Transcatheter aortic valve implantation in patients with high-risk symptomatic native aortic regurgitation (ALIGN-AR): a prospective, multicentre, single-arm study.

BACKGROUND: Surgery remains the only recommended intervention for patients with native aortic regurgitation. A transcatheter therapy to treat patients at high risk for mortality and complications with surgical aortic valve replacement represents an unmet need. Commercial transcatheter heart valves in pure aortic regurgitation are hampered by unacceptable rates of embolisation and paravalvular regurgitation. The Trilogy transcatheter heart valve (JenaValve Technology, Irvine, CA, USA) provides a treatment option for these patients. We report outcomes with transfemoral transcatheter aortic valve implantation (TAVI) in patients with pure aortic regurgitation using this dedicated transcatheter heart valve. METHODS: The ALIGN-AR trial is a prospective, multicentre, single-arm study. We recruited symptomatic patients (aged ≥18 years) with moderate-to-severe or severe aortic regurgitation at high risk for mortality and complications after surgical aortic valve replacement at 20 US sites for treatment with the Trilogy transcatheter heart valve. The 30-day composite primary safety endpoint was compared for non-inferiority with a prespecified performance goal of 40·5%. The primary efficacy endpoint was 1-year all-cause mortality compared for non-inferiority with a performance goal of 25%. This trial is registered with ClinicalTrials.gov, NCT04415047, and is ongoing. FINDINGS: Between June 8, 2018, and Aug 29, 2022, we screened 346 patients. We excluded 166 (48%) patients and enrolled 180 (52%) patients with symptomatic aortic regurgitation deemed high risk by the heart team and independent screening committee assessments. The mean age of the study population was 75·5 years (SD 10·8), and 85 (47%) were female, 95 (53%) were male, and 131 (73%) were White. Technical success was achieved in 171 (95%) patients. At 30 days, four (2%) deaths, two (1%) disabling strokes, and two (1%) non-disabling strokes occurred. Using standard Valve Academic Research Consortium-2 definitions, the primary safety endpoint was achieved, with events occurring in 48 (27% [97·5% CI 19·2-34·0]) patients (pnon-inferiority<0·0001), with new pacemaker implantation in 36 (24%) patients. The primary efficacy endpoint was achieved, with mortality in 14 (7·8% [3·3-12·3]) patients at 1 year (pnon-inferiority<0·0001). INTERPRETATION: This study shows the safety and effectiveness of treating native aortic regurgitation using a dedicated transcatheter heart valve to treat patients with symptomatic moderate-to-severe or severe aortic regurgitation who are at high risk for mortality or complications after surgical aortic valve replacement. The observed short-term clinical and haemodynamic outcomes are promising as are signs of left ventricular remodelling, but long-term follow-up is necessary. FUNDING: JenaValve Technology.

Cardiac Computed Tomography Angiography Anatomical Characterization of Patients Screened for a Dedicated Transfemoral Transcatheter Valve System for Primary Aortic Regurgitation.

Background: Cardiac computed tomography angiography was used to identify anatomical characteristics of the aortic root in patients with severe aortic regurgitation (AR) as compared to those with aortic stenosis (AS) to judge feasibility of transcatheter aortic valve replacement (TAVR) with the JenaValve Trilogy system. Methods: Cardiac computed tomography angiography was performed prior to planned TAVR for 107 patients with severe AR and 92 patients with severe AS. Measurements related to aortic root and coronary artery anatomy were obtained and compared between groups. Perimeter >90 mm and aortic annulus angle â€‹>70 degrees were defined as the theoretical exclusion criteria for TAVR. A combination of sinus of Valsalva diameter <30 mm and coronary height <12 mm was defined as high risk for coronary occlusion. Results: The mean age of patients in the AR group was 74.9 ± 11.2 years, 46% were women, and the mean Society of Thoracic Surgeons risk score for mortality was 3.6 ± 2.1. Comparatively, the mean age of patients in the AS group was 82.3 ± 5.53 years, 65% were women, and the mean Society of Thoracic Surgeonsrisk score was 5.5 ± 3.3. Annulus area, perimeter, diameter, and angle were larger in patients with severe AR. Sinus of Valsalva diameters and heights were larger in patients with severe AR. More AR patients were excluded based on perimeter (14 vs. 2%) and annulus angle (6 vs. 1%). More AS patients exhibited high-risk anatomy for left main coronary occlusion (21 vs. 7%) and right coronary occlusion (14 vs. 3%). The maximum dimension of the ascending aorta was larger in patients with severe AR (39 vs. 35 mm). The percentage of referred AR patients with significant aortopathy requiring surgical intervention was very low (only 1 AR patient with ascending aorta diameter >5.5 cm). Conclusions: A significantly larger proportion of patients with severe AR are excluded from TAVR as compared to AS due to large aortic annulus size and steep annulus angulation. By far the most prevalent excluding factor is aortic annulus size, with fewer patients excluded due to angulation. AR patients have lower-risk anatomy for coronary occlusion. Larger transcatheter valve sizes and further delivery system modifications are required to treat a larger proportion of AR patients.

