Pregnancy outcomes in women with Ebstein's anomaly: data from the Registry of Pregnancy And Cardiac disease (ROPAC).

OBJECTIVE: Ebstein's anomaly is a rare congenital cardiac condition and data regarding pregnancy outcomes in this patient group are scarce. We evaluated the maternal and perinatal risks of pregnancy in 81 women with Ebstein's anomaly. METHODS: The Registry of Pregnancy and Cardiac disease is a prospective global registry of pregnancies in women with structural cardiac disease. Pregnancy outcomes in women with Ebstein's anomaly were examined. The primary outcome was the occurrence of a major adverse cardiac event (MACE) defined as maternal mortality, heart failure, arrhythmia, thromboembolic event or endocarditis. Secondary endpoints were obstetric and perinatal outcomes and the influence of pregnancy on tricuspid valve regurgitation as well as right atrial and ventricular dimensions. RESULTS: In the 81 women with Ebstein's anomaly (mean age 29.7±6.1 years, 46.9% nulliparous), MACE occurred in 8 (9.9%) pregnancies, mostly heart failure (n=6). There were no maternal deaths. Prepregnancy signs of heart failure were predictive for MACE. Almost half of the women were delivered by caesarean section (45.7%) and preterm delivery occurred in 24.7%. Neonatal mortality was 2.5% and 4.9% of the infants had congenital heart disease. In the subgroup in which prepregnancy and postpregnancy data were available, there was no difference in tricuspid valve regurgitation grade or right atrial and ventricular dimensions before and after pregnancy. CONCLUSIONS: Most women with Ebstein's anomaly tolerate pregnancy well, but women with prepregnancy signs of heart failure are at higher risk for MACE during pregnancy and should be counselled accordingly.

Treatment of advanced heart failure in adults with congenital heart disease: a narrative review and clinical cases.

Background and Objective: The number of adults with congenital heart disease (ACHD) is increasing worldwide. Almost all congenital cardiac lesions can be successfully treated due to the progress in neonatal surgery and pediatric cardiology with a high likelihood of surviving until adulthood. However, ACHD frequently develop sequelae related to the initial cardiac anomaly. Heart failure (HF) is one of the most common complications associated with a high morbidity and mortality. Methods: The authors did search the PubMed database regarding relevant content covering publications up to March 2022. Relevant manuscripts were classified according to the impact factor of the journal, being a guideline manuscript, a position paper by a society or a comprehensive review of the current literature. Key Content and Findings: Optimal HF treatment remains an unmet need in ACHD. In particular, advanced HF therapy with cardiac resynchronization therapy, ventricular assist devices or organ transplantation is still very different and more specific in ACHD compared to non-ACHD. This review aims to compile international views and evidence from the literatures on the treatment of advanced HF in ACHD. Current challenges, but also the success of different treatment strategies in ACHD are illustrated by clinical cases. Conclusions: The main finding of the review is that data is still scarce regarding ACHD with advanced HF and international efforts to collect data regarding these patients needed to improve the current standard of care.

Single-dose of adrecizumab versus placebo in acute cardiogenic shock (ACCOST-HH): an investigator-initiated, randomised, double-blinded, placebo-controlled, multicentre trial.

