bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term echocardiographic assessment of descendants of gestational breast cancer patients exposed to anthracycline-based chemotherapy
Authors: Oneto Fernandez M , Gonzalez-Manzanares R , Garcia-Duran C , Mesa Rubio D , Ruiz Ortiz M , Delgado Ortega M , Rodriguez Almodovar A.M , Romo Penas E , De La Haba J , Castillo Dominguez J.C
Published: November 2020

Background

Breast cancer is the most common cancer in women and the leading cause of cancer death in women. Although gestational breast cancer (GBC) accounts only for a small amount of diagnosis, the incidence is increasing due to delayed childbearing.

Treating GBC is a significant challenge, having to maintain a balance between effective treatment for the patient and safety for the descendants.

Anthracycline-based chemotherapy (AC) remains to be the systemic treatment of choice in many GBC patients.

Although AC in GBC appears to be safe for the descendants, data on the long-term cardiotoxic effects of AC are scarce.

Purpose

To evaluate long-term cardiotoxicity on descendants of GBC patients exposed to AC during pregnancy or breastfeeding.

Methods

We retrospectively recruited descendants of GBC patients and classified them according to AC exposure (case group and non-exposed control group). We performed a thorough echocardiographic assessment.

Results

We identified 7 GBC patients that received AC during pregnancy (n=6) or breastfeeding (n=1). All of them were diagnosed during the second or third trimester. Median cumulative anthracycline dose was 508mg/m2.

A total of 8 cases and 5 controls were recruited. Median age at echocardiographic assessment was 10 years in cases and 8 years in controls. None of them had known prior cardiac disease. Echocardiographic parameters were within normal values in both groups (Table 1).

Conclusion

A long-term echocardiographic assessment showed no abnormalities in a series of descendants of GBC exposed to AC during pregnancy or breastfeeding. This study may contribute to a better understanding of the safety for the descendants of AC during pregnancy or breastfeeding.

Funding Acknowledgement

Type of funding source: None
Incident cardiovascular events and risk of subsequent cancer diagnosis
Authors: Fardman A , Oppenheim A , Banschick G.D , Rabia R , Segev S , Klempfner R , Fourey D , Percik R , Grossman E , Maor E
Published: November 2020

Background

Cardiovascular disease (CVD) and cancer share common risk factors. This study investigated the association of CVD diagnosis and the risk of future cancer.

Methods

We evaluated asymptomatic self-referred adults aged 40–79 years who participated in a screening program. All subjects were free of CVD and cancer at baseline. CVD was defined as the composite of acute coronary syndrome, percutaneous coronary intervention or stroke. Cancer and mortality data were available for all subjects from national registries. Primary end-point was development of cancer during follow up. Cox regression models were applied with CVD as a time-dependent covariate and death as a competing risk event.

Results

Final study population included 15,486 subjects. Median age was 50 years (Interquartile range [IQR] 44–55) and 72% were men. During median follow up time of 11 years (IQR 6–15) 1,028 (7%) subjects developed CVD, 1,281 (8%) developed cancer and 499 (3%) died. Most common cancer types were prostate among men (N=277, 1.8%) and breast among women (N=187, 1.2%). Time dependent survival analysis showed that subjects who developed CVD during follow up were 60% more likely to develop cancer (95% Confidence Interval [CI] 1.3–1.95, p<0.001). However, after adjustment for known predictors of cancer, the association of incident CVD with cancer diagnosis was no longer significant (p=0.21). Interaction analysis demonstrated that the association of incident CVD with the risk of future cancer diagnosis was age dependent such that in younger subjects (<50 years; N=7,649) incident CVD was associated with a significant 2 fold increased risk of subsequent cancer diagnosis (95% CI 1.2–3.6, p=0.014) while in older subjects incident CVD was not associated with increased risk of cancer in the multivariable model (p for interaction =0.035; Figure 1).

Conclusions

Incident CVD is independently associated with 2-fold increased risk of subsequent cancer diagnosis among young adults. Our analysis underscores the importance of cancer surveillance among young patients following a CVD event.

Figure 1

Funding Acknowledgement

Type of funding source: None
Amygdalar activity among patients with head and neck cancer predicts cerebrovascular events: a retrospective FDG PET/CT Cohort Study
Authors: Hassan M , Abohashem S , Wang Y , Jones O'connor M , Alvi R.M , Zlotoff D.A , Bakar R.B , Osborne M.T , Chan A.W , Wirth L.J , Awadalla M.A , Addison D , Tawakol A , Neilan T
Published: November 2020

Background

Radiation therapy for head and neck cancer (HNC) associates with an increase in cerebrovascular events. Amygdalar metabolic activity (AmygA), a measure of stress-associated neurobiological activity, associates with cardiovascular events in patients without cancer. In this study, we tested whether AmygA was associated with cerebrovascular events among patients treated with radiation therapy.

Methods

The associations between AmygA (at cancer staging) and subsequent cerebrovascular events as well as inflammatory biomarkers and arterial inflammation, were tested among consecutive patients with HNC treated with radiation therapy who underwent 18F-FDG-PET/CT.

Results

Among 240 patients (59±13 years; 30% female, 48% had stage 4 disease), there were 26 events over a median follow-up period of 3 years (IQR: 1.7–5.1). AmygA at cancer staging was associated with subsequent cerebrovascular events, an effect that remained significant after adjustment for age, sex, and cerebrovascular risk factors (adjusted hazard ratio 1.47, 95% CI 1.04–2.09, P=0.031). The association persisted when the analysis was restricted to patients with no prior history of CV disease and even among those with lower predicted CV risk (P<0.001). Higher AmygA at cancer staging also associated with serum inflammatory markers and arterial inflammation (P<0.05 each).

