New Approaches to Assessment and Management of Tricuspid Regurgitation Before Intervention.

Severe tricuspid regurgitation (TR) is a progressive condition associated with substantial morbidity, poor quality of life, and increased mortality. Patients with TR commonly have coexisting conditions including congestive heart failure, pulmonary hypertension, chronic lung disease, atrial fibrillation, and cardiovascular implantable electronic devices, which can increase the complexity of medical and surgical TR management. As such, the optimal timing of referral for isolated tricuspid valve (TV) intervention is undefined, and TV surgery has been associated with elevated risk of morbidity and mortality. More recently, an unprecedented growth in TR treatment options, namely the development of a wide range of transcatheter TV interventions (TTVI) is stimulating increased interest and referral for TV intervention across the entire medical community. However, there are no stepwise algorithms for the optimal management of symptomatic severe TR before TTVI. This article reviews the contemporary assessment and management of TR with addition of a medical framework to optimize TR before referral for TTVI.

Clinical Trial Inclusion and Impact on Early Adoption of Medical Innovation in Diverse Populations.

BACKGROUND: Inadequate inclusion in clinical trial enrollment may contribute to health inequities by evaluating interventions in cohorts that do not fully represent target populations. OBJECTIVES: The aim of this study was to determine if characteristics of patients with heart failure (HF) enrolled in a pivotal trial are associated with who receives an intervention after approval. METHODS: Demographics from 2,017,107 Medicare patients hospitalized for HF were compared with those of the first 10,631 Medicare beneficiaries who received implantable pulmonary artery pressure sensors. Characteristics of the population studied in the pivotal CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) clinical trial (n = 550) were compared with those of both groups. All demographic data were analyzed nationally and in 4 U.S. regions. RESULTS: The Medicare HF cohort included 80.9% White, 13.3% African American, 1.9% Hispanic, 1.3% Asian, and 51.5% female patients. Medicare patients <65 years of age were more likely to be African American (33%) and male (58%), whereas older patients were mostly White (84%) and female (53%). Forty-one percent of U.S. HF hospitalizations occurred in the South; demographic characteristics varied significantly across all U.S. regions. The CHAMPION trial adequately represented African Americans (23% overall, 35% <65 years of age), Hispanic Americans (2%), and Asian Americans (1%) but underrepresented women (27%). The trial's population characteristics were similar to those of the first patients who received pulmonary artery sensors (82% White, 13% African American, 1% Asian, 1% Hispanic, and 29% female). CONCLUSIONS: Demographics of Centers for Medicare and Medicaid Services beneficiaries hospitalized with HF vary regionally and by age, which should be considered when defining "adequate" representation in clinical studies. Enrollment diversity in clinical trials may affect who receives early application of recently approved innovations.

Early Assessment of Cardiac Allograft Vasculopathy Risk Among Recipients of Hepatitis C Virus-infected Donors in the Current Era.

BACKGROUND: Transplantation of hearts from hepatitis C virus (HCV)-positive donors has increased substantially in recent years following development of highly effective direct-acting antiviral therapies for treatment and cure of HCV. Although historical data from the pre-direct-acting antiviral era demonstrated an association between HCV-positive donors and accelerated cardiac allograft vasculopathy (CAV) in recipients, the relationship between the use of HCV nucleic acid test-positive (NAT+) donors and the development of CAV in the direct-acting antiviral era remains unclear. METHODS AND RESULTS: We performed a retrospective, single-center observational study comparing coronary angiographic CAV outcomes during the first year after transplant in 84 heart transplant recipients of HCV NAT+ donors and 231 recipients of HCV NAT- donors. Additionally, in a subsample of 149 patients (including 55 in the NAT+ cohort and 94 in the NAT- cohort) who had serial adjunctive intravascular ultrasound examination performed, we compared development of rapidly progressive CAV, defined as an increase in maximal intimal thickening of ≥0.5 mm in matched vessel segments during the first year post-transplant. In an unadjusted analysis, recipients of HCV NAT+ hearts had reduced survival free of CAV ≥1 over the first year after heart transplant compared with recipients of HCV NAT- hearts. After adjustment for known CAV risk factors, however, there was no significant difference between cohorts in the likelihood of the primary outcome, nor was there a difference in development of rapidly progressive CAV. CONCLUSIONS: These findings support larger, longer-term follow-up studies to better elucidate CAV outcomes in recipients of HCV NAT+ hearts and to inform post-transplant management strategies.

