bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of mitral valve diseases in the newborn – a large population-based study of newborns
Authors: Bjerrekaer J , Voegg R.O.B , Farooqui A , Boerresen M , Raja A.A , Pihl C , Norsk J , Bundgaard H , Iversen K
Published: November 2020

Background

Mitral valve abnormalities (MVA) include mitral valve regurgitation (MR), mitral valve prolapse (MVP), Barlow's mitral valve disease, and parachute MV. The prevalence of MVA has yet to be determined in an unselected population of newborns.

Objective

To determine the prevalence of MVA in unselected newborns and to assess the left ventricular (LV) structure and function in the neonatal heart with MR.

Methods

Transthoracic echocardiography (TTE) was performed within 28 days after birth in unselected neonates consecutively included in a prospective, multicenter, population-based study (2016–2018 (n=25,751)). TTE's were systematically reviewed for MR, MVP, Barlow's MV disease, and parachute MV. In a subgroup of 400 newborns with MR, the regurgitation was further classified as either traceable MR, mild MR, or moderate/severe MR based on the ratio of the trans-mitral jet in systole over the diastolic filling duration using M-mode in the 4-chamber view of the LV.

Results

Of 25,751 included newborns, we found a prevalence of MVA of 26.7%. (6,883/ 25,751). The prevalence of MR was 26.2%, MVP was 0.35%, Barlow's disease was 0.13%, and parachute mitral valve was 0.027%. MR was more frequent in females compared to males (50.4 vs 48.2%, p<0.01). Newborns with MR had enlarged left atrial diameter (11.91±2.03 mm vs 11.53±2.02 mm, p<0.01) and LV end-diastolic and end-systolic diameter (LVIDd 19.98±1.88 mm vs 19.87±1.83 mm, p<0.01, LVIDs 13.48±1.47 mm vs 13.31±1.41 mm, p<0.01), thicker LV posterior wall (2.19±0.60 mm vs 2.05±0.52 mm, p<0.01), increased early and atrial mitral inflow velocities (MV E velocity (0.65±0.14 m/sec vs 0.61±0.13 m/sec, p<0.01), MV A velocity (0.60±0.13 m/sec vs 0.57±0.13 m/sec, p<0.01)), but lower fractional shortening (32.54±4.22% vs. 32.96±4.17%, p<0.01) as compared to newborns without MVA.

In subgroup analysis MR severity was classified as traceable in 44% (175/400) of cases, mild MR in 52% (209/400) of cases and moderate/severe MR in 4% (16/400) of cases. Comparing traceable MR with moderate/severe MR (19.48±1.88 mm vs 20.96±2.64 mm, p=0.01) and comparing mild MR with moderate/severe MR (19.85±1.92 mm vs 20.96±2.64 mm, p=0.04) showed significant increases in LV end-diastolic diameter.

Conclusion

Over one fourth of all newborns had a MV abnormality of which mitral regurgitation accounted for the vast majority. The presence of MR was associated with asymmetric LV remodeling and discrete changes in LV function. Subgroup analysis revealed that increment in MR severity was primarily associated with an increase in LV end-diastolic diameter.

Funding Acknowledgement

Type of funding source: Public hospital(s). Main funding source(s): Herlev-Gentofte Hospital
Acute coronary syndromes in nonagenarians: do we have reliable risk scores?
Authors: Vidal P , Cepas Guillen P.L , Caldentey G , Martinez Gomez E , Borrego-Rodriguez J , Echarte Morales J , Minguito Carazo C , Alonso Orcajo N , Llagostera M , Castillo M , Viana Tejedor A , Quiroga X , Freixa X , Fernandez-Vazquez F , Sabate M
Published: November 2020

Introduction

GRACE score is strongly validated to determine the probability of death in acute coronary syndrome (ACS), nevertheless its usefulness in nonagenarians, a population with frequently associated comorbidities, is less stablished. BARTHEL and CHARLSON scores might be useful tools to predict outcomes in this population.

Objective

The aim of this study was to evaluate the potential applicability of GRACE score and two comorbidity scores (CHARLSON and BARTHEL) to estimate prognosis in nonagenarians with ACS.

Material and methods

We retrospectively included all consecutive patients equal to or older than 90 years old admitted with non-ST (NSTEMI) or ST segment elevation myocardial infarction (STEMI) in four tertiary care centers between 2005 and 2018. Patients with type 2 myocardial infarction were excluded. We collected patients' baseline characteristics and procedural data. In-hospital and at 1-year follow-up all-cause and cardiovascular mortality were assessed. Risk score accuracy was evaluated by area under the curve ROC (AUC).

Results

A total of 444 patients (mean age 92.6±2.4 years, 60% females) were analyzed.

Approximately half of them (n=241, 54%) with STEMI and the remainder (n=203, 46%) with NSTEMI. Global GRACE-AUC for in-hospital and 1-year all-cause mortality were moderate (0.64; 95% CI: 0.59–0.69 and 0.62; 95% CI: 0.57–0.67, respectively). Only in the NSTEMI group, the GRACE-AUC was better to predict in-hospital mortality, 0.70 (95% CI: 0.63–0.77). Neither CHARLSON nor BARTHEL showed better predictive results than GRACE score (AUC ≤0.60).

Conclusion

GRACE score has moderate accuracy to estimate mortality in nonagenarian patients with ACS. BARTHEL and CHARLSON scores do not improve the predictive value of GRACE score. An individualized approach is required to make therapeutic decisions in this special population.

