bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti-Mullerian hormone concentrations are inversely associated with subclinical atherosclerosis in premenopausal women
Authors: Delialis D , Lamprinoudaki I , Stergiotis S , Patras R , Chatzivasileiou P , Augoulea A , Anagnostis P , Armeni E , Rizos D , Kaparos G , Alexandrou A , Georgiopoulos G , Kontogiannis C , Fotellis D , Stamatelopoulos K
Published: November 2020

Background

Anti-Müllerian hormone (AMH) constitutes a marker of ovarian reserve and appears to have a predictive role regarding the time of menopause. Moreover, AMH is associated with adverse cardiac events. History of premature menopause and early onset of menopause have been associated with increased risk of cardiovascular (CV) disease. In addition, menopausal transition and duration of menopause have been associated with increased burden of subclinical atherosclerosis. However, the association between AMH as a marker of female reproductive age with atherosclerosis in premenopausal women is currently unknown.

Purpose

To investigate whether AMH concentrations are associated with markers of early atherosclerosis in healthy, normally menstruating women.

Methods

In a cross-sectional study, vascular structure and function were assessed by measurement of carotid and femoral intima-media thickness (IMT), lipid profile and serum AMH concentrations were assessed. Exclusion criteria were clinically overt CV disease, abnormal ovulatory cycles, polycystic ovarian syndrome, acute infection or chronic inflammatory disease, risk factors for CV disease and any medication

Results

Seventy premenopausal women, aged 32.7±6.5 years, were included. Mean AMH levels were lower in smokers than in non-smokers and negatively associated with total cholesterol (TC) levels. An inverse association between mean AMH concentrations and IMT in all segments was observed. No correlation with other markers of subclinical atherosclerosis or traditional CV risk factors was found. After multi-variable adjustment for traditional CV risk factors, the association between AMH concentrations combined IMT and carotid bulb IMT, remained significant.

Conclusions

In healthy, normally ovulating women, low AMH concentrations are associated with an adverse lipid profile and subclinical atherosclerosis, independently of traditional CV risk factors. This finding suggest a role of decreased follicular reserve with atherosclerotic disease.

Funding Acknowledgement

Type of funding source: None
Diabetic cardiovascular autonomic neuropathy in children
Authors: Gumeniuk O.L.G.A , Bolotova N , Averianov A , Chernenkov I.U
Published: November 2020

Diabetic cardiovascular autonomic neuropathy (CAN) encompasses damage to the autonomic nerve fibers innervating the heart and blood vessels, resulting in abnormalities in heart rate control and vascular dynamics.

Clinical symptoms associated with CAN include resting tachycardia, postural hypotension, dizziness, syncope, exercise intolerance, silent myocardial infarction.

The earliest finding of CAN, even at the subclinical stage, is a decrease in heart rate variability (HRV)

Purpose

To study CAN prevalence and understand the diagnostic capabilities of HRV - tests of diabetic cardiovascular autonomic neuropathy in children with type 1 diabetes.

Methods

100 children with type 1 diabetes were assessed for CAN (age 15.2 yrs [9.0–17.8], duration 6.5 yrs [4.0–10.6], HbA1c 8.1% 6.3–9.7]). The degree of compensation of diabetes was estimated according to criteria ISPAD Consensus Guidelines, 2018. Optimal level (HbA1c <7.0%) of compensation was revealed in 62% of children (group I) and nonoptimal in 38% of children (group II). For evaluation of the CAN we used HRV - tests: RR 30:15 ratio, ΔRR quiet breath, ΔRR deep breath, BP response to standing.

Results

Diabetic cardiovascular autonomic neuropathy was diagnosed in 41 children: in group I – in 6 (29%) and in group II – 35 (71%) children (p=0.00001). The prevalence of DCN correlated with HbA1c level in children and adolescents (groups I and II): ΔRR quiet breath r=−0.47 & r=−0.9; ΔRR deep breath r=−0.65 & r=−0.85; RR30:15 r=−0.77 & r=−0.88 respectively. Prevalence of CAN increased parallel to type 1 diabetes duration (p<0.01).

Conclusions

Diabetic cardiovascular autonomic neuropathy in children with type 1 diabetes was diagnosed in 41%. Prevalence of diabetic cardiovascular autonomic neuropathy increases parallel to type 1 diabetes duration (p<0.01). In this study we found an association between HRV indexes and HbA1c level. This provides support for HRV - testing to assess diabetic cardiovascular autonomic neuropathy in children.

Funding Acknowledgement

Type of funding source: None
Vascular ring surgery – can we do better?
Authors: Amir G , Soffair N , Frenkel G , Bruckheimer E , Nachum E , Rotshtein A , Sheinfeld T , Birk E
Published: November 2020

Background

Vascular anomalies of the Aortic arch can cause respiratory symptoms in children due to tracheal compression. Treatment consists of division of the vascular rings, nevertheless data regarding mid- term results is scarce. The purpose of this study was to evaluate clinical results of vascular ring surgery.

Methods

Between2007–2014, 85 children underwent vascular ring surgery. 51 had Double Aortic Arch (DAA, 60%), 31 Right Arch with Aberrant Subclavian Artery (RAA & ALSA, 36.5%) and 3 had RAA, mirror image branching & left ductus arteriosus (3.5%). Mean age and weight at operation were 12.4±13months and 8.6±4.1 kg respectively. Mid-term follow-up included clinical follow up by a pulmonologist (38 patients, 44.7%) and a telephone questionnaire (71 patients, 83%) performed 57±25.7 months after surgery.

