Prevalence Of Disease Research Articles

Absence of coronary artery disease in high-risk sickle cell anemia patients: a new illustration supporting the protective effect of Bilirubin against atherosclerosis?

Abstract Background Sickle cell anemia (SCA) is associated with both cardiac and systemic vascular disorders, which are the leading cause of morbi-mortality. Although these patients cumulate multiple cardiovascular (CV) risk factors, along with chronic inflammation and endothelial activation, some pre-clinical studies underlined a paradoxical protection against atherosclerosis. Purpose The aim of this study was to evaluate the prevalence of coronary artery disease in a high-risk SCA population. Methods From January 2019 to December 2023, consecutive adult patients with SCA were prospectively included in the DREPACOEUR registry to specifically analyze cardiac structure and function. They all had a comprehensive CV evaluation at steady-state in day-hospital including clinical exam, cardiac imaging, rhythm monitoring along with biology analysis. Only patients that underwent coronary imaging (CT coronary angiogram) were included in this study. Results Ninety patients were included. Mean age was 44±12, 50% were male with a high prevalence of systemic hypertension (57%), obstructive sleep apnea (21%) and 10% smokers. Only one patient had history of diabetes while no dyslipidemia (or lipid lowering therapy) was reported. Heart function was mainly preserved with a mean left ventricular ejection fraction (LVEF) of 58±5%. Expectedly, patients showed low hemoglobin level 8,7±1.4g/dL with high hemolysis markers. Glomerular filtration rate was 109 [62; 122] mL/min/m² with 21% having chronic kidney disease. Plasmatic LDLc level was low (0.7±0.3g/L, with 20% <0.5g/l) while triglycerides (TG) were highly variable (1.1±0.7mg/dL). Strikingly, no patient showed signs of significant coronary artery disease, with 87% presenting a calcium score of 0, 77% had a CAD-RADS of 0 while no patient was higher than 2. Correlation and linear regression analysis were performed to find independent parameters associated with LDLc and TG. Total bilirubin was the only variable that correlated with both LDLc and TG (R= -0.37, p<0.001 and R= -0.33, p=0.001 respectively). Conclusion Despite systemic vasculopathy and chronic inflammation, ageing SCA patients showed no significant coronary artery disease. These data are in line with pre-clinical studies suggesting a lipid-lowering role of bilirubin and its protective effect against atherosclerosis.

All-cause, cancer and cardiovascular mortality among South Asians living in the UK: Follow-up of the London Life Sciences Population (LOLIPOP) cohort

Abstract Background Although South Asians are the largest ethnic minority group in the UK, and the largest ethnic group worldwide, few studies have investigated patterns of mortality in South Asians. Methods We investigated 16,391 South Asian and 6,970 European men and women living in the UK, and participating in the London Life Sciences Prospective Population study. Participants were recruited in 2002-2008, and survival determined to 2019. We examined relationships of clinical, anthropometric, and lifestyle risk factors to mortality outcomes. Findings: Compared to Europeans, South Asians had higher prevalence of diabetes, cardiovascular disease, and hypertension, higher waist-hip ratio, fasting glucose, insulin and triglycerides, but lower smoking rates and HDL cholesterol (all P<0.001). Age and sex adjusted all-cause mortality was lower (Hazard Ratio (HR): 0.75 [0.68-0.81], P<0.001), all-cancer mortality was lower (HR 0.50 [0.43-0.58], P<0.001), and coronary heart disease (CHD) mortality was higher (HR 1.29 [1.05-1.60], P<0.01) in South Asians compared to Europeans. Mortality rates were ~50% lower for 9 of the 10 most common cancers in South Asians. After adjusting for risk factors, ethnic differences were attenuated only for CHD mortality. Interpretation: All-cause and cancer mortality are lower, but CHD mortality is higher, in South Asians compared to Europeans. Measured risk factors do not explain lower all-cause and all-cancer mortality, but do account for higher CHD mortality. Our findings provide evidence for population-specific exposures protective against cancers in South Asians, as well as the motivation to further improve cardiovascular risk reduction in this major ethnic group.

Association of a history of acute kidney injury with major adverse cardiovascular events in chronic kidney disease patients

Abstract Background/introduction Acute kidney injury (AKI) is strongly associated with major adverse cardiovascular events (MACE), particularly heart failure, in both general and critically ill populations. A recent study questioned whether this association holds true only for patients without chronic kidney disease (CKD). Purpose To evaluate the association of a history of AKI with MACE in a large real-world CKD population defined using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Methods A retrospective cohort study was conducted using Merative® Explorys electronic health records (>54 million patients) from Jan 2010 to Dec 2019. Six cohorts of CKD patients (diagnosed or not) were created, one for each stage (1-5). Patients were required to have two consecutive abnormal eGFR, uACR/uPCR results within 3-18 months to determine CKD stage, to have at least a 12-months lookback period, and no history of end-stage kidney disease. CKD classification was not mutually exclusive (individual patients could contribute to multiple stages). Index date was the date of the second abnormal test. History of AKI was defined using ICD diagnosis codes, not through biological changes. We followed each patient until the occurrence of a composite of MACE including death, coronary events [acute coronary syndrome + coronary revascularization], any stroke, hospitalization for heart failure, or loss to follow-up, or for up to 5 years. We used multivariable Cox proportional hazards regression to estimate associations between the history of AKI and the risk of MACE during follow-up, adjusted for the following confounders: age, sex, ethnicity, systolic blood pressure, eGFR, BMI, CV history, diabetes, and any CKD diagnosis at baseline. Results Most of the 969,394 patients included in at least one CKD stage cohort were in stage 3a (see table) and Caucasian. Mean ages were 57-75y and 42%-64% were females across the 5 CKD stages. The prevalence of pre-existing CV disease increased from 24% in stage 1 to 57% in stage 4. The proportion of patients with a history of AKI increased from 4% in stage 1 to 36% in stage 4, as well as, the proportion of patients with a ICD code for CKD diagnosis at baseline (3% to 44%). The 5-year incidence of the composite of MACE increased from 25.1% in stage 1 to 65.8% in stage 5. Death was the most frequent event across all stages. In multivariable analysis, a history of AKI was associated with increased risk of MACE (hazard ratios, HR 1.19 to 1.32), all-cause death (HR 1.12 to 1.86), and hospitalization for Heart Failure (HR 1.59 to 1.98) for all CKD stages, and coronary events for stage 2 to 5 (HR 1.14 to 1.22), but not stroke. Conclusion Patients with CKD and a history of AKI are at higher risk of adverse CV outcomes, especially hospitalization for heart failure. This study suggest that these patients should receive cardio -protective intervention.

