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.

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.

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.

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.

In-hospital outcomes of a minimally invasive off-pump left thoracotomy approach using a centrifugal continuous-flow left ventricular assist device.

BACKGROUND: Minimally invasive left thoracotomy (MILT) and off-pump implantation strategies have been anecdotally reported for implantation of the HeartWare ventricular assist device (HVAD). We analyzed our experience with off-pump MILT implantation techniques and compared early in-hospital outcomes with conventional on-pump sternotomy (CS) implantation strategy. METHODS: Between January 2013 and February 2014, 51 patients underwent HVAD implantation and were included in this study. Thirty-three patients had CS, whereas 18 patients underwent off-pump MILT. To compare outcomes of these techniques, a multivariate analysis using propensity score modeling was performed after adjusting for age, INTERMACS, Kormos and Leitz-Miller (LM) scores. RESULTS: Mean age at implant was 57 (range 18 to 69) years, and overall in-hospital mortality was 8%. Univariate analysis revealed a statistically significant reduction in days on inotropes (p = 0.04), and a trend toward reduced intra-operative blood product administration (p = 0.08) in the MILT group. There was no difference in intensive-care-unit length of stay (p = 0.5), total length of stay (p = 0.76), post-operative blood product administration (p = 0.34) and total time on mechanical ventilation (p = 0.32). After adjusting for age, INTERMACS profile and Kormos and LM scores, no statistically significant differences were observed between the MILT and CS groups. CONCLUSIONS: An off-pump MILT implantation strategy can be utilized as a safe surgical approach for patients undergoing HVAD implantation. Further large collaborative studies are needed to identify advantages of the MILT approach.

Hemodynamic transesophageal echocardiography after left ventricular assist device implantation.

OBJECTIVE: The authors hypothesized that the clinical profile of patients undergoing hTEE after continuous flow left ventricular assist device (CF-LVAD) implant would be in patients with greater acuity, more blood product utilization, and longer length of ICU stay, and that hTEE would change clinical management. DESIGN: Retrospective review. SETTING: University hospital. PARTICIPANTS: One hundred consecutive patients receiving a CF-LVAD. INTERVENTIONS: Retrospective review using a standardized electronic form of a miniaturized disposable transesophageal echocardiography probe that documented not only physical findings but also changes in hemodynamic management (hTEE) in CF-LVAD patients. MEASUREMENTS AND MAIN RESULTS: Of the 100 patients, 41 received an hTEE probe. The INTERMACS score, Leitz-Miller Score, and Kormos score indicated the hTEE group had a statistically significant greater risk of morbidity and mortality. Interoperatively, the hTEE group received more blood products and was more likely to have an open chest. Postoperatively, the hTEE group received more blood products, had a longer total length of stay, and had increased mortality. ICU length of stay, days on inotropes and days on mechanical ventilation were not statistically significant between the 2 groups. Information obtained from hTEE changed ICU management in 72% of studies. CONCLUSION: Retrospective review of CF-LVAD patients revealed that postoperative hTEE is used in sicker CF-LVAD patients and frequently leads to changes in ICU clinical management.

Perioperative blood product use: a comparison between HeartWare and HeartMate II devices.

BACKGROUND: The HeartWare (HW) (Framingham, MA) and the HeartMate II (HM II) (Thoratec Inc, Pleasanton, CA) continuous-flow left ventricular assist devices (CF-LVADs) are commonly used to bridge patients to transplantation. We hypothesized that there are differences in perioperative blood product (BP) use and chest tube (CT) output between CF-LVAD types. METHODS: We retrospectively evaluated BP use in 71 patients who were implanted with a CF-LVAD (HM II = 38; HW = 33) by median sternotomy for bridge to transplantation (BTT) indications from 2009 to 2013. Detailed BP use data were collected during the intraoperative and postoperative periods and included packed red blood cells, platelets, fresh frozen plasma, and cryoprecipitate. RESULTS: Preoperative characteristics (age, left ventricular ejection fraction, previous sternotomy, ischemic cause), and risk stratification scores (Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS]) profile, Leitz-Miller score, Kormos score) were comparable between groups (all p > 0.05). Total average intraoperative and postoperative BP use was different between device types: HW = 8.3 ± 13 versus HM II = 12.6 ± 14.0 units (p = 0.002) and HW = 6.1 ± 12.0 units compared with HM II = 13.5 ± 24.1 units (p = 0.022), respectively. Average postoperative CT output for HW (3,231 ± 3,648 mL) and HM II (3,463 ± 3,050) (p < 0.008) were different between device types. Multivariate analysis revealed that a higher preoperative Leitz-Miller score, implantation of an HM II CF-LVAD, previous sternotomy, and a longer duration of cardiopulmonary bypass (CPB) time were independently associated with increased need for BP use, whereas only use of the HM II device and a longer bypass time predicted a greater CT output. CONCLUSIONS: Compared with HM II, implantation of the HW CF-LVAD was associated with reduced intraoperative and postoperative BP use and decreased CT output. Increased awareness of device-related differences in bleeding and BP use may improve CF-LVAD patient outcomes.

