Cecilia Vecoli

Background: New-onset postoperative atrial fibrillation (NOAF) is the most prevalent arrythmia after cardiac surgery with a significant clinical and economic impact. Therefore, simple and practical biomarkers for NOAF prediction remain a clinical priority. Increasing evidence indicates that malnutrition is linked to postoperative complications, including the onset of atrial fibrillation. The Prognostic Nutritional Index (PNI), which reflects the immunonutritional and inflammatory status through serum albumin concentration and lymphocyte count, has emerged as a reliable prognostic indicator in cardiovascular disease. The present study aimed to investigate the association between PNI and the development of NOAF in patients undergoing surgical aortic valve replacement (SAVR). Methods: A total of 241 consecutive patients who underwent AVR for severe aortic stenosis or regurgitation were enrolled in this study. The population was stratified into two groups according to the development of NOAF (NOAF group) or the lack thereof (no NOAF group). Results: In both univariate and multivariate logistic regression analyses adjusted for several established NOAF determinants, age and PNI, both as continuous variables, were independently associated with NOAF in both univariate (OR = 1.03; CI 95% = 1.01–1.06, p = 0.009, and OR = 0.9; CI 95% = 0.8–0.9, p = 0.01, respectively) and multivariate models (OR = 1.02; CI 95% = 1.01–1.06, p = 0.05, and OR = 0.9; CI 95% = 0.8–0.9, p = 0.03, respectively). When PNI was analyzed by tertiles, patients in the lowest tertile (PNI < 41.5) showed a significantly higher risk of developing NOAF at both univariate (OR = 1.9; CI 95% = 1.2–2.8, p = 0.004) and multivariate analysis (OR = 1.6; CI 95% = 1–2.6, p = 0.03), whereas age lost statistical significance (OR = 1.0; 95% CI = 0.9–1.05; p = 0.06). Furthermore, when the study population was divided into two groups based on the median age (70 years), PNI values differed significantly between NOAF and no NOAF patients only in patients under 70 years (p = 0.01). In this younger subgroup, PNI remained an independent predictor of NOAF, both when considered as a continuous variable (OR = 0.86; CI 95% = 0.74–0.98, p = 0.02), and nominal variable (PNI < 41.5, OR = 0.88; CI 95% = 0.80–0.97, p = 0.01). Conclusions: Overall, these findings identify PNI as an independent predictor of NOAF following SAVR, particularly in patients younger than 70 years. This study underlines the potential clinical value of preoperative nutritional assessment for risk stratification. Incorporating nutritional parameters such as PNI into current predictive models may enhance the accuracy of prognostic evaluation and support targeted perioperative management strategies.

Aims: Metabolic syndrome (Mes) and diabetes are emerging cardiometabolic determinants of coronary atherosclerotic disease (CAD) risk besides LDL-cholesterol (LDL-C) and established risk factors. We aimed to assess whether, in patients with chronic coronary syndrome (CCS), cardiometabolic risk is prevalent and independently associated with residual CAD risk in subjects with low LDL-C. Methods and results: The cross-sectional HURRICANE study (Health improvement by Understanding RR In CAd and NEw targets for treatment) included 479 patients with CCS (mean age 65 ± 11 years, 70% male), undergoing cardiac computed tomography angiography (CCTA). A severe/extensive CAD or a moderate-high CAD risk were defined, on patient level, by CCTA-derived CAD-RADS2 and Leiden scores. Metabolic syndrome was present in 31% of patients, diabetes or pre-diabetes in 21% and 26%, severe/extensive CAD and moderate-high Leiden score in 51% and in 61%, more frequently in the two lower LDL-C categories. Multivariate logistic regression models, included age, sex, smoking status, family history, LDL-C categories (<70, 70–99 100–129, and ≥130 mg/dL), MeS, or its components and medications. Independent predictors of moderate-high Leiden score were age, male sex, the lowest LDL-C category and MeS (OR 2.12, 95% CI: 1.26–3.56) or pre-diabetes (OR 1.90, 95% CI: 1.12–3.21) and diabetes (OR 6.13, 95% CI: 1.93–19.45). In the lowest LDL-C group, higher CAD-RADS2 and Leiden scores were more frequent in patients with cardiometabolic risk. Conclusion: Results of this cross-sectional study suggest that dysregulation of glucose metabolism is the prevalent component of residual cardiometabolic and coronary atherosclerotic risk in patients with CCS and low LDL-C under current treatment.

