B. Soleimani

Management of left ventricular distension during peripheral extracorporeal membrane oxygenation for cardiogenic shock

The application of peripheral veno-arterial extracorporeal membrane oxygenation in the management of inotrope-refractory cardiogenic shock has proven controversial because of concerns about sub-optimal drainage of the left heart, resulting in left ventricular distension and pulmonary oedema. In this article, we will discuss the pathophysiological basis and clinical implications of left ventricular distension following institution of peripheral extracorporeal life support. We will also review the clinical strategies used to circumvent left ventricular distension and pulmonary oedema in these patients.

Role of Alloantibodies in the Pathogenesis of Graft Arteriosclerosis in Cardiac Transplantation

Graft arteriosclerosis (GA) remains the leading obstacle to long‐term survival of cardiac allografts. The pathogenesis of this chronic disease, though perceived to be multifactorial, is most likely immune‐driven. Based on clinical and experimental observations, the humoral arm of the immune system has long been suspected to play a pivotal role in the disease process. In this article, we shall review the evidence generated from key clinical and experimental studies on the role of alloantibodies in GA. We will argue that although the strong correlation between the presence of anti‐donor antibodies in clinical and experimental GA is highly suggestive of a pathogenic role for alloantibodies, a direct causal link between GA and the humoral arm of the alloresponse cannot yet be established based on the currently available evidence, and may in fact be one of a number of pathogenic processes that potentiate this vasculopathy. Finally, in this article, we shall discuss some of the potential mechanisms by which alloantibodies may exert their pathogenic effect in GA.

Development of aortic insufficiency in patients supported with continuous flow left ventricular assist devices.

Development of aortic insufficiency (AI) in patients supported with continuous flow left ventricular assist devices (LVAD) can adversely affect pump performance. In this study, we examined the incidence of new AI after LVAD implant at our institution. Pre- and postoperative echocardiograms of 66 patients who received HeartMate II or Heartware LVAD at our institution since June 2008 were reviewed for presence of new AI. Median LVAD support duration was 221 days. New AI developed in 6 patients (9.5%) after a median time of 374.5 days of support. There were no cases of severe or symptomatic AI. There was no significant difference between the AI incidence between HeartMate II and Heartware recipients. For patients who remained on LVAD support at 6 and 12 months, freedom from AI was 100% and 68.4%, respectively. Age, destination therapy status, and duration of support were predictors of new AI after LVAD implant. In conclusion, AI develops frequently during long-term support with continuous flow LVADs, particularly in those supported for longer than 6 months. As we move to the era of long-term LVAD support and destination therapy, further studies with longer follow-ups are required to determine the progression and clinical significance of AI in these patients.

The incidence, risk factors, and outcomes associated with late right-sided heart failure in patients supported with an axial-flow left ventricular assist device

BACKGROUND Early right-sided heart failure (RHF) after left ventricular assist device (LVAD) implantation is associated with increased mortality, but little is known about patients who develop late RHF (LRHF). We evaluated the incidence, risk factors, and clinical impact of LRHF in patients supported by axial-flow LVADs. METHODS Data were analyzed from 537 patients enrolled in the HeartMate II (HM II; Thoratec/St. Jude) destination therapy clinical trial. LRHF was defined as the development of clinical RHF accompanied by the need for inotropic support occurring more than 30 days after discharge from the index LVAD implant hospitalization. Clinical variables, quality of life, rehospitalizations, and survival were compared between patients with and without LRHF. RESULTS LRHF developed in 41 patients (8%), with a median time to LRHF of 480 days. A higher preoperative blood urea nitrogen and increased central venous pressure-to-pulmonary capillary wedge pressure ratio were independent predictors of LRHF. The Michigan and HMII RHF risk scores were both associated with an increased likelihood of LRHF (p < 0.05). Patients with LRHF had worse quality of life according to the Kansas City Cardiomyopathy Questionnaire (61 ± 26 vs 70 ± 21; p < 0.05), poorer functional capacity by 6-minute walk distance (275 ± 189 m vs 312 ± 216 m; p < 0.05), and more rehospitalizations (6 vs 3; p < 0.001). LRHF was associated with decreased survival (p < 0.001). CONCLUSIONS LRHF is an important complication in patients with LVADs and is associated with worse quality of life, reduced functional capacity, more frequent hospitalizations, and worse survival compared with those without LRHF.

