bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary percutaneous coronary intervention in the oldest-old age: clinical outcomes and predictors of in-hospital mortality in nonagenarians patients with ST-segment elevation myocardial infarction
Authors: Pinton F.A , Prado G.F , Bezerra C.G , Mariani Junior J , Campos C.M , Almeida B.O , Caixeta A.M , Franken M , Lemos P.A
Published: November 2020

Introduction

Owing to the ageing of the population, nonagenarian patients are increasingly present in catheterization laboratories, part of them with ST-segment elevation myocardial infarction (STEMI). Primary percutaneous coronary intervention (PCI) is the recommended reperfusion therapy in patients with STEMI, provided it can be performed promptly. However, elderly patients are usually excluded from clinical trials and few data are available about nonagenarians referred for primary PCI.

Purpose

The aim of the present study was to evaluate clinical characteristics and in-hospital outcomes of nonagenarians STEMI patients undergoing primary PCI.

Methods

We retrospectively analyzed clinical, angiographic and in-hospital outcomes of death, re-infarction and stroke of primary PCI in nonagenarian STEMI patients, included in the Brazilian PCI Registry (CENIC) between June 2006 and March 2016. Predictors of in-hospital mortality of this population were determined through multivariate analysis.

Results

Over a period of 10 years, 847 nonagenarians were enrolled in the CENIC Registry, and 252 presented with STEMI and underwent a primary PCI. The population was predominantly female (55.2%), with a median age of 92 years (interquartile range 4 years, maximum of 105 years) and 63.9% in Killip class I at admission. Median door-to-balloon time was 90±60 minutes. Double or triple-vessel disease was found in 63%. It was used 1.3 stent per patient, 8.9% drug-eluting stents. The femoral access route was preferred in 82.1% of patients and glycoprotein IIb/IIIa inhibitors was given to 9.9%. In-hospital mortality in the period was 10.7% and re-infarction occurred in 0.5%. No cases of stroke have been reported. The only predictor of hospital mortality was Killip class (OR 7.1, 95% CI 2.7–18.5, p<0.001).

Conclusion

In a real-world setting, primary PCI in nonagenarian STEMI patients can be performed with good clinical outcomes and acceptable in-hospital mortality rate and must be recommended even in oldest-old age patients. Killip class was the only predictor of in-hospital mortality in this population.

Funding Acknowledgement

Type of funding source: None
Echocardiography for the 10-year prediction of cardiomyopathy in long-term survivors of childhood cancer
Authors: Leerink J.M , Van Der Pal H.J.H , Feijen E.A.M , Meregalli P.G , Pourier M.S , Merkx R , Bellersen L , Van Dalen E.C , Loonen J , Pinto Y.M , Kapusta L , Kremer L.C.M , Mavinkurve-Groothuis A.M.C , Kok W.E.M
Published: November 2020

Background

Childhood cancer survivors (CCS) treated with anthracyclines and/or chest-directed radiotherapy receive life-long echocardiographic surveillance to detect cardiomyopathy early. Current risk stratification and surveillance frequency recommendations are based on anthracycline- and chest-directed radiotherapy dose. We assessed the added prognostic value of an initial left ventricular ejection fraction (EF) measurement at >5 years after cancer diagnosis.

Patients and methods

Echocardiographic follow-up was performed in asymptomatic CCS from the Emma Children's Hospital (derivation; n=299; median time after diagnosis, 16.7 years [inter quartile range (IQR) 11.8–23.15]) and from the Radboud University Medical Center (validation; n=218, median time after diagnosis, 17.0 years [IQR 13.0–21.7]) in the Netherlands. CCS with cardiomyopathy at baseline were excluded (n=16). The endpoint was cardiomyopathy, defined as a clinically significant decreased EF (EF<40%). The predictive value of the initial EF at >5 years after cancer diagnosis was analyzed with multivariable Cox regression models in the derivation cohort and the model was validated in the validation cohort.

Results

The median follow-up after the initial EF was 10.9 years and 8.9 years in the derivation and validation cohort, respectively, with cardiomyopathy developing in 11/299 (3.7%) and 7/218 (3.2%), respectively. Addition of the initial EF on top of anthracycline and chest radiotherapy dose increased the C-index from 0.75 to 0.85 in the derivation cohort and from 0.71 to 0.92 in the validation cohort (p<0.01). The model was well calibrated at 10-year predicted probabilities up to 5%. An initial EF between 40–49% was associated with a hazard ratio of 6.8 (95% CI 1.8–25) for development of cardiomyopathy during follow-up. For those with a predicted 10-year cardiomyopathy probability <3% (76.9% of the derivation cohort and 74.3% of validation cohort) the negative predictive value was >99% in both cohorts.

Conclusion

The addition of the initial EF >5 years after cancer diagnosis to anthracycline- and chest-directed radiotherapy dose improves the 10-year cardiomyopathy prediction in CCS. Our validated prediction model identifies low-risk survivors in whom the surveillance frequency may be reduced to every 10 years.

Calibration in both cohorts

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Dutch Heart Foundation
The histone deacetylase SIRT1 mediates the proper DNA repair response by targeting histone H2AX to protect against doxorubicin-induced cardiotoxicity
Authors: Kuno A , Hosoda R , Horio Y
Published: November 2020

Background

Failure of DNA repair and accumulation of damaged DNA have been implicated in the pathogenesis of doxorubicin-induced cardiotoxicity. SIRT1, an NAD+-dependent histone deacetylase, is known to positively regulate DNA repair. One of the earliest events in DNA damage response (DDR) is phosphorylation of histone H2AX on Ser139 catalyzed by kinases including ATM (mutated in ataxia-telangiectasia). However, it remains unknown whether SIRT1 protects the heart from doxorubicin-induced cardiotoxicity by regulating histone H2AX.

