bluuebunny/crossref_metadata_2025_split huggingface dataset:
Echocardiographic phenogrouping by machine learning for risk stratification in the general population
Authors: Sabovcik F , Cauwenberghs N , Vens C , Kuznetsova T 
Published: November 2020

Abstract

Background
Improved taxonomical classification of routinely measured echocardiographic parameters is needed for better phenotypic characterisation of the asymptomatic stages of cardiac maladaptation. This would create opportunities to intervene early in the course of the heart disease and prevent progression to more advanced stages and adverse events.

Purpose
We tested the hypothesis that an unbiased clustering analysis utilizing echocardiographic indexes reflecting left heart structure and function and hemodynamic measurements could identify phenotypically distinct groups of asymptomatic individuals in the general population.

Methods
We prospectively studied 1407 community-dwelling individuals (mean age, 51.0 years; 51.5% women), in whom we performed clinical and echocardiographic examination at baseline and collected cardiac events on average 8.5 years later. Cardiac phenotypes that were correlated at r&gt;0.8 were filtered, leaving 15 less redundant echocardiographic and hemodynamic features for phenogrouping. We employed two methods of unsupervised machine learning: agglomerative hierarchical clustering and Gaussian mixture using expectation minimization algorithm. The optimal number of phenogroups was chosen based on the combination of the cohesion/separation approach (silhouette index) and stability. Cox regression was used to demonstrate the clinical validity of phenogroups.

Results
Overall, both methods agreed with respect to cluster assignment (RI=0.75). Unbiased clustering analyses classified study participants into 3 distinct phenogroups that differed markedly in cardiac structure/function indexes and hemodynamics used for cluster analysis (Figure, left panel). Indeed, phenogroup 3 had the worst left ventricular diastolic function (ie, lowest e' velocity and left atrial reservoir strain, but highest E/e', deceleration time, and left atrial volume index), highest left ventricular mass index, as well as highest systolic blood pressure and pulse pressure (Figure, left panel). The phenogroups were also different in other clinical characteristics and incidence of cardiac events (Figure, right panel). Even after adjustment for traditional risk factors, phenogroup 3 had the highest risk of cardiac events as compared to cluster 1 (Figure, right panel).

Conclusions
Unsupervised learning algorithms integrating routinely measured cardiac imaging and hemodynamic data can provide a clinically meaningful classification of cardiac health in asymptomatic individuals. This approach might facilitate early detection of cardiac maladaptation and improve risk stratification.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): Research Foundation Flanders
Characteristics of cardiac rehabilitation programs in Latin America and the Caribbean, and estimation of capacity and needs in the region
Authors: Chacin A , Grace S.L , Anchique-Santos C , Supervia M , Turk-Adawi K , Britto R , Scantlebury D , Araya-Ramirez F , Gonzalez G , Burdiat G , Salmon R , Mamataz T , Medina-Inojosa J , Lopez-Jimenez F 
Published: November 2020

Abstract

Background
Cardiac rehabilitation (CR) is an established model of cardiovascular (CV) prevention that has proven benefits. Availability, characteristics and need of CR programs in Latin-American and Caribbean (LAC) countries remains poorly characterized. This study aims to establish the availability, capacity, density and aspects of CR delivery in LAC.

Methods
A cross-sectional survey was administered to CR programs in 24 LAC. Local CV organizations and societies identified CR programs. Characteristics of individual CR program were reviewed including: funding sources, core components, healthcare providers, and dose (number of sessions per weeks X total number of weeks) of CR. National CR capacity (median number of patients a program could serve per year X number of programs per country), density (Ischemic Heart Disease [IHD] incidence per year/ national capacity), need (IHD incidence per year- national capacity) and occupancy (median number patients program served per year/national capacity) were computed based on survey responses.

