Log-rank Test Research Articles

Sex differences in aortic prognosis in Marfan patients, a retrospective longitudinal study from the REPAG registry

Abstract Introduction Previous studies(1-4) have suggested a more favourable aortic outcome among women with Marfan syndrome (MFS), although the precise underlying mechanism remains not completely understood. In this retrospective longitudinal study, we aim to evaluate sex differences in aortic events in a large cohort of Marfan patients seen in 11 tertiary centres in Spain. Methods Patients with diagnosis of Marfan syndrome (MFS) were included. Data on aortic events (AE) including elective aortic surgeries, acute aortic syndrome or death were incorporated. Survival free of the combined endpoint of death or first aortic event (elective aortic surgery or acute aortic syndrome) was compared between male and female by the Kaplan-Meier curves, log-rank test and subsequent Cox regression analysis. Results A total of 442 patients with MFS where included, 48.2% female and 56.2% index cases. Although systemic score and proband proportion was not different between both sexes, the diagnosis was earlier in males (p=0.01) (Table). Furthermore, among adult patients, males exhibited greater height, weight, and body surface area (BSA). Absolute aortic root diameter at baseline was greater in males, but not BSA-indexed diameters or z-scores. Combined endpoint of death or aortic event was observed in 192 patients (120 male, 72 female, p=<0.00001). Female sex had better survival free of the combined endpoint in a multivariable Cox analysis (HR 0.41 95% CI=0.30–0.55) with a mean survival free of the combined endpoint of 41.3yrs in male and 61.4 years in females (p<0.0001) (Figure).Although a higher proportion of elective aortic interventions as first event was observed in males (66.7% vs 52.8%), the proportion of type A dissections was similar between both sexes (26.7 vs 26.4%) with increased frequency of type B dissections in females as first aortic event (4.2 vs 15.3%) (p=0.026) Conclusions Male patients with MFS present higher aortic root diameters but similar BSA-indexed and zscores than females. Survival free of first aortic event or death is reduced in male with MFS, with greater frequency of elective aortic intervention. Although this last is driven by absolute aortic diameter, no increase on type A dissection was observed in women. These findings might suggest a potentially less aggressive manifestation of proximal aortic disease in women with MFS.Table:Comparison male and female Marfan

Efficacy of meropenem against ceftazidime-avibactam-resistant Klebsiella pneumoniae producing KPC-31, KPC-33, KPC-90, KPC-106 and KPC-114.

Klebsiella pneumoniae producing KPC variants conferring resistance to ceftazidime-avibactam often remain susceptible to meropenem, suggesting a potential therapeutic use of this antibiotic. In this study, the efficacy of clinically relevant concentrations of meropenem was evaluated against high-risk clones of ceftazidime-avibactam-resistant K. pneumoniae strains producing KPC variants, in a tandem in vitro time-kill/in vivo Galleria mellonella survival model. In vitro/in vivo efficacy of meropenem against ceftazidime-avibactam-resistant K. pneumoniae of CG16, CG25 and CG258, producing KPC-31, KPC-33, KPC-90, KPC-106 and KPC-114 variants, was evaluated using EUCAST dosing recommendation adjusted to the G. mellonella model. For in vivo assays, untreated, meropenem (40 mg/kg × 1)-treated and ceftazidime-avibactam (40 mg/kg ceftazidime-10 mg/kg avibactam × 1)-treated groups were established, with 60 larvae per group. Kaplan-Meier curves, log-rank tests, univariate Cox regression and hazard ratios (HR) were used to assess treatment effects (P < 0.05). For all KPC-variant producers, time-kill assays showed >3 log-kills reduction (-6.91 ± 1.28 SD) after 6 h interaction when exposed to 8-32 mg/L meropenem MIC values (i.e. ≥ × 4 MIC). In the assessment of in vivo efficacy of meropenem, at the 4-day follow-up, mortality rates were 96.7% (untreated), 83.3% (ceftazidime-avibactam-treated) and 13.3% (meropenem-treated) (P < 0.05). Univariate Cox regression analysis showed significantly lower risk in the meropenem group compared to untreated group [HR 0.02 (95% CI: 0.01-0.05)]. These pre-clinical results might support use of meropenem as a potential alternative for treatment of infections due to KPC-variant producers displaying in vitro susceptibility to meropenem.

Identification of ischemia with no obstructive coronary arteries using 13N-ammonia positron emission tomography-derived myocardial strain ratio

Abstract Background Ischemia with no obstructive coronary arteries (INOCA) is a chronic health problem with poor prognosis and remains challenging to diagnose. 13N-ammonia positron emission tomography (NH3-PET) is the most reliable method for detecting INOCA. We recently developed a unique myocardial strain analysis for NH3-PET to detect ischemia-related motion abnormalities. Purpose We examined the usefulness of NH3-PET strain analysis to identify patients with INOCA. Methods Overall, 98 patients with non-obstructive coronary arteries who underwent adenosine-stress NH3-PET were enrolled. INOCA was defined based on the ESC guidelines. Using an original feature-tracking algorithm dedicated to NH3-PET, the circumferential strain was calculated. Myocardial strain ratio (MSR) was defined as the ratio of strains at stress and rest. In addition, global myocardial flow reserve (MFR) was obtained. Results Finally, forty-seven patients were diagnosed with INOCA, and 51 without INOCA. Global MFR were significantly lower in patients with INOCA than in those without INOCA (1.82 ± 0.52 vs. 2.65 ± 0.65, p&amp;lt;0.0001). MSR were significantly lower in patients with INOCA than in those without INOCA (0.94 ± 0.11 vs. 1.04 ± 0.12, p&amp;lt;0.001). Receiver-operating characteristic analysis showed that using the optimal cutoff of the MSR, INOCA could be diagnosed with area under the curve of 0.71. At a median follow-up of 957 days, Kaplan–Meier analysis revealed that the survival rate worsened in patients with INOCA and low MSR (log-rank test, p&amp;lt;0.001). Conclusions MSR derived from feature-tracking of NH3-PET is reduced in patients with INOCA. It might suggest a predictive value to identify microvascular dysfunction or related motion abnormalities in patients with INOCA.

