In-depth characterization of pulmonary arterial hypertension in mixed connective tissue disease: a French national multicentre study.

OBJECTIVE: Pulmonary arterial hypertension (PAH) is a leading cause of death in MCTD. We aimed to describe PAH in well-characterized MCTD patients. METHODS: MCTD patients enrolled in the French Pulmonary Hypertension Registry with a PAH diagnosis confirmed by right heart catheterization were included in the study and compared with matched controls: MCTD patients without PAH, SLE patients with PAH and SSc patients with PAH. Survival rates were estimated by the Kaplan-Meier method and risk factors for PAH in MCTD patients and risk factors for mortality in MCTD-PAH were sought using multivariate analyses. RESULTS: Thirty-six patients with MCTD-PAH were included in the study. Comparison with MCTD patients without PAH and multivariate analysis revealed that pericarditis, polyarthritis, thrombocytopenia, interstitial lung disease (ILD) and anti-Sm antibodies were independent predictive factors of PAH/PH in MCTD. Estimated survival rates at 1, 5 and 10 years following PAH diagnosis were 83%, 67% and 56%, respectively. MCTD-PAH presentation and survival did not differ from SLE-PAH and SSc-PAH. Multivariate analysis revealed that tobacco exposure was an independent factor predictive of mortality in MCTD-PAH. CONCLUSION: PAH is a rare and severe complication of MCTD associated with a 56% 10-year survival. We identified ILD, pericarditis, thrombocytopenia and anti-Sm antibodies as risk factors for PAH in MCTD and tobacco exposure as a predictor of mortality in MCTD-PAH.

Blood, Cellular, and Tissular Calcineurin Inhibitors Pharmacokinetic-Pharmacodynamic Relationship in Heart Transplant Recipients: The INTRACAR Study.

BACKGROUND: After heart transplantation, calcineurin inhibitors (CNI) (cyclosporin A and tacrolimus) are key immunosuppressive drugs to prevent graft rejection. Whole-blood concentration (C blood )-guided therapeutic drug monitoring (TDM) is systematically performed to improve graft outcomes. However, some patients will still experience graft rejection and/or adverse events despite CNI C blood within the therapeutic range. Other pharmacokinetic parameters, such as the intragraft, or intracellular concentration at the CNI site of action could refine their TDM. Nonetheless, these remain to be explored. The objective of the INTRACAR study was to describe the relationship between whole blood, intragraft, and intracellular CNI concentrations as well as their efficacy in heart transplant recipients (HTR). METHODS: In a cohort of HTR, protocol endomyocardial biopsies (EMB) were collected to assess rejection by anatomopathological analysis. Part of the EMB was used to measure the intragraft concentrations of CNI (C EMB ). C blood and the concentration inside peripheral blood mononuclear cells, (C PBMC ), a cellular fraction enriched with lymphocytes, were also monitored. Concentrations in the 3 matrices were compared between patients with and without biopsy-proven acute rejection (BPAR). RESULTS: Thirty-four HTR were included, representing nearly 100 pharmacokinetic (PK) samples for each CNI. C blood , C EMB , and C PBMC correlated for both CNI. BPAR was observed in 74 biopsies (39.6%) from 26 patients (76.5%), all except one was of low grade. None of the PK parameters (C blood , C EMB , C PBMC , C EMB/blood , and C PBMC/blood ) was associated with BPAR. CONCLUSIONS: In this cohort of well-immunosuppressed patients, no association was observed for any of the PK parameters, including C blood , with the occurrence of BPAR. However, a trend was noticed for the C EMB and C EMB/blood of cyclosporin A. Further studies in higher-risk patients may help optimize the use of C EMB and C PBMC for CNI TDM in HTR.

Durability of Mitral Valve Replacement With a Third-generation Bioprosthesis.

