Cost-Effectiveness of Vericiguat in Patients With Heart Failure With Reduced Ejection Fraction: The VICTORIA Randomized Clinical Trial.

BACKGROUND: The VICTORIA trial (Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction) demonstrated that, in patients with high-risk heart failure, vericiguat reduced the primary composite outcome of cardiovascular death or heart failure hospitalization relative to placebo. The hazard ratio for all-cause mortality was 0.95 (95% CI, 0.84-1.07). In a prespecified analysis, treatment effects varied substantially as a function of baseline NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, with survival benefit for vericiguat in the lower NT-proBNP quartiles (hazard ratio, 0.82 [95% CI, 0.69-0.97]) and no benefit in the highest NT-proBNP quartile (hazard ratio, 1.14 [95% CI, 0.95-1.38]). An economic analysis was a major secondary objective of the VICTORIA research program. METHODS: Medical resource use data were collected for all VICTORIA patients (N=5050). Costs were estimated by applying externally derived US cost weights to resource use counts. Life expectancy was projected from patient-level empirical trial survival results with the use of age-based survival modeling methods. Quality-of-life adjustments were based on prospectively collected EQ-5D-based utilities. The primary outcome was the incremental cost-effectiveness ratio, comparing vericiguat with placebo, assessed from the US health care sector perspective over a lifetime horizon. Cost-effectiveness was estimated using the total VICTORIA cohort, both with and without interaction between treatment and baseline NT-proBNP. RESULTS: Life expectancy modeling results varied according to whether the observed heterogeneity of treatment effect by baseline NT-proBNP values was incorporated into the modeling. Including the interaction term, the vericiguat arm had an estimated quality-adjusted life expectancy of 4.56 quality-adjusted life-years (QALYs) compared with 4.13 QALYs for placebo (incremental discounted QALY, 0.43). Without the treatment heterogeneity/interaction term, vericiguat had 4.50 QALYs compared with 4.33 QALYs for placebo (incremental discounted QALY, 0.17). Incremental discounted costs (vericiguat minus placebo) were $28 546 with the treatment interaction and $20 948 without it. Corresponding incremental cost-effectiveness ratios were $66 509 per QALY allowing for treatment heterogeneity and $124 512 without heterogeneity. CONCLUSIONS: Vericiguat use in the VICTORIA trial met criteria for intermediate value, but the incremental cost-effectiveness ratio estimates were sensitive to whether the analysis accounted for observed NT-proBNP treatment effect heterogeneity. The cost-effectiveness of vericiguat was driven by the projected incremental life expectancy among patients in the lowest 3 quartiles of NT-proBNP. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02861534.

Sodium-glucose co-transporter-2 inhibitors are associated with kidney benefits at all degrees of albuminuria: A retrospective cohort study of adults with diabetes.

AIM: To estimate the real-world effectiveness of sodium-glucose co-transporter-2 inhibitors (SGLT2is) versus dipeptidyl peptidase-4 inhibitors (DPP4is) at reducing loss of kidney function and adverse kidney events in adults with varying levels of albuminuria. MATERIALS AND METHODS: In this retrospective cohort study using administrative data, we matched new SGLT2i users 1:2 to DPP4i users on diabetes therapy, chronic kidney disease (CKD) stage, albuminuria and time-conditional propensity score. Albuminuria was defined by spot urine albumin or equivalent as mild, moderate or severe. Linear regression was used to model the estimated glomerular filtration rate (eGFR), and Poisson regression for a composite kidney outcome (> 40% loss of eGFR, kidney replacement therapy or death from kidney causes) and all-cause mortality. RESULTS: SGLT2i users (n = 19 238, median age 57.9 years, female 40.9%) had mostly nil/mild albuminuria (70.7%). SGLT2is were associated with a 1.36 (95% CI 0.98-1.74) mL/min/1.73m2 (P < .001) acute (≤ 60 days) decline in eGFR, relative to DPP4is. Thereafter, SGLT2is were associated with 1.04 (95% CI 0.93-1.15) mL/min/1.73m2 (P < .001) less annual eGFR loss. SGLT2i users had fewer adverse kidney outcomes (incidence rate ratio [IRR] 0.58 [0.47-0.71]; P < .001), but not all-cause mortality (IRR 0.82 [0.66-1.01]; P = .06). Outcomes were similar considering only those with nil/mild albuminuria. CONCLUSIONS: SGLT2is may prevent eGFR decline and reduce the risk of adverse kidney events in adults with diabetes and nil or non-severe albuminuria.

