bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of CABG and PCI in NSTE-ACS patients with three-vessel coronary artery disease
Authors: Li T , Yuan J
Published: October 2021

Background

Evidence is lacking on the choice between coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) in the specific setting of non-ST-segment elevation acute coronary syndrome (NSTE-ACS), especially for complex cases with three-vessel coronary artery disease (TVD).

Purpose

To compare PCI and CABG in NSTE-ACS patients with TVD; to explore effects of age and sex on outcomes of different revascularisation strategies.

Methods

The present study was a post hoc analysis of data from a single-centre prospective cohort of 8,943 patients with TVD [(angiographically confirmed stenosis of ≥50% in all three main epicardial coronary arteries (left anterior descending, left circumflex, and right coronary arteries), with or without left main lesion]. Patients were consecutively enrolled from April 2004 to February 2011 to evaluate their prognosis after receiving three different treatments. The study contained 2,812 patients (PCI, n=1,559; CABG, n=1,253) after excluding 1,489 with ST-segment elevation myocardial infarction, 3,532 with stable coronary artery disease, and 1,110 receiving conservative treatment.

The patients were divided into three age groups and two sex groups. Subgroup analyses were performed according to presence of diabetes, pre-procedural synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score, and presence of left main lesion. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction and stroke.

Results

During a median follow-up of 6.7 years, the risk of MACCE was significantly lower after CABG than after PCI in all patients (HR=0.6764, 95% CI: 0.5528–0.8277), two younger age groups (<65 years: HR=0.6617, 95% CI: 0.4947–0.8852; 65–74 years: HR=0.6997, 95% CI: 0.5124, 0.9556), and male (HR=0.6682, 95% CI: 0.5263–0.8482) (Figure 1). No significant interaction between age and revascularization strategies was observed, neither was it between sex and revascularization strategies. Notably, compared with PCI, CABG was associated with significantly higher risk of MACCE in women ≥75 years of age (HR=3.2716, 95% CI: 1.4213–7.5308, interaction p with sex=0.0007, interaction p with age=0.0024). Effects of age and sex on outcomes of different revascularisation strategies remained neutral regardless of patients' diabetic status, pre-procedural SYNTAX score, and presence of left main lesion (Figure 2).

Conclusion

CABG is superior to PCI in terms of MACCE regardless of patients in most NSTE-ACS patients with TVD except women ≥75 years of age. However, we found no significant age- or sex-related difference in prognosis of CABG relative to PCI.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Key Research and Development Program of China Figure 1. Cumulative incidence for MACCEFigure 2. HR of CABG relative to PCI
Associations between the PARIS ischaemic and bleeding risk scores and 1-year mortality in an all-comers Australian national PCI cohort
Authors: Chandrasekhar J , Chowdhury E , Eccleston D , Delacroix S , Worthley S
Published: October 2021

Background

Prediction scores can complement bedside clinical risk assessment in patients undergoing PCI.

Purpose

We sought to validate the PARIS ischaemic and bleeding risk scores in a national cohort of all-comer PCI patients in Australia, and to examine impact on 1-year mortality.

Methods

We retrospectively analysed the GenesisCare Outcomes multicentre Registry of prospectively collected data in patients undergoing PCI from 2008–2020. The ischaemic and bleeding scores were assessed in separate cohorts. Patients were included if all defining variables were available. The ischaemic integer score included diabetes, acute coronary syndrome, current smoking, GFR <60ml/min, prior PCI or CABG, and patients were grouped according as low (0 to 2), intermediate (3 or 4), and high (≥5) thrombotic risk. The bleeding integer score included age, body mass index, current smoking, GFR <60ml/min, anaemia and discharge on triple therapy after PCI, and patients were grouped as low (0 to 3), intermediate (4 to 7) and high (≥8) bleeding risk. One-year ischaemic and in-hospital bleeding endpoints were examined. Adjusted risk of 1-year mortality was assessed accounting for age, sex, family history, smoking, vascular disease, presentation status, hypertension, diabetes, obesity and dyslipidaemia.

Results

A total of 16,961 patients were included in the ischaemic risk cohort and 6431 patients in the bleeding risk cohort. The patient distributions by risk category for both scores are shown in the figure. Increasing ischaemic risk was associated with greater incidence of in-hospital (0.2% vs. 0.5% vs. 0.5%, p=0.01), and 1-year death (0.7% vs. 2.1% vs. 3.1%). Increasing bleeding risk was associated with greater in-hospital death (0.0% vs. 0.3% vs. 0.9%, p<0.01) and bleeding (0.6% vs. 0.9% vs. 3.2%, p<0.01), and greater 1-year death (0.3% vs. 1.4% vs. 2.8%, p<0.01). At 1-year compared to the low bleeding risk group, high risk patients had lower use of aspirin, P2Y12 inhibitors and statins. Similarly, compared to low ischaemic risk group, high-risk patients had lower use of aspirin and statins but higher use of P2Y12 inhibitors. With both risk scores, compared to low-risk patients, high-risk patients had significantly greater adjusted risk of 1-year mortality (See Figure).

Conclusions

The PARIS ischaemic and bleeding risk scores were associated with greater risk of in-hospital and medium-term adverse outcomes after PCI to 1-year. Prospective use of the scores can assist in guiding adherence to secondary prevention and optimal anti-thrombotic strategies to improve overall outcomes.

Funding Acknowledgement

Type of funding sources: None.
Platelet reactivity and immature platelets in patients with Covid-19
Authors: Cohen A , Harari E , Cipok M , Bryk G , Karp Lador N , Mann T , Mayo A , Lev E I
Published: October 2021

Background

Coronavirus disease 2019 (Covid-19) is associated with high incidence of thromboembolic events, both venous and arterial. Currently, there are no clinical or laboratory markers to guide antithrombotic therapy in COVID-19 patients. Immature platelets represent a population of hyper-reactive platelets associated with arterial thrombotic events.

