Early neutrophil gelatinase-associated lipocalin (NGAL) measurement could rule out future acute kidney injury in patients with acute coronary syndrome-Prospective observational study.

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.

Sex-related differences in the association between septal wall thickness and survival.

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.

Coronary microvascular dysfunction in patients with Takotsubo syndrome.

BACKGROUND: The pathophysiology of Takotsubo syndrome (TTS) remains incompletely understood. While coronary microvascular dysfunction (CMD) is a potential pathophysiologic mechanism, evidence is limited. OBJECTIVES: We sought to evaluate CMD in patients with TTS. METHODS: Consecutive patients diagnosed with TTS were included and underwent coronary angiography with invasive microvascular function evaluation, including fractional flow reserve, Coronary Flow Reserve (CFR), Index of Microcirculatory Resistance (IMR), and Resistive Reserve Ratio (RRR). Patients had an echocardiography evaluation during their index admission and at approximately 6 weeks. RESULTS: Thirty patients were included (mean age 74 ±9, 90 % female). Twenty-five patients (83 %) had at least one abnormal coronary microvascular function parameter. Abnormal parameters included CFR<2.5 in 20 patients (67 %), IMR>25 in 18 patients (60 %), and RRR<3.5 in 25 (83 %). Longer time from symptoms to angiography correlated with a higher CFR (r = 0.51, P<0.01), and had an area under the receiver operating characteristic curve of 0.793 (95 % CI 0.60-0.98) for pathologic CFR. Patients with emotional trigger had a lower rate of pathologic IMR compared with non-emotional trigger (36 % vs 81 %, p = 0.01). Follow up echocardiography performed at a median of 1.5 months (IQR 1.15-6) showed an improvement in left ventricular ejection fraction for all patients (from mean of 40 % to 57 %). CONCLUSION: CMD was present in most patients with TTS. The role of microvascular function in TTS may vary according to the clinical presentation and RRR may be more sensitive for the diagnosis of CMD in TTS.

Prediction of recurrent heart failure hospitalizations and mortality using the echocardiographic Killip score.

AIM: Examine the performance of a simple echocardiographic "Killip score" (eKillip) in predicting heart failure (HF) hospitalizations and mortality after index event of decompensated HF hospitalization. METHODS: HF patients hospitalized at our facility between 03/2019-03/2021 who underwent an echocardiography during their index admission were included in this retrospective analysis. The cohort was divided into 4 classes of eKillip according to: stroke volume index (SVI) < 35ml/m2 > and E/E' ratio < 15 > . An eKillip Class I was defined as SVI ≥ 35ml/m2 and E/E' ≤ 15 and was used as reference. RESULTS: Included 751 patients, median age 78.1 (IQR 69.3-86) years, 59% men, left ventricular ejection fraction 45 (IQR 30-60)%, brain natriuretic peptide levels 634 (IQR 331-1222)pg/ml. Compared with eKillip Class I, a graded increase in the combined endpoint of 30-day mortality and rehospitalizations rates was noted: (Class II: HR 1.77, CI 0.95-3.33, p = 0.07; Class III: HR 1.94, CI 1.05-3.6, p = 0.034; Class IV: HR 2.9, CI 1.64-5.13, p < 0.001 respectively), which overall persisted after correction for clinical (Class II: HR 1.682, CI 0.9-3.15, p = 0.105; Class III: HR 2.104, CI 1.13-3.9, p = 0.019; Class IV: HR 2.74, CI 1.54-4.85, p = 0.001 respectively) or echocardiographic parameters (Class II: HR 1.92, CI 1.02-3.63, p = 0.045; Class III: HR 1.54, CI 0.81-2.95, p = 0.189; Class IV: HR 2.04, CI 1.1-3.76, p = 0.023 respectively). Specifically, the eKillip Class IV group comprised one-third of the patient population and persistently showed increased risk of 30-day HF hospitalizations or mortality following multivariate analysis. CONCLUSION: A simple echocardiographic score can assist identifying high-risk decompensated HF patients for recurrent hospitalizations and mortality.

