Convalescent Plasma Antibody Levels and the Risk of Death from Covid-19.

BACKGROUND: Convalescent plasma has been widely used to treat coronavirus disease 2019 (Covid-19) under the presumption that such plasma contains potentially therapeutic antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be passively transferred to the plasma recipient. Whether convalescent plasma with high antibody levels rather than low antibody levels is associated with a lower risk of death is unknown. METHODS: In a retrospective study based on a U.S. national registry, we determined the anti-SARS-CoV-2 IgG antibody levels in convalescent plasma used to treat hospitalized adults with Covid-19. The primary outcome was death within 30 days after plasma transfusion. Patients who were enrolled through July 4, 2020, and for whom data on anti-SARS-CoV-2 antibody levels in plasma transfusions and on 30-day mortality were available were included in the analysis. RESULTS: Of the 3082 patients included in this analysis, death within 30 days after plasma transfusion occurred in 115 of 515 patients (22.3%) in the high-titer group, 549 of 2006 patients (27.4%) in the medium-titer group, and 166 of 561 patients (29.6%) in the low-titer group. The association of anti-SARS-CoV-2 antibody levels with the risk of death from Covid-19 was moderated by mechanical ventilation status. A lower risk of death within 30 days in the high-titer group than in the low-titer group was observed among patients who had not received mechanical ventilation before transfusion (relative risk, 0.66; 95% confidence interval [CI], 0.48 to 0.91), and no effect on the risk of death was observed among patients who had received mechanical ventilation (relative risk, 1.02; 95% CI, 0.78 to 1.32). CONCLUSIONS: Among patients hospitalized with Covid-19 who were not receiving mechanical ventilation, transfusion of plasma with higher anti-SARS-CoV-2 IgG antibody levels was associated with a lower risk of death than transfusion of plasma with lower antibody levels. (Funded by the Department of Health and Human Services and others; ClinicalTrials.gov number, NCT04338360.).

Access to and safety of COVID-19 convalescent plasma in the United States Expanded Access Program: A national registry study.

BACKGROUND: The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma. METHODS AND FINDINGS: Mayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician-principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had-or were at risk of progression to-severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate at the state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions, as well as assessing enrollment in metropolitan areas and less populated areas that did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low (<1%), and the overall crude 30-day mortality rate was 25.2% (95% CI, 25.0% to 25.5%). This registry study was limited by the observational and pragmatic study design that did not include a control or comparator group; thus, the data should not be used to infer definitive treatment effects. CONCLUSIONS: These results suggest that the EAP provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The study design of the EAP may serve as a model for future efforts when broad access to a treatment is needed in response to an emerging infectious disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT#: NCT04338360.

Mitigation of Exercise Oscillatory Ventilation Score by Cardiac Resynchronization Therapy.

BACKGROUND: Exercise oscillatory ventilation (EOV) is a consequence of ventilatory control system instability and is commonly observed in patients with advanced heart failure (HF); it is associated with adverse prognosis. The goal of this study was to evaluate the effects of cardiac resynchronization therapy (CRT) on oscillatory ventilation as quantified by a proposed EOV score. METHODS AND RESULTS: Consecutive patients with HF (N = 35) who underwent clinically indicated CRT, cardiopulmonary exercise testing and carbon dioxide (CO2) chemosensitivity by rebreathe before and 4-6 months after CRT were included in this post hoc analysis. With CRT, EOV scores improved in 22 patients (63%). In these patients, left ventricular ejection fraction, left atrial volume, brain natriuretic peptide concentration, and CO2 chemosensitivity significantly improved after CRT (P < 0.05). Furthermore, minute ventilation per unit CO2 production significantly decreased, and end-tidal CO2 increased at rest and at peak exercise post-CRT. Multiple regression analysis showed only the change of CO2 chemosensitivity to be significantly associated with the improvement of the EOV score (b = 0.64; F = 11.3; P = 0.004). In the group without EOV score improvement (n = 13), though left ventricular ejection fraction significantly increased with CRT (P = 0.015), no significant changes in ventilation or gas exchange were observed. CONCLUSION: The EOV score was mitigated by CRT and was associated with decreased CO2 chemosensitivity.

Real-world experience with leadless cardiac pacing.

