Coronary Artery Ectasia as an Autoimmune Disease Paradigm in a Cross-Sectional Case-Control Study.

Coronary artery ectasia (CAE) is defined as local or generalized aneurysmal dilatation of the coronary arteries. CAE likely represents an exaggerated form of excessive vascular wall remodeling in different clinical settings such as atherosclerosis, vasculitides, connective tissue disorders, hereditary collagen defects, bacterial infections, and congenital malformations. In the present case-control study, we investigated whether the incidental finding of CAE in patients who undergo coronary angiography is associated with presence of autoimmune reactivity. From 2019 to 2022, we identified all consecutive patients with CAE (n = 319) on elective or emergency coronary angiography (n = 7,458). We furthermore included 90 patients with nonectatic coronary arteries as a control group. Antinuclear antibody (ANA) titer was measured in both groups using the indirect immunofluorescence method from peripheral blood samples. The prevalence of CAE in our study cohort was 4.3%. Among patients with CAE (n = 319), presence of positive Antinuclear antibody (ANA) titer was identified in 128 patients (40%). Only 18 patients (20%) from the control group had positive ANA titer. There was a statistically significant greater percentage of patients with positive ANA titer among patients with CAE than among controls (chi-square = 12.39; p <0.001), with an odds ratio of 2.68. Among patients with CAE, there is an increased prevalence of positive ANA titer, suggesting an underlying autoimmune disease. Screening for autoimmune reactivity could be a reasonable diagnostic strategy in patients who undergo coronary angiography with an incidental finding of coronary ectasia because the number needed to screen for positive ANA titer in this subgroup of patients is only 5.

Effect of Sacubitril/Valsartan on circulating catecholamine levels during a 6-month follow-up in heart failure patients. Timeo Danaos et dona ferentes?

We assessed the effect of Sacubitril/Valsartan on circulating catecholamine levels in patients with HF in an observational cohort study. We included 108 consecutive HF patients attending our HF Outpatients Clinic who were eligible to Sacubitril/Valsartan according to the PARADIGM-HF inclusion and exclusion criteria. We furthermore included 58 stable HF patients under optimal medical therapy as a control group. Norepinephrine and epinephrine were measured with immunoradiometric assays at baseline, at 3- and at 6-month time follow-up. Compared to baseline levels there was no change at three months in epinephrine (p = 0.177) or norepinephrine (p = 0.815) concentrations. At 6 months norepinephrine remained unchanged (p = 0.359). However, at 6 months we observed a significant increase in epinephrine levels compared to baseline [66 pg/mL (37-93) vs 38 pg/mL (18-74), p < 0.001]. In the control group no change was observed in epinephrine levels compared to baseline (p = 0.838). This study is the first to report on the effect of the new drug Sacubitril/Valsartan on circulating catecholamine levels in HF patients. Our data show a significant increase in epinephrine levels during a 6 month follow up in stable HF patients.

Comparison of novel LDL cholesterol equations in myocardial infarction patients: Clinical impact on risk re-classification and lipid treatment goals on secondary prevention.

BACKGROUND AND AIMS: Numerous low-density lipoprotein (LDL) calculating equations for more accurate estimation have emerged. With the present study, we assessed the clinical impact of implementing novel equations in terms of risk reclassification and LDL treatment goals in myocardial infarction (MI) patients. METHODS: This was a post-hoc analysis of a prospective acute MI cohort study. We enrolled 805 consecutive patients presenting with acute MI. Patients with high triglyceride levels (>400 mg/dL) were excluded. In the remaining 773 acute MI patients, LDL cholesterol levels were calculated using 12 different equations including the Friedewald equation. Each patient was categorized into a 5-scale risk strata scheme according to baseline LDL cholesterol levels. Moreover, ΔLDL cholesterol (change in LDL cholesterol levels to achieve the <55 mg/dL LDL treatment goal) was calculated for each patient. RESULTS: Mean levels and distribution of LDL cholesterol were significantly different compared to those derived from the Friedewald equation. Net reclassification improvement (NRI) analysis, as well as heat maps, showed that this re-categorization had no significant impact on prognostic terms (NRI ranged from -6.1% to 5.9% with p values > 0.05 for each comparison). Statistically significant differences were observed in ΔLDL cholesterol levels between each one of the novel equations and the Friedewald equation. CONCLUSIONS: Novel LDL cholesterol calculating equations are not associated with a clinically significant risk re-classification in MI patients. In addition, use of these novel equations may have an impact on assessing potency of hypolipidemic therapy use in secondary prevention as far as succeeding lipid treatment goals in MI patients.

Application of 17 Contrast-Induced Acute Kidney Injury Risk Prediction Models.

