Alessandra Laricchia

Role of the Renin-Angiotensin-Aldosterone system in the pathogenesis of atherosclerosis

Renin-angiotensin-aldosterone (RAAS) is a hormone system which acts on multiple physiologic pathways primarily by regulating blood pressure and fluid balance, but also by local autocrine and paracrine actions. In pathophysiologic conditions RAAS also contributes to the development of atherosclerosis and its various manifestations, both directly and indirectly through the actions on other systems. RAAS mainly acts as a promoter of atherosclerosis by its action on vessels, and by promoting the development of hypertension, insulin resistance and diabetes, obesity, vascular and systemic inflammation. As RAAS plays a key role in the pathogenesis of cardiovascular diseases, RAAS genes have been extensively studied as candidate genes for atherosclerosis and coronary artery disease. Several polymorphisms of its genes have been found to be in relationship with atherosclerosis and cardiovascular diseases. In this review we will discuss these issues and present the most recent advances about this topic.

Plasma levels of active Von Willebrand factor are increased in patients with first ST-segment elevation myocardial infarction: A multicenter and multiethnic study

Aims: Von Willebrand factor (VWF), a key player in hemostasis and thrombosis, is released from endothelial cells during inflammation. Upon release, VWF is processed by ADAMTS13 into an inactive conformation. The aim of our study was to investigate whether plasma levels of active VWF, total VWF, ADAMTS13, osteoprotegerin (OPG) and the ratios between VWF and ADAMTS13 are risk factors for first ST-segment elevation myocardial infarction (STEMI). Methods and results: We assessed 1026 patients with confirmed first STEMI and 652 control subjects from China, Italy and Scotland, within six hours after their cardiovascular event. Median plasma levels of total VWF, active VWF, OPG and ratios VWF/ADAMTS13 were increased, while plasma levels of ADAMTS13 were decreased in patients compared to controls. The odds ratio (OR) of STEMI in patients with high plasma levels of active VWF was 2.3 (interquartile range (IQR): 1.8–2.9), total VWF was 1.8 (1.4–2.3), ADAMTS13 was 0.6 (05–0.8), OPG was 1.6 (1.2–2.0) and high VWF/ADAMTS13 ratios was 1.5 (1.2–2.0). The OR for total VWF, active VWF and ratios VWF/ADAMTS13 remained significant after adjustment for established risk factors, medical treatment, C-reactive protein, total VWF, ADAMTS13 and OPG. When we adjusted for levels of active VWF, the significance of the OR for VWF and ratios VWF/ADAMTS13 disappeared while the OR for active VWF remained significant. Conclusions: We found evidence that plasma levels of active VWF are an independent risk factor for first STEMI in patients from three different ethnic groups. Our findings confirm the presence of VWF abnormalities in patients with STEMI and may be used to develop new therapeutic approaches.

Identification of High-Risk Patients After ST-Segment–Elevation Myocardial Infarction

Background— The incidence of angiographic no reflow (NR) and microvascular obstruction (MVO) at cardiac magnetic resonance is significantly different. The aim of this study was to investigate the occurrence of NR and MVO in a cohort of consecutive patients with ST-segment–elevation myocardial infarction treated with primary percutaneous coronary interventions. Methods and Results— In this prospective study, 88 consecutive ST-segment–elevation myocardial infarction patients were enrolled within 12 hours from symptoms onset. All patients underwent cardiac magnetic resonance between 2 and 5 days after primary percutaneous coronary interventions. NR was defined as thrombolysis in myocardial infarction flow grade ⩽2 and as myocardial blush grade <2. Presence of early or late MVO was assessed 4 and 10 to 15 minutes after gadolinium injection. Thirty-one patients (36%) had evidence of NR, whereas 58 (67%) had MVO. One NR patient did not have MVO. In contrast, NR was present in 30 of 58 MVO patients. MVO patients had higher troponin T peak (P<0.0001), larger late gadolinium enhancement area (P<0.0001), and lower left ventricular ejection fraction (P<0.001) because of an increased end-systolic volume (P=0.015). In contrast, patients with NR had higher troponin T peak (P=0.006) but similar late gadolinium enhancement area (P=0.24) compared with those without NR. Major cardiovascular adverse events–free survival was worse in patients with MVO (P=0.014), although it was similar in patients with and without NR (P=0.33). The independent predictors of major cardiovascular adverse events were MVO (hazard ratio, 3.418; P=0.046) and ischemic time (hazard ratio, 1.016; P<0.001). MVO was a strong predictor of target lesion revascularization occurrence (P=0.017 for log-rank test). Conclusions— Compared with coronary angiography performed soon after recanalization of the culprit artery, cardiac magnetic resonance performed during index hospitalization provides better prognostic stratification of ST-segment–elevation myocardial infarction patients treated with primary percutaneous coronary interventions. Another novel finding of our study is a significantly increased rate of clinically driven target lesion revascularization in the index event culprit vessel in patients with MVO.

