bluuebunny/crossref_metadata_2025_split huggingface dataset:
A 3D-TTE left atrial function study in cardio-oncology patients
Authors: Ferreira V , Cruz Coutinho M , Almeida Morais L , Aguiar Rosa S , Moura Branco L , Galrinho A , Timoteo A T , Branco Mano T , Cardoso I , Castelo A , Garcia Bras P , Oliveira S , Cruz Ferreira R 
Published: October 2021

Abstract

Introduction
Transthoracic Doppler echocardiography (TTE) remains the standard imaging method to evaluate cancer therapeutics-related cardiac dysfunction (CTRCD). 3D-TTE with strain analysis is a novel technique, proved useful for earlier detection of left ventricular (LV) function impairment. However, diastolic and left atrial (LA) function impact is less studied.

Purpose
To assess LA volumetric and LA strain (LAS) features by 3D-TTE in cardio-oncology patients.

Methods
A prospective study of female breast cancer patients (P) submitted to therapy (TH) who underwent serial monitoring by 2D and 3D-TTE. Standard 2D, 3D-TTE and LAS parameters were evaluated, including longitudinal (LALS) and circumferential strain (LACS) during conduit (cd), contraction (ct) and reservoir (r) phases. P were evaluated at T0, T1 and T2 (before, ≥6 and ≥12 months after starting TH). CTRCD was defined as an absolute decrease in 2D LVEF &gt;10% to a value &lt;54% or a relative decrease in 2D GLS &gt;15%, according to literature. P with previous cancer treatment, coronary artery disease, significant valvular disease, and atrial arrhythmias were excluded.

Results
98 P (mean age 54.6±12.0 years-old), mostly treated with anthracyclines (78.6%, cumulative dose 268.2±77.6mg/m2), anti-HER (70.4%) and radiotherapy (80.6%) were included. 2D LV and LA volumes had a significantly raise from baseline to T1 (2D LVEDV 82.2±18.8 vs 91.9±18.8 mL, p=0.019 and LA 43.3±12.9 vs 49.8±13.3 mL, p=0.005). 2D and 3D LVEF were significantly reduced during TH, however remaining within the limits of normality. 2D GLS was also impaired at T1 (−19.9±2.6% vs −18.6±3.1%, p=0.009). During a mean follow-up of 14.1±8.1months, 31 P (31.6%) developed CTRCD. 3D LV and LA volumes also globally increased at T1 comparing to baseline with partially recovery at T2. Maximum LA volume was significantly higher at T1 (39.1±9.3 vs 43.6±10.6 ml, p=0.024). 3D LA ejection fraction (T0 53.7±9.7%, T1 53.4±8.6%, T2 49.9±8.6%, pT0-T2=0.039) and LAS values tended to progressively worse during TH. LA dilation (vol&gt;34ml/m2) at baseline was correlated to dysfunction in contraction phase at T1 (LACSct −19.6±8.6 vs −17.3±4.6%, p=0.024). LACSr has substantially decreased from baseline to T2 (31.4±11.6 vs 27.0±10.4%, p=0.05). In univariate analysis, delta LALSr (T1-T0) was a predictor of CTRCD (mean −5.2% vs 1.9%, p=0.05).

Conclusion
CTRCD was frequent during the earlier phase of breast cancer treatment. LA function was also affected, mirroring LV volumetric and functional changes. Diastolic dysfunction, assessed through LA reservoir strain, was impaired in association with CTRCD. 3D-TTE usefulness in the surveillance and monitoring of CTRCD goes beyond systolic LV function assessment, allowing a detailed LA function analysis.

Funding Acknowledgement
Type of funding sources: None.
Usefulness of a new risk score in identifying patients with CML at increased risk of cardiovascular toxicities
Authors: Alagna G , Di Lisi D , Santoro M , Accurso V , Madaudo C , Calcullo D , Siragusa S M , Galassi A R , Novo G 
Published: October 2021

Abstract

Background
Anti-BCR-ABL tyrosine kinase inhibitors (TKIs) dramatically improved the prognosis of patients with Chronic Myeloid Leukemia (CML) however they have been associated with cardiovascular (CV) complications.

Purpose
The primary aim of our study was to compare the usefulness of two different tools to stratify the risk of developing cardiovascular adverse events in haematology patients treated with ponatinib or nilotinib.