Effect of pre-procedural blood pressure on one-year cardiovascular events after percutaneous coronary intervention in patients with acute myocardial infarction

Abstract Background Although high systolic blood pressure (SBP) and low diastolic blood pressure (DBP) are associated with adverse cardiovascular outcomes in coronary artery disease, their impact on patients with acute myocardial infarction (AMI) remains unclear. Methods This multicenter prospective study included 874 AMI patients undergoing percutaneous coronary intervention (PCI) with pre-procedural blood pressure recorded. Patients with cardiogenic shock and missing blood pressure data were excluded. The patients were categorized based on SBP (high ≥120 mmHg, low &amp;lt;120 mmHg) and DBP (high ≥70, low &amp;lt;70 mmHg) into four groups: high SBP and high DBP (HSHD), high SBP and low DBP (HSLD), low SBP and high DBP (LSHD), and low SBP and low DBP (LSLD) group. The primary endpoint was a composite of all-cause mortality, myocardial infarction, stroke, and major bleeding. Results The average age of the patients was 68.9 years, with a mean pulse pressure of 58 ± 19 mmHg. The Kaplan-Meier curves showed significant differences in the primary endpoints among the four groups (Log-rank test, p &amp;lt;0.001). At 12 months, the primary endpoint occurrence was highest in the HSLD group (13.3%) and lowest in the LSHD group (2.4%). Additionally, multivariate Cox regression analysis revealed that the HSLD group, compared to the HSHD group, was independently correlated with an increased risk of cardiovascular events (hazard ratio 2.43, 95% confidence interval 1.16-5.11; p = 0.019). Conclusion Pre-procedural HSLD serves as an independent predictor and is associated with one-year adverse cardiovascular outcomes in AMI patients.Patient diagramKaplan-Meier one-year outcome

Acute kidney injury (AKI) in cardiac intensive care unit patients: a real challenge to overcome

Abstract Introduction Acute kidney injury (AKI) is a major cause of morbidity and mortality in intensive care units (ICUs), but in cardiac intensive care unit (CICU), despite the evidence of a causal link between cardiac illness and AKI, few data are available (1). Purpose We analyzed the predictive factors of AKI in CICU, as well as the impact of AKI on the long-term prognosis of patients admitted to CICU. Methods We reviewed the medical data of patients admitted to our CICU over a 2-year period. We excluded patients with chronic kidney disease prior to admission. We defined AKI according to the KDIGO (Kidney Disease Improving Global Outcomes) classification based on serum creatinine and urine output. To determine the predictive factors, we performed a logistic regression analysis, and to determine the prognostic impact of AKI, we performed a Cox proportional hazards regression, taking all-cause mortality at 30 months as the main study outcome. p-values less than 0.05 were considered statistically significant Results We included in our study 1581 patients hospitalized in our unit over a 2-year period, 70.4% of whom were men and 29.6% women. Among these patients, 291 presented with AKI (18.4%), 35.5% classified as KDIGO 1, 42% as KDIGO 2, and 22.5% as KDIGO 3. For the admission diagnosis of patients with AKI, STEMI came first at 56.3%, followed by NSTEMI at 17.3%, acute heart failure at 9.3%, pulmonary embolism at 2.1%, severe arrhythmias at 7.9%, and valvular disease at 1.1%. Among patients in the KDIGO 3 group, 54% benefited from a renal replacement strategy. La morta For factors predictive of AKI, and after adjustment for variables significant in univariate analysis, we objectified the following factors: arterial hypertension (OR=1.92, p&amp;lt;0.001), Diabetes (OR=1.50, p=0.007), KILLIP&amp;gt;2 at admission (OR=1.75, p=0.003), Ejection fraction&amp;lt;40% at admission (OR=1. 93, p&amp;lt;0.001), right ventricular systolic dysfunction (OR=2.95, p&amp;lt;0.001), anemia with Hb&amp;lt;10g/dl (OR=2.95, p&amp;lt;0.001), cardiogenic shock (OR=3.02, p&amp;lt;0.001), high-grade conduction disorder (OR=2.7, p=0.003) and bleeding events (OR=5.93, p&amp;lt;0.001) (Table 1-figure 1). For all-cause mortality at 30 months, 204 events were observed, 104 in the AKI group (35%), and 100 in the non-AKI group (7.75%) (p&amp;lt;0.001), and AKI was independently associated with the outcome studied for all KDIGO classes with for stage 1 (HR = 1.33; p=0.03), stage 2 (HR = 2.28; p&amp;lt;0. 001), and stage 3 (HR = 5.71; p&amp;lt;0.001), adding to this diabetes (HR = 1.96; p&amp;lt;0.001), cardiogenic shock (HR = 2.27; p&amp;lt;0.001) and finally EF&amp;lt;35% at discharge (HR = 1.53; p=0.001) (Table 2-figure 1). The Kaplein-Meier survival analysis showed a significant difference between the rates of mortality between the different KDIGO at 30-months, with a log-rank test p&amp;lt;0.001 (Figure 2). Conclusion We can conclude that AKI remains a real challenge for admitted patients, since long-term mortality in this group is very high.Figure 1.Figure 2.

