Novel Nebulized Milrinone Formulation for the Treatment of Acute Heart Failure Requiring Inotropic Therapy: A Phase 1 Study.

BACKGROUND: Nonintravenous inotropic-delivery options are needed for patients with inotropic-dependent heart failure (HF) to reduce the costs, infections and thrombotic risks associated with chronic central venous catheters and home infusion services. METHODS: We developed a novel, concentrated formulation of nebulized milrinone for inhalation and evaluated the feasibility, safety and pharmacokinetic profile in a prospective, single-arm, phase I clinical trial. We enrolled 10 patients with stage D HF requiring inotropic therapy during a hospital admission for acute HF. Milrinone 60 mg/4 mL was inhaled via nebulization 3 times daily for 48 hours. The coprimary outcomes were adverse events and pharmacokinetic profiles of inhaled milrinone. Acute changes in hemodynamic parameters were secondary outcomes. RESULTS: A concentrated nebulized milrinone formulation was well tolerated, without hypotensive events, arrhythmias or inhalation-related adverse events requiring discontinuation. Nebulized milrinone produced serum concentrations in the goal therapeutic range with a median plasma milrinone trough concentration of 39 (17-66) ng/mL and a median peak concentration of 207 (134-293) ng/mL. There were no serious adverse events. From baseline to 24 hours, mean pulmonary artery saturation increased (60% ± 7%-65 ± 5%; P = 0.001), and mean cardiac index increased (2.0 ± 0.5 mL/min/1.73m2-2.5 ± 0.1 mL/min/1.73m2; P = 0.001) with nebulized milrinone. CONCLUSIONS: In a proof-of-concept study, a concentrated, nebulized milrinone formulation for inhalation was safe and produced therapeutic serum milrinone concentrations. Nebulized milrinone was associated with improved hemodynamic parameters of cardiac output in a population with advanced HF. These promising results require further investigation in a longer-term trial in patients with inotrope-dependent advanced HF.

Impact of Biopsy Proven Liver Fibrosis on Patients Undergoing Evaluation and Treatment for Advanced Heart Failure Surgical Therapies.

There is a paucity of data regarding the impact of liver fibrosis on patients with stage D heart failure (HF). We conducted a retrospective study (January 1, 2017 to December 12, 2020) in patients with stage D HF who underwent liver biopsy as part of their advanced HF therapy evaluation. Baseline characteristics and 1-year outcomes were compared between no- or mild-to-moderate-fibrosis (grade 0 to 2) and advanced-fibrosis (grade 3 to 4) groups. Of 519 patients with stage D HF, 136 who underwent liver biopsy (113 [83%] no or mild-to-moderate fibrosis and 23 [17%] advanced fibrosis) were included. A total of 71 patients (52%) received advanced HF therapies (23 heart transplantation, 48 left ventricular assist devices). One-year mortality was higher among patients with advanced fibrosis (52% vs 18%, p <0.001). Further subgroup analysis suggested a trend toward increased 1-year mortality among patients with advanced fibrosis who underwent advanced therapies (37% vs 13%, p = 0.09). There was a trend of lower likelihood of receiving advanced HF therapies in the advanced-fibrosis group, only 1 heart transplantation and 7 left ventricular assist devices, but it did not reach statistical significance (35% vs 56%, p = 0.06). After adjustment for confounders, degree of liver fibrosis was an independent predictor of mortality (odds ratio 6.2; 95% 1.27 to 30.29, p = 0.02). We conclude that advanced liver fibrosis is common among patients with stage D HF who undergo evaluation for advanced HF surgical therapies and significantly increases 1-year mortality. Further larger studies are needed to support our findings.

Use of Extracorporeal Membrane Oxygenation as Bridge to Replacement Therapies in Cardiogenic Shock: Insights From the Extracorporeal Life Support Organization.

