Association of Effective Regurgitation Orifice Area to Left Ventricular End-Diastolic Volume Ratio With Transcatheter Mitral Valve Repair Outcomes: A Secondary Analysis of the COAPT Trial.

Importance: Transcatheter mitral valve repair (TMVr) plus maximally tolerated guideline-directed medical therapy (GDMT) reduced heart failure (HF) hospitalizations (HFHs) and all-cause mortality (ACM) in symptomatic patients with HF and secondary mitral regurgitation (SMR) compared with GDMT alone in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT) trial but not in a similar trial, Multicenter Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation (MITRA-FR), possibly because the degree of SMR relative to the left ventricular end-diastolic volume index (LVEDVi) was substantially lower. Objective: To explore contributions of the degree of SMR using the effective regurgitation orifice area (EROA), regurgitant volume (RV), and LVEDVi to the benefit of TMVr in the COAPT trial. Design, Setting, and Participants: This post hoc secondary analysis of the COAPT randomized clinical trial performed December 27, 2012, to June 23, 2017, evaluated a subgroup of COAPT patients (group 1) with characteristics consistent with patients enrolled in MITRA-FR (n = 56) (HF with grade 3+ to 4+ SMR, left ventricular ejection fraction of 20%-50%, and New York Heart Association function class II-IV) compared with remaining (group 2) COAPT patients (n = 492) using the end point of ACM or HFH at 24 months, components of the primary end point, and quality of life (QOL) (per the Kansas City Cardiomyopathy Questionnaire overall summary score) and 6-minute walk distance (6MWD). The same end points were evaluated in 6 subgroups of COAPT by combinations of EROA and LVEDVi and of RV relative to LVEDVi. Interventions: Interventions were TMVr plus GDMT vs GDMT alone. Results: A total of 548 participants (mean [SD] age, 71.9 [11.2] years; 351 [64%] male) were included. In group 1, no significant difference was found in the composite rate of ACM or HFH between TMVr plus GDMT vs GDMT alone at 24 months (27.8% vs 33.1%, P = .83) compared with a significant difference at 24 months (31.5% vs 50.2%, P < .001) in group 2. However, patients randomized to receive TMVr vs those treated with GDMT alone had significantly greater improvement in QOL at 12 months (mean [SD] Kansas City Cardiomyopathy Questionnaire summary scores: group 1: 18.36 [5.38] vs 0.43 [4.00] points; P = .01; group 2: 16.54 [1.57] vs 5.78 [1.82] points; P < .001). Group 1 TMVr-randomized patients vs those treated with GDMT alone also had significantly greater improvement in 6MWD at 12 months (mean [SD] paired improvement: 39.0 [28.6] vs -48.0 [18.6] m; P = .02). Group 2 TMVr-randomized patients vs those treated with GDMT alone tended to have greater improvement in 6MWD at 12 months, but the difference did not reach statistical significance (mean [SD] paired improvement: 35.0 [7.7] vs 16.0 [9.1] m; P = .11). Conclusions and Relevance: A small subgroup of COAPT-resembling patients enrolled in MITRA-FR did not achieve improvement in ACM or HFH at 24 months but had a significant benefit on patient-centered outcomes (eg, QOL and 6MWD). Further subgroup analyses with 24-month follow-up suggest that the benefit of TMVr is not fully supported by the proportionate-disproportionate hypothesis. Trial Registration: ClinicalTrials.gov Identifier: NCT01626079.

High Transpulmonary Artery Gradient Obtained at the Time of Left Ventricular Assist Device Implantation Negatively Affects Survival After Cardiac Transplantation.

