bluuebunny/crossref_metadata_2025 huggingface dataset:
Current patterns of pharmacological treatment for coronary heart disease based on the Russian cohort of the hospital arm of the EUROASPIRE V survey
Authors: Pogosova N , Boytsov S A , Ausheva A K , Sokolova O Y , Pozdnyakov Y M , Salbieva A O , Karpova A V , Yusubova A I , Arutyunov A A
Published: October 2021

Background

Several drug classes have shown their ability to improve risk factors control and prognosis in coronary heart disease (CHD). Therefore, it is important to monitor the prescription patterns on a regular basis to ensure that all the eligible patients receive the potentially lifesaving medications.

Purpose

To describe prescription and uptake of main guideline-recommended drug classes in men and women with history of acute coronary syndromes (ACS) or cardiac revascularization enrolled into the hospital care arm of EUROASPIRE V (European Action on Secondary and Primary Prevention by Intervention to Reduce Events) study in Russian centers vs the whole study population.

Methods

The hospital arm of EUROASPIRE V was a cross sectional survey covering multiple European countries including Russia. Within each country one or more hospitals were selected where consecutive pts (both genders, ≥18 and <80 years of age) hospitalized for myocardial revascularization procedures or for ACS were retrospectively identified. Identified patients were invited for interview, which had to take place ≥6 months and <2 years after the index hospitalization. Pharmacological treatment was assessed based on the prescriptions in the discharge letters and during the interview.

Results

A total of 399 pts (women, 27.1%) have been interviewed in Russia vs 8261 pts (women, 25.8%) in the whole survey. The mean age of the Russian cohort at interview was 62.8±8.7 years in Russia vs 63.6±9.6 years in all EUROASPIRE V pts. The table below represents the proportion of pts prescribed and actually receiving main drug classes. Both in the Russian cohort and in the whole study population the proportion of patients receiving essential drug classes didn't differ much by gender. In Russian centers, 95.9% of men and 91.7% of women received antiplatelets (vs 92.8% and 91.8%, respectively, in the whole study population). For statins the corresponding numbers were 86.9% for men and 91.7% for women in Russia (vs 82.2% and 76.8%), for beta-blockers – 82.5 in both genders (vs 80.8% and 81.8%), for ACE inhibitors and/or ARBs 78.0% in men and 80.6% in women (vs 75,3% and 75.0%).

Conclusion

Current prescription of guideline-recommended drug classes in the Russian cohort of EUROASPIRE V survey is close to the average European levels and doesn't demonstrate any obvious gender gaps. However, there is still room for improvement. In particular, this applies to the maintenance of prescriptions made at discharge, especially of statins, in the long term.

Funding Acknowledgement

Type of funding sources: None. Table 1
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

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 <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

Background

In Japanese guidelines, target value of low-density lipoprotein cholesterol (LDL-C) <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 <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 <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; <70mg/dL (n=57), 70 to <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 <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 <70mg/dL than LDL-C 70 to <100mg/dL and LDL-C ≥100mg/dL (p<0.01 and p<0.001, respectively). In sub-analysis, high-risk group with LDL-C <70 mg/dL had lower incidence of recurrent-ACS than LDL-C 70 to <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 <70mg/dL (p=0.41). Moreover, in patients with achieved LDL-C <100mg/dL (n=192), multivariate analysis identified that LDL-C (HR: 1.032, p<0.01) and HbA1c (HR: 1.330, p<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 <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

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

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>0.05). After 4 months, patients on dulaglutide and dapagliflozin combination improved HbA1c (7.9±1.5% vs 6.59±0.6%, p<0.001), PBR (2.3±0.3 vs. 2.1±0.2 μm, p<0.05), PWV (11.9±0.3.5 vs. 10.9±2.2m/s, p<0.05), cSBP (128.5±23.6 vs. 121.1±15.7 mmHg, p<0.05) and UACR (413.66±352.57 vs. 248.06±203.5 mg/g, p<0.001). There were no statistically significant differences in PBR (2.1±0.3 vs. 2.2±0.3 μm, p>0.05), PWV (10.7±3.4 vs. 12±3.3m/s, p>0.05), cSBP (125.4±21.2 vs. 127±20.1 mmHg, p>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<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

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

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<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

