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Background: There is limited data on the association between inflammation and the formation of early left ventricular thrombus (LVT) following ST-elevation myocardial infarction (STEMI). This study aimed to explore the predictive value of several inflammatory biomarkers for LVT formation following STEMI., Methods and Results: Our cohort included 2534 consecutive patients admitted to the cardiac intensive care unit (CICU) with STEMI. The final analysis included 51 patients with LVT and 102 patients without LVT, matched for age, sex, anterior infarct and ejection fraction. Upon admission, patients with LVT had higher white blood cell counts (WBC) (12.8 ± 7 vs. 12.4 ± 4 ×10 3 /µL, p = 0.01), higher absolute neutrophil counts (10.5 ± 4 vs. 8.6 ± 4 ×10 3 /µL, p = 0.003), neutrophil-to-lymphocyte ratio (8.2 ± 6 vs. 4.8 ± 4, p = 0.04), and C-reactive protein (CRP) levels (35.9 ± 62 vs. 18.6 ± 40 mg/L, p = 0.04). Peak values for WBC and CRP were also higher in the LVT group (17.8 ± 8 vs. 14.6 ± 5 ×10 3 /µL, p = 0.003 and 95.8 ± 82 vs. 64.2 ± 76 mg/L, p = 0.02, respectively). In univariate regression analysis, WBC upon admission (OR: 1.12, 95% CI: 1.02-1.21, p = 0.02), peak WBC (OR: 1.09, 95% CI: 1.02-1.17, p = 0.009), neutrophil count upon admission (OR: 1.15, 95% CI: 1.04-1.26, p = 0.004), and peak CRP (OR: 1.01, 95% CI: 1-1.01, p = 0.03) predicted LVT formation, which was also evident in multivariate regression models., Conclusion: WBC and neutrophil counts upon admission, as well as peak WBC and CRP, have additional predictive value for LVT formation following STEMI, beyond classical risk factors., (© 2024 The Author(s). Clinical Cardiology published by Wiley Periodicals, LLC.)

Background: Acute kidney injury (AKI) is a common and serious complication of ST-elevation myocardial infarction (STEMI). AKI and chronic kidney disease (CKD) are highly heterogeneous, leaving a wide gap between them. Therefore, the term acute kidney disease (AKD) was implemented, describing prolonged renal injury between 7 and 90 days. We aimed to evaluate the prevalence and predictors of AKD among STEMI patients., Methods: This retrospective observational study included 2940 consecutive patients admitted with STEMI between 2008 and 2022. Renal function was assessed upon admission and routinely thereafter. Renal outcomes were evaluated according to KDIGO criteria, with AKD defined as persistent renal injury of between 7 and 90 days., Results: Two hundred and fifty-two subjects with STEMI and AKI were included; of them, 117 (46%) developed AKD. Among baseline CKD patients, higher rates of AKD were observed (60% vs. 46%). KDIGO index ≥ 2 was an independent predictor for AKD in in subjects without baseline CKD (AOR 2.63, 95% CI 1.07-6.53). In subjects with baseline CKD, older age and higher creatinine were independent predictors for AKD. Subjects with AKD had a higher 1-year mortality rate (HR 3.39, 95% CI 1.71-6.72, p < 0.01). This trend was mainly driven by the CKD subpopulation where higher mortality rates for AKD on CKD were observed (HR 5.26, 95% CI 1.83-15.1, p < 0.01)., Conclusion: AKD is common among STEMI patients with AKI. The presence of CKD and higher KDIGO stage should prompt strict monitoring for early diagnosis, treatment, and prevention of renal function deterioration., (© 2024 The Author(s). Clinical Cardiology published by Wiley Periodicals, LLC.)

Background and Aims: The diagnosis of acute kidney injury (AKI) is of importance among patients with ST segment elevation (STEMI) undergoing primary coronary intervention (PCI). It is often delayed given the need in serial measurements of creatinine or other serum markers. Neutrophil gelatinase-associated lipocalin (NGAL) is a proven marker for AKI, although its role as an early predictor in this setting was scarcely addressed before and was the aim of our study., Methods: Prospective observational study including 133 patients with STEMI treated with PCI. Plasma NGAL was drawn immediately before PCI (NGAL-0) and 24 h after (NGAL-24). Similar analysis of C-reactive protein (CRP) was performed for additional comparison., Results: Mean age was 62 ± 13 years, 78% were men, and 20 (15%) developed AKI after admission. Patients with AKI after admission demonstrated higher levels of NGAL-0 (164 vs. 95 ng/mL; p  < 0.001) and NGAL-24 (142 vs. 93 ng/mL; p  < 0.001). Levels of NGAL-0 and NGAL-24 were similar within the AKI and non-AKI groups. Using ROC curve analysis, NGAL-0 had best predictive ability for AKI development (AUC 0.841, 95% CI 0.80-0.96), compared with NGAL-24 (0.783, 95% CI 0.74-0.85), CRP-0 (0.701, 95% CI 0.58-0.83), and CRP-24 (0.781, 95% CI 0.66-0.90). The optimal NGAL-0 cutoff for AKI prediction was 125 ng/mL, with 70% sensitivity, 84% specificity, and 94% negative predictive value., Conclusions: Among STEMI patients, NGAL measurement upon admission are associated with AKI and may serve as a reliable marker for early AKI detection. Future studies may direct risk stratification using this single test can direct personalized evaluations during the admission, and focused interventions to prevent AKI., Competing Interests: Nils Erik Magnusson is an advisor for Bioporto Diagnostics yet Bioporto did not fund any part of this study. All other authors have no competing interests to declare and no relevant financial relationships., (© 2024 The Author(s). Health Science Reports published by Wiley Periodicals LLC.)