BACKGROUND: Leadless cardiac pacing (LCP) has emerged as a new modality for permanent pacing. We sought to describe comparative outcomes between LCP and transvenous pacemakers. METHODS: Patients receiving LCP (Micra [Medtronic, Minneapolis, MN, USA] and Nanostim [St. Jude Medical/Abbott Laboratories, Chicago, IL, USA]) between 2014 and 2017 at the Mayo Clinic Heart Rhythm Enterprise practice (Rochester, MN, USA; Jacksonville, FL, USA; and Scottsdale, AZ, USA) were identified. We identified 1:1 age- and sex-matched controls receiving single-chamber transvenous ventricular pacemakers (TVP). Statistical analyses were performed with JMP 13.0.0 (SAS, Institute Cary, NC, USA). RESULTS: Ninety patients underwent LCP implantation (73 Micra and 17 Nanostim) with a median follow-up duration of 62 (interquartile range 28-169) days. Both groups had 100% successful device implant rates. There were no differences in procedure-related major (0% vs 1%) or minor complications (8% vs 3%) in the LCP versus TVP groups (P > 0.05). Excluding Nanostim patients, there was a lower rate of device-related revision or extraction in the Micra versus TVP groups (0% vs 5%, P = 0.028). Device endocarditis was more common in the TVP group (0% vs 3%, P = 0.04). Estimated longevity was greater for the LCP group (median 12.0 vs 10.0 years, P < 0.0001). An increase in severity of tricuspid valve regurgitation (TR) by ≥2 grades occurred in none of the LCP patients, and in 19% of the TVP patients (P = 0.017). CONCLUSION: There are no significant differences in procedural complications among patients receiving LCP versus TVP. The Micra group had lower rates of device-related revision/extraction compared to the TVP group. Patients with leadless pacemaker were less likely to develop endocarditis or worsening TR.

Modulation of ventilatory reflex control by cardiac resynchronization therapy.

BACKGROUND: Heart failure (HF) is characterized by heightened sensitivities of the CO2 chemoreflex and the ergoreflex which promote increased ventilatory drive manifested as increased minute ventilation per volume of expired CO2 (VE/VCO2). The aims of this study were to evaluate the effects of cardiac resynchronization therapy (CRT) on carbon dioxide (CO2) chemosensitivity and the arterial CO2 setpoint. METHODS AND RESULTS: Consecutive HF patients (n = 35) who underwent clinically indicated CRT were investigated by means of cardiopulmonary exercise testing and CO2 chemosensitivity evaluation with the use of a rebreathe method before and 4-6 months after CRT. Pre- and post-CRT measures were compared with the use of either paired t test or Wilcoxon test. Decreased peak VE/VCO2 (44 ± 10 vs 40 ± 8; P < .01), CO2 chemosensitivity (2.2 ± 1.1 vs 1.7 ± 0.8 L min(-1) mm Hg(-1); P = .04), and increased peak end-tidal CO2 (29 ± 5 vs 31 ± 5 mm Hg; P < .01) were also observed after CRT. Multivariate analysis adjusted for age and sex showed the decrease of peak VE/VCO2 from before to after CRT to be most strongly associated with the increase of peak end-tidal CO2 (ß = -0.84; F = 21.5; P < .0001). CONCLUSIONS: Decrease of VE/VCO2 after CRT is associated with decreased CO2 chemosensitivity and increase of the arterial CO2 setpoint, which is consistent with decreased activation of both the CO2 chemoreflex and the ergoreflex.

Cardiac device complications in the cognitively impaired.