Clinical Experience With Sternotomy Versus Subcostal Approach for Exchange of HeartMate II Left Ventricular Assist Device

BACKGROUND The safety and efficacy of exchanging the HeartMate II (Thoratec Corp, Pleasanton, CA) left ventricular assist device (LVAD) through a less invasive subcostal approach remains unclear. METHODS We reviewed the records of 17 patients who underwent exchange of their HeartMate II device at our institution since 2007. We divided the cohort into devices exchanged through a subcostal (SC) approach versus a median sternotomy (MS) approach and obtained data pertaining to the short- and long-term outcomes. RESULTS Nine patients had pump exchange through an MS approach versus 8 patients who underwent an SC approach. The mean duration of support with the first pump was 540 ± 450 days. The reason for exchange was electromechanical failure (7 patients), thrombosis (8 patients), and infection (2 patients). There were no 30-day perioperative deaths with either approach. Compared with sternotomy, patients who underwent an SC approach had significantly shorter operative times (131 vs 222 minutes; p = 0.001) and lower reoperation rates for bleeding (0 vs 44.4%; P = 0.05) and required fewer transfused blood products (packed red cells, 3.5 units vs 7.1 units; p < 0.05; cryoprecipitate, 50.7 mL vs 209.3 mL; p = 0.01; and platelets, 292 mL versus 762 mL; p < 0.05). Additionally, patients who underwent an SC approach had shorter postoperative stays in the intensive care unit (ICU) (5 days vs 13.8 days; p < 0.05) and shorter total hospital stays (16.4 days vs 27.2 days; p < 0.05). Long-term survival after mean follow-up of 260 days for the SC group and 232 days for the sternotomy group was 75% and 33%, respectively. CONCLUSIONS Exchange of the HeartMate II pump can be accomplished with low morbidity and mortality and good long-term outcomes through a less invasive SC approach.

Smooth muscle cell proliferation but not neointimal formation is dependent on alloantibody in a murine model of intimal hyperplasia.

Transplant coronary artery disease is the pre‐eminent cause of late cardiac allograft failure. It is primarily characterized by a concentric intimal hyperplasia, which we designate transplant intimal hyperplasia (TIH). Although the pathogenesis of TIH is predominately immune driven, the specific role of alloantibodies in the disease process remains undefined. In this study we investigated the contribution of alloantibodies to the development of TIH in a murine model. Orthotopic, carotid artery transplantation was performed between B10A(2R) (H‐2h2) donor mice and B‐cell deficient μMT–/– knockout or wild‐type C57BL/6 (H‐2b) recipients in the absence of immunosuppression. Grafts were harvested at 35 days and subjected to planimetry and immunohistochemistry. Alloantibodies were detectable in wild‐type recipients within 7 days of transplantation and recipients developed marked TIH at 35 days. Allografts harvested from B‐cell deficient recipient mice also developed TIH, which was comparable in severity with wild‐type recipients. However, whereas allografts from wild‐type recipients showed marked intimal smooth muscle cell (SMC) proliferation, the neointima in B‐cell deficient recipients lacked SMCs. Post‐transplantation administration of anti‐donor serum to μMT–/– recipients restored neointimal SMC population but did not influence the severity of TIH. Significant neointimal formation occurs in the absence of alloantibodies but lacks a SMC component. Therefore, SMC migration and proliferation is antibody dependent.

Sharing the Care of Mechanical Circulatory Support Collaborative Efforts of Patients/Caregivers, Shared-Care Sites, and Left Ventricular Assist Device Implanting Centers

Left ventricular assist devices (LVADs) improve longevity, as well as functional capacity and quality of life in patients with medically refractory heart failure.1–5 During the 6 years since the US Food and Drug Administration approval of the first commercially available continuous flow LVAD in 2008, the number of patients supported by these devices has grown exponentially. The most recent report from the Interagency Registry for Mechanically Assisted Circulatory Support recorded nearly 2500 North American LVAD implants in 2013 at >150 implanting centers.6 Approximately 40% of LVADs are implanted as an indefinite form of support (ie, destination therapy [DT]), and nearly half of patients are surviving >4 years.6 This combination of improved survival and evolving implant strategies has led to an increasing number of LVAD recipients being integrated into the community and we are observing the growth of an ambulatory LVAD population with a unique set of clinical needs. There are 2 predominant strategies of LVAD implantation. Patients who are not eligible for transplantation because of issues such as advanced age may be considered for an LVAD as DT, implying that they will live the rest of their lives with the LVAD. This is in contrast to patients who undergo LVAD implantation as a temporary support device, to support them while awaiting transplantation. This later strategy is defined as a bridge-to-transplantation, following which, the device will be explanted. Centers implanting LVADs without concomitant transplant programs (designated DT centers) have emerged to provide this therapy, averting the need for travel to more distant transplant centers. Such DT centers operate in conjunction with a VAD/transplant partner in the care of patients awaiting transplantation. Because LVAD implant centers are frequently remotely located from the patients that they serve, a model of shared-care has developed, whereby the continued care of …