Conduction disorders following transcatheter aortic valve replacement using acurate Neo2 transcatheter heart valve: A propensity matched analysis.

BACKGROUND: The ACURATE neo2 transcatheter aortic valve was developed to improve paravalvular leak (PVL) rates while maintaining low rates of conduction disturbances and permanent pacemaker implantation (PPMI) seen with its predecessor. We aimed to compare conduction disturbances rates of transcatheter aortic valve replacement (TAVR) using ACURATE Neo2 with other commonly used valves. METHODS: A retrospective analysis of the Israeli TAVR registry between the years 2014-2023 was performed to compare conduction disturbances and PVL rates, and procedural outcomes, among patients treated with ACURATE neo2, Edwards Sapien 3 (S3), and Evolut PRO valves. Propensity score matching was performed to compare groups with similar characteristics. RESULTS: Following exclusion of patients with non-femoral access, unknown valve type, older-generation valves, and less commonly used valves or (n = 4387), our analysis included 3208 patients undergoing TAVR using ACURATE neo2, Edwards S3, and Evolut PRO valves. Propensity matched groups comprised 169 patients each. Rates of any conduction disturbances [left bundle branch block (LBBB), atrioventricular block, or PPMI] were lower in the ACURATE neo2 group compared to both other valves [15.8 %, S3-37.5 % (p < 0.001), Evolut PRO-27.5 % (p = 0.02)] as were LBBB rates [9.0 %, S3-31.3 % (p < 0.001); Evolut PRO-20.1 % (p = 0.01). Atrioventricular block and PPMI rates were lower without statistical significance, as were rates of above-moderate PVL. CONCLUSIONS: In this analysis, TAVR using ACURATE neo2 was associated with a lower composite rate of conduction disturbances in comparison to the Evolut PRO and Edwards S3 valves, mainly due to lower left bundle branch block rates, with non-significantly lower rates of PPMI and PVL.

Electromechanical Window and Spontaneous Ventricular Tachyarrhythmias in Takotsubo Syndrome.

QT interval prolongation is common in patients hospitalized with Takotsubo syndrome (TTS), however, only a minority experience ventricular tachyarrhythmias. Our aim was to characterize the electromechanical window (EMW) in patients with TTS and to evaluate its association with ventricular tachyarrhythmias. We preformed aretrospective analysis of 84 patients hospitalized with TTS in the Tel-Aviv Medical Center between 2013 and 2022. All patients underwent a comprehensive echocardiographic evaluation and the EMW was calculated by subtracting the QT interval from the QRS onset to the aortic valve closure obtained from a continuous-wave Doppler for the same beat. Of the 84 patients with TTS, 74 (88%) were female and the mean age was 70 ± 11 years. The mean left ventricular ejection fraction was 42 ± 8%. The EMW was negative in 81 patients (96%), and the mean EMW was -69 ± 50 ms. Ventricular tachyarrhythmias occurred in 7 patients (8%). The EMW of patients who experienced ventricular tachyarrhythmias was more negative than patients who did not (-133 ± 23 ms vs -63 ± 48 ms, p = 0.001). In the univariate analysis, EMW and QT were associated with ventricular tachyarrhythmias (univariate odds ratio [OR]EMW 1.03, 95% confidence interval [CI] 1.01 to 1.05, p = 0.003 and univariate ORQTc 1.02, 95% CI 1.01 to 1.03, p = 0.02); however, only EMW remained significant in the multivariate analysis (OREMW 1.03 95% CI 1.03 to 1.05, p = 0.023). EMW was more effective than corrected QT interval in identifying patients who had ventricular tachyarrhythmias (AUCEMW: 0.89, 95% CI 0.82 to 0.97 vs AUCQTc 0.77, 95% CI 0.61 to 0.93, p = 0.02), and a cut-off value of -108 ms was predictive of ventricular tachyarrhythmias with a sensitivity of 86% and a specificity of 79%. In conclusion, EMW is negative in patients with TTS and is associated with increased risk for ventricular tachyarrhythmias. The role of EMW in the risk stratification of patients with TTS warrants further investigation.