AIM: Preoperatively elevated pulmonary vascular resistance (PVR) is a contraindication to heart transplantation (HT). Transpulmonary pressure gradient (TPG) is one of the main variables used in PVR determination (ie, PVR = TPG/cardiac output). Unlike PVR, which is subject to the shortcoming of cardiac output estimation, TPG is directly measured. We aimed to evaluate the relationship of TPG obtained before left ventricular assist device (LVAD) implantation on post-HT survival. METHODS AND RESULTS: A total of 490 patients were implanted with Heartmate II LVADs in the multicenter Heartmate II Bridge-to-Transplantation clinical trial, and 416/490 had pre-LVAD TPG data available. Outcomes during LVAD support and after HT stratified by both PVR and TPG were studied. The median pre-LVAD TPG was 10 mm Hg. Baseline demographic and clinical characteristics were similar for patients with and without TPG >10 mm Hg. Outcomes during LVAD support (ie, recovery to LVAD explantation, HT, or ongoing device support) for patients below and above the median TPG were similar. However, post-HT 1-year survival rate was significantly higher for patients with TPG ≤10 mm Hg compared with those with TPG >10 mm Hg (91% vs 80%; P = .016). Analysis based on the median PVR of 2.68 Wood units did not stratify post-HTx 1-year survival rates between the groups (89% vs 83%; P = .25). CONCLUSIONS: Elevated TPG, rather than high PVR, before LVAD implantation was associated with increased mortality following HT. Pre-LVAD TPG may be useful to identify a cohort that requires close follow-up with serial hemodynamic monitoring before HT.

Novel Cardiac Coordinate Modeling System for Three-Dimensional Quantification of Inflow Cannula Malposition of HeartMate II LVADs.

Optimal function of left ventricular assist devices (LVADs) depends on proper alignment of the inflow cannula (IC). Quantitative guidelines for IC angulation are lacking because of variation in cardiac geometry and difficulty in analyzing three-dimensional (3D) cannula orientation relative to the left ventricle (LV). Based on contrast-enhanced computed tomography images from five normal and five clinically malpositioned IC cases in patients with HeartMate II LVADs, we developed a method for 3D quantification of IC malpositioning. Using Mimics image software (Materialise, Leuven, Belgium), the native heart, major arteries, and LVAD were segmented to create patient-specific 3D models, allowing LV cavity volume and long-axis length to be measured directly. The deviation of the IC was quantified in a cylindrical coordinate system at the IC insertion point relative to the mitral valve and septum, and IC occlusion was assessed by the distance between cannula inlet and the proximal endocardium. Compared with normal cases, patients with malpositioned pumps had shorter LV length (p = 0.03) and reduced pump pocket depth (p = 0.009). Malpositioned pumps may experience greater obstruction by the nearby myocardium. This quantitative 3D modeling tool may help identify different modes of pump malalignment and migration and may facilitate preoperative planning and minimally invasive approaches via virtual LVAD implantation.

Early intervention for lactate dehydrogenase elevation improves clinical outcomes in patients with the HeartMate II left ventricular assist device: Insights from the PREVENT study.

BACKGROUND: Hemolysis, assessed by elevated serum lactate dehydrogenase (LDH), is strongly associated with HeartMate II pump thrombosis (PT). However, it is unknown whether early intervention for elevated LDH circumvents the risk of serious PT requiring pump exchange. We sought to evaluate the relationship between elevated LDH and clinical outcomes, the effectiveness of early medical intervention, and risk factors for elevated LDH. METHODS: We studied 268 patients in the prospective, multicenter PREVENT study who had 2 or more LDH measurements at ≥30 days post-implant. Elevated LDH was defined as LDH ≥2.5× upper limit of normal (ULN) for 2 consecutive measurements. RESULTS: Fourteen percent of patients had elevated LDH. Stroke-free survival at 6 months was lower in patients with elevated LDH vs patients with normal LDH (83 ± 6% vs 93 ± 2%, p = 0.035). Elevated LDH resolved without intervention in 19% of patients, with intensified medical therapy in 43% and required surgical intervention in 38%. For patients receiving only medical therapy, survival was 94 ± 6% at 6 months post-treatment. In this subgroup, resolution of symptoms with intensified medical therapy was sustained in 15 of 16 patients, with PT occurring in 1 patient at 171 days after initial treatment for elevated LDH (202 days post-implant). Early medical intervention at moderately elevated LDH (2.5× to 3.2× ULN), as compared with higher levels (>3.2× ULN), led to more sustained resolution of symptoms without subsequent PT or need for surgical intervention (91% vs 26% at 6 months post-treatment, p = 0.002). CONCLUSIONS: Early medical intervention can successfully resolve moderate LDH elevations (2.5× to 3.2× ULN) with a low incidence of death or PT at 6 months post-treatment.