Cost-effectiveness of transcatheter edge-to-edge repair in secondary mitral regurgitation.

BACKGROUND: Transcatheter edge-to-edge mitral valve repair (TMVr) improves symptoms and survival for patients with heart failure with reduced left ventricular ejection fraction (HFrEF) and severe secondary mitral regurgitation despite guideline-recommended medical therapy (GRMT). Whether TMVr is cost-effective from a UK National Health Service (NHS) perspective is unknown. METHODS: We used patient-level data from the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial to perform a cost-effectiveness analysis of TMVr +GRMT versus GRMT alone from an NHS perspective. Costs for the TMVr procedure were based on standard English tariffs and device costs. Subsequent costs were estimated based on data acquired during the trial. Health utilities were estimated using the Short-Form 6-Dimension Health Survey. RESULTS: Costs for the index procedural hospitalisation were £18 781, of which £16 218 were for the TMVr device. Over 2-year follow-up, TMVr reduced subsequent costs compared with GRMT (£10 944 vs £14 932, p=0.006), driven mainly by reductions in heart failure hospitalisations; nonetheless, total 2-year costs remained higher with TMVr (£29 165 vs £14 932, p<0.001). When survival, health utilities and costs were projected over a lifetime, TMVr was projected to increase life expectancy by 1.57 years and quality-adjusted life expectancy by 1.12 quality-adjusted life-years (QALYs) at an incremental cost of £21 980, resulting in an incremental cost-effectiveness ratio (ICER) of £23 270 per QALY gained (after discounting). If the benefits of TMVr observed in the first 2 years were maintained without attenuation, the ICER improved to £12 494 per QALY. CONCLUSIONS: For patients with HFrEF and severe secondary mitral regurgitation similar to those enrolled in COAPT, TMVr increases life expectancy and quality-adjusted life expectancy compared with GRMT at an ICER that represents good value from an NHS perspective.

Respiratory Non-Invasive Venous Waveform Analysis for Assessment of Respiratory Distress in Coronavirus Disease 2019 Patients: An Observational Study.

OBJECTIVES: Due to the rapid rate of severe acute respiratory syndrome coronavirus 2 transmission and the heterogeneity of symptoms of coronavirus disease 2019, expeditious and effective triage is critical for early treatment and effective allocation of hospital resources. DESIGN: A post hoc analysis of respiratory data from non-invasive venous waveform analysis among patients enrolled in an observational study was performed. SETTING: Vanderbilt University Medical Center. PATIENTS: Peripheral venous waveforms were recorded from admission to discharge in enrolled coronavirus disease 2019-positive patients and healthy age-matched controls. INTERVENTIONS: Data were analyzed in LabChart 8 to transform venous waveforms to the frequency domain using fast Fourier transforms. The peak respiratory frequency was normalized to the peak cardiac frequency to generate a respiratory non-invasive venous waveform analysis respiratory index. Paired Fisher exact tests were used to compare each patient's respiratory non-invasive venous waveform analysis respiratory index at admission and discharge. A nonparametric one-way analysis of variance was used for multiple comparisons between patients with coronavirus disease 2019 and healthy controls for respiratory non-invasive venous waveform analysis respiratory index. MEASUREMENTS AND MAIN RESULTS: Fifty coronavirus disease 2019-positive patients were enrolled between April 2020, and September 2020, and 45 were analyzed; 34 required supplemental oxygen and 11 did not. The respiratory non-invasive venous waveform analysis respiratory index was significantly higher for the 34 patients with coronavirus disease 2019 who received supplemental oxygen (median, 0.27; interquartile range, 0.11-1.28) compared with the 34 healthy controls (median, 0.06; interquartile range, 0.03-0.14) (p < 0.01). For patients with coronavirus disease 2019 who received supplemental oxygen, respiratory non-invasive venous waveform analysis respiratory index was significantly lower at hospital discharge (p = 0.02; 95% CI, 0.10-1.9) compared with hospital admission (median = 0.12; interquartile range, 0.05-0.56). For patients with coronavirus disease 2019, a respiratory non-invasive venous waveform analysis respiratory index of 0.64 demonstrated sensitivity of 92%, specificity of 47%, and positive predictive value of 93% for predicting requirement of supplemental oxygen during the hospitalization. CONCLUSIONS: Respiratory non-invasive venous waveform analysis respiratory index represents a novel physiologic respiratory measurement with a promising ability to triage early care and predict the need for oxygen support therapy in coronavirus disease 2019 patients.

