BACKGROUND:The authors report the intention-to-treat results for the C-GUARDIANS (Safety and Efficacy of the CGuard™ Carotid Stent System in Carotid Artery Stenting) pivotal trial in carotid artery stenting patients considered high risk for carotid endarterectomy, treated with this novel stent and followed for 1 year. OBJECTIVES:The authors sought to evaluate the safety and efficacy of the MicroNet-covered stent in treating patients with significant carotid stenosis at high risk of adverse events from carotid endarterectomy. METHODS:The trial is a prospective, multicenter, single-arm trial (NCT04900844). The primary endpoint was a composite of the incidence of death, all stroke, and myocardial infarction (DSMI) through 30 days postprocedure, and ipsilateral stroke from 31 to 365 days postprocedure. Secondary endpoints included the incidence of DSMI and of each individual component through 30 days, as well as the incidence of ipsilateral strokes through 30-day and 1-year follow-up. All events were adjudicated by an independent clinical events committee. RESULTS:Between July 2021 and June 2023, 316 patients with asymptomatic ≥80% or symptomatic ≥50% carotid lesions were treated with this novel stent at 24 sites in the United States and European Union using approved embolic protection systems. The DSMI rate through 30 days was 0.95% (3/316). DSMI at 30 days and ipsilateral stroke at 1 year was 1.93% (6/296). Target lesion revascularization through 1 year was 1.0% (3/299). CONCLUSIONS:The C-GUARDIAN trial demonstrated low rates of DSMI through 30 days, and ipsilateral stroke through 1 year. No unexpected adverse device effects or unexpected serious adverse device effects were reported. These results demonstrate that carotid artery stenting with this novel stent is safe, effective and durable, and supports the potential neuroprotective properties of this unique micro mesh-covered stent.

BACKGROUND:Growing evidence shows a major outcome impact and undertreatment of tricuspid regurgitation (TR), but large and comprehensive contemporary reports of management and outcome at the nationwide level are lacking.METHODS:We gathered all consecutive patients admitted with a diagnosis of likely functional TR in 2014-2015 in France from the Programme de Médicalisation des Systèmes d'Information national database and collected rate of surgery, in-hospital mortality, 1-year mortality, or heart failure (HF) readmission rates.RESULTS:In 2014-2015, 17,676 consecutive patients (75 ± 14 years of age, 51% female) were admitted with a TR diagnosis. Charlson index was ≥ 2 in 56% of the population and 46% presented with HF. TR was associated with prior cardiac surgery, ischemic/dilated cardiomyopathy, or mitral regurgitation in 73% of patients. Only 10% of TR patients overall and 67% of those undergoing mitral valve surgery received a tricuspid valve intervention. Among the 13,654 (77%) conservatively managed patients, in-hospital mortality, 1-year mortality, and 1-year mortality or HF readmission rates were 5.1%, 17.8%, and 41%, respectively, overall, and 5.3%,17.2%, and 37%, respectively, among those with no underlying medical conditions (8-fold higher than predicted for age and gender).CONCLUSIONS:This nationwide cohort of patients admitted with TR included elderly patients with frequent comorbidities/underlying cardiac diseases. In patients conservatively managed, mortality and morbidity were considerably high over a short time span. Despite this poor prognosis, only 10% of patients underwent a tricuspid valve intervention. These nationwide data showing a considerable risk and potential underuse of treatment highlight the critical need to develop strategies to improve the management and outcomes of TR patients.

