Association of Renin-Angiotensin-Aldosterone System Inhibitors With Clinical Outcomes, Hemodynamics, and Myocardial Remodeling Among Patients With Advanced Heart Failure on Left Ventricular Assist Device Support.

BACKGROUND: We evaluated the potential benefits of renin-angiotensin-aldosterone system inhibitors (RAASi) in patients with left ventricular assist device support. METHODS AND RESULTS: A total of 165 consecutive patients undergoing left ventricular assist device implant and alive at 6-month on support were studied. RAASi status after 6-month visit along with clinical reasons for nonprescription/uptitration were retrospectively assessed. The primary outcome was a composite of heart failure hospitalization or cardiovascular death between 6 and 24 months after left ventricular assist device implant. Remodeling and hemodynamic outcomes were explored by studying the association of RAASi new prescription/uptitration versus unmodified therapy at 6-month visit with the change in echocardiographic parameters and hemodynamics between 6 and 18 months. After the 6-month visit, 76% of patients were on RAASi. Patients' characteristics among those receiving and not receiving RAASi were mostly similar. Of 85 (52%) patients without RAASi new prescription/uptitration at 6-month visit, 62% had no apparent clinical reason. RAASi were independently associated with the primary outcome (adjusted hazard ratio, 0.31 [95% CI, 0.16-0.69]). The baseline rates of optimal echocardiographic profile (neutral interventricular septum, mitral regurgitation less than mild, and aortic valve opening) and hemodynamic profile (cardiac index ≥2.2 L/min per m2, wedge pressure <18 mm Hg, and right atrial pressure <12 mm Hg) were similar between groups. At 18 months, patients receiving RAASi new prescription/uptitration at 6 months had higher rates of optimal hemodynamic profile (57.5% versus 37.0%; P=0.032) and trends for higher rates of optimal echocardiographic profile (39.6% versus 22.9%; P=0.055) compared with patients with 6-month unmodified therapy. Optimal 18-month hemodynamic and echocardiographic profiles were associated with the primary outcome (log-rank=0.022 and log-rank=0.035, respectively). CONCLUSIONS: RAASi are associated with improved outcomes and improved hemodynamics among mechanically unloaded patients.

Mechanical life support algorithm developed by simulation for inpatient emergency management of recipients of implantable left ventricular assist devices.

Background: Published guidance concerning emergency management of left ventricular assist device (LVAD) recipients is both limited and lacking in consensus which increases the risk of delayed and/or inappropriate actions. Methods: In our specialist tertiary referral centre we developed, by iteration, a novel in-hospital resuscitation algorithm for LVAD emergencies which we validated through simulation and assessment of our multi-disciplinary team. A Mechanical Life Support course was established to provide theoretical and practical education combined with simulation to consolidate knowledge and confidence in algorithm use. We assessed these measures using confidence scoring, a key performance indicator (the time taken to restart LVAD function) and a multiple-choice question (MCQ) examination. Results: The mean baseline staff confidence score in management of LVAD emergencies was 2.4 ± 1.2 out of a maximum of 5 (n = 29). After training with simulation, mean confidence score increased to 3.5 ± 0.8 (n = 13).Clinical personnel who were provided with the novel resuscitation algorithm were able to reduce time taken to restart LVAD function from a mean value of 49 ± 8.2 seconds (pre-training) to 20.4 ± 5 seconds (post-training) (n = 42, p < 0.0001).The Mechanical Life Support course increased mean confidence from 2.5 ± 1.2 to 4 ± 0.6 (n = 44, p < 0.0001) and mean MCQ score from 18.7 ± 3.4 to 22.8 ± 2.6, out of a maximum of 28 (n = 44, p < 0.0001). Conclusion: We present a simplified LVAD Advanced Life Support algorithm to aid the crucial first minutes of resuscitation where basic interventions are likely to be critical in assuring good patient outcomes.

Midterm outcomes of venovenous extracorporeal membrane oxygenation as a bridge to lung transplantation: Comparison with nonbridged recipients.