Results

In most patients, symptomatic relief occurred in less than 6 months (table 1). Mid –term follow up revealed that although most parents described a significant improvement in their child's respiratory symptoms (95%), a significant number of patients described some residual respiratory symptoms (table 2). We did not find any significant association between age at surgery (under 6 month), or vascular ring anatomy (DAA vs. RAA&ASA) and the presence of residual symptoms at follow up

Conclusions

Surgical division of vascular rings results in a significant clinical improvement within one year, nevertheless many patients remain symptomatic to some degree. We found no association between the age at surgery or anatomic variant to the presence of symptoms in mid- term follow up. Further evaluation whether a more aggressive surgical approach is warranted in order to decrease the incidence long-term symptoms.

Funding Acknowledgement

Type of funding source: None
Predicting non-elective hospital readmission or death using a composite assessment of cognitive impairment and frailty in elderly inpatients with cardiovascular diseases
Authors: Yao S , Wang H , Yang J , Sun N
Published: November 2020

Background

Cardiovascular disease (CVD) and related complications are significant healthcare problems in the growing elderly population. Metabolic factors are the predominant risk factors for CVD, sedentary behaviour and physical inactivity are major modifiable risk factors for CVD. Age-associated cognitive decline and impairment are associated with an increased mortality. Cognitive and physical components of frailty have pathophysiologic rationale as risk factors for CVD. There is a clinical need to identify more practical screens that can assist us to definite cognitive impairment and physical frailty, then to determine which patients with CVD are at high risk of adverse outcomes, early management of these high-risk patients can reduce readmission rates, healthcare spending, and improve quality of care.

Purpose

We aimed to assess the utility of a combination developed using the mini-mental state examination + clock drawing test and the Fried phenotype for predicting non-elective hospital readmission or death within 6-month in elderly inpatients with CVD.

Methods

A single center prospective cohort was conducted between September 2018 and February 2019. Inpatients aged 65 years or older were recruited. All enrolled patients received a comprehensive geriatric assessment during hospitalization. The Kaplan-Meier curves were used to estimate the cumulative incidence of events. The multivariate Cox regression model was used to analyze the association between frailty and cognitive status and the non-elective hospital readmission or death.

Results

A total of 542 patients were included; and a total of 113 patients (20.9%) died or were readmitted at 6-month. Overall 20% screened positive for cognitive impairment, including 8% were cognitive impairment combined with physical frailty, which were more older, more common in women and non-married group, had a lower education and a higher risk of malnutrition. Frail participants with normal (hazard ratio [HR]: 1.73, 95% confidence intervals [CI]: 1.06–2.82, P=0.028) and impaired cognition (HR: 2.50, 95% CI: 1.27–4.91, P=0.008) had a higher risk of non-elective hospital readmission or death than robust patients, after adjustment for age, sex, education level, marital status, the presence of diabetes mellitus, heart failure, and previous stroke.

Conclusions

The presence of physical frailty and cognitive frailty were powerful predictors of non-elective hospital readmission or death in elderly inpatients with CVD, and taking cognitive impairment into account in the frailty model may allow better prediction of adverse outcomes of frailty in the short time.

Kaplan-Meier survival curves

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): Beijing Municipal Science & Technology Commission, Chinese Academy of Medical Sciences
Outcomes of nonagenarians with acute coronary syndrome
Authors: Echarte Morales J , Cepas Guillen P.L , Caldentey G , Martinez Gomez E , Borrego-Rodriguez J , Vidal P , Llagostera M , Viana Tejedor A , Benito Gonzalez T , Flores-Umanzor E , Quiroga X , Perez De Prado A , Freixa X , Sabate M , Fernandez-Vazquez F
Published: November 2020

Background

Myocardial infarction (MI) in nonagenarians is associated with high morbidity and mortality. Nonetheless, this population has typically been underrepresented in cardiovascular clinical trials.

Objective

The aim of this study was to evaluate outcomes of nonagenarian patients presenting with MI who underwent either conservative or invasive management.

Methods

We retrospectively included all consecutive patients equal to or older than 90yo admitted with non-ST segment elevation (NSTEMI) or ST segment elevation MI (STEMI) in four tertiary care centers between 2005 and 2018. Patients with type 2 myocardial infarction were excluded. We collected patients' baseline characteristic and procedural data. In-hospital and at 1-year follow-up all-cause mortality and major adverse cardiovascular events were assessed.

Results

523 patients (mean age 92.6±2 years; 60% females) were analyzed. Overall, 184 patients (35.2%) underwent percutaneous coronary intervention (PCI), increasing over the years, mostly in STEMI group (from 16% of patients in 2005 to 75% in 2018). PCI was preferred in those subjects with less prevalence of disability for activities of daily living (p<0.01). The use of a radial access (76.6%) and bare metal stents (52.7%) was predominant. No significant differences were found in the incidence of major bleeding events or MI-related mechanical complications between both strategies. During index hospitalization, 99 (18.9%) patients died. Whereas no differences were found in the NSTEMI group (p=0.61), a significant lower in-hospital mortality was observed in STEMI group treated with PCI (p<0.01). At one-year follow up, 203 (38.8%) patients died, most of them due to a cardiovascular cause (60.6%). PCI was related to a lower all-cause mortality in either NSTEMI (p<0.01) or STEMI groups (p<0.01) however, lower cardiovascular mortality was only found in STEMI group (p=0.03).