BACKGROUND: There has been increasing use of extracorporeal membrane oxygenation (ECMO) as bridge to heart transplant (orthotopic heart transplant [OHT]) or left ventricular assist device (LVAD) over the last decade. We aimed to provide insights on the population, outcomes, and predictors for the selection of each therapy. METHODS: Using the Extracorporeal Life Support Organization Registry between 2010 and 2019, we compared in-hospital mortality and length of stay, predictors of OHT versus LVAD, and predictors of in-hospital mortality for patients with cardiogenic shock that were bridged with ECMO to OHT or LVAD. One hundred sixty-seven patients underwent LVAD versus 234 patients who underwent OHT. RESULTS: The overall use of ECMO has increased from 1.7% in 2010 to 22.2% in 2019. Mortality was similar between groups (LVAD: 28.7% versus OHT: 29.1%) while length of stay was longer for OHT (LVAD: 49.6 versus OHT: 59.5 days, P=0.05). Factors associated with OHT included prior transplant (odds ratio [OR]=31.26 [CI, 3.84-780.5]), use of a temporary pacemaker (OR=6.5 [CI, 1.39-50.15]), and increased use of inotropes on ECMO (OR=3.77 [CI, 1.39-11.07]), whereas LVAD use was associated with weight (OR=0.98 [CI, 0.97-0.99]), cardiogenic shock presentation (OR=0.40 [CI, 0.21-0.78]), previous LVAD (OR=0.01 [CI, 0.0001-0.22]), respiratory failure (OR=0.28 [CI, 0.11-0.70]), and milrinone infusion (OR=0.32 [CI, 0.15-0.67]). Older age (OR=1.07 [CI, 1.02-1.12]), cannulation bleeding (OR=26.1 [CI, 4.32-221.3]), and surgical bleeding (OR=6.7 [CI, 1.26-39.9]) in patients receiving LVAD and respiratory failure (OR=5 [CI, 1.17-23.1]) and continuous renal replacement therapy (OR=3.82 [CI, 1.28-11.9]) in patients receiving OHT were associated with increased mortality. CONCLUSIONS: ECMO use as a bridge to advanced therapies has increased over time, with more patients undergoing LVAD than OHT. Mortality was equal between the 2 groups while length of stay was longer for OHT.

The use of enoxaparin as bridge to therapeutic INR after LVAD implantation.

BACKGROUND: Left ventricular assist devices (LVAD) have been increasingly used in the treatment of end-stage heart failure. While warfarin has been uniformly recommended in the long-term as anticoagulation strategy, no clear recommendation exists for the post-operative period. We sought to evaluate the feasibility of enoxaparin in the immediate and early postoperative period after LVAD implantation. METHODS: This is a two-center, retrospective analysis of 250 consecutive patients undergoing LVAD implantation between January 2017 and December 2018. Patients were bridged postoperatively to therapeutic INR by either receiving unfractionated heparin (UFH) or low molecular weight heparin (LMWH). Patients were followed while inpatient and for 3 months after LVAD implantation. The efficacy outcome was occurrence of first and subsequent cerebrovascular accident while safety outcome was the occurrence of bleeding events. Length of stay (LOS) was also assessed. RESULTS: Two hundred fifty and 246 patients were analyzed for index admission and 3-month follow up respectively. No statistically significant differences were found between the two groups in CVA (OR = 0.67; CI = 0.07-6.39, P = 0.73) or bleeding events (OR = 0.91; CI = 0.27-3.04, P = 0.88) during index admission. Similarly, there were no differences at 3 months in either CVAs or bleeding events (OR = 0.85; 0.31-2.34; p = 0.76). No fatal events occurred during the study follow-up period. Median LOS was significantly lower (4 days; p = 0.03) in the LMWH group. CONCLUSIONS: LMWH in the immediate and early postoperative period after LVAD implantation appears to be a concurrently safe and efficacious option allowing earlier postoperative discharge and avoidance of recurrent hospitalizations due to sub-therapeutic INR.

A novel, highly discriminatory risk model predicting acute severe right ventricular failure in patients undergoing continuous-flow left ventricular assist device implant.