Background: In many conditions characterised by septal hypertrophy, females have been shown to have worse outcomes compared to males. In clinical practice and research, similar cutoff points for septal hypertrophy are still used for both sexes. Here, we explore the association between different cutoff points for septal hypertrophy and survival in relation to sex., Methods and Results: We performed a retrospective analysis of consecutive patients undergoing echocardiography between March 2010 and February 2021 in a large tertiary referral centre. A total of 70,965 individuals were included. Over a mean follow-up period of 59.1 ± 37 months, 9631 (25 %) males and 8429 (26 %) females died. When the same cutoff point for septal hypertrophy was used for both sexes, females had worse prognosis than males. The impact of septal hypotrophy on survival became statistically significant at a lower threshold in females compared to males: 11.1 mm (HR 1.13, CI 95 %:1.03-1.23, p = 0.01) vs 13.1 mm (HR 1.21, CI 95 %: 1.12-1.32, p < 0.001). However, when indexed wall thickness was used, the cutoff points were 6 mm/body surface area (BSA) (HR 1.08, CI 95 %: 1-1.18, p = 0.04) and 6.2 mm/BSA (HR 1.07, CI 95 %: 1-1.15, p = 0.05) for females and males, respectively., Conclusions: Septal hypertrophy is associated with increased mortality at a lower threshold in females than in males. This may account for the worse prognosis reported in females in many conditions characterised by septal hypertrophy. Applying a lower absolute value or using indexed measurements may facilitate early diagnosis and improve prognostication in females., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Introduction: The C-reactive protein (CRP)-troponin-test (CTT) comprises simultaneous serial measurements of CRP and cardiac troponin and might reflect the systemic inflammatory response in patients with acute coronary syndrome. We sought to test its ability to stratify the short- and long-term mortality risk in patients with non-ST elevation myocardial infarction (NSTEMI)., Methods: We examined 1,675 patients diagnosed with NSTEMI on discharge who had at least two successive measurements of combined CRP and cardiac troponin within 48 h of admission. A tree classifier model determined which measurements and cutoffs could be used to best predict mortality during a median follow-up of 3 years [IQR 1.8-4.3]., Results: Patients with high CRP levels ( > 90th percentile, >54 mg/L) had a higher 30-day mortality rate regardless of their troponin test findings (16.7% vs. 2.9%, p < 0.01). However, among patients with "normal" CRP levels ( < 54 mg/L), those who had high troponin levels ( > 80th percentile, 4,918 ng/L) had a higher 30-day mortality rate than patients with normal CRP and troponin concentrations (7% vs. 2%, p < 0.01). The CTT test result was an independent predictor for overall mortality even after adjusting for age, sex, and comorbidities (HR = 2.28 [95% CI 1.56-3.37], p < 0.01 for patients with high troponin and high CRP levels)., Conclusions: Early serial CTT results may stratify mortality risk in patients with NSTEMI, especially those with "normal" CRP levels. The CTT could potentially assess the impact of inflammation during myocardial necrosis on the outcomes of patients with NSTEMI and identify patients who could benefit from novel anti-inflammatory therapies., (© 2024 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Introduction: Acute kidney injury (AKI) is a clinically relevant and common complication among patients with acute coronary syndrome. Neutrophil gelatinase-associated lipocalin (NGAL), secreted from different cells including renal tubules, has been widely studied as an early marker for kidney injury. However, chronic kidney disease (CKD) could impact NGAL levels and alter their predictive performance. Some studies attempted to address this issue by setting different cutoff values for patients with CKD, with limited success to date. Our aim was to evaluate a novel estimated glomerular filtration rate (eGFR)-adjusted "indexed NGAL" and its ability to predict in-hospital AKI among patients with ST elevation myocardial infarction., Methods: We performed a prospective, observational, single center study involving patients with ST elevation myocardial infarction admitted to the coronary intensive care unit. Serum samples for baseline NGAL were collected within 24 h following hospital admission. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. In-hospital AKI was determined as occurring after ≥ 24 h from admission. To perform an individualized adjustment, we used the result of 24 h NGAL divided by the eGFR measured upon admission to the hospital (Indexed-NGAL; I-NGAL)., Results: Our cohort includes 311 patients, of whom 123 (40%) had CKD, and 66 (21%) suffered in-hospital AKI. NGAL levels as well as I-NGAL levels were significantly higher in patients with AKI (136 vs. 86, p < 0.01 and 3.13 VS. 1.06, p < 0.01, respectively). Multivariate analysis revealed I-NGAL to be independently associated with AKI (OR 1.34 (1.10-1.58), p < 0.01). I-NGAL had a higher predictive ability than simple NGAL results (AUC-ROC of 0.858 vs. 0.778, p < 0.001)., Conclusion: Adjusting NGAL values according to eGFR yields a new indexed NGAL value that enables better prediction of AKI regardless of baseline kidney function., (© 2023. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Background: Several reports suggested that compliance with acute kidney injury care bundles among hospitalized patients resulted in improved kidney and patient outcomes. We investigated the effect of acute kidney injury care bundle utilization on the incidence of acute kidney injury and renal outcomes in a large cohort of myocardial infarction patients treated with percutaneous coronary intervention., Methods: We included patients with myocardial infarction admitted following percutaneous coronary intervention between January 2008 and December 2020. From January 2016, acute kidney injury care bundle was implemented in our cardiac intensive care unit. Acute kidney injury care bundle consisted of simple standardized investigations and interventions, including strict monitoring of serum creatinine and urine analysis, planning investigations, treatment, and guidance about seeking nephrologist advice. Patients' records were evaluated for the occurrence of acute kidney injury, its severity, and recovery, before and after the implementation of acute kidney injury care bundle., Results: We included 2646 patients (1941 patients in the years 2008-2015 and 705 patients in the years 2016-2020). Implementation of care bundles resulted in a significant decrease in the occurrence of acute kidney injury from 190/1945 to 42/705 (10-6%; p < 0.001), with a trend for lower acute kidney injury score > 1 (20% vs. 25%; p = 0.07) and higher acute kidney injury recovery (62% vs. 45%, p = 0.001). Using a multivariable regression model, the use of care bundles resulted in a 45% decrease in the relative risk for acute kidney injury (HR 0.55, 95% CI 0.37-0.82, p < 0.001)., Conclusion: Among patients with ST-elevation myocardial infarction, treated with percutaneous coronary intervention and admitted to our cardiac intensive care unit over the period January 2008-December 2020, compliance with acute kidney injury care bundle was independently associated with a significant decrease in occurrence of acute kidney injury and with better renal outcomes following acute kidney injury. Further interventions, such as e-alert systems for acute kidney injury, could improve utilization of the acute kidney injury care bundle and optimize its clinical benefits., (© 2023. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Background: Inflammatory biomarkers are known to rise and have predictive value for adverse outcomes in patients with acute coronary ischemia. One of those biomarkers is neutrophil gelatinase-associated lipocalin (NGAL). To date, only very few studies have assessed the prognostic value of NGAL in this setting. We investigated the prognostic utility of elevated NGAL levels on clinical outcomes among ST-elevation myocardial infarction patients., Methods: High NGAL was defined as values within the 4th quartile. Patients were assessed for major in-hospital adverse clinical events (MACE). Multivariable logistic regression and area under the receiver operating characteristic curve (AUC) were used to further evaluate NGAL association for MACE and discrimination ability., Results: A total of 273 patients were included. patients with high NGAL were at increased risk for MACE (62% vs. 19%; odds ratio 6.88, 95% confidence interval, 3.77-12.54, P  < 0.001). After propensity score matching, the incidence of MACE was significantly higher in patients with high vs. low NGAL levels (69% vs. 6%, P  = 0.002). In multivariable regression, high NGAL level was independently associated with MACE. The discrimination ability of NGAL to identify MACE (AUC 0.823), is significantly better than that of other inflammatory markers., Conclusion: Among ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention, high NGAL levels are associated with adverse outcomes, independent of traditional inflammatory markers., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Neutrophil gelatinase-associated lipocalin (NGAL) is an inflammatory biomarker related to acute kidney injury (AKI). Including 1892 consecutive patients with ST-elevation myocardial infarction (STEMI), in which NGAL was measured in 1624 (86%) on admission and in a consecutive subgroup at 6-12 h (n = 163) and 12-24 h (n = 222) after admission, this study aimed to evaluate the prognostic value of NGAL in predicting AKI and mortality. Patients were stratified based on whether their admission NGAL plasma concentration was greater than or equal to/less than the median. The primary endpoint was a composite of the first occurrence of AKI or all-cause death within 30 days. AKI was classified by the maximal plasma creatinine increase from baseline during index admission as KDIGO1 (<200% increase) or KDIGO23 (≥200% increase) according to the Kidney Disease Improving Global Outcomes (KDIGO) system. Admission NGAL > the median was independently associated with a higher risk of severe AKI (KDIGO2-3) and 30-day all-cause mortality when adjusted for age, admission systolic blood pressure and high-sensitivity C-reactive protein, left-ventricular ejection fraction, known kidney dysfunction, and cardiogenic shock with an odds ratio (95% confidence interval) of 2.26 (1.18-4.51), p = 0.014. Finally, we observed increasing predictive values in a subgroup during the first day of hospitalization suggesting that assessment of NGAL should be delayed for optimal prognostic purposes.

Background: Among chronic kidney disease (CKD) patients, baseline neutrophil gelatinase-associated lipocalin (NGAL) may reflect the severity of renal impairment. No data exists on serial changes in serum NGAL levels in CKD patients before and after percutaneous coronary intervention (PCI)., Objectives: To evaluate serial serum NGAL levels relation to contrast induced acute kidney injury (CI-AKI) following PCI., Methods: The study included 58 patients with CKD who underwent elective PCI. Plasma NGAL measurements were performed before (pre-NGAL) and 24 hours following (post-NGAL) PCI. Patients were followed for CI-AKI and changes in NGAL levels. Receiver operator characteristic identified the optimal sensitivity and specificity for pre-NGAL levels compared with post-NGAL for patients with CI-AKI., Results: Overall CI-AKI incidence was 33%. Both pre-NGAL (172 vs. 119 ng/ml, P < 0.001) and post-NGAL (181 vs. 121 ng/ml, P < 0.001) levels were significantly higher in patients with CI-AKI, but no significant changes were detected. Pre-NGAL levels were similar to post-NGAL levels in predicting CI-AKI (area under the curve 0.753 vs. 0.745). Optimal cutoff value for pre-NGAL was 129 ng/ml (sensitivity of 73% and specificity of 72%, P < 0.001). Post-NGAL levels > 141 ng/ml were independently associated with CI-AKI (hazard ratio [HR] 4.86, 95% confidence interval [95%CI] 1.34-17.64, P = 0.02) with a strong trend for post-NGAL levels > 129 ng/ml (HR 3.46, 95%CI 1.23-12.81, P = 0.06)., Conclusions: In high-risk patients, pre-NGAL levels may predict CI-AKI. Further studies on larger populations are needed to validate the use of NGAL measurements in CKD patients.

