bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics associated with prevalent atrial fibrillation and risk profile for future atrial fibrillation among those in sinus rhythm in an elderly population in the ELSA Brasil Study
Authors: Pianca E G , Boccalon B , Foppa M , Pinto-Filho M M , Brant L C C , Ribeiro A L P , Duncan B B , Santos A B S
Published: October 2024

Background

Atrial fibrillation (AF) is an arrhythmia that can lead to limiting symptoms and increases the risk of stroke and heart failure (HF).

Purpose

To evaluate the association of clinical, electrocardiographic, and echocardiographic parameters with prevalent AF or flutter (AFF), and the risk profile for future AFF according to Charge-AF and EHR scores in an elderly population.

Methods

The ELSA-Brasil is a prospective cohort study designed to investigate cardiovascular disease and diabetes in 15,105 men and women, civil servants from universities or research institutions in six cities of Brazil. We included all participants in ELSA-Brasil aged 60 and over whose diagnosis of AFF could be assessed and had echocardiography performed at the study's baseline. From the initial sample with participants ≥ 60 years (n = 3,263), 400 participants were excluded due to missing data about AFF, and 775 who did not have echocardiographic studies.

Results

There were 88 (4.2%) participants with AFF at baseline among the 2,088 (65 ± 4.1 years; 53% women) included in this analysis. Those with AFF were older (66.8 ± 4.4 vs 65 ± 4.0 y-o) and had a higher prevalence of HF (16% vs 3.1%), previous myocardial infarction (14.8% vs 3.8%), left bundle branch block (LBBB: 4.6% vs 0,9%), prolonged QT interval (7.9% vs 2.0%), supraventricular extrasystoles (4.6% vs 1.2%), and sinus bradycardia (11.3% vs 2.9%). AFF individuals also presented larger left atrial volume index - LA (33.3 mL/m2 versus 27 mL/m2), left ventricular end-diastolic diameter (4,63 ± 0,6 cm versus 4,47 ± 0,4 cm) and lower left ventricular ejection fraction (LVEF: 63.6 ± 9.1% vs 67.4 ± 6.4%) that non-AFF (all p-values <0.05). In multivariable analysis, prevalent HF, LBBB, larger LA, and lower LVEF were independently associated with the presence of AFF. Among those in sinus rhythm at study baseline, both risk models showed that most individuals in our sample were at low risk. In the Charge-AF, 63% of individuals were identified as presenting low risk (<2.5%), and 12% of the sample was categorized as high risk, with a risk of five-year AFF greater than 5%. Similarly, in the EHR, 67% of participants were classified as low risk, and 13% were considered high risk.

Conclusion

We found that AFF was present in 4.2% of the subset of older participants in a cohort composed of free-living individuals in Brazil. The presence of AFF was associated with HF history, altered cardiac electrical activity, LA dilation, and worse LV systolic function. Among those with sinus rhythm, 12-13% were considered at high risk of developing AFF (> 5% in five years) based on two clinical scores. Clinical surveillance and monitoring of electrocardiography and echocardiography parameters may help the early identification of risk factors for AFF.
Left atrial morpho-functional parameters and their correlation with other phenotypic and functional characteristics of hypertrophic cardiomyopathy
Authors: Pagourelias E , Boulmpou A , Kotzadamis D , Alexandridis G , Ntelios D , Papadopoulos C E , Vassilikos V P
Published: October 2024

Background

Left atrial (LA) volume index (LAVI), LA reservoir strain (LARS) and total atrial conduction time (TACT) (estimated by tissue Doppler imaging) are morphological and functional parameters reflecting LA structural and electrical remodeling, connected to atrial fibrillation development and heart failure progression in various substrates. In hypertrophic cardiomyopathy (HCM), correlation of the above-mentioned parameters with other disease characteristics is not fully investigated.

Purpose

Aim of this study was to estimate the prevalence of atrial myopathy characteristics such as increased LAVI, impaired LARS and elongated TACT in a cohort of HCM patients without AF history and investigate their correlation with other phenotypic and functional characteristics of the disease such as left ventricular (LV) hypertrophy magnitude, fibrosis extent and diastolic dysfunction grade.

Methods

We included 100 HCM patients (54±21 years, 75% male, maximum wall thickness 19±3.4mm) without history of atrial fibrillation who have consecutively undergone 2D-speckle tracking echocardiography and cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE). TACT and LARS measurement is shown on left panel. Burden of fibrosis (percentage of LV mass) was defined by LGE extent (>5 standard deviations compared to nulled myocardium) in CMR slices.

Results

All HCM patients had preserved EF (60±7.5%), while 28 (28%) presented outflow tract obstruction and 10 (10%) diastolic dysfunction stage≥2. LGE was observed in 64 patients (64%) occupying 8±5% of left ventricular (LV) mass. Mean TACT was 140±22 msec, with LAVI being 32±16 mL/m2 and LARS 26±14%. Among HCM demographic, phenotypic and functional characteristics tested, age and LV mass index were found to be the only independent regressors of TACT (r=0.54, p<0.0005 and r=0.44, p=0.002 respectively, right upper panel), while E/E’ (r=-0.44, p=0.003) and fibrosis extent (r=0.36, p=0.02) were the strongest predictors of LARS and LAVI values respectively (right lower panel).

