bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in cardiovascular risk in the general population of low and high altitude residents in Peru. HIGH Altitude CArdiovascular REsearch Latin America Population Study (HIGHCARE-LAPS)
Authors: Bilo G , Villafuerte F C , Zanotti L , Soranna D , Nava S , Rusconi V , Pengo M F , Croce A , Lombardi C , Macarlupu J L , Bermudez D , Sosa J M , Carcamo C P , Zambon A , Parati G
Published: October 2024

Introduction

Living at high altitude (HA) is associated with profound changes in cardiovascular physiology, mostly caused by chronic hypoxia. Available data from high income countries (Switzerland, Austria) suggest beneficial effects of moderate altitude residence in terms of cardiovascular risk. Little is known, however, about cardiovascular risk profile in long-term residents of higher altitudes from low-income countries.

Aim

To compare cardiovascular risk estimated with validated score in population-based samples of permanent residents of low and high-altitude communities in Peru.

Methods

Study participants (adults permanently residing at either low or high altitude) were recruited by sex- and age-stratified random multistage cluster sampling from the general population of urban areas at different altitudes in Peru (lowlanders: <500 m above sea level, highlanders: cities at 3287 m, 3824 m and 4330 m). For all participants questionnaire-based information, conventional blood pressure (BP; 3 seated measurements with a validated oscillometric device) and laboratory variables were obtained. Based on the collected data atherosclerotic cardiovascular disease (ASCVD) risk was estimated according to Pooled Cohort Equations (PCE, previously calibrated in South American population). Participants below 40 years of age, with ASVCD history, with LDL-C≥190 mg/dL or on LDL-C lowering therapy were excluded from this analysis.

Results

The analysis included 146 lowlanders and 373 highlanders, most of whom had low 10-year ASVCD risk, with the median estimated risk being significantly higher among lowlanders. Comparisons between the groups in terms of principal variables of interest are reported in the Table. The highlanders were slightly younger, had lower BMI, conventional BP, HDL cholesterol, lower prevalence of antihypertensive medication and of diabetes, and higher heart rate. In a multivariable model the difference in ASCVD risk between lowlanders and highlanders was significant (p=0.0009) after adjusting for BMI and socio-economic variables but not after systolic BP was included in the model (p=0.800).

Conclusions

Residence at HA is associated with a lower estimated ASCVD risk in the general population of Peru, mainly because of lower BP levels. Considering that the prognostic value of cardiovascular risk estimates in highland populations is unknown, longitudinal cohort studies would be required to assess whether this finding is associated with a lower rate of cardiovascular events.
Fitness to fly: assessing cardiac disease among Air Force pilots
Authors: Certo Pereira J , Monge J , Baptista A , Reis P , Dores H
Published: October 2024

Introduction

Aviation is a risk activity, particularly in pilots with cardiovascular (CV) disease. The occurrence of acute clinical events during flight may have catastrophic implications, justifying the relevance of cardiologic evaluation in Aviation Medicine. However, the evidence about the impact of CV diseases in this population is scarce.

Aim

To study the cardiac causes of incapacitation among pilot candidates and pilots of the Portuguese Air Force (PoAF) over a period of 20 years.

Methods and results

A retrospective analysis of cardiac causes of incapacitation between January 1999 and December 2018 was performed, both in PoAF candidates and pilots. In this period, the overall number of candidates was 2529 and the number of PoAF pilots was 760. Among the candidates, 41% (N=1086) were considered unfit, of which 4% (N=39) due to cardiac causes (all men aged 17-25), namely valvular diseases (N=27) and conduction/heart rhythm disturbances (N=12). Among the pilots, 2% (N=18) were considered unfit, mainly due to cardiac disease (50%; N=9). These pilots considered unfit pilots due to cardiac disease were men with mean age of 47±9 (30-60) years old, all unfit due to acute myocardial infarction, none occurring during flight.

Conclusion

Cardiac diseases were an uncommon cause of incapacitation among the pilot aviator candidates, but it was the main cause among the pilots of the PoAF during two decades, all due to acute myocardial infarction. Cardiac evaluation in Aviation Medicine is essential, focusing on CV risk stratification and preclinical detection of coronary artery disease.Figure 1
Defibrillator shocks and their effect on objective asian patient outcomes: results of the painfree SST clinical trial
Authors: Kondo Y , Sears S F , Bart G , Sterns L D , Schloss E J , Meijer A , Auricchio A , Kurita T
Published: October 2024

Background

The implantable cardioverter defibrillator (ICD) reduces mortality in patients at risk of sudden cardiac death. However, the effect of ICD shock on device-measured activity is unknown. The aim of this analysis was to analyze the acute and long-term effects of ICD shock on objective behavioral data.

Methods

The PainFree SST study was a prospective, multicenter, global study that enrolled 2770 patients including 225 from from Asia (181 from Japan, 25 from India, and 19 from Malaysia). Patient physical activity was determined from the device built-in accelerometer. The device translates the accelerometer output into a count of active minutes, which is stored as a daily total value in device memory for a rolling window of 425 days. Obviously, activity is measured only after device implantation. Early after implant, activity is reduced due to the procedure and thus not representative. Therefore, no baseline can be reported for activity. The follow-up activity data was analyzed with a linear mixed model, with a random effect for patient and an auto-regressive correlation matrix for subsequent measurements of individual patients.