Results
At least one CR program was identified per LAC country (total 255 programs across 24 countries). Data was collected in 20 of the 24 countries. Responses were received from 139/255 programs (median program response rate=55%; Table 1). Over 50% (n=73) of programs were funded by multiple sources (government, hospital/clinic, private health insurance); Self-payment was reported by 63% programs, in which 24 (33.8%) patients paid over 50% of the cost. Guideline-indicated conditions were accepted in 77% or more programs. Physiotherapists (n=106, 76.3%), cardiologists (n=105, 75.5%) and dietitians (n=79, 56.8%) were the most common healthcare providers on CR teams. Regionally, programs offered 9 (IQR = 8–10) core components (patient education, exercise prescription and initial assessment delivered by nearly all programs). Median CR was 36 (IQR = 24–56) sessions/patient. Twenty-seven (20.9%) programs offered alternative CR models (e.g., home or community-based and hybrid models). Median national capacity was 500 CR spots/country (IQR= 200–2300). Regional density was 1 CR spot per 24 incident IHD patients per year. Greatest need in absolute terms for CR was observed in Brazil, Dominican Republic and Mexico (all with &gt;150,000 spots needed per year to manage incident IHD patients; Table 1). Occupancy ranged from over 100% in Colombia to 15% in Chile (median=60%, IQR = 32%–81%), Table 1.

Conclusion
In LAC countries, there is very limited capacity to meet the need for CR. Nature of CR services varied regionally.

Funding Acknowledgement
Type of funding source: None
A predictive model of pcsk-9 inhibitors eligibility in coronary and dyslipidemic patients
Authors: Dima I , Soulis D , Terentes-Printzios D , Skoumas I , Aznaouridis K , Tousoulis D , Vlachopoulos C 
Published: November 2020

Abstract

Purpose
Dyslipidemia is a major cardiovascular risk factor and treatment is mostly based on statins and ezetimibe. PCSK-9 inhibitors are monoclonal antibodies that reduce LDL-c levels and have shown significant reduction of cardiovascular risk in high risk patients. Data regarding potential eligibility for PCSK-9, is limited especially when referring to the recent guidelines.

Methods
Eligibility was calculated using a proprietary adjustable software, which stores data and patient information and thus by using different criteria it can determine potential candidates for PCSK-9 inhibitors. For this purpose, 2000 patients were enrolled prospectively. Our study population was comprised of inpatients diagnosed either with acute coronary syndromes (ACS) or with chronic coronary disease (cCAD) and outpatients from Lipids' Clinic (OLC) (n=407, n=1087, n=506, respectively). In order to test eligibility, three different LDL thresholds were used in our model for high and very high risk groups: a) 70mg/dl and 55mg/dl, respectively, as recommended by the recently updated 2019 ESC/EAS Guidelines for Dyslipidaemia b) 100mg/dl and 70mg/dl, respectively, as recommended by the 2016 ESC/EAS Guidelines for Dyslipidaemias and c) 130mg/dl and 100mg/dl respectively, as mandated by our National Health Care system but also applicable in other countries.

Results
The eligible percentages for the three thresholds were 18.85%, 9.75% and 2.15%, in the total population (TP) respectively and it varied according to clinical status. Subgroup analysis of eligible population revealed the trends in each group (Figure 1). The increase toward more recent guidelines was mostly attributed to the increasing number of coronary patients who become eligible as our criteria become stricter.

Conclusions
Our predictive model provides a realistic estimation of PCSK-9 inhibitors potential eligibility in coronary and dyslipidaemic patients and thus it can become a useful tool for the use of PCSK-9 in health care systems.
Figure 1

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): Amgen Hellas LTD
Inter-individual variability in LDL-C reductions with inclisiran – data from ORION-10 and ORION-11
Authors: Wright R.S , Raal F.J , Kallend D , Stoekenbroek R , Koenig W , Leiter L.A , Landmesser U , Schwartz G.G , Wijngaard P.L.J , Kastelein J.J.P , Ray K.K 
Published: November 2020

Abstract

Introduction
Inclisiran, an investigational siRNA, has been shown to effectively and durably lower LDL-C in Phase 3 trials. Inter-individual variability in LDL-C reductions has been documented for statin therapy and ezetimibe.

Purpose
To evaluate the inter-individual variability in LDL-C lowering with inclisiran.

Methods
The Phase 3 ORION-10 and ORION-11 trials randomized patients with established ASCVD (or risk-equivalents) who had LDL-C &gt;70 mg/dl despite maximally tolerated statins to inclisiran or placebo (1:1). Inclisiran sodium 300 mg was administered s.c. at baseline, three months later, then every six months. Co-primary endpoints were the LDL-C reduction from baseline to Day 510 and the time adjusted average % change in LDL-C reduction after Day 90 and up to Day 540. Measures of response variability were pre-specified secondary endpoints. This analysis examines the inter-individual variability of LDL-C reductions at day 510 using pooled data from both trials.

