Chronic Kidney Disease Research Articles

Differences in the optimization of pharmacological treatment in patients with heart failure and reduced ejection fraction and advanced chronic kidney disease

Abstract Introduction Chronic kidney disease is very prevalent in patients with HF, makes their treatment difficult and worsens their prognosis, especially when it is advanced CKD (glomerular filtration rate <30 mL/min/m2). Renal insufficiency increases the risk of drug intolerance and an increase in serious side effects, which can lead to underuse, with consequent negative effects on patient prognosis. Purpose To analyze in a contemporary registry of HF patients followed in specialized HF units in Spain the achievement of dose targets for the most used drugs in HF with reduced ejection fraction (HFrEF) and the impact of advanced CKD. Methods We analyzed 914 patients with HFrEF consecutively included between 2019 and 2021 in the registry of the SEC-Excelente-IC quality accreditation program of the Spanish Society of Cardiology in 45 centers. We evaluated the proportion of patients treated with ACEI, ARA, ARNI, MRA, beta-blockers and SGLT2 inhibitors at the registry inclusion visit, the causes of non-prescription, and the achievement of the maximum dose recommended in the ESC clinical practice guidelines or the maximum tolerated dose in these patients, comparing the GFR groups, greater or less than 30 ml/min/m2. Results Of the 914 patients, 8.9% had a GFR<30 mL/min/m2. Their age was 76.9±9.7 years, 39.7% women, mean LVEF 32.8±9-6%. Patients with GFR<30 received in a significantly lower proportion all HF drugs except diuretics, ARBs and potassium chelators: sacubitril-valsartan 30.5% vs 59.2%; MRAs 31.7 vs 77.8%; SGLT2 inhibitors 34.1 vs 52.9% (p<0.001; Figure 1). The main reason for non-use was intolerance/contraindication for beta-blockers and "other" for the rest of the drugs (Figure 1). The proportion of patients in whom the maximum recommended, or maximum tolerated dose was reached was low in both groups, less than 40-50% for all drugs except MRA. There were no significant differences between the two groups in relation to the degree of renal dysfunction, although there was a tendency for the recommended doses to be obtained more frequently in the group with lower GFR (Figure 2). Conclusions In our contemporary cohort of real-life patients with HFrEF and advanced CKD, the use of recommended drugs for HF was significantly lower than in those patients with better renal function. However, where they were used, maximum recommended or tolerated doses were achieved in a higher proportion of patients. This indicates that with adequate selection it is possible to achieve the objectives proposed by the clinical practice guidelines in this complex group of patients.

Impact of coronary revascularization on clinical outcomes of post-acute myocardial infarction patients with left ventricular thrombus

Abstract Background Left ventricular thrombus (LVT) is an uncommon, but dangerous complication seen in post-acute myocardial infarction (AMI). With advances in percutaneous coronary intervention (PCI) techniques, the incidence of post-AMI LVT has declined in the contemporary era. However, a minority of patients do not undergo coronary revascularisation due to medical contraindications or patient preference. This study aimed to evaluate the clinical characteristics and outcomes of post-AMI LVT patients treated with and without coronary revascularisation. Methods This was a retrospective study of 263 consecutive post-AMI patients diagnosed with LVT from November 2012 to January 2021, retrieved from a echocardiography database. Patients were stratified by the presence or absence of revascularisation treatment. Baseline clinical characteristics, treatment and outcomes data were collected and analysed. Results The median follow-up duration was 2.9 years (IQR: 0.9 – 4.7). A majority of post-AMI LVT patients underwent revascularisation via PCI (71.5%, n = 188), CABG (4.2%, n = 11) or thrombolysis (0.4%, n = 1). Unrevascularised patients (24.0%, n = 63) were older (p <0.001), more likely to be female (p <0.001), and had more co-morbidities such as previous stroke (p <0.001), heart failure (p = 0.001), chronic kidney disease (p = 0.020), and malignancy (p = 0.021). More unrevascularised patient had NSTEMI (p < 0.001), and significantly fewer were treated with triple therapy (p < 0.001). Incidence of LVT resolution was lower (p < 0.001) while all-cause mortality was higher (p < 0.001) for unrevascularised patients on univariate survival analyses. On multivariable Cox regression, revascularisation status was not an independent predictor of LVT resolution, bleeding, stroke, or all-cause mortality outcomes. Conclusion While unrevascularised post-AMI LVT patients had poorer outcomes compared to revascularised patients overall, revascularisation status itself was not independently associated with poorer clinical outcomes. Optimising medical therapy such as triple therapy remains a key treatment goal for post-AMI LVT patients.