Use of Outpatient Intravenous Calcitropes for Heart Failure in the United States.

BACKGROUND: Outpatient calcitrope infusions-that is, the cardiac inotropes milrinone and dobutamine-are often used for bridge to transplantation and palliation in advanced heart failure, but few data exist about the real-world use of these agents. METHODS AND RESULTS: We used the Symphony Integrated DataVerse of commercial, managed Medicare, and Medicaid insurance claims of approximately 280 million people (2012-2020) to determine the incidence and characteristics of ambulatory calcitrope use. Demographics were calculated, including geographic densities at the metropolitan statistical area level. A population projection normalized for age, sex, and location was extrapolated to the total US population. Ambulatory dispensing of milrinone was found in 10,533 outpatients, 1867 in 2019. Ambulatory dobutamine use was found in 4967 outpatients, 836 in 2019. The 2019 total US projection was 3411 for milrinone and 1281 for dobutamine. The mean age was 62 years for milrinone and 68 for dobutamine. Males represented 70% of use. There were differences between drugs in geographic distribution, with more milrinone use in the Northeast and South and more dobutamine use in the Midwest. Duration of use was 4.6 ± 7.2 months for milrinone and 1.8 ± 4.0 months for dobutamine. Of the patients receiving milrinone, 30.6% subsequently underwent cardiac transplantation or left ventricular assist device placement, whereas 10% receiving dobutamine went on to advanced therapies. Less than 0.5% of patients received calcitropes while enrolled in hospice care. CONCLUSIONS: More than 4000 patients receive outpatient infusion of calcitropes annually in the outpatient setting. Men are much more likely to receive these medications. A minority of the use is as a bridge to advanced therapies. Geographic variability in use suggests better evidence and consistent guidelines may be helpful.

Cost-impact analysis of baroreflex activation therapy in chronic heart failure patients in the United States.

BACKGROUND: The study evaluated the cost of baroreflex activation therapy plus guideline directed therapy (BAT + GDT) compared to GDT alone for HF patients with reduced ejection fraction and New York Heart Association Class III or II (with a recent history of III). Baroreflex activation therapy (BAT) is delivered by an implantable device that stimulates the baroreceptors through an electrode attached to the outside of the carotid artery, which rebalances the autonomic nervous system to regain cardiovascular (CV) homeostasis. The BeAT-HF trial evaluated the safety and effectiveness of BAT. METHODS: A cost impact model was developed from a U.S. health care payer or integrated delivery network perspective over a 3-year period for BAT + GDT versus GDT alone. Expected costs were calculated by utilizing 6-month data from the BeAT-HF trial and existing literature. HF hospitalization rates were extrapolated based on improvement in NT-proBNP. RESULTS: At baseline the expected cost of BAT + GDT were $29,526 per patient more than GDT alone due to BAT device and implantation costs. After 3 years, the predicted cost per patient was $9521 less expensive for BAT + GDT versus GDT alone due to lower rates of significant HF hospitalizations, CV non-HF hospitalizations, and resource intensive late-stage procedures (LVADs and heart transplants) among the BAT + GDT group. CONCLUSIONS: BAT + GDT treatment becomes less costly than GDT alone beginning between years 1 and 2 and becomes less costly cumulatively between years 2 and 3, potentially providing significant savings over time. As additional BeAT-HF trial data become available, the model can be updated to show longer term effects.

Clinical outcomes and healthcare expenditures in the real world with left ventricular assist devices - The CLEAR-LVAD study.

