bluuebunny/crossref_metadata_2025 huggingface dataset:
Three dimensional speckle tracking echocardiography in breast cancer patients receiving chemotherapy: incidence and clinical outcomes of subclinical right ventricular systolic dysfunction
Authors: Francisco U , Cruz-Tan M K , Cornelio G T
Published: October 2022

Background

The data about the influence of chemotherapy on right ventricular (RV) function and mechanics are scarce and conflicting. Due to the special geometric structure and unique wall motion of the RV, routine techniques for echocardiographic assessment of the RV has challenges. However, 3-dimensional echocardiography (3DE) tracks changes in RV volumes in real time, including the inflow and outflow tracts and the apex throughout the cardiac cycle. 3DE evaluation of RV function and morphology has been compared to cardiac magnetic resonance and is accurate, feasible, and reproducible

Methods

This study conducted was a retrospective cohort study which included 75 breast cancer patients who underwent chemotherapy at a tertiary hospital from January 2019 to May 2021 to determine clinical outcomes of patients among those who developed an abnormal right ventricular longitudinal free wall strain and global longitudinal strain in terms of all-cause mortality, development of overt right ventricular systolic dysfunction, and adverse cardiovascular events.

Results

There was a striking statistically significant difference in terms of right ventricular ejection fraction among those who developed an abnormal right ventricular global longitudinal strain at 6 and 12 months post-chemotherapy with a p-value of 0.001 and 0.000 respectively. The difference between the 2 groups of patients in terms of right ventricular global longitudinal strain 6 and 12 months after chemotherapy was also statistically significant (p=0.000). As for the left ventricle, the LV ejection fraction and global longitudinal strain were also statistically significantly different at 12 months post-chemotherapy. Among those who developed an abnormal RV global longitudinal strain, the LV global longitudinal strain was also subsequently lower compared to the normal subgroup at 12 months post-treatment.

Conclusion

Although the sample size was small, the development of abnormal RV GLS post-chemotherapy was generally associated with subsequent development of overt heart failure, increased all-cause mortality, and CV death. The use of echocardiographic RV GLS surveillance to guide chemotherapy is crucial to enhance clinical outcomes and survival.

Funding Acknowledgement

Type of funding sources: None.
Sequential assessment of cardiac function after CART therapy in accordance with the grade of CRS
Authors: Sunayama I , Min K , Orihara Y , Yoshihara S , Yoshihara K , Matsumoto Y , Nishimura K , Naito Y , Goda A , Tamaki H , Higasa S , Asakura M , Ishihara M
Published: October 2022

Introduction

As Chimeric Antigen Receptor T-cell (CAR-T) therapy gains its clinical advantage in the management of diffuse large B cell lymphoma (DLBCL), accumulating evidence shows that it often accompanies cardiac dysfunction. Previous retrospective studies indicated the potential involvement of cytokine release syndrome (CRS) in cardiac dysfunction after CAR-T therapy, but no prospective study has reported the time course of cardiac dysfunction. Moreover, the relationship between the severity of CRS and cardiac dysfunction after CAR-T therapy remains unclear.

Purpose

The objectives of this study are to prospectively examine the sequential changes in cardiac markers overtime after CAR-T therapy and to clarify the association between the grade of CRS and cardiac markers.

Methods

In this prospective observational study, 30 DLBCL patients who underwent CAR-T therapy from July 2020 to March 2022 were enrolled. Before and after the treatment, the level of cardiac biomarkers and echocardiographic index were sequentially collected. We classified all patients into two groups according to the severity of CRS after CAR-T therapy, namely low-CRS group (CRS <2) and high-CRS group (CRS ≥2). Cardiac biomarkers and echocardiographic parameters were further analyzed in both groups.

Results

The average age of participants was 59.6 years, and 9 patients (30%) were female. The average duration of DLBCL was 2.7 years. The CRS showed its peak severity on day 3. The number of patients in low- and high-CRS group was 13 and 17, respectively and tocilizumab was administrated for 46% and 71% of the patients in low- and high-CRS group, respectively. At the baseline before CAR-T therapy, there were no significant differences in cardiac parameters between the two groups. During the follow-up, sequential measurements of cardiac biomarkers revealed that high-CRS group showed significantly higher NT-proBNP level compared to that of low-CRS group (NT-proBNP; 90pg/ml vs. 623pg/ml, p=0.0001, respectively) and both had their peak on day 3, whereas troponin T level did not show any differences. Likewise, sequential measurements of echocardiographic parameters revealed that high-CRS group showed significantly increased E/A compared to low-CRS group on day 7 (E/A; 0.77 vs. 0.90, p=0.021, respectively), but not in the later phase. The parameters for systolic function including GLS and EF and parameters for diastolic function such as E/e' and LAVI did not alter among the two groups throughout the follow-up.

Conclusion

In the patients who underwent CAR-T therapy for DLBCL, the elevation of NT-proBNP level and increase in E/A was transiently observed within a week and correlated with the severity of CRS.

Funding Acknowledgement

Type of funding sources: None.
Use of emgliflozine in cardiotoxicity treatment. EMPACARD-treatment registry. Six-months follow-up
Authors: Daniele A J , Gregorietti V , Costa D , Lopez-Fernandez T
Published: October 2022

Background

Despite improvements in cancer management, cancer treatment related cardiac dysfunction (CTRCD) is a growing medical problem that impact cancer patients' prognosis, especially when it leads to early interruptions of effective anticancer therapies. Heart failure (HF) therapies are recommended in patients who develop symptomatic CTRCD or asymptomatic decrease in left ventricular ejection fraction (LVEF). However, the beneficial effect of sodium-glucose co-transporter 2 (SGLT2) inhibitors was not prospectively tested in patients with cancer and CTRCD

Purpose

EMPACARD-treatment is a prospective registry aiming at evaluating the usefulness of empagliflozin on left ventricular remodelling in patients with metastatic breast cancer and refractory CTRCD.