Prognostic impact of lean diabetes mellitus on aortic stenosis

Abstract Background Obesity and type 2 diabetes mellitus (DM) has traditionally been thought to coexist. Lean DM is a distinct condition defined by body mass index (BMI) < 25, associated with elevated insulin resistance, rapid beta-cell failure, absence of ketosis and malnutrition. Lean DM has been linked to poor cardiovascular outcomes, but remains an understudied entity in valvular heart disease. Purpose This study aims to demonstrate the prognostic implications of lean DM on aortic stenosis (AS). Methods Between 2011 to 2021, 700 consecutive patients with index echocardiographic diagnoses of aortic stenosis were stratified into 4 groups, namely lean (BMI < 25) DM, lean non-DM, obese (BMI > 25) DM, and obese non-DM. Demographics, co-morbidities, echocardiographic findings and clinical outcomes were collected. Clinical outcomes were compared using Kaplan-Meier curves and a multivariate Cox regression model was constructed. Results 396 (56.6%) patients were female, and 435 (62.1%) patients were of Chinese ethnicity. 279 (39.9%) patients had DM, of whom 155 (55.6%) patients had lean DM. The mean BMI in the lean group was 21.4 ± 2.4 kg/m² compared to 29.5 ± 4.9 kg/m² in the obese group. Irregardless of BMI, higher proportions of DM patients were on baseline antiplatelets and statins compared to non-DM patients. Echocardiographically, obese DM had smaller indexed left ventricular volumes and mass - left ventricular end diastolic volume index (LVEDVi) (65.7 ± 21.7 ml/m² vs. 70.8 ± 23.6 ml/m², p = 0.002) and left ventricular mass index (LVMi) (115.7 ± 31.9 g/m² vs. 116.3 ± 36.5 g/m², p = 0.401) compared to lean DM respectively. Obese DM was associated with more cardiovascular risk factors compared to lean DM in terms of hypertension (91.9%, n = 114 vs. 89.0%, n = 138, p < 0.001), hyperlipidaemia (82.3%, n = 102 vs. 73.5%, n = 114, p < 0.001) and chronic kidney disease (50.8%, n = 62 vs. 45.5%, n = 70, p < 0.001). On the contrary, lean DM was associated with more cardiovascular sequelae of acute myocardial infarction (36.8%, n = 57 vs. 24.2%, n = 30, p < 0.001) compared to obese DM. AS patients with lean DM experienced the highest significant all-cause mortality (71%, n = 110 in lean DM vs. 58.9%, n = 73 in obese DM vs. 49.1%, n = 86 in obese non-DM vs. 65%, n = 160 in lean non-DM, p < 0.001) compared to all other groups. On the contrary, AS patients with lean DM had the lowest heart failure incidence (17.4%, n = 27 in lean DM vs. 23.4%, n = 29 in obese DM vs. 33.1%, n = 58 in obese non-DM vs. 23.2%, n = 57 in lean non-DM, p = 0.009). On multivariate analyses adjusted for age, comorbidities, and echocardiographic parameters, lean DM was an independent predictor of worse all-cause mortality in AS patients (HR 1.60, CI: 1.19 - 2.16, p = 0.010). Conclusion Lean DM in AS patients was associated with worse all-cause mortality. Lean DM was a prognostic marker of all-cause mortality in patients with AS.Figure 1

Awareness and perceptions of cardiologists towards systemic inflammation in atherosclerotic cardiovascular disease: A multi-national survey across 5 geographical regional sub-groups

Abstract Background Despite improvement in the management of atherosclerotic cardiovascular disease and chronic kidney disease (ASCVD+CKD), cardiovascular (CV) mortality remains unacceptably high. Evidence suggests that systemic inflammation (SI) is one of the key drivers for disease progression, yet clinical perceptions towards SI amongst cardiologists is poorly understood. Purpose FLAME-ASCVD (systemic inFLAMmation and rolE of hsCRP as a biomarker in AtheroSclerotic CardioVascular Disease) survey assessed cardiologist’s perceptions and awareness towards the role of SI and high sensitivity C-reactive protein (hsCRP) in patients (pts.) with ASCVD+CKD. Overall results were reported earlier1 and here we present results by sub-groups across 5 geographical regions. Methods This was a multinational, cross-sectional, online survey-based study conducted during March-May 2023. Eligible participants were cardiologists (interventional and general) who treated ≥15 ASCVD+CKD pts./month and practiced for ≥3 years. To minimize selection bias, specific study objective was not disclosed until eligibility criteria was met. An online questionnaire was used. Analysis included 5 sub-groups: Europe (EU: France, Germany, Italy, UK), Asia Pacific (AP: Australia, India), East Asia (EA: China, Japan), LatAm (LA: Brazil), Middle East (ME: Saudi Arabia). Descriptive statistics were used. Results Of the 1755 respondents, 602 eligible cardiologists (~60/country) completed the survey across the EU (n=241), AP (n=121), EA (n=120), LA (n=60), and ME (n=60). Hypertension, hyperlipidaemia, and lifestyle (diet/exercise) were consistently amongst the top 3-5 CV risk factors discussed with pts, across all regions. SI as a CV risk factor was discussed consistently less across regions (overall 10th at 43%, ³9th across regions, EU: 30%) (Table 1). Across regions, >70% of cardiologists acknowledged an intention to consider testing for SI, with the lowest being in the EU at 46%. Of those in the EU who did not consider testing, 53% (n=129) cited lack of medication as the reason. Across all regions, SI was consistently perceived as a risk factor for recurrent CV events (³65%) and residual inflammatory risk (47-85%), yet a noticeable proportion (52-92%) cardiologists acknowledged a need to learn more about SI in ASCVD+CKD (highest in ME, 92%). While overall (aided: 47% [n= 571]; unaided: 24%) considered hsCRP test for SI, few variations were observed (EA/AP/EU, aided: 55/52/33 and unaided: 22/24/03) (Table 2). Proven efficacy of hsCRP test, availability of medication for SI, and guideline recommendation were acknowledged as unmet needs to inform clinical care in ASCVD+CKD. Conclusion In this survey across regional sub-groups, discussion of SI as a CV risk factor was consistently low. Barring few noticeable variations in testing patterns in EU, perceptions towards SI were generally consistent. There is a need for better understanding and guidance on SI and hsCRP testing in practice.