Results
The analysis included 3178 individuals (92% on statins). At Day 90, 97% of inclisiran-treated patients had an LDL-C reduction. At Day 510, the median percent reduction in LDL-C levels from baseline was 57.3% in the inclisiran group (interquartile range, 44%-70%). An LDL-C reduction ≥50% was reached by 1359 (86.6%) inclisiran-treated patients versus 97 (6.2%) placebo patients at any visit (odds ratio [OR] 97.6, 95% confidence interval [CI] 76–126). An LDL-C reduction ≥30% was reached by 1523 (97.0%) inclisiran-treated patients versus 371 (23.7%) placebo patients (OR 104.5, 95% CI 76–143). At Day 510, 921 patients (65.1%) in the inclisiran group had a reduction ≥50% in LDL-C compared to 34 patients (2.4%) in the placebo group, and 1228 (86.8%) had a reduction ≥30% compared to 148 (10.5%), respectively. Among placebo-treated patients, there was a substantial proportion with notable increases in LDL-C at Day 510 (figure).

Conclusion
In Phase 3 trials, inclisiran on top of maximally tolerated statins provided reliable, consistent and durable reductions in LDL-C. A large percentage of subjects randomized to inclisiran achieved substantial reductions (&gt;50%) in LDL-C and nearly all achieved at least a 30% reduction suggesting inclisiran is potentially a promising novel therapy for patients needing sustained LDL-C reductions.
Waterfall plot of pooled trials

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): The Medicines Company
The current LDL-C target &lt;1.4mmol/l of the ESC is achieved in less than 16% of patients with Coronary Heart Disease despite effective lipid-lowering therapy: data from the LLT-R registry
Authors: Noack F , Schwaab B , Voeller H , Eckrich K , Guha M , Bongarth C , Heinze V , Schlitt A 
Published: November 2020

Abstract

Background
In the current guideline of the ESC, in patients with very high cardiovascular risk such as coronary heart disease (CHD) a treatment target for LDL-C &lt;1.4mmol/l and/or a halving of the initial value are defined. It is unclear whether these treatment targets are achievable with standard therapy including statins and/or ezetemibe.

Methods
The primary objective of this prospective, multi-centre register study was the question of the guidance-based adaptation and adherence to lipid-lowering therapy during and after a cardiac rehabilitation in 1,100 patients with CHD up to 12 months after discharge from the six rehabilitation clinics involved. Patients were included from 2016 to 2018.

Results
The median age of the 1,100 patients was 63.4±10.4 years, the mean BMI was 28.5±4.7kg/m2, and 24.1% of patients were female. 12.2% were active smokers, 91.6% reported dyslipoproteinemia, 33.9% suffered from diabetes mellitus and 86.5% from hypertension.
The majority of patients were included with the main indications NSTEMI (31.6%), STEMI (29.6%) and after CABG surgery (26.4%).
The proportion of patients treated with statins was more than 94% when admitted and discharged from the rehabilitation clinic, as well as in 3- and 12-months follow-ups.
Approximately 9% of patients were treated with ezetemibe at baseline. On discharge from the rehabilitation clinic 23% of patients were treated with ezetemibe, which remains stable at 3 and 12 months.
PCSK9 inhibitors were used in 0.1–0.3% of patients at all times.
The adjustment of LLT during three week cardiac rehabilitation resulted in median LDL-C values of 2.27mmol/l (1.80/2.84) at baseline, 1.97mmol/l (1.57/2.47) on discharge (p&lt;0.001 compared to baseline), 1.94mmol/l (1.57/2.49) after three months and 1.94mmol/l (1.53/2.40) after 12 months.
The proportion of patients with LDL-C &lt;1.4mmol/l was 9% at baseline, 15.7% on discharge (p&lt;0.001 compared to baseline), 15.6% at three-month follow-up and 15.1% at 12-month follow-up (Figure 1).