Methods

Metastatic breast cancer patients, who develop refractory CTRCD during or after anthracycline chemotherapy and/or HER2 targeted therapies were prospectively included in our study and treated with empagliflozin 10mg/day on top of their current HF therapies. Refractory CTRCD was defined as symptomatic HF in patients treated with optimal doses of neurohormonal HF therapies, including sacubitril/valsartan. Clinical and echocardiographic variables were analysed to determine the potential benefits of empagliflozin on left ventricular remodelling (LVEF and left ventricular diastolic diameter (LVDD)), NT-proBNP levels, NHYA class and 6 minutes walking test (6MWT). The median follow-up was 6 months.

Continuous variables were summarized as medians with interquartile ranges (IQR) and compared with Wilcoxon's test for paired samples. Categorical values were expressed as percentages and compared with the chi-squared test. Statistical significance was considered with a p-value of less than 0.05. All analyses were performed with R version 4.1.1.

Results

19 metastatic breast cancer patients were included. Baseline characteristics and HF treatments are described in table 1. One patient received a heart transplant, and there were no deaths. At 6 months follow up LVEF significantly improved from 30% (IQR 27.5–32) to 38% (IQR (33.5–39), (p<0.001), NT-proBNP decreased from 1342 pg/ml (IQR (977–1756) to 784 pg/ml (IQR 641–1099.5) (p<0.0001), and similar improvements were observed in LVDD and 6MWT (Table 2). NYHA functional class improved in 95% of patients from class III to I or II at 6 months follow-up (p<0.003).

Conclusions

Guideline-based HF therapy, including empagliflozin improves LV remodelling in patients with cancer and refractory CTRCD. Empagliflozin might be a promising treatment option in patients with refractory CTRCD

Funding Acknowledgement

Type of funding sources: None.
HFA-ICOS cardiovascular toxicity risk score validation in CARDIOTOX registry
Authors: Rivero Santana B , Caro Codon J , Juarez Olmos V , Martinez Monzonis A , Zatarain-Nicolas E , Moliner P , Cadenas Chamorro R , Severo Sanchez A , Valbuena Lopez S , Zamora Aunon P , Gomez Prieto P , Gonzalez Juanatey J R , Lopez-Sendon J , Lopez De Sa E , Lopez-Fernandez T
Published: October 2022

Background

Cancer therapy-related cardiovascular toxicity (CTox) is a growing medical problem and baseline cardiovascular (CV) risk assessment is recommended in all patients scheduled to receive potentially cardiotoxic cancer therapy. Based on literature review, the Heart Failure Association (HFA) Cardio-Oncology working group and the International Cardio-Oncology Society (ICOS) proposed a risk score to predict CTox but, it has not been validated.

Purpose

To validate the HFA-ICOS anthracycline risk assessment score in the CARDIOTOX registry cohort (NCT02039622).

Methods

The CARDIOTOX registry is a prospective multicenter study aiming at identifying factors related with CTox and assessing the utility of clinical, biochemical, and echo parameters for the early detection of CV disease during and after cancer therapy. A total of 1324 adult patients were prospectively included from April 2012 to October 2017. Data was collected at baseline, 3 weeks and 3, 6, 12, 18 and 24 months after initiation of treatment. Clinical follow-up was extended until January 2020. All patients receiving anthracycline chemotherapy were stratified according to HFA-ICOS risk score and Kaplan-Meier survival curves were analyzed to estimate the risk of all-cause mortality and anthracycline chemotherapy-related CV complications defined by HFA-ICOS risk score (left ventricular dysfunction (LVD), heart failure (HF) and arrhythmias).

Results

A total of 1066 patients were included in the analysis. Baseline characteristics are summarized in table 1. 571 patients (53.6%) meet low, 333 (31.2%) medium, 152 (14.3%) high and 10 (0.9%) very-high HFA-ICOS CTox risk criteria. 197 patients (18.4%) died of any cause during follow-up. CV death occurred in 4 patients (2%), all caused by HF. Any degree of CTox was identified in 519 (48.7%) patients during the 110 months follow-up (73 (6.8%) developed clinical HF/HF hospitalization, 29 (2.7%) asymptomatic LVEF <50%; 27 (2.5%) clinically relevant arrhythmias and 390 (36.6%) an asymptomatic increase in cardiac biomarkers or a relative decrease in GLS>15%). Figures 1A and 1B showed the cumulative mortality rate and CTox rate during follow-up. CTox and all-cause mortality rates increased significantly according to the estimated baseline HFA-ICOS score.

Conclusions

HFA-ICOS risk score categorizes patients according to their risk of developing anthracycline chemotherapy-related CTox, showing a good ability to predict both all-cause mortality and CTox.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Instituto de Salud Carlos III (PI13/00559).
Prognostic impact of coronary artery calcifications in patients with newly diagnosed prostate cancer
Authors: Stoedkilde-Joergensen N , Bugge Tinggaard A , Winther S , Ejlersen J A , Boettcher M
Published: October 2022

Background

Patients diagnosed with prostate cancer (PCa) are known to be at increased risk of cardiovascular events. Because of the ageing population and better cancer treatment, the number of these patients is increasing. A prostate-specific membrane antigen positron emission tomography (PSMA-PET) is guideline recommended as part of the diagnostic workup. This scan includes a non-ECG-gated computed tomography (CT) of the thorax, allowing assessment of coronary artery calcifications (CAC). It is not well-established, whether estimation of CAC based on this CT scan can identify patients with increased risk of major adverse cardiac events (MACE) and thus possibly improve therapy and prognosis.

