P = 0.75), or by the end of follow-up (37.8% vs 41.5%, P = 0.64). For those patients who had symptomatic AF recurrence, the average time to recurrence was 6.2 ± 9.0 months in the On AA group and 4.2 ± 7.2 months in the Off AA group (P = 0.27). CONCLUSIONS: There was no statistically significant difference in the rate of symptomatic AF recurrence between the On AA and Off AA groups in this study. The use of AA medications at the time of ablation does not appear to affect procedural outcomes in this population.

Health-related quality of life in kidney transplant patients with diabetes.

OBJECTIVE: We sought to assess the disutility associated with diabetes in the kidney transplant population. METHODS: We enrolled 233 kidney transplant recipients age 18-74 from a Midwestern hospital outpatient department. Recipients with multiple or multi-organ transplants, those with laboratory evidence that suggests acute cellular damage (creatinine-kinase > 200 U/L), or a diagnosis of acute renal failure or acute rejection were excluded from the analysis (n = 33). Participants health-related quality of life (HRQOL) were evaluated using the Euro-QoL-5 Dimension (EQ-5D), Health Utility Index Mark III (HUI-III), and the Short Form-6D (SF-6D), which was calculated from the generic section (SF-12) of the Kidney Disease Quality of Life 36 (KDQOL-36). We estimated health utilities associated with diabetes using general linear modeling after adjusting for demographic, socioeconomic, and clinical characteristics. RESULTS: The adjusted health disutilities associated with diabetes were clinically and statistically significant: EQ-5D (Δ = 0.05; p < 0.01), HUI-III (Δ = 0.09; p < 0.01), and SF-6D (Δ = 0.04, p < 0.01). There was no difference between diabetic patients with good glycemic control (mean serum glucose <126 mg/dL in the three months prior to enrollment) and patients with poor glycemic control. CONCLUSIONS: Among kidney transplant patients between the ages of 18-74, non-diabetics have significantly higher HRQOL scores on the EQ-5D, HUI-III, and SF-6D compared with patients with diabetes.

Increased thrombosis susceptibility and altered fibrin formation in STAT5-deficient mice.

To explore the effect(s) of growth hormone signaling on thrombosis, we studied signal transduction and transcription factor 5 (STAT5)-deficient mice and found markedly reduced survival in an in vivo thrombosis model. These findings were not explained by a compensatory increase in growth hormone secretion. There was a modest increase in the activity of several procoagulant factors, but there was no difference in the rate or magnitude of thrombin generation in STAT5-deficient mice relative to control. However, thrombin-triggered clot times were markedly shorter, and fibrin polymerization occurred more rapidly in plasma from STAT5-deficient mice. Fibrinogen depletion and mixing studies indicated that the effect on fibrin polymerization was not due to intrinsic changes in fibrinogen, but resulted from changes in the concentration of a circulating plasma inhibitor. While thrombin-triggered clot times were significantly shorter in STAT5-deficient animals, reptilase-triggered clot times were unchanged. Accordingly, while the rate of thrombin-catalyzed release of fibrinopeptide A was similar, the release of fibrinopeptide B was accelerated in STAT5-deficient plasma versus control. Taken together, these studies demonstrated that the loss of STAT5 resulted in a decrease in the concentration of a plasma inhibitor affecting thrombin-triggered cleavage of fibrinopeptide B. This ultimately resulted in accelerated fibrin polymerization and greater thrombosis susceptibility in STAT5-deficient animals.

Effect of Text Message Reminders and Vaccine Reservations on Adherence to a Health System COVID-19 Vaccination Policy: A Randomized Clinical Trial.