Background: We aimed to test the differences in peak VO 2 between males and females in patients diagnosed with heart failure (HF), using combined stress echocardiography (SE) and cardiopulmonary exercise testing (CPET)., Methods: Patients who underwent CPET and SE for evaluation of dyspnea or exertional intolerance at our institution, between January 2013 and December 2017, were included and retrospectively assessed. Patients were divided into three groups: HF with preserved ejection fraction (HF p EF), HF with mildly reduced or reduced ejection fraction (HF mr EF/HF r EF), and patients without HF (control). These groups were further stratified by sex., Results: One hundred seventy-eight patients underwent CPET-SE testing, of which 40% were females. Females diagnosed with HF p EF showed attenuated increases in end diastolic volume index ( P = 0.040 for sex × time interaction), significantly elevated E/e' ( P < 0.001), significantly decreased left ventricle (LV) end diastolic volume:E/e ratio ( P = 0.040 for sex × time interaction), and lesser increases in A-VO 2 difference ( P = 0.003 for sex × time interaction), comparing to males with HF p EF. Females diagnosed with HF mr EF/HF r EF showed diminished increases in end diastolic volume index ( P = 0.050 for sex × time interaction), mostly after anaerobic threshold was met, comparing to males with HF mr EF/HF r EF. This resulted in reduced increases in peak stroke volume index ( P = 0.010 for sex × time interaction) and cardiac output ( P = 0.050 for sex × time interaction)., Conclusions: Combined CPET-SE testing allows for individualized non-invasive evaluation of exercise physiology stratified by sex. Female patients with HF have lower exercise capacity compared to men with HF. For females diagnosed with HF p EF, this was due to poorer LV compliance and attenuated peripheral oxygen extraction, while for females diagnosed with HF mr EF/HF r EF, this was due to attenuated increase in peak stroke volume and cardiac output. As past studies have shown differences in clinical outcomes between females and males, this study provides an essential understanding of the differences in exercise physiology in HF patients, which may improve patient selection for targeted therapeutics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Rozenbaum, Granot, Sadeh, Havakuk, Arnold, Shimiaie, Ghermezi, Barak, Ben Gal, Shacham, Keren, Topilsky and Laufer-Perl.)

Background: An association between excessively prolonged QT and ventricular arrhythmia in patients with ST-elevation myocardial infarction has been described; however, the QT dynamics, characterization, and long-term predictive value are not well known., Objective: To characterize QT interval dynamics in patients undergoing ST elevation myocardial infarction (STEMI) and determine its association with mortality., Methods: A retrospective analysis of 4,936 consecutive patients, hospitalized for STEMI between 01/2013-12/2021. Patients with less than three electrocardiograms (ECGs) during index hospitalization were excluded. Baseline demographics, cardiovascular history, clinical risk factors, treatment measures, laboratory results, and mortality data were retrieved from the hospital's electronic medical records., Results: We included 1,054 patients and 5,021 ECGs in our cohort with a median follow-up of 6 years [interquartile range (IQR) 4.3-7.4 years]. The QT was longer in women in comparison to men (428.6 ms ± 33.4 versus 419.8 ms ± 32.52, P -value = 0.001). QT prolongation was greater in females, elderly patients, and patients with STEMI caused by occlusion of the left anterior descending (LAD) coronary artery. We determined QT cutoff to be 445 ms. This value of QT divided our cohort upon arrival into a long QT group (217 patients, 26% of the cohort) and a "normal" QT group (835 patients, 74% of the cohort). The long QT group experienced an increase in combined short and long terms all-cause mortality. The QT upon arrival, on day 2 of hospitalization, and before discharge from the hospital, correlated with long-term mortality., Conclusion: QT duration is often prolonged during STEMI; this prolongation is associated with increased mortality and adverse events. Gender is an important mediator of QT dynamics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mann, Moses, Yesaulov, Hochstadt, Granot, Rosso, Shacham and Chorin.)

Introduction: Acute kidney injury (AKI) is a common and serious complication in critically ill patients, particularly those with ST-elevation myocardial infarction (STEMI). Mechanical ventilation (MV) is often needed when respiratory deterioration occurs and is continuously associated with higher risk for AKI. Whether MV is an independent predictor for AKI in STEMI patients has not been evaluated before. We aimed to determine a potential association between MV and the occurrence of AKI in STEMI patients., Methods: A single-center retrospective cohort in a tertiary referral hospital. We evaluated consecutive patients that were admitted to the cardiac intensive care unit with acute STEMI between 2008 and 2019. Patients were divided into groups based on their need for MV upon admission. To minimize baseline differences between the two groups, propensity matching was performed. The primary outcome was the occurrence of AKI after intubation and secondary outcomes included severe AKI (&gt;2 times the baseline creatinine) and renal recovery., Results: 2,929 patients were included and of them, 143 (5%) were intubated. After using the propensity matching, 138 pairs were available for analysis with similar demographic and clinical characteristics. MV was a predictor for AKI (Table 2, odds ratio [OR]: 3.3, 95% confidence interval [CI]: 1.9-5.6) and severe AKI (OR: 6.3, 95% CI: 2.5-16). These results remained significant after adjusting for the occurrence of a new heart failure and bleeding. Early or partial renal recovery was similar between the groups., Conclusion: MV is independently associated with the occurrence of AKI and severe AKI. The possible mechanism might be temporary, reflected by similar rates of renal recovery., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Primary percutaneous coronary intervention (PCI) is the preferred treatment strategy for patients with ST-elevation myocardial infarction (STEMI); however, its efficacy remains unclear in very older adult patients with STEMI., Methods: This retrospective single-center observational study included 530 patients aged &gt;75 years admitted to Tel Aviv Sourasky Medical Center with a diagnosis of acute STEMI. Primary PCI was performed for patients with symptoms ≤12 hours in duration, while the other patients were conservatively treated. We evaluated 30-day mortality and complications occurring during hospitalization based on data from patient records., Results: Among the study patients, only 28/530 (5%) were conservatively treated. In-hospital complications, including the use of inotropes or intra-aortic balloon counterpulsation and the need for mechanical ventilation, did not differ significantly between the groups. The only parameter that showed a trend toward significance was the incidence of heart failure during hospitalization (p=0.042). The risk for 30-day mortality was substantially higher in the conservative treatment group than in the invasive treatment group (27% vs. 10%; p = 0.02)., Conclusion: Our data suggested that despite concerns regarding the safety of the primary PCI strategy in the older adult STEMI population, this treatment strategy was associated with a survival benefit.

Patients undergoing percutaneous coronary interventions (PCIs) are prone to a wide range of complications; one complication that is constantly correlated with a worse prognosis is acute kidney injury (AKI). Gender as an independent risk factor for said complications has raised some interest; however, studies have shown conflicting results so far. We aimed to investigate the possible relation of gender to the occurrence of AKI in STEMI patients undergoing PCI. This retrospective observational study cohort included 2967 consecutive patients admitted with STEMI between the years 2008 and 2019. Their renal outcomes were assessed according to KDIGO criteria (AKI serum creatinine ≥ 0.3 mg/dL from baseline within 48 h from admission), and in-hospital complications and mortality were reviewed. Our main results show that female patients were older (69 vs. 60, p < 0.001) and had higher rates of diabetes (29.2% vs. 23%, p < 0.001), hypertension (62.9% vs. 41.3%, p < 0.001), and chronic kidney disease (26.7% vs. 19.3%, p < 0.001). Females also had a higher rate of AKI (12.7% vs. 7.8%, p < 0.001), and among patients with AKI, severe AKI was also more prevalent in females (26.1% vs. 14.5%, p = 0.03). However, in multivariate analyses, after adjusting for the baseline characteristics above, the female gender was a non-significant predictor for AKI (adjusted OR 1.01, 95% CI 0.73−1.4, p = 0.94) or severe AKI (adjusted OR 1.65, 95% CI 0.80−1.65, p = 0.18). In conclusion, while females had higher rates of AKI and severe AKI, gender was not independently associated with AKI after adjusting for other confounding variables. Other comorbidities that are more prevalent in females can account for the difference in AKI between genders.

Mortality from acute ST elevation myocardial infarction (STEMI) was significantly reduced with the introduction of percutaneous catheterization intervention (PCI) but remains high in patients who develop acute kidney injury (AKI). Previous studies found overweight to be protective from mortality in patients suffering from STEMI and AKI separately but not as they occur concurrently. This study aimed to establish the relationship between AKI and mortality in STEMI patients after PCI and whether body mass index (BMI) has a protective impact. Between January 2008 and June 2016, two thousand one hundred and forty-one patients with STEMI underwent PCI and were admitted to the Tel Aviv Medical Center Cardiac Intensive Care Unit. Their demographic, laboratory, and clinical data were collected and analyzed. We compared all-cause mortality in patients who developed AKI after PCI for STEMI and those who did not. In total, 178 patients (10%) developed AKI and had higher mortality (p < 0.001). Logistic regression analysis was performed to determine the relationship between AKI, BMI, and mortality. AKI was significantly associated with both 30-day and overall mortality, while BMI had a significant protective effect. Survival analysis found a significant difference in 30-day and overall survival between patients with and without AKI with a significant protective effect of BMI on survival at 30 days. AKI presents a major risk for mortality and poor survival after PCI for STEMI, yet a beneficial effect of increased BMI modifies it.