Discussion
In the context of cardiac rehabilitation, an effective adjustment of LLT is carried out, which resulted in a significant reduction of LDL-C. However, despite a high percentage of patients on statins and ezetemibe, the proportion of patients in the new target range &lt;1.4mmol/l was only achievable in a small percentage and the question arises whether these treatment targets can be achieved without additional administration of PCSK9 inhibitors in majority of patients with CHD.
Figure 1

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): This study was supported by an unrestricted grant from Sanofi-Aventis Germany.
Carotid artery temperature reduction with statin therapy in patients with familial hyperlipidemia syndromes
Authors: Benetos G , Galanakos S , Koutagiar I , Skoumas I , Oikonomou G , Karanasos A , Drakopoulou M , Stathogiannis K , Plytaria S , Xanthopoulou M , Latsios G , Synetos A , Tousoulis D , Toutouzas K 
Published: November 2020

Abstract

Background
Familial hypercholesterolemia (FH) syndromes constitute an important risk factor for premature atherosclerosis. Microwave radiometry (MWR) assess non-invasively carotid artery temperatures reflecting inflammation. Recent data support that statin therapy, that constitutes the cornerstone for the treatment of FH, reduces systemic inflammation.

Purpose
To investigate the impact of statin therapy either with simvastatin or with combination simvastatin plus ezetimibe on carotid artery temperatures.

Methods
Consecutive patients with diagnosis of either heterozygous hypercholesterolemia (hFH) or combined hyperlipidemia (FCH) not under statin therapy for at least 6 months were included in the study. FH pts were assigned to either simvastatin 40 mg or simvastatin 40 mg plus ezetimibe 10mg according to the discretion of the physician. FH patients who refused statin therapy were used as control group for the assessment of statins effect. In all subjects, common carotid intima-media thickness (ccIMT) was measured in the last 2 cm of the far wall of both common carotids close to the carotid bifurcation and ΔT (maximum-minimum) temperature measurements were performed across each carotid during MWR evaluation. Examinations were performed at baseline and after 6 months. Blood's lipid profile was also obtained in all patients.

Results
In total 115 patients were included in the study. Of them 40 patients received simvastatin (19 hFH and 11 FCH), 41 simvastatin + ezetimibe (31hFH and 10 FCH) and 34 (21 hFH and 13 FCH) no statin. There was no difference at baseline in ccIMT and ΔT measurements between hFH and FCH patients (0.10±0.03 vs 0.10±0.02, p=0.74 and 0.88±0.38 vs 0.84±0.32, p=0.52, respectively). Patients who refused statin therapy did not show any reduction in ccIMT and ΔT measurements between baseline and follow up (ccIMT: 0.10±0.02 vs 0.09±0.02, p=0.06 and ΔT: 0.72±0.26 vs 0.70±0.26). In contrast, there was a significant reduction in ccIMT and ΔT for patients under both simvastatin (0.10±0.03 vs 0.09±0.01, p=0.004 for ccIMT and 0.83±0.34 vs 0.63±0.24, p=0.04 for ΔT) and simvastatin + ezetimibe therapy (0.11±0.03 vs 0.09±0.02, p&lt;0.001 and 1.00±0.38 vs 0.69±0.23, p&lt;0.001 for ΔT). Patients under combination therapy reduced more significantly their carotid artery temperatures compared to patients under simvastatin monotherapy or patients without statin (−0.31±0.46 vs −0.2±0.40 vs −0.01±0.37, ANOVA p=0.04, Figure 1).

Conclusions
Both simvastatin and simvastatin + ezetimibe therapy among the beneficial effect on IMT, reduced carotid wall inflammation in FH pts.
Figure 1

Funding Acknowledgement
Type of funding source: None
Role of physical fitness in the obesity paradox. Long-term major adverse cardiovascular events in the Women's Ischemia Syndrome Evaluation (WISE)
Authors: Quesada O , Wei J , Suppogu N , Kelsey S.F , Reis S , Shaw L , Sopko G , Handberg E.M , Pepine C.J , Bairey Merz C.N 
Published: November 2020

Abstract

Background
Emerging data suggests there is an “obesity paradox” where obesity may be protective against cardiovascular morbidity and mortality in patients with cardiovascular disease. However, weight status primarily assessed through body mass index (BMI) is limited in its ability to discern contributions from fat vs. lean muscle mass. Most studies on BMI have not accounted for physical fitness, which is a known modifier of weight status and a potential mediator of effects of obesity on major adverse cardiovascular events (MACE).

