scholarly journals Impact of Sirolimus as a Primary Immunosuppressant on Myocardial Fibrosis and Diastolic Function Following Heart Transplantation

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Hilmi Alnsasra ◽  
Rabea Asleh ◽  
Jae K. Oh ◽  
Joseph J. Maleszewski ◽  
Amir Lerman ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Myocardial Fibrosis ◽  
Fibrosis Progression ◽  
Pulmonary Capillary ◽  
Delta Change ◽  
Myocardial Biopsies ◽  
The Impact ◽  
Wedge Pressure

Background Myocardial fibrosis is an important contributor for development of diastolic dysfunction. We investigated the impact of sirolimus as primary immunosuppression on diastolic dysfunction and fibrosis progression among heart transplantation recipients. Methods and Results In 100 heart transplantation recipients who were either treated with a calcineurin inhibitor (CNI) (n=51) or converted from CNI to sirolimus (n=49), diastolic function parameters were assessed using serial echocardiograms and right heart catheterizations. Myocardial fibrosis was quantified on serial myocardial biopsies. After 3 years, lateral e′ increased within the sirolimus group but decreased in the CNI group (0.02±0.04 versus −0.02±0.04 m/s delta change; P =0.003, respectively). Both pulmonary capillary wedge pressure and diastolic pulmonary artery pressure significantly decreased in the sirolimus group but remained unchanged in the CNI group (−1.50±2.59 versus 0.20±2.20 mm Hg/year; P =0.02; and −1.72±3.39 versus 0.82±2.59 mm Hg/year; P =0.005, respectively). A trend for increased percentage of fibrosis was seen in the sirolimus group (8.48±3.17 to 10.10±3.0%; P =0.07) as compared with marginally significant progression in the CNI group (8.76±3.87 to 10.56±4.34%; P =0.04). The percent change in fibrosis did not differ significantly between the groups (1.62±4.67 versus 1.80±5.31%, respectively; P =0.88). Conclusions Early conversion to sirolimus is associated with improvement in diastolic dysfunction and filling pressures as compared with CNI therapy. Whether this could be attributed to attenuation of myocardial fibrosis progression with sirolimus treatment warrants further investigation.

scholarly journals THE IMPACT OF SIROLIMUS AS A PRIMARY IMMUNOSUPPRESSANT ON MYOCARDIAL FIBROSIS AND DIASTOLIC FUNCTION FOLLOWING HEART TRANSPLANTATION

2021 ◽  
Vol 77 (18) ◽  
pp. 643
Author(s):  
Hilmi Alnsasra ◽  
Rabea Asleh ◽  
Jae Oh ◽  
Joseph Maleszewski ◽  
Amir Lerman ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Diastolic Function ◽  
Myocardial Fibrosis ◽  
The Impact

scholarly journals Heart Transplantation in a 14-Year-Old Boy in the Presence of Severe Out-of-Proportion Pulmonary Hypertension due to Restrictive Left Heart Disease: A Case Report

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Martin Schwienbacher ◽  
Ulrich Schweigmann ◽  
Nikolaus Neu ◽  
Elisabeth Schermer ◽  
Corinna Velik-Salchner ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Heart Transplantation ◽  
Neonatal Period ◽  
Transpulmonary Pressure ◽  
Heart Catheterization ◽  
Mitral Insufficiency ◽  
Hemodynamic Parameters ◽  
Left Heart ◽  
Pulmonary Capillary ◽  
Wedge Pressure

A 14-year-old boy after balloon valvuloplasty of severe aortic valve stenosis in the neonatal period was referred for heart-lung transplantation because of high grade pulmonary hypertension and left heart dysfunction due to endocardial fibroelastosis with severe mitral insufficiency. After heart catheterization, hemodynamic parameters were invasively monitored: a course of levosimendan and initiation of diuretics led to a decrease of pulmonary capillary wedge pressure (from maximum 35 to 24 mmHg). Instead of an expected decrease, mean pulmonary artery pressures (mPAP) increased up to 80 mmHg with increasing transpulmonary pressure gradient (TPG) up to 55 mmHg. Oral bosentan and intravenous epoprostenol then led to a ~50% decrease of mPAP (TPG between 16 and 22 mmHg). The boy was listed solely for heart transplantation which was successfully accomplished 1 month later.

P3789Circulating biomarkers of myocardial fibrosis and cellular apoptosis in patients with atrial fibrillation and heart failure with preserved ejection fraction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M S Dzeshka ◽  
E Shantsila ◽  
V A Snezhitskiy ◽  
G Y H Lip
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Angiotensin Ii ◽  
Ejection Fraction ◽  
Matrix Metalloproteinase ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Myocardial Fibrosis ◽  
Volume Index ◽  
Preserved Ejection Fraction

