Cost Effectiveness of an Electrocardiographic Deep Learning Algorithm to Detect Asymptomatic Left Ventricular Dysfunction.

OBJECTIVE: To evaluate the cost-effectiveness of an artificial intelligence electrocardiogram (AI-ECG) algorithm under various clinical and cost scenarios when used for universal screening at age 65. PATIENTS AND METHODS: We used decision analytic modeling to perform a cost-effectiveness analysis of the use of AI-ECG to screen for asymptomatic left ventricular dysfunction (ALVD) once at age 65 compared with no screening. This screening consisted of an initial screening decision tree and subsequent construction of a Markov model. One-way sensitivity analysis on various disease and cost parameters to evaluate cost-effectiveness at both $50,000 per quality-adjusted life year (QALY) and $100,000 per QALY willingness-to-pay threshold. RESULTS: We found that for universal screening at age 65, the novel AI-ECG algorithm would cost $43,351 per QALY gained, test performance, disease characteristics, and testing cost parameters significantly affect cost-effectiveness, and screening at ages 55 and 75 would cost $48,649 and $52,072 per QALY gained, respectively. Overall, under most of the clinical scenarios modeled, coupled with its robust test performance in both testing and validation cohorts, screening with the novel AI-ECG algorithm appears to be cost-effective at a willingness-to-pay threshold of $50,000. CONCLUSION: Universal screening for ALVD with the novel AI-ECG appears to be cost-effective under most clinical scenarios with a cost of <$50,000 per QALY. Cost-effectiveness is particularly sensitive to both the probability of disease progression and the cost of screening and downstream testing. To improve cost-effectiveness modeling, further study of the natural progression and treatment of ALVD and external validation of AI-ECG should be undertaken.

Implications of Left Ventricular Dysfunction at Presentation for Infants with Coarctation of the Aorta.

Infants with aortic coarctation may present with left ventricular (LV) dysfunction which may complicate the postoperative course and lead to increased healthcare costs. We aimed to define the prevalence of moderate to severe left ventricular (LV) systolic dysfunction, evaluate time to recovery, and compare health care costs. Single-center retrospective cohort study at a tertiary care hospital was conducted. Infants < 6 months old at diagnosis with aortic coarctation were identified using surgical codes for coarctation repair between January 2010 and May 2018. Moderate to severe dysfunction was defined as ejection fraction (EF) < 40%. Of 160 infants studied, 18 (11%) had moderate to severe LV dysfunction at presentation. Compared to those with better LV function, infants with moderate to severe LV dysfunction were older at presentation (12 vs. 6 days, p = 0.004), had more postoperative cardiac intensive care unit (ICU) days (5 vs. 3, p < 0.001), and more ventilator days (3.5 vs. 1, p < 0.001). The median time to normal LV EF (≥ 55%) was 6 days postoperatively (range 1-230 days). Infants presenting with moderate to severe LV dysfunction had higher index hospitalization costs ($90,560 vs. $59,968, p = 0.02), but no difference in cost of medical follow-up for the first year following discharge ($3,078 vs. $2,568, p = 0.46). In the current era, > 10% of infants with coarctation present with moderate to severe LV dysfunction that typically recovers. Those with moderate to severe dysfunction had longer duration of mechanical ventilation and postoperative cardiac ICU stays, likely driving higher costs of index hospitalization.

Levosimendan in patients with reduced left ventricular function undergoing isolated coronary or valve surgery.