Various risk models with differing discriminatory power and predictive accuracy have been used to predict right ventricular failure (RVF) after left ventricular assist device (LVAD) placement. There remains an unmet need for a contemporary risk score for continuous flow (CF)-LVADs. We sought to independently validate and compare existing risk models in a large cohort of patients and develop a simple, yet highly predictive risk score for acute, severe RVF. Data from the Mechanical Circulatory Support Research Network (MCSRN) registry, consisting of patients who underwent CF-LVAD implantation, were randomly divided into equal-sized derivation and validation samples. RVF scores were calculated for the entire sample, and the need for a right ventricular assist device (RVAD) was the primary endpoint. Candidate predictors from the derivation sample were subjected to backward stepwise logistic regression until the model with lowest Akaike information criterion value was identified. A risk score was developed based on the identified variables and their respective regression coefficients. Between May 2004 and September 2014, 734 patients underwent implantation of CF-LVADs [HeartMate II LVAD, 76% (n = 560), HeartWare HVAD, 24% (n = 174)]. A RVAD was required in 4.5% (n = 33) of the patients [Derivation cohort, n = 15 (4.3%); Validation cohort, n = 18 (5.2%); P = 0.68)]. 19.5% of the patients (n = 143) were female, median age at implant was 59 years (IQR, 49.4-65.3), and median INTERMACS profile was 3 (IQR, 2-3). RVAD was required in 4.5% (n = 33) of the patients. Correlates of acute, severe RVF in the final model included heart rate, albumin, BUN, WBC, cardiac index, and TR severity. Areas under the curves (AUC) for most commonly used risk predictors ranged from 0.61 to 0.78. The AUC for the new model was 0.89 in the derivation and 0.92 in the validation cohort. Proposed risk model provides very high discriminatory power predicting acute severe right ventricular failure and can be reliably applied to patients undergoing placement of contemporary continuous flow left ventricular assist devices.

Left Lateral Thoracotomy for Centrifugal Continuous-Flow Left Ventricular Assist Device Placement: An Analysis from the Mechanical Circulatory Support Research Network.

Continuous-flow left ventricular assist devices (CF-LVADs) have revolutionized the management of patients with advanced heart failure. Alternative implant strategies are increasingly used for device placement. We reviewed our experience from the Mechanical Circulatory Support Research Network registry with the HeartWare centrifugal CF-LVAD (HVAD). From May 2004 to August 2015, 1,150 patients underwent primary CF-LVAD implantation at our institutions. Within this group, a total of 283 patients (25%) were implanted with the HVAD. A minimally invasive left lateral thoracotomy (MILT) implant strategy was used in 53 patients (20%), of which 22 (42%) were implanted off-pump. Median age at implant was 59 years and 183 patients (65%) were implanted as bridge-to-transplantation. Follow-up was 100% complete for a total of 302 patient-years of support. In-hospital mortality was 4.9% (14 patients), and was comparable between the conventional sternotomy (CS) and MILT cohorts (p = 0.15). Patients in the MILT cohort had a shorter median length of stay (p < 0.01) and had a lower incidence of postimplant pump thrombus (p = 0.02). Cumulative survival at the end of follow-up reached 84%, and was comparable between the two groups (p = 0.298). Multivariate analysis identified preoperative bilirubin level as the only independent predictor of survival. Surgical technique had no impact on survival. In this large, multicenter experience, data demonstrate excellent survival and adverse event profiles for patients supported with the HVAD technology, regardless of surgical implant technique. With constant advancements in device technology along with our increasing clinical experience with the newer techniques, minimally invasive LVAD implantation continues to evolve as a valuable alternative to CS in selected patients.

Temporal Differences in Outcomes During Long-Term Mechanical Circulatory Support.

BACKGROUND: Device indications have changed for placement of continuous-flow left ventricular assist devices (CF-LVADs). We performed a multicenter analysis evaluating temporal variations in outcomes after CF-LVAD implantation. METHODS & RESULTS: We retrospectively defined 3 time intervals to reflect changes in CF-LVAD technology (period 1, 2004-2009; period 2, 2010-2012; and period 3, 2012-2014). A total of 1,064 patients (Heartmate II [HMII] = 835; Heartware [HVAD] = 229) underwent CF-LVAD implantation from May 2004 to October 2014. Device utilization was different between periods: period 1: HMII = 134 (100%); period 2: HMII = 480 (88%) and HW = 63 (12%); and period 3: HMII = 221 (57%) and HW = 166 (43%); P < .001. Despite few baseline group differences, adjusted survivals were similar among the time periods (P = .96). Adjusted multivariable analysis revealed age (per 10-year increase) and Interagency Registry for Mechanically Assisted Circulatory Support category (1 vs all others) as the only independent predictors of mortality: P < .001 and P = .008, respectively. Furthermore, it also showed the later periods to be at an increased risk of adverse events: 1) pump thrombosis (periods 2 and 3); and 2) gastrointestinal bleeding (period 3). CONCLUSIONS: Despite significant differences in device types, indications, and patient characteristics, post-implantation survivals were similar across time intervals. The most recent cohort seems to be at an increased risk of gastrointestinal bleeding and pump thrombosis.

