Mid-term survival after continuous-flow left ventricular assist device versus heart transplantation.

There is a paucity of data about mid-term outcome of patients with advanced heart failure (HF) treated with left ventricular assist device (LVAD) in Europe, where donor shortage and their aging limit the availability and the probability of success of heart transplantation (HTx). The aim of this study is to compare Italian single-centre mid-term outcome in prospective patients treated with LVAD vs. HTx. We evaluated 213 consecutive patients with advanced HF who underwent continuous-flow LVAD implant or HTx from 1/2006 to 2/2012, with complete follow-up at 1 year (3/2013). We compared outcome in patients who received a LVAD (n = 49) with those who underwent HTx (n = 164) and in matched groups of 39 LVAD and 39 HTx patients. Patients that were treated with LVAD had a worse risk profile in comparison with HTx patients. Kaplan-Meier survival curves estimated a one-year survival of 75.5 % in LVAD vs. 82.3 % in HTx patients, a difference that was non-statistically significant [hazard ratio (HR) 1.46; 95 % confidence interval (CI) 0.74-2.86; p = 0.27 for LVAD vs. HTx]. After group matching 1-year survival was similar between LVAD (76.9 %) and HTx (79.5 %; HR 1.15; 95 % CI 0.44-2.98; p = 0.78). Concordant data was observed at 2-year follow-up. Patients treated with LVAD as bridge-to-transplant indication (n = 22) showed a non significant better outcome compared with HTx with a 95.5 and 90.9 % survival, at 1- and 2-year follow-up, respectively. Despite worse preoperative conditions, survival is not significantly lower after LVAD than after HTx at 2-year follow-up. Given the scarce number of donors for HTx, LVAD therapy represents a valid option, potentially affecting the current allocation strategy of heart donors also in Europe.

Giant cell myocarditis successfully treated with antithymocyte globuline and extracorporeal membrane oxygenation for 21 days.

: A 31-year-old man presenting with cardiogenic shock and left ventricular ejection fraction of 10% received the diagnosis of giant cell myocarditis by endomyocardial biopsy. The patient was successfully treated with high-dose inotropes, intra-aortic balloon pump and venoarterial extracorporeal membrane oxygenation for 21 days associated with combined immunosuppression (thymoglobulin, steroids, cyclosporine). Immunosuppression including thymoglobulin is the regimen associated with the highest probability of recovery in case of giant cell myocarditis. Immunosuppression needs time to be effective; thus, hemodynamic support must be guaranteed. In the present case, we observed that full recovery can be obtained up to 21 days of support with extracorporeal membrane oxygenation and adequate immunosuppression.

Relationship between early inflammatory response and clinical evolution of the severe multiorgan failure in mechanical circulatory support-treated patients.

BACKGROUND: The mechanical circulatory support (MCS) is an effective treatment in critically ill patients with end-stage heart failure (ESHF) that, however, may cause a severe multiorgan failure syndrome (MOFS) in these subjects. The impact of altered inflammatory response, associated to MOFS, on clinical evolution of MCS postimplantation patients has not been yet clarified. METHODS: Circulating cytokines, adhesion molecules, and a marker of monocyte activation (neopterin) were determined in 53 MCS-treated patients, at preimplant and until 2 weeks. MOFS was evaluated by total sequential organ failure assessment score (tSOFA). RESULTS: During MCS treatment, 32 patients experienced moderate MOFS (tSOFA < 11; A group), while 21 patients experienced severe MOFS (tSOFA ≥ 11) with favorable (B group) or adverse (n = 13, C group) outcomes. At preimplant, higher values of left ventricular ejection fraction (LVEF) and estimated glomerular filtration rate (eGFR) were the only parameter independently associated with A group. In C group, during the first postoperative week, high levels of interleukin-8 (IL-8) and tumor necrosis factor (TNF)-α, and an increase of neopterin and adhesion molecules, precede tSOFA worsening and exitus. CONCLUSIONS: The MCS patients of C group show an excessive release to IL-8 and TNF-α, and monocyte-endothelial activation after surgery, that might contribute to the unfavourable evolution of severe MOFS.