OBJECTIVE: In the Levosimendan in Patients with Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass (LEVO-CTS) trial, no differences in clinical outcomes were observed between levosimendan and placebo in a broad population of patients undergoing cardiac surgery. In previous studies, the benefits of levosimendan were most clearly evident in patients undergoing isolated coronary artery bypass grafting (CABG) surgery. In a prespecified analysis of LEVO-CTS, we compared treatment-related outcomes and costs across types of cardiac surgical procedures. METHODS: Overall, 563 (66.4%) patients underwent isolated CABG, 97 (11.4%) isolated valve, and 188 (22.2%) combined CABG/valve surgery. Outcomes included the co-primary 4-component composite (30-day mortality, 30-day renal replacement, 5-day myocardial infarction, or 5-day mechanical circulatory support), the 2-component composite (30-day mortality or 5-day mechanical circulatory support), 90-day mortality, low cardiac output syndrome (LCOS), and 30-day medical costs. RESULTS: The 4- and 2-component outcomes were not significantly different with levosimendan and placebo in patients undergoing CABG (15.2% vs 19.3% and 7.8% vs 10.4%), valve (49.0% vs 33.3% and 22.4% vs 2.1%), or combined procedures (39.6% vs 35.9% and 24.0% vs 19.6%). Ninety-day mortality was lower with levosimendan in isolated CABG (2.1% vs 7.9%; hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.11-0.64), but not significantly different in valve (8.3% vs 2.0%; HR, 4.10; 95% CI, 0.46-36.72) or combined procedures (10.4% vs 7.6%; HR, 1.39; 95% CI, 0.53-3.64; interaction P = .011). LCOS (12.0% vs 22.1%; odds ratio, 0.48; 95% CI, 0.30-0.76; interaction P = .118) was significantly lower in levosimendan-treated patients undergoing isolated CABG. Excluding study drug costs, median and mean 30-day costs were $53,707 and $65,852 for levosimendan and $54,636 and $67,122 for placebo, with a 30-day mean difference (levosimendan - placebo) of -$1270 (bootstrap 95% CI, -$8722 to $6165). CONCLUSIONS: Levosimendan was associated with lower 90-day mortality and LCOS in patients undergoing isolated CABG, but not in those undergoing isolated valve or combined CABG/valve procedures.

In-hospital left ventricular thrombus following ST-elevation myocardial infarction.

BACKGROUND: In-hospital left ventricular (LV) thrombus following acute ST-elevation myocardial infarction (STEMI) has not been evaluated on a national scale and was the focus of this investigation. METHODS: We used the 2003 to 2013 Nationwide Inpatient Sample database to identify adults ≥18 years old with a principal diagnosis code of ST-elevation myocardial infarction. Patients were divided into two groups defined by the presence or absence of LV thrombus. Clinical characteristics and in-hospital outcomes were studied using relevant statistics. Multiple linear and logistic regression models were conducted to identify factors associated with LV thrombus. RESULTS: Of 1,035,888 STEMI patients hospitalized in the U. S from 2003 to 2013, 1982 (0.2%) developed acute in-hospital LV thrombus. Compared to no LV thrombus, patients with LV thrombus were more likely to have in-hospital complications; acute ischemic and hemorrhagic stroke, acute renal failure, gastrointestinal bleed, cardiogenic shock, in-hospital cardiac arrest and mortality. They also had longer mean length of stay and higher hospital charges. Factors associated with LV thrombus included: anterior/anterolateral STEMI, acute or chronic heart failure with reduced ejection fraction, atrial fibrillation, LV aneurysm, Left heart valvular disease, acute or chronic deep venous thrombosis/pulmonary embolism and alcohol abuse. Patients with LV thrombus were less likely to be female [AOR 0.66, 95% CI (0.51-0.84)]. CONCLUSION: The identification of factors associated with early development of LV thrombus following STEMI, will help direct resources for specific high-risk group and prompt cost-effective therapies. Gender variability in LV thrombus development warrants further investigations.

Examining the cost-effectiveness of baseline left ventricular function assessment among breast cancer patients undergoing anthracycline-based therapy.

BACKGROUND: There is a lack of consensus to guide which breast cancer patients require left ventricular function assessment (LVEF) prior to anthracycline therapy; the cost-effectiveness of screening this patient population has not been previously evaluated. METHODS: We performed a retrospective analysis of the Yale Nuclear Cardiology Database, including 702 patients with baseline equilibrium radionuclide angiography (ERNA) scan prior to anthracycline and/or trastuzumab therapy. We sought to examine associations between abnormal baseline LVEF and potential cardiac risk factors. Additionally, we designed a Markov model to determine the incremental cost-effectiveness ratio (ICER) of ERNA screening for women aged 55 with stage I-III breast cancer from a payer perspective over a lifetime horizon. RESULTS: An abnormal LVEF was observed in 2% (n = 14) of patients. There were no significant associations on multivariate analysis performed on self-reported risk factors. Our analysis showed LVEF screening is cost-effective with ICER of $45,473 per QALY gained. For a willingness-to-pay threshold of $100,000/ QALY, LVEF screening had an 81.9% probability of being cost-effective. Under the same threshold, screening was cost-effective for non-anthracycline cardiotoxicity risk of RR ≤ 0.58, as compared to anthracycline regimens. CONCLUSIONS: Age, preexisting cardiac risk factors and coronary artery disease did not predict a baseline abnormal LVEF. While the prevalence of an abnormal baseline LVEF is low in patients with breast cancer, our results suggest that cardiac screening prior to anthracycline is cost-effective.