Effect of Milrinone Infusion on Pulmonary Vasculature and Stroke Work Indices: A Single-Center Retrospective Analysis in 69 Patients Awaiting Cardiac Transplantation.

BACKGROUND: Although milrinone infusion is reported to benefit left ventricular function in chronic left heart failure, few insights exist regarding its effects on pulmonary circulation and right ventricular function. METHODS: We retrospectively reviewed right heart catheterization data at baseline and during continuous infusion of milrinone in 69 patients with advanced heart failure and analyzed the effects on ventricular stroke work indices, pulmonary vascular resistance and pulmonary arterial compliance. RESULTS: Compared to baseline, milrinone infusion after a mean 58 ± 61 days improved mean left ventricular stroke work index (1540 ± 656 vs. 2079 ± 919 mmHg·mL/m2, p = 0.0007) to a much greater extent than right ventricular stroke work index (616 ± 346 vs. 654 ± 332, p = 0.053); however, patients with below median stroke work indices experienced a significant improvement in both left and right ventricular stroke work performance. Overall, milrinone reduced left and right ventricular filling pressures and pulmonary and systemic vascular resistance by approximately 20%. Despite an increase in pulmonary artery capacitance (2.3 ± 1.6 to 3.0 ± 2.0, p = 0.013) and a reduction in pulmonary vascular resistance (3.8 ± 2.3 to 3.0 ± 1.7 Wood units), milrinone did not reduce the transpulmonary gradient (13 ± 7 vs. 12 ± 6 mmHg, p = 0.252), the pulmonary artery pulse pressure (25 ± 10 vs. 24 ± 10, p = 0.64) or the pulmonary artery diastolic to pulmonary capillary wedge gradient (2.0 ± 6.5 vs. 2.4 ± 6.0, p = 0.353). CONCLUSION: Milrinone improved left ventricular stroke work indices to a greater extent than right ventricular stroke work indices and had beneficial effects on right ventricular net input impedance, predominantly via augmentation of left ventricular stroke volume and passive unloading of the pulmonary circuit. Patients who had the worst biventricular performance benefited the most from chronic milrinone infusion.

Outcomes of Patients Receiving Temporary Circulatory Support Before Durable Ventricular Assist Device.

BACKGROUND: Temporary circulatory support (TCS) is used to stabilize patients in critical cardiogenic shock and bridge patients to a durable ventricular assist device (VAD). Whether TCS confers increased risk at the time of VAD implant is unknown. METHODS: Prospectively collected data from five institutions was retrospectively reviewed. All profile 1 through profile 3 patients implanted with a continuous-flow VAD (n = 804) were categorized into three groups: TCS (n = 68); non-TCS profile 1 (n = 70); and non-TCS profile 2-3 (n = 666). RESULTS: End-organ function and hemodynamics were worse before TCS than in non-TCS profile 1 patients: creatinine (1.7 ± 0.1 mg/dL versus 1.3 ± 0.06 mg/dL, p = 0.003); and right atrial pressure (16 ± 0.8 mm Hg versus 13 ± 1.1 mm Hg, p = 0.048). The TCS restored cardiac output before durable VAD (4.9 ± 0.2 L/min), and was comparable to profile 2-3 patients (4.3 ± 0.05 L/min) and better than profile 1 patients (4.0 ± 0.2 L/min, p = 0.002). Markers of hepatic function such as bilirubin were impaired before VAD in TCS and profile 1 patients (2.0 ± 0.2 mg/dL) compared with profile 2 and 3 patients (1.1 ± 0.03, p < 0.001). The incidence of postoperative right ventricular failure necessitating a right VAD was 21% for TCS patients and non-TCS profile 1 patients compared with 2% for profile 2-3 patients (p < 0.001). Profile 1 and TCS patients had similar 1-year survival (70% and 77%, p = 0.57), but inferior survival as compared with profile 2 and 3 patients (82%, p < 0.001). On multivariable analysis, TCS increased the hazard of death twofold. CONCLUSIONS: Temporary circulatory support restores hemodynamics and reverses end-organ dysfunction. Nevertheless, these patients have high residual risk with postoperative morbidity and mortality that parallels profile 1 patients without TCS. Caution is suggested in downgrading risk for TCS patients with improved hemodynamic stability.