Objectives

To determine indices of immature platelets and platelet reactivity in Covid-19 patients.

Methods

This prospective study compared consecutive COVID-19 patients (n=47, median age = 56 years) to patients with acute myocardial infarction (AMI, n=100, median age = 59 years) and a group of stable patients with cardiovascular risk factors (n=64, median age=68 years). Immature platelet fraction (IPF) and immature platelet count (IPC) were determined by the Sysmex XN-3000 auto-analyzer on admission and at subsequent time-points.

Results

IPF% on admission was higher in the Covid-19 group than the stable group and similar to the AMI group (4.8% [IQR 3.4–6.9], 3.5% [2.7–5.1], 4.55% [3.0–6.75], respectively, p=0.005 for Covid-19 vs. stable). IPC on admission was also higher in the Covid-19 group than the stable group and similar to the AMI group (10.8×109/L [8.3–18.1], 7.35×109/L [5.3–10.5], 10.7×109/L [7.7–16.8], respectively, P<0.0001 for Covid-19 vs. stable). The maximal IPF% among the Covid-19 group was higher than the stable group and similar to the AMI group. The maximal IPC in the Covid-19 group was higher than the maximal IPC in both the stable and AMI groups (Covid-19: 14.4×109/L [9.4–20.9], AMI: 10.9×109/L [7.6–15.2], P=0.0035, Stable: 7.55×109/L [5.55–10.5], P<0.0001).

Conclusions

Patients with Covid-19 have increased immature platelets indices compared to stable patients with cardiovascular risk factors, and as the disease progresses also compared to AMI patients. Enhanced platelet turnover and reactivity may, therefore, have a role in the development of thrombotic events in Covid-19 patients.

Funding Acknowledgement

Type of funding sources: None. IPF in COVID-19, AMI and stable groups
Association of quality indicators for acute myocardial infarction and mortality: feasibility and validation study using linked nationwide registry data
Authors: Aktaa S , Yadegarfar M E , Wu J , Rashid M , De Belder M , Deanfield J , Schiele F , Minchin M , Mamas M A , Gale C P
Published: October 2021

Background

Quality indicators (QIs) have been increasingly used as tools to assess and improve the quality of care for acute myocardial infarction (AMI). However, it is not known if it is feasible to use the 2020 iteration of international AMI QIs using routinely collected data and, if so, whether higher performance is associated with improved outcomes.

Objective

To investigate if routine data are available to measure care quality against the 2020 European Society of Cardiology (ESC) Association for Acute Cardiovascular Care (ACVC) QIs for AMI, investigate whether higher performance is associated with reduced mortality, and to report quality of care during the COVID-19 pandemic.

Methods

Cohort study of linked data from the AMI and percutaneous coronary intervention (PCI) registries in England and Wales with outcome data from the Civil Registration of Deaths Register between 2017 and 2020 (representing 236 743 patients from 186 hospitals). Baseline ischaemic risk was estimated using the Global Registry of Acute Coronary Events (GRACE) risk score. The likelihood of attainment for each QI based on GRACE risk was quantified using logistic regression and the association with mortality at 30 days, 6 months, 1 year and long-term (maximum 1243 days) was obtained from Cox proportional hazard models.

Results

Of 26 QIs, 17 (65.3%) could be directly measured using nationwide registry data and were each inversely associated with risk-adjusted 1-year and long-term mortality. At 30 days, the measured QIs with exception of early invasive coronary angiography for non-ST elevation myocardial infarction, were associated with improved survival, and the QIs that had the greatest magnitude for a reduction in mortality were the prescription of secondary prevention medications at discharge; hazard ratio 0.13 (95% CI 0.12–0.14) for statins, 0.16 (95% CI 0.15–0.18) for adequate P2Y12 inhibition, and 0.18 (95% CI 0.17–0.20) for dual antiplatelet therapy (Figure 1). The magnitude of association between the composite QI (CQI) and survival attenuated over time, with greater long-term survival gains observed for the high GRACE risk compared with low- and intermediate-risk (Figure 2). During the first UK lockdown there was an improvement in the attainment for 62.5% of the measured QIs compared with before the COVID-19 pandemic, with a higher attainment for the CQI (43.8% to 45.2%, odds ratio 1.06, 95% CI 1.02–1.10).

Conclusion

Care quality for AMI may be evaluated using routinely collected clinical data from the national registries, whereby higher performance is associated with reduced mortality. Such QIs will have a role in monitoring hospital care as demonstrated for COVID-19.

Funding Acknowledgement

Type of funding sources: None. Figure 2. QI association with long-term mortality
Adherence to guideline-recommended care following acute myocardial infarction: impact on clinical outcomes at 90 days and 1 year
Authors: Gabriel S , Liberman J N , Alexander J E , Allen K B
Published: October 2021

Background

Guideline-recommended care is effective for secondary prevention following acute myocardial infarction (AMI); however, most pharmacotherapies take time to become efficacious and not all patients comply with treatment. It is well established that the risk of recurrent cardiovascular (CV) events is high following an AMI; however, the clinical burden of recurrent CV events among guideline-treated patients, specifically in the 90-day period post-AMI, has been relatively unexplored.

Purpose

To evaluate adherence to guideline-recommended care and determine how it impacts clinical outcomes at 90 days and 1 year post-discharge in a U.S. population.

