Predictors of left ventricular ejection fraction in high-risk percutaneous coronary interventions.

Revascularization completeness after percutaneous coronary intervention (PCI) is associated with improved long-term outcomes. Mechanical circulatory support [intra-aortic balloon pump (IABP) or Impella] is used during high-risk PCI (HR-PCI) to enhance peri-procedural safety and achieve more complete revascularization. The relationship between revascularization completeness [post-PCI residual SYNTAX Score (rSS)] and left ventricular ejection fraction (LVEF) in HR-PCI has not been established. We investigated LVEF predictors at 90 days post-PCI with Impella or IABP support. Individual patient data (IPD) were analyzed from PROTECT II (NCT00562016) in the base case. IPD from PROTECT II and RESTORE-EF (NCT04648306) were naïvely pooled in the sensitivity analysis. Using complete cases only, linear regression was used to explore the predictors of LVEF at 90 days post-PCI. Models were refined using stepwise selection based on Akaike Information Criterion and included: treatment group (Impella, IABP), baseline characteristics [age, gender, race, New York Heart Association Functional Classification, LVEF, SYNTAX Score (SS)], and rSS. Impella treatment and higher baseline LVEF were significant predictors of LVEF improvement at 90 days post-PCI (p ≤ 0.05), and a lower rSS contributed to the model (p = 0.082). In the sensitivity analysis, Impella treatment, higher baseline LVEF, and lower rSS were significant predictors of LVEF improvement at 90 days (p ≤ 0.05), and SS pre-PCI contributed to the model (p = 0.070). Higher baseline LVEF, higher SS pre-PCI, lower rSS (i.e. completeness of revascularization), and Impella treatment were predictors of post-PCI LVEF improvement. The findings suggest potential mechanisms of Impella include improving the extent and quality of revascularization, and intraprocedural ventricular unloading.

Cost-effectiveness of an insertable cardiac monitor in a high-risk population in the US.

BACKGROUND: Insertable cardiac monitors (ICMs) are a clinically effective means of detecting atrial fibrillation (AF) in high-risk patients, and guiding the initiation of non-vitamin K oral anticoagulants (NOACs). Their cost-effectiveness from a US clinical payer perspective is not yet known. The objective of this study was to evaluate the cost-effectiveness of ICMs compared to standard of care (SoC) for detecting AF in patients at high risk of stroke (CHADS2 ≥ 2), in the US. METHODS: Using patient data from the REVEAL AF trial (n = 393, average CHADS2 score = 2.9), a Markov model estimated the lifetime costs and benefits of detecting AF with an ICM or with SoC (specifically intermittent use of electrocardiograms and 24-h Holter monitors). Ischemic and hemorrhagic strokes, intra- and extra-cranial hemorrhages, and minor bleeds were modelled. Diagnostic and device costs, costs of treating stroke and bleeding events and medical therapy-specifically costs of NOACs were included. Costs and health outcomes, measured as quality-adjusted life years (QALYs), were discounted at 3% per annum, in line with standard practice in the US setting. One-way deterministic and probabilistic sensitivity analyses (PSA) were undertaken. RESULTS: Lifetime per-patient cost for ICM was $31,116 versus $25,330 for SoC. ICMs generated a total of 7.75 QALYs versus 7.59 for SoC, with 34 fewer strokes projected per 1000 patients. The model estimates a number needed to treat of 29 per stroke avoided. The incremental cost-effectiveness ratio was $35,528 per QALY gained. ICMs were cost-effective in 75% of PSA simulations, using a $50,000 per QALY threshold, and a 100% probability of being cost-effective at a WTP threshold of $150,000 per QALY. CONCLUSIONS: The use of ICMs to identify AF in a high-risk population is likely to be cost-effective in the US healthcare setting.

Cost-effective analysis of automated programming optimization in cardiac resynchronization therapy: Holistic Markov modelling.