Abstract Aims Heart failure (HF) carries a poor prognosis, and the impact of concomitant mitral regurgitation (MR) is not well understood. This analysis aimed to estimate the incremental effect of MR in patients newly diagnosed with HF. Methods and results Data from the IBM® MarketScan® Research Databases were analysed. Included patients had at least one inpatient or two outpatient HF claims. A 6 month post‐period after HF index was used to capture MR diagnosis and severity. HF patients were separated into three cohorts: without MR (no MR), not clinically significant MR (nsMR), and significant MR (sMR). Time‐to‐event analyses were modelled to estimate the clinical burden of disease. The primary outcome was a composite endpoint of death or cardiovascular (CV)‐related admission. Secondary outcomes were death and CV hospitalization alone. All models controlled for baseline demographics and co‐morbidities. Patients with sMR were at significantly higher risk of either death or CV admission compared with patients with no MR [hazard ratio (HR) 1.26; 95% confidence interval (CI) 1.15–1.39]. When evaluating death alone, patients with sMR had significantly higher risk of death (HR 1.24; 95% CI 1.08–1.43) compared with patients with no MR. When evaluating CV admission alone, patients with MR were at higher risk of hospital admission vs. patients with no MR, and the magnitude was dependent upon the MR severity: sMR (HR 1.55; 95% CI 1.38–1.74) and nsMR (HR 1.23; 95% CI 1.08–1.40). Conclusions Evidence of MR in retrospective claims significantly increases the clinical burden of incident HF patients. Time to death and CV hospitalizations are increased when MR is clinically significant.

Background Although US recent data suggest that mitral regurgitation (MR) is severely undertreated and carries a poor outcome, population‐based views on outcome and management are limited. We aimed to define the current treatment standards, clinical outcomes, and costs related to MR at the nationwide level. Methods and Results In total, 107 412 patients with MR were admitted in France in 2014 to 2015. Within 1 year, 8% were operated and 92% were conservatively managed and constituted our study population (68% primary MR and 32% secondary MR). The mean age was 77±15 years; most patients presented with comorbidities. In‐hospital and 1‐year mortality rates were 4.1% and 14.3%, respectively. Readmissions were common (63% at least once and 37% readmitted ≥2 times). Rates of 1‐year mortality or all‐cause readmission and 1‐year mortality or heart failure readmission were 67% and 34%, respectively, and increased with age, Charlson index, heart failure at admission, and secondary MR etiology; however, the event rate remained notably high in the primary MR subset (64% and 28%, respectively). The mean costs of hospital admissions and of readmissions were 5345±6432 and 10 080±10 847 euros, respectively. Conclusions At the nationwide level, MR was a common reason for admission and affected an elderly population with frequent comorbidities. Less than 10% of patients underwent a valve intervention. All subsets of patients who were conservatively managed incurred high mortality and readmissions rates, and MR represented a major societal burden with an extrapolated annual cost of 350 to 550 million euros (390–615 million US dollars). New strategies to improve the management and outcomes of patients with both primary and secondary MR are critical and warranted.

This study aimed to quantify survival rates for patients with tricuspid regurgitation (TR) using real-world data. Several clinical conditions are associated with TR, including heart failure (HF), other valve disease (OVD), right-sided heart disease (RSHD), and others that impact mortality. Optum data from January 1, 2007, through December 31, 2018 included patients age ≥18 years with TR and 12 months of continuous health plan enrollment before TR. Exclusion criteria were end-stage renal disease or known/primary organ pathology. Cohorts were created hierarchically: (1) TR with HF; (2) TR with OVD (no HF); (3) TR with RSHD only (no OVD or HF); (4) TR only. Survival was estimated using a Cox hazard model with an interaction term for TR severity and adjusted for patient demographics and Elixhauser co-morbidities. A total of 33,686 met study inclusion (1) TR with HF (26.6%); (2) TR with OVD (36.7%); (3) TR with RSHD only (17.1%); (4) TR only (19.6%). TR patients (regardless of severity) with HF, OVD or RSHD had an increased risk of mortality compared with patients with TR alone. TR severity was also significantly associated (hazard ratio = 1.33; p = 0.0002) with an increased risk of all-cause mortality. In conclusion, TR severity is significantly associated with an increased risk of all-cause mortality, independent of associated conditions including HF, OVD, or RSHD. In patients with severe TR, the mortality risk is most pronounced for patients who had RSHD without HF or OVD before their TR diagnosis.

