bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex-related differences in cardiovascular risk factor accumulation and incident heart failure: data from the PREVEND observational cohort
Authors: Dronkers J , Meems L.M.G , Van Veldhuisen D.J , Meyer S , Kieneker L.M , Gansevoort R.T , Bakker S.J.L , Rienstra M , De Boer R.A , Suthahar N ,   University Medical Centre Groningen, Department of Cardiology, AB 31 Hanzeplein 1, 9713GZ, Groningen, the Netherlands
Published: October 2021

Purpose

To examine whether cardiovascular risk factor development over time would associate differently with incident heart failure (HF) in women and men.

Methods

In the PREVEND (Prevention of Renal and Vascular End-stage Disease) cohort, we calculated the incidence rates (IR) of HF and cardiovascular risk factors using Poisson regression. We examined sex-related differences in relative rates of HF according to cardiovascular risk factor development using IR-ratio (IRR=IRrisk-factor/IRno-risk-factor) and Cox regression models.

Results

Among 8592 participants (mean age 49.8 years; 50.1% women), 241 men and 133 women developed HF over 12.5 (12.2–12.9) years, resulting in an overall HF incidence rate of 5.12 (per 1000 person-years) in men versus 2.69 in women. Men also had higher incidence rates of diabetes (IRmen: 7.23 vs IRwomen: 4.46), hypertension (IRmen: 27.93 vs IRwomen: 21.35) and myocardial infarction (IRmen: 3.73 vs IRwomen: 1.33). Relative rates of HF in individuals developing obesity, diabetes and MI were comparable in both sexes (P>0.05), but development of hypertension more strongly associated with incident HF in women (IRRwomen: 6.49; 95% CI: 3.04–13.87 vs IRRmen: 2.34; 95% CI: 1.38–3.95, P=0.030). Similar trends were observed in an adjusted Cox-regression model (women:men HR: 2.93; 95% CI: 1.15–7.45; p=0.024).

Conclusions

Cardiovascular risk factors develop more often in men and associate with higher absolute rates of HF in men. However, in individuals developing hypertension, the relative rate of HF is higher in women compared to men. Our results suggest that aggressive and sex-specific risk factor management may be helpful to prevent incident HF.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Netherlands Heart Foundation;Public EU grant - European Research Council
Additive prognostic value of cardiac biomarkers in patients with chronic obstructive pulmonary disease and heart failure
Authors: Aimo A , Vergaro G , Januzzi J , Richards A.M , Lam C.S.P , Latini R , Bayes-Genis A , Brunner-La Rocca H.P , De Boer R , Ueland T , Gaggin H.K , Anand I , Troughton R , Passino C , Emdin M
Published: October 2021

Background

Chronic obstructive pulmonary disease (COPD) is a frequent comorbidity in patients with heart failure (HF). We assessed the influence of COPD on circulating levels and prognostic value of 3 HF biomarkers: N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), and soluble suppression of tumorigenesis-2 (sST2).

Methods

Individual data from patients with chronic HF, known COPD status and NT-proBNP, hs-TnT, sST2 values (n=13328) were analysed.

Results

As compared to patients without COPD, those with COPD (n=2155, 16%) were older (age 71 years [64–77] vs. 66 [57–75]; p<0.001), more frequently men (79% vs. 74%; p<0.001), had more severe dyspnoea (43% in New York Heart Association [NYHA] class III-IV vs. 31%; p<0.001), slightly worse renal function (median estimated glomerular filtration rate [eGFR] 58 mL/min/1.73 m2 [43–73] vs. 60 [46–77]; p<0.001), higher NT-proBNP (1508 ng/L [650–3363] vs. 1239 ng/L [479–2911]; p<0.001), hs-TnT (22 ng/L [13–38] vs. 17 ng/L [9–30]; p<0.001), and sST2 (31 ng/mL [23–45] vs. 29 [21–43]; p=0.040). In both the COPD and no-COPD subgroups, the best cut-offs of the 3 biomarkers refined the prediction of 1- and 5-year all-cause and cardiovascular mortality and 1- to 12-month HF hospitalization over a prognostic model including age, sex, ischemic aetiology, eGFR, HF categories, NYHA III-IV, beta-blocker use and the NT-proBNP cut-off alone.

Conclusions

Among patients with HF, those with COPD have higher circulating cardiac biomarkers. Patient classification based on COPD-specific cut-offs refines risk reclassification for all-cause and cardiovascular mortality and HF hospitalization and might be helpful for decision making and management.

Funding Acknowledgement

Type of funding sources: None.
Predictability of cardiotoxicity at a Belgian cardio-oncology clinic without mandatory physician referral
Authors: Jacobs J , Guler I , Janssens S , Van Aelst L.N.L
Published: October 2021

Background and purpose

Increased morbidity and mortality caused by side-effects of cancer treatment on cardiovascular function mandates careful monitoring and shared decision-making in cardio-oncology clinics. We report the experience of the cardio-oncology clinic at a large Belgian tertiary care center, without mandatory physician referral, and investigated the predictability of cardiotoxicity based on pre-existing cardiovascular risk factors, specific cancer treatment and existing risk scores of the American Society of Clinical Oncology (ASCO) and Mayo Clinic.

Methods

We included all patients seen at the outpatient cardio-oncology clinic between May 2018 and September 2020. We defined cardiotoxicity as a decline in ejection fraction (EF) of 10% in asymptomatic patients and 5% in symptomatic patients. Approval of the ethical committee was obtained (S65084).

