bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetically rheumatoid arthrits and risk of comorbidities: a Mendelian randomization study
Authors: Fokina A , Fill J , Klappacher G 
Published: November 2020

Abstract

Background
Ample observational evidence indicates that patients with rheumatoid arthritis (RA) are at increased risk of developing comorbid conditions, in particular cardiovascular disease. The pathogenesis of these comorbidities is still largely unknown. For effective preventive measures, it would however be important to discriminate between those that are causally linked with rheumatoid arthritis and those that are the results of concomitant treatments or other confounding factors.

Purpose
Our objective was to explore whether genetically determined manifestation of RA was associated with any comorbidities, in particular cardiovascular disease, by conducting a 2-sample Mendelian randomization (MR) study on publicly available summary statistics from genome-wide association study (GWAS) consortia.

Methods
Genetic instruments for RA were obtained from a GWAS of 14,361 autoantibody-positive individuals with RA and 43,923 controls of European descent (Okada et al. 2014). The CARDIoGRAMplusC4D consortium comprising 60,801 cases with coronary artery disease and 123,504 controls was used to evaluate the associations with cardiovascular outcomes applying inverse variance–weighted meta-analysis, weighted-median analysis, Mendelian randomization–Egger regression, and multivariable Mendelian randomization. Genetic instruments for RA were further tested for association with other etiologically related traits by using publicly available GWAS data.

Results
Genetic predisposition to RA was not associated with higher risk of coronary artery disease (beta coefficient [b] ± standard error [se] = 0.02±0.03; P=0.4913), and myocardial infarction (b ± se = 0.03±0.03; P=0.3338). In contrast, IgA nephropathy (b ± se = 0.47±0.18; P=0.0225) and triglyceride levels were significantly related as outcomes to genetically determined RA as exposure. Other significantly related outcomes were the manifestation of squamous cell lung cancer (b ± se = 0.17±0.08; P=0.0496), serous ovarian cancer (b ± se = 0.13±0.05; P=0.0202), and prostate cancer (b ± se = 0.06±0.02; P=0.0041).

Conclusions
Despite the high prevalence of coronary artery disease and myocardial infarction among RA patients in observational studies, cardiovascular outcomes were not significantly associated with RA by Mendelian randomization. This paradox might partly be explained by the traits such as IgA nephropathy and elevated triglyceride levels that could act as mediators for the increased cardiovascular risk by their causal link with genetically determined RA.

Funding Acknowledgement
Type of funding source: Public hospital(s). Main funding source(s): Medical University of Vienna, Austria
Mothers with post-partum hypertension and kidney damage after pre-eclampsia should receive ACE inhibitors rather than methyldopa
Authors: Gaisin I , Iskchakova A.S , Maximov N.I , Valeeva R.M , Shilina L.V , Sava N.P 
Published: November 2020

Abstract

Background
Both hypertension (HT) and pre-eclampsia (PE) have been recognized as an important cause of chronic kidney disease (CKD) in women. There are no uniform recommendations for the treatment of HT with kidney damage after PE yet.

Methods
In a case-control, open-label 1-year study, 54 post-partum women (aged 25–37 years) with grade 2 (53.7%) or 3 (46.3%) HT and kidney damage [48 patients (88.9%) had moderately increased albuminuria (30–299 mg/g), 6 (11.1%) – severely increased albuminuria (&gt;300 mg/g), 32 (59.3%) – mildly decreased eGFR (60–89 mL/min/1.73 m2 (BSA)) and 3 (5,6%) – mildly to moderately decreased eGFR (45–59 mL/min/1.73 m2)] after early-onset PE (with delivery at &lt;34+0 weeks of gestation) superimposed to HT received either adjusted-dose ACE inhibitors – ACEi (33 non-feeding mothers: 19 – perindopril, 5 – ramipril, 9 – perindopril and indapamide SR combination) or methyldopa (21 nursing women). No significant differences observed between two groups at baseline.