Conclusions

Atrial myopathy parameters seem to correlate with various morphological and functional characteristics of HCM. Atrial electro-mechanical delay assessed through TDI based TACT correlates significantly with LVMI, whereas LARS and LAVI are strong regressors of elasticity properties, partially expressed through diastolic function and underlying fibrosis.
Pyroptosis is not likely to play a major role in anthracycline-induced cytotoxicity in H9c2 cardiomyocytes and human cardiac endothelial cells
Authors: Salim H Y , Yellon D M , Davidson S M
Published: October 2024

Background

Although anthracyclines are widely used as effective chemotherapeutic agents, anthracycline-induced cardiotoxicity (AIC) causes significant morbidity and mortality. The precise mechanism of AIC remains elusive, although apoptosis may be involved. Recent research suggests pyroptosis, a programmed lytic cell death pathway, might also contribute to AIC. Although studies have focused on AIC in the myocardium, emerging evidence suggests that AIC may also affect vascular cells. Furthermore, the cytotoxicity of doxorubicin (DOX) or its supposed active metabolite, doxorubicinol (DOXOL), has not been widely investigated in cardiac vascular cells.

Purpose

This study examines the hypothesis that pyroptosis plays a role in DOX and DOXOL cytotoxicity in H9c2 immortalised rat cardiac myoblasts and two types of human cardiac endothelial cells.

Methods

In vitro experiments were conducted to ascertain dose-dependent toxicity in H9c2, and cardiac endothelial cells following treatment with DOX or DOXOL.

The type of cell death was determined by assessing cell morphology and fluorescent staining with markers of apoptosis (Annexin V) and lytic cell death (Propidium Iodide PI) following DOX or DOXOL treatment in comparison to known inducers of pyroptosis (LPS & Nigericin).

Western blot experiments were conducted to study the expression of GSDMD (involved in pyroptosis), and caspase 3 (involved in apoptosis), following DOX or DOXOL. A human monocytic acute myeloid leukaemia cell line (THP-1 cells) was used as a positive control for pyroptosis.

Results

Dose-dependent cell death following DOX treatment was higher than with DOXOL in both H9c2 and cardiac endothelial cells. DOX caused apoptotic changes in all cell types. In contrast, DOXOL had weaker effects, inducing early apoptosis. No cleavage (activation) of GSDMD or caspase 3 was detected after DOX or DOXOL. Interestingly, in THP-1 cells, DOX induced predominantly apoptotic cell death, whereas DOXOL induced predominantly pyroptotic cell death, assessed both morphologically and by caspase 3 and GSDMD cleavage.

Conclusion

DOX and DOXOL primarily induce apoptotic cell death in H9c2 cardiomyocytes and cardiac endothelial cells. Interestingly, DOXOL, supposedly the active metabolite, was less cytotoxic than DOX. THP-1 cells undergo apoptotic or pyroptotic cell death with DOX or DOXOL, respectively. In conclusion, anthracycline-induced cytotoxicity is likely to be due to apoptotic injury rather than pyroptosis.
Safety and effectiveness of sodium-glucose co-transporter 2 inhibitors in active cancer patients with heart failure: results of the observational TOSCA trial
Authors: Canale M L , Fabiani I , Delle Donne M G , Barletta V , Capati E , Frediani L , Arena G , Chianca M , Zucchelli G , De Caterina R , Emdin M , Casolo G , Amoroso D , Allegrini G , Camerini A
Published: October 2024

Background

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) currently represent a pillar of heart failure (HF) treatment. However, cancer patients have not been included in landmark randomized controlled trials (RCTs), and data on safety and effectiveness in this population are lacking.

Purpose

Purpose of present study was to evaluate safety and effectiveness of SGLT2i in active cancer patients with HF.

Methods

TOSCA is a multi-centre observational trial including patients (≥ 18 years) with active cancer (diagnosis < 3 years) receiving SGLT2i for HF treatment. Patients were enrolled in two (prospective and retrospective) cohorts. The primary endpoint was safety (incidence of known and unexpected side effects). The secondary endpoint was effectiveness (ejection fraction (EF) increase, New York Heart Association (NYHA) class change, HF-related events). Exploratory endpoints included drug-drug interactions with anticancer and supportive care drugs, treatment of cancer therapy-related cardiac dysfunction (CTRCD), and changes in NT-proBNP.

Results

Eighty-three pts were enrolled (59 prospective - 24 retrospective). Median age was 71 (range 44-92) yrs, M/F 48/52%. The main cancer sites were breast, gastrointestinal tract, and hematological malignancies. Most cases (62%) received an active treatment (mainly chemotherapy) while on SGLT2i. Prevalent aetiology was drug-induced HF (37%) with reduced EF as the prevalent clinical presentation (39%). Prescribed agents were dapagliflozin in 60% and empagliflozin in 40% of cases on top of conventional guideline-directed medical therapy, with a median treatment duration of 3 (range 3-25) months. The incidence of urinary tract infection was 2.5%. No cases of genital infection, hypoglycemia, diabetic ketoacidosis, acute renal injury, thrombosis, and bone fractures were reported. Mean overall EF slightly increased (44.1% vs. 46.6%), and NYHA class improved (class improvement in 16%). Unplanned cardiology visits (1.2%), i.v. diuretics (1.2%), coronary angiography (5%), emergency access (2.5%), and new HF episodes (3.7%) rates were low. SGLT2i appeared effective in 31 cases of CTRCD. A relative reduction in mean NT-proBNP levels (2748 vs 1125pg/mL) was observed. No drug-drug interactions were reported.