Association between sodium-glucose cotransporter-2 inhibitors and arrhythmic outcomes in patients with diabetes and pre-existing atrial fibrillation.

AIMS: Prior studies suggest that sodium-glucose cotransporter-2 inhibitors (SGLT2is) may decrease the incidence of atrial fibrillation (AF). However, it is unknown whether SGLT2i can attenuate the disease course of AF among patients with pre-existing AF and Type II diabetes mellitus (DM). In this study, our objective was to examine the association between SGLT2i prescription and arrhythmic outcomes among patients with DM and pre-existing AF. METHODS AND RESULTS: We conducted a population-based cohort study of adults with DM and AF between 2014 and 2019. Using a prevalent new-user design, individuals prescribed SGLT2i were matched 1:1 to those prescribed dipeptidyl peptidase-4 inhibitors (DPP4is) based on time-conditional propensity scores. The primary endpoint was a composite of AF-related healthcare utilization (i.e. hospitalization, emergency department visits, electrical cardioversion, or catheter ablation). Secondary outcome measures included all-cause mortality, heart failure (HF) hospitalization, and ischaemic stroke or transient ischaemic attack (TIA). Cox proportional hazard models were used to examine the association of SGLT2i with the study endpoint. Among 2242 patients with DM and AF followed for an average of 3.0 years, the primary endpoint occurred in 8.7% (n = 97) of patients in the SGLT2i group vs. 10.0% (n = 112) of patients in the DPP4i group [adjusted hazard ratio 0.73 (95% confidence interval 0.55-0.96; P = 0.03)]. Sodium-glucose cotransporter-2 inhibitors were associated with significant reductions in all-cause mortality and HF hospitalization, but there was no difference in the risk of ischaemic stroke/TIA. CONCLUSION: Among patients with DM and pre-existing AF, SGLT2is are associated with decreased AF-related health resource utilization and improved arrhythmic outcomes compared with DPP4is.

Economic Analysis of AbClo, a Novel Abdominal Fascia Closure Device, for Patients With an Open Abdomen Following Trauma or Acute Abdominal Surgery.

BACKGROUND: Open Abdomen (OA) cases represent a significant surgical and resource challenge. AbClo is a novel non-invasive abdominal fascial closure device that engages lateral components of the abdominal wall muscles to support gradual approximation of the fascia and reduce the fascial gap. The study objective was to assess the economic implications of AbClo compared to negative pressure wound therapy (NPWT) alone on OA management. METHODS: We conducted a cost-minimization analysis using a decision tree comparing the use of the AbClo device to NPWT alone among patients with midline laparotomy for trauma or acute abdominal surgery who were ineligible for primary fascial closure. The time horizon was limited to the length of the inpatient hospital stay, and costs were considered from the perspective of the US Medicare payer. Clinical effectiveness data for AbClo was obtained from a randomized clinical trial. Cost data was obtained from the published literature. Probabilistic and deterministic sensitivity analyses were performed. The primary outcome was incremental cost. RESULTS: The mean cumulative costs per patient were $76 582 for those treated with NPWT alone and $70,582 for those in the group treated with the AbClo device. Compared to NPWT alone, AbClo was associated with lower incremental costs of -$6012 (95% CI -$19 449 to +$1996). The probability that AbClo was cost-savings compared to NPWT alone was 94%. CONCLUSIONS: The use of AbClo is an economically attractive strategy for management of OA in in patients with midline laparotomy for trauma or acute abdominal surgery who were ineligible for primary fascial closure.

Cost-Effectiveness of Coronary Artery Bypass Surgery Versus Medicine in Ischemic Cardiomyopathy: The STICH Randomized Clinical Trial.