Results

The majority were women (68%), with almost half (44%) having metastatic disease. Mean age was 63.4±16.0 years. The most frequent oncological diagnoses were breast cancer (33%) and haematological diseases (24%). Patients most frequently received radiation therapy (42%), anthracyclines (39%) and antimetabolites (35%). Mean follow-up was 443±245 days.

Receiver operating characteristic (ROC) analysis of predictors of cardiotoxicity showed an area under the curve (AUC) of 0.580 (CI 95% bootstrap: 0.525–0.642) for cardiovascular risk factors alone, and an AUC of 0.613 (CI 95% bootstrap: 0.550–0.676) when treatment was added to the model. The ASCO risk score poorly predicted cardiotoxicity (sensitivity 64%, specificity 52%). The Mayo Clinic cardiotoxicity risk score was the best predictor of cardiotoxicity with an AUC of 0.685 (CI 95% bootstrap: 0.625–0.743).

Discussion

Classic cardiovascular risk factors alone, or in combination with the proposed cancer treatment cannot adequately predict cardiotoxicity risk. The Mayo Clinic Cardiotoxicity Risk score outperformed the ASCO risk score but requires further refinement to enhance adequate cardiovascular risk prediction. For future model building, we hypothesize that an all-comer population of oncological patients should be used as a derivation cohort, regardless of previous or current cardiac issues, risk factors or type of therapy. Admittedly, individual susceptibility due to genetic, epigenetic and environmental predisposition cannot be adequately incorporated into a risk score and emphasizes the need for individual cardiotoxicity risk evaluation using bed to bench tools such as the use of induced pluripotent stem cell derived cardiac or vascular cells to assess the susceptibility of individual patients to cancer drug-induced cardiovascular toxicities. In the absence of adequate risk prediction tools, we advocate standardized screening of all patients before oncological treatment starts.

Funding Acknowledgement

Type of funding sources: None. Figure 1. Cardiotoxicity
Prognostic value of self-reported subjective exercise capacity in patients with acute dyspnea
Authors: Belkin M , Wussler D , Michou E , Strebel I , Kozhuharov N , Sabti Z , Nowak A , Shrestha S , Lopez-Ayala P , Albus M B , Danier I , Simmen C , Diebold M , Breidthardt T , Mueller C ,   Cardiovascular Reasearch Institute Basel
Published: October 2021

Background

Quantitative assessment of self-reported exercise capacity as provided by the Duke Activity Status Index (DASI) is a validated measure of exercise capacity in stable ambulatory patients.

Objectives

This study aimedto test whether the quantification of self-reported exercise capacityusing the DASI may aid physicians in the risk stratification of patients presenting with acute dyspnea to the emergency department (ED).

Methods

Basics in Acute Shortness of Breath EvaLuation (BASEL V) was a prospective cohort study recruiting dyspneic patients at the ED. The prognostic value and accuracy of theDASI assessed shortly after presentation were quantified using Cox regression analyses and the Area under the curve (AUC).

Results

Among 1019 patients eligible for this analysis 529 (51.9%) had an adjudicated final diagnosis of acute heart failure, 75 (7.4%) and 297 (29.1%) patients died within 90 and 720 days after presentation. Unadjusted hazard ratios (HR) and multivariable adjusted hazard ratios (aHR) for 90-day and 720-day mortality increased continuously from the fourth (best self-reported exercise capacity) to the first DASI-quartile (worst self-reported exercise capacity). For 720-day mortality in the first quartile theHR was 9.1 (95%-CI 5.5–14.9) (aHR 6.1 [95%-CI 3.7–10.1]), in the second quartile 6.4 (95%-CI 3.9–10.6) (aHR 4.4 [95%-CI 2.6–7.3]), while in the third quartile the HR was 3.2 (95%-CI 1.9–5.5) (aHR 2.4 [95%-CI 1.4–4.0]). The prognostic accuracy of the DASI was moderate-to-high and higher than that of B-type natriuretic peptide (BNP) and NT-proBNP (N-terminal pro-BNP) concentrations, e.g. for 720-day mortality prediction AUC 0.70 versus 0.64, p=0.020; 0.72 versus 0.68, p=0.074.

Conclusions

Quantification of self-reported subjective exercise capacityusing the DASI provides moderate-to-high prognostic accuracy in patients presenting with acute dyspnea to the ED and may aid physicians in further risk stratification.

Funding Acknowledgement

Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union, the Swiss National Science Foundation. Duke Activity Status Index
Sex-related differences in mortality following an admission for acute heart failure across left ventricular ejection fraction spectrum
Authors: Santas Olmeda E , Palau P , De La Espriella R , Minana G , Soler M , Lorenzo M , Nunez G , Chorro F J , Nunez J
Published: October 2021

Background

Prognosis in heart failure (HF) may differ between women and men. However, data is conflicting and sex-related differences in prognosis may be determined by left ventricular ejection fraction (LVEF) status. We sought to evaluate the prognostic differences between women and men with HF following an admission for acute HF (AHF).

Methods

We included 4,812 patients consecutively admitted for AHF in a multicenter registry from 3 hospitals in Valencia (Spain). Study endpoints were all-cause, cardiovascular (CV), and HF-related mortality at 6-months follow-up. Multivariable Cox regression models were fitted to investigate sex-related differences across LVEF status.

