bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dapagliflozin improves radial and longitudinal strain, increases pAMPK and reduces myocardial and renal NF-kB expression in preclinical models of doxorubicin cardiotoxicity through NLRP3 and Myd-88
Authors: Maurea N , Canale M L , Bisceglia I , Iovine M , Palma G , Luciano A , Bruzzese F , Barbieri M , Maurea C , Zito F , Sabetta R , Montella M , Franco R , Quagliariello V 
Published: June 2023

Abstract

Funding Acknowledgements
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ricerca Corrente, Ministero della Salute.

Background
Doxorubicin-mediated adverse cardiovascular events are among the leading causes of morbidity and mortality in breast cancer patients. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently been shown to be of therapeutic value in patients with type 2 diabetes, chronic kidney disease, and heart failure with reduced ejection fraction (HFrEF), conditions that commonly coexist and are interrelated pathophysiologically.

Purpose
We hypothesized that Dapagliflozin (an SGLT2i), administered during doxorubicin, could improve cardiac function in preclinical models.

Methods
Female C57Bl/6 mice were untreated (Sham, n=6) or treated for 10 days with doxorubicin i.p at 2.17 mg/kg (DOXO, n=6), DAPA at 12 mg/kg (DAPA, n=6) or doxorubicin combined to DAPA (DOXO-DAPA, n=6). Ejection fraction, radial and longitudinal strain were analyzed through transthoracic echocardiography (Vevo 2100). Cardiac tissue expression of NLRP3 inflammasome, Myd88, DAMPs (galectine 3 and calgranulinS100), pAMPK, NF-kB, and 13 chemokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF) were quantified through ELISA and western blot methods.

Results
DAPA improved significantly the EF and prevented the reduction of radial and longitudinal strain after 10 days of treatment with doxorubicin. A reduced expression of NLRP3, MyD88, DAMPs and NF-kB in cardiac tissues was seen in DOXO-DAPA group compared to DOXO mice (p&lt;0.001). Cardiac expression of IL-1β, IL-6, TNF-α, G-CSF and GM-CSF were significantly reduced after treatment with DAPA indicating anti-inflammatory properties. Expression of pAMPK was strongly enhanced in DAPA-DOXO compared to DOXO group. Levels of Calgranulin S100 and galectine-3 were strongly enhanced in DOXO group; on the other hand their expression were reduced by 47.7 and 52.3% in DAPA-DOXO group vs DOXO (p&lt;0.005). Hystology evaluation indicate reduction NF-kB expression in myocardial and renal tissue in DOXO-DAPA vs DOXO. Radial strain (RS) is 38.8% in DAPA-DOXO vs 14.1% in DOXO groups (P &lt; 0.05); longitudinal strain (LS) is – 23.4 % in DAPA-DOXO vs – 10.5% in DOXO groups (P &lt; 0.001).

Conclusion
In this preclinical study, DAPA is able to improve cardiac function and reduce biomarkers involved in heart failure and fibrosis. The overall picture of the study pushes the use of DAPA in prevention of cardiomyopathies induced by anthracyclines in cancer patients.
Impact of the longitudinal changes of myocardial remodeling on cardiovascular outcomes of kidney transplantation recipients
Authors: Cho D , Kang S H , Choi J M , Gwon J G , Park S M , Kim M G 
Published: June 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Kidney transplantation (KT) improves the hemodynamic burden associated with volume overload, and anemia in patients with chronic kidney disease, but cardiovascular disease remains the leading cause of death after KT. This study evaluated the longitudinal change of eccentric and concentric myocardial remodeling and its impact on cardiovascular outcomes after KT.

Methods
A total of 600 patients who underwent echocardiography before and 3 years after KT were included from a multi-center observational cohort (KNOW-KT). Conventional echocardiograph evaluated left ventricular ejection fraction (LV EF), LV mass index (LVMI) LV end-diastolic dimension (LVEDD), and relative wall thickness (RWT) at baseline and after KT, and the changes of these parameters and their effect on the cardiovascular events were investigated.