Results
After comprehensive follow-up, blood pressure (BP) was not found to differ between ACEi and methyldopa groups (123.2±2.4/78.5±1.5 mmHg vs. 136.2±4.8/86.2±3.2 mmHg respectively, p&gt;0.05) with more strict BP control on ACEi. There were significant differences in albuminuria reduction, in favour of ACEi (–207.2 mg/24 h vs. –33.7 mg/24 h, p&lt;0.01) and in eGFR increasing (+19.4 mL/min/1.73 m2 (BSA) vs. +6.6 mL/min/1.73 m2 (BSA), p=0.029), as well as in decrease of left ventricular (LV) mass index (−31.2 g/m2 vs. −16.7 g/m2, p=0.038) and increase of LV ejection fraction (+8.2% vs. +1.9%, p=0.022). Treatment with ACEi more improved endothelial function, non-invasively assessed by flow-mediated dilatation of a brachial artery using high-resolution ultrasound (+10% vs. +3.4%, p=0.035) and decreased intima media thickness (−0.33 mm vs. −0.17 mm, p=0.009).
In a year, all methyldopa patients had albuminuria, C1 stage of CKD was in 13 (61.9%) women, CKD C2 in 8 (38.1%). In ACEi group, CKD C1 had 7 (21.2%) mothers (p&lt;0.01), C2 – none (p&lt;0.01).

Conclusion
Non-feeding women with grade 2 or 3 post-partum HT and renal damage after early-onset PE get greater heart, kidney and vessels benefits from 1-year ACEi treatment than nursing mothers from methyldopa.

Funding Acknowledgement
Type of funding source: None
Evidence of platelet dysfunction in congenital cyanotic heart disease: relevance to palliative systemic-pulmonary shunt and haemostatic parameters
Authors: Hassan F , Agha H , Khalil M , Gabr H , Alsoda S 
Published: November 2020

Abstract

Introduction
Platelets in congenital cyanotic heart disease (CCHD) were occasionally characterized by significantly enhanced expression of P-selectin in resting circulating platelets as well as their augmented activation in response to stimulating agents. P-selectin is present in the alpha granule membrane as well as Weibel-Palade body membrane of endothelial cells. It is translocated to platelet membrane after activation; thus, its expression on platelet surface is an indicator of platelet activation in vivo. The occurrence of the prothrombotic variant of GPIIIa in cyanotic children may be associated with enhanced activation of circulating platelets.

Purpose
To study the platelet functions in patients with CCHD by determination of Pselectin expression and the GPIIIa polymorphism and to correlate these findings with other clinical, radiological, and laboratory parameters in these patients.

Methods
This study included 47 patients, with cyanotic congenital heart disease with decreased pulmonary blood flow, attending the Pediatric Cardiology Clinic. They were divided into two groups: Group I: 31 patients with congenital cyanotic heart disease before cardio surgery Group II: 16 patients with congenital cyanotic heart disease 3–6 months after palliative or corrective cardio surgery, Group III: 12 age and sex matched normal children were included in the study as control group. They were subjected to Flow-cytometric evaluation of platelet activation by Pselectin expression: P-selectin expression was estimated using monoclonal antibody.-Typing of GPIIIa gene polymorphism was done.

Results
Statistically significant higher P-selectin levels were found in patients compared with controls being significantly higher in patients &lt;3 years of age. There was significant negative correlation between P-selectin level and O2 in patients. The incidence of prothrombotic variant A2 was described as phenotype positive. Statistically significant higher levels of P-selectine were found in positive phenotype patients than positive phenotype controls

Conclusion
Enhanced platelet activation may be an important contributor in the high thrombotic liability in congenital cyanotic heart disease. This may be attributed in part to genetic factors

Funding Acknowledgement
Type of funding source: None
Prevalence of aortic valve regurgitation in a large population-based study of newborns
Authors: Farooqui A , Bjerrekaer J.K , Boerresen M.F , Voegg R.O , Pihl C.A , Norsk J.B , Bundgaard H , Iversen K.K 
Published: November 2020

Abstract

Background
Congenital aortic valve regurgitation (AVR) has been estimated to be present in 0.25 per 1,000 live births globally. The true prevalence in an unselected large-scale cohort remains unknown. Presence of congenital AVR could indicate a structural valve abnormality and may result in long-term strain on the heart.

Aim
To find the true prevalence of AVR in a large cohort of unselected newborns.

Methods
Between April 2016 and October 2018, 25,752 newborns were consecutively included in a population-based prospective multicenter cohort and examined with transthoracic echocardiography within the first 30 days of life. Examinations with AVR were categorized as trivial AVR by the presence of a trivial diastolic transvalvular flow, or as non-trivial AVR by the presence of a significantly larger and visually observable transvalvular flow. In newborns with non-trivial AVR, the vena contracta, the duration of the transvalvular flow, and the duration of the diastole were measured. The cases were matched 1:4 with newborns with no AVR based on sex, gestational age at birth, birth weight and age at time of examination.

