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.

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.

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.

Giant intracranial aneurysms treated with deep hypothermia and circulatory arrest.

The use of deep hypothermic circulatory arrest (DHCA), using groin cannulation with the chest closed (CCDHCA), has improved the surgical treatment of large and giant cerebral aneurysms. Twelve consecutive ASA I-II patients (10 women and 2 men), with a mean age of 35 years (range 14 to 55 y) underwent DHCA for clipping or trapping of their aneurysm (giant, n=10; large, n=2; 42% posterior circulation), under balanced general anesthesia. Intraoperative standard monitors were completed with jugular oxygen saturation, pulmonary artery, pulmonary artery occlusion, central venous pressures, electroencephalography, evoked potentials, and cerebral (subdural), and core temperature. At the start of circulatory arrest, brain temperature was 15.1+/-1.1 degrees C (range 13.5 to 17.5), and core temperature 14.1+/-1.1 degrees C (range 12.7 to 17.0). Mean circulatory arrest time was 26.5+/-13.9 minutes (range 9 to 54) and anesthesia lasted 14+/-1 hours. Only one patient underwent DHCA with standard sternotomy, because of aortic insufficiency. Follow-up (up to 70 mo) revealed no deaths and Glasgow Outcome Scale at 6 months revealed good recovery in 9, moderate disability in 1, and severe disability in 2 patients. Selected patients with large/giant intracranial aneurysms, deemed unapproachable by conventional surgical techniques, were successfully treated using CCDHCA. Mortality rate was 0% and neurologic complications occurred in 25% of the patients.

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.

Echocardiographic approach in a new left ventricular assist device: Impella Recover 100.

Echocardiographic evaluation represents a basic tool for the treatment of patients undergoing ventricular assist device implant. Impella Recover 100 is a new left intraventricular assist device proposed for short-term mechanical circulatory support to be implanted without cardiopulmonary bypass. We report our experience with echocardiographic monitoring on a patient with ischemic cardiomyopathy who underwent Impella Recover 100 implant as a bridge to heart transplant. During the surgical procedure echocardiography had an essential role for anatomic evaluation of the heart and correct intraventricular positioning of the device. Moreover, during the whole period of assistance, echocardiography contributed to assessment of patient-device interaction and to check the device when malfunction was suggested.

Fulminant myocarditis during HIV seroconversion: recovery with temporary left ventricular mechanical assistance.

A 32-year-old male was admitted to our intensive care unit for low cardiac output syndrome. Echocardiography was suggestive of extensive hypokinesia and the ejection fraction was 0.22. Serological tests, including anti-HIV antibodies (ELISA), were negative. The patient was intubated and an intra-aortic balloon pump was inserted. Twenty-four hours after admission a paracorporeal left ventricular assist device (LVAD-MEDOS) was implanted. The left ventricular function showed progressive improvement with normalization of the ejection fraction on day 19. The device was removed on day 20. Before discharge, the patient admitted that he had had unprotected sex with numerous male acquaintances; anti-HIV testing turned positive. The final diagnosis was fulminant myocarditis during HIV seroconversion.

[The use of a "transgastric oblique" transesophageal echocardiographic view to visualize the right ventricular inflow-outflow tract. Clinical applications]. / La proiezione ecocardiografica transesofagea "transgastrica obliqua" per la visualizzazione del tratto di afflusso-efflusso ventricolare destro. Applicazioni nella pratica clinica.

This paper describes the transesophageal echocardiographic "oblique transgastric" view to assess the right ventricular inflow-outflow tract. With this approach it is possible to view the right atrium, tricuspid valve, right ventricular inflow and outflow tracts, and the main pulmonary artery. In 2 clinical cases we evaluated the clinical feasibility of this approach in the diagnostic phase; in 31 patients who underwent cardiac transplantation we examined the advantages of this noninvasive hemodynamic monitoring. An advantage of transgastric view compared with esophageal standard views at 30-60 degrees, is the feasibility to obtain the velocity-time integral of the outflow tract systolic flow to calculate cardiac output by the pulsed Doppler sample volume orientation, which in this view is parallel to pulmonary arterial flow; moreover, it is possible to evaluate pulmonary artery pressures from pulmonary and tricuspid regurgitation.

[Transesophageal and transthoracic echocardiography in the monitoring of a new endovascular left ventricle assist device]. / L'ecocardiografia transesofagea e transtoracica nel monitoraggio di un nuovo sistema endovascolare di assistenza ventricolare sinistra.

We report our experience with echocardiography to guide the placement of a new left ventricular assist device, the Impella Recover 100, and to monitor its functioning. We monitored the introduction of 4 Impella Recover 100 devices in 2 patients by means of the transesophageal approach in the operating room, and thereafter we monitored the functioning of the devices by means of the multisection transthoracic approach in the intensive coronary care unit. The first Impella placement was performed in a patient as a "bridge" to heart transplantation, whereas the other three placements were performed in a patient as "recovery" for acute myocarditis. In all patients transesophageal echocardiography turned out to be a valuable tool to monitor the introduction and the perioperative hemodynamic management of the Impella device. In the early postoperative phase, transthoracic echocardiography allowed us to assess any pump displacement, and optimize biventricular function and adequate inotropic support. In conclusion, transthoracic and transesophageal echocardiography resulted in a valuable method for monitoring the correct placement and functioning of the left ventricular assist device Impella Recover 100.

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.

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.

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.

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.

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 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.