BACKGROUND: Automated optimization algorithm (AdaptivCRT; Medtronic, Mounds View, MN, USA) allowing automated optimization of cardiac resynchronization therapy (CRT), has been introduced. However, little is known concerning its cost-effectiveness. This study aims to evaluate the potential economic benefits of AdaptivCRT of CRT. METHODS: Markov modelling was informed by empirical data sourced from the AdaptivCRT Clinical Trial. Published meta-analyses were used to derive the impact of increasing response to hospitalization and mortality risks. Response was assessed via the clinical composite score. RESULTS: Deterministic results suggested a mean survival of 10.97 years with adaptive algorithms against 10.5 years without (+0.47 in favour of novel algorithms). Heart failure hospitalization costs were modelled to ¥1,382,753 (US $12,686) with novel devices against ¥1,524,747 (US $13,989) with previous technology models. Sensitivity analyses show CRT with Adaptive algorithm was projected to provide cost savings in all scenarios. CONCLUSIONS: The use of AdaptivCRT was projected to improve average patient survival and avoid costs in a Japanese healthcare setting.

The importance of early evaluation after cardiac resynchronization therapy to redefine response: Pooled individual patient analysis from 5 prospective studies.

BACKGROUND: Cardiac resynchronization therapy (CRT) reduces mortality and improves outcomes in appropriately selected patients with heart failure (HF); however, response may vary. OBJECTIVE: We sought to correlate 6-month CRT response assessed by clinical composite score (CCS) and left ventricular end-systolic volume index (LVESVi) with longer-term mortality and HF-related hospitalizations. METHODS: Individual patient data from 5 prospective CRT studies-Multicenter InSync Randomized Clinical Evaluation (MIRACLE), Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE ICD), InSync III Marquis, predictors of response to cardiac resynchronization therapy (PROSPECT), and Adaptive CRT-were pooled. Classification of CRT response status using CCS and LVESVi were made at 6 months. Kaplan-Meier analyses were used to assess time to mortality. Cox proportional hazards regression models were used to compute hazard ratios (HRs) for the 3 levels of CRT response: improved, stabilized, and worsened. Adjusted models controlled for baseline factors known to influence both CRT response and mortality. HF-related hospitalization was compared between CRT response categories using incidence rate ratios. RESULTS: Among a total of 1603 patients, 1426 and 1165 were evaluated in the CCS and LVESVi outcome assessments, respectively. Mortality was significantly lower for patients in the improved (CCS: HR 0.22; 95% confidence interval [CI] 0.15-0.31; LVESVi: HR 0.40; 95% CI 0.27-0.60) and stabilized (CCS: HR 0.38; 95% CI 0.24-0.61; LVESVi: HR 0.41; 95% CI 0.25-0.68) groups than in the worsened group for both measures after adjusting for potential confounders. CONCLUSION: Patients with a worsened CRT response status have a high mortality rate and HF-related hospitalizations. Stabilized patients have a more favorable prognosis than do worsened patients and thus should not be considered CRT nonresponders.

Cost-effectiveness of left ventricular assist devices as destination therapy in the United Kingdom.

AIMS: Continuous-flow left ventricular assist devices (LVADs) as destination therapy (DT) are a recommended treatment by National Institute for Health and Care Excellence England for end-stage heart failure patients ineligible for cardiac transplantation. Despite the fact that DT is frequently used as an LVAD indication across other major European countries and the United States, with consistent improvements in quality-of-life and longevity, National Health Service (NHS) England does not currently fund DT, mainly due to concerns over cost-effectiveness. On the basis of the recently published ENDURANCE Supplemental Trial studying DT patients, we assessed for the first time the cost-effectiveness of DT LVADs compared with medical management (MM) in the NHS England. METHODS AND RESULTS: We developed a Markov multiple-state economic model using NHS cost data. LVAD survival and adverse event rates were derived from the ENDURANCE Supplemental Trial. MM survival was based on Seattle Heart Failure Model estimates in the absence of contemporary clinical trials for this population. Incremental cost-effectiveness ratios (ICERs) were calculated over a lifetime horizon. A discount rate of 3.5% per year was applied to costs and benefits. Deterministic ICER was £46 207 per quality-adjusted life year (QALY). Costs and utilities were £204 022 and 3.27 QALYs for the LVAD arm vs. £77 790 and 0.54 QALYs for the MM arm. Sensitivity analyses confirmed robustness of the primary analysis. CONCLUSIONS: The implantation of the HeartWare™ HVAD™ System in patients ineligible for cardiac transplantation as DT is a cost-effective therapy in the NHS England healthcare system under the end-of-life willingness-to-pay threshold of £50 000/QALY, which applies for VAD patients.

Burden of oral anticoagulation in embolic stroke of undetermined source without atrial fibrillation.

