Long-term effects of primary graft dysfunction after heart transplantation.

BACKGROUND: We studied the incidence of primary graft dysfunction (PGD), its impact on in-hospital and follow-up outcomes and searched for independent risk factors. METHODS: During an 18-year period, 508 individuals underwent heart transplantation at our institution. Patients were diagnosed with none, mild, moderate or severe PGD according to ISHLT criteria. RESULTS: Thirty-eight patients (7.5%) met the ISHLT criteria for mild PGD, 92 (18.1%) for moderate PGD and 23 (4.5%) for severe PGD. Patients were classified into none/mild PGD (77.4%) and moderate/severe PGD (22.6%) groups. In-hospital mortality was 12.4% (7.8% for none/mild PGD and 28.7% for moderate/severe PGD; p < .001). Survival at 1, 5, and 15 years was 85.5 ± 1.9% versus 67.2 ± 4.5%, 80 ± 2.2% versus 63.5 ± 4.7%, and 60.4 ± 3.6% versus 45.9 ± 8.4%, respectively (p < .001). Excluding the events occurring during the first month of follow-up, survival was comparable between the two groups (93.1 ± 1.4% vs. 94.7 ± 2.6 at 1 year and 65.6 ± 3.8% vs. 70.4 ± 10.4% at 15 years, respectively; p = .88). Upon multivariate logistic regression analysis preoperative mechanical circulatory support (odds ratio [OR] = 5.86) and preoperative intra-aortic balloon pump (IABP) (OR = 9.58) were independently associated with moderate/severe PGD. CONCLUSIONS: Our results confirm that PGD is associated with poor in-hospital outcome. The poor outcome does not extend beyond the first month of follow-up, with comparable survival between patients with none/mild PGD and moderate/severe PGD in the short and long-term. Mechanical circulatory support and preoperative IABP were found to be independent risk factors for moderate/severe PGD.

Nonoperative Management of a Recurrent Postoperative Inguinal Lymphatic Leak via Negative-Pressure Wound Therapy: A Case Report.

ABSTRACT: Lymphatic leaks are common following common femoral vessel exposure for cardiac surgical procedures. The management of this complication can be difficult and is often uncomfortable for the patient. This case report describes the successful nonoperative treatment of a recurrent lymphatic leak from an inguinal surgical wound via negative-pressure wound therapy. Negative pressure may be considered a minimally invasive, effective, and acceptable way to treat postoperative lymphatic leaks at the groin.

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.

Type 2 diabetes mellitus is associated with faster degeneration of bioprosthetic valve: results from a propensity score-matched Italian multicenter study.

BACKGROUND: The present study was aimed at determining the impact of type 2 diabetes mellitus (DM) on postoperative bioprosthetic structural valve degeneration. METHODS AND RESULTS: Twelve Italian centers participated in the study. Patient data refer to bioprosthetic implantations performed from November 1988 to December 2009, which resulted in 6184 patients (mean age 71.3±5.4 years, 60.1% male) being enrolled. Of these patients, 1731 (27.9%) had type 2 DM. The propensity score-matching algorithm successfully matched 1113 patients with type 2 DM with the same number of no-DM patients. The postmatching standard differences were less than 0.1 for each of the covariates, and 64.2% of DM patients were matched. The early (30 days) mortality rate was 7.8% (n=87) versus 2.9% (n=33) in patients with or without type 2 DM (P<0.001), respectively. Seven-year freedom from valve deterioration was significantly lower in patients with DM (73.2% [95% confidence interval, 61.6-85.5] versus 95.4% [95% confidence interval, 83.9-100], P<0.001). In Cox regression models with robust SEs that accounted for the clustering of matched pairs, DM was the strongest predictor of structural valve degeneration (hazard ratio 2.39 [95% confidence interval 2.28-3.52]). When we allowed for interaction between type 2 DM and other key risk factors, DM remained a significant predictor beyond any potentially associated variable. CONCLUSIONS: Patients with type 2 DM undergoing bioprosthetic valve implantation are at high risk of early and long-term mortality, as well as of structural valve degeneration.

Impact of normalization strategy on cardiac expression of pro-inflammatory cytokines: evaluation of reference genes in different human myocardial regions after Left Ventricular Assist Device support.