Results
AVR was identified in 329 newborns (1.3%). Of these, 260 were classified as trivial AVR, 69 (0.27%) were non-trivial AVR. Non-trivial AVR had significantly larger aortic roots at all points of measurement compared to controls (mean±SD): aortic valve annulus (7.3 (0.73) vs. 7.0 (0.63) mm), Sinus of Valsalva (10.3 (1.0) vs. 9.7 (1.0) mm), sino-tubular junction (8.4 (0.8) vs. 8 (0.8) mm), and ascending aorta (10 (0.9) vs. 9.4 (1.1) mm) (p&lt;0.01 for all). Left ventricular dimensions and function did not significantly differ between the cases and controls. The presence of a non-trivial AVR was highly associated with a bicuspid aortic valve (9 (13.0%) vs. 3 (1.1%), p&lt;0.001).

Conclusions
We found a prevalence of congenital AVR of 1.3% in a large cohort of unselected newborns, which is higher than previously reported. One in five of all AVR found were classified as non-trivial. Newborns with non-trivial AVR presented with larger aortic root and ascending aorta dimensions. Newborns with non-trivial AVR also had a ten-fold higher occurrence of bicuspid aortic valve compared to controls.

Funding Acknowledgement
Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Hjerteforeningen
The Peguero-Lo Presti criteria has the highest diagnostic accuracy for the diagnosis of left ventricular hypertrophy in the elderly
Authors: Tavares C.A.M , Samesima N , Hajjar L.A , Godoy L.C , Hirano E.M.P , Facin M , Jacob Filho W , Farkouh M.E , Pastore C.A 
Published: November 2020

Abstract

Background
Left Ventricular Hypertrophy (LVH) is an independent predictor of mortality and cardiovascular morbidity and the 12-lead ECG is recommended as a universal screening for patients with hypertension. However, the ECG has low sensitivity and there is limited data in patients 70 years or older. The recently published Peguero-Lo Presti (PLP) criteria had improved accuracy compared with other ECG criteria but with very few patients with age ≥70 years included.

Purpose
To compare the accuracy of the PLP criteria versus the traditional ECG criteria for detecting LVH in patients ≥70 years.

Methods
Retrospective single-center study. Patients were included if they were 70 years or older and underwent an ECG and echocardiogram (gold standard) less than 180 days apart from jan/2017 to mar/2018. Patients with left or right bundle branch block, non-sinus rhythm or ventricular paced rhythm were excluded. All tracings were independently reviewed by two cardiologists, blinded to the echocardiogram. The PLP criteria was compared against Cornell voltage (CV), Sokolow-Lyon voltage (SL), and Romhilt-Estes 4 and 5 (RE) criteria. LVH was defined as a left ventricular mass index &gt;115 g/m2 in males and &gt;95 g/m2 in females, according to the echocardiogram. McNemar's test, F1 score, and the area under the Receiver Operating Characteristic curves (AUC) were used to compare the diagnostic performance of the tests

Results
A total of 592 patients were included (mean age 77.5 years, SD: 5.9; 50.8% were women). The PLP criteria had increased sensitivity compared with both the SL and CV criteria (p&lt;0.0001 for both comparisons) and RE5 (p=0.042). PLP also had better specificity than the RE4 criteria (p&lt;0.0001) and the highest F1 accuracy score (Table 1). The AUC of the PLP was significantly higher than the AUC of the CV and RE criteria (0.70 vs 0.66 vs 0.64, respectively, p&lt;0.05) and numerically higher than the SL criteria (AUC=0.67, p=0.311, Figure 1).

Conclusion
Compared to the traditional ECG criteria for LVH, the PLP criteria had the highest diagnostic accuracy in elderly patients.
Figure 1. AUC of the ECG criteira

Funding Acknowledgement
Type of funding source: None
Cardiovascular effects of chimeric antigen receptor t-cell therapy for refractory or relapsed non-hodgkin lymphoma
Authors: Ganatra S , Redd R , Hayek S , Parikh R , Azam T , Yanik G , Spendley L , Nikiforow S , Jacobson C , Nohria A 
Published: November 2020

Abstract

Purpose
Cardiovascular complications of chimeric antigen receptor T-cell (CAR T-cell) therapy are poorly understood. We examined the incidence, predictors and impact of new or worsening cardiomyopathy in patients undergoing CAR T-cell therapy.

Methods
All patients with refractory or relapsed non-Hodgkin's lymphoma, undergoing CAR T-cell therapy at collaborative institutes underwent serial echocardiograms at baseline and within 7 days after developing high-grade cytokine release syndrome (CRS), and were followed for all-cause mortality. New or worsening cardiomyopathy was defined as a reduction in left ventricular ejection fraction (LVEF) &gt;10% from baseline to &lt;50% during the index hospitalization.

