Use of dofetilide in adult patients with atrial arrhythmias and congenital heart disease: A PACES collaborative study.

BACKGROUND: Arrhythmia management has become the major treatment challenge in adult patients with congenital heart disease (ACHD). OBJECTIVE: We sought to investigate the utility and safety profile of dofetilide for atrial arrhythmias in ACHD. METHODS: A retrospective chart review was performed. We included patients (age ≥18 years) with congenital heart disease who had atrial fibrillation (AF) or intra-atrial reentrant tachycardia treated with dofetilide. RESULTS: We identified 64 patients with a mean age at initiation of 42 ± 14 years. ACHD type included single ventricle (n = 19, 30%), transposition of the great arteries (n = 14, 22%), atrial septal defect (n = 9, 14%), tetralogy of Fallot (n = 8, 12%), atrioventricular canal defect (n = 5, 8%), mitral/aortic stenosis (n = 7, 11%), and other (n = 2, 3%). Thirty-five (55%) had atrial fibrillation, and 29 (45%) had intra-atrial reentrant tachycardia. A total of 3 (4.7%) patients had major inpatient adverse events: torsades de pointes (n = 1, 1.5%), ventricular tachycardia (n = 1, 1.5%), and corrected QT prolongation requiring discontinuation (n = 1, 1.5%). Dofetilide was discontinued in 1 patient because of sinus node dysfunction, and another patient discontinued therapy before discharge because of persistent arrhythmia. Of the patients who were discharged on dofetilide (n = 59, 92%), 40 (68%) had adequate rhythm control and 19 (32%) had partial rhythm control. After a median follow-up of 3 years, 29 (49%) patients remained on dofetilide and 2 (3%) patients died. Reasons for discontinuation included waning effect (n = 16, 57%), side effects (n = 5, 18%), noncompliance (n = 2, 7%), successful ablation (n = 3, 11%), high cost (n = 1, 3.5%), and unknown (n = 1, 3.5%). CONCLUSION: Dofetilide remains a viable antiarrhythmic drug option in this challenging population. At 3 years, 49% remained on dofetilide. Close monitoring of renal function, concomitant medications, and corrected QT interval is required.

Safety of oral dofetilide for rhythm control of atrial fibrillation and atrial flutter.

BACKGROUND: Although dofetilide is widely used in the United States for rhythm control of atrial fibrillation, there is limited postapproval safety data in the atrial fibrillation population despite its known risk of Torsade de pointes (TdP). METHODS AND RESULTS: We conducted a retrospective chart review of a cohort of 1404 patients initially loaded on dofetilide for atrial fibrillation suppression at the Cleveland Clinic from 2008 to 2012 to evaluate the incidence and risk factors for in-hospital adverse events and the long-term safety of continued use. Of the 17 patients with TdP during loading (1.2%), 10 had a cardiac arrest requiring resuscitation (1 death), 5 had syncope/presyncope, and 2 were asymptomatic. Dofetilide loading was stopped for 105 patients (7.5%) because of QTc prolongation or TdP. Variables correlated with TdP were (1) female sex, 2) 500-µg dose, (3) reduced ejection fraction, and (4) increase in QTc from baseline. One-year all-cause mortality was higher in patients who continued dofetilide compared with those who discontinued use (hazard ratio, 2.48; 95% confidence interval, 1.08-5.71; P=0.03). Those patients who had a TdP event had higher one-year all-cause mortality than those who did not (17.6% versus 3% at 1 year; P<0.001). CONCLUSIONS: Dofetilide loading has a low but finite risk of TdP and other adverse events that warrant the current Food and Drug Administration-mandated practice of inpatient monitoring during drug loading. In this cohort, all-cause mortality was higher at 1 year in those patients continued on dofetilide and in those patients who experienced TdP while loading.

Outcomes of nonpharmacologic treatment of atrial fibrillation in patients with hypertrophic cardiomyopathy.