The predictive role of renal function and systemic inflammation on the onset of de novo atrial fibrillation after cardiac surgery

Background The association between postoperative atrial fibrillation (POAF) and renal function was previously grounded in patients undergoing coronary artery bypass grafting through unknown mechanisms. We aim to investigate the association between renal function and POAF in a cohort composed mostly of patients undergoing valve surgery and to explore the role of inflammation as a pathogenic mechanism linking renal dysfunction and arrhythmogenesis. Methods Altogether 444 patients who underwent cardiac surgery without previous history of atrial fibrillation were analysed. Serum creatinine and high sensitivity C-reactive protein (hs-CRP) concentrations were obtained at baseline and on the 3rd, 8th and 15th postoperative day; estimated glomerular filtration rate (eGFR) was calculated by the Modified Diet Renal Disease (MDRD) formula. Patients were divided into three groups on the basis of baseline eGFR. Results Overall, 173 (39%) patients developed POAF, 29.5% in the group with normal eGFR (≥90 ml/min/1.73 m2), 43.3% among patients with eGFR 60–90 ml/min/1.73 m2 and 55.6% in the group with eGFR ≤60 ml/min/1.73 m2. Patients developing POAF had lower eGFR on all the samples. At baseline preoperatively hs-CRP levels did not differ in the two groups. On multivariate analysis, age and eGFR were identified as independent predictors of POAF. The risk of POAF progressively increased from mild impairment (odds ratio (OR) 1.59, 95% confidence interval (CI) 1.01–2.50) to severe reduction of renal function (OR 2.35, 95% CI 1.25–4.48). Conclusions Age and eGFR were identified as the strongest predictors of POAF in a population largely composed of valve surgery patients. Renal function, even from early stage, is independently associated with the increasing risk of developing POAF.

Pharmacological and nonpharmacological treatment after cardiac surgery.

Open-heart surgery has become a common procedure. Postcardiac surgery management is a critical issue and represents a crucial period in terms of physical recovery. Cardiac rehabilitation is increasingly considered as an integral component of the continuum of care for patients with cardiovascular disease. Its usefulness is now widely accepted, and therefore, it is recommended in most contemporary cardiovascular clinical practice guidelines. Similarly, early pharmacological management can modulate the pathophysiological alterations after cardiac surgery, leading to an improvement in the early and long-term outcome. In this review, we will present recent advances in postcardiac surgery management, focusing on the pathophysiology of the perioperative period and on recent evidences in pharmacological and rehabilitative strategies.