BACKGROUND: The STICH Randomized Clinical Trial (Surgical Treatment for Ischemic Heart Failure) demonstrated that coronary artery bypass grafting (CABG) reduced all-cause mortality rates out to 10 years compared with medical therapy alone (MED) in patients with ischemic cardiomyopathy and reduced left ventricular function (ejection fraction ≤35%). We examined the economic implications of these results. METHODS: We used a decision-analytic patient-level simulation model to estimate the lifetime costs and benefits of CABG and MED using patient-level resource use and clinical data collected in the STICH trial. Patient-level costs were calculated by applying externally derived US cost weights to resource use counts during trial follow-up. A 3% discount rate was applied to both future costs and benefits. The primary outcome was the incremental cost-effectiveness ratio assessed from the US health care sector perspective. RESULTS: For the CABG arm, we estimated 6.53 quality-adjusted life-years (95% CI, 5.70-7.53) and a lifetime cost of $140 059 (95% CI, $106 401 to $180 992). For the MED arm, the corresponding estimates were 5.52 (95% CI, 5.06-6.09) quality-adjusted life-years and $74 894 lifetime cost (95% CI, $58 372 to $93 541). The incremental cost-effectiveness ratio for CABG compared with MED was $63 989 per quality-adjusted life-year gained. At a societal willingness-to-pay threshold of $100 000 per quality-adjusted life-year gained, CABG was found to be economically favorable compared with MED in 87% of microsimulations. CONCLUSIONS: In the STICH trial, in patients with ischemic cardiomyopathy and reduced left ventricular function, CABG was economically attractive relative to MED at current benchmarks for value in the United States. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT00023595.

Cost-Effectiveness of Catheter Ablation Versus Antiarrhythmic Drug Therapy in Atrial Fibrillation: The CABANA Randomized Clinical Trial.

BACKGROUND: In the CABANA trial (Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation), catheter ablation did not significantly reduce the primary end point of death, disabling stroke, serious bleeding, or cardiac arrest compared with drug therapy by intention-to-treat, but did improve the quality of life and freedom from atrial fibrillation recurrence. In the heart failure subgroup, ablation improved both survival and quality of life. Cost-effectiveness was a prespecified CABANA secondary end point. METHODS: Medical resource use data were collected for all CABANA patients (N=2204). Costs for hospital-based care were assigned using prospectively collected bills from US patients (n=1171); physician and medication costs were assigned using the Medicare Fee Schedule and National Average Drug Acquisition Costs, respectively. Extrapolated life expectancies were estimated using age-based survival models. Quality-of-life adjustments were based on EQ-5D-based utilities measured during the trial. The primary outcome was the incremental cost-effectiveness ratio, comparing ablation with drug therapy on the basis of intention-to-treat, and assessed from the US health care sector perspective. RESULTS: Costs in the first 3 months averaged $20 794±SD 1069 higher with ablation compared with drug therapy. The cumulative within-trial 5-year cost difference was $19 245 (95% CI, $11 360-$27 170) and the lifetime mean cost difference was $15 516 (95% CI, -$2963 to $35,512) higher with ablation than with drug therapy. The drug therapy arm accrued an average of 12.5 life-years (LYs) and 10.7 quality-adjusted life-years (QALYs). For the ablation arm, the corresponding estimates were 12.6 LYs and 11.0 QALYs. The incremental cost-effectiveness ratio was $57 893 per QALY gained, with 75% of bootstrap replications yielding an incremental cost-effectiveness ratio <$100 000 per QALY gained. With no quality-of-life/utility adjustments, the incremental cost-effectiveness ratio was $183 318 per LY gained. CONCLUSIONS: Catheter ablation of atrial fibrillation was economically attractive compared with drug therapy in the CABANA Trial overall at present benchmarks for health care value in the United States on the basis of projected incremental QALYs but not LYs alone.

2023 HRS/EHRA/APHRS/LAHRS Expert Consensus Statement on Practical Management of the Remote Device Clinic.

Remote monitoring is beneficial for the management of patients with cardiovascular implantable electronic devices by impacting morbidity and mortality. With increasing numbers of patients using remote monitoring, keeping up with higher volume of remote monitoring transmissions creates challenges for device clinic staff. This international multidisciplinary document is intended to guide cardiac electrophysiologists, allied professionals, and hospital administrators in managing remote monitoring clinics. This includes guidance for remote monitoring clinic staffing, appropriate clinic workflows, patient education, and alert management. This expert consensus statement also addresses other topics such as communication of transmission results, use of third-party resources, manufacturer responsibilities, and programming concerns. The goal is to provide evidence-based recommendations impacting all aspects of remote monitoring services. Gaps in current knowledge and guidance for future research directions are also identified.

