The protective role of GATA6+ pericardial macrophages in pericardial inflammation.

Prior research has suggested that GATA6+ pericardial macrophages may traffic to the myocardium to prevent interstitial fibrosis after myocardial infarction (MI), while subsequent literature claims that they do not. We demonstrate that GATA6+ pericardial macrophages are critical for preventing IL-33 induced pericarditis and attenuate trafficking of inflammatory monocytes and granulocytes to the pericardial cavity after MI. However, absence of GATA6+ macrophages did not affect myocardial inflammation due to MI or coxsackievirus-B3 induced myocarditis, or late-stage cardiac fibrosis and cardiac function post MI. GATA6+ macrophages are significantly less transcriptionally active following stimulation in vitro compared to bone marrow-derived macrophages and do not induce upregulation of inflammatory markers in fibroblasts. This suggests that GATA6+ pericardial macrophages attenuate inflammation through their interactions with surrounding cells. We therefore conclude that GATA6+ pericardial macrophages are critical in modulating pericardial inflammation, but do not play a significant role in controlling myocardial inflammation or fibrosis.

Association of thrombophilia prospective detection with hemocompatibility related outcomes in left ventricular assist device patients.

INTRODUCTION: Inherited thrombophilias represent a concerning risk factor due to a proclivity to an aberrant clot formation. However, in patients with left ventricular assist device (LVAD), their impact on bleeding and thrombotic complications remains still poorly understood. The aim of the present study was to evaluate the effect of thrombophilic mutation directed anticoagulation therapy on adverse clinical outcomes in LVAD patients. MATERIALS AND METHODS: About 138 consecutive patients indicated for LVAD implant (HeartMate II, Abbott, Plymouth, USA) were prospectively screened for three major thrombophilic mutations: factor II (prothrombin), factor V Leiden, and homozygous methylenetetrahydrofolate reductase (MTHFR). Subsequently, discordant individualized anticoagulation targets of INR 2.5-3.0 in thrombophilia positive and INR 1.8-2.2 in negative patients were established; notably without anti-platelet agents given the center standard of care. RESULTS: Mean age was 50 ± 12.7 years, 83% male. Mean duration of support was 464.5 days (SD 482.9; SEM 41.1) and median of 310 days (IQR 162; 546). Full thrombophilia positive cohort analysis has not revealed any significant impact on event free survival. In contrast, detailed analysis of specific thrombophilias subsets has revealed Factor II prothrombin mutation as a significant predisposition for the pump thrombosis risk (SHR 10.48; p = 0.001) despite more aggressive prespecified anticoagulation target. Moreover, the incidence of bleeding events in prothrombin group was also significantly increased (SHR 6.0; p = 0.03). CONCLUSIONS: Our observations suggest that specific thrombophilias in LVAD patients may pose different intensity predisposition for thrombotic complications. Factor II (prothrombin) positive mutation was identified as significant risk factor associated with the pump thrombosis.

Increased pulsatility index is associated with adverse outcomes in left ventricular assist device recipients.

AIMS: Recipients of left ventricular assist devices (LVAD) are exposed to increased risk of adverse clinical events. One of the potential contributing factors is non-pulsatile flow generated by LVAD. We evaluated the association of flow patterns in carotid arteries and of increased arterial stiffness with death and cerebrovascular events in LVAD recipients. METHODS AND RESULTS: We analysed data from 83 patients [mean age 54 ± 15 years; 12 women; HeartMate II (HMII), n = 34; HeartMate 3 (HM3), n = 49]. Pulsatile and resistive indexes, atherosclerotic changes in carotid arteries (measured by duplex ultrasound), and arterial stiffness [measured by Endo-PAT 2000 as the augmentation index standardized for heart rate (AI@75)] were evaluated 3 and 6 months after LVAD implantation. Sixteen patients died during follow-up (27.3 months; interquartile range 15.7-44.3). After adjusting for the main variables examined, the pulsatility index measured at 3 months was positively associated with increased hazard ratios (HR) for death and cerebrovascular events [HR 9.8, 95% confidence interval (CI) 1.62-59.42], with HR increasing after adding AI@75 to the model (HR 18.8, 95% CI 2.44-145.50). In HM3 recipients, HR was significantly lower than in HMII recipients (HR 0.31, 95% CI 0.11-0.91), but the significance disappeared after adding AI@75 to the model (HR 0.33, 95% CI 0.09-1.18). CONCLUSIONS: The risk of death and cerebrovascular events in LVAD recipients is associated with increased pulsatility index in carotid arteries and potentiated by increased arterial stiffness. The same risk is attenuated by HM3 LVAD implantation, but this effect is weakened by increased arterial stiffness.