BACKGROUND: Several distinctly engineered left ventricular assist devices (LVADs) are in clinical use. However, contemporaneous real world comparisons have not been conducted, and clinical trials were not powered to evaluate differential survival outcomes across devices. OBJECTIVES: Determine real world survival outcomes and healthcare expenditures for commercially available durable LVADs. METHODS: Using a retrospective observational cohort design, Medicare claims files were linked to manufacturer device registration data to identify de-novo, durable LVAD implants performed between January 2014 and December 2018, with follow-up through December 2019. Survival outcomes were compared using a Cox proportional hazards model stratified by LVAD type and validated using propensity score matching. Healthcare resource utilization was analyzed across device types by using nonparametric bootstrap analysis methodology. Primary outcome was survival at 1-year and total Part A Medicare payments. RESULTS: A total of 4,195 de-novo LVAD implants were identified in fee-for-service Medicare beneficiaries (821 HeartMate 3; 1,840 HeartMate II; and 1,534 Other-VADs). The adjusted hazard ratio for mortality at 1-year (confirmed in a propensity score matched analysis) for the HeartMate 3 vs HeartMate II was 0.64 (95% CI; 0.52-0.79, p< 0.001) and for the HeartMate 3 vs Other-VADs was 0.51 (95% CI; 0.42-0.63, p < 0.001). The HeartMate 3 cohort experienced fewer hospitalizations per patient-year vs Other-VADs (respectively, 2.8 vs 3.2 EPPY hospitalizations, p < 0.01) and 6.1 fewer hospital days on average (respectively, 25.2 vs 31.3 days, p < 0.01). The difference in Medicare expenditures, conditional on survival, for HeartMate 3 vs HeartMate II was -$10,722, p < 0.001 (17.4% reduction) and for HeartMate 3 vs Other-VADs was -$17,947, p < 0.001 (26.1% reduction). CONCLUSIONS: In this analysis of a large, real world, United States. administrative dataset of durable LVADs, we observed that the HeartMate 3 had superior survival, reduced healthcare resource use, and lower healthcare expenditure compared to other contemporary commercially available LVADs.

National Landscape of Hospitalizations in Patients with Left Ventricular Assist Device. Insights from the National Readmission Database 2010-2015.

The number of patients with left ventricular assist devices (LVAD) has increased over the years and it is important to identify the etiologies for hospital admission, as well as the costs, length of stay and in-hospital complications in this patient group. Using the National Readmission Database from 2010 to 2015, we identified patients with a history of LVAD placement using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code V43.21. We aimed to identify the etiologies for hospital admission, patient characteristics, and in-hospital outcomes. We identified a total of 15,996 patients with an LVAD, the mean age was 58 years and 76% were males. The most common cause of hospital readmission after LVAD was heart failure (HF, 13%), followed by gastrointestinal (GI) bleed (11.8%), device complication (11.5%), and ventricular tachycardia/fibrillation (4.2%). The median length of stay was 6 days (3-11 days) and the median hospital costs was $12,723 USD. The in-hospital mortality was 3.9%, blood transfusion was required in 26.8% of patients, 20.5% had acute kidney injury, 2.8% required hemodialysis, and 6.2% of patients underwent heart transplantation. Interestingly, the most common cause of readmission was the same as the diagnosis for the preceding admission. One in every four LVAD patients experiences a readmission within 30 days of a prior admission, most commonly due to HF and GI bleeding. Interventions to reduce HF readmissions, such as speed optimization, may be one means of improving LVAD outcomes and resource utilization.

Sex-specific differences in access and response to medical and device therapies in heart failure: State of the art.

Women with heart failure (HF) are more symptomatic than their male counterparts. Despite deriving similar benefits from both medical and devices therapies, women continue to be underrepresented in clinic trials. Important sex-based disparities exist in enrollment in clinical trials and access to medical and device-based therapies, in part stemming from differences in medical and psychosocial comorbidities. Disparities in access to beneficial interventions likely contribute to the greater symptom burden identified in women with HF. Improved focus on the enrollment of women in clinical trials will allow a better understanding of the underpinnings of these disparities and improve the care of women with HF.

Report from the 2018 consensus conference on immunomodulating agents in thoracic transplantation: Access, formulations, generics, therapeutic drug monitoring, and special populations.