Figure 1. ROC-GRACE curves

Funding Acknowledgement

Type of funding source: None
Cardiovascular risk factors during cancer treatment: prevalence, incidence and prognostic relevance
Authors: Caro Codon J , Lopez-Fernandez T , Alvarez-Ortega C , Zamora Aunon P , Rodriguez Rodriguez I , Gomez Prieto P , Buno Soto A , Canales Albendea M , Feliu Batlle J , Rodriguez Fraga O , Martinez Monzonis A , Gonzalez-Costello J , Serrano Antolin J.M , Gonzalez-Juanatey J.R , Lopez-Sendon J.L
Published: November 2020

Background

The actual usefulness of CV risk factor assessment in the prognostic evaluation of cancer patients treated with cardiotoxic treatment remains largely unknown.

Design

Prospective multicenter study in patients scheduled to receive anticancer therapy related with moderate/high cardiotoxic risk.

Methods

A total of 1324 patients underwent follow-up in a dedicated cardio-oncology clinic from April 2012 to October 2017. Special care was given to the identification and control of CV risk factors. Clinical data, blood samples and echocardiographic parameters were prospectively collected according to protocol, at baseline before cancer therapy and then at 3 weeks, 3 months, 6 months, 1 year, 1.5 years and 2 years after initiation of cancer therapy.

Results

At baseline, 893 patients (67.4%) presented at least 1 risk factor, with a significant number of patients newly diagnosed during follow-up. Individual risk factors were not related with worse prognosis during a 2-year follow-up. However, a higher Systemic Coronary Risk Estimation (SCORE) was significantly associated with higher rates of severe cardiotoxicity and all-cause mortality [HR 1.79 (95% CI 1.16–2.76) for SCORE 5–9 and HR 4.90 (95% CI 2.44–9.82) for SCORE ≥10 when compared with patients with lower SCORE (0–4)].

Conclusions

This large cohort of patients treated with a potentially cardiotoxic regimen showed a significant prevalence of CV risk factors at baseline and significant incidence during follow-up. Baseline cardiovascular risk assessment using SCORE predicted severe cardiotoxicity and all-cause mortality. Therefore, its use should be recommended in the evaluation of cancer patients.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): This study was partially funded by the Fondo Investigaciones Sanitarias (Spain), Centro de Investigaciόn Biomédica en Red Cardiovascular CIBER-CV (Spain)
Transcatheter aortic valve replacement in patients with severe aortic stenosis and active cancer: a systematic review and meta-analysis
Authors: Bendary A , Ramzy A.R , Bendary M.B , Salem M.S
Published: November 2020

Background

Patients with severe aortic stenosis (AS) and concomitant active cancer (AC) are considered high-risk patients and usually are not allowed to undergo surgical valve replacement. Transcatheter aortic valve replacement (TAVR) may be an attractive option for them; however, little is known about the outcomes of TAVR in this subset of complex patients.

Methods and results

In this meta-analysis, Medline, Cochrane Library and Scopus databases were searched (anytime up to April 2019) for studies evaluating the outcomes of TAVR in patients with or without AC. We assessed pooled estimates (with their 95% confidence intervals [CIs]) of the risk ratio (RR) for the all-cause mortality at the 30-day and 1-year follow-ups, a 4-point safety outcome (any bleeding, stroke, need for a pacemaker and acute kidney injury) and a 2-point efficacy outcome (device success and residual mean gradient [mean difference]). Three studies (5162 patients) were included. Of those patients, a total of 368 patients (7.1%) had AC. Apart from a significantly higher need for a postprocedural pacemaker (RR 1.29, 95% CI: 1.06–1.58, P=0.01), TAVR in AC patients resulted in similar outcomes for safety and efficacy at the 30-day follow-up compared to those without AC. Patients with AC experienced similar rates of the all-cause mortality at the 30-day follow-up compared to those without (RR 0.92, 95% CI: 0.53 to 1.59, P=0.76); however, the all-cause mortality was significantly higher in patients with AC at the 1-year follow-up (RR 1.71, 95% CI: 1.26 to 2.33, P=0.0006). This mortality difference was independent of cancer stage (advanced or limited) at the 30-day follow-up but not at the 1-year follow-up; only patients with limited cancer stages showed similar all-cause mortality rates compared to those without cancer at the 1-year follow-up (RR 1.22, 95% CI: 0.79 to 1.91, P=0.37).

Conclusion

TAVR in patients with AC is associated with similar 30-day and potentially worse 1-year outcomes compared to those in patients without AC. The 1-year all-cause mortality appears to be dependent on the cancer stage. Involving a specialized oncologist who usually considers cancer stage in the decision-making process and applying additional preoperative scores such as frailty indices might refine the risk assessment process among these patients.

All-cause mortality (cancer vs no)

Funding Acknowledgement

Type of funding source: None
Effect of enalapril on left ventricular longitudinal strain in patients with hematologic malignancies after bone marrow transplantation
Authors: Katogiannis K , Ikonomidis I , Stamouli M , Makavos G , Frogoudaki A , Vrettou A.R , Birba D , Thymis I , Tsilivarakis D , Liori S , Tsirigotis P , Iliodromitis E.K
Published: November 2020

Background and aims

Chemotherapy is known for its potential adverse effects on myocardium. Optimal medical treatment for heart failure may reverse myocardial dysfunction in the early stages of toxicity development. We hypothesized that early initiation of treatment with Angiotensin Converter Enzyme inhibitor (ACE-i) enalapril could prevent cardiotoxicity.

Patients and methods

60 patients (mean age 46,3±12,9 years old, 19 male) with preserved ejection fraction, who suffered from hematologic malignancies (lymphoma, leukemia) and underwent bone marrow transplantation and were randomized to receive 2,5 mg enalapril bid daily or placebo. We measured at baseline, before transplantation, and after three months: i) Global Longitudinal Strain of left ventricle (LV) (GLS), ii) Left Ventricular Epicardial Strain (GLSepi), iii) Left Ventricular Endocardial Strain GLSendo), by speckle tracking imagind iv) Left Ventricular End Diastolic Volume, Left Ventricular End Systolic Volume and Left Ventricular Ejection Fraction (LVEF-Simpson's Method).

