bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic impact of the presence and management of coronary artery disease in patients undergoing TAVI
Authors: Custodio P , Madeira S , Teles R , Almeida M , Mendes M
Published: October 2021

Introduction

Approximately half of transcatheter aortic valve implantaton (TAVI) candidates have coronary artery disease (CAD). Controversial results have been reported regarding the effect of the presence/severity of CAD and its management on clinical outcomes post-TAVI.

Aim

To describe the presence, extension, severityand management of CAD pre-TAVIand to evaluate its impact on 2-yearmortality in areal world all comers population.

Methods and population

Single centre retrospective analysis from a prospectively collected institutional registry (VCROSS) including 517 patients that underwent TAVI for severe aortic stenosis between January 2009 and December 2018. Patients who underwent pre TAVI CA in the context of ACS or at other institution were excluded n=138. Ultimately 380 entered the analysis. Obstructive CAD was defined as stenosis >50% in in major epicardial vessels (>2.5 mm). The total number of major epicardial with obstructive CAD was reported as was assessed the number of those left untreated. Univariate analysis was performed to assess 1) differences between patients with or without CAD and between those with significant CAD who have or have not undergone PCI, 2) variables associated with 2-year mortality. Binary logistic regression was performed to identify independent predictors of 2-year mortality including the presence of significant CAD and the type of management.

Results

A total of 380 patients were included, 55.3% male with an average age of 83YO (±6.3), mean Euroscore II of 4.35. 76 had previous coronary artery bypassgrafting (CABG) and 136 had previous PCI (43 had both). 55 patients (14.4%) presented with normal coronary arteries, 120 (31.6%) with non-obstructive CAD and 205 (54%) with obstructive CAD. Out of the latter, 112 (29.5%) underwent PCI. Statistically significant differences were found between obstructive CAD vs non-obstructive patients in terms of age, previous history of ICP and CABG. In the subgroup population with obstructive CAD, no statistically significant differences was found in the PCI vs non PCI group, apart from previous history of ICP and CABG – Figure 1. Diabetes mellitus, previous history of percutaneous coronary intervention (PCI) and reduced ejection fraction (rEF – defined has <50% echocardiographically) had a negative prognosticimpact in the 2 year mortality of the 380 patients. 2-year mortality was 14,5% (55 patients).The presence and management of CAD pre TAVI had no impact in 2-year mortality, when accounting for the differences in previous ICP history, CABG, age, and rEF.

Conclusion

The presence and type of management of obstructive CAD in this real world all comers registry did not impact the prognosis at 2 years.

Funding Acknowledgement

Type of funding sources: None.
Risk prediction in patients with classical Low-flow, low-gradient aortic stenosis undergoing TAVI
Authors: Ludwig S , Gruhl L , Gossling A , Seiffert M , Westermann D , Sinning J M , Sugiura A , Adam M , Mauri V , Frank D , Seoudy H , Rudolph T K , Potratz M , Conradi L , Schofer N
Published: October 2021

Background

Patients with classical low-flow, low-gradient aortic stenosis (LFLG AS) undergoing transcatheter aortic valve implantation (TAVI) are known to suffer from poor prognosis. Risk prediction is difficult and predictors of outcome are scarce in this complex patient subset.

Purpose

This study aimed to develop a simple score system for risk prediction in patients with classical LFLG AS scheduled for TAVI including baseline clinical, echocardiographic and computed tomography (CT) parameters.

Methods

Among 9,150 patients undergoing TAVI (2008–2019) at five German centers, patients with classical LFLG AS were screened for availability of sufficient CT data for aortic valve calcification (AVC) quantification. Score variables were defined as all variables included into the best performing multivariable regression model. Score performance was assessed by Kaplan-Meier analysis for the endpoint of 1-year all-cause as well as c-index calculation.

Results

A total of 718 patients were included into the study. Predictors of all-cause mortality were male sex (HR 1.27 [0.98, 1.65], p=0.068), chronic obstructive pulmonary disease (HR 1.59 [1.21,2.08], p<0.001), atrial fibrillation (HR 1.33 [1.03,1.70], p=0.026), stroke volume index (HR 0.96 [0.94, 0.98], p<0.001), non-transfemoral access (HR 1.44 [1.09,1.91], p=0.011), pulmonary hypertension (HR 1.58 [1.20,2.08], p=0.0012) and low AVC density (HR 1.49 [1.16,1.90], p=0.0016). A score system was developed ranging from 0 points to 11 points. Kaplan-Meier analysis for low (0–2 points), moderate (3–6 points) and high score (>6 points) demonstrated 1-year mortality rates of 20.9%, 28.9% and 64.3% (p<0.001), respectively. C-index for prediction of 1-year mortality was 0.69 (95%-CI 0.65–0.84). The RELiEF TAVI score outperformed classical risk prediction models like the logistic euroSCORE (c-index 0.60 [95%-CI 0.51–0.72], p=0.013), the EuroSCORE II (c-index 0.57 [95%-CI 0.45–0.70], p=0.039) and the STS PROM (c-index 0.60 [0.48–0.70], p=0.035).

Conclusions

The RELiEF TAVI score is based on simple clinical, echocardiographic and CT parameters and might serve as a helpful tool for risk prediction in the vulnerable subset of patients with classical LFLG AS scheduled for TAVI.