In 2009, the International Society for Heart and Lung Transplantation recognized the importance and challenges surrounding generic drug immunosuppression. As experience with generics has expanded and comfort has increased, substantial issues have arisen since that time with other aspects of immunomodulation that have not been addressed, such as access to medicines, alternative immunosuppression formulations, additional generics, implications on therapeutic drug monitoring, and implications for special populations such as pediatrics and older adults. The aim of this consensus document is to address critically each of these concerns, expand on the challenges and barriers, and provide therapeutic considerations for practitioners who manage patients who need to undergo or have undergone cardiothoracic transplantation.

Change in admission blood glucose from chronic glycemic status in acute heart failure hospitalization and 30-day outcomes: A retrospective analysis.

BACKGROUND: Admission blood glucose (BG) has demonstrated contradictory association with 30-day mortality in acute heart failure (AHF) hospitalization. To explore these contradictory findings, we aimed to determine if admission BG reflects an acute change from chronic glucose control and investigate the association between the admission and chronic BG change (ΔBG) with 30-day mortality in AHF. METHODS: We analyzed patients (n = 1045) age ≥ 65 with Centers of Medicare Services benefits and known 30-day all-cause mortality hospitalized with AHF at an academic medical center from 2009 to 2016. We included diabetic (n = 736) and non-diabetic (n = 309) patients with recent Hemoglobin A1c (HbA1c). We defined ΔBG as the difference in the admission and chronic BG, calculated from HbA1c. RESULTS: Admission BG was 126 (101, 167) mg/dl and was moderately elevated (≥170 mg/dl) in 25% of admissions. The median (IQR) ΔBG was -7 (-29, 26) mg/dl, with 74% of all admissions (66% diabetic, 92% non-diabetic) presenting within ±50 mg/dl of the chronic BG. Admission BG was not associated with mortality. ΔBG > +100 mg/dl displayed increased 30-day mortality (18.6% vs 6.9%, p < 0.001) compared to -26 to +25 mg/dl. When admission BG was >200 mg/dl (n = 166), a ΔBG > +100 mg/dl was present in 77% of those deceased vs 31% of those alive at 30 days (p = 0.003; positive likelihood ratio = 5.7). ΔBG > +100 mg/dl was strongly associated with 30-day mortality risk (OR 6.4, 95% CI 2.3-18.9; p = 0.0005) after multivariate adjustment. CONCLUSIONS: Admission BG predominantly reflects chronic glycemic status. Increased change in admission from chronic BG was associated with increased 30-day mortality.

Bioanalytical Assessment of Plasma Concentrations of Angiotensin-Converting Enzyme II Inhibitors and Angiotensin Receptor Blockers: A Pilot Study Among Patients Hospitalized With Acute Heart Failure.

BACKGROUND: Although angiotensin-converting enzyme II inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) improve chronic heart failure (HF) outcomes, their potential harms and benefits in acute HF (AHF) is less clear. STUDY QUESTION: We explored the relationship between ACEI or ARB plasma concentrations among patients with AHF with in-hospital change in estimated glomerular filtration rate (eGFR). DATA SOURCES AND STUDY DESIGN: From August 2016-June 2017, patients with AHF prescribed an outpatient ACEI or ARB were enrolled before AHF treatment. All patients were given twice their home dose of diuretic intravenously and received clinical care at the discretion of the medical team. Of 61 patients in the parent study, saved plasma from 34 who were prescribed an outpatient ACEI or ARB was included in this substudy. MEASURES AND OUTCOMES: Liquid chromatography-tandem mass spectrometry was performed to assess ACEI or ARB plasma concentrations before AHF treatment. Change in eGFR was computed using the Chronic Kidney Disease Epidemiology Collaboration equation, which adjusts for age, sex, and race; diuretic dose and enrollment eGFR were used to adjust for HF severity. Multiple linear regression adjusting for enrollment eGFR and diuretic dose was performed to examine the relationship between drug concentration (undetectable/low vs. in/above-range) and in-hospital change in eGFR. RESULTS: Of 34 patients with AHF, median age was 63 years (interquartile range, 58-78 years), 19 (55.9%) were women, median eGFR at enrollment was 55.6 mL/min (interquartile range, 35.2-75.3 mL/min), and for 11 (32.4%), no ACEI or ARB was detectable in plasma. Medication concentrations in- or above-reference range were associated with in-hospital decrease in eGFR of 8.3 mL/min (95% confidence interval, 15.3-1.3 mL/min decrease), after adjusting for enrollment eGFR and diuretic treatment. CONCLUSIONS: Bioanalytical assessment of medication levels may be useful to guide in-hospital ACEI and ARB therapy for patients with AHF.

