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.

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.

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.

High released lactate by epicardial fat from coronary artery disease patients is reduced by dapagliflozin treatment.

BACKGROUND AND AIMS: Dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, improves glucose uptake by epicardial adipose tissue (EAT). However, its metabolism might raise the lactate production and acidosis under hypoxia conditions, i.e. coronary artery disease (CAD), or lipogenesis and, in consequence, expand adipose tissue. Since lactate secreted by adipose tissue is correlated with tissue stress and inflammation, our aim was to study glucose metabolism by epicardial fat in CAD and its regulation by dapagliflozin. METHODS: Paired EAT and subcutaneous adipose tissue (SAT) biopsies from 49 patients who underwent open-heart surgery were cultured and split into three equal pieces, some treated with and others without dapagliflozin at 10 or 100 µM for 6 h. Anaerobic glucose metabolites were measured in supernatants of fat pads, and acidosis on adipogenesis-induced primary culture cells was analysed by colorimetric or fluorescence assays. Gene expression levels were assessed by real-time polymerase chain reaction. RESULTS: Our results showed that dapagliflozin reduced the released lactate and acidosis in epicardial fat (p < 0.05) without changes in lipid storage-involved genes. In addition, this drug induced gene expression levels of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α), a mitochondrial biogenesis-involved gene in both EAT and SAT (p < 0.05). After splitting the population regarding the presence of CAD, we observed higher lactate production in EAT from these patients (2.46 [1.75-3.47] mM), which was reduced after treatment with dapagliflozin 100 µM (1.99 [1.08-2.99] mM, p < 0.01). CONCLUSIONS: Dapagliflozin improved glucose metabolism without lipogenesis-involved gene regulation or lactate production, mainly in patients with CAD. These results suggest an improvement of glucose oxidation metabolism that can contribute to cardiovascular benefits.

Myocardial infarction with non-obstructive coronary arteries: A comprehensive review and future research directions.

Acute coronary syndromes constitute a variety of myocardial injury presentations that include a subset of patients presenting with myocardial infarction with non-obstructive coronary arteries (MINOCA). This acute coronary syndrome differs from type 1 myocardial infarction (MI) regarding patient characteristics, presentation, physiopathology, management, treatment, and prognosis. Two-thirds of MINOCA subjects present ST-segment elevation; MINOCA patients are younger, are more often female and tend to have fewer cardiovascular risk factors. Moreover, MINOCA is a working diagnosis, and defining the aetiologic mechanism is relevant because it affects patient care and prognosis. In the absence of relevant coronary artery disease, myocardial ischaemia might be triggered by an acute event in epicardial coronary arteries, coronary microcirculation, or both. Epicardial causes of MINOCA include coronary plaque disruption, coronary dissection, and coronary spasm. Microvascular MINOCA mechanisms involve microvascular coronary spasm, takotsubo syndrome (TTS), myocarditis, and coronary thromboembolism. Coronary angiography with non-significant coronary stenosis and left ventriculography are first-line tests in the differential study of MINOCA patients. The diagnostic arsenal includes invasive and non-invasive techniques. Medical history and echocardiography can help indicate vasospasm or thrombosis, if one finite coronary territory is affected, or specify TTS if apical ballooning is present. Intravascular ultrasound, optical coherence tomography, and provocative testing are encouraged. Cardiac magnetic resonance is a cornerstone in myocarditis diagnosis. MINOCA is not a benign diagnosis, and its polymorphic forms differ in prognosis. MINOCA care varies across centres, and future multi-centre clinical trials with standardized criteria may have a positive impact on defining optimal cardiovascular care for MINOCA patients.

Proposal of a novel clinical score to predict heart failure incidence in long-term survivors of acute coronary syndromes.