Relationship between pre-implant interleukin-6 levels, inflammatory response, and early outcome in patients supported by left ventricular assist device: a prospective study.

PURPOSE: The immune response is crucial in the development of multi-organ failure (MOF) and complications in end-stage heart failure patients supported by left ventricular assist device (LVAD). However, at pre-implant, the association between inflammatory state and post-LVAD outcome is not yet clarified. Aim of the study was to assess the relationship among pre-implant levels of immune-related cytokines, postoperative inflammatory response and 3-month outcome in LVAD-patients. METHODS: In 41 patients undergoing LVAD implantation, plasma levels of interleukin (IL)-6, IL-8, crucial for monocyte modulation, and urine neopterin/creatinine ratio (Neo/Cr), marker of monocyte activation, were assessed preoperatively, at 3 days, 1 and 4 weeks post-LVAD. MOF was evaluated by total sequential organ failure assessment (tSOFA) score. Intensive care unit (ICU)-death and/or post-LVAD tSOFA ≥11 was considered as main adverse outcome. Length of ICU-stay, 1 week-tSOFA score, hospitalisation and 3-month survival were considered additional end-points. RESULTS: During ICU-stay, 8 patients died of MOF, while 8 of the survivors experienced severe MOF with postoperative tSOFA score ≥11. Pre-implant level of IL-6 ≥ 8.3 pg/mL was identified as significant marker of discrimination between patients with or without adverse outcome (OR 6.642, 95% CI 1.201-36.509, p = 0.030). Patients were divided according to pre-implant IL-6 cutoff of 8.3 pg/ml in A [3.5 (1.2-6.1) pg/mL] and B [24.6 (16.4-38.0) pg/mL] groups. Among pre-implant variables, only white blood cells count was independently associated with pre-implant IL-6 levels higher than 8.3 pg/ml (OR 1.491, 95% CI 1.004-2.217, p = 0.048). The ICU-stay and hospitalisation resulted longer in B-group (p = 0.001 and p = 0.030, respectively). Postoperatively, 1 week-tSOFA score, IL-8 and Neo/Cr levels were higher in B-group. CONCLUSIONS: LVAD-candidates with elevated pre-implant levels of IL-6 are associated, after intervention, to higher release of monocyte activation related-markers, a clue for the development of MOF, longer clinical course and poor outcome.

[Proposal for updated listing criteria for heart transplantation and indications to implant of left ventricular assist devices]. / Evoluzione delle indicazioni al trapianto cardiaco e all'impianto di dispositivi di assistenza ventricolare sinistra.

Heart transplantation (HTx) is considered to be the gold standard treatment for advanced heart failure (HF) but it is available only for a minority of patients, due to paucity of donor hearts (278 HTx were performed in 2011 in Italy). Patients listed for HTx have a prolonged waiting time (that is about 2.3 years in the 2006-2010 time period in Italy) that is superior compared with patients who receive HTx (median time around 6 months), to underline the presence of an allocation system that prioritizes candidates in critical conditions. Patients listed for HTx have a poor quality of life and their annual mortality is around 8-10%. Another 10-15% of HTx candidates are removed from the waiting list each year because they are no longer suitable for transplantation. On the other hand, continuous-flow left ventricular assist devices (LVADs) have been demonstrated to improve survival and quality of life of patients with advanced/refractory HF. LVAD therapy can represent a valid alternative to HTx, and it is recommended for patients with advanced HF in the recent edition of the European Society of Cardiology guidelines on HF management. In the United States, a larger number of centers compared with European ones started to apply a strategy of LVAD implant for many patients who meet clinical criteria for listing for HTx. Data from our center concerning the last 6 years of LVAD implant (51 implants since 2006) reported a 75.5% survival rate at 1 year. In Italian series, as in our center, current HTx survival is only slightly superior (83% survival rate at 1 year), based on data from the Italian National Transplant Center. We report a proposal for updated listing criteria for HTx and indications for LVAD implant in patients with advanced acute and chronic HF. Criteria for identifying suitable patients for HTx and/or LVAD considering the shortage of donors are discussed.

