Chronic Kidney Disease Research Articles

Predictors of acute ischemic strokes and subsequent mortality in patients hospitalized for percutaneous coronary interventions

Abstract Background Acute ischemic strokes (AIS) occurring post percutaneous coronary intervention (PCI) are an infrequent but severe complication, resulting in increased mortality rates and morbidity in survivors. Purpose We aimed to investigate independent predictors of AIS and subsequent mortality in patients hospitalized for PCI in a nationwide cohort. Methods A retrospective analysis using on ICD-10-GM and OPS-codes obtained from 2006-2021 from the German Federal Statistical Office was performed. Patients with a peri-interventional AIS aged ≥18 years which were admitted for PCI were included in this analysis. A stepwise regression analysis was employed to identify factors independently associated with AIS and to determine variables linked to in-hospital mortality. Results From 4,910,430 PCI cases registered from 2006-2021, AIS occurred in 4,098 (0.08%) patients. Patients with an AIS were 70.9±11.3 years of age, predominantly male (65.3%) and displayed a high burden of comorbidities such as diabetes (36.1%), a prior medical history of atrial fibrillation (34.6%) and chronic kidney disease (19.4%). In patients with AIS, 27.4% presented with a ST-elevation myocardial infarction (STEMI), whilst 38.9% were admitted with a Non-STEMI. Concerning procedural characteristics, 84.2% underwent a coronary stent implantation, and in 5.5% cases a coronary thrombectomy was carried out. Important predictors of peri-interventional AIS after a PCI were: carotid artery disease, history of stroke, presentation with myocardial infraction, atrial fibrillation, and coronary thrombectomy. For variables like hyperlipoproteinemia, obesity and stent implantation an inverse association was noted (also see Figure 1A). With regard to mortality, during a mean in-hospital stay of 18 ± 15.1 days, a total of 18.1% (n=742) patients died. We identified several independent predictors of mortality including clinical presentation with cardiogenic shock, dialysis and STEMI as indication for PCI. A negative correlation with in-hospital mortality was seen for variables such as arterial hypertension and coronary stent implantation (see Figure 1B for full set of independently associated variables). Conclusion In a nationwide cohort of patients hospitalized for PCI over 16 years, we identified important predictors of AIS including carotid artery disease and coronary thrombectomy. Moreover, a substantial rate of in-hospital mortality as well as several predictors of death were recognized. Our findings might help clinicians identify patients undergoing PCI who are at highest risk for ischemic cerebral complications and subsequent mortality.

The importance of comorbidities in idiopathic and associated with connective tissue disease pulmonary arterial hypertension: from the Spanish Registry of Pulmonary Hypertension (REHAP Registry)

Abstract Introduction Comorbidities play a major role in the prognosis of patients with pulmonary arterial hypertension (PAH). These comorbidities are present in more than 80% of patients diagnosed in the last years with idiopathic PAH (iPAH) and their presence is associated with increased morbidity and mortality although its influence on PAH associated with connective tissue disease (PAH-SSc) is unknown. We studied the impact of comorbidities on iPAH and PAH-SSc in the Spanish population. Methods We collected patients diagnosed with iPAH, heritable, associated with drug or toxine exposure and PAH-SSc between 2014 and 2023 from the Spanish Registry of Pulmonary Hypertension. Patients are classified into: no comorbidities, 1-2 comorbidities and ≥3 comorbidities. We analyzed the impact of comorbidities in baseline characteristics, exercise capacity and hemodynamic profile, as well as in the risk profile and initial treatment. Survival analyses estimated by Kaplan-Meier analysis using the log-rank test and Cox proportional hazard analyses were performed to determine the effects of baseline characteristics on survival. Results 757 patients were selected for this study. The characteristics of the patients are shown in Table 1. As the number of comorbidities increases (0/1-2/≥3) we found higher age (49/59/67 years; p<0.001), higher percentage of male sex (12.9/29.9/43.4%; p<0.001) and higher FC III at diagnosis (42.7/46.9/59.6%; p=0.013). We observed a shorter distance in 6MWD, higher NT-proBNP levels, lower DLCO and a less unfavorable hemodynamic profile (PAPm, PAWP, CI and PVR). The most frequent comorbidities were a history of smoking (46.4%), followed by arterial hypertension (41.5%), obesity (24.6%) and chronic kidney disease (19.2%). Diabetes mellitus, although less frequent, reached more than 55% in patients with ≥3 comorbidities (p<0.001). The presence of ≥ 3 comorbidities was more frequent in iPAH than PAH-SSc (p<0,001). Intermediate risk profile was the most common (58.4%) and this reached 68.7% in those with ≥3 comorbidities due to a lower number of patients in a low-risk profile (p<0.001). A statistically significant lower survival (p<0.001) was observed in patients with ≥ 3 comorbidities; however, we found no differences between 0 and 1-2 comorbidities at 7-year follow-up (Figure 1). Variables associated with mortality were male sex (HR 1.88, 95% CI 1,26 – 2.8), age (HR 1.04, 95% CI 1.02 – 1.06) and the presence of ≥3 comorbidities (HR 1.49, 95% CI 0.98 – 2.27), not the presence of connective tissue diseases, which were not associated with increased mortality in our study. Conclusions The presence of comorbidities in iPAH and PAH-SSc is very frequent in the Spanish population. They are associated with a worse clinical profile, risk profile, lower use of oral double theraphy and prostacyclins. The presence of ≥3 comorbidities is associated with worse survival, not the presence of 1-2 comorbidities or connective tissue disease.