Conclusion

An invasive approach was performed in over a third of nonagenarian patients, carrying prognostic implications and with a few numbers of complications. PCI seems to be the preferred strategy for STEMI in this high-risk population in spite of age.

Figure 1

Funding Acknowledgement

Type of funding source: None
Thromboembolic events and major bleeding in frail patients with incident atrial fibrillation: a nationwide cohort study
Authors: Hojen A.A , Soegaard M , Nielsen P.B , Skjoeth F , Coleman C.I , Lip G.Y.H , Larsen T.B
Published: November 2020

Background

Growing evidence suggests that frail patients presenting with atrial fibrillation (AF) are less likely to receive adequate oral anticoagulant therapy (OAC) despite high thromboembolic risk. There is a paucity of evidence investigating clinical outcomes in different antithrombotic strategies.

Purpose

To assess thromboembolic events, bleeding, and all-cause mortality according to OAC treatment regimen in a Danish nationwide cohort of frail patients with AF

Method

We included all patients with non-valvular AF between 2011 and 2018 who were aged ≥64 years and had a frailty risk score >5 according to the ICD-10 based Hospital Frailty Risk Score. Patients with an OAC indication other than atrial fibrillation were excluded. The cohort was stratified by treatment regimen: warfarin, NOACs standard dose, NOACs reduced dose, or no OAC, determined by treatment status within 60 days before and 30 days after AF diagnosis. Patients were followed from 30 days after AF diagnosis (index date) for the occurrence of thromboembolic events and major bleeding. Cumulative incidence functions were used to depict development of outcome risk over time using on the Aalen–Johansen estimator assuming death as competing risk.

Results

We identified 31,745 frail AF patients (mean age 80.7 years, 53.8% female); 16540 (52.1%) received no OAC, 2993 (9.4%) received warfarin, 6181 (19.5%) received standard dose NOACs, and 6031 (19.0%) revived reduced dose NOACs. Risk of developing the outcomes over time is depicted in Figure 1. At 1-year follow-up, the absolute risk of thromboembolic events was 5.0% for patients with no OAC, 4.2% for reduced dose NOACs, 4.1% for warfarin, and 3.4% for standard dose NOACs. Bleeding risk was 6.1% for warfarin, 5.4% for reduced dose NOACs, 5.2% for No OAC, and 5.1% for standard dose NOACs.

Conclusions

Most patients in this nationwide cohort of elderly frail AF patients received no OAC, which was associated with a high risk of thromboembolism. The associated risk of thromboembolism was lower in patients receiving other studied treatment modalities, which might suggest a benefit of OAC across different antithrombotic strategies in frail AF patients. However, differences in risk profile and patient specific factors are likely to influence our observations, and studies investigating the comparative effectiveness and safety of NOACs including dosage regimens in frail AF patients are warranted.

Figure 1. Cumulative risk of events

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Bayer AG
Differential impact of obstructive and restrictive ventilatory patterns on incident heart failure with preserved versus reduced ejection fraction in late-life
Authors: Ramalho S , Claggett B.L , Kitzman D.W , Chang P.P , Cipriano Junior G , Solomon S.D , Skali H , Shah A.M
Published: November 2020

Background

Subclinical pulmonary dysfunction predicts cardiovascular (CV) outcomes, especially heart failure (HF). However, the impact of reduced percent predicted forced vital capacity (ppFVC) and forced expired volume in 1 second (FEV1)/FVC on different incident HF phenotypes in late-life is unclear.

Purpose

Determine the associations of FEV1/FVC and ppFVC with incident HF with preserved (HFpEF) and reduced (HFrEF) ejection fraction in late-life.

Methods

In the Atherosclerosis Risk in Communities longitudinal cohort study, 3,854 HF-free participants who underwent echocardiography and spirometry at the fifth study visit (2011–2013). The relation between pulmonary function and incident adjudicated HFpEF and HFrEF were examined using multivariable Cox proportional hazards models adjusted for demographics, body mass index, coronary artery disease, atrial fibrillation, hypertension, diabetes, and NT-proBNP.

Results

Mean age was 75±5 years, 40% were male, 19% black, and 6% current smokers. Mean FEV1/FVC was 72±8, and ppFVC was 98±17%. At a median follow-up of 5.6 years, lower ppFVC was independently associated with incident HFpEF, but not HFrEF (Table). Lower FEV1/FVC ratio was associated with higher risk of incident HFrEF but not HFpEF in models adjusted for demographics, which did not persist after further adjustment for clinical risk factors.

Conclusion

The relationships of reduced ppFVC and FEV1/FVC with incident HF differ significantly by HF phenotype.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services
Frailty syndrome as an independent predictor of unfavorable outcome in patients undergoing coronary artery bypass grafting
Authors: Krivoshapova K , Barbarash O.L , Wegner E.A , Terentyeva N.A , Grigorieva I.I , Masenko V.L , Kokov A.N
Published: November 2020

Purpose

To assess the prevalence of frailty in the preoperative period and to evaluate its effect on the risk of complications and adverse outcomes in patients undergoing coronary artery bypass grafting (CABG).