Direct aortic access for transcatheter self-expanding aortic bioprosthetic valves implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has been designed to treat elderly patients with severe aortic stenosis at high risk for operation; however, these patients are also often affected by severe iliac-femoral arteriopathy that prohibits the transfemoral approach. METHODS: From May 2008 to January 2012, 400 patients were evaluated for TAVI at our center; of these, 141 patients (64 men; mean age 81.3±8 years) with severe symptomatic aortic stenosis and no reasonable surgical option due to excessive risk were eligible for CoreValve (137 patients; Medtronic Inc, MN) or Sapien (Edwards Lifesciences, CA) implantation. Twenty-five patients (all affected by severe peripheral vasculopathy, including five re-do procedures), with a mean The Society of Thoracic Surgeons mortality score 11%±6%, underwent CoreValve implantation directly from the ascending aorta through a right anterior minithoracotomy. This case series was reviewed to evaluate the clinical outcomes of these patients. A combined team of cardiologists, cardiac surgeons with expertise in hybrid procedures, and anesthetists performed all the procedures. RESULTS: In all patients after valve deployment, the mean aortic gradient immediately dropped to 5 mm Hg or less, and the angiographic grade aortic insufficiency was 1 or less in 22 patients. One patient was converted to the transfemoral approach due to an extremely fragile aortic wall, but the patient died of abdominal aorta aneurysm rupture on postoperative day 1. Procedural success was obtained in the remaining 24 patients. A left ventricle tear in 1 patient was successfully surgically treated. Four patients required a permanent pacemaker implantation. Thirty-day mortality was 8% (2 patients). All discharged patients improved their New York Heart Association functional class and functional capacity, and echocardiograms demonstrated good valve performance up to 2 years (mean valve gradient, 9 mm Hg). During follow-up, 1 patient died of cachexia and another of bone marrow aplasia. CONCLUSIONS: TAVI with the direct aortic approach is safe and feasible, offering a new attractive option to treat selected high-risk patients with severe aortic stenosis and peripheral vasculopathy, including those requiring a re-do procedure, and has emerged as a valuable alternative route to transapical access.

Severity of oxidative stress and inflammatory activation in end-stage heart failure patients are unaltered after 1 month of left ventricular mechanical assistance.

This study investigates the impact of early left ventricular (LV)-mechanical unloading on systemic oxidative stress and inflammation in terminal heart failure patients and their impact both on multi organ failure and on intensive care unit (ICU) stay. Circulating levels of urinary 15-isoprostane-F(2t) (8-epi-PGF2(α)) and pro-inflammatory markers [plasma interleukin (IL)-6, IL-8, and urinary neopterin, a monocyte activation index] were analyzed in 20 healthy subjects, 22 stable end-stage heart failure (ESHF) patients and in 23 LV assist device (LVAD) recipients at pre-implant and during first post-LVAD (PL) month. Multi-organ function was evaluated by total Sequential Organ Failure Assessment (tSOFA) score. In LVAD recipients the levels of oxidative-inflammatory markers and tSOFA score were higher compared to other groups. After device implantation 8-epi-PGF2(α) levels were unchanged, while IL-6, and IL-8 levels increased during first week, and at 1month returned to pre-implant values, while neopterin levels increased progressively during LVAD support. The tSOFA score worsened at 1 PL-week with respect to pre-implant value, but improved at 1 PL-month. The tSOFA score related with IL-6 and IL-8 levels, while length of ICU stay related with pre-implant IL-6 levels. These data suggest that hemodynamic instability in terminal HF is associated to worsening of systemic inflammatory and oxidative milieu that do not improve in the early phase of hemodynamic recovery and LV-unloading by LVAD, affecting multi-organ function and length of ICU stay. This data stimulate to evaluate the impact of inflammatory signals on long-term outcome of mechanical circulatory support.