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&amp;lt;0.001), higher percentage of male sex (12.9/29.9/43.4%; p&amp;lt;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&amp;lt;0.001). The presence of ≥ 3 comorbidities was more frequent in iPAH than PAH-SSc (p&amp;lt;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&amp;lt;0.001). A statistically significant lower survival (p&amp;lt;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.

SGLT2 inhibitors in patients with amyloidosis and heart failure: a worldwide retrospective cohort study

Abstract Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the combined risk of death and hospitalization in patients with heart failure with reduced or preserved left ventricular ejection fraction. However, evidence of their impact on patients with heart failure due to amyloidosis is lacking. Purpose To evaluate the effects of SGLT2 inhibitors on mortality and hospitalization in patients with amyloidosis and heart failure. Methods In this retrospective cohort study, we used real-world data from 108 healthcare organizations worldwide from the global health research collaborative network TriNetX. We identified 24,619 patients with amyloidosis and heart failure without exposure to SGLT2 inhibitors (control group) and 2,988 patients with amyloidosis and heart failure under treatment with SGLT2 inhibitors (SGLTi group). We performed propensity score matching for demographic and clinical characteristics and Kaplan–Meier plots, log-rank tests, and Cox proportional hazard models were calculated. The outcomes were 12-month all-cause death and 12-month hospitalization. Results After propensity score matching, 2,237 patients were analyzed in each group. During the 12-month follow-up, 198 (8.8%) patients died in the SGLT2i group, and 431 (19.2%) patients died in the control group (hazard ratio 0.51, 95% CI 0.43-0.61). In the SGLT2i group, 974 (44.5%) patients were hospitalized, and in the control group, 1508 (53.5%) patients were hospitalized (hazard ratio 0,79, 95% CI 0.72-0.86). The Kaplan-Meier curves are shown in Figure 1. Conclusions In conclusion, in this retrospective cohort study with a large number of patients with amyloidosis and heart failure, SGLT2 inhibitors were associated with a lower 12-month all-cause mortality and hospitalization. Further evidence from randomized controlled studies are needed to confirm the efficacy of SGLT2 inhibitors in patients with cardiac amyloidosis.Figure 1.Kaplan-Meier curves

Prognostic values of lipoprotein(a) levels for secondary prevention of acute coronary syndrome among patients who underwent primary percutaneous coronary intervention

Abstract Background Lipoprotein(a) [Lp(a)] is known to be a residual risk factor for acute coronary syndrome(ACS). However, in the current era where primary percutaneous coronary intervention (PCI) and lipid-lowering therapies have advanced, the role of Lp(a) levels in secondary prevention among ACS patients remains unclear. Purpose The purpose of this study is to determine whether Lp(a) levels play a role in secondary prevention by studying patients with ACS who underwent primary PCI and survived discharge. Methods Consecutive ACS patients who were admitted to our institution between December 2016 and March 2021, requiring primary PCI and were discharged alive were enrolled for the current study (n = 471). Of these patients, those with the following circumstances were excluded: (1) multidisciplinary treatment such as mechanical ventilation management and percutaneous cardiopulmonary support (n = 74), (2) incomplete clinical data (n = 34), (3) ACS classified as other than type 1 in the universal definition (n = 6), and (4) unknown prognosis at 6 months after discharge (n = 8). A total of 349 consecutive patients were included in the current study. They were divided into two groups according to Lp(a) levels: Lower Lp(a) group (Lp(a) &amp;lt; 30 mg/dL, n = 277) and Higher Lp(a) group (Lp(a) ≥ 30 mg/dL, n = 72). The primary endpoints were major adverse cardiac events (MACEs), composite of all cause death, nonfatal myocardial infarction, nonfatal stroke and congestive heart failure requiring admission. Event-free survival curves were estimated using Kaplan-Meier method and log-rank test was used to detect statistically significant differences. In addition, influence of Lp(a) levels on MACE was examined using three cox regression analyses. Model 1 was adjusted for age, gender and body mass index, model 2 was adjusted for hypertension, diabetes and chronic kidney disease (CKD), model 3 was adjusted for old myocardial infarction (OMI), smoking and multivessel disease, respectively. Results The mean age was 67.0 ± 12.8 years, and 70.5% were male. The median serum Lp(a) levels of the entire population was 14 mg/dL (interquartile range, 7 to 26). There were no significant differences about baseline patient’s characteristics, laboratory findings, and medications at discharge including statin treatment. The MACE was observed in 15.5% of the Lower Lp(a) group and 20.8% of the Higher Lp(a) group (p=0.29). No difference was observed about MACE between the two groups (log-rank p=0.45). After adjusting for cardiovascular risk factors, Lp(a) levels were not associated with MACEs in all three models. However, in model 2 and model 3, CKD and OMI were associated with MACEs (hazard ratio 4.29, 95% confidence interval 2.17 to 8.46, p &amp;lt; 0.001, hazard ratio 3.02, 95% confidence interval 1.39 to 6.51, p = 0.005, respectively). Conclusions In the current era, Lp(a) levels are not associated with secondary prevention among ACS patients who underwent primary PCI.

