Clinical usefulness of gene-expression profile to rule out acute rejection after heart transplantation: CARGO II.

AIMS: A non-invasive gene-expression profiling (GEP) test for rejection surveillance of heart transplant recipients originated in the USA. A European-based study, Cardiac Allograft Rejection Gene Expression Observational II Study (CARGO II), was conducted to further clinically validate the GEP test performance. METHODS AND RESULTS: Blood samples for GEP testing (AlloMap(®), CareDx, Brisbane, CA, USA) were collected during post-transplant surveillance. The reference standard for rejection status was based on histopathology grading of tissue from endomyocardial biopsy. The area under the receiver operating characteristic curve (AUC-ROC), negative (NPVs), and positive predictive values (PPVs) for the GEP scores (range 0-39) were computed. Considering the GEP score of 34 as a cut-off (>6 months post-transplantation), 95.5% (381/399) of GEP tests were true negatives, 4.5% (18/399) were false negatives, 10.2% (6/59) were true positives, and 89.8% (53/59) were false positives. Based on 938 paired biopsies, the GEP test score AUC-ROC for distinguishing ≥3A rejection was 0.70 and 0.69 for ≥2-6 and >6 months post-transplantation, respectively. Depending on the chosen threshold score, the NPV and PPV range from 98.1 to 100% and 2.0 to 4.7%, respectively. CONCLUSION: For ≥2-6 and >6 months post-transplantation, CARGO II GEP score performance (AUC-ROC = 0.70 and 0.69) is similar to the CARGO study results (AUC-ROC = 0.71 and 0.67). The low prevalence of ACR contributes to the high NPV and limited PPV of GEP testing. The choice of threshold score for practical use of GEP testing should consider overall clinical assessment of the patient's baseline risk for rejection.

Activated Hemostatic Biomarkers in Patients with Implanted Left Ventricle Assist Devices: Are Heparin and/or Clopidogrel Justified?

BACKGROUND: Adequate anticoagulation represents a major problem for left ventricle assist device (LVAD) utilization in patients awaiting heart transplantation as well as for regeneration of the native heart. The proper management of hemostatic abnormalities during LVAD support may improve survival by reducing the incidence of hemorrhagic and/or thromboembolic complications. CASE REPORT: A 40-year-old man with implanted pulsatile LVAD due to dilated cardiomyopathy received aspirin and warfarin. The patient underwent serial weekly monitoring of hemostatic biomarkers including international normalization ratio, prothrombin time, prothrombin activity, activated partial thromboplastin time, fibrinogen, D-dimer, platelet aggregation induced by adenosine diphosphate and arachidonic acid, platelet count, and mean platelet volume. The external pump was exchanged three times - twice because of a clot formation in the blood chamber of the pump, and once according to the standard protocol. RESULTS: LVAD use was consistently associated with enhanced adenosine diphosphate-induced platelet aggregation independent from the timing of clot formation or external pump exchange. Among coagulation indices, increased D-dimer holds predictive value for clot formation. The fibrinogen level peaked before the first pump exchange and was twice as high than the average values. Gradual improvement in exercise capacity was observed 2 years after implantation, after which the patient underwent a controlled stress test in the stop mode of the LVAD and the device was successfully explanted. CONCLUSIONS: Serial assessment of hemostatic biomarkers may benefit and triage LVAD patients. Consistent platelet activation during long-term LVAD may justify the addition of clopidogrel, while high D-dimer and/or elevated fibrinogen may indicate adding heparin to the conventional antithrombotic regimen. Randomized evidence is needed to test such a hypothesis.

Performance of gene-expression profiling test score variability to predict future clinical events in heart transplant recipients.