Funding Acknowledgement

Type of funding sources: None. RELiEF TAVI Score
Predicting pacemaker dependency after TAVI with pre-procedural MSCT
Authors: Gama F , Goncalves P A , Abecasis J , Ferreira A M , Freitas P , Cavaco D , Gabriel H M , Brito J , Raposo L , Adragao P , Almeida M S , Mendes M , Teles R C
Published: October 2021

Background and aim

High degree conduction disturbances is a burdensome complication of transcatheter aortic valve implantation (TAVI). There is limited data whether such disorders are permanent or reversible. Anatomic surrogates, such as membranous septum [MS, a distance marker from aortic annulus to His-bundle surge] and calcium distribution within aortic valve have been associated with pacemaker (PM) implantation. The aim of our study was to assess predictors of long-term pacemaker dependency following TAVI.

Methods

Single center prospectively included patients that underwent pacemaker implantation following TAVI (March 2017 to September 2020). Patients who were lost to follow up, with bicuspid aortic valve, previously implanted PM and non-available or low quality MSCT exam were excluded. On MSCT, MS length was measured on modified coronal view, the aortic-valvular complex (AVC) was characterized by leaflet sector and calcium distribution was assessed on a J-score threshold of 850-Hounsfield units. Pacemaker dependency was assessed by reducing ventricular pacing to 30 bpm and defined by subsequent complete AV dissociation in patients in sinus rhythm or an escape rhythm <50 bpm in atrial fibrillation, in addition of >90% pacing percentage since implantation.

Results

From the 352 patients with inclusion criteria, 67 underwent PM implantation (19%) and 55 included in the analysis (male 33.9%, median age=85) (Figure). Median time for pacemaker implantation was 3 days [interquartile range (IQR) 3–5 days], mostly due to complete auriculo-ventricular block (76.4%, N=42). PM dependency occurred in 14 out of 55 (25.5%) patients at mean follow up of 500±363 days. Patients with PM dependency tended to have deeper implantation depth, (6.2 mm vs 5.5 mm, p=0.096) and a significantly shorter MS (5.8 mm vs 6.8 mm, P-value = 0.031) (Table). Increasing MS length was independently associated with a lower risk of PM dependency [odds ratio (OR) 0.58 per mm; 95% CI: 0.35–0.98, p=0.04] regardless prosthesis choice. MS length under 5 mm had 97.6% specificity (95% CI: 87.1–99.9) and 85.7% positive predictive value for pacemaker dependency (AUC=76.7; 95% CI 63.3–87).

Conclusion

Our findings highlight the importance of MSCT-derived MS length to stratify the risk of long term need for pacemaker. Patients with short MS (<5mm) in addition to conduction abnormality following TAVI had a high likelihood of PM dependency on the long term and should be considered for prompt PM implantation.

Funding Acknowledgement

Type of funding sources: None.
Paravalvular leaks: short and long-term outcomes of surgical versus percutaneous closure
Authors: Molina Ramos A I , Sabatel-Perez F , Becerra-Munoz V , Rodriguez-Capitan J , Carrasco-Chinchilla F , Sanchez-Espin G , Alonso-Briales J , Melero-Tejero J M , Hernandez-Garcia J M , Gomez-Doblas J J
Published: October 2021

Introduction

Paravalvular leaks (PVL) appear in 5–17% of patients who undergo surgical valve replacement, causing heart failure (HF), haemolytic anaemia, or both in 2–5% of cases. Surgical intervention (SI) is the first line treatment, although transcatheter intervention (TI) is gaining ground as an alternative. However, there are no randomized studies comparing both techniques.

Purpose

The aim of this study is to compare the short and long-term outcomes in patients with symptomatic PVL undergoing SI or TI.

Methods

We conducted a retrospective analysis of all patients who underwent SI or TI for PVL between 2004 and 2020 in our institution. The primary endpoint (PE) was the composite of cardiovascular mortality, readmission for HF and reintervention for PVL up to 24 months after the procedure. The secondary endpoints were admission length, technical and procedural success, and rate of complications. The definition of technical success was the correct placement of the device with no impaired function of the valve prosthesis and with ≤ grade II residual regurgitation. Procedural success was defined when there was technical success with no presentation of intervention-related complications.

Results

Picture 1 provides information about the clinical and procedural characteristics, initial outcome and outcome during follow-up. A total 85 procedures, 39 transcatheter (45.9%) and 46 surgical (54.1%), were performed on 67 patients. The patients who underwent TI were older (67.5 versus 61.4 years; p=0.03) had a worse functional class (NYHA III-IV 100% versus 80%; p=0.02), a lower frequency of previous endocarditis (22.2% versus 52.2%; p=0.03) and higher surgical risk (EuroScore 18.7 versus 10.4 and EuroScore II 8.6 versus 5.6; both p=0.001). The hospital stay was significantly shorter for TI (10.2 versus 30.4 days; p=0.009). Additionally, although without statistical significance, there was a lower frequency of complications (41% versus 58.7; p=0.16) and less technical success (69.2% versus 86.7%; p=0.052). There were no differences between procedure success (61.5% versus 71.1%, p=0.49). Regarding PE, at 24 months there were no differences in event-free survival (TI 55.9% versus SI 64.1%; Log-Rank p=0.8) (Picture 2).

Conclusion

The main finding of our study was the absence of significant differences in the short and long-term outcomes (composite of cardiovascular mortality, readmission for HF and reintervention) between surgical versus percutaneous closure. In conclusion, transcatheter intervention must be considered as a good alternative, particularly in high-risk surgical patients.

Funding Acknowledgement

Type of funding sources: None. Picture 1. Baseline characteristicsPicture 2
Percutaneous access versus surgical cutdown in TAVI: vascular and bleeding complications
Authors: Stathogiannis K , Latsios G , Oikonomou G , Synetos A , Drakopoulou M , Soulaidopoulos S , Toskas P , Xanthopoulou M , Lalou E , Kolyviras A , Tzifos V , Benetos G , Karmpalioti M , Tsioufis C , Toutouzas K
Published: October 2021

Background

Access options for transcatheter aortic valve implantation (TAVI) are vital, since use of large sheaths may lead to access-related complications and bleeding.