Hemocompatibility-Related Outcomes in the MOMENTUM 3 Trial at 6 Months: A Randomized Controlled Study of a Fully Magnetically Levitated Pump in Advanced Heart Failure.

BACKGROUND: The HeartMate 3 (HM3) Left Ventricular Assist System (LVAS) (Abbott) is a centrifugal, fully magnetically levitated, continuous-flow blood pump engineered to enhance hemocompatibility and reduce shear stress on blood components. The MOMENTUM 3 trial (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3) compares the HM3 LVAS with the HeartMate II (HMII) LVAS (Abbott) in advanced heart failure refractory to medical management, irrespective of therapeutic intention (bridge to transplant versus destination therapy). This investigation reported its primary outcome in the short-term cohort (n=294; 6-month follow-up), demonstrating superiority of the HM3 for the trial primary end point (survival free of a disabling stroke or reoperation to replace the pump for malfunction), driven by a reduced need for reoperations. The aim of this analysis was to evaluate the aggregate of hemocompatibility-related clinical adverse events (HRAEs) between the 2 LVAS. METHODS: We conducted a secondary end point evaluation of HRAE (survival free of any nonsurgical bleeding, thromboembolic event, pump thrombosis, or neurological event) in the short-term cohort (as-treated cohort n=289) at 6 months. The net burden of HRAE was also assessed by using a previously described hemocompatibility score, which uses 4 escalating tiers of hierarchal severity to derive a total score for events encountered during the entire follow-up experience for each patient. RESULTS: In 289 patients in the as-treated group (151 the HM3 and 138 the HMII), survival free of any HRAE was achieved in 69% of the HM3 group and in 55% of the HMII group (hazard ratio, 0.62; confidence interval, 0.42-0.91; P=0.012). Using the hemocompatibility score, the HM3 group demonstrated less pump thrombosis requiring reoperation (0 versus 36 points, P<0.001) or medically managed pump thrombosis (0 versus 5 points, P=0.02), and fewer nondisabling strokes (6 versus 24 points, P=0.026) than the control HMII LVAS. The net hemocompatibility score in the HM3 in comparison with the HMII patients was 101 (0.67±1.50 points/patient) versus 137 (0.99±1.79 points/patient) (odds ratio, 0.64; confidence interval, 0.39-1.03; P=0.065). CONCLUSIONS: In this secondary analysis of the MOMENTUM 3 trial, the HM3 LVAS demonstrated greater freedom from HRAEs in comparison with the HMII LVAS at 6 months. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT02224755.

Outcomes in HeartMate II Patients With No Antiplatelet Therapy: 2-Year Results From the European TRACE Study.

BACKGROUND: Current recommendations of antithrombotic therapy for HeartMate II (HMII) patients include the use of both an anticoagulant and an antiplatelet agent. Because bleeding is still the most frequent adverse event, the TRACE (STudy of Reduced Anti-Coagulation/Anti-platelet Therapy in Patients with the HeartMatE II) study was initiated to evaluate the incidence of adverse events in HMII patients on reduced antithrombotic (RT) therapy. METHODS: HMII patients (n = 101) from nine centers were enrolled in the European arm of TRACE and were managed on a single anticoagulant (vitamin K antagonist) with no antiplatelet agents. An analysis of bleeding and thrombotic adverse events from all 101 patients with 2-year follow-up after initiation of RT therapy is reported here. RESULTS: Median age was 56 years (range, 18 to 72 years), 93% were men, 70% had an Interagency Registry for Mechanically Assisted Circulatory Support profile 1 to 3, and 82% received the HMII as a bridge to transplantation. Ninety-two percent were placed on RT therapy as a center standard of care or due to physician preference and 6% as a response to bleeding. Median HMII support duration on RT therapy was 25 months (range, 1 to 93 months). Median international normalized ratio was 2.31 [quartile 1 to quartile 3: 2.07 to 2.60]. At 2 years, freedom from bleeding, ischemic stroke, hemorrhagic stroke, and pump thrombosis after initiation of RT therapy was 81% ± 6%, 96% ± 2%, 94% ± 3%, and 94% ± 3%, respectively. CONCLUSIONS: The 2-year analysis of the observational European TRACE study suggests that managing HMII patients with a vitamin K antagonist with a target international normalized ratio of 2.3 without antiplatelet therapy may help to reduce the incidence of major bleeding without increasing the risk of thromboembolic events, including ischemic stroke and pump thrombosis.