Results

2,243 (46.6%) patients were women and 2,569 (53.4%) were men. 2,608 (54.2%) patients had HF with preserved ejection fraction. At 6-months follow-up, 645 patients died (13.4%), being 544 (11.3%) and 416 (8.6%) CV and HF-related deaths, respectively. LVEF was not independently associated to mortality risk (HR=1.02; 95% CI 0.99–1.05; p=0.135). After multivariate adjustment, we found no sex-related differences in all-cause mortality (p-value for interaction=0.168). However, a significant interaction between sex and the risk of CV and HF mortality was found across LVEF status (p-value for interaction= 0.030 and 0.007; respectively). Compared to men, women had a significant lower risk of CV-mortality and HF-mortality at LVEF<25% and <42%, respectively. On the contrary, women showed a higher risk of HF-mortality at the upper extreme of LVEF (>75%) (Figure, panel A and B).

Conclusions

Following an admission for AHF, no sex-related differences were found in the risk of all-cause mortality. However, compared to men, women showed a lower risk of CV and HF-mortality at the lower extreme of LVEF. On the contrary, they showed a higher risk of HF-death at the upper extreme.

Funding Acknowledgement

Type of funding sources: None.
Follistatin-like 3 (FSTL3) levels are increased in acute heart failure patients
Authors: Chen D , Untaru R , Liu S , Assadi-Khansari B , Croft A , Kelly C , Ajaero C , Chua S J , Boyle A J , Horowitz J D , Ngo D , Sverdlov A ,   Cardiovascular Team/ Hunter Medical Research Institute
Published: October 2021

Introduction

Follistatin-like 3 (FSTL3) is a secreted protein that has been suggested to play an important role in modulating cardiac remodeling and hypertrophy. In this study, we aim to determine whether: 1) FSTL3 is incrementally elevated in patients with HF vs those with other cardiovascular disease (CVD); and 2) increased FSTL3 is associated with 2 or more hospital admissions due to major adverse CV events (MACE) within 1 year.

Methods and results

We measured circulating levels of FSTL3 using commercially available ELISA (R&D systems) in a total of n=696 patients. FSTL3 levels were compared between: 1) healthy-aging volunteers with no prior major CVD (n=267, age 67±6 years) and 2) patients admitted to cardiology unit for various CVD (n=429, age 66±14 years); among those (n=178, age 68±13 years) had HF. Patients with HF had 2-fold higher FSTL3 levels vs healthy age-matched controls vs those with other CVD (p<0.001). Occurrences of MACE were recorded up to 1 year for patients admitted to cardiology unit. On univariate analyses, patient with 2 or more MACE within 1 year (n=91, 27%) had significant elevated FSTL3 levels (P=0.003), is associated with older age (P<0.005). On multivariate analysis, high FSTL3 levels (P=0.034) is an independent predictor of 2 or more MACE admissions within 1 year after adjusting for age, clinical comorbidities and medications.

Conclusions

FSTL3 is incrementally increased in patients with HF and is associated with poorer prognosis. Elevated FSTL3 levels is associated with increased risks of cardiac hospital readmissions for patients with multiple CV morbidities.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NSW Ministry of Health EMC Fellowship (Australia)
Stroke volume but not ejection fraction predicts prognosis in acute heart failure
Authors: Barki M , Losito M , Caracciolo M M , Bandera F , Rovida M , Alfonzetti E , Guazzi M
Published: October 2021

Background

Heart failure (HF) patients are categorized according to left ventricular ejection fraction (LVEF), being such index both easily feasible and prognostic. However, the risk stratification of patients hospitalized for acute decompensated heart failure (ADHF) according to the absolute value of LVEF at presentation is unexplored and its prognostic significance has not been tested against stroke volume indexed (SVi).

Purpose

To examine the prognostic impact of SVi versus LVEF in patients hospitalized for ADHF (wet and warm phenotype).

Methods

Eighty-five ADHF patients (mean age 75.6±10.4 years, 59% males) were prospectively enrolled within 24–48 hours from admission to the emergency department. In the acute phase all patients underwent a complete transthoracic echocardiography (TTE) and lung ultrasonography (LUS) associated with blood sample and a thorough clinical examination. Patients were then stratified into two groups according to the presence or the absence of a preserved SVi at admission (SVi ≥35 ml/m2).

Results

During a median follow-up (FU) time of 12 months (IQR months 8–15 months) we observed a CV event rate of 28.2%. During the FU period 14 patients (16.5%) were re-hospitalized for ADHF, 7 patients died for CV reason (8.2%), 1 patient underwent mitral valve replacement for severe chronic mitral regurgitation, 1 patient was re-hospitalized for cardiac resynchronization therapy and 1 subject was re-hospitalized for acute coronary syndrome.

Interestingly, patients that had a preserved TTE-derived SVi at admission (SVi ≥35 ml/m2) exhibited a significantly higher survival, when compared to subjects that showed an impairment of cardiac output at rest (SVi <35 ml/m2) (log-rank: HR 5.5 CI 95% 2.1–14.3; p=0.04) (Figure 1). On the other hand, LVEF was not independently associated with the endpoint and HFrEF, HFmrEF and HFpEF patients showed a comparable median survival (Figure 2).

Conclusions

Although the categorization of LVEF in CHF patients bears a pivotal classificatory and prognostic role, its assessment in ADHF, may lack of prognostic value especially when compared to SVi which represents a better parameter to define high-risk subjects who benefit from closer monitoring.

Funding Acknowledgement

Type of funding sources: None.
Utilising clinical data to personlaise boundary conditions significantly improves the accuracy of angiography based virtual FFR
Authors: Gosling R , Gunn E , Wei H L , Gu Y , Rammohan V , Hughes T , Hose D R , Lawford P V , Gunn J P , Morris P D
Published: October 2021

Background

Angiography-derived computed (virtual) fractional flow reserve (vFFR) permits the assessment of coronary physiology without the need for a pressure wire or hyperaemia. However, accuracy is limited by assumptions made about coronary microvascular resistance (CMVR) [1]. We hypothesised that machine learning may allow us to “tune” our estimate of the CMVR to increase the accuracy of vFFR.