Purpose

In this study, we investigated whether SIRT1 plays a role against doxorubicin-induced cardiotoxicity by regulating histone H2AX and therefore DDR.

Methods and results

We used tamoxifen-inducible cardiomyocyte-specific SIRT1 knockout (SIRT1-cKO) mice. Knockout was induced at 2 month of age, and mice without Cre recombinase served as wild type (WT). Mice were treated with vehicle (Veh) or doxorubicin (4 IP injections of 5 mg/kg/week) starting at 3 month of age. Echocardiography showed that fractional shortening (FS) before doxorubicin was similar in WT (34%) and SIRT1-cKO (34%). However, FS at 1 week after final doxorubicin was lower in SIRT1-cKO than WT (26% vs. 30%, P<0.05). Myocardial ANP mRNA level was 2.4-fold higher in SIRT1-cKO than WT after doxorubicin. Apoptotic cells analyzed by TUNEL-positive nuclei were similar in Veh-treated SIRT1-cKO and WT (0.125 vs. 0.073%) but were more increased by doxorubicin in SIRT1-cKO than WT (0.384 vs 0.194%, P<0.05). Immunoblotting showed that doxorubicin significantly increased myocardial levels of phospho-Ser139-histone H2AX (p-H2AX) and phospho-Ser1981-ATM (p-ATM) in WT. However, the doxorubicin-induced increase in p-H2AX level was significantly attenuated in SIRT1-cKO despite similar p-ATM levels after doxorubicin between WT and SIRT1-cKO.

In H9c2 cardiomyocytes, doxorubicin treatment (10 μM) increased both p-ATM and p-H2AX levels, but siRNA-mediated knockdown (KD) of SIRT1 attenuated doxorubicin-induced phosphorylation of H2AX without changing p-ATM level. Cell death after doxorubicin was enhanced in SIRT1-KD cells compared to control cells (13.2% vs 8.6%, P<0.05). Immunostaining showed that SIRT1 colocalized with histone H2AX in the nucleus. Treatment with a SIRT1 inhibitor Ex527 increased level of acetylated H2AX at 5th lysine residue, suggesting that SIRT1 regulates histone H2AX via deacetylation.

Conclusion

These data suggest that SIRT1 plays a protective role against doxorubicin-induced cardiotoxicity via regulation of H2AX phosphorylation to mediates proper DDR.

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): Japan Society for the Promotion of Science
Biomarkers for detection of anthracycline-induced cardiomyopathy in childhood cancer survivors: a case-control study in the Dutch LATER cohort study
Authors: Leerink J.M , Feijen E.A.M , Mavinkurve-Groothuis A.M.C , Tissing W.J.E , Louwerens M , Van Den Heuvel-Eibrink M.M , Versluys A.B , Van Dulmen-Den Broeder E , De Vries A.C.H , Van Der Pal H.J.H , Kapusta L , Loonen J , Pinto Y.M , Kremer L.C.M , Kok W.E.M
Published: November 2020

Introduction

Plasma biomarkers may aid in the surveillance for anthracycline-induced cardiomyopathy (ACM) in long-term childhood cancer survivors and provide insight into the pathophysiological mechanisms involved. In this pilot study, we aimed to identify new plasma markers associated with ACM.

Methods

A case-control study within the Dutch Late Effects After Childhood Cancer Cohort study (Dutch LATER) was conducted. We compared 184 plasma markers (Olink) between ACM cases (LVEF<45%) and anthracycline treated controls (LVEF≥53%), matched on sex, time since cancer diagnosis and anthracycline dose. Associations of plasma markers with ACM were assessed with conditional logistic regression. Pathway analysis was performed with STRING (string-db.org). Significant markers were evaluated in multivariable models next to anthracyclines dose, sex and time after cancer.

Results

In total, 28 ACM cases (median anthracycline dose 351 mg/m2; median age at study 38 years, 29% chest radiotherapy) and 29 controls (median anthracycline dose 300 mg/m2; median age at study 44 years, 7% chest radiotherapy) were included. Eight markers were significantly associated with ACM (Table 1) and were implicated in ventricular wall stress, apoptosis, inflammation and endothelial dysfunction (Figure 1). The AUC of the model including only the clinical variables was 0.73 (95% confidence interval (CI) 0.60–0.86), and improved to 0.82 (95% CI 0.71–0.94) with the addition of NT-proBNP and further to 0.86 (95% CI 0.76–0.97) with the addition of all 8 markers.

Conclusion

In this biomarker discovery study, 8 markers related to ventricular wall stress, apoptosis, inflammation and endothelial dysfunction were associated with ACM. We intend to validate these markers quantitatively in the Dutch LATER cohort study.

Figure 1. Pathway analysis of significant markers

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Dutch Heart Foundation Grant; Amsterdam University Funding
Differential effect of anthracycline and trastuzumab cancer therapeutic related vascular toxicity in patients with breast cancer
Authors: Anastasiou M , Oikonomou E , Vogiatzi G , Siasos G , Flora Z , Antonopoulos A.S , Tsalamandris S , Bamias A , Dimopoulos M.A , Tousoulis D
Published: November 2020

Introduction

Both anthracyclines and trastuzumab are key regiments for the treatment of breast cancer, but their concurrent use is contraindicated because of their cardiotoxicity. Their effects on vascular function have been less well studied.

Purpose

We explored the effects of the anthracycline-based chemotherapy followed by trastuzumab-based treatment on endothelial function and arterial stiffness in patients with breast cancer.