BACKGROUND: Cardiogenic shock has a high mortality on optimal therapy. Adrenomedullin is released during cardiogenic shock and is involved in its pathophysiological processes. This study assessed treatment with the humanised, monoclonal, non-neutralising, adrenomedullin antibody adrecizumab, increasing circulating concentrations of adrenomedullin in cardiogenic shock. METHODS: In this investigator-initiated, placebo-controlled, double-blind, multicentre, randomised trial (ACCOST-HH), patients were recruited from four university hospitals in Germany. Patients were eligible if they were 18 years old or older and hospitalised for cardiogenic shock within the last 48 h. Exclusion criteria were resuscitation for longer than 60 min and cardiogenic shock due to sustained ventricular tachycardia or bradycardia. Adult patients in cardiogenic shock were randomly assigned (1:1) to intravenous adrecizumab (8 mg/kg bodyweight) or placebo using an internet-based software. A block randomisation procedure was applied with stratification by age (older vs younger than 65 years), sex (male vs female), and type of underlying cardiogenic shock (acute myocardial infarction vs other entities). Investigators, patients, and medical staff involved in patient care were masked to group assignment. The primary endpoint was number of days up to day 30 without the need for cardiovascular organ support, defined as vasopressor therapy, inotropes, or mechanical circulatory support (or both) assessed in the intention-to-treat population. Safety outcomes included therapy-emergent serious adverse events, severe adverse events, adverse events, suspected unexpected serious adverse reactions, study drug-related mortality, and total mortality. The trial was registered at ClinicalTrials.gov, NCT03989531, and EudraCT, 2018-002824-17, and is now complete. FINDINGS: Between April 5, 2019, and Jan 13, 2021, 150 patients were enrolled: 77 (51%) were randomly assigned to adrecizumab and 73 (49%) to placebo. All patients received the allocated treatment. The number of days without the need for cardiovascular organ support was not different between patients receiving adrecizumab or placebo (12·37 days [95% CI 9·80-14·94] vs 14·05 [11·41-16·69]; adjusted mean difference -1·69 days [-5·37 to 2·00]; p=0·37). Serious adverse events occurred in 59 patients receiving adrecizumab and in 57 receiving placebo (odds ratio 0·92 [95% CI 0·43-1·98]; p=0·83). Mortality was not different between groups at 30 days (hazard ratio 0·99 [95% CI 0·60-1·65]; p=0·98) or 90 days (1·10 [0·68-1·77]; p=0·71). INTERPRETATION: Adrecizumab was well tolerated in patients with cardiogenic shock but did not reduce the need for cardiovascular organ support or improve survival at days 30 and 90. FUNDING: Adrenomed AG and University Hospital of Hamburg.

Study design and rationale of the pAtients pResenTing with cOngenital heaRt dIseAse Register (ARTORIA-R).

AIM: Due to improved therapy in childhood, many patients with congenital heart disease reach adulthood and are termed adults with congenital heart disease (ACHD). ACHD often develop heart failure (HF) as a consequence of initial palliative surgery or complex anatomy and subsequently require advanced HF therapy. ACHD are usually excluded from trials evaluating heart failure therapies, and in this context, more data about heart failure trajectories in ACHD are needed to guide the management of ACHD suffering from HF. METHODS AND RESULTS: The pAtients pResenTing with cOngenital heaRt dIseAse Register (ARTORIA-R) will collect data from ACHD evaluated or listed for heart or heart-combined organ transplantation from 16 countries in Europe and the Asia/Pacific region. We plan retrospective collection of data from 1989-2020 and will include patients prospectively. Additional organizations and hospitals in charge of transplantation of ACHD will be asked in the future to contribute data to the register. The primary outcome is the combined endpoint of delisting due to clinical worsening or death on the waiting list. The secondary outcome is delisting due to clinical improvement while on the waiting list. All-cause mortality following transplantation will also be assessed. The data will be entered into an electronic database with access to the investigators participating in the register. All variables of the register reflect key components important for listing of the patients or assessing current HF treatment. CONCLUSION: The ARTORIA-R will provide robust information on current management and outcomes of adults with congenital heart disease suffering from advanced heart failure.

Heart failure in adults with congenital heart disease: a narrative review.

The number of adults with congenital heart disease (ACHD) has increased over the last decades due to advancements in medical care, including interventional and surgical therapies. We are therefore more frequently challenged by the long-term consequences of palliative or corrective surgery carried out during childhood. Although patients with ACHD may develop conditions related to general cardiovascular risk factors, such as coronary artery disease, the most common complications leading to morbidity and mortality are arrhythmias, heart failure and thromboembolic events. For the management of arrhythmias, current recommendations regarding ablation and device therapy must be considered, whilst also taking into account the anatomical limitations of their congenital heart defect or surgical pathways. Heart failure treatment in acute and chronic settings must also consider the particular anatomy present, including the nature of the systemic ventricle. Treatments strategies for ACHD are typically extrapolated from the respective guidelines in non-ACHD patients, despite a lack of evidence to support this strategy. Right heart failure can be especially challenging to manage in conditions where either a systemic right ventricle or shunt lesions resulting in volume and/or pressure loading of the right ventricle are present. All physicians and cardiologists in particular should be acquainted with the most common diseases in ACHD, their complications and management regime, especially with regards to heart failure as this is a common reason for acute presentation in the emergency department.