Methods

303 patients undergoing preoperative management for elective primary CABG were recruited in the study. The study cohort was divided into three groups depending on the PRISMA-7 scores suggesting the presence or absence of frailty and the presence of prefrailty. Statistical analysis was performed using the commercially available software package STATISTICA 8.0.360.0 for Windows (StatSoft, Inc., USA) and SPSS Statistics v. 17.0.0.

Results

46 (15%) patients had frailty, while 49 (16%) patients were diagnosed with prefrailty. 208 (69%) patients did not have any signs of frailty. All three groups had significant age differences, therefore only elderly patients aged of 67.0±6.5 years with frailty were allocated for subsequent analysis (prefrailty group - 62.3±7.4 years old, patients without frailty - 60.0±7.7 years, p=0.003). Patients with frailty or prefrailty more often suffered from diabetes mellitus (patients without frailty - 19.2%, prefrailty group - 30.6% and frailty group - 28.3%, p=0.05), arterial hypertension (69.2%, 93.9% and 95.7%, respectively, p<0.001), atrial fibrillation or flutter (7.2%, 14.3% and 19.6%, respectively, p=0.03), chronic heart failure class 3–4 (7.2%, 10.2% and 8.7%, respectively, p=0.002), and peripheral arterial disease (22.6%, 38.8% and 58.7%, respectively, p<0.001). Three groups were comparable in main clinical and demographic parameters. There were no significant differences found in the incidence of postoperative atrial fibrillation or flutter (15.9%, 8.2% and 6.5%, respectively, p=0.07) and infections (1.9%, 0% and 4.3%, respectively, p=0.640). The incidence of myocardial infarction in the intra- and early postoperative period after CABG did not differ significantly between the groups (0.5%, 2% and 0%, respectively, p=0.328) as well as the incidence of stroke (2.4%, 2% and 0%, respectively, p=0.640). Patients with frailty and prefrailty had significantly higher cerebrovascular and cardiovascular mortality compared to those without frailty (8.2%, 2.2% and 0.5%, respectively, p=0.001).

Conclusion

Almost 15% of patients referred to CABG suffered from frailty. The presence of prefrailty or frailty increases the risk of death in the early postoperative period after CABG.

Funding Acknowledgement

Type of funding source: None
Impact of old and very old age on outcomes in patients with acute ischemic stroke undergoing endovascular therapy
Authors: Proietti M , Mascolo A.P , Maramma F , Morosetti D , Da Ros V , Gandini R , Alemseged F , Diomedi M , Koch G , Sallustio F
Published: November 2020

Background and purpose

Only a restricted number of elderly patients has been included in the majority of recent endovascular stroke trials. We provided an analysis about differences in outcomes after mechanical thrombectomy (MT) according to age.

Methods

A retrospective analysis of an observational registry of patients with anterior large vessel acute ischemic stroke was performed. Main analysis was performed comparing patients <80 vs. ≥80 years old. A sensitivity analysis was performed comparing 3 age groups: i) <80 years; ii) 80–84 years; iii) ≥85 years. Outcomes were: i) any hemorrhagic infarction; ii) alive with disability; iii) death; iv) a composite outcome of alive with disability/death.

Results

615 patients were identified. 227 (36.9%) patients were ≥80 years old, with 115 (18.5%) ≥85 years old. Elderly (≥80 years) patients showed a higher modified Rankin Scale (mRS) at discharge and 3-months follow-up (F=9.819, p=0.001) [Figure 1]. Comparing the three groups (<80 years, 80–84 years, ≥85 years) a progressively higher mRS was found at discharge and 3 months follow-up (F=4.899, p=0.008). A progressively higher rate of death and composite outcome between the age groups was found, both in the main and sensitivity analyses. In the logistic regression analysis age ≥80 years was found associated with an increased risk of death (odds ratio [OR]: 2.25, 95% confidence interval [CI]: 1.27–4.00) and showed a trend in higher risk for composite outcome (OR: 1.61, 95% CI: 0.92–2.281). No difference was found between 80–84 years and <80 years patients, while very elderly (≥85 years) had an increased risk of death (OR: 2.85, 95% CI: 1.60–5.10) and composite outcome (OR: 2.37, 95% CI: 1.30–4.33).

Conclusions

In our analysis elderly patients have an increased risk of death and composite outcome of disability and death. In particular, this risk appears to be significantly higher in very elderly patients (≥85 years old).

Figure 1. mRS according to main analysis

Funding Acknowledgement

Type of funding source: None
Patterns of anticoagulation for atrial fibrillation in cancer patients referred for cardio-oncological evaluation
Authors: Toma M , Rrapaj E , Giovinazzo S , Sarocchi M , Stronati G , Dello Russo A , Porto I , Spallarossa P , Guerra F , Ameri P
Published: November 2020

Background

Direct oral anticoagulants (DOAC) are the standard of care for the prophylaxis of non-valvular atrial fibrillation (NVAF)-cardioembolism, but their use in oncological patients has been limited so far.

Methods

We retrospectively reviewed the records of the patients referred to two cardio-oncology outpatient units between January 2017 and July 2019, and selected those presenting with NVAF, CHA2DS2-VASc ≥1 for men and ≥2 for women, and cancer on active treatment. The following were considered as contraindications to DOAC: severe chronic kidney disease; anti-neoplastic therapy unknown or with potential moderate-to-severe adverse interactions; cirrhosis or liver metastases. Clinical characteristics of patients on DOAC (group 1), on VKA or LMWH with at least 1 contraindication to DOAC (group 2), and on VKA or LMWH despite not having contraindications to DOAC (group 3) were compared by chi-square or ANOVA.