OBJECTIVES: Venovenous extracorporeal membrane oxygenation (VV-ECMO) is increasingly being used in acutely deteriorating patients with end-stage lung disease as a bridge to transplantation (BTT). It can allow critically ill recipients to remain eligible for lung transplants (LTx) while reducing pretransplant deconditioning. We analyzed early- and midterm postoperative outcomes of patients on VV-ECMO as a BTT and the impact of preoperative VV-ECMO on posttransplant survival outcomes. METHODS: All consecutive LTx performed at our institution between January 2012 and December 2018 were analyzed. After matching, BTT patients were compared with nonbridged LTx recipients. RESULTS: Out of 297 transplanted patients, 21 (7.1%) were placed on VV-ECMO as a BTT. After matching, we observed similar 30-day mortality between BTT and non-BTT patients (4.6% vs. 6.6%, p = .083) despite a higher incidence of early postoperative complications (need for ECMO, delayed chest closure, and acute kidney injury). Furthermore, preoperative VV-ECMO did not appear associated with 30-day or 1-year mortality in both frequentist and Bayesian analysis (odds ratio [OR]: 0.35, 95% confidence interval: 0.03-3.49, p = .369; OR: 0.27, 95% credible interval: 0.01-3.82, p = 84.7%, respectively). In sensitivity analysis, both subgroups were similar in respect to 30-day (7.8% vs. 6.5%, p = .048) and 1-year mortality (12.5% vs. 18%, p = .154). CONCLUSIONS: Patients with acute refractory respiratory failure while waiting for LTx represent a high-risk cohort of patients. VV-ECMO as a BTT is a reasonable strategy in adult patients with acceptable operative mortality and 1-year survival comparable to non-BTT patients.

Postoperative acute kidney injury and renal replacement therapy after DCD lung transplantation.

Acute kidney injury (AKI) after lung transplantation (LTx) is a common complication. We aimed to assess whether donation after circulatory death (DCD) is associated with an increased risk of AKI and renal replacement therapy (RRT) in the early postoperative period compared to the donation after brain death (DBD). Retrospective data on a cohort (N = 95) of LTx patients (DCD n = 17, DBD n = 78) characterized by no use of ex-vivo lung perfusion were analyzed for the incidence of AKI within 30 postoperative days and incidence of RRT within 7 and 30 days. After optimal full matching, an imbalance remained between the DCD and DBD patients in respect to intraoperative use of cardiopulmonary bypass (CPB). Therefore, a further subset (n = 77) was defined that excluded CPB patients, and matching was repeated (DCD n = 13 vs. DBD n = 63) resulting in a fair balance on a range of preoperative characteristics and intraoperative use of ECMO. In both matched subsets, DCD was associated with around twice higher risk of AKI and RRT within 7 and 30 postoperative days. In conclusion, data suggest that DCD could be associated with worse early renal outcomes in a subset of LTx patients and justify further studies on the topic in order to refine further renal care pathways perioperatively.

Anticoagulation in syncardia total artificial heart recipients: anti-factor Xa or activated partial thromboplastin time?

Although the activated partial thromboplastin time (aPTT) has historically been the method of choice for anticoagulation monitoring in patients undergoing mechanical circulatory support with intravenous unfractionated heparin, it is being progressively superseded by the anti-factor Xa (anti-Xa) method. A retrospective single-arm, single-centre analysis of 20 patients who underwent total artificial heart implantation entailed simultaneous determinations of aPTT and anti-Xa. Agreement between these parameters was assessed using the Bland-Altman method. Despite a positive correlation between aPTT and anti-Xa, normal target ranges were poorly aligned: from 5th to 30th postoperative day, for anti-Xa values of 0.2 and 0.4 U/ml corresponding aPTT values were 52.1 and 65.2 s, 7.9 and 14.8 lower than predicted values, respectively. This was not associated with thromboembolic sequalae. It was not possible to demonstrate a significant relationship between the predictor variables (postoperative day; white blood cell count; C-reactive protein concentration; alanine transaminase and alkaline phosphatase level; bilirubin; haemoglobin; albumin and total protein concentration) and the agreement between aPTT and anti-Xa levels. In summary, when anti-Xa levels were used to guide anticoagulation therapy, corresponding aPTT levels were low with respect to target range. Methodology applied in this study is generalizable to other forms of mechanical circulatory support.