Purpose

To determine the access-related vascular and bleeding complications of patients undergoing transfemoral TAVI.

Methods

Consecutive patients scheduled for transfemoral TAVI were retrospectively grouped according to vascular access [percutaneous access (p-TAVI) and surgical cutdown (sc-TAVI)]. Primary end points were vascular and bleeding complications, based on the VARC-II criteria.

Results

Totally, 187 patients were included in the analysis (p-TAVI: 124 patients; sc-TAVI: 63 patients). Mean procedure time was shorter in the p-TAVI group compared to the sc-TAVI group (45.65±6.17 min versus 64.05±15.73 min, p<0.001). Contrast use was lower in the p-TAVI group compared to the sc-TAVI group (81.18±15.96 ml versus 106.75±25.67 ml, p<0.001), which resulted in higher rates of acute kidney injury in the sc-TAVI group (13% versus 1%, p=0.01). Vascular access complications occurred numerically but not statistically more often in the p-TAVI group compared to the sc-TAVI group (11% versus 5% for minor complications and 6% versus 3% for major complications respectively, p=0.10). Patients in the p-TAVI group had the same minor and major bleeding complications compared to the sc-TAVI group (11% versus 8% for minor, 10% versus 6% for major bleeding complications respectively, p=0.49), but no life-threatening bleeding (0% versus 1.5%).

Conclusions

Transfemoral access options in TAVI (surgical cutdown or percutaneous) have similar efficacy and should be offered in TAVI patients if and when appropriate.

Funding Acknowledgement

Type of funding sources: None.
An assessment of ethnic and environmental influences on the phenotypes of hypertension
Authors: Iyeku A C , Jalaludeen N , Ojji D B , Cheriyan J , McEniery C M , Wilkinson I B
Published: October 2021

Background

Hypertension is a growing global concern with developing countries now having the highest prevalence. Environmental factors such as socioeconomic status and diet, together with ethnicity-related factors may influence the development of hypertension and its complications such as left ventricular hypertrophy (LVH). However, the relative contributions of environment and ethnicity to these outcomes remain poorly understood.

Purpose

To test the hypothesis that black hypertensives living in Nigeria would have a higher prevalence of hypertensive target organ damage (i.e. LVH and dysfunction) compared with black hypertensives living in the UK.

Methods

We conducted a three-arm comparative study based on self-defined ethnicity and country of residence. We carried out detailed cardiovascular phenotyping in untreated Black hypertensives (n=53) living in Nigeria (BNig), untreated Black (BUK) hypertensives (n=25), and untreated White (WUK) hypertensives (n=59) living in the UK. We measured brachial and central blood pressure and undertook 2D echocardiography in all the participants. In addition, we collected serum and 24-hour urine biochemistry.

Results

The three groups had similar mean age and BMI (Table 1). The BNig group had significantly higher brachial SBP (P=0.01) and LV mass index (LVMI); P<0.001) compared with the BUK group. Furthermore, both BNig & BUK groups each had significantly higher brachial SBP (BNig: 162mmHg, BUK: 151mmHg) and LVMI (BNig: 100.9g/m2, BUK:86.4 g/m2) compared with the WUK group (Brachial SBP: 144mmHg, LVMI: 82.2g/m2). The prevalence of concentric LVH was similar in the two UK groups (BUK: 10%, WUK: 12%) but higher in the BNig group (41%). Septal early diastolic velocity was significantly lower in BNig group (7.0cm/s) compared to BUK (10.0cm/s) and WUK (10.0 cm/s). After adjusting for 24-hour sodium, brachial SBP (162mmHg) in the BNig group was still significantly higher compared with the other two groups [F(2,109)=13.805, BK (151mmHg, P=0.032), White UK (145mmHg, P<0.001)). However, after controlling for SBP, difference in LVMI persisted only between the BNig (EMM: 98.4 g/m2) versus WUK (EMM: 84.2 g/m2) groups, with no significant difference in BNig vs BUK (86.6g/m2, P=0.156) [F(2,128)=4.245, p=0.016].

Conclusion

Our data suggest that higher SBP and salt intake do not explain all of the environmental differences in the prevalence of LVH and LV dysfunction in hypertensive patients drawn from different ethnicities and environments, suggesting that other factors are likely to play an important role. Further work is in a larger group is required to confirm these findings.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Niger Delta Development Commission
Right ventricular longitudinal systolic strain as a predictor of new onset heart failure with preserved ejection fraction in hypertensive patients
Authors: Marketou M , Kochiadakis G , Patrianakos A , Maragkoudakis S , Theodosaki O , Zervakis S , Anastasiou I , Fragkiadakis K , Plevritaki A , Papadaki S , Parthenakis F
Published: October 2021

Purpose

Accurate assessment of right ventricular (RV) systolic function is important, as it is an established prognostic marker in cardiac diseases. Speckle-tracking echocardiography is a sensitive tool for detection of subclinical left ventricular impairment in essential hypertension. We associated RV function using longitudinal peak systolic strain (GLS) in patients with essential hypertension with the risk of future development of heart failure with preserved ejection fraction (HFpEF).

Methods

We performed a retrospective observational study that included 452 patients with essential hypertension (266 males, aged 63±18 years) and 175 normotensives (100 males, aged 66±15 years). Standard echocardiography was performed at the initial visit. 2D speckle tracking echocardiography with evaluation of longitudinal strain in each segment of the RV (basal: RVLS-B; mid: RVLS-M, apical: RVLS-A) and global RV free-wall strain (RVLS-G) were also performed. We studied the cases of new onset HFpEF in hypertensive patients.