Results
After KT, LV EF, LVMI, and the myocardial eccentricity represented by LVEDD were significantly improved for 3 years (LV EF; 61.4±7.9 to 64.8±6.0 %, LVMI; 113.4 ± 31.8 to 94.4 ± 23.4 g/m2, LVEDD; 51.2 ± 5.6 to 47.1 ± 4.8 mm), however, the myocardial concentricity represented by RWT were increased from 0.39 ± 0.07 to 0.41 ± 0.07. The proportion of LV concentric remodeling significantly increased after KT compared to the baseline (Figure 1). In the correlation analysis between the change of echocardiographic and clinical parameters, the change of LVEDD was associated with change of hemodynamic stress such as hemoglobin or systolic blood pressure, whereas the change of RWT showed significant association with change of metabolic stress such as HbA1c and triglycerides. There were 30 major adverse cardiovascular events (MACE, myocardial infarction, angina, or strokes) after KT, and the incidence of MACE significantly increased in patients with the increased RWT group, but not in the increased LVEDD group after KT (Figure 2). In multivariate analysis corrected for baseline echocardiographic parameters, age, sex, diabetes, etc., an increase in RWT, independently predicted the occurrence of MACE (HR 2.20 CI 1.21–3.99, p&lt;0.01), but other echocardiographic parameters including LVEF, LVMI, and LVEDD did not.

Conclusions
Longitudinal changes in myocardial concentricity is associated with the metabolic stress and have a significant impact on the new onset cardiovascular disease in KT patients. Improving metabolic burden after KT should be considered as an important strategy for amelioration of cardiac remodeling and adverse event.
Echocardiographic myocardial stiffness for the diagnosis and tissue characterization of cardiac amyloidosis
Authors: Benz D , Sadeghi A , Rafter P , Clerc O , Canseco Neri J , Ho C Y , Cuddy S A M , Falk R H , Dorbala S 
Published: June 2023

Abstract

Funding Acknowledgements
Type of funding sources: Foundation. Main funding source(s): Swiss National Science Foundation Philips Healthcare.

Introduction
Intrinsic cardiac elastography in echocardiography estimates myocardial stiffness by measuring the propagation of the myocardial stretch generated by atrial contraction. The aims of the present study were (A) to assess its value in differentiating cardiac amyloidosis (CA) from hypertrophic cardiomyopathy (HCM) and healthy volunteers (controls), and B) to correlate it with an established marker of cardiac amyloid burden and fibrosis.

Methods
This prospective study evaluated myocardial stiffness in 52 participants with CA (n=27), HCM (n=9) and controls (n=16) by ultra-high-frame rate (above 250 frames/sec) ultrasound imaging using diverging beam mode. The slope of the isovelocity wave front was measured as the intrinsic velocity propagation of myocardial stretch (iVP, in m/s). Additionally, participants with CA and HCM underwent comprehensive transthoracic echocardiography including quantification of global longitudinal strain (GLS) by speckle-tracking imaging. The relative apical sparing (RELAPS) ratio was calculated as the average GLS of apical segments / average GLS of midventricular and basal segments. Extracellular volume (ECV) by native and post-contrast T1 mapping from cardiac magnetic resonance (CMR) was quantified in 12 participants with CA and 4 with HCM.

Results
iVP was significantly higher in CA (i.e., 2.6 m/s [1.7–3.8]) than in HCM (1.2 m/s [1.0–1.8], p = 0.001) and controls (1.4 m/s [1.3–1.5], p = 0.004) but did not differ between HCM and controls (p = 0.928; Panel A). The diagnostic accuracy of iVP to identify CA was 82% and similar to the RELAPS ratio (i.e., 84%). iVP &gt; 2.0 m/s has a sensitivity, specificity, positive predictive value and negative predictive value of 59%, 100%, 100%, and 69% to diagnose CA among the 52 participants. There was a strong correlation of iVP with ECV (rho=0.747, p = 0.001; Panel B). In contrast, iVP correlated weakly to moderately with GLS (rho=0.514, p = 0.001), RELAPS ratio (rho=0.433, p = 0.008), E/e’ (rho=0.413, p = 0.014) and NT-proBNP (rho=0.476, p = 0.006).

Conclusions
Echocardiographic myocardial stiffness is highly specific to diagnose cardiac amyloidosis and provides unique insights into myocardial tissue composition.
Early lesion visualization after catheter ablation for atrial fibrillation: rationale and preliminary results of the CALAMARI study
Authors: Guglielmo M , Rier S , De Zan G , Van Driel V , Ramanna H , Van Der Bilt I 
Published: June 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Incomplete atrial lesion is related to high atrial fibrillation (AF) recurrence after Pulmonary vein antrum isolation (PVAI).

