Optical Coherence Tomography in the Assessment and Management of Cardiac Allograft Vasculopathy.

PURPOSE OF REVIEW: Cardiac Allograft vasculopathy (CAV) is a major barrier to improving outcomes after heart transplantation. Coronary angiography has very low sensitivity to detect early CAV and intravascular ultrasound (IVUS) only improves it to some extent. In this article, we detail the current evidence surrounding use of Optical Coherence tomography (OCT) in patients with CAV. RECENT FINDINGS: OCT has the ability to recognize CAV at earlier stages with intimal thickness < 150 µm, can characterize CAV in almost pathologic / microscopic detail - plaque characteristics are better visualized and novel early features such as layered fibrotic plaques and microchannels have been identified. Progression of CAV can be monitored also, with promise shown in automated serial measurements also. OCT has significantly advanced our understanding of the pathophysiology-as well as permits precise monitoring and surveillance of the disease. Potential treatment options could also be evaluated using OCT.

Aortic valve disorders and left ventricular assist devices.

Aortic valve disorders are important considerations in advanced heart failure patients being evaluated for left ventricular assist devices (LVAD) and those on LVAD support. Aortic insufficiency (AI) can be present prior to LVAD implantation or develop de novo during LVAD support. It is usually a progressive disorder and can lead to impaired LVAD effectiveness and heart failure symptoms. Severe AI is associated with worsening hemodynamics, increased hospitalizations, and decreased survival in LVAD patients. Diagnosis is made with echocardiographic, device assessment, and/or catheterization studies. Standard echocardiographic criteria for AI are insufficient for accurate diagnosis of AI severity. Management of pre-existing AI includes aortic repair or replacement at the time of LVAD implant. Management of de novo AI on LVAD support is challenging with increased risks of repeat surgical intervention, and percutaneous techniques including transcatheter aortic valve replacement are assuming greater importance. In this manuscript, we provide a comprehensive approach to contemporary diagnosis and management of aortic valve disorders in the setting of LVAD therapy.

Extracorporeal membrane oxygenation as a bridge to advanced heart failure therapies.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a key support modality for cardiogenic shock. The 2018 United Network for Organ Sharing (UNOS) heart transplant allocation algorithm prioritizes VA-ECMO patients. OBJECTIVE: To evaluate the role of VA-ECMO in bridging to advanced heart failure therapies. METHODS: We analyzed adult patients from the multicenter Extracorporeal Life Support Organization registry receiving VA-ECMO for cardiac support or resuscitation between 2016 and 2021 in the United States, comparing bridge-to-transplant (BTT) and non-BTT intent patients, as well as pre- vs post-2018 patients, on a wide range of demographic and clinical outcome predictors. RESULTS: Of 17,087 patients, 797 received left ventricular assist device (LVAD)/heart transplant, 7,931 died or had poor prognosis, and 8,359 had expected recovery at ECMO discontinuation. Patients supported with BTT intent had lower clinical acuity than non-BTT candidates and were more likely to receive LVAD/transplant. The proportion of patients who received VA-ECMO as BTT and received LVAD/transplant increased after 2018. Post-2018 BTT patients had significantly lower clinical acuity and higher likelihood of transplant than both post-2018 non-BTT patients and pre-2018 BTT patients. ECMO complications were associated with lower likelihood of transplant but were significantly less common post-2018 than pre-2018. CONCLUSIONS: After implementation of the 2018 UNOS allocation system, ECMO utilization as BTT or LVAD has increased, and the acuity of BTT intent patients cannulated for ECMO has decreased. There has not yet been an increase in more acute ECMO patients getting transplanted. This may partially explain the post-transplant outcomes of ECMO patients in the current era reported in UNOS.

Outcomes of Venovenous Extracorporeal Membrane Oxygenation in Viral Acute Respiratory Distress Syndrome.