Conclusions

SGLT2i appear to be safe and effective in active cancer patients with HF, with potential cardioprotective effect. No new safety warnings were recorded.
Unraveling immune checkpoint inhibitors effects on atherosclerosis: mechanisms and preventive approaches
Authors: Nardi Agmon I , Leshem-Lev D , Shavit R , Gurevitz C , Rahat O , Gueta T , Hochhauser E , Eisen A , Kornowski R
Published: October 2024

Background

Immune checkpoint inhibitors (ICIs) represent a novel and rapidly evolving field in cancer treatment. Despite increasing reports of accelerated atherosclerosis and ICI-related atherosclerotic cardiovascular (CV) events in clinical studies and case reports, there is a notable lack of data concerning the underlying mechanisms, appropriate monitoring, and potential interventions.

Objectives

To explore the role of ICIs in triggering and/or accelerating the atherosclerotic process, with a specific focus on the involvement of CD8+ T-cells. Additionally, we aimed to evaluate and compare the potential beneficial effects of statins and Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors on atherosclerosis under ICIs treatment.

Methods

Thirty 8-week-old C57BL mice were divided into six groups as follows: (1) Control, normal diet; (2) Control, atherogenic diet; (3) Atherogenic diet + anti PD-1; (4) Atherogenic diet + statins + anti-PD1; (5) Atherogenic diet + PCSK9-i + anti PD-1; (6) Atherogenic diet + PCSK9 inhibitors. At 16 weeks, the carotid arteries and heart were removed for histological examination, and serum was withdrawn for blood work and further analysis.

Results

Anti-PD1 treatment resulted in extensive lymphocytic infiltration of the carotid intima, primarily constituted of CD8+ T cells. This infiltration was significantly attenuated when statins or PCSK-9 inhibitors were used in conjunction with anti-PD1 treatment. Serum analysis for CD4+ and CD8+ T cells by ELISA revealed no difference in CD4+ abundance between the groups. However, plasma CD8+ T cells were significantly increased with anti-PD1 treatment, and furthermore, when PCSK9 inhibitors were used in combination; but not when statins were used.

Conclusion

The induction of CD8+ T cell infiltration in the arterial carotid walls by anti-PD-1 was prevented with the use of either statins or PCSK9 inhibitors. In the plasma, while statins reduced the hyper-expression of CD8+ T cells observed under PD-1 treatment, PCSK9 inhibitors enhanced this expression. This may provide a first indication of the potential benefit of PCSK9 inhibitor treatment for both preventing arterial inflammation and enhancing the desired anti-tumor immune response under ICIs treatment.

Figure legend:

1A. A cross-section of the carotid artery after 16 weeks of treatment, stained with H&E. Magnification is X100.

1B. A cross-section of the carotid artery after 16 weeks of treatment, stained with anti-CD8 Ab. Magnification is X100.

1C. quantitative CD8+ T cells staining in the carotid arteries.

1D. quantitative results of ELISA for plasma CD8+ T cells.
The predictive value of coronary artery calcium deposit for cardiovascular events in patients treated with immune checkpoint inhibitor therapy
Authors: Soleman M S , Rozenbaum Z R , Gvili Perelman M G V , Topilsky Y T , Banai S B , Carver J C , Laufer-Perl M
Published: October 2024

Background

Immune checkpoint inhibitors (ICIs) are now a standard of care for the treatment of wide variety of cancers, due to their dramatically improved patient's outcomes. Nevertheless, their use may lead to significant cardiovascular immune-related adverse events (CV irAEs).

Objectives

We aimed to assess whether pre-treatment coronary artery calcium (CAC) deposit may play as a risk factor for CV irAEs development in patients treated with ICIs therapy.

Methods

A retrospective single center cohort of patients treated with ICIs therapy, who performed pre-treatment chest computed tomography. Visual CAC assessment was performed, categorized to positive or negative calcium deposit in the coronary arteries. Patients with pre-existing ischemic heart disease were excluded. The primary endpoint was to evaluate the association between positive CAC deposit and the composite CV irAEs, including myocarditis, acute coronary syndrome, heart failure, and arrhythmias. The secondary endpoint was to evaluate its association to all-cause mortality.

Results

The cohort included 238 patients, with mean age 65±13 years and 53% male representative. The most prevalent type of cancer was lung (36%) and the prominent ICIs regimen was pembrolizumab (54%). High incidence of cardiac risk factors was observed, including hypertension (39%), hyperlipidemia (35%) and diabetes (23%). Overall, 145 (61%) patients were included in the positive CAC deposit group. No significant differences were observed between the positive and negative groups regarding cancer type, ICIs therapy and baseline cardiac risk factors or medical therapy. Over a 12-months follow-up period, positive CAC deposit was not associated with the development of CV irAEs (p=0.139), or increased all-cause mortality (p=0.884).

Conclusion

The presence of pre-treatment positive CAC deposit did not demonstrate a predictive role in assessing the risk of CV irAEs or all-cause mortality in patients treated with ICIs.
Pregnancy and inherited aortopathies: insights from specialized care
Authors: Sola Garcia E , Garcia Garcia A M , Casian M , Cauldwell M , Watt-Coote I , Sharma R , Marciniak A , Tome Esteban M
Published: October 2024

Background

Genetic counselling, pregnancy follow-up and delivery planning in women with aortopathy should be conducted by a multidisciplinary team in an expert centre.

Purpose

Our objective was to analyze the impact of pregnancy on aortopathy outcomes in a centre specialized in inherited cardiovascular conditions in the United Kingdom.

