Higher ACE2 expression levels in epicardial cells than subcutaneous stromal cells from patients with cardiovascular disease: Diabetes and obesity as possible enhancer.

AIMS: Obesity, diabetes and cardiovascular disease are associated with COVID-19 risk and severity. Because epicardial adipose tissue (EAT) expresses ACE2, we wanted to identify the main factors associated with ACE2 levels and its cleavage enzyme, ADAM17, in epicardial fat. MATERIALS AND METHODS: Epicardial and subcutaneous fat biopsies were obtained from 43 patients who underwent open-heart surgery. From 36 patients, biopsies were used for RNA expression analysis by real-time PCR of ACE1, ACE2 and ADAM17. From 8 patients, stromal vascular cells were submitted to adipogenesis or used for studying the treatment effects on gene expression levels. Soluble ACE2 was determined in supernatants by ELISA. RESULTS: Epicardial fat biopsies expressed higher levels of ACE2 (1.53 [1.49-1.61] vs 1.51 [1.47-1.56] a.u., P < .05) and lower ADAM17 than subcutaneous fat (1.67 [1.65-1.70] vs 1.70 [1.66-1.74] a.u., P < .001). Both genes were increased in epicardial fat from patients with type 2 diabetes mellitus (T2DM) (1.62 [1.50-2.28] vs 1.52 [1.49-1.55] a.u., P = .05 for ACE2 and 1.68 [1.66-1.78] vs 1.66 [1.63-1.69] a.u., P < .05 for ADAM17). Logistic regression analysis determined that T2DM was the main associated factor with epicardial ACE2 levels (P < .01). The highest ACE2 levels were found on patients with diabetes and obesity. ACE1 and ACE2 levels were not upregulated by antidiabetic treatment (metformin, insulin or thiazolidinedione). Its cellular levels, which were higher in epicardial than in subcutaneous stromal cells (1.61 [1.55-1.63] vs 1 [1-1.34]), were not correlated with the soluble ACE2. CONCLUSION: Epicardial fat cells expressed higher levels of ACE2 in comparison with subcutaneous fat cells, which is enhanced by diabetes and obesity presence in patients with cardiovascular disease. Both might be risk factors for SARS-CoV-2 infection.

Long term prognostic benefit of complete revascularization in elderly presenting with NSTEMI: real world evidence.

The benefit of complete revascularization in elderly patients with non-ST elevation myocardial infarction (NSTEMI), and multivessel disease remains debated (MVD). The aim of our study was to determine the current long-term prognostic benefit of complete revascularization in this population. A retrospective cohort study of 1722 consecutive elderly NSTEMI patients was performed. Among the study participants 30.4% (n = 524) were completed revascularizated and in 69.6% (n = 1198) culprit vessel only revascularization was performed. A propensity score analysis was performed and we divided the study population into two groups: complete revascularization (n = 500) and culprit vessel only revascularization (n = 500). The median follow-up was 45.7 months, the all cause mortality (44.5% vs 30.5%, p < 0.001) (HR 0.74 (0.57-0.97); p = 0.035) and cardiovascular mortality (32.6% vs 17.4%, p < 0.001) (HR = 0.67 (0.47-0.94); p = 0.021) were significantly lower in patients with complete revascularization. In our study, we observed a long-term benefit of complete revascularization in elderly NSTEMI and MVD patients. Elderly patients should also be managed according to current guidelines to improve their long-term prognosis.

Cholinergic activity regulates the secretome of epicardial adipose tissue: Association with atrial fibrillation.

Botulinum toxin injection on epicardial fat, which inhibits acetylcholine (ACh) release, reduced the presence of atrial fibrillation (AF) in patients after heart surgery. Thus, we wanted to study the profile of the released proteins of epicardial adipose tissue (EAT) under cholinergic activity (ACh treatment) and their value as AF predictors. Biopsies, explants, or primary cultures were obtained from the EAT of 85 patients that underwent open heart surgery. The quantification of muscarinic receptors (mAChR) by real-time polymerase chain reaction or western blot showed their expression in EAT. Moreover, mAChR Type 3 was upregulated after adipogenesis induction (p < 0.05). Cholinergic fibers in EAT were detected by vesicular ACh transporter levels and/or acetylcholinesterase activity. ACh treatment modified the released proteins by EAT, which were identified by nano-high-performance liquid chromatography and TripleTOF analysis. These differentially released proteins were involved in cell structure, inflammation, or detoxification. After testing the plasma levels of alpha-defensin 3 (inflammation-involved protein) of patients who underwent open heart surgery ( n = 24), we observed differential levels between the patients who developed or did not develop postsurgery AF (1.58 ± 1.61 ng/ml vs. 6.2 ± 5.6 ng/ml; p < 0.005). The cholinergic activity on EAT might suggest a new mechanism for studying the interplay among EAT, autonomic nervous system dysfunction, and AF.