Purpose

To determine whether routine clinical data can personalise CMVR and improve the accuracy of vFFR on an individual case basis.

Methods

Patients with chronic coronary syndromes underwent coronary angiography with FFR assessment. Vessel-specific CMVR was computed using a 3D- computational fluid dynamics simulation with invasively measured proximal and distal pressures. Predictive models were created using non-linear autoregressing moving average with exogenous inputs (NARMAX) modelling with computed CMVR as the dependent variable. vFFR was computed using previously described methods [2]. Three simulations were run, using: 1) a generic CMVR value (Model A); 2) a NARMAX-predicted CMVR based upon a panel of simple clinical data (Model B); and 3) a NARMAX-predicted CMVR incorporating echocardiographic data (Model C). The diagnostic and quantitative accuracy of each model was compared with directly measured FFR.

Results

Eighty four patients underwent coronary angiography with FFR assessment in 157 vessels. Mean age was 64 (±0.1) years and 64 (76%) were male. Mean FFR was 0.79 (±0.15). Mean CMVR was 1.01e+10 Pa/m3 s–1. vFFR error with Model A was ±0.10, with Model B was ±0.07 (p<0.001) and with Model C was ±0.05 (p<0.001) (Table 1).

Conclusion

vFFR is dependent upon not only the epicardial stenosis, but also the CMVR, estimation of which can be personalised based upon clinical and echocardiographic data. This can be used to increase the accuracy of vFFR.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): British Heart Foundation Clinial Research Training FellowshipNIHR i4i grant Table 1
Genomic prediction of cardiovascular events in a coronary Southern European population
Authors: Mendonca F , Mendonca M I , Santos M , Temtem M , Sousa J A , Sousa A C , Henriques E , Freitas S , Rodrigues M , Borges S , Guerra G , Drumond A , Palma Dos Reis R ,   GENEMACOR study
Published: October 2021

Background

Traditional and clinical risk factors are indicators of atherosclerosis over time and strong independent predictors of cardiovascular events, but it is unknown whether other genetic markers could provide information about the evolution of atherosclerotic coronary artery disease (CAD).

Objective

We propose identifying the genetic predisposition to atherosclerotic plaque progression and events occurrence, through a study cohort from GENEMACOR study population.

Methods

We performed a study with a cohort of 1,712 patients who underwent coronary angiography with more than 70% stenosis of at least one main coronary vessel, during a mean follow-up of 5 years (amplitude range 20 years). 33 SNPs associated with risk of CAD in previous GWAS, were genotyped by TaqMan assays methodology. The best model in the bivariate analysis at 95% CI with all genetic variants was generated, to investigate their association with prognostic and events occurrence. The hazard function at a set of confounding-variables was determined to evaluate their relationship with the event's incidence by the Cox survival analysis regression model. Finally, we constructed Kaplan–Meier cumulative-event curves for the significant variants.

Results

The analysis revealed two SNPs associated with the progression of atherosclerosis and events occurrence: rs12190287 G>C in the TCF21 gene on chromosome 10 (dominant model; OR=1.542; 95% CI 1.069 – 2.224; p=0.020) and the rs1333049 G>C in the CDKN2-AS1 gene on chromosome 9 (recessive model; OR=1.228; 95% CI 1.001 – 1.518; p=0.050). The Kaplan-Meier cumulative event curves in the TCF21 variant rs12190287 G> C showed that the GC+CC vs GG genotype was associated with a worse prognosis (log-rank test, p=0.016) and the CDKN2B-AS1 rs1333049 G> C revealed that the CC vs GG+GC genotype also presented severe prognosis and more events at the end of the follow-up period (log-rank test, p=0.046).

Conclusion

We have identified two SNPs associated with the prognosis of CAD, rs12190287 of TCF21 gene and rs1333049 of CDKN2-AS1 gene. Both are in non-coding enhancer regions and regulate transcriptional mechanisms shared among multiple CAD risk loci and could provide new insights into CAD's pathophysiology identifying core mechanisms for therapeutic intervention modulating the disease risk.

Funding Acknowledgement

Type of funding sources: None.
Frequency and prognostic impact of periprocedural myocardial infarction determined by various MI definitions in patients with chronic coronary syndromes undergoing percutaneous coronary intervention
Authors: Ueki Y , Otsuka T , Bar S , Koskinas K , Losdat S , Heg D , Zanchin T , Siontis G , Praz F , Haner J , Susuri N , Stortecky S , Pilgrim T , Windecker S , Raber L
Published: October 2021

Background

Several definitions of peri-procedural myocardial infarction (MI) requiring different biomarker thresholds with or without ancillary criteria for myocardial ischemia are currently recommended without being fully validated in real-world patients with chronic coronary syndrome (CCS) undergoing percutaneous coronary intervention (PCI).

Objectives

We aimed to evaluate the prevalence and prognostic value of high-sensitivity cardiac troponin-based peri-procedural MI according to contemporary MI definitions using a large real-world PCI cohort.

Methods

In CCS patients undergoing elective PCI enrolled to the Bern PCI registry (NCT02241291) between 2010 and 2018, peri-procedural myocardial injury and infarction were assessed according to the 4th and 3rd universal definition of MI (UDMI), academic research consortium (ARC)-2, and Society for Cardiovascular Angiography and Interventions (SCAI) criteria. The primary endpoint was cardiac death at 1 year.