Methods

All women with aortopathy referred to our centre due to pregnancy between 2016 and 2023 were retrospectively analyzed. Demographic, clinical, obstetric, genetic, electrocardiographic, and multimodal imaging variables were collected.

Results

Between 2016 and 2023, 22 women with aortopathy were referred to our centre for pregnancy follow-up and delivery planning. Among them, 14 (63.6%) had Marfan syndrome (FBN1+), 4 (18.2%) family history of aortic dissection without known genetic mutations, 2 (9.1%) bicuspid aortic valve with aortic dilation and 2 (9.1%) Loeys-Dietz syndrome (SMAD3+). The average number of births per patient was 1.55. Among those with an identified mutation, 4 (25%) underwent preimplantation diagnosis. In total, there were 40 pregnancies resulting in 34 live births. 15 women (68.2%) had an aortic root dimension <40mm and 7 (31.8%) ≥40mm. There were 4 (26.7%) and 5 (71.4%) patients in each group under beta-blockers. Out of the total 40 pregnancies, there were 6 (15%) miscarriages, all in the first trimester, 2 (5%) cases of preeclampsia and 1 (2.5%) case of gestational diabetes. There were no statistically significant differences between these complications and the aortic root dimension (8 (20%) <40mm vs 1 (2.5%) ≥40mm; p = 0.160) or the absence or presence of treatment (3 (7.5%) vs 6 (15%); p = 0.769). Regarding delivery, 16 patients (72.7%) underwent vaginal delivery and 6 (27.3%) has a caesarean section. After delivery, there were 6 cases of major bleeding, 4 (10%) after vaginal delivery and 2 (5%) after caesarean (p=0.376). One patient had a subacute type A aortic dissection in the context of Marfan syndrome with an aortic root of 40mm before pregnancy. No significant differences were observed in the occurrence of these complications based on the aortic root dimension (5 (12.5%) <40mm vs 2 (5%) ≥40mm; p = 0.928) or the absence or presence of treatment (2 (5%) vs 5 (12.5%) respectively; p = 0.591). 100% of the patients survived pregnancy and the postpartum period.

Conclusions

Our findings underscore the complexity of managing aortopathy during pregnancy. This highlights the importance of a comprehensive risk assessment for precise pregnancy and delivery planning.
Worse ischemic symptoms and cardiac function in women with suspected ischemia with no obstructive coronary artery disease and adverse pregnancy outcomes history
Authors: Quesada O Q , Oneglia A O , Lauzon M L , Tapp D T , Maughan J M , Wei J W , Shufelt C S , Tamarappoo B T , Pepine C P , Nelso M N , Bairey Merz N B M
Published: October 2024

Background

Adverse pregnancy outcomes (APO) are associated with increased maternal risk of cardiovascular disease (CVD) and mortality. Ischemia with no obstructive coronary artery disease (INOCA) is predominant in women, however the association of APO history with INOCA is poorly understood.

Purpose

To compare clinical characteristics, symptoms, cardiac structure and function and coronary microvascular dysfunction in women suspected to have INOCA with or without a history of APO.

Methods

Women’s Ischemia Syndrome Evaluation (WISE) CVD (NCT00832702) and WISE pre-HFpEF (NCT02582021) prospective cohorts of women with suspected INOCA were merged and utilized to determine among women with at least 1 prior pregnancy whether a history of APO was associated with ischemic symptoms, and to characterize CMRI measured left ventricle (LV) structure and function, myocardial deformation (systolic and diastolic strain) and coronary microvascular dysfunction on invasive coronary functional testing (CFT). Self-reported APO was defined as hypertensive disorder of pregnancy (HDP), gestational diabetes, preterm birth (<37-week gestation), low birth weight (<5lbs).

Results

In a cohort of 469 women with suspected INOCA, (mean average age 55 [SD 10.2] years) and at least 1 prior pregnancy, 138 (29%) had history of at least 1 APO. Among women with history of APO, 78 reported HDP, 50 gestational diabetes, 27 pre-term birth, 8 low birth weight. Women with a history of APO were younger, had higher rates of hypertension and diabetes, higher BMI and lower SAQ and DASI scores compared to those with no history of APO (Table). LV ejection fraction (EF) was lower and early diastolic strain rate/LVEDP was higher in women with APO history compared to those without APO history.

Conclusion(s)

In cohort of women with INOCA, history of APO was highly prevalent. Despite younger age, women with history of APO had higher rates of CVD risk factors, worse ischemic symptoms and functional capacity, lower EF, and higher filling pressures. Our findings suggest a potential for APO history to better identify women with worse prognosis that warrants further investigation and aggressive management.
Subclinical myocardial disfunction detected by left ventricle myocardial work impairment in patients with long standing human inmmunodeficiency virus infection
Authors: Gascuena R , Gomez Diego J , Cervero M , Torres R , Morales T , Jimenez Azzaoui B , Ayllon J , Ruesgas R , Esteban A
Published: October 2024

Heart failure is a known complication in patients living with human inmmunodeficiency virus (HVI) infection. Detection of subclinical disfunction is nowadays possible by echocardiographic strain techniques. Myocardial work is a novel technique based on global longitudinal strain (GLS) that measures global work efficiency of left ventricle (GWE) and would allow early detection of subclinical myocardial damage.

Methods

We performed a cross sectional echocardiographic study of patients with long standing HIV infection, and no previous cardiopathy, assessing GLS of left ventricle (LV), left atrium (LA) and free wall of right ventricle (RV-FW GLS). We identified patients with subclinical disfunction expressed by an impaired GWE , and studied its determinants by lineal regression.