BACKGROUND: Patients with preexisting mild cognitive impairment or dementia may be at increased risk for developing cardiac device complications due to an impaired ability to follow postimplant care instructions. We sought to determine whether rates of infection, lead dislodgement, or appropriate or inappropriate implantable cardioverter defibrillator (ICD) shocks are increased in this population. METHODS: Medical charts of 561 patients with mild cognitive impairment or dementia who underwent pacemaker (PM) or ICD implantation between January 2002 and October 2009 at Mayo Clinic were identified. A total of 134 patients who were diagnosed with cognitive impairment or dementia before device implantation or within 1 year of implantation were compared with 134 matched controls. Information was collected on patient characteristics, comorbid medical conditions, ejection fraction, complications, device type, device therapy, and mortality. Device information was prospectively entered into a database and retrospectively reviewed. RESULTS: Of the 134 patients with mild cognitive impairment and dementia, 99 underwent PM implantation and 35 underwent ICD implantation. Compared to controls, there was no difference in patient characteristics, ejection fraction, or comorbidities except for diabetes, which was more prevalent in the cognitively impaired and demented group (18.7% vs 30.6%, P = 0.02). There was no difference in device therapy and complications (14.4% vs 5.8%, P = 0.268). However, there was a decreased survival in patients with cognitive impairment and dementia when compared to the control group (42% vs 67% at 5 years, P = 0.007). CONCLUSION: Patients with cognitive impairment and standard device indications are not at increased risk for device complications and therapy but their survival is much lower than in matched controls. The cause of this lower survival is unknown but may be related to the underlying neurological disease. Presence of cognitive impairment should therefore be considered when contemplating implantation of a cardiac device.

Left ventricular lead position for cardiac resynchronization: a comprehensive cinegraphic, echocardiographic, clinical, and survival analysis.

AIMS: We sought to determine the clinical and survival outcomes of cardiac resynchronization therapy (CRT) associated with left ventricular (LV) lead location. The lateral left ventricle has been considered the optimal LV lead location for CRT. METHODS AND RESULTS: Left ventricular lead cinegrams taken in 30° right and left anterior oblique views were evaluated in 457 recipients of CRT with a pacemaker or a defibrillator from 1 January 2002 to 31 December 2008 in this retrospective study. Left ventricular lead placement was prioritized at implantation into posterolateral (PL), anterolateral (AL), middle cardiac, and anterointerventricular coronary veins. Using echocardiographic LV 16-segment analysis, we grouped the leads as anterior, AL, PL, and posterior locations. New York Heart Association (NYHA) class and echocardiography were assessed before and after CRT. Clinical and survival outcomes after CRT were compared among the four LV lead locations.  Patient baseline demographic characteristics were similar among these four groups. Improvement in NYHA class was significantly greater in the AL (P= 0.04) and PL (P= 0.03) locations than in the anterior location. There was a tendency for greater improvement in LV ejection fraction among the AL (P= 0.11) and PL (P= 0.08) locations than the anterior location. Kaplan-Meier survival estimate at 4 years varied for location: AL, 72%; anterior, 48%; PL, 62%; and posterior, 72% (P= 0.003). CONCLUSION: Cardiac resynchronization therapy recipients are profiting from all lead positions. However, LV lead placed in the AL and PL positions is more preferential for achieving optimal CRT benefit than leads placed in the anterior position.

Impact of radiocontrast use during left ventricular pacemaker lead implantation for cardiac resynchronization therapy.

AIMS: The risk of contrast-induced nephropathy (CIN) with radiocontrast use during left ventricular (LV) lead placement for cardiac resynchronization therapy (CRT) is unknown. It is unclear as to whether minimizing contrast use impacts adequacy of LV lead placement. METHODS AND RESULTS: A retrospective analysis was performed of all LV leads placed for CRT at Mayo Clinic, Rochester, MN from 16 March 2001 to 1 April 2009. The primary goal was to assess risk of CIN and adequacy of lead placement depending on the amount of contrast administered during CRT placement. Contrast-induced nephropathy was defined as a ≥25% increase in serum creatinine ≥48 h post-procedurally. Adequacy of lead placement was assessed in a blinded fashion by review of procedural fluoroscopic and post-procedural radiographic images. Eight hundred and twenty-two subjects were divided based on the amount of procedural contrast used into tertile 1 (<55 mL, 257 patients), tertile 2 (55-94 mL, 261 patients), and tertile 3 (≥95 mL, 304 patients). Contrast-induced nephropathy occurred in 5.4% of patients in tertile 1, 5.4% in tertile 2 and 11.8% in tertile 3 (P = 0.004). Among the tertiles, lead positioning was optimal in 95, 80 and 66%, respectively (P < 0.0001). Fluoroscopic time was 34 ± 23, 42 ± 26, and 48 ± 30 min in tertiles 1, 2, and 3 (P < 0.0001). CONCLUSION: Risk of CIN with CRT implantations was substantial. Increased volume of radiocontrast used for LV lead placement was associated with substantially increased risk of CIN. Minimal contrast use was associated with decreased procedural times without adverse impact on adequacy of lead placement.

