Hydroxychloroquine and Risk of Long QT Syndrome in Rheumatoid Arthritis: A Veterans Cohort Study With Nineteen-Year Follow-up.

OBJECTIVE: Recent evidence suggests that hydroxychloroquine use is not associated with higher 1-year risk of long QT syndrome (LQTS) in patients with rheumatoid arthritis (RA). Less is known about its long-term risk, the examination of which was the objective of this study. METHODS: We conducted a propensity score-matched active-comparator safety study of hydroxychloroquine in 8,852 veterans (mean age 64 ± 12 years, 14% women, 28% Black) with newly diagnosed RA. A total of 4,426 patients started on hydroxychloroquine and 4,426 started on another nonbiologic disease-modifying antirheumatic drug (DMARD) and were balanced on 87 baseline characteristics. The primary outcome was LQTS during 19-year follow-up through December 31, 2019. RESULTS: Incident LQTS occurred in 4 (0.09%) and 5 (0.11%) patients in the hydroxychloroquine and other DMARD groups, respectively, during the first 2 years. Respective 5-year incidences were 17 (0.38%) and 6 (0.14%), representing 11 additional LQTS events in the hydroxychloroquine group (number needed to harm 403; [95% confidence interval (95% CI)], 217-1,740) and a 181% greater relative risk (95% CI 11%-613%; P = 0.030). Although overall 10-year risk remained significant (hazard ratio 2.17; 95% CI 1.13-4.18), only 5 extra LQTS occurred in hydroxychloroquine group over the next 5 years (years 6-10) and 1 over the next 9 years (years 11-19). There was no association with arrhythmia-related hospitalization or all-cause mortality. CONCLUSIONS: Hydroxychloroquine use had no association with LQTS during the first 2 years after initiation of therapy. There was a higher risk thereafter that became significant after 5 years of therapy. However, the 5-year absolute risk was very low, and the absolute risk difference was even lower. Both risks attenuated during longer follow-up. These findings provide evidence for long-term safety of hydroxychloroquine in patients with RA.

Cardiovascular Safety of Hydroxychloroquine in US Veterans With Rheumatoid Arthritis.

OBJECTIVE: Hydroxychloroquine (HCQ) may prolong the QT interval, a risk factor for torsade de pointes, a potentially fatal ventricular arrhythmia. This study was undertaken to examine the cardiovascular safety of HCQ in patients with rheumatoid arthritis (RA). METHODS: We conducted an active comparator safety study of HCQ in a propensity score-matched cohort of 8,852 US veterans newly diagnosed as having RA between October 1, 2001 and December 31, 2017. Patients were started on HCQ (n = 4,426) or another nonbiologic disease-modifying antirheumatic drug (DMARD; n = 4,426) after RA diagnosis, up to December 31, 2018, and followed up for 12 months after therapy initiation, up to December 31, 2019. RESULTS: Patients had a mean ± SD age of 64 ± 12 years, 14% were women, and 28% were African American. The treatment groups were balanced with regard to 87 baseline characteristics. There were 3 long QT syndrome events (0.03%), 2 of which occurred in patients receiving HCQ. Of the 56 arrhythmia-related hospitalizations (0.63%), 30 occurred in patients in the HCQ group (hazard ratio [HR] associated with HCQ 1.16 [95% confidence interval (95% CI) 0.68-1.95]). All-cause mortality occurred in 144 (3.25%) and 136 (3.07%) of the patients in the HCQ and non-HCQ groups, respectively (HR associated with HCQ 1.06 [95% CI, 0.84-1.34]). During the first 30 days of follow-up, there were no long QT syndrome events, 2 arrhythmia-related hospitalizations (none in the HCQ group), and 13 deaths (6 in the HCQ group). CONCLUSION: Our findings indicate that the incidence of long QT syndrome and arrhythmia-related hospitalization is low in patients with RA during the first year after the initiation of HCQ or another nonbiologic DMARD. We found no evidence that HCQ therapy is associated with a higher risk of adverse cardiovascular events or death.