BACKGROUND: Our aim was to evaluate the durability of a third-generation porcine bioprosthesis (Epic porcine xenograft; Abbott Cardiovascular Inc, St Paul, MN) in the mitral position, according to patients' age at surgery. METHODS: Four hundred eighty-two mitral valve replacements using the Epic valve at a single center were included (2009-2018). Perioperative and early postoperative data were prospectively collected. A systematic follow-up was performed (99% complete, 1609.5 patient-years; average, 3.8 ± 2.5). Standardized definitions of valve-related events were adopted. Mean patient age at mitral valve replacement was 68.1 ± 10.4 years. RESULTS: Operative mortality was 9.3%. There were 5 early valve-related reoperations, mainly due to recurrent infectious endocarditis. Global survival at 8.8 years was 69.5% ± 5%. Nine structural valve deterioration (SVD) events occurred during follow-up (3 receiving reoperations, 4 transcatheter mitral valve replacement valve-in-valve, and 2 medical treatment only). The freedom from SVD at 5 and 10 years was 97.4% ± 1.2% and 89.6% ± 4.4% (actuarial) and 97.8% ± 1% and 91.9% ± 3.3%, respectively (competing risks). After stratification into subgroups by age at surgery (≤59 years, 50.8%; 60-69, 32.8%; ≥70, 16.4%) there was no significant intergroup difference in freedom from SVD (log-rank P = .24). The overall freedom from any reintervention for SVD at 10 years was 90.5% ± 4.4% (actuarial) and 92.7% ± 3.3% (competing risks), with no intergroup difference (log-rank P = .14). The freedom from any valve-related complication at 8.4 years was 83.2% ± 4.5% (actuarial). CONCLUSIONS: The Epic bioprosthesis shows good durability at 5 to 10 years in the mitral position.

Pulmonary Hypertension in Patients with Common Variable Immunodeficiency.

PURPOSE: Common variable immunodeficiency (CVID) is known to cause infectious, inflammatory, and autoimmune manifestations. Pulmonary hypertension (PH) is an unusual complication of CVID with largely unknown characteristics and mechanisms. METHODS: We report the clinical, functional, hemodynamics, radiologic and histologic characteristics, and outcomes of CVID-associated PH patients from the French PH Network. RESULTS: Ten patients were identified. The median (range) age at CVID diagnosis was 36.5 (4-49) years and the median delay between CVID and PH diagnosis was 12 (0-30) years. CVID-associated PH affected predominantly women (female-to-male ratio 9:1). Most patients were New York Heart Association functional class III with a severe hemodynamic profile and frequent portal hypertension (n = 6). Pulmonary function tests were almost normal in 70% of patients and showed a mild restrictive syndrome in 30% of patients while the diffusing capacity for carbon monoxide was decreased in all but one patient. High-resolution computed tomography found enlarged mediastinal nodes, mild interstitial infiltration with reticulations and nodules. Two patients had a CIVD-interstitial lung disease, and one presented with bronchiectasis. Pathologic assessment of lymph nodes performed in 5 patients revealed the presence of granulomas (n = 5) and follicular lymphoid hyperplasia (n = 3). At last follow-up (median 24.5 months), 9 patients were alive, and one patient died of Hodgkin disease. CONCLUSION: PH is a possible complication of CVID whose pathophysiological mechanisms, while still unclear, would be due to the inflammatory nature of CVID. CVID-associated PH presents as precapillary PH with multiple possible causes, acting in concert in some patients: a portal hypertension, a pulmonary vascular remodeling, sometimes a pulmonary parenchymal involvement and occasionally an extrinsic compression by mediastinal lymphadenopathies, which would be consistent with its classification in group 5 of the current PH classification.

Is Rifampin Use Associated With Better Outcome in Staphylococcal Prosthetic Valve Endocarditis? A Multicenter Retrospective Study.

BACKGROUND: International guidelines recommend rifampin-based combinations for staphylococcal prosthetic valve endocarditis (PVE). However, no robust clinical data support this recommendation, and rifampin tolerability is an issue. We aimed to evaluate the impact of rifampin for the treatment of staphylococcal PVE. METHODS: An observational retrospective cohort study of all adults with staphylococcal PVE (modified Duke criteria) was conducted in 3 referral centers for endocarditis, during years 2000-2018. Primary outcome measurement was 1-year mortality. RESULTS: We enrolled 180 patients with PVE due to Staphylococcus aureus (n = 114, 63.3%), or coagulase-negative staphylococci (n = 66, 36.7%), on bioprosthesis (n = 111, 61.7%), mechanical valve (n = 67, 37.2%), or both (n = 2). There were 132 males (73.3%), and mean age was 70.4 ± 12.4 years. Valvular surgery was performed in 51/180 (28.3%) cases. Despite all isolates were susceptible to rifampin, only 101 (56.1%) were treated with rifampin, for a median duration of 33.0 days, whereas 79 (43.9%) received no rifampin. Baseline characteristics were similar in both groups. One-year mortality was, respectively, 37.6% (38/101), and 31.6% (25/79), in patients treated with, or without, rifampin (P = .62). Relapse rates were 5.9% (6/101), and 8.9% (7/79), P = .65. Patients treated with rifampin had longer hospital length-of-stay: 42.3 ± 18.6 vs 31.3 ± 14.0 days (P < .0001). On multivariate analysis, only cerebral emboli (odds ratio [OR] 2.95, 95% confidence interval [CI], 1.30-6.70, P = .009), definite endocarditis (OR 7.15, 95% CI, 1.47-34.77, P = .018), and methicillin-resistant S. aureus (OR 6.04, 95% CI, 1.34-27.26, P = .019), were associated with 1-year mortality. CONCLUSIONS: A large proportion (43.9%) of staphylococcal PVE received no rifampin. One-year survival and relapse rates were similar in patients treated with or without rifampin.

