Outcomes of outflow graft stenting in HeartMate 3 left ventricular assist devices: A systematic review and individual patient data meta-analysis.

PURPOSE: LVAD outflow graft stenosis continues to remain prevalent with a high complication rate. We sought to pool the existing evidence on indications, utilization patterns, and outcomes of transcatheter interventions for outflow graft stenosis in the HeartMate 3 LVAD. METHODS: An electronic search was performed to identify all studies in the English literature reporting on HeartMate 3 LVAD outflow graft stenting. Patient-level data were extracted for analysis. RESULTS: Thirteen published reports and one unpublished case comprising a total of 28 patients were included. Median patient age was 68.5 years [Interquartile range: 58, 71] and 25.9% (7/27) were female. Dyspnea [60.7% (17/28)] was the most common presenting symptom. Low flow alarms were present in 60% (15/25) of patients. Findings included external compression [35.7% (10/28)], graft twist [21.4% (6/28)], graft twist and external compression [14.3% (4.28)], intraluminal thrombus [10.7% (3/28)], graft twist and intraluminal thrombus [3.6% (1/28)], and pseudoaneurysm of outflow graft [3.6% (1/28)]. Median time from LVAD implantation to stenting was 2.1 years [1.4, 3]. Immediate flow normalization after stenting was observed in 85.7% (24/28). The 30-day mortality was 12% (3/25). Overall mortality was 12% (3/25) at a median follow-up of 3.9 months [1, 17]. CONCLUSION: Outflow graft stenting in the HeartMate 3 LVAD appears to be a reasonable treatment option for outflow graft stenosis, with low overall rates of complications and mortality. Further refinement of indications and approaches may improve outcomes.

Predicted heart mass based on ideal body weight for donor-to-recipient size matching.

BACKGROUND: Predicted heart mass (PHM) is a commonly used tool for donor-to-recipient size matching. However, incorporating body weight as part of PHM can be considered problematic given its high variability, and low metabolic nature of fat. We sought to assess whether substituting the actual donor and recipient weight with the ideal body weight (IBW) would affect the association of donor-to-recipient PHM ratio with 1-year and overall survival after heart transplantation. METHODS: The United Network for Organ Sharing (UNOS) database was queried for adult patients who received a primary heart transplant between January 2000 and September 2021. RESULTS: Both PHM and ideal PHM (IPHM) ratios were associated with one-year (PHM: p = .003; IPHM: p = .0007) and overall (PHM: p = .02; IPHM: p = .02) survival. In the continuous analysis with restricted cubic splines, both PHM (p = .0003) and IPHM (p = .00001) were associated with relative hazards of death. CONCLUSION: IPHM is significantly associated with post-transplant survival and may be a useful compliment to PHM.

Association of Heart Transplant Volume with Presence of Lung Transplant Programs and Heart Transplant's SRTR One-year Survival Rating.

BACKGROUND: Several factors affect heart transplant (HTx) and lung transplant (LTx) program outcomes. Variabilities in institutional and community characteristics have been shown to influence survival. At present, half of HTx centers in the United States do not possess a concomitant LTx program. This study sought to better understand the characteristics of HTx with and without LTx programs. METHODS: Nationwide transplant data were collected from the Scientific Registry of Transplant Recipients (SRTR) in August 2020. SRTR star rating ranges from tier 1 (lowest) to tier 5 (highest). HTx volumes and SRTR star ratings for survival were compared between the centers with heart-only (H0) programs and the centers with heart-lung (HL) programs. RESULTS: SRTR star ratings were available for 117 transplant centers with one or more HTx reported. The median number of HTx performed over 1 year was 16 (interquartile range [IQR]: 2-29). The number of HL centers (n = 67, 57.3%) were comparable to H0 centers (n = 50, 42.7%; p = 0.14). The HTx volume at the HL centers (28 [IQR: 17-41]) exceeded the HTx volume at the H0 centers (13 [IQR: 9-23]; p < 0.01), but were comparable to the LTx volume at the HL centers (31 [IQR: 16-46]; p = 0.25). The median HTx one-year survival rating was 3 (IQR: 2-4) at both the H0 and HL centers (p = 0.85). The HTx and LTx volumes were positively associated with the respective 1-year survivals (p < 0.01). CONCLUSION: While the presence of an LTx program is not directly associated with HTx survival, it has a positive association with the HTx volume. The HTx and LTx volumes are positively associated with the 1-year survival.