Cost-effectiveness of a risk-stratified approach to cardiac resynchronisation therapy defibrillators (high versus low) at the time of generator change.

OBJECTIVE: Responders to cardiac resynchronisation therapy whose device has a defibrillator component and who do not receive a therapy in the lifetime of the first generator have a very low incidence of appropriate therapy after box change. We investigated the cost implications of using a risk stratification tool at the time of generator change resulting in these patients being reimplanted with a resynchronisation pacemaker. METHODS: A decision tree was created using previously published data which had demonstrated an annualised appropriate defibrillator therapy risk of 2.33%. Costs were calculated at National Health Service (NHS) national tariff rates (2016-2017). EQ-5D utility values were applied to device reimplantations, admissions and mortality data, which were then used to estimate quality-adjusted life-years (QALYs) over 5 years. RESULTS: At 5 years, the incremental cost of replacing a resynchronisation defibrillator device with a second resynchronisation defibrillator versus resynchronisation pacemaker was £5045 per patient. Incremental QALY gained was 0.0165 (defibrillator vs pacemaker), resulting in an incremental cost-effectiveness ratio (ICER) of £305 712 per QALYs gained. Probabilistic sensitivity analysis resulted in an ICER of £313 612 (defibrillator vs pacemaker). For reimplantation of all patients with a defibrillator rather than a pacemaker to yield an ICER of less than £30 000 per QALY gained (current NHS cut-off for approval of treatment), the annual arrhythmic event rate would need to be 9.3%. The budget impact of selective replacement was a saving of £2 133 985 per year. CONCLUSIONS: Implanting low-risk patients with a resynchronisation defibrillator with the same device at the time of generator change is not cost-effective by current NHS criteria. Further research is required to understand the impact of these findings on individual patients at the time of generator change.

Air Pollution, Cardiovascular Outcomes, and Social Disadvantage: The Multi-ethnic Study of Atherosclerosis.

BACKGROUND: Social factors may enhance health effects of air pollution, yet empirical support is inconsistent. The interaction of social and environmental factors may only be evident with long-term exposures and outcomes that reflect long-term disease development. METHODS: We used cardiac magnetic resonance imaging data from the Multi-Ethnic Study of Atherosclerosis to assess left-ventricular mass index (LVMI) and left-ventricular ejection fraction (LVEF). We assigned residential concentrations of fine particulate matter (PM2.5), oxides of nitrogen, and nitrogen dioxide in the year 2000 to each participant in 2000 using prediction models. We examined modifying roles of four measures of adversity: race/ethnicity, racial/ethnic residential segregation, and socioeconomic status and psychosocial adversity as composite indices on the association between air pollution and LVMI or LVEF. RESULTS: Compared with whites, blacks showed a stronger adjusted association between air pollution and LVMI. For example, for each 5 µg/m greater PM2.5 level, whites showed a 1.0 g/m greater LVMI (95% confidence interval = -1.3, 3.1), while blacks showed an additional 4.0 g/m greater LVMI (95% confidence interval = 0.3, 8.2). Results were similar for oxides of nitrogen and nitrogen dioxide with regard to black race and LVMI. However, we found no evidence of a modifying role of other social factors or ethnic groups. Furthermore, we found no evidence of a modifying role for any social factors or racial/ethnic groups on the association between air pollution and LVEF. CONCLUSIONS: Our results suggest that racial group membership may modify the association between air pollution and cardiovascular disease.

Cost-effectiveness of natriuretic peptide-based screening and collaborative care: a report from the STOP-HF (St Vincent's Screening TO Prevent Heart Failure) study.