The Jarvik 2000 Left Ventricular Assist Device: Results of the United States Bridge to Transplant Trial.

The Jarvik 2000 bridge to transplant investigational device exemption study was a multicentered, prospective study of 150 UNOS status I patients implanted with the Jarvik 2000 between 2005 and 2012. During the study period, there were numerous modifications of the system that included converting from pin to cone bearings. Results were analyzed for three cohorts: total (n = 150), pin (n = 128), and cone (n = 22). Baseline demographics included age (52 ± 13), gender (79% male), size (BSA 1.98), and etiology (37% idiopathic dilated cardiomyopathy; 43% Ischemic). Seventy percent of patients were either INTERMACS 1 or 2. The primary endpoint-defined as successful transplantation or listing at 180 days (prespecified at 65%; 95% lower CI: 57%)-was successfully achieved for the total cohort (67.3%; 95% CI: 59.5%-74.3%; p = 0.006). In subgroup analysis of the more contemporary, cone-bearing group, the primary endpoint was met in 91% (95% CI: 72%-97.5%; p = 0.001). Compared with pin patients, cone-bearing patients had less hemolysis as well as decreased end-organ dysfunction. Functional and quality of life scores improved after implantation independent type of bearing. In conclusion, despite a particularly sick patient population, the Jarvik 2000 was shown to be effective in supporting the advanced HF patient.

Impact of Race on Clinical Outcomes After Implantation With a Fully Magnetically Levitated Left Ventricular Assist Device: An Analysis From the MOMENTUM 3 Trial.

BACKGROUND: Heart failure disproportionately affects Black patients. Whether differences among race influence outcomes in advanced heart failure with use of a fully magnetically levitated continuous-flow left ventricular assist device remains uncertain. METHODS: We included 515 IDE (Investigational Device Exemption) clinical trial patients and 500 Continued Access Protocol patients implanted with the HeartMate 3 left ventricular assist device in the MOMENTUM 3 study (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3). Outcomes were compared between Black and White left ventricular assist device recipients for the primary end point of survival free of disabling stroke or reoperation to replace or remove a malfunctioning device at 2 years, overall survival, adverse events, 6-minute walk distance, and quality of life scores. RESULTS: Of 1015 HeartMate 3 patients, 675 were self-identified as White and 285 as Black individuals. The Black patient cohort was younger, more obese and with a history of hypertension, and more nonischemic cause of heart failure, relative to the White patient group. Black and White patients did not experience a difference in the primary end point (81.1% versus 77.9%; hazard ratio, 1.08 [95% CI, 0.76-1.54], P=0.6568). Black patients were at higher risk of adverse events (calculated as events per 100 patient-years), including bleeding (75.4 versus 63.5; P<0.0001), stroke (9.5 versus 7.2; P=0.0183), and hypertension (10.1 versus 3.2; P<0.0001). The 6-minute walk distance was not different at baseline and 6 months between the groups, however, the absolute change from baseline was greater for White patients (median: +183.0 [interquartile range, 42.0-335.3] versus +163.8 [interquartile range, 42.3-315.0] meters, P=0.01). The absolute quality of life measurement (EuroQoL group, 5-dimension, 5-level instrument visual analog scale) at baseline and 6 months was better in the Black patient group, but relative improvement from baseline to 6 months was greater in White patients (median: +20.0 [interquartile range, 5.0-40.0] versus +25.0 [interquartile range, 10.0-45.0]; P=0.0298). CONCLUSIONS: Although the survival free of disabling stroke or reoperation to replace/remove a malfunctioning device at 2 years with the HM 3 left ventricular assist device did not differ by race, Black HeartMate 3 patients experienced a higher morbidity burden and smaller gains in functional capacity and quality of life when compared with White patients. These findings require efforts designed to better understand and overcome these gaps through systematic identification and tackling of putative factors. Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02224755 and NCT02892955.