Levosimendan improves the early prognosis of patients with Non ST-segment elevation myocardial infarction and Killip class > II

Abstract Background Levosimendan is an inotropic agent known for its calcium-sensitizing myofilament effect and ATP-dependent potassium channel opening mechanism, which enhances myocardial contractility without increasing oxygen consumption. Despite its potential benefits, the impact of levosimendan on the prognosis of patients with myocardial infarction remains uncertain and requires further investigation through larger-scale studies. Purpose This study aimed to investigate the effect of levosimendan on the short-term prognosis of patients with Non-ST-segment elevation myocardial infarction (NSTEMI) and Killip> II. Methods The data for this study were derived from the Health and Medical Big Data Superplatform, comprising a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospitals in the City from 2010 to 2023. A total of 12472 patients with NSTEMI and Killip > II were included. Patients were divided into the levosimendan group and the non-leosimendan group based on whether levosimendan was used during hospitalization. Propensity score matching (PSM) was employed to balance covariates between the two groups. Multivariate Cox regression was used to evaluate the relationship between levosimendan and clinical outcomes. Covariates adjusted in PSM included age, sex, Killip class, early PCI, previous PCI, previous medical conditions (diabetes, hypertension, ischemic stroke, and chronic kidney disease), and medications during hospitalization (aspirin, clopidogrel, indobufen, ticagrelor, statins, cedilanid, recombinant human brain natriuretic peptide [rhBNP], milrinone, dopamine, dobutamine, and angiotensin converting enzyme inhibitor/angiotensin receptor blockers [ACEI/ARB]). The primary endpoint was major cardiovascular and cerebrovascular adverse events (MACCE), defined as the composite endpoint of cardiac death, myocardial infarction, and ischemic stroke within 3 months. Results The levosimendan group comprised 782 patients, while the non-leosimendan group included 11690 patients. After PSM, the covariates were balanced, resulting in 756 well-matched pairs. In PSM patients, the levosimendan group exhibited a significantly lower incidence of MACCE (aHR, 0.573; 95%CI, 0.466–0.704; p < 0.001) and cardiac death (aHR, 0.500; 95%CI, 0.399-0.626; p < 0.001). However, there was no significant difference in the incidence of myocardial infarction and ischemic stroke. Conclusions Levosimendan was associated with a lower incidence of MACCE within 3 months in patients with NSTEMI and Killip> II, mainly driven by lower incidence of cardiac death. However, these findings are based on observational data and require confirmation through adequately powered, randomized, controlled trials.

Impaired systemic microvascular function in patients with resistant arterial hypertension and microalbuminuria: an observational study

Abstract Background Systemic arterial hypertension (SAH) is one of the most prevalent diseases worldwide and is known to be associated with alterations of microvascular function. It is well known that microalbuminuria (MAU) is considered an early marker of renal and cardiac injury in SAH and is an independent risk factor for cardiovascular events in this population. Additionally, it is associated with altered endothelial function, which occurs from the early stages and can be considered an early marker. In some cases, SAH presents as resistant arterial hypertension (RAH), resulting in a worse prognosis compared to individuals with non-resistant hypertension. Moreover, MAU is associated with higher mortality, independent of glomerular filtration rate. Endothelial dysfunction is also a risk marker found in different conditions and can add to MAU in patients with RAH. Purpose To investigate systemic microvascular function in patients with RAH, with or without MAU. Methods 64 patients with RAH, of both genders (50% men), were evaluated, with 32 having MAU and 32 without MAU (defined as a urinary albumin/creatinine ratio between 30 and 300 mg/g in a routine urine sample). Microvascular function assessment was performed using a laser speckle system, allowing analysis of cutaneous microvascular flow. Flow measurements were expressed in arbitrary perfusion units (APU) divided by the mean arterial pressure to obtain cutaneous vascular conductance (CVC). A post-occlusive reactive hyperemia (PORH) test was performed, with brachial artery occlusion using a sphygmomanometer 50 mmHg above systolic pressure for 3 minutes; cutaneous flow was measured after release of the occlusion. Results Patients with or without MAU did not differ in terms of age, frequency of diabetes, and chronic kidney disease. The peak CVC values during PORH were 0.64 ± 0.15 and 0.55 ± 0.15 APU/mmHg in RH and RH + MAU patients, respectively (P=0.03). The delta values (peak – baseline) during PORH were 0.31 ± 0.11 and 0.25 ± 0.09 APU/mmHg in RH and RH + MAU patients, respectively (P=0.04)(Figure 1). Conclusions PORH-induced vasodilation was found to be reduced in patients with RAH and MAU compared to patients without MAU. This finding shows alteration of endothelium-dependent vasodilation mechanisms in these patients, indicating reduced systemic microvascular endothelial function. Endothelial dysfunction may be associated with glomerular permeability changes, contributing to MAU and further increasing the risk for these patients. This suggests the need for more intensive therapeutic interventions and better risk stratification for these patients, as endothelial dysfunction can be found in the early stages of the disease.Figure 1

Association of Triglycerides, HDL, and Waist Circumference with eGFR in patients in private practice

Background: Chronic kidney disease (CKD) is one of the leading causes of mortality and morbidity all over the world. On the other hand, metabolic syndrome has been reported to be associated with adverse renal outcomes. Among the components of metabolic syndrome, diabetes and hypertension are established causes of renal impairment. However, the association of Triglycerides (TGs), High density lipoprotein (HDL), and Waist Circumference (WC) with renal function independently remains understudied. Objectives: The objective of this study was to determine the association of triglycerides, HDL, waist circumference with estimated glomeruar filtration rate (eGFR). Materials and Methods: This cross-sectional study enrolled 100 subjects attending as outpatient in Ibn Sina Diagnostic Centre, Uttara from July 2023 to December 2023. Renal impairment was measured by estimated glomerular filtration rate (eGFR). The eGFR was calculated using the modified modification of diet in renal disease (MDRD) equation. Statistical analyses were performed by using SPSS 25.0 (Statistical Package for Social Science, Inc., Chicago, IL, USA). Continuous variables were expressed as means±standard deviation, and categorical variables as frequencies and proportions. The relationships between renal function with triglycerides, HDL and WC were assessed by correlation coefficient. A p-value <0.05 was considered significant. Results: Among 100 subjects the overall incidence of renal impairment is 13 (13%). Waist Circumference (WC) and high Triglyceride (TG) have inverse relation with eGFR means significant association in developing renal impairment. Conclusion: This study suggests triglyceride and central obesity progress with renal impairment. Therefore, early monitoring and management of triglycerides and central obesity in CKD patients may help in decreasing the progression of the disease and, hence, mortality in CKD patients. EWMCJ Vol. 12, No. 1&2, January-July 2024: 4-8