Methods
A real-life retrospective observational study was carried out on 58 patients (32 M, 26 W; mean age ± SD: 59±15) affected by CML treated with TKIs for a median period of 43±31 months. Patients were divided in groups according to CV risk estimated with SCORE and the 2020 CV risk assessment proposed by the Cardio-Oncology Study Group of the ESC/ICOS. Cardiac evaluation and echocardiogram were performed in all patients. The recorded CV adverse events were: myocardial ischemia, peripheral vascular diseases, new-onset or progression of preexisting carotid atherosclerosis, arterial hypertension, arrhythmias.

Results
According to SCORE, 46% of patients were at high-very high risk (group A1) and 54% at low-moderate risk (group B1). Applying the ESC/ICOS risk stratification tools, 60% were at high-very high risk (group A2) and 40% at low-medium risk (group B2). 21 CV adverse events were observed. CV adverse events were significantly more frequent in group A1 than group B1 (p value = 0,0003) when considered overall, they were significantly more frequent in group A2 than group B2 either overall (p=0,0004) or considered individually (myocardial ischemia: p=0,01; peripheral arterial disease: p=0,03). See Table 1. Moreover, the ESC/ICOS risk stratification tools was significantly more sensitive than SCORE (p=0,0004) in identifying patients at higher risk of cardiovascular toxicity. See Table 2.
No patients treated with Ponatinib showed CV adverse events during follow up. It is worth of notice that all patients before starting treatment underwent cardio-oncological evaluation, risk factors correction and preventive treatment with aspirin. They also were treated with the lowest dose of TKI. None of the patients treated with nilotinib over 4 years and with multiple lines of therapy, experiencing adverse events, received aspirin in primary prevention.

Conclusions
Our study shows that the ESC/ICOS risk stratification tools is very sensitive and more performing than SCORE for risk stratification of cardiotoxicity in haematology patients treated with TKIs. It also suggests that baseline CV risk assessment, CV risk factors correction and preventive treatment with aspirin aid in reducing CV adverse events in patients treated with ponatinib.

Funding Acknowledgement
Type of funding sources: None. Table 1Table 2
Long-term prognosis after ST-elevation myocardial infarction in cancer patients
Authors: Heemelaar J C , Polomski E A S , Mertens B J A , Jukema J W , Schalij M J , Antoni M L 
Published: October 2021

Abstract

Purpose
To assess survival trends after ST-elevation myocardial infarction (STEMI) in patients with a prior cancer diagnosis and to evaluate the drivers of prognosis over a follow-up period of five years.

Methods
Patients with a known cancer diagnosis, admitted with STEMI between 2004–2014 and treated with primary PCI were recruited from the STEMI-clinical registry of our institution. Detailed information on cancer diagnosis, -stage, and treatment regimen were collected from the institutional and national cancer registry system and all patients were followed prospectively.

Results
In the 215 included patients the cumulative incidence of all-cause death after 5 years of follow-up was 38.2% (N=61). The cause of death was predominantly malignancy-related (N=29, 47.4% of deaths) and only 9 patients (14.8% of deaths) died of a cardiovascular cause.
After correcting for age and sex – a recent cancer diagnosis (&lt;1yr relative to &gt;10 yr, HR 3.405 [95% CI: 1.552–7.470], p=0.002), distant metastasis at presentation (HR 2.603 [1.236–5.481], p=0.012), ongoing cancer treatment at presentation (HR 1.878 [1.015–3.475], p=0.045) and natural logarithm of maximum creatinine kinase level (HR 1.345 [1.044–1.733], p=0.022) were significant predictors of long-term mortality.
While prevalent renal insufficiency showed significant association with all-cause mortality (HR 2.302 [1.289–4.111], p=0.005), other known determinants of long-term prognosis after STEMI – a history of diabetes mellitus (HR 1.250 [0.566–2.761], p=0.581), hypertension (HR 0.623 [0.393–1.085], p=0.150), and culprit vessel left anterior descending artery or left main artery (HR 1.066 [0.641–1.771], p=0.806) were not significantly associated with survival at 5-years follow-up.

Conclusion
Cancer patients admitted with STEMI have a poor survival with one third of patients died at 5 year follow up. Cancer was the most common cause of death and malignancy-related factors made a significant impact on prognosis, while most of the established cardiovascular determinants of prognosis were not significantly associated with long-term survival.

Funding Acknowledgement
Type of funding sources: None. Cumulative incidence curve
Pregnancy in women with bicuspid aortic valve
Authors: Belkadi S , Milleron O , Eliahou L , Arnoult F , Delorme G , Ould Ouali N , Jadoui S , Jondeau G 
Published: October 2021

Abstract

Background
Aortic dissection during pregnancy is uncommon, however, the risk of aortic dissection is increased if there is underlying aortopathy. Bicuspid aortic valve (BAV) is common in the general population and is associated with the presence of an aortic aneurysm, but this condition is mostly asymptomatic and ignored in women of childbearing age. Data on pregnancy in patients with BAV are scarce, and guidelines on this topic are based on the consensus opinion of experts. The risk of occurrence of aortic dissection as a function of aortic diameter during pregnancy remains poorly known in women with BAV.