Does renal dysfunction and method of bridging support influence heart transplant graft survival?

BACKGROUND: Renal insufficiency is common in status 1B patients supported with inotropes or a continuous flow left ventricular device (CF-LVAD) as a bridge to heart transplantation. We evaluated the association of renal function and inotrope versus CF-LVAD support on posttransplant graft survival in status 1B patients. METHODS: The Scientific Registry for Transplant Recipients database was analyzed for posttransplant survival in status 1B patients bridged with inotropes or CF-LVAD who underwent transplantation between 2003 and 2012. Pretransplant renal function was measured by estimating glomerular filtration rate (GFR) and was stratified as less than 45 mL · min(-1) · 1.73 m(-2), 45 to 59, and 60 or greater. Univariate Kaplan-Meier and multivariate Cox regression models were used to evaluate the main effects of GFR strata and inotropes versus CF-LVAD, and the interaction effect of GFR strata by CF-LVAD, on graft survival. RESULTS: This study included 4,158 status 1B patients (74% male, aged 53 ± 12 years). Of those, 659 patients had a CF-LVAD (HeartMate-II [Thoratec, Pleasanton, CA], n = 638; HVAD [HeartWare, Framingham, MA], n = 21), and 3,530 were receiving inotropes (31 CF-LVAD patients were also receiving inotropes). Kaplan-Meier analyses demonstrated reduced graft survival (p = 0.022) in patients with pretransplant GFR less than 45 versus GFR 45 to 59 (p = 0.062) and versus GFR 60 or greater (p = 0.007), and no effect of inotrope versus CF-LVAD support on graft survival (p = 0.402). Multivariate analysis demonstrated that, after adjusting for the main effects of GFR stratum, CF-LVAD, and inotropes, status 1B patients bridged with a CF-LVAD and GFR in the lowest stratum had reduced graft survival (interaction effect p = 0.040). CONCLUSIONS: Pretransplant renal insufficiency was associated with reduced posttransplant graft survival in status 1B patients. This risk is increased for patients bridged with a CF-LVAD (versus inotropes) who have GFR in the lowest stratum.

Combined usage of stem cells in end-stage heart failure therapies.

Remarkable achievements have been made in the clinical application of mechanical circulatory support and cardiac transplantation for patients with end-stage heart failure. Despite the successes, complications associated with these therapies continue to drive cardiac regenerative research utilizing stem cell based therapies. Multiple stem cell lineages hold clinical promise for cardiac regeneration-mostly through cellular differentiation, cellular fusion, and paracrine signaling mechanisms. Bone marrow-derived endothelial progenitor cells are among the most intriguing and controversial cell types currently being investigated. Formidable barriers exist, however, in finding the ideal cardiac regenerative stem cell, such as identifying specific lineage markers, optimizing in vitro cellular expansion and improving methods of stem cell delivery. Hybrid approaches of cardiac regeneration using stem cell therapies in conjunction with immunomodulation after cardiac transplantation or with mechanical circulatory support produce cutting edge stem cell technologies. This review summarizes the current knowledge and therapeutic applications of stem cells in patients with end-stage heart failure, including stem cell therapy after implantation of mechanical circulatory support and cardiac transplantation.

Left thoracotomy HeartWare implantation with outflow graft anastomosis to the descending aorta: a simplified bridge for patients with multiple previous sternotomies.

Advances in mechanical circulatory support have been critical in bridging patients awaiting heart transplantation. In addition, improvement in device durability has enabled left ventricular assist device therapy to be applied as destination therapy in those not felt to be transplant candidate. Because of the increasing complexity of patients, there continues to be a need for alternative strategies for device implantation to bridge high-risk patients awaiting heart transplantation, wherein the risks of numerous previous sternotomies may be prohibitive. We present a unique technique for placement of the HeartWare ventricular assist device via left anterior thoracotomy to the descending aorta in a patient awaiting heart transplantation with a history of multiple previous sternotomies.

Dynamic pulmonary artery obstruction causing right ventricular failure after cardiac transplantation in a patient with Mustard-Senning corrected d-transposition of the great arteries.

Patients with congenital d-transposition of the great arteries (d-TGA) undergoing palliative atrial baffle surgery in infancy often develop systemic ventricular failure in adulthood. If they undergo cardiac transplantation, they are prone to morphologic right ventricular (RV) failure secondary to severe pulmonary hypertension as a result of systemic ventricular failure. We report a case of a patient with d-TGA and biventricular ventricular failure requiring heart transplantation (HT) that developed RV failure postoperatively because of dynamic pulmonary artery (PA) obstruction at the anastomotic site of PA. Obstruction at the site of PA anastomosis due to torsion or redundancy of the donor or recipient PA is a rare but treatable cause of postoperative RV failure. In this case, rapid identification of the etiology of RV failure and implementation of corrective therapies before the development of end-organ dysfunction, resulted in complete RV recovery and normal allograft function. This case represents the first known report of dynamic PA anastomoticobstruction resulting in RV failure after HT that was corrected with pulmonary arterioplasty, and RV assist device resulting in complete recovery.