Methods

A retrospective analysis was conducted using the IBM Health Marketscan Commercial Claims and Encounters database (July 1, 2013–June 1, 2016). In U.S. individuals with a primary diagnosis of AMI, adherence to evidence-based care was assessed in terms of claims for guideline-recommended interventions: completed physician follow-up visit within 30 days of discharge, participation in cardiac rehabilitation, and adherent (PDC ≥0.8) to beta-blocker, antiplatelet, statin, and ACE inhibitor/ARB drug classes in the year following discharge. Rates of rehospitalisation (all-cause and cardiac) and recurrent AMI events within 90 days and 1 year post-AMI were evaluated.

Results

Of the 21,977 patients included in the analysis, the majority (80.9%) visited a physician within 30 days of discharge, but few (15.4%) entered cardiac rehabilitation or were adherent to all guideline-recommended drug classes (17.1%). Even in patients fully compliant with guideline-recommended care (3.1% of the total population), event rates were high in the first year post-MI (recurrent AMI: 1.6%; cardiac rehospitalisation: 8.9%; all-cause hospitalisation 13.3%) with a large proportion of the events occurring in the first 90 days: 75%, 58.4%, and 51.1% respectively. Adherence to all drug classes significantly reduced the risk of all-cause and cardiac rehospitalisation but did not reduce the risk of recurrent AMI events (OR=1.03 [95% CI 0.73–1.46] at 90 days and OR=0.80 [95% CI 0.60–1.07] at 1 year) when compared to patients not receiving guideline-recommended pharmacotherapy.

Conclusions

Even among patients receiving guideline-recommended treatment following discharge, the risk of recurrent events remained high at both 90 days and 1 year in patients following an AMI. Novel approaches to reducing the risk of early recurrent AMI, in particular, are needed.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): CSL Behring
Efficacy and safety of ticagrelor versus prasugrel in smokers and nonsmokers with acute coronary syndromes
Authors: Lahu S , Ndrepepa G , Gewalt S , Schuepke S , Bernlochner I , Aytekin A , Neumann F J , Menichelli M , Richardt G , Laugwitz K L , Schunkert H , Kastrati A , Mayer K
Published: October 2021

Background

The efficacy and safety of ticagrelor versus prasugrel according to smoking status in patients with acute coronary syndromes (ACS) are not known.

Purpose

The aim of this study was to assess the efficacy and safety of ticagrelor versus prasugrel according to smoking status in patients with ACS undergoing invasive evaluation.

Methods

This pre-specified analysis of the ISAR-REACT 5 trial included 1349 smokers and 2652 nonsmokers randomised to receive ticagrelor or prasugrel. The primary endpoint was the incidence of death, myocardial infarction, or stroke; the secondary endpoint was the incidence of Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding. Both endpoints were assessed at 12 months after randomisation.

Results

There was no significant treatment arm-by-smoking status interaction regarding the efficacy outcome. The primary endpoint occurred in 47 patients (7.0%) in the ticagrelor group and 41 patients (6.2%) in the prasugrel group in smokers (hazard ratio [HR]=1.15; 95% confidence interval [CI] 0.76–1.75; P=0.510) and in 133 patients (10.2%) in the ticagrelor group and 94 patients (7.2%) in the prasugrel group in nonsmokers (HR=1.44 [1.10–1.87], P=0.007; Pint=0.378). The secondary endpoint occurred in 27 patients (4.6%) in the ticagrelor group and 33 patients (5.6%) in the prasugrel group in smokers (HR=0.81 [0.49–1.35]; P=0.412) and in 66 patients (6.0%) in the ticagrelor group and 46 patients (4.4%) in the prasugrel group in nonsmokers (HR=1.38 [0.94–2.01]; P=0.097).

Conlusions

Although there was no significant interaction between smoking and treatment effect, the present findings suggest a greater advantage of prasugrel over ticagrelor in nonsmoker vs. smoker patients with ACS.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): German Centre for Cardiovascular Research;Deutsches Herzzentrum München, Germany
Prognostic value of left ventricular ejection fraction and symptom severity in patients with moderate aortic stenosis
Authors: Stassen J , Butcher S C , Hirasawa K , Singh G K , Pio S M , Amanullah M R , Chew N , Ewe S H , Kong W , Cohen D J , Genereux P , Leon M B , Marsan N A , Delgado V , Bax J J
Published: October 2021

Background

Moderate aortic stenosis (MAS) is associated with an increased risk of adverse events. Risk assessment in these patients, however, has not been thoroughly investigated.

Purpose

To investigate the independent determinants of survival in patients with MAS, stratified by left ventricular ejection fraction (LVEF) and severity of symptoms at the time of first diagnosis.

Methods

Patients with an echocardiographic diagnosis of tricuspid MAS (aortic valve area >1.0 and ≤1.5cm2) were identified. Patients were stratified by LVEF (LVEF ≥60%, LVEF 50–59%, or LVEF <50%) and NYHA functional class (NYHA I, NYHA II, or NYHA III-IV) at time of MAS diagnosis. The relationship between LVEF, NYHA Class, and the composite of death or aortic valve replacement (AVR) was explored using univariable and multivariable proportional hazards regression.

Results

Of 2003 patients with MAS (mean age 73±10 years, 51% men, AVA 1.22±0.15 cm2), 1063 (53%), had LVEF≥60%, 550 (27%) LVEF 50–59% and 390 (20%) LVEF<50%. Among 1763 patients with available NYHA class data, 1036 (59%) patients were in NYHA I, 435 (25%) in NYHA II and 292 (16%) in NYHA III-IV. During a median follow-up of 34 (13–60) months, 1323 (67.1%) patients underwent AVR (31.1%) or died (36.0%) without AVR. Patients with LVEF<50% and within the 50–59% range had significantly higher event rates compared with patients with an LVEF≥60% (log rank p<0.001; figure 1A). Likewise, patients with NYHA II and NYHA III-IV had significantly worse outcomes compared with patients in NYHA I (log rank p<0.001, figure 1B). On multivariable analysis, LVEF 50–59% (HR: 1.17; 95% CI: 1.02 – 1.35; p=0.028), LVEF <50% (HR: 1.36; 95% CI: 1.15 – 1.61; p<0.001), NYHA II (HR: 1.84; 95% CI: 1.59 – 2.13; p<0.001) and NYHA III-IV (HR: 2.38; 95% CI: 2.03 – 2.79; p<0.001) were independently associated with worse outcome (figure 2).