Implantation of durable left ventricular assist device in patient with postmyocardial infarction ventricular septal defect.

Ventricular septal defect (VSD) is a severe complication of myocardial infarction (MI) with a high mortality rate. We report a case of a large post-MI VSD treated with percutaneous venoarterial extracorporeal membrane oxygenation (VA-ECMO) to restore hemodynamic stability and to avoid surgery in the acute setting. VSD closure with endoventricular patch and implantation of biventricular assist device (BiVAD) was arranged sixteen days after MI. Because of no signs of myocardial recovery, implantation of durable left ventricular assist device (LVAD) as a bridge to transplant was provided, leaving right ventricular assist device (RVAD) to right ventricle recovery. RVAD was explanted 18 days after durable LVAD placement and the patient was discharged home two months after MI. The use of durable LVAD is a unique solution that can be applied in selected patients with MI-VSD and heart failure.

The Effect of Artificial Pulsatility on the Peripheral Vasculature in Patients With Continuous-Flow Ventricular Assist Devices.

BACKGROUND: Implantation of left-ventricular assist systems (LVASs) has become the standard of care for advanced heart failure (HF). The absence of pulsatility in previous devices contributes to vascular and endothelial dysfunction related to atherosclerotic or vascular complications. We hypothesized that the artificial pulsatility provided by the HeartMate 3 (HM3) (Abbott, Chicago, IL) LVAS would exert a favourable effect on the vasculature. METHODS: In 32 patients implanted with HM3 (5 female patients, mean age 55 ± 13.6 years), the reactive hyperemia index (RHI) and peripheral augmentation index (AI), markers of endothelial function and arterial stiffness, were measured with an EndoPAT2000 before and in the third and sixth month after implantation. RHI and AI data from 30 HeartMate II (HM II) (Abbott) recipients in the third and sixth month after implantation, from 15 patients with advanced HF without LVASs and from 13 healthy volunteers were also analyzed. RESULTS: In HM3 recipients, the mean RHI significantly decreased at 3 and 6 months after implantation. The RHI was substantially lower at baseline than that of healthy or the HF reference group. Increasing AI values, indicating worsening arterial stiffness, were also observed. Similar trends were observed in HM II recipients between the third and sixth months but with higher absolute values of RHI and AI. CONCLUSIONS: We detected impaired vascular function in HM3 patients and provided additional evidence on the negative effect of low pulsatility on vascular function after LVAS implantation. The results suggest that the artificial pulsatility of the HM3 does not avert the progression of endothelial dysfunction.

Innate Lymphoid Cells Play a Pathogenic Role in Pericarditis.