Results

Of a total of 3,831 patients, 264 (6.9%) met the inclusion criteria (Figure 1). One-hundred fourteen (43.2%) were in group 1, 61 (23.1%) in group 2 (18 on VKA, 43 on LMWH), and 65 (24.6%) in group 3 (27 on VKA, 38 on LMWH). Anticoagulation was omitted in 24 (9.1%) cases for various reasons: spontaneous bleeding (5), anaemia and/or thrombocytopenia (5), frailty (4), CHA2DS2-VASc 1 (3), pharmacological interactions (1), single episode of NVAF (1); and not clearly motivated in 5 subjects.

The only significant difference between the 3 groups was serum creatinine concentration (Table 1). Of note, only 10% of subjects in group 1 received an inappropriate DOAC dose, while LMWH was under-dosed for 18% of patients in group 2 and 31% of patients in group 3 (P=0.002).

Conclusions

In the setting of a dedicated cardio-oncology consultation, DOAC and VKA are most often appropriately prescribed to cancer patients with NVAF. However, there is residual use of LMWH, not infrequently at non-anticoagulant dosage. This is a non-evidence based common practice in clinical oncology that clearly must be abandoned

Figure 1

Funding Acknowledgement

Type of funding source: None
Exercise cardiac MRI unmasks cardiac dysfunction in childhood and adolescent cancer survivors with reduced cardiopulmonary fitness
Authors: Foulkes S , Costello B , Howden E.J , Janssens K , Dillon H , Toro C , Fraser S.F , Daly R.M , Elliott D.A , Conyers R , La Gerche A
Published: November 2020

Background

Young cancer survivors are at increased risk of impaired cardiopulmonary fitness (VO2peak) and heart failure. Assessment of exercise cardiac reserve may reveal sub-clinical abnormalities that better explain impairments in fitness and long term heart failure risk.

Purpose

To investigate the presence of impaired VO2peak in pediatric cancer survivors with increased risk of heart failure, and to assess its relationship with resting cardiac function and cardiac reserve

Methods

Twenty pediatric cancer survivors (aged 8–24 years) treated with anthracycline chemotherapy underwent cardiopulmonary exercise testing to quantify VO2peak, with a value <85% of predicted defined as impaired VO2peak. Resting cardiac function was assessed using 3-dimensional echocardiography, with cardiac reserve quantified from resting and peak exercise heart rate (HR), stroke volume index (SVi) and cardiac index (CI) using exercise cardiac magnetic resonance imaging.

Results

12 of 20 survivors (60%) had impaired VO2peak (97±14% vs. 70±16% of age and gender predicted). There were no differences in echocardiographic or CMR measurements of resting cardiac function between survivors with normal or impaired VO2peak. However, those with reduced VO2peak had diminished cardiac reserve, with a lesser increase in CI (Fig. 1A) and SVi (Fig. 1B) during exercise (Interaction P=0.001 for both), whilst the HR response was similar (Fig. 1C; P=0.71).

Conclusions

Resting measures of cardiac function are insensitive to significant cardiac dysfunction amongst pediatric cancer survivors with reduced VO2peak. Measures of cardiopulmonary fitness and cardiac reserve may aid in early identification of survivors with heightened risk of long-term heart failure.

Figure 1

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): National Heart Foundation
Cardioprotection using strain-guided management of potentially cardiotoxic cancer therapy: 1 year results of the SUCCOUR trial
Authors: Negishi T , Thavendiranathan P , Penicka M , Lemieux J , Aakhus S , Miyazaki S , Shirazi M , Galderisi M , Cho G.Y , Popescu B.A , Kosmala W , Negishi K , Marwick T.H
Published: November 2020

Background

Conventional criteria for diagnosis of chemotherapy-related cardiac dysfunction (CTRCD) are dependent on the recognition of heart failure (HF) symptoms and/or changes in LVEF. However, the low sensitivity of EF for minor changes in LV function may delay initiation of cardio-protective therapy (CPT). Global longitudinal strain (GLS) is a robust and sensitive marker of LV dysfunction (LVD), but existing observational data are insufficient to justify changing the diagnostic criteria for CTRCD.

Purpose

To identify whether GLS guidance of CPT would improve cardiac function of at risk patients undergoing potentially cardiotoxic chemotherapy, compared with usual care.

Methods

In this international multicenter prospective randomized controlled trial, 331 pts from 23 international sites taking anthracyclines with another risk factor for HF were randomly allocated into 166 undergoing GLS-guided (CPT for >12% relative reduction in GLS using Echopac software) and 165 EF-guided (CPT for >10% absolute reduction of EF). Pts were followed over 1 year for the primary end-point (ΔEF) with 3D echo (3DE); 2D echo (2DE) was used when 3D images were unsuitable for measurement. Development of CTRCD (EF reduction of 10% to <55%) was a secondary endpoint.