BACKGROUND: Limited data exist regarding the outcome of atrial fibrillation (AF) surgery and catheter ablation in patients with hypertrophic cardiomyopathy (HCM). OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of nonpharmacologic treatment of AF in HCM. METHODS: One hundred forty-seven patients (46 female, age 55 ± 11 years, ejection fraction [EF] 58% ± 8%) with symptomatic paroxysmal (58%), persistent (31%), and long-standing persistent AF (11%) refractory to antiarrhythmic drugs who presented for their first catheter ablation (n = 79) or AF surgery (n = 68) were included. RESULTS: After follow-up of 35 months (interquartile range 13, 60), 29% of patients who underwent catheter ablation and 51% of those who had undergone AF surgery had no documented recurrent atrial arrhythmia after a single procedure. Repeat ablation was performed in 55% of patients with recurrent arrhythmia in the catheter group and 24% in the surgery group, increasing the success rate to 39% and 53%, respectively, after 1 or more procedures. Predictors of success after the first procedure in a multivariable setting included higher baseline EF and male gender. Persistent or long-standing AF and log of AF duration were associated with lower success. Major complications occurred in 6% of the catheter ablation group and 18% of the AF surgery group. During follow-up, 16 patients died (9 in catheter group, 7 in surgery group) and 1 underwent heart replacement. Lower baseline EF and older age were independently associated with death. CONCLUSION: Catheter ablation and AF surgery are associated with symptomatic improvement in HCM patients. However, long-term success is lower and complications are higher than previously reported.

Atrial fibrillation in heart failure: stroke risk stratification and anticoagulation.

For an individual patient with both atrial fibrillation and heart failure, stroke risk is one of the most prominent mitigating factors for subsequent morbidity and mortality. Although the CHADS2 stroke risk score is the most widely used score for risk stratification, it does not take into account the risk factors of vascular disease, female gender, or the age group 65-74 years, for which there is increasing evidence. There is also evidence that diastolic heart failure is as much a risk factor for stroke as systolic heart failure. The new oral anticoagulants dabigatran, rivaroxaban and apixaban appear to be appropriate agents in the heart failure population with atrial fibrillation and risk factors for stroke although there are dose-adjustments for renal insufficiency and these medications are contraindicated in advanced renal disease. As with the atrial fibrillation population as a whole, bleeding risk should be considered for every patient with heart failure prior to making recommendations regarding anticoagulation.

Does CHA2DS2-VASc improve stroke risk stratification in postmenopausal women with atrial fibrillation?

BACKGROUND: Risk stratification of atrial fibrillation patients with a congestive heart failure (C), hypertension (H), age ≥ 75 (A), diabetes (D), stroke or transient ischemic attack (TIA) (S2) (CHADS2) score of <2 remains imprecise, particularly in women. Our objectives were to validate the CHADS2 and congestive heart failure (C), hypertension (H), age ≥ 75 (A2), diabetes (D), stroke, TIA or prior thromboembolic disease (S2)- vascular disease (V), age 65-74 (A), female gender (S) (CHA2DS2-VASc) stroke risk scores in a healthy cohort of American women with atrial fibrillation and to determine whether CHA2DS2-VASc further risk-stratifies individuals with a CHADS2 score of <2. METHODS: We identified a cohort of 5981 women with atrial fibrillation not on warfarin at baseline (mean age 65.9 ± 7.2 years) enrolled in the Women's Health Initiative and followed for a median of 11.8 years. Univariate and multivariate proportional hazards analyses were used to examine these 2 risk scores, with main outcome measures being annualized event rates of ischemic stroke or transient ischemic attack stratified by risk score. RESULTS: Annualized stroke/transient ischemic attack rates ranged from 0.36% to 2.43% with increasing CHADS2 score (0-4+) (hazard ratio [HR] 1.57; 95% confidence interval [CI], 1.45-1.71 for each 1-point increase) and 0.20%-2.02% with increasing CHA2DS2-VASc score (1-6+) (HR 1.50; 95% CI, 1.41-1.60 for each 1-point increase). CHA2DS2-VASc had a higher c statistic than CHADS2: 0.67 (95% CI, 0.65-0.69) versus 0.65 (95% CI, 0.62-0.67), P <.01. For CHADS2 scores <2, stroke risk almost doubled with every additional CHA2DS2-VASc point. CONCLUSIONS: Although both CHADS2, and CHA2DS2-VASc are predictive of stroke risk in postmenopausal women with atrial fibrillation, CHA2DS2-VASc further risk-stratifies patients with a CHADS2 score <2.