A multi-institutional outcome analysis of patients undergoing left ventricular assist device implantation stratified by sex and race.

BACKGROUND: Earlier studies have demonstrated disparities in patients undergoing left ventricular assist device (LVAD) implantation when stratified according to sex and race. Because very few data exist from large investigations, we reviewed data from the registry of the Mechanical Circulatory Support Research Network. METHODS: Between May 2004 and September 2014, 734 patients underwent primary LVAD implantation at our institutions. Median age at implant was 57 (range 18 to 82) years and there were 577 males (80%). Race included Caucasian (C) in 586 patients (82%), African-American (AA) in 112 (16%), and other (O) in 21 (3%). Between sexes, significant pre-operative differences most commonly included median age at implant (males 60 years, females 57 years), ischemic etiology (53% vs 35%) and mean INTERMACS profile (2.9 vs 2.5). Between races, significant pre-operative differences most commonly included median age at implant (C = 61 vs AA = 51 vs O = 51), New York Heart Association functional class (85% vs 100% vs 92%) and ischemic etiology (55% vs 24% vs 40%). RESULTS: There were no significant differences in survival at 1, 3 or 5 years by sex or race. Similarly, there were no differences in time-related freedom from stroke, drive-line infection, gastrointestinal bleeding or pump thrombus by sex or race. After controlling for differences, neither sex nor race was associated with survival (p = 0.09 and p = 0.18, respectively), stroke (p = 0.28 and p = 0.21), drive-line infection (p = 0.9 and p = 0.92), gastrointestinal bleed (p = 0.48 and p = 0.45) or pump thrombus (p = 0.99 and p = 0.8). CONCLUSIONS: In this large, multi-institutional analysis, although some pre-operative clinical characteristics varied, they did not translate into any significant differences in late survival or complications while on LVAD support.

Ventricular Assist Device Therapy in Older Patients With Heart Failure: Characteristics and Outcomes.

BACKGROUND: Limited data exist on outcomes in patients ≥70 years of age supported with the use of continuous-flow left ventricular assist devices (LVADs). METHODS: Data on 1149 continuous-flow LVAD recipients was queried from the Mechanical Circulatory Support Research Network. Groups were assigned based on age: ≥70 years ("older patients") and <70 years. The primary outcome was survival at one-year based on age grouping. RESULTS: Compared with younger patients (54.3 ± 11.2 y; n = 986), older patients (73.4 ± 3.0 y) constituted only 14% of LVAD implants. Older patients had similar rates of device thrombosis (P = .47) and stroke (P = .44), but survival-free of gastrointestinal bleeding (GIB) at 1 year was lower compared with younger patients (58% vs 69%; P < .01). Unadjusted survival at 1 year in older patients was 75% compared with 84% in younger patients, and at 2 years 65% versus 73% (P = .18). Age ≥70 years was not associated with increased mortality (adjusted hazard ratio [aHR] 0.94, 95% confidence interval [CI] 0.70-1.26; P = .67). Preoperative creatinine (aHR 1.57, 95% CI: 1.30-1.89, P < .0001), bilirubin (aHR 1.22, 95% CI 1.05-1.42; P = .010), and ischemic cardiomyopathy (aHR 1.43, 95% CI 1.11-1.84; P = .005) portended increased risk of death. In older patients, the only predictor of mortality was creatinine (HR 2.1, 95% CI 1.2-3.4; P = .007). Creatinine ≥1.4 mg/dL was associated with a 1-year survival of 65%, compared with 84% when the creatinine was <1.4 mg/dL (P = .009). CONCLUSION: Age >70 years is an important consideration when assessing LVAD risk, but other correlates may be more predictive of LVAD survival. Older patients without renal dysfunction have survival similar to younger patients. Older patients should be counseled about age-correlated risks, including higher rates of GIB.