Efficacy of sotagliflozin by diabetes duration: a secondary analysis of SCORED

Abstract Background Sotagliflozin is a sodium-glucose cotransporter (SGLT) 1 and SGLT2 inhibitor. SCORED randomized patients with type 2 diabetes (DM) and high cardiovascular (CV) risk to sotagliflozin or placebo. Purpose We evaluated if diabetes duration affects HF and CV outcomes when comparing sotagliflozin with placebo in SCORED, as diabetes duration can modify CV risk. Methods SCORED enrolled patients with DM (hemoglobin A1c ≥7%), chronic kidney disease (glomerular filtration rate of 25-60 mL/minute per 1.73 m2), and CV risk factors. Patients were randomized to sotagliflozin compared with placebo. Patients in SCORED were stratified by diabetes duration, into categories of <10 years, 10-19 years, or ≥20 years. The primary endpoint was total CV death, hospitalization for HF, or urgent visit for HF. Secondary endpoints were total hospitalization for HF or urgent visit for HF, as well as total CV death, nonfatal myocardial infarction, and nonfatal stroke (MACE). Outcomes were assessed using marginal proportional hazard models stratified according to HF criteria and geographic region where non-CV death was a competing terminal event. Subgroup analyses were assessed with natural cubic splines of interaction between treatment and continuous diabetes duration. Results In SCORED, 10,579 (99.9%) of 10,584 patients had complete data on diabetes duration, with 2412 (22.8%), 4424 (41.8%), 3743 (25.9%) having diabetes duration of <10, 10-19, and ≥20 years respectively. Median (Q1, Q3) diabetes duration was 16.4 years (10.4, 22.4 years), while mean hemoglobin A1c was 8.6%, 8.7%, and 8.7% respectively by diabetes duration. The rate of the primary endpoint was lower in the sotagliflozin group (5.6 events per 100 patient-years [p-y]) compared with the placebo group (7.5 events per 100 p-y) (HR: 0.74; 95% CI: 0.63, 0.88). Event rates among diabetes duration subgroups indicated that rates in both the placebo group and relative treatment benefit increased with increasing diabetes duration, with 5.6 vs 5.8 events per 100 p-y, 6.1 vs 7.4 events per 100 p-y, and 4.6 vs 8.5 events per 100 p-y for diabetes duration <10, 10-19, and ≥20 years respectively. Spline analysis indicated increasing treatment benefit with increasing duration when modeled continuously (Figure Panel A; PSpline=0.02). Similar findings were observed for the secondary HF outcome of hospitalization for HF or urgent visit for HF, with increased treatment benefit with duration (Figure Panel B; PSpline=0.10). Total MACE was lower in the sotagliflozin group (4.8 events per 100 patient-years) than in the placebo group (6.3 events per 100 patient-years) (HR: 0.77; 95% CI: 0.65, 0.91), without significant difference in relative treatment benefit by duration (Figure Panel C; PSpline=0.30). Conclusions Sotagliflozin improved HF and MACE outcomes in patients with high CV risk, with increasing treatment benefit for HF outcomes among patients with longer diabetes duration.

Interpretable machine learning model for predicting long-term cardiovascular mortality risk in chronic kidney disease patients using SHAP explainers

Abstract Background Patients with chronic kidney disease (CKD) exhibited a pronounced burden of cardiac mortality. However, early prediction of cardiovascular mortality risk in CKD patients remains an unmet medical need. Purpose This study aimed to evaluate the performance of machine learning (ML) algorithms and identify the most influential factors in predicting long-term cardiac mortality among CKD patients. Methods Six ML models were developed, with the most effective one chosen for predicting and categorising patients into high-risk and low-risk groups based on the maximal Youden’s index. Differences in survival rates were assessed using the log-rank test on Kaplan-Meier curves. Cox regression analysis was employed to investigate the relationship between ML-predicted risk scores and mortality. Furthermore, the SHapley Additive exPlanations (SHAP) method was implemented to provide personalised explanations for model decisions. Results The auto-encoder (AE) model achieved the highest AUC of 0.94, with a sensitivity of 80.95% and specificity of 96.34%. Compared to individuals in low-risk group, those in high-risk group exhibited a significantly elevated risk of cardiovascular mortality (adjusted hazard ratio [HR]: 48.24; P <0.001). According to the SHAP model, age, C-reactive protein, blood urea nitrogen and hypertension were identified as the four most influential factors in the AE model. Conclusions Our study successfully developed an AE machine learning model for predicting 10-year cardiovascular mortality among CKD patients. The combination of ML model and SHAP aids doctors in understanding key features in the model, improving their insight into decision-making related to disease severity assessment, thus facilitating early preventive strategies in clinical practice.