Direct transatrial transcatheter SAPIEN valve implantation through right minithoracotomy in a degenerated mitral bioprosthetic valve.

Transcatheter valve implantation into failing surgical mitral bioprosthetic valves have been reported. This strategy avoids performing high-risk repeat cardiac surgery in elderly patients with multiple comorbidities. All these patients have been treated by a transapical approach. We report a case of failing bioprosthetic mitral valve in an 82-year-old woman successfully treated with a 29-mm Edwards SAPIEN balloon expandable bioprosthesis (Edwards Lifesciences, Irvine, CA) with direct left atrial approach through a right anterior thoracotomy. Our experience demonstrates the technical feasibility and safety of this approach. Therefore, mitral valve-in-surgical valve implantation may be a viable treatment alternative in carefully selected patients.

Association of pre-operative interleukin-6 levels with Interagency Registry for Mechanically Assisted Circulatory Support profiles and intensive care unit stay in left ventricular assist device patients.

BACKGROUND: Inflammatory mechanisms are associated with worse prognosis in end-stage heart failure (ESHF) patients who require left ventricular assist device (LVAD) support. Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles describe patient condition at pre-implant and outcome. This study assessed the relationship among inflammation patterns and INTERMACS profiles in LVAD recipients. METHOD: Thirty ESHF patients undergoing LVAD implantation as bridge to transplant were enrolled. Blood and urine samples were collected pre-operatively and serially up to 2 weeks post-operatively for assessment of inflammatory markers (plasma levels of interleukin [IL]-6, IL-8, IL-10, and osteopontin, a cardiac inflammatory-remodeling marker; and the urine neopterin/creatinine ratio, a monocyte activation marker). Multiorgan function was evaluated by the total sequential organ failure assessment (tSOFA) score. Outcomes of interest were early survival, post-LVAD tSOFA score, and intensive care unit (ICU) length of stay. RESULTS: Fifteen patients had INTERMACS profiles 1 or 2 (Group A), and 15 had profiles 3 or 4 (Group B). At pre-implant, only IL-6 levels and the IL-6/IL-10 ratio were higher in Group A vs B. After LVAD implantation, neopterin/creatinine ratio and IL-8 levels increased more in Group A vs B. Osteopontin levels increased significantly only in Group B. The tSOFA score at 2 weeks post-LVAD and ICU duration were related with pre-implant IL-6 levels. CONCLUSIONS: The INTERMACS profiles reflect the severity of the pre-operative inflammatory activation and the post-implant inflammatory response, affecting post-operative tSOFA score and ICU stay. Therefore, inflammation may contribute to poor outcome in patients with severe INTERMACS profile.

Direct transaortic CoreValve implantation through right minithoracotomy in patients with patent coronary grafts.

Transcatheter aortic valve implantation has rapidly gained credibility as a valuable alternative to conventional aortic valve replacement in patients with severe aortic stenosis, who are otherwise left untreated owing to the perceived high risk of operative mortality. However, these patients are often also affected by severe iliofemoral arteriopathy, rendering the transfemoral approach unfeasible. Different alternative access routes have been used in these patients, such the transapical and the subclavian routes. We report our experience of direct aortic access through a right anterior minithoractomy to implant a self-expanding aortic valve bioprosthesis in two patients who had previously undergone coronary artery bypass graft surgery.

How to remove the CoreValve aortic bioprosthesis in a case of surgical aortic valve replacement.