Results

Of 331 randomized patients, 24 withdrew before follow-up imaging was performed (2 died, and rest withdrew or were lost to follow-up). Among 307 patients (age 54±12 years, 94% women) with follow-up 1.0±0.2 years, 277 had breast cancer, 30 had lymphoma/leukemia. HF risk factors were prevalent: 89 (29%) had hypertension and 39 (13%) had diabetes mellitus. The most common chemotherapy regimen during this study was the combination of anthracycline and trastuzumab. The baseline 3D LVEF was 61±5%, and GLS was −20.8±3.2%. At 1 year follow-up, 31 (10%) met CTRCD and was reduced in the GLS-guided arm (Table 1), although new LV dysfunction (EF<55%) and change of EF were not different.

Conclusion

In this international multicentre trial, the incidence of CTRCD was reduced by strain-guided cardioprotection. Although the final EF and the number of pts developing EF <55% was not altered by strain-guided therapy, this reduces meaningful reduction of EF to the abnormal range. The results support the use of GLS in surveillance for CTRCD.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): General Electric Medical Systems
Cardiac fibroblast activation protein density indicative of cardiovascular disease and remodeling
Authors: Heckmann M , Reinhardt F , Daniel F , Katus H.A , Haberkorn U , Leuschner F , Lehmann L.H
Published: November 2020

Background

Fibroblast activation protein (FAP) plays an important role in cardiac wound healing and remodelling. Although initially developed as a theranostic ligand for metastasized cancer, FAPI tracers have recently been used to study cardiac remodelling following myocardial infarction in small animal models. Aim of our analysis was to evaluate the activity of fibroblast activation protein via (FAPI) PET-CT scans in human hearts.

Methods

FAPI-PET-CT scans of 229 patients of two consecutive cohorts (initial cohort: n=185; confirmatory cohort: n=44) suffering from metastasized cancer were analysed using a 17-segment model of the left ventricle. Patient characteristics included age, sex, cancer entity, body mass index, renal function, thyroid stimulating hormone, cardiovascular risk factors, previous radiation to the chest, chemotherapies received, and current cardiac medication. Multivariate regression models were created using data from the initial cohort by selecting variables according to Akaike's information criterion in a step-down approach. Linear regression models were used for signal prediction to find potential outliers with unexpectedly high signal intensities. The created models were subsequently evaluated in the confirmatory cohort for reproducibility.

Results

Signal intensity were significantly higher in patients with overweight, diabetes and following radiation to the chest. Our prediction model performed well in both cohorts. A focal enrichment pattern was more frequently observed in patients with known cardiovascular risk factors.

Conclusions

FAPI-PET-CT scans represent a new imaging modality to potentially investigate active cardiac remodelling. High signal intensities are associated with cardiovascular risk factors and metabolic disease. Furthermore, high cardiac FAPI signal intensities are suggestive of an underlying cardiac disease.

Funding Acknowledgement

Type of funding source: None
A look at peripartum cardiomyopathy over the last decade: a single centre study in a US minority population
Authors: Mahabir S , Acuna-Morin E , Becerra-Gonzales V , Maning J , Dantas Ferreira Fernandes A , Chaparro S
Published: November 2020

Background

The incidence of Peripartum Cardiomyopathy (PPCM) has been increasing and is estimated at 1 in 2000 live births in the United States. We explored the PPCM population at our institution – a South Florida cohort comprised largely of Haitian and Hispanic patients making it a distinct population compared to previously published data.

Purpose

To better understand the demographics and determinants of recovery in this minority population.

Methods

We retrospectively identified PPCM patients from January 2009 to January 2019 using ICD 10 codes. Data on baseline characteristics was collected from the electronic medical record. Our primary endpoint was to evaluate myocardial recovery as characterised by an ejection fraction (LVEF) greater than 50%. Secondary outcomes included the incidence of cardiac devices implantation, transplantation, and recurrent pregnancies.

Results

52 patients were identified in the study period. Sixty-seven percent of patients were African American, 15% Hispanic, 10% Haitian and 8% were Caucasian. At the time of diagnosis, mean age was 29 years (95% CI 27.0–30.4), mean BMI 33 (95% CI 29.9–35.9) and mean LVEF 19% (95% CI: 16.4–22.7). Amongst the co-morbidities reported, hypertension (33%), pre-eclampsia (13%) and diabetes (12%) were the most prevalent. The time to diagnosis differed significantly; 32% were diagnosed at the time of delivery and of the remaining diagnosed post-delivery, average time to diagnosis was 12 weeks (95% CI: 4.3–19.4). Only 13% had recovery of their LVEF, 56% did not recover and 16% had no follow-up LVEF documented. Amongst the patients who did not recover, 41% had right ventricular dysfunction and the commonest valvopathy seen was moderate to severe mitral regurgitation. Interestingly, 29% of the patients had documented recurrent pregnancies after their initial diagnosis.

Conclusion

Elevated BMI, hypertension and pre-eclampsia are commonly seen in this PPCM minority population suggesting that patients seen in antenatal clinic with these features should be closely followed for progression to PPCM. The lack of follow-up echocardiograms and high incidence of recurrent pregnancy supports the need for a dedicated registry for PPCM patients to improve follow-up surveillance which may result in improved long-term mortality and recovery in these patients.