Trans-ventricular catheter device-based closure of postmyocardial infarction ventricular septal defect following coronary artery bypass grafting: A staged hybrid approach.

A 66-year-old woman with a history of hypertension, ischemic stroke, and rheumatoid arthritis presented to the hospital with severe angina pectoris and dyspnea and was diagnosed with myocardial infarction (MI). Coronary angiography revealed multisystem coronary artery occlusive disease. Due to refractory myocardial ischemia/evolving MI, emergency coronary artery bypass grafting (CABG) was undertaken. Intraoperative transesophageal echocardiography additionally revealed an apical muscular ventricular septal defect (VSD). Concomitant VSD repair was deferred due to the absence of surface evidence of transmural MI for left ventriculotomy, in the setting of pre-existing severe left ventricular dysfunction. An initial totally percutaneous attempt to close the VSD postoperatively failed. A hybrid surgical/catheter-based VSD closure was performed on postoperative day 4, with a successful outcome. The patient did well postoperatively and currently is alive in good condition. To the best of our knowledge, this is the first report of a staged (post-CABG) and hybrid surgical/catheter-based technique without the utilization of cardiopulmonary bypass.

Transforming growth factor ß1 alters the 3'-UTR of mRNA to promote lung fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterized by the pathological remodeling of air sacs as a result of excessive accumulation of extracellular matrix (ECM) proteins, but the mechanism governing the robust protein expression is poorly understood. Our recent findings demonstrate that alternative polyadenylation (APA) caused by NUDT21 reduction is important for the increased expression of fibrotic mediators and ECM proteins in lung fibroblasts by shortening the 3'-untranslated regions (3'-UTRs) of mRNAs and stabilizing their transcripts, therefore activating pathological signaling pathways. Despite the importance of NUDT21 reduction in the regulation of fibrosis, the underlying mechanisms for the depletion are unknown. We demonstrate here that NUDT21 is depleted by TGFß1. We found that miR203, which is increased in IPF, was induced by TGFß1 to target the NUDT21 3'-UTR, thus depleting NUDT21 in human and mouse lung fibroblasts. TGFß1-mediated NUDT21 reduction was attenuated by the miR203 inhibitor antagomiR203 in fibroblasts. TGFß1 transgenic mice revealed that TGFß1 down-regulates NUDT21 in fibroblasts in vivo Furthermore, TGFß1 promoted differential APA of fibrotic genes, including FGF14, RICTOR, TMOD2, and UCP5, in association with increased protein expression. This unique differential APA signature was also observed in IPF fibroblasts. Altogether, our results identified TGFß1 as an APA regulator through NUDT21 depletion amplifying pulmonary fibrosis.

Axillary Impella insertion under regional nerve block: A case report.

Percutaneous coronary interventions with the Impella (Abiomed, MA) catheter-based, micro-axial mechanical left ventricular assist device is a safe option for patients undergoing higher risk interventions. However, severe peripheral arterial disease limits vascular access for Impella insertion. Upper extremity arterial access has been traditionally obtained under general anesthesia. We present the first case, to our knowledge, of using peripheral nerve blocks for Impella 3.5 CP insertion into the axillary artery.

Clinically Important Misclassification of Aortic Valve Stenosis Severity Using Non-Invasive Techniques: Simultaneous Echocardiography and Cardiac Catheterization During Transcatheter Aortic Valve Implantation in Awake Patients.