The effect of physical activity on biochemical myocardial markers in patients with CKD 5D

Abstract Purpose of the study to study the effects of intradialytic physical activity on myocardial markers in patients with chronic kidney disease. Materials and methods The study included 103 patients with CKD5d aged 18 to 65 years. The average HD experience is 8.45±0.57 months. When all patients were included in the study, natriuretic peptide (NUP), myocardial fraction of creatine phosphokinase (CPK-MB), and myocardial fraction of troponin (troponin T) were determined in the blood before the hemodialysis procedure, 60-90 minutes after cessation of HD. Results The study showed that intradialytic physical activity contributes to a significant reduction in the amplitude of the increase in the concentration of markers of myocardial necrosis and NUP compared with standard HD by the 60-90th minute of HD (+7.66% versus +18.04% for NUP, 87.2% versus +172 .8% for CPK-MB and +66.09% versus +263% for troponin T, p<0.001 significance of comparison between HD regimens for all three markers). And also by the end of HD against the background of HD with FN, there was a decrease in the concentration of NUP and CPK-MB, in contrast to the dynamics with standard HD (+4.17% versus 19.84% and +28.9% versus 137.1%, respectively, p<0.001 significance of the difference between HD modes for both markers). The concentration of troponin T at the end of HD with FN progressively increased, but the relative dynamics were significantly lower than during standard HD (+719.3% versus +867.8%, p<0.001). Conclusion thus, intradialytic physical activity helps to reduce markers of myocardial damage in the blood compared to standard HD and possibly has a preventive effect on cardio myocytes.

Long-Term Impact of Infertility and Assisted Reproductive Technology on Cardio-Renal Health in Sweden

Abstract Background The use of Assisted Reproductive Technology (ART), such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), is rising in Europe. These treatments involve high doses of hormones to increase oocyte collection. While most safety studies in women have focused on cancer risks, the association with cardio-renal diseases remains under-explored. This study examines whether the use of ART is linked to coronary ischemic disease (CHD), stroke, brain hemorrhage, other cerebrovascular diseases, chronic kidney disease, and aortic aneurysm/dissection, while also exploring the association between infertility and these conditions. Methods A nationwide cohort study was conducted using Swedish national registries, following all nulliparous women who gave birth between 1982 and 2002 until the end of 2017. Descriptive statistics and inverse probability weighted Kaplan-Meier curves to adjust for body mass index, maternal age, country of origin, smoking, and year of delivery, were used to compare 1) women who conceived with or without ART, 2) women who used IVF or ICSI respectively to women with known infertility that conceived without ART, and 3) women with and without known infertility. Results Compared to all other women, women undergoing ART were at elevated risk for CHD, stroke, and other cerebrovascular diseases, but after adjustment for underlying risk factors, including infertility, no substantial differences were seen. As a group, women with known infertility were at elevated risk of CHD and stroke, also after adjustment for known background factors. Conclusions Data suggest that the use of ART does not increase the long-term risk of cardio-renal diseases. Nonetheless, infertility itself is associated with a higher risk of CHD and stroke. Key messages • Infertility, more so than the use of ART, is linked to elevated risks of CHD and stroke. • Preventive measures for these conditions should be considered for women with infertility.

Unraveling the association between chronic inflammatory demyelinating polyradiculoneuropathy and peritoneal Dialysis

BackgroundChronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare disease seen in the general population and has been reported as showing an increased incidence in the peritoneal dialysis (PD) population, as documented in case reports.MethodsWe conducted a case-control study using data from the Taichung Veterans General Hospital electric medical record database from the years 2010 to 2023. We defined cases as CIDP with End-stage kidney disease (ESKD) and controls as without CIDP. A logistic regression analysis was used to investigate the association between CIDP and dialysis modality, age, gender, dialysis duration, plasma potassium > 5.5 mEq/L and < 2.5 mEq/L, and intact parathyroid hormone (i-PTH) > 613 pg/mL.ResultsOur findings suggest that PD may be a risk factor in the ESKD population (Odds ratio: 5.125, C.I.: 1.078 ~ 24.372, p = 0.040) according to logistic regression analysis. Dialysis duration, gender, diabetes mellitus, HbA1c > 7%, hypokalemia, hyperkalemia, and hyperparathyroidism did not show an association with CIDP.ConclusionThere seems to be an association between PD and CIDP in this case-control study. Possible mechanisms may involve systemic inflammation induced by peritoneal dialysate exchange or the content of the dialysate. Further studies are still needed.

Age-based comparison of patients with heart failure treated with sacubitril-valsartan in France: a real-world evaluation

Abstract Background Sacubitril-Valsartan (S/V) was approved in Europe in 2015, for treatment of adults with symptomatic chronic heart failure with reduced left ventricular ejection fraction (HFrEF). In France, S/V had benefited from an early access program (2015-2018) and became available in community pharmacy since October 2018. Purpose Our study aimed to describe characteristics of patients who received S/V in France and to assess real-life mortality in this population regarding age. Methods This non-interventional retrospective study utilized existing claims data from the French National Healthcare Data System (SNDS) allowing long-term follow-up of patients who benefited from at least one reimbursement of S/V. Patient data between April 2012 and December 2020 were extracted from the database. Prespecified subgroup analyses were conducted for subjects aged &amp;lt;75 and ≥75 y to describe characteristics of patients at first reimbursement of S/V. Cardiovascular mortality and all-cause mortality were estimated using Kaplan-Meier method. Results Between 2015 and 2020, 104,910 patients initiated S/V and were followed for an average of 20 months; 42.6% (44,743 patients) were ≥75 y. Mean (SD) age difference between the 2 subgroups was 20.3 years [62.2 (9.6) vs 82.5 (5.2) in patients &amp;lt;75 and ≥75 y respectively]. Patients ≥75 y had a higher prevalence of atrial fibrillation (50.6% vs 31.2%) and chronic renal failure (20.9% vs 10.1%) and were less co-treated with mineralocorticoid-receptor antagonists (21.8% vs 40.5%) and ß-Blockers (64.0% vs 73.8%) compared to those &amp;lt;75 y. Three months after first dispensation, 48.3%, 35.3%, and 16.4% of patients aged ≥75 y received S/V dosages of 24/26mg, 49/51mg, and 97/103mg respectively, compared to 31.4%, 38.2%, and 30.4% for patients aged &amp;lt;75 y. The mean (SD) exposure period was 14.7 (13.6) months in patients ≥75 y vs 19.0 (15.5) months in &amp;lt;75 y patients. As expected, given the age difference, patients ≥75 y had a higher probability of all-cause mortality at 12-month 16.5% vs 6.2% in patients &amp;lt;75 y. Furthermore, 12-month cardiovascular mortality – evaluated during the early access program period (2015-2017) – in patients ≥75 y was 11.0% vs 4.8% in patients &amp;lt;75 y. Figures 1 and 2 show survival curves for cardiovascular mortality and all-cause mortality of these 2 subgroups. Of interest, cardiovascular mortality rate at 12 months was 7% in this study, compared to 6% in PARADIGM-HF, and all-cause mortality at 12-month was higher (10,6% vs 7%), likely due to the profile of the patients, who were older and have more comorbidities in real life. Finally, very few patients were hospitalized for reasons related to angioedema, 16/44,743 in ≥75 y patients and 26/60,167 in those &amp;lt;75 y. Conclusion This is the first French real-world study providing exhaustive nationwide data on S/V mortality over a period of almost 6 years in a very large population of elderly with a mean age of 70.9 y vs 63.8 y in PARADIGM-HF.Figure 1Figure 2