OBJECTIVE: Prevention of recurrent stroke in patients with embolic stroke of undetermined source (ESUS) is challenging. The advent of safer anticoagulation in the form of direct oral anticoagulants (DOACs) has prompted exploration of prophylactic anticoagulation for all ESUS patients, rather than anticoagulating just those with documented atrial fibrillation (AF). However, recent trials have failed to demonstrate a clinical benefit, while observing increased bleeding. We modeled the economic impact of anticoagulating ESUS patients without documented AF across multiple geographies. METHODS: CRYSTAL-AF trial data were used to assess ischaemic stroke event rates in ESUS patients confirmed AF-free after long-term monitoring. Anticipated bleeding event rates (including both minor and major bleeds) with aspirin, dabigatran 150 mg, and rivaroxaban 20 mg were sourced from published meta-analyses, whilst a 30% ischaemic stroke reduction for both DOACs was assumed. Cost data for clinical events and pharmaceuticals were collected from the local payer perspective. RESULTS: Compared with aspirin, dabigatran and rivaroxaban resulted in 17.9 and 29.9 additional bleeding events per 100 patients over a patient's lifetime, respectively. Despite incorporating into our model the proposed 30% reduction in ischaemic stroke risk, both DOACs were cost-additive over patient lifetime, as the costs of bleeding events and pharmaceuticals outweighed cost savings associated with the reduction in ischaemic strokes. DOACs added £5953-£7018 per patient (UK), €6683-€7368 (Netherlands), €4933-€9378 (Spain), AUD$5353-6539 (Australia) and $26,768-$32,259 (US) of payer cost depending on the agent prescribed. Additionally, in the U.S. patient pharmacy co-payments ranged from $2468-$12,844 depending on agent and patient plan. In all settings, cost-savings could not be demonstrated even when the modelling assumed 100% protection from recurrent ischaemic strokes, due to the very low underlying risk of recurrent ischaemic stroke in this population (1.27 per 100 patient-years). CONCLUSIONS: Anticoagulation of non-AF patients may cause excess bleeds and add substantial costs for uncertain benefits, suggesting a personalised approach to anticoagulation in ESUS patients.

Economic value of insertable cardiac monitors in unexplained syncope in the United States.

INTRODUCTION: Early use of insertable cardiac monitor (ICM) is recommended for patients with unexplained syncope following initial clinical workup, due to its superior ability to establish symptom-rhythm correlation compared with conventional testing (CONV). However, ICMs incur higher upfront costs, and the impact of additional diagnoses and resulting treatment on downstream costs and outcomes is unclear. We aimed to evaluate the cost-effectiveness of ICM compared with CONV for the diagnosis of arrhythmia in patients with unexplained syncope, from a US payer perspective. METHODS: A Markov model was developed to estimate lifetime costs and benefits of arrhythmia diagnosis with ICM versus CONV, considering all related diagnostic and arrhythmia-related treatment costs and consequences. Cohort characteristics and costs were informed by original claims database analyses. Risks of mortality, syncopal recurrence, injury due to syncope and quality of life consequences from syncopal events were identified from the literature. RESULTS: ICM was less costly and more effective than CONV. Most of the observed US$4532 cost savings were attributed to reduced downstream diagnostic testing. For every 1000 patients, ICM was projected to yield an additional 253 arrhythmia diagnoses and lead to treatment in an additional 168 patients. The ICM strategy resulted in overall improved outcomes (0.30 quality-adjusted life years gained), due to a reduction in syncope recurrence and injury resulting from arrhythmia treatment. The results were robust to changes in the base case parameters but sensitive to the model time horizon, underlying probability of syncope recurrence and prevalence of arrhythmias. CONCLUSIONS: Our model projected that early ICM for the diagnosis of unexplained syncope reduced long-term costs, and led to an improvement in overall clinical outcomes by shortening time to arrhythmia treatment. The cost of ICM was outweighed by savings arising from fewer downstream diagnostic episodes, and the increased cost of treatment was counterbalanced by fewer syncope-related event costs.

Economic implications of adding a novel algorithm to optimize cardiac resynchronization therapy: rationale and design of economic analysis for the AdaptResponse trial.