Incidence of contrast-induced acute kidney injury in a large cohort of all-comers undergoing percutaneous coronary intervention: Comparison of five contrast media

BACKGROUND There is controversy as to whether iso-osmolar contrast media (IOCM) are associated with lower risk of contrast-induced acute kidney injury (CI-AKI), compared with low-osmolar contrast media (LOCM). We aimed to evaluate if a differential risk of CI-AKI exists after percutaneous coronary intervention (PCI) according to different contrast media (CM) types. METHODS We performed a single-center retrospective study in a cohort of all-comers undergoing PCI between January 2012 and December 2016. CI-AKI was defined as an increase in serum creatinine ≥0.3 mg/dl or ≥50% within 72 h from PCI. IOCM were represented by iodixanol, whereas four different LOCM were utilized (ioversol, iopromide, iomeprol, iobitridol). Multiple-treatment inverse probability of treatment weighting (IPTW)-adjusted logistic regression analysis was performed to identify whether CM type was an independent predictor of CI-AKI. RESULTS We included 2648 subjects (ioversol, n = 272; iopromide, n = 818; iomeprol, n = 611; iobitridol, n = 460; iodixanol, n = 487). CI-AKI occurred in 300 patients (11.7%) overall, with no differences across CM groups (ioversol 13.0%, iopromide 11.5%, iomeprol 10.2%, iobitridol 13.9%, iodixanol 11.3%; p = 0.42). CI-AKI requiring dialysis was observed in 8 patients (0.3%) overall (p = 0.50). On IPTW-adjusted analysis, none of the LOCM was associated with a significantly different risk of CI-AKI compared with iodixanol: ioversol OR 0.986 (95% confidence interval [CI] 0.611-1.591), iopromide OR 0.870 (95% CI 0.606-1.250), iomeprol OR 0.904 (95% CI 0.619-1.319), iobitridol OR 1.258 (95% CI 0.850-1.861). CONCLUSIONS In a large cohort of all-comers undergoing PCI, there were no differences in the adjusted risk of CI-AKI across 4 LOCM, compared with iodixanol.

Anatomic and procedural associations of transcatheter heart valve displacement following Evolut R implantation: Anatomic and procedural associations of transcatheter heart valve displacement following Evolut R implantation

This study aimed to predict the displacement of self‐expanding transcatheter heart valves (THV) during final deployment.

Contrast-Induced Nephropathy After Percutaneous Coronary Intervention for Chronic Total Occlusion Versus Non-Occlusive Coronary Artery Disease

Contrast volume is associated with the incidence of contrast-induced nephropathy (CIN), and CIN risk could be particularly high in chronic total occlusion (CTO) percutaneous coronary intervention (PCI). Our aim was to evaluate the incidence of CIN in patients who underwent CTO versus non-CTO PCI. All PCIs performed at our institution from January 2012 to December 2016 were included in this study. CIN was defined as an increase of ≥0.3 mg/dl or ≥50% from baseline within 72 hours. Multivariable logistic regression analysis was performed to identify independent predictors of CIN. A total of 2,580 patients were included (n = 309 CTO PCI and n = 2271 non-CTO PCI). Estimated glomerular filtration rate was lower in the non-CTO group (73.9 ± 27.3 vs 77.1 ± 24.7 ml/min/1.73/m2, p = 0.05). Patients in the non-CTO PCI group presented more often with acute coronary syndrome (47% vs 15%, p < 0.001). Contrast volume (347 ± 159 vs 215 ± 107 ml, p < 0.001) and contrast-volume-to-creatinine-clearance ratio (4.7 ± 2.1 vs 3.2 ± 1.8, p < 0.001) were higher in the CTO group. There was no difference in CIN rates between CTO and non-CTO groups (9.4% vs 12.1%, p = 0.17). This was confirmed in a sensitivity analysis including only patients who underwent PCI in a stable clinical setting (7.7% vs 8.5%, p = 0.66). On multivariate analysis hypotension during/before PCI (odds ratio [OR] 2.86), acute coronary syndrome (OR 1.86), age (OR 1.54), female sex (OR 1.51), left ventricular ejection fraction (OR 0.64), diabetes mellitus (OR 1.49), and contrast volume (OR 1.17) were independent predictors of CIN, while CTO PCI was not. In conclusion, CTO PCI is associated with similar rates of CIN, compared with non-CTO PCI. These findings persisted on sensitivity and multivariable analyses.