Methods

46 female patients (54.56±11.5 years old) with breast cancer scheduled for anthracycline-based chemotherapy followed by the combination of trastuzumab and taxane were enrolled. Trastuzumab was continued until the completion of one-year treatment. All participants underwent assessment of the brachial flow mediated dilatation (FMD), endothelial independent dilatation (EID), carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx) at baseline (BL), at the end of anthracycline treatment (FU1), 3 months following initiation of trastuzumab with taxane (FU2) and at the completion of treatment with trastuzumab (FU3).

Results

Over the follow-up period (15 months) there was significant deterioration in FMD (p=0.04) (Table 1, Figure 1). Importantly, while there was no significant difference in FMD between BL vs FU1 (p=0.6), FMD has been significantly deteriorated over the treatment with trastuzumab with taxane FU1 vs FU2 (p=0.01) and FU2 vs FU3 (p=0.01) (Table 1, Figure 1). EID did not change over the follow-up period (Figure 1). Similarly, PWV has been significantly increased over the follow up period (p=0.03). There was no significant difference in PWV BL vs FU1 (p=0.1), however PWV has been significantly increased over the treatment with trastuzumab with taxane FU1 vs FU 2 (p=0.02) and FU2 vs FU3 (p=0.01) (Table 1, Figure 1). A similar pattern of impairment was observed with AIx (Table 1, Figure 1).

Conclusion

We report a significant adverse effect of the anthracycline- and trastuzumab-based therapy on the arterial stiffness and endothelial function. This effect is more considerable after the exposure to trastuzumab.

Figure 1. Changes of FMD, PWV, Alx, EID during FU

Funding Acknowledgement

Type of funding source: None
Characterisation of patients with concomitant cancer in significant aortic stenosis
Authors: Sia C , Ngiam N , Chew N , Loi J.W.B , Tan B.Y.Q , Sim H.W , Kong W.K.F , Tay E.L.W , Yeo T.C , Poh K.K
Published: November 2020

Background

There is an increasing incidence of cancer worldwide, while aortic stenosis is the most common valvular heart disease. However, management of aortic stenosis (AS) in patients with cancer remains poorly understood. The presence of concomitant AS in patients with cancer may confer added morbidity and mortality.

Methods

We studied 727 consecutive patients with index echocardiographic diagnosis of moderate to severe aortic stenosis (aortic valve area <1.5cm2). These patients were divided in patients with or without concomitant cancer. Baseline clinical and echocardiographic parameters were compared by appropriate univariate analyses. Kaplan-Meier curves were constructed to compare mortality, admissions for congestive cardiac failure and aortic valve replacement between the groups.

Results

Eighty-five (11.7%) patients had concomitant cancer with moderate to severe AS. Of those, 45 (52.9%) had active cancer. The group with cancer was similar in terms of age, body mass index, clinical comorbidities compared to the group without cancer. AS severity and echocardiographic profile was similar except for a lower LVIDd (43.6±12.0 vs 47.4±8.9mm, p<0.001), and LV mass index (103.1±43.2 vs 116.6±41.5, p=0.005). There was higher mortality in the cancer group (log-rank 17.6, p<0.001), similar incidence of admissions for cardiac failure (log-rank 0.58, p=0.446) and a lower incidence of aortic valve replacement (log-rank 3.96, p=0.047) compared to the group without cancer. Patients with AS who received cancer treatment did better than those that did not receive cancer treatment.

Conclusion

Concomitant cancer in patients with moderate to severe AS was associated with increased mortality, and a lower incidence of aortic valve replacement. Further studies are warranted to investigate the role of valve replacement in patients with cancer.

Figure 1

Funding Acknowledgement

Type of funding source: None
Lifetime risk of cardiovascular-renal disease in type 2 diabetes: a population-based study in 473399 individuals
Authors: Zhang R , Mamza J , Morris T , Godfrey G , Asselbergs F , Denaxas S , Hemingway H , Banerjee A
Published: November 2020

Background

Lifetime risks of cardiovascular (CV) and renal diseases are high, particularly in type 2 diabetes (T2D), but rarely studied together, and relative disease contributions are unknown. Knowledge of lifetime risk of cardiovascular-renal disease (CVRD) will better reflect disease burden in T2D.

Purpose

To investigate the lifetime risks (LTRs) of composite and individual components of major adverse reno-cardiovascular events, MARCE in T2D patients.

Method

In a population-based cohort study using national electronic health records, we studied 473399 individuals aged 45–99 years with T2D in England 2007–2018. The LTR of composite and individual components of MARCE (including CV death and CVRD: heart failure, HF; chronic kidney disease stage 3 and above, CKD; myocardial infarction, MI; stroke or peripheral artery disease, PAD) were estimated. LTRs by baseline CVRD comorbidity status were compared with individuals free from CVRD at baseline, accounting for the competing risk of death.

Results

Among T2D patients aged ≥45 years, the LTR of MARCE was 80% for individuals free from CVRD at baseline. LTR of MARCE was 97%, 93%, 98%, 89% and 91% for individuals with specific CVRD comorbidities for HF, CKD, MI, stroke and PAD, respectively at baseline. Within the CVRD-free cohort, LTR of CKD was highest at 54%, followed by CV death (41%), HF (29%), stroke (20%), MI (19%) and PAD (9%). Compared to CVRD-free, HF, MI and CKD at baseline were associated with the highest LTR of MARCE and its component diseases (Table).