Results

110 patients, 78.2% male, median age 53.3 (51.2-55.4) were included. Time from diagnosis was 20.5 (18.6-22.3) years. Myocardial work strain analysis showed an impaired GWE: 91.9% (90.9-92.9);p<0.001) and a GW index of 1840.8 mmHg%(1758.7-1922.9):p<0.001. The rest of deformation parameters laid into normal range: LV GLS was -19.5% (-19.0- -20.0) GLS dispersion 55.1 (50.1-60.1), LA GLS (reservoir) 32.8% (31.2-34.5), and RV free wall GLS -22.3% (-21.4 - -23.2).

By univariate analysis, determinants of impaired GWE were age, Score2 risk, time from HIV diagnosis, QRS Interval duration, long QTc Interval, LV ejection fraction (LVEF),diastolic disfunction by doppler tissue imaging, CD4 count nadir, initial and maximun viral load, and exposure to didanosine treatment. After adjustment by cardiovascular risk and diastolic function (Ea velocity by tissue Doppler) , GWE impaired depended on duration of infection (Beta 0.3;95%CI:0.04-0.56;p=0.023), initial viral load (Beta -1.1;95%CI:-2.1- -0.02;p=0.046) and exposure to stavudine (Beta -6.3;95%IC: -11.5- -1.1;p=0.019).

Conclusions

Subclinical myocardial disfunction is prevalent in long standing HIV infection. Global work efficiency is a very sensitive parameter for detection, even in patients with normal GLS values, and it was related to duration of infection, initial viral load, and exposure to stavudine in our patients.Determinants of Global Work Efficiency
Prognostic value of C-reactive protein / albumin ratio for amputation and/or mortality after lower extremity revascularization in haemodialysis patients with peripheral artery disease
Authors: Takahashi H , Kumada Y , Kawai N , Ishida N , Nakamura Y , Ito R , Oshima S , Izawa H , Ozaki Y , Murohara T , Ishii H
Published: October 2024

Background

Hypoalbuminemia, a manifestation of protein-energy wasting (PEW) or malnutrition, which is commonly observed in patients with chronic kidney disease, is associated with increasing cardiovascular risk. Recently, C-reactive protein (CRP) / albumin ratio has been developed as a newly surrogate marker of the PEW because the PEW seems to result not only from an inadequate diet but also rather be induced by chronic inflammatory status. The aim of this study was to clarify whether pre-procedural CRP/albumin ratio levels could predict amputation and/or mortality after lower extremity revascularization for peripheral artery disease (PAD) in patients on haemodialysis (HD).

Methods

A total of consecutive 1,850 HD patients successfully undergoing lower extremity revascularization (494 bypass surgery and 1,356 endovascular therapy) were enrolled in this study. Patients were divided into tertiles according to pre-procedural CRP/albumin ratio levels; low (<0.6, n=619), middle (0.6-3.7, n=609) and high tertile (>3.7, n=622). They were followed up for up to 8-year. The primary endpoint was defined as amputation and/or mortality.

Results

During follow-up period (median of 53 months), 162 major amputation (8.8%) was performed and 508 patients (27.5%) died. Cumulative incidence rates of amputation and/or mortality at 8-year were 47.4%, 56.2% and 70.0% in low, middle and high tertile of CRP/albumin ratio, respectively (p<0.0001). After adjustment for male, age, traditional risk factors, body mass index, history of coronary artery disease or stroke, procedure (bypass vs. endovascular therapy), infrapopliteal disease and ulcer/gangrene, the CRP/albumin ratio was identified as an independent predictor for amputation and/or mortality [adjusted hazard ratio (aHR) 1.39, 95% confidence interval (CI) 1.12-1.72, p=0.0028 for middle vs. low tertile, and aHR 2.53, 95% CI 2.07-3.09, p<0.0001 for high vs. low tertile, respectively]. Similar results were also observed even for major amputation and mortality, respectively (aHR 2.73, 95% CI 1.77-4.31 for amputation and aHR 2.32, 95% CI 1.82-2.97 for mortality with p<0.0001 for high vs. low tertile in both, respectively, Figure).

Conclusion

Pre-procedural CRP/albumin ratio could predict both of amputation and mortality after lower extremity revascularization, and could stratify the risk in HD patients with PAD. Measurement of CRP/albumin ratio in such high-risk population may be useful because this newly surrogate marker of the PEW is simple and can be easily obtained in daily practice.
Surgical reduction of a high-flow dialysis fistula has long-term positive effects of the heart
Authors: Valerianova A , Buryskova Salajova K , Malik J
Published: October 2024

Introduction

Part of chronic haemodialysis patients develop a high-flow arteriovenous fistula (AVF). The volume overload caused by the presence of a high-flow AVF leads to increased cardiac output, dilation of cardiac chambers, increased pulmonary artery pressure or even to the development of high-output heart failure. Our previous data showed a positive effect of AVF flow-reducing surgery in 6 weeks follow-up.

Purpose

The purpose of this study was to analyse the long-term effect of AVF blood flow (Qa) reduction on cardiac structure and function.

Methods

We included patients with high-flow AVFs (defined as Qa over 1500 mL/min) indicated for blood flow reduction surgery for heart failure symptoms or pre-defined echocardiographic changes (left ventricular hypertrophy, severe secondary valvular regurgitations, or pulmonary hypertension). Echocardiography was performed one day before the surgery, the 6 weeks, 6 months, and 12 months thereafter. Qa was measured by ultrasound during the same visits.