Results

The median follow up was 85 months (22–122). RVLS-G, RVLS-B and RVLS-M were significantly impaired in hypertensives compared to controls (RVLS-G: −16.1±9.7 vs −20.0±5.1, RVLS-B: −11.7±3.7 vs −20.6±3.3, RVLS-M: −16.3±5.4 vs −20.7±4.9, p<0.05 for all). No significant difference was detected for the RVLS-A (−20.1±3.8 for hypertensives vs −21.31±6.5 for controls, p=NS). Thirty two hypertensive patients developed HFpEF (7%). A cut-off RVLS-G worse than −17% was significantly associated with new onset HFpEF (p<0.001) in those patients. A multivariate Cox regression analysis showed that RVLS-G had independent significant prognostic value for the risk of HFpEF (HR: 10.5, 95% confidence interval (CI): 7.3–25.4).

Conclusions

Essential hypertension leads to a decrease of RVLS which is strong predictor of a new onset HFpEF. Future studies are needed to assess the significance of these findings and the effects of treatment.

Funding Acknowledgement

Type of funding sources: None.
The predictive value of central aortic blood pressure on new onset stroke and differences between brachial blood pressure in a Chinese hypertensive population, a prospective cohort study
Authors: Cao C T Y , Ding D C C , Huang H X
Published: October 2021

Objectives

This study aimed to investigate the association between noninvasive central aortic blood pressure and the risk of first stroke in a Chinese community–based population, meanwhile compare the prediction ability of central SBP and peripheral SBP.

Methods

A total of 8473 Chinese participants without history of stroke and atrial fibrillation at baseline were selected from “Hypertension and Stroke Prevention and Control Project” for analysis. The endpoint of the study was first total stroke and stroke subtypes (ischemic stroke and hemorrhagic stroke). Cox proportional hazards regression, smoothing curve fitting, subgroup analysis, and Kaplan-Meier curve were used to analysis the relationship between central/peripheral systolic blood pressure and first stroke.

Results

Participants were 60.9±9.6 years old, 63.5% were males, and 96.1% had hypertension. After a mean 3.3-year follow-up, the incidence of first total stroke, first ischemic stroke and first hemorrhagic stroke were 5.1%, 4.6%, and 0.5%, respectively. In multivariate logistic-regression analyses, central and peripheral SBP were both independently associated with first total stroke and first ischemic stroke after adjusting for various confounders. Peripheral SBP's significant association with first total and ischemic stroke disappeared when combined analyzed with central SBP, whereas central SBP was still significantly related with first total and ischemic stroke after adjustment of peripheral SBP. For first hemorrhagic stroke, no significant differences were observed between central SBP and peripheral SBP. Subgroup analysis showed that the central SBP-first stroke association was significantly stronger in males (HR: 1.38; 95% CI: 1.16, 1.63) than in females (HR: 1.10; 95% CI: 0.97, 1.24; P-interaction = 0.028).

Conclusions

Among the Chinese community–based population, central SBP is a stronger predictor compared with peripheral SBP for first stroke, especially ischemic stroke.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Key R&D Projects, JiangxiOutstanding Person Foundation
The association between central ambulatory blood pressure and end-organ damage
Authors: Lu I N , Yu S K , Smith J , Woodcock-Smith J , Jalaludeen N , Cheriyan J , Wilkinson I , McEniery C
Published: October 2021

Background/Introduction

Central blood pressure (BP) measured in the clinic relates more strongly to end-organ damage and may be superior to brachial BP in predicting cardiovascular events. Measurement of central ambulatory BP (ABP) is now possible and emerging data suggest that central ABP is better correlated with left ventricular mass index (LVMI) than brachial ABP.1,2 However, the association between central ABP and other measures of end-organ damage remains unclear.

Purpose

We investigated the association between brachial or central ABP and end-organ damage, in a large community-based population of untreated individuals.

Method

1091 participants (mean age 45±18 years; 589 females) had simultaneous measurements of brachial and central ABP over 24 hours, using the Mobil-O-Graph device. Central ABP was derived using two waveform calibration methods (1: mean/diastolic BP; 2: systolic/diastolic BP). Participants also underwent measurement of aortic pulse wave velocity (aPWV; SphygmoCor device) in the clinic. In a subset of 675 individuals, LVMI was assessed by echocardiography and in 610 individuals, carotid intima-media thickness (CIMT) was measured, using ultrasound. 24-hour and daytime brachial and central ambulatory systolic BP (ASBP) and pulse pressure (APP) were considered.

Results

The Pearson's coefficient for each correlation is listed in Table 1. LVMI was most strongly correlated with 24-hour central ASBP, using calibration method 1 (MAP/DBP; r=0.403, P<0.001). CIMT was most strongly correlated with daytime central ASBP, again derived from calibration method 1 (r=0.341, p<0.001), whereas aPWV measured in the clinic, was most strongly correlated with 24-hour central ASBP, derived from calibration method 2 (SBP/DBP; r=0.441, P<0.001). Based on z statistics, all correlations reported above were significantly stronger than equivalent correlations using brachial ASBP (P<0.001 for all three comparisons of correlation coefficients).

Conclusion

Measurement of central ABP relates more closely to end-organ damage than equivalent measures based on brachial ABP. Central ABP may provide valuable additional information concerning cardiovascular risk above and beyond brachial ABP.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): British Heart Foundation
External validation of prediction models for obstructive coronary artery disease in patients with suspected stable coronary artery disease
Authors: Bjerking L , Winther S , Hansen K W , Galatius S , Boettcher M , Prescott E
Published: October 2021

Background

Pre-test probability (PTP) is an important tool in the diagnostic work-up for obstructive coronary artery disease (CAD) but must be calibrated to the declining disease prevalence in patients referred to diagnostic testing.

