Inorganic Nitrite to Amplify the Benefits and Tolerability of Exercise Training in Heart Failure With Preserved Ejection Fraction: The INABLE-Training Trial.

OBJECTIVE: To determine whether nitrite can enhance exercise training (ET) effects in heart failure with preserved ejection fraction (HFpEF). METHODS: In this multicenter, double-blind, placebo-controlled, randomized trial conducted at 1 urban and 9 rural outreach centers between November 22, 2016, and December 9, 2021, patients with HFpEF underwent ET along with inorganic nitrite 40 mg or placebo 3 times daily. The primary end point was peak oxygen consumption (VO2). Secondary end points included Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS, range 0 to 100; higher scores reflect better health status), 6-minute walk distance, and actigraphy. RESULTS: Of 92 patients randomized, 73 completed the trial because of protocol modifications necessitated by loss of drug availability. Most patients were older than 65 years (80%), were obese (75%), and lived in rural settings (63%). At baseline, median peak VO2 (14.1 mL·kg-1·min-1) and KCCQ-OSS (63.7) were severely reduced. Exercise training improved peak VO2 (+0.8 mL·kg-1·min-1; 95% CI, 0.3 to 1.2; P<.001) and KCCQ-OSS (+5.5; 95% CI, 2.5 to 8.6; P<.001). Nitrite was well tolerated, but treatment with nitrite did not affect the change in peak VO2 with ET (nitrite effect, -0.13; 95% CI, -1.03 to 0.76; P=.77) or KCCQ-OSS (-1.2; 95% CI, -7.2 to 4.9; P=.71). This pattern was consistent across other secondary outcomes. CONCLUSION: For patients with HFpEF, ET administered for 12 weeks in a predominantly rural setting improved exercise capacity and health status, but compared with placebo, treatment with inorganic nitrite did not enhance the benefit from ET. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02713126.

Efficacy and Safety of Transvenous Lead Extraction in the Device Laboratory and Operating Room Guided by a Novel Risk Stratification Scheme.

OBJECTIVES: The goal of this study was to evaluate a novel risk stratification scheme to categorize patients on the basis of risk to either an operating room or device laboratory with rescue strategy. BACKGROUND: Lead extraction can be complicated by lethal issues such as vascular and cardiac rupture. Currently, the optimal site for lead extraction has not been well established. METHODS: A risk stratification scheme was developed from previously available risk factors for major complications. Patients were prospectively risk stratified between October 2013 and January 2016. High-risk procedures were performed in the operating room with ready surgical services; intermediate-risk procedures were performed in the device laboratory. RESULTS: In total, 349 leads were removed from 187 patients (age 61.0 ± 17.2 years; 66.3% men) over 27 months. Seventy-two patients (38.5%) were categorized as high risk. Median implant duration of the oldest lead per patient was 11.2 years (interquartile range: 7.9 to 14.9 years) in the operating room group versus 2.6 years (interquartile range: 1.6 to 4.9 years) in the device laboratory group (p < 0.001). Clinical success in the operating room (95.8%) and device laboratory (99.1%) groups was similar (p = 0.16). A higher incidence of major complications occurred in the high-risk group (operating room group: 6.9%; device laboratory: 0.0%; p = 0.007). In-hospital mortality (operating room group: 8.3%; device laboratory: 2.6%; p = 0.09) and long-term (2-year) survival (operating room: 70.8%; device laboratory: 84.4%; p = 0.07) rates were similar. CONCLUSIONS: Use of a novel risk stratification scheme in guiding the selection of operating room versus device laboratory for lead extraction is feasible, safe, and efficacious. Intermediate-risk procedures can be performed safely in the device laboratory with rescue strategy, without excess surgical resource utilization.

Mortality After Magnetic Resonance Imaging of the Brain in Patients With Cardiovascular Implantable Devices.

BACKGROUND: Use of magnetic resonance imaging (MRI) brain is restricted in patients with cardiovascular implantable electronic devices (CIEDs). We proposed to determine whether mortality difference exists for patients with non-MRI-conditional CIEDs undergoing brain MRI compared with controls. METHODS AND RESULTS: Retrospective analysis of prospectively collected data was performed to compare all-cause mortality in patients with CIEDs undergoing brain MRI (CIED-MRI) with 3 control groups matched for age, sex, imaging year, and type of CIED: (1) no CIED, brain MRI (no-CIED-MRI); (2) CIED, brain computerized tomography (CT) scan (CIED-CT); and (3) no CIED, brain CT (no-CIED-CT). The primary outcome was a significant difference (P<0.05) between estimated mortality rates. Secondary outcomes were changes in device function before and after brain MRI. The estimated all-cause mortality at 5 years for the CIED-MRI group [mean age (±SD), 68.2 years (15.3 years); 61.2% men] was not significantly different from patients who underwent CT with or without a device (CIED-CT group: hazard ratio, 0.814; 95% confidence interval, 0.593-1.117; P=0.2; no-CIED-CT group: hazard ratio, 1.149; 95% confidence interval, 0.818-1.613; P=0.4). There was a significant increase in mortality between CIED-MRI and no-CIED-MRI groups (hazard ratio, 1.463; 95% confidence interval, 1.019-2.099; P=0.04). CONCLUSIONS: Brain MRI in patients with CIEDs does not carry an increased mortality risk compared with brain CT and can be performed with adherence to appropriate procedural protocols.