Incidence and factors associated with mitral valve reoperation in patients undergoing intervention for mitral regurgitation: a nationwide cohort study

Abstract Background When intervention is needed for the treatment of mitral regurgitation, the risk of reoperation is of concern for both patients and physicians. As such, contemporary and nationwide data on the incidence and factors associated with mitral reoperation can provide crucial information to support patient education and clinical follow-up after intervention. Purpose To examine the incidence of mitral reoperation in patients operated for mitral regurgitation. Second, to assess whether reoperation rates differed according to time since surgery and identify potential factors associated with reoperation. Methods Using Danish nationwide registries, patients undergoing first-time surgery for mitral regurgitation 1996–2021 were identified. Exclusion included first-time surgery due to endocarditis. According to index surgery, the population was categorized into 1) mitral repair; 2) mechanical prosthesis; 3) bioprosthesis. Patients were followed from date of discharge. Cumulative incidence of reoperation was examined using competing risk analysis during a maximum of 20-years follow-up. Crude incidence rates of reoperation were reported from 0-6 months and for overall study period. Multivariate Cox analysis was used to examine factors associated with reoperation. Results We identified 7,063 patients: 4,680 (66.3%) with repair (72% male, median age 66), 1,273 (18.0%) with mechanical prosthesis (52% male, median age 59), and 1,110 (15.7%) with bioprosthesis (57% male, median age 74). Median follow-up was 7.2 years, 10.7 years, and 4.5 years, respectively. At end of follow-up, cumulative incidences were 7.7% for repair, 6.8% for mechanical prostheses, and 7.5% for bioprostheses. Of these, reoperation was preceded by endocarditis in 8.0%, 21.5%, and 30.4% of the respective patient groups. The cumulative incidence function demonstrates that the highest proportion of reoperations occurred within first six months, Figure 1. From 0-6 months following surgery, incidence rates per 100 person-years were 9.1 for repair, 11.7 for mechanical prostheses, and 18.4 for bioprostheses, while this was 8.6, 9.4, and 17.0, respectively for the overall study period. Factors associated with increased rate of reoperation were heart failure (HR=1.80, 95% CI 1.40-2.32), chronic renal failure (HR=1.48, 95% CI 1.11-1.98) and chronic obstructive pulmonary disorder (COPD) (HR=1.34, 95% CI 1.01-1.77), Figure 2. Compared to mitral repair, mechanical prostheses were associated with lower rate of reoperation (HR=0.57, 95% CI 0.42-0.78), while there was no statistically significant difference between repair and bioprostheses (HR=1.10, 95% CI 0.81-1.50). Conclusion In patients operated for mitral regurgitation, cumulative incidences of reoperation with a maximum of 20-year follow-up were 7.7% for repair, 6.8% for mechanical prostheses, and 7.5% for bioprostheses. Comorbidities such as heart failure, renal failure and COPD were associated with increased risk of reoperation.Figure 1Figure 2

Hospital and one-year outcomes following a hypertensive urgency or emergency: a major challenge

Abstract Introduction Hypertension is an important issue, and recommendations are constantly evolving based on the latest research findings and directions. Hypertensive emergencies are defined as a severe elevation of blood pressure associated with organ damage. End organ damage was defined as the presence of one of the following findings: encephalopathy, ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, acute heart failure, acute coronary syndrome, or aortic dissection. Furthermore, malignant hypertension is a HE characterized by small artery fibrinoid necrosis in the kidney, retina and brain. All these definitions are confusing, but what about their evolution? Objective:The present study aims to analyze the mortality in the short and long term (12months), the survival of the hypertensive patients, the frequency of malignant hypertension and hypertensive retinopathy. Methods For this purpose, we conducted a prospective study including all patients who followed or were diagnosed with hypertension and admitted to the emergency department for hypertensive urgency/emergency, from January to March 2023; after that, we studied the evolution of these patients for one year until January 2024. Demographic data, disease history, blood pressure, clinical presentation on admission, target organ involvement, ophthalmological examination and evolution during hospitalization were studied. Statistical analysis was performed using SPSS software. Preeclampsia and chronic renal failure were excluded.Result: Our work brought together 300 patients, mainly female, with an average age of 63.4. One hundred fifteen were admitted for HE and 185 for HU. The most common presenting symptoms at admission were headache, focal neurologic deficit and dyspnea. Malignant hypertension was identified in 9 patients based on optical coherence tomography angiography by identifying subclinical microvascular damage, and investigation is still in progress searching for hypertensive retinopathy grade III-IV Keith-Wagner in the second group. Patients were mainly hospitalized for hypertensive emergencies. Regarding their therapeutic management, except for the acute lowering of blood pressure in stroke, there was no consensus initially; ideally was to determine which organs are affected to assess the need for specific intervention other than lowering blood pressure. Overall, 49 had died from HE n=44/115(vs n=5/185 for HU). Of these, 33 have died at the Hospital (mortality was higher for HE and attributable to neurovascular emergencies rather than cardiovascular emergencies) and ten at 12 months. Conclusion Properly managing patients who come to the Emergency Department for BP elevation faces many difficulties. Can we still talk about hypertensive emergencies/urgency, discuss retinal lesions, and the importance of hypertension monitoring? However, all those definitions can be potentially life-threatening; these results justify better follow-up and treatment for these patients.