Patient-Reported Outcome Measures in Cardiovascular Disease: An Evidence Map of the Psychometric Properties of Health Status Instruments.

BACKGROUND: Patient-reported outcomes (PROs) are important measures of treatment effect and can be used to inform the approval of cardiovascular drugs and devices by the U.S. Food and Drug Administration (FDA). PURPOSE: To catalogue the health status patient-reported outcome measures (PROMs) validated in cardiovascular diseases (CVDs), describe their psychometric properties, and assess adherence with both FDA recommendations and the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) framework. DATA SOURCES: MEDLINE, EMBASE, CINAHL, and Allied and Complementary Medicine Database from inception to August 2022. STUDY SELECTION: Studies that developed and/or validated health status PROMs in CVD populations. DATA EXTRACTION: Two study authors extracted data on CVD type, PROM psychometric properties, and adherence to FDA recommendations. The risk of bias informing the development or validation of PROMs was assessed using the COSMIN framework. DATA SYNTHESIS: Fifty health status PROMs (described in 83 studies) were identified, of which 45 were disease specific and 5 were generic. Eleven (22%) of the 50 PROMs validated in CVDs had minimally important differences (MIDs) established, and 8 (16%) reported on the validation of all psychometric properties recommended by the FDA. By COSMIN standards, only 2 PROMs (4%) had all of their psychometric properties rated as sufficient in quality, and 32 PROMs (64%) had less than 50% of psychometric properties rated as sufficient. LIMITATION: The quality of reporting varied across included studies. CONCLUSION: Of 50 PROMs validated in CVDs, only a small minority reported on the validation of all FDA-recommended psychometric properties, had psychometric properties rated as sufficient by COSMIN, or had MIDs established. Given the use of PROMs to guide FDA approvals of drugs and devices in CVDs, there is a need for better adherence to quality standards in PROM validation. PRIMARY FUNDING SOURCE: None.

Left Atrial Appendage Occlusion Versus Oral Anticoagulation in Atrial Fibrillation : A Decision Analysis.

BACKGROUND: Left atrial appendage occlusion (LAAO) is a potential alternative to oral anticoagulants in selected patients with atrial fibrillation (AF). Compared with anticoagulants, LAAO decreases major bleeding risk, but there is uncertainty regarding the risk for ischemic stroke compared with anticoagulation. OBJECTIVE: To determine the optimal strategy for stroke prevention conditional on a patient's individual risks for ischemic stroke and bleeding. DESIGN: Decision analysis with a Markov model. DATA SOURCES: Evidence from the published literature informed model inputs. TARGET POPULATION: Women and men with nonvalvular AF and without prior stroke. TIME HORIZON: Lifetime. PERSPECTIVE: Clinical. INTERVENTION: LAAO versus warfarin or direct oral anticoagulants (DOACs). OUTCOME MEASURES: The primary end point was clinical benefit measured in quality-adjusted life-years. RESULTS OF BASE-CASE ANALYSIS: The baseline risks for stroke and bleeding determined whether LAAO was preferred over anticoagulants in patients with AF. The combined risks favored LAAO for higher bleeding risk, but that benefit became less certain at higher stroke risks. For example, at a HAS-BLED score of 5, LAAO was favored in more than 80% of model simulations for CHA2DS2-VASc scores between 2 and 5. The probability of LAAO benefit in QALYs (>80%) at lower bleeding risks (HAS-BLED score of 0 to 1) was limited to patients with lower stroke risks (CHA2DS2-VASc score of 2). Because DOACs carry lower bleeding risks than warfarin, the net benefit of LAAO is less certain than that of DOACs. RESULTS OF SENSITIVITY ANALYSIS: Results were consistent using the ORBIT bleeding score instead of the HAS-BLED score, as well as alternative sources for LAAO clinical effectiveness data. LIMITATION: Clinical effectiveness data were drawn primarily from studies on the Watchman device. CONCLUSION: Although LAAO could be an alternative to anticoagulants for stroke prevention in patients with AF and high bleeding risk, the overall benefit from LAAO depends on the combination of stroke and bleeding risks in individual patients. These results suggest the need for a sufficiently low stroke risk for LAAO to be beneficial. The authors believe that these results could improve shared decision making when selecting patients for LAAO. PRIMARY FUNDING SOURCE: None.