BACKGROUND: A single non-invasive gene expression profiling (GEP) test (AlloMap®) is often used to discriminate if a heart transplant recipient is at a low risk of acute cellular rejection at time of testing. In a randomized trial, use of the test (a GEP score from 0-40) has been shown to be non-inferior to a routine endomyocardial biopsy for surveillance after heart transplantation in selected low-risk patients with respect to clinical outcomes. Recently, it was suggested that the within-patient variability of consecutive GEP scores may be used to independently predict future clinical events; however, future studies were recommended. Here we performed an analysis of an independent patient population to determine the prognostic utility of within-patient variability of GEP scores in predicting future clinical events. METHODS: We defined the GEP score variability as the standard deviation of four GEP scores collected ≥315 days post-transplantation. Of the 737 patients from the Cardiac Allograft Rejection Gene Expression Observational (CARGO) II trial, 36 were assigned to the composite event group (death, re-transplantation or graft failure ≥315 days post-transplantation and within 3 years of the final GEP test) and 55 were assigned to the control group (non-event patients). In this case-controlled study, the performance of GEP score variability to predict future events was evaluated by the area under the receiver operator characteristics curve (AUC ROC). The negative predictive values (NPV) and positive predictive values (PPV) including 95 % confidence intervals (CI) of GEP score variability were calculated. RESULTS: The estimated prevalence of events was 17 %. Events occurred at a median of 391 (inter-quartile range 376) days after the final GEP test. The GEP variability AUC ROC for the prediction of a composite event was 0.72 (95 % CI 0.6-0.8). The NPV for GEP score variability of 0.6 was 97 % (95 % CI 91.4-100.0); the PPV for GEP score variability of 1.5 was 35.4 % (95 % CI 13.5-75.8). CONCLUSION: In heart transplant recipients, a GEP score variability may be used to predict the probability that a composite event will occur within 3 years after the last GEP score. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT00761787.

Pacemaker Implantation Following Heart Transplantation - Incidence and Risk Factors. Single-Center Experience.

BACKGROUND: Bradyarrhythmias, requiring pacemaker (PM) implantation, are common complications following orthotopic heart transplantation (HTx). Currently used heart transplantation methods are primarily the bicaval technique and the total heart transplantation technique. The aim of the study was to assess the incidence and risk factors, including donor parameters, of conduction disorders requiring pacing after HTx. METHODS: A population of 111 (52 ± 13 years, 91 (82%) men) heart recipients was divided into a group requiring PM implantation post-HTx and a group not requiring PM. We compared groups in terms of donor parameters, time of graft ischemia, transport and transplantation, and surgical techniques as the potential risk factors for significant bradyarrhythmias. RESULTS: Ten of 111 patients with HTx (9%) required PM implantation. The indication in 7 cases was sinus node dysfunction (SND), in 3 patients it was complete atrioventricular block (AV-block). In the PM group, the age of 48 ± 6 vs 40 ± 11 years (P = .0227) and the body mass index (BMI) 28 ± 3 vs 26 ± 4 kg/m2 (P = .0297) of the donor were significantly higher. There was no influence of organ transport time, ischemia time, and transplantation time. All patients requiring PM implantation were transplanted using the bicaval anastomosis: 10 (100%) vs 71 (70%) in the group not requiring PM (P = .044). CONCLUSIONS: The need for PM implantation post-HTx despite using new techniques is still common, especially in the group operated with the bicaval method. In addition, higher donor's age and BMI are risk factors of PM implantation, what is of importance as qualification criteria of donor hearts have been gradually extended.

The early safety profile of simultaneous vaccination against influenza and Respiratory Syncytial Virus (RSV) in patients with high-risk heart failure.

The safety of simultaneous vaccination for Respiratory Syncytial Virus (RSV) and influenza in vulnerable high-risk heart failure (HF) patients remains unclear. In an open-label, prospective study, 105 patients received concurrent influenza (Vaxigrip Tetra, season 2023/2024, Sanofi) and RSV (Arexvy, GSK) vaccinations from September 15th to November 17th, 2023. Adverse events were collected on the fourth-day post-vaccination. Overall, the vaccination was well tolerated, with the most common reaction being injection site pain (63 %). General symptoms occurred in 33 % of patients, predominantly fatigue (23 %), myalgia (12 %), and headache (9 %). Grade 3 reactions were observed in 6 % of patients, and a few experienced temperature elevation or flu-like symptoms, managing them with antipyretics. Notably, there were no exacerbations of HF, hospitalizations, or deaths within a week post-vaccination. This study indicates the safety of simultaneous influenza and RSV vaccination in high-risk HF patients, with a low incidence of mild adverse events.

Does the induction immunotherapy (basiliximab) influence the early acute cellular rejection index after orthotopic heart transplantation?- Preliminary assessment report.

