Spontaneous coronary artery dissection in women in the generative period: clinical characteristics, treatment, and outcome-a systematic review and meta-analysis.

Introduction: Spontaneous coronary artery dissection (SCAD) is a non-traumatic and non-iatrogenic separation of the coronary arterial wall. Materials and methods: This systematic review and meta-analysis is reported following the PRISMA guidelines and is registered in the PROSPERO database. A literature search was focused on female patients in generative period (16-55 of age) with acute coronary syndrome (ACS) caused by SCAD, and comparison from that database NP-SCAD (spontaneous coronary artery dissection in non pregnant women) and P-SCAD (spontaneous coronary artery dissection in pregnant women). Results: 14 studies with 2,145 females in the generative period with ACS caused by SCAD were analyzed. The median age was 41 years (33.4-52.3 years). The most common risk factor was previous smoking history in 24.9% cases. The most common clinical presentation of ACS was STEMI in 47.4%. Conservative treatment was reported in 41.1%. PCI was performed in 32.7%, and 3.8% of patients had CABG surgery. LAD was the most frequently affected (50.5%). The prevalence of composite clinical outcomes including mortality, non-fatal MI and recurrent SCAD was 3.3% (95% CI: 1.4-5.1), 37.7% (95% CI: 1.9-73.4) and 15.2% (95% CI: 9.1-21.3) of patients. P-SCAD compared to NP-SCAD patients more frequently had STEMI (OR = 3.16; 95% CI: 2.30-4.34; I2 = 64%); with the left main and LAD more frequently affected [(OR = 14.34; 95% CI: 7.71-26.67; I2 = 54%) and (OR = 1.57; 95% CI: 1.06-2.32; I2 = 23%)]; P-SCAD patients more frequently underwent CABG surgery (OR = 6.29; 95% CI: 4.08-9.70; I2 = 0%). NP-SCAD compared to P-SCAD patients were more frequently treated conservatevly (OR = 0.61; 95% CI: 0.37-0.98; I2 = 0%). In P-SCAD compared to NP-SCAD mortality rates (OR = 1.13; 95% CI: 0.06-21.16; I2 = not applicable) and reccurence of coronary artery dissection (OR = 2.54; 95% CI: 0.97-6.61; I2 = 0%) were not more prevalent. Conclusion: The results of this meta-analysis indicated that patients with P-SCAD more frequently had STEMI, and events more frequently involved left main and LAD compared to NP-SCAD patients. Women with NP-SCAD were significantly more often treated conservatively compared to P-SCAD patients. P-SCAD compared to NP-SCAD patients did not have significantly higher mortality rates or recurrent coronary dissection.

Management and outcomes of spontaneous coronary artery dissection: a systematic review of the literature.

Background: Contemporary management of spontaneous coronary artery dissection (SCAD) is still controversial. This systematic review of the literature aims to explore outcomes in the patients treated with conservative management vs. invasive strategy. Methods: The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed when we extensively searched three electronic databases: PubMed, ScienceDirect, and Web of Science, for studies that compared conservative vs. invasive revascularization treatment outcomes for patients with SCAD from 2003 to 2023. The outcomes of interest were all-cause death and major adverse cardiovascular events (MACE), including acute coronary syndrome (ACS), heart failure (HF), need for additional revascularization, target vessel revascularization (TVR), SCAD recurrence, and stroke. Results: The systematic review included 13 observational studies evaluating 1,801 patients with SCAD. The overall mean age was 49.12 +/- 3.41, and 88% were females. The overall prevalence of arterial hypertension was 33.2%, hyperlipidemia, 26.9%, smoking, 17.8%, and diabetes, 3.9%. Approximately 48.5% of the patients were diagnosed with non-ST elevated myocardial infarction (NSTEMI), 36.8% with ST elevated myocardial infarction (STEMI), 3.41% with unstable angina, 0.56% with stable angina, and 0.11% were diagnosed with various types of arrhythmias. The left anterior descending artery (LAD) was the most common culprit lesion in 51% of the patients. There were initially 65.2% of conservatively treated patients vs. 33.4% that underwent percutaneous coronary intervention (PCI) or 1.28% that underwent coronary artery bypass graft (CABG). SCAD-PCI revascularization was associated with a variable range of PCI failure. The most common complications were hematoma extension and iatrogenic dissection. SCAD-PCI revascularization frequently required three or more stents and had residual areas of dissection. The overall reported in-hospital and follow-up mortality rates were 1.2% and 1.3%, respectively. The follow-up range across studies was 7.3-75.6 months. The authors reported variable prevalence of MACE, recurrent SCAD up to 31%, ACS up to 27.4%, TVR up to 30%, repeat revascularization up to 14.7%, UA up to 13.3%, HF up to 17.4%, and stroke up to 3%. Conclusion: Our results highlight that conservative treatment should be the preferred method of treatment in patients with SCAD. PCI revascularization is associated with a high prevalence of periprocedural complications. SCAD poses a considerable risk of MACE, mainly associated with TVR, ACS, and recurrent SCAD.