Importance and limits of cardiovascular risk factors on the prediction of SCD using machine learning approach

Abstract Background SCD is mainly due to lethal ventricular arrhythmias and occurs often among patients with ischemic heart disease. SCD and ischemic heart disease share a similar pattern of cardiovascular risk factors (CVRF). Commonly developed risk scores have been focused on cardiac-related risk factors. We aimed to investigate whether non-CVRF variables could enhance predictive performance beyond standard CVRF of SCD. Method We compared 2 different strategies for variable inclusion. First, we built a prediction model containing EHR data restricted to cardiovascular diseases and risk factors (CVD MR model) that occurred up to 5 years before SCD. We selected all available main cardiovascular variables as surrogate markers for coronary artery disease, stroke, diabetes, hypertension, smoking status, obesity, lipid disorders and chronic renal failure. On the other hand, our global approach (ALL MR model) includes all medical records codes, without any prior selection. To estimate the risk of SCD over three months, we trained a machine learning model on EHR data representing 8,566,229 drug prescriptions and 801,352 hospital diagnoses up to five years prior to SCD. The data were obtained from a cohort of 12,338 SCD in France and 12,338 controls from 2011 to 2015. We then validated the results on two external cohorts: one temporal in the same area between 2016 and 2020 with 11,620 SCD and 11,620 controls and one geographical from the USA with 892 SCD and 892 controls from 2013 to 2021. Results The CVD MR + ML model (CatBoost algorithm) yielded moderate performances with an AUC of 0.68 (95%CI 0.65-0.68), a sensitivity of 45%.(95%CI 42-47) and a specificity of 82% (95%CI 80-84). We found that the EHR model with all medical records (All MR + ML model) offered better performances. In the derivation cohort, this model achieved an AUC of 0.80 (95% CI: 0.78–0.82) with a sensitivity of 67% (95% CI 64-69), a specificity of 80% (95% CI 78-82) (Figure 1). The logistic regression (All MR + LR) applied on all medical records performed better than the CatBoost algorithm when restricted to CVD medical records (Figure 1). Conclusion The inclusion of all potential variables beyond the usual CVRF significantly improves the performances of SCD prediction models, independently of the methods (AI and logistic regression). Figure 1 : Receiver operating characteristic curves of the different models (ALL MR + ML, ALL MR + LR, CVD MR + ML and CVD MR + LR) in the derivation cohort and two validation cohorts (temporal and geographical)Figure 1.ROC curves

The role of comorbidities for hospital outcome of patients with severe acute pulmonary embolism treated with thrombolytic therapy

Abstract Background The association between the outcome of severe acute pulmonary embolism treated with thrombolytic therapy and the presence of common comorbidities is fairly known. Methodology In this study we investigated the influence of common comorbidities (arterial hypertension, atrial fibrillation, heart failure, coronary disease, diabetes mellitus, active malignant disease, chronic obstructive lung disease, chronic renal failure, anemia and previous stroke) to hospital mortality and the composite of major and clinically relevant non-major bleeding at 7 days from hospital admission in patients with severe acute PE treated with thrombolytic therapy enrolled in the Regional PE Registry from the 4 west-Balkan countries. Univariate and multivariable regression analysis (adjusted to age and the presence of arterial hypotension – systolic blood pressure below 90 mmHg) was used to establish association between comorbidities and hospital outcome of acute PE treated with thrombolysis. Results 2068 patients enrolled with computed tomography pulmonary angiography proven acute, symptomatic PE, and of them 645 patients had features of intermediate-high PE (right ventricle dysfunction with positive biomarkers without severe hypotension) and 283 patients had high-risk PE with arterial hypotension. Of them, 394 (42.5%) were treated with thrombolytic therapy (245 with intermediate-high and 149 with high-risk PE). Overall hospital mortality was 17.0% and the composite of major and clinically relevant non-major bleeding at 7 days was 17.5% (11.2% was major bleeding). Among all tested comorbidities, only 3-staged renal failure (OR 3.56, 95%CI 1.78-7.15, p&amp;lt;0.001 for creatinine clearance 30-59 ml/min compare to clearance ≥ 60 ml/min; and OR 6.01, 95%CI 2.35-15.37, p&amp;lt;0.001 for creatinine clearance &amp;lt;30 ml/min versus ≥ 60 ml/min), and the presence of either paroxysmal or chronic atrial fibrillation had significant higher risk for hospital mortality adjusted to age and the presence of arterial systolic hypotension (OR 2.11, 95% 1.03-4.29, p=0.04). Between all presented comorbidities only the presence of diabetes mellitus type 2 was independently associated with the higher risk for bleeding on thrombolytic therapy OR adjusted to age 2.03, 95%CI 1.126-3.659, p=0.019. Conclusion Creatinine clearance and atrial fibrillation were the independent predictors of hospital death and diabetes mellitus type 2 for bleeding in patients with severe acute PE who were treated with thrombolysis.