Triggers of type 2 myocardial infarction: implications for long-term prognosis

Abstract Background Type 2 myocardial infarction (T2MI) is characterized by a mismatch between myocardial oxygen supply and demand, unrelated to acute coronary thrombosis. This discrepancy arises from triggers, which may or may not be of cardiac origin. Common cardiac triggers include coronary artery spasm, coronary embolism, and arrhythmias, whereas non-cardiac triggers encompass factors such as anemia, hypertension/hypotension, sepsis, renal damage, and respiratory failure. However, identifying these triggers isn't always straightforward. Aim Our study aimed to identify, whenever possible, the triggers contributing to the oxygen supply-demand mismatch in T2MI cases, as defined by the Fourth Universal Definition of Myocardial Infarction. Additionally, we sought to explore the correlation between these triggers and patient prognosis. Methods We enrolled all consecutive patients diagnosed with non-ST-segment elevation myocardial infarction (NSTEMI) who met the criteria for T2MI and underwent coronary angiography within 72 hours of diagnosis. Patients were categorized into three groups based on the trigger causing T2MI: cardiac, non-cardiac, and unidentified. The primary endpoint was the occurrence of major adverse cardiovascular events (MACEs), including all-cause mortality, new myocardial infarction, hospitalization for heart failure, and ischemic stroke, during long-term follow-up. We estimated MACE-free survival using Kaplan-Meier curves and compared it among the three groups using the log-rank test. Multivariable logistic regression analysis was performed to identify independent predictors of MACE. Results The final cohort comprised 598 T2MI patients, with 308 having a cardiac trigger, 147 having a non-cardiac trigger, and 143 with an unidentified trigger. The mean age of the overall population was 69.6±13.1 years, with a median follow-up time of 25 (13-49) months. Kaplan-Meier curves demonstrated statistically significant differences in MACEs based on the trigger causing T2MI (p&amp;lt;0.001). Specifically, patients with an unidentified trigger exhibited a better prognosis, while those with a non-cardiac trigger had a worse prognosis during long-term follow-up. Multivariable logistic regression analysis confirmed that not having an identified trigger is an independent protective factor for MACEs (HR 0.63, 95% CI 0.45-0.89, p=0.009, unidentified trigger vs cardiac + non-cardiac trigger). Conclusions T2MI is prevalent in clinical practice, yet reliable outcome predictors remain elusive. Our findings indicate a relationship between the type of trigger precipitating T2MI and patient prognosis, notably demonstrating that the absence of a specific identifiable trigger is linked to a more favorable long-term outcome. Further studies are needed to better define the prognostic stratification of these patients.MACE-free survival Kaplan Meier

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 &amp;lt;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.

Impact of agitation status during intensive care on functional outcomes and mortality in patients with cardiovascular disease

Abstract Background Agitation in patients during intensive care is a frequent complication. Several studies have reported that restlessness and agitation are risk factors for prolonged intensive care unit (ICU) stay and poor prognosis. Since patients with cardiovascular disease (CVD) requiring intensive care are ageing and thereby easily affected by responses, including changes in mental status, optimal management of sedation and agitation statuses during ICU stay is considered crucial. However, the influence of different agitation levels during CVD treatment in the ICU on clinical outcomes after ICU discharge is still unclear. Purpose To investigate the associations of the agitation level during ICU stay with mortality after ICU admission and functional outcomes at hospital discharge. Methods We studied 2236 patients (mean age 67.8±0.3 years) who were admitted to the ICU of a university hospital for CVD treatment and whose highest Richmond Agitation-Sedation Scale (RASS) ≥0, measured daily during ICU stay. In addition to clinical characteristics, we investigated the incidence of all-cause mortality during hospitalization and after hospital discharge. We also measured functional outcomes at discharge among 1625 patients, including 6 minutes walk distance (6MWD), Mini-Cog test, and Patient Health Questionnaire-2 (PHQ-2) as physical, cognitive, and mental functions, respectively. In statistical analysis, patients were divided into three groups based on the highest RASS levels during ICU stay in each patient (Calm: RASS=0, Restless: RASS=1, Agitation: RASS≥2). Kaplan-Meier analysis with a log-rank test and the multivariate Cox proportional hazard model were used to clarify whether higher agitation levels were associated with all-cause mortality. Moreover, the differences between the agitation levels and functional outcomes at hospital discharge were compared using the analysis of covariance. Results During the median follow-up of 1.9 years, all-cause death occurred in 280 patients (12.5%), with an incidence rate of 5.57/100 person-years. The Restless and Agitation groups showed higher mortality than the Calm group (P&amp;lt;0.001), and higher agitation levels in the ICU were significantly associated with a higher rate of all-cause mortality (adjusted hazard ratio: 1.37, 95% confidence interval: 1.19–1.57, P&amp;lt;0.001). Furthermore, as compared with the Calm group, the Restless and Agitation groups showed significantly lower levels of 6MWD (all P&amp;lt;0.001) and Mini-cog (P=0.004 and P&amp;lt;0.001, respectively) and a higher PHQ-2 (all P&amp;lt;0.001), even after adjusting for clinical confounders. Conclusions Agitation during ICU stay in CVD patients was associated with low functional outcomes at hospital discharge and high mortality rate after discharge, irrespective of agitation level. Detailed information on the agitation status during intensive care may be an important indicator in developing management and treatment strategies for patients with CVD admitted to ICU.