The study aimed to determine the influence of induction therapy on the acute cellular rejection (ACR) index in adult heart transplant recipients during the one-year observation. The study population consisted of 256 consecutive adult patients (pts), aged 51.5 (±11.9) years, 199 (77%) men treated with orthotopic heart transplantation (OHT) in the period between 2015 and 2020 in a single high-volume heart transplant center. The endomyocardial biopsies (EMBs) were performed according to the protocol consisting of 7 protocolary EMBs for up to 3 months and 10 EMBs for up to one year after OHT. The rejection index (ACRI) was calculated as the number of scheduled EMBs with the ACR ≥ 2 divided by the total number of protocolary EMBs. The study population was divided into two groups according to the application of basiliximab. The total number of pts. who received basiliximab was 10 (3.9%). The main indications for the usage of the induction therapy were heart retransplantation, mechanical circulatory support (MCS), severe renal insufficiency (eGFR <30 mL/min/1.73 m2), and a panel of reactive antibody (PRA) > 10%. In the group with induction, the mean age was 49 (±14) years; 3 (30%) patients had the MCS prior to OHT, and 3 (30%) patients had heart retransplantation. Four (40%) patients had diabetes mellitus, and 4 (40%) patients had severe renal insufficiency. As maintenance therapy during the observation period, tacrolimus was given to 10 (100%) patients, everolimus to 2 (20%) patients, and MPA to 9 (90%) patients. In the group with no induction, the mean age was 51.8 (±12) years, MCS was used in 56 (23%) patients, 2 (0.8%) patients were retransplanted; 10 (4%) patients had eGFR <30 mL/min/1.73 m2 and 58 (24%) patients had diabetes. Tacrolimus was administered to 243 (99%) patients, cyclosporine to 3 (1%), everolimus to 40 (16%), and mycophenolate to 245 (99.6%) heart recipients. The median one-year ACRI was 0.0, IQR:0.0-0.08 in the group with induction vs. 0.077, IQR: 0.0-0.154 with no induction; p = 0.11. ACRI up to three months was significantly higher in the entire cohort in comparison to up to one year (P < 0.01). The multivariate analysis showed that only everolimus implementation and younger age at the time of transplant influenced patients' mortality rate (P < 0.01). Significant graft rejections (≥ 2R ISHLT) are most common in the first three months after OHT. Patients who are initially at high risk of significant cellular rejection may benefit from induction therapy.

Nailfold Videocapillaroscopy for Non-Invasive Assessment of Microcirculation and Prognostic Correlation with Endothelial Dysfunction, Cardiovascular Risk Factors, and Non-HLA Antibodies in Heart Transplant Recipients: A Pilot Study.

Early identification of allograft vasculopathy and the concomitant elimination of adverse risk factors is essential for improving the long-term prognosis of heart transplant (HTx) recipients with underlying cardiovascular disease (CVD). The major aim of this pilot study was to conduct a non-invasive imaging evaluation of the HTx patient microcirculation by employing nailfold video-capillaroscopy (NVC) in a well-characterized patient and control cohort, and to correlate these data with endothelial cell function, accompanied by studies of traditional cardiovascular risk factors and non-HLA antibodies in HTx recipients. Ten patients undergoing HTx (mean age of 38 ± 14 years) were recruited for the study and compared to a control group of 12 well-matched healthy volunteers (mean age 35 ± 5 years) with normal body mass index (BMI). Detailed medical records were collected from all individuals. NVC was performed using CapillaryScope 200 MEDL4N microscope. For functional readout and correlation analysis, endothelial cell network formation in conjunction with measurements of patient serum levels of vascular endothelial growth factor (VEGF) and non-HLA autoantibodies directed against the angiotensin II type-1-receptor (anti-AT1R-Ab), endothelin-1 type-A-receptor (anti-ETAR-Ab), protease-activated receptor-1 (anti-PAR-1-Ab), and VEGF-A (anti-VEGF-A-Ab) were studied. Our NVC analysis found that the average apical loop diameter of nailfold capillaries was significantly increased in HTx recipients (p = 0.001). In addition, HTx patients with more prominent changes in capillaroscopic patterns were characterized by the presence of traditional cardiovascular risk factors, and HTx patients had increased levels of anti-AT1R-ab, anti-ETAR-ab, and anti-VEGF-A-Ab (p = 0.017, p = 0.025, and p = 0.003, respectively). Capillary diameters most strongly correlated with elevated serum levels of troponin T and triglycerides (R = 0.69, p = 0.028 and R = 0.81, p = 0.004, respectively). In conclusion, we found that an abnormal NVC pattern in HTx patients is associated with traditional CVD risk factors and that NVC is a useful non-invasive tool to conveniently monitor changes in the microvasculature of HTx patients.