Involuntary commitment and medical education on mental health diseases across Europe

Abstract Background Psychiatric diseases are projected to become one of the greatest contributors to the global burden of disease by 2030, already presenting as one of the principal causes of DALYs lost in Europe. Given the particular nature of psychiatric disorders, national legislatures have been enacted by each European country regarding the possibility of involuntary psychiatric treatment. As practical implementations vary greatly from country to country, we wish to analyse how different attitudes to involuntary treatment affect health outcomes, so as to propose a uniform guideline for European medical practitioners. We also wish to analyse whether medical education targeted at communication with psychiatric patients has an effect on involuntary treatment rates and general mental well-being. Methods We conducted a systematic review on PubMed to identify studies pertaining to how legislature on involuntary commitment varies between European countries, as well as to what extent it is utilised. We also looked at the extent of medical education on psychiatric diseases. Results Preliminary results show that involuntary hospitalisation rates vary greatly within Europe, with certain countries being almost 20 times more likely to utilise such measures than others, notwithstanding similar mental illness prevalence. Results do not seem correlated to legislation types. Conclusions Given the vastly different use of involuntary commitment, a more standardised European approach should be implemented, especially in sight of the growing prevalence and burden of disease of psychiatric illnesses. Furthermore, an often-overlooked aspect of medical education is how to understand and communicate effectively with patients dealing with mental diseases: we advocate for continuous education, regardless of medical specialty. Key messages • Involuntary hospitalisation rates vary greatly across Europe, but the effects of this phenomenon have been poorly studied. We propose a more unified approach to maximise the efficacy of such a law. • We advocate for a more thorough education of health professionals on mental illnesses, regardless of medical specialty, in sight of the growing prevalence of such diseases.

Electrocardiographic criteria for the diagnosis of left ventricular hypertrophy in patients with severe aortic stenosis

Abstract Introduction There is a lack of data regarding the performance of current electrocardiographic (EKG) criteria for left ventricular hypertrophy (LVH) in patients with severe aortic stenosis (AS). Purpose To test the performance of the current EKG scores to diagnosis LVH in AS patients, and also to compare the performance of a new proposed score. Methods The present study evaluated 80 patients with severe AS that underwent cardiac magnetic resonance to diagnose LVH, defined as left ventricular indexed mass of 95 g/m² for female and 115 g/m² for male patients. The EKG criteria used for left ventricular hypertrophy were Sokolow-Lyon criteria, Romhilt-Estes point score system, Cornell voltage criteria and Peguero-Lo Presti criteria. Results Among the 80 patients included in analysis, 58.7% were male and the mean age was 64±8 years. There was a high prevalence of comorbidities, highlighting diabetes (32.5%), hypertension (67.5%), atrial fibrillation (5.0%) and coronary artery disease (11.3%). Regarding echocardiogram, the median left ventricle ejection fraction was 64 (56-68)% and the median indexed aortic valve area was 0.43 (0.35-0.49) cm²/m². Cardiac magnetic resonance analysis demonstrated a mean left ventricle mass of 168±55g, and the LVH incidence was 26.3%. Regarding EKG, Strain pattern was found in 49.1% of the patients, Cornell voltage criteria was positive in 51.3%, Sokolow-Lyon criteria in 51.3%, Romhilt-Estes point score system in 42.5% and Peguero-Lo Presti criteria in 61.3%. Discriminative capacity of electrocardiographic criteria for LVH is shown in Figure 1. Peguero-Lo Presti score had the best diagnostic accuracy in the overall population and in male sex (AUC 0.776), while Cornell voltage criteria had the best diagnostic accuracy in female patients (AUC 0.776). Based on linear regression model, the proposed score was created to predict LVH at cardiac magnetic resonance: 48 + (1.3 x Deepest S wave) + (0.5 x S wave in V1 or V2 plus R wave in V5). The proposed score cutoff value of 90.5 mm had a sensitivity of 0.765 and specificity of 0.707 (for male sex: 0.769 and 0.655, respectively; for female sex: 0.750 and 0.759, respectively). Compared to the scores described in the literature, the proposed score had the best area AUC for the overall population (Figure 1), for female and male patients (AUC 0.796, 0.819 and 0.780, respectively). Conclusion In patients with severe AS, the proposed score had the best diagnostic accuracy compared to the scores described in the literature for LVH identification, followed by Peguero-Lo Presti score, even when analyzed based on gender. Besides, the proposed score had also acceptable sensitivity and specificity for LVH detection.AUC of electrocardiographic scores.