Conclusions

Baseline LVEF and symptom severity are associated with worse outcomes in patients with MAS. Although current guidelines recommend conservative management for MAS, randomized trials appear warranted to determine whether AVR at an earlier stage would be beneficial in these patients.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): ESC Training Grant Appehab724.157064741 Figure 1. Kaplan-Meier outcome curvesFigure 2. Cox regression analysis
Tricuspid regurgitation in ischemic mitral regurgitation patients – prevalence, predictors for outcome and long-term follow-up
Authors: Koren O , Darawsha H D , Rozner E H U D , Turgeman Y O A V
Published: October 2021

Background

Functional tricuspid regurgitation (FTR) is common in left-sided heart pathology involving the mitral valve. The incidence, clinical impact, risk factors, and natural history of FTR in the setting of ischemic mitral regurgitation (IMR) are less known.

Method

We conducted a cohort study based on data collected from January 2012 to December 2014. Patients diagnosed with IMR were eligible for the study. The median follow-up was five years. The primary outcome is defined as FTR developing at any stage.

Results

Among the 134 IMR patients eligible for the study, FTR was detected in 29.9% (N=40, 20.0% mild, 62.5% moderate, and 17.5% severe). In the FTR group, the average age was 60.7±9.2 years (25% females), the mean LV ejection fraction (LVEF) was 37.3±6.45 [%], LA area 46.4±8.06 [mm2], LV internal diastolic diameter (LVIDD) 59.6±3.94 [mm], RV fractional area change (RVFAC) 22.3±4.36 [%], systolic pulmonary artery pressure (SPAP) 48.4±9.45 [mmHg]. Independent variables associated with FTR development were age ≥65y [OR 1.2], failed revascularization, LA area ≥42.5 [mm2] [OR 17.1], LVEF ≤24% [OR 32.5], MR of moderate and severe grade [OR 419.4], moderate RV dysfunction [OR 91.6] and pulmonary artery pressure of a moderate or severe grade [OR 33.6]. During follow-up, FTR progressed in 39 (97.5%) patients. Covariates independently associated with FTR progression were lower LVEF, RV dysfunction, and PHT of moderate severity. LA area and LVIDD were at the margin of statistical significance (p=0.06 and p=0.05, respectively).

Conclusion

In our cohort study, FTR development and progression due to IMR was a common finding. Elderly patients with ischemic MR following unsuccessful PCI are at higher risk. FTR development and severity are directly proportional to LV ejection fraction, to the extent of mitral regurgitation, and SPAP. FTR tends to deteriorate in the majority of patients over a mean of 5-y follow-up.

Funding Acknowledgement

Type of funding sources: None.
Efficacy and safety of alcohol septal ablation in adolescents and young adults with symptomatic hypertrophic obstructive cardiomyopathy
Authors: Lawin D , Lawrenz T , Radke K , Stellbrink C
Published: October 2021

Background

In young patients suffering from hypertrophic obstructive cardiomyopathy (HOCM) surgical myectomy is still considered as the gold standard for septal reduction therapy.

Purpose

To assess the safety and efficacy of alcohol septal ablation (ASA) for reduction of left ventricular outflow tract gradient (LVOTG) and symptoms in HOCM patients ≤25 years.

Methods and results

All ASA procedures performed at our institution between 2002 and 2020 were retrospectively allocated to a patient group ≤25 years (group 1) and a reference group >25 years (group 2). Patients were evaluated at baseline and chronic follow-up (FU) after 6 months. 1,264 procedures were analysed in group 2 (58.6±13.5 years) and 41 procedures in group 1 (20.9±3.3 years). Proportion of family history of sudden cardiac death was higher in group 1 (56.1% vs. 24.6% in group 2; p<.0001). We more often found a previously implanted cardiac device in group 1 (31.7% vs. 9.0% in group 2; p<.0001) and the interventricular septal diameter (IVSD) was higher in young patients at baseline (26.0±6.5 mm vs. 21.3±4.4 mm in group 2; p<.0001). LVOTG at baseline did not differ between the groups (54.4±24.4 mmHg in group 1 vs. 52.4±36.6 mmHg in group 2 (p=n.s.). Relief of symptoms was shown for both groups at FU compared to baseline (group 1: mean NYHA class 2.5 at baseline and 1.3 at FU; p<.0001; group 2: mean NYHA class 2.7 at baseline and 1.4 at FU; p<.0001). Compared to baseline IVSD was significantly reduced at FU (20.3±8.2 mm in group 1 at FU; 16.8±5.7 mm in group 2 at FU; p<.0001 for each group compared to baseline). LVOTG improved significantly during FU (25.5±20.0 mmHg in the young patients; 22.1±21.7 mmHg in the reference group; p<.0001 for each group compared to baseline). Mortality was 0.0% in patients ≤25 years and 0.9% in the reference group.

Conclusion

Our data demonstrate safety and efficacy of ASA to improve LVOT obstruction and symptoms in young adults and adolescents (14–25 years) suffering from symptomatic HOCM. Therefore, ASA may be considered also for this patient population. However, these results may only hold for experienced centres and, thus, invasive procedures in young patients should be reserved to centres with the required expertise.