Narrative review of Ebstein's anomaly beyond childhood: Imaging, surgery, and future perspectives.

Ebstein's anomaly is a rare congenital heart disease with malformation of the tricuspid valve and myopathy of the right ventricle. The septal and inferior leaflets adhere to the endocardium due to failure of delamination. This leads to apical displacement of their hinge points with a shift of the functional tricuspid valve annulus towards the right ventricular outflow tract with a possibly restrictive orifice. Frequently, a coaptation gap yields tricuspid valve regurgitation and over time the "atrialized" portion of the right ventricle may dilate. The highly variable anatomy determines the clinical presentation ranging from asymptomatic to very severe with need for early operation. Echocardiography and magnetic resonance imaging are the most important diagnostic modalities to assess the tricuspid valve as well as ventricular morphology and function. While medical management of asymptomatic patients can be effective for many years, surgical intervention is indicated before development of significant right ventricular dilatation or dysfunction. Onset of symptoms and arrhythmias are further indications for surgery. Modified cone reconstruction of the tricuspid valve is the state-of-the-art approach yielding the best results for most patients. Alternative procedures for select cases include tricuspid valve replacement and bidirectional cavopulmonary shunt depending on patient age and other individual characteristics. Long-term survival after surgery is favorable but rehospitalization and reoperation remain significant issues. Further studies are warranted to identify the optimal surgical strategy and timing before adverse right ventricular remodeling occurs. It is this article's objective to provide a comprehensive review of current literature and an overview on the management of Ebstein's Anomaly. It focuses on imaging, cardiac surgery, and outcome. Additionally, a brief insight into arrhythmias and their management is given. The "future perspectives" summarize open questions and fields of future research.

Anticoagulation management in adult patients with congenital heart disease: a narrative review.

With improvements in treatment of congenital heart disease more paediatric patients are surviving with palliative or corrective interventions during childhood, thus becoming adults with congenital heart disease (ACHD). Overall, the ACHD population is at a higher risk of arrhythmias and stroke. The abnormal structure and function of their corrected hearts suggests that in addition to established stroke risk factors, such as prior stroke or older age, additional stroke risk factors need to be considered to determine the risk and establish the indication for oral anticoagulation (OAC) in ACHD patients. In structurally normal hearts non-vitamin-K oral anticoagulants (NOACs) offer at least equal stroke prevention with a better safety profile compared to vitamin K antagonists (VKA) in patients with atrial fibrillation (AF) or pulmonary embolism. Current guidelines recommend NOACs in ACHD patients with simple lesions and indication for OAC, while there is less certainty about their safety in ACHD patients with moderate or complex congenital heart disease such as patients with transposition of the great arteries (TGA) after atrial switch operation (Senning or Mustard operation), Fontan circulation or congenital corrected transposition of the great arteries (ccTGA). This review summarises the available evidence characterising stroke risk in patients with ACHD and the use of anticoagulants and interventional therapies to reduce that risk.

Massive pulmonary embolism with intra-hospital cardiac arrest and full recovery of right ventricular function after veno-arterial extracorporeal membrane oxygenation therapy: a case report.

BACKGROUND: Massive pulmonary embolism (PE) with shock constitutes a life-threatening disease, challenging physicians with the need for fast decision-making in an emergency situation. While thrombolytic treatment or thrombectomy are considered the treatment of choice in high-risk PE, these strategies might not be able to unload the right ventricle (RV) fast enough in some patients with severe cardiogenic shock. CASE SUMMARY: We present a case of a patient with massive bilateral central PE who presented in cardiogenic shock, rapidly deteriorating to cardiac arrest. After successful re-establishing spontaneous circulation, the patient remained highly unstable, necessitating a treatment strategy ensuring a quick stabilization of the circulation. Therefore, we decided to use veno-arterial extracorporeal membrane oxygenation (vaECMO) as a supportive strategy allowing for autolysis of the lung to dissolve the thrombi (bridge to recovery). We were able to wean the patient from vaECMO support within 4 days and documented a complete recovery of right ventricular in echocardiography before hospital discharge. DISCUSSION: The concept of vaECMO treatment alone might be a valuable alternative in selected patients with massive PE and cardiogenic shock, in whom thrombolytic therapy might not unload the RV fast enough.