Importance: Many organizations implemented COVID-19 vaccination requirements during the pandemic, but the best way to increase adherence to these policies is unknown. Objective: To evaluate if behavioral nudges delivered through text messages could accelerate adherence to a health system's COVID-19 vaccination policy. Design, Setting, and Participants: This randomized clinical trial was conducted within Ascension health system from October 11 to November 8, 2021. Participants included health system employees in the Midwest or South US who were not adherent with the vaccination policy 1 month before its deadline. Data were analyzed from November 17, 2021, to February 25, 2022. Interventions: Participants were randomly assigned to control or to receive a text message intervention that stated a vaccine had been reserved for the participant, with a scheduled date for vaccination within a 2-week period. Participants could reschedule to a different date within the period or upload a copy of their vaccination card. Follow-up text message reminders were sent the day before and the day of the appointment. Main Outcomes and Measures: The primary outcome was adherence to the health system's vaccination policy during the 2-week intervention. Secondary outcomes included time to vaccination during a 4-week follow-up period. Results: The sample included 2000 participants (mean [SD] age, 36.4 [12.3] years; 1724 [86.2%] women), with 1000 participants randomized to the control group and 1000 participants randomized to the intervention group. Overall, there were 164 Hispanic participants (8.2%), 46 non-Hispanic Asian participants (2.3%), 202 non-Hispanic Black participants (10.1%), and 1418 non-Hispanic White participants (70.9%). By the end of the 2-week intervention, 363 participants in the text message nudge group (36.3%) and 318 participants in the control group (31.8%) were adherent with the vaccination policy, representing a significant increase of 4.9 (95% CI, 0.8 to 9.1) percentage points in adjusted analyses comparing the nudge group with the control group (P = .02). Among participants who became adherent by the end of the 4-week follow-up period, the text message nudge significantly reduced time to adherence by a mean of 2.4 (95% CI, 2.1 to 4.7) days (P < .001) and a median of 5.0 (95% CI, 2.5 to 7.7) days (P < .001) compared with the control group. At 4 weeks, overall vaccination adherence was no longer different between groups (control: 477 participants [47.7%]; intervention: 472 participants [47.2%]). Conclusions and Relevance: This randomized clinical trial found that a behavioral nudge delivered through text messages accelerated adherence to a health system's COVID-19 vaccination policy but did change overall adherence by the time of the policy deadline. Trial Registration: ClinicalTrials.gov Identifier: NCT05037201.

Drug Interactions Affecting Oral Anticoagulant Use.

Oral anticoagulants (OACs) are medications commonly used in patients with atrial fibrillation and other cardiovascular conditions. Both warfarin and direct oral anticoagulants are susceptible to drug-drug interactions (DDIs). DDIs are an important cause of adverse drug reactions and exact a large toll on the health care system. DDI for warfarin mainly involve moderate to strong inhibitors/inducers of cytochrome P450 (CYP) 2C9, which is responsible for the elimination of the more potent S-isomer of warfarin. However, inhibitor/inducers of CYP3A4 and CYP1A2 may also cause DDI with warfarin. Recognition of these precipitating agents along with increased frequency of monitoring when these agents are initiated or discontinued will minimize the impact of warfarin DDI. Direct oral anticoagulants are mainly affected by medications strongly affecting the permeability glycoprotein (P-gp), and to a lesser extent, strong CYP3A4 inhibitors/inducers. Dabigatran and edoxaban are affected by P-gp modulation. Strong inducers of CYP3A4 or P-gp should be avoided in all patients taking direct oral anticoagulant unless previously proven to be otherwise safe. Simultaneous strong CYP3A4 and P-gp inhibitors should be avoided in patients taking apixaban and rivaroxaban. Concomitant antiplatelet/anticoagulant use confers additive risk for bleeding, but their combination is unavoidable in many cases. Minimizing duration of concomitant anticoagulant/antiplatelet therapy as indicated by evidence-based clinical guidelines is the best way to reduce the risk of bleeding.

Drug Interactions Affecting Antiarrhythmic Drug Use.

Antiarrhythmic drugs (AAD) play an important role in the management of arrhythmias. Drug interactions involving AAD are common in clinical practice. As AADs have a narrow therapeutic window, both pharmacokinetic as well as pharmacodynamic interactions involving AAD can result in serious adverse drug reactions ranging from arrhythmia recurrence, failure of device-based therapy, and heart failure, to death. Pharmacokinetic drug interactions frequently involve the inhibition of key metabolic pathways, resulting in accumulation of a substrate drug. Additionally, over the past 2 decades, the P-gp (permeability glycoprotein) has been increasingly cited as a significant source of drug interactions. Pharmacodynamic drug interactions involving AADs commonly involve additive QT prolongation. Amiodarone, quinidine, and dofetilide are AADs with numerous and clinically significant drug interactions. Recent studies have also demonstrated increased morbidity and mortality with the use of digoxin and other AAD which interact with P-gp. QT prolongation is an important pharmacodynamic interaction involving mainly Vaughan-Williams class III AAD as many commonly used drug classes, such as macrolide antibiotics, fluoroquinolone antibiotics, antipsychotics, and antiemetics prolong the QT interval. Whenever possible, serious drug-drug interactions involving AAD should be avoided. If unavoidable, patients will require closer monitoring and the concomitant use of interacting agents should be minimized. Increasing awareness of drug interactions among clinicians will significantly improve patient safety for patients with arrhythmias.

Sinus Tachycardia: a Multidisciplinary Expert Focused Review.