We find that cardiac group 2 innate lymphoid cells (ILC2s) are essential for the development of IL-33-induced eosinophilic pericarditis. We show a pathogenic role for ILC2s in cardiac inflammation, in which ILC2s activated by IL-33 drive the development of eosinophilic pericarditis in collaboration with cardiac fibroblasts. ILCs, not T and B cells, are required for the development of pericarditis. ILC2s transferred to the heart of Rag2-/-Il2rg-/- mice restore their susceptibility to eosinophil infiltration. Moreover, ILC2s direct cardiac fibroblasts to produce eotaxin-1. We also find that eosinophils reside in the mediastinal cavity and that eosinophils transferred to the mediastinal cavity of eosinophil-deficient ΔdblGATA1 mice following IL-33 treatment migrate to the heart. Thus, the serous cavities may serve as a reservoir of cardiac-infiltrating eosinophils. In humans, patients with pericarditis show higher amounts of ILCs in pericardial fluid than do healthy controls and patients with other cardiac diseases. We demonstrate that ILCs play a critical role in pericarditis.

Evaluation of low-intensity anti-coagulation with a fully magnetically levitated centrifugal-flow circulatory pump-the MAGENTUM 1 study.

BACKGROUND: The HeartMate 3 left ventricular assist system is engineered to avoid pump thrombosis, yet bleeding complications persist. We investigated the safety of low-intensity anti-coagulation in patients with the HeartMate 3. METHODS: The Minimal AnticoaGulation EvaluatioNTo aUgment heMocompatibility (MAGENTUM 1) pilot study is a prospective, single-arm study of low-intensity warfarin anti-coagulation in patients implanted with the HeartMate 3 pump. After standard warfarin anti-coagulation (international normalized ratio [INR] 2.0 to 3.0) and aspirin for 6 weeks post-implant, patients were transitioned to a lower INR target range of 1.5 to 1.9. The primary end-point was a composite of survival free of pump thrombosis, disabling stroke (modified Rankin score [MRS] >3), or major bleeding (excluding peri-operative bleeding) with at least 6-month post-implant follow-up. Time in therapeutic range (TTR) was measured to assess anti-coagulation target efficacy using the Rosendaal method. A safety algorithm to monitor for signs of pump thrombosis was developed and implemented. RESULTS: We enrolled 15 patients (mean age 57.3 ± 13.3 years), 13 men with advanced heart failure (67% with INTERMACS Profiles 2 or 3), irrespective of therapeutic goal of bridge-to-transplant or destination therapy. The primary end-point was met in 14 of 15 (93 ± 6%) patients; 1 patient developed recurrent gastrointestinal bleeding. The TTR during the reduced anti-coagulation phase (6 weeks to 6 months) was 75.3 ± 8.6%. No thrombotic events occurred. CONCLUSIONS: This pilot study suggests low-intensity anti-coagulation targeting an INR between 1.5 and 1.9 is achievable and safe with the HeartMate 3 cardiac pump in the short-term phase, 6-months post-implant. A large-scale trial is now warranted.

Comparison of Cystatin C and NGAL in Early Diagnosis of Acute Kidney Injury After Heart Transplantation.

BACKGROUND Acute kidney injury (AKI) is a risk factor for adverse hospital outcomes in recipients of a heart transplantation (HTx). Timely recognition of AKI is crucial for the initiation of proper treatment. We hypothesized that serum or urine biomarkers can predict AKI. MATERIAL AND METHODS In this prospective study we evaluated 117 consecutive patients after HTx. AKI was defined as an increase of the serum creatinine level by ≥50% or a worsening of the renal function requiring renal replacement therapy during the first post-HTx week. We serially sampled serum cystatin C (S-cystatin C) as a marker of glomerular filtration and urinary neutrophil gelatinase-associated lipocalin (U-NGAL) as a marker of tubular damage. RESULTS A cohort of 30 patients (25.6%) fulfilled the criteria of AKI. S-cystatin C allowed the earliest separation between the AKI and non-AKI groups, with a significant difference present as soon as 3 h after surgery and it persisted on days 7, 10, and 30. The increase in S-cystatin C preceded the serum creatinine elevation by 4 days. In a multivariate analysis, S-cystatin C >1.6 mg/L at 3 h after HTx predicted AKI with OR 4.3 (95% CI: 1.6-11.5). U-NGAL was significantly higher at day 3 in the AKI group (p=0.003) and elevated S-cystatin C (≥2.54 mg/L on day 7) could predict 1-year mortality in these HTx recipients. CONCLUSIONS Our study showed that the measurement of S-cystatin C at 3 h after surgery may help to identify patients with high risk for renal complications. A persistent elevation of S-cystatin C also predicts 1-year mortality.