Diagnosis and treatment of angiographically unclear coronary lesions.

Although selective coronary angiography is the gold standard diagnostic technique for coronary lesions, this method does not provide all information regarding pathophysiologic mechanisms. We herein describe a patient in their early 60s with a 3-month history of pronounced angina. Coronary angiography revealed a central line of illumination in the proximomedial segment of the right coronary artery, suggesting a chronic coronary dissection/recanalized thrombus, along with positive remodeling and TIMI grade 2 flow. Optical coherence tomography showed a recanalized thrombus and multiple lumens separated by thin septa. Because of the significantly reduced flow and signs of ischemia in the right coronary artery irrigation territory, we decided to perform percutaneous coronary intervention. Post-treatment optical coherence tomography indicated optimal apposition and expansion of the stents with positive remodeling of the blood vessel. We believe that decisions regarding treatment modalities should be guided by the presence or absence of ischemia. Lesions that are causing myocardial ischemia should be revascularized; otherwise, medical treatment can be utilized.

An analysis of published cases of cutting balloon use in spontaneous coronary artery dissection.

Introduction: SCAD involves a sudden tear or separation within the layers of the coronary artery wall, resulting in blood flow obstruction and subsequent myocardial ischemia. Materials and methods: A comprehensive literature search was conducted to identify relevant published cases of cutting balloon use in patients diagnosed with spontaneous coronary artery dissection. Electronic databases including PubMed, MEDLINE, Embase, Cochrane Library and Google Scholar were systematically searched from inception until the present using terms "cutting balloon," "SCAD," "acute coronary syndrome," "intramural hematoma," and "angioplasty." Results: A total of 32 published cases of cutting balloon use in spontaneous coronary artery dissection were analyzed in this study. The majority of the patients included in the analysis were female without prior history of cardiovascular disease. The median age of the SCAD population was approximately 46 years. The most frequently affected artery in SCAD cases was the Left Anterior Descending artery. Intravascular ultrasound was utilized more frequently than other modalities of adjunctive imaging techniques. The most frequent complication was the distal propagation of hematoma. Despite the successful dilation achieved with the cutting balloon, in some cases stenting was required to provide additional support. Conclusion: The results of this analysis demonstrate that cutting balloon use in SCAD cases yields favorable outcomes.

Drugs for spontaneous coronary dissection: a few untrusted options.