OBJECTIVE: New device therapies have expanded the strategies for treating heart failure (HF) patients. Unloading of the heart with a left ventricular assist device (LVAD) can lead to the reversal of many remodeling changes whose underlying mechanisms are not yet completely known. Molecular analysis might play a role in obtaining further insight into the regulatory mechanisms of this process. A critical step in an RT-PCR study is the selection of reference genes for data normalization. This study aimed to determine an optimal combination of stably expressed reference genes in different regions of the human heart in order to study the effects of LVAD implants on cardiac remodeling, and in particular to check their reliability on the evaluation of pro-inflammatory cytokine expression. DESIGN AND METHODS: We validated nine of the most commonly used reference genes in human myocardium samples obtained at heart transplantation from patients with LVAD implant (n=30 from a total of six patients) and from heart transplant (HT from a total of seven patients) recipients as controls (n=35). Samples from both left (LV) and right (RV) ventricles were analyzed. The normalization strategy was tested by analyzing mRNA expression of IL-6, IL-8 and TNF-α, whose protein levels were measured by immunometric assay. RESULTS: The most stable gene combinations changed according to the experimental groups (the LVAD and HT groups and the different myocardial regions). Considering all the cardiac samples as a whole, the three most stably expressed genes were PPIA, RPL13A, and YWHAZ (M=0.70). Using the best normalization strategy, a significant increase in IL-6, IL-8 mRNA expression was observed in LVAD samples compared to HT (p<0.0001). Similar results were obtained by protein analysis. CONCLUSIONS: Our results underline the importance of always selecting reference genes for the specific system studied. The most appropriate normalization strategy is of pivotal importance for understanding the molecular mechanisms associated with the pathophysiology of HF, such as inflammation.

Histological findings following use of CoSeal in a patient with a left ventricular assist device.

Adhesions are a formidable challenge in patients undergoing reoperative cardiac surgery, particularly in those supported by an intracorporeal left ventricular assist device (LVAD) and undergoing heart transplantation. This report describes the pathological findings following the clinical use of a surgical sealant (CoSeal, Baxter Healthcare, Fremont, CA), in a patient who underwent LVAD implantation. On the treated surfaces, a minimal amount of adhesions were observed, whereas in untreated surfaces adhesions were present.

The role of the minimally invasive beating heart technique in reoperative valve surgery.

OBJECTIVE: We reviewed our experience to assess potential advantages of minimally invasive surgery without aortic clamping over conventional median sternotomy and cardioplegic arrest during reoperative valve surgery. METHODS: From August 2008 to August 2010, 22 reoperative valve procedures were performed through a minimally invasive approach without aortic cross-clamping [no-clamp group (NCG)]. Postoperative results were compared to a matched population in terms of sex, age, and type of surgery, and operated through median sternotomy with aortic cross-clamping and cardioplegic arrest [clamp group (CG)]. RESULTS: We performed 17 mitral valve replacements (MVRs), one mitral valve repair, one MVR associated to a tricuspid plasty (TVP), and three isolated TVP in both groups. Cardiopulmonary bypass (CPB) time was 166 and 163 minutes in NCG and CG, respectively. Intra-aortic balloon pump was necessary in two (NCG) and three (CG) patients. Two patients died in both groups from multiorgan failure. Biochemical analysis showed no significant differences in perioperative lactate or creatine kinase-MB values. CONCLUSIONS: Redo valve surgery with an unclamped aorta is feasible, effective, and at least as safe as surgery using cardioplegic arrest. There was, however, no difference in biochemical or clinical outcomes from conventional surgery using aortic clamping and cardioplegic techniques.

Mechanical Hemolysis Complicating Transcatheter Interventions for Valvular Heart Disease: JACC State-of-the-Art Review.

Mechanical intravascular hemolysis is frequently observed following procedures on heart valves and uncommonly observed in native valvular disease. In most cases, its severity is mild. Nevertheless, it can be clinically significant and even life threatening, requiring multiple blood transfusions and renal replacement therapy. This paper reviews the current knowledge on mechanical intravascular hemolysis in valvular disease, before and after correction, focusing on pathophysiology, approach to diagnosis, and impact of other hematological conditions on the resultant anemia. The importance of a multidisciplinary management is underscored. Laboratory data are provided about subclinical hemolysis that is commonly observed following the implantation of surgical and transcatheter valve prostheses and devices. Finally, clinical scenarios are reviewed and current medical and surgical treatments are discussed, including alternative options for inoperable patients.

Cavernous hemangioma replacing the septal leaflet of the tricuspid valve.

Heart valve hemangioma is a rare finding. Here, we report a case of a hemangioma completely replacing the septal leaflet of the tricuspid valve. Preoperative imaging studies and operative anatomy are described.