INTRODUCTION: HF remains a frequent complication following MI and adversely affects prognosis. The objective of this study was to identify predictors of HF following MI and to design a risk score for its prediction. METHODS: Retrospective study of all consecutive patients admitted for MI. Primary end point was time to incident HF. Patients with previous history of HF were excluded. Death was modelled as competing risk. RESULTS: 5737 patients were included. Mean age was 66.32±12.80. During a median follow-up of 47.0months (23.0-73.0), 686 patients (12%) developed HF. Age, diabetes mellitus, peripheral artery disease, renal insufficiency, chronic obstructive pulmonary disease, persistent atrial fibrillation, haemoglobin, troponin peak, diuretic at admission, ventricular function, and revascularization were independent predictors for HF development. According to this multivariate regression analysis, we developed a novel score that allows for the identification of patients at high (≥16), medium (9-15) and low risk (<9) for HF development, with an AUC of 0.77 (IC 95%, 0.76-0.78; p=0.008). CONCLUSIONS: Clinical comorbidities were determinant for the development of HF following MI. A simple score effectively categorize patients into low, intermediate, and high-risk. This could be important in order to intensify medical treatment or consider additional interventions.

Nutritional status is related to heart failure severity and hospital readmissions in acute heart failure.

BACKGROUND: Malnutrition is common in hospitalized heart failure (HF) patients and predicts adverse outcomes. The relationship between nutritional status and outcomes in HF has been partially studied. Our aim was to determine the relationship between the nutritional status and the long-term prognosis in patients hospitalized for acute HF. METHODS: We analyzed 145 patients admitted consecutively to a cardiology department for acute HF. Nutritional status was measured with the CONUT method, a validated scale based on laboratory testing (albumin; cholesterol; lymphocytes) during hospitalization. Patients were classified as normal, mildly, moderately or severely malnourished, and followed in a HF clinic. RESULTS: The mean aged of the population was 69.6years and 61% of patients were men, 54 had previous HF hospitalization (37%), 112 had hypertension (77%), 67 were diabetic (46%) and 135 had class III or IV NYHA (93%). Forty eight patients (33%) had normal nutritional status, 75 were mildly malnourished (52%), and 22 were moderately or severely malnourished (15%). Age, sex, hypertension, diabetes mellitus, or NYHA class among the three groups were not statistically different. ProBNP was directly correlated with the nutritional status. After a mean follow-up of 326days, 27 had a HF hospitalization (19%) and 61 (42,1%) had a hospitalization not related to HF. The analysis by Kaplan-Meier curves and log rank test showed that these differences were statistically significant. CONCLUSION: Malnutrition is common in patients hospitalized for HF. It seems to be a mediator of disease progression and determines a poor prognosis especially in advanced stages.

Discrepancy between stress electrocardiographic changes and nuclear myocardial perfusion defects in the prognostic assessment of patients with chest pain.

OBJECTIVES: The aim of the present study was to determine the long-term prognostic value provided by the exercise electrocardiographic (ECG) response to nuclear myocardial perfusion imaging (MPI) in the evaluation of patients with chest pain, focusing on patients with a discrepancy between the two tests. METHODS: A total of 1460 consecutive patients (777 female; 62.6 ± 11.4 years) undergoing exercise myocardial single-photon emission computed tomography (SPECT) were included. The endpoint was the occurrence of acute coronary syndrome, heart failure or cardiac death during follow-up. RESULTS: Ischemic ECG changes were observed during stress testing in 271 patients (18.5%) and 362 patients (24.7%) had positive (abnormal) exercise MPI results. There was a discrepancy between ECG and SPECT findings in 471 patients (32.2%). During the follow-up period (14.0-39.6 months), 224 patients (15.3%) presented cardiac events. The hazard ratios (HR) of ECG and MPI results to predict events were 1.506 (95% CI: 1.113-2.039) and 10.481 (95% CI: 7.799-14.080), respectively. In patients with negative MPI, the ECG response did not predict events (HR 1.214 [95% CI: 0.646-2.282]), the same as in patients with positive MPI (HR 1.203 [95% CI: 0.848-1.705]). Only in hypertensive patients with positive SPECT did the ECG show significant prognostic value (HR 1.937 [95% CI: 1.030-3.642]). In multivariate analysis, positive MPI proved an independent long-term prognostic factor (HR 10.536 [95% CI: 7.759-14.308]), but not ECG (HR 1.356 [95% CI: 0.994-1.850]). CONCLUSION: MPI results (normal vs. abnormal) had strong predictive value and discrepant ECG results had no significant additive prognostic value.