Funding Acknowledgement

Type of funding sources: None. Table 1. Baseline characteristics. ASA = alcohol septal ablation. ICD = implantable cardioverter-defibrillator. IVSD= interventricular septum diameter. LA = left atrium. LVOTG = left ventricular outflow tract gradient. n.s. = not significant. PM = pacemaker. SCD = sudden cardiac death. SM = septal myectomy.Figure 1. Echocardiographic parameters in patients ≤25 years at baseline and follow-up (FU) 6 months after alcohol septal ablation. ****p<.0001. A. Interventricular septum diameter (IVSD). B. Left ventricular outflow tract gradient (LVOTG).
Amyloid deposits and fibrosis on left ventricular endomyocardial biopsy correlate with extracellular volume in cardiac amyloidosis
Authors: Aimo A , Pucci A , Musetti V , Barison A , Vergaro G , Genovesi D , Giorgetti A , Masotti S , Arzilli C , Prontera C , Pastormerlo L E , Coceani M A , Martini N , Passino C , Emdin M
Published: October 2021

Background

The relative contribution of amyloid and fibrosis to extracellular volume expansion in cardiac amyloidosis (CA) has never been defined.

Methods

We included all patients diagnosed with amyloid light-chain or transthyretin (AL/ATTR) CA at a tertiary referral center between 2014 to 2020 and undergoing a left ventricular (LV) endomyocardial biopsy (EMB).

Results

Patients (n=37) were more often male (92%), with a median age of 72 years (68–81). Lambda+ AL was found in 14/19 AL cases (38%) and kappa+ AL in 5/19 (14%), while TTR was detected in the other 18 cases (48%). Amyloid deposits accounted for 15% of tissue sample area (10–30%), without significant differences between AL and ATTR. All patients displayed myocardial fibrosis, with a median extent of 15% of tissue samples (10–23%, range 5–60%), in the absence of spatial overlap with amyloid deposits. Interstitial fibrosis was often associated with mild and focal subendocardial fibrosis. The extent of fibrosis or the combination of amyloidosis and fibrosis did not differ significantly between ATTR and AL subgroups. In 20 patients with myocardial T1 mapping at cardiac magnetic resonance (CMR), the combined amyloid and fibrosis extent displayed a modest correlation with extracellular volume (ECV; r=0.661, p=0.001). The combined amyloid and fibrosis extent correlated with high-sensitivity troponin T (p=0.035) and N-terminal pro-B-type natriuretic peptide (p=0.002) serum levels.

Conclusions

Extracellular spaces in CA are enlarged to a similar extent by amyloid deposits and fibrotic tissue. Their combination can better explain the increased ECV at CMR and circulating biomarkers than amyloid extent alone.

Funding Acknowledgement

Type of funding sources: None.
Orthostatic hypotension in hereditary ATTR Val30Met amyloidosis: predictors and associated clinical features
Authors: Dias De Frias A F , Rodrigues P , Costa R , Pereira A , Alexandre A , Hipolito Reis A , Torres S
Published: October 2021

Introduction

The prevalence of orthostatic hypotension (OH) in patients with mutated transthyretin (TTR) amyloidosis (mATTR) is 40–60%. According to previous studies, OH is frequent and an early feature in patients with Val30Met mutation (the most prevalent form of mATTR).

Aim

To characterize TTR Val30Met patients with OH and to identify clinical characteristics associated with OH development.

Methods

Retrospective study of consecutive Val30Met TTR patients with suspected cardiac involvement observed at our cardiology clinic during 2019. Two groups were defined: group 1: patients without OH; group 2: patients with OH. Data was obtained by chart review. Statistically significant predictors of OH were found using logistic regression.

Results

We included a total of 248 patients (group 1 – 173; group 2 – 75). Group 1 patients were 52% male, median age 45 [interquartile range (IQR) 39–55] and median age at onset 34 (IQR 29,75–46,25) years. Left ventricle hypertrophy [LVH, defined as maximal LV wall thickness (LVT) ≥12 mm] occurred in 26,5%, with median maximal LVT 10 mm (IQR 9–12); 49,7% had conduction disturbances, 30,6% gastrointestinal (GI), 17,3% genitourinary (GU) manifestations and 5% were in Coutinho staging ≥2/3. Group 2 had 56% male, median age of 49 years at evaluation (IQR 42–65) and 35 years at onset (IQR 30–59). LVH was present in 42,9%, with median maximal LVT 11 mm (IQR 10–14); 74,7% had conduction disturbances, 56% GI and 42,7% GU manifestations and 21% were in Coutinho staging ≥2/3.

In univariate analysis, higher age (p=0,005), presence of LVH (p=0,009), conduction disturbances (p<0,001), GU manifestations (p<0,001) and higher Coutinho staging (p<0,001) were all associated with the presence of OH, while age at onset was not (p=0,648). In multivariate analysis, only Coutinho staging [odds ratio (OR) 2.609; 95% confidence interval (95% CI) 1.344–5.065] and GU manifestations (OR 3,151; 95% CI 1,595–6,225) were found to be significant predictors of OH.

Conclusion

Our study suggests that OH is more associated with GU manifestations and Neurologic staging, than with amyloid cardiomyopathy or age, suggesting a predominant neurogenic component. The prevalence of OH in our sample of Val30Met patients was lower than previously described.

Funding Acknowledgement

Type of funding sources: None.
Beta-blocker exposure and long-term survival in patients with transthyretin amyloid cardiomyopathy
Authors: Barge-Caballero G , Barge Caballero E , Lopez-Perez M , Bilbao-Quesada R , Gonzalez-Babarro E , Gomez-Otero I , Lopez-Lopez A , Gutierrez-Feijoo M , Varela-Roman A , Gonzalez-Juanatey C , Diaz-Castro O , Crespo-Leiro M
Published: October 2021

Aims

To investigate a potential association between beta-blocker exposure and long-term survival in patients with transthyretin amyloid cardiomyopathy (ATTR-CM).

