Agnieszka Ciarka

Circulating apoptotic endothelial cells and apoptotic endothelial microparticles independently predict the presence of cardiac allograft vasculopathy.

OBJECTIVES Maintenance of endothelial homeostasis may prevent the development of cardiac allograft vasculopathy (CAV). This study investigated whether biomarkers related to endothelial injury and endothelial repair discriminate between CAV-negative and CAV-positive heart transplant recipients. BACKGROUND CAV is the most important determinant of cardiac allograft survival and a major cause of death after heart transplantation. METHODS Fifty-two patients undergoing coronary angiography between 5 and 15 years after heart transplantation were recruited in this study. Flow cytometry was applied to quantify endothelial progenitor cells (EPCs), circulating endothelial cells (CECs), and endothelial microparticles. Cell culture was used for quantification of circulating EPC number and hematopoietic progenitor cell number and for analysis of EPC function. RESULTS The EPC number and function did not differ between CAV-negative and CAV-positive patients. In univariable models, age, creatinine, steroid dose, granulocyte colony-forming units, apoptotic CECs, and apoptotic endothelial microparticles discriminated between CAV-positive and CAV-negative patients. The logistic regression model containing apoptotic CECs and apoptotic endothelial microparticles as independent predictors provided high discrimination between CAV-positive and CAV-negative patients (C-statistic 0.812; 95% confidence interval: 0.692 to 0.932). In a logistic regression model with age and creatinine as covariates, apoptotic CECs (p = 0.0112) and apoptotic endothelial microparticles (p = 0.0141) were independent predictors (C-statistic 0.855; 95% confidence interval: 0.756 to 0.953). These 2 biomarkers remained independent predictors when steroid dose was introduced in the model. CONCLUSIONS The high discriminative ability of apoptotic CECs and apoptotic endothelial microparticles is a solid foundation for the development of clinical prediction models of CAV.

Trends in the use of mechanical circulatory support as a bridge to heart transplantation across different age groups

INTRODUCTION Numerous cohort analyses suggest rapidly increasing use of mechanical circulatory support (MCS) as a bridge to heart transplantation (HTx), but the role of age in selection for MCS remains unknown. METHODS We assessed adult HTx in the International Society for Heart And Lung Transplantation Registry between 2005 and 2013 and we determined MCS use by recipient age group and transplant year. Multivariable logistic regression models were constructed to identify variables associated with continuous flow (CF) left ventricular assist device (LVAD) use within each age group. RESULTS Among 16,480 HTx recipients the percentage of overall MCS use increased from 23% to 38%, 21% to 41%, and 17% to 42% in age groups 18-39 years, 40-59 years and over 60 years, respectively. This effect was mainly due to an increase in CF LVAD use and primarily in HTx recipients aged over 60. In multivariable analyses, male gender and blood group O were significantly associated with CF LVAD use in all age groups. CONCLUSIONS Bridge to transplant MCS use increased dramatically between 2005 and 2013 primarily due to increased use of CF LVAD and primarily in higher ages. Pre-HTx CF LVAD use was more frequent in men and blood group O.

Transapical transcatheter aortic valve implantation in a heart transplant recipient with severely depressed left ventricular function

Transcatheter aortic valve implantation (TAVI) is becoming a valuable alternative to surgical aortic valve replacement in non-operable and high-risk surgical patients. As the population of heart donors and recipients ages, the prevalence of degenerative valvular disease after transplantation will increase. The optimal treatment strategy of valvulopathies in these patients with extensive comorbidity is still unknown because of insufficient published experience. We present a heart transplant recipient with renal failure, systolic heart failure and severe aortic stenosis who was successfully treated with transapical TAVI.

Assessment of mechanical dyssynchrony can improve the prognostic value of guideline-based patient selection for cardiac resynchronization therapy

Aim To determine if incorporation of assessment of mechanical dyssynchrony could improve the prognostic value of patient selection based on current guidelines. Methods and results Echocardiography was performed in 1060 patients before and 12 ± 6 months after cardiac resynchronization therapy (CRT) implantation. Mechanical dyssynchrony, defined as the presence of apical rocking or septal flash was visually assessed at the baseline examination. Response was defined as ≥15% reduction in left ventricular end-systolic volume at follow-up. Patients were followed for a median of 59 months (interquartile range 37-86 months) for the occurrence of death of any cause. Applying the latest European guidelines retrospectively, 63.4% of the patients had been implanted with a Class I recommendation, 18.2% with Class IIa, 9.4% with Class IIb, and in 9% no clear therapy recommendation was present. Response rates were 65% in Class I, 50% in IIa, 38% in IIb patients, and 40% in patients without a clear guideline-based recommendation. Assessment of mechanical dyssynchrony improved response rates to 77% in Class I, 75% in IIa, 62% in IIb, and 69% in patients without a guideline-based recommendation. Non-significant difference in survival among guideline recommendation classes was found (Log-rank P = 0.2). Presence of mechanical dyssynchrony predicted long-term outcome better than guideline Classes I, IIa, IIb (Log-rank P < 0.0001, 0.006, 0.004, respectively) and in patients with no guideline recommendation (P = 0.02). Comparable results were observed using the latest American Guidelines. Conclusion Our data suggest that current guideline criteria for CRT candidate selection could be improved by incorporating assessment of mechanical asynchrony.