Trends in myocardial infarction rates and case fatality by anatomical location in four United States communities, 1987 to 2008 (from the Atherosclerosis Risk in Communities Study).

Although the incidence of and mortality after ST-segment elevation myocardial infarction (STEMI) is decreasing, time trends in anatomical location of STEMI and associated short-term prognosis have not been examined in a population-based community study. We determined 22-year trends in age- and race-adjusted gender-specific incidences and 28-day case fatality of hospitalized STEMI by anatomic infarct location among a stratified random sample of 35- to 74-year-old residents of 4 communities in the Atherosclerosis Risk in Communities study. STEMI infarct location was assessed by 12-lead electrocardiograms from the hospital record and was coded as anterior, inferior, lateral, and multilocation STEMIs using the Minnesota code. From 1987 to 2008, a total of 4,845 patients had an incident STEMI; 37.2% were inferior STEMI, 32.8% were anterior, 16.8% occurred in multiple infarct locations, and 13.2% were lateral STEMI. For inferior, anterior, and lateral STEMIs in both men and women, significant decreases were observed in the age-adjusted annual incidence and the associated 28-day case fatality. In contrast, for STEMI in multiple infarct locations, neither the annual incidence nor the 28-day case fatality changed over time. The age- and race-adjusted annual incidence and associated 28-day case fatality of STEMI in anterior, inferior, and lateral infarct locations decreased during 22 years of surveillance; however, no decrease was observed for STEMI in multiple infarct locations. In conclusion, our findings suggest that there is room for improvement in the care of patients with multilocation STEMI.

Real-time ultrasound guidance reduces total and major vascular complications in patients undergoing pulmonary vein antral isolation on therapeutic warfarin.

BACKGROUND: Vascular complications are a known risk of catheter-based pulmonary vein antral isolation (PVAI). Procedure-related thromboembolic events necessitate full-dose anticoagulation, which worsens outcomes in the event of vascular access injury. OBJECTIVE: Real-time ultrasound allows direct visualization of vascular structures. We hypothesized that ultrasound use with venipuncture reduces vascular complications associated with PVAI. METHODS: Retrospective analysis of all adverse events occurring with PVAI was performed during two periods: 2005-2006 when ultrasound was not used and 2008-2010 when ultrasound was routinely employed. All patients received full-dose IV heparin during PVAI. In the no ultrasound cohort, only 14 % underwent PVAI without stopping warfarin, while 91 % of patients in the ultrasound cohort were on continued warfarin. Only patients deemed at high risk for thromboembolism with a periprocedural international normalized ratio (INR) less than 2 were bridged with subcutaneous low-molecular-weight heparin. RESULTS: Ultrasound reduced total vascular complications (1.7 vs. 0.5 %, p < 0.01) and decreased the incidence of major vascular complications by sevenfold. Warfarin with INR ≥ 1.2 on the day of PVAI was associated with more vascular complications (4.3 vs. 1.2 %, p < 0.01). Ultrasound guidance overcame the risk associated with warfarin therapy. Vascular complications in anticoagulated patients with INR ≥ 1.2 using ultrasound guidance were two- and ninefold lower than those in patients not using ultrasound with an INR < 1.2 (0.5 vs. 1.2 %, p < 0.05) and INR ≥ 1.2 (0.5 vs. 4.3 %, p < 0.01), respectively. CONCLUSION: Ultrasound-guided venipuncture improves the safety profile of PVAI, reducing vascular complications in patients on warfarin to levels below those with no ultrasound and off warfarin.

The homocysteine hypothesis: still relevant to the prevention and treatment of cardiovascular disease?

Although evidence suggests that the homocysteine hypothesis is still relevant as a predictor of cardiovascular risk, we cannot conclude that measuring the homocysteine level is useful in guiding treatment. Furthermore, studies of primary and secondary prevention show no evidence that taking folic acid or other B vitamins lowers the risk of cardiovascular events.