Transcatheter aortic valve implantation has been introduced as a treatment modality applied to high-risk surgery patients with severe symptomatic aortic stenosis, and it has been demonstrated to be an efficient and safe treatment option. Litzler and colleagues reported a case of a bailout of a transcatheter aortic valve implantation because of severe paravalvular leaks, using a 23-mm Edwards-SAPIEN Valve (Edwards Lifesciences, Irvine, CA), with conversion to conventional surgical aortic valve replacement. The authors reported an easy valve removal despite the impaction of the stent in the cusps of the native valve. Thyregod and colleagues reported a surgical valve replacement in a patient with a dysfunctional CoreValve self-expanding aortic valve bioprosthesis 4 months after implantation.

Transcatheter self-expandable aortic valve implantation after undersized mitral annuloplasty.

No data are available in the literature regarding the effectiveness and safety of transcatheter aortic valve implantation in patients who underwent previous mitral valve ring repair. Concerns exist related to the possible interference between the percutaneous aortic valve and the mitral annuloplasty ring. We report our experience with percutaneous aortic self-expandable valve implantation in a 76-year-old woman affected by severe aortic stenosis, previously operated on for "undersized" mitral annuloplasty repair of severe functional mitral regurgitation in dilated cardiomyopathy. No deformation of the nitinol tubing of the CoreValve device (CoreValve, Inc, Irvine, CA), neither distortion nor malfunction nor change of the conformation of the mitral ring occurred. No change in mitral function and regurgitation was evident at echocardiography monitoring, which was performed during the implant.

Transcatheter aortic valve implantation after heart transplantation.

Conventional cardiac surgical procedures after orthotopic heart transplantation are generally uncommon. We report the case of a 67-year-old man who had severe symptomatic aortic stenosis develop 9 years after heart transplantation. After joint evaluation of the cardiovascular team, transcatheter aortic valve implantation was preferred due to patient medical conditions. The CoreValve prosthesis (Medtronic, Minneapolis, MN) was inserted percutaneously into the femoral artery. At 4 months postoperatively, the patient is asymptomatic in New York Heart Association functional class II. This case report provides evidence that transcatheter aortic valve implantation is safe and suitable for selected patients with severe aortic stenosis and a history of heart transplantation that must improve allograft function.

Veno-arterial extracorporeal membrane oxygenation using Levitronix centrifugal pump as bridge to decision for refractory cardiogenic shock.

OBJECTIVES: Cardiogenic shock still carries a very high mortality. We adopted veno-arterial extracorporeal membrane oxygenation using the Levitronix centrifugal pump (Levitronix LLC, Waltham, Massachusetts) as a first-line treatment of cardiogenic shock in a "bridge to decision" strategy. This article provides our experience of this clinical approach. METHODS: Since 1988, 160 ventricular assist devices have been implanted at our hospital for heart failure. Since 2005, 15 consecutive patients have been treated with veno-arterial extracorporeal membrane oxygenation for refractory cardiogenic shock. Veno-arterial extracorporeal membrane oxygenation has been implanted either centrally or peripherally. RESULTS: Mean age was 44.7 ± 20.0 years (2-78 years). There were 5 women. Veno-arterial extracorporeal membrane oxygenation was implanted peripherally in 8 cases (53.4%) and centrally in the remaining 7 (46.6%). Mean veno-arterial extracorporeal membrane oxygenation duration was 11.5 ± 8.1 days (range, 1-30). No patient experienced any neurologic event or vascular complication at the cannulation site. Twelve patients (80%) were weaned from veno-arterial extracorporeal membrane oxygenation or bridged to either a long-term left ventricular assist device or heart transplantation. Three patients died during veno-arterial extracorporeal membrane oxygenation support secondary to multi-organ failure. Seven patients (46.6%) were discharged from the hospital, with a 100% survival at follow-up. The survivors include 2 patients affected by fulminant myocarditis, who were bridged to recovery, and 5 patients who were bridged to heart transplantation. Survivors were younger than nonsurvivors (mean age, 28.5 vs 58.8 years, respectively). CONCLUSIONS: In our experience, the use of veno-arterial extracorporeal membrane oxygenation as bridge to decision has been effective to promptly restore adequate systemic perfusion, allowing further time to evaluate myocardial recovery or candidacy for ventricular assist device or heart transplantation. Younger patients, with no or mild end-organ injury, had the best outcomes. Peripheral cannulation decreases the surgical trauma and makes emergency implantation possible, even in the intensive care unit.