Purpose

To externally validate the published basic and clinical PTP models in a contemporary angina cohort with low prevalence of CAD and to compare with the reference European Society of Cardiology 2019 PTP (ESC 2019 PTP).

Methods

The validation cohort consisted of 42.328 patients (54% women, age ≥30 years, no previous CAD) with symptoms of CAD referred for cardiac computed tomography angiography in the western region of Denmark from 2008–2017 (3.3 million inhabitants). Obstructive CAD was defined from either invasive angiography as stenosis >50%, or when performed, from FFR <0.8 in coronary arteries with diameters >2 mm.

The basic prediction model included type of angina, sex, and age, and the clinical model added diabetes, family history of CAD, and dyslipidemia. The ESC 2019 PTP was calculated from age, sex, and angina symptoms. Discrimination, calibration, and negative predictive value (NPV) were measured for all three models.

Results

Obstructive CAD was present in 3718 (8.8%). In the ESC 2019 PTP model, the basic model, and the clinical model 19.5%, 48.5%, and 55.7% were classified as very low risk and only 1.6%, 3.7%, and 3.5% of these had obstructive CAD, respectively (figure 1). Discrimination was similar for the three models with AUC of 0.76 (95% CI 0.75–0.77), 0.74 [0.73–0.75], and 0.76 [0.75–0.76], for the ESC 2019 PTP, basic, and clinical model, respectively. At the clinically relevant very low predicted probability (≤5%) of CAD, the clinical and basic model were very well calibrated, whereas the ESC 2019 PTP model overestimated the CAD prevalence. NPV at cut-off ≤5% were 98.4% [98.1–98.7] for the ESC 2019 PTP model, 96.3% [96.1–96.6] for the basic model, and 96.5% [96.3–96.7] for the clinical model. At cut-off <15%, NPVs were 96.1% [95.8–96.3] for the ESC 2019 PTP model, 94.5% [94.2–94.7] for the basic model, and 94.2% [94.0–94.5] for the clinical model.

Conclusion

In a population with a prevalence of 8.8% obstructive CAD, a clinical prediction model including diabetes, family history of CAD, and dyslipidemia in addition to the variables of the ESC 2019 PTP model ruled out 36.2% more patients than the ESC 2019 PTP model (23.592 vs. 8245 patients) while only overlooking 1.9% more cases of obstructive CAD when choosing a cut-off ≤5%. Use of this model is therefore potentially cost saving.

Funding Acknowledgement

Type of funding sources: None. Figure 1Figure 2
The associations of serum homoarginine to long-term prognosis in patients with chronic coronary syndrome and non-obstructive coronary artery disease
Authors: Storesund S K , Ueland P M , Svingen G , Lonnebakken M T , Nygard O , Pedersen E R
Published: October 2021

Background

Although generally at lower risk than those with obstructive CAD, patients with non-obstructive CAD (NOCAD) are heterogeneous concerning long-term prognosis. Notably, reversible ischemia due to vascular dysfunction is a frequent finding in NOCAD patients (1). The endogenous, non-proteinogenic amino acid homoarginine (hArg) increases the availability of nitric oxide (NO) and thereby the NO-dependent vasodilatation (2). Several studies have reported a strong inverse relation between serum hArg levels and cardiovascular disease (CVD) risk among patients with obstructive CAD. However, the prognostic implications of serum hArg levels in NOCAD patients have not been explored previously.

Purpose

We evaluated serum hArg as a predictor of long-term risk of CVD mortality among patients with NOCAD.

Methods

1046 patients with chronic coronary syndrome (CCS) underwent elective coronary angiography during 2000–2004, with the findings of NOCAD. Serum hArg was measured by liquid chromatography-tandem mass spectrometry in samples that had been frozen and stored at −80°C. The association of serum hArg to CVD mortality risk was visualized in a generalized additive regression plot and further explored using Cox regression. The models included age, sex, body mass index, hypertension, diabetes, smoking status, serum LDL cholesterol and estimated glomerular filtration rate as independent covariables. We evaluated model discrimination and risk classification by calculating C-statistics and net reclassification improvement (NRI >0), respectively.

Results

Median (25th-75th percentiles) age at inclusion was 57 (51–65) years, 48.5% were women and median (25th-75th percentiles) level of serum hArg was 1.87 (1.47–2.38) μmol/L. During median (25th- 75th percentiles) 14.1 (13.2–15.4) years of follow-up 5.7% of the patients died from CVD. The multivariable adjusted hazard ratio (95% confidence interval) per SD increment of (log transformed) hArg was 0.53 (0.40–0.70) in relation to CVD mortality. The multivariable model without biomarker provided a C- statistics for CVD mortality of 0.79 which increased to 0.82 by the addition of serum-hArg to the model (Δ area =0.03, P=0.01). Further, serum hArg provided a high NRI (95% CI) of 0.53 (0.40–0.70), P<0.001.