Conclusions

Amygdalar activity, a quantifiable biomarker of stress-associated brain activity, associated with subsequent cerebrovascular events among patients with cancer treated with radiation therapy.

Funding Acknowledgement

Type of funding source: None
Mitochondrial dysfunction associated with AC mode of chemotherapy intake
Authors: Avagimyan A.A , Mrochek A.G , Sarrafzadegan N , Konradi A.O , Aznauryan A.V , Chernova A.A , Oganov R.G , Mkrtchyan L.H , Ionov A.Y.U , Chelidze K.H , Petrosyan R.R , Petrosyan A.R , Aznauryan A.Z , Navasardyan G.A , Ostoumova O.D
Published: November 2020

Since the establishment of the anthracycline drugs cardiotoxigenic effect, the most widely accepted mechanistic base for their iatrogenic cardiotoxicity was connected with excessive and inadequate intensification of LPO. However, ineffectiveness of the antioxidant and multivitamin regimens of cardio-protection caused the necessity of finding new pathogenic targets, exposure to which will prevent the development of cardiovascular symptoms. Such a target became the nuclear topoisomerases, the study results of which served as the foundation for the creation of dexrazoxan, the only drug with this regard approved by the FDA. However, our interest was attracted towards the mitochondrial topoisomerases, since the integrity of the mitochondrial apparatus of cardiomyocytes is the basic link in maintaining the physiological morpho-functional balance of cardiomyocytes. At the same time, it is established that in the cell doxorubicin is predominantly accumulated in the mitochondria, which also makes emphasizes onto the prospects of studying this issue.

Purpose

Purpose of the study was to investigate the influence of AC mode of chemotherapy (adriamicin (doxorubicin) + cyclophosphomide) on the mitochondrial topoisomerases levels.

Methods

60 inbred mice of the C57BL/6J line with genotype a,H-2b were used. The experimental animals were divided into 2 groups: in the first group polychemotherapy in AC mode was applied; in the second group (placebo group) saline solution was used. Doxorubicin (Sigma Aldrich) was administered at a dose of 4 mg/kg and cyclophosphamid (Sigma Aldrich) at a dose of 2 mg/kg were administered intravenously. There were 4 courses conducted with the intervals of 21 days between them. The study results were recorded in 6 days after the last cycle of chemotherapy. The total duration of experiment was 90 days. The following types of topoisomerases have been studied: Top2β, Top3α, and Top1mt.

Results

The results of the first group showed a decrease in the Top2β level by 2.4±0.4%, Top3α - by 0.7±0.5, and Top1mt - by 49.5±11.7% (p=0.05). When analyzing the results of the second group no statistically significant changes were recorded.

Conclusion

The fact of AC mode of chemotherapy administered should be taken as a predictor of destabilization of the mitochondrial topoisomerases signaling, in particular of the Top1mt, which in turn, causes the development of mitochondrial dysfunction and results the energy imbalance in cardiomyocytes.

Funding Acknowledgement

Type of funding source: None
Severe preeclampsia is associated with postpartum diastolic dysfunction and non-dipping blood pressure profile pattern
Authors: Abdel Ghany M , Rashed M , Abbas A , Youssef A.M.R , Sayed M
Published: November 2020

Background

Left ventricular diastolic dysfunction and non-dipping profile, detected by ambulatory blood pressure monitoring (ABPM), are two features recorded to be associated with sustained hypertension. Both are predictors of an increased cardiovascular morbidity later in life. Complete normalization of blood pressure (BP) in preeclampsia is detected over a variable period of time.

Methods

A prospective cohort study was conducted in a tertiary university hospital including normotensive women with a history of preeclampsia in the current pregnancy enrolled within the first week postpartum. All cases were subjected to 24 h-ABPM and 2D trans-thoracic echocardiography three months post postpartum concomitantly with a clinical evaluation. Chi2-test was used to compare the qualitative data while student t-test was used to compare the quantitative data. Multivariate regression analysis was used for prediction of non-dippers and diastolic dysfunction in our cohort.

Results

Hundred twenty eight women were included in the study. Their mean age was 28.6±5.1 years and the mean basal BP was 123.1±6.4/74.6±5.9 mm Hg. Out of the studied women, 90 (70.3%) women were dippers and 38 (29.7%) women were non-dippers. It was noticed that diastolic dysfunction was presented in 28 (73.7%) of non-dippers while none of dippers had diastolic dysfunction. Women with severe preeclampsia had higher frequency of non-dipper (35.5% vs. 24.2%; P=0.02) and diastolic dysfunction (29% vs. 15%; P=0.01) in comparison to those women with mild preeclampsia. Severe preeclampsia and previous history of preeclampsia were significant predictors for non-dipping status (OR=1.1, 95% CI: 0.05–10.56 and 1.4, 95% CI: 0.30–4.26 respectively, R2 = 0.7; P<0.001). They were also predictors for diastolic dysfunction in our studied population (OR = 1.6, 95% CI: 1.1–2.2 and 1.3, 95% CI: 1.2–2.2 respectively, R2 = 0.6; P<0.05).

Conclusion

Women with a history of preeclampsia have the risk for developing cardiovascular events later in life. The severity and recurrence of preeclampsia were significant predictors for both non-dipping profile and diastolic dysfunction.