Development of a Combined Heart and Carotid Artery Transplant Model to Investigate the Impact of Acute Rejection on Cardiac Allograft Vasculopathy

BACKGROUND Cardiac allograft vasculopathy (CAV) is the leading cause of late allograft loss after heart transplantation. Although clinical studies are suggestive of an association between episodes of acute rejection and subsequent emergence of CAV, direct experimental evidence in support of a causal relationship is lacking. METHODS We developed a new murine model of CAV in which a carotid artery and a heart graft are simultaneously transplanted into a single recipient. Transplants were performed across full or partial major histocompatibility complex (MHC) mismatched strain combinations. The heart grafts were either syngeneic with the carotid graft or from a third-party strain. Carotid arteries were harvested after 30 days and evaluated by morphometry and immunohistochemistry. RESULTS In the fully mismatched combination, all heart grafts were rejected within 7 days, as determined by loss of pulsation. At 30 days, carotid allografts in the combined transplant group had significantly more intimal hyperplasia compared with isolated carotid allografts. The neointima consisted of abundant smooth muscle cells and leukocytes. Intimal hyperplasia was also significantly enhanced by acute rejection of the third-party donor heart. In the partial MHC mismatched combination, the heart graft survived indefinitely, and this was associated with diminished intimal hyperplasia in the cotransplanted carotid artery compared with the isolated carotid allograft. CONCLUSION We present direct experimental evidence that CAV is promoted by acute parenchymal rejection of the heart. This interaction between acute rejection and CAV is mediated by both allospecific and non-allospecific processes. Effective therapeutic strategy against CAV should therefore target non-allospecific mediators as well as prevent episodes of acute rejection.

Long-Term Survival in Patients Receiving a Continuous-Flow Left Ventricular Assist Device

BACKGROUND Long-term survivors after implantation of left ventricular assist devices (LVADs) are increasing in prevalence. We describe the characteristics and outcomes in patients surviving longer than 4 years on LVAD support. METHODS We performed a multicenter, retrospective analysis of patients surviving at least 4 years on continuous-flow LVAD (CF-LVAD) support with a HeartMate II at centers participating in the Evolving Mechanical support Research Group. RESULTS Between 2005 and 2010, 156 long-term survivors were identified with a mean survival of 7.1 years (95% confidence interval: 6.7 to 7.5 years). The mean age was 58.2 ± 15.2 years and 30.1% were women. Readmission rate was low at 1.1 events per patient per year with the most common reasons leading to readmission being infection (0.10 readmissions per patient per year) and gastrointestinal bleeding (0.07 readmissions per patient per year). Two years after implantation, 97% of patients were either New York Heart Association functional class I or II, with 92% at 4 years. CONCLUSIONS Patients surviving 4 years on CF-LVAD support can anticipate ongoing long-term survival with sustained improvements in functionality and low rates of rehospitalization.

Severity of end-organ damage as a predictor of outcomes after implantation of left ventricular assist device.

The optimal timing of left ventricular assist device (LVAD) implantation in the management of advanced heart failure remains controversial. We hypothesize that in patients with cardiogenic shock, the severity of end-organ dysfunction as determined by the sequential organ failure assessment (SOFA) score is a determinant of outcomes after LVAD implantation. We determined the preoperative SOFA score and short- and long-term outcomes of 97 consecutive patients who received HeartMate II or HeartWare LVAD at our institution since January 2007. Kaplan-Meier analysis was used to compare long-term survival across SOFA score subgroups. The overall 30 day mortality was 10.1%, with no significant difference among SOFA score subgroups. Patients with scores ≥9 had significantly longer hospital stay (26 ± 6 vs. 18 ± 10 days, p = 0.03). One-year survival for SOFA scores 0–2, 3–5, 6–8, and ≥9 was 94%, 75%, 64%, and 29%, respectively. SOFA score was significantly lower in survivors at 6, 9, 12, 24, and 36 months. SOFA score did not predict adverse outcomes of bleeding, cerebrovascular events, infection, or pump exchange. These results show that preoperative SOFA score is a powerful predictor of outcomes after LVAD implantation. Long-term outcomes can be significantly improved by early intervention before emergence of end-organ dysfunction.