Purpose
To investigate demographic and echocardiographic characteristics and aortic events associated with pregnancy in women with BAV and to estimate ascending aortic diameter at the time of pregnancy.

Methods
We performed a retrospective study using data from our tertiary centre. All women seen at our centre between 1996 and 2020 with BAV, at least 1 pregnancy, and no genetic syndrome were included. We have collected data from echocardiograms performed in and out of our centre and aortic events.
Assuming from the literature an annual aortic dilation rate of 0.2 mm at the sinus of Valsalva and 0.4 mm at the tubular ascending aorta, we estimated ascending aortic size and Z-score at the time of pregnancy.

Results
We identified 47 women with BAV with occurrence of 103 pregnancies. The median age of BAV diagnosis was 43 years. The aorta was measured at a median of 13.3 years since the last delivery. At BAV diagnosis, the median largest ascending aortic diameter was 44mm, and the median Z-score was +4.3. Ascending aortic diameter was ≥40mm in 37/47 (79%) and Z-score ≥2 in 44/47 (94%).
No aortic dissection was observed during pregnancy and postpartum in all 103 pregnancies.
At the time of pregnancy, the estimated median diameter of the ascending aorta was 37mm and the estimated median Z-score was +3.3. The largest aortic diameter during pregnancy was estimated to be ≥40mm in 36/103 pregnancies, ≥45mm in 13/103, and ≥50mm in 1/103; Z-score was estimated to be ≥2 in 81/103 and ≥4 in 40/103.
Type A aortic dissection occurred in 1 woman, 13 years after pregnancy, and type B aortic dissection in 1 woman, 14 years after pregnancy. Planned surgery was performed in 8 women at a median of 17.5 years after the last pregnancy: 1 isolated aortic valve replacement and 7 prophylactic aortic surgeries associated with aortic valve surgery.

Conclusions
In our population of women with BAV, pregnancy is not associated with the occurrence of aortic dissection even though, when estimating aortic diameter at the time of pregnancy, the rate of aortic dilation was high (Z-score ≥2 in 81/103 pregnancies). Prospective studies of a large population of women with BAV are needed to assess the risk of aortic complication during pregnancy according to aortic diameter.

Funding Acknowledgement
Type of funding sources: None.
Long term prognostic utility of exercise capacity in renal transplant candidates
Authors: Tan S , Thang Y W , Mulley W R , Polkinghorne K , Ramkumar S , Cheng K , Rehmani H , Brown A J , Moir S , Cameron J D , Nicholls S J , Mottram P M , Nerlekar N 
Published: October 2021

Abstract

Background
Pharmacological stress testing is commonly performed for cardiovascular risk stratification in potential renal transplant candidates due to a perceived inability for these patients to exercise. We have previously reported that exercise stress testing is feasible in renal transplant candidates but the prognostic utility of exercise capacity in this patient group is not known.

Purpose
This study prospectively evaluated the effect of exercise capacity on the risk of major adverse cardiovascular events (MACE), defined as a composite of cardiac death, non-fatal myocardial infarction, and stroke, in renal transplant candidates undergoing exercise stress echocardiography (ESE) for pre-transplant cardiovascular assessment.

Methods
We evaluated 898 consecutive patients with chronic kidney disease stage 4/5 who underwent symptom-limited treadmill ESE over 5-year mean follow-up. Exercise capacity was measured by age and sex predicted metabolic equivalents (METs). The primary outcome was achievement of predicted METs with first MACE. Cox proportional hazard multivariable modelling was used to determine MACE predictors with transplantation treated as a time-varying covariate. We also performed secondary analysis using a 7 MET threshold.

Results
There were 106 MACE with an annual cumulative risk of 2.4%. During follow-up, 525 (58%) received transplantation. Achievement of predicted METs (48%) (hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.29–0.82, p=0.007) and transplantation (HR 0.52, 95% CI 0.30–0.91, p=0.02) were independently associated with reduced MACE. Similar results were observed using a 7 MET threshold achieved by 734 (82%) patients. Patients achieving predicted METs had no difference in MACE regardless of subsequent transplantation (HR 0.78, 95% CI 0.32–1.92, p=0.59). Patients who achieved predicted METs and did not receive transplantation had similar outcomes to those that did not achieve predicted METs and received transplantation (HR 0.97, 95% CI 0.42–2.25, p=0.95).