Native Renal Arteries Denervation as a Therapy of Refractory Hypertension in Patient after Heart and Kidney Transplantation-5 Years of Observation.

This case report describes a 59-year-old male patient after heart and kidney transplantation, subsequently diagnosed with refractory hypertension since implemented antihypertensive pharmacotherapy consisting of six agents did not provide a substantial therapeutic response. Elevated blood pressure and its impact on a hypertrophied transplanted heart and impaired renal graft function have led to a significant deterioration in the patient's cardiovascular risk profile. To address this issue, a native renal arteries denervation was performed. It resulted in a noteworthy decrease in both systolic and diastolic pressure values, thus manifesting a positive hypotensive effect. Furthermore, a sustainable reduction of left ventricular mass and stabilization in kidney graft function were noticed. The presented case provides evidence that renal denervation can be an efficacious complementary treatment method in individuals who received kidney and heart grafts as it leads to a decrease in cardiovascular risk.

Patient-Related Preoperative Clinical Factors Influencing 1-Year Survival After Orthotopic Heart Transplantation - A Single Center Polish Experience.

BACKGROUND End-stage heart failure is a growing problem in Poland. Orthotopic heart transplantation remains the best treatment option. Although increasing, the number of heart transplants is disproportionately low compared with patient need. Therefore, it is crucial to identify factors contributing to improvement of heart transplantation outcomes. To find factors providing best survival and optimal recipient selection, we analyzed pretransplant patient-related clinical factors. MATERIAL AND METHODS Between May 2015 and May 2020, we performed 258 cardiac transplants at our institution. We reviewed possible patient-related clinical factors affecting the 1-year survival of our patients and analyzed factors related to survival. Mean age at transplant was 53.5 (±11.8) years; 22.9% of patients were women. Preoperative factors were analyzed using univariable and multivariable analyses. RESULTS In this cohort, 31.8% were diabetic, 43% had ischemic etiology of heart failure, and 15.3% had reversible pulmonary hypertension. Mechanical circulatory support was used in 22%. During 1-year observation, 64 (24.8%) patients died. Univariable analysis showed ischemic etiology (hazard ratio [HR]=2.05, CI=1.227-3.429; P=0.01) and left ventricular assist device were associated with 1-year risk of death (HR=1.953, CI=1.090-3.499; P=0.02). Urgent listing trended toward worsened prognosis (HR=1.509, CI=0.95-2.397; P=0.08). Multivariable analysis showed ischemic etiology (HR=1.81, CI=1.075-3.059; P=0.03), total mechanical circulatory support (HR=1.93, CI=1.080-3.437; P=0.03), decreased eGFR (HR=0.987, CI=0.975-0.998; P=0.03), and protein level (HR=0.97, CI=0.951-0.998; P=0.04) were independently associated with worse 1-year survival after transplantation. CONCLUSIONS Ischemic etiology and mechanical circulatory support were the most important preoperative factors. Malnutrition and renal failure were additional risk factors. Age alone did not influence 1-year survival.

Occurrence of Professional Burnout and Severity of Depressive Symptoms among Cardiac Nurses: A Cross-Sectional Study.

Nurses with depression are not only likely to suffer themselves, but it may have an impact on their coworkers and potentially the quality of care they provide. This study aimed to determine the prevalence of depression and its association with burnout in cardiac nurses. A group of 400 cardiac nurses (361 women and 39 men) was enrolled. The standardized tools such as Maslach Burnout Inventory (MBI), Beck Depression Inventory (BDI), and Patient Health Questionaire-9 (PHQ-9) were used. A high level of professional burnout regarding emotional exhaustion was observed in 53.3% of nurses, high depersonalization in 52.5%, and low personal accomplishment in 72.8%. PHQ-9 and BDI were shown to correlate significantly and positively with all three MBI subscales (p < 0.05). High depressive symptoms and occupational burnout were correlated with depression (p < 0.05). In conclusion, nurses were found to have high levels of depression and professional burnout, which may have resulted in a negative impact on the quality of patient care. Identification of burnout in cardiac nurses is necessary to consider interventions to prevent stress and depression.