AIMS: Although cardiac resynchronization therapy (CRT) has proven beneficial in several randomized trials, a subset of patients have limited clinical improvement. The AdaptivCRT algorithm provides automated selection between synchronized left ventricular or biventricular pacing with optimization of atrioventricular delays. The rationale and design of the economic analysis of the AdaptResponse clinical trial are described. RATIONALE: The costs associated with HF hospitalization are substantial and are compounded by a high rate of readmission. HF hospitalization payments range from $1,001 for Greece to $12,235 for US private insurance. When examining the breakdown of HF-related costs, it is clear that approximately 55% of the hospitalization costs are directly attributable to length of stay. Notably, the mean costs of a CRT patient in need of a HF-related hospitalization are currently estimated to be an average of $10,679. METHODS: The economic analysis of the AdaptResponse trial has two main objectives. The hospital provider objective seeks to test the hypothesis that AdaptivCRT reduces the incidence of all-cause re-admissions after a heart failure admission within 30 days of the index event. A negative binomial regression model will be used to estimate and compare the number of readmissions after an index HF hospitalization. The payer economic objective will assess cost-effectiveness of CRT devices with the AdaptivCRT algorithm relative to traditional CRT programming. This analysis will be conducted from a U.S. payer perspective. A decision analytic model comprised of a 6-month decision tree and a Markov model for long term extrapolation will be used to evaluate lifetime costs and benefits. CONCLUSION: AdaptivCRT may offer improvements over traditional device programming in patient outcomes. How the data from AdaptResponse will be used to demonstrate if these clinical benefits translate into substantial economic gains is herein described.

Cost-Effectiveness of a Small Intrapericardial Centrifugal Left Ventricular Assist Device.

There is limited data on the cost-effectiveness of continuous-flow left ventricular assist devices (LVAD) in the United States particularly for the bridge-to-transplant indication. Our objective is to study the cost-effectiveness of a small intrapericardial centrifugal LVAD compared with medical management (MM) and subsequent heart transplantation using the respective clinical trial data. We developed a Markov economic framework. Clinical inputs for the LVAD arm were based on prospective trials employing the HeartWare centrifugal-flow ventricular assist device system. To better assess survival in the MM arm, and in the absence of contemporary trials randomizing patients to LVAD and MM, estimates from the Seattle Heart Failure Model were used. Costs inputs were calculated based on Medicare claim analyses and when appropriate prior published literature. Time horizon was lifetime. Costs and benefits were appropriately discounted at 3% per year. The deterministic cost-effectiveness analyses resulted in $69,768 per Quality Adjusted Life Year and $56,538 per Life Year for the bridge-to-transplant indication and $102,587 per Quality Adjusted Life Year and $87,327 per Life Year for destination therapy. These outcomes signify a substantial improvement compared with prior studies and re-open the discussion around the cost-effectiveness of LVADs.

Cost-Effectiveness of Thoracotomy Approach for the Implantation of a Centrifugal Left Ventricular Assist Device.

This study reports the first analysis regarding cost-effectiveness of left ventricular assist device (LVAD) implantation via thoracotomy. Cost-effectiveness of LVADs implanted via the traditional surgical approach of sternotomy has been improved through the years because of technological advances, along with understanding the importance of patient selection and postimplant management have on positively affecting outcomes. Given the positive clinical outcomes of the thoracotomy approach, we seek to study the cost-effectiveness of a centrifugal LVAD via this less invasive approach. We developed a Markov model. Survival and quality of life inputs (QALY) for the LVAD arm were based on data from the LATERAL clinical trial. For the Medical Management arm, survival was derived from the Seattle Heart Failure Model. The heart transplant probability was derived from INTERMACS. Survival after heart transplantation used International Society for Heart and Lung Transplantation data. Cost inputs were calculated based on Medicare data and past literature. The incremental cost-effectiveness ratio was found to be $64,632 per quality adjusted life year and $57,891 per life year in the bridge to transplant indication. These results demonstrate further improvement in the overall cost-effectiveness of LVAD therapy and confirm implantation of LVADs via a less invasive approach as being cost-effective.

Cost-effectiveness analysis of implantable cardiac devices in patients with systolic heart failure: a US perspective using real world data.