Prevention of limb ischemia and edema during peripheral venoarterial extracorporeal membrane oxygenation in adults.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a mechanical circulatory support indicated for the advanced treatment of refractory heart failure. The cannulation of the femoral vessels may be complicated by distal limb ischemia by arterial hypoperfusion and severe edema by venous obstruction. We describe a modified cannulation technique in order to prevent ischemia and edema of the inferior limb during VA-ECMO.

Technique to prevent inadvertent paramedian sternotomy.

Previous reports documented the relationship between inadvertent paramedian sternotomy and postoperative sternal instability and dehiscence.We describe a modification of the technique of median sternotomy in order to prevent inadvertent paramedian sternotomy and related wound complications.

Focus on Very Late Hepatocellular Carcinoma Recurring After Liver Transplantation: A Case Report and Literature Review.

Hepatocellular carcinoma (HCC) recurring after liver transplantation (LT) is a major clinical concern, occurring in up to 20% and being the most frequent cause of death in this setting. Usually recurrence occurs within the first 2 years, whereas late and very late recurrences are rare. We report a 71-year-old woman with HCC recurrence after 25 years from LT, an event never reported before. Diagnosis was achieved with a progressive increase of alpha-fetoprotein (AFP) followed by a computed tomography scan, showing a mediastinal, upper diaphragmatic, right paracaval mass of 5 cm in size. The lesion was treated with a surgical approach involving a multidisciplinary team including hepatobiliary, thoracic, and cardiovascular surgeons. A sternotomy and mass removal was performed without the need of an extracorporeal bypass. A complete resection of the tumor was achieved, with a drop in AFP and without signs of recurrence after 1-year follow up. In conclusion, the possibility of late HCC recurrences after LT, despite being rare, underlines the need of a standardized, cost-benefit, optimal strategy of a long-term surveillance. From a surgical point of view, our case is unusual for the site and the character of the lesion, and for the absence of the need of an extracorporeal bypass during the operation.

Safety of centrifugal left ventricular assist device in patients previously treated with MitraClip system.

INTRODUCTION: No data regarding the safety of continuous-flow left ventricular assist device (CF-LVAD) implantation in patients with previous MitraClip have been reported. Thus, it remains unknown whether an initial treatment strategy with MitraClip therapy might complicate future heart failure management in patients who are also considered for CF-LVAD. METHODS: We retrospectively identified 6 patients (median age of 62 years; 2 women) who had been treated with MitraClip, that were eventually implanted with a CF-LVAD (all Heartware HVAD) in 3 hospitals between 2013 and 2018. RESULTS: Patients were treated in 4 cases with 2 clips, and in 2 cases with 1 clip. Median time from MitraClip implantation to CF-LVAD implant was 282 days (interquartile range 67 to 493), and median time on CF-LVAD support was 401 days (interquartile range 105 to 492 days). Two patients underwent a heart transplant, 3 patients died on support, and 1 is alive on support. In all cases, there was a reduction of functional mitral regurgitation without MitraClip-related complications. CONCLUSIONS: Based on this small case series, implantation of a CF-LVAD appears safe in patients with a previously positioned MitraClip system, at least, with 1 or 2 clips in place, with no need for additional mitral valve surgery.

HeartWare-HVAD for end-stage heart failure: a review of clinical experiences with ≥50 patients.

INTRODUCTION: Despite the improvements in medical and surgical treatments, the incidence of end-stage heart failure (ESHF) continues to increase. Different mechanical systems have been adopted to support failing left ventricles. Among continuous-flow devices, the HeartWare-HVAD was the first to use a centrifugal pump rather than an axial one. Areas covered: In this review article, we provide an overview of the HeartWare-HVAD as a ventricular assist device for ESHF, discussing indications, echocardiographic assessment, surgical techniques, outcomes, concerns and controversies. Scientific literature was reviewed with a MEDLINE search strategy combining 'HeartWare' or 'HVAD' with 'heart failure'. A total of 263 papers were found using the reported search. From these, 16 were identified to provide the best evidence on the subject reporting outcomes in ≥50 patients. Expert commentary: HeartWare-HVAD is a minute device that provides full circulatory support in patients with ESHF. Its main indication remains bridge to heart transplantation (HTx). Median sternotomy is the preferred technique of implantation although less invasive procedures have been described. Early outcomes are satisfactory. Nevertheless, some fearing complications still occur during the mid- and long-term follow-up. Further technical developments and optimal medical management will guarantee better outcomes.