Method of pacing does not affect the recurrence of syncope in carotid sinus syndrome.

INTRODUCTION: Pacemaker therapy is effective in reducing recurrent syncope in patients with symptomatic carotid sinus hypersensitivity (CSH), yet the optimal pacing modality for this syndrome is not known. The objective of this study is to prospectively investigate the impact of three pacing methods (DDDR vs DDDR with sudden bradycardia response [SBR] vs VVI) on recurrent syncope and quality of life. METHODS: Twenty-one patients with symptomatic CSH (syncope or near syncope) were randomized to VVI, DDDR, or DDDR with SBR on a double-blinded basis in a sequential crossover fashion with 6 months in each mode. The primary endpoints were recurrent events and quality of life (assessed by SF-36). The mean number of events and SF-36 scores were compared. RESULTS: At baseline, over the preceding 6 months, there were a total of 29 syncopal events and 258 presyncopal events among 21 patients. Following pacing in any mode, the total number of these syncopal events reduced to two in two patients (P < 0.001) and 17 presyncopal events (P < 0.001) in 12 patients. The mean number of events was not significantly different between the three pacing methods. SF-36 scores revealed some minor benefits of DDDR pacing versus baseline in the categories, but no pacing method was found to be superior. CONCLUSIONS: The study was unable to confirm the initial study hypothesis of a superiority of one pacing modality over another. Quality of life measures allude to potential benefit from DDDR pacing alone.

Effect of long-term right ventricular pacing in young adults with structurally normal heart.

BACKGROUND: Right ventricular pacing increases the risk of heart failure in adults with structural heart disease. The impact of prolonged right ventricular pacing in adults without structural heart disease is not fully characterized and may depend on interactions of pacing with abnormal substrate predisposing to ventricular dysfunction. METHODS AND RESULTS: We assessed the effect of right ventricular pacing in patients who underwent pacemaker implantation for isolated congenital atrioventricular block between 1964 and 2005. To assess for immunologic contribution to cardiac dysfunction, outcomes were compared between patients with (Ab(+)) and without (Ab(-)) antinuclear antibody during adulthood and an age- and sex-matched Olmsted County, Minnesota, population. Of 103 patients (mean+/-SD age, 32+/-19 years), 18 were Ab(+). Long-term survival free of new heart failure after pacemaker implantation in isolated congenital atrioventricular block patients was worse than in the matched population (P<0.001). This difference was attributable to the development of heart failure in 12 Ab(+) patients (67%; P<0.001), without differences between Ab(-) patients (2%) and the matched population (2%; P=0.7). Compared with baseline, at last follow-up, left ventricular ejection fraction did not decline in Ab(-) (53+/-9% to 57+/-12%) but decreased in Ab(+)(52+/-10% to 38+/-12%; P=0.03) patients. Survival was similar in Ab(-) patients and the Minnesota population (98%; P=0.7) but worse in Ab(+) patients (79%; P<0.01). CONCLUSIONS: The natural history of patients with isolated congenital atrioventricular block who require pacing depends upon their antibody status. Antinuclear antibody status was a predictor for the development of heart failure and death. Long-term right ventricular pacing alone does not appear to be associated with development of heart failure, deterioration in ventricular function, or reduced survival in Ab(-) isolated congenital atrioventricular block patients.

No increased bleeding events with continuation of oral anticoagulation therapy for patients undergoing cardiac device procedure.

