bluuebunny/crossref_metadata_2025_split huggingface dataset:
Achilles tendon thickness assessed by X-ray predicting a pathogenic mutation in familial hypercholesterolemia gene
Authors: Tada H , Hori M , Matsuki K , Ogura M , Nohara A , Kawashiri M , Hadara-Shiba M 
Published: October 2021

Abstract

Background
The 2017 Japan Atherosclerosis Society (JAS) familial hypercholesterolemia (FH) criteria adopts a cut off value of ≥9 mm of Achilles tendon thickness (ATT) detected by X-ray as one of the three key items. This threshold was determined based on an old data assessing ATT of 36 non-FH individuals published in 1977. Although the specificity of this clinical criteria is extremely high due to a strict threshold, there are substantial number of patients with FH whose ATT &lt;9 mm. We aimed to determine a cut off value of ATT detected by X-ray to differentiate FH and non-FH based on genetic diagnosis.

Methods
The individuals (male/female = 486/501) with full assessments of genetic analyses for FH-genes (LDLR, and PCSK9), serum lipids, and ATT detected by X-ray at Kanazawa University Hospital and National Cerebral and Cardiovascular Center Research Institute were included in this study. Receiver operating characteristic (ROC) analyses were performed to determine a better cut off point of ATT predicting a pathogenic mutation of FH.

Results
ROC analyses revealed the best cut off values of ATT as 7.6 mm for male, and 7.0 mm for female with the sensitivities and specificities of 0.83 and 0.83 for male and 0.86 and 0.85 for female, respectively. If the thresholds of ATT of 8.0/7.5 mm and 7.5/7.0 mm were applied to diagnose of male/female FH, the sensitivities/specificities predicting a pathogenic mutation of FH by the 2017 JAS FH clinical criteria would be 0.82/0.90 and 0.85/0.88, respectively.

Conclusions
These results suggest that the cut-off value of ATT detected by X-ray is obviously lower than 9.0 mm adopted by the 2017 JAS FH clinical criteria.

Funding Acknowledgement
Type of funding sources: None.
The effectiveness of strict low-density lipoprotein cholesterol management in secondary prevention of Japanese patients
Authors: Endo A , Yasuda Y , Kawahara H , Kagawa Y , Sakamoto T , Ouchi T , Watanabe N , Yamaguchi K , Yoshitomi H , Tanabe K 
Published: October 2021

Abstract

Background
In Japanese guidelines, target value of low-density lipoprotein cholesterol (LDL-C) &lt;100mg/dL is recommended as standard management for secondary prevention of coronary artery disease. On the other hand, the guidelines also state that LDL-C targeting &lt;70mg/dL should be considered in high-risk patients. However, the effectiveness of strict LDL-C management in the prevention of long-term coronary event recurrence in Japanese patients remains unclear.

Purpose
The purpose of the present study was to evaluate whether the strict management of LDL-C targeting &lt;70 mg/dL was effective to prevent recurrence of acute coronary syndrome (ACS) than standard management in patients with previous percutaneous coronary intervention (PCI).

Methods
From January 2007 to August 2020, we performed coronary angiography in 359 patients with previous PCI who were suspected of having signs of recurrent cardiac ischemia. Patients were stratified into three groups according to achieved LDL-C value; &lt;70mg/dL (n=57), 70 to &lt;100mg/dL (n=135) and ≥100mg/dL (n=167). In addition, patients who had previous ACS and/or diabetes mellitus were defined as high-risk group, and sub-analysis by their achieved LDL-C values was performed in high-risk group and non-high-risk group. Endpoint was recurrence of ACS. Moreover, risk factors associated with recurrent-ACS were examined in patients with LDL-C &lt;100 mg/dL.