Funding Acknowledgement

Type of funding source: Public hospital(s). Main funding source(s): Orman Heart Hospital-Assiut University; Women Health Hospital-Assiut University
Cardiac surgery during pregnancy: what is the optimal timing of intervention? A meta-analysis of individual patient data
Authors: Van Steenbergen G , Tsang Q.H.Y , Kimmenade R.R.J , Van Der Heijden O.W.H , Vart P , Roos-Hesselink J.W , Li W.W.L , Verhagen A.F.T.M
Published: November 2020

Background

Cardiac disease can manifest or worsen during pregnancy and some cases urges cardiac surgery. According to current guidelines, the second trimester is supposed to be the optimal time frame. However, evidence for this recommendation is poor.

Objective

We evaluate whether an optimal period to undergo cardiac surgery during pregnancy can be identified, focusing on both maternal and foetal outcomes.

Methods

All studies published in Medline up to February 8th, 2018 on maternal and/or foetal outcome of cardiac surgery during pregnancy that included individual patient data were identified. Three groups were analysed: all identified patients (total population), patients who underwent caesarean section (CS) prior to cardiac surgery (subgroup A) and patients who underwent cardiac surgery with the foetus in utero (subgroup B). For the total population and subgroup B, logistic regression analysis was performed to find predictors of maternal and foetal outcome.

Results

We identified 142 studies including 328 patients of which 114 underwent CS prior to cardiac surgery (subgroup A). Maternal mortality in the total population was 5.2% and did not differ significantly among trimester (p=0.634). Foetal mortality in the total population was lowest in the third trimester (9.4%, p<0.01) and CS prior to surgery significantly reduced risk of foetal mortality in a multivariate model (OR 0.09, CI 0.02–0.35). Subgroup analysis showed foetal mortality of 7.0% in subgroup A and 33.6% in subgroup B (p<0.01). Trimester was not identified as a significant predictor for foetal and/or maternal mortality in subgroup B. See table 1.

Conclusion

Maternal mortality of cardiac surgery during pregnancy is not significantly influenced by trimester. Foetal mortality after maternal cardiac surgery is very high. When the fetus is viable, CS prior to cardiac surgery should be considered in the third trimester. If not feasible or safe to postpone surgery, trimester stage should not delay cardiac surgery.

Funding Acknowledgement

Type of funding source: None
Protease inhibitor-contaning antiretroviral therapy effects on QT interval and heart rate: a cross-sectional study
Authors: Rodriguez Szaszdi D , Bogran Castro D , Alvarado Sosa J
Published: November 2020

Background

HIV has been associated with QT prolongation and it is believed this is from drug interaction as well as HIV infection. In vitro studies have showed that protease inhibitors block potassium channel HERG, suggesting that these drugs can cause drug-induced QT prolongation. Few case-reports have showed that protease inhibitors can cause drug-induced bradycardia, but data is still limited.

Objective

To describe the correlation between HIV infection and the duration of QT interval and to evaluate the effects that protease inhibitors-containing antiretroviral regime have on the duration of QT interval and cardiac frequency.

Methods

A cross-sectional study was made. Participants were assigned to 3 groups: HIV positive with antiretroviral therapy which included protease inhibitors (HIV+ with treatment), treatment-naïve HIV positive and HIV negative. None of the participants had past medical history of cardiovascular disease or use of known QT prolonging medication. 12-lead ECG were made to all participants. QT interval and cardiac frequency were measured to be compared between the 3 groups and the results were analyzed by the statistical test ANOVA.

Results

A total of 213 participants were enrolled, 84 in the HIV+ with treatment, 45 in the HIV+ treatment-naïve, and 84 HIV-. 63% of the participants were males. The treatment-naïve HIV+ group only had 5 female participants. This study did not find a relation between HIV infection or protease inhibitor use and an increase in the duration of QT interval in males. For females, this study found an association between HIV infection and longer QT interval duration, as seen in the mean of each group: 442.8 ms for treatment-naïve HIV+ group, 422.42 ms for protease inhibitor HIV+ with treatment group and 420.34 ms HIV- group. It was found that the use of antiretroviral regime with protease inhibitor was associated with a decrease in cardiac frequency, as seen in each group's cardiac frequencies: HIV+ with treatment group: 63.34 bpm, treatment-naïve HIV positive: 79.77 bpm and control group: 69.3 bpm.

Conclusion

We did not find correlation between HIV infection, the use of protease inhibitor-containing antiretroviral regime and QT interval prolongation in males, as opposed to females, where it was shown that QT interval duration is longer in the HIV+ treatment-naïve group. It was also observed that the use of protease inhibitor-containing antiretroviral regime was associated with a decrease in cardiac frequency.

Funding Acknowledgement

Type of funding source: None
HIV may indirectly accelerate coronary artery disease through enhancing the effects of conventional and non-conventional cardiovascular risk factors
Authors: Kolossvary M , Fishman E.K , Gerstenblith G , Bluemke D.A , Mandler R.N , Kickler T.S , Bazr S , Chen S , Lai S , Lai H
Published: November 2020

Background/Introduction

Cross-sectional studies are inconsistent on the potential independent adverse effects of human immunodeficiency virus (HIV)-infection on coronary artery disease (CAD). Furthermore, there is no information on the potential effects of HIV-infection on plaque volumes. Also, only the independent effects of HIV-infection on CAD have been investigated.

Purpose

In a prospective longitudinal observational cohort, we wished to assess whether HIV-infection accelerates CAD independently, or by acting in synergistic fashion with conventional and nonconventional cardiovascular risk factors to accelerate disease progression as assessed by clinical and volumetric parameters of CAD on coronary CT angiography (CCTA).