Results

Figure 1 shows average daily activity between 90 days before and 90 days after a shock. The dashed vertical line indicates the day of shock. Both patients from Asia and from other countries show a drop in activity after a shock with recovery in the subsequent 30-60 days. The curve for Asian patients is more variable than the curve for other countries due to the lower number of patients (there were 33 Asian patients with shocks contributing data). Figure 2 shows average daily activity before and after ATP therapy. Any post shock measurement is excluded. Contrary to the temporary reduction in activity around a shock (Figure 1), ATP therapies do not seem to have an impact on activity. In patients from the other countries, activity is significantly reduced when patients are hospitalized (-66.3 minutes/day, p<0.0001), but not in Asian patients (-5.1 minutes/day, p=0.71). Both in Asian and other countries, activity is significantly reduced after an ICD shock (Asian: -47.5 minutes/day, p=0.0002; Other countries: -21.5 minutes/day, p<0.0001). The effect of shock for Asian is greater than the other countries (p=0.054). In the month after the shock there is a significant recovery, +34.8 minutes/day in Asian patients (p=0.0077) and +7.7 minutes/day in patients from other countries (p=0.031). The recovery is trended to be bigger in Asian patients (p=0.058).

Conclusions

ICD shocks have a lasting adverse impact on objective, device-measured physical activity, particularly among Asian individuals. Successful management of patients with an ICD necessitates specific attention to clinically relevant behavioral outcomes, aiming to expedite recovery and facilitate a return to activities of daily living, with a particular focus on the Asian population.
A flattening systolic blood pressure response at the end of ramp exercise testing is not associated with all-cause mortality
Authors: Carlen A , Lindow T , Cauwenberghs N , Elmberg V , Brudin L , Ekstrom M , Hedman K
Published: October 2024

Purpose

Systolic blood pressure (SBP) is expected to rise linearly during ramp exercise, but sometimes plateaus before the end of exercise. We aimed to examine the predictive value of a plateauing SBP response at the end of a cycle exercise test.

Methods

We analyzed 9,001 consecutive patients aged ≥18 years with maximal cycle ergometer ramp tests, after excluding subjects with valvulopathy, pacemaker, arrhythmia during the test, or body mass index (BMI) >40kg/m², as well as tests with resting SBP <80mmHg or >200mmHg, exercise SBP <100 mmHg, <2 SBP measurements during the second half of the test or a test duration <4 minutes. The data were cross-linked with nationwide registries for mortality and in- and outpatient hospital diagnoses. The difference in SBP between the two last SBP measurements was standardized to the difference in Watts between the same time points, categorized as i) an SBP decrease (drop), ii) an SBP increase of <2.5 mmHg per 10 Watts increase (flat), iii) an SBP increase of 2.5-15 mmHg/10 Watts (intermediate), and iv) an SBP increase >15 mmHg/10 Watts representing the 97.5th percentile (steep). Hazards ratios (HR, [95% confidence interval, CI]) for all-cause mortality were calculated, stratified for exercise capacity (peak Watt % of predicted) with the intermediate SBP response as reference. Adjustments were made for age, sex, BMI, resting SBP, baseline diagnosis of ischemic heart disease, heart failure, chronic obstructive pulmonary disease, and the use of beta-blockers or anti-hypertensive medication.

Results

Decreasing, flat, intermediate, and steep SBP responses at the end of exercise were present in 1.1%, 25.6%, 70.8% and 2.5% of patients respectively (Table 1). During median follow-up 8.6 years (interquartile range 5.9–11.6 years) there were 844 deaths. When compared to an intermediate SBP response, a flat SBP response was not associated with all-cause mortality in any of the exercise capacity strata: lowest tertile of Wmax%pred unadjusted HR 0.88 (95% CI 0.69–1.11), middle tertile HR 0.91 (95% CI 0.66–1.24), and highest tertile HR 0.95 (95% CI 0.64–1.41), with HRs remaining non-significant after adjustment for covariates (Table 2).

Conclusion

In patients referred for exercise testing, a flattening SBP response at the end of exercise was not associated with increased all-cause mortality risk compared to an intermediate SBP response, consistent across the different exercise capacity strata.
Incidental detection and quantification of coronary artery calcification in ungated thoracic computed tomography for prognostic assessment. Preliminary results from the ICARUS registry
Authors: Marcos Garces V , Minguez Diaz De Alda S , Merenciano-Gonzalez H , Villa-Sanchez C A , Perez-Pelegri M , Gavara J , Bertolin-Boronat C , Iraola-Viana D , Perez N , Rios-Navarro C , De Dios E , Canoves J , Sanchis J , Moratal D , Bodi V
Published: October 2024

Background

Coronary artery calcium (CAC) score improves cardiovascular risk stratification in asymptomatic individuals. However, whether CAC can be quantified in ungated thoracic computed tomography (uTCT) performed for other indications, and if this CAC score associates with cardiovascular outcomes, hasn’t been confirmed yet.

Purpose

We aim to analyse the extension of CAC and its prognostic value in terms of major adverse cardiovascular events (MACE) in patients who underwent uTCT for other indications.

Methods

We analysed a preliminary sample of 115 uTCT performed in 2015 in our hospital. We studied the presence and extension of CAC and quantified the global CAC score by Agatston method using validated software. Patients were categorized according to Coronary Artery Calcium Data and Reporting System (CAC-DRS) categories. Cardiovascular risk factors, lipidic control and pharmacological therapy of the cohort were registered. We analysed the time to first 3P-MACE, defined as cardiovascular death, non-fatal myocardial infarction and non-fatal stroke, whichever occurred first. A p-value <0.05 was considered statistically significant.