The association between exercise-induced ventricular premature contractions and long-term mortality in patients without coronary artery disease

Abstract Background/Introduction The treadmill exercise test is widely used clinical test to determine cardiovascular risk and mortality, regardless of clinical risk factors (1). ST-segment changes detected in the exercise test are shown to predict myocardial ischemia (2) and premature ventricular complexes (PVCs) are frequently observed during exercise stress testing (3). Exercise-related PVC is observed in 14% to 23% of healthy individuals without significant heart disease (4,5). The literature on the role of PVCs observed during treadmill exercise testing in predicting prognosis is controversial. Purpose Therefore, we aimed to evaluate the clinical results of PVCs seen during exercise testing in patients who had been diagnosed with non-obstructive coronary artery disease after coronary angiography. Methods The study population consisted of 1624 consecutive patients who were considered high risk according to the Duke treadmill risk score and had no significant stenosis on coronary angiogram from January 2016 to April 2021. Patients with previous history of coronary revascularization, previous myocardial infraction, heart failure, moderate or severe heart valve disease, congenital heart disease, cardiomyopathy, bundle branch block, and left ventricular hypertrophy were excluded from the study. The primary endpoints of the study were long-term all-cause mortality of patients who had PVCs during the exercise test or during the resting phase. Results The long-term mortality was observed in 53 patients out of 1624 patients in the mean follow-up of 47 months. PVCs was observed in 293 (18.7%) patients without long-term mortality, while PVCs was observed in 24 (45.3%) patients with long-term mortality (p&amp;lt;0.001). The model adjusted for all covariates showed that the presence of PVCs in the recovery phase (p&amp;lt;0.007, HR (95% CI) 2.244 (1.244 – 4.047)) and advanced age (p&amp;lt;0.001, HR (95% CI) 1.194 (1.143 – 1.247)) were associated with long-term all-cause mortality (Figure 1). Considering Kaplan-Meier curve, individuals with PVCs in recovery had significantly higher risk of long-term mortality compared with those with without PVCs (log-rank statistic: 22.47, p&amp;lt;0.001) (Figure 2). Conclusion(s) The study highlights that PVCs monitored in the recovery phase of the treadmill exercise test were associated with long -term mortality in patients without structural heart disease and coronary artery disease.Figure 2Figure 1

Treatment of kidney disease: an analytical decision model at a Swiss university hospital

Abstract Background An observational hospital-based cohort study, where the kidney disease staging is identified as a digital marker, and the association between the standardised staging of Kidney Disease (KD) and the outcomes is assessed along the treatment process. Methods The clinical and administrative data for all patients are stored in the Clinical Data Warehouse. A specific digital marker for an exact KD staging is applied. Three retrospective patient cohorts for exact and imprecise staging and missing diagnosis are defined and compared regarding the in-hospital mortality, all-cause mortality and disease progression. Results In total, 83146 hospitalisations of 40421 patients with KD, treated in 2014-2023 (2016-2023 will be updated) were identified; the number of the first hospitalisations with exact staging was 847 (2%), unprecise 29934 (72%) and missing diagnosis (26%). The demographic and baseline factors distribution between groups was tested with no association (chi-squared test statistic). The median survival time with a 95% CI was 7.94 (7.66, 8.81) years for the exact and 7.47 (7.42, 7.53) for the imprecise staging group. A log-rank and loglikelihood tests indicated a significant difference in survival between the groups, p &amp;lt; 0.0001. The Cox regression model shows a statistically significant difference in Hazard Ratio; KD staging, age, Elixhauser van Walraven index, treatment, nephrotoxic medication, contrast agent application, and AKI were identified as the significant covariates, C-statistic 0.730, Likelihood ratio test, Wald test, log-rank score on 42 df, p &amp;lt; 2e-16. ANOVA analysis confirmed a significant difference in cost distribution between the groups. An economic decision model proposal integrates the findings, combining a profile-level Markov cohort with a Discreet Time-To-Event Simulation DICE. Conclusions The study demonstrates a better outcome regarding all-cause mortality, in-hospital mortality, and costs if a standardised KD staging was applied. Key messages • Intuition (clinical judgement) and standardised kidney disease staging perform differently regarding clinical outcomes and costs. • The study demonstrates a better outcome regarding all-cause mortality, in-hospital mortality, and costs if a standardised KD staging was applied.

One-year outcomes of patients with hypertrophic cardiomyopathy according to levels of inflammatory biomarkers

Abstract Background Hypertrophic cardiomyopathy (HCM) is a vastly heterogeneous sarcomere disorder unified by maximal left ventricular (LV) thickness increases. The lifetime relative risk of morbidity in HCM is four-fold higher than in the general population, primarily driven by arrhythmias and heart failure (HF). Numerous prognostic features have been identified, but our ability to identify high-risk patients of progression remains rudimentary. Small retrospective studies have shown that systemic inflammation is associated with adverse outcomes in patients with HF; others, small and single-center, have also shown associations between adverse outcomes and inflammation in HCM. Purpose We aimed to determine whether elevated levels of inflammatory biomarkers are associated with an increased risk of acute heart failure (AHF) and mortality at 1 year in a large cohort of patients with HCM across multiple centers in the United States (US). Methods In this retrospective study, using the US cohort of 60 healthcare organizations in the TriNetX database, we included more than 85,000 adult patients with HCM (ICD-10-CM codes I42.1 and I42.2) between 2004 and 2024. Patients were divided according to predetermined cut-offs of different inflammatory biomarkers (C-reactive protein [CRP], &amp;lt;2 mg/L vs. 2-100 mg/L; white blood cells [WBC], &amp;lt; vs. ≥ the median [8x10^3/µL]; neutrophils [Neu], &amp;lt; vs. ≥ the median [5x10^3/µL]). These cohorts were then 1:1 propensity score matched (PSM) for age, sex, and race. We used Kaplan-Meier survival curves to derive cumulative incidence curves (as 1 minus Kaplan-Meier survival estimates) for AHF (ICD-10-CM codes I50.21, I50.23, I50.31, I50.33, I50.41, I50.43) or death, and we compared them with the Log-rank (Mantel-Cox) test. We also derived Hazard Ratios (HR) with 95% Confidence Interval (CI) from Cox regression analysis to compare the outcomes within the groups at 1-year. Results After PSM, patients with HCM and CRP levels between 2-100 mg/L experienced higher rates of the composite outcome (19.6% vs. 12.2%, Log-rank p&amp;lt;0.001; HR 1.67, 95% CI [1.29-2.16]), as well as the separate outcomes of death (14.7% vs. 6.8%, Log-rank p&amp;lt;0.001; HR 2.23, 95% CI [1.68-2.98]) and AHF (10.9% vs. 7.5%, Log-rank p&amp;lt;0.001; HR 1.49, 95% CI [1.07-2.07]), compared to those with CRP &amp;lt;2 mg/L (Table 1)(Figure 1). Similarly, patients with Neu ≥5x10^3/µL reported higher incidences of the composite outcome (20.3% vs. 13.2%, Log-rank p&amp;lt;0.001; HR 1.62, 95% CI [1.55-1.68]) and the separates outcomes, compared to those with Neu &amp;lt;5x10^3/µL (Table 1) (Figure 1). Patients with WBC ≥8x10^3/µL also had increased rates of the composite outcome (19.4% vs. 14.1%, Log-rank p&amp;lt;0.001; HR 1.43, 95% CI [1.38-1.48]) and the separate outcomes, compared to those with WBC &amp;lt;8x10^3/µL (Table 1)(Figure 1). Conclusions In the first large 'real world' analysis of patients with HCM, elevated levels of inflammatory biomarkers were associated with worse outcomes of death and acute heart failure.