Results
After follow-up (median 6.1 years), 99 patients (28%) had recurrent-ACS. Recurrent-ACS was significantly lower in patients with LDL-C &lt;70mg/dL than LDL-C 70 to &lt;100mg/dL and LDL-C ≥100mg/dL (p&lt;0.01 and p&lt;0.001, respectively). In sub-analysis, high-risk group with LDL-C &lt;70 mg/dL had lower incidence of recurrent-ACS than LDL-C 70 to &lt;100 mg/dL (p=0.03). Similar tendency was found in non-high-risk group (p=0.08). There was no difference of recurrent-ACS between high-risk group and non-high-risk group in patients with LDL-C &lt;70mg/dL (p=0.41). Moreover, in patients with achieved LDL-C &lt;100mg/dL (n=192), multivariate analysis identified that LDL-C (HR: 1.032, p&lt;0.01) and HbA1c (HR: 1.330, p&lt;0.01) were independent predictors of recurrent-ACS. In these patients, whether or not they were in the high-risk group was not a significant predictor (p=0.61).

Conclusions
Strict management of LDL-C targeting &lt;70 mg/dL should be considered for a wider range of Japanese patients as well as for Westerners to prevent recurrence of ACS in secondary prevention.

Funding Acknowledgement
Type of funding sources: None. Probability of freedom from ACS
A real-world analysis of characteristics and lipid-lowering therapy use in patients initiating treatment with evolocumab in Sweden
Authors: Svensson M K , James S , Ravn-Fischer A , Pantev E , Sorio-Vilela F , Villa G , Cars T , Gustafsson S , Hagstrom E 
Published: October 2021

Abstract

Background/Introduction
Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors reduce low-density lipoprotein cholesterol (LDL-C) levels and the risk of cardiovascular events in patients with atherosclerotic cardiovascular disease (ASCVD) in clinical trials. In January 2019, evolocumab reimbursement recommendation in Sweden was broadened to include patients on maximally tolerated oral lipid-lowering therapy (LLT) and either ASCVD and LDL-C ≥2.5 mmol/L, or familial hypercholesterolemia (FH) with no ASCVD and LDL-C ≥3.0 mmol/L.

Purpose
Describe characteristics and LLT use in patients initiating treatment with evolocumab in the context of the 2019 reimbursement recommendation in Sweden.

Methods
Cross-sectional, population-based, retrospective, observational study of patients initiating treatment with evolocumab between January 2019 and June 2020. Data were obtained from national healthcare registers and electronic medical records, covering more than half of the Swedish population.

Results
Out of 1560 patients included, 41% had LDL-C available ≤3 months prior to treatment initiation with evolocumab. Among those with LDL-C available, 79% had ASCVD and 19% had definite, probable or possible FH with no ASCVD. Mean pre-treatment LDL-C levels were 3.7 and 5.0 mmol/L for patients with ASCVD, and FH with no ASCVD, respectively. Most of the patients, 84.6% and 80.0%, respectively, had been ever treated with both statins and ezetimibe. However, 28.0% and 38.3% of them, respectively, were not on oral LLT at the time of treatment initiation with evolocumab. Patient characteristics and LLT use are presented in Table 1.

Conclusions
Patients initiating treatment with evolocumab in Sweden had pre-treatment LDL-C levels far from treatment targets, despite being at very high risk for cardiovascular events. Most of the patients had been treated with both statins and ezetimibe in the past. However, almost a third of them were not using oral LLT at the time of treatment initiation with evolocumab. The conditions in the 2019 evolocumab reimbursement recommendation in Sweden were generally met.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Amgen
The combination of dulaglutide and dapagliflozin improves arterial stiffness, endothelial glycocalyx and albuminuria vs DPP-4 inhibitors independently of glycemic control
Authors: Korakas E , Ikonomidis I , Thymis J , Kountouri A , Katogiannis K , Benas D , Prentza V , Balampanis K , Pliouta L , Kousathana F , Kostelli G , Dimitriadis G , Raptis A , Lambadiari V 
Published: October 2021

Abstract

Background
Studies in recent years have shown that dulaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), and dapagliflozin, a sodium-glucose cotransporter-2 inhibitor (SGLT-2i), improve or prevent diabetic nephropathy and macrovascular complications in patients with type 2 diabetes mellitus (T2DM).