Active Clearance of Chest Tubes Reduces Re-Exploration for Bleeding After Ventricular Assist Device Implantation.

Chest tubes are utilized to evacuate shed blood after left ventricular assist device (LVAD) implantation, however, they can become clogged, leading to retained blood. We implemented a protocol for active tube clearance (ATC) of chest tubes to determine if this might reduce interventions for retained blood. A total of 252 patients underwent LVAD implantation. Seventy-seven patients had conventional chest tube drainage (group 1), whereas 175 patients had ATC (group 2). A univariate and multivariate analysis adjusting for the use of conventional sternotomy (CS) and minimally invasive left thoracotomy (MILT) was performed. Univariate analysis revealed a 65% reduction in re-exploration (43-15%, p < 0.001), and an 82% reduction in delayed sternal closure (DSC; 34-6%, p <0.001). In a sub-analysis of CS only, there continued to be statistically significant 53% reduction in re-exploration (45% vs. 21%, p = 0.0011), and a 77% reduction in DSC (35% vs. 8%, p < 0.001) in group 2. Using a logistic regression model adjusting for CS versus MILT, there was a significant reduction in re-exploration (odds ratio [OR] = 0.44 [confidence interval {CI} = 0.23-0.85], p = 0.014) and DSC (OR = 0.20 [CI = 0.08-0.46], p <0.001) in group 2. Actively maintaining chest tube patency after LVAD implantation significantly reduces re-exploration and DSC.

Outcomes of Patients Implanted Using a Left Thoracotomy Technique for a Miniaturized Centrifugal Continuous-Flow Pump.

As ventricular-assist devices (VADs) are increasingly employed in heart failure management, a leading cause of mortality, new literature is consistently published on less-invasive implantation techniques. Although early perioperative outcomes have been shown to be favorable with minimally invasive left thoracotomy (LT) approaches compared with conventional sternotomy (CS), studies comparing long-term outcomes are lacking. We set out to evaluate long-term follow up between LT and CS approach. In a single center, retrospective review, data on patients with similar demographic profiles were collected. HeartWare (HVAD) implantation was performed by either CS or LT. Analysis was performed on perioperative adverse outcomes, and 6 month postoperative adverse events. Primary objectives of the study included comparative outcomes of morbidity and mortality between both groups at 180 days postimplantation. Eighty-one (n = 81) bridge to transplant (BTT) patients underwent CS or LT HVAD implantation. Perioperative transfusion (p = 0.04) favored the LT cohort compared with CS, with a median of 6 units and 8 units transfused for each group, respectively. No survival difference was observed between both groups at 6 months postimplantation (p = 0.52). Clinical outcomes at an average of 6 month follow up showed no difference in adverse events, including common postoperative VAD complications such as infection and right heart failure. Miniaturization of LVAD size and improvement in technology has allowed expansion of interest in alternative surgical approaches for HVAD implantation. For BTT patients, no difference in early outcome was observed 6 months after implantation using a left LT versus CS technique.

Outcomes After Concomitant Procedures with Left Ventricular Assist Device Implantation: Implications by Device Type and Indication.