Recent practice guidelines recommended the use of new stress, functional, and damage biomarkers in clinical practice to prevent and manage acute kidney injury (AKI). Biomarkers are one of the tools used to define various AKI phenotypes and provide prognostic information regardless of an acute decline in renal function. We investigated the incidence and possible implications of AKI phenotypes among ST elevation myocardial infarction patient treated with primary coronary intervention. We included 281 patients with STEMI treated with PCI. Neutrophil gelatinase associated lipocalin (NGAL) was utilized to determine structural renal damage and functional AKI was determined using the KDIGO criteria. Patients were stratified into four AKI phenotypes: no AKI, subclinical AKI, hemodynamic AKI, and severe AKI. Patients were assessed for in-hospital adverse events (MACE). A total of 46 patients (44%) had subclinical AKI, 17 (16%) had hemodynamic AKI, and 42 (40%) had severe AKI. We observed a gradual and significant increase in the occurrence of MACE between the groups being highest among patients with severe AKI (10% vs. 19% vs. 29% vs. 43%; p < 0.001). In a multivariable regression model, any AKI phenotype was independently associated with MACE with an odds ratio of 4.15 (95% CI 2.1−8.3, p < 0.001,) for subclinical AKI, 4.51 (95% CI 1.61−12.69; p = 0.004) for hemodynamic AKI, and 12.9 (95% CI 5.59−30.1, p < 0.001) for severe AKI. In conclusion, among STEMI patients, AKI is a heterogeneous condition consisting of distinct phenotypes, addition of novel biomarkers may overcome the limitations of sCr-based AKI definitions to improve AKI phenotyping and direct potential therapies.

Transcatheter aortic valve replacement (TAVR) has become the mainstay of treatment for patients with severe AS. Since the TAVR population and patients’ outcomes have dramatically changed over the last decade, updated data regarding contemporary practice and trends are pertinent to clinical use. We performed a retrospective observational analysis of consecutive patient who underwent TAVR for symptomatic severe AS between the years 2009 and 2021 in a single high-volume center. Patients were divided into four equal time groups based on the procedure date (2009−2012, 2013−2015, 2016−2018 and 2019−2021). A total of 1988 patients were included in this study and divided into four groups, with 321, 482, 565 and 620 patients in groups 1−4, respectively. Significant trends were seen in baseline characteristics of a few parameters, including lower age, lower procedural risk and reduced rates of comorbidity (p for trend < 0.0001 for all factors mentioned above). A shift was seen in the procedural technique with lower balloon pre-dilatation and higher device success rates (p for trend < 0.0001). The post-procedural period changed over the years with fewer pacemaker placements (p < 0.0001) and reduced rates of AKI and post-procedural bleed (p value 0.02 and <0.0001, respectively). Furthermore, overall hospital stay was shortened from 7 ± 7.1 days to 2.3 ± 1.7 (p < 0.0001). Finally, patient follow up revealed reduced mortality rates at 30 days (p < 0.0001) and 1 year (p = 0.013). Multivariate regression revealed that a late implantation date was an independent protector from mortality (HR 0.84, p = 0.002). In conclusion, our study demonstrated that TAVR has become a safer practice over the years with reduced rates of morbidity and mortality.

Physicians use Holter electrocardiography (ECG) monitoring to evaluate some patients with syncope in the internal medicine department. We questioned whether Holter ECG should be used in the presented setting. Included were all consecutive patients admitted with syncope to one of our nine internal medicine departments who had completed a 24 h Holter ECG between 2018 and 2021. A diagnostic Holter was defined as one which altered the patient’s treatment and met ESC/ACC/AHA diagnostic criteria. A total of 478 Holter tests were performed for syncope evaluation during admission to an internal medicine department in the study period. Of them, 25 patients (5.2%) had a diagnostic Holter finding. Sinus node dysfunction was the most frequent diagnostic recording (13 patients, 52%). In multivariant analysis, predictors for diagnostic Holter were older age (OR 1.35, 95% CI 1.08−1.68), heart failure with preserved ejection fraction (OR 4.1, 95% CI 1.43−11.72), and shorter duration to Holter initiation (OR 0.73, 95% CI 0.56−0.96). There was a positive correlation between time from admission to Holter and hospital stay, r(479) = 0.342, p < 0.001. Our results suggest that completing a 24 h Holter monitoring during admission to the internal medicine department should be restricted to patients with a high pre-test probability to avoid overuse and possible harm.

Elevated concentrations of C-reactive protein (CRP) early during an acute coronary syndrome (ACS) may reflect the magnitude of the inflammatory response to myocardial damage and are associated with worse outcome. However, the routine measurement of both CRP and cardiac troponin simultaneously in the setting of ST-segment myocardial infarction (STEMI) is not used broadly. Here, we sought to identify and characterize individuals who are prone to an elevated inflammatory response following STEMI by using a combined CRP and troponin test (CTT) and determine their short- and long-term outcome. We retrospectively examined 1186 patients with the diagnosis of acute STEMI, who had at least two successive measurements of combined CRP and cardiac troponin (up to 6 h apart), all within the first 48 h of admission. We used Chi-Square Automatic Interaction Detector (CHAID) tree analysis to determine which parameters, timing (baseline vs. serial measurements), and cut-offs should be used to predict mortality. Patients with high CRP concentrations (above 90th percentile, >33 mg/L) had higher 30 day and all-cause mortality rates compared to the rest of the cohort, regardless of their troponin test status (above or below 118,000 ng/L); 14.4% vs. 2.7%, p < 0.01. Furthermore, patients with both high CRP and high troponin levels on their second measurement had the highest 30-day mortality rates compared to the rest of the cohort; 21.4% vs. 3.7%, p < 0.01. These patients also had the highest all-cause mortality rates after a median follow-up of 4.5 years compared to the rest of the cohort; 42.9% vs. 12.7%, p < 0.01. In conclusion, serial measurements of both CRP and cardiac troponin might detect patients at increased risk for short-and long-term mortality following STEMI. We suggest the future use of the combined CTT as a potential early marker for inflammatory-prone patients with worse outcomes following ACS. This sub-type of patients might benefit from early anti-inflammatory therapy such as colchicine and anti-interleukin-1ß agents.

Background: Acute kidney injury (AKI) is a frequent complication in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). Identification of different AKI recovery patterns may improve patient prognostic stratification. We investigated the clinical relevance of AKI recovery patterns among STEMI patients undergoing PCI. Methods: A retrospective study of 2943 STEMI patients undergoing PCI. The incidence of renal impairment, in-hospital complications, short and long-term mortality, were compared between patients without AKI, with early recovery defined as a return to baseline creatinine within 72 h, and no AKI recovery/delayed recovery defined as all other AKI cases. Results: A total of 255 (8.7%) patients developed AKI, of whom 124/255 (49%) patients had an early recovery, whereas 131/255 (51%) had no AKI recovery/delayed recovery. Patients without recovery were more likely to have in-hospital complications and higher long-term mortality (36.64% vs. 7.25%%; p < 0.001). In a multivariable regression model, the mortality hazard ratio (HR) for long term mortality remained significant for patients with no/delayed recovery AKI (HR 7.76, 95% CI 4.69 to 12.86, p < 0.001), and a strong trend among patients with resolving AKI (HR 2.09, 95% CI 0.933−4.687, p = 0.071). Conclusions: Among STEMI patients undergoing PCI, the recovery pattern of AKI is a valuable prognostic marker.

Background: Elevated serum neutrophil gelatinase-associated lipocalin (NGAL) levels reflect both inflammatory reactions and renal tubular injury. Recently, associations with endothelial dysfunction and plaque instability were also proposed. We investigated the prognostic utility of elevated NGAL levels for renal and clinical outcomes among ST-segment elevation myocardial infarction (STEMI) patients treated with primary coronary intervention (PCI). Methods: We performed a prospective, observational, open-label trial. High NGAL was defined as values within the third tertile (>66 percentile). Results: A total of 267 patients were included (mean age 66 ± 14 years, 81% males). Short-term adverse outcomes were consistently increased in the high NGAL group with more acute kidney injury, lower mean left ventricular ejection fraction, higher 30-day mortality, and higher incidence for the composite outcome of major adverse cardiac events (MACE). In a multivariate logistic regression model, high NGAL emerged as a strong and independent predictor for MACE (OR 2.07, 95% CI 1.15−3.73, p = 0.014). Conclusions: Among STEMI patients undergoing primary PCI, elevated NGAL levels are associated with adverse renal and cardiovascular outcomes, independent of traditional inflammatory markers. Further studies are needed to assess the potentially unique role of NGAL in cardio−renal interactions.