BACKGROUND: Suitability for transcatheter aortic valve (AV) implantation (TAVI) is determined by using transthoracic echocardiography (TTE), although left-sided cardiac catheterization (LCC) provides directly measured pressure data. TAVI in awake patients permits simultaneous comparison of TTE and LCC under physiologically relevant left ventricular loading conditions. We hypothesized that clinically important discrepancies between TTE and LCC would be identified. METHODS AND RESULTS: TAVI was performed in 108 awake patients undergoing intra-procedural TTE and LCC between January 1, 2016 and December 31, 2016, based upon pre-procedure TTE data. Intra-procedural assessments simultaneously were performed before and after prosthesis implantation. Based upon mean trans-AV systolic ejection pressure gradient (MSEPG), AS was graded as: mild (<20 mm Hg; grade 1), moderate (20 - <40 mm Hg; grade 2), or severe (≥40 mm Hg; grade 3). In 79 of the 108 (73.1%) patients, intra-procedural TTE and LCC assessments were concordant. In 2 of the 108 (1.9%) patients, TTE overestimated AS severity by ≥1 grade. In 27 of the 108 (25.0%) patients, TTE underestimated AS severity by ≥1 grade. In total, AS severity reclassification occurred in 29 (26.9%) patients. Overall, TTE underestimated MSEPG by 8.9 ± 1.2 mm Hg (TTE MSEPG versus LCC MSEPG; P < .001). CONCLUSION: Current TTE criteria appear to frequently and importantly underestimate AS severity. Because decision-making regarding TAVI often exclusively is based upon TTE data, these findings suggest either a continued role for LCC in the diagnostic assessment of AS in patients who do not meet standard TTE criteria or lowering TTE cutoffs for TAVI.

Coronary artery bypass grafting to treat coronary arterial occlusion incurred during orthotopic heart transplantation.

We report a case of left circumflex coronary artery occlusion sustained during orthotopic heart transplantation. Emergent coronary artery bypass grafting was performed, with recovery of cardiac function. The etiology and management of this complication are reviewed.

Low-Flow Extracorporeal Carbon Dioxide Removal Using the Hemolung Respiratory Dialysis System® to Facilitate Lung-Protective Mechanical Ventilation in Acute Respiratory Distress Syndrome.

Extracorporeal carbon dioxide removal (ECCO2R) permits reductions in alveolar ventilation requirements that the lungs would otherwise have to provide. This concept was applied to a case of hypercapnia refractory to high-level invasive mechanical ventilator support. We present a case of an 18-year-old man who developed post-pneumonectomy acute respiratory distress syndrome (ARDS) after resection of a mediastinal germ cell tumor involving the left lung hilum. Hypercapnia and hypoxemia persisted despite ventilator support even at traumatic levels. ECCO2R using a miniaturized system was instituted and provided effective carbon dioxide elimination. This facilitated establishment of lung-protective ventilator settings and lung function recovery. Extracorporeal lung support increasingly is being applied to treat ARDS. However, conventional extracorporeal membrane oxygenation (ECMO) generally involves using large cannulae capable of carrying high flow rates. A subset of patients with ARDS has mixed hypercapnia and hypoxemia despite high-level ventilator support. In the absence of profound hypoxemia, ECCO2R may be used to reduce ventilator support requirements to lung-protective levels, while avoiding risks associated with conventional ECMO.

Treatment of Multiple Myeloma in a Heart Transplant Recipient.

Malignancy following solid organ transplant remains a significant threat to the survival of cardiac transplant recipients. Plasma cell dyscrasias including multiple myeloma have been encountered in this population, and medication treatments traditionally used to treat these disorders demonstrate immunomodulatory effects that may have implications on the transplanted allograft. Lenalidomide is an immunomodulatory agent that has been used to treat plasma cell disorders, including light-chain amyloidosis (AL) and multiple myeloma, and represents such a class of medications in which the risks and benefits in the solid organ transplant population remain to be fully elucidated. This report highlights a clinical practice issue where the treatment of a patient's multiple myeloma with lenalidomide may have potentiated an episode of severe acute cellular rejection and further demonstrates the need for future investigation of the optimal treatment of plasma cell disorders including AL amyloidosis and multiple myeloma following solid organ transplantation.