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome that is often overlooked, misdiagnosed, and maltreated. Medical treatment poses a significant challenge because of the lack of randomized studies to guide treatment. The initial clinical presentation should guide medical and interventional management. Fibrinolytic agents and anticoagulants should be avoided because they could favor hematoma propagation. In patients with SCAD, antiplatelet therapy should be prescribed especially dual antiplatelet therapy (DAPT) consisting of aspirin and clopidogrel, whereas potent P2Y12 inhibitors, e.g., ticagrelor and prasugrel, should be avoided. If a stent was used, DAPT should be continued for 12 months. Aspirin only can be an option for patients without "high-risk" angiographic features-thrombus burden, critical stenosis, and decreased coronary flow. Beta-blocking (BB) agents should be used to prevent recurrence of SCAD. There is a general agreement that angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, mineralocorticoid antagonists, and loop diuretics should be used in patients with SCAD experiencing the symptoms of heart failure and a decrease in left ventricular ejection fraction below 50%. Although without firm evidence, statins can be used in SCAD due to their pleiotropic properties. The results of a randomized trial on the use of BB and statins are awaited. Aggregation of data from national registries might point out truly beneficial medications for patients with SCAD.

Pathophysiology of spontaneous coronary artery dissection: hematoma, not thrombus.

Spontaneous coronary artery dissection (SCAD) accounts for 1.7%-4% of all acute coronary syndrome presentations, particularly among young women with an emerging awareness of its importance. The demarcation of acute SCAD from coronary atherothrombosis and the proper therapeutic approach still represents a major clinical challenge. Certain arteriopathies and triggers are related to SCAD, with high variability in their prevalence, and often, the cause remains unknown. The objective of this review is to provide contemporary knowledge of the pathophysiology of SCAD and possible therapeutic solutions.

Invasive imaging modalities in a spontaneous coronary artery dissection: when "believing is seeing".

Spontaneous coronary artery dissection (SCAD) is a rare but increasingly recognized cause of acute coronary syndrome (ACS) with recent advancements in cardiac imaging facilitating its identification. However, SCAD is still often misdiagnosed due to the absence of angiographic hallmarks in a significant number of cases, highlighting the importance of meticulous interpretation of angiographic findings and, when necessary, additional usage of intravascular imaging to verify changes in arterial wall integrity and identify specific pathoanatomical features associated with SCAD. Accurate diagnosis of SCAD is crucial, as the optimal management strategies for patients with SCAD differ from those with atherosclerotic coronary disease. Current treatment strategies favor a conservative approach, wherein intervention is reserved for cases with persistent ischemia, patients with high-risk coronary anatomy, or patients with hemodynamic instability. In this paper, we provide a preview of invasive imaging modalities and classical angiographic and intravascular imaging hallmarks that may facilitate proper SCAD diagnosis.

The follow-up of myocardial injury and left ventricular function after spontaneous coronary artery dissection.

Monitoring patients with spontaneous coronary dissection (SCAD) is critical in their care, as there are no accepted recommendations. To this end, finding clinical or imaging predictors of recurrent events in these patients is essential for predicting adverse events and guiding treatment decisions between conservative medical therapy and percutaneous coronary intervention. Myocardial injury and left ventricular function after SCAD can be variable parameters that require monitoring. Echocardiography and cardiac magnetic resonance are two useful imaging techniques to do so. This review aims to analyze previously published results on monitoring myocardial injury and left ventricular function in SCAD patients while highlighting the potential benefits of contemporary imaging techniques that could further improve patient care in the future.

Rationale and design of the ESC Heart Failure III Registry - Implementation and discovery.

AIMS: Heart failure outcomes remain poor despite advances in therapy. The European Society of Cardiology Heart Failure III Registry (ESC HF III Registry) aims to characterize HF clinical features and outcomes and to assess implementation of guideline-recommended therapy in Europe and other ESC affiliated countries. METHODS: Between 1 November 2018 and 31 December 2020, 10 162 patients with chronic or acute/worsening HF with reduced, mildly reduced, or preserved ejection fraction were enrolled from 220 centres in 41 European or ESC affiliated countries. The ESC HF III Registry collected data on baseline characteristics (hospital or clinic presentation), hospital course, diagnostic and therapeutic decisions in hospital and at the clinic visit; and on outcomes at 12-month follow-up. These data include demographics, medical history, physical examination, biomarkers and imaging, quality of life, treatments, and interventions - including drug doses and reasons for non-use, and cause-specific outcomes. CONCLUSION: The ESC HF III Registry will provide comprehensive and unique insight into contemporary HF characteristics, treatment implementation, and outcomes, and may impact implementation strategies, clinical discovery, trial design, and public policy.