Relation of Body Mass Index to Outcomes in Patients With Heart Failure Implanted With Left Ventricular Assist Devices.

We aimed at characterizing the impact of low and high body mass index (BMI) on outcomes after left-ventricular assist device (LVAD) surgery and define the predictors of mortality in patients with abnormal BMI (low/high). This study was conducted in 19 centers from 2006 to 2016. Patients were divided based on their baseline BMI into 3 groups of BMI: low (BMI ≤18.5 kg/m²); normal (BMI = 18.5 to 24.99 kg/m²) and high (BMI ≥25 kg/m²) (including overweight (BMI = 25 to 29.99 kg/m²), and obesity (BMI ≥30 Kg/m²)). Among 652 patients, 29 (4.4%), 279 (42.8%) and 344 (52.8%) had a low-, normal-, and high BMI, respectively. Patients with high BMI were significantly more likely men, with more co-morbidities and more history of ventricular/supra-ventricular arrhythmias before LVAD implantation. Patients with abnormal BMI had significantly lower survival than those with normal BMI. Notably, those with low BMI experienced the worst survival whereas overweight or obese patients had similar survival. Four predictors of mortality for LVAD candidates with abnormal BMI were defined: total bilirubin ≥16 µmol/L before LVAD, hypertension, destination therapy, and cardiac surgery with LVAD. Depending on the number of predictor per patients, those with abnormal BMI may be divided in 3 groups of 1-year mortality risk, i.e., low (0 to 1 predictor: 29% and 31%), intermediate (2 to 3 predictors, 51% and 52%, respectively), and high (4 predictors: 83%). In conclusion, LVAD recipients with abnormal BMI experience lower survival, especially underweight patients. Four predictors of mortality have been identified for LVAD population with abnormal BMI, differentiating those a low-, intermediate-, and high risks of death.

Phenotype and Outcomes of Pulmonary Hypertension Associated with Neurofibromatosis Type 1.

Rationale: Pulmonary hypertension (PH) associated with neurofibromatosis type 1 (NF1) is a rare and largely unknown complication of NF1.Objectives: To describe characteristics and outcomes of PH-NF1.Methods: We reported the clinical, functional, radiologic, histologic, and hemodynamic characteristics, response to pulmonary arterial hypertension (PAH)-approved drugs, and transplant-free survival of patients with PH-NF1 from the French PH registry.Measurements and Main Results: We identified 49 PH-NF1 cases, characterized by a female/male ratio of 3.9 and a median (minimum-maximum) age at diagnosis of 62 (18-82) years. At diagnosis, 92% were in New York Heart Association functional class III or IV. The 6-minute-walk distance was 211 (0-460) m. Pulmonary function tests showed low DlCO (30% [12-79%]) and severe hypoxemia (PaO2 56 [38-99] mm Hg). Right heart catheterization showed severe precapillary PH with a mean pulmonary artery pressure of 45 (10) mm Hg and a pulmonary vascular resistance of 10.7 (4.2) Wood units. High-resolution computed tomography images revealed cysts (76%), ground-glass opacities (73%), emphysema (49%), and reticulations (39%). Forty patients received PAH-approved drugs with a significant improvement in functional class and hemodynamic parameters. Transplant-free survival at 1, 3, and 5 years was 87%, 54%, and 42%, respectively, and four patients were transplanted. Pathologic assessment showed nonspecific interstitial pneumonia and major pulmonary vascular remodeling.Conclusions: PH-NF1 is characterized by a female predominance, a low DlCO, and severe functional and hemodynamic impairment. Despite a potential benefit of PAH treatment, prognosis remains poor, and double-lung transplantation is an option for eligible patients.