Results

The two treatment groups had similar age, sex atherosclerotic risk factors and cardiotoxic medication befeor and after bone marroe transplantation. Compared to baseline, patients treated with enalapril did not show a deterioration of LV GLS and GLSepi [(GLS = −20.2±3.6% vs 19.7±3.7%, p=0.540), (GLSepi = −17.9±3.1% vs −17.2±3.2%, p=0.422)], Conversely, patients treated with placebo group, presented a significant impairment of LV GLS and GLSepi [(GLS = −20.2±1.8% vs 18.9±2.1%, p=0.041, GLSepi = −17.8±1.5% vs −16.6±1.7%, p=0.028)] three months after bone marrow transplantation. No significant changes were found in LVEF after treatment with enalapril (58.6±17.6% vs 59.4±9.2%, p=0.692) or the placebo (59.4±6.6% vs 59.7±6.8%, p=0.892).

Conclusions

Treatment with enalapril prevented deterioration of myocardial deformation three months after bone marrow transplantation in patients with hematologic malignancies and preserved ejection fraction.

Funding Acknowledgement

Type of funding source: None
The effects of doxorubicin on left and right atrial mechanics in patients with lymphoma
Authors: Vahabi S , Kharati-Koopaei E , Stewart M , Hancock H , Norouzi M , Maddox J , Austin D
Published: November 2020

Background

Despite the associated dose-dependent cardiotoxicity, anthracyclines continue to form the backbone of modern chemotherapy regimens. Speckle Tracking Echocardiography (STE) has been a popular method of quantifying cardiac function but most studies have focused on left ventricular function. Research into the effects of anthracyclines on left atrial (LA) and right atrial (RA) function continues to be neglected.

Purpose

To investigate the effects of doxorubicin, a commonly used anthracycline, on both the LA and RA systolic and diastolic strain and strain-rate parameters in two groups of patients with lymphoma: Group 1 (G1) with a conventional drop in ejection fraction (EF <53%), and Group 2 (G2) without.

Methods

We retrospectively studied 46 patients treated for lymphoma between 2015 and 2018; G1 (n=12) and G2 (n=34). Echocardiograms performed at baseline (T0), mid-chemotherapy (T1), and post-chemotherapy (T2), were analysed by using offline vendor-independent software (TomTec, 2D Cardiac Performance Analysis). Using 2D STE, LA and RA reservoir, conduit and contractile strains, systolic and diastolic strain-rates were measured. Multi-level longitudinal model was used for statistical analysis.This study was ethically approved by the Health Research Association (REC Reference 18/SS/0139).

Results

Median age was 64 years (IQR 51–74 years) in G1, and 65 years (IQR 57–73 years) in G2. In G1, there was no significant change in LA reservoir strain with time, however a significant decline with an average mean difference of −7.52 was seen between T0 to T2 (p=0.016) in G2. LA conduit strain did not significantly change in either group with incremental doses of doxorubicin. However, LA contraction strain was seen to significantly increase in G1 between T1 to T2 (p=0.045) with an average change of 7.23. LA peak systolic strain rate, and late diastolic strain rate did not show any significant change with time in both groups. Yet, a significant increase was seen in LA early diastolic strain rate between T0 to T2 (p=0.017) in G1 but not G2. No significant changes were seen in the RA strain parameters in both groups.

Conclusion

In patient with a reduction in LV function, a significant change was noted in the left atrial contraction strain and early diastolic strain rate with incremental doses of doxorubicin. These changes shows the close relationship between the LA and LV, and the importance of LA in providing a compensatory mechanism for a decline in LV function secondary to anthracycline cardiotoxicity.

Funding Acknowledgement

Type of funding source: None
Severity and type of lymphoma are associated with aortic 18-fluorodeoxyglucose (FDG) positron emission tomographic uptake assessed by FDG PET/CT imaging
Authors: Koutagiar I , Georgakopoulos A , Pouli A , Sioni A , Giannouli S , Solomou E , Terentes-Printzios D , Karakitsios I , Kafouris P , Gaitanis A , Petrocheilou A , Pianou N , Tousoulis D , Vlachopoulos C , Anagnostopoulos C
Published: November 2020

Introduction

There is increasing evidence that metabolic disease burden in lymphoma influence patients' outcome.However, the impact of disease severity on cardiovascular system remains unknown.

Purpose

To assess whether lymphoma is associated with arterial inflammation by examining the relationship between disease metabolic burden and arterial fluorodeoxyglucose (FDG) uptake.

Methods

Sixty-two patients (43 male, mean age 58±18 years) with Hodgkin (n=29) or non-Hodgkin lymphoma (n=33) before chemotherapy and two separate control groups of 14 and 16 healthy individuals for Hodgkin and non-Hodgkin population respectively, with similar age, sex and cardiovascular risk factors,underwent FDG position emission tomography (FDG-PET/CT) imaging.Disease severity was quantified by metabolic tumor volume (MTV) and total lesion glycolysis (TLG) corresponding to standard uptake values (SUV) ≥41% or ≥2.5 of maximum SUV within lymphoma regions, and aortic FDG uptake by target-to-background ratio (TBR). Serum high sensitivity-C-reactive protein (hs-CRP), white blood count (WBC), ratio of neutrophils to lymphocytes (N/L), albumin and lactic acid dehydrogenase (LDH) values were measured for patient group.