Prognostic value of nutrition status in the response of cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) is indicated in symptomatic heart failure (HF) patients after achieving optimal medical therapy. However, there are still a large percentage of patients who do not respond to CRT. Malnutrition is a frequent comorbidity in patients with HF, and it is associated with a poorer prognosis. Here, we evaluate the nutritional status of patients assessed by Controlling Nutritional Status (CONUT) score and its association with structural remodeling and cardiovascular events. METHODS: We investigated the effect of CONUT on HF/death in 302 consecutive patients with a CRT device implanted between 2005 and 2015 in a single tertiary center. We categorized the patients into three groups: normal nutritional status (CONUT 0-1), mild malnutrition (CONUT 2-4) and moderate-severe malnutrition (CONUT ≥ 5). Changes in nutritional status were assessed in patients with mild-to-severe malnutrition prior to CRT. RESULTS: One hundred and forty-eight patients exhibited normal nutritional status (49.0%), 99 patients exhibited mild malnutrition (32.8%) and 55 patients exhibited moderate-severe malnutrition (18.2%). CONUT scores of at least 2 were associated with higher risk of HF/death compared with CONUT 0-1. Significant left ventricular (LV) reverse remodeling was noted in patients with better nutritional status. In addition, those malnutrition patients at baseline that improved nutritional state exhibited fewer HF/death events at follow-up. CONCLUSION: CONUT score prior to CRT was an independent risk factor of death/HF and was correlated with LV reverse remodeling. Improvements in CONUT score during long-term follow-up were associated with a reduction in the rate of HF/death.

Remnant cholesterol in patients admitted for acute coronary syndromes.

BACKGROUND: Remnant cholesterol has been identified as one of leading lipid values associated with the incidence of coronary heart disease. There is scarce evidence on its distribution and prognostic value in acute coronary syndrome (ACS) patients. METHODS AND RESULTS: We included all consecutive patients admitted for ACS in two different centres. Remnant cholesterol was calculated by the equation: total cholesterol minus LDL cholesterol minus HDL cholesterol, and values ≥30 were considered high. Among the 7479 patients, median remnant cholesterol level was 28 mg/dL (21-39), and 3429 (45.85%) patients had levels ≥30 mg/dL. Age (r: -0.29) and body mass index (r: 0.44) were the variables more strongly correlated. At any given age, patients with overweigh or obesity had higher levels. In-hospital mortality was 3.75% (280 patients). Remnant cholesterol was not associated to higher in-hospital mortality risk (odds ratio: 0.89; P = 0.21). After discharge (median follow-up of 57 months), an independent and linear risk of all-cause mortality and heart failure (HF) associated to cholesterol remnant levels was observed. Remnant cholesterol levels >60 mg/dL were associated to higher risk of mortality [hazard ratio (HR): 1.49 95% CI 1.08-2.06; P = 0.016], cardiovascular mortality (HR: 1.49 95% CI 1.08-2.06; P = 0.016), and HF re-admission (sub-HR: 1.55 95% CI 1.14-2.11; P = 0.005). CONCLUSIONS: Elevated remnant cholesterol is highly prevalent in patients admitted for ACS and is inversely correlated with age and positively with body mass index. Remnant cholesterol levels were not associated to higher in-hospital mortality risk, but they were associated with higher long-term risk of mortality and HF.

Elevated remnant cholesterol is highly prevalent in patients admitted for ACS and is related to body mass index and negatively with age. Remnant cholesterol it is not associated to higher in-hospital mortality risk, but it confers higher long-term risk of mortality and heart failure.