Purpose

This study aims to assess CAC and evaluate whether high calcium scores predict the risk of MACE in patients newly diagnosed with PCa.

Methods

We identified 634 consecutive patients diagnosed with PCa and undergoing PSMA-PET from 2016 to 2019 in an area of 300.000 residents. In total, 63 patients were excluded due to prior revascularization. The remaining 571 patients (mean age 69.9±6.7 years) were included. Patients were followed until June 2021 or until an event occurred (mean follow-up 962±372 days). We used a standard cardiac CT software to assess CAC. Information on MACE defined as all-cause mortality, stroke and myocardial infarction were obtained from electronic patient files. We divided patients into five groups based on their coronary artery calcium score (CACS): 0–10, 11–99, 100–399, 400–999, and + 1000. Cox regression analysis was used to compute the hazard ratios (HR) for MACE with CACS 0–10 as reference while adjusting for age, hypertension diabetes, and treatment with aspirin and statins.

Results

We found a significantly increasing risk of MACE with increasing CACS after adjustment for risk factors. For CACS 100–399 (n=136): HR 2.10 (95% CI: 0.98–4.51, p=0.056), for CACS 400–999 (n=79): HR of 2.99 (95% CI: 1.35–6.59, p=0.007) and for CACS +1000 (n=150): HR 3.06 (95% CI: 1.37–6.85, p=0.006) (Figure 1). Cardiovascular disease prevention treatment with statins and aspirin was 53% and 16% in patients with CACS 400–999 and 52% and 19% in patients with CACS + 1000.

Conclusion

In patients with PCa, estimating coronary calcium score based on non-ECG-gated CT scans, which are performed as part of the diagnostic workup, predicts the occurrence of MACE. In the patient group with the highest CAC, a four-year event rate of 24% was found. In combination with the finding of infrequent use of statin and aspirin, this emphasizes the possibility of early detection of high CAC in patients with PCa and illustrates the potential for more extensive use of preventive treatment. Future studies should investigate the effect of preventive treatment being initiated in patients with PCa and high CAC.

Funding Acknowledgement

Type of funding sources: None.
Pregnancy outcomes in women with Ebstein's anomaly: data from the EORP Registry of Pregnancy and Cardiac Disease (ROPAC)
Authors: Van Der Zande J A , Tutarel O , Ramlakhan K P , Johson M R , Hall R , Roos-Hesselink J W
Published: October 2022

Background

Ebstein's anomaly is a rare congenital cardiac condition characterized by displacement of the posterior and septal leaflets of the tricuspid valve towards the apex of the right ventricle. The ESC Guidelines for the management of cardiovascular diseases during pregnancy categorize women with uncomplicated Ebstein's anomaly as modified World Health Organization (mWHO) risk class II. However, data regarding pregnancy outcomes in women with Ebstein's anomaly are scarce.

Purpose

To evaluate the maternal and perinatal risks of pregnancy in women with Ebstein's anomaly.

Methods

All patients with Ebstein's anomaly who had been included in the Registry of Pregnancy and Cardiac Disease (ROPAC), which is an international, prospective, observational registry of pregnant women with underlying cardiac disease (n=5739), were evaluated. The primary outcome was the occurrence of a major adverse cardiac event, defined as maternal mortality, heart failure, arrhythmia, thromboembolic events or endocarditis. The secondary outcomes were obstetric and perinatal outcomes and the influence of pregnancy on tricuspid valve regurgitation.

Results

Thirty-six hospitals in 22 countries enrolled 81 women with Ebstein's anomaly (mean age 29.7 years, 46.9% nulliparous). Seven (8.6%) women had a history of tricuspid valve repair and a further eight (9.9%) of tricuspid replacement. Most women (67.9%) were in NYHA class I. At least one major adverse cardiac event occurred in 8 (9.9%) pregnancies, including heart failure (n=6), supraventricular arrhythmia (n=3) and thromboembolic events (n=2). There was no maternal death. Almost half of the women underwent a Caesarean section (49%) and preterm delivery occurred in 24.7%. Neonatal mortality was 2.5% and four (4.9%) infants had neonatal congenital heart disease. Serial echocardiographic data pre- and postpregnancy were available in 14 women. There was no clear deterioration in tricuspid regurgitation (see Picture 1).

Conclusion

Although mortality was zero, in 10% of the pregnant women with Ebstein's anomaly a major adverse cardiac event occurred, most frequently heart failure or arrhythmia. Therefore, women with Ebstein's anomaly should be categorized as mWHO risk class II at least, but perhaps more correctly as II–III. Preconception counseling is crucial, so that women are aware of the potential risks of maternal morbidity, preterm delivery and congenital heart disease and the need for careful monitoring during pregnancy.

Funding Acknowledgement

Type of funding sources: None.
A nationwide cohort study on the impact of gestational diabetes on future cardiovascular events
Authors: Bullough S , Lip G Y H , Fauchier G , Herbert J , Sharp A , Bisson A , Ducluzeau P H , Fauchier L
Published: October 2022

Background

The link between hypertensive disease in pregnancy and future cardiovascular events is well established, as is the increased risk of developing type 2 diabetes mellitus after gestational diabetes (GDM). What is less well understood is the impact of GDM on future cardiovascular events. The literature is conflicting although suggestive that the risk of cardiovascular events with a history of GDM is 2 fold higher.

Purpose

Using the largest cohort to date and utilising robust data acquisition procedures and follow up we assessed the prognostic value of GDM for future cardiovascular events.