Temporal and age-related trends in risk factors for development of atrial fibrillation in peripartum patients

Abstract Background Incidence of atrial fibrillation (AF) in pregnancy has steadily increased over the past two decades and may be related to changes in rates of AF risk factors. Objective To characterize trends in the prevalence of AF risk factors among patients with peripartum AF. Methods TrinetX, a large national healthcare database, was used to identify patients with peripartum AF from 2017-2022. Inclusion criteria were female patients aged >18 years old who received a diagnosis of AF within one month prior to and one year after a diagnosis of pregnancy. Annual prevalence of pre-existing AF risk factors, including diabetes, chronic kidney disease (CKD), obesity, and hypertension, were obtained, normalized to the annual number of peripartum AF cases, and followed. In a second analysis, student’s t-test and standardized mean difference were used to compare the rates of AF risk factors between patients with peripartum AF and pregnant patients with no history of AF within the same time frame. Comparisons were performed across age ranges. Results From 2017-2022, there were 6,465 patients with peripartum AF and 2,852,348 pregnant patients with no AF. There was an increase in the proportion of peripartum AF patients with pre-existing obesity (16.7% to 18.5%) and hypertension (28.9% to 33.7%). In comparing pregnant patients with no AF history with peripartum AF patients, the standardized mean difference for rates of all risk factors increased with age group. The peripartum AF group had significantly higher rates of all risk factors across all age groups (p < 0.0001 for all groups). Conclusion Rates of pre-existing obesity and hypertension increased among patients with peripartum AF, which could be a factor in increasing rates of peripartum AF. Differences in rates of AF risk factors between peripartum AF patients and pregnant patients with no AF were more pronounced at older age groups.

Survival in very elderly patients with severe aortic stenosis submitted to TAVI compared to the general population

Abstract Introduction Severe aortic stenosis (AS) is the most common acquired valvular heart disease. Transcatheter aortic valve implantation (TAVI) is indicated as an alternative to surgery in patients (pts) with severe AS above 75 years old (yo) regardless of surgical risk. The prevalence of severe AS increases with age. In the very elderly, i.e. > 85yo, the presence of severe AS is often accompanied with important comorbidities and frailty. To improve pts assessment in the heart team, it is essential to characterize the outcomes of previous interventions in this challenging group of patients and that was the goal of the present study. Methods Single-center retrospective analysis, on prospectively collected data, of consecutive patients ≥85yo undergoing TAVI between 2015 to 2021. Successful TAVI, major procedural complications and 1-year mortality rates were defined according to the VARC-3 definition. Observed survival was compared to an age-matched population using life expectancy tables available at the portuguese National Statistics Institute. Simulated survival curves for an age-matched population were performed using an expected hazard rate of 0.14. This was a conservative approach assuming that mortality rate remained constant in the population during follow-up. Results A total of 767 pts underwent TAVI during the study period. Of these, 349 pts were ≥85yo and were included in our study. Median age was 87yo [IQR 86-89], 60% female (n = 211) with a median Euroscore II of 5% [IQR 4-7]. A total of 98 pts (28%) had previous coronary artery disease, 300 pts (85%) had chronic kidney disease and 22 pts (6%) had a previous stroke. Median mean aortic valve gradient was 49mmHg [IQR 42-60] and left ventricle ejection fraction was 55% [IQR 50-56]. 268 pts (77%) underwent an elective TAVI and the remaining 23% were urgent procedures after hospital admission. The transfemoral approach was used in 334 pts (96%) and 258 pts (74%) implanted a self-expanding valve. Median in-hospital time was 6 days [IQR 4-11] and most common complications were permanent pacemaker implantation (n=59, 17%) and major access-related complications (n=17, 5%). All-cause mortality at 30 days and 1 year were 2.1% (n=7) and 13.1% (n=46), respectively. This compares similarly to the group of younger pts (<85yo) which presented a 30 day and 1 year mortality of 2.8% and 12.8%, respectively. Among very-elderly, 35 pts (10%) were readmitted in the first-year post TAVI. The mean survival time in our cohort was 4.9 years compared to expected 6.2 years (figure, log-rank < 0.01). The mortality rate at one year was 13% (n = 46) in our cohort compared to expected mortality of 14% (n = 50), not statistically significant. Conclusion In this study, very old patients submitted to TAVI had a 1-year mortality rate similar to age-matched population and a mean survival time of more than 4 years, albeit inferior to an age-matched population.

Association of third-trimester N-terminal pro-brain natriuretic peptide levels and pre-eclampsia development

Abstract Background Pre-eclampsia shares numerous risk factors with cardiovascular diseases and is associated with postpartum cardiovascular complications. Natriuretic peptides, outside pregnancy valid biomarkers for detecting subclinical cardiac dysfunction, are typically elevated at the time of pre-eclampsia diagnosis. However, their role before disease manifestation is still puzzling. Aims To assess whether third-trimester natriuretic peptide levels are associated with a diagnosis of pre-eclampsia in pregnant individuals. Methods This study measured NT-proBNP levels in third-trimester samples of 1454 pregnant individuals prior to disease manifestation. Pre-eclampsia was diagnosed using the American College of Obstetrics and Gynecology (ACOG) criteria. Linear regression analyses were performed, and multivariable adjustments were done for age, body mass index (BMI), preexisting hypertension, diabetes, and chronic kidney disease. Odds ratios were calculated per doubling of NT-proBNP levels. Results Of the 1454 individuals, 118 (7.6 %) developed pre-eclampsia. The median week of gestation for blood sampling was 29.0 (IQR 28.4 – 29.4) in both groups (p = 0.68). Individuals with pre-eclampsia manifestation had higher BMI, were more often nulliparous, and had lower placental growth factor levels (all p < 0.01). Higher NT-proBNP levels were associated with a lower risk of pre-eclampsia, which persisted after controlling for confounders (adjusted odds ratio (OR), 0.84; 95 % CI, 0.70 - 1.00). This inverse relationship was particularly pronounced in cases of late-onset pre-eclampsia, defined as onset after 34 + 0 weeks of gestation. Specifically, for preterm pre-eclampsia between weeks 34 + 0 and 36 + 9, the adjusted OR was 0.78 (95 % CI, 0.56-1.09), and for term pre-eclampsia at or after week 37 + 0, the adjusted OR was 0.77 (95 % CI, 0.61 - 0.95). Conversely, a positive association was observed between NT-proBNP levels and the occurrence of early-onset pre-eclampsia < 34 + 0 weeks, with an adjusted OR of 1.69 (95 % CI, 1.00 - 2.91). Causal mediation analyses indicated that the association between higher BMI and pre-eclampsia mediated only a minor fraction (11.5 % [95 % CI, 4.3 % - 36.0 %, p < 0.01]) of the observed association. Conclusion These findings reveal the complex interplay between third-trimester NT-proBNP levels and the risk of pre-eclampsia. They unravel an inverse association for late-onset disease but a contrasting positive correlation for early-onset cases in temporal proximity to NT-proBNP assessment. The latter may reflect acute physiological responses to pre-eclampsia nearing diagnosis. However, the inverse relationship observed for later manifestations underscores the importance of further research to dissect the underlying pathophysiological mechanisms, which suggest cardiovascular maladaption to pregnancy prior to pre-eclampsia manifestation.