Purpose
The aim of this study is to determine whether the combination of dulaglutide and dapagliflozin exerts improves arterial stiffness, endothelial glycocalyx and albuminuria in T2DM compared to dipeptidyl-peptidase 4 inhibitors (DPP-4is).

Methods
Overall 37 patients with T2DM were included in our study. 21 patients were transitioned from DPP-4is to dulaglutide and dapagliflozin (treatment group) and were followed immediately prior (baseline) and 4 months after the initiation of treatment. 16 patients, matched for sex, age and glycemic control, remained on treatment with DPP-4is (control group). In each visit we measured a) Carotid-femoral PWV b) central systolic blood pressure (cSBP) c) perfused boundary region (PBR) of the sublingual arterial microvessels, d) urinary albumin-to-creatinine ratio (UACR), e) glycosylated hemoglobin (HbA1c).

Results
There were no statistically significant differences in cardiovascular markers, UACR and HbA1c at baseline (p&gt;0.05). After 4 months, patients on dulaglutide and dapagliflozin combination improved HbA1c (7.9±1.5% vs 6.59±0.6%, p&lt;0.001), PBR (2.3±0.3 vs. 2.1±0.2 μm, p&lt;0.05), PWV (11.9±0.3.5 vs. 10.9±2.2m/s, p&lt;0.05), cSBP (128.5±23.6 vs. 121.1±15.7 mmHg, p&lt;0.05) and UACR (413.66±352.57 vs. 248.06±203.5 mg/g, p&lt;0.001). There were no statistically significant differences in PBR (2.1±0.3 vs. 2.2±0.3 μm, p&gt;0.05), PWV (10.7±3.4 vs. 12±3.3m/s, p&gt;0.05), cSBP (125.4±21.2 vs. 127±20.1 mmHg, p&gt;0.05) and UACR (240.8±103.6 vs. 204.9±119.6 mg/g), in the control group, despite a statistically significant improvement of HbA1c (8.2±1.9% vs 7.3±1.3%, p&lt;0.01).

Conclusions
The combination of dulaglutide and dapagliflozin improves arterial stiffness, endothelial glycocalyx and albuminuria compared to DPP-4is in patients with T2DM.

Funding Acknowledgement
Type of funding sources: None.
Effect of SGLT2 inhibition on coronary microvascular function in patients with type 2 diabetes
Authors: Suhrs H E , Bove K , Nilsson M , Zander M , Prescott E 
Published: October 2021

Abstract

Background
Treatment with sodium-glucose cotransporter 2 (SGLT2) inhibitor reduces risk of cardiovascular death and heart failure but the underlying mechanisms remain poorly understood. It has been suggested that a shift in fuel source in the myocardium from glucose and free fatty acids to the more energy efficient ketogenesis reduces oxidative stress involved in coronary microvascular damage, leading to improved coronary microvascular function.

Purpose
To test the hypothesis that treatment with the SGLT2 inhibitor empagliflozin improves non-endothelial dependent coronary microvascular function.

Methods
We included 26 patients with type 2 diabetes in a double blinded, placebo-controlled cross-over study. Participants were treated with empagliflozin 25 mg and placebo for 12 weeks, interrupted by 2 weeks wash-out period. The primary outcome was change in coronary microvascular function, assessed as coronary flow velocity reserve (CFVR) and measured with transthoracic doppler echocardiography. Secondary endpoints were change in echocardiographic parameters of cardiac systolic function and 184 cardiovascular protein biomarkers.

Results
Nineteen patients completed both study periods according to protocol. There was a significant weight loss and reduction in Hba1c after empagliflozin treatment (table). We found no improvement in CFVR and parameters of cardiac systolic function. We observed a general tendency of reduction in level of cardiovascular biomarkers after empagliflozin treatment (figure) with significant difference between empagliflozin and placebo for 27 proteins, including IL18, ST2, YKL40, ACE2 and leptin.