Cost-Effectiveness of Transcatheter Mitral Valve Repair Versus Medical Therapy in Patients With Heart Failure and Secondary Mitral Regurgitation: Results From the COAPT Trial.

BACKGROUND: The COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) demonstrated that edge-to-edge transcatheter mitral valve repair (TMVr) with the MitraClip resulted in reduced mortality and heart failure hospitalizations and improved quality of life compared with maximally tolerated guideline-directed medical therapy (GDMT) in patients with heart failure and 3 to 4+ secondary mitral regurgitation. Whether TMVr is cost-effective compared with GDMT in this population is unknown. METHODS: We used data from the COAPT trial to perform a formal patient-level economic analysis of TMVr+GDMT versus GDMT alone for patients with heart failure and 3 to 4+ secondary mitral regurgitation from the perspective of the US healthcare system. Costs for the index TMVr hospitalization were assessed using a combination of resource-based accounting and hospital billing data (when available). Follow-up medical care costs were estimated on the basis of medical resource use collected during the COAPT trial. Health utilities were estimated for all patients at baseline and 1, 6, 12, and 24 months with the Short Form Six-Dimension Health Survey. RESULTS: Initial costs for the TMVr procedure and index hospitalization were $35 755 and $48 198, respectively. Although follow-up costs were significantly lower with TMVr compared with GDMT ($26 654 versus $38 345; P=0.018), cumulative 2-year costs remained higher with TMVr because of the upfront cost of the index procedure ($73 416 versus $38 345; P<0.001). When in-trial survival, health utilities, and costs were modeled over a lifetime horizon, TMVr was projected to increase life expectancy by 1.13 years and quality-adjusted life-years by 0.82 years at a cost of $45 648, yielding a lifetime incremental cost-effectiveness ratio of $40 361 per life-year gained and $55 600 per quality-adjusted life-year gained. CONCLUSIONS: For symptomatic patients with heart failure and 3 to 4+ secondary mitral regurgitation, TMVr increases life expectancy and quality-adjusted life expectancy compared with GDMT at an incremental cost per quality-adjusted life-year gained that represents acceptable economic value according to current US thresholds. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01626079.

Trends in Utilization and Outcomes of Pulmonary Artery Catheterization in Heart Failure With and Without Cardiogenic Shock.

BACKGROUND: The pulmonary artery catheter (PAC) has been used in a wide range of critically ill patients. It is not indicated for routine care of heart failure (HF), but its role in cardiogenic shock (CS) has not been clarified. METHODS AND RESULTS: We conducted a retrospective cohort study with the use of the National Inpatient Sample and identified a total of 9,431,944 adult patients admitted from 2004 to 2014 with the primary diagnosis of HF (n = 8,516,528) or who developed CS (n = 915,416) during the index hospitalization. Overall, patients with PAC had increased hospital costs, length of stay, and mechanical circulatory support use. In patients with HF, PAC use was associated with higher mortality (9.9% vs 3.3%, OR 3.96; P < .001) but the excess of mortality declined over time. In those with CS, PAC was associated with lower mortality (35.1% vs 39.2%, OR 0.91; P < .001) and in-hospital cardiac arrest (14.9% vs 18.3%, OR 0.77; P < .001); this paradox persisted after propensity score matching. CONCLUSIONS: The use of PAC in CS has decreased from 2004 to 2014, although its use is now associated with improved outcomes, which may reflect better selection of patients or better use of the information to guide therapies. Our data provide reassurance that PAC use in this population is an appropriate strategy.

Risk Assessment in Patients with a Left Ventricular Assist Device Across INTERMACS Profiles Using Bayesian Analysis.