Outcomes and factors associated with mortality in patients with atrial fibrillation and heart failure: FARAONIC study.

BACKGROUND: Heart failure (HF) and atrial fibrillation (AF) are common and coexistent conditions. HYPOTHESIS: To investigate the adverse events and mortality risk factors in patients with AF and HF treated with rivaroxaban in Spain. METHODS: Multicenter, prospective and observational study with a follow-up of 2 years, that included adults, with a diagnosis of nonvalvular AF and chronic HF, anticoagulated with rivaroxaban at least 4 months before being enrolled. RESULTS: A total of 672 patients from 71 Spanish centers were recruited, of whom 658 (97.9%) were included in the safety analysis and 552 (82.1%) in the per protocol analysis. At baseline, the mean age was 73.7 ± 10.9 years, 65.9% were male, 51.3% had HF with preserved ejection fraction and 58.7% were on New York Heart Association functional class II. CHA2 DS2 -VASc was 4.1 ± 1.5. During the follow-up, 11.6% of patients died and around one-quarter of patients were hospitalized or visited the emergency department, being HF worsening/progression the main cause (51.1%), with a 2.9% of thromboembolic events and 2.0% of acute coronary syndromes. Major bleeding occurred in 3.1% of patients, with 0.5% experiencing intracranial bleeding but no fatalities. Compliance with HF treatment was associated with a lower risk of death (hazard ratio: 0.092; 95% confidence interval: 0.03-0.31). CONCLUSIONS: Among patients with HF and AF anticoagulated with rivaroxaban, incidences of thromboembolic or hemorrhagic complications were low. The most important factor for improving survival was compliance with HF drugs, what strengths the need for early treatment with HF disease-modifying therapy and anticoagulation.

Differential prognosis of patients that are candidates for standard, short or prolonged dual antiplatelet treatment discharged after an acute coronary syndrome.

BACKGROUND: Current evidence supports the efficacy of prolonged dual antiplatelet treatment (DAPT) for patients at high-ischemic risk and low bleeding risk as well as the efficacy and safety of short DAPT in high-bleeding risk (HBR) patients. METHODS: We evaluated patterns of DAPT candidates in all patients discharged in 2 hospitals after an acute coronary syndrome (ACS). Patients categorized in 3 groups: 1) short-DAPT candidates if they met 1 major o 2 minor criteria for HBR, by the 2019 ARC-HBR criteria; 2) prolonged-DAPT candidates if were not HBR and had recurrent ACS, complex percutaneous coronary interventions or diabetes; 3) standard 12 months DAPT if were not include in the previous 2 groups. Major bleeding (MB) was registered according to 3 or 5 of the BARC consortium definitions. RESULTS: We included 8252 patients and 3215 (39 %) were candidates for abbreviated DAPT, 3119 (37.8 %) for prolonged DAPT, and 1918 (23.2 %) for 12 m DAPT. Relevant differences were observed between the 3 categories beyond the bleeding risk. Median follow-up was 57 months. Multivariate analysis identified higher risk of all-cause mortality (HR: 1.96 95 % CI 1.45-2.67; p < 0.001), cardiovascular mortality (HR: 2.10 95 % CI 1.39-3.19; p < 0.011), MACE (HR: 1.69 95 % 1.50-2.02; p < 0.001) and MB (sHR: 3.41 95 % CI 1.45-8.02; p = 0.005) in candidates to short DAPT. Candidates to prolonged DAPT had higher risk of MACE (HR: 1.17 95 % CI 1.02-1.35; p = 0.027). CONCLUSIONS: Almost two thirds of patients discharged after an ACS would be candidates for short or prolonged DAPT and these patients are at higher risk of MACE and mortality.

Clinical Profiling and Biomarkers for Post-Operative Atrial Fibrillation Prediction in Patients Undergoing Cardiac Surgery.