Association of Thrombolysis in Myocardial Infarction Myocardial Perfusion Grade with cardiovascular magnetic resonance measures of infarct architecture after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction.

BACKGROUND: Primary percutaneous coronary intervention (pPCI) routinely restores normal epicardial flow among patients with ST-segment elevation myocardial infarction (STEMI). However, impairment of myocardial perfusion frequently persists. The goal of this analysis was to determine whether impaired myocardial perfusion was associated with cardiovascular magnetic resonance-defined abnormalities in infarct architecture, including infarct size (IS), infarct surface area (ISA), infarct border zone (IBZ), and infarct complexity (IC). METHODS: Thirty-one patients with STEMI treated with pPCI were included in the analysis. Cardiovascular magnetic resonance was performed within 7 days of presentation and repeated at 3 months. Infarct complexity was defined as the ratio of actual ISA to an idealized smooth ISA and normalized to IS. RESULTS: Impaired Thrombolysis in Myocardial Infarction Myocardial Perfusion Grade (TMPG) (<3) was associated with larger ISA at baseline (78.2 +/- 25.3 cm(2) vs 40.3 +/- 30.3 cm(2), P = .02) and follow-up (58.8 +/- 27.5 cm(2) vs 26.3 +/- 20.2 cm(2), P = .03) and larger IBZ at follow-up (7.8% +/- 2.7% vs 4.1% +/- 3.3%, P = .02). At follow-up, ISA, when normalized to IS, was significantly higher among patients with impaired myocardial perfusion (TMPG <3) (6.9 +/- 2.5 vs 5.9 +/- 2.4 cm(2)/%, P = .03). Thrombolysis in MI myocardial perfusion grade <3 was also associated with increased IC at follow-up (52% +/- 12% vs 33% +/- 16%, P = .01). CONCLUSIONS: Impaired TMPG is associated with larger ISA, IBZ, and increased IC. At 3 months, TMPG remained associated with ISA and IC after adjusting for IS, suggesting that impaired TMPG after pPCI is associated with infarct architecture after healing, independent of IS.

Association of angiographic perfusion score following percutaneous coronary intervention for ST-elevation myocardial infarction with left ventricular remodeling at 6 weeks in GRACIA-2.

UNLABELLED: Higher angiographic perfusion score (APS) following percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) has been shown to be associated with improved clinical outcomes. The association between APS after STEMI and left ventricular remodeling as assessed by volumetric parameters derived from left ventriculography has not been assessed. METHODS: The APS (the arithmetic sum of the TIMI Flow Grade (TFG) and TIMI Myocardial Perfusion grade (TMPG) before and after percutaneous coronary intervention (PCI), range of 0-12) was assessed in 168 patients from the GRACIA-2 trial. Left ventriculograms performed in the 30 degrees right anterior oblique projection were obtained among 148 patients at initial angiography (prior to PCI) and at 6 weeks. The association of APS with markers of left ventricular remodeling at 6-weeks was examined using left ventricular ejection fraction, delta end systolic volume, delta stroke volume and wall motion index. RESULTS: Full perfusion (APS 10-12), as compared to partial perfusion (APS 4-9) or failed perfusion (APS 0-3), was associated with a greater left ventricular ejection fraction (61.6% +/- 10.0 vs. 56.9% +/- 12.5 vs. 49.8% +/- 16.9, P = 0.015), a decrease in left ventricular end systolic volume indicating favorable remodeling (mean -4.1 cc +/- 17.3 vs. +2.0 cc +/- 17.3 vs. +9.8 cc +/- 16.1, P = 0.015), a greater improvement in left ventricular stroke volume (mean +13.7 cc +/- 17.1 vs. +6.7 cc +/- 15.5 vs. +1.2 cc +/- 13.4, P = 0.009) and a decreased wall motion index (number of chords in the hypokinetic region) (mean 15.1 +/- 16.4 vs. 21.4 +/- 20.5 vs. 32.9 +/- 22.1, P = 0.026) at 6 weeks. CONCLUSION: In conclusion, among patients treated with combined reperfusion and revascularization strategies for STEMI, higher APS is associated with more favorable markers of left ventricular remodeling and improved 6-week left ventricular function.