Ventricular assist device using a thoracotomy-based implant technique: Multi-Center Implantation of the HeartMate 3 in Subjects With Heart Failure Using Surgical Techniques Other Than Full Median Sternotomy (HM3 SWIFT).

OBJECTIVES: The HeartMate 3 (Abbott) left ventricular assist device provides substantial improvement in long-term morbidity and mortality in patients with advanced heart failure. The Implantation of the HeartMate 3 in Subjects With Heart Failure Using Surgical Techniques Other Than Full Median Sternotomy study compares thoracotomy-based implantation clinical outcomes with standard median sternotomy. METHODS: We conducted a prospective, multicenter, single-arm study in patients eligible for HeartMate 3 implantation with thoracotomy-based surgical technique (bilateral thoracotomy or partial upper sternotomy with left thoracotomy). The composite primary end point was survival free of disabling stroke (modified Rankin score >3), or reoperation to remove or replace a malfunctioning device, or conversion to median sternotomy at 6-months postimplant (elective transplants were treated as a success). The primary end point (noninferiority, -15% margin) was assessed with >90% power compared with a propensity score-matched cohort (ratio 1:2) derived from the Multi-Center Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 continued access protocol. RESULTS: The study enrolled 102 patients between December 2020 and July 2022 in the thoracotomy-based arm at 23 North American centers. Follow-up concluded in December 2022. In the Implantation of the HeartMate 3 in Subjects With Heart Failure Using Surgical Techniques Other Than Full Median Sternotomy study group, noninferiority criteria was met (absolute between-group difference, -1.2%; Farrington Manning lower 1-sided 95% CI, -9.3%; P < .0025) and event-free survival was not different (85.0% vs 86.2%; hazard ratio, 1.01; 95% CI, 0.58-2.10). Length of stay with thoracotomy-based implant was longer (median, 20 vs 17 days; P = .03). No differences were observed for blood product utilization, adverse events (including right heart failure), functional status, and quality of life between cohorts. CONCLUSIONS: Thoracotomy-based implantation of the HeartMate 3 left ventricular assist device is noninferior to implantation via standard full sternotomy. This study supports thoracotomy-based implantation as an additional standard for surgical implantation of the HeartMate 3 left ventricular assist device.

Veno-Arterial Extracorporeal Membrane Oxygenation for Cardiogenic Shock.

Cardiogenic shock (CS) is a clinical condition characterized by inadequate tissue perfusion in the setting of low cardiac output. CS is the leading cause of death following acute myocardial infarction (AMI). Several temporary mechanical support devices are available for hemodynamic support in CS until clinical recovery ensues or until more definitive surgical procedures have been performed. Veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) has evolved as a powerful treatment option for short-term circulatory support in refractory CS. In the absence of randomized clinical trials, the utilization of ECMO has been guided by clinical experience and based on data from registries and observational studies. Survival to hospital discharge with the use of VA-ECMO ranges from 28-67%. The initiation of ECMO requires venous and arterial cannulation, which can be performed either percutaneously or by surgical cutdown. Components of an ECMO circuit include an inflow cannula that draws blood from the venous system, a pump, an oxygenator, and an outflow cannula that returns blood to the arterial system. Management considerations post ECMO initiation include systemic anticoagulation to prevent thrombosis, left ventricle unloading strategies to augment myocardial recovery, prevention of limb ischemia with a distal perfusion catheter in cases of femoral arterial cannulation, and prevention of other complications such as hemolysis, air embolism, and Harlequin syndrome. ECMO is contraindicated in patients with uncontrolled bleeding, unrepaired aortic dissection, severe aortic insufficiency, and in futile cases such as severe neurological injury or metastatic malignancies. A multi-disciplinary shock team approach is recommended while considering patients for ECMO. Ongoing studies will evaluate whether the addition of routine ECMO improves survival in AMI patients with CS who undergo revascularization.

In a large-volume multidisciplinary setting individual surgeon volume does not impact LVAD outcomes.