Conclusions
Exercise capacity is associated with reduced long-term MACE in renal transplant candidates undergoing ESE for pre-transplant cardiovascular assessment. Achievement of age and sex predicted METs confers excellent prognosis independent of subsequent transplantation.

Funding Acknowledgement
Type of funding sources: None.
Prevention of contrast-induced nephropathy with urine alkalinization: the TEATE study
Authors: Lombardi M , Molisana M , Genovesi E , De Innocentiis C , Limbruno U , Misuraca L , Di Vito L , Zimarino M , Renda G , Di Nicola M , De Caterina R 
Published: October 2021

Abstract

Background
Contrast-induced acute kidney injury (CI-AKI) after coronary angiography and percutaneous interventions (PCI) impacts on hospitalization duration and mortality. Pre-procedural hydration is the sole strategy currently recommended for preventing CI-AKI. The role of sodium bicarbonate (SB) although attractive, since urine alkalinization suppresses the production of reactive oxygen species, is still controversial, and the optimal dosing to attain adequate urine alkalinization is still undefined.

Purpose
The PrevenTion of contrast-inducEd nephropathy with urine alkalinization (TEATE) study was a prospective 3-center 3-arm single-blind randomized controlled trial testing the hypothesis that adequate urine alkalinization is associated with CI-AKI prevention. Secondary endpoints were the efficacy of SB vs saline in achieving adequate urine alkalinization and reducing the incidence of CI-AKI compared with saline.

Methods
Patients candidate to coronary angiography and/or PCI with moderate-to-severe chronic kidney disease [eGFR of 15 to 60 mL/min/1.73 m2, by the Modification of Diet in Renal Disease Study equation (MDRD)] were randomly assigned to saline hydration (control), oral SB or i.v. SB. The study protocol was registered. We evaluated urinary pH at the time of hospitalization, immediately before coronary angiography and 24–48 hours after angiography. According to urine pH immediately before the procedure, patients were divided in two groups above or below a pH cut-off of 6.

Results
We enrolled a total of 241 patients: 81 were randomly assigned to the control group, 82 to i.v. SB and 78 to oral SB. Patients achieving a urinary pH &gt;6 before angiography had a lower incidence of CI-AKI (46%) than patients with urinary pH ≤6 (54%) [OR=0.48 (95% CI 0.25–0.9) p=0.023]. The number of patients with urine pH &gt;6 was higher in both the i.v. (71%) and the oral SB (65%) groups compared to the hydration-only group (44%, p=0.004). We found however no difference in the incidence of CI-AKI in the 3 treatment arms (20% in hydration alone, 21% in oral SB group and 22% in iv SB group) (p=0.94). Subgroup analyses according to basal urine pH and eGFR ranges failed to identify statistically significant differences in the development of CI-AKI according to treatment allocation.

Conclusions
Urinary pH before the administration of contrast medium is an inverse correlate of CI-AKI incidence, and SB is superior to hydration alone in achieving urinary alkalinization. Since, however, SB did not reduce the incidence of CI-AKI, we conclude that urinary pH is a marker and not a mediator of CI-AKI.

Funding Acknowledgement
Type of funding sources: None.
PCSK9 inhibitor therapy and guideline treatment targets for cardiovascular disease and familial hypercholesterolaemia
Authors: Suresh A , Theodoraki A , Ward E , Feher M D 
Published: October 2021

Abstract

Background
Updated trial data on the benefits of low-density lipoprotein cholesterol (LDL-C) reduction on cardiovascular outcomes have been incorporated into 2019 ESC/EAS guidelines and 2020 UK-based NICE guidance. Treatment targets for secondary cardiovascular disease (CVD) prevention are LDL-C &lt;1.4mmol/L (ESC/EAS) and non-high-density lipoprotein &lt;2.5mmol/L (equates to LDL-C &lt;1.8mmol/L; NICE). Guidelines also recommend ≥50% LDL-C reduction in patients with CVD or Familial Hypercholesterolaemia (FH). Targets are often not achieved with oral statin +/− ezetimibe due to reduced efficacy or tolerability, warranting a switch to PCSK9 inhibitor therapy. However, there is limited data on whether this achieves LDL-C targets for both CVD and FH in real world clinical practice.

Purpose
To assess attainment of LDL-C treatment targets using PCSK9 inhibitor mono- or combination therapy in routine clinical care for patients with FH or CVD.