ISHLT transplant registry: Youthful investment – The path to progress

Cite this article as: Evan P. Kransdorf, Hirsch S. Mehta, Keyur B. Shah, Darko Vucicevic, Eugene DePasquale, Livia Goldraich, Agnieszka Ciarka, Marco Masetti, Jong-Chan Youn, Claire Irving, Feras Khaliel, Martin Schweiger, Patricia Uber, Mandeep R. Mehra and Josef Stehlik, ISHLT transplant registry: Youthful investment – The path to progress, Journal of Heart and Lung Transplantation, http://dx.doi.org/10.1016/j.healun.2017.07.024

Urinary proteomic signatures associated with β-blockade and heart rate in heart transplant recipients

Objectives Heart transplant (HTx) recipients have a high heart rate (HR), because of graft denervation and are frequently started on β-blockade (BB). We assessed whether BB and HR post HTx are associated with a specific urinary proteomic signature. Methods In 336 HTx patients (mean age, 56.8 years; 22.3% women), we analyzed cross-sectional data obtained 7.3 years (median) after HTx. We recorded medication use, measured HR during right heart catheterization, and applied capillary electrophoresis coupled with mass spectrometry to determine the multidimensional urinary classifiers HF1 and HF2 (known to be associated with left ventricular dysfunction), ACSP75 (acute coronary syndrome) and CKD273 (renal dysfunction) and 48 sequenced urinary peptides revealing the parental proteins. Results In adjusted analyses, HF1, HF2 and CKD273 (p ≤ 0.024) were higher in BB users than non-users with a similar trend for ACSP75 (p = 0.06). Patients started on BB within 1 year after HTx and non-users had similar HF1 and HF2 levels (p ≥ 0.098), whereas starting BB later was associated with higher HF1 and HF2 compared with non-users (p ≤ 0.014). There were no differences in the urinary biomarkers (p ≥ 0.27) according to HR. BB use was associated with higher urinary levels of collagen II and III fragments and non-use with higher levels of collagen I fragments. Conclusions BB use, but not HR, is associated with a urinary proteomic signature that is usually associated with worse outcome, because unhealthier conditions probably lead to initiation of BB. Starting BB early after HTx surgery might be beneficial.

URINARY PROTEOMIC SIGNATURES ASSOCIATED WITH BETA-BLOCKADE AND HEART RATE IN HEART TRANSPLANT RECIPIENTS

Objective: Heart transplant (HTx) recipients have a high heart rate (HR), because of graft denervation and are frequently started on &bgr;-blockade (BB). We assessed whether BB and HR post HTx are associated with a specific urinary proteomic signature. Design and method: In 336 HTx patients (mean age, 56.8 years; 22.3% women), we analyzed cross-sectional data obtained 7.3 years (median) after HTx. We recorded medication use, measured HR during right heart catheterization, and applied capillary electrophoresis coupled with mass spectrometry to determine the multidimensional urinary classifiers HF1 and HF2 (known to be associated with left ventricular dysfunction), ACSP75 (acute coronary syndrome) and CKD273 (renal dysfunction) and 48 sequenced urinary peptides revealing the parental proteins. Results: In adjusted analyses, HF1, HF2 and CKD273 (p <  = 0.024) were higher in BB users than non-users with a similar trend for ACSP75 (p = 0.06). Patients started on BB within 1 year after HTx and non-users had similar HF1 and HF2 levels (p >  = 0.098), whereas starting BB later was associated with higher HF1 and HF2 compared with non-users (p <  = 0.014). There were no differences in the urinary biomarkers (p >  = 0.27) according to HR. BB use was associated with higher urinary levels of collagen II and III fragments and non-use with higher levels of collagen I fragments. Conclusions: BB use, but not HR, is associated with a urinary proteomic signature that is usually associated with worse outcome, because unhealthier conditions probably lead to initiation of BB. Starting BB early after HTx surgery might be beneficial.