BACKGROUND: In complex operations surgeon volume may impact outcomes. We sought to understand if individual surgeon volume affects left ventricular assist device (LVAD) outcomes. METHODS: We reviewed primary LVAD implants at an experienced ventricular assist devices (VAD)/transplant center between 2013 and 2019. Cases were dichotomized into a high-volume group (surgeons averaging 11 or more LVAD cases per year), and a low-volume group (10 or less per year). Propensity score matching was performed. Survival to discharge, 1-year survival, and incidence of major adverse events were compared between the low- and high-volume groups. Predictors of survival were identified with multivariate analysis. RESULTS: There were 315 patients who met inclusion criteria-45 in the low-volume group, 270 in the high-volume group. There was no difference in survival to hospital discharge between the low (91.9%) and high (83.3%) volume matched groups (p = .22). Survival at 1-year was also similar (85.4% vs. 80.6%, p = .55). There was no difference in the incidence of major adverse events between the groups. Predictors of mortality in the first year included: age (hazards ratio [HR]: 1.061, p < .001), prior sternotomy (HR: 1.991, p = .01), increasing international normalized ratio (HR: 4.748, p < .001), increasing AST (HR: 1.001, p < .001), increasing bilirubin (HR: 1.081, p = .01), and preoperative mechanical ventilation (HR: 2.662, p = .005). Individual surgeon volume was not an independent predictor of discharge or 1-year survival. CONCLUSION: There was no difference in survival or adverse events between high and low volume surgeons suggesting that, in an experienced multidisciplinary setting, low-volume VAD surgeons can achieve similar outcomes to their high-volume colleagues.

Thoracoabdominal Normothermic Perfusion in Donation After Circulatory Death.

Donation after circulatory death is emerging as an alternative pathway to donation after brain death to expand the cardiac organ donor pool. We describe the surgical technique and circuit configuration for in-situ organ reperfusion with thoracoabdominal normothermic regional perfusion using portable venoarterial extracorporeal membrane oxygenation.

Pulmonary Function Testing Pre-heart Transplant Predicts Posttransplant Survival.

Although pulmonary function testing (PFT) is typically performed for heart transplant evaluation, the prognostic utility of PFTs after transplantation is unknown. We evaluated whether PFT parameters were correlated with outcomes following heart transplantation. METHODS: International Society for Heart and Lung Transplantation Thoracic Organ Transplant Registry data were utilized. Survival was assessed using Kaplan-Meier method and compared via log-rank test. Cox proportional hazard modeling was used to evaluate univariate and multivariate predictors of survival. RESULTS: Eight hundred two patients pretransplant PFT data were available for evaluation. Forced expiratory volume in 1 s (FEV1) < 50% predicted (P < 0.0001), and forced vital capacity (FVC) < 50% predicted each had significantly higher mortality (P = 0.001) compared with patients with FEV1 or FVC 50%-80% or >80%. FEV1/FVC < 0.7 was not associated with increased mortality. FEV1 and FVC below 50% both predicted longer lengths of stay (P = 0.028 for FEV1 and P = 0.0075 for FVC). After adjusting for male gender, age, body mass index, smoking history, chronic obstructive pulmonary disease, creatinine, albumin, and total bilirubin, FEV1 < 50% (hazard ratio, 4.91; P < 0.0001; 95% confidence interval, 2.69-8.94) and FVC < 50% (hazard ratio, 2.75; P = 0.003; 95% confidence interval, 1.4-5.4) both remained independent predictors of mortality. CONCLUSIONS: Abnormal pulmonary function (FEV1 or FVC below 50% of predicted) pre-heart transplantation is associated with increased mortality and longer lengths of stay posttransplant.

Percutaneous Deactivation of Left Ventricular Assist Devices.

Left ventricular assist device (LVAD) deactivation may be considered in cases of left ventricular recovery, pump thrombosis, infection, and end-of-life palliation. Surgical pump explantation remains the principal method, but percutaneous deactivation presents a safe and effective alternative. We have developed a formal program for percutaneous LVAD deactivation within our advanced heart failure program including patient selection criteria, preprocedure testing, a procedural algorithm, and a postprocedure care plan. Patient selection for percutaneous LVAD deactivation required review by an interdisciplinary heart transplant team including reason for deactivation, cardiac function, surgical risk, and patient preference. All candidates underwent LVAD ramp studies with both transthoracic echocardiography and right heart catheterization assessment. Deactivation was performed under general anesthesia with transesophageal echocardiography guidance. Three Amplatzer Vascular Plug IIs (Abbott, St. Paul, MN) were deployed in the LVAD outflow cannula with the proximal edge of the third plug aligned with the aortic anastomosis of the graft as guided by angiography and 3-dimensional transesophageal echocardiography. In a separate procedure, the LVAD drive line was transected below the skin, which was closed surgically over the driveline stump. Anticoagulation was continued for at least 3 months. Since initiation in January 2017, our program has performed 7 percutaneous LVAD deactivation procedures. All procedures have been successful, 5 of the patients remain medically managed, and 2 have proceeded to heart transplant. Percutaneous LVAD deactivation provides an alternative to surgical explantation. A percutaneous LVAD deactivation program is an important component of an advanced heart failure program.

Recurrent pump thrombosis is common after axial continuous-flow left ventricular assist device exchange.