Methods

Overall, 300 asymptomatic individuals without cardiovascular symptoms but with CCTA-confirmed coronary plaques (210 males, age: 48.0±7.2 years) with or without HIV (226 HIV-infected) prospectively underwent CCTA at two time points (mean follow-up: 4.0±2.3 years). Agatston-score, number of coronary plaques, segment stenosis score were calculated, and we also segmented the coronary plaques to enumerate total, noncalcified (−100–350HU) and calcified (≥351HU) plaque volumes. Linear mixed models were used to assess the effects of HIV-infection, atherosclerotic cardiovascular disease (ASCVD) risk, years of cocaine use and high-sensitivity C-reactive protein on CCTA markers of CAD.

Results

In univariate analysis, there was no significant difference in CAD characteristics between HIV-infected and -uninfected, neither at baseline nor at follow-up (p>0.05 for all). Furthermore, there was no significant difference in annual progression rates between the two groups (p>0.05 for all). By multivariate analysis, HIV was not associated with any CAD parameter (p>0.05 for all). However, among HIV-infected individuals, each year of cocaine use significantly increased all CAD parameters (p<0.05 for all), while ASCVD risk score was significantly associated with CAD parameters except for Agatston-score (p<0.05). These associations were only present among HIV-infected individuals.

Conclusion(s)

Instead of directly worsening CAD, HIV may promote CAD through increased susceptibility to conventional and nonconventional cardiovascular risk factors. Therefore, aggressive management of both conventional and nonconventional cardiovascular risk factors is needed to reduce cardiovascular burden of HIV-infection.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institutes of Health, National Institute on Drug Abuse
Visit-to-visit systolic blood pressure variability associates with vascular thrombosis in hemodialysis patients
Authors: Wu C.C , Lin P.S , Hsieh M.Y , Chen T.Y , Lin T.T , Chuang S.Y
Published: November 2020

Background

Blood pressure variability (BPV) is an independent risk factor for cardiovascular events and death in general population. Hemodialysis patients have higher BPV and higher vascular events than general population. However, the impact of BPV on vascular events of hemodialysis patients is not clear.

Purpose

To determine the association of BPV with vascular outcomes in patients on maintenance hemodialysis.

Method

In this prospective multi-center study, we enrolled 927 maintenance hemodialysis patients from Jan, 2017 to Dec, 2017. We used the coefficient of variation (CV) and the variance independent of mean (VIM) of predialysis systolic blood pressure (SBP) derived from the first 3 months (36 dialysis sessions) after enrollment as the metrics of BPV. Patients were prospectively followed at 3-month interval. Outcomes included death, systemic vascular thrombosis (nonfatal myocardial infarction, ischemic stroke, and acute limb ischemia), and dialysis vascular access thrombosis.

Results

In all, 707 subjects with at least 20 measurements were included in the analysis. Patients' mean age was 66 years and 50% of patients were male. Baseline factors associated higher BPV included diabetes, high co-morbidity scores, low albumin, high systolic and diastolic blood pressure. The mean pre-dialysis SBP CV was 10.9% and VIM was 28.9%. The median follow-up duration was 2.5 years, during which 103 deaths, 81 systemic vascular thrombosis, and 155 dialysis access thrombosis occurred. In unadjusted model, we found that the highest BPV tertile had a 52% increased risk of vascular thrombosis than the lowest BPV tertile (HR=1.52, 95% CI 1.23–1.86, P<0.001). After multivariable adjustment (including age, diabetes, co-morbidity score, albumin, baseline systolic and diastolic BP), this association remained statistically significant (HR=1.47, 95% CI=1.18–1.84, P=0.001). Systolic BPV was associated with either systemic vascular thrombosis (HR=1.44, 95% CI=1.08–1.93, P=0.01) or dialysis vascular access thrombosis (HR=1.55, 95% CI=1.16–1.82, P=0.001).

Conclusion

In the cohort of patients on maintenance hemodialysis, high pre-dialysis systolic BPV was associated a higher risk of vascular thrombosis events, both for systemic vascular thrombosis and dialysis vascular access thrombosis.

Funding Acknowledgement

Type of funding source: Public hospital(s). Main funding source(s): National Taiwan University Hsinchu Branch
Patterns and trends of idarucizumab use in an Italian region: a probabilistic record-linkage approach in a real-life setting
Authors: Lombardi N , Brilli V , Crescioli G , Bettiol A , Ippazio C.A , Mazzaglia G , Fumagalli S , Mannaioni G , Vannacci A , Gini R
Published: November 2020

Background

Idarucizumab is a specific reversal agent for dabigatran, a direct oral anticoagulant. In 2015, idarucizumab was approved in Europe to quickly restore coagulation and it is currently subject to additional safety monitoring. The drug is administered only during inpatient or emergency care: in such settings, its use is poorly captured by most real-world databases.

Purpose

To retrieve individual level information on idarucizumab use from an Italian record-linkage claims database in order to describe main characteristics of users.

Methods

Italy has a regional-based, universal coverage healthcare system. Healthcare delivered to each inhabitant of Tuscany, an Italian region, is registered in a record-linkage claims database (RLCD). This information can be traced at individual level using an encrypted identification code, except in the case of medicines administered in Inpatients or Emergency Care (IEC), where only date and ward of administration are recorded. All person-years (PYs) exposed to dabigatran from January 2015 to December 2018 were calculated from RLCD, using defined daily doses (DDDs) to estimate duration of each recorded dispensation. Idarucizumab use during the study period was identified from IEC, and incidence rate was calculated over PYs of dabigatran use. To identify subjects treated with idarucizumab, emergency admissions and hospital discharge records were probabilistically linked to dabigatran users, matching date and ward of admission as retrieved from RLCD. A further selection was made by a manual check of the diagnoses compatible with the indications of use of idarucizumab. Linked users were described in terms of indication and followed-up for 30 days to assess mortality.