Comparison of mortality scores performance in transcatheter aortic valve replacement: suiting up to percutaneous intervention

Abstract Introduction As transcatheter aortic valve replacement (TAVR) is increasingly relevant for patients with severe symptomatic aortic stenosis, having a reliable procedure specific risk-prediction tool is paramount to provide high-quality care. Surgical scores as the EuroScore II and the Society of Thoracic Surgeons (STS) score II have been widely used to identify patients with high surgical risk in whom percutaneous treatment might be more favorable. However, current literature lacks a consensual specific predictive model for short-term and mid-term prognosis in patients undergoing transcatheter aortic valve implantation (TAVI). Purpose We aimed to access short and midterm (30 days and one year) mortality and to access the ability of a directly adapted score in estimating mortality in a real-world population. Methods We conducted a retrospective observational study in patients who implanted TAVR in a single center. Surgical mortality scores – EUROSCORE II and STS score II – and adapted score Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) transcatheter valve therapy (TVT) score were used to estimate mortality. Predictive abilities of these three scores were compared using area under the receiver operating characteristics (ROC) curve for 30-day and one year mortality. Results From January 2018 to December 2021, 416 patients were submitted to TAVR procedure in our center. The mean age was 83+-6 years old and 229 (55%) were female. 94% had hypertension, 80% dyslipidemia, 40% diabetes mellitus, 35% coronary artery disease, 32% chronic kidney disease. Mean ejection fraction was 56%. During a mean follow-up (FUP) of 816 ± 492 days, 30-day mortality was 1,7% and after 1 year mortality rate was 12,2% (higher than reported in PARTNER 3 trial, 8,5%). The Mean EuroSCORE was 3,4±3,2, mean STS-II 3,9±1,8 and mean value for STS/ACC-TVT score was 3,55±1,34. ROC curve analysis showed a significantly higher discriminative power of STS/ACC-TVT (AUC 0,749, 95% CI 0,681-0,818) compared with surgical scores (p=0,001) – figure 1. We also divided population into quartiles and compared the mortality rate at 30 days and 1 year in each quartile using either STSII or STS/ACC-TVT; As can be seen in figure 2, mortality rates correlated better with the STS/ACC-TVT score than with the STS score. Conclusion A score adapted to a TAVI population showed better predictive capacity than traditional surgical scores. Less preponderance of previous surgical status, relevance of access site and more adapted weight of age might explain the best performance of STS/ACC-TVT score. Surgical scores are helpful in choosing treatment option, but adapted scores are better to predict pos-TAVR mortality.

Arterial stiffness for predicting major adverse cardiovascular events in post-infarcted patients

Abstract Introduction According to recent 2021 ESC prevention guidelines arterial stiffness (aortic pulse wave velocity –PWV, augmentation index - Aix) predicts future major adverse cardiovascular events (MACE). Both parameters have a prognostic relevance in different patient population (hypertension, diabetes, chronic kidney disease), however in post-infarcted, very high cardiovascular risk population the exact prognostic value for PWV and Aix needs to be clarify. Purpose We evaluated PWV and Aix cut-off values for MACE prediction and validated the prognostic relevance of high stiffness parameters in post-infarcted patients. Methods Oscillometric based pulse wave analysis method (Arteriograph) was applied for calculating arterial stiffness. We aimed to evaluate PWV and Aix cut-off values for predicting MACE (comprising all-cause death, non-fatal myocardial infarction, ischemic stroke, hospitalization for heart failure and coronary revascularization) in post-infarcted, very high cardiovascular risk patient population. 114 patients (89 male, average age: 62,5±10,5 years) were investigated in this long term, median 16,2 (IQR: 6,5-17,4) years follow-up study. Results Strong, significant correlation was found between PWV and Aix values (Spearman rho: 0,648, p<0,001). Totally 140 MACE events occurred during the 16,2 years follow-up period. Optimized PWV and Aix cut-off values for MACE prediction were calculated (PWV: 9,84 m/s, AUC: 0,754 (95% CI: 0,66-0,85), p<0,001; Aix: 34,8 %, AUC: 0,67 (95% CI: 0,57-0,77), p<0,05) by ROC analysis (Figure 1.). Kaplan-Meier analysis in both parameters showed a significantly lower event-free survival in case of high PWV and Aix values (p<0,05; Figure 2.). Multivariate Cox regression analysis revealed PWV and Aix as an independent predictor of MACE (PWV HR: 1,32 (95% CI: 1,15-1,53), p<0,001; Aix HR:1,04 (95% CI: 1,01-1,08), p<0,05). Conclusions Arterial stiffness, particularly elevated PWV predicts MACE in post-infarcted, very high cardiovascular risk patient population. All these findings emphasize the clinical relevance for the future measurement of arterial stiffness might contribute to improve individual risk stratification in patients after myocardial infarction.ROC analysis for the prediction of MACEKaplan-Meier curves for MACE

Prognostic value of C-reactive protein / albumin ratio for amputation and/or mortality after lower extremity revascularization in haemodialysis patients with peripheral artery disease

Abstract 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.