Our study assessed the relationship between the duration of venovenous extracorporeal membrane oxygenation (V-V ECMO) and patient outcomes. We studied patients undergoing V-V ECMO support for acute respiratory distress syndrome (ARDS) between 2009 and 2017 who were reported to the Extracorporeal Life Support Organization registry. We evaluated survival, major bleeding, renal failure, pulmonary complications, mechanical complications, neurologic complications, infection, and duration of V-V ECMO support. Multivariable regression modeling assessed risk factors for adverse events. Of the 4,636 patients studied, the mean support duration was 12.2 ± 13.7 days. There was a progressive increase in survival after the initiation of V-VECMO, peaking at a survival rate of 73% at 10 days of support. However, a single-day increase in V-V ECMO duration was associated with increased bleeding events (odds ratio [OR] 1.038; 95% confidence interval [CI]: 1.029-1.047; p < 0.0001), renal failure (OR 1.018; 95% CI: 1.010-1.027; p < 0.0001), mechanical complications (OR 1.065; 95% CI: 1.053-1.076; p < 0.0001), pulmonary complications (OR 1.04; 95% CI: 1.03-1.05; p < 0.0001), and infection (OR 1.04; 95% CI: 1.03-1.05; p < 0.0001). V-V ECMO progressively increases survival for ARDS over the first 10 days of support. Thereafter, rising complications associated with prolonged durations of support result in a progressive decline in survival.

A Case Report of Severe Factor XI Deficiency during Cardiac Surgery: Less Can Be More.

Severe congenital Factor XI (FXI) deficiency (<20% normal activity) can be associated with significant bleeding disorders, and there has been great concern for severe bleeding following cardiac surgery requiring cardiopulmonary bypass (CPB) in this patient population. Over the past four decades remarkably different approaches to this problem have been taken, including the administration of blood volumes of fresh frozen plasma, administration of activated recombinant Factor VII, and diminutive administration of heparin. We describe a case wherein the patient was assessed in the perioperative period with a point-of-care, viscoelastic hemostasis device (ROTEM), with changes in the intrinsic/Factor XII-dependent coagulation pathway determined before, during, and after CPB. Fresh frozen plasma was administered in small amounts (5−7.5 mL/kg) just before surgery began and just before cessation of CPB. Administering fresh frozen plasma to the patient to nearly normalize in vitro ROTEM hemostasis values at times when hemostasis was needed resulted in no important bleeding occurring or need of further transfusion of other blood products. In conclusion, by using small amounts of fresh frozen plasma guided by ROTEM, an evidenced-based, precision medicine approach resulted in optimized patient care and outcome.

Five-meter walk test before transcatheter aortic valve replacement and 1-year noncardiac mortality.

Objective: The purpose of this study is to assess whether the 5-m walk test is associated with 1-year mortality after transcatheter aortic valve replacement. Methods: Included in the analysis were 304 patients who received the 5-m walk test and underwent transcatheter aortic valve replacement from September 2012 to March 2019. They were classified into 3 groups based on their test score: ≤7, >7, and unable to walk. Preprocedure characteristics, postprocedure outcomes, and follow-up outcomes were compared between the groups. Results: For the 5-m walk test, 145 had a score ≤7 (Group N), 111 had a score >7 (Group S), and 48 were unable to walk (Group I). Average age in years was 80.2 ± 8.7 years in Group N, 81.2 ± 9.4 years in Group S, and 79.4 ± 9.2 in Group I (P = .23). The aortic valve mean gradient at discharge was 9.5 ± 4.1 mm Hg in Group N, 10.4 ± 5.5 mm Hg in Group S, and 8.2 ± 4.2 mm Hg in Group I (P = .05). The discharge survival was 97.2% in Group N, 96.4% in Group S, and 95.8% in Group I (P = .76). One-year survival was 92.8% in Group N, 84.1% in Group S, and 75% in Group I (P < .01) after adjusting for preprocedure characteristics. Noncardiac death was 5.1% in Group N, 13.1% in Group S, and 22.7% in Group I (P = .03). This indicates that the 5-m walk test was a risk factor for 1-year mortality. More specifically, a poor 5-m walk test score was associated with 1-year noncardiac mortality. Conclusions: The 5-m walk test score before transcatheter aortic valve replacement was associated with 1-year mortality, especially noncardiac mortality. It may help identify patients at high risk for 1-year mortality.