Patients with Fontan circulation are at lifelong risk for a range of complications involving multiple organ systems. As survival into adulthood increases, there is an urgent need to refine strategies for long-term follow-up and the early detection of Fontan-related sequelae. This narrative review aims to provide a comprehensive summary of the current evidence regarding the use of circulating blood biomarkers as non-invasive tools for assessing and monitoring Fontan physiology. We critically analyzed available studies investigating serum biomarkers related to key pathological mechanisms associated with Fontan failure, encompassing not only cardiac dysfunction but also systemic inflammation, endothelial dysfunction, hepatic and renal impairment, and altered bone metabolism. Several biomarkers have shown promise in reflecting global systemic impairments as well as end-organ involvement in Fontan patients. However, current data are insufficient to support evidence-based clinical recommendations for standardized specific biomarkers, mainly due to the small sample sizes, heterogeneous patient populations, and limited longitudinal data in the available studies. Only a large-scale, prospective, multi-center, and multidisciplinary research will permit us to identify a panel of specific biomarkers of clinical utility in this population. Artificial intelligence (AI) and machine learning (ML) approaches could be applied to integrate all these heterogeneous datasets. Furthermore, “omics”-based studies, including proteomics, metabolomics, lipidomics, and microRNA profiling, hold great potential for uncovering novel biomarkers and pathophysiological pathways, ultimately paving the way for precision medicine in the management of Fontan patients.

Background: Several blood biomarkers have shown a major role in predicting major adverse complications (MACs) in patients who have undergone cardiac surgery. Here, we aimed to investigate the possible role of the blood urea nitrogen (BUN) to serum albumin ratio (BAR) and the inflammatory prognostic index (IPI) in predicting major adverse complication after surgical aorta valve replacement (SAVR). Methods: The clinical, echocardiographic, and clinical-chemistry laboratory data of 195 patients who underwent SAVR were evaluated. The post-surgical MACs (death, surgical re-exploration, myocardial infarction and cerebral ischemia) during the hospitalization were recorded. Univariate and multivariate logistic regression analyses were studied by comparing the basic clinical features, echocardiographic parameters, and patients’ hematological indices between patients with or without MACs. Results: The mean age was 66.1 years, and 62.5% were males. Logistic regression analysis showed that the left atrium volume (LAV), BAR, and IPI as either continuous or categorical variables were independently associated with MACs. Moreover, we found a combined effect of higher LAV with a higher value of BAR or IPI. Combined higher levels of LAV and BAR increased the risk of developing MACs by 9.8 (CI 95% = 2.8–34.3, p = 0.0003), while higher values of LAV and IPI increased the risk of developing MACs by 4.5. Conclusions: Higher levels of BAR and IPI, alone or in combination with higher LAVs, showed an independent predictive value of MACs after SAVR. These findings strongly support the importance of evaluating easily available biomarkers of the pre-operative status of patients in order to predict adverse outcomes.

Aortic valve stenosis (AVS) is the most common valvular heart disease that was considered, for a long time, a passive degenerative disease due to physiological aging. More recently, it has been recognized as an active, modifiable disease in which many cellular processes are involved. Nevertheless, since aging remains the major risk factor for AVS, a field of research has focused on the role of early (biological) aging and its dependent pathways in the initiation and progression of AVS. Telomeres are regions at the ends of chromosomes that are critical for maintaining genome stability in eukaryotic cells. Telomeres are the hallmarks and molecular drivers of aging and age-related degenerative pathologies. Clonal hematopoiesis of indeterminate potential (CHIP), a condition caused by somatic mutations of leukemia-associated genes in individuals without hematologic abnormalities or clonal disorders, has been reported to be associated with aging. CHIP represents a new and independent risk factor in cardiovascular diseases, including AVS. Interestingly, evidence suggests a causal link between telomere biology and CHIP in several pathological disorders. In this review, we discussed the current knowledge of telomere biology and CHIP as possible mechanisms of aortic valve degeneration. We speculated on how a better understanding of the complex relationship between telomere and CHIP might provide great potential for an early diagnosis and for developing novel medical therapies to reduce the constant increasing health burden of AVS.

Optimal medical treatment in patients with stable coronary artery disease (CAD) reduced morbidity and mortality but left a substantial residual risk (RR) of disease progression and events. According to recent evidence, insulin resistance or pre-diabetes together with elevated levels of triglycerides, low levels, and functionality of HDL-cholesterol, often associated with a chronic inflammatory state, are deemed to be relevant components of cardiometabolic and vascular RR. In the present project, we aim at discovering specific individual genetic/molecular profiles subtending emerging cardiometabolic and vascular risk patterns and associated with more severe stable CAD phenotypes. To this end, we will analyse clinical data, blood samples, and imaging data already gathered in a retrospective population of 561 patients with suspected stable coronary disease and will develop integrated predictive models of severity and extent of disease defined by qualitative and quantitative analysis of coronary plaques by cardiac computed tomography. The new predictive models, which will incorporate relevant clinical and genetic/molecular variables associated with more severe coronary atherosclerosis, will be validated in a similar prospective population of patients and extended to the prediction of progression (at 1 year follow-up) of coronary disease phenotypes, occurring despite optimal medical treatment. Registration ClinicalTrials.gov ID: NCT06601153