Results
Among 187 consecutive CAR T-cell therapy patients, 116 (50 Grade ≤1 CRS, 66 Grade ≥2 CRS) had &gt;1 echocardiogram performed and were included in this analysis. The median age was 63 (range 19–80) years, 42% were women, 91% were Caucasian. A total of 12 (10.3%) patients developed new or worsening cardiomyopathy with a decline in LVEF from 58±6% to 36±7% within a median of 12.5 (range 2–24) days of CAR T-cell infusion. In multivariable analyses, older age, prior stem cell transplantation, baseline angiotensin-converting enzyme inhibitor use and CRS grade ≥2 were associated with the development of cardiomyopathy. Patients who developed cardiomyopathy were more likely to require vasopressor support (p=0.004) and mechanical ventilation (p=0.014). LVEF improved in 9/12 (75%) patients. CAR T-cell associated cardiomyopathy did not impact overall mortality or cancer response to CAR-T cell therapy.

Conclusions
Patients undergoing CAR T-cell therapy are at risk of developing cardiomyopathy and hemodynamic instability. Pre-CAR T-cell therapy cardiovascular risk stratification and echocardiogram surveillance during therapy should be considered for prompt identification and mitigation of cardiac complications.
Predictors of Cardiomyopathy Development

Funding Acknowledgement
Type of funding source: Private hospital(s). Main funding source(s): Anju Nohria, MD is supported by the Gelb Master Clinician Award at Brigham and Women's Hospital.
Sacubitril/valsartan improves heart failure functional class, left ventricular systolic and diastolic function and neurohumoral status in patients with anthracycline-induced cardiomyopathy
Authors: Vitsenya M , Potekhina A , Gavryushina S , Ibragimova N , Masenko V , Ageev F 
Published: November 2020

Abstract

Anthracycline-induced cardiomyopathy (AC-CMP) is more resistant or even refractory to conventional heart failure (HF) treatments and has a higher mortality rate as compared to HF associated with other diseases. Sacubitril/valsartan (S/V) significantly reduces cardiovascular mortality and hospitalization rate in HF patients with reduced left ventricular ejection fraction (HFrEF). There is lack of evidence of S/V efficacy and safety in patients with AC-CMP.
We aimed to assess the efficacy and tolerability of S/V in patients with AC-CMP.

Methods
We enrolled 20 patients with anthracycline-induced HFrEF who met the indication criteria for S/V. Median age was 61 [51.5; 67], 100% women, 8 (40%) hypertensive, 1 (5%) diabetic. Seventeen (85%) patients had breast and 3 (15%) hematological cancers. Median time from anthracycline therapy was 3 [1; 11] years. Surgery due to cancer and radiation therapy were performed in 15 (75%) cases. All patients had been receiving ACE inhibitors or angiotensin II receptor blockers and were switched to S/V. 85% of patients were treated with beta-blockers, 60% – mineralocorticoid antagonists, 50% – loop diuretics. The exam (at admission and after 6 months) included 6-MWT, echo/speckle tracking, creatinine, potassium and NTproBNP level.

Results
Eleven (55%) patients achieved the target dose of S/V. The mean S/V dose was 289±149.1 mg. Symptomatic hypotension, hyperpotassemia or creatinine level elevation were the reasons for S/V dose reduction in 8, 1 and 2 patients, respectively. S/V wasn't withdrawn in any patient. No hospitalization due to HF or need for loop diuretics increase occurred during the follow-up. After 6 months 6-MWD increased from 416 [347.5; 477.5] to 465 [395; 513.5] m, p=0.0004. NYHA functional class improved in 50% of patients. We revealed LVEDVI decrease (61.7 [55.9; 71.6] to 57.1 [53.4; 60.1] ml/m2 p=0.002), LVEF and GLS increase (39 [34.7; 41] to 45 [39; 47]%, p=0.001 and 11 [8.7; 13.9] to 13.4 [11.9; 15.5]%, p=0.002, respectively), LAVI decrease (40.7 [32; 43.9] to 31.3 [28.6; 37.4] ml/m2, p=0.003), E/A and E/e ratios decrease (1.37 [0.7; 2.23] to 0.69 [0.64; 0.83], p=0.04, and 13 [11.3; 17.8] to 10.7 [6.9; 13.6], p=0.01, respectively). NTproBNP blood level declined from 1659 [1090; 2316] to 377 [206.8; 920] pg/ml, p&lt;0.001. There was change in serum creatinine level but in normal ranges (from 70.3 [66.8; 80; 6] to 77 [68.6; 96.3] micromol/l, p=0.02). No significant changes in potassium level were observed.