Results

MTV and TLG measurements correlated significantly with hs-CRP, WBC,N/L ratio,albumin and LDH table 1.Patients with non-Hodgkin or Hodgkin lymphoma had increased aortic TBR compared to controls (p=0.001 and p=0.023, respectively).Aortic TBR was higher in patients with stage III-IV disease compared to those with stage I-I (p=0.046).There were significant associations between aortic FDG uptake and MTV values, which remained significant after adjustment for confounders (β=0.353, p=0.001, adjusted R2=0.318 for MTV41%, β=0.442, p=0.001, adjusted R2=0.269 for MTV2.5), Figure 1.

Conclusions

Aortic wall FDG uptake is related with disease severity indicating a vascular effect of lymphoma, as well as a new potential role of molecular imaging in cardio-oncology for evaluating disease severity and its consequences to vascular beds with a single examination.

Figure 1

Funding Acknowledgement

Type of funding source: None
Neoplastic markers in Takotsubo syndrome. Results from a prospective registry
Authors: Santoro F , Mallardi A , Leopizzi A , Vitale E , Zimotti T , Ieva R , Iacoviello M , Brunetti N.D
Published: November 2020

Background

Takotsubo syndrome (TTS) is an acute heart failure syndrome with significant rate of in and out-of hospital mayor cardiac adverse events (MACE).

Aim of this study

Evaluate the possible role of neoplastic biomarkers (CA 15.3, CA-19.9 and Carcinoembryonic Antigen (CEA)) as prognostic marker at short- and long-term follow-up in subjects with TTS.

Methods

Ninety consecutive subjects with TTC were enrolled and followed for a median of 3 years. Circulating levels of CA-15.3, CA-19.9, CEA were evaluated at admission, after 72 h and at discharge. Incidence of MACE during hospitalization and follow-up were recorded.

Results

Forty-three (46%) patients experienced MACE during hospitalization. These patients were older (78±9 vs 72±12 p=0.01), had lower LVEF (32±7 vs 38±8 p=0,01) and increased levels of CEA (4.3±6.2 vs 2.2±1.5 ng/ml p=0.03). CEA and CA 19.9 levels at admission were statistically correlated with CRP and NT-proBNP levels (both p<0.05).

At long term follow-up CEA and CA 19.9 levels (higher than median) were associated with increased risk of death (log rank p<0.01 (both) RR=5.3 CI 95% 1.9–14.8 p<0.01; RR=7.8 CI 95% 2.4–25.1 p<0.01 respectively). At multivariate analysis including age, sex and admission LVEF, CEA and CA 19.9 levels higher than median were an independent predictor of MACE at long term (p<0.01 RR 3.5 CI 1.6–7.3).

Conclusion

CEA and CA 19.9 serum levels are associated with higher risk of in-hospital MACE and death at long-term.

Funding Acknowledgement

Type of funding source: None
Aortic coarctation in pregnancy: outcomes and predictors for cardiovascular and hypertensive complications. Data from the ESC Registry of Pregnancy and Cardiac disease (ROPAC)
Authors: Ramlakhan K.P , Tobler D , Greutmann M , Schwerzmann M , Baris L , Yetman A.J , Nihoyannopoulos P , Manga P , Boersma H , Johnson M.R , Hall R , Roos-Hesselink J.W
Published: November 2020

Background

Pregnancy in women with repaired aortic coarctation (CoA) has a moderately increased risk (mWHO II-III) of an adverse cardiovascular, obstetric or fetal event, but prospective data to validate this estimated risk is scarce.

Purpose

We examined maternal and fetal outcomes in pregnant women with unrepaired and repaired CoA to identify predictors of adverse outcomes.

Methods

Pregnancies in women with CoA were selected from the worldwide prospective Registry of Pregnancy and Cardiac Disease (ROPAC, n=5739). The frequency and predictors of major adverse cardiac events (MACE, defined as maternal cardiac death, heart failure, atrial fibrillation/flutter, ventricular tachyarrhythmia, endocarditis, thromboembolic events, aortic dissection and acute coronary syndrome), and hypertensive complications (defined as pregnancy-induced hypertension, (pre)eclampsia or HELLP syndrome) were analyzed.

Results

Of 303 pregnancies in women with CoA (median age 30 years, median pregnancy duration 39 weeks), 10% were in women with unrepaired CoA and 27% in women with pre-existing hypertension. There were no maternal deaths. There were 4 neonatal deaths of which 3 occurred after a spontaneous extreme preterm birth. MACE occurred in 4.3% of pregnancies, predominantly involving heart failure (3.3%). MACE rate was similar in unrepaired vs repaired CoA (3.4% vs 4.4%, p=0.814). Predictors of MACE included pre-pregnancy clinical signs of heart failure (OR 31.8, 95% CI 6.8–147.7), LVEF <40% (OR 10.4, 95% CI 1.8–59.5), NYHA class >1 (OR 11.4, 95% CI 3.6–36.3), cardiac medication use (OR 4.9, 95% CI 1.3–18.3) and living in an emerging country (OR 4.88, 95% CI 1.58–15.07). Hypertensive complications occurred in 6.3%, more often in the subgroup with pre-existing hypertension (11% vs 5%, p=0.040). Pre-existing hypertension was the only predictor (OR 2.6, 95% CI 1.01–6.6). Caesarean section was performed in 50% of the total cohort.