Results

During the study period, 26,821 PYs of dabigatran use were observed, and 112 administrations of idarucizumab were recorded, corresponding to 4.2 (95% CI: 3,4–5,0) per 1,000 PYs. Overall, 103 idarucizumab administrations (92.0%) were linked to at least one patient, while 50 (44.6%) were uniquely linked to 47 patients. Most of them were men (55.3%), aged ≥80 years (68.1%). Indications were emergency surgical procedures and life-threatening bleeding in 17 (36.1%) and in 30 subjects (63.9%), respectively. Overall, 30-days mortality was 17.0% (N=8).

Conclusions

This analysis demonstrates the potential of the Tuscany database in retrieving patient-level information on idarucizumab use and sets the stage for post-marketing surveillance on its safety profile in a real-life setting.

Funding Acknowledgement

Type of funding source: None
The distribution of anti-factor Xa activity value, PT and APTT at peak and trough times in patients with direct anti-factor Xa inhibitors
Authors: Ono R , Fukushima K , Yamazaki T , Takahashi H , Hori Y
Published: November 2020

Background

Although patients taking direct oral anticoagulants (DOACs) do not require routine coagulation monitoring, the distribution of anti-factor Xa activity (AXA) values, prothrombin time (PT), PT-international normalized ratio (INR) and activated partial thromboplastin time (APTT) in patients on apixaban, edoxaban and rivaroxaban therapy is still not clear.

Purpose

The aim is to set the standard values of AXA values, PT, PT-INR and APTT in patients using DOACs.

Methods

We measured AXA, using chromogenic assay with the HemosIL Liquid Heparin kit, PT, PT-INR and APTT at trough and peak times in 224 patients with non-valvular atrial fibrillation and venous thromboembolism, of whom 90 received apixaban, 100 received edoxaban and 34 received rivaroxaban. The peak time was defined as 3 hours after the intake of apixaban or rivaroxaban, and 2 hours after the intake of edoxaban. The trough time was defined as that immediately before the intake. The AXA values, PT, PT-INR and APTT were measured at least 72 hours after the start of treatment. The dosage of DOACs is defined according to the prescribing information in Japan.

Results

(The order of results below is apixaban, edoxaban and rivaroxaban, respectively.) The average AXA values were 2.29, 0.23 and 0.39 (IU/mL) at trough time, and 3.04, 1.01 and 1.70 (IU/mL) at peak time. The average PT values were 17.9, 12.9 and 13.1 (s) at trough time, and 19.7, 15.5 and 17.5 (s) at peak time. The average PT-INR values were 1.49, 1.07 and 1.08 at trough time, and 1.65, 1.29 and 1.45 at peak time. The average APPT values were 34.5, 31.3 and 32.0 (s) at trough time, and 39.5, 35.9 and 39.8 (s) at peak time.

Conclusion

Our findings reveal the standard values of AXA, PT, PT-INR and APTT in patients using apixaban, edoxaban and rivaroxaban in each dosage. The DOACs should be changed if the measured value is out of those standard values in 90% confidence interval.

Funding Acknowledgement

Type of funding source: None
The usefulness of total thrombus-formation analysis system for predicting high bleeding risk in coronary artery disease patients taking anticoagulants who underwent percutaneous coronary intervention
Authors: Nakanishi N , Kaikita K , Mitsuse T , Tsujita K
Published: November 2020

Background

Although anticoagulants are widely used for prevention of cerebral infarction in patients with atrial fibrillation (AF), venous thrombosis, and valvular disease, it is possible that anticoagulants increase bleeding events in daily medical practices. Recently, we reported that the total thrombus-formation analysis system (T-TAS) was useful for evaluating bleeding risk in coronary artery disease (CAD) patients.

Aim

We examined whether T-TAS was practical for predicting bleeding risk in CAD patients taking anticoagulants who underwent percutaneous coronary intervention (PCI).

Methods

This study was the retrospective analysis of the 500 consecutive CAD patients who underwent PCI. Blood samples obtained on the day of PCI were used in T-TAS to compute the thrombus formation area under the curve (AUC) (AR10-AUC30, AUC for AR chip). We divided the total number of study patients into two groups according to the presence of anticoagulants; 53 CAD patients with triple therapy (TT) and 447 CAD patients with dual antiplatelet therapy (DAPT). We compared clinical characteristics and prognosis between the two groups. The primary endpoint was 1-year bleeding events that were defined by ISTH bleeding criteria. We excluded the CAD patients who underwent emergency PCI, and who were treated for hemodialysis.

Results

All patients took aspirin and clopidogrel, or aspirin and prasugrel at baseline. Compared to the patients with DAPT, the patients with TT had atrial fibrillation and history of stroke. The AR10-AUC30 levels were significantly lower in the patients with TT than the patients with DAPT (median [interquartile range] 1402.6 [1095.1–1609.8] vs. 1679.8 [1526.4–1783.3], p<0.001). Thirty-five patients (7%) had bleeding events during follow-up [11 cases (20.8%) in the patients with TT, 24 cases (5.4%) in the patients with DAPT]. Kaplan-Meier curve analysis showed a worse 1-year bleeding event-free survival rate in the patients with TT compared with the patients with DAPT (p<0.001). Receiver operating characteristic analysis showed that AR10-AUC30 levels significantly predicted bleeding events (AUC 0.653, 95% CI 0.555–0.751; p=0.003) and the cut-off point was 1586.4 by Youden index in the present study. In multivariate Cox hazards analysis, low AR10-AUC30 level (≤1586.4) (hazard ratio 2.99; 95% CI 1.46–6.11; p=0.003) and taking warfarin (hazard ratio 3.02; 95% CI 1.24–7.34; p=0.015) were significant predictors for 1-year bleeding events.