Conclusion

We demonstrated a strong inverse relationship between serum hArg and long-term risk of CVD mortality among patients with NOCAD. Our study adds to previous literature linking low hArg with vascular dysfunction and adverse CVD prognosis. The potential clinical usefulness of serum hArg measurements for the identification of a high-risk phenotype in NOCAD warrants further evaluation.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): The Western Norway Regional Health Authority
Impact of cumulative exposure to LDL cholesterol on cardiovascular events in patients with familial hypercholesterolemia
Authors: Tada H , Okada H , Nohara A , Yamagishi M , Takamura M , Kawashiri M
Published: October 2021

Aims

Recent studies suggest that cumulative exposure to LDL-cholesterol (LDL-C) leads to the development of atherosclerotic cardiovascular disease (ASCVD). However, few studies have investigated whether this link extends to individuals with familial hypercholesterolemia (FH), a relevant patient population. We aimed to determine whether cholesterol-year-score, an indicator of cumulative exposure to LDL-C, is associated with ASCVD events among Japanese patients with FH

Methods and results

We retrospectively investigated the health records of 1,050 patients with clinical FH diagnosis who were referred to our institute between April 1990 and March 2019. We used Cox proportional hazards models adjusted for established ASCVD risk factors to assess the association between cholesterol-year-score and major adverse cardiovascular events (MACEs), including death from any cause or hospitalization due to ASCVD events. Cholesterol-year-score was calculated as LDL-C max × [age at diagnosis / statin initiation] + LDL-C at inclusion × [age at inclusion − age at diagnosis / statin initiation]. The median follow-up period for MACE evaluation was 12.3 (interquartile range, 9.1–17.5) years, and 177 patients experienced MACEs during the observation period. Cholesterol-year-score was significantly associated with MACEs (hazard ratio [HR], 1.35; 95% confidence interval, 1.07–1.53; P=0.0034, per 1,000 mg-year/dL), independent of other traditional risk factors including age and LDL-C, based on cross-sectional assessment. Cholesterol-year-score improved the discrimination ability of other traditional risk factors for ASCVD events (C-index, 0.901 versus 0.889; P=0.00473).

Conclusion

Cumulative LDL-C exposure was strongly associated with MACEs in Japanese patients with FH, warranting early diagnosis and treatment initiation in these patients.

Funding Acknowledgement

Type of funding sources: None.
Potential cardiovascular risk reduction with evolocumab in the real world: a simulation in patients with a history of myocardial infarction from the HEYMANS register
Authors: Ray K , Bridges I , Bruckert E , Perrone-Filardi P , Annemans L , Sibartie M , Dhalwani N , Villa G
Published: October 2021

Background/Introduction

FOURIER included 22,351 patients with a history of myocardial infarction (MI) and a median low-density lipoprotein cholesterol (LDL-C) of 2.4 mmol/L. Reducing LDL-C with evolocumab reduced the risk of major cardiovascular (CV) events by 1.3%, in absolute terms, over 2.2 years. Whether similar benefits might be observed in real-world evidence from evolocumab use is unknown.

Purpose

Simulate CV risk and assess the potential CV risk reduction among a large European cohort of evolocumab users with a history of MI.

Methods

We used interim data from HEYMANS, a register of patients initiating evolocumab in routine clinical practice across 12 European countries, from August 2015 with follow-up through July 2020. Demographic and clinical characteristics, lipid-lowering therapy (LLT), and lipid values were collected from routine medical records (6 months prior to evolocumab initiation through 30 months post initiation). Patients with a history of MI were considered and two sub-cohorts were created: recent MI (MI ≤1 year before evolocumab initiation) and remote MI (MI >1 year before evolocumab initiation). For each patient, we 1) simulated their CV risk using three different sources, correcting for age and LDL-C: i) the REACH equation, ii) FOURIER, iii) an observational study including FOURIER-like patients; 2) calculated their absolute LDL-C reduction on evolocumab; 3) simulated their relative risk reduction (RRR) by randomly sampling from the inverse probability distribution of the rate ratio per 1 mmol/L from the key secondary endpoint in the FOURIER landmark analysis; 4) calculated their absolute risk reduction (ARR) and number needed to treat (NNT) over 2 years (recent MI) or 10 years (remote MI).

Results

Our analysis included 90 recent MI and 489 remote MI patients initiating evolocumab in clinical practice per local reimbursement criteria, with up to 24 months follow-up. Median (inter-quartile range) age was 59 (53–67) and 61 (53–68) years in recent MI and remote MI patients, respectively. LDL-C before evolocumab was 3.8 (3.2–4.6) and 3.6 (3.0–4.5) mmol/L. Absolute LDL-C reduction on evolocumab was 2.2 (1.4–2.8) and 2.2 (1.6–2.8) mmol/L, meaning relative LDL-C reduction of 60% (44%-73%) and 62% (47%-72%), respectively. Predicted ARR with evolocumab was substantial, whether over 2 years (recent MI) or over 10 years (remote MI). See Table 1.

Conclusions

This cohort of evolocumab users in clinical practice had a higher baseline LDL-C and CV risk than patients enrolled in FOURIER. LDL-C reduction and RRR were very similar in recent MI and remote MI patients. However, patients with a recent MI had a higher short-term CV risk and therefore showed a larger ARR on evolocumab.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Amgen
Impact of smoking cessation on depression after acute coronary syndrome
Authors: Krasieva K , Clair C , Gencer B , Carballo D , Klingenberg R , Raber L , Windecker S , Rodondi N , Matter C M , Luscher T F , Mach F , Muller O , Nanchen D
Published: October 2021

Background

Smoking and depression are two risk factors for acute coronary syndrome (ACS) that often go hand-in-hand, as smokers are more likely to be depressed and people that are depressed are more likely to be smokers. Smoking cessation in depressed patients with ACS may worsen depressive symptoms, which could increase the risk of recurrence of cardiac events and decrease adherence to other cardiac risk-reducing lifestyle changes.

Purpose

We aimed to investigate the evolution of depression according to smoking cessation one-year after ACS. Furthermore, we investigated if there was a higher incidence of one-year depression among ACS smokers who quit in comparison to continuous smokers.