Conclusions

Pregnancies in women with CoA are safe, well tolerated and MACE and hypertensive complication rates are low. These findings support mWHO risk score reevaluation to mWHO II for women with CoA without cardiac impairment.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): ESC EURObservational Research Programme (EORP)
RNA interference targeting apolipoprotein C-III with ARO-APOC3 in healthy volunteers mimics lipid and lipoprotein findings seen in subjects with inherited apolipoprotein C-III deficiency
Authors: Schwabe C , Scott R , Sullivan D , Baker J , Clifton P , Hamilton J , Given B , San Martin J , Melquist S , Watts G.F , Goldberg I , Knowles J.W , Hegele R , Ballantyne C
Published: November 2020

Background

Individuals with triglycerides (TGs) ≥1,000 mg/dL (11.1 mmol/L) are at increased risk of acute pancreatitis. Genetic studies indicate that individuals with apolipoprotein C-3 (APOC3) loss-of-function mutations have low TGs, reduced cardiovascular risk and no observed adverse phenotype. RNA interference (RNAi) with ARO-APOC3 has shown deep and durable knockdown (KD) of APOC3 after single doses in healthy volunteers (HVs, presented at AHA 2019) with good tolerability. We report here initial results using multiple doses of ARO-APOC3 to silence APOC3 expression in HVs.

Methods

ARO-APOC3 was administered subcutaneously to HVs on days 1 and 29 at doses of 10, 25 or 50 mg (n=4 per group). Measured parameters included plasma concentrations of APOC3, LDL-C, TGs, VLDL-C and HDL-C.

Results

All HVs have received both doses and follow-up for most parameters is available through week (wk) 14 (10 wks after second dose) for the 10 and 25 mg doses and through wk 10 for 50 mg. Mean nadir for APOC3 levels occurred at wk 3 for 10 mg (−73%) and remained similar at wk 10 (−66%), at wk 6 for 25 mg (−90%) with no change at wk 10 and at wk 2 for 50 mg (−94%) unchanged at wk 8. TGs fell faster in the 50 mg group (wk 1: 10 mg −41%; 25 mg −47%; 50 mg −72%). By wk 6 the 25 and 50 mg results were similar (−68% and −74%, respectively) and remained similar through wk 14. 10 mg was less active with a nadir of −56% and mean reductions between 42% and 56% post-nadir. VLDL-C values mirrored TGs. LDL-C reductions were more modest and did not manifest a dose response. Mean nadirs (−23–26%) occurred 4–6 wks after the first dose, again with minimal change through 10–14 wks of follow-up. Consistent with genetic studies, HDL-C increased to a maximum at approximately wk 8 (10 mg +42%, 25 mg +48%, 50 mg +84%). ARO-APOC3 was well tolerated without serious or severe adverse events or dropouts related to drug. The most common adverse events were mild injection site AEs and headache.

Conclusions

Genetic deficiency of APOC3 is associated with substantial reductions in TGs, VLDL-C and increases in HDL-C without an adverse phenotype. Using RNAi to selectively suppress APOC3 production mimics these lipid and lipoprotein effects, with a duration of at least 10 weeks following a second dose and with good tolerability over 16 wks using doses ranging from 10 to 50 mg. Investigation of optimal dosing regimen is ongoing, especially with respect to dosing interval. This therapeutic approach has potential for treating patients with chylomicronemia at risk of pancreatitis.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Arrowhead Pharmaceuticals
Fenofibrate or omega-3 fatty acid use is associated with lower long term outcomes from propensity matched analysis of 141972 patients with diabetes in Korean national health insurance cohort
Authors: Jo S.H , Kim H.S , Han S.J , Kim S.A
Published: November 2020

Background

We investigated the clinical effectiveness of fenofibrate or omega 3-fatty acid in patients with diabetes for long term.

Methods

Using Korean National Health Insurance data base, 141972 eligible patients with diabetes were selected. We divided the patients into 2 groups with propensity matching 1:2 ratio, fenofibrate/omega 3 fatty acid users (Fen-O, n=42353) or no users (n=14880). We followed up for 6-years for primary endpoint of death, myocardial infarction (MI), stroke and individual outcomes including cardiac death.

Results

Primary endpoint was significantly lower in Fen-O group as compared to no users, 2.35% vs. 1.58% (HR 0.673, CI: 0.633–0.715, P<0.001) in crude and 2.35% vs. 1.58% (HR 0.641, CI: 0.565–0.728) after adjusting age, sex, medical history analysis, body mass index, LDL-C and HDL-C). All cause death (0.76% vs. 1.24% [HR 0.664, CI: 0.625–0.706], p<0.0001), cardiac death (0.11% vs. 1.19% [HR 0.610, CI: 0.486–0.765, p=0.0001) and stroke (0.57% vs. 0.79%, [HR 0.723, CI: 0.594–0.881, P=0.0013) were significantly lower in Fen-O group. In the survival analysis, Fen-O group showed significantly lower primary outcome rate which is proportional with the days of intaking fenofibrate or omega 3 fatty acid (log rank <0.001),

Conclusions

Use of fenofibrate or omega 3 fatty-acid was associated with lower rate of composite of death, MI, stroke in diabetes patient for 6 year follow-up with large population.

Funding Acknowledgement

Type of funding source: None
Silencing of lipocalin-2 and its receptor improved cardiomyocytes viability via decreasing iron uptake, mitochondrial fission, mitophagy and apoptosis under iron overload condition
Authors: Kumfu S , Chattipakorn S.C , Chattipakorn N
Published: November 2020

Background

Iron overload cardiomyopathy is a common cause of death in iron overload patients. L-type calcium channels (LTCC) and T-type calcium channels (TTCC) have been shown to play important roles for iron uptake into the heart under iron overload condition. Recently, cardiomyocytes which exposed to lipocalin-2 (LCN-2) have been shown to increase apoptosis due to excessive intracellular iron accumulation. However, the mechanistic roles of LCN-2 and LCN-2 receptor (LCN-2R) as iron transporters in cardiomyocytes under iron overload condition have never been investigated.