Aims: Heart failure with reduced ejection fraction (HFrEF) has a substantial impact on costs and patients' quality-of-life. This study aimed to estimate the cost-effectiveness of implantable cardioverter defibrillators (ICD), cardiac resynchronization therapy pacemakers (CRT-P), cardiac resynchronization therapy defibrillators (CRT-D), and optimal pharmacologic therapy (OPT) in patients with HFrEF, from a US payer perspective.Materials and methods: The analyses were conducted by adapting the UK-based cost-effectiveness analyses (CEA) to the US payer perspective by incorporating real world evidence (RWE) on baseline hospitalization risk and Medicare-specific costs. The CEA was based on regression equations estimated from data from 13 randomized clinical trials (n = 12,638). Risk equations were used to predict all-cause mortality, hospitalization rates, health-related quality-of-life, and device-specific treatment effects (vs. OPT). These equations included the following prognostic characteristics: age, QRS duration, New York Heart Association (NYHA) class, ischemic etiology, and left bundle branch block (LBBB). Baseline hospitalization rates were calibrated based on RWE from Truven Health Analytics MarketScan data (2009-2014). A US payer perspective, lifetime time horizon, and 3% discount rates for costs and outcomes were used. Benefits were expressed as quality-adjusted life-years (QALYs). Incremental cost-effectiveness analysis was conducted for 24 sub-groups based on LBBB status, QRS duration, and NYHA class.Results: Results of the analyses show that CRT-D was the most cost-effective treatment at a $100,000/QALY threshold in 14 of the 16 sub-groups for which it is indicated. Results were most sensitive to changes in estimates of hospitalization costs.Limitations: Study limitations include small sample sizes for NYHA I and IV sub-groups and lack of data availability for duration of treatment effect.Conclusions: CRT-D has higher greater cost-effectiveness across more sub-groups in the indicated patient populations against as compared to OPT, ICD, and CRT-P, from a US payer perspective.

Adherence to heart failure management medications following cardiac resynchronization therapy.

Objective: The purpose of this study is to assess the real-world impact of cardiac resynchronization therapy (CRT) on adherence to heart failure (HF) medications.Methods: MarketScan administrative health care claims data from 2008 to 2014 among patients with HF were used. The date of first CRT implantation served as the index date. Adherence to guideline-directed medical therapy (GDMT) classes were compared during pre- and post-index periods using proportion of days covered (PDC). Comparisons between the two periods were made using the Wilcoxon sign-rank test for continuous PDC and McNemar's test for dichotomized PDC.Results: Increases in medication adherence were observed for major classes of HF GDMT medications. Specifically, adherence to angiotensin-converting enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARB), beta blockers (BB), and furosemide increased by 22, 24, 32, and 28% (all p < .001), respectively, in the 12 months pre to 12 months post-CRT. Large increases between the pre- and post-CRT period were also observed when considering adherence as dichotomized PDC ≥0.80 in the 12 months pre- versus post-CRT.Conclusion: Adherence to HF medications significantly improved among HF patients post-CRT implantation. Further research is needed to better understand the underlying determinants of this effect, including whether the effect is attributable to factors such as enhanced patient monitoring and improved access to high-quality specialized HF care among patients receiving CRT.

Economic value and cost-effectiveness of biventricular versus right ventricular pacing: results from the BLOCK-HF study.

Aims: The Biventricular vs Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK-HF) demonstrated that biventricular (BiV) pacing resulted in better clinical and structural outcomes compared to right ventricular (RV) pacing in patients with atrioventricular (AV) block and reduced left ventricular ejection fraction (LVEF; ≤50%). This study investigated the cost-effectiveness of BiV vs RV pacing in the patient population enrolled in the BLOCK-HF trial. Methods: All-cause mortality, New York Heart Association (NYHA) Class distribution over time, and NYHA-specific heart failure (HF)-related healthcare utilization rates were predicted using statistical models based on BLOCK-HF patient data. A proportion-in-state model calculated cost-effectiveness from the Medicare payer perspective. Results: The predicted patient survival was 6.78 years with RV and 7.52 years with BiV pacing, a 10.9% increase over lifetime. BiV pacing resulted in 0.41 more quality-adjusted life years (QALYs) compared to RV pacing, at an additional cost of $12,537. The "base-case" incremental cost-effectiveness ratio (ICER) was $30,860/QALY gained. Within the clinical sub-groups, the highest observed ICER was $43,687 (NYHA Class I). Patients receiving combined BiV pacing and defibrillation (BiV-D) devices were projected to benefit more (0.84 years gained) than BiV pacemaker (BiV-P) recipients (0.49 years gained), compared to dual-chamber pacemakers. Conclusions: BiV pacing in AV block patients improves survival and attenuates HF progression compared to RV pacing. ICERs were consistently below the US acceptability threshold ($50,000/QALY). From a US Medicare perspective, the additional up-front cost associated with offering BiV pacing to the BLOCK-HF patient population appears justified.