Síndrome coronario agudo con y sin elevación del segmento ST: ¿cómo darles igualdad de oportunidades? / Acute coronary syndrome with or without st-segment elevation: how can we equalize patients’ prospects?

La activación y la agregación plaquetarias son clave en la progresión de la trombosis arterial y el principal objetivo terapéutico del manejo del síndrome coronario agudo. Actualmente, además de inhibir la formación de tromboxano A2 con ácido acetilsalicílico, se recomienda inhibir otra vía complementaria de la agregación plaquetaria para asegurar la eficacia del tratamiento y prevenir la trombosis coronaria. Los profármacos tienopiridínicos, como clopidogrel y prasugrel, y el derivado pirimidínico ticagrelor son las alternativas más extendidas. En esta revisión se discuten las indicaciones de estos fármacos antiagregantes y su evidencia científica en relación con el síndrome coronario agudo con y sin elevación del segmento ST (AU)

Platelet activation and aggregation play key roles in the development of arterial thrombosis. Accordingly, they provide the principle therapeutic targets in patients with acute coronary syndrome. At present, in addition to using aspirin to inhibit the formation of thromboxane A2 , it is also recommended that another complementary platelet aggregation pathway should be inhibited to ensure that treatment is effective and to prevent coronary thrombosis. Thienopyridine prodrugs, such as clopidogrel and prasugrel, and the pyrimidine derivative ticagrelor are the most widely used agents. This review includes a discussion of indications for these antiplatelet drugs and summarizes the scientific evidence for their use in patients with acute coronary syndrome, with or without ST-segment elevation (AU)

Walking beyond the GRACE (Global Registry of Acute Coronary Events) model in the death risk stratification during hospitalization in patients with acute coronary syndrome: what do the AR-G (ACTION [Acute Coronary Treatment and Intervention Outcomes Network] Registry and GWTG [Get With the Guidelines] Database), NCDR (National Cardiovascular Data Registry), and EuroHeart Risk Scores Provide?

OBJECTIVES: This study sought to compare the in-hospital prognostic values of the original and updated GRACE (Global Registry of Acute Coronary Events) risk score (RS) and the AR-G (ACTION [Acute Coronary Treatment and Intervention Outcomes Network] Registry and the GWTG [Get With the Guidelines] Database) RS in acute coronary syndromes (ACS). To evaluate the utility of recalculating risk after percutaneous coronary intervention (PCI) with newer RS models (NCDR [National Cardiovascular Data Registry] and EHS [EuroHeart Score] RS). BACKGROUND: Defined in 2003, GRACE is among the most popular systems of risk stratification in ACS. An updated version of GRACE has since appeared and new RS have been developed, aiming to improve risk prediction. METHODS: From 2004 to 2010, 4,497 consecutive patients admitted to a single center in Spain with an ACS were included (32.1% ST-segment elevation myocardial infarction, 19.2% unstable angina). Discrimination (C-statistic) and calibration (Hosmer-Lemeshow [HL]) indexes were used to assess performance of each RS. A comparative analysis of RS designed to predict post-PCI mortality NCDR and EHS RS versus the GRACE and AR-G RS was performed in a subgroup of 1,113 consecutive patients included in the study. RESULTS: There were 265 in-hospital deaths (5.9%). Original and updated GRACE RS and the AR-G RS all demonstrated good discrimination for in-hospital death (C-statistics: 0.91, 0.90 and 0.90, respectively) with optimal calibration (HL p: 0.42, 0.50, and 0.47, respectively) in all spectra of ACS, according to different managements (PCI vs. conservative) and without significant differences between the 3 different RS. In patients undergoing PCI, EHS and NCDR RS (C-statistic = 0.80 and 0.84, respectively) were not superior to GRACE RS (C-statistic = 0.91), albeit in the subgroup of patients undergoing PCI who were categorized as high risk using the GRACE RS, both EHS and NCDR have contributed to decrease the false positive rate generated by using the GRACE RS. CONCLUSIONS: Despite having been developed over 8 years ago, the GRACE RS still maintains its excellent performance for predicting in-hospital risk of death among ACS patients.