What does routinely-collected electronic health record data tell us about the use of heart failure medication among older people in Wales? Making progress but could do better

Abstract Background European Society of Cardiology 2021 guidelines recommend 4 pillars of treatment to reduce mortality for those with heart failure (HF) and reduced ejection fraction (HFrEF): pillar 1) angiotensin converting enzyme inhibitor (ACE-I)/angiotensin receptor blocker (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), pillar 2) beta-blocker (BB), pillar 3) mineralocorticoid receptor antagonist (MRA), pillar 4) sodium-glucose co-transporter 2 inhibitor (SGLT2i). When there is heart failure with preserved ejection fraction (HFpEF), guidelines recommend diuretics to alleviate congestion and treatment of risk factors such as hypertension and diabetes. Prior to 2021, United Kingdom guidelines did not include SGLT2i. Purpose To examine how HF treatment is recorded in routinely-collected electronic health record (EHR) data for older people in Wales, and to explore how that has changed since 2015. Methods We conducted a retrospective, population-level, observational study using linked anonymised EHR data in Wales (2015-22). 737,230 individuals were aged 65y+ in the study period (21.5% of population in 2022). Of these, 65,010 had a code for heart failure in their primary or secondary care records. We excluded 13,990 individuals with fewer than 12 months data pre- or post-diagnosis. We looked forward, from HF diagnosis, for codes associated with specific medications. Results The final cohort comprised 51,020 individuals aged 65y and over with a diagnosis of heart failure between 2015-2022. Incidence and prevalence of heart failure increased across the study period (1.4-1.5% and 8.5-9.1% respectively). Preceding cardiovascular diagnoses included hypertension (69.5%), atrial fibrillation (36.7%), myocardial infarction (30.5%), coronary artery disease (25.7%), and valve disease (17.7%). Diabetes (41.7%), chronic kidney disease (30.9%) and cancer (26.4%) were the most common comorbidities. The subtype of HF (HFrEF or HFpEF) was only evident in 5,850. Treatments recorded most often were loop diuretics, ACE-I, and BB (Table 1). SGLT2i codes increased in 2020/2021(Figure 1). At 10-12 months post diagnosis, the proportion with simultaneous pillar combinations was; 27.4% 1 + 2, 12.5% 1, 2 + 3, and only 2% 1, 2, 3 + 4. Conclusions In Wales, there is a need to improve the coding of HF subtype in primary care records. We suggest interpreting data with the assumption that approximately half of the cohort are likely to have HFrEF. While the cohort proportion on ACE-I or beta-blockers may be appropriate, the proportion with more than 1 simultaneous pillar of treatment recorded appears low. The use of SGLT2i in codes is increasing. These results are important in evaluating health service delivery and in establishing baseline data from which to monitor improvements.

Amiodarone-related thyroid dysfunction and associated outcomes in patients with heart failure - a matched case-control study

Abstract Aim The association between amiodarone-related thyroid dysfunction and the risk of worsening heart failure (HF) or death has been reported with conflicting results. Methods The study cohort was patients with HF and without a history of thyroid dysfunction (defined by medical treatment or diagnosis) who initiated treatment with amiodarone in the period 1996-2021. Within this cohort, those who developed thyroid dysfunction (cases) were identified and matched 1:3 on age, sex, calendar year, duration of HF, and time since initiation of amiodarone with patients (controls) from the same cohort and followed for the primary outcome of HF hospitalization or all-cause death at 1-year, assessed by Kaplan Meier curves and Cox regression models adjusted for ischemic heart disease, chronic kidney disease, malignancy, atrial fibrillation and ventricular tachycardia. Results The study cohort comprised 21,947 patients, of whom 4,137 (19%) developed thyroid dysfunction following initiation of amiodarone. After matching, the study population consisted of 4,063 cases (mean age 69 years, 68% men, 41.6% developed thyroid dysfunction within the first year after initiation of amiodarone) and 10,940 matched controls, (Figure 1). The index date was the date of thyroid dysfunction for cases, and for matched controls a date at a similar distance since amiodarone initiation. At 1-year follow-up, the primary outcome occurred in 1,543 (38.0%) cases and 3,681 (33.6%) matched controls (reference), adjusted hazard ratio (HR) 1.13 (95%, confidence interval CI 1.07-1.20), although this was solely driven by HF hospitalization (28.9% vs 21.8%; HR 1.32 (95% CI 1.23-1.41), whereas all-cause death was lower among cases (18.2% vs. 20.4%, HR 0.85 (95% CI 0.78-0.93), (Figure 2). Conclusions Among HF patients treated with amiodarone, the development of thyroid dysfunction was associated with an increased risk of HF hospitalization or all-cause death, but this was solely driven by the excess risk of HF hospitalization, whereas it was associated with a lower risk of all-cause death. The absence of excess mortality indicates that thyroid complications are manageable in this vulnerable population of patients with HF.Figure 1 Flowchart of the populationFigure 2 Cumulative risk

Comparative clinical outcomes of amphilimus-eluting stents in diabetic versus non-diabetic patients