Clinical characteristics and outcomes of patients with adult congenital heart disease listed for heart and heart‒lung transplantation in the Eurotransplant region.

BACKGROUND: The therapeutic success in patients with congenital heart disease (CHD) leads to a growing number of adults with CHD (adult CHD [ACHD]) who develop end-stage heart failure. We aimed to determine patient characteristics and outcomes of ACHD listed for heart transplantation. METHODS: Using data from all the patients with ACHD in 20 transplant centers in the Eurotransplant region from 1999 to 2015, we analyzed patient characteristics, waiting list, and post-transplantation outcomes. RESULTS: A total of 204 patients with ACHD were listed during the study period. The median age was 38 years, and 62.3% of the patients were listed in high urgency (HU), and 37.7% of the patients were in transplantable (T)-listing status. A total of 23.5% of the patients died or were delisted owing to clinical worsening, and 75% of the patients underwent transplantation. Median waiting time for patients with HU-listing status was 4.18 months and with T-listing status 9.07 months. There was no difference in crude mortality or delisting between patients who were HU status listed and T status listed (p = 0.65). In multivariable regression analysis, markers for respiratory failure (mechanical ventilation, hazard ratio [HR]: 1.41, 95% CI: 1.11-1.81, p = 0.006) and arrhythmias (anti-arrhythmic medication, HR: 1.42, 95% CI: 1.01-2.01, p = 0.044) were associated with a higher risk of death or delisting. In the overall cohort, post-transplantation mortality was 26.8% after 1 year and 33.4% after 5 years. CONCLUSIONS: Listed patients are at high risk of death without differences in the urgency of listing. Respiratory failure requiring invasive ventilation and possibly arrhythmias requiring anti-arrhythmic medication indicate worse outcomes on waiting list.

Pregnancy in adults with congenital heart disease.

Congenital heart disease (CHD) is present in 0.8-0.9% of live births. Prevalence of CHD is constantly increasing during the last decades in line with the treatment options for patients ranging from the surgical as well to the interventional spectrum. Most of the women with underlying CHD reach adulthood due to excellent surgical and interventional treatment options and most of them desire pregnancy. In Western countries, maternal heart disease is the major cause of mortality during pregnancy, thus risk estimation should be therefore individualized depending on the underlying CHD, functional class and treatment options. Pre-pregnancy counselling is mandatory in all women, especially in patients with high risk but even in patients with low risk, a plan for labor and delivery should be outlined in a heart pregnancy team. This review addresses the key element of pre-counselling, planning and successful disease management in patients with CHD during pregnancy.

Right Ventricular Index for Risk Stratification of Patients with Pulmonary Arterial Hypertension.

BACKGROUND: Right ventricular (RV) dysfunction is a major prognostic predictor in pulmonary arterial hypertension (PAH). OBJECTIVES: The objective of this study was to assess the prognostic impact of a newly developed index merging haemodynamic parameters into 1 variable. METHODS: We retrospectively assessed 2 cohorts of 248 patients (164 from Hamburg and 84 from Heidelberg) with invasively diagnosed PAH. During a median follow-up time of 3.6 years (3.1 and 4.0 years for Hamburg and Heidelberg, respectively), the composite endpoint of all-cause mortality and lung transplantation occurred in 57 patients (53 and 4 patients for Hamburg and Heidelberg, respectively). The RV index was developed in the Hamburg cohort and validated in the Heidelberg cohort: (right atrial pressure × pulmonary vascular resistance)/mixed venous oxygen saturation. RESULTS: Patients with a high RV index had a higher incidence of the combined endpoint in Kaplan-Meier analyses in the Hamburg and Heidelberg cohort (p = 0.017 and p = 0.034, respectively). The calculated RV index cut-off value was 91 and identified patients with a worse outcome in the Hamburg cohort and showed a trend in the Heidelberg cohort (p < 0.001 and p = 0.089, respectively). The RV index in Cox regression hazard models was an independent predictor of outcomes after adjustment for sex and age in both cohorts (Hamburg: hazard ratio [HR] 1.26 [95% CI 1.08, 1.47], p = 0.0027; Heidelberg: HR 2.27 [95% CI 1.46, 3.51], p < 0.001). A nomogram based on these results allowed risk stratification. CONCLUSION: Merging 3 haemodynamic variables into 1 variable, the RV index increased the prognostic power up to an independent risk factor. The RV index is easy to calculate and allows the construction of a nomogram for an individualized risk assessment.

