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.

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.

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.

Contributions of extravascular and intravascular cells to fibrin network formation, structure, and stability.

Fibrin is essential for hemostasis; however, abnormal fibrin formation is hypothesized to increase thrombotic risk. We previously showed that in situ thrombin generation on a cell's surface modulates the 3-dimensional structure and stability of the fibrin network. Currently, we compared the abilities of extravascular and intravascular cells to support fibrin formation, structure, and stability. Extravascular cells (fibroblasts, smooth muscle) supported formation of dense fibrin networks that resisted fibrinolysis, whereas unstimulated intravascular (endothelial) cells produced coarse networks that were susceptible to fibrinolysis. All 3 cell types produced a fibrin structural gradient, with a denser network near, versus distal to, the cell surface. Although fibrin structure depended on cellular procoagulant activity, it did not reflect interactions between integrins and fibrin. These findings contrasted with those on platelets, which influenced fibrin structure via interactions between beta3 integrins and fibrin. Inflammatory cytokines that induced prothrombotic activity on endothelial cells caused the production of abnormally dense fibrin networks that resisted fibrinolysis. Blocking tissue factor activity significantly reduced the density and stability of fibrin networks produced by cytokine-stimulated endothelial cells. Together, these findings indicate fibrin structure and stability reflect the procoagulant phenotype of the endogenous cells, and suggest abnormal fibrin structure is a novel link between inflammation and thrombosis.

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.

Percutaneous Coronary Intervention or Coronary Artery Bypass Grafting: Intervention in Older Persons with Acute Coronary Syndrome-Part I.

This is Part I of a two-part article on treatment of acute coronary syndrome in the older population. Part I analyzes the differential utilization of invasive therapies with respect to age and heart disease. Part II (to be published in the next issue of Clinical Geriatrics) will summarize information from the literature on acute coronary syndrome outcomes from invasive treatments (percutaneous coronary interventions or coronary artery bypass grafting) among older persons.

Percutaneous Coronary Intervention or Coronary Artery Bypass Grafting: Intervention in Older Persons with Acute Coronary Syndrome-Part II.

This is Part II of a two-part article on treatment of acute coronary syndrome in the older population. Part I (published in the October issue of Clinical Geriatrics) analyzed the differential utilization of invasive therapies with respect to age and heart disease. Part II summarizes information from the literature on acute coronary syndrome outcomes from invasive treatments (percutaneous coronary interventions or coronary artery bypass grafting) among older persons.