Guidelines for performing concomitant procedures (CPs) in patients undergoing continuous flow-left ventricular assist device (CF-LVAD) implantation are unclear. The impact of an increased surgical complexity outside the constraint of landmark clinical trials has not been reported. From May 2004 to December 2013, 614 patients (499 males, 81%) underwent CF-LVAD implant at our institutions. Median age was 57 ± 13 years and 364 (59%) were bridge to transplantation (BTT). Survival and device-related complications were analyzed and stratified based on the surgical intervention. A total of 398 patients (65%) underwent CF-LVAD implantation without CPs. The remaining patients (35%, n = 216) were grouped according to various CPs. Survival was comparable between groups and not influenced by the CP, device type, or indication for implant. Time-to-first device-related adverse event was shorter in patients with CPs. Regression analysis revealed only increased age (p = 0.03), increase in baseline creatinine (p = 0.002), cardiopulmonary bypass time (p = 0.03), and decreased body mass index (p = 0.03) were predictors of mortality, whereas only age (p = 0.006) and prior sternotomy (p = 0.02) were related to adverse device-related events. Performing CPs leads to comparable survival and device-related outcomes after implant. The decision to perform CPs should be balanced with age, preoperative renal dysfunction, and projected complexity of surgery.

Can an Alternative Outflow Strategy be Utilized for High-Risk Bridged Patients with Previous Cardiac Surgery?

The HeartWare ventricular assist device (HVAD) is an implantable continuous-flow centrifugal pump that has allowed the development of sternal-sparing techniques, with the use of alternative outflow strategies. We compared early outcomes for patients bridged with the conventional versus alternative outflow graft strategy. From January 2013 to October 2014, 89 patients with HVAD implantation were identified. Survival was analyzed with Kaplan-Meier methods, and a log-rank test was used to compare outcomes between groups. Thirty patients (34%) had ≥1 previous sternotomy before HVAD implantation. Eight patients (27%) were approached using an alternative outflow graft technique with outflow graft connection to the descending aorta (n = 4, 50%) or left subclavian artery (n = 4, 50%), whereas 22 (73%) were implanted via a conventional sternotomy approach with the outflow graft to the ascending aorta. Preoperative characteristics (age, Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS], and Lietz-Miller score) were comparable between groups (all p > 0.05). Median follow-up was 4.7 (2.8-9.3) months of support. Outcomes were comparable between conventional and alternative outflow groups; survival at 6 months was 74% for the conventional group and 83% in the alternative outflow group. An alternative outflow graft strategy can be utilized to support bridged patients with a history of prior sternotomy.

Driveline Infection Risk with Utilization of a Temporary External Anchoring Suture After Implantation of a Left Ventricular Assist Device.

Driveline infections (DLI) are a cause of morbidity after continuous-flow left ventricular assist device (CF-LVAD) implantation. Because driveline trauma contributes to DLI, we assessed whether intraoperative placement of a temporary external anchoring suture (EAS) influenced DLI rate. We analyzed 161 consecutive patients with CF-LVAD (HMII 82; HW 79) implantation. Two groups were defined: placement of EAS (n = 85) or No EAS (n = 76). For NO EAS patients, the driveline was permanently anchored internally to the rectus fascia. Cox proportional analysis was performed to assess the effect of EAS on time to first confirmed DLI. Baseline characteristics were comparable between groups (all p = 0.3). Mean follow-up time was 0.93 years. A total of 18 (11.1%) patients developed confirmed culture positive DLI, with "first infection" rate of 0.13 events/year. Mean time to confirmed DLI was 0.69 years. Driveline infection was less likely (hazard ratio [HR] = 0.28, 0.95 confidence interval [CI] = 0.06-1.25, p = 0.056) to occur in NO EAS (2/18) then in EAS (16/18). Confirmed DLI was comparable between device types (p = 0.3). Multivariable regression adjusted for age, BMI, blood product use, device type, and diabetes showed equivocal effect of EAS (HR = 0.33, 0.95 CI = 0.07-1.54, p = 0.12). Patients with a temporary EAS may have an increased risk of confirmed DLI after device implantation.

Treatment of device thrombus in the HeartWare HVAD: Success and outcomes depend significantly on the initial treatment strategy.