AIMS: Prevention of cardiovascular disease and heart failure (HF) in a cost-effective manner is a public health goal. This work aims to assess the cost-effectiveness of the St Vincent's Screening TO Prevent Heart Failure (STOP-HF) intervention. METHODS AND RESULTS: This is a substudy of 1054 participants with cardiovascular risk factors [median age 65.8 years, interquartile range (IQR) 57.8:72.4, with 4.3 years, IQR 3.4:5.2, follow-up]. Annual natriuretic peptide-based screening was performed, with collaborative cardiovascular care between specialist physicians and general practitioners provided to patients with BNP levels >50 pg/mL. Analysis of cost per case prevented and cost-effectiveness per quality-adjusted life year (QALY) gained was performed. The primary clinical endpoint of LV dysfunction (LVD) with or without HF was reduced in intervention patients [odds ratio (OR) 0.60; 95% confidence interval (CI) 0.38-0.94; P = 0.026]. There were 157 deaths and/or emergency hospitalizations for major adverse cardiac events (MACE) in the control group vs. 102 in the intervention group (OR 0.68; 95% CI 0.49-0.93; P = 0.01). The cost per case of LVD/HF prevented was €9683 (sensitivity range -€843 to €20 210), whereas the cost per MACE prevented was €3471 (sensitivity range -€302 to €7245). Cardiovascular hospitalization savings offset increased outpatient and primary care costs. The cost per QALY gain was €1104 and the intervention has an 88% probability of being cost-effective at a willingness to pay threshold of €30 000. CONCLUSION: Among patients with cardiovascular risk factors, natriuretic peptide-based screening and collaborative care reduced LVD, HF, and MACE, and has a high probability of being cost-effective. TRIAL REGISTRATION: NCT00921960.

Routine echocardiography screening for asymptomatic left ventricular dysfunction in childhood cancer survivors: a model-based estimation of the clinical and economic effects.

BACKGROUND: Childhood cancer survivors treated with cardiotoxic therapies are recommended to have routine cardiac assessment every 1 to 5 years, but the long-term benefits are uncertain. OBJECTIVE: To estimate the cost-effectiveness of routine cardiac assessment to detect asymptomatic left ventricular dysfunction and of angiotensin-converting enzyme inhibitor and ß-blocker treatment to reduce congestive heart failure (CHF) incidence in childhood cancer survivors. DESIGN: Simulation model. DATA SOURCES: Literature, including data from the Childhood Cancer Survivor Study. TARGET POPULATION: Childhood cancer survivors. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: Interval-based echocardiography assessment every 1, 2, 5, or 10 years, with subsequent angiotensin-converting enzyme inhibitor or ß-blocker treatment for patients with positive test results. OUTCOME MEASURES: Lifetime risk for systolic CHF, lifetime costs, quality-adjusted life expectancy, and incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE ANALYSIS: The lifetime risk for systolic CHF among 5-year childhood cancer survivors aged 15 years was 18.8% without routine cardiac assessment (average age at onset, 58.8 years). Routine echocardiography reduced lifetime risk for CHF by 2.3% (with assessment every 10 years) to 8.7% (annual assessment). The ICER for assessment every 10 years was $111 600 per quality-adjusted life-year (QALY) compared with no assessment. Assessment every 5 years had an ICER of $117 900 per QALY, and ICERs for more frequent assessment exceeded $165 000 per QALY. RESULTS OF SENSITIVITY ANALYSIS: Results were sensitive to treatment effectiveness, absolute excess risk for CHF, and asymptomatic left ventricular dysfunction asymptomatic period. The probability that assessment every 10 or 5 years was preferred at a $100 000-per-QALY threshold was 0.33 for the overall cohort. LIMITATION: Treatment effectiveness was based on adult data. CONCLUSION: Current recommendations for cardiac assessment may reduce CHF incidence, but less frequent assessment may be preferable.

Cost-effectiveness of the children's oncology group long-term follow-up screening guidelines for childhood cancer survivors at risk for treatment-related heart failure.