Sex differences in severe aortic stenosis undergoing surgical replacement

Abstract Background Aortic stenosis (AS) is the most common valvular heart disease in developed countries. Sex differences have been described in AS pathophysiology and left ventricular (LV) remodelling, as well as clinical presentation and response to therapies (1). However, sex differences in LV function parameters, namely global longitudinal strain (GLS), have been scarcely explored so far. Purpose To investigate sex differences, taking into account GLS, in patients with severe AS referred to surgical aortic valve replacement (SAVR). Methods The study population was from a single centre, prospective registry of patients with severe native valve AS who were referred for SAVR between June 2020 to October 2022. Severe AS was defined by standard guideline criteria (2). All patients underwent an echocardiogram immediately before and at least 3 months after surgery. Results Table 1 recapitulates sex differences in our population (n=119, 43% women). No differences in age or cardiovascular (CV) risk factors were noted. Clinical presentation and AS etiology were also similar. At baseline, women had lower EuroSCORE (p=0.039), creatinine (p <0.001), and haemoglobin levels (p=0.001). The echocardiogram showed a higher mean aortic valve gradient in women (Gmean, 62 vs. 50 mmHg, p=0.002). Women also had higher relative wall thickness (RWT, 0.49 vs. 0.42, p=0.037), despite lower LV mass index (124.9 vs. 136.6 g/m², p=0.037). Regarding LV function, women showed higher EF (64% vs. 60%, p=0.002) and GLS (16.5% vs. 14.6%, p=0.006) values. This is partially explained by the higher prevalence of concomitant coronary artery disease (CAD) in men, more frequently subjected to a concomitant coronary artery bypass graft than women (CABG, 38% vs. 8%, p <0.001). Post-operative complications had similar rates in men and women. After a median follow-up of 16 (6-18) months, death from any cause (6.0% vs. 1.5%, p=0.186) and rehospitalization for CV causes (14.0% vs. 4.0%, p=0.055) tended to be more frequent among women. When considering patients with severe AS alone (n=89), women had higher Gmean (64 vs. 53 mmHg, p=0.035) and EF (65% vs. 62%, p=0.045) but similar GLS (16.9% vs. 16.6%, p=0.230) as compared to men (Figure 2). At follow-up, EF and GLS failed to improve in both sexes and no differences were noted between women and men (EF 60% vs. 60%, p=0.476; GLS 15.9% vs. 16.0%, p=0.976). Conclusions In a population of all-comers patients with severe AS undergoing SAVR, women showed higher Gmean, EF, and GLS values. This is partially due to the higher prevalence of a concomitant CAD in men. When considering patients with AS alone, women still had higher EF and Gmean than men, despite a similar GLS. Future larger prospective studies with longer follow-up are needed in order to further characterize such differences and correlate them with specific outcomes.

Heart failure and advanced chronic kidney disease: differences in characteristics, treatment and outcomes in patients with glomerular filtration rate greater or less than 30 ml/minute/m2

Abstract Introduction Heart failure (HF) is a serious health problem and continues to have a high mortality and incidence of decompensation, despite advances in its management. Chronic kidney disease (CKD) is very prevalent in patients with HF, hinders their treatment and worsens their prognosis, especially when it is advanced CKD (glomerular filtration rate-GFR <30 ml(min/m2). It is important to know the differential characteristics of these patients to improve their management. Purpose To analyze in a contemporary registry of HF patients followed in specialized HF units in Spain the differences in clinical characteristics and treatment between patients with HF and advanced CKD. Methods We analyzed data from the registry of the SEC-Excelente-IC quality accreditation program of the Spanish Society of Cardiology, with 1716 patients with HF included between 2019 and 2021 by 45 specialized HF units accredited by the SEC. Patients were included consecutively in two 1-month cutoffs (March and October) in that period. The clinical and demographic characteristics and comorbidities of the patients were compared according to GFR < or > 30ml/min/m2. Results Of the 1,716 patients, 11.1% had a GFR<30 and 88.9% >30 mL/min/m2. Figure 1 shows the main clinical characteristics and comorbidities of the 2 groups. Median LVEF was similar in both groups: 42 (30-58) vs 38% (29-54). The group with advanced CKD was older (77±9.6 vs 70.5±12.6 years; p<0.001), had greater HF severity (more admissions for HF in the last year, worse NYHA functional class and longer evolution time), and a higher prevalence of coronary heart disease, hypertension, diabetes mellitus, cognitive impairment, anemia, iron deficiency and hyponatremia. There were no differences in sex, BMI, serum potassium or other comorbidities (Figure 1). Figure 2 shows the treatment received in each group. Patients with GFR <30 received in a significantly lower proportion all drugs for HF (p<0.001), except diuretics and potassium binders (ACEI/ARA, sacubitril-valsartan, MRA, beta-blockers, digoxin and SLGT2 inhibitors), and less cardiac rehabilitation (5.2 vs 10.4%; p=0.029). Incidence of one-year mortality was significantly higher in patients with GFR<30 ml/min/m2 (37.2 vs 14.4 per 100 persons-year, p<0.001), as were HF hospitalizations (61.3 vs 33.0; p<0.001) and HF decompensations without hospitalization (24.1 vs 11; p<0.001). Conclusions In our contemporary cohort of real-life HF patients, the prevalence of advanced CKD was 11.1%. These patients had a higher severity of HF, despite which, the utilization of HF drugs, including SGLT2 inhibitors was much lower than in those with GFR >30 ml/min/m2. One-year mortality, HF hospitalization and HF decompensations were almost 3-times higher. This treatment trend needs to be modified to improve the prognosis of these patients.

Outcome of pregnancy in women with unrepaired atrial septal defect - study of a single tertiary centre

Abstract Background Patients with unrepaired atrial septal defect (ASD) are prone to develop arrhythmia, right heart failure and to suffer paradoxical embolism. The risk might be even bigger during pregnancy due to the hemodynamic changes combined with the hypercoagulable state. Purpose To evaluate maternal, foetal, and neonatal outcome of pregnancy in women with unrepaired ASD. Methods A retrospective study of 43 pregnancies in 24 women with unrepaired ASD was performed in our tertiary centre from 2004. Previous maternal cardiovascular events and events during pregnancy (maternal, neonatal, and obstetric) were documented. Results 24 women with unrepaired ASD (median age: 27.5 ± 6.2) had 43 pregnancies resulting in one termination, 4 miscarriages and 38 live births. 55% were primigravida and 2 twin pregnancies were documented. At baseline 2 women (10.5%) were in NYHA functional class II and signs of right ventricle (RV) volume overload were detected on echocardiography in 18 cases (47%). 2 women had a history of supraventricular tachycardia. Median gestation at delivery was 39 ± 2.6 weeks. No thromboembolic events, pulmonary hypertension, or desaturation occurred during pregnancy. However maternal cardiovascular complications all affected women with RV volume overload: 2 cases (5.2%) of supraventricular tachycardia, 2 (5.2%) cases with NYHA functional class deterioration and 1 case (2.6%) of syncope were documented. Only one obstetric event; preeclampsia occured. Neonatal complications were as follows: premature delivery in 3 cases (7.9%) and recurrence of congenital heart disease (CHD) in 4 pregnancies (10.5%). After the pregnancy device or surgical closure of the ASD was indicated for 11 women (45.8%). Since then, five already underwent device closure, one had surgical repair, while five women are still waiting for intervention. Conclusions Our results align with the mWHO classification. Pregnancy with an unrepaired ASD is well tolerated and has a low risk of neonatal and maternal cardiovascular events. However, women with right ventricle volume overload are prone to develop arrhythmia or right heart failure during pregnancy. Therefore, cardiology follow-up during pregnancy should be decided on an individual basis. In our cohort no thromboembolic events were documented during pregnancy, however the prevalence of congenital heart disease in the foetus was higher compared to the literature.