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.

Outcomes of Adult Patients with Small Body Size Supported with a Continuous-Flow Left Ventricular Assist Device.

There is insufficient data on patients with small body size to determine if this should be considered a risk factor for continuous-flow left ventricular assist device (CF-LVAD) support. We sought to evaluate survival outcomes, adverse events, and functional status of CF-LVAD patients with body surface area (BSA) <1.5 m in a large national registry. Adults with BSA < 1.5 m (n = 128) implanted with a HeartMate II (HMII)-LVAD from the Interagency Registry for Mechanically Assisted Circulatory Support registry from April 2008 to December 2012 formed this cohort. Outcomes were compared with HMII bridge to transplant (BTT) and destination therapy (DT) post approval studies. The majority of patients were female (n = 106, 83%). A total of 64% (n = 82) were implanted for BTT and 36% (n = 46) for DT. The median BSA (range) was 1.44 (1.19-1.49) and 1.45 (1.25-1.49) m for BTT and DT, respectively. Overall survival 1 year post implant was 81% ± 5% for BTT and 84% ± 6% for DT. The most common adverse events for BTT and DT patients were bleeding (0.91, 0.88 events/patient year) and driveline infection (16%, 0.28 events/patient year). Six months post implantation, 87% of BTT and 77% of DT patients were New York Heart Association functional class I or II. Post implant survival, functional status improvement, and adverse event profile for adult BTT and DT HMII patients with BSA < 1.5 m are favorable and comparable with outcomes published in the overall patient population.

Evaluation of von Willebrand factor with a fully magnetically levitated centrifugal continuous-flow left ventricular assist device in advanced heart failure.

BACKGROUND: Contemporary continuous-flow left ventricular assist devices (CF-LVADs) are associated with degradation of von Willebrand factor (vWF) high-molecular-weight multimers (HMWMs), a critical factor supporting platelet function. We hypothesized that the HeartMate 3 fully magnetically levitated LVAD, designed to reduce circulatory shear stress, favorably influences these hemostatic parameters. METHODS: Fifteen consecutive HeartMate 3 LVAD patients were compared with 11 consecutive HeartMate II controls. Serial plasma samples were collected pre-implant and on Days 2, 7, 30 and 45 post-operatively. Changes in vWF HMWMs were evaluated by 2 independent, study-blind hematologists and confirmed using densitometry-based computerized software. Ristocetin cofactor (RiCO) and vWF antigen (vWF Ag) were measured using standard protocols with enzyme-linked immunosorbent assay. RESULTS: HeartMate 3 patients and HeartMate II controls had a mean age of 67.3 ± 1.4 and 52.8 ± 2.5 years, respectively (INTERMACS Profiles 2 to 4 in 93.3% and 91%, respectively). HeartMate 3 group demonstrated a significantly greater preservation of HMWMs compared with the HeartMate II group, with the most prominent decrease occurring by Day 2 post-operatively and sustained through 45 days (71.94% vs 31.16%, p = 0.001). Laboratory values (normalized to baseline) for RiCO activity, vWF Ag and RiCO:vWF Ag ratio remained in the functional range with no statistically significant differences observed between groups. CONCLUSION: The HeartMate 3 LVAD is associated with enhanced hemocompatibility compared with the HeartMate II LVAD, as demonstrated by the improved preservation of vWF HMWMs, In contrast, effects on HMWM degradation appeared to be dissociated from functional attributes. Further confirmation of these findings in randomized clinical trials is warranted.

Reduce Driveline Trauma Through Stabilization and Exit Site Management: 30 Days Feasibility Results from the Multicenter RESIST Study.