Methods

All female patients discharged from French hospitals in 2013 with at least 5 years of subsequent follow-up were identified. Those with a previous major adverse cardiovascular event, history of hypertensive disease, pre-existing diabetes or under the age of 18 years old were excluded. They were grouped depending on their history of GDM. After propensity score matching, patients with GDM were matched 1:1 with patients with no GDM. Hazard ratios for cardiovascular events during follow-up were adjusted by age at baseline.

Results

A total of, 1,738,101 women were included in the analysis, leaving 1,141,743 women (mean age 52.2, SD 19.7) once exclusion criteria were applied: 6998 (0.6%) had a history of GDM and the mean follow-up was 5.1 years (SD 1.3 years). Those with a history of GDM had a lower risk of new onset heart failure (HF) (hazard ratio [HR] 0.66, 95% confidence interval [CI]: 0.45–0.98) and all-cause death (HR 0.61, 95% CI 0.47–0.79). There was no significant difference in risk for myocardial infarction (HR 0.88, 95% CI 0.38–2.03), ischaemic stroke (HR 0.94, 95% CI 0.55–1.63), new onset atrial fibrillation (AF) (HR 0.61, 95% CI 0.33–1.11), cardiovascular death (HR 1.25, 95% CI 0.47–3.36) and major cardiovascular events (i.e. in-hospital cardiovascular death, myocardial infarction, ischaemic stroke or new-onset HF (MACE-HF)) (HR 0.75, 95% CI 0.56–1.01).

Conclusions

In a large contemporary analysis of female patient seen in French hospitals and utilising a robust data set we present the largest population analysis of the association between GDM and future cardiovascular events. Those with a history of GDM do not have a higher risk of myocardial infarction, ischaemic stroke, new onset AF, cardiovascular death or MACE-HF. Contrary to what is widely thought, a history of GDM confers a lower risk of new onset HF and all-cause death when compared to those women with no history of GDM.

Funding Acknowledgement

Type of funding sources: None.
A prediction model for aberrant cardiac remodelling in women after preeclampsia; Queen of Hearts study
Authors: Mohseni-Alsalhi Z , Janssen E B N J , Delmarque J , Van Kuijk S M J , Spaanderman M E A , Ghossein-Doha C
Published: October 2022

Background

Preeclampsia, a hypertensive pregnancy disorder, is strongly associated with aberrant left ventricular remodelling up to ten years after delivery and heart failure later in life. To detect occult cardiac abnormalities, echocardiography is necessary but not feasible for all these women. A prediction model for aberrant cardiac remodelling to be used in primary care may guide towards intensified follow-up for those at risk or tempered follow-up for low-risk individuals.

Purpose

To develop a prediction model for aberrant left ventricular remodelling in former pregnant women weighing their complicated pregnancy.

Methods

In this large cohort study, we included women (aged ≥18 years) with a history of preeclampsia or normotensive pregnancy at a postpartum interval of 6 months until 30 years. Comprehensive cardiovascular assessment was performed, including echocardiography, 30-minutes blood pressure measurements and circulating biomarkers. The procedures were in accordance with institutional guidelines and adhered to the principles of the Declaration of Helsinki. Aberrant cardiac remodelling based on echocardiography was defined as either left ventricular concentric remodelling or left ventricular hypertrophy. A prediction model based on clinical and circulating markers was developed using univariable and multivariable logistic regression with backward elimination. Internal validation was performed using Heuristic shrinkage factor. Performance of the final model was evaluated in terms of discrimination by the area under the receiver operating characteristic (AUC-ROC) curve.

Results

We included 1466 women, of which 93 (6.3%) with left ventricular concentric remodelling and/or left ventricular hypertrophy (mean ± SD age, 43±10 years) and 1373 (93.7%) without left ventricular concentric remodelling and/or left ventricular hypertrophy (40±8 years). The final prediction model was based on the predictors age, waist circumference, systolic blood pressure, Homeostatic Model Assessment of Insulin Resistance (HOMAIR), and preeclampsia (y/n) (Table 1). After internal validation, this prediction model showed a good discriminative ability of AUC-ROC-curve 0.71 (95% CI 0.661–0.758) (Figure 1).

Conclusion

We developed a good-performing prediction model for aberrant cardiac remodelling in former pregnant women based on five conventional variables that could contribute to risk-guided follow-up after preeclampsia aiming at intensifying follow-up for those at risk and tempered follow-up for low-risk women.

Funding Acknowledgement

Type of funding sources: None.
Outcomes in pregnant women with valvular heart disease from sub Saharan Africa transferred to a developed nation. A distinct care model
Authors: Ferreira V , Garcia Bras P , Castelo A , Santos A , Viveiros A , Ilhao Moreira R , Machado A I , Alves M , Cruz Ferreira R
Published: October 2022

Background

Pregnant women with valvular heart disease (VHD) in African countries still bear a disproportionate burden of maternal morbidity and mortality, due to the reduced accessibility to health care and the scarcity of skilled professionals. It is unclear if outcomes would be improved by care-delivery model changes.

Purpose

We performed a clinical audit of African pregnant women with VHD who were transferred for their care from five countries to our cardio-obstetrics unit, during a twenty-year period, through a memorandum of agreement of international cooperation.

Methods

A retrospective analysis of 81 pregnancies (P) in 45 African women with VHD (median age 24, IQR 22–29 years) from 2001 to 2020. The main outcome measures were major maternal complications and perinatal outcome.

Results

History of rheumatic heart disease was determined in 74.1% of the P. Most women were in NHYA I or II before P (79.0%), 43.2% had previous cardiac medication and 60.5% were anticoagulated (33.3% with acenocoumarol and 27.2% with warfarin). 59.3% of P had at least one valvular prosthesis, including 38 mechanical prosthetic valve (MPV) and 10 biological valves. 22.2% had prior surgical or percutaneous VHD correction, excluding prosthesis implantation. At baseline, impaired left ventricular ejection fraction was found in 12.3%. Previous arrhythmic event, stroke or infectious endocarditis were found in 12.3%, 8.6% and 6.2% of P, respectively.