BACKGROUND: Childhood cancer survivors treated with anthracyclines are at high risk for asymptomatic left ventricular dysfunction (ALVD), subsequent heart failure, and death. The consensus-based Children's Oncology Group (COG) Long-Term Follow-up Guidelines recommend lifetime echocardiographic screening for ALVD. OBJECTIVE: To evaluate the efficacy and cost-effectiveness of the COG guidelines and to identify more cost-effective screening strategies. DESIGN: Simulation of life histories using Markov health states. DATA SOURCES: Childhood Cancer Survivor Study; published literature. TARGET POPULATION: Childhood cancer survivors. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: Echocardiographic screening followed by angiotensin-converting enzyme (ACE) inhibitor and ß-blocker therapies after ALVD diagnosis. OUTCOME MEASURES: Quality-adjusted life-years (QALYs), costs, incremental cost-effectiveness ratios (ICERs) in dollars per QALY, and cumulative incidence of heart failure. RESULTS OF BASE-CASE ANALYSIS: The COG guidelines versus no screening have an ICER of $61 500, extend life expectancy by 6 months and QALYs by 1.6 months, and reduce the cumulative incidence of heart failure by 18% at 30 years after cancer diagnosis. However, less frequent screenings are more cost-effective than the guidelines and maintain 80% of the health benefits. RESULTS OF SENSITIVITY ANALYSIS: The ICER was most sensitive to the magnitude of ALVD treatment efficacy; higher treatment efficacy resulted in lower ICER. LIMITATION: Lifetime non-heart failure mortality and the cumulative incidence of heart failure more than 20 years after diagnosis were extrapolated; the efficacy of ACE inhibitor and ß-blocker therapy in childhood cancer survivors with ALVD is undetermined (or unknown). CONCLUSION: The COG guidelines could reduce the risk for heart failure in survivors at less than $100 000/QALY. Less frequent screening achieves most of the benefits and would be more cost-effective than the COG guidelines.

The cost-effectiveness of primary prophylactic implantable defibrillator therapy in patients with ischaemic or non-ischaemic heart disease: a European analysis.

AIMS: It remains unclear whether primary prophylactic implantable cardioverter-defibrillator (ICD) therapy is cost-effective compared with a 'no ICD strategy' in the European health care setting. We performed a cost-effectiveness analysis for a cohort of patients with a left ventricular ejection fraction <40% and ischaemic or non-ischaemic heart disease. METHODS AND RESULTS: A Markov decision analytic model was used to evaluate long-term survival, quality-adjusted life years (QALYs), and lifetime costs for a cohort of patients with a reduced left ventricular function without previous arrhythmias, managed with a prophylactic ICD. Input data on effectiveness were derived from a meta-analysis of primary prophylactic ICD-only therapy randomized trials, from a prospective cohort study of ICD patients, from a health care utilization survey, and from the literature. Input data on costs were derived from a micro-cost analysis. Data on quality-of-life were derived from the literature. Deterministic and probabilistic sensitivity analysis was performed to assess the uncertainty. Probabilistic sensitivity analysis demonstrated a mean lifetime cost of €50 685 ± €4604 and 6.26 ± 0.64 QALYs for patients in the 'no ICD strategy'. Patients in the 'ICD strategy' accumulated €86 759 ± €3343 and an effectiveness of 7.08 ± 0.71 QALYs yielding an incremental cost-effectiveness ratio of €43 993/QALY gained compared with the 'no ICD strategy'. The probability that ICD therapy is cost-effective was 65% at a willingness-to-pay threshold of €80 000/QALY. CONCLUSION: Our results suggest that primary prophylactic ICD therapy in patients with a left ventricular ejection fraction <40% and ischaemic or non-ischaemic heart disease is cost-effective in the European setting.

Cost-effectiveness of cardiac resynchronization therapy in patients with asymptomatic to mild heart failure: insights from the European cohort of the REVERSE (Resynchronization Reverses remodeling in Systolic Left Ventricular Dysfunction).