Current risk stratification models to predict outcomes after a left ventricular assist device (LVAD) are limited in scope. We assessed the performance of Bayesian models to stratify post-LVAD mortality across various International Registry for Mechanically Assisted Circulatory Support (INTERMACS or IM) Profiles, device types, and implant strategies. We performed a retrospective analysis of 10,206 LVAD patients recorded in the IM registry from 2012 to 2016. Using derived Bayesian algorithms from 8,222 patients (derivation cohort), we applied the risk-prediction algorithms to the remaining 2,055 patients (validation cohort). Risk of mortality was assessed at 1, 3, and 12 months post implant according to disease severity (IM profiles), device type (axial versus centrifugal) and strategy (bridge to transplantation or destination therapy). Fifteen percentage (n = 308) were categorized as IM profile 1, 36% (n = 752) as profile 2, 33% (n = 672) as profile 3, and 15% (n = 311) as profile 4-7 in the validation cohort. The Bayesian algorithms showed good discrimination for both short-term (1 and 3 months) and long-term (1 year) mortality for patients with severe HF (Profiles 1-3), with the receiver operating characteristic area under the curve (AUC) between 0.63 and 0.74. The algorithms performed reasonably well in both axial and centrifugal devices (AUC, 0.68-0.74), as well as bridge to transplantation or destination therapy indication (AUC, 0.66-0.73). The performance of the Bayesian models at 1 year was superior to the existing risk models. Bayesian algorithms allow for risk stratification after LVAD implantation across different IM profiles, device types, and implant strategies.

First granted example of novel FDA trial design under Expedited Access Pathway for premarket approval: BeAT-HF.

BACKGROUND: The Food and Drug Administration (FDA) initiated the Expedited Access Pathway (EAP) to accelerate approval of novel therapies targeting unmet needs for life-threatening conditions. EAP allows for the possibility of initial FDA approval using intermediate end points with postapproval demonstration of improved outcomes. OBJECTIVE: Describe the EAP process using the BeAT-HF trial as a case study. METHODS: BeAT-HF will examine the safety and effectiveness of baroreflex activation therapy (BAT) in heart failure patients with reduced ejection fraction using an Expedited and Extended Phase design. In the Expedited Phase, BAT plus guideline-directed medical therapy (GDMT) will be compared at 6 months postimplant to GDMT alone using 3 intermediate end points: 6-minute hall walk distance, Minnesota Living with Heart Failure Questionnaire, and N-terminal pro-B-type natriuretic peptide. The rate of heart failure morbidity and cardiovascular mortality will be compared between the arms to evaluate early trending using predictive probability modeling. Sample size of 264 patients randomized 1:1 to BAT + GDMT versus GDMT alone provides 81% power for the Expedited Phase intermediate end points. For the Extended Phase, the heart failure morbidity and cardiovascular mortality end point is based on an expected event rate of 0.4 events/patient/year in the GDMT arm. With an adaptive sample size selection design for robustness to inaccurate assumptions, a sample size of 480-960 randomized patients followed ≥2 years allows detecting a 30% reduction in the primary end point with a power of 97.5%. CONCLUSION: Through a unique collaboration with FDA under the EAP, the BeAT-HF trial design allows for the possibility of approval of BAT, initially for symptom relief and subsequently for outcomes improvement.

Cardiovascular Outcomes Assessment of the MitraClip in Patients with Heart Failure and Secondary Mitral Regurgitation: Design and rationale of the COAPT trial.

BACKGROUND: Patients with heart failure (HF) and symptomatic secondary mitral regurgitation (SMR) have a poor prognosis, with morbidity and mortality directly correlated with MR severity. Correction of isolated SMR with surgery is not well established in this population, and medical management remains the preferred approach in most patients. The Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial was designed to determine whether transcatheter mitral valve (MV) repair with the MitraClip device is safe and effective in patients with symptomatic HF and clinically significant SMR. STUDY DESIGN: The COAPT trial is a prospective, randomized, parallel-controlled, open-label multicenter study of the MitraClip device for the treatment of moderate-to-severe (3+) or severe (4+) SMR (as verified by an independent echocardiographic core laboratory) in patients with New York Heart Association class II-IVa HF despite treatment with maximally tolerated guideline-directed medical therapy (GDMT) who have been determined by the site's local heart team as not appropriate for MV surgery. A total of 614 eligible subjects were randomized in a 1:1 ratio to MV repair with the MitraClip plus GDMT versus GDMT alone. The primary effectiveness end point is recurrent HF hospitalizations through 24 months, analyzed when the last subject completes 12-month follow-up, powered to demonstrate superiority of MitraClip therapy. The primary safety end point is a composite of device-related complications at 12 months compared to a performance goal. Follow-up is ongoing, and the principal results are expected in late 2018. CONCLUSIONS: HF patients with clinically significant SMR who continue to be symptomatic despite optimal GDMT have limited treatment options and a poor prognosis. The randomized COAPT trial was designed to determine the safety and effectiveness of transcatheter MV repair with the MitraClip in symptomatic HF patients with moderate-to-severe or severe SMR.