Antihypertensive drug treatment and susceptibility to SARS-CoV-2 infection in human PSC-derived cardiomyocytes and primary endothelial cells.

The pathogenicity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been attributed to its ability to enter through the membrane-bound angiotensin-converting enzyme 2 (ACE2) receptor. Therefore, it has been heavily speculated that angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy may modulate SARS-CoV-2 infection. In this study, exposure of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and human endothelial cells (hECs) to SARS-CoV-2 identified significant differences in protein coding genes involved in immunity, viral response, and cardiomyocyte/endothelial structure. Specifically, transcriptome changes were identified in the tumor necrosis factor (TNF), interferon α/ß, and mitogen-activated protein kinase (MAPK) (hPSC-CMs) as well as nuclear factor kappa-B (NF-κB) (hECs) signaling pathways. However, pre-treatment of hPSC-CMs or hECs with two widely prescribed antihypertensive medications, losartan and lisinopril, did not affect the susceptibility of either cell type to SARS-CoV-2 infection. These findings demonstrate the toxic effects of SARS-CoV-2 in hPSC-CMs/hECs and, taken together with newly emerging multicenter trials, suggest that antihypertensive drug treatment alone does not alter SARS-CoV-2 infection.

Thrombocytosis and neutrophilia associated with oxygenator failure and protamine reaction after cardiopulmonary bypass: a case report and literature review.

Thrombocytosis has been feared as a source of thrombotic complications during the conduct of cardiopulmonary bypass (CPB) for patients undergoing cardiac procedures. We present a patient urgently requiring repair/replacement of three heart valves that had preexisting myelofibrosis with thrombocytosis (platelet count of 800,000 per µl) and neutrophilia (40,000 per µl). Despite achieving an activated clotting time > 500 s with heparin and antithrombin concentrate administration prior to CPB, the pump oxygenator and reservoir demonstrated significant clot just prior to restoration of the patient's circulation. The patient subsequently suffered a severe protamine reaction that was successfully managed. A review of the literature of similar patients and the relevant cellular and biochemical mechanisms in this setting are presented, with potential therapeutic approaches to prevent such complications noted.

Antiplatelet and anticoagulation strategies for left ventricular assist devices.

Left ventricular assist devices (LVAD) have revolutionized the management of advanced heart failure. However, complications rates remain high, among which hemorrhagic and thrombotic complications are the most important. Antiplatelet and anticoagulation strategies form a cornerstone of LVAD management and may directly affect LVAD complications. Concurrently, LVAD complications influence anticoagulation and anticoagulation management. A thorough understanding of device, patient, and management, including anticoagulation and antiplatelet therapies, are important in optimizing LVAD outcomes. This article provides a comprehensive state of the art review of issues related to antiplatelet and anticoagulation management in LVADs. We start with a historical overview, the epidemiology and pathophysiology of bleeding and thrombotic complications in LVADs. We then discuss platelet and anticoagulation biology followed by considerations prior to, during, and after LVAD implantation. This is followed by discussion of anticoagulation and the management of thrombotic and hemorrhagic complications. Specific problems, including management of heparin-induced thrombocytopenia, anticoagulant reversal, novel oral anticoagulants, artificial heart valves, and noncardiac surgeries are covered in detail.

Short-Term Risk of Bilateral Internal Mammary Artery Grafting in Diabetic Patients.