Pump Position Impacts HeartMate II Left Ventricular Assist Device Thrombosis.

The PREVENtion of HeartMate II pump Thrombosis through clinical management (PREVENT) study was a multicenter, prospective investigation to evaluate the rate of pump thrombosis (PT) with adoption of a uniform set of surgical and medical practices for left ventricular assist device implantation. We sought to quantify pump position at baseline and retrospectively define a pump position associated with poor clinical outcomes. Chest x-rays at baseline were prospectively obtained per protocol. Pump pocket depth, inflow cannula (IC) angle relative to the pump, and IC angle relative to the vertical were measured. Pumps falling in the tail-ends of the IC angle and pump pocket depth distributions were categorized as having an extreme pump position within the PREVENT study. Patients with extreme pump position had a significantly higher risk of confirmed and suspected PT, hemolysis, and elevated lactate dehydrogenase. In a multivariable analysis of survival free of confirmed PT, extreme pump position was an independent risk factor (hazard ratio = 3.6; 95% confidence interval = 1.5-8.9; p = 0.006) when adjusting for differences in pump speed and anticoagulation level. Our analysis shows that HeartMate II pump position at implant can significantly impact event-free survival and the incidence of adverse events at 6 months.

Warfarin and Aspirin Versus Warfarin Alone for Prevention of Embolic Events in Patients with a HeartMate II Left Ventricular Assist Device.

Acquired von Willebrand disease increases bleeding risk in patients implanted with a continuous-flow left ventricular assist device. Lower aspirin (ASA) doses decrease the risk of bleeding without an increased risk of embolic events. No published studies in the United States have compared the incidence of bleeding and thrombotic events between antithrombotic regimens with and without ASA. A single-center, retrospective analysis was conducted of adult patients implanted with a HeartMate II (HM II). Patients received warfarin and ASA 81 mg daily or warfarin alone. The primary end-point was a composite of death, bleeding events, and thrombotic events from the date of HM II implantation to first event or 18 months. Secondary end-points included the individual components of the primary end-point and the proportion of patients alive with HM II or transplanted. The Wilcoxon rank sum test and Fisher's exact test were used for statistical analysis. Of the 76 patients meeting inclusion criteria, 44 received warfarin and ASA and 32 received warfarin alone. Baseline characteristics were similar between groups. Warfarin alone was not associated with an increased risk of the primary composite outcome (53 vs. 59%, respectively, p = 0.64). No significant difference was observed in any bleeding event (34 vs. 43%, respectively, p = 0.48) nor any thrombotic event (9 vs. 11%, respectively, p = 1.00) with warfarin alone compared with warfarin and ASA. Elimination of antiplatelet therapy from the HM II antithrombotic regimen was associated with no significant difference in the composite outcome of bleeding events, thrombotic events, or death, nor the individual components of each end-point.

PREVENtion of HeartMate II Pump Thrombosis Through Clinical Management: The PREVENT multi-center study.