A retrospective study on real world, 2-stent left main bifurcation PCI using DK crush technique with IVUS guidance - a single center experience

Abstract Objectives The aim of this study is to investigate clinical outcome of the IVUS guided 2-stent bifurcation strategy using DK crush technique performed in a complex Left Main (LM) bifurcation lesions defined according to DEFINITION study in our local setting. We seek to assess the composite endpoint of target vessel failure (TVF) at 9-12 months. Methods All patients underwent IVUS guided 2-stent Bifurcation PCI with DK crush technique for complex LM bifurcation lesions defined by the DEFINITION criteria performed in a heart institute from 1.1.2019 to 31.7.2023 were included..Patient baseline characteristics, post-procedural and 12-months follow-up outcomes including cardiac death,myocardial infarction (MI),rate of target vessel failure (TVF),rate of stent thrombosis (ST) and major adverse coronary event (MACE) were analysed.Exclusion criteria are patients age &amp;lt;18 years and previous stenting in the target vessel Results A total of 50 patients were included in this analysis. Mean age was 64.3±9.1 years with predominant males (n= 38, 76%).Majority were hypertensive (n=37, 74%) and diabetes mellitus accounted for 32 (64%) cases.Patients with pre-existing coronary artery disease were 39 (78%) cases. 40% presented with history of recent myocardial infarction (MI), 12% had new onset angina and 6% had heart failure. Pre-existing chronic renal failure (18%) and history of CVA (2%). Among chronic renal failure cases, 50% had eGFR &amp;lt;50 during index procedure.Additionally, previous PCI was performed in 22 cases (44%) and 2 previous CABG cases included (4%).Majority of the cases were performed as staged elective procedure ( n=45, 90%) and others were indicated for ACS ( n=5, 10%). Radial approach was predominantly preferred with 25 cases (50%), where additional 5 cases (10%) were converted to femoral approach due to severe radial spasm. Among these 50 cases, 1 case required additional PCI to CTO LAD and mid LCX, while 7 cases (14%) had calcified lesions requiring scoring / cutting balloons and atherectomy device utilization for adequate lesion preparation prior to bifurcation stenting.All 50 patients received combination of both aspirin and a P2Y12 inhibitors for 12 months. Follow up done at at 30-day, 60-days and 1 year after the index procedure.Clinical follow-up were available in 46 (92%) patients only.4 cases were lost to follow up due to logistic reasons. At 1 year follow-up, cardiac death occurred in 5 (10.9%) patients, out of which 3 (6.5%) cases were cardiac related and 2 (4.4%) are non-cardiac. Major adverse cardiac events (MACE) and target vessel failure (TVF) occurred in total 4 (8.7%) cases, where 3 (6.5%) cases resulted in cardiac death and 1 (2.2%) case had MI and clinically driven target lesion revascularization. Conclusion Our experience demonstrates that IVUS guided, upfront 2-stent Bifurcation PCI using DK crush technique for complex bifurcation lesions is effective and safe with a low MACE and TLR rate at 1 year follow-up.

GLP1-RA versus DPP4 inhibitors on cardiovascular outcomes: A three-year real-world analysis

Abstract Background Cardiovascular outcome trials of GLP1-RAs have massively impacted the clinical practice in the management of patients with type 2 diabetes. The cardiovascular protective properties of GLP1-RA compared to DPP4 have been demonstrated in an observational setting before, however recent methodological developments have enabled clinically relevant effect estimation. Aim This study aimed to evaluate the real-world cardiovascular outcomes of GLP1-RA versus DPP4 inhibitors in patients with type 2 diabetes and high cardiovascular risk. Methods In this study, we utilized the Danish nationwide registers to identify new users of GLP1-RA or DPP4 therapies from 2012 to 2022. Participants were required to be either at least 50 years of age and have one or more of the following conditions: hypertension, chronic obstructive pulmonary disease, cardiovascular disease, or chronic renal disease or be at least 60 years of age and have hypertension. Additionally, their glycated hemoglobin (HbA1c) levels needed to be 53 mmol/mol or higher within the year preceding their first prescription date for these therapies. The index date was defined as the initial prescription date, and comorbidities and medicine use were evaluated up to 10 years prior to this date. Individuals who had filled prescriptions for SGLT2 inhibitors within six months prior to their index date were excluded from the study. The outcome of interest was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (MACE). Patients were followed for up to three years until MACE, all-cause mortality, emigration, or until the end of follow-up on December 31, 2022. To assess the three-year risk of MACE, the Aalen Johansson estimator was used. A casual inference framework was employed estimating the three-year average treatment effect using g-formula based on Cox regression with competing risk. Results A total of 26,190 individuals were included, with 19,494 initiating DPP4 inhibitor therapy and 6,696 initiating GLP1-RA therapy. The three-year risk of MACE was 8.56% (95% confidence interval [CI]: 8.11 to 9.00) for the DPP4 initiator group, compared to 4.76% (95% CI: 4.08 to 5.43) for the GLP1-RA initiator group. Emulating what would have happened had all included individuals initiated GLP1-RA treatment versus had all initiated treatment with DPP4, accounting for age, sex, income, education, degree of urbanization, diabetes duration, baseline hba1c level, co-medicine, and co-morbidities, we estimated an three-year average treatment effect of -2.05% (95% CI:-2.92;-1.18) , p-value&amp;lt;0.001) for GLP1-RA initiation versus DPP4 initiation for MACE. Conclusion Our findings suggest that GLP1-RA use is associated with a significantly lower risk of MACE compared to DPP4 inhibitors in a real-world population of patients with type 2 diabetes and high cardiovascular risk. This supports the cardiovascular protective role of GLP1-RA in clinical practice.