The percutaneous lead management kit (PLMK) was developed for the HeartMate 2 (HM2) left ventricular assist device (LVAD) to reduce trauma at the exit site and to maintain a clean environment. REduce Driveline Trauma through StabIlization and Exit Site ManagemenT (RESIST) was a multicenter, prospective, nonrandomized study designed to evaluate the feasibility of the PLMK for managing the HM2 driveline exit site. Fifty patients were enrolled at five sites at a median of 495 days post-HM2 implant; 92% (46 of 50) of patients used the PLMK for a minimum of 30 days. At 30 days, more patients found the PLMK to be extremely comfortable (80% vs. 37%, p < 0.001) and extremely effective at stabilizing the driveline (82% vs. 40%, p < 0.001) compared with each center's standard of care. Frequency of dressing changes was 6-7 days or higher for 85% of the patients with PLMK. Three patients developed driveline infection while on PLMK (6%, 0.15 events per patient year), and 35 patients continued to use the PLMK after 6 months. The PLMK is easy to use, increases patient comfort, and increases driveline stability with a dressing change frequency of 6-7 days.

Preoperative Determinants of Quality of Life and Functional Capacity Response to Left Ventricular Assist Device Therapy.

BACKGROUND: Left ventricular assist devices (LVADs) improve survival, quality of life (QOL), and functional capacity (FC) among patients with end-stage heart failure. Few data are available regarding characteristics associated with QOL and FC response. METHODS AND RESULTS: Patients enrolled in the Heartmate II clinical trials that were alive with ongoing LVAD support at 6 months were included. QOL response criteria included scoring above the lowest quartile on either the Minnesota Living With Heart Failure Questionnaire or the Kansas City Cardiomyopathy Questionnaire. FC responder criteria included improvement in 6-minute walk distance (6MWD) >70 meters from baseline, a 6MWD >220 meters at 6 months, or New York Heart Association functional class I or II. Independent variables associated with QOL nonresponse included history of diabetes (odds ratio [OR] 1.82, 95% confidence interval [CI] 1.20-2.78), lower mean pulmonary arterial pressure (OR 0.97, 95% CI 0.95-0.99), or a Heartmate II right ventricular risk score >2 (OR 1.77, 95% CI 1.00-3.12). Variables associated with FC nonresponse included history of COPD (OR 1.92, 95% CI 1.22-3.03) or diabetes (OR 1.52, 95% CI 1.01-2.27). Compared with responders, QOL and FC nonresponders had reduced long-term survival. CONCLUSIONS: Preoperative comorbidities, including diabetes, COPD, and right heart failure, may limit the QOL and FC response to LVAD therapy and should be considered during the shared decision-making process.

Radiologic assessment of HeartMate II position: Minimal pump migration after long-term support.

BACKGROUND: Surgical positioning of the HeartMate II (HMII) left ventricular assist device assuring an unobstructed blood flow path is essential for optimal device function and hemodynamic support. We report a non-invasive radiologic assessment of HMII position after implant and long-term follow-up. METHODS: We reviewed 132 consecutive patients (age 64 ± 14 years; 86% male; 60% destination therapy) implanted with an HMII from January 2009 to December 2012 and followed for them for up to 4 years. A radiologist measured pump position, pocket depth and cannula angles using chest radiography. Changes over time were determined in 64 of these patients with pairs of radiographs immediately after implant and at an average of 2.0 ± 0.7 years of follow-up. RESULTS: The axis of the pump relative to the spine was 92 ± 10° at baseline and 94 ± 9° at 2 years (n = 64, p = 0.02), and inflow cannula angles averaged 21 ± 13° from vertical at baseline and 20 ± 12° at 2 years (p = not statistically significant). More than 90% of angle measurements showed <15° movement over the follow-up duration. There was a small but significant superior pump migration from a depth of 12.7 ± 2.7 cm to 10.4 ± 2.6 cm (p < 0.001). There were no cannula obstructions or instances of right ventricular assist device use. The 30-day operative mortality was 3.0%. Prolonged inotrope dependence occurred in 5.3% (7 of 126) of patients, and low rates of pump thrombosis of 0.018 event/patient-year (0 at 3 months) and stroke 0.074 event/patient-year were noted. CONCLUSION: Non-invasive radiographic measurements of surgical pump placement designed to avoid pump and cannula malposition demonstrate stable position with minimal pump migration.

Incidence, risk, and consequences of atrial arrhythmias in patients with continuous-flow left ventricular assist devices.