Funding Acknowledgement

Type of funding source: None
RNAi inhibition of angiopoietin-like protein 3 (ANGPTL3) with ARO-ANG3 mimics the lipid and lipoprotein profile of familial combined hypolipidemia
Authors: Watts G.F , Schwabe C , Scott R , Gladding P , Sullivan D , Baker J , Clifton P , Hamilton J , Given B , San Martin J , Melquist S , Knowles J.W , Goldberg I , Hegele R , Ballantyne C
Published: November 2020

Background

Elevated LDL-C and triglyceride rich lipoproteins (TRLs) are independent risk factors for cardiovascular disease (CVD). Genetic deficiency of angiopoietin-like protein 3 (ANGPTL3) is associated with reduced circulating levels of LDL-C, triglycerides (TGs), VLDL-C, HDL-C and reduced CVD risk, with no described adverse phenotype. ARO-ANG3 is a RNA interference drug designed to silence expression of ANGPTL3. Single doses of ARO-ANG3 have been shown to reduce ANGPTL3, TGs, VLDL-C and LDL-C in healthy volunteers (HVs, AHA 2019). We report the effects of multiple doses of ARO-ANG3 in HVs with a focus on the duration of action.

Methods

ARO-ANG3 was administered subcutaneously to HVs on days 1 and 29 at doses of 100, 200 or 300 mg (n=4 per group). Measured parameters included ANGPTL3, LDL-C, TGs, VLDL-C and HDL-C. Follow up is ongoing.

Results

All HVs have received both doses and follow-up is currently through week 16 (12 weeks after second dose). Mean nadir for ANGPTL3 levels occurred 2 weeks after the second dose (−83–93%) with minimal change for 200 and 300 mg but 16% recovery for 100 mg at week 16. Mean TGs and VLDL-C reached nadir earlier (3 wks, −61–65%) without apparent dose response and minimal change for any dose at wk 16. LDL-C nadir occurred 4–6 wks after the second dose (−45–54%), again with minimal evidence for dose response or change through wk 16. HDL-C was reduced 14–37% at wk 16. ARO-ANG3 was well tolerated without serious or severe adverse events or dropouts related to drug. The most common adverse events have been headache and upper respiratory infections.

Conclusions

Genetic deficiency of ANGPTL3 is a cause of familial combined hypolipemia and is associated with a decreased risk of CVD. Using RNAi to selectively suppress ANGPTL3 production reproduces these genetic effects with a duration of at least 12 weeks following a second dose and with good tolerability over 16 wks. ANGPTL3 inhibition results in lowering of LDL-C and TRLs which may confer protection against CVD in patients with atherogenic mixed dyslipidemia.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Arrowhead Pharmaceuticals
Clinical outcomes after reversal of dabigatran in daily practice: real-world use of idarucizumab 2015–2019
Authors: Haastrup S , Hellfritzsch M , Nybo M , Hvas A.M , Grove E.L
Published: November 2020

Background

Idarucizumab was introduced in Europe in December 2015 as an antidote to dabigatran. Whether reversing the anticoagulant effect of dabigatran actually reduces the risk of bleeding complications and mortality remains sparsely described. No randomized placebo-controlled trial evaluating the efficacy of idarucizumab has been conducted. Therefore, evaluation of real-world data is of major importance to further investigate the use of idarucizumab in daily clinical practice.

Purpose

We aimed to investigate the real-world use of idarucizumab and associated clinical outcomes.

Methods

The study was conducted as an observational case series. Using our regional electronic patient record, all patients treated with idarucizumab from market introduction to end of 2019 were identified. We had complete coverage of the use of idarucizumab at a large University Hospital in Denmark. During Spring 2020, we will also include patients from regional hospitals.

Results

A total of 39 patients were treated with idarucizumab. All patients but one received dabigatran due to atrial fibrillation. Indications for idarucizumab use were “need for acute surgery” in 21 (54%), “bleeding” in 14 (36%), “prior to thrombolysis” in two (5%), and “dabigatran intoxication” due to renal failure in two (5%, one presenting with bleeding and one patient without). No patients were treated with activated carbon or dialysis. A total of five patients (13%) experienced bleeding within 30 days after infusion and none had thromboembolic complications. After 30 days follow-up, 32 (82%) patients were alive and 29 restarted anticoagulant treatment (19 lowmolecular-weight heparin, 11 dabigatran, one rivaroxaban, and one apixaban).

Conclusion

Among patients treated with idarucizumab, few experienced adverse outcomes and the 30-day survival rate was high. In line with observations from the REVERSE-AD trial, our data supports that idarucizumab is safe in patients experiencing life-threatening bleeding or needing acute surgery.

Funding Acknowledgement

Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Unrestricted research grant from Boehringer Ingelheim
Association between chronic kidney disease and outcomes among admissions for acute ischemic stroke receiving thrombolysis
Authors: Weeda E
Published: November 2020

Background

Patients with chronic kidney disease may have hemostatic defects that increase the risk of bleeding following the administration of thrombolysis.

Purpose

We assessed the association between chronic kidney disease and intracerebral hemorrhage in acute ischemic stroke admissions receiving thrombolysis.

Methods

Using administrative data from the 2013 and 2014 National Inpatient Sample, adult acute ischemic stroke admissions treated with thrombolysis were identified. Patients with chronic kidney disease were identified via diagnostic coding. We used multivariable logistic regression to estimate the odds of intracerebral hemorrhage in patients with chronic kidney disease after adjustment for age and comorbidities. The association between chronic kidney disease and in-hospital mortality was also evaluated.