INTRODUCTION: Contrast-induced acute kidney injury (CI-AKI) is a frequent complication of percutaneous coronary interventions (PCI). Various groups have developed and validated risk scores for CI-AKI. Although the majority of these risk scores achieve an adequate accuracy, their usability in clinical practice is limited and greatly debated. OBJECTIVE: With the present study, we aimed to prospectively assess the diagnostic performance of recently published CI-AKI risk scores (up to 2018) in a cohort of patients undergoing PCI. METHODS: We enrolled 1,247 consecutive patients (80% men, mean age 62 ± 10 years) treated with elective or urgent PCI. For each patient, we calculated the individual CI-AKI risk score based on 17 different risk models. CI-AKI was defined as an increase of ≥25% (liberal) or ≥0.5 mg/dL (strict) in pre-PCI serum creatinine 48 h after PCI. RESULTS: CI-AKI definition and, therefore, CI-AKI incidence have a significant impact on risk model performance (median negative predictive value increased from 85 to 99%; median c-statistic increased from 0.516 to 0.603 using more strict definition criteria). All of the 17 published models were characterized by a weak-to-moderate discriminating ability mainly based on the identification of "true-negative" cases (median positive predictive value 19% with liberal criterion and 3% with strict criterion). In none of the models, c-statistic was >0.800 with either CI-AKI definition. Novel, different combinations of the >35 independent variables used in the published models either by down- or by up-scaling did not result in significant improvement in predictive performance. CONCLUSIONS: The predictive ability of all models was similar and only modest, derived mainly by identifying true-negative cases. A new approach is probably needed by adding novel markers or periprocedural characteristics.

Long-term impact of acute kidney injury on prognosis in patients with acute myocardial infarction.

BACKGROUND: Little evidence exists regarding the long-term impact of acute kidney injury (AKI) during index hospitalisation for acute myocardial infarction (AMI). We prospectively assessed the long-term prognostic significance of the occurrence of in-hospital AKI in a multicentre cohort of patients admitted with AMI. METHODS: Data were obtained from 518 AMI patients with a median follow-up of 5.6 (IQR 4.6-6.5) years. Patients were followed up regarding the occurrence of death, major adverse cardiovascular events (MACE), and any deterioration in kidney function. RESULTS: From the study cohort, 84 patients (16%) had developed AKI at discharge during index hospitalisation. 96 patients died during follow-up, MACE occurred in 90 patients, and 30 patients showed evidence of deterioration in kidney function. Patients with AKI at hospital discharge had a three-fold increased mortality risk (HR 3.2, 95% CI 2.1-4.8; P < 0.001). This association was independent of possible confounding by variables that could influence prognosis (HR 1.9 95% CI 1.1-3.2; P = 0.028) evident only up to three years during follow-up. During long-term follow-up, patients with AKI during their index hospitalisation had a significantly (P = 0.027) higher incidence of MACE (26%) than those who did not develop AKI (15%). Patients with AKI had a higher incidence of deteriorating kidney function (10%) than those without AKI (5%) during follow-up, but this difference was not significant (P = 0.124). CONCLUSIONS: Our findings emphasise in addition to the need for appropriate long term follow-up in such patients, an increased mortality and morbidity during the first three years after the index event.

Independent and additive prognostic ability of serum carboxy-terminal telopeptide of collagen type-I in heart failure patients: a multi-marker approach with high-negative predictive value to rule out long-term adverse events.

BACKGROUND: Altered myocardial extracellular matrix turnover has been proposed as a major determinant of myocardial remodelling. Carboxy-terminal telopeptide of collagen type-I (CITP) represents a collagen type-I degradation-derived serum peptide. In this study we examined the independent and additive prognostic value of serum concentrations of CITP compared with well-known mortality predictors such as the N-terminal pro-brain natriuretic peptide (NT-proBNP) in chronic heart failure (CHF) patients. METHODS: We studied 196 consecutive patients (126 male, mean age 69 ± 10 years), who were admitted for acute decompensation of the CHF syndrome. The study entry point was determined at the discharge of the patients after achieving a stable compensated status. The primary endpoint was cardiac mortality during a 12-month follow-up. RESULTS: In the multivariate Cox proportional hazard model the levels of CITP remained a predictor of survival (hazards ratio 0.4 95% confidence interval 0.21-0.76, P = 0.005), independent of NT-proBNP levels. The stratified log-rank test (P < 0.001) showed that CHF patients characterized by low levels of both biomarkers had better survival (hazards ratio 0.12 95% confidence interval 0.04-0.35, P < 0.001) compared with patients characterized by high levels of both biomarkers. The negative predictive value of the combined measure for long-term adverse events was 94%. CONCLUSION: Serum levels of CITP were shown to be an independent and strong prognostic marker regarding survival in CHF patients. Furthermore, CITP levels had an additive prognostic value compared with NT-proBNP levels. These findings underline the detrimental role of myocardial fibrosis in the progression of heart failure and suggest a novel multi-marker approach for risk stratification in the CHF syndrome.