This study compares the morbidity and mortality at 30 days following the use of bilateral internal mammary arteries (BIMA) vs a single internal mammary artery (SIMA) at the time of coronary artery bypass grafting (CABG) in patients with a preoperative HbA1c. Patients undergoing CABG from January 2008 to December 2016 reported to the Society of Thoracic Surgeons database were retrospectively reviewed. The patients were divided into 2 groups: use of BIMA or use of SIMA and propensity matched. To assess the effect of preoperative HbA1c, both groups were further divided into 5 subgroups: patients without diabetes mellitus (DM), or patients with DM and a preoperative HbA1c level in one of four groups (< 7%, 7-9%, 9-11%, or >11%). The postoperative outcomes in both the BIMA and SIMA groups were compared. There were 700,504 and 28,115 patients with measured preoperative HbA1c levels in the SIMA and BIMA groups, respectively. Propensity score matching identified 23,635 comparable patients in each group for analysis. There was no difference in postoperative mortality between the BIMA and SIMA groups (1.3% vs 1.2%). The incidences of sternal wound infection (SWI) in patients undergoing placement of BIMA vs SIMA were: 0.8% vs 0.4% with no DM (P < 0.0001), 1.9% vs 1.0% with HbA1c < 7% (P < 0.001), 2.4% vs 1.2% with HbA1c 7-9% (P < 0.001), 2.8% vs 1.4% with HbA1c 9-11% (P = 0.02), 4.1% vs 1.5% with HbA1c > 11% (P = 0.01). Based on the incidence of SWI, BIMA is a reasonable approach with an HbA1c<7%.

Arrhythmias in Relation to Mortality After Transcatheter Aortic Valve Replacement.

BACKGROUND: The purpose of this study was to identify predictors of mortality and potentially modifiable factors related to arrhythmias in patients that undergo transcatheter aortic valve replacement (TAVR). Patients that undergo TAVR are at risk for complete heart block requiring pacemaker implant. Additionally, other arrhythmias, specifically atrial fibrillation (AF), are common in this population. It is unclear how arrhythmias and their management contribute to mortality risk. METHODS: The study analyzed 176 patients who underwent TAVR at a single center. Factors associated with pacemaker implantation within 30 days were analyzed by logistic regression. Factors associated with mortality were analyzed by Kaplan-Meier and Cox regression analyses. RESULTS: Mean age was 80 ± 8.5 years. AF was present in 69 patients, and 39 received anticoagulation. Post-TAVR, a pacemaker was implanted in 25 patients within 30 days. Over a follow up of 566 ± 496 days, 49 patients died. In multivariable analysis, right bundle branch block remained significant (odds ratio 4.212, P = 0.012) for pacemaker implant within 30 days. The AF (hazard ratio [HR] 3.905, P = 0.001), albumin level (HR 0.316, P = 0.034), and diabetes (HR 2.323, P = 0.027) were predictors of death in a multivariate analysis, while pacemaker implant within 30 days was not. Patients with AF who were anticoagulated had improved survival in a stratified Kaplan-Meier analysis compared with those who were not anticoagulated (P = 0.0001). CONCLUSION: AF, diabetes, and low albumin levels are independently associated with mortality after TAVR. In particular, patients with AF who are not anticoagulated are at highest risk for death. Efforts to identify AF and consider anticoagulation should be emphasized.

Degenerated TAVR Within Degenerated Surgical Bioprosthetic Valve Treated With Second TAVR.

Transcatheter aortic valve replacement within a degenerated surgical bioprosthetic aortic valve is increasing in frequency. We present a rare case of a patient requiring a second TAVR placed within a previous placed degenerated transcatheter aortic valve, which was implanted in a degenerated surgical bioprosthetic aortic valve. (Level of Difficulty: Advanced.).

Predictors of Oxygenator Exchange in Patients Receiving Extracorporeal Membrane Oxygenation.

Thrombosis within the membrane oxygenator (MO) during extracorporeal membrane oxygenation (ECMO) can lead to sudden oxygenator dysfunction with deleterious effects to the patient. The purpose of this study was to identify predictors of circuit exchange during ECMO. This is a single-center, retrospective study of all patients who received ECMO at our institution from January 2010 to December 2015. Changes in potential markers were compared on Day 3 vs. Day 0 before MO exchange. Of the 150 patients who received ECMO, there were 58 MO exchanges in 35 patients. Mean ECMO duration was 21.1 (±12.7) days. D-dimer (DD) (µg/mL) (mean difference -2.6; 95% confidence interval [CI]: -4.2 to -1.1; p = .001) increased significantly in the 3 days leading up to MO exchange, whereas fibrinogen (mg/dL) (mean difference 90.7; 95% CI: 41.8-139.6; p = .001), platelet (PLT) count (1,000/µL) (mean difference 23.3; 95% CI: 10.2-36.4; p = .001), and heparin dose (units/h) (mean difference 261.7; 95% CI: 46.3-477.1; p = .02) decreased. Increasing DD or decreasing fibrinogen, PLT count, or heparin dose may indicate an impending need for MO exchange in patients receiving ECMO. Early identification of these changes may help prevent sudden MO dysfunction.

