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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims: Obesity is associated with increased risk of heart failure (HF). This risk may be modulated by improved cardiorespiratory fitness (CRF) as CRF is associated with favourable health outcomes. Thus, we assessed the interaction between body mass index (BMI), CRF and HF.Methods and Results: Cardiorespiratory fitness and BMI were assessed in 20 254 US male veterans (mean age 58.0 ± 11.3 years), who completed a maximal exercise treadmill test between 1987 and 2017. All had no evidence of ischaemia or HF prior to the exercise test. They were classified based on age-stratified quartiles of peak metabolic equivalents (METs) achieved as: least-fit (4.5 ± 1.3), low-fit (6.7 ± 1.3), moderate-fit (8.1 ± 1.1), and high-fit (11.2 ± 2.4); and according to BMI as normal weight (18.5-24.9 kg/m2 ), overweight (25-29.9 kg/m2 ), and obese (≥ 30.0 kg/m2 ). During a median follow-up of 13.4 years, there were 2979 HF events (10.8 events/1000 person-years). HF risk was significantly higher in the obese category [hazard ratio (HR) 1.22, 95% confidence interval (CI) 1.10-1.36; P < 0.001], but was no longer significant after further adjustment for METs. When compared to the least-fit, HF risk declined progressively with increased CRF within all BMI categories. The risk was 63% (HR 0.37, 95% CI 0.30-0.47; P < 0.001), 66% (HR 0.37, 95% CI 0.28-0.40; P < 0.001), and 73% (HR 0.27, 95% CI 0.22-0.34; P < 0.001) lower for high-fit individuals within normal weight, overweight and obese categories, respectively.Conclusions: Increased CRF was associated with progressively lower HF risk regardless of BMI, suggesting that the elevated HF risk associated with obesity may be modulated by improved CRF. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

Abstract: 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. [ABSTRACT FROM AUTHOR]

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, ΔTI, 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 ΔTI 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, ΔTI, was negative preceding 66% of VT/VF episodes, and significantly below zero. (PACE 2010; 33:960–966) [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Increased QT Variability (QTVI) is predictive of life threatening arrhythmias in vulnerable patients. The predictive value of QTVI is based on resting ECGs, and little is known about the effect of acute exercise on QTVI. The relation between QTVI and arrhythmic vulnerability markers such as T-wave alternans (TWA) has also not been studied. This study examined the effects of exercise on QTVI and TWA in patients with arrhythmic vulnerability. Methods: Digitized ECGs were obtained from 47 ICD patients (43 males; age 60.9 ± 10.1) and 23 healthy controls (18 males; age 59.7 ± 9.5) during rest and bicycle exercise. QTVI was assessed using a previously validated algorithm and TWA was measured as both a continuous and a categorical variable based on a priori diagnostic criteria. Results: QTVI increased with exercise in ICD patients (−0.79 ± 0.11 to 0.36 ± 0.08, P < 0.001) and controls (−1.50 ± 0.07 to −0.19 ± 0.12, P < 0.001), and QTVI levels were consistently higher in ICD patients than controls during rest and exercise (P < 0.001). The magnitude of QTVI increase from baseline levels was not larger among ICD patients versus controls (P > 0.20). Among ICD patients, elevated exercise QTVI was related to lower LV ejection fraction and inducibility of ischemia (P < 0.05). QTVI at rest correlated with exercise TWA (r = 0.54, P = 0.0004). Conclusions: QT variability increases significantly with exercise, and exercise QTVI is related to other well-documented markers of arrhythmic vulnerability, including low ejection fraction, inducible ischemia, and TWA. Resting QTVI may be useful in the risk stratification of individuals incapable of performing standard exercise protocols. [ABSTRACT FROM AUTHOR]

This is the case of a 77-year-old man with hypertension, diabetes, ischemic cardiomyopathy, heart failure, and an extensive device history. In May 2005, he underwent implantation of a right-sided biventricular implantable cardioverter defibrillator (ICD) system (Medtronic Insync Maximo 7303), Capsure Fix Novus 4076 atrial lead (Medtronic), Sprint Fidelis 6949 right ventricular (RV) dual coil ICD lead (Medtronic), and Attain OTW Bipolar 4194 left ventricular (LV) lead (Medtronic). In September 2007, he was using his right arm to dig a ditch and lay bricks. The next day while holding up a newspaper to read, he received multiple shocks. He was taken to a local emergency room where his ICD was reprogrammed to prevent shocks, and he was transferred to our facility for management. [ABSTRACT FROM AUTHOR]

Objective: To study fluctuations in intracardiac atrial fibrillation (AF) cycle length (CL). Background: Sites of short AF CL may be good ablation targets, and cycle lengthening predicts ablation success. However, the optimum method for measuring AF CL, and its stability, are unclear. We hypothesized that autocorrelation better estimates AF CL than spectral dominant frequency (DF), which is susceptible to double counting, using monophasic action potentials (MAPs) to separate atrial activation from artifact. Methods: In 28 patients with paroxysmal or persistent AF, we analyzed 49 AF epochs using MAPs at the high (HRA) and low (LRA) right atrium. We estimated AF CL over 2 seconds, 10 seconds, and 2 minutes using spectral DF and autocorrelation in MAPs and filtered bipoles. Results: In the HRA, manually measured CL was 167 ± 25 ms. Spectral DF poorly estimated AF CL in bipolar signals (R = 0.31; P = NS), due to double counting, but accurately estimated MAP CL (R = 0.73, P < 0.001). Autocorrelation estimated MAP (R = 0.92; P < 0.001) and bipolar (R = 0.83; P < 0.001) CL, with lower errors than spectral DF (P < 0.0001). Over time, changes in DF consistently preceded reciprocal changes in organization (P < 0.001). Finally, excluding inaccurate spectra, DF and AF organization differed between HRA and LRA over 2 seconds, but correlated over 10 seconds and 2 minutes (P < 0.05). Conclusions: AF CL is better estimated by autocorrelation than spectral DF, particularly for bipoles, and stable when measured for >10 seconds. Notably, changes in AF CL preceded reciprocal changes in organization, yet changes in organization did not precede changes in AF CL. These results may help to interpret AF CL fluctuations. [ABSTRACT FROM AUTHOR]

Implantable pacemaker cardioverter defibrillators are now available with biphasic waveforms, which have been shown to markedly improve defibrillation thresholds (DFTs). However, in a number of patients the DFT remains high. Also, DFT may increase after implantation, especially if antiarrhythmic drugs are added. We report on the use of a subcutaneous patch in the pectoral position in 15 patients receiving a transvenous defibrillator as a method of easily reducing the DFT. A 660-mm2 patch electrode was placed beneath the generator in a pocket created on the pectoral fascia. The energy required for defibrillation was lowered by 56% on average, and the system impedance was lowered by a mean of 25%. This maneuver allowed all patients to undergo a successful implant with adequate safety margin. [ABSTRACT FROM AUTHOR]