The trans-subclavian retrograde approach for transcatheter aortic valve replacement: single-center experience.

OBJECTIVE: Aortic valve disease is the most common acquired valvular heart disease in adults. With the increasing elderly population, the proportion of patients with symptomatic aortic stenosis who are unsuitable for conventional surgery is increasing. Transcatheter aortic valve implantation has rapidly gained credibility as a valuable alternative to surgery to treat these patients; however, they often have severe iliac-femoral arteriopathy, which renders the transfemoral approach unusable. We report our experience with the trans-subclavian approach for transcatheter aortic valve implantation using the CoreValve (Medtronic CV Luxembourg S.a.r.l.) in 6 patients. METHODS: In May 2008 to September 2009, 6 patients (mean age of 82 ± 5 years), with symptomatic aortic stenosis and no reasonable surgical option because of excessive risk, were excluded from percutaneous femoral CoreValve implantation because of iliac-femoral arteriopathy. These patients underwent transcatheter aortic valve implantation via the axillary artery. Procedures were performed by a combined team of cardiologists, cardiac surgeons, and anesthetists in the catheterization laboratory. The CoreValve 18F delivery system was introduced via the left subclavian artery in 6 patients, 1 with a patent left internal thoracic to left anterior descending artery graft. RESULTS: Procedural success was obtained in all patients, and the mean aortic gradient decreased 5 mm Hg or less immediately after valve deployment. One patient required implantation of a permanent pacemaker. One patient required a subclavian covered stent implantation to treat a postimplant artery dissection associated with difficult surgical hemostasis. One patient was discharged in good condition but died of pneumonia 40 days after the procedure. All patients were asymptomatic on discharge, with good mid-term prosthesis performance. CONCLUSIONS: Transcatheter aortic valve implantation via a surgical subclavian approach seems safe and feasible, offering a new option to treat select, inoperable, and high-risk patients with severe aortic stenosis and peripheral vasculopathy.

Off-pump coronary revascularization in chronic dialysis-dependent patients: early outcomes at a single institution.

INTRODUCTION: Atherosclerotic vascular disease is the leading cause of morbidity and mortality in patients with end-stage renal disease. Several authors reported that chronic dialytic patients have a high operative risk when submitted to coronary artery bypass grafting (CABG) on cardiopulmonary bypass (CPB) whereas little information exists about off-pump myocardial revascularization in these patients. MATERIAL AND METHODS: Between January 2000 and December 2008, 17 consecutive patients (12 men, mean age of 62.3 +/- 12.3 years) with end-stage renal failure maintained on chronic hemodialysis underwent isolated off-pump CABG at our center. To evaluate this approach we compared the outcomes of off-pump revascularization with those obtained in the same period in 23 patients (20 men, mean age of 64.0 +/- 9.7 years), with the same preoperative features, who underwent conventional CABG on the arrested heart using CPB. RESULTS: Off-pump revascularization in end-stage renal disease patients showed a satisfactory incidence of mortality and morbidity rates. When compared with conventional CPB CABG group, off-pump patients had a lower incidence of bleeding, transfusions, ventilation support time, length of inotropic support and perioperative myocardial infarction. Also ICU and hospital stay and incidence of new-onset atrial fibrillation were lower in off-pump CABG patients. CONCLUSION: In our experience, avoidance of CPB in end-stage renal disease patients was associated with an acceptable incidence of postoperative complications and of major adverse events. Off-pump CABG is a safe and effective method of myocardial revascularization in chronically dialyzed patients that should strongly be taken in consideration when planning the surgical strategy in this selected cohort of patients, although multicentric prospective randomized controlled trials are strongly recommended.