During P, deterioration in NYHA functional class occurred in 42.0% and 9.9% required initiation or intensified cardiac medication. For MPV, 51% maintained a vitamin K antagonist, 15.7% used LMWH from 6 to 12th weeks and 9.8% used LMWH throughout P. Valve thrombosis occurred in 4 women (4.9% of P), with one maternal death in a patient with double MPV.

Hemorrhagic complications happened in 8.6% of P, all anticoagulated, in immediate postpartum or puerperal period. The 81 P resulted in 56 live births (69.1%), with a medium birth weight of 3026±471g. Delivery by caesarean section was performed in 28.3% of newborns. The incidence of miscarriage was 23.5% and fetal malformations occurred in 14.8%, with warfarin embryopathy in 4 cases. In univariate analysis, the presence of valvular protheses (p=0.001), and anticoagulation (p=0.001) were related to unsuccessful P. In multivariate analysis, VKA therapy was the unique independent predictor of unsuccessful P (p=0.048).

Conclusion

With the multidisciplinary care provided, pregnancy was relatively well tolerated and successful for women transferred from sub–Saharan Africa. However, the presence of a valvular prothesis is associated with unsuccessful pregnancy even in a developed nation. Efforts other than the implantation of a MPV should be pursued vigorously in sub Saharan Africa.

Funding Acknowledgement

Type of funding sources: None.
Left ventricular morphology in patients with aortic coarctation and bicuspid aortic valve: novel insights from a statistical shape modelling framework
Authors: Sophocleous F , Standen L , Doolub G , Laymouna R , Bucciarelli-Ducci C , Caputo M , Manghat N , Hamilton M , Curtis S , Biglino G
Published: October 2022

Background

The functional implications of left ventricular (LV) morphological characterization in congenital heart disease (CHD) are not widely explored.

Purpose

This study qualitatively and quantitatively assessed LV shape associations with a) LV function and b) thoracic aortic morphology in patients with aortic coarctation (CoA) with/without bicuspid aortic valve (BAV).

Methods

A statistical shape modelling (SSM) framework was employed to analyse three-dimensional (3D) LV shapes from cardiac magnetic resonance (CMR) imaging data in n=110 cases including: isolated CoA (n=25), CoA+BAV (n=30), isolated BAV (n=30), and age-matched healthy controls (n=25). Average 3D templates (Picture 1) and deformations were computed. Correlations between shape data and CMR-derived morphometric parameters (i.e. sphericity, conicity) as well as CMR-derived global and apical strain values were assessed to elucidate possible functional implications. The relationship between LV shape features and arch architecture (i.e. gothicity, tortuosity) was also explored by means of regression analysis.

Results

The LV template was shorter and more spherical in CoA patient (Picture 1), as also confirmed by statistical analysis of the SSM-derived shape modes. LV sphericity, which was higher in CoA, was associated (p≤0.04) with lower global longitudinal, radial and circumferential strain, irrespective of the presence of aortic stenosis and/or regurgitation. Conversely, neither LV morphology nor LV strain was not associated with arch architecture.

Conclusions

Differences in LV morphology were observed between CoA and BAV patients. Increasing LV sphericity was associated with reduced strain, independent of aortic arch architecture and functional aortic valve disease.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): British Heart Foundation and NIHR BRC
Impact of lifetime concentration of mannose on renal function: insights from Mendelian randomization
Authors: Mazidi M , Shekoohi N , Katsiki N , Banach M
Published: October 2022

Background

Mannose is a sugar monomer of the aldohexose series of carbohydrates, important in human metabolism, especially in the glycosylation of certain proteins. There is a handful of controversial data from observational studies on the serum levels of mannose and risks of renal disease.

Purpose

We performed a Mendelian Randomization (MR) analysis to obtain unconfounded estimates of the casual associations between genetically instrumented serum mannose, estimated glomerular filtration rate (eGFR) and the risk for chronic kidney disease (CKD defined as eGFR <60 ml/min/1.73 m2).

Methods

MR was implemented by using summary-level data from the largest ever genome-wide association studies (GWAS) conducted on serum mannose and renal function. Inverse variance weighted method (IVW), weighted median (WM)-based method, MR-Egger, MR-Robust Adjusted Profile Score (RAPS), MR-Pleiotropy RESidual Sum and Outlier (PRESSO) were also applied. Sensitivity analysis was conducted using the leave-one-out method. The analyses were performed in the total population, in non-diabetics and in patients with type 2 diabetes mellitus (T2DM).

Results

Serum mannose concentrations were not significantly associated with CKD risk (IVW: beta=1.018, p=0.273), but they were negatively related to eGFR in the total population (IVW: beta=−0.137, p=0.003), the non-diabetics (IVW: beta=−0.126, p=0.018) and the T2DM patients (IVW: beta=−0.344, p=0.004). None of the MR-Egger estimates showed heterogeneity, and the MR-PRESSO analysis did not find any possibility of outliers for all of the estimates. The pleiotropy test also indicated a low chance of pleiotropy for all estimations (p>0.242), as did the MR-RAPS analysis. Leave-one-out method demonstrated that the observed associations were not driven by single-nucleotide polymorphisms.

Conclusions

Our results highlighted that individuals with genetically higher serum mannose levels have a significantly lower eGFR, regardless of the presence or absence of T2DM. However, no association between serum mannose concentrations and the risk of CKD was observed.