Methods

Real world prospective registry of 128 consecutive patients with ATTR-CM recruited in 7 hospitals. The long-term survival of patients who were receiving beta-blockers (n=65) at baseline was compared with the one of untreated controls (n=63), by means of both unweighted and inverse probability of treatment weighting (IPTW) Cox's regression analyses. Tolerance and side effects of beta-blockers were recorded. Median study follow-up was 520 days.

Results

Patients with ATTR-CM who were receiving beta-blockers at baseline showed statistically significant lower all-cause mortality than untreated controls (figure 1), as compared either by means of unweighted Cox's regression (hazard ratio = 0.31; 95% CI 0.12–0.19; p=0.015), or by means of Cox's regression with IPTW (hazard-ratio = 0.18; 95% CI 0.08–0.41; p<0.001). The protective effect of beta-blockers was stronger in the subgroups of ATTR-CM patients with previous atrial fibrillation/flutter, previous heart failure hospitalization, left ventricular ejection fraction <50%, NTproBNP>1000 pg/ml, and NYHA class III or IV (figure 2). The overall rate of beta-blocker suspension due to side effects in the study population was 25% (95% CI 15.5%–34.5%). Bradycardia and hypotension were the most frequent side effects leading to drug withdrawal.

Conclusions

In this real world, prospective, multi-institutional registry, patients with ATTR-CM who received beta-blockers presented lower all-cause mortality than untreated controls.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): PFIZERSOCIEDAD GALLEGA DE CARDIOLOGIA Figure 1. SurvivalFigure 2. Subgroup analysis
Pericardiocentesis vs conservative management in patients with asymptomatic, chronic, large, idiopathic, C-reactive negative pericardial effusion
Authors: Lazarou E , Lazaros G , Antonopoulos A S , Karavidas A , Tsioufis C , Tousoulis D , Vlachopoulos C
Published: October 2021

Background/Introduction

Pericardial effusion (PE) prognosis largely depends on the underlying etiology.

Purpose

We sought to assess the outcome of patients with asymptomatic, chronic (>3 months), large (diastolic echo-free space >2 cm), idiopathic (without apparent etiology), C-reactive protein (CRP) negative PE, undergoing either pericardiocentesis or conservative management.

Methods

A total of n=61 patients aged 66.8±15.6 years (women n=32, 53%) were enrolled in this study. Patients were treated by pericardiocentesis (n=39) or conservatively (n=22) at the discretion of treating physician and personal preference. The median follow-up was 24 months (interquartile range: 15 to 36).

Results

Among those patients undergoing pericardiocentesis, PE re-accumulation (any) occurred in 30 cases (76.9%) with large re-accumulation occurring in 41% of patients. Patients with re-accumulation had higher baseline maximum PE diameter (30±1.5mm vs. 25±1.5mm, p=0.02). In patients managed conservatively effusion size remained overall stable in 17 cases (77%), regressed in 3 cases (14%) and increased leading to near or overt tamponade in 2 cases (9,1%). Complicated course occurred in 5 cases (12.8%) of patients undergoing pericardiocentesis [4 cases of cardiac tamponade (10.2%) and 1 recurrent pericarditis] and in 2 conservatively treated patients (cardiac tamponade). Notably, pericardiocentesis was not helpful in establishing new diagnoses and guide treatment. The complications free survival rate was not significantly different between patients undergoing pericardiocentesis and those treated conservatively (long rank chi2=0.504, p=0.478) (Figure 1).

Conclusions

In conclusion, in asymptomatic patients with chronic, large, hemodynamically irrelevant, CRP negative, idiopathic PE, conservative management seems a more reasonable approach in most cases.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Exaggerated elastin turnover in childhood and adolescence in Marfan syndrome – correlation with age – new insights from the AIMS trial
Authors: Iskandar Z , Dodd M , Stuart G , Caputo M , Clayton T , Chin C , Gibb J , Child A , Jin X Y , Flather M , Huang J T J , Choy A M
Published: October 2021

Background

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder caused by mutations in the Fibrillin1 gene (FBN1) that leads to impaired elastin formation and extra-cellular matrix homeostasis. Elastin synthesis and related lamellae formation in the aorta is completed in the newborn. Thereafter further elastin turnover is thought to be minimal during life. Elastin homeostasis is little studied in patients with MFS who have been reported to have reduced elastin in their aorta and are at risk of aortic dilatation and consequent life-threatening dissection. It is not clear if elastin loss is due to reduced elastin formation in utero or accelerated degradation during life. However, aortopathy develops early in MFS with 70% of patients developing aortic dilatation by the age of 20 years. Therefore, the longitudinal and circumferential aortic growth that occurs in childhood may involve elastic lamellae remodelling that is impaired in MFS. Desmosine is the cross-link component in the elastin molecule and is exclusively released from mature elastin breakdown, thus is a physiologically relevant biomarker of elastin turnover. We hypothesise that physiologic aortic growth is associated with elastic lamellae remodelling and increased elastin turnover, detected by elevated plasma desmosine (pDES), and that elastin turnover is exaggerated during the fast-growing period in MFS.

Purpose

The aims of this study were 1. To investigate the relationship between elastin turnover and age in the control subjects, and 2. To compare the elastin turnover in MFS with control subjects.

Methods

pDES was measured by stable isotope dilution LC-MS/MS in 113 MFS subjects (48% male, mean age 18.2±9.4 (SD) years), mean aortic root 33.8±2.1mm and Z-score 3.4±2.1 in the AIMS trial at baseline before intervention, and in 109 healthy controls (46% male, mean age 26.1±9.5 years).