Purpose

We hypothesized that the LCN-2 and LCN-2R are alternate iron uptake pathways into cardiomyocytes under iron overload condition.

Methods

H9c2 cardiomyocytes were treated with either LCN-2 siRNA or LCN-2R siRNA for 72 hr or LTCC blocker (verapamil), TTCC blocker (TTA-P2), or iron chelator deferiprone (DFP) for 1 hr. After treatment, cells were exposed to ferric ammonium citrate (FAC, Fe3+) or FAC + 1mM ascorbic acid (Fe2+) at 200 μM for 48 hr. Intracellular iron level, cell viability, mitochondrial dynamics, mitophagy and apoptosis were determined.

Results

Both Fe2+ and Fe3+ treated groups showed significantly increased intracellular iron uptake, decreased cell viability, increased mitochondrial fission, mitophagy and apoptotic protein expression in cardiomyocytes. Under Fe2+ overload condition, treatments with LTCC blocker, TTCC blocker, and DFP could significantly decrease intracellular iron accumulation and increase cell viability via decreasing mitochondrial fission, mitophagy and cleaved caspase-3 (Figure), whereas both LCN-2 and LCN-2R siRNA treatment had no beneficial effects on these parameters. Under Fe3+ overload condition, treatment with LCN-2 siRNA, LCN-2R siRNA, and DFP showed beneficial effects on those parameters, whereas neither LTCC nor TTCC blocker provided these benefits (Figure 1).

Conclusion

Silencing of LCN-2 and LCN-2R increased cardiomyocyte viability via decreasing iron uptake, mitochondrial fission, mitophagy and apoptosis under Fe3+ iron overload condition. Meanwhile, treatment with calcium channel blockers improved cardiomyocytes viability via decreasing iron uptake, mitochondrial fission, mitophagy and apoptosis under Fe2+ iron overload condition. All of these findings suggested that LTCC and TTCC played important roles for Fe2+ uptake, whereas LCN-2 and LCN-2R were essential for Fe3+ uptake into the cardiomyocytes under iron overload conditions.

Figure 1. Cell viability and apoptosis

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Thailand Research Fund and NSTDA Research Chair Grant (NC)
Relationship between burnout and nursing practice environment in pediatric cardiology: a cross-sectional study
Authors: Bagnasco A , Zanini M , Dasso N , Rossi S , Catania G , Sasso L
Published: November 2020

Introduction

The relationship between burnout and patient safety is widely demonstrated in the literature. Recent studies have shown that in pediatrics the burnout rates are even higher, thus increasing young patients' exposure to risks. Pediatric cardiology is often characterized by acute onset in the pre-natal period and requires long periods of hospitalization. Strategies to reduce burnout and its impact on patient safety is a priority.

Purpose

To test the relationship between nursing work environment and emotional exhaustion in nurses in pediatric cardiology.

Methods

Data were drawn from the database of a larger study, RN4CAST@IT-Ped, a cross-sectional study in which 13 Italian hospitals were involved.

Convenience sampling was adopted, and inclusion criteria were nurses providing direct routine care in wards. For this study, only data relating to nurses working in Pediatric Cardiology were extracted.

The data were collected through a web survey from September 2017 to January 2018. The questionnaire investigated several aspects relating to care and nursing staff including workload, skill mix, work environment measured with PES-NWI, and emotional exhaustion with the Maslach Burnout Inventory. Descriptive statistical analyses were conducted to describe the sample and variables taken into consideration; a binomial logistic regression model was built to test the relationships between the dependent variable “high Emotional Exhaustion” and the independent variables “PES-NWI composite score”, adjusted for “workload” and “skill mix”.

Results

The responses from eighty-five pediatric nurses from 7 units (mixed cardiology-cardiac surgery, cardiology, arrhythmology, cardiac surgery and a cardiology intensive care unit), in 5 hospitals, were analyzed.

These findings show that with the same skill mix and workload, the improvement of the workplace environment conditions decreased by 81% (OR 0.192; 95% CI 0.062–0.591) the risk that nurses working in pediatric cardiology would develop a high level of Emotional Exhaustion.

Conclusions

Demonstrating the association between emotional exhaustion and work environment in pediatric cardiology is only a first step towards improvement. Workplace environment includes relational, logistic, and organizational aspects that require further investigation to ensure that nursing in pediatric cardiology is even safer and of better quality in all its key aspects: urgency, intensity, chronicity and complexity.

Funding Acknowledgement

Type of funding source: None
Effect of psychosocial factors and heart ate variability on blood pressure control in patient with primary hypertension:A path analysis
Authors: Chen T.Y , Kao C.W
Published: November 2020

Background

Hypertension (HTN) is one of the major factors driving the global burden of cardiovascular diseases. About 40% of the adults are affected by elevated blood pressure around the world. The etiology of HTN is multifactorial, including psychological distress, especially symptoms of anxiety and depression. A few meta-analyses and longitudinal studies have reported an association between symptoms of anxiety, depression and HTN. Social support is an important factor in the regulation of emotions in HTN patients. The autonomic nervous system (ANS) plays an important role in the homeostatic control of the cardiovascular system. The measurement of heart rate variability (HRV) is used to evaluate ANS regulation in clinical research.The HRV is also a predictor of cardiovascular-cause events and mortality. Previous studies have identified the association of cardiovascular diseases with social support, anxiety, and depression. Some recent studies have also evaluated the relationship between HRV and cardiovascular diseases. However, very few studies have investigated the association of psychosocial factors, HRV, and blood pressure in patients with HTN.

Purpose

The purpose of this study was to evaluate the effect of psychosocial factors including social support, symptoms of anxiety/depressive, and heart rate variability on mean arterial blood pressures in patients with primary hypertension.