Bimodal distribution of atrial fibrillation burden in 3 distinct cohorts: What is 'paroxysmal' atrial fibrillation?

BACKGROUND: Burden of atrial fibrillation (AF), as a continuous measure, is an emerging alternative classification often assumed to increase linearly with progression of disease. Yet there are no descriptions of AF burden distributions across populations. METHODS: We examined patterns of AF burden (% time in AF) across 3 different cohorts: outpatients with AF undergoing Holter monitoring in a national registry (ORBIT-AF II), routine outpatients undergoing Holter monitoring in a tertiary healthcare system (UHealth), and patients >= 65 years with cardiac implantable electronic devices (Merlin.netTM linked to Medicare). RESULTS: We included 2,058 ORBIT-AF II patients, 4,537 UHealth patients, and 39,710 from Merlin.net. Mean age ranged from 56 to 77 years, sex ranged from 40% to 61% male, and mean CHA2DS2-VASc scores ranged from 2.2 to 4.9. Across all cohorts, AF burden demonstrated skewed frequency towards the extremes, with the vast majority of patients having either very low or very high AF burden. This bimodal distribution was consistent across cohorts, across clinically-documented AF types (paroxysmal v persistent), patients with or without a known AF diagnosis, and among patients with different types of cardiac implantable electronic devices. CONCLUSIONS: Across 3 broad, diverse cohorts with continuous monitoring, distribution of AF burden was consistently skewed towards the extremes without an even, linear distribution or progression. As AF burden is increasingly recognized as a descriptor and potential risk-stratifier, these findings have important implications for future research and patient care.

Association between economic and arrhythmic burden of paroxysmal atrial fibrillation in patients with cardiac implanted electronic devices.

BACKGROUND: As the prevalence of atrial fibrillation (AF) increases, a greater understanding of the costs associated with AF care is required. While individuals with greater arrhythmic burden may interact with the health system more frequently, the relationship between AF burden and costs remains undefined. METHODS: In a longitudinal patient cohort with paroxysmal AF and newly implanted cardiovascular implantable electronic devices (CIED) (2010-2016), we linked CIED remote-monitoring data with Medicare claims to assess the association between the 30-day averaged device-detected daily percentage of time in AF ("AF burden") and healthcare costs. RESULTS: Among 39,345 patients, the mean age was 77.1 ± 8.7 years, 60.7% were male, and the mean CHA2DS2-VASc score was 4.9 ± 1.3. The mean total 1-year costs were $18,668 ± 29,173, driven by hospitalization costs where two-thirds of admissions were due to heart failure. Increasing AF burden was associated with increasing costs: $17,860 ± 28,525 for 0% daily AF burden; $18,840 ± 29,104 for 0-5% daily AF burden; and $20,968 ± 31,228 for 5-98% daily AF burden. There was a linear relationship between AF burden expressed as a continuous variable and 1-year costs (adjusted cost rate ratio 1.031 per 10% daily duration in AF, 95% confidence interval 1.023-1.038; P < .001). CONCLUSIONS: Among older patients with paroxysmal AF and CIEDs, increasing AF burden is associated with higher healthcare costs. As the observational study design is unable to determine causal relationships, prospective study is required to explore the intriguing hypothesis that targeted AF strategies, including comorbidity management, that reduce AF burden may also reduce the high annual costs associated with AF.

Postural orthostatic tachycardia syndrome is associated with significant employment and economic loss.