Post-operative atrial fibrillation (POAF) is the most common arrhythmia in the post-operative period after cardiac surgery. We aim to investigate the main clinical, local, and/or peripheral biochemical and molecular predictors for POAF in patients undergoing coronary and/or valve surgery. Between August 2020 and September 2022, consecutive patients undergoing cardiac surgery without previous history of AF were studied. Clinical variables, plasma, and biological tissues (epicardial and subcutaneous fat) were obtained before surgery. Pre-operative markers associated with inflammation, adiposity, atrial stretch, and fibrosis were analyzed on peripheral and local samples with multiplex assay and real-time PCR. Univariate and multivariate logistic regression analyses were performed in order to identify the main predictors for POAF. Patients were followed-up until hospital discharge. Out of 123 consecutive patients without prior AF, 43 (34.9%) developed POAF during hospitalization. The main predictors were cardiopulmonary bypass time (odds ratio (OR) 1.008 (95% confidence interval (CI), 1.002-1.013), p = 0.005), and plasma pre-operative orosomucoid levels (OR 1.008 (1.206-5.761). After studying differences regarding sex, orosomucoid was the best predictor for POAF in women (OR 2.639 (95% CI, 1.455-4.788), p = 0.027) but not in men. The results support the pre-operative inflammation pathway as a factor involved in the risk of POAF, mainly in women.

Longer-Term Results of a Universal Electronic Consultation Program at the Cardiology Department of a Galician Healthcare Area.

BACKGROUND: Telemedicine models play a key role in organizing the growing demand for care and healthcare accessibility, but there are no described longer-term results in health care. Our objective is to assess the longer-term results (delay time in care, accessibility, and hospital admissions) of an electronic consultation (e-consultation) outpatient care program. METHODS: Epidemiological and clinical data were obtained from the 41 258 patients referred by primary care to the cardiology department from January 1, 2010, to December 31, 2019. Until 2012, all patients were attended in an in-person consultation (2010-2012). In 2013, we instituted an e-consultation program (2013-2019) for all primary care referrals to cardiologists that preceded patients' in-person consultations when considered. We used an interrupted time series regression approach to investigate the impact of the e-consultation on (1) delay time (days) in care and (2) hospital admissions. We also analyzed (3) total number and referral rate (population-adjusted referred rate) in both periods (in-person consultation and e-consultation), and (4) the accessibility was measured as number of consultations and variation according to distance from municipality and reference hospital. RESULTS: During the e-consultation, the demand increased (7.2±2.4% versus 10.1±4.8% per 1000 inhabitants, P<0.001), and referrals from different areas were equalized. The reduction in delay to consultation during the in-person consultation (-0.96 [95% CI, -0.951 to -0.966], P<0.001) was maintained with e-consultations (-0.064 [95% CI, 0.043-0.085], P<0.001). After the implementation of e-consultation, we observed that the increasing of hospital admission observed in the in-person consultation (incidence rate ratio, 1.011 [95% CI, 1.003-1.018]), was stabilized (incidence rate ratio, 1.000 [95% CI, 0.985-1.015]; P=0.874). CONCLUSIONS: Implementing e-consultations in the outpatient management model may improve accessibility of care for patients furthest from the referral hospital. After e-consultations were implemented, the upward trend of hospital admissions observed during the in-person consultation period was stabilized with a slight downward trend.

Prognostic impact of renal function trajectories in patients with STEMI and kidney dysfunction undergoing primary percutaneous coronary intervention: An analysis of ten years all-comers registry.

BACKGROUND: Renal dysfunction in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) indicates a poor long-term prognosis. However, the prognostic value of the improvement or stabilisation of renal function during follow-up has not yet been assessed. This study aimed to investigate the long-term predictive impact of the improvement or stabilisation of renal function after one year of follow-up in patients with STEMI undergoing pPCI with renal dysfunction at discharge. METHODS: This prospective, single-centre cohort study included 2170 consecutive patients with STEMI who underwent pPCI. The glomerular filtration rate (GFR) was determined at hospital discharge and one-year follow-up. The median clinical follow-up was 72 months. RESULTS: Among the 2004 patients, 393 (19.6%) had a GFR <60 ml/min, and 1611 (80.4%) had a GFR ≥ 60 ml/min at discharge. Among patients with GFR <60 ml/min, data at one-year follow-up were available for 342. Of these patients, 127 (32%) showed improvement in renal function (defined as improvement in the Kidney Disease Improving Global Outcomes (KDIGO) chronic kidney disease (CKD) classification), 47 (12%) showed worsening of renal function (defined as worsening of the KDIGO CKD classification), and 168 (43%) showed no category changes. Improvement or stabilisation of GFR at one year of follow-up was associated with a reduction of major adverse cardiovascular events (MACE) [HR 0.51, 95% CI: 0.35-0.75, p = 0.001] and all-cause mortality [HR 0.54, 95% CI: 0.34-0.84, p = 0.007] during follow-up. CONCLUSIONS: The improvement or stabilisation of renal function at one-year follow-up in patients with STEMI and renal dysfunction is associated with a better long-term prognosis.