Funding Acknowledgement

Type of funding sources: None.
Impact of sodium-glucose co-transporter 2 inhibitors on cardiovascular outcomes in patients with chronic kidney disease: Hong Kong-wide, observational, propensity score matched analysis
Authors: Sun W , Yan B
Published: October 2022

Purpose

The impact of SGLT2i on patients with advanced chronic kidney disease (CKD) is limited. We aimed to compare hospitalization for heart failure (HHF) and cardiovascular (CV) death between new users of SGLT2i versus non-users across the spectrum of CKD stages.

Methods

We retrospectively analyzed 22,657 patients with CKD who were prescribed SGLT2i between August 2015 and August 2020 in 16 public hospitals in Hong Kong. Propensity-matched cohorts of SGLT2i users and non-users (n=3,704 per group) were generated on the basis of age, gender, baseline eGFR, co-morbidities and medications. Time to HHF and CV death was analyzed using COX proportional hazards model. Subgroup analysis was performed to detect heterogeneity of effect across stages of CKD.

Results

Of the whole cohort (N=22,657), the percentage of SGLT2i users in CKD stage G1 to G5 were 82.1%, 49.0%, 19.8%, 10.3%, 4.3%, and 1.6%, respectively. SGLT2i users and non-users groups were well balanced at baseline (mean age 64.7±12.7, female 37.1%), with a median follow-up of 2.8 (IQR: 1.1–5.1) years (22876.5 person-years). Overall, SGLT2i was associated with reduced risk of HHF (Hazards Ratio (HR) 0.12 (95% CI (0.10–0.16) and CV death (HR 0.17 (95% CI (0.12–0.25), compared with non-users. Subgroup analysis demonstrated benefit of SGLT2i on CV death in G3 to G5 groups but not in patients in earlier CKD stages (P for interaction <0.001) (Table). Reduction in risk of HHF was comparable across all CKD stages (P for interaction = 0.1).

Conclusion

Utilization of SGLT2i was associated with significant reduction in HHF and CV death in patients with moderate to severe CKD in a real-world setting. Our results suggest significant heterogeneity in CV death reduction with the largest benefit in patients with stage G3a and more advanced CKD.

Funding Acknowledgement

Type of funding sources: None.
CAD in kidney transplant recipients: a real-world assessment pre-ISCHEMIA-CKD
Authors: Rocha B , Amador R , Maltes S , Cunha G , Mateus C , Aguiar C , Weigert A , Mendes M
Published: October 2022

Background

The ISCHEMIA-CKD trial has shown that an initial invasive strategy, as compared to conservative treatment, did not reduce the risk of death and non-fatal myocardial infarction, nor did it improve quality-of-life in patients with advanced chronic kidney disease (CKD) and coronary artery disease (CAD) with moderate-to-severe ischemia. Similar findings were reported in patients with CKD enlisted for kidney transplantation (KT). We aimed to evaluate screening and treatment CAD strategies in patients who ultimately underwent KT at our center.

Methods

This is a single-center study of consecutive patients who received a KT from 2015 to 2020. Obstructive CAD was defined whenever one of the following criteria was met: lesion with a stenosis >70% (or >50%, if left main disease) or CAD requiring revascularization, as per the Heart Team discussion. CAD evaluation refers to non-invasive or invasive coronary angiography and/or stress testing, irrespective of clinical scenario.

Results

A total of 324 patients underwent KT [mean age 55±12 years; 65.1% male; CKD most often due to hypertensive or diabetic nephropathy and polycystic kidney disease – 41.8%; median time from renal replacement therapy (RRT) to KT – 60 (40–88) months]. A flow-chart summarizing CAD diagnosis over time is depicted in Figure 1. Overall, 119 (36.7%) patients had CAD evaluation prior to KT, of whom 21 underwent myocardial revascularization – 8, 12 and 1 patients with acute coronary syndrome (ACS), chronic coronary syndrome (CCS) and silent ischaemia, respectively. At a median time of 46 (25–66) months after KT, 36 (11.1%) more patients had CAD evaluation, of whom 8 underwent percutaneous myocardial revascularization – 6 and 2 for ACS and CCS, respectively. Those with obstructive CAD were older (64 vs 54 years-old; p<0.001), with a higher burden of cardiovascular (CV) risk factors (p<0.001) and more likely to have had a CV death (9.5 vs. 1.0%; p=0.025) or CV hospitalization (38.1 vs. 13.4%; p=0.007). CAD status (revascularized vs. non-revascularized) was not associated with improved major outcomes at follow-up. We found no strong predictors of CAD requiring revascularization post-KT, including time from RRT to KT. There were no patients with refractory angina, left main disease or reduced left ventricular ejection fraction (<40%) in need of myocardial revascularization over follow-up.

Conclusions

Obstructive CAD was uncommon in our cohort of patients who received a KT, most of whom with asymptomatic or mildly (monthly angina) symptomatic CCS or non-fatal ACS. These findings, together with the most recent evidence, may argue against routine CAD screening in all patients being enlisted for KT. Notwithstanding, randomized evidence is eagerly awaited to further guide treatment decisions in the post-ISCHEMIA-CKD era.

Funding Acknowledgement

Type of funding sources: None.
The difference in prognostic value between high-sensitive cardiac troponin T and I for long-term major adverse cardiovascular events in hemodialysis patients
Authors: Wongcharoen W , Ratnachina K , Noppakun K , Phrommintikul A
Published: October 2022

Background

Previous studies using conventional cardiac troponin (cTn) assays have shown conflicting results in the predictability of major adverse cardiovascular events (MACEs) in hemodialysis patients.