Conclusions
Despite a significant weight loss and reduction in Hba1c after empagliflozin treatment, we found no effect on non-endothelial dependent coronary microvascular function in patients with type 2 diabetes mellitus. Improvement in multiple biomarkers may indicate underlying mechanisms but need confirmation in larger studies.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): The Danish Council for Independent Research Table 1. Change in outcome parametersFigure 1. Change in biomarker levels
Effect ofglucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors and their combination on left atrial strain and arterial function
Authors: Ikonomidis I , Katogiannis K , Thymis J , Kousathana F , Pavlidis G , Kountouri A , Balampanis K , Korakas E , Prentza V , Simou A , Tsilivarakis D , Lambadiari V 
Published: October 2021

Abstract

Background
We investigated the effects of insulin, glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and their combination on left atrial function of patients with type 2 diabetes mellitus and we searched for a relation with arterial function.

Methods
A total of 213 patients (59,5±9,1 year old, 161 male) with type 2 diabetes mellitus treated with metformin were randomized to insulin (n=46 served as controls), liraglutide (n=40), empagliflozin (n=46) or their combination (GLP-1RA + SGLT-2i) (n=50) as add-on. We measured at baseline and 6 months posttreatment: (a) perfused boundary region of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness), (b) pulse wave velocity (PWV) and central systolic blood pressure, (c) global left ventricular Longitudinal strain, (d) left atrial strain.

Results
Six months after intervention, all patients improved left atrial reservoir strain (GLP1RA 30,7±9,3 vs 33,9±9,7%, p=0,011 / SGLT2i 30±8,3 vs 32,3±7,3%, p=0,04 / GLP1 & SGLT2i 29,1±8,7 vs 31,3±8,2, p=0,007) in comparison with controls (33±8,3% vs 32,8±7,4, p=0,829). Also, patients treated with GLP1RA and their combination improved left atrial conduction strain (p&lt;0.05). GLP-1RA or GLP-1RA + SGLT-2i provided a greater improvement in GLS compared with insulin or SGLT-2i (controls −18,5±3,9% vs −19,1±3%, p=0,202 / GLP1RA −18,2±4,1% vs −19,1±3,5%, p=0,03 / SGLT2i −19±4,1% vs −19,1±3,8%, p=0,764 / GLP1 & SGLT2i −16,7±3,9% vs −17,5±4,3%, p=0,026). SGLT-2i or GLP-1RA and SGLT-2i showed a greater decrease of PWV (Controls 12,06±3,02 vs 11,62±2,79 m/sec, p=0,142 / GLP1 11,54±2,91 vs 11,45±2,52 m/sec, p=0,822 / SGLT2 11,86±2,51 vs 11,33±2,28 m/sec, p=0,047 / GLP1 & SGLT2 12,01±2,46 vs 10,85±1,79 m/sec, p=0,021) and central and brachial systolic blood pressure than insulin or GLP-1RA. At baseline, there was a correlation of LA reservoir strain with PWV (r=−0,209, p=0,008), central SBP (r=−0,151, p=0,030), EF (r=0,214, p=0,004), GLS (r=−0,279, p=0,009). At 6 months follow up, there was a correlation of LA reservoir strain with PWV (r=0,217, p=0,003), central SBP (r=0,214, p=0,004), EF (r=−0,221, p=0,049), GLS (r=0,275, p=0,014).

Conclusions
Treatment with GLP-1RA, SGLT-2i, and their combination for 6 months showed a greater improvement of left atrial function compared to insulin treatment in parallel with improvement arterial and myocardial function.