BACKGROUND: Switching warfarin for heparin has been a practice for managing periprocedural anticoagulation in high-risk patients undergoing device-related procedures. We sought to investigate whether continuation of warfarin sodium therapy without heparin bridging is safe and, when it is continued, the optimal international normalized ratio (INR) without increased bleeding risk at time of device-related procedure. METHODS AND RESULTS: We retrospectively studied 766 consecutive patients taking warfarin long term who underwent device-related procedures. Patients were grouped by treatment: discontinued warfarin (-warfarin, n = 243), no interruption of warfarin (+warfarin, n = 324), and discontinued warfarin with heparin bridging (+heparin, n = 199). The study primary endpoint was systemic bleeding or formation of moderate or severe pocket hematoma within 30 days of the procedure. Thirty-one (4%) patients had bleeding events, including pocket hematoma in 29 patients. The bleeding events occurred more often for +heparin (7.0%) than -warfarin (2.1%) or +warfarin (3.7%, P = 0.029). For +warfarin group, INR of 2.0-2.5 at time of procedure did not increase bleeding risk compared with INR less than 1.5 (3.7% vs 3.4%; P = 0.72), but INR greater than 2.5 increased the bleeding risk (10.0% vs 3.4%; P = 0.029). Concomitant aspirin use with warfarin significantly increased bleeding risk than warfarin alone (5.6% vs 1.4%, P = 0.02). Median length of hospitalization was significantly shorter for +warfarin than +heparin (1 vs 6 days; P < 0.001). CONCLUSION: Continuation of oral anticoagulation therapy with an INR level of <2.5 does not impose increased risk of bleeding for device-related procedures, although precaution is necessary to avoid supratherapeutic anticoagulation levels.

Anodal stimulation: an underrecognized cause of nonresponders to cardiac resynchronization therapy.

OBJECTIVE: The purpose of this study was to determine if anodal stimulation accounts for failure to benefit from cardiac resynchronization therapy (CRT) in some patients. BACKGROUND: Approximately 30-40% of patients with moderate to severe heart failure do not have symptomatic nor echocardiographic improvement in cardiac function following CRT. Modern CRT devices allow the option of programming left ventricular (LV) lead pacing as LV tip to right ventricular (RV) lead coil to potentially improve pacing thresholds. However, anodal stimulation can result in unintentional RV pacing (anode) instead of LV pacing (cathode). METHODS: Patients enrolled in our center's CRT registry had an echocardiogram, 6-minute walk (6MW), and Minnesota Living with HF Questionnaire (MLHFQ) pre-implant and 6 months after CRT. Electrocardiograms (12 lead) during RV, LV, and biventricular (BiV) pacing were obtained at the end of the implant in 102 patients. Anodal stimulation was defined as LV pacing QRS morphology on EKG being identical to RV pacing or consistent with fusion with RV and LV electrode capture. LV end systolic volume (LVESV) was measured by echo biplane Simpson's method and CRT responder was defined as 15% or greater reduction in LVESV. RESULTS: Of the 102 patients, 46 (45.1%) had the final LV lead pacing configuration programmed LV (tip or ring) to RV (coil or ring). 3 of the 46 subjects (6.5%) had EKG findings consistent with anodal stimulation, not corrected intraoperatively. All anodal stimulation patients were nonresponders to CRT by echo criteria (reduction in LVESV 13.3 ± 0.6%, increase in EF 5.0 ± 1.4%) compared to 46% responders for those without anodal stimulation, (change in LVESV 18.7 ± 25.6%, EF 7.6 ±10.9%). None of the anodal stimulation patients were responders for the 6 minute walk, compared to 32 of 66 (48%) of those without anodal stimulation. CONCLUSION: Anodal stimulation is a potential underrecognized and ameliorable cause of poor response to CRT.

Program and patient characteristics for the United States Expanded Access Program to COVID-19 convalescent plasma.

BACKGROUND: The United States (US) Expanded Access Program (EAP) to COVID-19 convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease-2019 (COVID-19). While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents particularly for vulnerable racial and ethnic minority populations who were disproportionately affected by the pandemic. The objective of this study is to report on the demographic, geographic, and chronological access to COVID-19 convalescent plasma in the US via the EAP. METHODS AND FINDINGS: Mayo Clinic served as the central IRB for all participating facilities and any US physician could participate as local physician-principal investigator. Registration occurred through the EAP central website. Blood banks rapidly developed logistics to provide convalescent plasma to hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal trends in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate on a state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions as well as assessing enrollment in metropolitan and less populated areas which did not have access to COVID-19 clinical trials.From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. A majority of patients were older than 60 years of age (57.8%), male (58.4%), and overweight or obese (83.8%). There was substantial inclusion of minorities and underserved populations, including 46.4% of patients with a race other than White, and 37.2% of patients were of Hispanic ethnicity. Severe or life-threatening COVID-19 was present in 61.8% of patients and 18.9% of patients were mechanically ventilated at time of convalescent plasma infusion. Chronologically and geographically, increases in enrollment in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled patients in the EAP, including both in metropolitan and less populated areas. CONCLUSIONS: The EAP successfully provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The efficient study design of the EAP may serve as an example framework for future efforts when broad access to a treatment is needed in response to a dynamic disease affecting demographic groups and areas historically underrepresented in clinical studies.