Long-term prognosis and predictors of death in chronic Chagas cardiomyopathy in women and men

Abstract Background Chronic Chagas cardiomyopathy (CCC) is one of the leading causes of heart failure (HF) in Latin America and carries high morbidity and mortality. Previous studies showed conflicting results in epidemiological and clinical evidence of a gender-associated risk of death in patients with HF due to CCC. Purpose This study analysed the long-term prognosis and the main predictors of death in women and men with HF due to CCC. Methods From March 2009 to January 2023, we followed a cohort of outpatients with HF due to CCC. Specific serological tests diagnosed Chagas disease. Baseline data included clinical characteristics and echocardiographic findings. Statistical analyses were performed using the Kaplan-Meier (K-M) method to analyse time-to-event data and Cox proportional hazards methods to search for predictors of death. Results We studied 739 patients, with a mean age of 57.0 ± 12.1 years, 387 (52%) male. Women had a higher mean age (58.4 ± 11.7 vs. 55.8 ± 12.3 years; p=0.001), had a higher mean baseline left ventricular ejection fraction (LVEF) (44.3±14.5 % vs. 37.0±14.5%; p<0.001) and a smaller left ventricular diastolic diameter (LVDD) (56.8±8.9 vs. 62.5±9.4 mm; p<0.001). Over a median follow-up period of 10 years, 213 (56%) men and 169 (44%) women died (K-M: log-rank p=0.043; Figure). Men received more beta-blocker therapy (52.4% vs. 47.6%; p=0.040) and had a higher prevalence of chronic kidney disease (CKD) (p=0.003) and stroke (p=0.007). HFpEF was more prevalent in women and HFrEF in men (p<0.001). Device implantation and transplant were similar between women and men. Cox regression analysis for death adjusted for age, sex, myocardial infarction, diabetes, CKD, stroke, atrial fibrillation (AF), and LVEF showed LVEF (HR= 0.98;95%CL:0.97-0.98), age (HR=1.03;95%CL1.02-1.04) and CKD (HR= 1.32;95%CL:1.10-1.64) as the main predictors of death. In men, the main predictors were age (HR=1.02;95%CL:1.01-1.04), CKD (HR=1.409;95%CL:1.07-1.86), and LVEF (HR=0.98;95%CL:0.97-0.99), and in women AF (HR=1.41;95%CL:1.03-1.91), age (HR=1.03;95%CL:1.01-1.04), and LVEF (HR=0.97;95%CL:0.96 -0.98). Conclusion women had a better prognosis than men, but gender was not an independent predictor of death. Prevention of comorbidities, especially CKD in men and AF in women, and higher beta-blocker therapy can significantly reduce the death rate in women and men with HF from CCC.

Clinical phenotypes in relation to outcomes in heart failure patients with cardiac resynchronization therapy and defibrillators (CRT-D): an unsupervised cluster analysis

Abstract Background Patients with heart failure undergoing CRT are an heterogenous and complex population. Selecting patients before implantation is essential to obtain a favorable response to CRT-D. Data-driven cluster analysis may be an approach to identify different patients’ phenotypic categories. Purpose To identify different clusters of patients with CRT-D who share similar clinical phenotypes, and to evaluate the associations between clusters and clinical outcomes, using cluster analysis. Methods Three agglomerative hierarchical cluster analysis were performed in CRT-D patients seen between 2010 and 2019 in French hospitals. Associations between clusters and death at one year and death during whole follow-up (FU) were evaluated using Cox regression analyses. Results The study included 23,029 CRT-D patients with no prior history of VT/VF/cardiac arrest (mean age 67.7 ± 9.9 years; 78.8 % male), who were analyzed in relation to 3 ways, as follows: the first group was a 50% random sample of all patients (n = 11,514), the second group included patients dead at 1 year (n = 1,604) and the third group included those alive at 3 years FU (n = 14,228). A cluster analysis was performed on each group. Four clusters were identified in the first group: Cluster 1 identified young patients with dilated cardiomyopathy and low prevalence of coronary artery disease (CAD), cardiovascular (CV) risk factors and comorbidities (chronic kidney disease, lung and liver disease) (low-risk phenotype); Cluster 2 was composed of male patients with CAD but low burden of CV risk factors and comorbidities (CAD phenotype); Cluster 3 included CRT recipients with several CV risk factors but low prevalence of comorbidities (CV risk factors phenotype); Cluster 4 identified old patients with high prevalence of CAD, atrial fibrillation, CV risk factors and comorbidities (clinical complex phenotype). These phenotypes were maintained in the other two groups (dead at 1 year and alive at 3 years FU), with the highest consistency for low-risk and high-risk phenotypes(Cluster 1 and 4 respectively). Compared with Cluster 1, Clusters 2, 3 and 4 were independently associated with an increased risk of all-cause death at 1-year FU and during the whole FU (Cluster 2: HR 1.21, 95% CI 1.08 - 1.36; Cluster 3: HR 1.15, 95%CI 1.04 - 1.26; and Cluster 4: HR 1.79, 95%CI 1.65 - 1.96). There were high prevalences of CAD, atrial fibrillation, mitral regurgitation, and comorbidities (which are all predictors of CRT-nonresponse) not only in Cluster 4 at baseline, but also among patients who died at 1-year FU in all 4 clusters. Conclusion Cluster analysis identified four statistically driven groups of CRT recipients, with specific clinical phenotypes and associated with different risks for all-cause death. Identifying those patients at higher risk of adverse events might help in the selection of patients with heart failure undergoing CRT-D implantation, especially in relation to CRT-nonresponse.Risk of all-cause death in 4 clusters

Undiagnosed impaired glucose tolerance/diabetes mellitus and relationship with aortic stiffness in patients with acute coronary syndromes