Should PRECISE-DAPT be included for long-term prognostic stratification of diabetic patients with NSTEACS?

AIMS: There are insufficient data regarding risk scores validation in patients with diabetes mellitus and non-ST elevation acute coronary syndrome (NSTEACS). We performed a diabetes mellitus-specific analysis of cardiovascular outcomes after NSTEACS. We tested the predictive power of the Global Registry of Acute Coronary Events (GRACE) and PREdicting bleeding Complications In patients undergoing Stent implantation and subsEquent Dual Anti-Platelet Therapy (PRECISE-DAPT) scores. METHODS: This work is a retrospective analysis that included 7,415 consecutive NSTEACS patients from two Spanish Universitarian hospitals between the years 2003 and 2017. The area under the ROC curve among with and without diabetes mellitus patients was calculated, to evaluate the predictive power of both scores.  RESULTS: Among the study participants, 2124 patients (28.0%) were diabetic. The median follow-up was 54,3 months (IQR 24,7-80,0 months). Diabetic patients were more women (30.5% vs. 25.7%) and older (70.0 ± 10.8 vs. 65.3 ± 13.2 years old); they had higher GRACE (146 ± 36 vs. 137 ± 36), PRECISE-DAPT (15 ± 7 vs. 18 ± 9) at admission. Early invasive coronary angiography (≤ 24 h after admission) was performed more frequently in non-diabetic. We tested the predictive power of the GRACE and PRECISE-DAPT risk scores among diabetic and non-diabetic. PRECISE-DAPT risk score showed a good predictive power for all-cause mortality, cardiovascular mortality and MACE in diabetic admitted with NSTEACS, without differences compared to non-diabetic. CONCLUSIONS: PRECISE-DAPT risk score has an appropriate predictive power in diabetic patients admitted with NSTEACS compared to non-diabetic NSTEACS. However, GRACE would be predictive worse in diabetic during long-term follow-up in a large contemporary registry.

Differences Between Takotsubo and the Working Diagnosis of Myocardial Infarction With Nonobstructive Coronary Arteries.

Aim: Whether Takotsubo syndrome (TTS) should be classified within myocardial infarction with non-obstructive coronary arteries (MINOCAs) is still controversial. The aim of this work was to evaluate the main differences between TTS and non-TTS MINOCAs. Methods and Results: A cohort study based on two prospective registries: TTS from the RETAKO registry (N:1,015) and patients with non-TTS MINOCAs from contemporary records of acute myocardial infarction from five 5 national centers (N:1,080). Definitions and management recommended by the ESC were used. Survival analysis was based on the Cox regression analysis; propensity score matching (PS) was created to adjust prognostic variables. Takotsubo syndrome were more often women (85.9 vs. 51.9%; p < 0.001) and older (69.4 ± 12.5 vs. 64.5 ± 14.1 years; p < 0.001). Atrial fibrillation (AF) was more frequent in non-TTS MINOCAs (10.4 vs. 14.4%; p = 0.007). Psychiatric disorders were more prevalent in TTS (15.5 vs. 10.2%, p < 0.001). In-hospital mortality and complications were higher in TTS: 3.4 vs. 1.8%, (p = 0.015), and 25.8 vs. 11.5%, (p < 0.001). Global mortality before PS matching was 16.1% in non-TTS MINOCAs and 8.1% in TTS. Median follow-up was 32.4 months; after PS matching, TTS had fewer major adverse cardiovascular events (MACEs): hazard ratio (HR) 0.59; 95% CI 0.42-0.83. There were no differences in global mortality (HR 0.87; CI: 0.64-1.19), but TTS had lower cardiovascular mortality (HR 0.58; CI: 0.35-0.98). Conclusion: Compared to the rest of MINOCAs, TTS presents a different patient profile and a more aggressive acute phase. However, its long-term cardiovascular prognosis is better. These results support that TTS should be considered a separate entity with unique characteristics and prognosis.