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a debilitating form of chronic orthostatic intolerance that primarily affects women and causes substantial impairment in quality of life and function. Yet, there is minimal literature describing the employment and economic consequences of POTS. We explored these aspects of the POTS patient experience through a self-reported study designed using community-based participatory research principles. METHODS AND RESULTS: A comprehensive questionnaire, including employment and economic consequences, was developed in partnership with Dysautonomia International, a patient advocacy organization. The POTS community engaged in all stages of the research design and analysis. Participants were recruited through Dysautonomia International's website and social media channels. The analysis included 5,556 adult (age ≥18 years) participants with a physician-confirmed diagnosis of POTS. The majority of participants were female (95%). Forty-eight per cent of participants reported employment during the three months prior to the survey, and of these participants, 66.8% would work greater hours if not for illness limitations. Over two-thirds (70.5%) of participants have lost income due to POTS symptoms, with 36.0% of the total cohort losing more than $10,000 USD in the 12 months prior to the survey. Almost all (95%) participants reported POTS-related out-of-pocket medical expenses since diagnosis, with 51.1% of participants spending $10,000 USD or more. CONCLUSIONS: This is the largest study reporting the employment and economic challenges experienced by individuals with POTS. Exposure of these challenges emphasizes the need for earlier diagnosis and improved therapeutic strategies to reduce the negative individual and societal consequences of this disorder.

Trends in health care resource use and expenditures in patients with newly diagnosed paroxysmal supraventricular tachycardia in the United States.

BACKGROUND: Few data are available on the temporal patterns of health resource utilization (HRU) and expenditures around paroxysmal supraventricular tachycardia (PSVT) diagnosis. This study assessed the longitudinal trends in HRU and expenditures in the 3 years preceding and subsequent to PSVT diagnosis. METHODS: Adult patients (age 18-65 years) with newly diagnosed PSVT were identified using administrative claims from the IBM MarketScan Research Database between January 1, 2008 and December 31, 2016 and propensity-score matched (1:1) with non-PSVT controls. RESULTS: Among the 12,305 PSVT patients compared with matched controls, PSVT was associated with statistically significant higher annual rates of emergency department visits, physician office visits, inpatient hospitalizations, and diagnostic testing. HRU increased in the years preceding PSVT diagnosis, reaching its peak in the year following PSVT diagnosis. Over the 6-year follow-up period, PSVT was associated with higher mean annual per patient expenditures ($12,665) compared to matched controls ($6,004; P < .001). Upon diagnosis of PSVT, the mean expenditures per PSVT patient doubled from $11,714 in the year immediately preceding index diagnosis to $23,335 in the first postdiagnosis year. Inpatient services, diagnostic testing, and ablation procedures were the principle drivers of higher mean expenditures in the first year post-PSVT diagnosis versus the year prior to PSVT diagnosis. CONCLUSIONS: PSVT presents a substantial economic burden to health care systems. The annual expenditure per PSVT patient is within the range previously reported for atrial fibrillation. The increased HRU and expenditures in the year following diagnosis, which do not return to baseline, suggest a potential gap in non-interventional, long-term PSVT management.

Economic evaluation of an absorbable antibiotic envelope for prevention of cardiac implantable electronic device infection.

AIMS: Recent evidence suggests that an antibiotic impregnated envelope inserted at time of cardiac implantable electronic device (CIED) implantation may reduce risk of subsequent CIED infection compared with standard of care (SoC). The objective of the current work was to perform a cost-effectiveness analysis comparing an antibiotic impregnated envelope with SoC at time of CIED insertion. METHODS AND RESULTS: Decision analytic models were used to project healthcare costs and benefits of two strategies, an antibiotic impregnated envelope plus SoC (Env+SoC) vs. SoC alone, in a cohort of patients undergoing CIED implantation over a 1-year time horizon. Evidence from published literature informed the model inputs. Probabilistic and deterministic sensitivity analyses were performed. The primary outcome was the incremental cost per infection prevented, assessed from the Canadian healthcare system perspective. Envelope plus SoC was associated with fewer CIED infection (7 CIED infections/1000 patients) at higher total costs ($29 033 000/1000 patients) compared with SoC (11 CIED infections and $27 926 000/1000 patients). The incremental cost per infection prevented over 1 year was $274 416. Use of Env+SoC was cost saving only when baseline CIED infection risk was increased to 6% (vs. base case of 1.2%). CONCLUSIONS: A strategy of Env+SoC was not economically favourable compared with SoC alone, and the opportunity cost of widescale implementation should be considered. Future work is required to develop validated risk stratification tools to identify patients at greatest risk of CIED infection. The value proposition of Env+SoC improves when applying this intervention to patients at greatest infection risk.