Reversibility of severe mitral valve regurgitation after left ventricular assist device implantation: single-centre observations from a real-life population of patients

OBJECTIVES This study evaluates the impact of untreated preoperative severe mitral valve regurgitation (MR) on outcomes after left ventricular assist device (LVAD) implantation. METHODS Of the 234 patients who received LVAD therapy in our centre during a 6-year period, we selected those who had echocardiographic images of good quality and excluded those who underwent mitral valve replacement prior to or mitral valve repair during LVAD placement. The 128 patients selected were divided into 2 groups: Group A with severe MR (n = 65) and Group B with none to moderate MR (n = 63, 28 with moderate MR). We evaluated transthoracic echocardiography preoperatively [15 (7-28) days before LVAD implantation; median (interquartile range)] and postoperatively up to the last available follow-up [501 (283-848) days after LVAD]. We collected mortality, complications and clinical status indicators of the patient cohort. RESULTS We observed a significant decrease in the severity of MR after LVAD implantation (severe MR 51% pre- vs 6% post-LVAD implantation, P < 0.001). There was no difference between groups in terms of right heart failure, rate of urgent heart transplantation, pump thrombosis or ventricular arrhythmias. There was no difference in 1-year survival and 3-year survival (87.7% vs 88.4% and 71.8% vs 66.6% for Groups A and B, respectively, P = 0.97). CONCLUSIONS Preoperative severe MR resolves in the majority of patients early on after LVAD implantation and is not associated with worse clinical outcomes or intermediate-term survival.

AB0638 Cardiac transplant in systemic sclerosis-associated cardiomyopathy: monocentric experience of 3 cases

Background Cardiac involvement in systemic sclerosis (SSc) is a frequent complication, but end-stage cardiac failure remains uncommon and represents a poor prognosis. Heart-lung and lung transplant is an established treatment option for SSc-related pulmonary disease. Due to the limited published data, no recommendations exist for cardiac transplant in the context of SSc. Objectives We present our monocentric experience of 3 patients with SSc who underwent cardiac transplant for SSc-related end-stage heart disease (multiple hospitalisations due to failure of medical therapy and life-threatening complications). Results Case 1 is a 59-year-old male with limited cutaneous SSc. Antinuclear antibody (ANA) was negative. He had vascular (digital ulcers) and cardiac (heart failure (left ventricular ejection fraction (LVEF) 20%, NYHA class IV)) involvement, without major gastrointestinal or pulmonary involvement (no interstitial lung disease (ILD) or pulmonary arterial hypertension (PAH: assessed by right heart catheterization (RHC))). He underwent a cardiac transplant at the age of 51, after a disease duration of 6 years. Post-transplantation immunosuppressant therapy consists of tacrolimus and mycophenolic acid, initially associated with methylprednisolon, which is the standard immunosuppression protocol at our institution. Case 2 is a 55-year-old male with limited cutaneous SSc. ANA was positive, 1/320, speckled pattern, but no SSc-related autoantibody has been identified. He had gastrointestinal (upper gastrointestinal tract dysmotility), muscular (myositis) and cardiac (heart failure with secondary cardiac cirrhosis (LVEF 40%, NYHA class III)) involvement, without major pulmonary involvement (no ILD or PAH). He underwent a cardiac transplant at the age of 54, after a disease duration of 7 years. Standard immunosuppressants were initiated. Case 3 is a 50-year-old male with diffuse cutaneous SSc. ANA was negative. He had vascular (digital ulcers), gastrointestinal (upper gastrointestinal tract dysmotility) and cardiac (heart failure with secondary cardiac cirrhosis (LVEF 40%, NYHA class III)) involvement, without major pulmonary involvement (no ILD or PAH). He underwent a cardiac transplant at the age of 49, after a disease duration of 4 years. Standard immunosuppressants were initiated. At present, 1,5 years (case 2 and 3) and 8 years (case 1) after transplant, the donor hearts are still functioning well. No other SSc-related organ manifestations have occurred. Case 1 Case 2 Case 3 Sex, age Male, 59 years Male, 55 years Male, 50 years Type of SSc Limited Limited Diffuse Disease duration at Tx 6 years 7 years 4 years ANA Negative 1/320, speckled, no SSc-specific antibody Negative Pre-Tx NYHA class IV III III LVEF 20% 40% 40% RHC: mPAP in mmHg 26 20 31 RHC: PCWP in mmHg 20 14 28 Post-Tx NYHA class I I I LVEF 60% 55% 60% RHC: mPAP in mmHg 19 13 21 RHC: PCWP in mmHg 12 8 12 Tx: Transplant; mPAP: Mean pulmonary artery pressure; PCWP: Pulmonary capillary wedge pressure. Conclusions We present 3 patients with SSc who successfully underwent cardiac transplant for SSc-related end-stage heart disease. None had other major SSc-related organ involvement. This supports the limited published data that cardiac transplant is feasible and can be considered in end-stage SSc-related cardiomyopathy. Disclosure of Interest None declared