Impaired Baseline Renal Function May Not Influence Outcomes and Survival After Left Ventricular Assist Device Implantation.

BACKGROUND: We investigated changes in estimated glomerular filtration rate (eGFR) after left ventricular assist device (LVAD) implant and the impact on long-term outcomes. METHODS: A retrospective analysis was conducted for 255 patients with LVADs, divided into 2 groups based on preimplant eGFR (<60 or >60 mL/min/1.73 m2) and into 6 grades (grade 1, >90 mL/min/1.73 m2 normal; grade 2, 60-89 mild dysfunction; grade 3, 45-59 moderate; grade 4, 30-44 moderate to severe; grade 5, 15-29 severe; or grade 6, <15 kidney failure). Changes in eGFR and the impact on long-term outcome and survival were analyzed. RESULTS: One-month postimplant eGFR of the total cohort increased from a baseline of 75.19 ± 34.35 to 118.97 ± 67.62 mL/min/1.73 m2(P < .001). eGRF 4 years postimplant was higher than baseline but not significantly (P = .48). Patients with a preimplant eGFR > 60 followed the same pattern as the entire cohort. The preimplant eGFR < 60 group had a significant increase at 1 month (P < .001), eGFR remained significantly higher than baseline 4 years postimplant (P = .032), and there was a sustained transition to improved distribution of renal function grade after LVAD implant. Post-LVAD implant survival at 1, 3, and 5 years for baseline eGFR > 60 was 76%, 54%, and 48% and for eGFR < 60 was 71%, 60%, and 48%, respectively (P = .92). CONCLUSIONS: Patients with a low preimplant eGFR derive benefit from LVAD therapy, with eGFR remaining elevated above preimplant levels. Preimplant renal dysfunction did not impact negatively on long-term morbidity and mortality.

Utilization of extracorporeal membrane oxygenation in DCD and DBD lung transplants: a 2-year single-center experience.

Donation after circulatory death (DCD) has the potential to expand the lung donor pool. We aimed to assess whether DCD affected the need for perioperative extracorporeal membrane oxygenation (ECMO) and perioperative outcomes in lung transplantation (LTx) as compared to donation after brain death (DBD). All consecutive LTxs performed between April 2017 and March 2019 at our tertiary center were analyzed. Donor and recipient preoperative characteristics, utilization of ECMO, and perioperative clinical outcomes were compared between DCD and DBD LTx. Multivariate models (frequentist and Bayes) were fitted to evaluate an independent effect of DCD on the intra- and postoperative need for ECMO. Out of 105 enrolled patients, 25 (23.8%) were DCD LTx. Donors' and preoperative recipients' characteristics were comparable between the groups. Intraoperatively, mechanical circulatory support (MCS) was more common in DCD LTx (56.0% vs. 36.2%), but the adjusted difference was minor (RR = 1.16, 95% CI 0.64-2.12; P = 0.613). MCS duration, and first and second lung ischemia time were longer in the DCD group. Postoperatively, DCD recipients more commonly required ECMO (32.0% vs. 7.5%) and the difference remained considerable after adjustment for the pre- and intraoperative covariates: RR = 4.11 (95% CI 0.95-17.7), P = 0.058, Bayes RR = 4.15 (95% CrI 1.28-13.0). Sensitivity analyses (two DCD-DBD matching procedures) supported a higher risk of postoperative ECMO need in DCD patients. Incidence of delayed chest closure, postoperative chest drainage, and renal replacement therapy was higher in the DCD group. Early postoperative outcomes after DCD LTx appeared generally comparable to those after DBD LTx. DCD was associated with a higher need for postoperative ECMO which could influence clinical outcomes. However, as the DCD group had a significantly higher use of EVLP with more common ECMO preoperatively, this might have contributed to worse outcomes in the DCD group.

Minimally Invasive Left Ventricular Assist Device Implantation: A Comparative Study.