Conclusion

The lifetime risk of CV disease and CKD in T2D patients is estimated to be over 60% and 50% respectively (1–3). When considered together, the LTR of MARCE is 80% in CVRD-free T2D patients, while nearly all those with T2D and HF will develop MARCE over their lifetime. Of the individual components of MARCE, LTR of CKD and HF were the highest among CVRD-free T2D patients. Preventive measures in T2D patients should be a priority in clinical practice to mitigate the burden of these complications.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): AstraZeneca
High dialysis clearance of drugs predicts intradialytic hypertension in hemodialysis patients
Authors: Tokareva A , Borovkova N , Polyakova I
Published: November 2020

Introduction/Purpose

An acute drop in highly dialyzable antihypertensive drug levels is considered to be one of the pathophysiological mechanisms of blood pressure rise during hemodialysis (HD). The study aimed to assess the prevalence of intradialytic hypertension (ID-HTN) and identify the most significant risk factors of its development.

Methods

We performed a retrospective case-control single-center study of HD patients from January 1st, 2014 to December 30th, 2016. Baseline evaluation included recording of antihypertensive medications with a focus on dialyzability of drugs. ID-HTN was defined as an increase in systolic blood pressure more than 10 mmHg after HD session.

Results

We enrolled 131 HD patients (52% males, median age 55.7 [53.5; 58.0] years, dialysis vintage 59.3 [51.8; 66.8] months). 79 patients suffered from ID-HTN. Highly dialyzable drugs were used in 61% of patients, most often – in 68% of cases – in the group of beta-blockers, less often among inhibitors of angiotensin-converting enzyme (32%).

ID-HTN was associated with use of beta-blockers (Spearman's rank correlation coefficient (r)=0.212; p=0.015), moxonidine (r=0.313; p=0.001) and highly dialyzable drugs (r=0.440; p<0.0001). Using the identified risk factors, a prediction model for ID-HTN based on logistic regression was constructed: y = −1.015 + 1.720 × highly dialyzed drugs + 0.993 × moxonidine; p = exp (y) / (1 + exp (y)).

Table 1 displays actual and predicted values on the sample of HD patients.

Conclusion

In present study 60% of dialysis patients suffered from ID-HTN. Drugs with high dialysis clearance were widely used (61%) in dialysis population. Highly dialyzable drugs were associated with increased risk of ID-HTN (OR 5.585; 95% CI 2.49–12.54; p<0.0001). The low specificity (65.4%) of the prediction model limits its use in clinical practice.

Figure 1 shows the covariate-adjusted ROC curve by logistic regression model.

Funding Acknowledgement

Type of funding source: None
Vericiguat clinical pharmacology programme: biopharmaceutical properties and potential intrinsic and extrinsic factor effects
Authors: Boettcher M , Aliprantis A.O , Lobmeyer M , Meyer M , Mueck W , Trujillo M , Becker C
Published: November 2020

Introduction

The Phase III VICTORIA study (NCT02861534), which evaluated vericiguat vs placebo in patients with worsening chronic heart failure (WCHF) with ejection fraction <45%, demonstrated a significant reduction in the primary composite endpoint of cardiovascular death and HF hospitalisation.

Purpose

A comprehensive clinical pharmacological programme of 28 Phase I trials in >650 participants was performed to inform use of vericiguat.

Methods

Biopharmaceutical properties, pharmacokinetics (PK) and the potential for intrinsic factors to influence vericiguat dose administration were investigated. The PK and pharmacodynamic (PD) interaction potential of vericiguat with other drugs was assessed.

Results

Vericiguat had a mean half-life of approximately 24 h and high bioavailability when taken with food, leading to the recommendation of once daily dosing with food. Due to the multi-pathway metabolism and excretion profile of vericiguat, there was a low risk of PK drug–drug interactions (DDI; Table). No clinically relevant PD DDI were identified between vericiguat and aspirin, warfarin, sacubitril/valsartan or nitrates. There was a relatively minor influence of intrinsic factors on vericiguat PK.

Conclusion

This clinical pharmacology programme supports use of vericiguat in patients with WCHF who are characterised by multiple comorbidities and polypharmacy.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Funding for this research was provided by Bayer AG, Berlin, Germany and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA
Analysis of first plus recurrent cardiovascular (CV) and hospitalisation events in the CAROLINA trial
Authors: Marx N , McGuire D.K , Johansen O.E , Rosenstock J , Pfarr E , Mattheus M , George J.T , Espeland M.A , Zinman B
Published: November 2020

Background/Introduction

CAROLINA (cardiovascular outcome study of linagliptin versus glimepiride in type 2 diabetes) was a randomised controlled clinical trial designed to compare the effects of linagliptin with glimepiride on CV events and other outcomes in patients with relatively early type 2 diabetes at elevated CV risk.

Purpose

To characterise the effects on net CV disease and the hospitalisation burden of this population, we assessed the effects of linagliptin vs glimepiride on all first plus recurrent CV events and all cause hospitalisations.

Methods

Participants with relatively early type 2 diabetes, high CV risk and HbA1c 6.5–8.5% were randomized to linagliptin 5 mg or glimepiride 1–4 mg once daily on top of standard of care. Cox regression was used to produce hazard ratios for time to first event. A negative binomial model was used to produce event rate ratios for all events.

Results

A total of 6033 participants were enrolled (mean age 64.0 years, HbA1c 7.2%, body mass index 30.1 kg/m2, eGFR 77 ml/min/1.73 m2, median type 2 diabetes duration 6.3 years, urine albumin:creatine ratio 10 mg/g, 42% with CV disease, 4.5% with heart failure). Adding recurrent events increased the number of events for analysis from first event by 10% more to 77% across CV/heart failure outcomes and by 119% for all cause hospitalisations, with corresponding increases in rates per 100-patient years in both treatment groups (e.g. for the composite of CV death/MI/stroke from 2.1 to 2.8 for linagliptin and 2.1 to 2.9 for glimepiride) over a median follow up of 6.3 years. Results of analyses of first-event and first plus recurrent events are presented below (Fig).