Heart failure hospitalization reduction and cost savings achieved by improved delivery of effective biventricular pacing: economic implications of the OLE study under the US setting.

Background: The hOLter for Efficacy analysis (OLE) study demonstrated that current device pacing diagnostics overestimate the amount of cardiac resynchronization therapy (CRT) pacing that effectively stimulates the cardiac tissue. Sub-optimal pacing increases mortality, hospitalizations, and associated health-care costs. We sought to estimate the expected number of hospital admissions due to heart failure (HF) and its respective financial impact in patients with maximized effective pacing versus conventional pacing. Methods: A Markov model was developed to project HF hospitalizations and quantify the costs that could be avoided if pacing was maximally effective. OLE data were used to inform the prevalence of ineffective pacing among CRT patients and and average loss of pacing by causes. Adaptive CRT trial data quantified the reduction in underlying hospitalization risk by increasing effective pacing delivered. Survival was informed by a meta-analysis of 5 randomized clinical trials. Costs were analyzed from a US payer perspective. Results: Projected average hospitalizations totaled 4.58 over a lifetime horizon for CRT patients with conventional pacing. Maximizing effective pacing delivery was projected to avoid 1.83 HF admissions/patient over the lifetime. This equates to a savings of 40% (US$22,802) compared with conventional pacing from the Medicare perspective. In a sensitivity analysis, CRT with effective pacing was projected to provide cost savings in all scenarios. Conclusions: Maximized effective pacing leads to a lower number of HF hospitalizations, thus allowing significant cost offsets in the US setting.

Economic Value and Cost-Effectiveness of Cardiac Resynchronization Therapy Among Patients With Mild Heart Failure: Projections From the REVERSE Long-Term Follow-Up.

OBJECTIVES: This study investigated the cost effectiveness of early cardiac resynchronization therapy (CRT) implantation among patients with mild heart failure (HF). The differential cost effectiveness between CRT using a defibrillator (CRT-Ds) and CRT using a pacemaker (CRT-P) was also assessed. BACKGROUND: Cardiac resynchronization has been shown to be cost effective in New York Heart Association (NYHA) functional classes III/IV but is less studied in class II HF. The incremental costs of early CRT implementation in mild HF compared with the costs potentially avoided because of delaying disease progression to advanced HF are also unknown. Finally, combined biventricular pacing and defibrillator (CRT-D) devices are more expensive than biventricular pacemakers (CRT-P), but the relative cost effectiveness is controversial. METHODS: Data from the 5-year follow-up phase of REVERSE (REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction) were used. The economics were evaluated from the U.S. Medicare perspective based on published clinical projections. RESULTS: Probabilistic estimates yielded $8,840/quality-adjusted life year (QALY) gained (95% confidence interval [CI]: $6,705 to $10,804/QALY gained) for CRT-ON versus CRT-OFF (i.e., programmed "ON" or "OFF" at pre-specified post-implantation timings) and $43,678/QALY gained for CRT-D versus CRT-P (95% CI: $35,164 to $53,589/QALY gained) over the patient's lifetime. Results were robust to choice of patient subgroup and alterations of ±10% to key model parameters. An "early" CRT-D class II strategy totaled $95,292 compared with $91,511 for a "late" implantation. An "early" implant offered on average 1.00 year of additional survival for $3,781, resulting in an ICER of $3,795/LY gained. CONCLUSIONS: This study demonstrates CRT cost effectiveness in mild HF. The incremental CRT-D costs are justified by the anticipated benefits, despite increased procurement costs and shorter generator longevities. "Early" CRT-D implants have essential cost parity with "late" implants while increasing the patient's survival. (REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction [REVERSE]; NCT00271154).

Long-Term Extrapolation of Clinical Benefits Among Patients With Mild Heart Failure Receiving Cardiac Resynchronization Therapy: Analysis of the 5-Year Follow-Up From the REVERSE Study.