Sex-specific prognostic implications of new-onset atrial fibrillation in patients treated with dual chamber pacemakers

Abstract Background Right ventricular pacing induces ventricular dyssynchrony, which over time may result in left ventricular dysfunction, increased left ventricular filling pressures, and ensuing left atrial dilatation, with increased risk of atrial arrhythmias. Atrial fibrillation (AF) prior to device implant is associated with worse prognosis, but the prognostic effects of new-onset AF during pacemaker treatment are less well described. Purpose To describe risk factors, incidence, and prognostic effects of new-onset AF after treatment is initiated with a dual chamber pacemaker. To evaluate mortality and risk of heart failure diagnosis or hospitalisation for heart failure in patients who develop AF, compared to those who do not develop AF. Methods All patients without pre-existing heart failure or atrial fibrillation, who received a dual chamber pacemaker at a large-volume tertiary care center during the period 2005–2020 were included. Data was crossmatched between the national pacemaker registry, the population registry and national disease registries. The primary outcome was 10-year mortality, and the secondary outcome was new-onset heart failure. Results 37127 patients were included in the study, of which 14760 (30%) were female. Median age was 76.4 years [interquartile range, IQR, 68.0–83.1] and the most common indication for pacemaker implant was AV block (57.7%), see Table 1. Overall, 10-year survival was higher for female patients, compared to male patients, p&amp;lt;0.0001 (see Kaplan-Meier curve in Figure 1A). Patients who developed new-onset AF had more comorbidities, were slightly older and a higher percentage were men. During follow-up 3661 (9.9%) developed atrial fibrillation within two years (9.1% of female and 10.3% of male patients, p&amp;lt;0.001), at a median of 291 [88–461] days after implant. In multivariable Cox regression analysis with new-onset AF as time dependent covariable and adjusted for clinically relevant covariables, AF was an independent predictor of higher all-cause mortality (HR 1.43 [1.37–1.49], p&amp;lt;0.0001). Risk factors for new-onset AF included increasing age, male sex, hypertension, malignancy, diabetes, chronic obstructive lung disease, chronic renal disease, and sick sinus syndrome indication (all p&amp;lt;0.01). In separate analyses for men and women, the risk factors and magnitude of odds ratios were the same. Conclusion In patients treated with dual chamber pacemakers due to bradycardia or AV block, development of new-onset AF within two years was associated with a higher 10-year mortality. The risk of developing AF was higher for men, but the negative prognostic effect was more pronounced for women.Figure 1A.-B. K-M survival curves

An integrated approach to enhance vaccine uptake in chronic patients – the VacciNetwork project

Abstract Issue/problem Individuals with chronic illnesses are at a higher risk of infections and their complications. Vaccinations are crucial in reducing this risk and their integration in chronic care pathways can enhance vaccine uptake, but it requires a collaborative approach and increased awareness in care personnel, caregivers and patients. Description of the problem The Local Health Authority of Rome 2 (ASL Roma 2, with approx. 1.3 million residents) initiated an active promotion plan for recommended vaccinations in chronic patients in January 2023, and a Clinical Vaccinology Workbook was produced to guide healthcare workers in promoting vaccinations across various care settings. The plan aims to establish collaborative agreements with hospitals and territorial structures that manage these patients, integrating vaccination plans with clinical and healthcare pathways for a more holistic approach to chronic disease management, a model that could benefit similar populations globally. Results Data was extracted from administrative databases regarding vaccinations performed in 2022 and 2023 on fragile subjects, i.e., those with a marked ‘risk condition’, aged ≥18 years. The results showed that vaccine uptake was more than doubled (6675 vs. 2041; +227%). Notably, vaccinations rose among those with oncological-hematological diseases (+212%), asplenia (+185%), chronic kidney failure or on dialysis (+190%) and those with an HIV infection (+160%). Increases were also significant in other immunocompromised conditions (+194%). Lessons The practice underlines the importance of targeted vaccination programs within chronic care management. Collaborative healthcare frameworks can significantly improve vaccination rates, reducing the burden of infectious diseases in high-risk populations. These results underscore the potential applicability of such a model in other regions and countries, highlighting the universal relevance of integrated healthcare solutions. Key messages • Collaborative, integrated frameworks between clinical and vaccination services can represent a model for increasing vaccine uptake in chronic disease patients. • Strategic partnerships and education in healthcare settings can improve vaccination rates and contribute to more holistic chronic disease management.

Analysis of Nutritional Status, Body Composition, and Creatinine Levels in Hemodialysis Patients at Ibnu Sina Yw-Umi Hospital Makassar

Hemodialysis is an essential therapy for managing chronic kidney failure, helping to maintain homeostasis by removing excess fluids, solutes, and toxins from the body. The global increase in the prevalence of chronic kidney disease (CKD) has led to a rising demand for hemodialysis. This study aims to analyze the relationship between nutritional status, body composition, and creatinine levels in hemodialysis patients at Ibnu Sina YW-UMI Makassar Hospital. Using an observational cross-sectional design, the study involved 16 patients whose body mass index (BMI), muscle mass, fat mass, total body fluid, and visceral fat were measured before and after dialysis. The results revealed significant changes in nutritional status, body composition, and creatinine levels pre- and post-hemodialysis, analyzed through paired T-tests at a 0.05 confidence level. Most patients were male, aged over 45, with normal nutritional status but abnormal creatinine levels. Body composition analysis showed significant differences in muscle mass, fat mass, total body fluid, and visceral fat before and after hemodialysis, with patients with higher muscle mass tending to have elevated creatinine levels. This study emphasizes the importance of monitoring body composition and creatinine levels to support the health of hemodialysis patients and highlights the need for personalized nutritional and therapeutic interventions in CKD care. Further research is needed to explore the long-term impacts of hemodialysis on nutritional status and kidney function.