In selected patients with left ventricular assist device-associated infection or malfunction, pump exchange may become necessary after conservative treatment options fail and heart transplantation is not readily available. We examined the survival and complication rate in patients (⩾19 years of age) who underwent HeartMate II to HeartMate II exchange at our institution from 1 January 2010 to 28 February 2018. Clinical outcomes were analyzed and compared for patients who underwent exchange for pump thrombosis (14 patients), breach of driveline integrity (5 patients), and device-associated infection (2 patients). There were no differences in 30-day mortality (p = 0.58), need for temporary renal replacement therapy (p = 0.58), right ventricular mechanical support (p = 0.11), and postoperative stroke (p = 0.80) among groups. Survival at 1 year was 90% ± 7% for the whole cohort and 85% ± 10% for those who underwent exchange for pump thrombosis. In patients exchanged for device thrombosis, freedom from re-thrombosis and survival free from pump re-thrombosis at 1 year were 49% ± 16% and 42% ± 15%, respectively. No association of demographic and clinical variables with the risk of recurrent pump thrombosis after the first exchange was identified. Survival after left ventricular assist device exchange compares well with published results after primary left ventricular assist device implantation. However, recurrence of thrombosis was common among patients who required a left ventricular assist device exchange due to pump thrombosis. In this sub-group, consideration should be given to alternative strategies to improve the outcomes.

Can we expect improvements in outcomes with centrifugal vs axial flow left ventricular assist devices in patients transitioned from extracorporeal life support?

BACKGROUND: Several patient-related characteristics have been associated with inferior outcomes following durable left ventricular assist device (LVAD) implantation in patients transitioned from venoarterial extracorporeal membrane oxygenation (VA ECMO). The impact of LVAD pump type used is less well-known. METHODS: We compared outcomes between patents who received axial and centrifugal flow LVADs following stabilization with VA ECMO. RESULTS: From January 2011 to December 2018, we implanted 28 LVADs in patients transitioned from VA ECMO. This included 17 axial flow devices (HeartMate II LVAD, Abbott Laboratories, Chicago, IL) and 11 centrifugal flow pumps (eight HeartWare HVADs; Medtronic, Minneapolis, MN and three HeartMate 3 LVAS pumps; Abbott Laboratories, Chicago, IL). There was no difference in hospital mortality (23.5% vs 18.2%, P = .74) or 1-year survival (P = .31) between the devices. There were no differences in adverse event rates between the two pump types, apart from a higher rate of gastrointestinal bleeding in patients who received centrifugal flow pumps (1.44 events per 100 patient-months vs 14.67 events per 100 patient-months, P = .010). Preimplantation levels of alanine aminotransferase (hazard ratio [HR], 1.001; 95% confidence interval [CI], 1.000 to 1.002; P = .004) and elevated serum creatinine level (HR, 3.480; 95% CI, 1.121-10.807; P = .031) emerged as significant predictors of decreased 1-year survival. CONCLUSIONS: Preimplantation optimization of end-organ function is the single most important determinant of successful post-LVAD survival in patients transitioned from extracorporeal life support. There is no association of pump type with LVAD outcomes up to 1-year post implantation.

What are the results of venoarterial extracorporeal membrane oxygenation bridging to heart transplantation?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether heart transplantation is a viable treatment option in patients in refractory cardiogenic shock who could not be weaned off venoarterial extracorporeal membrane oxygenation (VA ECMO). Altogether, 373 papers were found using the reported search, of which 7 papers represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Evidence is derived from 3 papers based on registry analysis, 1 multi-institutional study and 3 single-institution reviews. Early post-transplant mortality of ECMO-bridged recipients ranges from 18.7% to 33.3% and 1-year survival from 44.6% to 72.0%. High acuity of recipient illness reflected by poor renal function, mechanical ventilation, advanced age, elevated serum lactate predict inferior outcome. We conclude that heart transplantation results in patients bridged with VA ECMO are inferior when compared to published outcome of non-bridged recipients. In the era of severe organ shortage and intense public and regulatory scrutiny of the results, the decision to transplant a patient directly of VA ECMO needs to be made on a case-by-case basis. Potential gain in decreasing the waiting list mortality of these critically ill patients needs to be weighed against poorer post-transplantation mortality rates and mid- and long-term outcomes.

A Fully Magnetically Levitated Left Ventricular Assist Device - Final Report.