OBJECTIVES: This study sought to assess the lifelong extrapolated patient outcomes with cardiac resynchronization therapy (CRT) in mild heart failure (HF), beyond the follow-up of randomized clinical trials (RCTs). BACKGROUND: RCTs have demonstrated short-term survival and HF hospitalization benefits of CRT in mild HF. We used data from the 5-year follow-up of the REVERSE (REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction) study to extrapolate survival and HF hospitalizations. We compared CRT-ON versus CRT-OFF and CRT defibrillators (CRT-D) versus CRT pacemakers (CRT-P). METHODS: Multivariate regression models were used to estimate treatment-specific all-cause mortality, disease progression, and HF-related hospitalization rates. Rank-preserving structural failure time (RPSFT) models were used to adjust for protocol-mandated crossover in the survival analysis. RESULTS: CRT-ON was predicted to increase survival by 22.8% (CRT-ON 52.5% vs. CRT-OFF 29.7%; hazard ratio [HR]: 0.45; p = 0.21), leading to an expected survival of 9.76 years (CRT-ON) versus 7.5 years (CRT-OFF). CRT-D showed a significant improvement in survival compared with CRT-P (HR: 0.47; 95% confidence interval [CI]: 0.25 to 0.88; p = 0.02) and were predicted to offer 2.77 additional life-years. New York Heart Association (NYHA) functional class II patients had a 30.6% higher HF hospitalization risk than class I (I vs. II incident rate ratio [IRR]: 0.69; 95% CI: 0.57 to 0.85; p < 0.001) and 3 times lower rate compared with class III (III vs. II IRR: 2.98; 95% CI: 2.29 to 3.87; p < 0.001). CONCLUSIONS: RPSFT estimates yielded results demonstrating clinically important long-term benefit of CRT in mild HF. CRT was predicted to reduce mortality, with CRT-D prolonging life more than CRT-P. NYHA functional class I/II patients were shown to have a significantly reduced risk of HF hospitalization compared with class III, leading to CRT reducing HF hospitalization rates.

Impact of a Novel Adaptive Optimization Algorithm on 30-Day Readmissions: Evidence From the Adaptive CRT Trial.

OBJECTIVES: This study investigated the impact of the Medtronic AdaptivCRT (aCRT) (Medtronic, Mounds View, Minnesota) algorithm on 30-day readmissions after heart failure (HF) and all-cause index hospitalizations. BACKGROUND: The U.S. Hospital Readmission Reduction Program, which includes a focus on HF, reduces Medicare inpatient payments when readmissions within 30 days of discharge exceed a moving threshold based on national averages and hospital-specific risk adjustments. Internationally, readmissions within 30 days of any discharge may attract reduced or no payment. Recently, cardiac resynchronization therapy (CRT) devices equipped with the aCRT algorithm allowing automated ambulatory device programming were introduced. The Adaptive CRT trial demonstrated the algorithm's safety and comparable outcome against a rigorous echocardiography-based optimization protocol. METHODS: We analyzed data from the Adaptive CRT trial, which randomized patients undergoing CRT defibrillation on a 2:1 basis to aCRT (n = 318) or to CRT with echocardiographic optimization (Echo, n = 160) and followed up these patients for a mean of 20.2 months (range: 0.2 to 31.3 months). Logistic regression with generalized estimating equation methodology was used to compare the proportion of patients hospitalized for HF and for all causes who had a readmission within 30 days. RESULTS: For HF hospitalizations, the 30-day readmission rate was 19.1% (17 of 89) in the aCRT group and 35.7% (15 of 42) in the Echo group (odds ratio: 0.41; 95% confidence interval [CI]: 0.19 to 0.86; p = 0.02). For all-cause hospitalization, the 30-day readmission rate was 14.8% (35 of 237) in the aCRT group compared with 24.8% (39 of 157) in the Echo group (odds ratio: 0.54; 95% CI: 0.31 to 0.94; p = 0.03). The risk of readmission after HF or all-cause index hospitalization with aCRT was also significantly reduced beyond 30 days. CONCLUSIONS: Use of the aCRT algorithm is associated with a significant reduction in the probability of a 30-day readmission after both HF and all-cause hospitalizations. (Adaptive Cardiac Resynchronization Therapy Study [aCRT]; NCT00980057).