Abstract Background Patients admitted with an acute coronary syndrome (ACS) often have unknown cardiovascular risk factors, such as impaired glucose tolerance (IGT) or diabetes mellitus (DM). Detecting these conditions is crucial to intensify appropriate therapies. Increased aortic stiffness, assessed by aortic pulse wave velocity (PWV), is associated with higher mortality in patients at high cardiovascular risk. Purpose Estimating the prevalence of IGT and DM and their relationship with increased aortic stiffness in patients admitted with an ACS. Methods Seventy-five consecutive patients admitted for ACS (21% women, mean age 63.6±11.1 ys), with fasting plasma glucose (PG) and glycated hemoglobin (HbA1c) not diagnostic for diabetes mellitus, underwent a fully standardized oral glucose tolerance test. All patients were also evaluated with the Arteriograph device, which applies a brachial cuff-based oscillometric method for the estimation of aortic PWV and arterial pulse waveform features. The automated vascular studies and OGTTs were performed after patient stabilization, at least 96 hours after admission. Results Forty-one patients (55% of the total study population) showed an abnormal OGTT response: 14 patients had a 2-h PG-OGTT ≥ 200 mg/dL, uncovering a diagnosis of DM, and 27 patients had a 2-h PG-OGTT ≥ 140 mg/dL, uncovering a diagnosis of IGT. Patients with DM showed no differences in terms of age, cardiovascular risk factors, Framingham risk score, C-reactive protein values, whereas a significant difference was observed in the number of diseased coronary vessels (2.2±0.8 vs 1.6±0.9, p=0.016) and PWV values (10.0±1.3 vs 8.8±1.6 m/s, p=0.028). Similarly, when considering all patients with an abnormal OGTT, a significant difference was observed in PWV values compared to patients with a normal OGTT (9.5±1.5 vs 8.4±1.7 m/s, p=0.032), as well as in estimated glomerular filtration rate (78±18 vs 83±23 mL/min/1.73mq, p=0.05), and peak troponin values (3698±2905 vs 2124±2561 ng/ml, p=0.02). At follow-up (mean time 51.7 months), no patients had died, but 5 patients had a new major cardiovascular event. Aortic pulse wave velocity values were different between patients with and without events (10.6±2.3 vs 8.6±1.4 m/s, p=0.024), and PWV was a significant predictor of events at univariate regression analysis (hazard ratio 1.93; 95 confidence intervals 1.01-3.69, p=0.047). Conclusions An unknown diagnosis of DM and/or IGT is very frequent in patients with ACS. Undiagnosed dysglycemic conditions are linked to a higher prevalence of coronary multivessel disease and increased aortic stiffness, which is also predictive of future cardiovascular events. A systematic screening with OGTT may help identifying patients at even higher cardiovascular risk, and tailoring secondary prevention strategies through personalized aggressive therapeutic interventions.

Increased risk of stroke in non-rheumatic valvular disease associated with antiphospholipid syndrome (APS): a US nationwide study 2017-2019

Abstract Introduction Antiphospholipid syndrome (APS) is an autoimmune syndrome characterized by the presence of antiphospholipid autoantibodies, arterial and venous thrombosis, recurrent pregnancy loss and thrombocytopenia. Cardiac manifestations are also common which include coronary artery disease (CAD), non rheumatic valvular heart disorders (NRVHD), myocardial dysfunction, intracardiac thrombi and pulmonary hypertension. Valvular lesions occur likely due to immune complex deposition on the valves, causing fibrosis, calcification and subsequently valvular deformities. Literature review suggests prevalence of NRVHD in APS population is 30% and left sided valves are more involved than right. An increased risk of stroke has also been seen in APS patients with valvular disorders. Purpose Studies report variations in incidence of NRVHD in association with APS. To estimate the prevalence of NRVHD and their correlation with APS, we conducted a retrospective database analysis of hospitalizations across the United States. Additionally we investigated whether this association indicates a increased risk of ischemic stroke in this specific subpopulation. Methods The national inpatient sample (NIS) from 2017-2019 was queried for adult patients (age>18 yrs) admitted with a primary or secondary diagnosis of APS. These patients were stratified for different NRVHD including tricuspid stenosis, tricuspid insufficiency, pulmonary stenosis, pulmonary regurgitation, mitral stenosis, mitral insufficiency (MI), aortic stenosis (AS), and aortic regurgitation. Baseline risk factors and cardiac complications were compared. Multiple regression analysis was performed to study the association of NRVHD with stroke as the primary outcome in the subpopulation of APS hospitalizations. Results A total of 567600 adult patients hospitalized with diagnosis of APS were identified from the NIS 2017-2019 database. Among those, 33,095 had NRVHD with a mean age of 69 years. Of these, prevalence of males was 52.41% compared to females of 47.59%. In the cohort of APS, patients with NRVHD had a higher prevalence of coronary artery disease (43.78% vs 20.41%), diabetes mellitus (30.65% vs 27.56%), prior stroke (10.42% vs 7.78%) than those without valvular disorders. Among the APS population the most prevalent NRVHD were mitral insufficiency (MI), 2.45% and aortic stenosis (AS), 2.13%. In the cohort of NRVHD in APS hospitalizations, the odds of stroke was found to be 1.3 times higher with statistical significance (confidence interval (CI): 1.13-1.48, p <0.001) adjusted for relevant clinical and demographic risk factors such as tobacco abuse, CAD, diabetes mellitus, prior stroke. Conclusion This study shows 6.2% prevalence of NRVHD in APS population, of which MI and AS were common. NRVHD is also associated with higher odds of stroke in APS. Further studies are warranted in identifying the risk of stroke with NRVHD in APS population and emphasizing the need for early detection.