Purpose
To investigate the relationship between BMI and physical fitness, measured by self-reported Duke Activity Status Index (DASI) score, with long-term MACE in women evaluated for suspected myocardial ischemia.

Methods
The National Heart, Lung, and Blood Institute Women's Ischemia Syndrome Evaluation (WISE) study is a multicenter prospective cohort study. From 1996–2000, 936 women were enrolled at the time of clinically indicated coronary angiography and assessed with a median follow up of 5.8 (range 0–9 years) for MACE. MACE was defined as a composite of death, nonfatal myocardial infarction, stroke, or congestive heart failure. Proportional hazards regression was used to estimate adjusted hazard ratios of MACE in relation to metabolic status and physical fitness. DASI scores ≥25, equivalent to ≥7 metabolic equivalents [METs]) was used as cut point to define high physical fitness, in our prior studies DASI &gt;25 approximates completion of the second stage of a Bruce treadmill protocol.

Results
Among the 899 women with complete data, 69.5% had low physical fitness (DASI scores &lt;25), 34.9% overweight (BMl ≥25 to 30), 40.5% obese (BMI ≥30). In fit women, obesity was associated with lower hazard ratio for MACE (HR 0.64, p=0.01); while low fitness in normal weight women was associated with 60% excess risk of MACE (HR 1.61, p=0.01) (Figure 1).

Conclusions
Among women undergoing coronary angiography for suspected myocardial ischemia, obesity was inversely related with long-term MACE in physically fit women. Our findings suggest that physical fitness may play a role in the obesity paradox. These results support the inclusion of fitness in understanding the relations between body weight and long-term MACE. The DASI is a simple, self reported tool that can identify higher-risk symptomatic women and should be considered in future investigations and routine examination of normal, overweight and obese women.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): U01 HL064829
Is metabolically healthy obesity indeed healthy at the microvascular level?
Authors: Tibirica E , Huguenin G , Rodrigues-Junior L , Pecanha D , Duque M , Escobar S , Duque A , Araujo C , Mediano M , Lorenzo A 
Published: November 2020

Abstract

Background
In the current “obesity epidemic”, obese individuals without insulin resistance, lipid disorders, or hypertension, have been called “metabolically healthy” (MHO) and considered to have intermediate cardiovascular risk, between that of healthy nonobese (HNO) individuals and of metabolically unhealthy obese (MUO). Nonetheless, this is controversial, as MHO may have subclinical abnormalities, and indeed may be a transitory state in the way to the unhealthy phenotype.

Purpose
To evaluate systemic microvascular reactivity in MHO, MUO and HNO.

Methods
Ten MHO, 10 MUO and 20 HNO individuals were studied. Obesity was considered as a BMI ≥30 kg/m2. The NCEP/ATPIII criteria, excluding waist circumference, were used to define the metabolically healthy phenotype (absence of all criteria) or unhealthy phenotype (presence of any of the criteria). Laser speckle contrast imaging coupled with skin acetylcholine (Ach) iontophoresis was employed to study cutaneous microvascular reactivity (endothelial-dependent vasodilatation), as a surrogate for systemic microvascular function, and cutaneous vascular conductance [CVC in arbitrary perfusion units of microvascular flow (APU)/mean arterial pressure (mmHg)] was measured.

Results
Mean age was 34.8, 36.7 and 32.3 years (P=0.17, ANOVA) and BMI was 20.7, 32.2 and 33.3 kg/m2 (P&lt;0.0001) for HNO, MHO and MUO, respectively. Both MHO and MUO had significantly decreased microvascular vasodilation in comparison to HNO (Figure 1). Of note, there was no significant difference between MHO and MUO regarding CVC (both similarly decreased when compared to the healthy controls).

Conclusions
This study underscores that MHO is not a “benign” condition, as it has adverse effects on microvascular function, similarly to those found in MUO. The study of cutaneous microvascular function may be useful to identify subclinical abnormalities in obese individuals who might deserve more intensive management.
Figure 1

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): FAPERJ - Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro - Brazil