Conclusions

The present findings suggested that the AR10-AUC30 level determined by T-TAS could be a useful marker for predicting high bleeding risk in CAD patients taking anticoagulants who underwent PCI.

Funding Acknowledgement

Type of funding source: None
Favorable therapeutic index of an orally-active small-molecule antagonist of the platelet protease-activated receptor-4, BMS-986141, compared with the P2Y12 antagonist ticagrelor in cynomolgus monkeys
Authors: Wong P , Banville J , Wexler R , Priestley E , Marinier A , Bouvier M , Gordon D , Yang J
Published: November 2020

Introduction

BMS-986141 is an orally-active small-molecule platelet thrombin receptor antagonist selective for the protease-activated receptor-4 (PAR4), a human platelet thrombin receptor.

Purpose

This study assessed effects of BMS-986141 vs. the P2Y12 antagonist ticagrelor, a standard of care antiplatelet agent, on arterial thrombosis (AT), mesenteric bleeding time (MBT) and platelet aggregation in monkeys.

Methods

Studies were conducted in models of electrically-mediated carotid artery thrombosis and MBT in anesthetized monkeys. Monkeys were given a single oral dose of BMS-986141 (0.05, 0.1, 0.5 mg/kg) or vehicle (n=8/group). At 2 hr post-dose, in vivo AT, MBT as well as ex vivo platelet aggregation were monitored in the same animal. Ticagrelor was studied as a comparator and given as IV bolus plus infusion at 0.0023+0.017 to 0.075+0.6 (mg/kg+mg/kg/h) (n=5–6/group). Thrombus weight reduction, MBT increase over vehicle, and platelet aggregation inhibition were determined. Peak platelet aggregation responses to activation peptides selective for PAR4 (PAR4-AP, 12.5 μM) and PAR1 (PAR1-AP, 18 μM), to collagen (5 μg/ml) and to ADP (20 μM) were determined by whole blood aggregometry.

Results

BMS-986141 inhibited platelet aggregation induced by PAR4-AP in human and monkey blood in vitro with comparable IC50 of 1.8±0.3 and 1.2±0.3 nM, respectively. BMS-986141 at 0.5 mg/kg completely inhibited platelet aggregation induced by PAR4-AP but not PAR1-AP, ADP and collagen, suggesting PAR4 receptor selectivity. In the AT model, BMS-986141 at 0.05, 0.1 and 0.5 mg/kg reduced thrombus weight by 36±7*, 63±8*, and 88±3%*, respectively (*P<0.05 vs. vehicle). BMS-986141 increased MBT by up to 1.2-fold. In a separate study, ticagrelor at 0.0023+0.017, 0.0068+0.055, 0.0255+0.18 and 0.075+0.6 (mg/kg+mg/kg/h IV) reduced thrombus weight by 19±8, 36±5*, 76±6* and 89±1%*, and increased MBT by respectively by 1.7-, 6.4-*, >10-*, and >10-fold*, respectively (*P<0.05 vs. vehicle).

Conclusion

Comparable antithrombotic efficacy was observed between BMS-986141 and ticagrelor in monkeys. BMS-986141 exhibited lower MBT compared with ticagrelor at equivalent antithrombotic doses. This study suggests that PAR4 antagonism provides a potentially safer antiplatelet therapy.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Research was supported by Bristol-Myers Squibb
Enhancing nurses self-efficacy by high-fidelity resuscitation simulation training: a pre-post study
Authors: Al Kalaldeh M
Published: November 2020

Introduction

Recent evidence support the use of High-fidelity simulation (HFS) among health care professional. Self-efficacy towards resuscitation competency is assumed to be influenced by HFS training that low fidelity simulation.

Purpose

This study aimed to examine the impact of the high-fidelity Resuscitation Simulation Training (RST) program on the nurse's self-efficacy.

Methods

A quasi-experiment, one-group pretest-posttest design was used. A total of 62 nurses enrolled the RST. Self-efficacy was assessed in both pretest and posttest phases using the Resuscitation Self-Efficacy Scale (RSES). Changes occurred in self-efficacy after conducting the study program and the potential influence of demographic characteristics were examined using descriptive and inferential statistics.

Results

Self-efficacy has significantly improved after the RST considering all self-efficacy dimensions; Recognition, Debriefing and recording, Responding and rescuing, and Reporting (P<0.05). This was also consistent with RSES assessment by the course instructors (t=−1.5, p=0.11). A moderate positive correlation was found between the RSES and the ACLS posttest written exam (r=0.303, p=0.017). While minimal influence of demographic characteristic was reported, nurses who had never been involved in resuscitation in the past had shown a significant improvement in their self-efficacy after the RSE.

Conclusion

The utilization of high-fidelity simulation training can improve nurse's self-efficacy regardless personal characteristics or experience.

Funding Acknowledgement

Type of funding source: None
Nurse management of glycemia in cardiac intensive care
Authors: Cappannelli S , Cosmi D , Rey L , Murrone A
Published: November 2020

Introduction

Scientific studies have shown that hypoglycaemia is an important risk factor for adverse events in cardiac intensive care. Nursing management of blood glucose, via protocol, is an important tool to avoid cases of hypoglycaemia.

Objective

We evaluate the efficacy and safety of a glycemia control protocol based on nursing management in diabetic patients in Intensive Care Unit.