Anticoagulant Bridge Comparison in Mechanical Circulatory Support Patients.

Maintaining mechanical circulatory support (MCS) device patients in a specified therapeutic range for anticoagulation remains challenging. Subtherapeutic international normalized ratios (INRs) occur frequently while on warfarin therapy. An effective anticoagulant bridge strategy may improve the care of these patients. This retrospective review of MCS patients with subtherapeutic INRs compared an intravenous unfractionated heparin (UFH) strategy with a subcutaneous enoxaparin or fondaparinux strategy. Native thromboelastography (n-TEG) was used to evaluate anticoagulant effect with coagulation index (CI) as the primary outcome measure. Enoxaparin 0.5 mg/kg subcutaneously (SC) every 12 hours or fondaparinux 2.5-5 mg SC daily were compared with an initial UFH rate of 5 units/kg/hr and titrated to stated n-TEG goal range. The anticoagulant groups UFH, enoxaparin, and fondaparinux were found to be statistically similar with regard to frequency in n-TEG goal range, above range (hypercoagulability), or below range (hypocoagulability). Clinical outcomes were similar among groups with three gastrointestinal bleeds in UFH, one in enoxaparin, and one in fondaparinux groups. Device thrombosis occurred in one UFH patient, while UFH and fondaparinux groups had one ischemic cerebrovascular accident event each. These strategies provided comparable n-TEG results and clinical outcomes when compared with intravenous UFH. Low-dose enoxaparin or fondaparinux may provide an alternative anticoagulant bridging option in MCS patients presenting with subtherapeutic INR.

Coronary Sinus Rupture Repair: Patency Is Important.

We report a case of coronary sinus (CS) injury with a retrograde cardioplegia catheter and repair that compromised CS patency. This resulted in acute global cardiac dysfunction shortly after weaning from bypass, which reversed after patch repair with confirmed CS patency. The case report shows that acute CS occlusion may not be tolerated in some humans.

Bileaflet Foldoplasty in Barlow’s Disease.

Mitral valve repair is a feasible and preferable option for the treatment of Barlow's disease. Complex valve repair techniques, in contrast, often lead to increased cross-clamp times and low cardiac output syndrome. A simple, fast, and reproducible foldoplasty technique to reduce anterior and posterior mitral leaflet heights may improve coaptation and reduce mitral regurgitation. Accordingly, herein are described minimally invasive, successful trans-septal and robotic approaches for a bileaflet foldoplasty technique in two patients with Barlow's disease.

Right ventricular functional analysis utilizing first pass radionuclide angiography for pre-operative ventricular assist device planning: a multi-modality comparison.