BACKGROUND: Pump thrombosis is a major adverse event in patients supported with a left ventricular assist device (LVAD). Treatment approaches include device exchange, lytic therapy, or augmentation of anticoagulation or antiplatelet therapy. The optimal strategy in the HeartWare HVAD Ventricular Assist System (HeartWare, Framingham, MA) is uncertain, and because few large studies have examined differing treatment outcomes, we have reviewed findings from the Mechanical Circulatory Support Research Network registry. METHODS: Between March 2009 and August 2014, 175 patients (133 male) underwent implantation of the HeartWare HVAD at institutions that comprise the Mechanical Circulatory Support Research Network. Median age at implant was 59 years (range, 18-76 years). Follow-up was available in all patients for a median of 6 months (maximum, 61 months) and for a total of 163 patient-years of support. There were 36 pump thromboses (using Interagency Registry for Mechanically Assisted Circulatory Support criteria) in 21 patients for a total event rate of 0.22 events/patient-year of support; 13 patients had 1 event, 4 had 2, 2 had 3, 1 had 4, and 1 had 5. The median time to the first thrombosis was 6.4 months, and to each subsequent thrombosis was 4, 3, 2, and 2 months, respectively. Primary treatment success was defined as the patient remaining alive and within the first 30 days of the initial treatment be free from stroke, recurrence of pump thrombosis, device exchange, or urgent transplantation (United Network of Organ Sharing Status 1A). Medical treatment was defined as tissue plasminogen activator, heparin plus glycoprotein IIb/IIIa inhibitor, or heparin alone, not followed by surgical treatment within 72 hours. RESULTS: Initial medical treatment was used in 29 episodes (tissue plasminogen activator in 24, heparin alone in 4, and heparin plus glycoprotein IIb/IIIa in 1) and surgical (device exchange) in 7. Medical treatment was successful in 14 of 29 episodes (48%). Complications of medical treatment included hemorrhagic stroke in 6 patients (21%), need for urgent device exchange/transplant in 6 (21%), and death in 3 (10%). Surgical treatment was successful in all 7 patients (100%). No significant early complications or early deaths occurred after device exchange. CONCLUSIONS: In this large multicenter analysis, we observed that medical therapy, as the initial treatment strategy for HeartWare HVAD thrombosis, is associated with low success (48%) and a significant risk of hemorrhagic stroke (21%) and death (10%). However, initial treatment with device exchange was uniformly successful and not associated with significant early morbidity or death. Although the optimal treatment approach for HeartWare HVAD pump thrombosis remains undecided, these data do not support the routine use of medical therapy as an initial treatment strategy.

Adverse neurologic events in patients bridged with long-term mechanical circulatory support: A device-specific comparative analysis.

BACKGROUND: Neurologic complications are among the principal causes of morbidity and mortality after continuous-flow left ventricular assist device (CF-LVAD) implantation. The aim of this study was to describe a focused "real-world" multicenter comparison of neurologic outcomes between HeartMate II (HMII) and HeartWare HVAD CF-LVAD recipients. METHODS: Between March 2009 and October 2014, 497 patients underwent primary CF-LVAD implantation as a bridge to transplantation at centers included in the Mechanical Circulatory Support Research Network; 314 patients (63%) received HMII, and 183 patients (37%) received HVAD. Ischemic cerebrovascular accident, hemorrhagic cerebrovascular accident, and transient ischemic attack were the neurologic outcomes assessed. RESULTS: Median follow-up time for HMII recipients was 0.95 years (0.48, 1.85, range) and for HVAD recipients was 0.44 years (0.19, 0.97, range) (p < 0.001). HMII recipients had significantly fewer neurologic events per patient year for ischemic cerebrovascular accident (0.071) and transient ischemic attack (0.012) compared with HVAD recipients (0.157 and 0.072, respectively). Univariate analysis showed that 51 HMII recipients (16%) had any neurologic event, whereas 34 HVAD recipients (19%) had any neurologic event (p = 0.504). After adjusting for pre-specified covariates (device type, age, sex, atrial fibrillation, diabetes, and Interagency Registry for Mechanically Assisted Circulatory Support profile), multivariable analysis showed only advanced age was able to predict neurologic events (p = 0.02). Neurologic events were comparable between HMII and HVAD recipients after multivariable analysis. CONCLUSIONS: CF-LVAD placement incurs a low but significant risk of neurologic complications in patients receiving CF-LVADs as a bridge to transplantation. Advancing age is a risk factor for any adverse neurologic outcome. This multicenter analysis demonstrated comparable hazard of adverse neurologic events among patients implanted with HMII or HVAD.