Material and methods

We conducted a retrospective analysis on 500 patients hospitalized for acute coronary syndrome or heart failure, with an average age of 75±12 years, clinically stable. The protocol used provides, on medical indication, the suspension of home therapy (both oral hypoglycemic agents and insulin) and the introduction of insulin therapy according to the scheme 0.2/0.5 IU/kg/day. The dosage lower than 0.2 IU/kg/day is used for patients in home therapy with oral hypoglycemic agents and basal blood sugar <150 mg/dl and the dose greater than 0.5 IU/kg/day for patients already on home insulin therapy and basal blood sugar> at 200 mg/dl. The intermediate dosage. 3–0.4 IU/kg/day is instead used in patients with glycaemia between 150 and 200 mg/dl regardless of home therapy. On the basis of the dosage schedule, the daily insulin requirement is obtained which is then administered at 50% as a slow analogue at 10 pm and at 50% as a rapid analogue, further divided into three doses with each main meal.

Once the initial therapy has been set, the nurse acts autonomously according to a correction algorithm (based on the calculation of the correction factor (FC) according to the formula FC = 3000/body weight in kg or FC = 1700/total daily dose of insulin > FC = reduction in blood glucose in mg/dl determined by 1 IU of insulin) which provides for the modification of insulin therapy based on the patient's weight and the blood glucose values measured with sticks at 8, 12, 18 and 22. If during hospitalization and/or discharge, inadequately controlled glycemic values persist, the patient is sent to diabetes advice and the current home therapy is resumed upon discharge or according to diabetes advice.

Results

We observed an excellent pre and post prandial glucose control with extremely reduced incidence of hypoglycaemia which occurred in only 3 cases, one of which with severe hypoglycaemia (glucose detected <40 mg/dl, resolved with the administration of glucose 33 20ml% followed by infusion of 10% glucose solution and glycemic stick after 15') for administration error and two with moderate hypoglycaemia (glucose detected between 40–70 mg/dl resolved with the reduction of 2 IU of rapid analogue and repeated stick post prandial).

Conclusions

A nursing management protocol for blood glucose values in patients with diabetes mellitus hospitalized for acute coronary syndrome or heart failure is safe and allows good control of blood glucose values.

Funding Acknowledgement

Type of funding source: None
Symptoms of depression at discharge after PCI are associated with an increased risk of 1-year mortality: findings from the national DenHeart study
Authors: Borregaard B , Nielsen S.N , Lassen J.F , Jensen L.O , Thrysoe L , Berg S.K , Moller J.E , Christensen A.V , Ekholm O , Mols R.E , Thorup C.B , Rasmussen T.B
Published: November 2020

Background

Although survival rates among patients with coronary artery disease have increased since the introduction of treatment with percutaneous coronary intervention, PCI, the effect of psychological factors such as symptoms of anxiety and depression on adverse outcomes are sparsely described.

Purpose

The objective of the current study was to investigate the association between symptoms of anxiety and depression and 1-year mortality after PCI.

Methods

A national cross-sectional survey at hospital discharge (responders, n=3,366) with register-based follow-up among patients having undergone elective or emergency PCI. Mental health was measured using the Hospital Anxiety and Depression Scale, HADS, and divided into symptoms of anxiety (HADS-A) and symptoms of depression (HADS-D). The association between mental health (HADS-A and HADS-D) and 1-year all-cause mortality were investigated with Cox Proportional Hazard models with time to death as the underlying time scale. The results are presented as hazard ratios (HR) with 95% confidence intervals (CI) and adjusted for sex, age and Tu-comorbidity score.

Results

At discharge, 32% of the population reported symptoms of anxiety (HADS-A ≥8) and 19% reported symptoms of depression (HADS-D ≥8). After one year, the mortality rate among patients being alive at discharge was 2.1%. All-cause mortality did not differ among patients reporting symptoms of anxiety compared to patients without symptoms of anxiety (2.3% vs 1.9%, p=0.454), whereas all-cause mortality was higher among patients reporting symptoms of depression compared to those, who did not (4.3% vs 1.6%, p≤0.001).

In the regression analyses, symptoms of anxiety (HADS-A ≥8) was not associated with 1-year mortality (HR 1.16 95% CI 0.70–1.92); however, symptoms of depression was (HADS-D ≥8, HR 2.27 95% CI 1.38–3.73, adjusted analyses). Based on the continuous scores of HADS-D, a one-point increase in scores was associated with a 12% higher risk of 1-year mortality (HR 1.12 95% CI 1.05–1.18) (Figure 1).

Conclusion

After PCI, nearly one-third of patient report symptoms of anxiety and one-fifth symptoms of depression. Symptoms of anxiety was not associated with 1-year mortality, whereas symptoms of depression increased the risk of 1-year mortality.

Figure 1

Funding Acknowledgement

Type of funding source: None
Clinical determinants and prognostic impact of osteoporosis in patients with chronic heart failure
Authors: Katano S , Yano T , Tsukada T , Kouzu H , Honma S , Inoue T , Takamura Y , Nagaoka R , Ohori K , Koyama M , Nagano N , Nishikawa R , Hashimoto A , Katayose M , Miura T
Published: November 2020

Background

Despite accumulating evidence of a close association between orthopedic fractures and chronic heart failure (CHF), the clinical risk factors of osteoporosis, defined as reduction in bone mineral densities (BMDs), in CHF patients have not been systematically analyzed. In addition, the impact of osteoporosis on prognosis of CHF remains unclear.

Aims

We aimed to clarify the prevalence, clinical risk factors, and prognostic impact of osteoporosis in CHF patients.

Methods

We retrospectively examined 303 CHF patients (75 years, [interquartile range (IQR), 66–82 years]; 41% female). BMDs at the lumber spine, femoral neck, and total femur were measured by dual-energy X-ray absorptiometry (DEXA), and osteoporosis was diagnosed when BMD at any of the three sites was less than 70% of Young Adult Mean.