BACKGROUND: Recommended structured clinical practices including implant technique, anti-coagulation strategy, and pump speed management (PREVENT [PREVENtion of HeartMate II Pump Thrombosis Through Clinical Management] recommendations) were developed to address risk of early (<3 months) pump thrombosis (PT) risk with HeartMate II (HMII; St. Jude Medical, Inc. [Thoratec Corporation], Pleasanton, CA). We prospectively assessed the HMII PT rate in the current era when participating centers adhered to the PREVENT recommendations. METHODS: PREVENT was a prospective, multi-center, single-arm, non-randomized study of 300 patients implanted with HMII at 24 participating sites. Confirmed PT (any suspected PT confirmed visually and/or adjudicated by an independent assessor) was evaluated at 3 months (primary end-point) and at 6 months after implantation. RESULTS: The population included 83% men (age 57 years ± 13), 78% destination therapy, and 83% Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profile 1-3. Primary end-point analysis showed a confirmed PT of 2.9% at 3 months and 4.8% at 6 months. Adherence to key recommendations included 78% to surgical recommendations, 95% to heparin bridging, and 79% to pump speeds ≥9,000 RPMs (92% >8,600 RPMs). Full adherence to implant techniques, heparin bridging, and pump speeds ≥9,000 RPMs resulted in a significantly lower risk of PT (1.9% vs 8.9%; p < 0.01) and lower composite risk of suspected thrombosis, hemolysis, and ischemic stroke (5.7% vs 17.7%; p < 0.01) at 6 months. CONCLUSIONS: Adoption of all components of a structured surgical implant technique and clinical management strategy (PREVENT recommendations) is associated with low rates of confirmed PT.

Reduction in driveline infection rates: Results from the HeartMate II Multicenter Driveline Silicone Skin Interface (SSI) Registry.

BACKGROUND: During left ventricular assist device implantation, a surgical tunneling technique to keep the entire driveline (DL) velour portion in the subcutaneous tunnel, resulting in a silicone-skin interface (SSI) at the exit site, has been adopted by many centers. To assess long-term freedom from DL infection associated with this technique, a multicenter SSI registry was initiated. It was hypothesized that the modified tunneling technique is associated with at least 50% reduction in DL infection at 1 year post-implant compared with the velour-to-skin method used in the HeartMate II (HMII) Destination Therapy (DT) trial. METHODS: SSI is a retrospective and prospective registry of patients who have received the HMII device. Results are reported from the retrospective cohort, which consists of 200 patients who were implanted during the period 2009-2012 with the SSI tunneling method and on HMII support for at least 10 months at the time of enrollment. The prevalence and incidence of DL infection after left ventricular assist device implantation in the SSI retrospective cohort were determined and compared with a control group of 201 patients also on HMII support for at least 10 months from the HMII DT clinical trial who were implanted during the period 2007-2009 using the traditional method in which a small section of the velour portion of the DL was externalized. RESULTS: The 1-year and 2-year prevalence rates of DL infection were 9% and 19% in the SSI patient group compared with 23% and 35% in the control group (hazard ratio 0.49, 95% confidence interval 0.33-0.73, p < 0.001). The event-per-patient year was 0.11 and 0.22 for the SSI and control groups, respectively (p < 0.001). Based on a multivariate analysis, age and DL exit side were the only independent variables associated with DL infection. Effects of management changes over the eras were not studied and could have contributed to the findings. CONCLUSIONS: These results suggest that leaving the entire DL velour portion below the skin is associated with 50% reduction in DL infection compared with results from the HMII DT trial.

Resource use trajectories for aged medicare beneficiaries with complex coronary conditions.

OBJECTIVE: To use coronary revascularization choice to illustrate the application of a method simulating a treatment's effect on subsequent resource use. DATA SOURCES: Medicare inpatient and outpatient claims from 2002 to 2008 for patients receiving multivessel revascularization for symptomatic coronary disease in 2003-2004. STUDY DESIGN: This retrospective cohort study of 102,877 beneficiaries assessed survival, days in institutional settings, and Medicare payments for up to 6 years following receipt of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). METHODS: A three-part estimator designed to provide robust estimates of a treatment's effect in the setting of mortality and censored follow-up was used. The estimator decomposes the treatment effect into effects attributable to survival differences versus treatment-related intensity of resource use. PRINCIPAL FINDINGS: After adjustment, on average CABG recipients survived 23 days longer, spent an 11 additional days in institutional settings, and had cumulative Medicare payments that were $12,834 higher than PCI recipients. The majority of the differences in institutional days and payments were due to intensity rather than survival effects. CONCLUSIONS: In this example, the survival benefit from CABG was modest and the resource implications were substantial, although further adjustments for treatment selection are needed.