Results

27 patients were included, 20 men and 7 women, aged 57 ± 13 years. The procedure led to an immediate decrease in Qa. However, we observed failure of the procedure within 1 year in 8 (= 30%) patients defined by increased Qa back to pre-surgery values. Detailed results are displayed in Table 1. Estimated pulmonary arterial systolic pressure and left atrial volume remained significantly lower after 1 year despite the Qa rise. Effective cardiac output (= difference of cardiac output and Qa) rose immediately and remained increased during the follow-up period despite the increase in AVF blood flow.

Conclusions

We observed a long-time positive effect of AVF blood flow reduction surgery on the heart despite a significant Qa rise. The effective cardiac output remained increased despite the gradual increase of Qa, probably due to the adaptation of systemic arterioles.
Plasma statin concentrations do not correlate with statin-induced myalgia
Authors: Ritvos M , Mombelli G , Ramste M , Laaperi M , Kauhanen D , Sinisalo J , Sirtori C , Thompson P D , Dube M P , Tardif J C , Laaksonen R
Published: October 2024

Aims

Statins are essential in cardiovascular prevention. Although well-tolerated, patient adherence is often suboptimal due to experienced musculoskeletal symptoms ranging from mild myalgia to rare life-threatening rhabdomyolysis. This study aimed to investigate the relationship between plasma concentrations of statin metabolites in patients experiencing myalgia without rhabdomyolysis.

Methods and results

Plasma concentrations of statin metabolites were quantitatively assessed using mass spectrometry across three case-control cohorts evaluating statin-induced myalgia. The analysis included a total of 373 patients from the MILANO study (N=85 with self -reported myalgia), the MONTREAL study (N=248 with clinically verified myalgia) and the STOMP study (N=40 with rechallenge-verified statin-induced myalgia). STOMP found no significant difference in the plasma concentrations of statin metabolites between statin naïve patients with myalgia (N=12) taking atorvastatin 80 mg daily and asymptomatic controls (N=28), including upon subsequent statin rechallenge. Both the MILANO and MONTREAL studies showed lower plasma concentrations of statin metabolites in patients with myalgias compared to controls. MILANO showed a significant difference in rosuvastatin lactone concentration in patients with myalgias compared to asymptomatic controls (P = 0.025). Similarly, MONTREAL showed significantly lower mean atorvastatin metabolite concentrations in affected patients versus controls (P values ranging from 0.0073 to 0.037). Atorvastatin dosages in MONTREAL ranged from 5 to 80 mg daily, the most frequent regimens being 20 mg (27% in cases; 24% in controls) and 40 mg (33% in cases; 37% in controls). Creatine kinase levels were measured in all cohorts and were not different between cases and controls.

Conclusion

Development of myalgias in patients with normal creatine kinase levels is not associated with higher statin metabolite plasma concentrations. Myalgias during statin therapy are not caused by pharmacokinetic abnormalities.
Glutathione s-transferase pi is a marker of loop diuretic resistance in patients with congestive heart failure exacerbation
Authors: Imiela T , Poplawski P , Zaborska B , Pilichowska - Paszkiet E , Bednarczyk T , Piszcz K , Budaj A
Published: October 2024

Background

Loop diuretic resistance (LDR) in patients with heart failure (HF) exacerbation is associated with worse clinical outcomes, greater symptom burden and mortality. Diagnosis and treatment of LDR remains a significant clinical dilemma.

Purpose

To assess the ability of different urine biomarkers to predict LDR in patients with HF exacerbation.

Methods

Consecutive patients with congestive HF exacerbation were prospectively included in the study. HF was diagnosed according to ESC 2021 HF Guidelines definition. Congestion was defined as a presence of one or more of the following signs: edema, ascites, pleural effusion. LDR was defined as persistent congestion on the 4th day of hospital stay despite high i.v. loop diuretic dose. Urine biomarkers released from different parts of the nephron (Kidney Injury Molecule-1 - KIM-1, N-acetyl-β-D-glucosaminidase - NAG, uromodulin, glutathione S-transferase Pi - pi-GST, aquaporin-2), transthoracic echo, clinical and biochemical parameters were evaluated on the 1st and 4th day of hospital stay. Results are presented as mean ±standard deviation or median (interquartile range).

Results

40 patients were included in the study with median age 84 (72,8; 86) years, median left ventricle ejection fraction (EF) 35.3 (26,5; 49) %, median NT-proBNP 8967.5 (3024; 15241) pg/ml. LDR was found in 14 (35%) patients. Univariate analysis identified the following risk factors for LDR: urine pi-GST concentration on admission and on the 4th day, right ventricle to pulmonary circulation coupling index (TAPSE/PASP ratio), presence of mitral regurgitation, serum creatine concentration, serum urea concentration, serum LDL concentration. Logistic regression analysis identified pi-GST concentration as a significant independent risk factor for LDR in this population: odds ratio (OR) 5.75 [95% confidence interval (CI) 1.271–25.990].

Conclusions

Urine pi-GST on admission and after 4 days of treatment might be a marker for a development of LDR in patients with congestive HF exacerbation.
121 year after Einthoven: show me the normal ECG?
Authors: Van Dam P , Malinowski K , Proniewska K K
Published: October 2024

Background

The clinical electrocardiogram (ECG) is measured about 120 years. The interpretations of the ECG is an art mastered by only few. Rhythm and Interval analysis is relative reliable and well supported by the available ECG machines. However, the interpretation of the ECG waveform and where it starts to deviate from the normal waveforms is poorly defined for the clinical practice. To support the anatomical relationship of the ECG, the PathECG has been developed as part of the CineECG tool, expanding the view on the ECG. In this study normal ECG distributions were created from a public available database to enable a) visual comparison of the ‘normality’ of the ECG and PathECG and b) build a predictive model to classify an ECG as normal or abnormal.