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 >12400 DPR, 18.8% in men with >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

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

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<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<0.001). Patients with decrease of >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<0.001) and higher levels of NT-proBNP (1079 [610.3–1988] versus 488 [215–777], p<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 >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<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.
Relationships between physical capacity and depression in heart failure patients undergoing hybrid comprehensive telerehabilitation vs usual care results of the TELEREH-HF randomized clinical trial
Authors: Piotrowicz E , Mierzynska A , Jaworska I , Opolski G , Banach M , Zareba W , Kowalik I , Pencina M , Orzechowski P , Szalewska D , Pluta S , Glowczynska R , Kalarus Z , Irzmanski R , Piotrowicz R
Published: October 2021

Introduction

The novel hybrid comprehensive telerehabilitation (HCTR) consisting of telecare (with psychological telesupport), telerehabilitation and remote monitoring of cardiovascular implantable electronic devices might be an option to improve both physical capacity and depressive symptoms.

Purpose

The aim of the study was to investigate the influence of HCTR on depressive symptoms and physical capacity in heart failure (HF) patients in comparison with usual care (UC) alone.

Methods

The present analysis formed part of a multicenter, randomized trial that enrolled 850 HF patients (New York Heart Association class I–III, left ventricular ejection fraction ≤40%). Patients were randomized 1:1 to HCTR plus UC or UC only. Patients underwent either an HCTR program (1 week in hospital and 8 weeks at home; exercise training 5 times weekly) or UC with observation. The psychological intervention in the HCTR group included supportive psychological counseling via mobile phone. The Beck Depression Inventory II (BDI II) score (cut point for depression ≥14) was used to assess depression and the physical capacity was measured by peak oxygen consumption (peak VO2). Measurements were made before and after a 9-week intervention (HCTR group)/ observation (UC group).

Results

Both groups were comparable in terms of demographic, clinical characteristics and medical therapy. In HCTR group at entry 23% of the sample (n=88/382) obtaining BDI-II scores ≥14 vs 27.5% (n=107/389) in UC group. The BDI II score at study entry was 9.8±6.6 and after intervention was 9.2±6.6, p=0.016 (HCTR group) vs at entry 10.6±8.2 and after observation 10.0±8.3, p=0.022 (UC group). There were no significant differences between groups regarding ΔBDI II score p=0.992. There was a significant improvement in physical capacity assessed by peak VO2 only in the HCTR group, both in patients with (p=0.033) and without (p<0.001) depression (Table 1). These beneficial effects have not been observed in UC group.

Conclusions

In heart failure patients, HCTR provided similar reduction of depressive symptoms as UC. Hybrid comprehensive telerehabilitation resulted in a significant improvement in physical capacity both in patients with and without depression.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): The National Centre for Research and Development, Warsaw, Poland.
Endurance training increases ventricular refractoriness and wavelength of the cardiac impulse without participation of parasympathetic postganglionic neurons. A study in isolated rabbit heart
Authors: Rodrigo-Garcia A , Such-Miquel L , Parra G , Calvo C J , Arias-Mutis O J , Lozano W M , Such L , Alberola A , Chorro F J , Zarzoso M
Published: October 2021

Background

Endurance physical training plays a protective role in against ventricular fibrillation (VF), but the exact underlying mechanisms are not completely understood. It is well-known that modifications in myocardial ventricular properties such as refractoriness, conduction velocity and wavelength are key in the initiation and maintenance of VF; furthermore, vagus nerve stimulation has prophylactic effects on malignant arrhythmias and VF. On the other hand, parasympathetic nervous system activity is increased in trained individuals, which in turn affects different ventricular electrophysiological properties. We hypothesized that physical training increases conduction velocity and wavelength, and that these changes are mediated by myocardial cholinergic neurons.

Methods

To test this hypothesis, ten rabbits were submitted to a six-week endurance training protocol and twenty controls were not trained (divided in control group, n=10 and sham group n=10). After training, rabbits were euthanized and their hearts excised, isolated and perfused in a Langendorff system. A pacing electrode and a plaque with 240 recoding electrodes acquiring at 1 KHz were positioned on the left ventricle (LV). Extraestimulus test using four different pacing cycle lengths (90% basal cycle length, 250, 200 and 150 ms) was performed before and after atropine (1μM, control and trained groups) or vehicle (tyrode, sham group) infusion. We studied 1) LV effective refractory period (ERP), 2) LV functional refractory period (FRP), 3) LV conduction velocity (CV), and 4) LV wavelength, determined as LV FRP x CV. Factorial ANOVA (mixed model) was used for statistical analysis (p<0.05).