Abstract Background Patients with diabetes mellitus (DM) are at an increased risk of experiencing adverse events following percutaneous coronary intervention (PCI). The Cre8 EVO stent, which releases a formulation of sirolimus with an amphiphilic carrier from laser-dug wells, has demonstrated clinical benefits specifically in diabetic populations. We aimed to explore the impact of DM on clinical outcomes in a large, real-world registry of all-comer patients treated with Cre8 and Cre8 EVO stents. Methods We did an investigator-initiated, prospective, single-arm observational trial at 28 sites in South Korea. The primary endpoint was a composite of cardiac death, target vessel-related myocardial infarction (MI), and clinically-driven repeat revascularization at 12 months. All-cause mortality was a key secondary endpoint. Results A total of 2,045 patients (66.0 ± 11.5 years of age; 76.2% male) were analyzed. Diabetic patients (n = 774; 37.8%) were more likely to be older, female, and have hypertension, dyslipidemia, or chronic kidney disease. There were 39 cases of primary events, 17 (2.5%) in the DM group and 22 (1.9%) in the non-DM group (hazard ratio, 1.34; 95% confidence interval, 0.74–2.41; log-rank p = 0.33). Overall, the primary endpoint occurred in 2.1% of patients, with a cardiac death rate of 0.4%, a target vessel-related MI rate of 0.3%, and a clinically driven TLR rate of 1.8%. Among the secondary endpoints, the DM group exhibited a significantly higher all-cause mortality rate compared to the non-DM group (2.0% vs. 0.9%; hazard ratio, 2.20; 95% confidence interval, 1.04–4.65). Conclusion In this real-world registry, diabetic patients treated with amphilimus-eluting stents demonstrated excellent safety and effectiveness at 12 months, with a similar occurrence of MACE compared to non-diabetics. These results underscore the potential for amphilimus-eluting stents to become a preferred option for PCI in diabetic patients, prompting further investigation into their long-term benefits and mechanisms of action.

Amyloid beta, a marker of vascular aging and cardiovascular disease, is associated with accelerated progression of renal dysfunction

Abstract Background Amyloid-beta (1-40) (Αb1-40), a proinflammatory and pro-atherosclerotic peptide, is involved in Alzheimmer’s disease and vascular aging and is considered an emerging prognostic marker of atherosclerotic cardiovascular disease (ASCVD) and heart failure. Because Ab1-40 clearance is largely dependent on renal function while clinical data consistently associate this peptide with renal function, we hypothesized that Ab1-40 circulating levels would serve as a predictor of progression of renal dysfunction. Purpose To examine the potential cross-sectional and prospective bidirectional association of Ab1-40 levels with renal function in a population with a wide range of ASCVD risk. Methods In the settings of the Athens Cardiometabolic registry, data from consecutively recruited subjects with (n=137) and without clinically overt ASCVD (n=674) with available both Ab1-40 plasma levels and GFR values (total n=811) were analyzed. Αb1-40 was measured by enzyme-linked immunosorbent assay and renal function was assessed by estimation of glomerular filtration rate (GFR). Of these subjects, 182 individuals consented to be followed up and re-assessed after a minimum period of 12 months in order to examine a potential bidirectional link between changes in Ab1-40 levels and GFR. Results Patients with increased Ab1-40 levels at baseline had significantly worse renal function, reflected as lower GFR values, compared with their counterparts with lower Ab1-40 levels (GFR= 74.8 vs 93.3 vs 100.2 ml/min/1.73m2 for high, middle and low tertile of Ab1-40 levels, p<0.001). Elevated Ab1-40 levels were associated with chronic kidney disease (CKD) stage 2 [odds ratio (OR)=2.29, 95% confidence intervals (CI)= 1.58-3.31, p<0.001] and CKD stage 3 (OR=3.67, 95% CI=2.37-5.70, p<0.001) at baseline. Furthermore, increased Ab1-40 at baseline was prospectively associated with accelerated progression of renal dysfunction as assessed by changes in GFR values between baseline and follow-up [mean adjusted rate of decrease=-7.20 (95% CI=-1.33, -13.07) for higher vs lowest tertiles of Ab1-40 levels across a follow-up period of 12 months, p=0.017 for interaction). On the contrary, baseline GFR values were not prospectively associated with Ab1-40 levels at follow-up visits (p>0.05). Conclusion In a population with a wide range of ASCVD risk, high Αb1-40 levels at baseline were associated both with renal function at baseline and with accelerated rate of progression of GFR deterioration at follow-up irrespective of its baseline levels. These findings suggest a mechanistic background for the established association of Ab1-40 with renal function and warrant further research to clarify the clinical value of monitoring its circulating levels as a novel biomarker which could reflect enhanced risk for renal dysfunction.

Effect of heart failure and atrial fibrillation on cardiorespiratory fitness in hemodialysis patients.

Heart failure (HF) and atrial fibrillation (AF) are highly prevalent in hemodialysis. They are well-known significant modifiers of the disease associations with cardiovascular outcomes, but there is a lack of evidence regarding the effects of HF and AF on cardiorespiratory fitness. This study is the first to examine the possible association of the presence of HF and AF with exercise intolerance in patients undergoing hemodialysis. This analysis included 40 sex- and age-matched participants [10 hemodialysis patients with HF or AF, 10 hemodialysis patients without HF or AF, 10 patients with HF or AF without chronic kidney disease (CKD) and 10 healthy controls] that underwent CPET and spirometry examinations. The total of patients with HF had preserved ejection fraction. VO2peak(ml/kg/min) showed a graded increase between hemodialysis patients with HF or AF, hemodialysis patients without HF or AF, non-CKD patients with HF or AF and controls (13.17 ± 2.45 vs 15.26 ± 3.29 vs 19.64 ± 5.84 vs 25.11 ± 6.94ml/kg/min, p < 0.001); VO2peak(ml/min) followed the same pattern (1172 ± 197 vs 1269 ± 314 vs 1817 ± 583 vs 1952 ± 592ml/min respectively, p = 0.001). VO2peak(%predicted), VO2AT(ml/kg/min), VO2AT(ml/min) and maximal work load significantly differed between the study groups, with a tendency for higher values from hemodialysis patients to non-CKD patients with HF or AF and to healthy controls. FEV1 and FVC levels were similar between the study groups. In the whole population, VO2peak(ml/kg/min) showed a positive correlation with hemoglobin (r = 0.663, p < 0.001) and negative correlations with high-sensitivity cardiac troponin I (r = -0.493, p = 0.001) and BNP (r = -0.479, p = 0.002). Hemodialysis patients have low exercise tolerance, and the presence of HF or AF is associated with further decreased values of VO2peak, the most important determinant of cardiorespiratory fitness.