Purpose

To create an objective and 3D visual comparison of an ECGs to "normal ECGs".

Methods

From the (Physionet) PTB-XL database (Germany) all verified ECGs with known gender were selected. From the these ECGs a median ventricular beat was automatically constructed and subsequently resampled to have a standardized number of samples (Figure: Normal ECGs on top of abnormal ECGs). These resampled ECGs were also converted to their equivalent PathECG. From the normal labeled ECGs (3124 female, 2283 male) distributions were created, representing the normal ECG for male, female or the combined group. With these distributions a percentage of ECG segments (QRS, ST, T wave) can be identified as being outside this distribution, and thus as potentially abnormal. A logistic regression model was fitted to determine the optimal outlier removal per segment for the ECG waveforms and the PathECG to classify and ECG as normal or abnormal per gender group. The performance was tested on the CPSC (Hong Kong) public available ECG database.

Results

The abnormal ECG data in both databases contained approximately 1/3 normal ECG, atrial and ventricular arrhythmias and 1/3 ischemia and conduction disorders. The performance (AUC) of the logistic regression model on the PTB-XL and CPSC data respectively was MALES: 87.5% - 81.5%, FEMALES: 86.7% - 83.7%, and COMBINED: 86.8%-82.9%. The visual overlay of the ECG significantly supports the identification of abnormal segments (Figure: Normal ECG distribution example).

Conclusions

The overlay of an ECG and PathECG on the normal distribution supports the identification and verification of abnormal ECGs. This method might increase the ability of less experienced ECG readers, like general practitioners, to identify patients that need to be transferred to a cardiologist. This method could also be used for the classification of P-waves, paediatric ECGs or ECGs in specific patient groups.Normal ECGs on top of abnormal ECGsNormal ECG distribution example
Prognostic assessment based on the trajectory of artificial intelligence-enabled electrocardiograms for age estimation
Authors: Hwang T , You S C , Kim S , Eom S , Boo D , Kim D , Kim T H , Uhm J S , Pak H N , Lee M H , Yu H T , Joung B
Published: October 2024

Background

Artificial Intelligence (AI) estimation of age using data from the 12-lead electrocardiogram (ECG) has demonstrated its utility as a biomarker in predicting the future risk of cardiac diseases and mortality. However, expected long-term outcomes based on temporal changes in the AI-ECG age gap remain unclear.

Purpose

This study aims to utilize the difference between ages predicted by AI-ECG and actual ages longitudinally for follow-up and to assess whether there are significant clinical differences in mortality among specific groups.

Methods

Among patients at a hospital who had not been used for the AI-ECG age prediction model (121,702 individuals, 522,261 ECGs), 6,685 individuals with 31,858 ECGs who had an index ECG and the subsequent ECG in the fifth year, with at least one intervening ECG were included for analysis. The absolute age gap, defined as the absolute difference between ECG-predicted and chronological age, was limited to ±10 for analysis. Latent class trajectory modeling was then utilized to classify groups based on the AI-ECG age gap.

Results

Data-driven analysis revealed four distinct trajectory groups based on age gap trajectories: Consistently Young ECG (27.2%), Reversed ECG Aging (35.3%), Accelerated ECG Aging (8.0%), and Consistently Old ECG (29.5%). Notably, the Accelerated ECG Aging group exhibited a significantly higher cumulative incidence of all-cause death (adjusted hazard ratio (HR) 1.66 (95% confidence interval (CI) 1.30-2.12, p-value <0.001) and non-cardiac death (adjusted HR 1.83 (95% CI 1.38-2.43, p-value <0.001) compared to the Consistently Young ECG group.

Conclusion

Among 4 distinct trajectories based on the changes in the AI-ECG age gap, Accelerated ECG Aging was associated with a heightened risk of all-cause mortality. Additional in-depth analysis of factors associated with Accelerated ECG Aging is warranted.
Development of an automated process for monitoring of amiodarone treatment
Authors: Sjoland H , Landahl J , Tammelin K , Lindgren M , Rosengren A , Papachrysos N , Filipsson Nystrom H , Johansson B I
Published: October 2024

Background

Amiodarone treatment requires repeated laboratory evaluations of thyroid and liver function due to risk of side effects during long-term administration. Robotic process automation (RPA) represents the use of software robots to automate repetitive and routine tasks typically performed by humans.

Purpose

We aimed to develop an RPA using a diagnostic classification algorithm and clinical support system for follow-up of amiodarone treatment.

Methods

Based on international guidelines and clinical specialist advisory we constructed an RPA which was studied in a test environment in parallel with routine amiodarone treatment. Expert advice was integrated through a series of collaborative workshops, ensuring alignment of the algorithm with current best practices in thyroid and liver disease management. The RPA provided recommendations on the time interval to next laboratory testing and suggestions for patient management to the physician, who was serving as a human-in-the-loop responsible for clinical decisions.

Results

After iterative improvements the RPA was evaluated against physician orders (n=390 paired orders) without technical failures. The recommended time interval to next follow-up was (mean ± SD) 4.5 ± 2.4 vs. 3.1 ± 1.4 months for RPA vs. physician (p<0.0001). While normal laboratory findings resulted in recommended follow-up in 6 months by the RPA (72.2%) this was only ordered in 9.9% by the physician (Figure). Physicians’ orders clustered between 3-4 months (58.5%). All patients diagnosed with new side effects (n=12) were detected and communicated correctly by the RPA, whereas only 8 were correctly detected and responded to by the physician (Table).