Mitral valve endocarditis due to Abiotrophia defectiva in a 14th week pregnant woman.

Infective endocarditis during pregnancy carries a high mortality risk, both for the mother and for the foetus and requires a multidisciplinary team in the management of complicated cases. We report our experience with a 39-year old patient, affected by an acute active mitral endocarditis due to Abiotrophia defectiva at the 14th gestational week, strongly motivated to continue the pregnancy. Our patient successfully underwent mitral valve replacement with a normothermic high-flow cardiopulmonary bypass under continuous intraoperative foetal monitoring. Caesarean section occurred at the 38th gestational week. The delivery was uneventful and both the mother and child are doing well at the 16-month follow-up.

Direct Flow valve-in-valve implantation in a degenerated mitral bioprosthesis.

AIMS: Mitral valve reoperations due to failing bioprostheses, in patients affected by multiple comorbidities, are associated with high morbidity and mortality. Transcatheter techniques may evolve as complementary approaches to surgery in these patients at high risk for surgery. METHODS AND RESULTS: We describe a case of Direct Flow 25 mm transcatheter valve implantation as valve-in-valve in a degenerated mitral bioprosthesis through a transapical approach in a 63-year-old man affected by dilated cardiomyopathy. The patient was affected by Carpentier-Edwards 29 mm severe regurgitation. The 25 mm Direct Flow bioprosthesis was advanced through the mitral bioprosthesis into the left atrium and then positioned using the three independent positioning wires. Transoesophageal echocardiography evidenced normal Direct Flow function with no paravalvular regurgitation and a low transmitral gradient of 4 mmHg. CONCLUSIONS: Our successful experience, characterised by a Heart Team approach and multidisciplinary patient care, demonstrated the technical feasibility and procedural safety of Direct Flow valve-in-valve mitral implantation.

A prospective comparison of mid-term outcomes in patients treated with heart transplantation with advanced age donors versus left ventricular assist device implantation.

OBJECTIVES: In Europe, the age of heart donors is constantly increasing. Ageing of heart donors limits the probability of success of heart transplantation (HTx). The aim of this study is to compare the outcome of patients with advanced heart failure (HF) treated with a continuous-flow left ventricular assist device (CF-LVAD) with indication as bridge to transplantation (BTT) or bridge to candidacy (BTC) versus recipients of HTx with the donor's age above 55 years (HTx with donors >55 years). METHODS: we prospectively evaluated 301 consecutive patients with advanced HF treated with a CF-LVAD (n = 83) or HTx without prior bridging (n = 218) in our hospital from January 2006 to January 2015. We compared the outcome of CF-LVAD-BTT (n = 37) versus HTx with donors >55 years (n = 45) and the outcome of CF-LVAD-BTT plus BTC (n = 62) versus HTx with donors >55 years at the 1- and 2-year follow-up. Survival was evaluated according to the first operation. RESULTS: The perioperative (30-day) mortality rate was 0% in the LVAD-BTT group vs 20% (n = 9) in the HTx group with donors >55 years (P = 0.003). Perioperative mortality occurred in 5% of the LVAD-BTT/BTC patients (n = 3) and in 20% of the HTx with donors >55 year group (P = 0.026). Kaplan-Meier curves estimated a 2-year survival rate of 94.6% in CF-LVAD-BTT vs 68.9% in HTx with donors >55 years [age- and sex-adjusted hazard ratio (HR) 0.25; 95% confidence interval (CI) 0.08-0.81; P = 0.02 in favour of CF-LVAD]. Considering the post-HTx outcome, a trend in favour of CF-LVAD-BTT was also observed (age- and sex-adjusted HR 0.45; 95% CI 0.17-1.16; P = 0.09 in favour of CF-LVAD), whereas CF-LVAD-BTT/BTC showed a similar survival at 2 years compared with HTx with donors >55 years, both censoring the follow-up at the time of HTx and considering the post-HTx outcome. CONCLUSIONS: Early and mid-term outcomes of patients treated with a CF-LVAD with BTT indication seem better than HTx with old donors. It must be emphasized that up to 19% of patients in the CF-LVAD/BTT group underwent transplantation in an urgent condition due to complications related to the LVAD. At the 2-year follow-up, CF-LVAD with BTT and BTC indications have similar outcome than HTx using old heart donors. These results must be confirmed in a larger and multicentre population and extending the follow-up.