Depression, anxiety, and quality of life as predictors of rehospitalization in patients with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is a severe condition, often co-occurring with depression and anxiety, that strongly affects the quality of life (QoL) in some patients. Conversely, depressive and anxiety symptoms are associated with a 2-3 fold increase in mortality risk and were shown to act independently of typical risk factors in CHF progression. The aim of this study was to examine the impact of depression, anxiety, and QoL on the occurrence of rehospitalization within one year after discharge in CHF patients. METHODS: 148 CHF patients were enrolled in a 10-center, prospective, observational study. All patients completed two questionnaires, the Hospital Anxiety and Depression Scale (HADS) and the Questionnaire Short Form Health Survey 36 (SF-36) at discharge timepoint. RESULTS: It was found that demographic and clinical characteristics are not associated with rehospitalization. Still, the levels of depression correlated with gender (p ≤ 0.027) and marital status (p ≤ 0.001), while the anxiety values ​​were dependent on the occurrence of chronic obstructive pulmonary disease (COPD). However, levels of depression (HADS-Depression) and anxiety (HADS-Anxiety) did not correlate with the risk of rehospitalization. Univariate logistic regression analysis results showed that rehospitalized patients had significantly lower levels of Bodily pain (BP, p = 0.014), Vitality (VT, p = 0.005), Social Functioning (SF, p = 0.007), and General Health (GH, p = 0.002). In the multivariate model, poor GH (OR 0.966, p = 0.005) remained a significant risk factor for rehospitalization, and poor General Health is singled out as the most reliable prognostic parameter for rehospitalization (AUC = 0.665, P = 0.002). CONCLUSION: Taken together, our results suggest that QoL assessment complements clinical prognostic markers to identify CHF patients at high risk for adverse events. CLINICAL TRIAL REGISTRATION: The study is registered under http://clinicaltrials.gov (NCT01501981, first posted on 30/12/2011), sponsored by Charité - Universitätsmedizin Berlin.

Chronic or Changeable Infarct Size after Spontaneous Coronary Artery Dissection.

Spontaneous coronary artery dissection (SCAD) could be the cause of acute myocardial infarction (AMI) and sudden cardiac death. Clinical presentations can vary considerably, but the most common is the elevation of cardiac biomarkers associated with chest discomfort. Different pathological etiology in comparison with Type 1 AMI is the underlying infarct size in this population. A 42-year-old previously healthy woman presented with SCAD. Detailed diagnostical processing and treatment which were performed could not prevent myocardial injury. The catheterization laboratory was the initial place for the establishment of a diagnosis and proper management. The management process can be very fast and sometimes additional imaging methods are necessary. Finding predictors of SCAD recurrence is challenging, as well as predictors of the resulting infarct scar size. Patients with recurrent clinical symptoms of chest pain, ST elevation, and complication represent a special group of interest. Therapeutic approaches for SCAD range from the "watch and wait" method to complete revascularization with the implantation of one or more stents or aortocoronary bypass grafting. The infarct size could be balanced through the correct therapeutical approach, and, proper multimodality imaging would be helpful in the assessment of infarct size.

Primary antiphospholipid syndrome as a cause of impaired left ventricular diastolic function: experience from a Serbian cohort.