Anticoagulation control challenges in patients with rheumatic heart disease and mechanical heart valves operated at a cardiac surgery center in a low-income country

Abstract Background Rheumatic heart disease (RHD) prevalence is very high in many low-income countries and valve replacement surgery can sometimes be the only available therapeutic strategy for the affected patients. Mechanical valves require lifelong anticoagulation and this can be very challenging in many poor countries where several barriers to effective anticoagulation monitoring and management are faced. Methods This is a retrospective study on 145 patients with RHD who underwent valve replacement surgery at a cardiac surgery center (CSC) in a low-income country between 2001 and 2022. The study aimed to evaluate the effectiveness of anticoagulation treatment to prevent thromboembolic events in patients with RHD with mechanical valves. The patients’ information such as social and demographic data, clinical features, surgical data and international normalized ratio (INR) records were collected and analyzed. Descriptive statistics were applied to the data and expressed as mean with standard deviation or simple frequencies and percentages. Results The mean age of the operated patients was 25.9 years (± 12.6) and 60% of them were female. Most of the patients (54%) were able to monitor their anticoagulation at the center and 8.2% of them monitored it in other hospitals. Three percent (3%) of the patients use a portable device to monitor their INR. These devices are provided by the CSC to help patients that live in distant provinces and are unable to go to the capital regularly. The device is held by one patient that is a focal point and helps monitor the INR of the other patients living in the same province. The INR results are communicated to the CSC by telephone text message. Seven percent (7%) of the operated patients haven’t monitored their INR for more than one year and 24.8% of them were lost to follow-up. Sixty-four percent (64%) of the patients who monitor their INR at the center have an optimal control of their anticoagulation therapy. Most of the patients that were lost to follow-up (N=20) and most of the patients that haven’t checked their INR for more than one year (N=7) are patients who had aortic valve replacements. At least 20% of the patients that live in capital of the country and close to the CSC don’t monitor their anticoagulation regularly. Conclusion The surgical outcomes in RHD patients who undergo mitral valve repair are usually satisfactory. However, valve replacement is often the only feasible alternative and anticoagulation monitoring and management in these patients can become a serious problem especially to those coming from areas with limited resources. Illiteracy and poverty play a major role as barriers to effective monitoring of anticoagulation therapy. Efforts must be made to increase access to facilities where INR can be monitored. Our experience showed us that providing portable devices for INR monitoring to the patients living in remote areas can be a favorable short-term solution.

Multi-modality deep learning model for prediction of chronic obstructive coronary artery disease

Abstract Background/Introduction The incidence of coronary artery disease (CAD) is on the rise with an increasing burden of stable ischemic heart disease (SIHD) and high prevalence of obesity, diabetes, hyperlipidemia, and other cardiovascular risk factors. Pre-test probability estimation for CAD based on demographic features and characterization of chest pain is insufficient to accurately assess whether further evaluation for CAD is warranted. Purpose To develop and validate a deep learning (DL) algorithm utilizing electrocardiogram (ECG) waveforms and clinical features to predict obstructive CAD. Methods Clinical data from subjects undergoing invasive angiography over a 4-year period at a quaternary care center exclusive of subjects who had concern for acute coronary syndromes were used for model training. ECGs obtained up to 5 years prior to angiography were included; ECGs were partitioned 8:1:1 for training, validation, and test datasets. Obstructive CAD was defined as receiving percutaneous coronary intervention during elective angiography. Convolutional neural network models were developed for ECG waveforms alone (DL-ECG), clinical features from standard risk scores (DL-Clinical), and the combination of ECG waveforms and clinical features (DL-ECG+Clinical); a commonly used pre-test probability estimation tool derived from the CAD Consortium study was used as a comparison (PTP). The models were evaluated based on area under the curve receiver operating characteristics (AUC). Shapley additive explanations (SHAP) analysis was performed to understand feature importance in the DL models. Results A total of 40,602 ECGs and 8,361 coronary angiograms from 7,201 patients were included in the analysis. The median age was 66 (IQR 56-75), 71.9% were men, 34.9% had hypertension, 30.6% had diabetes mellitus, and 39.0% had dyslipidemia. The PTP model (AUC 0.733 [0.717-0.750]) had similar performance as the DL-Clinical model (AUC 0.762 [0.746-0.778]). The DL-ECG model (AUC 0.741 [0.726-0.758]) had similar performance as both the clinical feature models. The DL-ECG+Clinical model (AUC 0.807 [0.793-0.822]) trained on ECG waveforms and clinical features had a superior performance (Figure 1). SHAP analysis for the DL-ECG+Clinical model revealed that ECG waveforms had the largest influence on the model’s output followed by age and chest pain type (Figure 2). Conclusions Multi-modality DL model utilizing ECG and commonly used features can improve prediction of obstructive CAD in SIHD compared to traditional pre-test probability estimates. Prospective research is warranted to determine whether incorporation of DL methods to ECG analysis effectively improves diagnosis and outcomes in obstructive CAD.Figure 1.Figure 2.

Rurality and outcomes in prostate cancer: role of socioeconomic status and educational attainment

Abstract Background/Introduction Patients diagnosed with prostate cancer (PC) have a higher cardiovascular disease (CVD) prevalence and mortality risk. Rurality have been associated with up to 33% higher CVD risk and 44% higher all-cause mortality risk in patients with PC. Purpose Analyze the impact of rurality (from both patient and provider perspectives) on the development of adverse outcomes after a PC diagnosis according to socioeconomic and educational status. Methods We included men aged ≥66 with a new primary PC diagnosis (defined as ICD-10 = C61) from 2009-2017 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. The primary outcomes were CVD (comprising heart failure, atrial fibrillation, acute myocardial infarction, peripheral artery disease, and ischemic stroke), PC-specific mortality (PCsm), cardiovascular disease mortality (CVDm), and all-cause mortality. Patients living in areas with a population of <2,500 or <20,000, not adjacent to a metropolitan area, were considered to have a positive rural status. The provider status (metropolitan vs. non-metropolitan) was defined according to the 2013 National Center for Health Statistics' Urban-Rural Classification Scheme for Counties. Low socioeconomic status (SES) was defined according to Yost Index quintiles. Low educational status was defined according to percentiles of people >25 years old with less than a high school diploma. Multivariable Fine-Gray models, accounting for competing mortality/type of mortality, and Cox regression models were applied. Results We included 75,221 patients with PC (Picture 1), of which 1,828 were from rural areas and 362 were from rural areas with providers from non-metropolitan areas. Among patients from rural areas under the care of non-metropolitan providers, 82.6% had low SES (Yost Index ≤ 2). In this subgroup, patients from rural areas with non-metropolitan providers had 30% higher CVD risk (sHR 1.30; 95% CI 1.04-1.62) and 44% higher all-cause mortality risk (sHR 1.44; 95% CI 1.14-1.83; Picture 2) when compared to patients with low SES from urban or rural areas with providers from metropolitan areas. Additionally, within patients from rural areas with non-metropolitan providers, the median % of people with only high school diploma was 38.3 (IQR 36.2-40.9). Among those with low educational status (≤41% of high school county-rate), patients from rural areas with non-metropolitan providers had a 35% higher associated CVD risk (sHR 1.35; 95% CI 1.06-1.71), 54% higher associated CVDm risk (sHR 1.54; 95% CI 1.01-2.36), and a 32% higher associated all-cause mortality risk (sHR 1.32; 95% CI 1.04-1.66). Conclusion Patients with PC from rural areas with non-metropolitan providers have higher rates of low SES and low educational status and suffer from up to 54% higher associated risks of adverse outcomes, emphasizing the role of multiple domains of the Social Determinants of Health in health outcomes.