Aim: This study evaluated how the presence of right-sided heart disease (RSHD), other valve disease (OVD) and heart failure (HF) impacts healthcare utilization in patients with tricuspid valve disease (tricuspid regurgitation [TR]). Materials & methods: Of the 33,686 patients with TR: 6618 (19.6%) had TR-only; 8952 (26.6%) had TR with HF; 12,367 (36.7%) had TR with OVD but no HF; and 5749 (17.1%) had TR with RSHD only. Results: The presence of RSHD, OVD or HF in patients with TR was independently associated with increased annualized hospitalizations, hospital days and costs relative to patients with TR alone. Conclusion: All three co-morbidities were associated with increased healthcare utilization, with HF showing the greatest impact across all measures.

Aim: This study aimed to quantify the healthcare burden of clinically significant tricuspid regurgitation (TR) in patients with and without heart failure (HF).Materials and Methods: Data were from the IBM MarketScan Research Databases from October 2011 to September 2016. Eligible patients met the following inclusion criteria: age ≥18 with a TR diagnosis, 12 months pre (baseline), and 6 months post (landmark) medical enrollment. The landmark period was used to categorize TR severity, defined as a record of pulmonary hypertension with ascites, lower extremity edema or hepatic insufficiency, or tricuspid valve surgery. Cohorts were defined based on TR etiology and severity: (1) no HF and no clinically significant TR; (2) HF with no clinically significant TR; (3) no HF with clinically significant TR; and (4) HF with clinically significant TR. Outcomes of interest were all-cause hospitalizations, hospital days, and expenditures. Multivariable models were fit for each of the annualized outcomes and adjusted for patient demographics, comorbidities, and other concomitant valve diseases.Results: There were 92,994 patients eligible for analysis. Patients with no HF and no clinically significant TR had the annualized healthcare burden of 0.20 all-cause hospitalizations (approximately one inpatient hospitalization every 5 years), 1.07 hospital days, and $17,478 in expenditures. The presence of clinically significant TR, alone or with HF, significantly increased healthcare utilization and expenditures. For patients with no HF with clinically significant TR, the annualized economic burden increased to 0.41 all-cause hospitalizations, 3.13 hospital days, and $29,985 in expenditures. For patients with HF and clinically significant TR, the annualized economic burden was even greater with 0.59 all-cause hospitalizations, 4.31 hospital days, and $42,255 in expenditures.Conclusion: The presence of clinically significant TR is associated with an increase in healthcare utilization and expenditures, irrespective of the presence of HF.

More evidence is needed to quantify the association between tricuspid regurgitation (TR) and mortality in patients with heart failure (HF).

Objectives Unbiased information regarding the surgical management of patients with mitral regurgitation (MR) at the nationwide level are scarce and mainly US-based. The Programme de Médicalisation des Systèmes d’Information, a mandatory national database, offers the unique opportunity to assess the presentation and outcomes of all consecutive mitral valve (MV) surgeries performed in France in the contemporary era. Methods We collected all MV surgeries performed for MR in France in 2014–2016. MR aetiology was classified as degenerative (DMR), secondary (SMR) or Other (rheumatic or congenital disease and infective endocarditis). Results During the 3-year period, 18 167 MV surgeries were performed in France (55% repair and 45% replacement; 52% isolated). Age was 66±12 years and 59% were male. Aetiology was DMR in 42%, SMR in 16% and other in 42% including 19% with uncertain aetiologies. Overall, in-hospital mortality was 6.5% and increased with age, female gender, Charlson Comorbidity Index, type of surgery (replacement vs repair), associated surgery (combined vs isolated) and MR aetiology (all p<0.01). In-hospital mortality and rate of death/readmission for heart failure (HF) at 1 year were 3.4% and 13%, respectively for DMR (2.4% and 11% for isolated DMR) and 7.8% and 27%, respectively for SMR (5.5% and 23% for isolated SMR). Repair rate was 55% overall, 68% in DMR and 72% for isolated DMR surgery (70% of all DMR). Repair rates decreased with age, Charlson Comorbidity Index and female sex (all p<0.0001). Conclusion In this cross-sectional contemporary prospective nationwide database, in-hospital mortality and 1 year rate of death and HF readmission were considerable overall and in all subsets. Repair rates were suboptimal overall especially in the elderly and women subsets. These results underline the need to develop strategies to improve management and outcomes of patients with both DMR and SMR.