OBJECTIVES: Cardiovascular manifestations, encountered in antiphospholipid syndrome, may develop as a consequence of acquired thrombophilia mediated by antiphospholipid antibodies and accelerated atherosclerosis as well. Our study aims to assess the impairment of the left ventricular diastolic performance, as early evidence of myocardial involvement in primary antiphospholipid syndrome (PAPS). METHODS: We analysed 101 PAPS patients, with the average age of 47.70±13.14y. Anticardiolipin antibodies (aCL IgG/IgM), anti-ß2 glycoprotein-I (anti-ß2GPI IgG/IgM), and lupus anticoagulant (LAC) were determined. Abnormal cut-off values used for left ventricular diastolic dysfunction (LVDD) were septal E ́<7 cm/sec, lateral E ́ <10 cm/sec, average E/E ́ ratio >14, LA volume index (LAVI) >34 mL/m2, and peak tricuspid regurgitation velocity >2.8 m/sec. LVDD was present if more than half parameters were with abnormal values. The results were compared to 90 healthy, age and sex-matched controls. RESULTS: LVDD was significantly more prevalent in PAPS patients compared to healthy controls (24.8% vs. 2.2%, p=0.001). In PAPS patients, it was signi cantly related to age, body mass index, hyperlipidaemia, thromboses and LAC positivity (p=0.0001, p=0.008, p=0.039, p=0.001, p=0.047 respectively). Patients with PAPS had higher LAVI (29.76±6.40 ml/m2 vs. 26.62±7.8 ml/m2, p=0.012), higher isovolumic relaxation time, lower lateral É velocity and lower E/É ratio compared to controls (p=0.0001, p=0.020, p=0.038, respectively). In multivariate analysis, thromboses in PAPS were significant, and independent predictors of LVDD. CONCLUSIONS: Thrombotic PAPS patients are at higher risk of LVDD development. Strong action against standard atherosclerotic risk factors and adequate therapy regimes seems to be crucial to preserve good diastolic performance of the left ventricle in PAPS.

Differences in left ventricular myocardial function and infarct size in female patients with ST elevation myocardial infarction and spontaneous coronary artery dissection.

Introduction: Differences in pathophysiology, clinical presentation, and natural course of ST-elevation myocardial infarction in female patients due to either spontaneous dissection (SCAD-STEMI) or atherothrombotic occlusion (type 1 STEMI) have been discussed. Current knowledge on differences in left ventricular myocardial function and infarct size is limited. The aim of this study was to assess baseline clinical characteristics, imaging findings, and therapeutic approach and to compare differences in echocardiographic findings at baseline and 3-month follow-up in patients with SCAD-STEMI and type 1 STEMI. Methods: This was a prospective multicenter study of 32 female patients (18-55 years of age) presenting with either SCAD-STEMI due to left anterior descending coronary artery (LAD) dissection or type 1 STEMI due to atherothrombotic LAD occlusion. Results: The two groups were similar in age, risk factors, comorbidities, and complications. SCAD-STEMI patients more often had Thrombolysis in Myocardial Infarction 3 flow, while type 1 STEMI patients were more often treated with percutaneous coronary intervention and dual antiplatelet therapy. Baseline mean left ventricular (LV) ejection fraction (LVEF) was similar in the two groups (48.0% vs. 48.6%, p = 0.881), but there was a significant difference at the 3-month follow-up, driven by an improvement in LVEF in SCAD-STEMI compared to type 1 STEMI patients (Δ LVEF 10.1 ± 5.3% vs. 1.8 ± 5.1%, p = 0.002). LV global longitudinal strain was slightly improved in both groups at follow-up; however, the improvement was not significantly different between groups (-4.6 ± 2.9% vs. -2.0 ± 2.8%, p = 0.055). Conclusions: The results suggest that female patients with SCAD-STEMI are more likely to experience improvement in LV systolic function than type 1 STEMI patients.

A review of the risk and precipitating factors for spontaneous coronary artery dissection.