Non-Fontan Adult Congenital Heart Disease Transplantation Survival Is Equivalent to Acquired Heart Disease Transplantation Survival.

BACKGROUND: As a result of improved diagnostic methods, medical treatment, surgical correction, and palliation in childhood, there is a growing number of adult patients with congenital heart disease (CHD) who may experience heart failure and subsequently require heart transplantation (HT). Because of complex anatomy, previous operations, and frequently increased pulmonary vascular resistance (PVR), these patients represent a group with a higher risk of early mortality after transplantation. METHODS: From May 1999 to December 2014, our institution performed 25 HTs in adult patients with end-stage CHD. We present our data and outcomes of transplantation in this group. RESULTS: The median age at transplantation was 38 years (range, 18.4-53.7 years). Survival was 88% at 30 days, 88% at 1 year, and 77% at 5 years. We identified long donor heart ischemic time (>4 hours) as an important risk factor for early mortality. There was no significant difference in the survival of patients undergoing transplantation for CHD and patients undergoing transplantation for other diagnoses. CONCLUSIONS: With careful donor and recipient selection, adults with end-stage CHD undergoing HT can achieve excellent early and midterm survival, comparable to the survival of patients who undergo transplantation for other diagnoses.

Aortic and Mitral Valve Replacement Due to Extensive Inflammatory Immunoglobulin G4-Related Pseudotumor.

A 64-year-old woman with extensive tumorous infiltration of the mitral and aortic valves underwent partial resection of a tumor of the left ventricular outflow tract and replacement of both affected valves. Histology revealed an inflammatory pseudotumor with a significant number of immunoglobulin-G4-positive plasma cells. The histologic and clinical findings suggested immunoglobulin-G4-related disease of the heart.

Bridge to transplantation with long-term mechanical assist device in adults after the Mustard procedure.

BACKGROUND: There is limited clinical experience with bridging to transplant with a left ventricular assist device (VAD) in patients with previously palliated transposition of great arteries. METHODS: Five adult patients presenting with systemic right ventricular failure 30 years after a Mustard operation were implanted with a HeartMate II VAD. The implant was completed using standard procedures with only minor modifications to accommodate right ventricular cannulation. RESULTS: All 5 patients were men, with a mean age of 31.5 ± 1.8 years and a median time since Mustard operation of 30 (range 28 to 32) years. All patients had sternal closure on Post-operative Day (POD) 1, and 2 patients required additional re-operation for bleeding. One patient required temporary support of the non-systemic ventricle. The mean duration of VAD support was 284 ± 177 days; 3 patients underwent heart transplant and 2 died on PODs 502 and 34, respectively. Both deaths were due to progressive heart failure and pump thrombosis. Comorbidities, anatomy and mediastinal scarring did not preclude implantation and heart failure symptoms improved in all patients. CONCLUSIONS: With the increased prevalence of late post-Mustard heart failure, bridge to transplant with a VAD may be a suitable treatment option for patients who are severely ill.

Tricuspid valve surgery in patients with idiopathic hypereosinophilic syndrome.

A 53-year-old female with idiopathic hypereosinophilic syndrome underwent recurrent tricuspid valve replacement for Löffler's endocarditis. We review the literature on tricuspid valve surgery in patients with this uncommon disorder.

Minimally invasive removal of a temporary RVAD.