Heart rate turbulence for prediction of heart transplantation and mortality in chronic heart failure.

BACKGROUND: Previous studies have shown conflicting results about the value of heart rate turbulence (HRT) for risk stratification of patients (pts) with chronic heart failure (CHF). We prospectively evaluated the relation between HRT and progression toward end-stage heart failure or all-cause mortality in patients with CHF. METHODS: HRT was assessed from 24-hour Holter recordings in 110 pts with CHF (54 in NYHA class II, 56 in class III-IV; left ventricular ejection fraction (LVEF) 30%+/- 10%) on optimal pharmacotherapy and quantified as turbulence onset (TO,%), turbulence slope (TS, ms/RR interval), and turbulence timing (beginning of RR sequence for calculation of TS, TT). TO > or = 0%, TS < or = 2.5 ms/RR, and TT >10 were considered abnormal. End point was development of end-stage CHF requiring heart transplantation (OHT) or all-cause mortality. RESULTS: During a follow-up of 5.8 +/- 1.3 years, 24 pts died and 10 required OHT. TO, TS, TT, and both (TO and TS) were abnormal in 35%, 50%, 30%, and 25% of all patients, respectively. Patients with at least one relatively preserved HRT parameter (TO, TS, or TT) (n = 98) had 5-year event-free rate of 83% compared to 33% of those in whom all three parameters were abnormal (n = 12). In multivariate Cox regression analysis, the most powerful predictor of end point events was heart rate variability (SDNN < 70 ms, hazard ratio (HR) 9.41, P < 0.001), followed by LVEF < or = 35% (HR 6.23), TT > or = 10 (HR 3.14), and TO > or = 0 (HR 2.54, P < 0.05). CONCLUSION: In patients with CHF on optimal pharmacotherapy, HRT can help to predict those at risk for progression toward OHT or death of all causes.

Comparison of long-term results of drug-eluting stent and bare metal stent implantation in heart transplant recipients with coronary artery disease.

BACKGROUND: Transplanted heart coronary artery disease (TxCAD) may occur in a significant proportion of patients following cardiac transplantation. Drug-eluting stents (DES) have been successfully used in patients with CAD, but their efficacy in TxCAD patients has not been well established. AIM: To compare long-term results of intracoronary implantation of DES and BMS in patients suffering from TxCAD. METHODS: We performed a retrospective analysis of all intracoronary stent implantations for TxCAD with at least one control coronary angiography performed during follow-up. We identified 28 DES (all sirolimus-eluting stents, SES) and 28 BMS implantations in 23 patients. The mean follow-up time was 410+/-58 days after DES, and 572+/-434 days after BMS implantation (p=0.004). We compared the occurrence of in-stent restenosis (ISR) in DES and BMS, and survival of patients in the context of risk factors that were identified for each stent implantation separately. RESULTS: There were 2 (7%) ISR revealed in DES patients (mean time from PCI to restenosis 492+/-58 days) vs. 17 (61%) ISR in BMS patients (mean time from PCI to restenosis 475+/-345 days) (p<0.001). There were 3 (18%) deaths in patients with DES, 4 (31%) in patients with BMS, and 1 (14%) in a patient with DES and BMS (NS). The risk factor profile was comparable, except for higher age at the time of transplantation (46+/-7 vs. 41+/-6 years, p=0.011) and stent implantation (54+/-7 vs. 49+/-6 years, p<0.001) for DES. CONCLUSION: Favourable long-term results of DES compared with BMS implantation for TxCAD suggest the preferential use of DES in heart transplant recipients.

Pulmonary vascular resistance as a potential marker of reactive pulmonary hypertension reduction following sildenafil therapy in patients disqualified from orthotopic heart transplantation.