Conclusions
In this pilot study S/V was well tolerated in patients with AC-CMP, but cardiologic assessment was needed for accurate dose adjustment. Therapy with S/V was associated with improvement in HF functional class and LV systolic and diastolic function as well as neurohumoral status in patients with AC-CMP.

Funding Acknowledgement
Type of funding source: None
Regional cardiac dysfunction determined by radiation dose in patients with breast cancer
Authors: Trivedi S , Tang S , Otton J , Delaney G , Holloway L , Liney G , Koh E , Thomas L 
Published: November 2020

Abstract

Background
Subclinical left ventricular (LV) dysfunction by 2D global longitudinal strain (GLS) immediately following radiotherapy (RT) and persisting at 12 months has been described in breast cancer (BC) patients. We hypothesised that persistent LV dysfunction may be regional and correlate with segmental RT.

Methods
Transthoracic echocardiograms were performed at baseline, 6 weeks and 12 months post-RT on 61 chemotherapy-naïve women with left sided BC.

Results
Anterior and anteroseptal regions received the highest radiation dose, and posterior and inferior segments the lowest radiation dose (Figure 1). Within each region, there was a progressive increase in the radiation dose received from base to apex. At 6 weeks, the greatest reduction in strain was observed in the anterior and anteroseptal regions, with the most significant reduction in strain in the apical segments. At 12 months, despite improvement in strain, the percentage reduction in strain was similar. There was a significant interaction between both region and segment, on the percentage change in strain at 6 weeks (p&lt;0.001) and at 12 months (p=0.007). Pairwise comparisons of apical to basal percentage change in strain demonstrated the most significant reductions in the anterior region at 6 weeks and 12 months (Table 1).

Conclusions
RT causes segmental myocardial dysfunction, with areas receiving the highest RT demonstrating the largest impairment in strain, with these changes persisting at 12 months. Long term correlation with adverse events is required.
Figure 1. Radiation dose by region and segment

Funding Acknowledgement
Type of funding source: None
Carcinoid heart disease: the role of echocardiography in predicting post-surgical outcomes
Authors: Brooke A , Ahmed R , Hodson J , Rooney S , Oelofse T , Singh H , Shah T , Steeds R.P 
Published: November 2020

Abstract

Background
Carcinoid heart disease (CHD) often complicates neuroendocrine tumours (NET). The prognosis of CHD without intervention is poor; 3 year survival is estimated at 31%. Surgical valve replacement is the only treatment for CHD, but is associated with high 30-day mortality (10–15%).

Purpose
The aim is to identify pre-operative transthoracic echocardiogram (PTTE) findings that could determine which patients have a high likelihood of post-surgical mortality at 1 year.

Methods
This retrospective observational cohort study recruited 88 patients with a confirmed diagnosis of CHD between 2005–19 at University Hospital Birmingham; 49 (56%) of these were treated surgically. Indications for surgery: stable NET, symptomatic severe valvular dysfunction, progressive RV dilatation or RV dysfunction, no significant comorbidities. All patients underwent a standard PTTE. PTTE parameters assessed: right ventricular (RV) size, RV function (qualitative), TAPSE, RV fractional area change, RV S wave velocity, left ventricular (LV) size, LV ejection fraction and valve velocities. Surgery was performed by a single surgical team with bioprosthetic valve replacements.

Results
Patients were followed up for a median of 15 months (IQR: 6–59) after surgery, during which time there were 33 deaths, giving a median survival time of 30 months (IQR: 7–85). Increasingly severe RV dilatation was significantly associated with shorter survival (p=0.032). The estimated survival rate at three years was 67% in those with normal RV size, compared to 24% in the severe RV group (Figure 1). RV basal diameter was assessed used ROC curve analysis for the outcome of one year survival and returned an area under the curve of 0.66 (SE=0.10). Youden's index identified RV diameter &gt;4.8cm to be the optimal cut-off for identifying high-risk patients. One year mortality rates were 26% (7/27) vs. 75% (9/12) in those with RV basal diameter of ≤4.8 vs. &gt;4.8cm (p=0.006).

Conclusion
A pre-operative right ventricular basal diameter &gt;4.8cm is associated with a near three-fold increase in post-operative mortality at one year. These findings highlight the importance of regular imaging in order to optimise the timing of surgery in patients with CHD.
Figure 1. Kaplan-Meier curve of post-op survival

Funding Acknowledgement
Type of funding source: None