BACKGROUND: Advanced heart failure treated with a left ventricular assist device is associated with a higher risk of right heart failure. Many advanced heart failures patients are treated with an ICD, a relative contraindication to MRI, prior to assist device placement. Given this limitation, left and right ventricular function for patients with an ICD is calculated using radionuclide angiography utilizing planar multigated acquisition (MUGA) and first pass radionuclide angiography (FPRNA), respectively. Given the availability of MRI protocols that can accommodate patients with ICDs, we have correlated the findings of ventricular functional analysis using radionuclide angiography to cardiac MRI, the reference standard for ventricle function calculation, to directly correlate calculated ejection fractions between these modalities, and to also assess agreement between available echocardiographic and hemodynamic parameters of right ventricular function. METHODS: A retrospective review from January 2012 through May 2014 was performed to identify advanced heart failure patients who underwent both cardiac MRI and radionuclide angiography for ventricular functional analysis. Nine heart failure patients (8 men, 1 woman; mean age of 57.0 years) were identified. The average time between the cardiac MRI and radionuclide angiography exams was 38.9 days (range: 1 - 119 days). All patients undergoing cardiac MRI were scanned using an institutionally approved protocol for ICD with no device-related complications identified. A retrospective chart review of each patient for cardiomyopathy diagnosis, clinical follow-up, and echocardiogram and right heart catheterization performed during evaluation was also performed. RESULTS: The 9 patients demonstrated a mean left ventricular ejection fraction (LVEF) using cardiac MRI of 20.7% (12 - 40%). Mean LVEF using MUGA was 22.6% (12 - 49%). The mean right ventricular ejection fraction (RVEF) utilizing cardiac MRI was 28.3% (16 - 43%), and the mean RVEF calculated by FPRNA was 32.6% (9 - 56%). The mean discrepancy for LVEF between cardiac MRI and MUGA was 4.1% (0 - 9%), and correlation of calculated LVEF using cardiac MRI and MUGA demonstrated an R of 0.9. The mean discrepancy for RVEF between cardiac MRI and FPRNA was 12.0% (range: 2 - 24%) with a moderate correlation (R = 0.5). The increased discrepancies for RV analysis were statistically significant using an unpaired t-test (t = 3.19, p = 0.0061). Echocardiogram parameters of RV function, including TAPSE and FAC, were for available for all 9 patients and agreement with cardiac MRI demonstrated a kappa statistic for TAPSE of 0.39 (95% CI of 0.06 - 0.72) and for FAC of 0.64 (95% of 0.21 - 1.00). CONCLUSION: Heart failure patients are increasingly requiring left ventricular assist device placement; however, definitive evaluation of biventricular function is required due to the increased mortality rate associated with right heart failure after assist device placement. Our results suggest that FPRNA only has a moderate correlation with reference standard RVEFs calculated using cardiac MRI, which was similar to calculated agreements between cardiac MRI and echocardiographic parameters of right ventricular function. Given the need for identification of patients at risk for right heart failure, further studies are warranted to determine a more accurate estimate of RVEF for heart failure patients during pre-operative ventricular assist device planning.

A dual therapy of off-pump temporary left ventricular extracorporeal device and amniotic stem cell for cardiogenic shock.

BACKGROUND: Temporary mechanical circulatory support device without sternotomy has been highly advocated for severe cardiogenic shock patient but little is known when coupled with amniotic stem cell therapy. CASE PRESENTATION: This case reports the first dual therapy of temporary left ventricular extracorporeal device CentriMag with distal banding technique and human amniotic stem cell injection for treating a severe refractory cardiogenic shock of an 68-year-old female patient. A minimally-invasive off-pump LVAD was established by draining from the left ventricle and returning to the right axillary artery with distal arterial banding to prevent right upper extremity hyperperfusion. Amniotic stem cells were injected intramyocardially at the left ventricular apex, lateral wall, inferior wall, and right subclavian vein. CONCLUSION: The concomitant use of the temporary minimally-invasive off-pump CentriMag placement and stem cell therapy not only provided an alternative to cardiopulmonary bypass and full-median sternotomy procedures but may have also synergistically enhanced myocardial reperfusion and regeneration.

Cardiac Regeneration in the Human Left Ventricle After CorMatrix Implantation.

CorMatrix is an organic extracellular matrix (ECM) derived from porcine small intestine submucosa and is used for pericardial closure and cardiac tissue repair. During explantation of a HeartMate II (Thoratec Corp, Pleasanton, CA) left ventricular assist device (LVAD) because of infection, CorMatrix was used to repair the left ventricular apex and aorta. Three months later, a HeartWare HVAD (HeartWare International, Inc, Framingham, MA) was implanted for recurrent heart failure. Excised apical CorMatrix samples showed cardiac tissue remodeling with viable cardiomyoblasts similar to native myocardium. Excised CorMatrix from the aorta showed organization of collagen and elastin similar to native aortic tissue.