Introduction: Spontaneous coronary artery dissection (SCAD) accounts for 1%-4% of cases of acute coronary syndrome (ACS). SCAD is caused by separation occurring within or between any of the three tunics of the coronary artery wall. This leads to intramural hematoma and/or formation of false lumen in the artery, which leads to ischemic changes or infarction of the myocardium. The incidence of SCAD is higher in women than in men, with a ratio of approximately 9:1. It is estimated that SCAD is responsible for 35% of ACS cases in women under the age of 60. The high frequency is particularly observed during pregnancy and in the peripartum period (first week). Traditional risk factors are rare in patients with SCAD, except for hypertension. Patients diagnosed with SCAD have different combinations of risk factors compared with patients who have atherosclerotic changes in their coronary arteries. We presented the most common so-called "non-traditional" risk factors associated with SCAD patients. Risk factors and precipitating disorders which are associated with SCAD: In the literature, there are few diseases frequently associated with SCAD, and they are identified as predisposing factors. The predominant cause is fibromuscular dysplasia, followed by inherited connective tissue disorders, systemic inflammatory diseases, pregnancy, use of sex hormones or steroids, use of cocaine or amphetamines, thyroid disorders, migraine, and tinnitus. In recent years, the genetic predisposition for SCAD is also recognized as a predisposing factor. The precipitating factors are also different in women (emotional stress) compared with those in men (physical stress). Women experiencing SCAD frequently describe symptoms of anxiety and depression. These conditions could increase shear stress on the arterial wall and dissection of the coronary artery wall. Despite the advancement of SCAD, we can find significant differences in the clinical presentation between women and men. Conclusion: When evaluating patients with chest pain or other ACS symptoms who have a low cardiovascular risk, particularly female patients, it is important to consider the possibility of ACS due to SCAD, particularly in conditions often associated with SCAD. This will increase the recognition of SCAD and the timely treatment of affected patients.

The hepatoprotective effect of aminoguanidine in acute liver injury caused by CCl4 in rats.

In this study, the hepatoprotective effect of aminoguanidine in acute liver damage caused by carbon tetrachloride-CCl4 at a dose of 1 mL/kg, i.p. was investigated in experimental rats. Ten days of preventive treatment with aminoguanidine before exposure to toxic CCl4, at a dose of 150 mg/kg, i.p., led to significant reduction in biochemical markers of acute liver injury-AST(p < 0.001), ALT (p < 0.01), SDH (p < 0.05) and reduction in pro-oxidative markers-H2O2 (p < 0.05), TOS (p < 0.01), TBARS, and LOOH (p < 0.001) in relation to rats treated only CCl4. Treatment with aminoguanidine resulted in a significant reduction in the consumption of antioxidant-GR (p < 0.01), GST, GPx, GSH (p < 0.001), and a decrease in pro-inflammatory-TNF-α (p < 0.01), IL-1ß, IL-6, NO and NGAL (p < 0.001) markers relative to animals exposed to CCl4 alone. Also, aminoguanidine pre-treatment leads to an increase in arginase activity (p < 0.001), and a decrease in citrulline concentration (p < 0.01), as well as polyamine catabolism enzyme activity-putrescin oxidase and spermine oxidase (p < 0.001) in comparison to the CCl4 group. Aminoguanidine led to a striking reduction of the necrotic field (p < 0.001), and a significant increase in the number of apoptotic hepatocytes (p < 0.001), as well as the proapoptotic markers-BAX and Caspase-3 (p < 0.05), compared to CCl4. The hepatoprotective mechanisms in CCl4 induce hepatotoxicity of aminoguanidine are based on the strong antioxidant effects, inhibition of pro-oxidative and pro-inflammatory mediators, as well as induction of damaged hepatocytes into apoptosis.

Conservatively treated intramyocardial dissecting haematoma of the interventricular septum as a rare complication of acute myocardial infarction: a case report.