Results

Of 13,993 admissions treated with thrombolysis for acute ischemic stroke, 12.4% (n=1,739) had chronic kidney disease. Intracerebral hemorrhage occurred in 7.6% of patients and 7.0% experienced in hospital mortality. Chronic kidney disease did not increase the odds of intracerebral hemorrhage (odds ratio [OR]=1.00; 95% confidence interval [CI]=0.83–1.20). The adjusted odds of in-hospital mortality were also no different in those with versus without chronic kidney disease (OR=1.19; 95% CI=0.99–1.42).

Conclusions

Among admissions treated with thrombolysis for acute ischemic stroke, chronic kidney disease was not associated with a higher adjusted odd of intracerebral hemorrhage. Chronic kidney disease did not increase the odds of in-hospital mortality.

Funding Acknowledgement

Type of funding source: Other. Main funding source(s): SmartState Medication Safety
Is “one size fits all” anti-aggregation really effective? Variability in the response to P2Y12 receptor inhibitors in obese patients
Authors: Playan Escribano J , Vivas Balcones D , Lugo Gavidia L.M , Gomez Polo J.C , Marcano Fernandez A.L , Bernardo E , Ortega M.A , De La Hera Galarza J.M , Tello-Montoliu A , Besteiro Vazquez A , Silva I , Marin F , Roldan I , Gomez-Hospital J.A , Ferreiro J.L
Published: November 2020

Background

Different “ex vivo” studies have shown both a greater platelet activation and higher rates of resistance to clopidogrel in obese patients. Although there is less evidence, less prasugrel activity has also been observed in these patients. Our aim was to study the variability of the response to clopidogrel, ticagrelor and prasugrel in obese patients, defined as a body mass index ≥30.

Methods

Prospective, multicenter, observational, pharmacodynamic study, conducted in a Spanish population of patients with an acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI) and double anti-aggregation with acetylsalicylic acid and a P2Y12 receptor inhibitor. Platelet function tests were performed the morning after the ICP and 30 days after it, including: 1) VerifyNow P2Y12 assay; 2) multiple electrode aggreometry (Multiplate); and 3) VASP analysis.

Results

Of the total patients included (988), 300 were obese (30.3%). The obese group was younger (62.8±12 years vs 64.9±12), had a higher incidence of arterial hypertension (76.3% vs. 56.7%), diabetes mellitus (35% vs. 27.5%); and lower incidence of chronic kidney disease (7.7% vs. 17%). There were no differences in the acute phase (day 1 after PCI) in the pharmacodynamic response to any of the P2Y12 inhibitors used. After 30 days, greater platelet aggregation (decreased response) was documented in obese patients treated with prasugrel according to VASP tests (PRI in non-obese 23.9±13% vs. 30.4±14.7% in obese, p 0.035) and MEA (area under the aggregation units curve in non-obese 251.7±104.1 vs 320±166.7 in obese, p 0.007) and a numerical trend with VerifyNow. A trend in the same direction was also observed in patients treated with clopidogrel that did not reach statistical significance with all the platelet function tests used. No differences were observed in the ticagrelor group.

Conclusion

Obese patients with an ACS treated with PCI have a worse response to thienopyridines than non-obese patients in the maintenance phase of antiaggregant treatment, while the response to ticagrelor is not affected by obesity. Completing the clinical follow-up proposed by the registry is necessary to know if these differences have an implication in cardiovascular events.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Fondo de Investigaciones Sanitarias (FIS)
Prospective external validation of PRECISE-DAPT score for prediction of bleeding and thrombosis after coronary stent implantation
Authors: Jaspattananon A , Wongpraparut N , Naowapanich S , Satsue S , Seesung S
Published: November 2020

Background

Optimal duration of dual antiplatelet therapy (DAPT) after coronary stent implantation depends on bleeding and thrombotic risk in an individual patient. The PRECISE-DAPT score is recommended for adjusting of optimal DAPT duration.

Purpose

To assess external validation of PRECISE-DAPT score for prediction of out-of-hospital bleeding and thrombosis after coronary stent implantation in prospective manner.

Methods

We prospectively enrolled patients who underwent coronary stent implantation and received DAPT in our institution during June 2018 through December 2019. Out-of-hospital bleeding and thrombotic events were assessed for validation of PRECISE-DAPT score.

Results

Six hundred and two patients were enrolled. The mean age was 65.0±11.7 years and 28.2% were female. STEMI, NSTEMI/UA and chronic coronary syndrome were 24.4%, 22.6%, 53% respectively. Prevalence of prior bleeding was 6.3%. Mean follow-up period was 312±72 days. Bleeding events were 5.1%. High PRECISE-DAPT score (score ≥25) had significantly higher bleeding events (9.4% vs 2.4%, P-value <0.001), which were divided into major TIMI bleeding (3.4% vs 0.3%, P-valve 0.003) and minor TIMI bleeding (6.0% vs 2.2%, P-valve 0.014). MACE (CV death, MI, stroke) were 7% and significantly higher in high PRECISE-DAPT score (10.7% vs 4.6%, P-valve 0.004), compared with low PRECISE-DAPT score.

Conclusions

In real-world prospective study, high PRECISE DAPT score (score ≥25) is associated with high bleeding and thrombotic events. Because of increased both events in high PRECEISE-DAPT score, shortening DAPT duration requires physician final decision-making to balance future bleeding and thrombosis.

Funding Acknowledgement

Type of funding source: Public hospital(s). Main funding source(s): Siriraj grants for medical research and education, Faculty of Medicine Siriraj Hospital, Mahidol University