Belatacept for renal rescue in lung transplant patients.

Renal failure causes morbidity and mortality after lung transplantation and is aggravated by exposure to nephrotoxic immunosuppressant (IS) drugs. We report an off-label experience using belatacept for lung transplant recipients with severe renal insufficiency to reduce nephrotoxic IS exposure. We analyzed data retrospectively from a consecutive series of lung transplant patients with renal insufficiency in whom belatacept treatment was initiated between June 2012 and June 2014 at the University of Maryland Medical Center. Eight patients received belatacept because of acute or chronic renal insufficiency (median) GFR 24 (IQR 18-26). Glomerular filtration rate (GFR) remained stable in two patients and increased in five. One patient with established renal and respiratory failure received only the induction dose of belatacept and died 4 months later of respiratory and multisystem organ failure. Calcineurin inhibitor or sirolimus exposure was safely withheld or reduced without moderate or severe acute rejection during ongoing belatacept in the other seven patients. FEV1 remained stable over the 6-month study interval. Belatacept use appears to permit safe transient reduction in conventional immunosuppressive therapy and was associated with stable or improved renal function in a small retrospective series of lung transplant recipients with acute or chronic renal insufficiency.

Gerbode Defect as a Result of Fungal Aortic Valve Endocarditis.

A 63-year-old male patient with HIV disease presented with dyspnea and complete heart block, and was found to have aortic valve (AV) endocarditis secondary to Candida parapsilosis infection. Echocardiography demonstrated AV endocarditis and possible aortic root versus subannular abscess with moderate AV regurgitation (AR), a ventricular septal defect (VSD) and possible left ventricular to right atrial shunt (Gerbode defect). Large AV vegetations, subannular abscess with an acquired membranous VSD, Gerbode defect, and tricuspid annular abscess at the insertion of septal leaflet were noted intraoperatively. The patient underwent AV replacement with a stented bioprosthesis, two-sided VSD patch closure, and tricuspid valve (TV) repair with an annuloplasty ring. The left-sided patch closed the VSD and facilitated AV replacement, while the right-sided patch facilitated the TV repair.

Will blood-informed design signal the fourth generation of cardiac assist devices?

Mechanical circulatory support devices have profoundly transformed the management of severe cardiothoracic disorders. While heart transplantation is the gold standard therapy for end-stage heart disease, long-term mechanical support devices are a viable alternative for those ineligible and/or those awaiting organ availability. Major technological advancements were made over first 5 decades of development, resulting in improved durability and survival with reduced adverse events. However, gains have tapered recently for various complications (e.g., internal bleeding, multisystem organ failure), which collectively represent a significant proportion of disability and/or mortality. Further, in light of mature ventricular assist devices failing during clinical trials or even after clinical approval (class I withdrawals), it is timely to consider: Are our preclinical assessment protocols vital in the design and development of mechanical circulatory support devices, providing a realistic and reliable profile of future clinical performance? This commentary explores this question and analyses development pathways through the lens of the various disciplines involved in the preclinical assessment of mechanical circulatory support technologies: Limitations in approaches to benchtop blood testing, computational design and simulation, and animal testing are discussed as likely contributors to some of the common hemocompatibility-related adverse events (HRAEs). While it is acknowledged that some shortcomings are pragmatic in nature, possible solutions are presented that will only be realized through truly transdisciplinary and open approaches that challenge the current nature of medical device development. We suggest that these can and must be overcome to diminish HRAEs and will potentially demarcate the fourth generation of cardiac assist devices.

Aortic tissue stiffness and tensile strength are correlated with density changes following proteolytic treatment.