Results

Among 4404 CCS patients, peri-procedural MI defined by the 4th UDMI, 3rd UDMI, ARC-2, and SCAI were observed in 14.9%, 18.0%, 2.0%, and 2.0% of patients, respectively. Cardiac mortality at 1 year in patients with peri-procedural MI defined by 4th UDMI, 3rd UDMI, ARC-2, and SCAI were 3.0%, 2.9%, 5.8%, and 10.0%, respectively. After multivariate adjustments, peri-procedural MI defined by the ARC-2 and SCAI were independently associated with cardiac death at 1 year, while those defined by the 4th and 3rd UDMI were not.

Conclusion

Among CCS patients undergoing PCI, periprocedural MIs defined by theARC-2 and SCAI occurred 7 to 9 times less frequently as compared with the 4th and 3rd UDMI, and were the only definitions significantly associated with cardiac mortality.

Funding Acknowledgement

Type of funding sources: None. Cardiac death at 1 year
Impact of morphine use on mortality in STEMI patients treated with primary PCI – results from a new registry
Authors: Szabo D , Szabo A , Edes I F , Becker D , Merkely B , Hizoh I
Published: October 2021

Background

Opioids decrease the effect of P2Y12 receptor inhibitors in vitro and observational reports suggest that morphine use may be associated with larger infarct size. Our research group showed previously, using a prospective single-centre registry, that periprocedural morphine use may have no impact on long-term mortality in STEMI patients treated with primary PCI and clopidogrel.

Purpose

We aimed to study this in vitro interaction on clinical outcomes in patients who were predominantly treated with the novel P2Y12 inhibitors prasugrel or ticagrelor, according to the current guidelines.

Methods

From May 2020 through February 2021, we collected demographic, anamnestic, procedural and laboratory data of 297 consecutive STEMI cases who were treated with primary PCI at our tertiary centre. Of them 126 patients (42.4%) received IV morphine during the periprocedural period. Outcome measure was time to all-cause mortality. The median follow-up time was 147 days (IQR 71–242 days), with 39 events. To adjust for confounding, a 1:1 propensity score-matching analysis (PSM) was performed using 186 cases. Absolute difference in survival was analysed using Kaplan-Meier survival curves and the logrank test, whereas the relative change was assessed by univariable Cox regression.

Results

An adequate balance on baseline covariates was achieved by the propensity score-matching. Kaplan-Meier analysis showed no statistically significant difference in all-cause mortality of the treatment groups neither in the original nor in the propensity score-matched population (p=0.220 and 0.762 respectively). In the matched population we found no difference in survival as the HR (Morphine/No Morphine) was 0.88 (95% confidence interval [CI]: 0.39–2.00), p=0.76.

Conclusion

Our preliminary data suggest that morphine may have no impact on mortality in STEMI patients treated with primary PCI and medical therapy according to the current guidelines including novel P2Y12 antagonists.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The research was supported by the Ministry of Innovation and Technology NRDI Office within the framework of the Artificial Intelligence National Laboratory Program. Kaplan-Meier curves: Original populationKaplan-Meier curves: PSM population
Risk scores for risk stratification in chronic coronary syndrome and their improvement by Gensini and SYNTAX scores
Authors: Blaum C , Bay B , Kroeger F , Gossling A , Lorenz T , Max L , Zeller T , Schnabel R , Clemmensen P , Westermann D , Kirchhof P , Blankenberg S , Seiffert M , Brunner F J , Waldeyer C
Published: October 2021

Introduction

There is a substantial residual risk in patients with chronic coronary syndrome (CCS). Risk scores could be useful tools to allocate intensified secondary preventive medications to address this residual risk. Whether their predictive value can be improved by addition of angiographic scores of the extent of coronary artery disease (CAD) is unknown.

Purpose

To test and compare the predictive value of three externally developed risk scores for CAD and to investigate the effect of addition of SYNTAX and Gensini scores.

Methods

We tested the TIMI risk score for secondary prevention (TRS 2°P), a risk score derived from the INVEST study, and the ABC-CHD model (see references 1–3) in 1280 patients with CCS from a contemporary observational CAD cohort ongoing since 2015 with a median follow-up of 3.6 years. In a second step we added SYNTAX and Gensini scores to the models. The endpoints tested were cardiovascular death and major adverse cardiovascular events (MACE), consisting of cardiovascular death, myocardial infarction and ischemic stroke.

Results

All investigated scores yielded continuously increasing event rates for MACE and cardiovascular death with increasing score points obtained. As an example Figure 1 displays 3-year rates for cardiovascular death and MACE against the points obtained in the TRS 2°P, whilst also displaying the distribution of patients amongst the risk categories. The three scores showed modest predictive value for occurrence of cardiovascular death (c-indices 0.60, 0.64, 0.70 for TRS 2°P, INVEST score, ABC-CHD score, respectively). Addition of both SYNTAX and Gensini scores to the models yielded c-indices of 0.66, 0.69 and 0.70 respectively (Figure 2a). Similar predictive values were observed for the occurrence of MACE (c-indices 0.59, 0.60, 0.64 for TRS 2°P, INVEST score, ABC-CHD score, respectively) as well after addition of both SYNTAX and Gensini scores (c-indices 0.62, 0.63, 0.64, see Figure 2b).

Conclusion

(I) Currently available risk scores are modestly predictive for the occurence of cardiovascular events in patients with CCS. (II) Addition of Gensini and SYNTAX scores improves their predictive value particularly in weaker risk scores.