C-Reactive Protein-to-Serum Chloride Ratio: A Novel Marker of All-Cause Mortality in Maintenance Haemodialysis Patients

Background and Objectives: hypochloremia is an emerging risk factor for mortality in patients with chronic kidney disease. The pathophysiological mechanisms of this finding are not very clear. Some studies suggest the influence of inflammation as a synergistic factor, so we set out to analyse the association of a novel C-reactive protein-to-serum chloride ratio (CRP/Cl−) with the prognosis of maintenance haemodialysis patients and to assess its relationship with fluid status and body composition measured by bioimpedance. Materials and Methods: the present work is a retrospective cohort study of maintenance haemodialysis patients from our chronic outpatient haemodialysis programme between 1 January 2022 and 31 December 2022. (n = 281). Survival time was collected for all patients and analysed using the Kaplan–Meier method. A Cox proportional hazards regression model was used to evaluate survival probabilities. Variables included in the model were selected using a stepwise selection procedure based on the corrected Akaike information criterion (AICc), which balances model fit and complexity. Results: during a median follow-up of 306 days, 34 patients died. Patients in the fourth quartile of the CRP/Cl− (&gt;0.118 mg/mEq) had higher overall mortality (log-rank test, p = 0.0011). In the Cox multivariate analysis, the variables significantly associated with higher mortality were higher modified Charlson index (MCI), lower body surface area (BSA), lower interdialytic weight gain (IDWG), and higher CRP/Cl− ratio. The latter variable was independently associated with higher overall mortality (adjusted hazard ratio = 1.027; 95% confidence interval [CI], 1.000–1.055 p = 0.0469). Conclusions: Higher CRP/Cl− ratio values were associated with higher all-cause mortality in our maintenance haemodialysis patients.

Circulating ACE2 and the association of endothelial progenitor cell in CAD patients

Abstract Background/Introduction Angiotensin-converting enzyme (ACE) 2 is the homologue of ACE, and the local up-regulation of ACE2 expression associates to antiatherosclerosis. ACE2 hydrolyzes the angiogensin II, which related to impair of endothelial progenitor cell (EPC) function. EPCs maintain the integrity of vascular endothelium in case of damage. Decreased number of EPCs associate thrombosis. Purpose To investigate the circulating ACE2 and the link to EPC in CAD patients. Methods Data from 650 patients with stable angina pectoris requiring invasive coronary angiography were enrolled. They were divided into two groups according to the median value of ACE2. Two interventional cardiologists diagnosed obstructive CAD by angiography review. Demographic characteristics and clinical outcomes were compared between groups. Results In all subjects (median age 67 years, male=66.9%), a higher ACE2 level indicates elder, higher prevalence of hypertension, diabetes mellitus and chronic kidney disease. Significant EPC elevation when CAD numbers increased in higher ACE2 group (SVD vs. DVD vs. MVD = 0.005 vs. 0.006 vs. 0.007, p value=0.044). In multivariate analysis, higher ACE2 is positively correlated to triple vessel disease (TVD vs. no CAD, adjusted odds ratio=1.627, 95% CI 1.026-2.579). Conclusions Our data demonstrated higher circulation ACE2 links to EPCs in CAD patients.

The 5-Item Modified Frailty Index (mFI-5) for risk stratification of patients with infective endocarditis undergoing cardiac surgery

Abstract Background population aging has led to an increased burden of frailty as an emerging global health issue, and variables for its quantification in patients with infective endocarditis (IE) are lacking in current surgical risks scores. The 5-item modified frailty index (mFI-5) score has shown to be effective in the prediction of surgical outcomes in other medical scenarios. Purpose this study aimed to assess the role of the mFI-5 in the prediction of surgical outcomes in patients with left-sided IE undergoing cardiac surgery. Methods a total of 112 cases of confirmed left-sided IE undergoing surgery, were consecutively collected and followed during one year after diagnosis in two tertiary hospitals between 2016 and 2021. The mFI-5 score included 5 baseline patient-specific comorbidities: diabetes, congestive heart failure, non-independent functional status (Barthel index &amp;lt;80), hypertension and chronic obstructive pulmonary disease (range 0-5), and patients were categorised as mFI-low (&amp;lt;2, n=65), and mFI-high (&amp;gt;=2, n=47). Results mean age was 66 [SD 15] years, 67% were men and community-acquired infections were 75%. As shown in Table 1, mFI-high patients were older and, aside from the specific comorbidities included in the score, with more chronic kidney disease. The most isolated pathogen was S. viridans (n=32), predominantly in mFI-low, in contrast to enterococcal and polymicrobial IEs, which were more frequent in mFI-high. Larger vegetations were reported in mFI-high [16 (10) vs 13 (9) mm, p 0.03], with no differences regarding infection site or periannular complications. Acute kidney injury, decompensated heart failure and higher natriuretic peptides were more common in mFI-high. Regarding mortality, in-hospital deaths were more frequent in mFI-high group. When analyzing mFI-score as a discrete variable, in-hospital mortality was associated with higher median scores values [2 (2) vs 1(1) points, p 0.02], being 2 points the optimal cutoff point for prediction [AUC 0.64 (95% CI 0.54-0.73), Fig.1A]. Among survivors who completed follow-up (n=82), rehospitalization and all-cause mortality rates in mFI-high exceeded those from mFI-low. Predictors of in-hospital and 1-year mortality were assessed by logistic regression (Fig. 1B), confirming the independent prognostic association of mFI-5-score in patients with IE undergoing surgery. Conclusions patients with IE undergoing cardiac surgery with higher mFI-5 scores were older, more predisposed to enterococcal and polymicrobial infections, and had a greater comorbidity burden with a more complicated clinical course. The mFI-score was independently associated with in-hospital mortality as well as rehospitalizations and 1-year mortality, positioning itself as an additional tool for risk stratification in this cluster of patients.Table 1Figure 1