BACKGROUND: In two interim analyses of this trial, patients with advanced heart failure who were treated with a fully magnetically levitated centrifugal-flow left ventricular assist device were less likely to have pump thrombosis or nondisabling stroke than were patients treated with a mechanical-bearing axial-flow left ventricular assist device. METHODS: We randomly assigned patients with advanced heart failure to receive either the centrifugal-flow pump or the axial-flow pump irrespective of the intended goal of use (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke or reoperation to replace or remove a malfunctioning device. The principal secondary end point was pump replacement at 2 years. RESULTS: This final analysis included 1028 enrolled patients: 516 in the centrifugal-flow pump group and 512 in the axial-flow pump group. In the analysis of the primary end point, 397 patients (76.9%) in the centrifugal-flow pump group, as compared with 332 (64.8%) in the axial-flow pump group, remained alive and free of disabling stroke or reoperation to replace or remove a malfunctioning device at 2 years (relative risk, 0.84; 95% confidence interval [CI], 0.78 to 0.91; P<0.001 for superiority). Pump replacement was less common in the centrifugal-flow pump group than in the axial-flow pump group (12 patients [2.3%] vs. 57 patients [11.3%]; relative risk, 0.21; 95% CI, 0.11 to 0.38; P<0.001). The numbers of events per patient-year for stroke of any severity, major bleeding, and gastrointestinal hemorrhage were lower in the centrifugal-flow pump group than in the axial-flow pump group. CONCLUSIONS: Among patients with advanced heart failure, a fully magnetically levitated centrifugal-flow left ventricular assist device was associated with less frequent need for pump replacement than an axial-flow device and was superior with respect to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755.).

Effect of diltiazem on exercise capacity after heart transplantation.

BACKGROUND: Sinus tachycardia (ST) is common after heart transplantation (HTx). The aim of the study was to evaluate the effect of diltiazem treatment during the first year after HTx on heart rate (HR), cardiac allograft function, and exercise capacity. METHODS: From the total cohort, 25 HTx recipients started diltiazem treatment 4±2 weeks after HTx and continued it for at least 1 year (diltiazem group). Each study case was matched to a control. All patients underwent hemodynamic assessment and cardiopulmonary exercise test (CPET) at 1 year after HTx. RESULTS: HR decreased in the diltiazem group from 99±11 bpm to 94±7 bpm (P=.03) and did not change in the controls (98±11 bpm vs 100±13 bpm, P=.14). The difference between the groups at 1 year after HTx was significant (P=.04). In the diltiazem group left ventricular (LV), stroke volume and ejection fraction increased (48±16 vs 55±17 mL, P=.02, and 60%±10% vs 62%±12% P=.03, respectively) but did not differ from controls. E/E' decreased (10.7±2.7 vs 7.3±1.9, P=.003) while cardiac index was higher (3.5±0.8 vs 3.1±0.5; P=.05) in the diltiazem group at 1-year follow-up. The absolute peak VO2 (21±4 vs 18±6 mL/kg/min; P=.05) and normalized peak VO2 (73%±17% vs 58%±14%; P=.004) were significantly higher in the diltiazem group. CONCLUSIONS: This study showed that diltiazem treatment reduces ST, may improve cardiac allograft function and exercise tolerance during the first year after HTx.

Unique antibody responses to malondialdehyde-acetaldehyde (MAA)-protein adducts predict coronary artery disease.

Malondialdehyde-acetaldehyde adducts (MAA) have been implicated in atherosclerosis. The purpose of this study was to investigate the role of MAA in atherosclerotic disease. Serum samples from controls (n = 82) and patients with; non-obstructive coronary artery disease (CAD), (n = 40), acute myocardial infarction (AMI) (n = 42), or coronary artery bypass graft (CABG) surgery due to obstructive multi-vessel CAD (n = 72), were collected and tested for antibody isotypes to MAA-modifed human serum albumin (MAA-HSA). CAD patients had elevated relative levels of IgG and IgA anti-MAA, compared to control patients (p<0.001). AMI patients had a significantly increased relative levels of circulating IgG anti-MAA-HSA antibodies as compared to stable angina (p<0.03) or CABG patients (p<0.003). CABG patients had significantly increased relative levels of circulating IgA anti-MAA-HSA antibodies as compared to non-obstructive CAD (p<0.001) and AMI patients (p<0.001). Additionally, MAA-modified proteins were detected in the tissue of human AMI lesions. In conclusion, the IgM, IgG and IgA anti-MAA-HSA antibody isotypes are differentially and significantly associated with non-obstructive CAD, AMI, or obstructive multi-vessel CAD and may serve as biomarkers of atherosclerotic disease.

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.

Plasmapheresis and heparin reexposure as a management strategy for cardiac surgical patients with heparin-induced thrombocytopenia.