Objectives
The CALAMARI study is a single-center, prospective, observational study with a longitudinal design. The primary aim is to assess PVAI lesion and its development over time using cardiovascular magnetic resonance (CMR). The secondary objective is to identify possible predictors of AF recurrence.

Methods
96 consecutive patients undergoing PVAI for paroxysmal AF will undergo four sequential CMR: 1) pre-PVAI CMR 2) post-PVAI CMR, immediately after the ablation 3) CMR one-day or one-week post-PVAI 4) CMR 3-months post-PVAI. Dark-blood short-inversion-time recovery (DB-STIR) will identify oedema. Pre- and post-contrast prepped inversion-recovery with long inversion time (IR-prep) and three-dimensional late gadolinium enhancement (3D-LGE) images will be used to visualize atrial lesion (AL). Qualitative and quantitative assessments of AL will be performed. Patients will be followed-up for 2 years to identify AF recurrence.

Preliminary results
Ten patients (63.1±5.7 years old, 80% male) completed a pre-PVAI CMR and a post-PVAI-CMR. The AL post-PVAI was visible in 9 patients (90%) using post-contrast IR-prep sequences and in 6 patients (60%) using pre-contrast IR-prep and 3D-LGE. Microvascular obstruction was identified in 7 (70%) patients using IR-prep-post-contrast. On DB-STIR, edema was visualized in all patients with a significant increase in the left atrium wall thickening in CMR post-PVAI vs. pre-PVAI CMR (6.4±2.9 vs. 3.4±1.5, p = 0.09).

Conclusion
Post-PVAI AL visualization with CMR is feasible in most patients. The CALAMARI study will better understand the AL modifications over time.
Functional tricuspid regurgitation after transcatheter closure of atrial septal defect
Authors: Hashimoto K 
Published: June 2023

Abstract

Funding Acknowledgements
Type of funding sources: None. Main funding source(s): none

Background
Significant functional tricuspid regurgitation (FTR) often improves during the long-term follow-up after transcatheter atrial septal defect (ASD) closure. However, the timing of TR improvement and its relationship with right ventricle (RV) reverse remodeling are unknown.

Methods
A total of 50 patients (age: mean age 58 +/- 16 years old, range:18–88; male: 66%) who underwent transcatheter ASD closure were enrolled. Echocardiography was performed at baseline, 1month and 1year after transcatheter ASD closure.

Results
TR improved significantly 1month after treatment compared to baseline, but no further significant improvement in TR severity was observed up to 1 year after treatment. Tricuspid annulus diameter decreased gradually over 1 year, while RV diameter decreased significantly at 1 month and throughout 1 year after treatment. (Figure).

Conclusion
Reverse remodeling of the RV was achieved immediately after ASD closure and continued thereafter, whereas significant improvement in TR severity was demonstrated only immediately after ASD closure. Meticulous follow-up with more intensive therapies should be considered for patients with residual significant TR after ASD closure.
Genetics, patterns of hypertrophy and fibrosis on myocardial mechanics in hypertrophic cardiomyopathy
Authors: Kim M J , Chung H M , Seo J W , Kim Y J , Park C H , Rim S J , Choi E Y 
Published: June 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Asymmetrical hypertrophy, myocyte disarray and fibrosis due to genetic cause are underlying pathology of hypertrophic cardiomyopathy (HCM). However, their contribution to myocardial functional mechanics are not extensively evaluated yet.

Purpose
In this study, we sought to investigate effects of genetic mutation, patterns of ventricular hypertrophy and fibrosis on myocardial mechanics in HCM.

Methods
In 133 patients with HCM, chamber geometry, segmental late gadolinium enhancement (LGE), extracellular volume fraction (ECV) by cardiac magnetic resonance imaging (CMR), echo-derived diastolic function analyses and genetic test were performed. Left ventricular (LV) segmental and global longitudinal strain (LS), circumferential strain (CS), and rotation were measured by feature tracking analysis of CMR.