INTRODUCTION: Dissection or rupture of the aorta is accompanied by high mortality rates, and there is a pressing need for better prediction of these events for improved patient management and clinical outcomes. Biomechanically, these events represent a situation wherein the locally acting wall stress exceed the local tissue strength. Based on recent reports for polymers, we hypothesized that aortic tissue failure strength and stiffness are directly associated with tissue mass density. The objective of this work was to test this novel hypothesis for porcine thoracic aorta. METHODS: Three tissue specimens from freshly harvested porcine thoracic aorta were treated with either collagenase or elastase to selectively degrade structural proteins in the tissue, or with phosphate buffer saline (control). The tissue mass and volume of each specimen were measured before and after treatment to allow for density calculation, then mechanically tested to failure under uniaxial extension. RESULTS: Protease treatments resulted in statistically significant tissue density reduction (sham vs. collagenase p = 0.02 and sham vs elastase p = 0.003), which in turn was significantly and directly correlated with both ultimate tensile strength (sham vs. collagenase p = 0.02 and sham vs elastase p = 0.03) and tangent modulus (sham vs. collagenase p = 0.007 and sham vs elastase p = 0.03). CONCLUSIONS: This work demonstrates for the first time that tissue stiffness and tensile strength are directly correlated with tissue density in proteolytically-treated aorta. These findings constitute an important step towards understanding aortic tissue failure mechanisms and could potentially be leveraged for non-invasive aortic strength assessment through density measurements, which could have implications to clinical care.

Alterations in Coronary Blood Flow and the Risk of Left Ventricular Distension in Venoarterial Extracorporeal Membrane Oxygenation.

Previous theoretical studies have suggested that veno-arterial extracorporeal membrane oxygenation (VA-ECMO) ought to consistently result in markedly increased left ventricular (LV) intracavitary pressures and volumes because of increased LV afterload. However, this phenomenon of LV distension does not universally occur and occurs only in a minority of cases. We sought to explain this discrepancy by considering the potential implications of VA-ECMO support on coronary blood flow and consequently improved LV contractility (the "Gregg" effect), in addition to the effects of VA-ECMO support upon LV loading conditions, in a lumped parameter-based theoretical circulatory model. We found that LV systolic dysfunction resulted in reduced coronary blood flow; VA-ECMO support augmented coronary blood flow proportionally to the circuit flow rate. On VA-ECMO support, a weak or absent Gregg effect resulted in increased LV end-diastolic pressures and volumes and increased end-systolic volume with decreased LV ejection fraction (LVEF), consistent with LV distension. In contrast, a more robust Gregg effect resulted in unaffected and/or even reduced LV end-diastolic pressure and volume, end-systolic volume, and unaffected or even increased LVEF. Left ventricular contractility augmentation proportional to coronary blood flow increased by VA-ECMO support may be an important contributory mechanism underlying why LV distension is observed only in a minority of cases.

Trans-aortic Valvular Ejection Fraction for Monitoring Recovery of Patients with Ventricular Systolic Heart Failure.

Durable mechanical circulatory support in the form of left ventricular (LV) assist device (LVAD) therapy is increasingly considered in the context of the recovery of native cardiac function. Progressive improvement in LV function may facilitate LVAD explantation and a resultant reduction in device-related risk. However, ascertaining LV recovery remains a challenge. In this study, we investigated the use of trans-aortic valvular flow rate and trans-LVAD flow rate to assess native LV systolic function using a well-established lumped parameter model of the mechanically assisted LV with pre-existing systolic dysfunction. Trans-aortic valvular ejection fraction (TAVEF) was specifically found to characterize the preload-independent contractility of the LV. It demonstrated excellent sensitivity to simulated pharmacodynamic stress tests and volume infusion tests. TAVEF may prove to be useful in the ascertainment of LV recovery in LVAD-supported LVs with pre-existing LV systolic dysfunction.

Application of 1,000 fps High-Speed Angiography to In-Vitro Hemodynamic Evaluation of Left Ventricular Assist Device Outflow Graft Configurations.