Results

Before parasympathetic blockade, LV FRP increased in trained animals (Figure, B) whereas no difference was found in LV CV between trained and control animals at any pacing cycle length (Figure, A). In consequence, LV wavelength increased in trained animals (Figure, C). There were no changes in LV ERP, FRP, CV and wavelength when comparisons were made within groups before and after atropine infusion. In sham animals, vehicle infusion or time-course of the experiment did not modify LV FRP, ERP, CV and wavelength.

Conclusion

Physical training increases LV wavelength, which can be one electrophysiological mechanism by which endurance training could protect against VF. Since modifications of ventricular refractoriness and wavelength do not seem dependent of intrinsic parasympathetic nervous system activity, other intrinsic mechanisms could be implied and warrant further research.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Instituto de Salud Carlos III, Generalitat Valenciana
Endocannabinoids and heart rate variability alterations after exposure to prolonged intensive physical exercise of the Hellenic Navy SEALs
Authors: Mourtakos S , Vassiliou G , Kontoangelos K , Philippou A , Bersimis F , Geladas N , Koutsilieris M , Sidossis L , Papageorgiou C H , Papageorgiou C
Published: October 2021

Background

Recent research indicates that endocanabinoids (eCB) and heart rate variability (HRV) are associated with stress-induced experiences. However, these underlying mechanisms have not been elucidated.

Purpose

The aim of the present study is to investigate if exposure to acute and chronic stress promotes measurable changes concurrently to the peripheral eCB ligands and the HRV.

Methods

13 candidates under intense preparation for their enlistment in the Hellenic Navy SEALs (H.N.S.) participated in the study. All subjects underwent mental state examination, while HRV variables in time and frequency domains recordings were acquired. Furthermore, at baseline and 30 days after prolonged and intensive physical exercise hair were collected in order to measure eCB ligands, such as anandamide (AEA), 2-arachidonoylglycerol (2-AG), and the N-acyl ethanolamine (NAE) molecules: palmitoylethanolamide (PEA) and oleoylethanolamide (OEA).

Results

Comparing basal hair concentrations of eCB ligands before and after intensive physical exercise, we found that AEA, PEA and OEA were notably increased (p<0.01, p<0.05 and p<0.01 respectively) whereas no differences were observed regarding the ligand 2-AG. Regarding time domain features of HRV, a strong positive correlation was found between mean HR, AEA and PEA [r(13)=0.934, p<0.05, (r(13)=0.902, p<0.05]. Regarding frequency domain, a strong negative correlation was found between low frequency (LF) HRV and PEA (r(13)=−0.853, p<0.01). No statistically significant associations were noted between high frequency HRV and EC ligands.

Conclusions

These findings suggest that endocannabinoid-HRV interrelations might share a short-term, and long-term adaptability of the changes in self-regulation associated with stress. Further studies are required to determine the validity of peripheral eCB signaling and HRV as a biomarker for different aspects of stress response.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Region of Attica
Apremilast improves endothelial glycocalyx and microvascular perfusion: a possible protective mechanism against COVID-19
Authors: Ikonomidis I , Pavlidis G , Thymis J , Rafouli-Stergiou P , Makavos G , Kostelli G , Katsimbri P , Lambadiari V , Parissis J , Kapniari E , Katogiannis K , Kountouri A , Korakas E , Theodoropoulos K , Papadavid E
Published: October 2021

Background/Introduction

The phosphodiesterase 4 inhibitor apremilast is an approved treatment option for psoriasis.

Purpose

We aimed to investigate the effects of apremilast on endothelial glycocalyx, vascular and left ventricular (LV) myocardial function in psoriasis.