Results

Mean age of the cohort was 60.8±16.1 years (53% male, 53% smokers). Mean LDL-cholesterol was 121.67±34.91 mg/dL, and 35.1% received lipid-lowering therapy. In more than half (n=59, 51.3%) of the population CAC was detected. Mean CAC score was 312.99±774.48 Agatston units, and patients were categorized in CAC-DRS category 1 (n=19, 16.5%), category 2 (n=15, 13%) and category 3 (n=25, 21.7%). Patients with CAC were older (71±10.1 vs. 50.1±14.2 years, p<0.001), had higher burden of cardiovascular risk factors and prevalence of chronic kidney disease (CKD; n=8, 13.6% vs. n=1, 1.8%, p=0.03) and higher levels of triglycerides (143.2±80.5 vs. 106.8±36.2 mg/dL, p=0.004), but not LDL-cholesterol. Eleven (9.6%) patients presented 3P-MACE during a mean follow-up of 6.55±2.82 years. CAC score independently predicted 3P-MACE (HR 1.06 [1.01-1.11] per 100 Agatston units, p=0.02) along with CKD (HR 6.94 [1.58-30.46], p=0.01) and basal glucose levels (HR 1.03 [1.02-1.04] per mg/dL, p<0.001).

Conclusions

CAC can be incidentally detected in more than half of our unselected cohort of patients undergoing uTCT for other indications. CAC score quantification by Agatston method is feasible in uTCT and associates with a higher risk of MACE during follow-up.Incidental CAC detection in uTCT
Association of adverse childhood experiences with adult-onset cardiometabolic conditions and prescription medicine use
Authors: Caglayan S , Gronnli O K , Hoye A
Published: October 2024

Association of adverse childhood experiences with adult-onset cardiometabolic conditions and prescription medicine use

Background and importance

Adverse childhood experiences are potentially preventable and traumatic events that occur during childhood. Childhood exposure to trauma is highly prevalent and adults who had adverse childhood experiences are at increased risk of developing physical conditions. However, effect of adverse childhood experiences on health outcomes remains underrecognized.

Aim

Here, we aimed to measure the association of cumulative adverse childhood experience with adult physical condition and use of prescription medicines in general population.

Methods

We conducted a cross-sectional analysis using the population-based health study including 21083 participants at age 40 years or older. Self-reported adverse childhood experiences before age at 18 years, present or previous cardiometabolic conditions, and present or previous use of medications prescribed for cardiometabolic conditions were used in our analysis. Cox proportional hazards regression was used to estimate age, sex, smoking, education, and income-adjusted risk of cardiometabolic condition and prescription medicine use after adverse childhood experiences. Association of multimorbidity and using multiple prescription medicines with adverse childhood experience was analyzed using generalized linear model with ordinal classification.

Results

We found that having a history of adverse childhood experience was associated with increased risk of subsequent cardiometabolic conditions; hazard ratios ranged from 1.117 (95% CI, 1.054 – 1.185) to 1.341 (95% CI, 1.181 – 1.522). Furthermore, adverse childhood experience was associated with multimorbidity of cardiometabolic conditions (odds ratio [OR], 1.195; 95% CI, 1.117 – 1.279) and increased risk of using multiple prescription medicines (OR, 1.131; 95% CI, 1.057 – 1.210). Notably, we observed the dose – effect relationships of cumulative adverse childhood experience to the increased risk of 5 among 6 cardiometabolic conditions and to the increased risk of using 4 among 6 prescription medicines. Furthermore, cumulative adverse childhood experience had the dose – effect associations with multimorbidity of cardiometabolic conditions (ORs ranged from 1.120 [95% CI, 1.033 – 1.214] to 1.526 [95% CI, 1.276 – 1.825]) and using multiple prescription medicines (ORs are 1.393 [95% CI, 1.195 – 1.624] and 1.572 [95% CI 1.315 1.879]).

Conclusions

and relevance: Our findings implicate cumulative adverse childhood experience as a risk factor for later cardiometabolic conditions and use of medicines prescribed for cardiometabolic conditions. Our results are significant by suggesting inquiry into adverse childhood experience exposure during clinical consultations, services to alleviate the burden and increasing resilience in addition to strategies aimed at prevention of cardiometabolic conditions might improve health outcomes.
Modifiable risk factors and incident cardiovascular events in gout patients
Authors: Ning Y , Tang M , An J , Zhao C , Zhang J , Gao W , Wei M , Tse G , Chan J , Waintraub X , Lei X , Saguner A , Yan Y , Wang D , Li G
Published: October 2024

Background

Gout is associated with increased risks of cardiovascular events. However, it remains uncertain whether achieving the control targets for risk factors can attenuate this risk. This study evaluated the association between the attainment of targeted seven risk factors and the incidence of major adverse cardiovascular events (MACCE) among patients with gout.

Methods

From the UK Biobank database, we analyzed data from participants diagnosed with gout at baseline (2006-2010). These individuals were followed to monitor the incidence of MACCE. Gout patients were stratified based on the achievement of seven predefined risk factor targets at baseline: body mass index 18.5-24.9, adherence to a high-quality diet, engagement in regular exercise, non-smoking status, abstention from alcohol, hemoglobin A1c <48 mmol/mol, and serum urate < 360 μmol/L. The primary outcome was the incidence of MACCE, encompassing all-cause death, stroke, or myocardial infarction. Cox model was used to identify independent predictors of MACCE.

Results

After a median follow-up of 14.1 years, 1,318 of 6,273 gout patients developed MACCE. Among individuals with gout, the risk of MACCE decreased stepwise with the number of optimally managed modifiable risk factors. For participants exhibiting 1, 2, 3, and ≥4 optimal modifiable factors, the hazard ratios (HRs) were 0.39 (95% confidence interval (CI): 0.26-0.58), 0.30 (95%CI: 0.20-0.44), 0.28 (95%CI: 0.19-0.41), and 0.24 (95%CI: 0.16-0.36) respectively, showing a significant trend towards risk reduction (Ptrend <0.001).