Background: The European Society of Cardiology (ESC) guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation (non-ST-segment elevation myocardial infarction [NSTEMI]) has recommended immediate (<2 h) percutaneous coronary intervention (PCI) in very-high risk patients and early (<24 h) PCI in high-risk patients., Hypothesis: To examine the ESC NSTEMI guidelines adherence in a nationwide survey in Israel using the Acute Coronary Syndrome Israeli Survey (ACSIS). We hypothesized that adherence to the guidlines' recommnded PCI timing in NSTEMI pateints will be inadequate, partly due to the inconsistent evidence regarding its effect on clinical outcomes., Methods: All NSTEMI patients who underwent PCI during the ACSIS surveys in 2016 and 2018 were included in the analysis., Results: Out of 1793 NSTEMI patients, 1643 (92%) patients underwent PCI, and door to balloon time was documented in 1078 of them. One hundred and fifty-six (14.5%) patients and 922 (85.5%) patients were defined as very high-risk and high-risk NSTEMI patients, respectively. Of the very high-risk NSTEMI patients, only 10 (6.4%) underwent immediate coronary angiography, and 50 (32.1%) underwent early coronary angiography. Acute heart failure 139 (89.1%) was the main reason for including NSTEMI patients in the very high-risk category. Of the high-risk patients, early coronary angiography was performed in only 405 (43.9%) patients. Patients in whom coronary angiography was postponed were older and had more comorbidities., Conclusions: Despite guidelines recommendations for immediate and early PCI in very high-risk and high-risk NSTEMI patients, respectively, most patients do not undergo immediate or early PCI according to contemporary guidelines. Further studies are needed to better understand the reasons for guidelines' nonadherence in those high-risk patients., (© 2022 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Background: Among patients with rhabdomyolysis, the leakage of intracellular skeletal muscle content such as creatine phosphokinase (CPK) into the bloodstream has been associated with an increased risk of acute kidney injury (AKI). We evaluated the possible relationship between serum CPK levels and AKI occurrence among patients with myocyte injury secondary to ST-elevation myocardial infarction (STEMI)., Methods: We retrospectively included 2794 patients with STEMI. Patients were stratified according to peak serum CPK levels into mild (<1000 U/L, n = 1603), moderate (1000-5000 U/L, n = 1111), and severe (>5000 U/L, n = 80) categories. The occurrence of AKI was defined by the KDIGO criteria as an increase in serum creatinine (sCR) ≥0.3 mg/dL within 48 h following PCI. The predictive value of CPK for the risk of AKI occurrence was assessed using multivariate logistic regression models., Results: The overall occurrence of AKI was 10.4%. Incidence of AKI showed a gradual increase between patients with mild, moderate, and severe serum CPK level elevations (7.8% vs. 11% vs. 26% respectively; p < 0.001). In multivariate logistic regression models, both moderate or higher (OR 1.6, 95% CI 1.1-2.2; p = 0.01) and severe (OR 2.8 95% CI 1.4-5.6; p = 0.004) serum CPK level elevations were independently associated with AKI., Conclusions: Among STEMI patients, elevated CPK levels were associated with AKI. This association is presumably independent; however, it remains unclear whether it is due to direct toxic (myoglobin-related) or hemodynamic effects (poor left ventricular function). Further studies are required to reveal the underlying mechanism.

Limited and inconsistent data are present regarding the importance of the time delay between symptom onset and balloon inflation in ST-segment elevation myocardial infarction (STEMI) patients. We aimed to investigate the possible influence of prolonging pain-to-balloon times (PBT) on in-hospital outcomes and mortality in a large cohort of patients with STEMI undergoing primary percutaneous coronary intervention. We retrospectively studied 2,345 STEMI patients (age 61 ± 13 years, 82% men) who underwent primary percutaneous coronary intervention. Patients were stratified according to PBT into 3 groups: ≤120 minutes, 121 to 360 minutes, and >360 minutes. Patients' records were assessed for the occurrence of in-hospital complications, 30-day, and 1-year mortality. Of the 2,345 study patients, 36% had PBT time ≤120 minutes, 40% had PBT of 121 to 360 minutes and 24% had PBT time >360 minutes. The major part of the total PBT (average 358 minutes) was caused by the time interval from symptom onset to hospital arrival, namely, pain-to-door time (average 312 minutes) in all 3 groups. Longer PBT was associated with a lower left ventricular ejection fraction, higher incidence of in-hospital complications, and higher 30-day mortality. In 2 multivariate cox regression models, a per-hour increase in PBT (hazard ratio 1.03 [95% confidence interval 1.00 to 1.06], p = 0.039) as well as PBT >360 minutes (hazard ratio 1.6 [95% confidence interval 1.1 to 2.5], p = 0.04) were both independently associated with an increased risk for 1-year mortality. In conclusion, PBT may be an accurate and independent marker for adverse events, pointing to the importance of coronary reperfusion as early as possible based on the onset of pain., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

C-reactive protein velocity (CRPv), defined as the change in wide-range CRP concentration divided by time, is an inflammatory biomarker associated with increased morbidity and mortality in patients with ST elevation myocardial infarction (STEMI) treated with primary percutaneous intervention (PCI). However, data regarding CRPv association with echocardiographic parameters assessing left ventricular systolic and diastolic function is lacking. Echocardiographic parameters and CRPv values were analyzed using a cohort of 1059 patients admitted with STEMI and treated with primary PCI. Patients were stratified into tertiles according to their CRPv. A receiver operating characteristic (ROC) curve was used to evaluate CRPv optimal cut-off values for the prediction of severe systolic and diastolic dysfunction. Patients with high CRPv tertiles had lower left ventricular ejection fraction (LVEF) (49% vs. 46% vs. 41%, respectively; p < 0.001). CRPv was found to independently predict LVEF ≤ 35% (HR 1.3 CI 95% 1.21-1.4; p < 0.001) and grade III diastolic dysfunction (HR 1.16 CI 95% 11.02-1.31; p = 0.02). CRPv exhibited a better diagnostic profile for severe systolic dysfunction as compared to CRP (area under the curve 0.734 ± 0.02 vs. 0.608 ± 0.02). In conclusion, For STEMI patients treated with primary PCI, CRPv is a marker of both systolic and diastolic dysfunction. Further larger studies are needed to support this finding.

Background: Among ST segment elevation myocardial infarction (STEMI), early hemodynamic changes may result in acute kidney injury (AKI) even prior to primary percutaneous coronary intervention (PCI); however, no information to date is present regarding the association between pain-to-balloon time (PBT) and AKI. We evaluated whether PBT predicts the risk of AKI among STEMI patients undergoing primary PCI., Methods: Medical records of 2,343 STEMI patients undergoing primary PCI were reviewed. Patients were stratified by PBT into 3 groups: ≤120, 121-360, and >360 min. Patients' records were assessed for the occurrence of AKI (defined by the KDIGO criteria as serum creatinine (sCr) elevation ≥0.3 mg/dL within 72 h after admission)., Results: Mean age was 61 ± 13 years, and 1,919 (82%) were male. Patients having longer PBT had more AKI complicating the course of STEMI (7% vs. 8% vs. 13%, p < 0.001) and had significantly higher sCr changes throughout hospitalization (0.08 mg/dL vs. 0.11 mg/dL vs. 0.17 mg/dL p < 0.001). In a multivariable logistic regression model, each 1-h increase in PBT was independently associated with a 2.2% increase in risk for AKI (odds ratio 1.022, 95% confidence interval: 1.01-1.04, p = 0.02)., Conclusion: Longer PBT may be an independent marker for the development of AKI in STEMI patients undergoing primary., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background: The extent and impact of obesity as an isolated risk factor for coronary artery disease is not clear since co-morbidities serve as confounders and may mask this association., Objectives: To examine whether obesity is associated with extensive coronary artery disease among metabolically healthy patients presenting with ST-elevation myocardial infarction (STEMI) and to explore the outcomes according to body mass index (BMI)., Methods: We stratified STEMI patients who had a metabolically healthy phenotype and available weight and height data according to BMI: 18.5-25 kg/m² (lean), 25.01-30 kg/m² (overweight), and > 30 kg/m² (obese)., Results: Overall 381 patients were included, 42% lean, 41% overweight, and 17% obese. Patients with increased BMIs had higher levels of low-density proteins and triglycerides (P < 0.05). Obese patients presented with the lowest rates of multi-vessel disease (12.9% vs. 22.9% for overweight and 28% for lean). In a univariable analysis, obese patients were 60% less likely to be diagnosed with multi-vessel disease (odds ratio 0.4, 95% confidence interval 0.2-0.9, P = 0.021) compared to lean patients. The association remained significant in a multivariable model adjusted for baseline characteristics (P = 0.029). There were no differences in 30-day or long-term mortality (median follow-up 3.2 years) among the groups (P > 0.1 for all comparisons)., Conclusions: Metabolically healthy phenotype obesity was associated with lower rates of multi-vessel disease despite higher levels of triglycerides. However, this association did not translate into increased mortality.