Outcomes of Left Ventricular Assist Device Implantation in Patients With Uncommon Etiology Cardiomyopathy.

The impact of uncommon etiology cardiomyopathies on Left-ventricular assist device (LVAD)-recipient outcomes is not very well known. This study aimed to characterize patients with uncommon cardiomyopathy etiologies and examine the outcomes between uncommon and ischemic/idiopathic dilated cardiomyopathy. This observational study was conducted in 19 centers between 2006 and 2016. Baseline characteristics and outcomes of patients with uncommon etiology were compared to patients with idiopathic dilated/ischemic cardiomyopathies. Among 652 LVAD-recipients included, a total of 590 (90.5%) patients were classified as ischemic/idiopathic and 62 (9.5%) patients were classified in the "uncommon etiologies" group. Main uncommon etiologies were: hypertrophic (n = 12(19%)); cancer therapeutics-related cardiac dysfunction (CTRCD) (n = 12(19%)); myocarditis (n = 11(18%)); valvulopathy (n = 9(15%)) and others (n = 18(29%)). Patients with uncommon etiologies were significantly younger with more female and presented less co-morbidities. Additionally, patients with uncommon cardiomyopathies were less implanted as destination therapy compared with ischemic/idiopathic group (29% vs 38.8%). During a follow-up period of 9.1 months, both groups experienced similar survival. However, subgroup of hypertrophic/valvular cardiomyopathies and CTRCD had significantly higher mortality compared to the ischemic/idiopathic or myocarditis/others cardiomyopathies. Conversely, patients with myocarditis/others etiologies experienced a better survival. Indeed, the 12-months survival in the myocarditis/others; ischemic/idiopathic and hypertrophic/CTRCD/valvulopathy group were 77%; 65%, and 46% respectively. In conclusion, LVAD-recipients with hypertrophic cardiomyopathy, valvular heart disease and CTRCD experienced the higher mortality rate.

Portopulmonary hypertension in the current era of pulmonary hypertension management.

BACKGROUND & AIMS: Long-term outcomes in portopulmonary hypertension (PoPH) are poorly studied in the current era of pulmonary hypertension management. We analysed the effect of pulmonary arterial hypertension (PAH)-targeted therapies, survival and predictors of death in a large contemporary cohort of patients with PoPH. METHODS: Data from patients with PoPH consecutively enrolled in the French Pulmonary Hypertension Registry between 2007 and 2017 were collected. The effect of initial treatment strategies on functional class, exercise capacity and cardiopulmonary haemodynamics were analysed. Survival and its association with PAH- and hepatic-related characteristics were also examined. RESULTS: Six hundred and thirty-seven patients (mean age 55 ± 10 years; 58% male) were included. Fifty-seven percent had mild cirrhosis, i.e. Child-Pugh stage A. The median model for end-stage liver disease (MELD) score was 11 (IQR 9-15). Most patients (n = 474; 74%) were initiated on monotherapy, either with a phosphodiesterase-5 inhibitor (n = 336) or with an endothelin-receptor antagonist (n = 128); 95 (15%) were initiated on double oral combination therapy and 5 (1%) on triple therapy. After a median treatment time of 4.5 months, there were significant improvements in functional class (p <0.001), 6-minute walk distance (6MWD) (p <0.0001) and pulmonary vascular resistance (p <0.0001). Overall survival rates were 84%, 69% and 51% at 1, 3 and 5 years, respectively. Baseline 6MWD, sex, age and MELD score or Child-Pugh stage were identified as independent prognostic factors. Survival from PoPH diagnosis was significantly better in the subgroup of patients who underwent liver transplantation (92%, 83% and 81% at 1, 3 and 5 years, respectively). CONCLUSION: Survival of patients with PoPH is strongly associated with the severity of liver disease. Patients who underwent liver transplantation had the best long-term outcomes. LAY SUMMARY: Portopulmonary hypertension is defined by the presence of pulmonary arterial hypertension in the context of chronic liver disease and is characterized by progressive shortness of breath and exercise limitation. The presence of severe pulmonary arterial hypertension in liver transplant candidates represents a contraindication for such a surgery; however, treatments targeting pulmonary arterial hypertension are efficacious, allowing for safe transplantation and conferring good survival outcomes in those who undergo liver transplantation.