Heart rate and prognosis of heart failure with reduced ejection fraction in women and men in sinus rhythm

Abstract Background Resting heart rate (HR) is a well-established therapeutic target for treating heart failure (HF). Beta-blockers are the primary drugs to reduce HR. Elevated HR is associated with higher mortality in heart failure with reduced ejection fraction (HFrEF). However, the influence of HR on mortality and predictors of death in women with HFrEF in sinus rhythm is not well understood. Purpose to analyse mortality for HR ≤60&amp;gt;bpm and ≤70&amp;gt;bpm in women and men. Methods From February 2017 to January 2022, we analysed the influence of resting HR (≤60&amp;gt; and ≤70&amp;gt;bpm) on mortality and predictors of death in women and men with HFrEF in sinus rhythm. Baseline data included clinical characteristics and echocardiographic findings. The HR used in the analysis was obtained at the closest outpatient visit to the death event. We used the adjustment for multiple comparisons for the log-rank test of Kaplan-Meier (K-M) and Cox proportional hazards methods to analyse mortality rates and search for death predictors for women and men. Results We analysed 2,984 patients, with a mean age of 61 ± 13.8 years, 1,922 (64.4%) men. Age, body mass index, myocardial infarction, diabetes, chronic kidney disease, stroke, carvedilol dosage, hospitalization, and initial left ventricular ejection fraction (LVEF) were similar in both genders. Over the follow-up period of 3.7±1.6 years, we observed an increase in LVEF in men (29.5%±6.7% vs. 36.7%±12.9%; p&amp;lt;0.001) and women (29.9%±6.4 vs. 38.0%±13.4%; p&amp;lt;0.001), and HR reduced in men (73.1±13.0 to 72.1±11.8 bpm; p=0.007) and women (72.8±12.7 to 71.8±11.3 bpm; p=0.026). Death incidence was higher in men (43.7% vs. 36.7%; p&amp;lt;0.001). The cumulative incidence of death was higher in men with HR&amp;gt;60bpm (K-M: log-rank p&amp;lt;0.001) and &amp;gt;70bpm (K-M: log-rank p=0.011) compared to women. Cox regression for death, adjusted for covariates with p&amp;lt;0.25, showed age (HR=1.01;95%CL:1.008-1.017; p&amp;lt;0.001), men (HR=0.80;95%CL:0.71-0.90; p&amp;lt;0.001), LVEF (HR=0.986;95%CL:0.98-0.99; p=0.001), and HR (HR=1.005;95%CL:1.00-1.01; p=0.025) as independent death variables. For men, the independent variables were age (HR=1.01;95%CL:1.01-1.02; p=0.002), LVEF (HR=0.98;95%CL:0.97-0.99; p=0.001), and HR (HR=1.008;95%CL:1.00-1.01; p=0.008), and for women, only the age (HR=1.02;95%CL:1.01-1.02; p&amp;lt;0.001). Conclusion Increased HR was an independent variable of death in men but not in women. Future studies are needed to determine the best reference HR for a chronotropic drug intervention to reduce mortality in women with HFrEF in sinus rhythm.

Association of metabolic phenotypes with cardiovascular events in primary and secondary prevention

Abstract Background Metabolic disorders are established risk factors for the development of coronary artery disease (CAD) and major adverse cardiovascular events (MACE). Although obesity is strongly related with the metabolic health status, its role as a cardiovascular risk modifier in the absence of metabolic disorders remains controversial. Recent implementation of nutrient-stimulated hormone-based therapies (NUSH) including glucagon-like peptide-1 (GLP-1) receptor agonists in the treatment of obesity even in metabolically healthy individuals requires further understanding to ensure optimal patient management. Purpose The aim of this study is to investigate the association of metabolic phenotypes with cardiovascular events in primary and secondary prevention of CAD. Methods We included patients over 18 years electively evaluated for CAD by invasive coronary angiography (ICA) between 2010 and 2021 in our tertiary referral centre in one of Europe’s largest university hospitals. Metabolic disorder was considered as the presence of diabetes, irrespective of additional risk factors, or hypertension and hyperlipidaemia, and obesity as a BMI of ≥30 kg/m², distinguishing four metabolic phenotypes: metabolically healthy/unhealthy nonobese/obese (MHN, MHO, MUN, MUO). The primary study endpoint MACE was defined as a composite of cardiovascular death, non-fatal myocardial infarction, ischemic stroke, and hospitalization for heart failure. Results The total study population included 12 760 patients (68 [58-76] years; 57.3% male), of whom 56.5% presented metabolically healthy (43.3% MHN; 13.1% MHO) and 43.5% unhealthy (28.3% MUN; 15.2% MUO). During a median follow up time of 3.91 (1.75-7.09) years, 2 592 (20.3%) MACE and 3 351 (26.3%) all-cause deaths occurred. Cox regression analysis adjusted for age, sex, and chronic kidney disease (CKD) showed different risk patterns for distinct metabolic phenotypes (Table 1). While we observed higher event rates in metabolically unhealthy compared to healthy individuals, obesity alone was not associated with increased events (Figure 1). However, metabolically healthy individuals experienced lower event rates with increasing BMI. Among patients without or with nonobstructive CAD, metabolic disease was strongly associated with increased subsequent coronary revascularization regardless of BMI. These patterns were similar across all endpoints irrespective of presence of obstructive or nonobstructive CAD. Conclusions Whereas metabolic disorders are strongly associated with adverse clinical events, obesity alone does not reflect the cardiovascular risk profile in patients with or without obstructive CAD. Thus, focusing on obesity alone for primary or secondary prevention appears unjustified. Particularly after the recent implementation of GLP-1 receptor agonists for the treatment of obesity, precise and individual risk stratification is essential to allow for an optimal personalized patient management.Figure 1Table 1