Background: Intramyocardial dissecting haematoma (IDH) is a rare and potentially life-threatening complication of acute coronary syndrome. So far only isolated case reports and case series have been published. Case summary: We report the case of a late presenting myocardial infarction (MI) complicated by IDH of the ventricular septum, following a successful percutaneous coronary intervention (PCI). The clinically inapparent septal mass was discovered during the routine transthoracic echocardiography and the final diagnosis of haematoma was made by magnetic resonance imaging. The patient remained clinically stable, and septal mass on repeated echocardiography showed gradual regression. Discussion: This report suggests that IDH can spontaneously resolve without surgical intervention. An urgent echocardiogram should be used to assess the vitality of the myocardial tissue, especially with late presenting MI with deep Q-waves on the electrocardiogram strip. Conservative treatment in haemodynamically stable patients with IDH following MI and PCI is a feasible solution.

Cardiac manifestations in primary antiphospholipid syndrome and their association to antiphospholipid antibodies' types and titers-cross-sectional study of Serbian cohort.

OBJECTIVES: Antiphospholipid syndrome (APS) is multisystem autoimmune coagulopathy with antiphospholipid antibodies (aPL) in its ground, manifested as a primary disease (PAPS) or in the setting of other conditions, most commonly systemic lupus erythematosus. The objective of this cross-sectional study was to investigate various cardiac manifestations and their possible relation to aPL type and titer in a Serbian cohort of PAPS patients. METHODS: A total of 360 PAPS patients were analyzed and aPL analysis included detection of anticardiolipin antibodies (aCL: IgG/IgM), anti-ß2glycoprotein I (ß2GPI: IgG/IgM), and lupus anticoagulant (LA). Cardiac manifestations investigated were valvular lesions (comprehending valvular thickening and dysfunction not related to age and pseudoinfective endocarditis), coronary artery disease (CAD) with specific insight for myocardial infarction (MI), chronic cardiomyopathy (CMP), and acute decompensated heart failure (ADHF) as well as pulmonary hypertension (PH) and intracardiac thrombus presence. RESULTS: The prevalence of cardiac manifestations overall was 19.6%. There was a strong association between age and the majority of cardiac manifestations, as well as standard atherosclerotic risk factors. aCL IgG-positive patients had a higher prevalence of valvular lesions (p = 0.042). LA presence was significantly related to MI (p = 0.031) and PH (p = 0.044). CMP and ADHF were significantly related to higher titers of aCl IgG (p = 0.033, p = 0.025 respectively). Age and smoking were independent risk predictors for MI in PAPS with meaningful risk for LA positivity (OR 2.567 CI 0.671-9.820 p = 0.168). CONCLUSIONS: Certain cardiac manifestations in PAPS were related to certain aPL type and/or titer levels, imposing confirmation in prospective studies. Preventive actions, comprehending proper anticoagulant/antithrombotic therapy, and intense action against standard atherosclerotic risk factors are of utmost importance in this group of patients. Key Points • In Serbian patients with primary antiphospholipid syndrome (PAPS), prevalence of non-criteria cardiac manifestations was 19.6% and they were significantly related to certain antiphospholipid antibodies and titers. • Lupus anticoagulant was a meaningful predictor of myocardial infarction, enabling possible risk stratification and proper preventive and therapeutical strategies in this subgroup of PAPS patients. • Patients with high titers of aCL IgG are more prone to acute decompensated heart failure occurence, imposing careful follow-up of these patients • Based on the analysis of the Serbian PAPS cohort, even being non-criterial, cardiology manifestations are significantly present and inclusion of cardiologists in treatment and follow-up of these patients should be implied from the diagnosis establishment.

Incremental prognostic value of a novel metabolite-based biomarker score in congestive heart failure patients.