Results

The prevalence of osteoporosis in the CHF patients was 40%. Patients with osteoporosis were older (79 [IQR, 74–86] vs. 72 [IQR, 62–80] years), included a large percentage of females, had slower gait speed and had lower body mass index (BMI). Loop diuretics and warfarin were used more frequently and direct oral anticoagulants (DOACs) were used less frequently in patients with osteoporosis than in patients without osteoporosis. Multivariate logistic regression analysis indicated that sex (odds ratio [OR] 5.07, 95% Confidence Interval [CI] 2.68–9.61, p<0.01), BMI (OR, 0.83; 95% CI, 0.75–0.91; p<0.01), gait speed (OR, 0.80; 95% CI, 0.70–0.92; p<0.01), loop diuretics use (OR, 2.52; 95% CI, 1.20–5.27; p=0.01) and no DOACs use (OR, 0.43; 95% CI, 0.19–0.96; p=0.04) were independently associated with osteoporosis. During the mean follow-up period of 290±254 days, 92 patients (30.4%) had adverse events. When patients with osteoporosis were divided into subgroups according to the number of sites with BMD of an osteoporosis level, Kaplan-Meier survival curves showed that the rate of adverse events (death and cardiovascular events) was higher in patients with osteoporotic BMD at two or more sites than in patients without osteoporosis (51% vs. 23%, p=0.03) (Figure). In multivariate Cox regression analyses, osteoporotic BMD at two or more sites was an independent predictor of adverse events after adjustment for age, sex, and NT-proBNP level (Hazard ratio, 1.74; 95% CI, 1.01–2.99; p=0.04).

Conclusion

The risk of osteoporosis may be increased in users of loop diuretics and may be decreased in users of DOACs in CHF patients. Extent of osteoporosis is a novel predictor of adverse events in CHF patients.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Japan Society for the Promotion of Science KAKENHI
Influence of long-term swimming exercises on cardiac index, life duality and level of depression in patients with heart failure with pEF and diabetes mellitus type 2
Authors: Shorikova D , Shorikov E.I , Khukhlina O.S , Shorikov P
Published: November 2020

Introduction

In the number of studies it was proved that specific physical activity can significantly improve the control of Heart Failure (HF). Physical exercises improve mobility, strength and cardiovascular fitness, can easily be performed in patients with HF.

Purpose

To investigate the effect of regular swimmings on cardiac output, life duality, anxiety and depressive symptoms in patients with HF and DM type 2.

Material and methods

62 patients (20 women and 42 men, mean age 55.3±7.9 years) with HFpEF and DM type 2 were included in prospective observation during 6 months. The intensity of physical activity was 6 points due to Borg scale (60–70.0%). Hospital Anxiety and Depression Scale (HADS), MLHFO and SF-36 surveys were used. The water temperature was 32°C throughout the study.

Results

It was set that lowest scores QL in patients with HF and DM type 2 were obtained on the scales of physical (PF, GH and RP) and psychological (RE, VE and SF) health components (p<0.05). The life duality in patients with HF and DM type 2 depended on the degree of physical activity. The reliable improvement of both physical (p<0.05) and psychological components (p<0.05) of health after regular swimming is proved (table). According to MLHFQ was set reducing the restriction of physical and social activity after regular swimming. Water exercises increased efficacy of pharmacological therapy on 61.8% (p<0.001) according to MLHFQ. According to the HADS scale anxiety and depression disorders were reduced from higher to lower level in 88.0% patients. After 6 months of swimming exercises it was set increasing of cardiac index by 12.0% (p<0.05).

Conclusions

It has been established that regular swimming exercises in patient with Heart Failure and Diabetes Mellitus type 2 has favourable effect for cardiac index by 12.0% (p<0.05), life duality (p<0.05) and decrease the level of anxiety and depression disorders (p<0.05).

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Health Service of Ukraine
Change in health-related quality of life among patients with a reduced ejection fraction initiating guideline-directed medical therapy
Authors: Burch A , Sears S.F , Doring M , Gummadi S , Robertson M , Sanchez R , Shroff G , Veltmann C
Published: November 2020

Background

Management of patients with heart failure (HF) should include patient reported outcomes (PROs). The Kansas City Cardiomyopathy Questionnaire is self-administered with subscales to evaluate HF symptom burden, physical limitations, social limitations (recreational participation), and quality of life (QoL). Change in PROs among newly diagnosed patients with HF and reduced ejection fraction (HFrEF) prescribed a wearable cardioverter defibrillator (WCD) and initiating guideline-directed medical therapy (GDMT) has not been assessed.

Purpose

Examine PROs over 180 days of receiving GDMT for newly diagnosed HFrEF.

Methods

Patients (n=93, 75.3% male) were enrolled ≤10 days post-hospitalization for new onset HF; all patients had an EF ≤35% and were prescribed a WCD. Health status, as measured by PRO was assessed at baseline, day 90, and day 180. Controlling for age and EF at baseline, changes in PROs over the 180-day study period were evaluated using repeated measures modeling. Pairwise comparisons with Bonferroni adjustments were used to compare adjacent timepoints. Higher scores reflect better health status.

Results

After controlling for age (mean 56±13.4) and baseline EF (mean 22±7.7) improvements in health status were observed. From baseline to day 90, physical limitation, symptom frequency, QoL, and the summary score all increased (Δ: 17.8, 23.7, 28.4, 23.7, respectively; all p's <0.05). From day 90 to day 180, only QoL continued to improve (Δ 7.5, p=0.001). Change in social limitations over time was not significant (p=0.42).

Conclusion

Patients report improved health status in the months following a new diagnosis of HFrEF when prescribed a WCD and GDMT.

Change in Quality of Life

Funding Acknowledgement

Type of funding source: None