This research showcases the development and validation of a therapeutic intensity score (TIS) for medically managed heart failure (HF) patients in claims data. This study used data from both Truven Health MarketScan Commercial Claims and Medicare Supplemental Databases and Optum Integrated Claims/EMR Databases. Patients had 1 inpatient or 2 outpatient claims for HF with a 6-month pre-period (baseline). A 6-month post-period (landmark) after HF index was used to allow for medication regimen to stabilize. Following the landmark period, patients were required to have 12 months of continuous medical and prescription drug plan enrollment with at least two records of HF medication refills. TIS was calculated based on patient's pharmacologic regimen. The drug categories included: ACE inhibitors, angiotensin receptor blockers, beta blockers, and diuretics among others. Within each category, each fill was assigned 1, 2, or 3 points depending on dose. The TIS algorithm was developed using Truven data and then validated using Optum data. The TIS in Optum was calculated and then evaluated for association with ejection fraction, severity based on New York Heart Association Functional (NYHA) classification: mild (score of 1 or 2) versus moderate/severe (score of 3 or 4), physician notes, and a published machine learning algorithm based on BNP, ejection fraction and weight. TIS distributions were similar across Truven and Optum: Truven (mean=6.1, median=6, SD=3.48); Optum (mean=6.9, median=6, SD=3.59). For HF patients in Optum, TIS was correlated with ejection fraction (-0.158; p<.0001) and NYHA (.055; p =.0141). One-way ANOVAs also indicated significant relationships between TIS and severity (mild, moderate, severe) based on the physician notes (F=3.35, p<.0361) and the machine learning algorithm (F=37.02, p<.0001). In retrospective administrative claims analyses, where clinical data such as physician notes or lab values are not available, a validated TIS can be a useful proxy for HF severity.

The authors report the procedural and 30-day results of the PASCAL Transcatheter Valve Repair System (Edwards Lifesciences, Irvine, California) in patients with mitral regurgitation (MR) enrolled in the multicenter, prospective, single-arm CLASP study. Severe MR may lead to symptoms, impaired quality of life, and reduced functional capacity when untreated. Eligible patients had grade 3+ or 4+ MR despite optimal medical therapy and were deemed appropriate for the study by the local heart team. All outcomes were assessed through 30 days post-procedure. Major adverse events (MAEs) were adjudicated by an independent clinical events committee, and echocardiographic images were assessed by a core laboratory. The primary safety endpoint was the rate of MAEs at 30 days. Between June 2017 and September 2018, 62 patients with grade 3+ or 4+ MR were enrolled. The mean age was 76.5 years, and 51.6% of patients were in New York Heart Association functional class III or IV, with 56% functional, 36% degenerative, and 8% mixed MR etiology. At 30 days, the MAE rate was 6.5%, with an all-cause mortality rate of 1.6% and no occurrence of stroke; 98% had MR grade ≤2+, with 86% with MR grade ≤1+ (p < 0.0001); and 85% were in New York Heart Association functional class I or II (p < 0.0001). Six-minute walk distance improved by 36 m (p = 0.0018), and Kansas City Cardiomyopathy Questionnaire and EQ-5D scores improved by 17 (p < 0.0001) and 10 (p = 0.0004) points, respectively. The PASCAL repair system showed feasibility and acceptable safety in the treatment of patients with grade 3+ or 4+ MR. MR severity, irrespective of etiology, was significantly reduced and accompanied by clinically and statistically significant improvements in functional status, exercise capacity, and quality of life. (The CLASP Study Edwards PASCAL Transcatheter Mitral Valve Repair System Study; NCT03170349 )