We describe a minimally invasive technique for the removal of a temporary right ventricular assist device (RVAD) that provided support concomitant with durable left ventricular assist device support. The RVAD cannulas are mobilized through a small subxiphoid incision at the cannula exit site. Both cannulas are transected subcutaneously, then occluded with plugs made of rolled bovine pericardium, and the skin is closed. The cannula remnants are left in place until heart transplantation is accomplished. To minimize risk of thrombus formation at the cannula tips and subsequent embolization into the right atrium or pulmonary artery, anticoagulation is increased to achieve an international normalized ratio (INR) in the range of 2.5-3.0.

Post-heart transplantation outcome of HeartMate II-bridged recipients requiring unplanned concomitant temporary right ventricular mechanical support.

OBJECTIVES: Second-generation axial-flow left ventricular assist devices (LVADs) have become an established therapy in bridging end-stage heart failure patients to cardiac transplantation. Despite the proven clinical success of these devices, some patients develop right ventricular (RV) failure after LVAD implantation. We sought to determine post-heart transplantation outcomes of HeartMate II (HMII)-bridged patients who developed postimplantation right ventricular failure and received Levitronix CentriMag for RV support in addition to LVAD. METHODS: This was a single-centre institutional report of 64 patients transplanted during 2007-2013 from a HeartMate II device. Patients were divided into two groups according to whether they received an isolated LVAD (n = 56) or required additional RV mechanical support (n = 8). These two groups were compared for early graft loss (death before discharge or retransplantation), major early post-transplant complications and 3-year graft survival. RESULTS: Early graft loss was 10.7% in isolated HMII and 25% in HMII + RVAD patients (P = 0.26). There were no observed differences in the rates of primary graft dysfunction (7.3 vs 0%, P = NS), renal failure (16.7 vs 12.5%, P = NS) and stroke (11.1 vs 25%, P = 0.273) between the two groups. Pulmonary artery resistance (odds ratio: 3.286, 95% confidence interval: 1.063-10.157, P = 0.039) was identified as a significant predictor for adverse outcome of mechanically-bridged heart transplant recipients. The 3-year graft survival rate was 86 ± 5% in isolated HMII and 75 ± 15% in HMII + RVAD patients, P = 0.326. CONCLUSIONS: Our data demonstrate that heart transplant recipients who required unplanned RV mechanical support after LVAD implantation achieved comparable rates of early graft loss, post-transplant renal failure and stroke rate in comparison with patients bridged with an isolated HeartMate II assist device. Three-year graft survival was equivalent between those two groups. Given the small sample size, further studies involving more patients are needed to support or challenge our conclusions.

Case report: atypical fungal obstruction of the left ventricular assist device outflow cannula.

We describe a very rare case of outflow cannula obstruction with fungal infectious thrombus formation. Discussion includes the etiology, diagnosis, and management of fungal infection complications related with long-term mechanical circulatory support. Left ventricular assist devices (LVADs) are increasingly used as bridge to transplant and permanent long-term therapy in the population with end-stage heart failure. Even though better clinical outcomes have been achieved with the newer-generation continuous-flow devices, infection complications are still a major risk for patients with continuous-flow LVAD implantation in long-term follow-up [Ann Thorac Surg 90:1270-1277, 2010]. Device-related infections can be categorized as driveline infections, pump-pocket infections, and LVAD-associated endocarditis [Expert Rev Med Devices 8: 627-634, 2011]. The microbiological profile is very heterogeneous; the most common pathogens are Staphylococcus, Pseudomonas, Streptococcus species, and Candida. Severe fungal infection may lead to dysfunction of the LVAD due to obstructive mass formation within the device. Due to the only anecdotal reports in the current literature, we present a very rare case of outflow fungal infectious thrombus formation leading to outflow cannula obstruction in patient with LVAD.

Fungal infections associated with long-term mechanical circulatory support-diagnosis and management.

Left ventricular assist devices (LVADs) are increasingly used as a treatment option for advanced heart failure. Fungal infections present a serious concern given the high association with major adverse events including death in this group of patients. The objective of this review is to summarize the incidence, risk factors, method for diagnosis, complication rate, and outcomes in patients with VADs who develop fungal infections.