Methods

A cross-sectional descriptive and correlative study was performed. Participants were recruited by convenience sampling from the Cardiovascular Outpatient Clinic at a Medical Center. Data were collected using structured questionnaires, including the Social Support and Hospital Anxiety and Depression Scales. While heart rate variability was measured by a handheld limb lead electrocardiogram recorder device, blood pressure was measured by an automatic sphygmomanometer. Data were analyzed by the structural equation path analysis by the IBM SPSS Amos 21.0 statistical software packages.

Results

This study included 301 patients with primary hypertension. The scores of the Social Support Scale had a significantly direct effect on the scores of Hospital Anxiety and Depression Scale. The Hospital Anxiety and Depression Scale scores had a significantly direct effect on the heart rate variability. The low frequency/ high-frequency ratio of heart rate variability had a significantly direct effect on the mean arterial blood pressures. The path model including all variables explained 45% variance in the mean arterial blood pressures and had good fit indices.

Conclusion

Findings from our research highlight the significance of how psychosocial factors can affect the autonomic nervous system and blood pressure control of patients with primary hypertension. These findings can aid in developing an intervention program for blood pressure management in future.

Funding Acknowledgement

Type of funding source: None
Growing up with a pacemaker
Authors: Poels P , Vermeulen J , Gewillig M , Meyns B , Willems R
Published: November 2020

Indications for pacemakers in young children are rare. In our university hospitals, on average 8 patients/year received a pacemaker in this age group between 2001 and 2015 for a drainage area of 4 million people. In 28% this is for congenital heart block and in 69% for bradycardia after surgical repair of congenital structural heart disease. Despite the extensive range of patient information about pacemakers, we felt a need for targeted material for young patients, who have an indication for a pacemaker, and their family. We wanted to provide this information to this specific group in a creative, accessible and clear way, taking into account their way of thinking. In addition, we also wanted to involve the near and wider environment of the child (family, school, sports club, etc.), and to provide them with tools to better deal with the medical situation.

For the little children we created a stop-motion story in which sinus node disease (SND) and AV block (AVB) are represented by a character: Bob Sparkle (Bob Prikkel in Dutch for SND) and Boris Sparkle (Boris Prikkel for AVB). Bob and Boris get into trouble and are rescued by Pacemaker, the third character in the films. This story is preceded by an informative part for parents and older children in which the normal functioning and conduction system of the heart is explained. Based on the films, we designed customized information brochures for +12 and −12 year-old children. The brochure for +12 includes the same information as the adult version, but in more comprehensible language. The figures Bob and Boris were added throughout this brochure as a sort of common thread. For the −12 group we designed 2 reading books in which the story of Bob / Boris is told. The −12 booklets can be included in a cover along with the +12 brochure, so that the parents can estimate for themselves what is most suitable for their child.

We conducted a survey on how this information was received by patients and their relatives.61 families were contacted by e-mail to fill in a questionnaire using a 5-point Likert Scale. The survey assessed the following three items: graphic design, intelligibility and aid in coping with illness. Currently we have received answers from 12 patients or their relatives.

Overall, there was a positive reception of the different informative tools (agree or strongly agree: booklets: 92.6%; brochure: 77.2%; films: 81.3%).

Funding Acknowledgement

Type of funding source: None
The association between anxiety measured with HADS and use of psychotropic medication among cardiac patients
Authors: Cromhout P.F , Christensen A.V.C , Joergensen M.B.J , Ekholm O.E , Juel K.J , Svendsen J.H.S , Rasmussen T.B.R , Borregaard B.B , Mols R.E.M , Thrysoee L.T , Thorup C.B.T , Berg S.K.B
Published: November 2020

Background

Anxiety among cardiac patients is highly prevalent and is associated to poor outcomes. Certain types of psychotropic medication are suspected of causing adverse events in cardiac patients. However, an association between symptoms of anxiety and use of psychotropic medication among cardiac patients has not yet been established.

Purpose

The objective was to explore the association between anxiety (measured by HADS-A) and use of psychotropic medication among cardiac patients.

Methods

All study participant were identified from the DenHeart study and data were a combination of patient-reported survey data and baseline and follow-up data from Danish national registers. Information on redeemed prescriptions of psychotropic medication was obtained from The Danish National Prescription Registry. Anxiety symptoms were defined by a HADS-A score≥8. Patients were defined as users of psychotropic medication if they had redeemed at least one prescription one and three years after discharge. Psychotropic medication was classified by Anatomical Therapeutic Chemical Classification (ATC) codes.

Multiple logistic regression analysis within one year and Cox regression analysis within three year from discharge was conducted to determine the association between symptoms of anxiety and use of psychotropic medication.

Results

Among the 12,913 cardiac patients included, a total of 3231 (28%) redeemed at least one prescription of psychotropic medication within one year and 4726 (37%) within three years after discharge. The most commonly used drugs were benzodiazepines and antidepressants. Among patients using psychotropic medication 1481 (46%) had a HADS-A score ≥8. Cardiac patients with symptoms of anxiety had significantly higher odds of using psychotropic medication within one year from discharge OR 2.47 (95% CI 2.25; 2.72). The increased risk of use of psychotropic medication was confirmed with a almost two-fold risk after three years, HR 1.92 (95% CI 1.80; 2.04), Table 1.