Methods

Ninety patients with psoriasis were randomized to receive apremilast (n=30), anti-tumor necrosis factor-a (etanercept, n=30), or cyclosporine treatment (n=30). At baseline and 4 months post-treatment, we measured: (1)Perfused boundary region (PBR) of the sublingual microvessels with a diameter 5–25μm using a dedicated camera (Sidestream Dark Field imaging, Microscan, Glycocheck). Increased PBR indicates reduced glycocalyx thickness. Perfused microvascular density (PMD), an index of microvascular perfusion, was also measured. (2)Pulse wave velocity (PWV - Complior; ALAM Medical) and central systolic blood pressure (cSBP), and (3)LV global longitudinal strain (GLS) and percent difference between peak twisting and untwisting at mitral valve opening (%dpTw-UtwMVO) using speckle-tracking echocardiography.

Results

Compared with baseline, PBR20–25 decreased only after apremilast treatment (−13% at 4 months, P<0.05) whereas no statistically significant changes in PBR20–25 were observed after etanercept or cyclosporine. Compared with etanercept and cyclosporine, apremilast resulted in a greater increase of PMD (+12% versus +3% versus +3%) and in a higher reduction of PWV (−10% versus −3% versus +8%) and cSBP (−8% versus −2% versus +7%) at 4 months. Apremilast showed a greater increase of GLS (+12% versus +5% versus +2%) and %dpTw-UtwMVO (+15% versus +3% versus +3%) than etanercept and cyclosporine (P<0.05 for all comparisons). Changes of PBR and PMD post-apremilast treatment correlated with a concomitant reduction of PWV and cSBP (P<0.05).

Conclusions

In psoriasis, apremilast confers a greater improvement of endothelial glycocalyx, microvascular perfusion and LV myocardial function compared with etanercept or cyclosporine treatment. Apremilast restores glycocalyx integrity and thus reduces vascular permeability to pro-inflammatory molecules. This may explain the beneficial effects of apremilast on COVID-19.

Funding Acknowledgement

Type of funding sources: None.
Sex differences in mortality in stable patients undergoing vasodilator stress cardiovascular magnetic resonance
Authors: Marcos Garces V , Minana G , Nunez J , Monmeneu J V , Lopez-Lereu M P , Gavara J , Rios-Navarro C , Perez N , De Dios E , Fernandez-Cisnal A , Nunez E , Chorro F J , Sanchis J , Bodi V
Published: October 2021

Introduction

The prognostic value and therapeutic implications of ischemia as derived from vasodilator stress cardiovascular magnetic resonance (CMR) could differ in men and women, but it has not been stablished.

Purpose

We assessed the influence of the ischemic burden as derived from CMR on the risk of death and the effect of revascularization across sex.

Methods

We evaluated 6,237 consecutive patients with known or suspected chronic coronary syndrome (CCS). Extensive ischemia was defined as >5 segments with perfusion deficit. Multivariate Cox proportional hazard regression models were used.

Results

A total of 2,371 (38.0%) patients were women and 583 (9.3%) underwent CMR-related revascularization. During a median follow-up of 5.13 years, 687 (11.0%) deaths were reported. We found an adjusted differential effect of CMR-derived ischemic burden across sex (p-value for interaction=0.039). Women exhibited an adjusted lower risk of death along most of the continuous ischemic burden but equalled men's risk when extensive ischemia was present. Likewise, CMR-related revascularization was shown to be differentially associated with the risk of mortality across sex (p-value for interaction=0.025). In patients with non-extensive ischemia, revascularization was related to a higher risk of death, with a greater extent in women. At higher ischemic burden, revascularization was associated with a lower risk in men, with more uncertain results in women.

Conclusions

CMR-derived ischemic burden allows predicting the risk of death and gives insight into the potential effect of revascularization in men and women with CCS. Compared to men, women with nonextensive ischemia displayed a lower risk and a similar risk with a higher ischemic burden. The impact of CMR-related revascularization on mortality risk was also significantly different according to ischemic burden and sex.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study was supported by the Instituto de Salud Carlos III and cofunded by the European Regional Development Fund (ERDF).
Rheumatic heart disease: a school-based experience in guinea bissau
Authors: Beltrani V , Tersalvi G , Romana Scopigni F , Bruzzone G , Assaiemo F , Biasco L , Pedrazzini G B , Valgimigli M
Published: October 2021

Introduction

Rheumatic heart disease (RHD) remains a major cardiovascular issue in developing countries. Currently, large population-based data regarding RHD in Guinea Bissau are lacking and most of the patients are diagnosed with advanced stages. Our school-based echocardiography screening aimed at determining the prevalence of RHD and its socioeconomic distribution in Guinea Bissau.