BACKGROUND: Although atrial arrhythmias (AAs) are common in heart failure, the incidence of AAs subsequent to the placement of left ventricular assist devices (LVADs) has not been elucidated. METHODS: Patients receiving a HeartMate II LVAD in the bridge to transplant (n = 490) and destination therapy (n = 634) trials were included (n = 1125). AAs requiring treatment were recorded, regardless of symptoms. Using Cox models with and without a 60-day blanking period, risk factors for early and late AAs were determined. RESULTS: In total, there were 271 AAs in 231 patients (21%), most of which occurred within the first 60 days. Patients with and without AAs had similar survival (p = 0.16). Serum creatinine (hazard ratio [HR] = 1.49 per unit increase, 1.18 to 1.88; p < 0.001) and ejection fraction (HR = 0.98 per 1% increase, 0.95 to 0.999; p = 0.04) were associated with AAs in a multivariable model. Although quality of life (QoL) and functional status improved in all patients, those with AAs had worse unadjusted QoL (p < 0.001) and a decreased rate of improvement in six-minute walk distance over six to 24 months postimplant (p = 0.016). CONCLUSIONS: Approximately one-fifth of LVAD patients have AAs, most commonly within the first 60 days of support. Preoperative creatinine is a strong risk factor for early and late AAs. Although AAs do not impact survival, they are associated with decreased functional status and QoL improvements during LVAD support.

Early elevations in pump power with the HeartMate II left ventricular assist device do not predict late adverse events.

BACKGROUND: The aim of this study was to evaluate the prevalence of early pump power elevation events in patients with the HeartMate II (HMII) and its impact on subsequent development of stroke and pump thrombosis. METHODS: We analyzed >45,000 measurements of pump power and pump speed measured during the initial hospitalization period and >12,000 follow-up measurements obtained from 138 consecutive patients implanted with a HMII between January 2009 and December 2012. An early power elevation (PEL) event was defined as power ≥10 W within the first 14 post-operative days. Patients were divided into two groups: those with an early PEL event and those without (NP). RESULTS: Median follow-up duration was 316 (range 2 to 1,264) days. Twenty-seven (20%) patients had early PEL events that lasted for a total duration of 4 (range 1 to 77) hours per patient. Pump speed averaged 9,400 rpm in both groups. Although patients in the PEL group had higher median power (7.1 [6.0 to 9.9] W vs 6.7 [5.7 to 7.8] W, p < 0.001) in the immediate post-operative period, there was no difference between the two groups noted at first follow-up (6.6 [5.9 to 8.7] W vs 6.7 [5.5 to 7.7] W, p = 0.940). No differences in the prevalence of hemorrhagic stroke (4% vs 3%, p = 0.56), ischemic stroke (0% vs 4%, p = 0.41), hemolysis (7% vs 5%, p = 0.32), pump thrombosis (7% vs 4%, p = 0.21) or survival (76% at 1 year in both groups) were found between the two groups. CONCLUSIONS: In this single-center experience, PEL events that occurred early all resolved by discharge. No relationship was found between early PEL events and subsequent development of pump thrombosis, hemorrhagic stroke or ischemic stroke.

Fontan hemodynamics from 100 patient-specific cardiac magnetic resonance studies: a computational fluid dynamics analysis.

OBJECTIVES: This study sought to quantify average hemodynamic metrics of the Fontan connection as reference for future investigations, compare connection types (intra-atrial vs extracardiac), and identify functional correlates using computational fluid dynamics in a large patient-specific cohort. Fontan hemodynamics, particularly power losses, are hypothesized to vary considerably among patients with a single ventricle and adversely affect systemic hemodynamics and ventricular function if suboptimal. METHODS: Fontan connection models were created from cardiac magnetic resonance scans for 100 patients. Phase velocity cardiac magnetic resonance in the aorta, vena cavae, and pulmonary arteries was used to prescribe patient-specific time-averaged flow boundary conditions for computational fluid dynamics with a customized, validated solver. Comparison with 4-dimensional cardiac magnetic resonance velocity data from selected patients was used to provide additional verification of simulations. Indexed Fontan power loss, connection resistance, and hepatic flow distribution were quantified and correlated with systemic patient characteristics. RESULTS: Indexed power loss varied by 2 orders of magnitude, whereas, on average, Fontan resistance was 15% to 20% of published values of pulmonary vascular resistance in single ventricles. A significant inverse relationship was observed between indexed power loss and both systemic venous flow and cardiac index. Comparison by connection type showed no differences between intra-atrial and extracardiac connections. Instead, the least efficient connections revealed adverse consequences from localized Fontan pathway stenosis. CONCLUSIONS: Fontan power loss varies from patient to patient, and elevated levels are correlated with lower systemic flow and cardiac index. Fontan connection type does not influence hemodynamic efficiency, but an undersized or stenosed Fontan pathway or pulmonary arteries can be highly dissipative.