Mortality in individuals treated with COVID-19 convalescent plasma varies with the geographic provenance of donors.

Successful therapeutics and vaccines for coronavirus disease 2019 (COVID-19) have harnessed the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evidence that SARS-CoV-2 exists as locally evolving variants suggests that immunological differences may impact the effectiveness of antibody-based treatments such as convalescent plasma and vaccines. Considering that near-sourced convalescent plasma likely reflects the antigenic composition of local viral strains, we hypothesize that convalescent plasma has a higher efficacy, as defined by death within 30 days of transfusion, when the convalescent plasma donor and treated patient were in close geographic proximity. Results of a series of modeling techniques applied to approximately 28,000 patients from the Expanded Access to Convalescent Plasma program (ClinicalTrials.gov number: NCT04338360) support this hypothesis. This work has implications for the interpretation of clinical studies, the ability to develop effective COVID-19 treatments, and, potentially, for the effectiveness of COVID-19 vaccines as additional locally-evolving variants continue to emerge.

Risk factors for implantable defibrillator lead fracture in a recalled and a nonrecalled lead.

INTRODUCTION: The Medtronic Sprint Fidelis implantable cardioverter defibrillator (ICD) lead was "recalled" in October 2007 after 268,000 implants worldwide due to increased failure risk. Manufacturer suggested monitoring has not been shown effective at preventing adverse events. Only limited data exist regarding clinical predictors of Fidelis lead fracture. We sought to identify risk factors for Fidelis fracture to guide clinical monitoring and compare its performance with a control lead. METHODS: Fractured lead cases were retrospectively reviewed for demographic data, implant technique, radiographic appearance and clinical presentation was analyzed. Lead survival was compared using Kaplan-Meir curves. RESULTS: Study patients (n = 1314) experienced 18 Fidelis and 6 Quattro lead fractures. Patients with failed Fidelis leads were younger than those with surviving leads (49.5 vs 64.6 years, P = 0.0066). Fidelis lead fractures often occurred around the time of physical activity. No other measured demographic or technique related factors were associated with lead fracture. Fidelis leads had significantly decreased survival compared with Quattro leads (89.3 vs 98.9% at 30 months). Patients less than 50 years old had significantly decreased lead survival compared with those older than 50 in both Fidelis (79.6% vs 96.5% at 24 months) and Quattro (93.4 vs 99.8%, P < 0.001 at 24 months) leads. CONCLUSIONS: Patients under age 50, with either Fidelis or Quattro ICD leads, are at increased risk of lead fracture compared with patients over 50, particularly around the time of intense physical activity. Aggressive monitoring and advisory programming appears warranted in patients with Fidelis leads as well as especially in younger patients.

Effect of Convalescent Plasma on Mortality among Hospitalized Patients with COVID-19: Initial Three-Month Experience.