Abstract Introduction Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) commonly coexist. AF is associated with left atrial (LA) and ventricular (LV) myocardial fibrosis, contributing to diastolic dysfunction in HFpEF. Many profibrotic pathways have been studied in AF and HFpEF, but scarce data are available on the role of circulating microparticles (MPs). Purpose To evaluate association of circulating biomarkers of fibrosis and MPs subsets with Doppler-derived parameters of diastolic function in AF and HFpEF. Methods We studied 274 patients with non-valvular AF and HFpEF (median age 62 years, 37% females). Paroxysmal AF was diagnosed in 150 patients (55%) and non-paroxysmal AF (persistent or permanent) in 124 (45%). Median CHA2DS2-VASc score was 3 in males and 4 in females. Transthoracic echocardiography was performed to assess LV diastolic function, including early mitral inflow velocity (E), E/A velocities ratio (on sinus rhythm), early mitral annular diastolic velocity (E') for LV septal and lateral basal regions, E/E' ratio, LA maximum volume index (LAVi), E-wave velocity deceleration time (DT), flow propagation velocity (Vp). Average values from ten consecutive cardiac cycles were calculated. E/E' ratio was chosen as valid and reproducible index of diastolic function in AF patients for regression analysis. Blood levels of galectin 3, interleukin-1 receptor-like 1 (ST2), transforming growth factor beta 1 (TGF-β1), procollagen type III aminoterminal propeptide (PIIINP), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), angiotensin II and aldosterone level were assayed as surrogate biomarkers of myocardial fibrosis and profibrotic signaling. Using microflow cytometry, numbers of platelet-derived (CD42b+), monocyte-derived (CD14+), endothelial (CD144+), and apoptotic MPs (Annexin V+) were quantified in plasma samples. Linear regression was used to reveal parameters associated with diastolic function assessed as E/E' ratio. Data were normalized with Box-Cox transformation. Results Grade I diastolic dysfunction was found in 149 (54%); 94 (34%), and 31 (11%) patients had grade II and grade III diastolic dysfunction, respectively. On univariate analysis, age (β=0.23, p=0.0001); male gender (β=-0.19, p=0.02); history of hypertension (β=0.15, p=0.02); AF type, i.e. progression from paroxysmal to permanent (β=0.14, p=0.02); AnV+ MPs (β=0.19, p=0.01); angiotensin II (β=0.13, p=0.04); ST2 (β=0.1, p=0.04); and TIMP-1 (β=0.13, p=0.03) were associated with E/E' ratio. Using stepwise multivariate regression, AnV+ MPs (β=0.15, p=0.01) and TIMP-1 (β=0.3, p=0.04) remained significant predictors of E/E' ratio, adjusted for age, gender, hypertension and AF type. Relation of E/E' to TIMP-1 and AnV+ MPs Conclusion Apoptotic (AnV+) MPs and TIMP-1 were independently associated with diastolic dysfunction in AF and HFpEF. These may contribute to the pathophysiology of AF and HFpEF, and complications related to the presence of both. Acknowledgement/Funding ESC Research Grant, EHRA Academic Research Fellowship Programme

scholarly journals Interatrial Septum Motion but Not Doppler Assessment Predicts Elevated Pulmonary Capillary Wedge Pressure in Patients Undergoing Cardiac Surgery

2014 ◽  
Vol 121 (4) ◽  
pp. 719-729 ◽  
Author(s):  
Darsim L. Haji ◽  
Mohamed M. Ali ◽  
Alistair Royse ◽  
David J. Canty ◽  
Sandy Clarke ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Coronary Artery ◽  
Diastolic Function ◽  
Area Under The Curve ◽  
Interatrial Septum ◽  
Coronary Artery Surgery ◽  
Curve Pattern ◽  
Pulmonary Capillary ◽  
Fixed Curve ◽  
Wedge Pressure

Abstract Background: Left atrial pressure and its surrogate, pulmonary capillary wedge pressure (PCWP), are important for determining diastolic function. The role of transthoracic echocardiography (TTE) in assessing diastolic function is well established in awake subjects. The objective was to assess the accuracy of predicting PCWP by TTE and transesophageal echocardiography (TEE) during coronary artery surgery. Methods: In 27 adult patients undergoing on-pump coronary artery surgery, simultaneous echocardiographic and hemodynamic measurements were obtained immediately before anesthesia (TTE), after anesthesia and mechanical ventilation (TTE and TEE), during conduit harvest (TEE), and after separation from cardiopulmonary bypass (TEE). Results: Twenty patients had an ejection fraction (EF) of 0.5 or greater. With the exception of E/e′ and S/D ratios, echocardiographic values changed over the echocardiographic studies. In patients with low EF, E velocity, deceleration time, pulmonary vein D, S/D, and E/e′ ratios correlated well with PCWP before anesthesia. After induction of anesthesia using TTE or TEE, correlations were poor. In normal EF patients, correlations were poor for both TEE and TTE at all five stages. The sensitivity and specificity of echocardiographic values were not high enough to predict raised PCWP except for a fixed curve pattern of interatrial septum (area under the curve 0.89 for PCWP ≥17, and 0.98 for ≥18 mmHg) and S/D less than 1 (area under the curve 0.74 for PCWP ≥17, and 0.78 for ≥18 mmHg). Conclusion: Doppler assessment of PCWP was neither sensitive nor specific enough to be clinically useful in anesthetized patients with mechanical ventilation. The fixed curve pattern of the interatrial septum was the best predictor of raised PCWP.

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