Impact of concurrent surgical valve procedures in patients receiving continuous-flow devices.

BACKGROUND: Preexisting valve pathology is common in patients with end-stage heart failure undergoing left ventricular assist device (LVAD) placement. The indications and subsequent benefits of performing valvular procedures in these patients are unclear. The objective of this study was to determine the impact of performing concurrent surgical valve procedures in a large cohort of patients receiving LVADs. METHODS: One thousand one hundred six patients received the HeartMate II (HMII) LVAD in the bridge to transplant (n = 470) and destination therapy (n = 636) clinical trials. Of these, 374 patients (34%) had concurrent cardiac surgery procedures as follows: 242 patients (21%) with 281 concurrent valve procedures (VP) (aortic 80, mitral 45, and tricuspid 156), and 641 patients had only HMII LVAD. The focus of this study was to determine the clinical outcomes of patients undergoing HMII + VP compared with those who received HMII alone. RESULTS: Patients undergoing HMII + VP were significantly older, had higher blood urea nitrogen levels and central venous pressure, and decreased right ventricular stroke work index; intraoperatively, the median cardiopulmonary bypass times were also longer. The unadjusted 30-day mortality was significantly higher in patients undergoing HMII + VP (10.3% vs 4.8% for LVAD alone, P = .005). Subgroup analysis of individual VPs showed that higher mortality occurred in patients with HMII plus 2 or more VPs (13.5%, P = .04) followed by trends for increased mortality with HMII plus mitral alone (11.5%, P = NS), HMII plus aortic alone (10.9%, P = NS), and HMII plus tricuspid (8.9%, P = NS) procedures. Of these various groups, only patients undergoing HMII + isolated aortic VP (P = .001) and HMII + multiple VPs (P = .046) had significantly worse long-term survival compared with patients undergoing HMII alone. Right heart failure and right ventricular assist device use was increased in patients undergoing VPs, but there was no difference in the incidence of bleeding or stroke. CONCLUSIONS: Patients frequently require concurrent VPs at the time of LVAD placement; these patients are sicker and have higher early mortality. Furthermore, right ventricular dysfunction is increased in these patients. Further studies to develop selection criteria for concurrent valve interventions are important to further improve clinical outcomes.

Pre-operative risk factors of bleeding and stroke during left ventricular assist device support: an analysis of more than 900 HeartMate II outpatients.

OBJECTIVES: This study sought to determine the pre-operative risk factors related to late bleeding, stroke, and pump thrombosis in patients with HeartMate II (HMII) left ventricular assist devices (LVADs) (Thoratec Corporation, Pleasanton, California) that might influence tailored improvements in patient management. BACKGROUND: Adverse events in LVAD patients remain high. It is unclear whether pre-operative characteristics influence the likelihood of the development of post-operative hemorrhagic or thrombotic complications. Knowing which patients are at greater risk might assist in tailoring anticoagulation therapy for certain patients. METHODS: Advanced heart failure patients (n = 956) discharged from the hospital after LVAD implantation in the HMII bridge to transplantation (n = 405) and destination therapy (n = 551) clinical trials were retrospectively evaluated. Bleeding requiring surgery or transfusion of >2 U of packed red blood cells, stroke (hemorrhagic and ischemic), and pump thrombosis were tracked from hospital discharge until patient outcome. RESULTS: Adverse event rates for post-discharge bleeding (0.67 events/patient-year) were higher than those for hemorrhagic stroke (0.05), ischemic stroke (0.04), and pump thrombosis (0.03). The main sites of bleeding included gastrointestinal (45% of events), wound (12%), and epistaxis (4%). Older age (>65 years) (hazard ratio [HR]: 1.31), lower pre-operative hematocrit (≤31%) (HR: 1.31), ischemic etiology (HR: 1.35), and female (HR: 1.45) were statistically significant multivariable risk factors for bleeding. Female (HR: 1.92) and 65 years of age and younger (HR: 1.94) were multivariable risk factors for hemorrhagic stroke, whereas female (HR: 1.84) and history of diabetes (HR: 1.99) were risk factors for ischemic stroke. Female (HR: 1.90) and higher body mass index (HR: 1.71/10 kg/m(2) increase) were also multivariable risk factors for pump thrombosis. CONCLUSIONS: The risk of bleeding and thrombotic events during LVAD support differs by patient demographics, including sex, age, body mass index, and etiology of heart failure. Further studies should focus on the potential of tailored anticoagulation strategies in these subgroups.