IMPORTANCE: Passive antibody transfer is a longstanding treatment strategy for infectious diseases that involve the respiratory system. In this context, human convalescent plasma has been used to treat coronavirus disease 2019 (COVID-19), but the efficacy remains uncertain. OBJECTIVE: To explore potential signals of efficacy of COVID-19 convalescent plasma. DESIGN: Open-label, Expanded Access Program (EAP) for the treatment of COVID-19 patients with human convalescent plasma. SETTING: Multicenter, including 2,807 acute care facilities in the US and territories. PARTICIPANTS: Adult participants enrolled and transfused under the purview of the US Convalescent Plasma EAP program between April 4 and July 4, 2020 who were hospitalized with (or at risk of) severe or life threatening acute COVID-19 respiratory syndrome. INTERVENTION: Transfusion of at least one unit of human COVID-19 convalescent plasma using standard transfusion guidelines at any time during hospitalization. Convalescent plasma was donated by recently-recovered COVID-19 survivors, and the antibody levels in the units collected were unknown at the time of transfusion. Main Outcomes and Measures: Seven and thirty-day mortality. RESULTS: The 35,322 transfused patients had heterogeneous demographic and clinical characteristics. This cohort included a high proportion of critically-ill patients, with 52.3% in the intensive care unit (ICU) and 27.5% receiving mechanical ventilation at the time of plasma transfusion. The seven-day mortality rate was 8.7% [95% CI 8.3%-9.2%] in patients transfused within 3 days of COVID-19 diagnosis but 11.9% [11.4%-12.2%] in patients transfused 4 or more days after diagnosis (p<0.001). Similar findings were observed in 30-day mortality (21.6% vs. 26.7%, p<0.0001). Importantly, a gradient of mortality was seen in relation to IgG antibody levels in the transfused plasma. For patients who received high IgG plasma (>18.45 S/Co), seven-day mortality was 8.9% (6.8%, 11.7%); for recipients of medium IgG plasma (4.62 to 18.45 S/Co) mortality was 11.6% (10.3%, 13.1%); and for recipients of low IgG plasma (<4.62 S/Co) mortality was 13.7% (11.1%, 16.8%) (p=0.048). This unadjusted dose-response relationship with IgG was also observed in thirty-day mortality (p=0.021). The pooled relative risk of mortality among patients transfused with high antibody level plasma units was 0.65 [0.47-0.92] for 7 days and 0.77 [0.63-0.94] for 30 days compared to low antibody level plasma units. CONCLUSIONS AND RELEVANCE: The relationships between reduced mortality and both earlier time to transfusion and higher antibody levels provide signatures of efficacy for convalescent plasma in the treatment of hospitalized COVID-19 patients. This information may be informative for the treatment of COVID-19 and design of randomized clinical trials involving convalescent plasma. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04338360.

Early safety indicators of COVID-19 convalescent plasma in 5000 patients.

BACKGROUNDConvalescent plasma is the only antibody-based therapy currently available for patients with coronavirus disease 2019 (COVID-19). It has robust historical precedence and sound biological plausibility. Although promising, convalescent plasma has not yet been shown to be safe as a treatment for COVID-19.METHODSThus, we analyzed key safety metrics after transfusion of ABO-compatible human COVID-19 convalescent plasma in 5000 hospitalized adults with severe or life-threatening COVID-19, with 66% in the intensive care unit, as part of the US FDA expanded access program for COVID-19 convalescent plasma.RESULTSThe incidence of all serious adverse events (SAEs), including mortality rate (0.3%), in the first 4 hours after transfusion was <1%. Of the 36 reported SAEs, there were 25 reported incidences of related SAEs, including mortality (n = 4), transfusion-associated circulatory overload (n = 7), transfusion-related acute lung injury (n = 11), and severe allergic transfusion reactions (n = 3). However, only 2 of 36 SAEs were judged as definitely related to the convalescent plasma transfusion by the treating physician. The 7-day mortality rate was 14.9%.CONCLUSIONGiven the deadly nature of COVID-19 and the large population of critically ill patients included in these analyses, the mortality rate does not appear excessive. These early indicators suggest that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19.TRIAL REGISTRATIONClinicalTrials.gov NCT04338360.FUNDINGMayo Clinic, Biomedical Advanced Research and Development Authority (75A50120C00096), National Center for Advancing Translational Sciences (UL1TR002377), National Heart, Lung, and Blood Institute (5R35HL139854 and R01 HL059842), National Institute of Diabetes and Digestive and Kidney Diseases (5T32DK07352), Natural Sciences and Engineering Research Council of Canada (PDF-532926-2019), National Institute of Allergy and Infectious Disease (R21 AI145356, R21 AI152318, and AI152078), Schwab Charitable Fund, United Health Group, National Basketball Association, Millennium Pharmaceuticals, and Octapharma USA Inc.

Safety Update: COVID-19 Convalescent Plasma in 20,000 Hospitalized Patients.