Results
Patients with sarcomere gene mutation (SM) had lower LV-CS (global and all three slices) along with higher prevalence of midwall type LGE, LGE amount and ECV. Despite global LS was not lower in SM, anteroseptal-LS was significantly impaired accompanying with higher septal wall thickness. To compensate impaired anteroseptal LS, basal endocardial rotation was paradoxically increased in SM. Augmented basal segmental was significantly related to obstructive HCM. In apical HCM, although apical segmental LS was significantly lower, higher apical rotation and preserved apical CS along with lower prevalence of SM. The E/e’ was significantly related to LV mass index, LGE extent but not with SM.

Conclusion
Circumferential myocardial function was significantly reduced in SM independent of fibrosis extent, suggesting primary phenotype. However, longitudinal fiber function was more related to hypertrophy regardless of SM. LV diastolic function was more related to LV mass, extent and degree of fibrosis including non-thickened myocardium regardless of SM.
How should right ventricle remodeling be assessed in women and men with chronic mitral regurgitation?
Authors: Berg-Hansen C E , Urheim S , Rogge B , Kokorina M , Valeur A , Cramariuc D 
Published: June 2023

Abstract

Funding Acknowledgements
Type of funding sources: Public Institution(s). Main funding source(s): Haukeland University Hospital

Introduction
Right ventricular (RV) dysfunction has a negative impact in patients with mitral regurgitation (MR), yet its assessment by two-dimensional (2D) echocardiography remains challenging. It is unclear which echocardiographic parameter best reflects RV remodeling in chronic MR.

Purpose
To assess 2D and three-dimensional (3D) measures of RV size and function in relation to MR severity.

Methods
Patients in the 3D-PRIME (3D Echocardiography and Cardiovascular Prognosis in Mitral Regurgitation) study with moderate or severe MR by combined transthoracic/transesophageal assessment and no other severe valve disease were examined at our heart valve clinic between 2020–2022. RV remodeling was assessed in 2D by the basal diameter, tissue Doppler peak systolic velocity at the lateral tricuspid ring (RV s´), tricuspid annular plane systolic excursion (TAPSE), and RV free wall longitudinal strain (RV FWS); and in 3D by end-diastolic volume (3D RVEDV), end-systolic volume (3D RVESV), ejection fraction (3D RVEF) and fractional area change (3D RVFAC).

Results
100 patients with moderate or severe MR (54 with degenerative MR; 26 with atrial functional MR; 20 with ventricular functional MR) were included. Women (n=38) had smaller MR regurgitation volumes and RV size, similar TAPSE and RV s´, but higher 3D RVEF, 3D RVFAC and RV strain normalized for 3D RVEDV (all p &lt;0.05). More severe RV remodeling with larger volumes, and lower 3D RVFAC (all p &lt;0.05), and 3D RVEF (p = 0.05) was detected in severe MR by 3D, but not by 2D RV measures (Figure).
In ROC analyses, 3D RVESV was strongest associated with severe MR (area under curve 0.68, p &lt;0.01, Figure). In linear regression analysis, increasing 3D RVESV was associated with higher body mass index, larger MR regurgitation volume, male sex, and larger 3D left atrial volumes (R2 0.48, p &lt;0.001).

Conclusion
RV remodeling in severe MR is detected by 3D, but not by routine 2D echocardiography. The 3D RV end-systolic size best reflects MR severity.
Coronary CT angiography a new promising tool in Heart transplanted patients: from clinical and economical benefits to coronary inflammation detection
Authors: Dellino C , Cozza E , Amato F , Savo M , De Conti G , Galzerano D , Tarantini G , Tessari C , Motta R , Gerosa G , Iliceto S , Pergola V 
Published: June 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Heart transplanted patients are usually monitored with invasive diagnostic techniques for detecting cardiac allograft vasculopathy (CAV). However coronary CT angiography (CCTA) is a new promising tool in the initial stages of CAV bringing clinical and economical benefits.

Purpose
1) assess the non-inferiority of CCTA in comparison to coronary angiography (CA), in terms of radiation and contrast dose, costs, hospitalization hours, complications and diagnostic accuracy; 2) analyse the different role of immunological and non-immunological risk factors predicting CAV in patients undergoing CCTA; 3) Investigate the rule of coronary inflammation through the pericoronary-fat-attenuation-index (pFAI) at CCTA in the progression of CAV.