Phenotype and outcome of pulmonary arterial hypertension patients carrying a TBX4 mutation.

INTRODUCTION: TBX4 mutation causes small patella syndrome (SPS) and/or pulmonary arterial hypertension (PAH). The characteristics and outcomes of PAH associated with TBX4 mutations are largely unknown. METHODS: We report the clinical, functional, radiologic, histologic and haemodynamic characteristics and outcomes of heritable PAH patients carrying a TBX4 mutation from the French pulmonary hypertension (PH) network. RESULTS: 20 patients were identified in 17 families. They were characterised by a median age at diagnosis of 29 years (0-76 years) and a female to male ratio of three. Most of the patients (70%) were in New York Heart Association (NYHA) functional class III or IV with a severe haemodynamic impairment (median pulmonary vascular resistance (PVR) of 13.6 (6.2-41.8) Wood units). Skeletal signs of SPS were present in 80% of cases. Half of the patients had mild restrictive or obstructive limitation and diffusing capacity of the lung for carbon monoxide (D LCO) was decreased in all patients. High-resolution computed tomography (HRCT) showed bronchial abnormalities, peri-bronchial cysts, mosaic distribution and mediastinal lymphadenopathies. PAH therapy was associated with significant clinical improvement. At follow-up (median 76 months), two patients had died and two had undergone lung transplantation. One-year, three-year and five-year event-free survival rates were 100%, 94% and 83%, respectively. Histologic examination of explanted lungs revealed alveolar growth abnormalities, major pulmonary vascular remodelling similar to that observed in idiopathic pulmonary arterial hypertension (IPAH) and accumulation of cholesterol crystals within the lung parenchyma. CONCLUSION: PAH due to TBX4 mutations may occur with or without skeletal abnormalities across a broad age range from birth to late adulthood. PAH is usually severe and associated with bronchial and parenchymal abnormalities.

Long-term follow-up of bioprosthetic aortic valve replacement in patients aged ≤60 years.

OBJECTIVE: To address the long-term durability of bioprostheses used for aortic valve replacement (AVR) in adult patients aged ≤60 years at the time of surgery. METHODS: Through a retrospective review of a prospectively collected database, we identified 416 bioprosthetic AVRs performed between 1977 and 2013. A prospective follow-up of valve-related and non-valve-related events was performed. RESULTS: Follow-up was 98.5% complete (2423.1 patient-years; average, 6 ± 5.5 years). At 15 years, overall survival was 62.1 ± 4.4%; freedom from valve-related death was 97.1 ± 1.6%. There were 68 SVD events (11.9 ± 28.8 years after surgery). Freedom from SVD at 15 years was 48.7 ± 5.5% for Kaplan-Meier analysis and 61.4 ± 4.3% for competing-risks analysis. After stratification into age subgroups (<40 years, ≥40 and <50 years, and ≥50 and ≤60 years), we observed no significant difference in freedom from SVD (P = .50). The average delay to SVD was not statistically different among subgroups (P = .30). There were 57 reoperations for SVD (11.8 ± 5.2 years after implantation). The 15 year freedom from reoperation for SVD was 55.4 ± 5.6% by Kaplan-Meier analysis and 67.1 ± 4.2% by competing-risks analysis. After stratification by age, freedom from reoperation for SVD was comparable (P = .13). Freedom from any valve-related complication or death was 42 ± 5% by Kaplan-Meier analysis and 54.4 ± 4.1% by competing-risks analysis. CONCLUSIONS: The lifetime risk of SVD is considerable in patients aged ≤60 years at the time of bioprosthesis implantation. Nonetheless, durability remains consistent during the first decade; additional data are required for the second decade. Patients' information is pivotal for valve choice (competing-risks method).

Heart transplantation in selected patients aged 60 years and older: a two-decade retrospective and multicentre analysis.