PURPOSE: We sought to determine the predictors of restoration of heart transplantation (HTx) candidacy in patients with systolic heart failure (HF) and reactive fixed pulmonary hypertension (RFPH) defined as pulmonary vascular resistance (PVR) > 2.5 Wood units (WU), transpulmonary gradient (TPG) > 12 mmHg or ≤2.5 WU with systolic arterial pressure ≤85 mmHg during vasoreactivity test, following sildenafil therapy. MATERIAL AND METHODS: Between 2007 and 2018 1136 patients were evaluated at our department as candidates for HTx. Thirty-five of them, who presented with systolic HF and were not eligible for HTx due to RFPH, were included in the study (31 men aged 55.1 ± 7.4 years). In all the patients sildenafil was introduced and up-titrated to a maximal tolerated dose in addition to optimal medical therapy. Patients were assessed at 3-6 months intervals. RESULTS: During median 11 months (interquartile range 6-18 months) reduction of RFPH enabling qualification for HTx was observed in 62.9% patients. Higher baseline PVR (OR 0.32; 95% CI (0.14-0.74) p < 0.001), pulmonary artery systolic pressure (PASP) (OR 0.94, 95% CI (0.88-0.99) p = 0.05), mean artery pulmonary pressure (mPAP) (OR 0.87, 95% CI (0.77-0.98) p = 0.02) and TPG (OR 082, 95% CI (0.70-0.96) p = 0.003) were negative predictors of RFPH reduction with sildenafil therapy. In multivariable analysis, lower PVR (p = 0.02) was identified as an independent predictor of RFPH reduction following sildenafil therapy. CONCLUSION: Sildenafil therapy can support PH reduction in systolic HF patients uneligible for HTx due to RFPH. Lower baseline PVR was identified as an independent predictor of PH reversibility with sildenafil enabling restoration of HTx candidacy.

Prevalence and Risk Factors of New-Onset Diabetes After Transplantation (NODAT).

BACKGROUND New-onset diabetes after transplantation (NODAT) is a serious complication after a solid organ transplant. NODAT occurs in 2% to 53% of all solid organ transplant recipients. The identification of high-risk patients and the implementation of measures to limit the development of NODAT can improve the long-term patient prognosis. MATERIAL AND METHODS Our study group consisted of 336 patients undergoing heart transplant. Patients with prior diabetes (60 patients) were excluded from analysis. The remaining 276 patients were divided in 2 groups: with NODAT (n=109) and without NODAT (n=167). Logistic regression analysis was used for NODAT risk factor assessment. RESULTS NODAT occurred in 109 (32%) out of 336 patients without diagnosed diabetes before heart transplantation. Risk factors for post-transplant diabetes mellitus, which was shown by the analysis of the collected data, were BMI at discharge (OR=1.082, CI 1.011-1.158, p=0.0233), history of diagnosed CMV infection (OR=1.464, CI 1.068-2.007, p=0.0179), and age over 51 years (OR=1.634, CI 1.274-2.095, p=0.0001). CONCLUSIONS 1. New-onset diabetes after transplantation (NODAT) or long-lasting hypoglycemia (over 2 years after transplantation) was diagnosed in 32% patients after heart transplantation developed. 2. The risk factors of NODAT were BMI at discharge and history of diagnosed CMV infection, and age over 51 years was an independent risk factor.

Short- and long-term outcomes of continuous-flow left ventricular assist device therapy in 79 patients with end-stage heart failure.

INTRODUCTION: An increasing number of patients with end­stage heart failure, along with a shortage of heart donors, necessitates the use of mechanical circulatory support. OBJECTIVES: This single­center retrospective study evaluated short- and long term outcomes of continuous­flow left ventricular assist device (CF LVAD) therapy in patients with end stage heart failure. PATIENTS AND METHODS: We collected and assessed data of 79 patients (77 men, 2 women; mean age, 50.3 years; mean INTERMACS profile, 3.1) implanted with a CF­LVAD between 2009 and 2017 (HeartMate 3 in 19 patients [24%]; HeartMate 2 in 9 [11.4%]; and HeartWare in 51 [64.6%]). RESULTS: The mean time on CF-LVAD support was 604 days (range, 1­1758 days). There were 2 device exchanges due to pump thrombosis and 1 explantation due to heart regeneration; 9 patients (11.4%) underwent heart transplant. Stroke (nondisabling, 48%) occurred in 27.8% of patients (ischemic in 9 patients; hemorrhagic, in 14; both types, in 1) despite the standardized anticoagulation regimen. Major gastrointestinal bleeding and pump thrombosis were reported in 13 patients (16.5%), while 18 patients (22.8%) developed driveline infections (recurrent in 15 patients [19%]). Hemorrhagic stroke and bacteremia had a negative impact on survival. Hemorrhagic stroke was the main cause of death. Survival probability was 0.9 at 1 month and 0.81, 0.71, 0.61, and 0.53 at 1, 2, 3, and 4 years, respectively. CONCLUSIONS: Although CF­LVAD support is associated with substantial adverse events, they do not significantly affect mortality (except hemorrhagic stroke and bacteremia). Novel devices seem to overcome these limitations, but larger studies are needed to support these findings.