Conclusion

No significant differences were observed between linagliptin and glimepiride for either first or first + recurrent CV or hospitalisation events. These data underscore the significant CV disease burden experienced even in relatively early type 2 diabetes and reinforce the similar CV safety between linagliptin and glimepiride, differing only on hypoglycaemia risk.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Boehringer Ingelheim and Eli Lilly and Company
Clinical outcome with NOACs vs VKAs in patients with atrial fibrillation and severe chronic kidney disease: results of a retrospective, multicenter, real-world study
Authors: Lio V , Pasceri V , Di Lullo L , Russo V , Fimiani F , Calabro' P , Petroni R , Grimaldi M , Renda G , Pignatelli P , Romano S , Penco M , Patti G
Published: November 2020

Background

Patients with atrial fibrillation (AF) and severe chronic kidney disease (CKD) are at higher risk of both bleeding and thromboembolic events. Non-vitamin K antagonist oral anticoagulants (NOACs) are licensed to be used in these patients, although they were excluded from phase III controlled randomized trials comparing NOACs vs warfarin in AF. Thus, current evidence on NOACs use in such setting of patients is not definitive.

Purpose

Aim of our multicenter study was to perform a real-world comparison of clinical outcome with NOACs vs vitamin K antagonist anticoagulants (VKAs) also in AF patients having an estimated glomerular filtration rate (eGFR) 15–29 mL/min.

Methods

We retrospectively included a total of 266 patients receiving NOACs (N=159) or VKAs (N=107). Primary outcome measure was the cumulative incidence of the net composite endpoint including ischemic stroke, systemic thromboembolism or any bleeding. Mean follow-up was 2.6 years.

Results

CHA2DS2-VASc and HAS-BLED scores at baseline were similar in the two groups (3.4±1.3 with NOACs vs 3.4±0.9 with VKAs and 3.1±1.0 vs 3.0±0.7, respectively); eGFR and hemoglobin values were also comparable (31.8±12.3 vs 32±11.9 mL/min and 10.2±2.1 vs 11.0±2.3 g/dL, respectively). NOACs were not inferior to VKAs for the primary net composite endpoint: incidence 20.7% vs 29.9%, p<0.01 for non-inferiority, p=0.11 for superiority. In proportional Cox regression model, hazard ratio for the primary outcome measure with NOACs use was 0.74 (95% CI 0.45–1.21, p=0.22). In the NOAC group there was a trend towards reduction in minor bleeding complications (p=0.08).

Conclusions

Our real-world data indicate that in patients with AF and severe renal failure NOACs are not inferior to VKAs for both safety and efficacy. The use of NOACs was associated with a numerically lower incidence of minor bleeding.

Funding Acknowledgement

Type of funding source: None
Pharmacokinetics of apixaban in patients with end stage renal disease on hemodialysis and atrial fibrillation: results from the RENAL-AF trial
Authors: Pokorney S , Garonzik S , Chertow G.M , Washam J.B , Mussina K , Bansal N , Gadegbeku C , Garcia D , Lopes R.D , Mahaffey K.W , Middleton J , Thadhani R , Thomas K.L , Winkelmayer W , Granger C.B
Published: November 2020

Background/Introduction

Apixaban use is increasing for stroke prevention in patients with atrial fibrillation (AF) and end stage renal disease (ESRD) on hemodialysis. There is uncertainty as to the optimal dose in this population in part related to the limited available pharmacokinetic (PK) data.

Purpose

We comprehensively evaluated the PK of apixaban collected over 1 month of apixaban dosing in 63 patients with AF and ESRD on hemodialysis.

Methods

Patients with AF and ESRD on hemodialysis were randomized to warfarin versus apixaban within the RENAL-AF trial with 5 mg BID dosing, except for 2.5 mg BID in those age ≥80 years or weight ≤60 kg. The 5 mg BID dose could be reduced to 2.5mg BID for minor bleeding. Day 1 PK data was collected on all patients pre- and post-hemodialysis. Day 3 and 1 month pre- and post-hemodialysis PK samples were collected in 49 patients. The timing of apixaban dosing and hemodialysis relative to PK samples was recorded. Dosing history, hemodialysis, and PK samples were chronologically integrated with patient specific data such as body size, age, race and gender. This dataset was combined with the ARISTOTLE dataset, and the published PK model from ARISTOTLE describing exposures in the AF population was updated to incorporate an additional clearance term for hemodialysis. The model estimated apixaban exposures (AUC) in RENAL-AF were compared to ARISTOLTE AUC values.

Results

There were 285 PK concentrations collected among 63 patients in the RENAL-AF trial. Patients had median age 69 years with 41% women (N=26) and a median weight of 84 kg (49, 157). The median AUCs for patients with ESRD on hemodialysis were 5,452 and 2,990 for patients treated with 5mg BID and 2.5mg BID doses, respectively. The median AUCs for patients treated with 5mg BID from ARISTOTLE increased from 2,802 for patients with class 1 CKD to 5,863 for class 4 CKD, while they increased from 2,392 for class 1 CKD to 2,881 for class 4 CKD in patients treated with 2.5mg BID. The median AUC for patients with ESRD on hemodialysis were within 50% of the exposure of patients from ARISTOTLE for all classes of CKD for the 2.5mg BID dose and for classes 2, 3A, 3B, and 4 CKD for the 5mg BID dose (Figure).

Conclusions

The steady state apixaban exposure data in patients with AF and ESRD on hemodialysis were modestly higher but consistent with the results of non-ESRD patients from ARISTOTLE, using 5 mg BID unless patients had age ≥80 years or weight ≤60 kg. Additional clinical outcomes data on the use of apixaban in patients with AF and ESRD on hemodialysis are needed.