Ticagrelor or prasugrel versus clopidogrel in patients with coronary heart disease

Abstract Introduction Antiplatelet therapy is pivotal in the management of coronary heart disease (CHD), especially after percutaneous coronary intervention (PCI). Clopidogrel has long been the cornerstone of dual antiplatelet therapy. However, newer agents like prasugrel and ticagrelor boast of faster onset of action and greater platelet inhibition, which may translate to improved outcomes. Purpose Our hypothesis is that prasugrel or ticagrelor are superior to clopidogrel in reducing cardiovascular mortality in chronic CHD patients. Methods We conducted a retrospective cohort study using the TriNetX network database, including patients with chronic CHD on dual antiplatelet therapy. A total of 1,420,165 patients on clopidogrel and 197,783 on prasugrel or ticagrelor were identified. We assessed the primary composite endpoint of cardiovascular mortality over a 5-year follow-up period, using event-free survival as our main outcome measure. Results The 5-year follow-up data revealed a significant difference in event-free survival between the groups. Patients on prasugrel or ticagrelor had a markedly higher event-free survival rate of 83.156% compared to 73.209% for those on clopidogrel. The Log Rank test showed a confidence interval of 1.544 to 1.592 with a highly significant p-value of &amp;lt;0.0001. Discussion The data suggest a clear benefit of prasugrel or ticagrelor over clopidogrel for event-free survival in CHD patients. This could be attributed to the more potent antiplatelet effects of these drugs, leading to reduced thrombotic events. Given the substantial sample size and robustness of the data, the findings advocate for a paradigm shift in the choice of more potent antiplatelet agents in clinical practice. Conclusion Our analysis supports the hypothesis that prasugrel or ticagrelor are associated with significantly lower cardiovascular mortality compared to clopidogrel in patients with chronic coronary heart disease.5-year Kaplan-Meier curves for mortality

Clinical outcomes according to residual cholesterol and inflammatory risk in patients undergoing PCI

Abstract Background Elevated concentrations of low-density lipoprotein cholesterol (LDL-c) and low grade vascular inflammation, commonly quantified using high-sensitivity C-reactive protein (hsCRP), have been demonstrated to be causal in the development of atherosclerotic disease. Whilst recent large-scale trials have investigated the relative impact of LDL-c and inflammation on cardiovascular outcomes, there is a scarcity of data in real-world patients undergoing percutaneous coronary intervention (PCI). Purpose To investigate the relative drivers of residual risk in patients with established statin treatment undergoing PCI in a contemporary large-scale cohort. Methods From January 2012 to February 2020 patients undergoing PCI at a tertiary center were included for current analysis. Patients were categorized into 4 subgroups according to different combinations of LDL-c and hsCRP concentrations at baseline: no residual cholesterol or inflammatory risk (LDL-c &amp;lt;70 mg/dL + hsCRP &amp;lt;2 mg/L), residual cholesterol risk (LDL-c ≥70 mg/dL + hsCRP &amp;lt;2 mg/L), residual inflammatory risk (LDL-c &amp;lt;70 mg/dL + hsCRP ≥2 mg/L), and combined residual cholesterol and inflammatory risk (LDL-c ≥70 mg/dL + hsCRP ≥2 mg/L). Individuals who presented with acute myocardial infarction, neoplastic disease and hsCRP concentrations &amp;gt;10 mg/l were excluded. The outcome of interest was major adverse cardiac events (MACE - composite of all-cause mortality, myocardial infarction, or stroke). A univariable cox regression model was calculated. Results Overall, 10,845 patients were included. In total, 3,210 patients displayed neither cholesterol nor inflammatory risk and 3,059 individuals had elevated cholesterol risk only. In 1,839 patients an inflammatory risk was noted, whilst 2,737 patients presented with combined cholesterol and inflammatory risk. Kaplan-Meier curves for 1-year follow-up are displayed in Figure 1. Patients with residual inflammatory risk had the highest event rate of the composite endpoint (5.2%), followed by patients with combined residual risk (3.5%), individuals with residual cholesterol risk (2.3%) and persons with neither cholesterol nor inflammatory risk (2.4%; p&amp;lt;0.0001 for log rank test across all groups). An association with MACE was solely documented for patients with residual inflammatory risk (HR: 2.09, 95% CI: 1.52 - 2.88; p&amp;lt;.001), and also borderline significant for combined cholesterol and inflammatory risk (HR: 1.41, 95% CI: 1.03 - 1.95; p=0.034), whilst this was not the case for patients with elevated cholesterol risk only (see Figure 2). Conclusion In a contemporary real-world cohort of statin treated patients undergoing PCI, inflammation irrespective of LDL-c concentrations was the driver for adverse cardiovascular outcomes. This data might be helpful to further define target populations for both intensified lipid-lowering as well as anti-inflammatory treatment approaches.