Conclusion

Among individuals with gout, there is a stepwise decrease in the risk of MACCE with every additional risk factor that is optimally controlled.Study flowStratified analysis for adjusted HRs
Utilization of endovascular thrombectomy in patients with antiphospholipid syndrome and acute ischemic stroke
Authors: Ali Z , Mufarrih S A M , Kanigalpula S P R K , Pothuru S P
Published: October 2024

Background

Antiphospholipid syndrome (APS) is a prothrombotic state and can cause acute ischemic stroke (AIS) particularly in younger individuals.

Purpose

Given the recent widespread adoption of endovascular thrombectomy (EVT) in patients with AIS, we aimed to evaluate the current trends and utilization of this technique in patients with APS.

Methods

We used National Readmission Database (NRD) to identify patients admitted between 2016 and 2020 with a primary diagnosis of AIS and a concurrent diagnosis of APS using relevant ICD-10 CM codes.

Results

Our analysis identified a total of 2,535,777 patients admitted for AIS, of which 7209 had a concomitant diagnosis of APS. The median age in patients with APS was 55 compared to 71 in non-APS patients (p < 0.001). APS patients also exhibited a lower prevalence of comorbidities such as coronary artery disease (4% vs. 28%; p < 0.001), congestive heart failure (CHF) (15% vs. 19%; p < 0.001), atrial fibrillation (14% vs. 26%), and diabetes (12% vs. 18%; p < 0.001). Systemic lupus erythematosus (SLE) was the most prevalent concurrent autoimmune disease in the APS cohort (19%). Patients with APS were significantly more likely to undergo EVT compared to their non-APS counterparts (5.2% vs. 3.5%; p < 0.001). Mortality was higher in non-APS likely due to older age compared to non-APS but didn’t reach statistical significance (4.4% vs 3.7%, p=0.070). Notably, the length of hospital stay was significantly higher for patients with APS (median: 6 days) compared to the non-APS group (median: 3 days; p < 0.001). Furthermore, we observed a steady increase in the utilization of EVT in patients with APS and AIS from 2016 (3.7%) to 2020 (6.8%; p = 0.02).

Conclusion

Our findings demonstrate that patients with AIS and concurrent APS are more likely to undergo endovascular thrombectomy, potentially due to a higher stroke burden. Additionally, the study revealed a progressive increase in the use of EVT for this specific patient population.
Dapagliflozin reduces epicardial adipose tissue in patients with heart failure with reduced ejection fraction and type 2 diabetes
Authors: Alghamdi M , Singh J , Lang C , Mordi I , Khan F
Published: October 2024

Introduction

Epicardial adipose tissue (EAT) accumulation is associated with adverse outcome in heart failure with preserved ejection fraction, however its role in HF with reduced ejection fraction (HFrEF) is less clear. The relationship between EAT thickness and their impact on patients who have diabetes and heart failure remains unclear. SGLT2 inhibitors such as dapagliflozin improve outcomes in heart failure and diabetes, however their mechanism of benefit is not well understood. The aim of our study was to assess whether dapagliflozin reduced EAT in patients with type 2 diabetes and HFrEF.

Methods

We performed an analysis of individuals with type 2 diabetes and HFrEF who were randomised to receive either dapagliflozin or a placebo for 12 months as part of the REFORM trial. Participants had cardiac magnetic resonance (CMR) scans at baseline and at 12 months. Epicardial fat was measured utilizing 4-chamber cine images to quantify adipose tissue between the myocardium and the visceral layer of the pericardium. This assessment was carried out using the single end-diastolic image, with measurements conducted by evaluators blinded to the randomisation status of participants.

Results

47 participants completed the stud. At baseline, not only EAT thickness and BMI level (placebo: 33, dapagliflozin 32, p=0.49) but also heart rate (74.39 bpm vs. 77.61 bpm, p=0.35), systolic blood pressure (132.75 mmHg vs. 135.00 mmHg, p=0.63), diastolic blood pressure (71.39 mmHg vs. 74.04 mmHg, p=0.33) and age (67 vs. 66, p=0.79) were comparable between the two groups. 23 randomised to placebo and 24 to dapagliflozin. Baseline EAT was similar in both groups (placebo: 11.54 cm², dapagliflozin 11.74 cm², p=0.414). After 12 months of treatment dapagliflozin caused a significant reduction in EAT compared to placebo (1.21 cm² vs. 0.09 cm², p=0.007).

Conclusion

Dapagliflozin significantly reduced epicardial adipose tissue compared to placebo in patients with type 2 diabetes and HFrEF. The reduction in EAT may play a role in the beneficial effects of dapagliflozin in heart failure patients.4 Ch CMRBox plot
Endometriosis, a prevalent disease, is associated with significant cardiac disease
Authors: Havers-Borgersen E , Hartwell D , Butt J H , Oestergaard L , Koeber L V , Fosboel E L
Published: October 2024

Background

Endometriosis, a chronic systemic gynecological disease affecting 10% of women in the reproductive age, shares pathophysiological characteristics with cardiovascular disease. However, data on the relationship between endometriosis and cardiac outcomes are scarce. Further research is needed to address this gap in knowledge as highlighted by recent calls from the European Heart Journal.

Purpose

To examine the incidence of the following outcomes both as a composite and individually: 1) ischemic events, 2) arrhythmias, and 3) heart failure among women with endometriosis compared with the background population.

Methods

Using Danish nationwide registries, all women with a diagnosis of endometriosis (1977-2021) were identified and matched with women from the background population in a 1:4 ratio based on year of birth. The incidence of 1) ischemic heart disease and ischemic stroke, 2) arrhythmias (including atrial flutter/fibrillation), and 3) heart failure were examined and compared between women with and without endometriosis.