Pre-operative health status and outcomes after continuous-flow left ventricular assist device implantation.

BACKGROUND: Health status predicts adverse outcomes in heart failure and cardiac surgery patients, but its prognostic value in left ventricular assist device (LVAD) placement is unknown. METHODS: We examined the association of pre-operative health status, as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), with survival and hospitalization after LVAD using the KCCQ score as a continuous variable and stratified by KCCQ score quartile plus missing KCCQ in 1,125 clinical trial participants who received the HeartMate II (Thoratec Corp, Pleasanton, CA) as destination therapy (n = 635) or bridge to transplantation (n = 490). RESULTS: The mean pre-operative KCCQ score was 29.4 ± 18.7 among survivors (n = 719), and 27.1 ± 18.3 (n = 406) in those who died. In time-to-event analysis for all available follow-up using health status as a continuous variable, the pre-operative KCCQ score did not correlate with overall mortality after LVAD implantation (p = 0.178). Small absolute differences were seen between the pre-operative KCCQ quartile and 30-day survival (Q4 95% vs. Q1 89% vs. missing 87%; p = 0.0009 for trend), 180-day survival (Q4 83% vs. Q1 76% vs missing 79%; p = 0.060 for trend), and days hospitalized at 180 days (Q4 29.8 ± 25.6 vs. Q1 34.1 ± 27.1 vs. missing 36.5 ± 29.9 days; p = 0.009 for trend). CONCLUSION: Our findings suggest that pre-operative health status has limited association with outcomes after LVAD implantation. Although these data require further study in a diverse population, mechanical circulatory support may represent a relatively unique clinical situation, distinct from heart failure and other cardiac surgeries, in which heart failure-specific health status measures may be largely reversed.

Outcomes of pediatric patients supported by the HeartMate II left ventricular assist device in the United States.

OBJECTIVE: The HeartMate II (HMII; Thoratec, Pleasanton, CA) continuous-flow left ventricular assist device (LVAD) is an established treatment modality for advanced heart failure in adults. The objective of this study was to evaluate outcomes of pediatric patients supported by the HMII LVAD. METHODS: This was a retrospective review of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) of patients supported with a HMII from April 2008 to September 2011. The primary cohort comprised pediatric patients aged 11 to 18 years. Outcomes were compared with a group of young adults aged 19 to 39 years who underwent HMII implant during the same period. Ischemic etiologies for heart failure were excluded. RESULTS: There were 28 pediatric patients, of whom 19 (68%) were males, 14 (46%) were African American, and 7 (25%) underwent device placement in a pediatric hospital. Competing outcomes analysis showed that at 6 months of follow-up, the composite of survival to transplantation, ongoing support, or recovery was 96% for the pediatric group, which was not significantly different from the young adult group (96%, p = 0.330). The 2 groups had similar INTERMACS profiles but differed in diagnosis, weight, and morbidities. Bleeding complications requiring surgical intervention were more common in the pediatric group. CONCLUSIONS: Pediatric outcomes with a HMII LVAD are comparable to that of young adults. As we continue to monitor this growing group, more sophisticated characterization and comparisons will be possible. Also, as technology progress and second- and third-generation devices are introduced, the number of children who will benefit from mechanical support will continue to grow.