AIMS: To assess the cost-effectiveness of cardiac resynchronization therapy (CRT) compared with optimal medical therapy in patients with New York Heart Association (NYHA) II heart failure (HF) or NYHA I with previous HF symptoms. METHODS AND RESULTS: A proportion in state model with Monte Carlo simulation was developed to assess the costs, life years and quality-adjusted life year (QALYs) associated with CRT-ON and -OFF over a 10 year time period. Data from 262 patients in the European cohort of the REVERSE clinical trial (QRS ≥ 120 ms, left ventricular ejection fraction ≤ 40%, CRT-ON, n = 180, CRT-OFF, n = 82) were used to model all-cause mortality, change in NYHA class and resource use. EQ-5D preference weights were taken from a previous cost-effectiveness model of CRT and unit costs from national UK databases. Costs and benefits were discounted at 3.5% p.a. Extensive deterministic and probabilistic sensitivity analyses were performed. Compared with CRT-OFF, 0.94 life years or 0.80 QALYs were gained in the CRT ON group at an additional cost of €11 455, yielding an incremental cost-effectiveness ratio of €14.278 per quality-adjusted life year (QALY) gained. At a threshold of €33 000 (£30 000) per QALY gained, the probability that CRT is cost-effective is 79.6%. Cardiac resynchronization therapy becomes cost effective after ∼4.5 years. Cardiac resynchronization therapy needs only to demonstrate a modest impact on all cause mortality (hazard ratio = 0.82) in order to demonstrate cost-effectiveness. The results are robust to changes in all other parameters. CONCLUSION: Cardiac resynchronization therapy is a cost-effective intervention for patients with mildly symptomatic HF and for asymptomatic patients with left ventricular dysfunction and previous HF symptoms.

When do new biomarkers make economic sense?

Cost-effectiveness and cost-utility studies are commonly used to make payment decisions for new drugs and expensive interventions. Such studies are relatively rare for evaluating the cost-utility of clinical laboratory tests. As medical costs continue to increase in the setting of decreased resources it is likely that new biomarkers may increasingly be examined with respect to their economic benefits in addition to clinical utility. This will represent an additional hurdle for routine use of new biomarkers. Before reaching the final economic hurdle new biomarkers will still need to demonstrate clinical usefulness. Thus a new biomarker will never make economic sense if it is not clinically useful. Once diagnostic accuracy and potential clinical usefulness is established there are several types of economic studies that new biomarkers may undergo. The most common of these are cost-utility studies which estimate the ratio between the cost of an intervention or test and the benefit it produces in the number of years gained in full health. The quantity used most often to describe this is amount of money per quality adjusted life year (QALY) gained. The threshold for being considered cost-effective is generally USD 50,000 per QALY gained. Examples of biomarkers that have been subjected to economic analyses will be provided.

Proportion of patients needing an implantable cardioverter defibrillator on the basis of current guidelines: impact on healthcare resources in Italy and the USA. Data from the ALPHA study registry.

AIMS: Implantable cardioverter defibrillators (ICD) improve survival in selected patients with left ventricular dysfunction or heart failure (HF). The objective is to estimate the number of ICD candidates and to assess the potential impact on public health expenditure in Italy and the USA. METHODS AND RESULTS: Data from 3513 consecutive patients (ALPHA study registry) were screened. A model based on international guidelines inclusion criteria and epidemiological data was used to estimate the number of eligible patients. A comparison with current ICD implant rate was done to estimate the necessary incremental rate to treat eligible patients within 5 years. Up to 54% of HF patients are estimated to be eligible for ICD implantation. An implantation policy based on guidelines would significantly increase the ICD number to 2671 implants per million inhabitants in Italy and to 4261 in the USA. An annual increment of prophylactic ICD implants of 20% in the USA and 68% in Italy would be necessary to treat all indicated patients in a 5-year timeframe. CONCLUSION: Implantable cardioverter defibrillator implantation policy based on current evidence may have significant impact on public health expenditure. Effective risk stratification may be useful in order to maximize benefit of ICD therapy and its cost-effectiveness in primary prevention.

Impact of age and medical comorbidity on the effectiveness of implantable cardioverter-defibrillators for primary prevention.

BACKGROUND: Although implantable cardioverter-defibrillators (ICDs) reduce mortality in primary prevention patients with left ventricular systolic dysfunction, recent studies have questioned their overall role in clinical practice, especially in older patients and those with major comorbid conditions. METHODS AND RESULTS: In a prospective cohort of 965 patients with ischemic and nonischemic cardiomyopathies (ejection fraction or=75), ischemic etiology, ejection fraction (>25% versus 0.05). Incremental cost-effectiveness ratios for ICD therapy were similar between patients aged >or=75 years and younger patients but rose slightly in those with multiple comorbid conditions. CONCLUSIONS: Routine use of ICDs in primary prevention patients with left ventricular systolic dysfunction was associated with lower all-cause mortality, even among older patients and those with major comorbid conditions. Although their use needs to be individualized, our findings suggest that these groups should not be routinely excluded from ICD treatment.