Results

After exclusion of women with ischemic events/arrhythmias/heart failure prior to index, 59,194 women with endometriosis and 238,352 matched controls were included (median age 37.1 years [IQR 29.8-44.4 years]). The women were followed for a median of 17 years and a maximum of 45 years. Overall, women with endometriosis were more comorbid and used more medications than their matched controls. The 40-year cumulative incidences of the composite outcome were 36.2% (95%CI 35.4-37.1%) and 30.2% (95%CI 29.8-30.7%) among women with and without endometriosis, whereas it were 23.8% (95%CI 23.0%-24.5%) and 18.8% (95%CI 18.5%-19.1%) for ischemic events, 20.1% (95%CI 19.4%-20.9%) and 17.2% (95%CI 16.8%-17.5%) for arrhythmias, and 7.5% (95%CI 7.0-8.0%) and 6.6% (95%CI 6.3-6.8%) for heart failure, respectively (Figure 1). The most common arrhythmia was atrial fibrillation/flutter constituting more than half of the events in both groups. In both unadjusted and adjusted analyses, women with endometriosis compared with controls had a significantly higher associated risks of the composite outcome (unadjusted HR 1.30 [95%CI 1.27-1.34], adjusted HR 1.29 [95%CI 1.25-1.32]), ischemic events (unadjusted HR 1.32 [95%CI 1.28-1.37], adjusted HR 1.31 [95%CI 1.26-1.35]), arrhythmias (unadjusted HR 1.25 [95%CI 1.20-1.30], adjusted HR 1.24 [95%CI 1.19-1.29]), and heart failure (unadjusted HR 1.07 [95%CI 1.01-1.14]), adjusted analysis (HR 1.05 [95%CI 0.98-1.12]).

Conclusions

Women with endometriosis have a higher associated long-term risk of significant cardiac outcomes compared with the background population. Despite the small relative differences, the high prevalence of endometriosis underscores the importance of these findings and emphasizes the need for enhanced understanding and prevention of its long-term cardiac outcomes.
Long term risk of heart failure in adult cancer survivors: a systematic review and meta-analysis
Authors: Wong J , Soh C , Wang B , Marwick T
Published: October 2024

Background

Evaluation of the cardiotoxic effects from cancer is most commonly evaluated at the time of chemotherapy. Although cancer survivorship populations are rapidly expanding, there is a paucity of evidence regarding the frequency and causes of heart failure (HF) >5 years after cardiotoxic therapy.

Objectives

This systematic review sought to investigate the relationship between cardiotoxic cancer therapies and late-onset HF.

Methods

We searched the EMBASE and MEDLINE databases for studies reporting HF in adult survivors (≥50 years old), who were ≥5 years post-breast/lymphoma cancer therapy. A random effects model was used to examine the associations of HF. A meta-regression analysis was implemented to determine causes of heterogeneity.

Results

Thirteen papers were included in the review and meta-analysis (Figure 1), comprising 190,259 participants (mean age 53.5 years, 93% female). The risk of HF was increased (overall log risk-ratio 0.39 (95%CI (0.16-0.62)), (Figure 2). Cardiotoxic treatment, compared with cancer alone, provided a similar risk (log risk ratio of 0.38 [95% CI 0.02-0.77]). In the breast cancer population ratio (11 studies) the overall heart failure log risk was 0.41 [95% CI 0.13-0.69]). Although heterogeneity was significant (I²=77.17), this was explained by differences in patient characteristics; once multivariable analysis accounted for follow up (0.99, 95%CI (0.97-0.99), p=0.047), age (1.14, 95%CI (1.04-1.25), p=0.003) and hypertension (0.95, 95%CI (0.92-0.98), p<0.001), residual heterogeneity was low (I²=28.73).

Conclusions

HF is increased in adult cancer survivors, associated with cardiotoxic cancer therapy and standard risk factors. Consideration should be given for selective screening for HF in this at-risk population.Fig 1:Literature Search Flow DiagramFig 2:Incident HF in Cancer Survivors
Assessment of right ventricular dysfunction in breast cancer patients undergoing anthracycline and trastuzumab treatment
Authors: Santa Ana-Bayona M J , Guerra E C , Espinola-Zavaleta N , Martinez-Dominguez P , Antonio-Villa N E , Espinosa-Fernandez J R , Alexanderson-Rosas E , Williams H
Published: October 2024

Background

Anthracyclines and trastuzumab continue to be within the most popular systemic agents used in breast cancer treatment. Nonetheless, their cardiotoxic effects contribute to significant morbidity and mortality, which have been extensively studied and acknowledged. Left ventricular impairment and remodeling due to chemo- and target-therapy induced cardiotoxicity has been well described. However, effects on right ventricular function have not been fully elucidated and are incompletely understood.

Purpose

We aim to comprehensively assess right ventricular function in breast cancer patients before and during treatment with anthracyclines and trastuzumab.

Methods

We prospectively evaluated echocardiographic right ventricle (RV) parameters in 160 women (median age 48, IQR 43.00 - 57.00) diagnosed with breast cancer undergoing treatment with doxorubicin, trastuzumab or its combination. These patients were referred to a national cardiac reference centre to assess cancer therapy related cardiovascular dysfunction (CTRCD) risk. Two-dimensional echocardiography with speckle tracking imaging of left ventricle (LV) and RV was performed at baseline, 3 and 6 months. Right ventricular function was assessed with tricuspid annular plane systolic excursion (TAPSE), S’wave of the tricuspid annulus (S'), fractional area change (FAC), and free wall strain (RV-FWS). We designed a composite variable of right ventricular dysfunction constituted by any decrease in systolic function as evidenced by standard cutoff values of TAPSE, FAC, S’wave and RV-FWS. Descriptive statistics were calculated. Categorical values were compared using either the Fisher’s exact test or Chi-squared test and differences between means were assessed with the Kruskal-Wallis test or the Wilcoxon test as appropriate.