Gender disparities in short-term outcomes of STEMI patients: the influence of universal health coverage

Abstract Background Even after the event, individuals recovering from ST-elevation myocardial infarction (STEMI) face lingering risks, including potential subsequent events and mortality. The introduction of Universal Health Coverage (UHC) seeks to enhance healthcare outcomes for all segments of the population. Purpose This study evaluates the effect of UHC on 30-day mortality in post-STEMI patients, focusing on medication access and treatment disparities. Using a gender-stratified approach, we analyze changes before and after UHC implementation to provide insights into the difference in therapy between genders and how gender influences healthcare outcomes for post-STEMI patients. Methods Analyzing two cohorts, Cohort 1 (211 STEMI patients, 2013-2014 pre-UHC) and Cohort 2 (365 STEMI patients, 2018-2020 post-UHC), this study employed the chi-square test to determine differences between genders and the Kaplan–Meier log-rank test to compare survival rates. Results Comparing pre- and post-UHC, we observed a significant increase in both medication and reperfusion therapy (p&amp;lt;0.001). However, even in both periods, women continued to have lower rates of medication and reperfusion compared to men (Men vs Women: Before UHC 14.3% vs 0%; After UHC 58.5% vs 47.9%). Within 30 days after the STEMI event, we noted a reduction in mortality rates across genders before and after UHC implementation, yet the decrease was less pronounced in women compared to men (Before UHC: Men 13.0%, Women 22.0%; After UHC: Men 8.2%, Women 18.3%). Conclusion UHC led to improvements in medication and reperfusion therapy for STEMI patients. Despite this progress, persistent gender disparities were observed, with women consistently having lower treatment rates. While mortality rates reduced for both genders, the decrease was less pronounced in women, especially after the implementation of UHC. These findings emphasize the need for targeted interventions to address gender-specific healthcare discrepancies within the scope of comprehensive health coverage.Baseline characteristicsMortality outcomes within 30 Days

Higher systolic blood pressure in left not right upper limb is associated with all-cause mortality risk in a community-based population

Abstract Background and Purpose Previous studies have shown that elevated inter-arm systolic blood pressure difference (SBPD) is a valuable indicator for assessing the risk of all-cause mortality. However, no research currently reports that the different impact of higher SBP in which upper limb on all-cause mortality risk. This study investigates which side of the upper limbs has a higher SBP that is more associated with all-cause mortality risk in a community population. Methods The subjects were from the a Atherosclerosis Cohort of the Department of Cardiology of our University First Hospital from 2012 to 2021, and those with missing data of brachial-ankle pulse wave velocity and a history of myocardial infarction or stroke in the baseline survey were excluded. The endpoint was defined as all-cause mortality. SBPD was defined as the difference between the systolic blood pressure of the right arm minus the systolic blood pressure of the left arm by the noninvasive arteriosclerosis detection device BP-203RPEIII (Omron, Japan). SBPD was categorized into four groups: 0-10 mmHg (right arm higher &amp;lt;10mmHg), ≥ 10 mmHg (right arm higher ≥ 10 mmHg ), -10 to &amp;lt; 0 mmHg (left arm higher ≤10 mmHg), and &amp;lt; -10 mmHg (left higher &amp;gt; 10mmHg). The relationship between SBPD and all-cause mortality risk was determined by multivariable Cox proportional hazards regression after adjusting for covariates (age, body mass index, gender, current smoking, current drinking, estimated glomerular filtration rate, diabetes, hypoglycemic treatment, total cholesterol, triglycerides, lipid-lowering treatment, and antihypertensive treatment). Results Totally, 8628 participants were included, with a mean age of 56.58 ± 8.97 years old, and 64.51% (5566) were female. Among them, 380 (4.40%) had an SBPD ≥ 10 mmHg, and 409 (4.74%) had an SBPD &amp;lt; -10 mmHg. During a median follow-up of 9.87 years, 442 cases of all-cause mortality (5.19%) occurred. The Kaplan-Meier curve suggested that the greater the difference in SBPD, the higher the cumulative risk of all-cause mortality. The Log-rank test showed a significant statistical difference (P= 0.0115). Compared to right arm higher &amp;lt;10mmHg group, the risk of all-cause mortality was not significantly elevated in right arm higher ≥ 10 mmHg (adjusted HR=1.17, 95% CI: 0.74-1.84, P=0.507) or left arm higher ≤10 mmHg group (adjusted HR=0.90, 95%CI: 0.74-1.11, P=0.329). However, the risk of all-cause mortality significantly increased by 59% in left higher &amp;gt; 10mmHg Group (adjusted HR=1.59, 95% CI: 1.10-2.30, P=0.013). The results remained significant after adjusting for peripheral right arm SBP (adjusted HR=1.56, 95% CI: 1.08-2.24, P=0.018). Conclusion This study found that a higher SBP in the left arm is associated with a higher risk of all-cause mortality in a Beijing community-based population, and they should be monitored and intervened more intensively.Hazard Ratios for all-cause mortalitySurvival curves for SBPD groups