Funding Acknowledgement

Type of funding sources: None. Figure 1Figure 2a (left) and 2b (right)
Prevalence of familial hypercholesterolemia in patients presenting with premature acute coronary syndrome
Authors: Hauguel M , Aidan V , Hergault H , Beauchet A , Pepin M , Prati G , Pilliere R , Ouadahi M , Josseran L , Rodon C , Rabes J P , Dubourg O , Massy Z , Mansencal N
Published: October 2021

Background

Familial hypercholesterolemia (FH) is a common genetic disorder responsible for premature and severe cardiovascular morbidity and mortality. The FH prevalence in patients who experienced a premature acute coronary syndrome (ACS) ranges from 5 to 50% according to previous studies and no comparison with FH prevalence in general population are available in those studies.

Purpose

We aimed to assess the prevalence of clinical FH among patients with premature acute myocardial infarction (MI) (age ≤50 years) and to compare it with FH prevalence in a control population (age ≤50 years), coming from the same population pool.

Methods

Patients with diagnosis of premature MI (age ≤50 years) referred to Ambroise Paré hospital from 2014 to 2018 were included. FH prevalence was estimated via the Dutch Lipid Clinic Network score, based on personal and familial history of premature cardiovascular disease, and LDL-cholesterol levels. FH was “possible” with a score between 3 and 5 points, “probable” with a score between 6 and 8 and “definite” with a score >8 and no FH was defined as a score <3. FH prevalence in patients with MI was compared to FH prevalence in a general population (age ≤50 years), coming from the prospective cohort CARVAR 92.

Results

Among the 457 patients with premature MI, 220 (48%) patients had no FH, 208 (46%) had a “possible” FH and 29 (6%) had a “probable” or “definite” FH. In the control population, 9900 subjects aged ≤50 years were identified: 9343 (94.37%) had no FH, 541 (5.46%) had a “possible” FH and 16 (0.16%) had a “probable” or “definite” FH. Considering subjects with “probable” or “definite” FH, FH prevalence was 37.5 times greater among patients with premature MI than in control population (p<0.0001).

Conclusion

Familial hypercholesterolemia is >30-fold more common in patients referred for premature MI than in general population of the same age, coming from the same population pool. This highlights the need for FH diagnosis after a first episode of MI to enhance lipid-lowering therapy and allow an early identification of family members.

Funding Acknowledgement

Type of funding sources: None.
Value of magnetocardiography in chronic coronary disease detection: results of multicenter trial
Authors: Chaikovsky I , Li T , Zhang W , Kazmirchyk A , Mjasnikov G , Lutay M , Lomakovsky O , Wenming J
Published: October 2021

Background

Diagnostic management of patients with chest pain remains a clinical challenge. Magnetocardiography (MCG) is non-invasive evaluation of the magnetic field of the heart that is produced by the electric activity of the myocardium. Previous studies have clearly demonstrated the potential of MCG in coronary artery disease (CAD) detection.

The objective of this multicenter trial is the investigation of value of MCG in diagnosis of mild and severe coronary artery disease using novel approach of magnetocardiographic current density vectors (CDV) maps evaluation.

Methods

This clinical trial was conducted in three GCP accredited institutions under the leadership of a General Hospital in China. The trials were designed for paired experiments with multi-center blind interpretation. Coronary angiography and coronary flow reserve fraction were used as a “gold standard”.

In total 133 persons (mean age 59±3,1 years), divided into 3 groups, were examined. The first group (61 subjects) was identified for patients with severe myocardial ischemia and met the criteria for revascularization: degree of coronary artery stenosis is ≥80% or coronary blood flow reserve score ≤0,8.

The second group (13 subjects) is patients whose myocardial ischemia is confirmed but has not yet reached the criteria for revascularization: coronary artery stenosis is between 50% and 80%, coronary blood flow reserve score >0,8.

The third group (59 subjects) is whom the “gold standard” confirmed that there is no coronary artery disease. This group is called the negative control group.

The MCG examination was performed using a 7-channel MCG system located in an unshielded room. Magnetocardiography recordings were taken from 36 positions at rest Based on the magnetic field distribution, set of subsequent current vectors maps were reconstructed with equidistant time step (10 ms) within the ST-T interval. Each of these maps was classified into two categories: normal map or pathological map. This classification is based on the analysis of the of the largest current density vectors direction and dipole or non-dipole structure of the map. Then, portion of pathological CDV maps within the ST-T interval was defined. Based of this portion, each MCG examination was was assigned to one of 3 groups: mild CAD, severe CAD or no CAD.

Results

The coincidence rate of each group was as follows: coincidence rate of severe CAD – 85,45%, coincidence rate of mild CAD – 77,78%, coincidence rate of control group was 87,10%. Sensitivity 93,75% and specificity 87,10% were achieved, PPS was 88,24%, NPV 93,10%. In terms of likelhood ratio results were as follows: a positive likelhood ratio of 7.27, negative likelhood ratio – 0.07.

Conclusion

MCG-examination seems to be a reliable method in the diagnosis of chronic severe and mild CAD. Further large-scale studies needed to confirm these findings.

Funding Acknowledgement

Type of funding sources: None.
The effect of immediate coronary angiography after cardiac arrest without ST-segment elevation on left ventricular function. A sub-study of the COACT randomised trial
Authors: Lemkes J , Spoormans E M , Demirkiran A , Leutscher M S G , Janssens G N , Van Der Hoeven N W , Jewbali L S D , Dubios E , Meuwissen M , Bosker H , Bleeker G , Vlachojannis G , Van De Ven P , Van Loon R , Van Royen N ,   COACT investigators
Published: October 2021

Background

The effect of immediate coronary angiography and percutaneous coronary intervention (PCI) in patients who are successfully resuscitated after cardiac arrest in the absence of ST-segment elevation myocardial infarction (STEMI) on left ventricular function is currently unknown.