Method

Data from 1,822 patients with ACS of the Swiss multicenter SPUM-ACS cohort study were analysed over a one-year follow-up period. Participants were classified in three groups based on smoking status one-year post-ACS – continuous smokers, smokers who quit within the year post-ACS, and non-smokers. Depression status at baseline and at one-year after the index ACS event was assessed with the Center for Epidemiologic Studies Depression scale (CES-D) and antidepressant drug use. A multivariate adjusted logistic regression model was used to calculate the risk ratio (RR) between groups.

Results

In comparison to depressed smokers who continued to smoke one year post-ACS, depressed smokers who quit smoking had an adjusted RR of 2.02 (95% CI 1.04–3.92) of improving their depression. Among 543 non-depressed ACS smokers, new depression at one-year was found in 57/266 (21.4%) smokers who quit, and 68/277 (24.6%) continuous smokers, with an adjusted RR of 0.89 (95% CI 0.58–1.36) of incidence of new depression.

Conclusion

Smokers with depression at the time of ACS who quit smoking improved more frequently their depression compared to those who continued smoking. Although not statistically significant, there was a smaller incidence of new depression among smokers who quit after ACS in comparison to continuous smokers.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation
Increased prevalence of premature coronary atherosclerosis after preeclampsia
Authors: Hauge M G , Damm P , Kofoed K F , Ersboell A S , Johansen M , Sigvardsen P E , Fuchs A , Kuhl J T , Nordestgaard B G , Koeber L , Gustafsson F , Linde J J
Published: October 2021

Background

Women with preeclampsia have increased risk of manifest coronary artery disease later in life. However, it remains unknown if and when premature coronary atherosclerotic stages can be identified. This knowledge could enable early intervention in women considered at high risk for future manifest coronary artery disease.

Purpose

Using cardiac computed tomography, we aimed to investigate the prevalence of premature coronary atherosclerosis in women with previous preeclampsia in comparison with women from the general population.

Methods

Women, aged 40–55 years, with previous preeclampsia were recruited in the CPH-PRECIOUS study and compared 1:1 with age- and parity-matched women from the CGPS. Both groups underwent a cardiac computed tomography, including a contrast-enhanced coronary computed tomography angiography and a non-contrast coronary artery calcium scoring, as well as an overall assessment of cardiovascular risk factors imbedded in an extensive questionnaire. Cardiac computed tomography examinations were analysed blindly. The main outcome of the study was the prevalence of any coronary atherosclerosis defined as any plaque at coronary computed tomography angiography or a calcium score >0 in case of a non-diagnostic coronary computed tomography angiography.

Results

A total of 1,424 women were included (715 women with previous preeclampsia and 709 controls from the general population). Women with previous preeclampsia were more likely to have cardiovascular risk factors (hypertension, dyslipidaemia, diabetes mellitus). The prevalence of any coronary atherosclerosis was significantly higher in the preeclampsia group (27.4% vs. 20.0%) (P=0.001). A calcium score >0 was also more prevalent in the preeclampsia group (16.6% vs. 11.8%) (P=0.009). Preeclampsia remained an independent risk factor for the presence of any coronary atherosclerosis after adjusting for cardiovascular risk factors (age, hypertension, dyslipidaemia, diabetes, smoking, body mass index, parity) (OR=1.37, 95% CI (1.05–1.79), P=0.021).

Conclusion

Women with previous preeclampsia are more likely show premature signs of coronary atherosclerosis compared with an age- and parity matched control group from the general population. Preeclampsia is an independent risk factor for premature coronary atherosclerosis.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): The Danish Heart FoundationSkibsreder Per Henriksen, R og Hustrus FondKong Christian den Tiendes FondBrødrene Hartmanns FondHans og Nora Buchards FondArvid Nilssons FondAnita og Tage Therkelsens FondLægefondenAase og Ejnar Danielsens FondHjertecentrets Forskningsudvalg (Rigshospitalet)Direktør Kurt Bønnelycke og Hustru Fru Grethe Bønnelyckes FondLægeforeningens ForskningsfondTorben & Alice Frimodt FondHenry og Astrid Møllers Fond
Low-dose rivaroxaban associated with lower incidence of all-cause mortality and bleeding complications in older patients with non-valvular atrial fibrillation
Authors: Chiou W R , Su M I , Lee Y H , Lin P L , Liu C W
Published: October 2021

Background

Low-dose rivaroxaban 10mg daily was used in the J-ROCKET AF trial, and it demonstrated the safety in Asian population. It remains unclear whether low-dose rivaroxaban vs. standard dose 20mg daily is associated with efficacy, safety, and net-clinical outcomes in older Asian patients with non-valvular atrial fibrillation.

Purpose

To evaluate the effects of low-dose rivaroxaban on efficacies and safeties in the old patients age more than 85 years.

Methods

We retrospectively enrolled the patients from medical records between Oct 2012 and Nov 2016. We used 2x2 factorial design by age of 85 years and use of low-dose rivaroxaban. The study outcomes were one-year all-cause mortality and bleeding complications.

Results

The study cohort consisted of 2,386 patients with the mean age 76.6 years (SD 10.5), 51.8% male, CHA2DS2Vsc 4.4 (SD 1.7) and HASBLED 1.6 (SD 1.0). In the age ≥85 group (n=593), low vs. standard dose rivaroxaban had a lower incidence of all-cause mortality (5.3% vs. 10.6%, P=0.021), whereas the incidence of all-cause mortality was greater in the low dose rivaroxaban compared with the standard dose in the age <85 group (3.7% vs. 1.8%, P=0.012). No significant differences of bleeding complication rates were found between the low- and standard-dose rivaroxaban regarding age <85 or ≥85 years. After adjusting for potential confounders, low dose rivaroxaban was associated with a decreased risk of all-cause mortality in the age ≥85 group (adjusted HR: 0.400 95% CI: 0.215–0.743, P=0.004), but the significant association was not found in the age <85 group (adjusted HR: 1.101 95% CI: 0.557–2.174, P=0.782).