Digoxin Initiation and Outcomes in Patients with Heart Failure (HFrEF and HFpEF) and Atrial Fibrillation.

BACKGROUND: Digoxin reduces the risk of heart failure hospitalization but has no effect on mortality in patients with heart failure without atrial fibrillation in the randomized controlled trial setting. Observational studies of digoxin use in patients with atrial fibrillation have suggested a higher risk for poor outcomes. Less is known about this association in patients with heart failure and atrial fibrillation, the examination of which was the objective of the current study. METHODS: We conducted an observational propensity score-matched study of predischarge digoxin initiation in 1768 hospitalized patients with heart failure and atrial fibrillation in the Medicare-linked Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry, balanced on 56 baseline characteristics (mean age, 79 years; 55% women; 7% African American). Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes were estimated for the 884 patients initiated on digoxin compared with 884 not initiated on digoxin. RESULTS: HRs (95% CIs) for 30-day, 2-year, and 4-year all-cause mortality were 0.80 (0.55-1.18; P = .261), 0.94 (0.87-1.16; P = .936), and 1.01 (0.90-1.14; P = .729), respectively. Respective HRs (95% CIs) for heart failure readmission were 0.67 (0.49-0.92; P = .014), 0.81 (0.69-0.94; P = .005), and 0.85 (0.74-0.97; P = .022), and those for all-cause readmission were 0.78 (0.64-0.96; P = .016), 0.90 (0.81-1.00; P = .057), and 0.91 (0.83-1.01; P = .603). These associations were homogeneous between patients with left ventricular ejection fraction ≤45% vs >45%. CONCLUSIONS: Among hospitalized older patients with heart failure (HFrEF and HFpEF) and atrial fibrillation, initiation of digoxin was associated with a lower risk of heart failure readmission but had no association with mortality.

Preoperative antibiotics and cardiovascular implantable electronic device infection: A cohort study in veterans.

BACKGROUND: Cefazolin is used as standard preoperative prophylaxis for a variety of surgical procedures that involve the skin. In contrast, vancomycin is recommended for a minority of patients, specifically those with an IgE-mediated allergy to beta-lactams and considered in patients with known colonization with methicillin-resistant Staphylococcus aureus or at high risk for such. Vancomycin, however, has been overprescribed, has nephrotoxicity risk, and may be less effective due to its inferior coverage of methicillin-susceptible S. aureus and lack of Gram-negative coverage. This study was performed to assess whether vancomycin use was associated with an increased incidence of cardiovascular implantable electronic device infection (CIEDI) as compared to that of cefazolin or other antistaphylococcal beta-lactam antibiotics. METHODS: The VA Informatics and Computing Infrastructure database, which included all veterans who underwent CIED placement or revision between 2008 and 2015, was used. A logistic regression model was constructed to estimate the adjusted odds of CIEDI. RESULTS: Overall, 10,454 CIED procedures were included, and 98% of them were performed in men with a mean age of 71 ± 12 years. The logistic regression analysis showed that vancomycin use alone or in combination with other antibiotics was associated with an increased risk of CIEDI (odds ratio 2.99 [1.76-5.06], P-value < 0.001), after controlling for other effects. CONCLUSIONS: Our study revealed that among patients who received surgical site infection prophylaxis for CIED placement or revision, there was: (1) an unanticipated high rate of vancomycin use, and (2) a threefold increase in the incidence of subsequent CIEDI among vancomycin recipient.

Statin use and the risk of cardiovascular implantable electronic device infection: A cohort study in a veteran population.