Exercise limitation in hypertrophic cardiomyopathy: combined stress echocardiography and cardiopulmonary exercise test.

AIMS: The study aims to investigate exercise-limiting factors in hypertrophic cardiomyopathy (HCM) using combined stress echocardiography and cardiopulmonary exercise test. METHODS AND RESULTS: A symptom-limited ramp bicycle exercise test was performed in the semi-supine position on a tilting dedicated ergometer. Echocardiographic images were obtained concurrently with gas exchange measurements along predefined stages of exercise. Oxygen extraction was calculated using the Fick equation at each activity level. Thirty-six HCM patients (mean age 67 ± 6 years, 72% men, 18 obstructive HCM) were compared with age and sex-matched 29 controls. At rest, compared with controls, E/E' ratio (6.26 ± 2.3 vs. 14 ± 2.5, P < 0.001) and systolic pulmonary artery pressures (SPAP) (22.6 ± 3.4 vs. 34 ± 6.2 mmHg, P = 0.023) were increased. Along with the stages of exercise (unloaded; anaerobic threshold; peak), diastolic function worsened (E/e' 8.9 ± 2.6 vs. 13.8 ± 3.6 P = 0.011; 9.4 ± 2.3 vs. 18.6 ± 3.3 P = 0.001; 8.7 ± 1.9 vs. 21.5 ± 4, P < 0.001), SPAP increased (23 ± 2.7 vs. 33 ± 4.4, P = 0.013; 26 ± 3.2 vs. 40 ± 2.9, P < 0.001; 26 ± 3.5 vs. 45 ± 7 mmHg, P < 0.001), and oxygen consumption (6.6 ± 1.7 vs. 6.8 ± 1.6, P = 0.86; 18.1 ± 2.2 vs. 14.6 ± 1.5, P = 0.008; 20.3 ± 3 vs. 15.1 ± 2.1 mL/kg/min, P = 0.01) was reduced. Oxygen pulse was blunted (6.3 ± 1.8 vs. 6.2 ± 1.9, P = 0.79; 10 ± 2.1 vs. 8.8 ± 1.6, P = 0.063; 12.2 ± 2 vs. 8.2 ± 2.3 mL/beat, P = 0.002) due to an insufficient increase in both stroke volume (92.3 ± 17 vs. 77.3 ± 14.5 P = 0.021; 101 ± 19.1 vs. 87.3 ± 15.7 P = 0.06; 96.5 ± 12.2 vs. 83.6 ± 16.1 mL, P = 0.034) and oxygen extraction (0.07 ± 0.03 vs. 0.07 ± 0.02, P = 0.47; 0.13 ± 0.02 vs. 0.10 ± 0.03, P = 0.013; 0.13 ± 0.03 vs. 0.11 ± 0.03, P = 0.03). Diastolic dysfunction, elevated SPAP, and the presence of atrial fibrillation were associated with reduced exercise capacity. CONCLUSIONS: Both central and peripheral cardiovascular limitations are involved in exercise intolerance in HCM. Diastolic dysfunction seems to be the main driver for this limitation.

Traditional Cardiovascular Risk Factors and Coronary Microvascular Dysfunction in Women and Men: A Single-Center Study.