Early angiography in elderly patients with non-ST-segment elevation acute coronary syndrome: The cardio CHUS-HUSJ registry.

BACKGROUND: In elderly patients with non-ST elevation acute coronary syndrome (NSTEACS), while routine invasive management is established in high-risk NSTEACS patients, there is still uncertainty regarding the optimal timing of the procedure. METHODS: This study analyzes the association of early coronary angiography with all-cause mortality, cardiovascular mortality, heart failure (HF) hospitalization, and major adverse cardiovascular events (MACE) in patients older than 75 years old with NSTEACS. This retrospective observational study included 7811 consecutive NSTEACS patients who were examined between the years 2003 and 2017 at two Spanish university hospitals. There were 2290 patients older than 75 years old. We compared their baseline characteristics according to the early invasive strategy used (coronarography ≤24 h vs. coronarography >24 h) after the diagnosis of NSTEACS. RESULTS: Among the study participants, 1566 patients (68.38%) underwent early invasive coronary intervention. The mean follow-up period was 46 months (interquartile range 18-71 months). This association was also maintained after propensity score matching: early invasive strategy was significantly related to lower all-cause mortality [HR 0.61 (95% CI 0.51-0.71)], cardiovascular mortality [HR 0.52 (95% CI 0.43-0.63)], and MACE [HR 0.62 (CI 95% 0.54-0.71)]. CONCUSIONS: In a contemporary real-world registry of elderly NSTEACS patients, early invasive management significantly reduced all-cause mortality, cardiovascular mortality, and MACE during long-term follow-up. BRIEF SUMMARY: In this real-world retrospective observational study that included 2451 patients older than 75 years old, 1566 patients (68.38%) underwent early invasive coronary intervention. After performing a propensity score matching, the early invasive strategy was still associated with lower all-cause mortality [HR (hazard ratio) 0.61, 95% CI (95% confidence interval) (0.51-0.71)], cardiovascular mortality [HR 0.52 (95%CI 0.43-0.63)], and MACE [HR 0.62 (95%CI 0.54-0.71)] during long-term follow-up.

New-onset heart failure after acute coronary syndrome in patients without heart failure or left ventricular dysfunction.

INTRODUCTION AND OBJECTIVES: Coronary heart disease is the leading cause of heart failure (HF). The aim of this study was to assess the risk of readmission for HF in patients with acute coronary syndrome without previous HF or left ventricular dysfunction. METHODS: Prospective study of consecutive patients admitted for acute coronary syndrome in 2 institutions. Risk factors for HF were analyzed by competing risk regression, taking all-cause mortality as a competing event. RESULTS: We included 5962 patients and 567 (9.5%) experienced at least 1 hospital readmission for acute HF. Median follow-up was 63 months and median time to HF readmission was 27.1 months. The cumulative incidence of HF was higher than mortality in the first 7 years after hospital discharge. A higher risk of HF readmission was associated with age, diabetes, previous coronary heart disease, GRACE score> 140, peripheral arterial disease, renal dysfunction, hypertension and atrial fibrillation; a lower risk was associated with optimal medical treatment. The incidence of HF in the first year of follow-up was 2.73% and no protective variables were found. A simple HF risk score predicted HF readmissions risk. CONCLUSIONS: One out of 10 patients discharged after an acute coronary syndrome without previous HF or left ventricular dysfunction had new-onset HF and the risk was higher than the risk of mortality. A simple clinical score can estimate individual risk of HF readmission even in patients without previous HF or left ventricular dysfunction.

A New Biomarker Tool for Risk Stratification in "de novo" Acute Heart Failure (OROME).