Bicuspid aortic valve and aortic coarctation in congenital heart disease-important aspects for treatment with focus on aortic vasculopathy.

Prevalence of congenital heart disease (CHD) is constantly increasing during the last decades in line with the treatment options for patients ranging from the surgical as well to the interventional spectrum. This mini-review addresses two of the most common defects with bicuspid aortic valve (BAV) and coarctation of the aorta (CoA). Both diseases are connected to aortic vasculopathy which is one of the most common reasons for morbidity and mortality in young patients with CHD. The review will focus as well on other aspects like medication and treatment of pregnant patients with BAV and CoA. New treatment aspects will be as well reviewed as currently there are additional treatment options to treat aortic regurgitation or aortic aneurysm especially in patients with valvular involvement and a congenital BAV thus avoiding replacement of the aortic valve and potentially improving the future therapy course of the patients.

Radiation exposure during the implantation of bioabsorbable vascular scaffolds versus drug-eluting stents in non-complex coronary lesions: a matched-cohort study.

BACKGROUND: Bioabsorbable vascular scaffolds (BVS) are a novel option for the treatment of coronary lesions in patients with stable coronary artery disease or acute coronary syndromes. We aimed to identify the influence of BVS implantation on radiation exposure and procedural outcomes compared to drug-eluting stents (DES) in daily clinical practice. METHODS: A retrospective single-center study was performed in patients undergoing percutaneous coronary intervention with BVS from 2013 to 2014. Only patients with exclusive BVS implantation (N.=78 procedures) were compared with a 2:1 matched cohort of exclusive DES-treated patients in the same period (N.=156 procedures). We used a four-step protocol to reduce radiation exposure in all procedures. Furthermore, a 12-month clinical follow-up was performed. RESULTS: Patients had similar baseline characteristics due to matching. Radiation exposure (1826 vs. 2167 cGy*cm2, P=0.673), procedure time (73 vs. 65 minutes, P=0.574), target vessel revascularization (1.3 vs. 1.3%, p=1.000 for PCI; 1.3 vs. 0.6%, P=0.616 for CABG), cardiovascular death (0.0 vs. 2.6%, P=0.304) or all-cause death (0.0 vs. 3.2%, P=0.172) were similar after implantation of BVS vs. DES. However, exposure to contrast agent (166 vs. 139 mL, P=0.028) was significantly higher in the BVS group. CONCLUSIONS: The implantation of BVS in combination with a simple four-step protocol is a feasible option for interventional treatment of non-complex coronary lesions without significant impact on radiation exposure or outcome measures in daily clinical routine.

Biomarkers for characterization of heart failure - Distinction of heart failure with preserved and reduced ejection fraction.