Disappearing and reappearing differences in drug-eluting stent use by race.

RATIONALE, AIMS AND OBJECTIVES: Drug-eluting coronary stents (DES) rapidly dominated the marketplace in the United States after approval in 2003, but utilization rates were initially lower among African American patients. We assess whether racial differences persisted as DES diffused into practice. METHODS: Medicare claims data were used to identify coronary stenting procedures among elderly patients with acute coronary syndromes (ACS). Regression models of the choice of DES versus bare mental stent controlled for demographics, ACS type, co-morbidities and hospital characteristics. Diffusion was assessed in the short run (2003-2004) and long run (2007), with the effect of race calculated to allow for time-varying effects. RESULTS: The sample included 381,887 Medicare beneficiaries treated with stent insertion; approximately 5% were African American. Initially (May 2003-February 2004), African American race was associated with lower DES use compared to other races (44.3% versus 46.5%, P < 0.01). Once DES usage was high in all patients (March-December 2004), differences were not significant (79.8% versus 80.3%, P = 0.45). Subsequent concerns regarding DES safety caused reductions in DES use, with African Americans having lower use than other racial groups in 2007 (63.1% versus 65.2%, P < 0.01). CONCLUSIONS: Racial disparities in DES use initially disappeared during a period of rapid diffusion and high usage rates; the reappearance of disparities in use by 2007 may reflect DES use tailored to unmeasured aspects of case mix and socio-economic status. Further work is needed to understand whether underlying differences in race reflect decisions regarding treatment appropriateness.

Epidemiology, management, and outcomes of sustained ventricular arrhythmias after continuous-flow left ventricular assist device implantation.

BACKGROUND: Left ventricular assist devices (LVADs) are pivotal treatment options for patients with end-stage heart failure. Despite robust left ventricular unloading, the right ventricle remains unsupported and susceptible to hemodynamic perturbations from ventricular arrhythmias (VAs). Little is known about the epidemiology, management, resource use, and outcomes of sustained VAs in continuous-flow LVAD patients. METHODS: We reviewed data from all consecutive patients receiving a continuous-flow LVAD at the University of North Carolina from January 2006 to February 2011. Patient demographics, pharmacotherapies, resource use, and outcomes were recorded. Descriptive statistics were generated, and multivariable logistic regression was used to assess the independent association of clinical variables on the development of postimplantation VAs. RESULTS: Of 61 patients, 26 (43%) had sustained VAs after LVAD. Most were male (65%), had history of hypertension (65%), and had nonischemic cardiomyopathy (62%). Patients with VAs after LVAD more often had preimplant VAs (62% vs 14%, P < .01), prior implantable cardioverter-defibrillator (92% vs 71%, P = .04), and history of implantable cardioverter-defibrillator discharge (38% vs 11%, P < .01). Although length of stay was similar, those with postimplant VAs had greater rehospitalization rates, greater antiarrhythmic drug use, and frequently required external defibrillation. Using multivariable logistic regression, only history of prior VA was associated with postimplant arrhythmias (odds ratio 13.7, P < .001). CONCLUSIONS: Ventricular arrhythmias in LVAD patients are common, often refractory to conservative therapy, and associated with frequent rehospitalization. Post-LVAD VAs, however, did not significantly impact survival or transplantation rates. Arrhythmia burden should be considered before LVAD placement, and future study should focus on the impact of VAs on quality of life.

Evaluating the effectiveness of a rapidly adopted cardiovascular technology with administrative data: the case of drug-eluting stents for acute coronary syndromes.