Funding Acknowledgement

Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Investigator sponsored grant from Bristol-Myers Squibb and Pfizer
The impact of discontinuation of aspirin within 24 months among the high risk patients who are receiving prolonged dual antiplatelet therapy after implantation of second-generation drug-eluting stents
Authors: Cho S.W , Kim D.Y , Park T.K , Lee J.M , Yang J.H , Song Y.B , Choi J.H , Choi S.H , Gwon H.C , Lee S.H , Hahn J.Y
Published: November 2020

Background

The clinical impact of discontinuation of aspirin within 24 months after PCI for high risk patients who are receiving prolonged dual antiplatelet therapy (DAPT) is not known. We investigated the long-term outcomes prolonged DAPT among high risk patients after second-generation drug-eluting stent (DES) implantation.

Methods and results

Of 2082 consecutive patients undergoing PCI using 2nd generation DES, we studied 637 patients at high risk either angiographically or clinically who received clopidogrel longer than 24 months and were event-free at 12 months after index PCI. Patients were divided into 2 groups: the clopidogrel monotherapy group (aspirin discontinued within 24 months) and the prolonged DAPT group. The primary outcome was major adverse cardiac and cerebrovascular events (a composite of all-cause death, non-fatal myocardial infarction, or stroke) between 12 and 36 months after the index procedure.

In propensity score-matched population, the risk of major adverse cardiac and cerebrovascular events (4.7%, 12/256 versus 4.3%, 11/256, hazard ratio (HR) 0.95, 95% confidence interval (CI) 0.42–2.16, p=0.91), all-cause mortality (3.1%, 8/256 versus 2.0%, 5/256, HR 0.70, CI 0.23–2.14), cardiovascular death (0.4%, 1/256 versus 0.8%, 2/256, HR 2.34, CI 0.21–25.80, p=0.49), non-fatal myocardial infarct (0.8%, 2/256 versus 0.4%, 1/256, HR 0.57, CI 0.05–6,32, p=0.65), stroke (0.8%, 2/256 versus 0.8%, 2/256, HR 1.09, CI 0.15–7.76, p=0.93) were not significantly different between patients receiving clopidogrel monotherapy and prolonged DAPT.

Conclusion

Compared to prolonged DAPT, aspirin discontinuation 12–24 months after PCI for high risk patients who received DAPT has similar long-term risk of major adverse cardiac and cerebrovascular events in patients after second-generation DES implantation.

Funding Acknowledgement

Type of funding source: None
Pharmacogenetic testing in the management of patients with prosthetic heart valves
Authors: Gorbunova E.V , Ponasenko A.V , Barbarash O.L
Published: November 2020

Background

This study examined clinical, demographic, anthropometric, and inheritance factors that influence individual sensitivity to warfarin therapy after heart valve surgery. The clinical significance of the pharmacogenetic approach was assessed using the individual time frame and time spent in the INR therapeutic range.

Purpose

To study the influence of the preemptive panel-based pharmacogenetic testing on the effectiveness and safety of anticoagulant therapy in patients with prosthetic heart valves.

Materials and methods

The study included 928 patients (519 men and 409 female) (mean age 56±10 years) living in Western Siberia, Russia. Mainly there were patients with rheumatic heart disease, heart failure III NYHA and atrial fibrillation in 35% of cases. Mechanical heart valve prostheses were used in 70% of cardiac surgery cases. Real-time polymerase chain reaction was used for molecular genetic testing for polymorphisms VKORC, CYP2C9*2, CYP2C9*3, and CYP4F2.

Results

The frequencies of alleles and genotypes of CYP2C9 and VKORC1 in the study population of patients with heart valves prosthetic correspond to the distribution in Caucasian populations. Correlation between the calculated and actual therapeutic doses of warfarin was found according to the B.F Gage algorithm. In analyzing the dependence of the actual therapeutic dose of warfarin on polymorphic variants of the CYP2C9 and VKORC1 genes, it was shown that all the studied variants were associated with a therapeutic dose of warfarin, which was significantly different in carriers of different genotypes. Genotypes A/A CYP2C9*3 and G/G VKORC1 were associated with the largest deviations of the actual therapeutic dose from the calculated one. The clinical effectiveness of the pharmacogenetic approach was assessed according to the prevalence of the studied polymorphic variants of the CYP2C9 and VKORC1 genes in patients with prosthetic heart valves in the Kemerovo region. As a result, two groups of patients were formed using the “copy pair” method, without statistically significant differences in genetic, clinical, demographic, and anthropometric data. Usage of the pharmacogenetic testing at the beginning of warfarin therapy twice reduced time required to select a therapeutic dose of the anticoagulant, while the time within therapeutic INR range was increased by 20.2%.

Conclusion

The use of the panel-based pharmacogenetic approach at the beginning of warfarin therapy in patients with prosthetic heart valves increases the effectiveness and safety of anticoagulant therapy in the early postoperative period.

Funding Acknowledgement

Type of funding source: None
Mixed reality interactive visualization of cardiovascular anatomy in interventional lab – clinical implementation in transvascular patent ductus arteriosus closure
Authors: Kasprzak J.D , Kierepka M , Zlahoda-Huzior A , Stanuch M , Zolna D , Serafin J , Kasprzak J.I , Witowski J , Lipiec P , Wdowiak-Okrojek K , Peruga J.Z
Published: November 2020

Aim

Three-dimensional (3D) noninvasively acquired datasets containing anatomical information about the heart are a modern option for procedural support during percutaneous cardiac interventions. We present initial experience of patent ductus arteriosus (PDA) closure with workflow integrated with innovative mixed reality display (MRD) to improve 3D perception and navigation in 3D computed tomography angiographic (CTA) datasets.