Circulating levels of a biomarker of collagen metabolism are associated with health-related quality of life in patients with chronic heart failure.

PURPOSE: Assessment of circulating levels of collagen-derived peptides has been proposed as a useful tool to monitor indirectly myocardial collagen metabolism in chronic heart failure (CHF) patients. The potential link between circulating concentrations of collagen metabolism biomarkers and health-related quality of life (HRQOL) has not been adequately evaluated. With the present study, we investigated the association between serum levels of collagen-derived peptides and HRQOL. METHODS: We studied 280 consecutive outpatients (of mean age 67 ± 10 years, 180 men) with CHF. Serum concentrations of carboxy-terminal telopeptide of collagen type I (CITP)-a marker of collagen type I degradation-were measured in all patients both at baseline and during a period of 6 months follow-up. HRQOL was assessed by Minnesota living with heart failure questionnaire (MLHFQ). RESULTS: CITP levels were significantly associated with MLHFQ scores both at baseline (r = 0.231, P < 0.001) and at 6 months follow-up (r = 0.145, P = 0.044). CITP levels remained significantly associated with MLHFQ score in multivariable linear regression analysis. Higher CITP levels were observed with higher MLHFQ scores (poor HRQOL) both at baseline (P = 0.001) and at 6 months (P = 0.041). Unadjusted analysis demonstrated a significant relationship between increasing CITP levels during 6 months follow-up and worsening HRQOL (r = 0.204, P = 0.001). The aforementioned correlation remained significant in multivariable linear regression analysis. CONCLUSION: Our findings show that increased CITP levels are associated with poorer HRQOL in patients with CHF. These findings are consistent with a link between a pathophysiologic mechanism, i.e., collagen metabolism and patient self-assessed health status in CHF.

Resolution of symptoms and serum peptides of collagen type I turnover in acute heart failure patients.

OBJECTIVES: Myocardial collagen content as a fundamental component of extracellular matrix, is altered in pathological states including heart failure (HF). Serum peptides related to myocardial collagen synthesis and degregation can be measured and may be used as indices of myocardial collagen turnover. The present study was undertaken to assess the hypothesis that resolution of acute decompensation of chronic HF is associated with changes in serum peptides related to collagen synthesis and degregation. METHODS AND RESULTS: Serum concentrations of the amino-terminal propetide of procollagen type I (PINP) and the carboxy-terminal telopeptide of collagen type I (CITP), indices of collagen type I synthesis and degradation, respectively, were determined at the time of admission and discharge in 156 patients (100 men, 68 +/- 10 years) with acute decompensation of chronic HF. A significant decrease (-3.5 ng/ml 95% CI -5.3/-1.6 ng/ml, P < 0.001) of PINP was observed whereas CITP levels were significantly increased (+ 0.04 ng/ml 95% CI 0.01-0.08 ng/ml, P = 0.031) at discharge compared to admission. CONCLUSIONS: Findings of the present study showed that serum indices of myocardial collagen turnover were changed significantly in a short period of time during the improvement of acute decompensation of chronic HF.

Serum levels of collagen type-I degradation markers are associated with vascular stiffness in chronic heart failure patients.

BACKGROUND: Chronic heart failure (CHF) induces peripheral vasoconstriction, endothelial dysfunction and arterial stiffness by activation of various neurohormonal pathways. The abnormal collagen turnover observed in CHF may be attributed not only to myocardial remodelling, but also to vascular remodelling. However, the effect of collagen metabolism on progressive large artery stiffening in the setting of CHF is understudied. AIMS: The present study was undertaken to investigate the association between circulating markers of collagen turnover and vascular stiffness in patients with CHF. METHODS: Eighty patients (mean age 65+/-11 years, 68 men) with stable CHF and in sinus rhythm, were studied. Serum concentrations of carboxy-terminal telopeptide of collagen type I (CITP) and amino-terminal propetide of procollagen type I (PINP), markers of collagen type I degregation and synthesis respectively, were measured in all patients. Pulse wave velocity (PWV) and augmentation index (AIx) of aortic pulse wave form, markers of arterial stiffness, were also determined by applanation tonometry. RESULTS: Peripheral PWV was inversely associated with serum CITP levels (r=-0.585, p<0.001). AIx although weakly was negatively correlated with serum CITP levels (r=-0.285, p=0.01). Multiple regression analysis showed that peripheral PWV remained independently associated with serum CITP levels after adjustment for all confounding variables. CONCLUSIONS: Findings from the present study imply a possible link between altered collagen metabolism and peripheral vascular stiffness in CHF.