Background: Inflammation is one of the mechanisms involved in heart failure (HF) pathophysiology. Thus, the acute phase reactant protein, orosomucoid, was associated with a worse post-discharge prognosis in de novo acute HF (AHF). However, the presence of anti-inflammatory adipokine, omentin, might protect and reduce the severity of the disease. We wanted to evaluate the value of omentin and orosomucoid combination for stratifying the risk of these patients. Methods and Results: Two independent cohorts of patients admitted for de novo AHF in two centers were included in the study (n = 218). Orosomucoid and omentin circulating levels were determined by ELISA at discharge. Patients were followed-up for 317 (3-575) days. A predictive model was determined for the primary endpoint, death, and/or HF readmission. Differences in survival were evaluated using a Log-rank test. According to cut-off values of orosomucoid and omentin, patients were classified as UpDown (high orosomucoid and low omentin levels), equal (both proteins high or low), and DownUp (low orosomucoid and high omentin levels). The Kaplan Meier determined a worse prognosis for the UpDown group (Long-rank test p = 0.02). The predictive model that includes the combination of orosomucoid and omentin groups (OROME) + NT-proBNP values achieved a higher C-index = 0.84 than the predictive model with NT-proBNP (C-index = 0.80) or OROME (C-index = 0.79) or orosomucoid alone (C-index = 0.80). Conclusion: The orosomucoid and omentin determination stratifies de novo AHF patients into the high, mild, and low risk of rehospitalization and/or death for HF. Its combination with NT-proBNP improves its predictive value in this group of patients.

Prognostic impact of left ventricular ejection fraction recovery in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: analysis of an 11-year all-comers registry.

AIMS: Left ventricular ejection fraction (LVEF) recovery after an ST-segment elevation myocardial infarction (STEMI) identifies a group of patients with a better prognosis. However, the association between long-term outcomes and LVEF recovery among patients with STEMI undergoing primary percutaneous coronary intervention (PCI) has not yet been well investigated. Our study aims to detect differences in long-term all-cause and cardiovascular mortality between patients who recover LVEF at 1-year post-PCI and those who do not, and search for predictors of LVEF recovery. METHODS AND RESULTS: This is a retrospective, single-centre study of 2170 consecutive patients admitted for STEMI in which primary PCI is performed. LVEF was determined at admission and at 1-year follow-up. The primary outcomes were long-term all-cause and cardiovascular mortality. Among the 2168 patients with baseline LVEF data, 822 (38%) had a LVEF < 50% and 1346 (62%) ≥ 50%. Among those with LVEF < 50%, LVEF data at 1-year were available in 554, and 299 (54.0%) presented with complete recovery (LVEF ≥ 50%). LVEF recovery was associated with a reduction in long-term all-cause and cardiovascular mortality (P < 0.0001). Female sex, treatment with ACEIs, lower creatinine levels, infarct-related artery different from the left main or left anterior descendent artery, and absence of prior ischaemic heart disease were independently associated with LVEF recovery. CONCLUSIONS: Nearly 40% of patients with STEMI undergoing primary PCI presented with LVEF depression at hospital admission. Among them, LVEF recovery at 1-year occurred in more than 50% and was independently associated with a significant decrease in long-term all-cause and cardiovascular mortality.

Prognostic benefit from an early invasive strategy in patients with non-ST elevation acute coronary syndrome (NSTEACS): evaluation of the new risk stratification in the NSTEACS European guidelines.

OBJECTIVES: The objective of our work is to evaluate the prognostic benefit of an early invasive strategy in patients with high-risk NSTACS according to the recommendations of the 2020 clinical practice guidelines during long-term follow-up. METHODS: This retrospective observational study included 6454 consecutive NSTEACS patients. We analyze the effects of early coronary angiography (< 24 h) in patients with: (a) GRACE risk score > 140 and (b) patients with "established NSTEMI" (non ST-segment elevation myocardial infarction defined by an increase in troponins) or dynamic ST-T-segment changes with a GRACE risk score < 140. RESULTS: From 2003 to 2017, 6454 patients with "new high-risk NSTEACS" were admitted, and 6031 (93.45%) of these underwent coronary angiography. After inverse probability of treatment weighting, the long-term cumulative probability of being free of all-cause mortality, cardiovascular mortality and MACE differed significantly due to an early coronary intervention in patients with NSTEACS and GRACE > 140 [HR 0.62 (IC 95% 0.57-0.67), HR 0.62 (IC 95% 0.56-0.68), HR 0.57 (IC 95% 0.53-0.61), respectively]. In patients with NSTEACS and GRACE < 140 with established NSTEMI or ST/T-segment changes, the benefit of the early invasive strategy is only observed in the reduction of MACE [HR 0.62 (IC 95% 0.56-0.68)], but not for total mortality [HR 0.96 (IC 95% 0.78-1.2)] and cardiovascular mortality [HR 0.96 (IC 95% 0.75-1.24)]. CONCLUSIONS: An early invasive management is associated with reduced all-cause mortality, cardiovascular mortality and MACE in NSTEACS with high GRACE risk score. However, this benefit is less evident in the subgroup of patients with a GRACE score < 140 with established NSTEMI or ST/T-segment changes.