Methods

We report incorporation of intraprocedural mixed-reality display of segmented CTA (computed tomography angiography) data using a voice- and gesture controlled head-mounted display during routine percutaneous occlusions of PDA in adults. A dedicated software pathway was used for files conversion, real-time Wi-Fi streaming of 3D rendering from PC to device and manipulation of spatial data during the procedures.

Results

Pre-recorded CTA studies of aorta and ductus were manually segmented and uploaded into custom designed 3D DICOM for realtime export to MRD device. 3D holograms were successfully displayed during the procedure by commercially available head-mounted display allowing touchless control and image sharing within cath-lab. Wiring of PDA aortic orifice was assisted by 3D hologram controlled by the imaging specialist and shared by the operator. Thus, MRD using evolving versions of custom software was successfully executed with segmented data presented as a semitransparent cubic hologram positioned in a convenient part of visual field allowing real-world action and with touchless control by medical team. Operator appreciated the use of MRD hologram realistically visualizing spatial relationships as practical aid to establish anatomical relationships and facilitate entry into ductus orifice. Procedures were successfully completed using arteriovenous guidewire loop to implant vascular occluders.

Conclusions

We demonstrate the methodology and software evolution (segmentation, data fusion) allowing practical implementation of intraprocedural mixed reality display of 3D CTA data, with sterile, touchless control of holographic image shared by interventional and imaging team to support percutaneous PDA closure.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): MEDAPP
Premature ventricular contraction detection system from the 12 leads ECG by artificial intelligence
Authors: Kim Y , Kim J.H , Lee M.Y , Kim Y.K
Published: November 2020

Background

Electrocardiographs (ECG) are obtained by a digital signal. However, they are still printed out of paper to read by physicians. Digitizing the analog ECG from the paper to digital signal make us much easier to access of bid data pool form the daily clinical practice and previous resources.

Objective

The goal of this study is to digitize paper ECG to detect premature ventricular contraction (PVC).

Methods

This system consists of 2 steps; digitization and PVC detection.

Results

First, for digitization, ECG are filtered by the specific cut-off value of red, green and blue, then the filtered ECG image is changed into gray scale. In order to extract ECG signal, the algorithm fine the only one of the biggest white body throughout the X-axis. The X and Y axis is matched with distance and amplitude, depending on dots per inch (DPI). Second, to detect PVC, ECG signal is filtered to eliminate baseline wandering. The characteristics of PVC is higher amplitude and longer duration than normal sinus rhythm, we set two criteria to detect the PVC: 1.5 times the duration, 1.2 points out of the amplitude. For the synchronization of timing, lead II rhythm strip was used by PVC detection and then the rest of 12-lead ECG is matched based on lead II synchronization (Figure 1). We applied this algorithm to the 300 real patient's ECG. 290 of 300 (96.7%) ECG are successfully digitized signal and PVC detection.

Conclusion

We successfully developed the algorithm analog ECG signal into digital signal to detect PVC. In the future, this method helps to gather big data from ECG papers to develop a new algorithm to localization of PVC.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Korean Heart Rhythm Society 2019 Research Fund
Use of social media by health care professionals: is patients' privacy respected?
Authors: Castrichini M , Nuzzi V , Sinagra G , Cleland J , Pellicori P
Published: November 2020

Background

The internet has a key role in sharing and expanding medical knowledge. Social networks offer health-care professionals the possibility to communicate, debate and learn from each other in real-time, thereby improving access to expertise and creating new knowledge. On Facebook, there are many groups that health-care professionals can join to discuss clinical cases. However, it is unknown if patient-privacy is respected and whether users are aware that they might be inadvertently involved in a criminal act for which they might be sued.

Methods

We identified the most popular Facebook group for cardiologists, “ECHO BOARD REVIEW forum” that has more than 47,000 users. We retrospectively evaluated all content posted by this group between February 6th and February 14th 2020. Information about the type of data posted, personal patient details, geographic location reported on images or videos, number of reactions and comments was collected. Privacy was considered fully violated when name and/or surname of the patient was identifiable. A comparison between the two cases (privacy preserved vs. privacy violated) was performed.

Results

Of 53 posts evaluated, 50 (94%) were echocardiograms; the remaining three cases were of an electrocardiogram, a cardiac magnetic resonance video and a coronary angiogram. The patient's identity was revealed in seven cases (13%). Compared to cases where identity was concealed, those revealing the patient's identify were more likely to report other important personal details including date of birth (n=0 (0%) vs 2 (29%)), age (n=14 (30%) vs 5 (71%)) and sex (n=15 (33%) vs 6 (86%)). The country (n=46, 87%), city (n=39, 74%), and hospital (n=34, 64%) where the cases were being evaluated were also frequently disclosed. Most cases were from Asia (n=23, 43%) or Africa (n=17, 32%). Of the 7 cases in which privacy was fully violated, 43% were from Africa, 27% were from South America and 14% were from Asia. In the majority of cases, the author of the post was seeking diagnostic help (n=33), less frequently a diagnosis was already made by the author (n=17). The median (interquartile range) number of comments/post was 12 (5–23), and of likes/post was 21 (12- 37), with no significant difference between cases in which privacy was violated or not.

Conclusion

Social media allows knowledge and expertise to be shared amongst health care professionals, but, alarmingly, violation of patient-confidentiality is common. In order to maintain patient-confidentiality and avoid breaking the law, strict rules should be applied to regulate the use of social media by health-care professionals.

Funding Acknowledgement

Type of funding source: None
Time-to-reperfusion in ST-segment elevation myocardial infarction undergoing inter-hospital transfer using WhatsApp smartphone application
Authors: Bendary A , Mansour A.M , Kabil H.K , Mostafa S.M
Published: November 2020

Aim

Current guidelines recommend that patients with ST-elevation myocardial infarction (STEMI) receive primary percutaneous coronary intervention (PCI) with a door-to-balloon (D2B) time of 90 minutes. This time frame has been difficult to achieve in developing countries. We aimed to test the hypothesis that using WhatsApp for inter-hospital transfer in STEMI primary PCI would result in shorter D2B time through avoiding emergency department (ED) waiting.