Background: Tricuspid regurgitation (TR) is associated with adverse prognosis in various patient populations, but currently no data is available about the prevalence and prognostic implication of TR in ST-segment elevation myocardial infarction (STEMI) patients., Objectives: To investigate the possible implication of TR among STEMI patients., Methods: We conducted a retrospective study of STEMI patients undergoing primary percutaneous coronary intervention (PCI) and its relation to major clinical and echocardiographic parameters. Patient records were assessed for the prevalence and severity of TR, its relation to the clinical profile, key echocardiographic parameters, in-hospital outcomes, and long-term mortality. Patients with previous myocardial infarction or known previous TR were excluded., Results: The study included 1071 STEMI patients admitted between September 2011 and May 2016 (age 61 ± 13 years; predominantly male). A total of 205 patients (19%) had mild TR while another 32 (3%) had moderate or greater TR. Patients with significant TR demonstrated worse echocardiographic parameters, were more likely to have in-hospital complications, and had higher long-term mortality (28% vs. 6%; P < 0.001). Following adjustment for significant clinical and echocardiographic parameters, mortality hazard ratio of at least moderate to severe TR remained significant (hazard ratio 2.44; 95% confidence interval 1.06-5.62; P = 0.036) for patients with moderate-severe TR., Conclusions: Among STEMI patients after primary PCI, the presence of moderate-severe TR was independently associated with adverse outcomes and significantly lower survival rate.

Background: Hepatic injury secondary to congestive heart failure is well described, however, only limited data exist about the possible impact of acute cardiac dysfunction on the liver. We aimed to explore the possible cardio-hepatic interaction in patients with myocardial infarction., Material and Methods: A single-center retrospective cohort study of 1339 ST elevation myocardial infarction (STEMI) patients who underwent primary coronary intervention between June 2012 to June 2019. Echocardiographic examinations were performed to assess left ventricular ejection fraction (LVEF) and central venous pressure (CVP). Patients were stratified into four groups by their LVEF and CVP levels: LVEF ≥ 45%, and CVP ≤ 10 mm/Hg ( n = 853), LVEF < 45% with CVP ≤ 10 mm/Hg ( n = 364), EF ≥ 45%, with CVP > 10 mm/Hg ( n = 61), and LVEF < 45% with CVP > 10 mm/Hg ( n = 61). Patients were evaluated for baseline and peak liver enzymes including alanine transaminase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), and bilirubin., Results: Greater severity of cardiac dysfunction was associated with worse elevation of liver enzymes. We found a graded increase in mean levels of maximal ALT, first and maximal ALP, and first and maximal GGT values. Using propensity score matching to estimate the impact of cardiac dysfunction on liver injury, we chose patients with the worst cardiac function parameters: (LVEF < 45% and CVP >10 mm/Hg; n = 61) and compared them to matched patients with better cardiac function ( n = 45). We found a significantly higher level of maximal ALT, first and maximal ALP, and GGT values in the group with the worst cardiac function parameters ( p < 0.05)., Conclusions: Among patients with STEMI, the combination of decreased LVEF and venous congestion was associated with liver enzymes elevation suggesting a possible cardio-hepatic syndrome.

Background: The risk of contrast-induced acute kidney injury (CI-AKI) following coronary intervention is particularly high among patients with chronic kidney disease (CKD). Among these patients, baseline neutrophil gelatinase-associated lipocalin (NGAL), a marker of tubular damage, reflects the severity of renal impairment. We evaluated whether the baseline serum NGAL level may be a marker for the development of CI-AKI following percutaneous coronary intervention (PCI)., Methods: Eighty-eight CKD patients treated with PCI were included. Serum NGAL levels were drawn upon hospital admission. Receiver operator characteristic (ROC) methods were used to identify the optimal sensitivity and specificity for the observed NGAL level compared with the estimated glomerular filtration rate (eGFR) calculated for patients with CI-AKI., Results: Overall CI-AKI incidence was 43%. Baseline serum NGAL levels were significantly higher in patients with CI-AKI than in patients without CI-AKI (150 vs. 103 ng/mL, p < 0.001). According to the ROC curve, baseline NGAL levels performed better than eGFR to predict CI-AKI (AUC 0.753 vs. 0.604), with the optimal cutoff value for baseline NGAL to predict CI-AKI being 127 ng/mL (sensitivity of 68% and specificity of 68%, p < 0.001). In a multivariate logistic regression model, the NGAL level >127 ng/mL ng/mL was independently associated with CI-AKI (HR 9.84, 95% CI: 1.96-40.3; p = 0.01)., Conclusion: Baseline serum NGAL levels in CKD patients may identify a high-risk population for CI-AKI following PCI. Further studies on larger populations are required to validate the potential utility of NGAL measurements in monitoring specific CKD-associated conditions.

Background: Tricuspid regurgitation (TR) is associated with adverse prognosis in various patient populations but currently no data is available about the prevalence and prognostic implication of TR in ST-segment elevation myocardial infarction (STEMI) patients., Objectives: To investigate the possible implication of TR among STEMI patients., Methods: We conducted a retrospective study of STEMI patients undergoing primary percutaneous coronary intervention (PCI), and its relation to major clinical and echocardiographic parameters. Patient records were assessed for the prevalence and severity of TR as well as the relation to the clinical profile, key echocardiographic parameters, in-hospital outcomes, and long-term mortality. Patients with previous myocardial infarction or known previous TR were excluded., Results: The study included 1071 STEMI patients admitted between September 2011 and May 2016 (age 61 ± 13 years; predominantly male). A total of 205 patients (19%) had mild TR while another 32 (3%) had moderate or greater TR. Patients with significant TR demonstrated worse echocardiographic parameters, were more likely to have in-hospital complications, and had higher long-term mortality (28% vs. 6%, P < 0.001). Following adjustment for significant clinical and echocardiographic parameters, mortality hazard ratio of at least moderate to severe TR remained significant (2.44, 95% confidence interval 1.06-5.6, P = .036) for patients with moderate to severe TR., Conclusions: Among STEMI patients after primary PCI, the presence of moderate to severe TR was independently associated with adverse outcomes and significantly lower survival rate.

Background: We aimed to describe the characteristics and in-hospital outcomes of ST-segment elevation myocardial infarction (STEMI) patients during the Covid-19 era., Methods: We conducted a prospective, multicenter study involving 13 intensive cardiac care units, to evaluate consecutive STEMI patients admitted throughout an 8-week period during the Covid-19 outbreak. These patients were compared with consecutive STEMI patients admitted during the corresponding period in 2018 who had been prospectively documented in the Israeli bi-annual National Acute Coronary Syndrome Survey. The primary end-point was defined as a composite of malignant arrhythmia, congestive heart failure, and/or in-hospital mortality. Secondary outcomes included individual components of primary outcome, cardiogenic shock, mechanical complications, electrical complications, re-infarction, stroke, and pericarditis., Results: The study cohort comprised 1466 consecutive acute MI patients, of whom 774 (53%) were hospitalized during the Covid-19 outbreak. Overall, 841 patients were diagnosed with STEMI: 424 (50.4%) during the Covid-19 era and 417 (49.6%) during the parallel period in 2018. Although STEMI patients admitted during the Covid-19 period had fewer co-morbidities, they presented with a higher Killip class (p value = .03). The median time from symptom onset to reperfusion was extended from 180 minutes (IQR 122-292) in 2018 to 290 minutes (IQR 161-1080, p < .001) in 2020. Hospitalization during the Covid-19 era was independently associated with an increased risk of the combined endpoint in the multivariable regression model (OR 1.65, 95% CI 1.03-2.68, p value = .04). Furthermore, the rate of mechanical complications was four times higher during the Covid-19 era (95% CI 1.42-14.8, p-value = .02). However, in-hospital mortality remained unchanged (OR 1.73, 95% CI 0.81-3.78, p-value = .16)., Conclusions: STEMI patients admitted during the first wave of Covid-19 outbreak, experienced longer total ischemic time, which was translated into a more severe disease status upon hospital admission, and a higher rate of in-hospital adverse events, compared with parallel period., Competing Interests: The authors have declared that no competing interests exist.