Purpose

To evaluate whether immediate coronary angiography and PCI improves left ventricular function in patients who are successfully resuscitated from cardiac arrest without STEMI.

Methods

This prespecified sub-study of the multicentre COACT trial evaluated 552 patients, successfully resuscitated from out-of-hospital cardiac arrest without signs of STEMI. Patients were randomized to either undergo immediate coronary angiography or delayed coronary angiography, after neurologic recovery. All patients underwent PCI if indicated. The main outcomes of this analysis were left ventricular ejection fraction and end-diastolic and systolic volumes assessed by cardiac magnetic resonance imaging or echocardiography.

Results

Data on left ventricular function was available for 397 patients. The mean (± standard deviation) left ventricular ejection fraction was 45.2% (±12.8) in the immediate angiography group and 48.4% (±13.2) in the delayed angiography group (mean difference: −3.19; 95% confidence interval [CI], −6.75 to 0.37). Median left ventricular end-diastolic volume was 177 ml in the immediate angiography group compared to 169 ml in the delayed angiography group (ratio of geometric means: 1.06; 95% CI, 0.95 to 1.19). In addition, mean left ventricular end-systolic volume was 90 ml in the immediate angiography group compared to 78 ml in the delayed angiography group (ratio of geometric means: 1.13; 95% CI 0.97 to 1.32).

Conclusion

In patients successfully resuscitated after out-of-hospital cardiac arrest and without signs of STEMI, immediate coronary angiography was not found to improve left ventricular dimensions or function compared with a delayed angiography strategy.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Netherlands Heart InstituteBiotronikAstraZeneca
CSL112 (human apolipoprotein A-I) infusion rapidly increases apoA-I exchange rate (AER) when administered to patients post myocardial infarction
Authors: Kingwell B A , Velkoska E , Diditchenko S , Greene B H , Wang S , Mears J , Wright S D , Gibson C M , Smith J D
Published: October 2021

Background

Cholesterol efflux capacity (CEC) measured using patient serum and cultured macrophages is considered a biomarker of high-density lipoprotein (HDL) functionality. This parameter is inversely related to incident cardiovascular events and declines in the days post-acute myocardial infarction (AMI). The apolipoprotein A-I (apoA-I) exchange rate (AER) may represent an alternative, clinically amenable cell-free measure of CEC, which has also been associated with incident cardiovascular events (1).

Purpose

To characterise the effects of human apoA-I (CSL112) infusion on AER over 48 hours when administered post AMI.

Methods

This analysis included 50 patients with available samples from the AEGIS-I (ApoA-I Event Reducing in Ischemic Syndromes I) randomized, double-blind, placebo-controlled, phase 2b pharmacokinetic/pharmacodynamic sub-study (2). Patients were randomized to receive four weekly infusions of either placebo (n=16), 2g (n=19) or 6g (n=15) CSL112 post AMI. Blood samples were drawn at baseline and at 2, 4, 6, 12, 24 and 48 hours post the first and fourth infusion for measurement of AER (1) as well as CEC (total, ABCA1 dependent and ABCA1 independent CEC) as previously described (3).

Results

CSL112 infusion increased AER dose-dependently, peaking at 2h (end of infusion) and returning to baseline by 24h post infusion (Figure 1). AER was significantly correlated with CEC (total, ABCA1 dependent and independent), HDL-cholesterol, apoA-I and phosphatidylcholine across all timepoints and similarly after both infusions (Table 1).

Conclusion

Infusion of CSL112 increased AER in a dose-dependent manner post AMI and may represent a clinically amenable biomarker of HDL functionality.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): CSL Ltd, Parkville, Australia Figure 1. Left: Time course data expressed as mean ± SEM and adjusted for baseline prior to each infusion. Using a linear mixed model for repeated measures, the 6g dose increased AER from baseline at timepoints from 2–12 hours (p<0.001), whereas the 2gm dose only increased AER between 2–6 hours (p<0.05). Right: Boxplots showing median, quartiles and min/max of Area Under the Curve (AUC) from 0–24 hours post infusion. Using one-way ANOVA the 6 g dose was significantly higher than placebo (p<0.05).Table 1
Trimetazidine as adjunctive therapy for decreasing major adverse cardiac events in coronary artery disease patients undergoing reperfusion strategy: a meta-analysis of randomized controlled trials
Authors: Saroca C G , Tan J D , Tiongco R H
Published: October 2021

Background

Trimetazidine as adjunctive therapy in cardioischemic patients has shown improvement in angina and left ventricular ejection fraction. Recent trials have conflicting evidence on its effect on hard clinical outcomes.

Purpose

The objective of this meta-analysis is to compare the efficacy of trimetazidine versus placebo in reducing cardiac mortality and major adverse cardiac events (MACE) in coronary artery disease patients after reperfusion strategy.

Methods

A literature search was done using the terms “coronary artery disease” OR “acute myocardial infarction” OR “stable angina pectoris” AND “percutaneous coronary intervention” OR “thrombolysi” OR “reperfusion” AND “trimetazidine” OR “trimetazidine dihydrochloride” AND “randomized controlled trial”. We included trials using trimetazidine versus placebo in coronary artery disease patients who underwent percutaneous coronary intervention or thrombolysis. Two reviewers independently applied eligibility criteria, assessed quality, and extracted data. The primary outcomes were cardiac mortality and combined major adverse cardiac events; secondary outcomes were repeat revascularization, heart failure after reperfusion, stent restenosis, recurrence of angina, and reinfarction. Risk ratios were calculated for pooled data using random effects and fixed effects models.