OBJECTIVE: To provide an update on key safety metrics after transfusion of convalescent plasma in hospitalized coronavirus 2019 (COVID-19) patients, having previously demonstrated safety in 5000 hospitalized patients. PATIENTS AND METHODS: From April 3 to June 2, 2020, the US Food and Drug Administration Expanded Access Program for COVID-19 convalescent plasma transfused a convenience sample of 20,000 hospitalized patients with COVID-19 convalescent plasma. RESULTS: The incidence of all serious adverse events was low; these included transfusion reactions (n=78; <1%), thromboembolic or thrombotic events (n=113; <1%), and cardiac events (n=677, ~3%). Notably, the vast majority of the thromboembolic or thrombotic events (n=75) and cardiac events (n=597) were judged to be unrelated to the plasma transfusion per se. The 7-day mortality rate was 13.0% (12.5%, 13.4%), and was higher among more critically ill patients relative to less ill counterparts, including patients admitted to the intensive care unit versus those not admitted (15.6 vs 9.3%), mechanically ventilated versus not ventilated (18.3% vs 9.9%), and with septic shock or multiple organ dysfunction/failure versus those without dysfunction/failure (21.7% vs 11.5%). CONCLUSION: These updated data provide robust evidence that transfusion of convalescent plasma is safe in hospitalized patients with COVID-19, and support the notion that earlier administration of plasma within the clinical course of COVID-19 is more likely to reduce mortality.

Catheter ablation for atrial fibrillation in patients with obesity.

BACKGROUND: Obesity is a risk factor for atrial fibrillation and other cardiovascular conditions. Our objective was to determine whether catheter-based ablation effectively treated atrial fibrillation in obese patients. METHODS AND RESULTS: Five hundred twenty-three consecutive patients with symptomatic, medication-refractory atrial fibrillation underwent catheter ablation. Patients were grouped by body mass index (lean, < 25 kg/m(2); overweight, 25 to 29.9 kg/m(2); obese, > or = 30 kg/m(2)). Outcome and quality of life were measured with a general health survey (Medical Outcomes Study 36-item Short-Form General Health Survey [SF-36]); patients were assessed before ablation and at 3 and 12 months after the procedure. Two hundred twenty-eight study patients (44%) were overweight, and 201 (38%) were obese. Twelve months after curative ablation, 72% of patients were free of atrial fibrillation without the use of antiarrhythmic agents; 84% were arrhythmia free when those receiving medication were included. Atrial fibrillation was eliminated in 75%, 72%, and 70% of the lean, overweight, and obese patients, respectively, at 12 months (P=0.41, trend test). SF-36 scores were lower for patients with higher body mass index (P<0.05) at baseline. SF-36 scores improved in every functional domain for all body mass index groups after ablation. The mean SF-36 total physical score increased from 59+/-20 at baseline to 77+/-19 in 12 months (P<0.001). The total mental health score improved from 66+/-18 to 79+/-16 in 12 months (P<0.001). CONCLUSIONS: Catheter ablation of atrial fibrillation was effective in obese patients. Coexistence of atrial fibrillation and obesity indicated lower SF-36 scores, but the improvement in quality of life was consistent across all body mass index categories.

Long-term stability of endocardial left ventricular pacing leads placed via the coronary sinus.

BACKGROUND: Left ventricular endocardial pacing leads placed via the coronary sinus (CS) are increasingly implanted to achieve cardiac resynchronization therapy (CRT); however, the long-term stability of these leads is unknown. We sought to determine the implant success and long-term stability of CS leads in our single center experience. METHODS: All consecutive patients who underwent CRT via implantation of the CS lead between January 1999 and December 2005 were included. Pacing thresholds at implant and during long-term follow-up were reviewed and the rate of acute (within 24 hours of implant) and chronic (>24 hours) lead failure was determined. RESULTS: A total of 512 patients (mean age 68 +/- 12 years; 409 [80%] male) underwent CRT device implantation and were included. The CS lead implantation was successful on the initial implantation in 487 patients (95%) and subsequently successful in six patients (24%) in whom initial attempts were unsuccessful. Acute lead failure occurred in 25 patients (5.1%) and was most commonly due to persistent extra-cardiac stimulation. The rate of chronic lead failure was 4% in the first year and remained stable during long-term follow-up. The CS lead pacing thresholds remained stable with only minimal increase (1.42 +/- 0.85 V/0.42 +/- 0.25 ms vs 1.51 +/- 1.05 V/0.47 +/- 0.29 ms; P = 0.04). CONCLUSIONS: Placement of a left ventricular pacing lead via the CS is feasible and safe in the vast majority of patients. Once placed, the CS leads remain stable with excellent pacing thresholds over the longer term.