Myofibrillolysis and fibrosis predicts myocardial insufficiency.

INTRODUCTION: Cardiocyte myofibrillolysis and interstitial fibrosis belong to histopathological changes in cardiomyopathies, leading to heart failure. AIM: To evaluate these changes in apical resection during left ventricular assist device (LVAD) implantation. MATERIAL AND METHODS: The studied group consisted of 40 patients with cardiomyopathy, and apical samples excised during left ventricular assist device implantation were studied (CM/VAD group, mean: 48.1 ±10 y/o). A control group consisted of 6 apical samples from healthy heart graft donors (mean: 29 ±2.3 years old). Area fraction (AF) was calculated for: fibrosis, cardiocytes with myofibrillolysis (MFL), non-myofibrillolytic cardiocytes (non-MFL). RESULTS: Single lymphocytes were seen in 18 (45%) cases in the CM/VAD group. Cardiomyopathy grade evaluated semiquantitatively in CM/VAD was: slight (25% of a group), moderate (35.5%), advanced (35.5%). CM/VAD cases showed nearly ten times higher fibrosis than the control group. The MFL cells occupied nearly a five times larger area in CM/VAD than in the control group, whereas non-MFL cells were found in the control group, as a predominant pattern. The linear regression calculated between fibrosis AF and types of cardiocytes indicated the depletion of cardiomyocytes with fibrosis increase. The control group presented insignificant dependency between fibrosis and MFL cells, suggesting the lack of replacement fibrosis. Significant negative dependence between fibrosis and non-MFL cardiocytes suggested remodeling in controls. Correlation analysis showed a strong relation between depletion of normal cardiocytes and progression of fibrosis. CONCLUSIONS: Progression of cardiomyopathy and fibrosis depends on the loss of cardiocytes rather than degeneration of these cells.

Prognostic utility of the N terminal prohormone of brain natriuretic peptide and the modified Model for End Stage Liver Disease in patients with end stage heart failure.

INTRODUCTION    The N terminal prohormone of brain natriuretic peptide (NT proBNP) is secreted by cardiomyocytes in response to increased wall stress resulting from pressure and volume overload. The modified Model for End Stage Liver Disease (modMELD) scale reflects the systemic effect of heart failure (HF), which includes end-organ congestion and subsequent hepatic and renal dysfunction. OBJECTIVES    The aim of this study was to assess the prognostic accuracy of NT proBNP and the modMELD score, as well as to compare their usefulness in the risk stratification of patients with end-stage HF awaiting orthotopic heart transplantation (OHT). PATIENTS AND METHODS    We retrospectively analyzed the data of 641 consecutive adult patients awaiting OHT between 2012 and 2016. Exclusion criteria included "urgent status", OHT, and removal from the waiting list. Clinical and laboratory data were obtained at the time of admission to the waiting list. The primary endpoint was all-cause mortality during a one-year follow up. RESULTS    In the overall population of 370 patients, the median age was 54.0 (46.0-60.0) years, and 87.6% of the patients were male. During the follow-up period, the mortality rate was 27.6%. The areas under the curve (AUCs) were 0.619 (95% CI: 0.557-0.681) for NT proBNP and 0.870 (95% CI: 0.833-0.906) for modMELD. The difference between the AUC for modMELD and NT proBNP was 0.251 (95% CI: 0.179-0.322, P <0.0001). CONCLUSIONS    The usefulness of NT proBNP in evaluating the prognosis of patients with end stage HF awaiting OHT is limited. The modMELD score is a better prognostic marker of waiting list mortality than the NT proBNP serum concentration.