AIMS: The Cardiac Lipid Panel (CLP) is a newly discovered panel of metabolite-based biomarkers that has shown to improve the diagnostic value of N terminal pro B type natriuretic peptide (NT-proBNP). However, little is known about its usefulness in predicting outcomes. In this study, we developed a risk score for 4-year cardiovascular death in elderly chronic heart failure (CHF) patients using the CLP. METHODS AND RESULTS: From the Cardiac Insufficiency Bisoprolol Study in Elderly trial, we included 280 patients with CHF aged >65 years. A targeted metabolomic analysis of the CLP biomarkers was performed on baseline serum samples. Cox regression was used to determine the association of the biomarkers with the outcome after accounting for established risk factors. A risk score ranging from 0 to 4 was calculated by counting the number of biomarkers above the cut-offs, using Youden index. During the mean (standard deviation) follow-up period of 50 (8) months, 35 (18%) subjects met the primary endpoint of cardiovascular death. The area under the receiver operating curve for the model based on clinical variables was 0.84, the second model with NT-proBNP was 0.86, and the final model with the CLP was 0.90. The categorical net reclassification index was 0.25 using three risk categories: 0-60% (low), 60-85% (intermediate), and >85% (high). The continuous net reclassification index was 0.772, and the integrated discrimination index was 0.104. CONCLUSIONS: In patients with CHF, incorporating a panel of three metabolite-based biomarkers into a risk score improved the prognostic utility of NT-proBNP by predicting long-term cardiovascular death more precisely. This novel approach holds promise to improve clinical risk assessment in CHF patients.

Early NT-proBNP and MR-proANP associated with QoL 1 year after acutely decompensated heart failure: secondary analysis from the MOLITOR trial.

Aim: Heart failure negatively impacts quality of life (QoL), which in turn contributes to an adverse long-term prognosis. We aimed at identifying biomarker trajectories after an episode of acutely decompensated heart failure (ADHF) that differ between patients showing average versus impaired QoL 1 year later, thus allowing to predict impaired QoL. Methods: Biomarkers were repeatedly measured throughout the year in 104 ADHF patients. QoL was assessed at discharge and 1 year after ADHF. Logistic regression and receiver operating characteristic analyses were used to identify predictors of impaired QoL while controlling psychosocial confounders. Results: MR-proANP predicted impaired physical and mental QoL. NT-proBNP measurements were important predictors for poor physical QoL. Conclusion: MR-proANP and NT-proBNP predict poor QoL after an epidode of ADHF. The trial is registered at http://clinicaltrials.gov as MOLITOR (IMpact of therapy optimisation On the Level of biomarkers in paTients with Acute and Decompensated ChrOnic HeaRt Failure) with unique identifier: NCT01501981.

The predictive value of Klotho polymorphism, in addition to classical markers of CKD-MBD, for left ventricular hypertrophy in haemodialysis patients.

PURPOSE: Cardiovascular events are the major reasons for mortality in haemodialysis patients. Fibroblast growth factor 23 (FGF23), Klotho protein and G-395A Klotho gene polymorphism have been associated with effects on the cardiovascular system. Our study investigates the interrelationship between Klotho protein gene variations, mineral-bone metabolism and left ventricular hypertrophy in patients undergoing chronic haemodialysis programme. MATERIALS AND METHODS: Patients (n = 142) were genotyped for G-395A Klotho gene. Components of mineral-bone metabolism, classical and non-classical (FGF23, Klotho and vitamin D) as well as echocardiographic examination were determined. Predictive models were designed to determine the significance of Klotho gene variations and mineral-bone metabolism components for left ventricle hypertrophy (LVH). RESULTS: A-allele carriers were longer on haemodialysis (p = 0.033), and had higher phosphorus levels (p = 0.016) while the level of Klotho protein was significantly lower (p = 0.001) compared to non-A-allele carriers. The best gains were achieved upon addition of allele A, and all three new markers; the AUC made significant improvement from 0.596 to 0.806 (p < 0.001), and improved net reclassification for 82.1% (95% CI 42.9-121.3%). CONCLUSIONS: The genetic background of A-allele carriers of the G-395A Klotho gene polymorphism increases the susceptibility patients to haemodialysis. A-allele carriers are at a higher risk for the development of cardiovascular complications. The addition of non-classical to classical mineral metabolism components improves prediction power to LVH.