Diabetes worsens the adverse association between myocardial diffuse fibrosis and left ventricular strain

Abstract Background Heart failure is a common cardiovascular complication to diabetes. Increased fibrosis of the myocardium has been suggested to be a mechanism, however, no convincing clinical evidence has so far been presented. A better understanding of how myocardial tissue characteristics influence functional aberration in diabetes could aid diagnosis, risk assessment and guide treatment. Native T1 is a CMR marker of diffuse fibrosis with diagnostic and prognostic value (1,2), and feature tracking (CMR-FT) strain is a sensitive measure of myocardial systolic function. In this study, we evaluated the association of CMR markers of fibrosis with markers of systolic function in individuals with and without diabetes. Purpose To understand the relationship between native T1 and myocardial strain and how diabetes may affect this. Methods Participants from the UK Biobank population imaging study were included. Left ventricular global longitudinal strain (GLS) was derived using a semi-automated batch processing software tool. Native T1 was derived from segmentation of the entire short axis slice using an automated quality control tool, excluding scans with predicted dice score of <0.7. Multivariable linear models were used with the strain metrics as the outcome variable and native T1 and diabetes as the exposure variables. These models were adjusted for age, sex, BMI, ethnicity, smoking and alcohol status, prevalent hypertension hypercholesterolaemia and coronary artery disease. The effect of interaction between diabetes and native T1 on GLS was examined by introducing an interaction term. Results In total 41,533 participants were included, of which 1957 had diabetes – see Table 1 for baseline characteristics. The average GLS measured for those with diabetes was -17% and was -18% for those without. The average native T1 in those with diabetes was 935ms and 933ms for those without on the background of greater prevalence of cardiovascular risk factors in those with diabetes. In model adjusted for all relevant co-variates, individuals with diabetes had worse GLS measured compared to those without diabetes (β-coefficient: 0.51, p value <0.001). Increasing fibrosis (native T1) was associated with worsening GLS (β-coefficient: 0.005, p value <0.001) in all participants. However, in those with diabetes, increasing native T1 was associated with a greater decline in GLS compared to those without diabetes (interaction term β-coefficient: 0.005, p value <0.001), with a relative impairment seen within normal ranges for native T1 - see Figure 1. Conclusion(s) This is the largest study of its kind to demonstrate a dose dependent relationship between increasing native T1, representing potential myocardial fibrosis, and myocardial strain, representing cardiac dysfunction. Our findings indicate that increased fibrosis alone does not explain the higher risk of HF in diabetes, other mechanisms, perhaps intracellular, might be at play.

Left atrial reservoir strain and global longitudinal strain associates with re-hospitalization and mortality in patients admitted for acute heart failure

Abstract Background Left atrial reservoir strain (LAr) and global longitudinal strain (GLS) have emerged as useful parameters for the assessment of left ventricular diastolic function and the estimation of left ventricular filling pressures. Yet, there remains a gap of knowledge regarding the possible association of LAr and GLS with re-hospitalization and mortality in patients with acute heart failure (HF). Aims This study aims to investigate the association between LAr and GLS with re-hospitalization and mortality in patients admitted for acute HF. Methods Out of 526 enrolled patients admitted for acute HF, 142 (mean age 71, 25% women) were systematically evaluated for LAr and GLS using speckle tracking echocardiography. Multivariable Cox regression analyses, adjusting age, sex, current smoking prevalent atrial fibrillation, hypertension, kidney disease and plasma glucose, were used to assess the associations between continuous values of LAr and GLS with all-cause mortality and HF-related re-hospitalization. Results The median follow-up time to death of any cause and HF rehospitalization was 39 (interquartile range 14-66) and 22 (4-51) months, respectively. During follow up, 63 (44%) patients died, and 63 (44%) were re-hospitalized due to HF. Lower values of LAr were significantly associated with higher risk of mortality (HR 0.93; 95%CI 0.89-0.98, p=0.008). Similarly, lower GLS was associated with higher risk of mortality (HR 0.94; 95%CI 0.89-0.99, p=0.045). Only lower values of LAr were associated with higher risk of HF re-hospitalization in the multivariable model (HR 0.93; 95%CI 0.88-0.98, p=0.004). Conclusion In this prospective, long-term follow-up study of patients with acute heart failure, lower values of LAr and GLS showed prognostic significance, with lower values being indicative of poorer outcomes. Notably, LAr was associated with higher risk of both death and rehospitalization for heart failure, whereas GLS was solely associated with higher mortality risk. These echocardiographic parameters could be further investigated for risk assessment of patients with heart failure in order to identify those at higher risk of rehospitalization and death, thereby facilitating targeted interventions to improve their prognosis.KM-curves for or the Quartiles of LAr

Comprehensive machine learning models for prediction of heart failure in 476,393 women and men from the UK Biobank reveal sex differences and underutilized risk factors