Results

This study included five trials involving a total of 26,977 patients. Trimetazidine in comparison to placebo was associated with lower cardiac mortality and combined MACE, but results were not significant. Among secondary outcomes, only stent restenosis was significantly reduced (risk ratio, 0.53; 95% CI, 0.34–0.83; p=0.006).

Conclusion

Trimetazidine as adjunctive therapy does not reduce cardiac mortality, combined MACE, repeat revascularization, heart failure, recurrence of angina and reinfarction in coronary artery disease patients after reperfusion. However, it does significantly reduce stent restenosis in the said population. Further trials should be conducted with more standard dosing regimens, duration of therapy, and similar severities of ischemic disease.

Funding Acknowledgement

Type of funding sources: None.
New onset atrial fibrillation in STEMI patients: main prognostic factors and clinical outcome
Authors: Barbieri L , Dal Zotto B , Tumminello G , Saviano M , Gentile D , Lucreziotti S , Frattini L , Tarricone D , Carugo S
Published: October 2021

Background

New onset atrial fibrillation (NOAF) is not a so rare condition among patients hospitalized for ST-segment elevation myocardial infarction (STEMI). Several studies showed that NOAF during an acute coronary syndrome (ACS) leads to increased mortality, both at short and long term. The indications for the treatment of patients with known AF undergoing percutaneous coronary interventions (PCI) are clear, while less is available about the management of NOAF during ACS and in particular during STEMI. The purpose of this study is therefore to evaluate mortality and clinical outcome of this high risk subgroup of patients.

Methods

We analysed 1455 consecutive patients undergoing coronary angiography and/or PCI for STEMI. CHA2DS2-VASc and HAS-BLED scores were calculated for all patients. In-hospital, 1-year and long-term follow up mortality was evaluated for all patients. Cerebral ischemic and hemorrhagic events were also evaluated as clinical endpoints at 1 year.

Results

NOAF was detected in 102 subjects, 62.7% males, with a mean age of 74.8±10.6 years. We found a high prevalence of main cardiovascular risk factors such as hypertension, dyslipidemia, smoke and renal failure. Mean ejection fraction (EF) was 43.5±12.1% and the mean atrial volume was increased (58±20.9 ml). The most represented type of MI at admission was anterior STEMI (46%). NOAF occurred mainly in the peri-acute phase and had a very variable duration (8.1±12.5 min). During hospitalization all patients were treated with Enoxaparin, but only 25.2% of them were discharged with long term oral anticoagulation (16.7% warfarin, 4.9% direct oral anticoagulant). The majority of patients had a CHA2DS2-VASc score >2 and a HAS-BLED score of 2 or 3. In-hospital mortality was 14.2%, while 1-year mortality was 17.2% and long term mortality 32.1% (median follow-up time 1820 days, range 341 to 3985). Through a logistic regression analysis we identified age as an independent predictor of mortality both at short and long term follow up, while EF was the only independent predictor for in-hospital mortality and arrhythmia duration for 1-year mortality. At 1-year follow up we recorded three ischemic strokes, while no bleeding complications.

Conclusions

STEMI patients who develop NOAF are a very high-risk population and are characterized by increased short and long term mortality. NOAF should be diagnosed and treated as soon as possible with a correct indication to long term OAC based on the ratio between ischemic and hemorrhagic risk.

Funding Acknowledgement

Type of funding sources: None.
Meta-analysis comparing sirolimus bioresorbable scaffolds versus everolimus-eluting metallic stents in coronary arterial disease
Authors: Prasad R P , Al-Abcha A A , Elshafie A , Radwan Y A , El-Sayed M ,   Michigan State University - Sparrow Hospital
Published: October 2021

Introduction

In the acute setting, thin-strut bioresorbable scaffolds (BRS) are noninferior versus the thin-strut drug-eluting stent. Recently, randomized controlled trials (RCTs) with long-term follow-up data have been published.

Purpose

To evaluate the long-term clinical outcomes of sirolimus BRS versus the benchmark everolimus DES.

Methods

We reviewed the literature and conducted a meta-analysis of all RCTs comparing sirolimus BRS versus metallic DES stents in patients with CAD. The primary outcomes were all-cause mortality and target vessel failure (TVF). Furthermore, secondary outcomes included cardiac mortality, target vessel myocardial infarction, ischemia-driven target lesion revascularization (TLR), and stent thrombosis (probable and definite). Statistical analysis was conducted using Review Manager 5.4. Two-sided p values of <0.05 were considered as statistical significance.

Results

A total of 15,930 patients were included with a median-weighted follow up period of 1.68 years. Heterogeneity was low-high across the trials (0–87%). All-cause mortality was insignificant between the two groups (OR 0.95; 95% CI 0.79–1.14; p=0.57) (Figure 1). The rate of TVF showed a trend favoring sirolimus BRS compared to everolimus DES with statistical significance (OR 0.84; 95% CI 0.73–0.98; p=0.02) (Figure 1). Ischemia-driven TLR also statistically favored sirolimus BRS (OR 0.64; 95% CI 0.53–0.77; p<0.ehab724.12301) (Figure 2). Otherwise, all other secondary outcomes favored sirolimus BRS without statistical significance (Figure 2).

Conclusion

This updated meta-analysis illustrates that in the long term setting sirolimus BRS has significantly decreased rate of TVF and ischemia-driven TLR as compared to everolimus DES. However, there was no statistical difference in the all-cause mortality or cardiac mortality.

Funding Acknowledgement

Type of funding sources: None.