BACKGROUND: Instrumental variable (IV) methods can correct for unmeasured confounding when using administrative (claims) data for cardiovascular outcomes research, but difficulties identifying valid IVs have limited their use. We evaluated the safety and efficacy of drug-eluting coronary stents (DES) compared with bare-metal stents (BMS) for Medicare beneficiaries with acute coronary syndromes using the rapid uptake of DES in clinical practice as an instrument. We compared results from IV with those from propensity score matching (PSM) and multivariable regression models. METHODS: This is a retrospective cohort study involving 62,309 fee-for-service beneficiaries 66 years and older treated with coronary stenting between May 2003 and February 2004. Outcomes were measured for 46 months after revascularization using claims data. RESULTS: Recipients of DES were younger, had a lower prevalence of myocardial infarction, and had fewer comorbidities compared with BMS recipients. Use of DES was associated with lower rates of mortality by PSM (hazard ratio [HR] 0.80, CI 0.77-0.83) but not by IV (HR 0.99, CI 0.87-1.11). Instrumental variable models estimated a larger reduction in repeat revascularization (HR 0.76, CI 0.63-0.89) than did PSM (HR 0.90, CI 0.87-0.93). CONCLUSIONS: Based on IV analysis, the increased utilization of DES relative to BMS among Medicare beneficiaries with acute coronary syndrome is associated with reduced rates of repeat revascularization and no difference in mortality. Instrumental variable approaches provide a useful complement to conventional approaches to cardiovascular outcomes research with administrative data.

Stress imaging use and repeat revascularization among medicare patients with high-risk coronary artery disease.

The optimal use of stress testing after coronary revascularization remains unclear, and overuse of stress testing might increase the rates of repeat revascularization. We analyzed the association at both the patient and regional level between the use of stress testing and repeat revascularization for a cohort of Medicare beneficiaries receiving revascularization within 30 days of an admission for symptomatic coronary artery disease. The sample consisted of 219,748 Medicare beneficiaries aged >65 years who received percutaneous coronary intervention or cardiac bypass artery grafting after hospital admission for symptomatic coronary artery disease in 2003 to 2004. Medicare claims data through 2008 identified the use of stress testing and repeat revascularization. The associations between the cumulative incidence of stress testing and repeat revascularization were analyzed using linear regression analysis. Within 6 years of the initial revascularization, the cumulative incidence of events was 0.61 for stress testing and 0.23 for repeat revascularization. Most (53.1%) repeat revascularizations were preceded by a stress test. Only 10.3% of repeat revascularization procedures were preceded by myocardial infarction. The 4-year cumulative incidence of repeat revascularization and stress testing varied between the Hospital Referral Regions represented by the sample, and the positive correlation between the rates by the health referral region accounted for only a small portion of the total health referral region variation in revascularization rates. In conclusion, stress testing is commonly performed among Medicare patients after the initial revascularization, and most repeat procedures are performed for stable coronary artery disease. The variation in stress testing patterns only explained a modest fraction of the regional variation in the repeat revascularization rates.

Risk-benefit trade-offs in revascularisation choices.

AIMS: When patients choose percutaneous coronary intervention (PCI) over coronary artery bypass grafting (CABG), they accept an increased long-term risk of repeat revascularisation in exchange for short-term morbidity benefits. This paper quantifies the risk-benefit trade-off faced by patients with multiple vessel coronary artery disease. METHODS AND RESULTS: Data from the Arterial Revascularisation Therapies Study are used to generate risk-benefit acceptability curves for PCI versus CABG. Risks are measured by the long-term likelihood of repeat revascularisation while benefits are measured by short-term reductions in pain or improvements in health-related quality of life (HRQL). PCI patients faced a risk of 0.81 additional revascularisation events over three years in exchange for being pain-free at one month. A patient would need to be willing to tolerate a risk of 1.06 additional revascularisation events at three years, in exchange for being pain free at one month to be 95% confident that choosing PCI over CABG is risk-effective for him/her. CONCLUSIONS: The risk-benefit framework outlined in this study provides information to enable physicians to help their patients weigh directly each procedure's risks and benefits. While trade-offs are typically measured in quality-adjusted life years, using pain reduction to reflect benefits may provide a more tangible framework for patients.