Conclusion

Low dose rivaroxaban was associated with a decreased risk of all-cause mortality in the patients with non-valvular atrial fibrillation and age ≥85 years.

Funding Acknowledgement

Type of funding sources: None.
Prevalence of cardiovascular risk in HIV positive patients
Authors: Pinto Velasquez J M , Velasquez Padilla J P
Published: October 2021

Introduction

HIV is considered a chronic disease which increases cardiovascular risk due to factors intrinsic to the patient, associated with HIV itself, such as immune activation, inflammation and immunodeficiency, as well as factors associate with antiretroviral therapy, mainly due to metabolic alterations. Coronary and/or cardiovascular risk is the probability of developing coronary or cardiovascular disease in a given period of time, usually 5 or 10 years, which can be estimated through different scales, which can be qualitative or quantitative.

Purpose

To determine cardiovascular risk according to Framingham and Q-risk scales in low (0 – 10%), intermediate (10.1 – 12%), and high (>20%), clinically characterized to patients with higher risk, relating and comparing vascular age with chronological age, and to assess cardiovascular risk according to antiretroviral therapy used.

Methods

A database was created using SPSS 25, summarizing data through frequencies and percentages, organized and presented in frequency and contingency tables. The association was evaluated through the chi-square test, being considered statistically significant when the p-value was <0.005, with a confidence interval of 95%, cross-sectional descriptive study whose population was HIV-positive patients attending the clinic for comprehensive care of HIV and chronic infections, conducted in 2019.

Results

301 patients were included, all presented cardiovascular risk, low (218), intermediate (75), high (8). Females (215 patients) higher risk than male (p 0.006), this risk increased gradually with age (p 0.005). The main associated comorbidities: diabetes mellitus (p 0.005), arterial hypertension (p 0.004) and smoking (p 0.006). The main clinical factors that determined cardiovascular risk: total cholesterol greater than 200 mg/dl (p 0.006), high density cholesterol <35mg/dl, (p 0.004) systolic blood pressure >130mmHG (p 0.004) and diastolic blood pressure >80mmHG (p 0.004). Patients using protease inhibitors as antiretroviral therapy had a higher cardiovascular risk (p 0.006). In all age groups, vascular age was higher than chronological age (2 years).

Conclusion

All HIV-positive patients included in the study presented a 10-year cardiovascular risk (low, intermediate and high), 86.7% of patients on protease inhibitors were at intermediate cardiovascular risk.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): Hospital infectiuos disease clinic
PCSK9 inhibition with alirocumab decreases plasma lipoprotein(a) concentration by a dual kinetic mechanism of action
Authors: Ying Q , Pang J , Chan D C , Barrett P H R , Watts G F
Published: October 2021

Background

Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL)-like particle, covalently bound to apolipoprotein(a) [apo(a)]. Recent trials show that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, such as alirocumab, decrease plasma Lp(a) levels and risk of atherosclerotic cardiovascular disease (ASCVD). The kinetic mechanism for lowering Lp(a) by PCSK9 inhibitors may differ according to pre-treatment apo(a) levels.

Purpose

We investigated the effect of alirocumab on Lp(a) metabolism in 21 long-term statin-treated patients [Lp(a) >0.5 g/L in all] with moderate-high (n=10) and high (n=11) apo(a) concentrations according to a cutoff of median apo(a) levels of 145 nmol/L.

Methods

Apo(a) kinetics were studied before and after 12-week treatment with alirocumab (150 mg subcutaneously fortnightly). Apo(a) fractional catabolic rate (FCR) and production rate (PR) were determined using intravenous D3-leucine administration, mass spectrometry and compartmental modelling.

Results

The plasma concentration and PR of apo(a) were significantly higher in patients with high apo(a) than in patients with moderate-high apo(a) levels (273±30 nmol/L vs 130±4.7 nmol/L and 6.0±0.69 nmol/kg/day vs 2.6±0.15 nmol/kg/day, respectively; P<0.001). The FCR of apo(a) was not significantly different between two groups (0.48±0.02 pools/day vs 0.45±0.01 pools/day, P>0.05). In patients with moderate-high apo(a) levels, alirocumab significantly lowered plasma apo(a) levels (−17%, P<0.01) and increased the FCR of apo(a) (+26%, P<0.001), but did not alter apo(a) PR. In contrast, alirocumab significantly lowered plasma apo(a) concentrations (−31%, P<0.001) via a dual mechanism that increased apo(a) FCR (+31%, P<0.001) and lowered PR (−9%, P<0.05) in patients with high apo(a) levels. The reductions in apo(a) concentration and PR with alirocumab in the high apo(a) group remained significant after adjusting for background statin when compared with patients with moderate-high apo(a) levels (P<0.05).

Conclusions

In statin-treated patients with elevated Lp(a), alirocumab may lower elevated plasma Lp(a) concentrations by a dual mechanism of increasing the catabolism and decreasing the production of Lp(a) particles, specifically in patients with relatively high apo(a) concentrations.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This independent research was funded by an Investigator Initiated Study Concept Research Grant from Regeneron Pharmaceuticals and Sanofi (Protocol No. LPS 14508). Figure 1Figure 2