Results

pDES levels were associated positively with age, body surface area and negatively with diastolic BP in the control group (p=0.05 and 0.21 respectively after correcting for age). In MFS subjects pDES also positively correlated with age and male sex (p<0.05). Interestingly, the age-dependent association with pDES showed a peak distribution in both control and MFS groups (Figure 1) where teenage children expressed the highest pDES levels. MFS subjects had significantly higher pDES compared to controls before the age of 20 (p=0.01) but in adulthood, there was no difference (Figure 2).

Conclusion

Elastin turnover is highly dynamic before early adulthood, and peaks in adolescence and is exaggerated in MFS, suggesting that this period of growth is critical in developing aortopathy.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): British Heart FoundationTENOVUS Scotland Figure 1Figure 2
Plasma metabolomics in perioperative period of defect repair in patients with pulmonary arterial hypertension associated with congenital heart disease
Authors: Yan Y , He Y.-Y , Chen J.-W , Fu Y.-X , Liu S , Hua L , Jiang X , Xu X.-Q , Lu D , Jing Z.-C , Han Z.-Y
Published: October 2021

Background

The pathophysiological alterations in response to shunt correction in patients with pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH) is still not clear.

Purpose

To explore the dynamic plasma metabolite profiling and its relationship with clinical characteristics in patients with CHD-PAH during the perioperative period of defect repair.

Methods

Plasma samples from 13 patients with CHD-PAH were harvested at four time points: before cardiopulmonary bypass (CPB) after anesthesia (Pre), immediately after CPB (T0), 24 h (T24), and 48 h (T48) after defect repair. The untargeted metabolomics strategy based on UPLC Q-TOF MS was used to detect the metabolites. Clinical measures were recorded at indicated time points.

Results

The sample distribution at four time points was well separated (Figure 1A, B). 193 metabolites were distinguished at different time points according to Variable Important in Projection (VIP) score (Figure 1C), enriched in pathways such as carnitine synthesis, phospholipid biosynthesis and oxidation of branched chain fatty acids (Figure 2A). 17 metabolites alterations were significantly correlated with gradients in mean pulmonary arterial pressure (mPAP) at T48 versus Pre, indicative of the response to defect correction (Figure 2B). Intriguingly, 4 out of the 17 (23.5%) metabolites including propionylcarnitine, butenylcarnitine, isobutyryl-L-carnitine and hexanoylcarnitine were enriched in oxidation of branched chain fatty acids. They were increased at both T24 and T48 (all P<0.05 except propionylcarnitine with P<0.05 at T24) (Figure 2C).

Conclusions

This is the first study to show the altered metabolic profiles of CHD-PAH patients in perioperative period of defect repair. Metabolites that respond to shunt correction could be a suitable non-invasive marker and would be of great value in disease monitoring and evaluating future therapeutic interventions.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): 13th Five-Year Plan–Precise Medicine–Key Research and Development Program–Clinical Cohort of Rare Disease; National Natural Science Foundation of China Figure 1. Overall analysis of metabolitesFigure 2. Shunt correction associated metabolites
Real-world, very long-term follow up survival of incident patients with pulmonary hypertension
Authors: Ferreira C , Festas T , Alves P , Freitas A , Almeida J P , Martinho S , Goncalves V , Castro G , Baptista R , Goncalves L
Published: October 2021

Background

Pulmonary hypertension (PH) is a clinical syndrome characterized by an increase in pulmonary artery pressure. Among the five groups of PH, pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) stand out due to their ominous prognosis without specific treatment. However, very long-term outcomes data are scarce.

Purpose

We aimed to assess the very long-term survival of PAH and CTEPH patients followed in a Portuguese PH referral center.

Methods

Between January 2009 and January of 2020, all incident PH cases were consecutively enrolled in a prospective cohort study. A total of 177 patients were followed up for a median of 5.0 [interquartile range 2.3–8.7] years. Kaplan-Meier survival analysis was used to estimate 1-, 5- and 9-year survival and multivariate regression was used to predict independent prognostic factors.

Results

Mean age was 49±20 years with a clear female preponderance (67%). The most common PH subgroups were congenital heart disease (PAH-CHD) (n=62; 35%), followed by CTEPH (n=52; 29,4%), connective tissue disease (PAH-CTD) (n=31; 17.5%), idiopathic/hereditary PAH (I/HPAH (n=22; 12.4%) and portopulmonary hypertension (PoPH) (n=8; 4.5%) (Table 1). PAH-specific drugs were used in 91% of the patients, dual combination therapy in 47.5%, and triple combination in 12.4%. The remaining 9% successfully received non-pharmacological treatment, namely cardiac surgery in PAH-CHD (n=7) and endarterectomy or angioplasty in CTEPH (n=9). Survival rates at 1-, 5- and 9-years were 97%, 80% and 66%, respectively. Age (hazard ratio [HR] 1.02; 95% CI 1.01–1.04; P=0.049), BNP [HR 2.04 (1.16–3.60); P=0.01], admission for decompensation of heart failure (HF) [HR 3.15 (1.71–5.83); P<0.001] and PH type [P=0.01] were predictors of all-cause mortality. PAH-CHD had the better long-term survival (9-year survival of 83%), whereas PAH-CTD and PoPH were associated with a worse prognosis (9-year survival of 24% and 28%, respectively) (Figure 1). Regarding admissions for decompensated right HF, BNP was an independent predictor [HR 3.39 (2.12– 5.43); P<0.001] and no difference was found between PH etiologies.

Conclusions

In this cohort of incident PH patients, the overall 9-year survival rate was 66%. PAH-CHD patients had better overall prognosis, while patients with PAH-CTD and PoPH had the worst prognosis. Additionally, older age, higher BNP and admission for HF were associated with higher mortality.