Funding Acknowledgement
Type of funding sources: None.
Exercise ECG testing in patients without known ischemic heart disease: predictors of ischemia of downstream vasodilator stress cardiac magnetic resonance
Authors: Merenciano Gonzalez H , Marcos-Garces V , Gabaldon-Perez A , Lorenzo-Hernandez M , Nunez-Marin G , Gavara J , Perez N , Rios-Navarro C , De Dios E , Bonanad C , Racugno P , Lopez-Lereu M P , Monmeneu J V , Chorro F J , Bodi V 
Published: October 2021

Abstract

Background
In routine clinical practice, patients with chest pain and suspected stable ischemic heart disease (SIHD) usually undergo an exercise ECG stress test (ExECG) for ischemia detection. However, since the sensitivity of this technique is relatively low, concerns exist that many patients could remain underdiagnosed. We intend to assess the clinical and ExECG predictors of ischemia on subsequent vasodilator stress cardiac magnetic resonance (vs-CMR) to help select which patients should undergo downstream testing after an initial ExECG.

Material and methods
We retrospectively included 197 patients without previous history of ischemic heart disease who underwent an ExECG and a subsequent vs-CMR in the year after this test and who didn't undergo a revascularization procedure in this time frame. Clinical, ExECG and vs-CMR variables were included in the registry. vs-CMR was considered positive if ischemia was evident in at least one myocardial segment on stress first-pass perfusion without concomitant necrosis on late gadolinium enhancement imaging. We performed univariate and multivariate analysis to check for the association of variables with the risk of ischemia on vs-CMR.

Results
Mean time from ExECG to vs-CMR was 88.69±84.32 days and 37 vs-CMR were positive for ischemia. Male sex, less exercise time, less % of maximum predicted exercise capacity, less maximum double product (heart rate x systolic blood pressure) and less double product reserve (DPR = maximum double product - basal double product) were associated with ischemia on vs-CMR on univariate analyses. However, the only independent predictors of ischemia on vs-CMR on multivariate binary logistic regression were male sex (HR 2.62 [CI 95%: 1.13–5.76], p=0.016) and less DPR (HR 0.90 [CI 95%: 0.84–0.97] per 1000 increase, p=0.006). The risk score derived from these two variables had a moderate predictive power (ROC curves, AUC 0.657, p=0.003). The best cut-off point for the DPR was 12400, as derived from the Youden index. It allowed stratification of the risk of ischemia on vs-CMR, which ranged from 9% in women with &gt;12400 DPR, 18.8% in men with &gt;12400 DPR, 24.1% in women with ≤12400 DPR to 42.9% in men with ≤12400 DPR (p=0.005, Figure 1).

Conclusions
Male sex and less double product reserve on ExECG can moderately predict the risk of ischemia on subsequent vs-CMR in patients presenting with chest pain and without previous SIHD. This can help select patients who benefit most from vs-CMR for diagnostic purposes.

Funding Acknowledgement
Type of funding sources: None. Figure 1
Predictors of long-term survival in patients undergoing residential cardiac rehabilitation (rCR) after transcatheter aortic valve replacement (TAVR): a multicenter retrospective study
Authors: Tarro Genta F , Marcassa C , Ceresa M , Scalvini S , Dalla Vecchia L A , Bussotti M , Iannuzzi G L , Rizzo C , Pedretti R F E , Giordano A , La Rovere M T 
Published: October 2021

Abstract

Purpose
To evaluate exercise-based rCR derived outcome predictors in patients referred after TAVR.

Methods
Data of 232 patients (aged 82±6 years, 45%males) admitted to an average 3-week rCR program after TAVR (walking, up to 30 minutes of cycling or treadmill session twice daily, respiratory and calisthenic training) from January 2009 to December 2017 and home discharged, were retrospectively collected at 10 rCR Divisions of Istituti Clinici Scientifici Maugeri. Comorbidity (cumulative illness rated state-comorbidity index) (CIRS-CI) score, echocardiography on admission, disability (Barthel Index) (BI) score at discharge, six minutes walking test distance (6MWT) on discharge and maximal training session intensity (MTSI expressed in METs per minutes) were collected. All-cause mortality was assessed up to 3 years after rCR discharge.