INTRODUCTION: Coronary microvascular dysfunction (CMD) is common in patients with and without obstructive epicardial coronary artery disease (CAD). Risk factors for the development of CMD have not been fully elucidated, and data regarding sex-associated differences in traditional cardiovascular risk factors for obstructive CAD in patients with CMD are lacking. METHODS: In this single-center, prospective registry, we enrolled patients with nonobstructive CAD undergoing clinically indicated invasive assessment of coronary microvascular function between November 2019 and March 2023. Associations between coronary microvascular dysfunction, traditional cardiovascular risk factors, and sex were assessed using univariate and multivariate regression models. RESULTS: Overall, 245 patients with nonobstructive CAD were included in the analysis (62.9% female; median age 68 (interquartile range: 59, 75). Microvascular dysfunction was diagnosed in 141 patients (57.5%). The prevalence of microvascular dysfunction was similar in women and men (59.0% vs. 57.0%; p = 0.77). No association was found between traditional risk factors for coronary atherosclerosis and CMD regardless of whether CMD was structural or functional. In women, but not in men, older age and the presence of previous ischemic heart disease were associated with lower coronary flow reserve (ß = -0.29; p < 0.01 and ß = -0.15; p = 0.05, respectively) and lower resistive reserve ratio (ß = -0.28; p < 0.01 and ß = -0.17; p = 0.04, respectively). CONCLUSION: For the entire population, no association was found between coronary microvascular dysfunction and traditional risk factors for coronary atherosclerosis. In women only, older age and previous ischemic heart disease were associated with coronary microvascular dysfunction. Larger studies are needed to elucidate risk factors for CMD.

Smoking and Respiratory Diseases in Patients with Coronary Microvascular Dysfunction.

BACKGROUND: Coronary microvascular disease (CMD) is common in patients with and without obstructive coronary artery disease, and is associated with adverse clinical outcomes. Respiratory-related variables are associated with pulmonary and systemic microvascular dysfunction, while evidence about their relationship with CMD is limited. We aim to evaluate respiratory-related variables as risk factors of CMD. METHODS: This is an observational, single-center study enrolling consecutive patients undergoing invasive evaluation of coronary microvascular function in the catheterization laboratory. Patients with evidence of obstructive coronary artery disease or with missing data were excluded. Associations between respiratory-related variables and indices of CMD were assessed using univariate and multivariate regression models. RESULTS: Overall, 266 patients (mean age 67 ± 11 years, 59% females) were included in the current analysis. Of those, 155 (58%) had evidence of CMD. Among the respiratory variables, independent predictors of CMD were current smoking (adjusted odds ratio [AOR] 2.5; 95% confidence interval [CI], 1.2-5; P = .01) and obstructive sleep apnea (AOR 5.7; 95% CI, 1.2-26; P = .03), while chronic obstructive pulmonary disease was not. Among ever-smokers, higher smoking pack-years was an independent risk factor for CMD (median 35 vs 25 pack-years, AOR 1.09; 95% CI, 1.04-1.13; P < .01), and was associated with higher rates of pathologic index of microcirculatory resistance and resistive reserve ratio. CONCLUSION: In patients undergoing invasive coronary microvascular evaluation, current smoking and obstructive sleep apnea are independently associated with CMD. Among smokers, higher pack-years is a strong predictor for CMD. Our findings should raise awareness for prevention and possible treatment options.

The CRP troponin test (CTT) stratifies mortality risk in patients with non-ST elevation myocardial infarction (NSTEMI).

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.

Prognostic impact of combined non-severe aortic stenosis and mitral regurgitation on clinical outcomes: a single-centre retrospective study.

OBJECTIVES: Though the concomitant occurrence of non-severe aortic stenosis (AS) and mitral regurgitation (MR) is highly prevalent, there are limited data to guide clinical decision-making in this condition. Here, we attempt to determine an aortic valve area (AVA) cut-off value associated with worse clinical outcomes in patients with combined non-severe AS and MR. METHODS: Single-centre, retrospective analysis of consecutive patients who underwent echocardiography examination between 2010 and 2021 with evidence of combined non-severe AS and MR. We excluded patients with ≥moderate aortic valve regurgitation or mitral stenosis, as well as patients who underwent any aortic or mitral intervention either prior or following our assessment (n=372). RESULTS: The final cohort consisted of 2933 patients with non-severe AS, 506 of them with >mild MR. Patients with both pathologies had lower cardiac output and worse diastolic function.Patients with an AVA ≤1.35 cm² in the presence of >mild MR had the highest rates of heart failure (HF) hospitalisations (HR 3.1, IQR 2.4-4, p<0.001) or mortality (HR 2, IQR 1.8-2.4, p<0.001), which remained significant after adjusting for clinical and echocardiographic parameters. CONCLUSION: Patients with combined non-severe AS and MR have a higher rate of HF hospitalisations and mortality. An AVA≤1.35 cm² in the presence of >mild MR is associated with worse clinical outcomes.