Funding Acknowledgement

Type of funding sources: None.
An original risk score to predict early major bleeding in acute pulmonary embolism: the Syncope, Anemia, Renal Dysfunction (PE-SARD) bleeding score
Authors: Chopard R , Piazza G , Falvo N , Ecarnot F , Besutti M , Capellier G , Schiele F , Badoz M , Meneveau N
Published: October 2021

Background

Improved prediction of the risk of early major bleeding in pulmonary embolism (PE) is needed to optimize acute management.

Methods

Using data from a multicenter prospective registry including 2,754 patients, we performed multivariable logistic regression analysis to build a risk score to predict early (up to hospital discharge) major bleeding events. We validated the endpoint model internally using bootstrapping in the derivation dataset by sampling with replacement for 500 iterations. We compared the performance of this novel score to that of the VTE-BLEED and RIETE models.

Results

Multivariate regression identified three predictors for the occurrence of 82 major bleeds (3.0%): Syncope (+1.5 points), Anemia defined by a hemoglobin level <12 g/dL (+2.5 points), and Renal Dysfunction defined by a glomerular filtration rate <60 mL/min (+1 point). The PE-SARD bleeding score was calculated by summing all the components. Overall, 52.2% of patients were classified as low bleeding-risk (score, 0 point), 35.2% intermediate-risk (score, 1–2.5 points), and 12.6% high-risk (score >2.5 points). Cumulative observed bleeding rates increased with increasing risk group, from 0.9% in the low-risk group to 9.0% in the high-risk group. The C-index was 0.744 (95% CI, 0.73–0.76) and Brier score 0.028 in the derivation cohort. Similar values were calculated from internal bootstrapping. Performance of the PE-SARD score was better than that observed with the VTE-BLEED and RIETE scores (figure).

Conclusions

The PE-SARD bleeding risk score is an original, user-friendly score to estimate the risk of early major bleeding in patients with acute PE.

Funding Acknowledgement

Type of funding sources: None. Figure 1
Response to anticoagulation in chronic thromboembolic pulmonary hypertension
Authors: Campean I C , Shafran I , Sadushi-Kolici R , Panzenboeck A , Skoro-Sajer N , Lang I M
Published: October 2021

Introduction

Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by fibrotic thrombus in the pulmonary arteries, likely originating from pulmonary embolism. Inadequate anticoagulation is one of the suspected mechanisms of disease in CTEPH. The aim of our study was to assess phenprocoumon dosing and genetic polymorphisms of vitamin K epoxide reductase complex subunit 1 (VKORC 1) that are known to affect the dose required to reach therapeutic range.

Methods

The ratio of mean weekly phenprocoumon dose in relation to mean INR levels was assessed in CTEPH patients on phenoprocoumon oral anticoagulation for at least 6 months, compared with PAH patients. VKORC 1 (–1639, –3730) single nucleotide polymorphisms (SNPs) were determined by polymerase chain reaction (PCR).

Results

In 225 patients (167 CTEPH, 58 PAH) mean treatment duration was 51.7±44.7 months, and mean age was 62.9±13.87 years (49.7% female). Median weekly dose of phenprocoumon was 10.5 mg (IQR 9.0–16.5) for PAH vs. 14.25 mg (IQR 10.5–18.0) in the CTEPH cohort (p=0.016). Although median INR was not significantly different among the two groups (2.28 vs. 2.40 in the PAH vs. CTEPH, respectively, p=0.084), achieving the mentioned INR require significantly higher weekly doses in the CTEPH group. While distribution of VKORC1 variants was according to the Hardy Weinberg equilibrium, patients with CTEPH and VKORC1 –1639 GG homozygous wild type required significantly higher phenprocoumon doses compared with VKORC1 –1639 AA homozygous mutants (P<0.001).

Conclusion

CTEPH patients require more vitamin K antagonists in relation to INR levels than PAH patients. Unmet phenprocoumon dosing requirements may be one mechanism of disease in CTEPH.

Funding Acknowledgement

Type of funding sources: None.
Population-based incidence and outcomes of acute aortic dissection in Japan
Authors: Yamaguchi T , Nakai M , Yano T , Matsuyama M , Miyamoto Y , Kodama T , Ogino H
Published: October 2021

Background

The population-based incidence and outcomes of acute aortic dissection (AAD) are still unknown because some patients are already dead on arrival at the hospital, and the accurate diagnosis of AAD is difficult due to the low autopsy rate for patients with cardiopulmonary arrest outside of the hospital. We performed a population-based review of all patients with AAD in a well-defined geographical area in the southern part of Japan between 2016 and 2018.

Methods

Data of all patients with AAD at our Hospital, which performs medical care for 120,000 residents, were collected retrospectively. The emergency medical service is dedicated to the transfer of all patients in this area to the MPNH. For all patients who were dead on arrival, the diagnosis of AAD was made by autopsy imaging (AI) using computed tomography. The age-adjusted incidence and mortality per 100,000 population were calculated using the Japanese population distribution model in 2015.

Results

The total incidence of AAD was 79 (type A: 64.5%, n=51). Of those, 60.8% (31/51) of patients with type A and 21.4% (6/28) with type B were dead on arrival and diagnosed by AI. The 30-day mortality rates after the onset of AAD were 74.5% (38/51) in type A and 25.0% (7/28) in type B. Excluding the dead-on-arrival patients, the 30-day mortality rates were 35.0% (7/20) in type A and 4.5% (1/22) in type B. The age-adjusted incidence and mortality of AAD per 100,000 inhabitants were 17.3 (type A: 11.3, type B: 6.0) and 9.6 (type A: 8.4, type B: 1.2), respectively. Both values were significantly higher in men than in women.

Conclusions

The population-based survey of emergency medical care for AAD showed that the age-adjusted incidence of AAD was two-fold higher than in previous reports, and the actual mortality rates after AAD onset were markedly higher due to the high incidence of dead-on-arrival.

Funding Acknowledgement

Type of funding sources: None. Representative CT images of type A AAD