Results
During a 3-year follow-up, there were 74 (32%) deaths. At univariate analysis, at discharge non survivors compared to survivors had significantly higher comorbidity rate (CIRS-ICC 5.2±2.3 vs 4.1±1.9, p=0.000) and disability level (BI 80.4±24 vs 88.8±17, p=0.000). Moreover, they had worse renal function (creatinine 1.6±0.9mg/dl vs 1.2±0.4, p=0.000), were more often on diuretic therapy (73% vs 53.2%, p=0.003) and on beta-blocker therapy (73% vs 57,6%, p=0.042) and had a markedly reduced functional capacity (6MWTD 221±100m vs 265±105m, p=0.001). At multivariate logistic stepwise analysis a lower comorbidity (CIRS-ICC), a more preserved renal function (creatinine level), a reduced use of diuretic therapy and 6MWT at discharge confirmed their power as independent predictors of survival at follow up (Table, Harrel's C = 0.707)

Conclusions
Patients attending rCR after TAVR are very old with significant comorbidity; overall mortality at 3-year follow-up after CR discharge is substantial. Our results suggest the need to implement ad-hoc long-term care strategies based on residual exercise capacity, comorbidity score and renal function for tailoring follow-up in patients discharged from rCR after TAVR.

Funding Acknowledgement
Type of funding sources: None. Table 1
Impact of cardiac rehabilitation on inflammation in patients with ischaemic cardiomyopathy
Authors: Costa R , Frias A , Campinas A , Fernandes P , Magalhaes S , Santos M , Torres S 
Published: October 2021

Abstract

Introduction
The benefits of cardiac rehabilitation (CR) in patients with ischaemic cardiomyopathy are well-known. However, inflammatory states have been associated to an increased risk of cardiovascular events.

Purpose
Evaluate the impact of CR in the serum levels of inflammatory biomarkers and identify potential predictors of that effect.

Methods
We retrospectively studied consecutive patients with ischaemic cardiomyopathy who completed a CR programme between 2011 and 2017. Patients underwent a supervised exercise training protocol, twice a week during a period of 8 to 12 weeks. Functional capacity was evaluated by metabolic equivalents assessed prior the beginning and 3 months after the programme with a symptom limited exercise treadmill test. Patients without levels of serum C-reactive protein at beginning and at the end of CR programme were excluded. Median variation of serum C-reactive protein was assessed and two groups were defined: one with levels above that and one with levels below.

Results
Of 250 patients (60.3±11.1 years, 84% male), 67% were admitted after an acute myocardial infarction. Left ventricular ejection fraction ≤40% before CR was present in 32% of individuals. Median levels of serum C-reactive protein before CR were 8.8 (3.1–21.7) mg/L and median variation after CRP was a decrease of 5.1 (0.9–17.7) mg/L (p&lt;0.001). Before CR, higher levels of serum C-reactive protein were seen in obese (15.7 [8–52.7] versus 8.8 [3.2–27.8], p=0.04) and those with higher NT-proBNP (p&lt;0.001). Patients with decrease of &gt;5.1mg/L of serum C-reactive protein had lower prevalence of hypertension (18% versus 30%, p=0.02), higher prevalence of obesity (16% versus 7%, p=0.03), lower levels of HDL cholesterol (38.3 [11.1] versus 43.2 [12.6], p&lt;0.001) and higher levels of NT-proBNP (1079 [610.3–1988] versus 488 [215–777], p&lt;0.001) at baseline. An increase of at least of 10% of functional capacity after CR was reached in 65% of patients, similar between groups. Patients with decrease of serum C-reactive protein &gt;5.1mg/L had also higher reduction of NT-proBNP after CR comparing to baseline (491.1 [142.7–948.5] versus 162.0 [30.9–295.2], p&lt;0.001).

Conclusions
Serum levels of inflammatory biomarkers decreased after CR in patients with ischaemic cardiomyopathy. Normotension, obesity, lower HDL and higher levels of natriuretic peptides are associated to a better response.

Funding Acknowledgement
Type of funding sources: None.