Elevated low-density lipoprotein (LDL) cholesterol is one of the leading causes of cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce LDL cholesterol levels with subsequent reductions in cardiovascular morbidity. Elevated aldosterone levels are also associated with a greater risk of cardiovascular morbidity. There are currently no published data on the impact of PCSK9 inhibitor monotherapy on the secretion of aldosterone. The aim of this study was to examine the effect of monotherapy with the PSCK9 inhibitor evolocumab on the lipid profile and aldosterone secretion level in high-risk cardiovascular patients. Lipid profile, sodium, potassium, aldosterone, cortisol, plasma renin activity, and adrenocorticotropic hormone (ACTH) levels were analyzed at baseline and after 3 months of evolocumab therapy. Each participant underwent a 250 mcg ACTH stimulation test upon study entry. Eight women and seven men were included in the study. Their median total cholesterol, LDL cholesterol, lipoprotein (a), apolipoprotein B100, and baseline and stimulated aldosterone levels were significantly lower after 3 months of evolocumab therapy. These heretofore unreported findings indicate that reductions in unstimulated and stimulated aldosterone secretion under evolocumab therapy could be associated with reductions in cardiovascular events, a possibility that warrants further investigation.

Background: Acute kidney injury (AKI) and anemia have been extensively studied in ST-elevation myocardial infarction (STEMI), yet the precise nature of their reciprocal relationship has not been elucidated in STEMI patients., Methods: We performed a retrospective analysis of 2096 consecutive patients admitted for STEMI between January 2008 and December 2018 and treated with primary coronary intervention. Patients were stratified into four groups according to the presence of baseline anemia and occurrence of AKI: without anemia or AKI, baseline anemia without AKI, AKI without baseline anemia and acute cardiorenal anemia syndrome (CRAS), defined as the occurrence of AKI in patients with baseline anemia. Patients' medical records were reviewed for in-hospital complications, 30-day and long-term mortality., Results: The mean age was 61 ± 13 years and 1682 patients (80%) were men. Ten percent of patients had baseline anemia without AKI, 7% had AKI without baseline anemia and 3% were classified as CRAS. We found increments between the four groups for occurrence of new onset atrial fibrillation and heart failure rates, presence of a critical state, and both 30-day and long-term mortality (P < 0.001 for all). Logistic regression models demonstrated that as compared to AKI alone, CRAS was associated with a higher risk for long-term mortality (HR 10.49; 95% CI 6.5-17.1) as compared to anemia (HR 3.32, 95% CI 2.1-5.2) and AKI (HR 7.71, 95% CI 5.1-11.7) alone (P < 0.001 for all)., Conclusions: Among STEMI patients, the interaction between anemia and AKI is associated with worse short and long-term outcomes and reflects the reciprocity of cardiac and renal exacerbations., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background. High-grade AV block (HGAVB) is a life-threatening condition. Acute kidney injury (AKI) which is usually caused by renal hypo-perfusion is associated with adverse outcomes. We aimed to investigate the association between AKI and HGAVB. Methods. This is a retrospective cohort comparing the incidence of AKI among patients with HGAVB requiring pacemaker implantation compared with propensity score matched controls. Primary outcome was the incidence of AKI at admission. Secondary outcomes were change in creatinine levels, AKI during stay, recovery from AKI, mortality and major adverse kidney events (MAKE). Results . In total, 80 HGAVB patients were compared to 400 controls. HGAVB patients had a higher proportion of admission AKI compared to controls (36.2% versus 21.1%, RR = 1.71 [1.21-2.41], p = 0.004). Creatinine changes from baseline to admission and to maximum during hospitalization, were also higher in HGAVB ( p = 0.042 and p = 0.033). Recovery from AKI was more frequent among HGAVB patients (55.2% vs. 25.9%, RR = 2.13 [1.31-3.47], p = 0.004) with hospitalization time, MAKE and crude mortality similar ( p > 0.158). Conclusions. AKI occurs in about one third of patients admitted with HGAVB, more frequent compared to controls. Patients with AKI accompanying HGAVB were likelier to recover from AKI. Further studies to explore this relationship could aid in clinical decision making for HGAVB patients.

Background: A subgroup of patients with acute kidney injury (AKI) do not fulfil the functional criteria for AKI diagnosis but show elevated levels of new biomarkers reflecting tubular injury, suggesting that these patients suffer "subclinical AKI". We investigated the incidence and possible implications of "subclinical AKI", compared to no and clinical AKI among ST elevation myocardial infarction patients (STEMI) treated with primary coronary intervention (PCI)., Methods: We included 223 patients with STEMI treated with PCI. Neutrophil gelatinase-associated lipocalin (NGAL) was used as a marker of renal tubular damage in the absence of functional AKI, with NGAL levels ≥100 ng/mL suggesting subclinical AKI. Patients were assessed for the occurrence of in-hospital adverse outcomes., Results: Of the study patients, 45 (25%) had subclinical AKI. These patients were more likely to have left ventricular ejection fraction ≤45% (33% vs. 23%. p = 0.01), in-hospital adverse outcomes (73% vs. 48%; p = 0.005), and a combination of the two. The multivariate regression model demonstrated that subclinical AKI was independently associated with in-hospital adverse outcomes (OR 3.71, 95% CI 1.30-10.62, p = 0.02)., Conclusions: Subclinical AKI is common among STEMI patients and is independently associated with adverse outcomes, even in the absence of functional AKI.

Background: Elevated C-reactive protein (CRP) was shown to be associated with an increased risk for new-onset atrial fibrillation (AF) in ST elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI); however, the optimal time frame to measure CRP for risk stratification is not known., Objectives: To evaluate the relation between the change in CRP over time (CRP velocity [CRPv]) and new-onset AF among STEMI patients treated with primary PCI., Methods: We included 801 STEMI patients who underwent PCI between 2007 and 2017 and had their CRP measured with a wide range assay (wr-CRP) at least twice during the 24 hours after admission. CRPv was defined as the change in wr-CRP concentration (mg/l) divided by the change in time (in hours) between the two measurements. Patient medical records were reviewed for occurrence of new-onset AF., Results: New onset AF occurred in 45 patients (6%). Patients with new onset AF had significantly higher median CRPv (1.27 vs. 0.43 mg/l/h, P = 0.002). New-onset AF during hospitalization occurred in 3.4%, 4.5 %, and 9.1% of patients in the first, second and third CRPv tertiles, respectively (P for trend = 0.006). In a multivariable logistic regression, adjusting for clinical variables the odds ratios for new onset AF was 1.93 (95% confidence interval 1.0-3.59, P = 0.04) for patients in the third CRPv tertile., Conclusions: CRPv might be an independent and rapidly measurable biomarker for new-onset AF following primary PCI in STEMI patients.

Background: Most studies investigated the value of neutrophil gelatinase-associated lipocalin (NGAL) as a marker of renal tubular injury only at a single time point. We investigated the possible utilization of NGAL level dynamics for the identification of different renal injury patterns in ST-elevation myocardial infarction (STEMI) patients., Methods: Blood samples for plasma NGAL in 132 STEMI patients were drawn immediately before and 24 h following primary coronary intervention. Abnormal elevation of NGAL levels was defined using the cardiac surgery-associated NGAL score with NGAL levels ≥100 ng/mL suggesting renal tubular damage. According to NGAL levels at 0 and 24 h, patients were stratified into 3 groups: no tubular damage (NGAL <100 ng/mL in both exams), reversible tubular damage (NGAL >100 ng/mL at 0 h but <100 ng/mL at 24 h), and persistent tubular damage (NGAL >100 ng/mL at both 0 and 24 h)., Results: Mean age was 62 ± 13 years, and 78% were men. Of these patients, 29/132 (22%) demonstrated reversible tubular damage, and 36/132 (27%) persistent tubular damage. Only 13/132 patients (10%) progressed to clinical acute kidney injury during hospitalization, all of whom had persistent tubular injury. In multivariate regression model, symptom duration was independently associated with persistent tubular damage, both as continues variable (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01-1.04; p = 0.04) and for symptom duration >360 min (OR 2.66, 95% CI 1.07-6.63; p = 0.03)., Conclusions: Renal tubular damage is common among STEMI patients. Dynamic NGAL measurement may differentiate between reversible and persistent tubular damage. Further trials are needed in order to assess the complex cardiorenal interactions., (© 2021 S. Karger AG, Basel.)