Results

TAPSE and S’ were significantly reduced from baseline, at 3 and 6 months, respectively (TAPSE: 21.62 ± 2.22, 21.00 ± 1.83, 20.72 ± 1.99, P=<0.001; S’:12.16 ± 1.91, 11.70 ± 1.76, 11.51 ± 1.53, P = 0.012) (Table 1). There were no significant changes in right ventricular echocardiographic parameters comparing patients with and without CTRCD, nevertheless, a notable proportion in both groups was observed (see Table 2).

Conclusions

There is a progressive decline in right ventricular systolic function over treatment with anthracyclines and trastuzumab. Even though RV dysfunction does not significantly differ between patients with or without cardiotoxicity, the high proportion observed highlights the need for comprehensive echocardiographic assessments.
Phenotype heterogeneity of SCN5A mutations in Brugada syndrome
Authors: Ribouleau G , Gourraud J B , Behar N , Mansourati J , Pierre B , Cotard V , Thollet A , Sacher F , Wiart F , Probst V
Published: October 2024

Introduction

Although SCN5A is the main gene associated with Brs syndrome (Brs), rare variants in this gene only affect 20 to 30 % of patients. Additionally, associated phenotype may differ even among relatives sharing the same mutation emphasizing a phenotype heterogeneity that is poorly understood for now.

Objective

Here we aim to investigate the association between the presence of SCN5A mutations and the expression of a BrS phenotype in large families.

Methods

Among Brugada patients enrolled in our prospective cohort, we included patients from families with affected proband carrier of a SCN5A mutation and at least 4 relatives carriers of the same SCN5A mutation. Patient without a spontaneous type 1 ECG and no pharmacological provocative test were excluded.

Results

A total of 463 individuals from 45 large families were enrolled. Among them, 258 (56%) were mutation carriers of one of the 33 identified SCN5A mutations.

After pharmacological test, 219 (47%) individuals were diagnosed with BrS, including 32 not carriers of the familial mutation. Seventy-five patients (30%), carriers of the familial SCN5A mutation, remain negative for Brugada syndrome after pharmacological test.

The prevalence of genotype-phenotype mismatch was 24%, including 32 BrS patients non carrier of the familial mutation (phenocopy) and 75 patients with the familial mutation but without BrS (30% of uncomplete penetrance).

Conclusion

Our data strongly suggest that SCN5A mutation is not either necessary nor sufficient to explain the occurrence of BrS phenotype. We now aim to identify which associated factors might interfere, focusing first on the genetic background of phenotype/genotype mismatched individuals.
Fibroblast activation in cardio-oncology
Authors: Loganath K , Craig N , Joshi S , Barton A , Gibson K , Wall L , Waight C , Oikinomidou O , Hall P , Newby D , Henriksen P , Dweck M
Published: October 2024

Introduction

Carcinoid heart disease is a rare disease affecting the right sided heart valves (1) while anthracycline cardiotoxicity is a dreaded sequelae of a common chemotherapeutic agent that can occur early or even years after exposure (2). Activated fibroblasts, a key factor in these diseases, can be imaged with 68Gallium-fibroblast activation protein inhibitor (68Ga-FAPI).

Method

12 patients with carcinoid syndrome, 12 patients with previous anthracycline exposure and 10 healthy volunteers underwent hybrid 68Ga-FAPI positron emission tomography and magnetic resonance imaging. Areas of fibroblast activation were quantified as mean and maximum target-to-background ratios (TBRmean and TBRmax).

Results

Carcinoid syndrome:

2 of the 12 patients had carcinoid heart disease [mean age 70, 50% female] (CHD) (Figure 1A). 68Ga-FAPI uptake was seen in the liver lesions of all patients with known carcinoid liver tumours. Of the 10 patients without cardiac involvement, 6 had significant tricuspid valve 68Ga-FAPI uptake (CHD- FAPI+) (Figure 1B) and 4 did not (CHD- FAPI-). Median tricuspid TBRmax was significantly higher in CHD + [2.38 (IQR 2.35-2.42)], than CHD- patients [CHD- FAPI+: 1.68 (IQR 1.65-1.73), CHD- FAPI-: 1.55 (IQR 1.53-1.65)], although this was higher than healthy volunteers [1.45 (IQR 1.43- 1.61; p<0.05). CHD- FAPI+ patients had significantly elevated urinary 5-HIAA levels compared to CHD- FAPI- patients [Median =188 mg/24hr (IQR 151-196) in CHD- FAPI+ vs 32mg/24hr ( IQR 12-73); p=0.03].

Anthracycline chemotherapy:

3 of the 12 patients had cardiotoxicity [mean age 61, 67% female]. Anthracycline patients had higher left ventricular myocardial 68Ga-FAPI uptake than healthy volunteers with cardiotoxicity patients having the highest. [TBRmean: Cardiotoxicity 1.46 (IQR 1.36- 1.53), No cardiotoxicity 1.37 (IQR 1.19- 1.49), Healthy volunteers 0.73 (IQR 0.66 - 0.81); p<0.01 (Figure 1E). Across the cohort a moderate negative correlation was observed between Left ventricular ejection fraction and 68Ga-FAPI activity (LV TBRmean r =-0.46 and TBRmax (r= -0.66)

Discussion

68 Ga-FAPI provides us the ability to assess fibroblast activation and for the first time demonstrated the key role of these cells in both these cardio-oncology conditions. Increased fibroblast activation is observed around the tricuspid valve in patients with carcinoid syndrome both in those with and without overt clinical disease. Similarly increased myocardial fibroblast activation is observed in patients exposed to anthracyclines even many years after exposure and where there is no overt evidence of cardiotoxicity.