Sodium-glucose co-transporter-2 inhibitors in patients treated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the prognosis of cancer. Diabetes mellitus (DM) has been shown to have a negative effect on patients treated with ICIs. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are effective antidiabetic therapies associated with reduced all-cause mortality and cardiovascular (CV) outcomes. OBJECTIVE: To evaluate the prognostic value of SGLT2i on all-cause mortality and cardiotoxicity among patients treated with ICIs. METHODS: We performed a retrospective analysis of patients diagnosed with cancer and type 2 DM (DM2) and treated with ICIs at our center. Patients were divided into two groups according to baseline treatment with or without SGLT2i. The primary endpoint was all-cause mortality and the secondary endpoint was MACE, including myocarditis, acute coronary syndrome, heart failure, and arrhythmia. RESULTS: The cohort included 119 patients, with 24 (20%) patients assigned to the SGLT2i group. Both groups exhibited a comparable prevalence of cardiac risk factors, although the SGLT2i group displayed a higher incidence of ischemic heart disease. Over a median follow-up of 28 months, 61 (51%) patients died, with a significantly lower all-cause mortality rate in the SGLT2i group (21% vs. 59%, p = 0.002). While there were no significant differences in MACE, we observed zero cases of myocarditis and atrial fibrillation in the SGLT2i, compared to 2 and 6 cases in the non-SGLT2i group. CONCLUSIONS: SGLT2i therapy was associated with a lower all-cause mortality rate in patients diagnosed with cancer and DM2 and treated with ICIs. Further studies are needed to understand the mechanism and evaluate its benefit on cardiotoxicity.

Coronary Sinus Narrowing Improves Coronary Microcirculation Function in Patients With Refractory Angina: A Multicenter Prospective INROAD Study.

BACKGROUND: The underlying mechanisms responsible for the clinical benefits following coronary sinus narrowing and pressure elevation remain unclear. The present study aims to investigate whether coronary sinus narrowing improves the indexes of coronary microcirculatory function. METHODS: Patients with refractory angina who had a clinical indication for reducer implantation underwent invasive physiological assessments before and 4 months after the procedure. The primary outcome was the change in the values of the index of microcirculatory resistance. Secondary end points included changes in coronary flow reserve and the resistive resistance ratio values. Angina status was assessed with the Canadian Cardiology Society class and the Seattle Angina Questionnaire. RESULTS: Twenty-four patients with a history of obstructive coronary artery disease and prior coronary revascularization (surgical and percutaneous) treated with reducer implantation were enrolled, and 21 of them (87%) underwent repeated invasive coronary physiological assessment after 4 months. The index of microcirculatory resistance values decreased from 33.35±19.88 at baseline to 15.42±11.36 at 4-month follow-up (P<0.001; mean difference, -17.90 [95% CI, -26.16 to -9.64]). A significant (≥20% from baseline) reduction of the index of microcirculatory resistance was observed in 15 (71.4% [95% CI, 47.8%-88.7%]) patients. The number of patients with abnormal index of microcirculatory resistance (≥25) decreased from 12 (57%) to 4 (19%; P=0.016). Coronary flow reserve increased from 2.46±1.52 to 4.20±2.52 (mean difference, 1.73 [95% CI, 0.51-2.96]). Similar findings were observed for resistive resistance ratio values. Overall, 16 patients (76.1%) had an improvement of 1 Canadian Cardiology Society class. Seattle Angina Questionnaire summary score increase of around 3 points (3.01 [95% CI, 1.39-4.61]). CONCLUSIONS: Coronary sinus reduction implantation is associated with a significant improvement in the parameters of coronary microcirculatory function. These findings provide insights into the improvement of angina symptoms and may have implications for the treatment of coronary microvascular dysfunction. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05174572.