Conclusions

An automated process constitutes a reliable alternative to the current fully manual management of amiodarone follow-up. It may reduce manual labour, frequency of laboratory testing and detect side effects with increased precision, thereby reducing costs and enhancing patient value. While the RPA shows promise, further research is needed to explore its adaptability to other treatment scenarios.
Validation of chest-belt ECG evaluation using artificial intelligence
Authors: Skala T , Vacha J , Vicha M , Klimes D , Taborsky M
Published: October 2024

Background

Simple, cheap wearables for long-term ECG monitoring with automatic analysis of all measurements using a bespoke artificial intelligence (AI) are scarce. Annotated single-lead ECG data from a chest-belt are missing.

Methods

We have developed a complex software environment to acquire raw ECG data from the Polar H10 chest-belt, and a bespoke, original AI to detect artifacts, QRS complexes and the presence of atrial fibrillation (AF) from chest-belt recordings. Original manually annotated ECG recordings from real patients from cardiology departments using the chest-belt and a public MIT-BIH database as reference were used for validation.

Results

QRS determination by AI (version Q4/23) in evaluating MIT-BIH database of ECG samples had a 97.67 % sensitivity and a 97.73 % positive predictive value. AF in MIT-BIH database was detected by AI with 90.31 % sensitivity and 92.09 % positive predictive value.

To assess AI accuracy in ECG from a chest-belt, 150 consecutive measurements using Polar H10 chest-belt (215 hours of ECG recordings in total) from individual patients were included in the analysis. Patients were not limited in any physical activity during measurements.

7.15 % of the length of all recordings (15.4 hours) was assessed as noise by AI and excluded from the analysis. AF lasting longer than 30 seconds was present in 14 of 150 (9.3 %) manually evaluated recordings.

QRS determination by AI in evaluating manually annotated chest-belt data had 99.76 % sensitivity and 99.74 % positive predictive value. AF in manually annotated chest-belt data was detected by AI with 92.86 % sensitivity and 100 % positive predictive value.

Conclusion

A chest-belt can be used to reliably detect QRS complexes and the presence of atrial fibrillation with high accuracy when using a bespoke artificial intelligence for the evaluation. Commonly available devices capable of long ECG measurements could be used for patient-empowered screening for important arrhythmias.Atrial fibrillation on chest-belt ECG
Physical activity habits among members of the Athens Medical Society in Greece
Authors: Lampsas S , Marinos G , Lamprinos D , Gialamas I , Pantelidis P , Goliopoulou A , Gounaridi M I , Pililis S , Anastasiou A , Theofilis P , Kalogera S , Chatziralli I , Lambadiari V , Siasos G , Oikonomou E
Published: October 2024

Introduction

Benefits of regular physical activity and exercise are well documented. Healthcare workers play a crucial role in counseling and appropriately referring their patients to adopt physical activity. However, doctors’ exercise habits range between different medical specialties and health service infrastructure.

Purpose

In this study, we assess physicians’ exercise performance according to the recommendations of 2020 ESC Guidelines.

Methods

The population of this cross-sectional study comprised 742 physicians of the Athens Medical Society (AMS), Greece. The study instrument was a self-administered questionnaire mailed in October 2023 to investigate physicians’ exercise habits, baseline characteristics of population, specialty, and health service infrastructure [Greek National Healthcare System (GNHS) or Private Practice (PP)]. European Society of Cardiology (ESC) Guidelines recommend at least 150 min/week of moderate-intensity exercise in all healthy adults. Subjects were divided in two groups according to their compliance to ESC Guidelines: 1. Moderate-intensity endurance exercise training per week ≥ 150 min (Group A); 2. Moderate-intensity endurance exercise training per week <150 min (Group B).

Results

The recommended exercise training per week goal is achieved by the majority of AMS members (53.4%) with an estimated mean exercise endurance training time of 240 ± 285 minutes. Between Group A and Group B there was no difference in age (50±12years vs. 50±13years, p=0.73), whereas there was significant difference in male sex prevalence (58% vs. 43%, p <0.001), in Body Mass Index (24.7 ± 3.8 kg/m2 vs. 26.2 ± 4.7 kg/m2, p <0.001), in Smoking habits (17.4% vs. 23.5%, p=0.04), in diabetes mellitus incidence (6.6% vs. 11.8%, p= 0.01) and in the use of activity monitoring wearables (45.2% vs. 29.8%, p<0.001). Interestingly, there was significant difference between GNHS and PP doctors representation in Group A and B with more doctors in the PP categorized in the Group A (p=0.008) (Figure 1). Importantly, logistic regression analysis revealed that even after adjustment for the aforementioned confounders there was significant under-representation of the GNHS in the Group A or otherwise doctors in the GNHS have 33% decrease odds of achieving the recommended exercise training per week (Odds Ratio: 0.676, 95%CI 0.484, 0.943, p=0.02) (Table 1).

Conclusion

A significant proportion of the AMS members follows the recommended ESC guidelines for minimum exercise training per week. Several factors affect their adherence to exercise time recommendation. Interestingly, AMS doctors working on the GNHS independently of other factors are less adherent to exercise recommendations. These findings emphasize the need to strengthen prevention strategies to AMS.