Left ventricular assist device (LVAD) is now a routine therapy for advanced heart failure. Minimally invasive approach via thoracotomy for LVAD implantation is getting popular due to its potential advantage over the conventional sternotomy approach in terms of reduced risk at re-operation due to sternal sparing. We compared the approaches (thoracotomy and sternotomy) to determine the superiority. Minimally invasive approach involved fitting of the LVAD inflow cannula into left ventricle apex via left anterior thoracotomy and anastomosis of outflow graft to ascending aorta via right anterior thoracotomy. In the sternotomy approach, both the procedures were performed via sternotomy. Outcomes in patients after LVAD implantation were compared depending on these approaches for the surgery. Two hundred and five continuous flow LVAD implantations performed between July 2006 and June 2015 at a single center were divided based on surgical approach, that is, sternotomy (n = 180) and thoracotomy (n = 25) groups. There was no significant difference between the groups in relation to patient demographics, preoperative hemodynamic parameters, laboratory markers, or risk factors. There was no significant difference between the groups in terms of postoperative hemodynamic parameters, laboratory markers, bleeding and requirement of blood products, intensive care unit, and hospital stay or complications of LVAD surgery. There were no significant differences in terms of long-term survival (Log-Rank P = 0.953), however, thoracotomy, compared to sternotomy approach, incurred significantly less requirement of temporary right ventricular assist (4 vs. 19.4%, P = 0.041). Minimally invasive bilateral thoracotomy approach for LVAD implantation in addition to benefits of sternal sparing avoids dilatation of right ventricle and reduces chances of right ventricular failure requiring temporary right ventricular assist.

Algorithms to guide ambulance clinicians in the management of emergencies in patients with implanted rotary left ventricular assist devices.

Advances in left ventricular assist device (LVAD) therapy have resulted in increasing numbers of adult LVAD recipients in the community. However, device failure, stroke, bleeding, LVAD thrombosis and systemic infection can be life-threatening emergencies. Currently, four LVAD systems are implanted in six UK transplant centres, each of which provides device-specific information to local emergency services. This has resulted in inconsistent availability and content of information with the risks of delayed or inappropriate decision-making. In order to improve patient safety, a consortium of UK healthcare professionals with expertise in LVADs developed universally applicable prehospital emergency algorithms. Guidance was framed as closely as possible on the standard ABCDE approach to the assessment of critically ill patients.

Short-term ventricular assist device as a bridge to decision in cardiogenic shock: is it a justified strategy?

PURPOSE: Low cardiac output syndrome is associated with significant mortality. In patients with refractory low cardiac output left ventricular assist devices (VAD) are used to re-establish cardiac output and to prevent death. However, long-term LVAD implantation in these is complicated by a high rate of right heart failure and mortality. Therefore, our strategy is to implant a short-term VAD (left or biventricular) as a bridge to decission. METHODS: We retrospectively analysed data from 66 patients who received a short-term LVAD support prior to implantation of a long-term LVAD or HTx between 2003 and 2014. We performed short-term LVAD (CentriMag; Thoratec) implantation via median sternotomy with percutaneous cannulas. Patients were included regardless of perioperative status and severity of heart failure. Patients suffering postcardiotomy cardiogenic shock, receiving isolated RVAD as well as posttransplant patients were excluded from this study. RESULTS: Mean duration of support in the survivor group was 35 ± 25 days versus 25 ± 25 days in the nonsurvivor group (n.s.), range from 1 to 109 days. The overall survival on support was 40 (60%) patients. In the survivor group 12 patients could be successfully weaned from the system, 12 patients received a heart transplant and in 16 a long-term VAD was implanted. In the nonsurvivor group the rate of preoperative extracorporeal life support, the rate of postoperative renal failure and multiorgan failure was significantly higher. CONCLUSIONS: Thanks to its capacity for full ventricular support, short-term univentricular or biventricular LevotronixCentriMag VAD currently represents an ideal solution for bridge-to-decision.

Multiorgan dysfunction related to chronic ketamine abuse.

Ketamine abuse is being increasingly reported worldwide. The drug can produce a dissociative state and hallucinations, making ketamine a favorite recreational agent among drug addicts. Chronic ketamine abuse can damage many organs, including the brain, heart, liver, gastrointestinal tract, and genitourinary system. We report a patient with chronic ketamine abuse who presented with severe cachexia, upper gastrointestinal involvement, hepatobiliary dysfunction, and acute kidney injury.