This analysis estimates the incremental burden of functional mitral regurgitation (FMR) in time to hospitalization or death for incident heart failure (HF) patients. Data from the Truven Health MarketScan between October 2011 and September 2016 was used. Patients with at least 1 inpatient or 2

Aim: This study sought to quantify the healthcare burden of Medicare patients with clinically significant mitral regurgitation (sMR). Materials & methods: Proxy definitions were used for sMR, including MR surgery, atrial fibrillation, pulmonary hypertension or >2 echocardiograms. Results: In this study, 11,173 patients had significant degenerative MR (sDMR); 25,402 had significant functional MR (sFMR); and 12,232 had significant uncharacterized MR (sUMR). Patients with sFMR (18,880) were more likely to be hospitalized and present to the emergency department compared with patients with sDMR (9,795) or sUMR (10,587). Annual healthcare expenditures for sMR patients were: US$29,328 for sFMR; US$17,112 for sUMR; and US$12,870 for sDMR. Conclusion: Novel therapeutic interventions merit further evaluation to reduce the substantial healthcare burden of sMR in the Medicare population.

The objective of this study was to quantify the financial healthcare burden of mitral regurgitation (MR) on medically managed heart failure (HF) patients. Data from the Truven Health MarketScan Commercial Claims and Medicare Supplemental Databases were analyzed. Included patients had a minimum of 1 inpatient or 2 outpatient claims for HF with a 6-month preperiod (baseline). A 6-month postperiod (landmark) after HF index was used to capture MR diagnosis and severity. Following the landmark period, patients had to have 12 months of continuous medical and prescription drug plan enrollment with at least 2 records of HF medication refills. A therapeutic intensity score was calculated based on HF medication usage. Medically managed HF patients were separated into 3 cohorts: without MR (no MR), insignificant MR (iMR), and significant MR (sMR). Healthcare utilization and all-cause expenditures were modeled to quantify the burden of MR. All models controlled for baseline demographics, co-morbid conditions, and HF therapeutic intensity. Medically managed incident HF patients with sMR had significantly more hospital days (1.91 vs 1.72 days; p = 0.0096) and annual expenditures ($23,988 vs $21,530; p < 0.0001) compared with no MR patients. No differences were identified when comparing iMR and no MR. When evaluating HF admissions, sMR patients had an estimated 50% greater HF admissions rate (0.036 vs 0.024; p < 0.0001) compared with no MR patients. Additionally, HF admits for iMR were 23% more than those with no MR (0.029 vs 0.024; p = 0.0064). In conclusion, evidence of MR in retrospective claims significantly increases the healthcare impact of medically managed HF patients. Both utilization and financial burden is more pronounced when MR is clinically significant. (C) 2019 Elsevier Inc. All rights reserved.

The development of treatments for heart failure (HF) is challenged by burdensome clinical trials. Reducing the need for extensive data collection and increasing opportunities for data compatibility between trials may improve efficiency and reduce resource burden. The Heart Failure Collaboratory (HFC) multi-stakeholder consortium sought to create a lean case report form (CRF) for use in HF clinical trials evaluating cardiac devices. The HFC convened patients, clinicians, clinical researchers, the U.S. Food and Drug Administration (FDA), payers, industry partners, and statisticians to create a consensus core CRF. Eight recent clinical trial CRFs for the treatment of HF from 6 industry partners were analyzed. All CRF elements were systematically reviewed. Those elements deemed critical for data collection in HF clinical trials were used to construct the final, harmonized CRF. The original CRFs included 176 distinct data items covering demographics, vital signs, physical examination, medical history, laboratory and imaging testing, device therapy, medications, functional and quality of life assessment, and outcome events. The resulting, minimally inclusive CRF device contains 75 baseline data items and 6 events, with separate modular additions that can be used depending on the additional detail required for a particular intervention. The consensus electronic form is now freely available for use in clinical trials. Creation of a core CRF is important to improve clinical trial efficiency in HF device development in the United States. This living document intends to reduce clinical trial administrative burden, increase evidence integrity, and improve comparability of clinical data between trials.