Utility of T-wave amplitude as a non-invasive risk marker of sudden cardiac death in hypertrophic cardiomyopathy.

OBJECTIVE: Sudden cardiac arrest (SCA) is the most devastating outcome in hypertrophic cardiomyopathy (HCM). We evaluated repolarisation features on the surface electrocardiogram (ECG) to identify the potential risk factors for SCA. METHODS: Data was collected from 52 patients with HCM who underwent implantable cardioverter defibrillator (ICD) implantation. Leads V2 and V5 from the ECG closest to the time of ICD implant were utilised for measuring the Tpeak-Tend interval (Tpe), QTc, Tpe/QTc, T-wave duration and T-wave amplitude. The presence of the five traditional SCA-associated risk factors was assessed, as well as the HCM risk-SCD score. RESULTS: 16 (30%) patients experienced aborted cardiac arrest over 8.5±4.1 years, with 9 receiving an ICD shock and 7 receiving ATP. On univariate analysis, T-wave amplitude was associated with appropriate ICD therapy (HR per 0.1 mV 0.79, 95% CI 0.56 to 0.96, p=0.02). Aborted SCA was not associated with a greater mean QTc duration, Tpeak-Tend interval, T-wave duration, or Tpe/QT ratio. Multivariate analysis (adjusting for cardinal HCM SCA-risk factors) showed T-wave amplitude in Lead V2 was an independent predictor of risk (adjusted HR per 0.1 mV 0.74, 95% CI 0.57 to 0.97, p=0.03). Addition of T-wave amplitude in Lead V2 to the traditional risk factors resulted in significant improvement in risk stratification (C-statistic from 0.65 to 0.75) but did not improve the performance of the HCM SCD-risk score. CONCLUSIONS: T-wave amplitude is a novel marker of SCA in this high risk HCM population and may provide incremental predictive value to established risk factors. Further work is needed to define the role of repolarisation abnormalities in predicting SCA in HCM.

Outcomes and Complications of Lead Removal: Can We Establish a Risk Stratification Schema for a Collaborative and Effective Approach?

BACKGROUND: Removal of an entire cardiovascular implantable electronic device is associated with morbidity and mortality. We sought to establish a risk classification scheme according to the outcomes of transvenous lead removal in a single center, with the goal of using that scheme to guide electrophysiology lab versus operating room extraction. METHODS: Consecutive patients undergoing transvenous lead removal from January 2001 to October 2012 at Mayo Clinic were retrospectively reviewed. RESULTS: A total of 1,378 leads were removed from 652 (age 64 ± 17 years, M 68%) patients undergoing 702 procedures. Mean (standard deviation) lead age was 57.6 (58.8) months. Forty-four percent of leads required laser-assisted extraction. Lead duration (P < 0.001) and an implantable cardioverter defibrillator (ICD) lead (P < 0.001) were associated with the need for laser extraction and procedure failure (P < 0.0001 and P = 0.02). The major complication rate was 1.9% and was significantly associated with longer lead duration (odds ratio: 1.2, 95% confidence interval: 1.1-1.3; P < 0.001). High-risk patients (with a >10-year-old pacing or a >5-year-old ICD lead) had significantly higher major events than moderate-risk (with pacing lead 1-10 years old or ICD lead 1-5 years old) and low-risk (any lead ≤1-year-old) patients (5.3%, 1.2%, and 0%, respectively; P < 0.001). CONCLUSIONS: Transvenous lead removal is highly successful, with few serious procedural complications. We propose a risk stratification scheme that may categorize patients as low, moderate, and high risk for lead extraction. Such a strategy may guide which extractions are best performed in the operating room.

Extraction of superfluous device leads: A comparison with removal of infected leads.