An early analysis of cost-utility of baroreflex activation therapy in advanced chronic heart failure in Germany.

BACKGROUND: This study aimed to evaluate cost-utility of baroreflex activation therapy (BAT) using the Barostim neo™ device (CVRx Inc., Minneapolis, MN, USA) compared with optimized medical management in patients with advanced chronic heart failure (NYHA class III) who were not eligible for treatment with cardiac resynchronization therapy, from a statutory health insurance perspective in Germany over a lifetime horizon. METHODS: A decision analytic model was developed using the combination of a decision tree and the Markov process. The model included transitions between New York Heart Association (NYHA) health states, each of which is associated with a risk of mortality, hospitalization, cost, and quality of life. The effectiveness of BAT was projected through relative risks for mortality (obtained by application of patient-level data to the Meta-analysis Global Group in Chronic Heart Failure risk prediction model) and hospitalization owing to worsening of heart failure (obtained from BAT Randomized Clinical Trial). All patients were in NYHA class III at baseline. RESULTS: BAT led to an incremental cost of €33,185 (95% credible interval [CI] €24,561-38,637) and incremental benefits of 1.78 [95% CI 0.45-2.71] life-years and 1.19 [95% CI 0.30-1.81] quality-adjusted life-years (QALYs). This resulted in an incremental cost-effectiveness ratio of €27,951/QALY (95% CI €21,357-82,970). BAT had a 59% probability of being cost-effective at a willingness-to-pay threshold of €35,000/QALY (but 84% at a threshold of €52,000/QALY). CONCLUSIONS: BAT can be cost-effective in European settings in those not eligible for cardiac resynchronization therapy among patients with advanced heart failure.

Pulmonary Artery Pressure-Guided Heart Failure Management Reduces 30-Day Readmissions.

BACKGROUND: This study examines the impact of pulmonary artery pressure-guided heart failure (HF) care on 30-day readmissions in Medicare-eligible patients. METHODS AND RESULTS: The CardioMicroelectromechanical system (CardioMEMS) Heart Sensor Allows Monitoring of Pressures to Improve Outcomes in New York Heart Association Class III Heart Failure Patients (CHAMPION) Trial included 550 patients implanted with a permanent MEMS-based pressure sensor in the pulmonary artery. Subjects were randomized to a treatment group (uploaded pressures were made available to investigators) or a control group (uploaded pressures were not made available to investigators). This analysis focuses on the 245 Medicare-eligible subjects for whom compliance with daily transmissions was 93% compared with 88% for the overall population. Medications were changed more often in the treatment group using pressure information compared with the control group using symptoms and daily weights alone. During the 515 days follow-up after implant, the overall rate of HF hospitalizations was 49% lower in the treatment group (60 HF hospitalizations, 0.34 events/patient-year) compared with control (117 HF hospitalizations, 0.67 events/patient-year; hazard ratio 0.51, 95% confidence interval 0.37-0.70; P<0.0001). Of the 177 HF hospitalizations, 155 qualified as an index HF hospitalization. All-cause 30-day readmissions were 58% lower in the treatment group (0.07 events/patient-year) compared with 0.18 events/patient-year in the control group (hazard ratio 0.42, 95% confidence interval 0.22-0.80; P=0.0080). CONCLUSIONS: Pulmonary artery pressure-guided HF management in Medicare-eligible patients led to a 49% reduction in total HF hospitalizations and a 58% reduction in all-cause 30-day readmissions. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00531661.