Left ventricular assist device (LVAD)-induced hemodynamics are characterized by fast-moving flow with large variations in velocity, making quantitative assessments difficult with existing imaging methods. This study demonstrates the ability of 1,000 fps high-speed angiography (HSA) to quantify the effect of the surgical implantation angle of a LVAD outflow graft on the hemodynamics within the ascending aorta in vitro . High-speed angiography was performed on patient-derived, three-dimensional-printed optically opaque aortic models using a nonsoluble contrast media, ethiodol, as a flow tracer. Outflow graft configuration angles of 45° and 90° with respect to the central aortic axis were considered. Projected velocity distributions were calculated from the high-speed experimental sequences using two methods: a physics-based optical flow algorithm and tracking of radio-opaque particles. Particle trajectories were also used to evaluate accumulated shear stress. Results were then compared with computational fluid dynamics (CFD) simulations to confirm the results of the high-speed imaging method. Flow patterns derived from HSA coincided with the impingement regions and recirculation zones formed in the aortic root as seen in the CFD for both graft configurations. Compared with the 45° graft, the 90° configuration resulted in 81% higher two-dimensional-projected velocities (over 100 cm/s) along the contralateral wall of the aorta. Both graft configurations suggest elevated accumulated shear stresses along individual trajectories. Compared with CFD simulations, HSA successfully characterized the fast-moving flow and hemodynamics in each LVAD graft configuration in vitro , demonstrating the potential utility of this technology as a quantitative imaging modality.

Atrial Fibrillation Ablation-induced Pulmonary Venous Occlusion Requiring Pneumonectomy.

A 71-year-old woman with a history of atrial fibrillation underwent a catheter-based ablation procedure. Months later, she presented with dyspnea and a left-sided pleural effusion. Diagnostic evaluation revealed left-sided pulmonary venous occlusion, with essentially absent left lung perfusion. The patient underwent left pneumonectomy, with left atrial appendage occlusion. Although lobectomy for pulmonary venous occlusion of a single vein after pulmonary vein isolation has been described, this appears to be a novel report of occluded pulmonary venous drainage of an entire lung necessitating pneumonectomy.

Multi-institutional Analysis of 505 Patients With Coronavirus Disease-2019 Supported With Extracorporeal Membrane Oxygenation: Predictors of Survival.

BACKGROUND: We reviewed our experience with 505 patients with confirmed coronavirus disease-2019 (COVID-19) supported with extracorporeal membrane oxygenation (ECMO) at 45 hospitals and estimated risk factors for mortality. METHODS: A multi-institutional database was created and used to assess all patients with COVID-19 who were supported with ECMO. A Bayesian mixed-effects logistic regression model was estimated to assess the effect on survival of multiple potential risk factors for mortality, including age at cannulation for ECMO as well as days between diagnosis of COVID-19 and intubation and days between intubation and cannulation for ECMO. RESULTS: Median time on ECMO was 18 days (interquartile range, 10-29 days). All 505 patients separated from ECMO: 194 patients (38.4%) survived and 311 patients (61.6%) died. Survival with venovenous ECMO was 184 of 466 patients (39.5%), and survival with venoarterial ECMO was 8 of 30 patients (26.7%). Survivors had lower median age (44 vs 51 years, P < .001) and shorter median time interval from diagnosis to intubation (7 vs 11 days, P = .001). Adjusting for several confounding factors, we estimated that an ECMO patient intubated on day 14 after the diagnosis of COVID-19 vs day 4 had a relative odds of survival of 0.65 (95% credible interval, 0.44-0.96; posterior probability of negative effect, 98.5%). Age was also negatively associated with survival: relative to a 38-year-old patient, we estimated that a 57-year-old patient had a relative odds of survival of 0.43 (95% credible interval, 0.30-0.61; posterior probability of negative effect, >99.99%). CONCLUSIONS: ECMO facilitates salvage and survival of select critically ill patients with COVID-19. Survivors tend to be younger and have shorter time from diagnosis to intubation. Survival of patients supported with only venovenous ECMO was 39.5%.