Abstract Background Machine learning (ML) models provide potential advantage over ‘traditional’ regression models in heart failure (HF) prediction. Objective To compare performances of Cox PH models and ML survival models for incident HF in men and women without prevalent ischemic heart disease (IHD). We also aimed to identify potential high-risk precursors otherwise ignored by conventional survival models, and to investigate differences between sex-specific models. Methods We included 476,393 participants (55.6% women) from the UK Biobank, after excluding participants with a history of HF or IHD, and defined sex-specific datasets. We predicted incident HF events using over 400 baseline characteristics. We constructed multivariable Cox PH models, which included all predictor variables and subsequently only those remaining after LASSO stability selection. We also developed two supervised ML models (Random Survival Forest (RSF), eXtreme Gradient Survival Boosting (XGBoost)). We identified the 15 most important sex-specific predictors in each model and performances were compared using the C-index. Models were validated using hold-out sets. Results During 12.3 ± 1.9 years of follow-up, 4680 (1.76%) women and 6631 (3.14%) men developed incident HF. XGBoost showed the best performance during model training (C-index, training: 0.89 in men, 0.97 in women; validation 0.77 in men, 0.80 in women). The multivariable Cox model performed second-best (C-index, training: 0.78 in men, 0.82 in women; validation: 0.76 in men, 0.78 in women). RSF performed slightly worse (C-index, training: 0.75 in men, 0.79 in women; validation: 0.75 in men, 0.79 in women) but did not show performance drop during validation. LASSO stability selection performed similar to RSF. Age, self-reported lifetime treatments and medications, cystatin-C, waist circumference and FEV1-scores were identified as strong risk factors in all models for both sexes. Reduced albumin levels and elevated HbA1c were more strongly associated with high risk in men, while elevated systolic BP showed higher importance in women. Traditional Cox models observed CRP as important only in men, while the ML models identified CRP as important for both sexes. Neutrophil count was considered a strong risk factor in both sexes in the traditional Cox models, yet it was not among the most important predictors in both ML models. Presence of other heart disease (which included a.o. pericardial disease, valve disorders and arrhythmias) was an important predictor variable only in the ML models. Conclusion ML models showed similar performance to Cox PH models for HF prediction. Despite this, differences in predictor importance were identified between models. Sex-specific risk predictors were found, and FEV1 score, which is not commonly included in existing models, was identified as an important risk factor. These results suggest that ML models may reveal additional insights that would otherwise remain unnoticed.

Estimated impact of inclisiran treatment on hyperlipidemia prevalence and cardiovascular disease events in NHANES dataset

Abstract Background Inclisiran, administered subcutaneously every 6 months, will result in the reduction of LDL-cholesterol levels of approximately 50%. We estimated the eligibility of the US population for Inclisiran treatment and its impact on blood lipids and CVD events. Methods We applied ORION trial eligibility criteria to US adults aged ≥ 18 years in the US NHANES 1999-2018 to estimate the US eligible population. Blood lipid alterations in ORION 10 were applied to estimate the impact on LDL-C levels and hyperlipidemia prevalence in the ASCVD population sample. We also used the Framingham CVD risk scores to estimate 10-year CVD risks in the ASCVD high-risk population sample based on ORION 11. The difference in estimated risks with and without Inclisiran administration, multiplied by the eligible population from NHANES data, represented the potentially preventable CVD events. Results We identified 651 ASCVD persons (projected to 5.55 million) who fit ORION 10 trial eligibility criteria and 359 ASCVD high-risk persons (projected to 2.53 million) who fit ORION 11 trial eligibility criteria for our analysis. We then analyzed the changes in these populations after Inclisiran treatment. Firstly, we estimated that approximately 3.9 million (72.8%) individuals would experience ≥50% LDL-C reductions. Secondly, we estimated that among the ASCVD patients, 5.07 million (91.3%) with elevated LDL-C, 0.25 million (22.8%) with reduced HDL-C, 1.24 million (95.2%) with elevated TC, and 0.65 million (32.4%) with elevated TG would potentially achieve a more reasonable blood lipid level. Finally, among those without CVD, the estimated 10-year CVD risks were 19% before and 13.8% after Inclisiran treatment, reflecting a 5.2% absolute (and 27.4% relative) reduction in risk translating to potentially 130,000 preventable CVD events over 10 years. Conclusion Inclisiran treatment in eligible US adults may substantially reduce hyperlipidemia prevalence and CVD events.core graphics

One-year outcomes of transcatheter mitral valve replacement in patients with severe mitral regurgitation

Abstract Background Mitral valve regurgitation (MR) is a prevalent valvular heart disease, and a subset of patients face challenges in undergoing surgical treatment. Transcatheter mitral valve replacement (TMVR) has emerged as a viable option for selected patients with severe MR deemed unsuitable for traditional valve surgery. Purpose This study aims to evaluate the feasibility, safety, durability, and clinical outcomes of a novel transapical mitral valve system (MitraFix valve) in treating moderate to severe MR patients. Methods The early feasibility study of the MitraFix TMVR transapical system is a multicenter, prospective, nonrandomized study. All patients underwent evaluation by a multidisciplinary heart team and were deemed suitable for mitral valve intervention. Clinical events were adjudicated by an independent clinical events committee. Results From June 2021 to July 2022, 10 patients (mean age: 71.2 ± 7.4 years, 40% male) were enrolled. The mean Society of Thoracic Surgeons(STS) predicted risk of mortality was 7.5 ± 2.7%. All implants were successful, with a mean operational time of 45.2 ± 25.9 min. One patient was converted to open cardiac surgery after successfully implanting the valve due to persistent apical bleeding. At 1-year follow-up, all-cause mortality was 20%, with a cardiovascular mortality at 10.0%. Among survival patients, 87.5% of surviving patients had MR ≤1+ and 75% patients were in NYHA functional class I or II at 1 year. The overall KCCQ score significantly increased from 55.8 (42.9, 72.9) points at baseline to 77.5 (73.7, 88.6) points at 1-year follow up (P = 0.012). Left ventricular ejection fraction showed no significant change from basline (51.5%) to 1 year (50.0%) (P=0.799). No evidence of mitral stenosis or left ventricular outflow tract (LVOT) obstruction was observed. Conclusions The MitraFix TMVR transapical system demonstrated excellent valve function, low mortality, sustained MR elimination and clinical improvement up to one year in this study. Further studies, encompassing a larger cohort of patients and an extended follow-up duration, are needed to confirm these findings.Change in MR and NYHA functional classChange in Quality-of-Life Assessment