Objective

We aimed to evaluate the prognostic values of high-sensitivity cTnT (hs-cTnT) and hs-cTnI assays for long-term MACEs in asymptomatic chronic hemodialysis patients.

Methods

A total of 198 asymptomatic patients undergoing regular hemodialysis (mean age 62.4±14.8 years) were enrolled in this study. Pre-dialysis hs-cTnT and hs-cTnI levels were measured at the time of study entry. The primary outcome was the prognostic value of hs-cTnT and hs-cTnI for all-cause mortality.

Results

At baseline, the median values of hs-cTnT and hs-cTnI were 61.1 ng/L (IQR 36.6–102.0 ng/L) and 18.4 ng/L (IQR 9.5–36.6 ng/L), respectively. During a median follow-up period of 408 days (IQR 343–415 days), 35 (17.7%) patients developed MACEs, and 20 (10.1%) patients died. The patients with hs-cTnT level above the highest quartile (>102 ng/L) had an increased risk of all-cause mortality (HR 3.34; 95% CI 1.39–8.04, P=0.007) and MACEs (HR 1.99; 95% CI 1.00–3.96, P=0.049), compared to those with lower hs-cTnT level. The association between hs-cTnT and all-cause mortality remained significant after adjustment for age, gender, and comorbidities. On the contrary, hs-cTnI level was not associated with long-term all-cause mortality and MACEs.

Conclusions

We demonstrated that level of hs-cTnT, but not hs-cTnI, was associated with higher risk of long-term mortality and MACEs. As a result, hs-cTnT may be a better prognostic factor than hs-cTnI in this population.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Faculty of Medicine Endowment Fund for medical research
Cardiac involvement in creatine deficiency syndrome
Authors: Del Franco A , Battini R , Kusmic C , Forini F S , L'Abbate S , Masotti S , Musetti V , Borrelli C , Barison A , Emdin M , Vergaro G
Published: October 2022

Background

Previous reports have demonstrated electrocardiographic and echocardiographic abnormalities consistent with early-stage cardiomyopathy in patients with creatine transporter (CrT) deficiency, but cardiac involvement has never been accurately characterized.

Purpose

To investigate the cardiac phenotype associated with creatine deficiency in a murine transgenic model and in patients with creatine deficiency syndrome (CDS).

Methods

Wild type and transgenic CrT−/y mice (n=20) were serially evaluated in vivo by electrocardiogram (EKG) and echocardiography for six months, and ex vivo by histological and biochemical analyses. Nine patients with CDS (n=4 with L-arginine:glycine amidinotransferase - AGAT- deficiency, n=5 with CrT deficiency) underwent blood samples, including cardiac biomarkers, EKG, Holter monitoring, echocardiography and cardiac magnetic resonance (CMR).

Results

Compared to wild type, CRT−/y mice showed a prolongation of QT interval (p=0.008) (Fig. 1), as well as significant reduction in cardiac ATP production from mitochondria (p<0.001) (Fig. 2). No differences were detected in the left ventricular systolic function, in terms of ejection fraction and global longitudinal strain, along the whole follow-up. Similarly, 3 patients with CrT deficiency also showed a prolonged QTc interval (median QTc 515 ms), while other 2 had a borderline QTc at Holter monitoring, while no tachyarrhythmias could be observed. No subject had abnormal systolic and diastolic function. At CMR, an increase of native T1 value was reported in the 4 subjects (median 1076 ms) with AGAT deficiency, 1 with an increase of extracellular volume matching with the detection of late gadolinium enhancement. Finally, subjects with AGAT deficiency showed an increase level of plasma norepinephrine. Familiar carriers (3 for AGAT and 1 for CrT) showed no notable cardiac functional alterations, except for QTc prolongation in 2 subjects.

Conclusion

Prolonged QT interval is observed in the murine model and in subjects with CrT deficiency. Biohumoral signs of neurohormonal activation and an initial replacement fibrosis – the latter suggested by the increase of native T1 – are identified in subjects with AGAT deficiency, but their clinical significance remains to be determined.

Funding Acknowledgement

Type of funding sources: None.
Distribution and cardiac outcomes of neuromuscular disorders referred to an inherited cardiac disease unit
Authors: Garcia Perez-Carlos M , Martinez-Garcia F , San Roman-Monserrat I , Sabater-Molina M , Navarro-Penalver M , Gil-Ortuno C , Munoz-Esparza C , Gimeno J R
Published: October 2022

Backgroud

Neuromuscular disorders may present with varied cardiac involvement, including myocardial and conduction tissue disease. Sudden death is a common adverse event of cardiomyopathy

Purpose

The objective was to present clinical characteristics of neuromuscular disorders referred to a dedicated inherited cardiac disease unit with special interest in the mode of presentation, clinical course and cardiac complications.

Methods

Cardiological anamnesis, 12-lead electrocardiogram and bidimensional echocardiogram were performed to every individual. Gadolinium cardiac MRI/24 hour-Holter/coronariography were performed in particular cases where results of previous tests made it mandatory.

Results

199 patients (aged 43.1±18.1 years, 45.2% females, 54.8% males) with neurological disorders evaluated in an inherited cardiac disease clinic from 2003–2021 were included. There were 20 (10.1%) dystrophynopathies, 20 (10.1%) limb girdle muscular dystrophy, 14 (7.0%) other muscular dystrophies (Emery-Dreifuss, facio-scapulo-humeral, oculopharyngeal), 70 (35.2%) myotonic myopathies (Steinert myotonic dystrophy, Becker myotonia congenita, Thomsen myotonia congenita), 7 (3.5%) myofibrillar myopathies, 14 (7.0%) congenital myopathies, 18 (9.0%) metabolic myopathies, 12 (6.0%) unknown origin inherited myopathies, 24 (12.1%) non-myopathic neurological diseases. There were 44 (22.11%) patients affected with a cardiomyopathy. 51/199 (25.6%) had conduction disturbances. 33/51 had pathological cardiac findings without clinical cardiomyopathy.