Sinus tachycardia (ST) is ubiquitous, but its presence outside of normal physiological triggers in otherwise healthy individuals remains a commonly encountered phenomenon in medical practice. In many cases, ST can be readily explained by a current medical condition that precipitates an increase in the sinus rate, but ST at rest without physiological triggers may also represent a spectrum of normal. In other cases, ST may not have an easily explainable cause but may represent serious underlying pathology and can be associated with intolerable symptoms. The classification of ST, consideration of possible etiologies, as well as the decisions of when and how to intervene can be difficult. ST can be classified as secondary to a specific, usually treatable, medical condition (eg, pulmonary embolism, anemia, infection, or hyperthyroidism) or be related to several incompletely defined conditions (eg, inappropriate ST, postural tachycardia syndrome, mast cell disorder, or post-COVID syndrome). While cardiologists and cardiac electrophysiologists often evaluate patients with symptoms associated with persistent or paroxysmal ST, an optimal approach remains uncertain. Due to the many possible conditions associated with ST, and an overlap in medical specialists who see these patients, the inclusion of experts in different fields is essential for a more comprehensive understanding. This article is unique in that it was composed by international experts in Neurology, Psychology, Autonomic Medicine, Allergy and Immunology, Exercise Physiology, Pulmonology and Critical Care Medicine, Endocrinology, Cardiology, and Cardiac Electrophysiology in the hope that it will facilitate a more complete understanding and thereby result in the better care of patients with ST.

Sex differences in thrombosis in mice are mediated by sex-specific growth hormone secretion patterns.

Sex differences in thrombosis are well described, but their underlying mechanism(s) are not completely understood. Coagulation proteins are synthesized in the liver, and liver gene expression is sex specific and depends on sex differences in growth hormone (GH) secretion--males secrete GH in a pulsatile fashion, while females secrete GH continuously. Accordingly, we tested the hypothesis that sex-specific GH secretion patterns cause sex differences in thrombosis. Male mice were more susceptible to thrombosis than females in the thromboplastin-induced pulmonary embolism model and showed shorter clotting times ex vivo. GH-deficient little (lit) mice were protected from thrombosis, and pulsatile GH given to lit mice restored the male clotting phenotype. Moreover, pulsatile GH administration resulted in a male clotting phenotype in control female mice, while continuous GH caused a female clotting phenotype in control male mice. Expression of the coagulation inhibitors Proc, Serpinc1, Serpind1, and Serpina5 were strongly modulated by sex-specific GH patterns, and GH modulated resistance to activated protein C. These results reveal what we believe to be a novel mechanism whereby sex-specific GH patterns mediate sex differences in thrombosis through coordinated changes in the expression of coagulation inhibitor genes in the liver.

Joint association of hyperuricemia and reduced GFR on cardiovascular morbidity: a historical cohort study based on laboratory and claims data from a national insurance provider.

BACKGROUND: Hyperuricemia is common in patients with chronic kidney disease (CKD). We assessed the relationship of increased serum uric acid levels with cardiovascular risk across levels of kidney function. STUDY DESIGN: Historical cohort study. SETTING & PARTICIPANTS: Study data were drawn from administrative records of a national private health insurer (2003-2006). We included all adult beneficiaries with concurrently measured serum creatinine and serum uric acid. Patients with acute kidney failure or undergoing renal replacement therapy at baseline were excluded. PREDICTORS: Serum uric acid concentration and estimated glomerular filtration rate (eGFR). OUTCOMES & MEASUREMENTS: Cardiovascular diagnoses (myocardial infarction, subacute coronary heart disease, heart failure, cerebrovascular disease, or peripheral arterial disease) ascertained from billing claims. Cox proportional hazard models were used to test the association of predictors with cardiovascular morbidity. Models were adjusted for sociodemographic characteristics, selected comorbid conditions, and laboratory results. RESULTS: In 148,217 eligible patients, mean eGFR was 84 mL/min/1.73 m(2) and the prevalence of CKD stages 3-5 was 6.0%. Hyperuricemia (serum uric acid >7 mg/dL) was found in 15.6% of patients. The 40-month cumulative incidence of cardiovascular events (mean follow-up, 15.3 months) was 8.1%. Cardiovascular risk was associated independently with uric acid level, and this association was stronger in patients with lower eGFRs. LIMITATIONS: Observational design, lack of information for mortality and potential confounders, single creatinine and uric acid assessment. CONCLUSIONS: Serum uric acid concentration was an independent correlate of cardiovascular morbidity, and this association was stronger in patients with severely decreased eGFR. This investigation provides a rationale for further study of serum uric acid-lowering interventions on cardiovascular risk in the general population and patients with CKD.

Impaired renal function is associated with worse self-reported outcomes after kidney transplantation.