BACKGROUND: Heparin-induced thrombocytopenia (HIT) complicates the management of patients presenting for cardiac surgery, because high-dose heparin anticoagulation for cardiopulmonary bypass is contraindicated in these patients. Alternative anticoagulants are available, but there are concerns about dosing, efficacy, monitoring, thrombosis, and hemorrhage. METHODS: A retrospective chart review between November 2004 and March 2008 retrieved perioperative clinical and laboratory data for 11 adult cardiac surgical patients with a preoperative history of HIT and a current positive antiheparin/platelet factor 4 (anti-HPF4) antibody titer, who were managed with plasmapheresis and heparin anticoagulation. RESULTS: The median (interquartile range) preoperative anti-HPF4 antibody titer was 0.8 (0.7-2.2). Three of the 11 patients (27%) died of causes unrelated to HIT and 1 of these patients (9%) developed an ischemic foot, in the setting of cardiogenic shock, not thought to be HIT-related. A single plasmapheresis treatment reduced titers by 50%-84%, and 6 patients had negative titers after treatment; none of the 3 patients with reduced titers developed clinical HIT. CONCLUSIONS: This case series describes an alternative management strategy using intraoperative plasmapheresis for patients presenting for cardiac surgery with acute or subacute HIT. Reducing antibody load can potentially decrease the thrombotic risk associated with high anti-HPF4 titers and decrease the urgency to initiate postoperative anticoagulation in this patient group at high risk of postoperative bleeding.

Modulation of the lipopolysaccharide receptor complex (CD14, TLR4, MD-2) and toll-like receptor 2 in systemic inflammatory response syndrome-positive patients with and without infection: relationship to tolerance.

The lipopolysaccharide (LPS) receptor complex consists of two interacting receptors (CD14 and TLR4) and an associated protein (MD-2). When engaged by LPS, as in gram-negative infection, this complex transduces a signal detected by MyD88 and passed onward by a cascade of the IRAKs, TRAF6, and NIK, resulting in activation of NF-kappaB. A similar cascade, mediated by TLR2, occurs with ligands derived from gram-positive bacteria. In vitro studies of human monocytes have shown that TLR4 mRNA is paradoxically upregulated in response to "tolerizing" doses of LPS. This study evaluated changes in vivo of blood monocyte CD14, TLR4, TLR2, and MD-2 mRNA by reverse transcription followed by real-time polymerase chain reaction in surgical intensive care unit patients and in normal controls. In addition cell-surface receptor expression of TLR2, TLR4, and CD14 was assessed by flow cytometry in patients and normal controls. Inflammation-induced acute tolerance to LPS was evaluated by ex vivo whole blood tumor necrosis factor alpha production and was significantly reduced in patients compared with controls, confirming LPS hyporesponsiveness. Monocyte mRNA and cell-surface receptor expression of TLR4 were increased 2.4-fold (P < 0.05) and 1.7-fold (P <.002), respectively, in patients compared with normal controls. Monocyte TLR2 mRNA, MD-2 mRNA and CD14 and TLR2 cell-surface expression were not significantly changed compared with controls. The present study suggests that the acute inflammatory condition associated with peripheral cellular LPS hyporesponsiveness is neither specific to prior infectious challenge nor can be ascribed to significant alterations in expression of the cell-surface LPS binding complex proteins.

Influence of the TNF-alpha and TNF-beta polymorphisms upon infectious risk and outcome in surgical intensive care patients.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a well-documented central inflammatory mediator in sepsis. Specific polymorphisms of the TNF-alpha and TNF-beta genes (TNF2 and LTA + 250, respectively) have been suggested to correlate with higher mortality in septic shock. This study sought to determine whether these polymorphisms of the TNF-alpha and -beta genes are associated with an increased risk of infection in an at-risk surgical intensive care population. MATERIALS AND METHODS: Forty-four consecutive patients with systemic inflammatory response syndrome were enrolled prospectively in the study. Genomic DNA was isolated from whole blood samples using standard phenol/chloroform extraction techniques. Specific fragments including the polymorphic sites of each gene were amplified by polymerase chain reaction, and restriction enzyme digestions were performed. Genotypes were determined by gel electrophoresis and confirmed by direct sequencing. RESULTS: Eighty-six percent of the patients were TNF1 homozygotes (G:G at -308 of the TNF-alpha promoter region), whereas 9% of the patients were homozygous for TNF2 (A:A). There was no difference in the incidence of sepsis, septic shock, or mortality between patients bearing the various alleles. Only 13.6% of the patients exhibited the G:G alleles for TNF-beta, whereas the homozygous A:A was present in 45.4% of the patients. CONCLUSION: The presence of the A allele at these polymorphic sites did not predispose critically ill surgical patients to either infection or septic shock.