Methods
Observational study in a single specialist lipid clinic, using retrospective case note review of patients prescribed PCSK9 inhibitor therapy according to NICE guidelines until February 2021. Anonymised clinical, demographic and biochemical data before and after commencement of PCSK9 inhibitor therapy were collected. Primary outcomes were attainment of guideline-defined LDL-C treatment targets: LDL-C &lt;1.8 mmol/L, LDL-C &lt;1.4mmol/L and ≥50% LDL-C reduction.

Results
A total of 55 patients (mean age 60.8±12.9 years, 58% male) on PCSK9 inhibitor therapy (98% alirocumab, 2% evolocumab; mean treatment duration 1.7±1.3 years) were identified. PCSK9 inhibitor therapy was commenced due to drug intolerance to statins (89%), ezetimibe (36%) and fenofibrate (25%). In patients with FH (n=18), 78%, 56% and 33% of patients achieved targets of ≥50% LDL-C reduction, LDL-C &lt;1.8 mmol/L and LDL-C &lt;1.4 mmol/L on treatment, respectively. In CVD patients (n=49), 84%, 51% and 27% achieved the same targets respectively (Table 1). In patients on PCSK9 inhibitor monotherapy (n=19), 21% and 5% achieved LDL-C targets &lt;1.8 mmol/L and &lt;1.4 mmol/L respectively, whereas in those on PCSK9 inhibitor + two or more additional oral lipid-lowering therapies, 87% and 60% achieved the same targets respectively (Table 2).

Conclusions
Most patients with FH or CVD achieve an LDL-C reduction of ≥50% from baseline with PCSK9 inhibitor therapy, however fewer achieve the LDL-C targets of &lt;1.8 mmol/L or &lt;1.4 mmol/L. Patients on PCSK9 inhibitor monotherapy are unlikely to reach LDL-C &lt;1.8 mmol/L and &lt;1.4mmol/L targets, whereas PCSK9 inhibitor combination therapies are more likely to do so. Additional lipid-lowering drugs are required with PCSK9 inhibitor therapy in most patients to reach guideline LDL-C targets.

Funding Acknowledgement
Type of funding sources: None.
Meta-analysis of cardiovascular outcome trials assessing the impact of glucagon-like peptide-1 receptor agonists on major cardiac arrhythmias
Authors: Boulmpou A , Patoulias D , Teperikidis E , Toumpourleka M , Vergopoulos S , Tsavousoglou C , Doumas M , Fragakis N , Vassilikos V , Papadopoulos C E 
Published: October 2021

Abstract

Background
Type 2 diabetes mellitus poses a significant health burden, whereas growing attention has been focused on the novel classes of antidiabetic drugs. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) constitute such a group of antidiabetic agents. In recent large, placebo-controlled randomized clinical trials (RCTs), GLP-1RAs have demonstrated beneficial cardiovascular effects. Nevertheless, the clear antiarrhythmic benefit has not been underlined yet.

Purpose
The purpose of the present analysis was to clarify the impact of antidiabetic treatment with GLP-1RAs on the several different types of cardiac arrhythmias, based on data extracted from relevant cardiovascular outcome trials.

Methods
We searched PubMed plus grey literature for all available cardiovascular and renal outcome, placebo-controlled RCTs utilizing GLP-1RAs versus placebo.

Results
We pooled data from 7 cardiovascular outcome trials with GLP-1RAs in a total of 55,943 randomized participants patients. When compared to placebo, treatment with GLP-1RAs did not provide a significant benefit in the risk for atrial fibrillation (RR = 0.81, 95% CI: 0.78–1.15, I2=51%) (Figure 1a), atrial flutter (RR=0.79, 95% CI: 0.53–1.16, I2=0%) (Figure 1b), ventricular fibrillation (RR=0.99, 95% CI: 0.48–2.04, I2=0%) (Figure 1c), ventricular tachycardia (RR=1.41, 95% CI: 0.87–2.28, I2=10%) (Figure 1d), atrial tachycardia (RR=0.63, 95% CI: 0.10–3.90, I2=24%) (Figure 2a), sinus node dysfunction (RR=0.70, 95% CI: 0.40–1.23, I2=0%) (Figure 2b), ventricular extrasystoles (RR=1.37, 95% CI: 0.56–3.30, I2=0%) (Figure 2c), second-degree atrioventricular block (RR=0.96, 95% CI: 0.52–1.74, I2=0%) (Figure 2d) or complete atrioventricular block (RR=0.78, 95% CI: 0.39–1.54, I2=38%) (Figure 2e).

Conclusions
In patients with type 2 diabetes mellitus, treatment with GLP-1RAs does not significantly affect the risk for major cardiac arrhythmias.

Funding Acknowledgement
Type of funding sources: None. Figure 1Figure 2