Predictors of appropriate shock after generator replacement in patients with an implantable cardioverter defibrillator.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) are indicated for the primary prevention of sudden cardiac death in patients with reduced left ventricular ejection fraction (LVEF). The ongoing risk/benefit profile of an ICD at generator replacement is unknown. This study aimed to identify predictors of appropriate ICD shocks and therapies after first ICD generator replacement, and its procedure-related complications. METHODS: We conducted a multicenter, retrospective cohort study including patients with primary prevention ICDs who underwent generator replacement between April 2005 and July 2015 at three Canadian centers. The primary and secondary outcomes were appropriate ICD shock and any appropriate ICD therapy, respectively. Procedure-related complication rates were also reported. RESULTS: Of the 219 patients in the cohort, 61 (28%) experienced an appropriate shock while 40 (18%) experienced appropriate antitachycardia pacing over a median follow up of 2.2 years. Independent predictors of appropriate ICD shocks included: LVEF at time of replacement (adjusted odds ratio [OR] 0.4 per 10% increase in LVEF, P < .001), a history of appropriate ICD shocks prior to replacement (OR 4.9, P < .001), and a history of inappropriate ICD shocks (OR 4.2, 95%, P < .002). Similar predictors were identified for the secondary outcome of any appropriate ICD therapy. Device-related complications were reported in 25 (11%) patients, with 1 (0.5%) resulting in death, 14 (6.3%) requiring site re-operation, and 6 (2.7%) requiring cardiac surgical management. CONCLUSION: Not all primary prevention ICD patients undergoing generator replacement will require appropriate device therapies afterwards. Generator replacement is associated with several risks that should be weighed against its anticipated benefit. A comprehensive assessment of the risk-benefit profile of patients undergoing generator replacement is warranted.

Effect of Implantable vs Prolonged External Electrocardiographic Monitoring on Atrial Fibrillation Detection in Patients With Ischemic Stroke: The PER DIEM Randomized Clinical Trial.

Importance: The relative rates of detection of atrial fibrillation (AF) or atrial flutter from evaluating patients with prolonged electrocardiographic monitoring with an external loop recorder or implantable loop recorder after an ischemic stroke are unknown. Objective: To determine, in patients with a recent ischemic stroke, whether 12 months of implantable loop recorder monitoring detects more occurrences of AF compared with conventional external loop recorder monitoring for 30 days. Design, Setting, and Participants: Investigator-initiated, open-label, randomized clinical trial conducted at 2 university hospitals and 1 community hospital in Alberta, Canada, including 300 patients within 6 months of ischemic stroke and without known AF from May 2015 through November 2017; final follow-up was in December 2018. Interventions: Participants were randomly assigned 1:1 to prolonged electrocardiographic monitoring with either an implantable loop recorder (n = 150) or an external loop recorder (n = 150) with follow-up visits at 30 days, 6 months, and 12 months. Main Outcomes and Measures: The primary outcome was the development of definite AF or highly probable AF (adjudicated new AF lasting ≥2 minutes within 12 months of randomization). There were 8 prespecified secondary outcomes including time to event analysis of new AF, recurrent ischemic stroke, intracerebral hemorrhage, death, and device-related serious adverse events within 12 months. Results: Among the 300 patients who were randomized (median age, 64.1 years [interquartile range, 56.1 to 73.7 years]; 121 were women [40.3%]; and 66.3% had a stroke of undetermined etiology with a median CHA2DS2-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, sex category] score of 4 [interquartile range, 3 to 5]), 273 (91.0%) completed cardiac monitoring lasting 24 hours or longer and 259 (86.3%) completed both the assigned monitoring and 12-month follow-up visit. The primary outcome was observed in 15.3% (23/150) of patients in the implantable loop recorder group and 4.7% (7/150) of patients in the external loop recorder group (between-group difference, 10.7% [95% CI, 4.0% to 17.3%]; risk ratio, 3.29 [95% CI, 1.45 to 7.42]; P = .003). Of the 8 specified secondary outcomes, 6 were not significantly different. There were 5 patients (3.3%) in the implantable loop recorder group who had recurrent ischemic stroke vs 8 patients (5.3%) in the external loop recorder group (between-group difference, -2.0% [95% CI, -6.6% to 2.6%]), 1 (0.7%) vs 1 (0.7%), respectively, who had intracerebral hemorrhage (between-group difference, 0% [95% CI, -1.8% to 1.8%]), 3 (2.0%) vs 3 (2.0%) who died (between-group difference, 0% [95% CI, -3.2% to 3.2%]), and 1 (0.7%) vs 0 (0%) who had device-related serious adverse events. Conclusions and Relevance: Among patients with ischemic stroke and no prior evidence of AF, implantable electrocardiographic monitoring for 12 months, compared with prolonged external monitoring for 30 days, resulted in a significantly greater proportion of patients with AF detected over 12 months. Further research is needed to compare clinical outcomes associated with these monitoring strategies and relative cost-effectiveness. Trial Registration: ClinicalTrials.gov Identifier: NCT02428140.