Methods

In the period from May 2018 to April 2019, 300 patients with STEMI treated with primary PCI were prospectively enrolled in a multi-center observational study covering 3 PCI-capable centers in our city. Patients were categorized into 3 groups: G-1; Self-presenting to the ED, G-2; Transferred by ambulance to the ED and G-3; those transferred from non-PCI capable centers directly to catheterization laboratory (bypassing the ED as possible) after the team was pre-activated through an ECG image sent using WhatsApp. The primary endpoint was between-groups difference in total ischemic and D2B times.

Results

All groups were matched regarding baseline criteria. WhatsApp use was associated with significantly shorter D2B time (166.5±33.8 vs 157.8±29.6 vs 120.8±35.2 minutes in groups 1, 2 and 3 respectively, P<0.001) and shorter total ischemic time (258.9±33.9 vs 249.6±29.4 vs 212.7±35.4 minutes in groups 1, 2 and 3 respectively, P<0.001). Linear regression showed that WhatsApp referral significantly reduces ED waiting time by about 20.4 minutes (95% CI −21.6 to −19.3 minutes, P<0.001).

Conclusion

Using WhatsApp for inter-hospital transfer in primary PCI is associated with significantly shorter D2B times.

Key time intervals among study groups

Funding Acknowledgement

Type of funding source: None
AI and telemedicine: total remote guidance of AMI management
Authors: Mehta S , Gibson M , Niklitschek S , Fernandez F , Villagran C , Escobar E , Vera F , Frauenfelder A , Vieira D , Quintero S , Merchant S , Tamayo C.J , Ceschim M , Vallenilla I , Prieto L
Published: November 2020

Background

For a decade, Latin American Telemedicine Infarct Network (LATIN) Telemedicine has transformed AMI management in Brazil, Colombia, Mexico, Chile, and Argentina. With a hub and spoke strategy, AMI coverage was expanded to 100 million population and 877,177 telemedicine encounters were performed. Cost savings from avoiding unnecessary transfer of patients was $291 million. We are now rapidly escalating on a path to making the telemedicine process “physician-free” by utilizing Artificial Intelligence (AI) protocols.

Purpose

To demonstrate that AI can replace a cardiologist for remote AMI telemedicine guidance.

Methods

The process of total AI guidance focused on both aspects of our telemedicine strategy – accurate AMI diagnosis and tele-guidance of the entire STEMI process. We developed our innovative approach by initially creating AI algorithms for computer-aided diagnosis. Next, we incorporated logistic variables (duration of chest pain, transfer times to LATIN hub, etc) to the algorithm for physician-free triage into thrombolysis, primary PCI and pharmaco-invasive management. The intent of creating AI algorithms was early STEMI detection and triage. After the patient was efficiently transferred to the hub, a final treatment decision was made by the hub cardiologists.

Results

Three crucial areas of telemedicine efficiency are being monitored – Time-to-Telemedicine Diagnosis (TTD), Door-In-Door-Out (DIDO) and Transfer Times (TT). All are showing improvements. Detailed results will be available at the time of presentation.

Conclusions

We are encouraged with the possibility of making the entire telemedicine guidance of AMI management “physician-free”. Next-Gen improvements are being contemplated by including a Single Lead EKG for AMI detection that will impact symptom-to-balloon times.

Funding Acknowledgement

Type of funding source: None
Tradicar, practical training program in Diabetes for today s cardiologist
Authors: Garcia Iglesias D , Rozado Castano J , Soroa M , Barja N , Junco A , Adeba A , Vigil-Escalera M , Alvarez R , Capin E , Rubin Lopez J.M , Colunga S , Moris De La Tassa C , Delgado E , De La Hera Galarza J.M
Published: November 2020

Introduction

Diabetes Mellitus (DM) is an importan Cardiovascular Risk-factor and glucose-lowering drugs have shown to improve cardiovascular prognosis. We believe that specific training programs in DM are necessary, and so we have developed a web platform (Tradicar.es) to guide and provide educational tools.

Objectives

To evaluate characteristics of DM patients and the impact on active glycemic control strategies after the continuous training system.

Methods

We have created a web platform that allows direct consult with experts in diabetes and cardiology, immediately obtaining a recommendation. In addition, users have to propose a treatment, to evaluate their training progression. Prospectively, all DM patients admitted (Apr/18-Feb/19) were included. Personal history and preadmission, proposed and recommended treatment are recorded. For the comparison between proposed and recommended treatment we used a Cohen kappa, and for the comparison between previous and prescribed treatment, a chi-square test was performed.

Results

117 patients were analyzed, 72 (64.9%) male, with a mean of 70.51 (±16.2) y.o. For other clinical variables see table.

An active strategy was taken in 105 patients (89.7%), which resulted in an increased prescription of antidiabetic treatment. Specifically, SGLT2i prescription was significantly increased from 12 (10.9%) to 40 (34.2%) patients, p<0.01. The coincidence index increases from 0.76 (±0.21) in the first 4 months, to 0.9 (±0.2) in the last 4 months, p=0.03.

Conclusions

The cardiovascular prognostic impact of new glucose-lowering treatments forces us to to update and expand our DM training. Electronic tools allow immediate contact and are essential to improve the medical care we offer.

Figure 1. A: Included patients (bars) and Cohen kappa (dots). B: Comparison of glucose-lowering drugs at hospitalization and discharge.

Funding Acknowledgement

Type of funding source: None