Costs of unstructured investigation of unexplained syncope: insights from a micro-costing analysis of the observational PICTURE registry.

AIMS: The observational PICTURE (Place of Reveal In the Care pathway and Treatment of patients with Unexplained Recurrent Syncope) registry enrolled 570 patients with unexplained syncope, documented their care pathway and the various tests they underwent before the insertion of an implantable loop recorder (ILR). The aims were to describe the extent and cost of diagnostic tests performed before the implant. METHODS AND RESULTS: Actual costs of 17 predefined diagnostic tests were characterized based on a combination of data from PICTURE and a micro-costing study performed at a medium-sized UK university hospital in the UK. The median cost of diagnostic tests per patient was £1114 (95% CI £995-£1233). As many patients received more than the median number of tests, the mean expenditure per patient was higher with £1613 (95% CI £1494-£1732), and for 10% of the patients the cost exceeded £3539. Tests were frequently repeated, and early use of specific and expensive tests was common. In the 12% of patients with types of tests entirely within the recommendations for an initial evaluation before ILR implant, the mean cost was £710. CONCLUSION: Important opportunities to reduce test-related costs before an ILR implant were identified, e.g. by more appropriate use of tests recommended in the initial evaluation, by decreasing repetition of tests, and by avoiding early use of specialized and expensive tests. A structured multidisciplinary approach would be the best model to achieve an optimal outcome.

Financial impact of adopting implantable loop recorder diagnostic for unexplained syncope compared with conventional diagnostic pathway in Portugal.

BACKGROUND: To estimate the short- and long-term financial impact of early referral for implantable loop recorder diagnostic (ILR) versus conventional diagnostic pathway (CDP) in the management of unexplained syncope (US) in the Portuguese National Health Service (PNHS). METHODS: A Markov model was developed to estimate the expected number of hospital admissions due to US and its respective financial impact in patients implanted with ILR versus CDP. The average cost of a syncope episode admission was estimated based on Portuguese cost data and landmark papers. The financial impact of ILR adoption was estimated for a total of 197 patients with US, based on the number of syncope admissions per year in the PNHS. Sensitivity analysis was performed to take into account the effect of uncertainty in the input parameters (hazard ratio of death; number of syncope events per year; probabilities and unit costs of each diagnostic test; probability of trauma and yield of diagnosis) over three-year and lifetime horizons. RESULTS: The average cost of a syncope event was estimated to be between 1,760€ and 2,800€. Over a lifetime horizon, the total discounted costs of hospital admissions and syncope diagnosis for the entire cohort were 23% lower amongst patients in the ILR group compared with the CDP group (1,204,621€ for ILR, versus 1,571,332€ for CDP). CONCLUSION: The utilization of ILR leads to an earlier diagnosis and lower number of syncope hospital admissions and investigations, thus allowing significant cost offsets in the Portuguese setting. The result is robust to changes in the input parameter values, and cost savings become more pronounced over time.

Cost-effectiveness of cryoballoon ablation for the management of paroxysmal atrial fibrillation.

AIMS: Cryoballoon ablation is an established treatment option for the management of patients with atrial fibrillation. We sought to evaluate the cost-effectiveness of cryoablation, compared with second-line anti-arrhythmic drug (AAD) therapy in patients with paroxysmal atrial fibrillation (PAF), from a UK payer perspective. METHODS AND RESULTS: We developed a state-transition (Markov) model to calculate the total costs and quality-adjusted life-years (QALYs) associated with cryoablation and AAD therapy in patients with PAF. A 5-year horizon was used for the base-case. Data from a recent study of cryoballoon ablation in patients with PAF were used to model short-term health outcomes and costs, together with longer term external evidence to populate subsequent time periods. Total discounted costs were £21 162 and £17 627 for the cryoballoon ablation and AAD arms, respectively. Total QALYs of 3.565 and 3.404 therefore led to an incremental cost-effectiveness ratio of £21 957 per QALY gained. Sensitivity analysis suggested that the key drivers of the results were the model time horizon, the costs of follow-up care in patients with recurrent AF, and the costs of the ablation procedure. CONCLUSION: Cryoballoon ablation provides increased quality-adjusted life expectancy compared with AAD at reasonable additional cost, representing good value for money in patients with PAF.