BACKGROUND: The rate of cardiovascular implantable electronic device infection (CIEDI) has increased, despite the use of perioperative antibiotics at the time of device placement or revision. This is due, in part, to the presence of multiple comorbid conditions in an elderly population, in general, who require CIED. Statins may have an antibacterial effect, although there is currently no evidence that the likelihood of CIEDI has been impacted by statin use. METHODS: A retrospective cohort study was performed to assess whether statins are associated with a reduced risk of CIEDI. The VA Informatics and Computing Infrastructure (VINCI) database, which includes all veterans who underwent CIED placement between 2008 and 2015, was used. A logistic regression model was constructed to estimate the adjusted risk of CIEDI among patients who were receiving statins after adjusting for confounding factors. RESULTS: Overall, 18,970 CIED procedures were included, and 98% of them were performed in men with a mean age of 71 ± 11 years. The rate of diabetes mellitus, heart failure, advanced chronic kidney diseases, CIEDI, positive methicillin-resistant Staphylococcus aureus nasal colonization, and statin use were 23%, 15.7%, 3.3%, 1.14%, 12.6%, and 56%, respectively. The logistic regression analysis showed that statins were significantly associated with a reduced risk of CIEDI; after controlling for other effects, the reduction was 66% (odds ratio 0.34 [0.2-0.59], P-value < 0.001). The effect of statins was confirmed by propensity score analysis. CONCLUSIONS: Our study showed that among patients receiving statins who had undergone CIED placement, there was a 66% reduction in subsequent CIEDI.

How Should Implantable Cardioverter-Defibrillator Lead Failures be Managed and What is the Role of Lead Extraction?

Despite remarkable advances in design, implantable cardioverter-defibrillator (ICD) leads remain the component most susceptible to failure, which often leads to substantial adverse clinical outcomes. This article focuses on management strategies when ICD lead systems fail. Two cases involving management decisions for ICD lead failures are presented and discussed. One involves a common mode of presentation, inappropriate shocks. The second involves an alert in a patient with a complex system and multiple comorbidities. Although a systematic approach is outlined, management decisions must be balanced by a risk-and-benefit assessment of the individual patient.

Long-term mortality outcomes according to the frequency of right ventricular pacing in veterans.

Background. Right ventricular pacing (RVP) has been associated with adverse outcomes, including heart failure and death. Minimizing RVP has been proposed as a therapeutic goal for a variety of pacing devices and indications. Objective. Quantify survival according to frequency of RVP in veterans with pacemakers. Methods. We analyzed electrograms from transtelephonic monitoring of veterans implanted with pacemakers between 1995 and 2005 followed by the Eastern Pacemaker Surveillance Center. We compared all cause mortality and time to death between patients with less than 20% and more than 80% RVP. Results. Analysis was limited to the 7198 patients with at least six trans-telephonic monitoring records (mean = 21). Average follow-up was 5.3 years. Average age at pacemaker implant was significantly lower among veterans with <20% RVP (67 years versus 72 years; P < .0001). An equal proportion of deaths during follow-up were noted for each group: 126/565 patients (22%) with <20% RVP and 1113/4968 patients (22%) with >80% RVP. However, average post-implant survival was 4.3 years with <20% RVP versus 4.7 years with >80% RVP (P < .0001). Conclusions. Greater frequency (>80%) of RVP was not associated with higher mortality in this population of veterans. Those veterans utilizing <20% RVP had a shortened adjusted survival rate (P = .0016).

Intrathoracic impedance preceding ventricular tachyarrhythmia episodes.

BACKGROUND: Heart failure is associated with ventricular tachyarrhythmias (VT/VF). Fluid accumulation during worsened heart failure may trigger VT/VF. Increased intrathoracic impedance has been correlated with fluid accumulation during heart failure. Implanted defibrillators capable of daily measures of intrathoracic impedance allow correlation of impedance with occurrence of VT/VF. We hypothesized that VT/VF episodes are preceded by decreases in intrathoracic impedance. The goal was to identify the relationship of intrathoracic impedance measured by implanted cardioverter defibrillators to the occurrence of VT/VF. METHOD: Implanted defibrillator follow-up data were obtained retrospectively. Those with Medtronic OptiVol (Medtronic Inc., Minneapolis, MN, USA), storing averaged daily and reference impedance values, were reviewed for VT/VF episodes. Impedance changes in the week leading up to VT/VF were analyzed. RESULTS: A total of 317 VT/VF episodes in a cohort of 121 patients' follow-up data were evaluated. Averaged daily intrathoracic impedance declined preceding 64% of VT/VF episodes, with an average decline of 0.46 +/- 0.35 Ohms from the day before the VT/VF episodes. However, the mean values of the averaged daily and reference impedance did not change significantly. A novel measure, DeltaTI, the sum of the daily differences between the averaged daily and reference impedance, was negative preceding 66% of VT/VF episodes (P < 0.001). The mean DeltaTI was -4.0 +/- 1.3 Ohms, which was significantly lower than the theoretically expected value of zero Ohms (P < 0.01). CONCLUSION: (1) Averaged daily impedance declined preceding 64% of VT/VF episodes, but the overall decline was of small magnitude; (2) a novel measure, DeltaTI, was negative preceding 66% of VT/VF episodes, and significantly below zero.