Methods

Children (5–15 years old) from the Bissau region were enrolled from March 2017 to April 2020 in selected primary and secondary schools. Every child underwent echocardiography and group A streptococcus swab test. Presence of RHD was defined according to the World Heart Federation criteria for individuals ≤20 years.

Results

A total of 6784 children were screened: 585 (8.6%) participants had a positive swab test and received single dose of benzathine-penicillin-G, with the majority, 417 (71.3%) living in rural areas.

A total of 6784 out-clinic echocardiography exams were performed; 1121 (16.5%) were positive for RHD (possible or definite), of which 606 (54.1%) were from rural areas.

Every child with RHD (definite or probable) was invited for an outpatient visit in a clinic in Bissau, 863 (77%) attended the visit and echocardiography was repeated. RHD was confirmed in 659 cases (58.8%).

Every child with confirmed RHD started secondary prophylaxis with BPG (or oral erythromycin in case of known penicillin allergy) every 21–28 days. At a median follow-up of 3 years only 391 (59.4%) continued regular administration.

Estimating a population of 798370 subjects aged 5–15 years, we calculated a national prevalence of silent RHD of 77522 subjects, almost 1 every 10 children.

Conclusions

A school-based echocardiographic screening has an important role in the detection of subclinical RHD. In our population the prevalence of RHD is 9.7% with a significant difference between rural and urban areas, which is an additional challenge for health care providers. Additionally, regular administration of secondary prophylaxis is jeopardised by high attrition rate and lost-to-follow-ups.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Public fundraising on social media and at local events
The predictive role of neutrophil-to-lymphocyte ratio in post-operative arrhythmias in pediatric patients after cardiopulmonary bypass surgery
Authors: Bucciarelli V , Bianco F , Biasi A , Primavera M , Baldinelli A , Colaneri M , Gallina S , Pozzi M
Published: October 2021

Background

Postoperative arrhythmias (POA) are a common complication after cardiac surgical repairs for congenital heart disease (CHD), representing a substantial source of morbidity, mortality and prolonged total in-hospital stay, with an incidence of 7.5–48% in postoperative pediatric cardiac patients. The etiology is multifactorial, and it has been related to the direct surgical manipulation of the cardiac conduction system, to the local tissue inflammation in the myocardium adjacent to the conduction system and to the arrhythmogenic effects of cardiopulmonary bypass (CPB), inotropes and electrolyte disturbances. Recently, the prognostic role of neutrophil-to-lymphocyte ratio (NLR), a novel inflammation marker, has been evaluated in pediatric patients after CPB surgery.

Purpose

To evaluate the predictive role of NLR in POA in a population of pediatric CHD patients after CPB.

Methods

We retrospectively collected perioperative clinical and laboratory data of 146 patients (age 8.27±10.79 years; male gender: 60.8%) consecutively admitted to the cardiac surgery intensive care unit (ICU) of our institute after elective cardiac surgery with CPB in 2018. We grouped and analyzed our population over NLR tertiles evaluated at 24 hours from CPB and types of POA: supraventricular (SVT) and junctional (JET). The prognostic value of NLR and its association with POA was analyzed.

Results

Diagnoses of 146 patients included atrial septal defect (n=36), ventricular septal defect (n=20), pulmonary atresia/stenosis (n=10), tetralogy of Fallot (n=20), endocardial cushion defect (n=8), left ventricular outflow tract obstruction (n=14), anomalous origin of coronary artery (n=6), complex CHD (n=13), interrupted/hypoplastic aortic arch (n=12), anomalous pulmonary artery venous return (n=3). The mean CPB time was 121.6±84.6 minutes. The median ICU hospitalization was 48 hours [Q1, Q3: 24, 96]. Twelve patients experienced POA: 6 SVT and 6 JET. The frequency of POA incremented over NLR-tertiles (P-Trend 0.017), while SVT onset was associated with higher values of NLR and C-reactive protein (P=0.034 and P=0.011, respectively). Patients in the second and third tertiles of NLR had a prolonged hospitalization (Log-rank, P=0.029), especially when associated with POA (Log-rank, P=0.012). At the multivariable analysis, higher age and NLR values were independently associated with SVT [OR per year 1.22; 95% CI (1.02, 1.25), P=0.043 and OR per point 1.91; 95% CI (1.29, 2.82), P=0.012, respectively], but not with JET.