Conclusion

Cardiac patients with symptoms of anxiety measured by HADS were significantly more likely to use psychotropic medication within one and three years after discharge than cardiac patients without symptoms of anxiety.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): Novo Nordisk Foundation
Diagnostic performance of 18-leads electrocardiography to distinguish takotsubo syndrome and acute anterior myocardial infarction
Authors: Shimizu M , Cho S , Hara K , Ohmori M , Kaneda T , Tateishi R , Yamakami Y , Shimada H , Manno T , Isshiki A , Kimura S , Fujii H , Suzuki M , Nishizaki M , Sasano T
Published: November 2020

Background

Electrocardiographic (ECG) features on acute phase of Takotsubo syndrome (TTS) is recognized to mimic that of acute anterior myocardial infarction (ant AMI). However, the difference of synthesized 18-leads ECG of both diseases was not elucidated.

Purpose

To elucidate diagnostic performance of 18-leads ECG to distinguish TTS and acute anterior AMI.

Methods

We firstly enrolled consecutive 40 patients of TTS, and among 500 ant AMI patients, one to two matching was done by their age and gender. Finally, 40+80 patients (74.5±11.2 years, 87 females) were enrolled, and ECG at onset of both group was estimated. Because of multicollinearity, all significant differences were compared by machine learning (Random Forest method).

Results

Prevalence of Q wave had no difference. Conversely, ST depression in TTS and ST elevation in ant AMI were significant differences in V7–9 leads. T-wave polarity of V3R-V9 leads were significantly different (flat T-wave in TTS and positive in ant AMI). Machine learning revealed T wave polarity in V7 lead had the highest feature importance.

Conclusion

18-leads ECG at onset had powerful diagnostic performance to distinguish the two diseases.

Funding Acknowledgement

Type of funding source: None
A single-center validation of the effectiveness in Obstructive Sleep Apnea screening with a photoplethysmography-based smart device
Authors: Chen Y , Wang W , Guo Y , Zhang H , Chen Y , Xie L
Published: November 2020

Background

Obstructive sleep apnea (OSA), the most common upper-airway disease, is closely associated with cardiovascular risk. However, the early detection of OSA is challenging, relying on polysomnography (PSG) or portable monitor (PM) in hospitals. A novel technology, photoplethysmography (PPG), has been developed for OSA screening. But there has been limited validation of PPG-based smart devices compared to PSG or PM.

Objective

This study aimed to investigate the feasibility and verify the validity of PPG-based smart devices in the detection of OSA in real-world settings.

Methods

A total of 119 consecutive outpatients, were recruited from the Chinese PLA General Hospital from Sep 29 to Nov 10, 2019. Participants were simultaneously tested with a smart watch, and PSG or PM for a whole night sleep.

Results

In all, 102 patients (48.5±13.7 years old, female 23.5%) were into the final analysis after excluding 17 patients with poor quality of PPG signals. Among them, 83 patients (81.3%) were diagnosed with OSA. Compared to PM, the corresponding accuracy, sensitivity and specificity of PPG-based smart device in predicting moderate to severe OSA patients ( Apnea Hypopnea Index, AHI ≥15) were 87.9% (95% Confidential Interval, CI: 78.8%–94.1%), 89.7% (95% CI: 75.8%–97.1%) and 86.0% (95% CI: 72.1%–94.7%), respectively. Compared to PSG, the accuracy, sensitivity and specificity in predicting all the sleep apnea patients (AHI ≥5) were 81.1% (95% CI: 72.1%–88.2%), 76.5% (95% CI: 50.1%–93.2%) and 100% (95% CI: 29.2%–100%), respectively. Moreover, for moderate to severe OSA patients (AHI ≥15), the predictive ability of PPG-based smart device in OSA was of no significant difference compared to PM (P=0.75) or PSG (P=0.52).

Conclusions

The PPG-based smart device demonstrated good performance in detecting OSA. Nevertheless, it requires further validation in a large-scale population on screening OSA.

Funding Acknowledgement

Type of funding source: None
Anti-cancer drugs associated with sudden death and ventricular arrhythmias: a cardio-oncology pharmacovigilance analysis
Authors: Mirabel M , Karapetiantz P , Marijon E , Le Beller C , Reda Al-Sayed Z , Boutouyrie P , Jouven X , Lillo-Lelouet A , Hulot J.S
Published: November 2020

Background

Experimental data have shown that some anticancer drugs can affect cardiac repolarization and induce life-threatening cardiac arrhythmias.

Objective

To identify anti-cancer drugs associated with the occurrence of sudden death (SD) and ventricular arrhythmias using the World Health Organization individual case safety report (ICSR) database, Vigibase.

Methods

The system organ class MEDRA was used to identify cases as ICSR with the terms sudden death, sudden cardiac death, cardiac arrest, ventricular fibrillation, ventricular tachycardia, ventricular arrhythmia and torsades de pointes (named as SD events) from Nov 1967 to Nov 2019. We used the ATC code L01 which regroups 219 antineoplastic agents. A disproportionality analysis was performed to estimate of relative Odds Ratio (ROR). Signals were considered significant when the lower boundary of the 99.97% confidence interval (ROR0.25) was ≥1.

Results

Among the 2,170,203 adverse events associated with anticancer drugs, 11,979 (0.55%) concerned SD events. A total of 49 molecules were significantly associated with SD events, among which 4 were withdrawn from market. These molecules were mainly anti-metabolites (20.0%), chemicals such as arsenic (17.8%,), anthracyclins (8.9%) and alkaloids (8.9%). When agents were grouped according to their mode of actions, the highest risks were observed for platinum-based drugs (n=1628 cases, ROR0.25=1.2) and anthracyclins (n=1323 cases, ROR0.25=1.3). While the risk for SD or severe arrhythmias was reported in the drug label for 29 agents (64.4%), we found that this risk was not identified or mentioned for 16 agents (35.5%).

Conclusions

We identified 49 anticancer drugs that are significantly associated with SD events overreporting. Appropriate monitoring and preventive measures should be considered for patients receiving these drugs.

Funding Acknowledgement

Type of funding source: None