Evaluation of coronary disease among patients undergoing transcatheter aortic valve implantation: propensity score matching analysis.

BACKGROUND: Chronic coronary syndrome (CCS) is common among elderly patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI). Current guidelines recommend performance of percutaneous coronary intervention (PCI) of any > 70% proximal coronary lesions prior to TAVI. AIMS: To evaluate the outcomes of two diagnostic approaches for CCS clearance pre-TAVI and to determine the reduction in the need of invasive angiography (IA). METHODS: We investigated 2219 patients undergoing TAVI for severe aortic stenosis at two large centers with different pre-procedural strategies for CCS assessment: pre-TAVI computed tomography angiography (CTA) with selective invasive angiography according to CTA results or mandatory IA. We preformed propensity score matching analysis using a 1:1 ratio. The final study cohort included 870 matched patients. Peri-procedural complications were documented according to the VARC-2 criteria. Mortality rates were prospectively documented. RESULTS: Mean age of the study population was 82 ± 7, of whom 55% were female. Patients in the IA group had significantly higher rates of pre-TAVI PCI compared to the CTA group (39% vs. 22%, p < 0.001). Following TAVI, peri-procedural myocardial infarction (MI) rates were similar between the two groups (0.3% vs. 0.7%, p value = 0.41), but spontaneous MI were significantly lower among the IA group (0% vs. 1.3%, p value = 0.03). Kaplan-Meier's survival analysis found that the cumulative probability of 1-year morality was similar between the two groups (p value log rank = 0.65). Cox regression analysis did not find association between CCS clearance strategy and outcome. CONCLUSIONS: In elderly patients, CTA-driven approach for CCS evaluation pre-TAVI is a valid strategy with similar outcome as compared to invasive approach. CTA strategy significantly reduces invasive procedures rates without compromising patient's outcome.

The prognostic value of beta-1 blockers in patients with non-small-cell lung carcinoma treated with pembrolizumab.

BACKGROUND: Immune checkpoint inhibitors (ICIs) such as pembrolizumab have revolutionized the treatment of metastatic non-small cell lung cancer (mNSCLC). Beta-adrenergic activation contributes to cancer initiation and progression. While non-selective beta-blocker were found to improve the efficacy of ICIs therapy, the role of beta-1 (ß1)-selective -blocker (ß1B) in lung cancer patients is unknown. OBJECTIVE: To evaluate the effect of ß1B on overall survival (OS) and progression-free survival (PFS) in patients diagnosed with mNSCLC and treated with pembrolizumab. METHODS: We performed a retrospective analysis of patients diagnosed with mNSCLC and treated with first-line pembrolizumab at our center. RESULTS: Of 200 eligible patients, 53 (27%) were pretreated with ß1B. Patients in the ß1B cohort were older (73 ± 8 vs. 67 ± 10 years, p < 0.001) with a higher prevalence of cardiac risk factors and cardiovascular (CV) diseases including ischemic heart disease (32% vs. 16%, p = 0.010), heart failure (9% vs. 3%, p = 0.043) and atrial fibrillation (23% vs. 3%, p < 0.001). Compared to the non-ß1B group, patient pretreated with ß1B had a significant shorter median OS (12 vs. 24 months, p = 0.004) and PFS (6 vs. 8 months, p < 0.001). In a multivariate analysis, including all CV risk factors and diseases, the use of baseline ß1B was a strong and independent predictor for accelerated disease progression (HR 1.92, 95%CI 1.32-2.79, p < 0.001) and shorter OS (HR 1.8, 95%, CI 1.18-2.75, p = 0.007). CONCLUSIONS: The use of baseline ß1B showed a strong and independent association for shorter OS and PFS in patients diagnosed with mNSCLC and treated with pembrolizumab.

Indexed neutrophil gelatinase associated lipocalin: a novel biomarker for the assessment of acute kidney injury.

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.