Conclusion

68Ga-FAPI imaging holds promise in evaluating the role of activated fibroblasts in the pathology of both carcinoid heart disease and cardiotoxicity, providing information beyond the current resolution of current clinical approaches.
Efficacy of pitavastatin in patients with HIV: a systematic review and meta-analysis of randomized controlled trials
Authors: Roca Mora M , Milani Reis A
Published: October 2024

Background

People with HIV (PWH) experience elevated cardiovascular disease (CVD) risk, exacerbated by antiretroviral therapy-induced dyslipidemia. Managing CVD risks in PWH presents significant challenges, notably due to the potential drug interactions. Pitavastatin is a statin with minimal interactions with antiretrovirals.

Methods

A systematic literature search of PubMed, Cochrane Library, and Embase databases was conducted up to March 1st, 2024, for studies comparing pitavastatin in PWH. Statistical software RStudio version 4.1.2 was used.

Results

Three studies with a total of 8045 participants were included in this analysis. Of these 4026 (50.04%) received pitavastatin. The mean age was 49.98 years and 69.38% were male. In the pooled analysis of studies, pitavastatin significantly reduced LDL cholesterol (MD -25.47; 95% CI -35.26 to -15.69; p<0.01; I² = 91%; Figure 1A) and non-HDL cholesterol (MD -27.53; 95% CI -41.19 to -13.87; p<0.01; I² = 91%; Figure 1B). Recently, the randomized trial to prevent vascular events in HIV study showed a reduction in adverse cardiovascular events and noncalcified plaque volume, as well as a reduction in inflammatory markers including oxidized LDL.

Conclusions

Pitavastatin offers a promising strategy for managing dyslipidemia and reducing CVD risk in PWH by reducing cholesterol, improving coronary plaque characteristics and inflammatory markers.
Prediction of incident major adverse cardiac events in patients starting haemodialysis for end stage kidney disease, using clinical laboratory cardiac biomarkers - a real world analysis.
Authors: Mcdowell G , Buckley B J R , Austin P , Lip G Y H , Rao A
Published: October 2024

Background and Aims

Despite its many advantages, haemodialysis (HD) is associated with increased cardiovascular mortality and morbidity, with some studies reporting 48% higher mortality within 2 years of starting HD. Cardiac biomarkers provide insight into cardiac structure and function, including myocyte stress, inflammation and fibrosis. We aimed to investigate the prognostic significance of routine cardiac biomarkers (troponin and natriuretic peptides) in the prediction of incident major adverse cardiac events (MACE) within 5 years if commencing HD.

Methods

A retrospective cohort study was performed using electronic medical records from a global federated research network from the US. The network was searched on 26th February 2023. The cohorts commenced HD post-diagnosis of end-stage kidney disease. Data censoring for MACE was invoked prior to the index event of HD. Cardiac biomarkers were the first reported result within 3 months of starting HD. Cohorts were grouped according to biomarker-specific thresholds and 1:1 propensity-score matched for age, gender and co-morbidities (hypertension, diabetes mellitus and smoking status). Logistical regression produced odds ratios with 95%CI for 5-year incident MACE. MACE was defined, a priori, as a composite of ischaemic heart disease, angina pectoris, acute myocardial infarction, heart failure, AF, stroke and all-cause mortality. All statistical analysis was performed on the online platform.

Results

The results are shown Tables 1(Troponin I and BNP alone) and 2 (Combined Troponin I and BNP). Results that reached statistical significance (p<0.05) are shown.

Conclusion

Routinely available cardiac biomarkers can predict MACE and cardiac outcomes in incident HD, although results differ between markers of myocyte injury (troponin) and stress (BNP). A combined approach may prove most beneficial. The results suggest the clinical need for CV mortality and morbidity risk profiling in incident dialysis using a combination of clinical and laboratory variables and the need for prospective validation.Table 1Table 2
Cardiovascular related polypharmacy and its association with liver and kidney impairment amongst individuals on lipid-lowering therapy: a cross-sectional study using primary care data
Authors: Trin C , Koh J W K , Orman Z O , Magliano D M , Zomer E Z , Ademi Z A , Moran C M , Talic S T
Published: October 2024

Background

Individuals with risk factors for cardiovascular disease (CVD) frequently require concurrent treatment with various medications, a phenomenon known as polypharmacy. This study aimed to investigate the association between CVD-related polypharmacy and the presence of liver and kidney impairment amongst patients receiving lipid-lowering therapy within the Australian primary care setting.

Methods

This study utilised electronic medical records from general practices retrieved between January 2013 and December 2023. Multivariate logistic regression identified independent risk factors associated with CVD-related polypharmacy, defined as the concurrent use of five or more CVD protective medications. The analysis included individuals on lipid lowering therapy who are at risk for CVD. The relationship between CVD-related polypharmacy and the presence of liver and kidney dysfunction was further assessed, defined by exceeding established reference ranges for relevant biomarkers (alanine aminotransferase [ALT], aspartate aminotransferase [AST], bilirubin, creatinine, and estimated glomerular filtration rate [eGFR]) as per Australian guidelines.

Results

A total of 13,568 participants (median age: 63 years [IQR 54-72], 54% males) were included. Independent factors associated with CVD-related polypharmacy included diabetes (OR=5.40, 95% CI: 4.96-5.93), chronic kidney disease (CKD) (OR=2.39, 95% CI: 2.00-2.86), hypertension (OR=1.91, 95% CI: 1.75-2.07), and smoking (OR=1.05, 95% CI: 0.97-1.14). Compared to the 18-35 age group, individuals aged ≥80 years displayed a significantly higher likelihood of CVD-related polypharmacy (OR=8.17, 95% CI: 5.47-12.21). While no significant association was observed between CVD-related polypharmacy and liver impairment (OR=1.19, 95% CI: 0.59-2.37), an independent positive association was identified with kidney impairment (OR=1.38, 95% CI: 1.24-1.54), adjusted for established CVD risk factors including age, sex, smoking, diabetes, hyperlipidaemia, hypertension, and CKD.

