Faculty Bibliography

Cardiac perforation by a pacemaker lead is a rare complication of pacemaker implantation. Presentation can vary from chest pain and shortness of breath to the patient being completely asymptomatic. Diagnosis is usually made by high-resolution computed tomography (HRCT) scan of the chest. Electrocardiograph (EKG) usually shows the absence of a paced rhythm, but it doesn't provide a definitive diagnosis. We describe a case of late cardiac perforation by an atrial pacemaker lead with no signs or symptoms of pericardial tamponade.

OBJECTIVE:To evaluate warfarin prescription, quality of international normalised ratio (INR) monitoring and of INR control in patients with atrial fibrillation (AF) and chronic kidney disease (CKD). METHODS:We performed a retrospective cohort study of patients with newly diagnosed AF in the Veterans Administration (VA) healthcare system. We evaluated anticoagulation prescription, INR monitoring intensity and time in and outside INR therapeutic range (TTR) stratified by CKD. RESULTS:Of 123 188 patients with newly diagnosed AF, use of warfarin decreased with increasing severity of CKD (57.2%-46.4%), although it was higher among patients on dialysis (62.3%). Although INR monitoring intensity was similar across CKD strata, the proportion with TTR≥60% decreased with CKD severity, with only 21% of patients on dialysis achieving TTR≥60%. After multivariate adjustment, the magnitude of TTR reduction increased with CKD severity. Patients on dialysis had the highest time markedly out of range with INR <1.5 or >3.5 (30%); 12% of INR time was >3.5, and low TTR persisted for up to 3 years. CONCLUSIONS:There is a wide variation in anticoagulation prescription based on CKD severity. Patients with moderate-to-severe CKD, including dialysis, have substantially reduced TTR, despite comparable INR monitoring intensity. These findings have implications for more intensive warfarin management strategies in CKD or alternative therapies such as direct oral anticoagulants.

Warfarin prevents stroke and prolongs survival in patients with atrial fibrillation and flutter (AF, collectively) but can cause hemorrhage. The time in international normalized ratio (INR) therapeutic range (TTR) mediates stroke reduction and bleeding risk. This study sought to determine the relation between baseline stroke, bleeding risk, and TTR. Using data from The Retrospective Evaluation and Assessment of Therapies in Atrial Fibrillation (TREAT-AF) retrospective cohort study, national Veterans Health Administration records were used to identify patients with newly diagnosed AF from 2003 to 2012 and subsequent initiation of warfarin. Baseline stroke and bleeding risk was determined by calculating CHA₂DS₂-VASc and HAS-BLED scores, respectively. Main outcomes were first-year and long-term TTR and INR monitoring rate. In 167,190 patients, the proportion of patients with TTR (>65%) decreased across increasing strata of CHA₂DS₂-VASc and HAS-BLED. After covariate adjustment, odds of achieving TTR >65% were significantly associated with high CHA₂DS₂-VASc or HAS-BLED score. INR monitoring rate was similar across risk strata. In conclusion, increased baseline stroke and bleeding risk is associated with poor INR control, despite similar rates of INR monitoring. These findings may paradoxically limit warfarin's efficacy and safety in high-risk patients and may explain observed increased bleeding and stroke rates in this cohort.

Almost 800,000 new or recurrent strokes occur every year. Atrial fibrillation, the most common cardiac arrhythmia, is a major risk factor for stroke, accounting for 15-20% of ischemic strokes. Apixaban is a direct inhibitor of Factor Xa that was approved in December 2012 by the US Food and Drug Administration (FDA) for the prevention of stroke in patients with non-valvular atrial fibrillation. It is part of a family of novel oral anticoagulants (NOACs) which has advantage over warfarin of less dosing variability, rapid onset of action and no INR monitoring required. Apixaban showed superiority to warfarin in both primary efficacy and primary safety outcomes by simultaneously showing both significantly lower rates of strokes and systemic embolism and a reduced risk of major clinical bleeding in clinical trials. Warfarin remains the anticoagulant of choice for patients with prosthetic heart valves and significant mitral stenosis. There are currently no head-to-head studies that directly compare the different NOACs with one another, but it is expected that there will be more trials in the future that will explore this comparison. Dabigatran is the only NOAC with an FDA approved reversal agent. However, a reversal agent for apixaban is being developed and was successful in recent clinical trials. This review summarizes the clinical trial data on apixaban for atrial fibrillation, compares apixaban to other NOACs and discusses apixaban use in clinical practice.

Atrial fibrosis appears to be a key factor in the genesis and/or perpetuation of atrial fibrillation (AF). The pathological distribution of atrial fibrosis is geographically consistent with the attachments between the posterior left atrium and the pericardium along the reflections where wall stiffness is increased and structural changes are found. While there is a wide range of complex etiological factors and electrophysiological mechanisms in AF, there is evidence for a common pathophysiological pathway that could account for deliberate substrate formation and progression of AF. Anatomical stresses along the atrium, mediated by the elastic modulus mismatch between atrial tissue and the pericardium, result in inflammatory and fibrotic changes which create the substrate for atrial fibrillation. This may explain the anatomical predominance of pulmonary vein triggers earlier in the development of atrial fibrillation and the increasing involvement of the atrium as the disease progresses. Ablative treatments that address the progressive nature of atrial fibrillation and fibrosis may yield improved success rates.