Age of diagnosis of neurological and cardiomyopathy conditions were 28.4±20.4 and 40.6±18.4 years old respectively. Reasons for diagnosis were symptoms (164, 82.4%), family screening (27, 13.6%), incidental finding (7, 3.5%), sudden death (1, 0.5%). 31 (15.6%) had atrial fibrillation, 17 (8.5%) required pacemaker and 15 (7.5%) ICD implantation. 32 (16.1%) patients died or had severe cardiac outcome. 7 (3.5%) had sudden death or equivalent, 3 (1.5%) heart-failure-death, 1 (0.5%) received cardiac transplantation, 18 (9.1%) had other-disease-related-death and 3 (1.5%) other disease non-cadiac-related-death).

Conclusion

Neuromuscular diseases require periodic cardiac evaluation. Despite onset of neurological symptoms usually precede cardiac involvement, the burden of cardiac involvement and complications is highly significant. Cause of death in neurological conditions with cardiac involvement is mostly driven by the severity of the cardiomyopathy.

Funding Acknowledgement

Type of funding sources: None.
A systematic review and meta-analysis on the effect of selective serotonin reuptake inhibitors on endothelial function
Authors: Delialis D , Mavraganis G , Dimoula A , Ajdini E , Bampatsias D , Dimopoulou A M , Sianis A , Maneta E , Neofytou O , Petropoulos I , Konstantinou G , Misegiannidis A , Kokras N , Stamatelopoulos K , Georgiopoulos G
Published: October 2022

Background

Depression and atherosclerotic cardiovascular disease (ASCVD) are commonly clustered in affected patients. Endothelial dysfunction is an early marker of ASCVD while also reported in patients with depression. Emerging evidence suggests that selective serotonin receptor inhibitors (SSRIs) may improve endothelial function. However, clinical studies assessing flow-mediated dilation (FMD), the gold-standard method to evaluate conduit artery endothelial function, in response to SSRIs treatment included limited number of patients and did not provide consistent results.

Purpose

In the present study we aim to evaluate the effect of SSRIs treatment on endothelial function assessed by longitudinal changes in FMD.

Methods

We performed a systematic review to retrieve and subsequently meta-analyze eligible studies in patients with depression who received SSRIs and had available measurements of FMD change before and after treatment.

Results

In 5 studies and 323 individuals in total, SSRIs were associated with increased FMD at the end of follow-up compared to baseline measurement (pooled mean change 1.97%, 95% CI 0.17, 3.77, P=0.032, I2=87.4%). These results did not substantially change when analysis was restricted to patients with history of atherosclerotic cardiovascular disease (ASCVD). Similarly, FMD changes were higher in individuals receiving SSRIs compared to not-treated subjects (pooled mean difference 2.5%. 95% CI 0.7, 4.2, P<0.001, I2=82.7%). Substantial heterogeneity regarding with respect to follow-up duration, demographics, and SSRIs agents.

Conclusion

SSRIs significantly improve FMD, the gold-standard marker of endothelial function. Further investigation is warranted for the role of FMD as a possible therapeutic biomarker in patients with depression and established or subclinical ASCVD.

Prospero registration: CRD42021252241

Funding Acknowledgement

Type of funding sources: None.
Role of global longitudinal strain in the assessment of left ventricular systolic function in patients with systemic lupus erythematosus: a systemic review and meta-analysis
Authors: Gegenava M , Gegenava T
Published: October 2022

Background

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized with high cardiovascular morbidity and mortality. However, cardiac involvement, especially at an early stages of the disease is largely underdiagnosed due to non-specific nature of the symptoms and low sensitivity of current diagnostic tools such as 2D conventional echocardiography derived left ventricular ejection fraction (LVEF), on the other hand, speckle tracking echocardiography (STE) derived left ventricular global longitudinal strain (LV GLS) has shown to be a reliable and sensitive tool for the diagnosis of subtle myocardial changes in various entities.

Purpose

The present study aimed to perform an extensive systemic review and meta-analysis of the current case-control studies based on the assessment of the left ventricular systolic function with standard and advanced echocardiographic methods.

Methods

The objectives, literature search strategies, inclusion and exclusion criteria, outcome measurements, and methods of statistical analysis were analyzed according to an established protocol of the cochrane collaboration steps and meta-analysis of observational studies in epidemiology recommendations (MOOSE).

Results

A total of 825 papers were collected according to our searching criteria, of those 20 studies including 1121 SLE patients and 1010 controls with evaluated LVEF and 8 studies including 387 patients and 283 controls with evaluated LV GLS were selected. We found, that overall patients with SLE exhibited lower levels of LVEF [weighted mean difference -WMD (95%CI) 0.336 (−0.423 to −0.248); p<0.001] (Fig. 1), although separately some included studies showed that the difference in terms of LVEF between SLE and the control group is not always significant. LV GLS was significantly lower in SLE patients as compared to controls [WMD (95%CI) −1.341 (−1.517 to −1.166); p<0.001] (Fig. 1), LV GLS was unequivocally lower in SLE patients (Fig. 2) in every reported study, moreover some studies showed significant association between deteriorated LV GLS and cardiovascular events.

Conclusions

LV systolic function as measured by LVEF and LV GLS is significantly affected in SLE patients. Data from meta-analysis suggest that STE derived LV GLS assessment potentially represents a new tool to improve precise and early assessment of LV function and may improve risk-stratification in patients with SLE.

Funding Acknowledgement

Type of funding sources: None.