Conclusion

This study suggests a positive association between CVD-related polypharmacy and increased risk of kidney impairment in Australian primary care. Further research is warranted to explore potential causal mechanisms and evaluate the efficacy of medication review strategies, enhanced kidney function monitoring, and potential medication deprescribing in managing patients at risk of CVD who are on multiple medications.
The role of anticoagulation in atrial high-rate episodes: a meta-analysis
Authors: Ahmed H , Mahmoud Ismayl M I , Manvir Mangat M M , Anirudh Palicherla A P , Andrew Goldsweig A G , Nandan Anavekar N A , Ahmed Aboeata A A
Published: October 2024

Background

The role of anticoagulation in patients with atrial high-rate episodes (AHRE), who have no prior history of atrial fibrillation or atrial flutter, is being extensively studied.

Purpose

Given the increased thrombo-embolic risk in patients who have atrial high-rate episodes, our aim was to evaluate whether anticoagulation leads to enhanced clinical outcomes compared to no anticoagulation (1).

Methods

We searched PubMed, EMBASE, and the Cochrane Library, through February 2024, for studies evaluating outcomes in patients with atrial high-rate episodes managed with oral anticoagulation (OAC) compared to those not managed with oral anticoagulation. Outcomes assessed were ischemic stroke, thromboembolic events, major bleeding, and all-cause mortality. A fixed-effects model was used to calculate pooled risk risk ratios (RR) and their 95% confidence intervals (CI).

Results

A total of 4 studies comprising 6788 patients were included. Anticoagulation was associated with a significant reduction in the risks of ischemic stroke (RR 0.66; 95% CI 0.49 - 0.90; P = 0.0084) and thromboembolic events (RR 0.70; 95% CI 0.55 - 0.89; P = 0.0037). Compared to atrial high-rate episodes not managed with anticoagulation, there was a significantly increased risk of major bleeding with anticoagulation (RR 1.57; 95% CI 1.23 - 2.00; P = 0.0002), while the risk of all-cause mortality was similar (RR 1.07; 95% CI 0.95 - 1.21; P = 0.2437).

Conclusion

Our study suggests that anticoagulation in patients with atrial high-rate episodes decreases the risks of ischemic stroke and thromboembolic events, while increasing the risk of major bleeding, compared patients not managed with anticoagulation. Our study does not show a mortality benefit with the use of anticoagulation in patients with atrial high-rate episodes. Further studies are needed to confirm the safety and efficacy of anticoagulation in atrial high-rate episodes.Forest Plots of Outcomes Assessed
Modulation of p300 acetylation to protect against doxorubicin-induced cardiotoxicity
Authors: Lee J , Connelly K
Published: October 2024

Background

Doxorubicin (DOX) is a widely-used anti-neoplastic agent, but the most common adverse reaction to its use is cardiotoxicity(1). DOX acts by producing reactive oxygen species (ROSs) that cause DNA damage(1,2), which activates various proteins, including the tumour suppressor p53 and the acetyltransferase p300. When activated, p300 acetylates and increases the activity of p53 which leads to increased apoptotic activity(3). Cardiotoxicity results because the heart has limited mechanisms to dispose of ROSs(4), and because cardiomyocytes have a low turnover rate(5).

Purpose

We examined the p300 inhibitor Theracurmin (THR)(6,7) as a candidate to prevent DOX cardiotoxicity using an in-vivo mouse model, and sought to elucidate the underlying molecular mechanisms using in-vitro studies.

Methods

C57BL/6 mice were pre-treated with THR or vehicle (as control), then administered DOX or vehicle. Cardiac function was evaluated by echocardiography and cardiac catheterization. In vitro studies used cardiac fibroblasts (FBs) and cardiac endothelial cells (ECs) pre-treated with THR, then with DOX, as in the animal studies. Western blotting and rt-qPCR was used to quantify protein and mRNA levels of genes in the p53-p300 pathway or related to apoptosis, oxidative stress, and cell cycle control.

Results

DOX-treated mice showed significant decreases in left ventricular (LV) ejection fraction (LVEF, p=0.0004), fractional shortening (FS, p=0.0012), and a significant increase in end-systolic volume (ESV, p=0.0004). We also showed a significant decrease in anterior (LVAW;d, p=0.005) and posterior (LVPW;d, p=0.005) wall thickness of the LV in these mice. However, when mice were pre-treated with THR prior to DOX administration, we saw significant increases in LVEF (p=0.045) and LVPW;d (p=0.015), and a significant decrease in ESV (p=0.0047) compared to those that were not pre-treated. In-vitro analyses demonstrated a significant increase in cleaved caspase 3 protein expression in DOX-treated ECs (p=0.007), that was not prevented by THR pre-treatment. In DOX-treated FBs, we saw a reduction in AKT mRNA (p=0.017) and increases in BAX 9p=0.008), P21 (p=0.0001), and GADD45 (0.037) mRNA expression. In DOX-treated ECs, we also saw significant increases in BAX (p=0.015) and P21 (p=0.011) mRNA expression. These changes in mRNA expression were not reversed with THR pre-treatment in either cell type.

Conclusion

THR pre-treatment successfully mitigated functional deficits and structural deficits associated with DOX cardiotoxicity. In-vitro studies show that THR pre-treatment was not sufficient to significantly prevent changes in key molecular targets associated with apoptosis. Further studies are required to elucidate the mechanism behind the observed functional changes.Abstract OverviewAbstract Results