OBJECTIVES: This study analysed survival and long-term outcomes of heart transplantation in patients aged 60 years and older. We also analysed the impact of a national graft allocation priority [Super Emergency (SE)] and compared survival with younger patients in our centres and in France. METHODS: We performed a multicentre (University Hospitals in Nantes, Rennes and Tours), 2-decade retrospective study between 1 January 1994 and 31 December 2013. Elderly recipients were placed on the same list as younger patients; the use of marginal donors remained occasional. RESULTS: A total of 212 patients aged between 60 and 68 years were included. The 1-, 5-, and 10-year survival rates were 83.2%, 77.4% and 63.8%, respectively, which were significantly worse than those of recipients aged <60 years (1-, 5-, and 10-year survival rates of 87.3%, 80.4% and 68.0%, respectively). The postoperative course was acceptable. The main cause of death was malignancy (29.8% in our cohort). Survival was similar between the first and second decades and among the SE group. Our population exhibited better survival than patients <60 years transplanted in France during the same period with 1-, 5-, and 10-year survival rates of 76.8%, 68.0% and 56.3%, respectively. Predictors of survival in the multivariate analysis included ischaemic cardiomyopathy [hazard ratio (HR) 4.1] and postoperative complications, such as dialysis (HR 9.5) and mechanical circulatory support (HR 4.2). CONCLUSIONS: We report positive postoperative course and long-term outcomes after heart transplantation in older recipients using conventional donors. Our satisfactory outcomes may be explained by the stringent selection of recipients combined with regular follow-up.

Impact of donor comorbidities on heart transplant outcomes in the modern era.

OBJECTIVES: The use of marginal donors with cardiovascular risk factors is increasing due to organ shortage but remains controversial in heart transplantation (HTx). We sought to investigate post-transplant outcomes in the recent era taking into account donor characteristics. METHODS: We reviewed 261 HTx performed in our hospital between January 1996 and March 2013. Donor characteristics were obtained from the national database. The incidence of primary graft dysfunction (PGD) and cardiac allograft vasculopathy (CAV) and overall survival were compared in 2 groups of HTx recipients: those receiving transplants from 1996 to 2004 (Group A, n = 120) and from 2005 to 2013 (Group B, n = 141). RESULTS: The mean age of the donors was 34 ± 12 years in Group A vs 42 ± 13 years in Group B ( P < 0.001). Donors in Group B had a higher body mass index (23 ± 2 vs 26 ± 5 kg/m 2 , P < 0.001), were more likely to be smokers (29.6% vs 52.9%, P < 0.001) and were more likely to have hypertension (5% vs 13.5%, P = 0.030). There was no difference in survival at 1 and 5 years (79% and 63% in Group A vs 80% and 62% in Group B, respectively; P = 0.551). The rate of PGD was 36% in Group A vs 40% in Group B ( P = 0.092). Freedom from CAV at 5 years was 64% and 61%, respectively ( P = 0.367). Among the characteristics of the donors, only hypertension was associated with reduced survival. CONCLUSIONS: The use of older cardiac donors with more cardiovascular comorbidities in the recent era did not impair the post-transplant outcomes. Donor hypertension was the only determinant of worse survival.

Three-year haemodynamic performance of the St Jude Trifecta bioprosthesis.

OBJECTIVES: To examine the haemodynamic performance of the St Jude Trifecta valve for aortic valve replacement (AVR) at 3 years after implantation. METHODS: In a single-centre, prospective, observational, independent study, we enrolled 122 patients who had AVR using a Trifecta bioprosthesis in the July 2010-June 2011 period. A clinical and echocardiographic in-house follow-up was scheduled. RESULTS: In our series, 14.7% of patients received a 19-mm, 28.7% had a 21-mm, 35.2% had a 23-mm and 21.3% had a greater-size prosthesis. There were no cases of operative mortality or of valve-related complications both early and at follow-up (except one sudden unexplained death). Completeness of the 3-year echocardiographic follow-up was 80% among survivors. The average mean transvalvular gradient (mTVG) at 3 years was 14.2, 10.8, 8.6, 7.1 and 6.8 mmHg (sizes 19 to 27/29, respectively). There was no statistically significant difference between average mTVGs measured immediately after implantation versus at the 3-year follow-up in the overall population. The average peak transvalvular gradient (pTVG) at 3 years was 25, 20, 16.8, 13.9 and 14.4 mmHg (sizes 19 to 27/29, respectively). The average indexed effective orifice area (iEOA) at 3 years was 0.8, 0.9, 1, 1.3 and 1.3 cm(2)/m(2) (sizes 19-27, respectively). The rate of moderate patient-prosthesis mismatch (PPM) at 3 years was 15.7%; there were two instances of severe PPM (2.2%). All cases of PPM occurred in the 19, 21 and 23 mm size subgroups. CONCLUSIONS: The Trifecta valve retains its excellent haemodynamic properties at the 3-year follow-up. The rate of PPM is considerably low.