Introduction: Elevated plasma levels of neutrophil gelatinase-associated lipocalin (NGAL) is a marker of tubular damage and aid in the early identification of acute kidney injury (AKI). We evaluated NGAL levels for identification of AKI superimposed on chronic kidney disease (CKD) vs. "de novo" AKI among ST elevation myocardial infarction (STEMI) patients undergoing primary coronary intervention (PCI)., Methods: 217 STEMI patients treated with PCI were prospectively included, 34 (16%) had baseline CKD. Plasma NGAL levels were drawn 24 h following PCI. Receiver-operator characteristic (ROC) methods were used to identify optimal sensitivity and specificity for the observed NGAL range in AKI patients with and without CKD., Results: Overall AKI incidence was 13%. NGAL levels were significantly higher for patients with AKI compared to no-AKI, irrespective of CKD. Different optimal cutoff value for NGAL to predict AKI were found for patients with CKD (133 ng/ml, sensitivity of 73% and specificity of 75%; AUC: 0.837, p < 0.001) and for non-CKD (104 ng/ml with sensitivity of 79% and specificity of 82%; AUC: 0.844, p < 0.001). In a multivariate logistic regression model, NGAL levels were independently associated with AKI in patients with and without CKD (HR 1.04, 95% CI: 1.01-1.08; p = 0.024; and HR 1.03, 95% CI: 1.01-1.04; p = 0.001), respectively., Conclusions: Elevated plasma NGAL levels identify patients who are at high-risk to develop AKI following primary PCI. Determining different cutoff values of plasma NGAL for de novo AKI and AKI superimposed on CKD may be necessary for accurate AKI diagnosis and risk stratification., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors. Published by Elsevier B.V.)

Subclinical hypothyroidism (SCH) is defined as an elevated serum thyroid-stimulating hormone (TSH) level with a normal serum-free thyroxine (FT4) level. SCH has been associated with an increased risk of adverse cardiovascular outcomes. We investigated possible associations of unknown SCH with in-hospital outcomes and short- and long-term all-cause mortality in a large cohort of patients with ST segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI). This retrospective, single-center observational study evaluated the TSH and FT4 levels of 1593 STEMI patients with no known history of hypothyroidism or thyroid replacement treatment who were admitted to the coronary care unit and underwent PCI between 1/2008 and 8/2017. SCH was defined as TSH levels ≥ 5 mU/mL in the presence of normal FT4 levels. Unknown SCH was detected in 68/1593 (4.2%) STEMI patients. These patients had significantly worse in-hospital outcomes compared to patients without SCH, including higher rates of acute kidney injury ( p = 0.003) and left ventricular ejection fraction ≤ 40% ( p = 0.03). Moreover, 30-day mortality ( p = 0.02) and long-term (mean 4.2 ± 2.3 years) mortality ( p = 0.007) were also significantly higher in patients with SCH. The thyroid function of STEMI patients should be routinely tested before they undergo a planned PCI procedure.

Background and Aims: Parasympathetic dysfunction is associated with increased risk for major adverse cardiovascular events (MACE). However, clinically validated biomarkers that reflect parasympathetic activity are not yet available. We sought to assess the ability of serum cholinesterase activity to predict long term survival in patients undergoing coronary angiography., Methods: We prospectively followed 1002 consecutive patients undergoing clinically indicated coronary angiography (acute coronary syndrome or stable angina). We measured blood acetylcholinesterase (AChE) activity using the acetylcholine analog acetylthiocholine. Mortality rates were determined up to 10 years of follow-up. We divided our cohort into 3 groups with low, intermediate and high AChE activity by a Chi-square automatic interaction detection method (CHAID)., Results: Patients with lower than cutoff levels of AChE (<300 nmol/min/ml) had higher mortality rates over 10 years of follow-up, after adjusting for conventional risk factors, biomarkers, clinical indication, and use of medications (HR = 1.6, 95% CI 1.1-2.5, p = 0.02). Patients with intermediate levels of AChE (300-582 nmol/min/ml) were also at increased risk for death (HR = 1.4, 95% CI 1.1-1.9, p = 0.02). AChE was inversely correlated with C-reactive protein, troponin I, fibrinogen and neutrophil/lymphocyte ratio levels., Conclusions: Patients presenting for coronary angiography with low levels of serum AChE activity are at increased risk for death during long term follow-up., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Acute pulmonary embolism (PE) is considered to be one of the most common cardiovascular diseases with considerable mortality. Conflicting data imply possible role for echocardiography in assessing this disease., Objectives: To determine which of the echo parameters best predicts short-term and long-term mortality in patients with PE., Methods: We prospectively enrolled 235 patients who underwent computed tomography of pulmonary arteries (CTPA) and transthoracic Echocardiography (TTE) within < 24 hours. TTE included a prospectively designed detailed evaluation of the right heart including right ventricular (RV) myocardial performance index (RIMP), RV end diastolic and end systolic area, RV fractional area change, acceleration time (AT) of pulmonary flow and visual estimation. Interpretation and performance of TTE were blinded to the CTPA results., Results: Although multiple TTE parameters were associated with PE, all had low discriminative capacity (AUC < 0.7). Parameters associated with 30-day mortality in univariate analysis were acceleration time (AT) < 81 msec (P = 0.04), stroke volume < 44 cc (P = 0.005), and RIMP > 0.42 (P = 0.05). The only RV independent echo parameter associated with poor long-term prognosis (adjusted for significant clinical, and routine echo associates of mortality) was RIMP (hazard ratio 3.0, P = 0.04). The only independent RV echo parameters associated with mortality in PE patients were RIMP (P = 0.05) and AT (P = 0.05). Addition of RIMP to nested models eliminated the significance of all other parameters assessing RV function., Conclusions: Doppler-based parameters like pulmonary flow AT, RIMP, and stroke volume, have additive value in addition to visual RV estimation to assess prognosis in patients with PE.

Objective: Acute kidney injury (AKI) is a frequent complication in patients with ST segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). While AKI occurring post-PCI has been well studied, the incidence and clinical significance of early renal impairment evident on hospital admission prior to PCI and which resolves towards discharge has not been investigated., Methods: We retrospectively studied 2339 STEMI patients treated with primary PCI. The incidence of renal impairment and in-hospital complications as well as short and long-term mortality were compared between patients who did not develop renal impairment, patients who developed post-PCI AKI and those who presented with renal impairment on admission but improved their renal function during hospitalization (improved renal function). Improved renal function was defined as continuous and gradual decrease of ⩾ 0.3 mg/dL in serum creatinine levels obtained at hospital admission., Results: One hundred and nineteen patients (5%) had improved renal function and 230 patients (10%) developed post-PCI AKI. When compared with patients with no renal impairment, improved renal function and post-PCI AKI were associated with more complications and adverse events during hospitalization as well as higher 30-day mortality. Long-term mortality was significantly higher among those with post-PCI AKI (63/230, 27%) following STEMI than those without renal impairment (104/1990, 5%; p <0.001), but there was no significant difference in long term mortality between patients with no renal impairment and those with improved renal function (5% vs . 7.5%, p =0.17)., Conclusion: In STEMI patients undergoing primary PCI, the presence of renal impairment prior to PCI which resolves towards discharge is not uncommon and is associated with adverse short-term outcomes but better long-term outcomes compared with post-PCI AKI.

Background: The global incidence of thyroid cancer (TC) has risen considerably during the last three decades, while prognosis is generally favorable. We assessed the long-term all-cause mortality in TC survivors compared to the general population, and its association with cardiovascular risk factors., Methods: Individuals diagnosed with TC during 2001-2014 (TC group) and age- and sex-matched individuals from the same Israeli healthcare system without thyroid disease or a cancer history (non-TC group) were compared. Cox regression hazard ratios (HRs) and 95% confidence intervals (95%CIs) for all-cause mortality were calculated by exposure status., Results: During a 15-year follow-up (median 8 years), 577 TC survivors out of 5677 (10.2%) TC patients and 1235 individuals out of 23,962 (5.2%) non-TC patients died. The TC survivors had an increased risk of all-cause mortality (HR = 1.89, 95%CI 1.71-2.10), after adjusting for cardiovascular risk factors already present at follow-up initiation. This increased risk was most pronounced in the 55- to 64-year-old age group (HR = 1.49, 95%CI 1.33-1.67). The TC survivors who died by study closure had more hypertension (14.6% vs. 10.3%, P = 0.002), more dyslipidemia (11.4% vs. 7.2%, P <  0.001), and more cardiovascular disease (33.6% vs. 22.3%, P = 0.05) compared to those who died in the non-TC group., Conclusions: This large cohort study showed higher all-cause mortality with a higher prevalence of hypertension, dyslipidemia, and cardiovascular disease among TC survivors compared to matched non-TC individuals. Primary and secondary prevention of cardiovascular risk factors in TC survivors is mandatory.