Methods
179 heart transplanted patients were retrospectively analysed: 78 performed a CCTA and 101 performed a CA between March 2021 and May 2022.

Results
CCTA and CA showed similar radiation doses (8.47 [1.46–30] versus 8.15 [1.38–87.34]; p = 0.796) and rate of complications (0 (0%) vs 3 (3%); p = 0,258). CCTA in comparison with CA required less hours of hospitalization (0.5 hours versus 23.7 12.31 hours; p&lt;0.001), lower costs (120 euros versus 2800 euros; p&lt;0.001) and less contrast agent (60.4 8.7 ml versus 95.68 47.6ml; p&lt;0.001). Diagnostic accuracy was similar between CCTA and CA (95% vs 100%; p = 0,169). Among the non immunological risk factors for CAV, only smoking showed a statistically significance in predicting CAV (p = 0.015). Among immunological risk factors, TNF was the only independent predictor in the progression of CAV (HR 8.23; IC 95% 1.47–45.81; p = 0.019). There were no statistically correlation between pFAI at CCTA either as a continuous variable or as a categorical variable (&gt;-70.1HU) and the progression of CAV (p = NS).

Conclusions
CCTA is similar to CA in terms of radiation dose and rate of complications and is superior in terms of hospitalization hours, costs and contrast agent injected. Diagnostic accurancy was equivalent between CCTA and CA. TNF was the only independent predictor in the progression of CAV. Pericoronary inflammation assessed by pFAI at CCTA was not associated with the progression of CAV.
Spontaneous coronary artery dissection: the role of Coronary CT angiography in the follow-up management
Authors: Dellino C , Continisio S , Montonati C , Mattesi G , Cozza E , Savo M , Galzerano D , Tarantini G , De Conti G , Motta R , Iliceto S , Pergola V 
Published: June 2023

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Spontaneous coronary artery dissection (SCAD) is one of the causes of acute coronary syndrome (ACS), myocardial infarction (MI) and sudden death (SD). Diagnosis is done with coronary angiography (CA); nevertheless, coronary computed tomography angiography (CCTA) is a new useful tool in the acute diagnosis and at follow-up. Treatment could involve a conservative approach or an invasive approach with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG).

Purpose
1) analyze the clinical and CCTA features at baseline of patients with a SCAD diagnosis; 2) evaluate the clinical and anatomic outcome at follow-up of patients with a SCAD diagnosis treated with a conservative or invasive approach; 3) evaluate in the conservative approach treated patients the clinical and anatomic outcome of those dismissed with single or double antiplatelet therapy.

Methods
A retrospective analysis of 57 patients affected by SCAD followed up with Coronary CT angiography (CCTA) between 2010 and 2022. Clinical and anatomic data were collected at baseline and at the follow-up (FU). The clinical endpoints evaluated were: all cause mortality, hospitalization for cardiovascular cause, SCAD or PCI ex-novo and MI; the anatomic endpoints were: patency of coronary artery and/or stents and length dissection changing from baseline.

Results
57 patients were divided in 2 groups: 46 (80,7%) patients underwent a conservative treatment and 11 (19,3%) patients a PCI treatment. Patients treated with PCI has a significative incidence of smokers (45,5% vs 15,2%; p = 0,042), peripherical arteriopathy (18,2% vs 0%; p = 0,034), higher troponin peak (40425,8 vs 13436; p = 0,011) and lower ejection fraction (51,4±11,0 vs 57,1±7,6; p = 0,050). Moreover the PCI population has a significant involvement of more than one coronary artery (72,7% vs 6,5%; p&lt;0,001), of the proximal tracts of the coronary arteries (22,8% vs 13 %; p = 0,001) and of the truncus communis (45,4% vs 0%; p&lt;0,001). At the follow up, there were no statistical differences for the clinical and anatomic endpoints between the conservative and invasive treated patients (p&gt;0,05). Among patients treated with conservative therapy, there were a significant recurrence of SCAD in those treated with DAPT than in those treated with SAPT (33,3% vs 5,9%; p = 0,033).

Conclusions
patients with SCAD managed with PCI have more cardiovascular risk factors, a major myocardial infarction extension and a more complex coronary arteries involvement; conservative management is comparable to the PCI treatment for the clinical and anatomic endpoints evaluated; DAPT at discharge was associated with a higher rate of SCAD recurrence at follow-up.