Prior fecal immunochemical test positivity is associated with adverse prognosis in patients with acute ST-segment elevation myocardial infarction

Abstract Backgrounds While fecal immunochemical testing (FIT) is commonly used for disease screening, its significance in other conditions, particularly in patients with ST-segment elevation myocardial infarction (STEMI), is not extensively researched. Purpose This study aimed to investigate the impact of prior positive FIT results on the clinical prognosis of patients with STEMI. Methods The data for this study were derived from the Health and Medical Big Data Superplatform, comprising a retrospective cohort of patients discharged from 72 hospitals from 2010 to 2023. A total of 76,157 patients with acute STEMI patients were enrolled. Positive FIT was defined as "+-" or higher on the fecal occult blood test. Propensity score matching (PSM) was employed to balance differences between the two groups. Kaplan-Meier analysis with log-rank tests compared endpoint risks between groups, and a multivariable Cox regression model adjusted for potential confounders. The primary endpoint was Net Adverse Clinical Event (NACE), including cardiac death, recurrent myocardial infarction, revascularization, stroke, cerebral hemorrhage, and gastrointestinal bleeding. Results After 1:3 PSM,2,148acute STEMI patients were included, with 537 having prior positive FIT and 1,611 without. Patients with prior positive FIT were more likely to have comorbidities such as hyperlipidemia, prior malignancy, post-coronary artery bypass grafting, renal insufficiency, and prior cerebral hemorrhage. The prior positive FIT group had a higher proportion of prior clopidogrel and indobufen usage, while aspirin use during follow-up was lower. Kaplan-Meier analysis demonstrated a significantly higher risk of NACE in acute STEMI patients with prior positive FIT (before PSM: log-rank P = 0.001, after PSM: log-rank P = 0.005, Figure 1）, as well as increased rates of Major Adverse Cardiac and Cerebral Events (MACCE), all-cause death, and gastrointestinal bleeding (log-rank P &amp;lt; 0.05 for all). Multivariate Cox-proportional hazard analysis adjusted for age, sex, percutaneous coronary intervention during hospitalization, diabetes, hypertension, ischemic stroke, atrial fibrillation, medication during hospitalization, and follow-up showed similar results (Figure 2). Conclusions This study reveals a significant association between prior positive FIT and higher rates of NACE, MACCE, all-cause death, and gastrointestinal bleeding in STEMI patients within 1 year. A history of positive FIT results could serve as a prognostic indicator in this specific patient population.

Prevalence, mechanisms and prognostic impact of dynamic mitral regurgitation unmasked by handgrip exercise in patients with hypokinetic non-dilated and dilated cardiomyopathy

Abstract Background Recent studies suggest that mitral regurgitation (MR) is a dynamic condition influenced by global and regional left ventricular (LV) remodeling as well as mitral valvular deformation. Exercise testing plays a substantial role in assessing the hemodynamic relevance of MR and is recommended by current guidelines. Handgrip exercise may serve as alternative exercise intervention to bicycle exercise, as it is easy to perform even bedside. However, there are no data yet, on the prevalence, mechanisms and prognostic impact of dynamic MR in patients with dilated cardiomyopathy using isometric exercise testing. Aims We aimed to assess the prevalence, hemodynamic consequences, and prognostic impact of exercise-induced changes in MR in patients with hypokinetic non-dilated and dilated cardiomyopathy. Methods Patients with hypokinetic non-dilated and dilated cardiomyopathy and at least mild MR who underwent handgrip echocardiography at the University Hospital Duesseldorf between January 2018 and September 2021 were enrolled.Patients were followed-up for one year to assess clinical outcomes. We assessed all-cause mortality, HF-associated hospitalizations, MV surgery, transcatheter edge-to-edge repair (TEER), left ventricular assist device implantation and heart transplantation during follow-up. Results Fifty-eight patients were included (mean age 70±15 years; 41% female; mean LVEF 37±10%). At rest, 28 patients (48%) presented with mild MR, and 30 patients (52%) had moderate MR. Fifteen patients (26%) with non-severe MR at rest, developed dynamic severe MR during handgrip exercise. Patients with dynamic severe MR had advanced MR at rest, larger left atrial dimensions, and increased mitral annulus diameter (all p&amp;lt;0.01). During exercise, LVEDVi, LVESVi and parameters of local left ventricular remodeling (tenting height, tenting area) were increased in patients with dynamic severe MR compared to those with non-severe MR (all p&amp;lt;0.05). During one-year follow-up, there was no difference regarding all-cause mortality and HF hospitalizations in patients with dynamic severe MR and non-severe MR (Log-rank test Chi2 0.262; p=0.609)(Figure 1). However, patients with dynamic severe MR more often underwent mitral valve surgery/intervention than patients with non-severe MR (Log-rank test Chi2 29.41; p&amp;lt;0.001)(Figure 1). Conclusion Our results demonstrate that the evaluation of non-ischemic MR only at rest underestimates the full severity of the lesion. Handgrip exercise unmasks severe MR in every fourth patient with non-severe MR at rest. These data may have implications for therapeutic decision-making in symptomatic patients with hypokinetic non-dilated and dilated cardiomyopathy and non-severe MR at rest. TEER might present an effective treatment option to improve clinical outcomes in patients with non-ischemic cardiomyopathy and non-severe MR at rest but dynamic severe MR during exercise.Figure 1