Cost-Effectiveness of Extended Electrocardiogram Monitoring for Atrial Fibrillation After Stroke: A Systematic Review.

BACKGROUND AND PURPOSE: Management of cryptogenic stroke involves the identification of modifiable risk factors, such as atrial fibrillation (AF). Extended rhythm monitoring increases AF detection rates but at an increased device cost compared with conventional Holter monitoring. The objective of the study was to identify and synthesize the existing literature on the cost-effectiveness of prolonged rhythm monitoring devices for AF detection in cryptogenic stroke. METHODS: We conducted a systematic review of available economic evaluations of prolonged ECG monitoring for AF detection following cryptogenic stroke compared with standard care. RESULTS: Of the 530 unique citations, 8 studies assessed the cost-utility of prolonged ECG monitoring compared with standard care following cryptogenic stroke. The prolonged ECG monitoring strategies included 7-day ambulatory monitoring, 30-day external loop recorders or intermittent ECG monitoring, and implantable loop recorders. The majority of cost-utility analyses reported incremental cost-effectiveness ratios below $50 000 per QALY gained; and two studies reported a cost-savings. CONCLUSIONS: There is limited economic literature on the cost-effectiveness of extended ECG monitoring devices for detection of atrial fibrillation in cryptogenic stroke. In patients with cryptogenic stroke, extended ECG monitoring for AF detection may be economically attractive when traditional willingness-to-pay thresholds are adopted. However, there was substantial variation in the reported ICERs. The direct comparison of cost-effectiveness across technologies is limited by heterogeneity in modeling assumptions.

Left ventricular ejection fraction reassessment post-myocardial infarction: Current clinical practice and determinants of adverse remodeling.

BACKGROUND: Left ventricular (LV) dysfunction may be sustained or aggravated during the convalescent months following an acute myocardial infarction (MI) and is difficult to predict. We sought to determine current practice patterns of LV ejection fraction (LVEF) reassessment during the months following MI and evaluate the predictors and clinical significance of LVEF change in a prospective post-MI patient cohort. METHODS: Patients with an acute MI between June 2010 and August 2014 were identified using the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease registry. Patients with initial LV dysfunction (LVEF <40% with first MI or <45% with multiple MI events) underwent a protocol-driven repeat LVEF assessment in follow-up if routine LVEF reassessment was not performed. RESULTS: Of 5,964 MI patients, follow-up LVEF assessments were attained for 442 of the 695 patients who had significant LV dysfunction. A sizable proportion (25%) had either no increase or a decline in LVEF. Adverse remodeling was associated with an anterior MI location, a greater peak serum troponin T, and a higher baseline LVEF at time of MI. Adverse LV remodeling conferred a 3-fold risk of death (hazard ratio 3.0, 95% CI 1.6-5.7, P=.001) adjusted for baseline LVEF, anterior MI location, and medication use. CONCLUSIONS: Current practice of LVEF reassessment during the convalescent months post-MI is suboptimal despite a sizeable proportion of patients that undergo adverse LV remodeling. Targeting processes affecting low rates of LVEF reassessment may reduce missed care opportunities and ensure that patients consistently receive appropriate evidence-based and guideline-recommended care.