BACKGROUND: Although increasingly more lead extraction was performed for superfluous leads, the extraction of such leads remains controversial. OBJECTIVE: The objective of this study was to determine the outcomes and complications of transvenous extraction of superfluous leads in a single center in the era of laser technology. METHODS: Four hundred eighty transvenous lead extraction procedures performed from January 2001 through October 2012 at Mayo Clinic (Rochester, Minnesota) were retrospectively reviewed. Of these, 123 procedures were performed for superfluous functional or nonfunctional leads. Data were collected from electronic medical records and an institutional database of cardiovascular implantable electronic devices. RESULTS: A total of 167 superfluous leads (mean [SD] lead duration 53 [53] months; median 34 months) were removed during the 123 procedures. Forty-one percent of procedures were for lead malfunction. The procedural complete-success rate was 96.7%. Major complications occurred in 1 patient (0.8%), who had a superior vena cava tear that required thoracotomy. Superfluous leads had been implanted for a shorter period of time than infected leads (mean [SD] 53 [53] vs 81 [59] months; P < .001). The procedural complete-success rate was higher for the removal of superfluous leads than for leads associated with infection (97% vs 92%; P = .05). CONCLUSION: Transvenous extraction of superfluous leads is highly successful, with few procedural complications. Extraction of superfluous leads at the time of device upgrade or lead revision is considered reasonable to avoid the increasing risk of extraction complications with lead aging.

Multicenter study of the safety and effects of magnetic resonance imaging in patients with coronary sinus left ventricular pacing leads.

BACKGROUND: Magnetic resonance imaging (MRI) in patients with left ventricular (LV) leads may cause tissue or lead heating, dislodgment, venous damage, or lead dysfunction. OBJECTIVE: The purpose of this study was to determine the safety of MRI in patients with LV pacing leads. METHODS: Prospective data on patients with coronary sinus LV leads undergoing clinically indicated MRI at 3 institutions were collected. Patients were not pacemaker-dependent. Scans were performed under pacing nurse, technician, radiologist, and physicist supervision using continuous vital sign, pulse oximetry, and ECG monitoring and a 1.5-T scanner with specific absorption rate <1.5 W/kg. Devices were interrogated pre- and post-MRI, programmed to asynchronous or inhibition mode with tachyarrhythmia therapies off (if present), and reprogrammed to their original settings post-MRI. RESULTS: MRI scans (n = 42) were performed in 40 patients with non-MRI conditional LV leads between 2005 and 2013 (mean age 67 ± 9 years, n = 16 [40%] women, median lead implant duration 740 days with interquartile range 125-1173 days). MRIs were performed on the head/neck/spine (n = 35 [83%]), lower extremities (n = 4 [10%]), chest (n = 2 [5%]), and abdomen (n = 1 [2%]). There were no overall differences in pre- and post-MRI interrogation LV lead sensing (12.4 ± 6.2 mV vs 12.9 ± 6.7 mV, P = .38), impedance (724 ± 294 Ω vs 718 ± 312 Ω, P = .67), or threshold (1.4 ± 1.1 V vs 1.4 ± 1.0 V, P = .91). No individual LV lead changes required intervention. CONCLUSION: MRI scanning was performed safely in non-pacemaker-dependent patients with coronary sinus LV leads who were carefully monitored during imaging without clinically significant adverse effect on LV lead function.

Safety of magnetic resonance imaging in patients with permanent pacemakers: a collaborative clinical approach.

OBJECTIVE: This study aimed to characterize the interactions of pacemakers with magnetic resonance imaging (MRI) and to identify device characteristics that could predict adverse interactions. BACKGROUND: The safety of MRI in patients with indwelling pacemaker systems remains uncertain. Previous studies demonstrated safety in most patients, but unpredictable, potentially concerning changes in pacemaker behavior have occurred. METHODS: We prospectively studied patients with pacemaker devices in situ who were not pacemaker dependent and in whom MRI was essential for adequate diagnosis and treatment. All patients were monitored by electrocardiography and pulse oximetry during scanning; devices were interrogated and cardiac enzymes were measured before and after scanning. RESULTS: Of 32 patients studied (46 MRI examinations), 28 patients had a dual-chamber system and one had a biventricular device. Regions scanned were the head and spine. Devices were reprogrammed to asynchronous pacing or sense-only mode in all except six patients before MRI. During six scanning episodes (five patients), "power-on" resetting of the device was noted. Magnet-mode pacing was noted during four episodes (three patients). Occasional premature ventricular contractions were noted in one patient. No significant changes in battery voltage, sensed P wave and R wave, pacing thresholds, lead impedance, or cardiac enzymes were noted immediately after MRI or at 1-month follow-up. CONCLUSIONS: Overall, no significant changes were seen in pacemaker device function, and no adverse clinical events were observed. A minority of patients with older devices had unpredictable changes in device behavior, which stresses the need for close monitoring during and careful device interrogation after scanning.