Management strategies when implanted cardioverter defibrillator leads fail: survey findings.

BACKGROUND: Defibrillator implanters have adopted different approaches to managing failures of multicomponent implanted cardioverter defibrillator (ICD) leads. Although recent publications identified single-component failures as common mechanisms of failure, there are no published data regarding how best to manage these failures. METHODS: An internet-based survey was conducted to identify current management strategies. Questions were asked regarding isolated failure of a high-voltage coil or of a pace/sense electrode, in order to identify the frequency of various techniques to correct these failures. RESULTS: A worldwide query collected strategies from 376 physicians identifying themselves as ICD-implanting physicians. Replies came from 28 countries, with the USA accounting for 83.2%. The survey was completed by 85.6% of respondents. Implant experience was >10 years for 61.1%, 3-10 years for 29.1%, and <3 years for 10.4%. When the right ventricular coil failed, 52% abandoned and 48% explanted the failed lead. In superior vena cava coil failure, 61.2% chose to simply exclude this coil, using the other intact lead components. For pace/sense defects, 53.1% chose to implant a new pace/sense lead or switch sensing electrodes, using the intact lead components. Medical literature (76.1%), personal experience (67.6%), and professional guidelines (63.7%) were strong decision-making influences. CONCLUSIONS: (1) Management decisions for single-component failures of ICD leads are complex; (2) Significant differences in management strategy exist among physicians; (3) Medical literature and professional guidelines are strong influences for these decisions; (4) A lead failure registry could help identify reasons for such differences and help guide management.

QRS duration and mortality in patients with congestive heart failure.

BACKGROUND AND OBJECTIVES: It has been suggested that prolongation of the QRS duration (>120 ms) is an independent risk factor for mortality in patients with cardiomyopathy. The purpose of this study was to examine the association between QRS duration and survival in patients with heart failure. METHODS: We performed a retrospective analysis to examine the association between QRS prolongation (> or =120 ms) and mortality. The study population included 669 patients with heart failure. Two groups, on the basis of baseline QRS duration <120 milliseconds or > or =120 milliseconds, were identified. The groups were compared with respect to total mortality and sudden death. Subgroups were also stratified by right bundle branch block and left bundle branch block, ejection fraction (EF) <30% and > or =30% to 40%, ischemic and nonischemic cardiomyopathy, amiodarone and placebo. RESULTS: Prolonged QRS was associated with a significant increase in mortality (49.3% vs 34.0%, P =.0001) and sudden death (24.8% vs 17.4%, P =.0004). Left bundle branch block was associated with worse survival (P =.006) but not sudden death. In patients with an EF <30%, QRS prolongation continued to be associated with a significant increase in mortality (51.6% vs 41.1%, P =.01) and sudden death (28.8% vs 21.1%, P =.02). In those with an EF of 30% to 40%, QRS prolongation was associated with a significant increase in mortality (42.7% vs 23.3%, P =.0036) but not in sudden death (13.3% vs 12.0%, P =.625). After adjustment for baseline variables, independent predictors of mortality were found to be prolongation of QRS (P =.0028, risk ratio 1.46) and depressed EF (P =.0001, risk ratio 0.965). Age, type of cardiomyopathy, and drug treatment group were not predictive of mortality. CONCLUSION: QRS prolongation is an independent predictor of both increased total mortality and sudden death in patients with heart failure.