Comparison of cardiac allograft vasculopathy in heart and heart-lung transplantations: a 15-year retrospective study.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is a major factor limiting long-term survival after heart transplantation (HTx). Specific determinants of CAV and long-term outcome after CAV occurrence have been poorly investigated after heart-lung transplantation (HLTx). METHODS: Between January 1996 and December 2006, 79 patients underwent HLTx (36.3 ± 12.2 years old; 47% men) and 141 patients underwent HTx (49.2 ± 12.3 years old; 77% men) at two different institutions. CAV grading was reviewed in both groups according to the 2010 standardized nomenclature of the International Society for Heart and Lung Transplantation. The mean post-transplant follow-up was 94 (1 to 181) months. RESULTS: Overall 10-year survival rate was 58% after HTx and 43% after HLTx (p = 0.11). The Grade 1 (or higher) CAV-free survival rate was 95% at 4 years and 69% at 10 years after HLTx, and 77% and 39%, respectively, after HTx (p < 0.01). Mean cyclosporine blood levels were similar between the groups at 3, 6, 12, 24 and 36 months. The main causes of mortality beyond 5 years after HTx and HLTx were malignancies and bronchiolitis obliterans, respectively. By multivariate analysis, recipients who developed >3 acute myocardial rejections during the first year post-transplant were exposed to a higher risk of CAV (95% CI 1.065 to 2.33, p = 0.02). Episodes of acute pulmonary rejection and bronchiolitis obliterans were not associated with an increased risk of CAV (p = 0.52 and p = 0.30). CONCLUSION: HLTx recipients appeared protected from CAV compared with HTx patients in this retrospective study. Repeated acute cardiac rejections were independent predictors of CAV. Unlike bronchiolitis obliterans, CAV had a very low impact on long-term survival after HLTx.

Heterotopic heart transplantation: where do we stand?

Orthotopic heart transplantation (OHT) is a well established and commonly utilized procedure for end-stage heart failure patients. Heterotopic heart transplantation (HHT) is a surgical procedure that allows the graft to be connected to the native heart in a parallel fashion. The main advantage of HHT is to assist the patient's native heart and to maintain circulation in the cases of severe acute rejection. HHT has also been proposed to overcome pulmonary hypertension, to increase the size of the donor pool and to decrease waiting times without increasing morbidity caused by the procedure. However, only a few papers have reported the short- or long-term results of HHT, and most of these studies have included <30 cases. OHT remains the standard technique and is preferable whenever the patient meets the current criteria and a suitable organ is available. HHT is far less useful than in the past because of the major advances in immunosuppression therapy and the development of long-term mechanical circulatory support. This study reviews the origin of HHT and discusses clinical developments, including their advantages and disadvantages.

Prolonged heparin and vitamin K antagonist regimen for early non-obstructive thrombosis of mechanical mitral valve prostheses.

BACKGROUND AND AIM OF THE STUDY: Transesophageal echocardiography (TEE) has been used to document the incidence of non-obstructive thrombosis (NOT) after mechanical prosthetic mitral valve replacement (MVR). The postoperative occurrence and unpredictable evolution of NOT complicate its management. The study aim was to examine the safety and efficacy of prolonged, combined administration of heparin and vitamin K antagonists (VKA) recommended for this indication. METHODS: All patients who underwent mechanical prosthetic MVR between July 1999 and December 2004 at the authors' institution were systematically studied with TEE immediately after surgery. Patients who presented with > or = 5 mm NOT were treated with combined heparin and VKA until TEE-confirmed resolution of the thrombus. RESULTS: Among 256 patients who underwent 263 MVRs (seven reinterventions), 47 (17.9%) presenting with > or = 5 mm NOT received combined heparin and VKA for between 7 and 115 days (median 17 days). No thromboembolic or hemorrhagic events or deaths were observed during this period of observation. Four patients were treated with danaparoid and VKA because of thrombocytopenia induced by heparin before the diagnosis of NOT. Over a mean follow up of 39 months, one patient died from cancer and another from the sequelae of a stroke. In total, there were five NOT recurrences, three of which were complicated by embolic events without sequelae within eight months, and one by a recurrent stroke. In addition, three patients without demonstrable NOT recurrence suffered transient ischemic attacks. CONCLUSION: Among this small sample of patients, combined heparin and VKA was well tolerated and effective, and could prevent reoperation or thrombolysis. These observations may warrant further study in a larger patient population.