Background: Elderly patients with severe aortic stenosis (AS) need individualized decision-making in their management in order to benefit in terms of survival and improvement of quality of life. Frailty, a common condition in elderly patients, needs to be considered when weighing treatment options. Aim: We aimed to evaluate outcomes including survival and functional parameters according to disability criteria at six years of follow-up in an older population treated for severe AS using a frailty-based management. Methods: We evaluated data derived from a pilot clinical project involving elderly patients with severe AS referred to a tailored management based on classification by Fried’s score into pre-frail, early frail, and frail and a multidimensional geriatric assessment. A Frailty, Inflammation, Malnutrition, and Sarcopenia (FIMS) score was used to predict the risk of mortality at six years of follow-up. Functional status was evaluated by telephonic interview. Results: At six years of follow-up, we found a survival rate of 40%. It was higher in the pre-frail patients (long rank < 0.001) and in the patients who underwent TAVR treatment (long rank < 0.001). The cut-off FIMS score value of ≥1.28 was an independent determinant associated with a higher risk of mortality at six years of follow-up (HR 2.91; CI 95% 1.7–5.1; p-value 0.001). We found a moderate increase of disability levels, malnutrition status, comorbidities, and number of drugs, but none of them self-reported advanced NYHA class III–IV heart failure. Conclusion: An accurate clinical–instrumental and functional geriatric evaluation in an elderly population with AS is required for a non-futile interventional treatment in terms of survival and functional status even in long-term follow-up.

Frailty degree plays a critical role in the decision-making and outcomes of elderly patients with severe aortic stenosis (AS). Acute heart failure (AHF) results in a severely worse clinical hemodynamic status in this population. This study aimed to evaluate the impact of AHF on frailty degree and outcomes in older patients referred for tailored interventional treatment due to AS. A total of 109 patients (68% female; mean age 83.3 ± 5.4), evaluated by a multidisciplinary path for “frailty-based management” of valve disease, were divided into two groups, one with (AHF+) and one without AHF (AHF-) and preserved ejection fraction (mean value EF: 57.4 ± 8.6). AHF occurred a mean value of 55 days before geriatric, clinical, and surgical assessment. A follow-up for all-cause mortality and readmission was conducted at 20 months. AHF+ patients showed a higher frequency of advanced frailty (53.3% vs. 46.7%, respectively), rehospitalization (35.5% vs. 12.8; p = 0.007), and death (41.9% vs. 12.8%; p < 0.001). In stepwise logistic regression analysis, AHF emerged as an independent risk factor for advanced frailty (OR: 3.8 CI 1.3–10.7; p = 0.01) and hospital readmission (OR: 3.6 CI 1.1–11.6; p = 0.03). In addition, preceding AHF was an independent determinant associated with a higher risk of mortality (HR 2.65; CI 95% 1.04–6.74; p-value 0.04). AHF is independently associated with advanced frailty and poor outcomes in elderly patients with severe AS. So, this population needs careful clinical and geriatric monitoring and the implementation of interventional therapy for AS in the early stages of frailty to avoid the occurrence of AHF and poor outcomes.

The endothelial nitric oxide synthase (eNOS) gene deficiency is known to cause impaired coronary vasodilating capability in animal models. In the general clinical population, the eNOS gene polymorphisms, able to affect eNOS activity, were associated with cardiometabolic risk features and prevalence of coronary artery disease (CAD). To investigate the association of eNOS Glu298Asp gene polymorphism, cardiometabolic profile, obstructive CAD and inducible myocardial ischemia in patients with suspected stable CAD. A total of 506 patients (314 males; mean age 62 ± 9 years) referred for suspected CAD was enrolled. Among these, 325 patients underwent stress ECG or cardiac imaging to assess the presence of inducible myocardial ischemia and 436 patients underwent non-invasive computerized tomography or invasive coronary angiography to assess the presence of obstructive CAD. Clinical characteristics and blood samples were collected for each patient. In the whole population, 49.6% of patients were homozygous for the Glu298 genotype (Glu/Glu), 40.9% heterozygotes (Glu/Asp) and 9.5% homozygous for the 298Asp genotype (Asp/Asp). Obstructive CAD was documented in 178/436 (40.8%) patients undergoing coronary angiography while myocardial ischemia in 160/325 (49.2%) patients undergoing stress testing. Patients with eNOS Asp genotype (Glu/Asp + Asp/Asp) had no significant differences in clinical risk factors and in circulating markers. Independent predictors of obstructive CAD were age, gender, obesity, and low HDL-C. Independent predictors of myocardial ischemia were gender, obesity, low HDL-C and Asp genotype. In the subpopulation in which both stress tests and coronary angiography were performed, the Asp genotype remained associated with increased myocardial ischemia risk after adjustment for obstructive CAD. In this population, low-HDL cholesterol was the only cardiometabolic risk determinant of obstructive CAD. The eNOS Glu298Asp gene polymorphism was significantly associated with inducible myocardial ischemia independently of other risk factors and presence of obstructive CAD.