CD5L, Macrophage Apoptosis Inhibitor, Was Identified in Epicardial Fat-Secretome and Regulated by Isoproterenol From Patients With Heart Failure.

OBJECTIVES: Neurohormonal dysfunction, which can regulate epicardial fat activity, is one of the main promoters of atrial fibrillation (AF) in patients with heart failure (HF). Our aim was to study the epicardial fat mediators for AF in patients with HF and its catecholaminergic regulation. METHODS: We have included 29 patients with HF who underwent cardiac surgery and were followed up for 5 years. Released proteins by epicardial adipose tissue (EAT) after isoproterenol treatment were identified by nano-high-performance liquid chromatography (HPLC) and triple time-of-flight (TOF) analysis. Common and differential identified proteins in groups of patients with AF before and after surgery were determined by the FunRich tool. Plasma and epicardial fat biopsy proteins were quantified by western blot. RESULTS: Our results identified 17 common released proteins by EAT, after isoproterenol treatment, from HF patients who suffered AF or developed new-onset AF during follow-up. Mostly, they were involved on inflammatory response and extracellular matrix. One of them was CD5L, a macrophage apoptosis inhibitor. Its secretion by isoproterenol treatment was validated on western blot. The CD5L levels on epicardial fat were also higher in the group of male patients who present or develop AF (0.44 ± 0.05 vs. 0.18 ± 0.15; p < 0.016). However, there were no differences regarding plasma levels. CONCLUSION: Our results suggest the role of epicardial fat CD5L as a mediator of AF and its possible paracrine effect by catecholaminergic activity.

Sex-related differences in long-term mortality and heart failure in a contemporary cohort of patients with NSTEACS. The cardiochus-HSUJ registry.

INTRODUCTION AND OBJECTIVES: There is insufficient data regarding sex-related prognostic differences in patients with a non-ST elevation acute coronary syndrome (NSTEACS). We performed a sex-specific analysis of cardiovascular outcomes after NSTEACS using a large contemporary cohort of patients from two tertiary hospitals. METHODS: This work is a retrospective analysis from a prospective registry, that included 5,686 consecutive NSTEACS patients from two Spanish University hospitals between the years 2005 and 2017. We performed a propensity score matching to obtain a well-balanced subset of individuals with the same clinical characteristics, resulting in 3,120 patients. Cox regression models performed survival analyses once the proportional risk test was verified. RESULTS: Among the study participants, 1,572 patients (27.6%) were women. The mean follow-up was 60.0 months (standard deviation of 32 months). Women had a higher risk of cardiovascular mortality compared with men (OR (Odds ratio) 1.27, CI (confidence interval) 95% 1.08-1.49), heart failure (HF) hospitalization (OR 1.39, CI 95% 1.18-1.63) and risk of all-cause mortality (OR 1.10, CI 95% 1.08-1.49). After a propensity score matching, female gender was associated with a significant reduction in the risk of total mortality (OR 0.77, CI 95% 0.65-0.90) with a similar risk of cardiovascular mortality (OR 0.86, CI 0.71-1.03) and HF hospitalization (OR 0.92, CI 95% 0.68-1.23). After baseline adjustment, the risk of all-cause mortality and cardiovascular mortality was lower in women, whereas the risk of HF remained similar among sexes. CONCLUSIONS: In a contemporary cohort of patients with NSTEACS, women are at similar risk of developing early and late HF admissions, and have better survival compared with men, with a lower risk of all-cause mortality and cardiovascular mortality. The implementation of NSTEACS guideline recommendations in women, including early revascularization, seems to be accompanied by improved early and long-term prognosis.