PURPOSE: We sought to determine the association between health-related quality of life (HRQOL) and graft function in renal transplant recipients. DESIGN AND METHODS: We enrolled 577 kidney transplant recipients aged 18-74 years (response rate 87%). Recipients with multiple or multi-organ transplantation, creatine kinase >200 U/L, acute renal failure or cellular rejection (n = 64), and without creatinine assessments in 3 months pre-enrollment (n = 127) were excluded. The questionnaire included Euro QOL 5 Dimensions (EQ-5D), Health Utility Index III (HUI-III), Kidney Disease Quality of Life-36 (KDQOL36) which include a generic section (RAND SF-12). Data on medical conditions, therapy regimens, and biochemistry results were extracted from clinical charts. We used general linear models adjusted for demographic, socioeconomic, and clinical characteristics to assess the association between HRQOL and severity of chronic kidney disease (CKD). RESULTS: Patients with more advanced CKD were more likely to be African-American, covered by public insurance, more likely to have shorter time after transplantation, higher phosphorus and lower hemoglobin, serum albumin, and calcium levels. All HRQOL scales were inversely associated with CKD severity. All associations were robust to adjustment for possible confounders. CONCLUSIONS: Several health-related quality of life dimensions may be affected by poor renal function after transplantation.

A Randomized, Double-Blind, Placebo-Controlled Trial of Intravenous Alcohol to Assess Changes in Atrial Electrophysiology.

OBJECTIVES: This study sought to identify acute changes in human atrial electrophysiology during alcohol exposure. BACKGROUND: The mechanism by which a discrete episode of atrial fibrillation (AF) occurs remains unknown. Alcohol appears to increase the risk for AF, providing an opportunity to study electrophysiologic effects that may render the heart prone to arrhythmia. METHODS: In this randomized, double-blinded, placebo-controlled trial, intravenous alcohol titrated to 0.08% blood alcohol concentration was compared with a volume and osmolarity-matched, masked, placebo in patients undergoing AF ablation procedures. Right, left, and pulmonary vein atrial effective refractory periods (AERPs) and conduction times were measured pre- and post-infusion. Isoproterenol infusions and burst atrial pacing were used to assess AF inducibility. RESULTS: Of 100 participants (50 in each group), placebo recipients were more likely to be diabetic (22% vs. 4%; p = 0.007) and to have undergone a prior AF ablation (36% vs. 22%; p = 0.005). Pulmonary vein AERPs decreased an average of 12 ms (95% confidence interval: 1 to 22 ms; p = 0.026) in the alcohol group, with no change in the placebo group (p = 0.98). Whereas no statistically significant differences in continuously assessed AERPs were observed, the proportion of AERP sites tested that decreased with alcohol (median: 0.5; interquartile range: 0.6 to 0.6) was larger than with placebo (median: 0.4; interquartile range: 0.2 to 0.6; p = 0.0043). No statistically significant differences in conduction times or in the proportion with inducible AF were observed. CONCLUSIONS: Acute exposure to alcohol reduces AERP, particularly in the pulmonary veins. These data demonstrate a direct mechanistic link between alcohol, a common lifestyle exposure, and immediate proarrhythmic effects in human atria. (How Alcohol Induces Atrial Tachyarrhythmias Study [HOLIDAY]; NCT01996943).

Outcomes in patients requiring cardioversion following catheter ablation of atrial fibrillation.

INTRODUCTION: Early recurrence of atrial tachyarrhythmias is commonly noted after catheter ablation of atrial fibrillation (AF). The long-term outcomes of patients who require cardioversion for persistent AF after AF ablation is not known. This study reports the outcomes of patients who underwent cardioversion for persistent AF or atrial flutter following an AF ablation procedure. METHODS: The patient population comprised 55 patients (mean age 58 +/- 10 years, 35% paroxysmal) who underwent catheter ablation of AF and subsequently required electrical cardioversion for persistent AF (45 patients) or atrial flutter (10 patients). Cardioversion was defined as early (within 90 days of the ablation procedure) or late (between 90 and 180 days following ablation). RESULTS: The mean follow-up duration was 15 +/- 8 months. Forty-six of the 55 patients (84%) patients experienced recurrence during follow-up. The average time to recurrence after cardioversion was 37 days. Of the 55 patients, 8 (15%) patients had a complete success, 11 (20%) patients had a partial success and 36 patients (65%) had a failed outcome. Seven of the 43 patients (16%) who underwent early cardioversion had a complete success as opposed to one of 12 patients (8%) who underwent late cardioversion (P = 0.49). CONCLUSIONS: This study shows that >80% of patients who undergo cardioversion for persistent AF or atrial flutter after AF ablation have recurrence. The timing of cardioversion did not affect the outcome. These findings allow clinicians to provide realistic expectations to patients regarding the long-term outcome and/or requirement for a second ablation procedure.