Conclusions

24-h post-CPB NLR can predict postoperative SVT in a population of pediatric CHD patients. Our data suggest that the NLR could be a useful, easy-to-obtain marker for postoperative outcome in pediatric patients who had undergone elective CPB.

Funding Acknowledgement

Type of funding sources: None.
Insights on clinical outcomes in according to age in patients undergoing Transcatheter Aortic Valve Replacement
Authors: Munoz-Garcia M , Munoz-Garcia E , Munoz Garcia A J , Dominguez-Franco A J , Alonso-Briales J H , Jimenez-Navarro M F , Hernandez-Garcia J M , Gomez-Doblas J J
Published: October 2021

Transcatheter Aortic Valve Replacement (TAVR) is considered the treatment in patients older or at high or intermediate risk. Results form contemporary randomized trials in low-risk patients will likely broaden the indication of TAVR, but the data regarding long-term are limited by older population.

The aim of this study was to evaluate the survival and the factors predicting mortality after TAVR in according to age.

Methods

From April 2008 to December 2019, the self-expandable and balloon-expandable prostheses were was implanted in 765 patients with symptomatic severe aortic stenosis with deemed high risk on base to age, <80 years and ≥80 years old. The rate of acute complications was defined by the combined endpoint of death, vascular complications, myocardial infarction, majopr bleeding or stroke.

Results

The mean age in patients <80 compared with ≥80 years, was 73.69±6.5 vs. 83.4±2.1 years and the logistic EuroSCORE and STS score were 15.9±11% vs. 18±11%, 4.8±3 vs. 6.3±4, p>0.001, respectively In-hospital mortality was 4% vs. 3.4%, p=0.404, and the rate of acute complications was 19.6 vs. 16.5%, p=0.168. The late mortality (beyond 30 days) was 36.9 vs. 35.2%, p=0.352.

When compared in both groups, there were no differences for the presence of threatening bleeding 3.4% vs. 3.2% (HR = 1.028 [IC95% 0.722–1.463], p=0.516), myocardial infarction 4% vs. 2.5% (HR = 1.263 [IC95% 0.814–1.960], p=0.167), stroke 8% vs. 9.1% (HR = 1.149 [IC95% 0.686–1.925], p=0.347) and acute kidney innjury 14.1% vs. 19.1% (HR=0.1.14 [IC95% 0.969–2.141], p=0.071) and there was difference in between groups in hospitalizations for heart failure 14.6% vs. 7.9% (HR = 1.398 [IC95% 1.075–1.817], p=0.008

Survival at 1, 3, and 5were similar in both groups (88% vs. 89.5%, 73.3 vs. 78.2%, 58.8 vs. 62.6%, log Rank 0.992, p=0.319), respectively, after a mean follow-up of 42.3±27 months.

The main predictors of cumulative mortality in young patients were: Charlson index [HR 1.18 (95% CI 1.06–1.30), p=0.001], Acute Kidney Injury [HR 2.21 (95% CI 1.42–3.47), p=0.001], Left ventricular ejection fraction [HR 1.02 (95% CI 1.009–1.035), p=0,001], and protective factor was a higher Karnosfky index [HR 0.98 (95% CI 0.97–0.99) p=0.006]. And in older patients were: Frailty [HR 1.67 (95% CI 1.13–2.47), p=0.010], COPD [HR 2.09 (95% CI 1.41–2.91), p=0,001], Stroke [HR 3.01 (95% CI 1.54–5.89), p=0.001] Charlson index [HR 1.14 (95% CI 1.02–1.27), p=0.015], Acute Kidney Injury [HR 1.57 (95% CI 1.06–2.32), p=0.001.

Conclusions

TAVR is associated with low complications rate in young and older patients. Survival during follow-up was similar in both groups, but the predictive factors of mortality differ, with greater impact on the comorbidtiy in the elderly patients

Funding Acknowledgement

Type of funding sources: None.