BACKGROUND: Heart failure (HF) incidence is rising worldwide and HF with preserved ejection fraction (HFpEF) represents nearly half of all cases. Treatment options are still limited in HFpEF in comparison to HF with reduced ejection fraction (HFrEF). METHODS: We analyzed biomarkers in the general population to characterize HFpEF and HFrEF and defined a biomarker index to differentiate HFpEF from HFrEF. Growth differentiation factor-15 (GDF-15), soluble source of tumorigenicity 2 (sST2), C-reactive protein (CRP) and NT-proBNP were measured in 5000 individuals of the population-based Gutenberg Health Study (GHS). The median follow-up time for all-cause mortality was 7.3years with 213 events. RESULTS: Identification of subjects with HF was improved by GDF-15 (p<0.001) in addition to NT-proBNP with an odds ratio (OR) of 1.4 (95% confidence interval [CI]:1.1-1.7). Discrimination of subjects with and without HF was slightly higher for GDF-15 (area under the ROC curve [AUC]:0.79 [95%CI:0.75-0.83]) compared to NT-proBNP (AUC:0.77 [95% CI:0.72-0.82]). For subjects with HF, differentiating HFpEF from HFrEF was feasible with the index ((CRP+GDF-15+sST2)/NT-proBNP) with an OR of 3.7 (95% CI:1.9-8.5) (p<0.001). The best biomarkers predicting all-cause mortality were NT-proBNP and GDF-15 with a hazard ratio (HR) of 1.9 (95% CI:1.6-2.2) and 1.7 (95%CI:1.6-1.9) (both p<0.001), respectively. CONCLUSION: GDF-15 was useful to detect prevalent HF in addition to NT-proBNP and was elevated in HFrEF and HFpEF, whereas NT-proBNP was higher in HFrEF than in HFpEF. All biomarkers were useful to predict mortality in the general population. The index of ((CRP+GDF-15s+sST2)/NT-proBNP) was able to discriminate HFpEF from HFrEF.

Cardiovascular Mortality in Chest Pain Patients: Comparison of Natriuretic Peptides With Novel Biomarkers of Cardiovascular Stress.

BACKGROUND: Natriuretic peptides are the standard biomarker for risk stratification in cardiovascular disease. Novel biomarkers of cardiovascular stress might allow refinement in risk stratification for patients with acute coronary syndrome (ACS). We tested the performance of these novel biomarkers for cardiovascular risk stratification in patients who presented with ACS. METHODS: In the AtheroGene study, 873 patients presented with ACS in the emergency department. Biomarkers measured were: B-type natriuretic peptide (BNP), N-terminal pro BNP (NT-proBNP), midregional proatrial natriuretic peptide, midregional proadrenomedullin (MR-proADM), copeptin, and troponin I. The median follow-up time was 4 years and during this time 50 patients died from cardiac causes. RESULTS: Cox regression analysis for the continuous variables NT-proBNP and BNP showed a hazard ratio (HR) of 1.9 and 1.8, respectively, for 1 SD increase (P < 0.001 and P = 0.003) in the fully adjusted model. Novel biomarkers with MR-proADM had an HR of 3.2, followed by midregional proatrial natriuretic peptide with an HR of 1.9 (both P < 0.001), and copeptin with an HR of 1.6 (P < 0.001). C-index revealed MR-proADM as the best discriminator for identifying patients with the outcome with a C-index = 0.8, and C-index was 0.72 for NT-proBNP (P for comparison = 0.017). Integrated discrimination improvement for MR-proADM was 0.059 compared with NT-proBNP (P = 0.016), thus providing background that MR-proADM was better to identify persons with the outcome. Troponin I levels at the time of admission were not significant for risk stratification. CONCLUSIONS: In patients who present with ACS the novel biomarker, MR-proADM was the best predictor for outcome. MR-proADM adds modest information and is useful for risk prediction in ACS patients.

SYNTAX score-0 patients: risk stratification in nonobstructive coronary artery disease.

BACKGROUND: The complexity of coronary artery disease (CAD) is a predictor of cardiovascular events in patients with >50 % diameter stenosis as determined by SYNTAX score. Here, we compare the Gensini score to SYNTAX in patients with CAD as well as apply the Gensini score in patients with nonobstructive CAD (NOB-CAD), defined by ≤50 % diameter stenosis, were the SYNTAX score cannot be utilized to define future risk. METHODS: The AtheroGene study enrolled 2316 patients [861/37.2 % with acute cardiovascular syndrome (ACS) and 1500/62.8 % with stable CAD (SCAD)]. Of these, 1966 had obstructive CAD (OB-CAD) with SYNTAX and Gensini scores available and 291 events with either cardiovascular mortality or non-fatal myocardial infarction were recorded. Furthermore, 350 patients had NOB-CAD with only Gensini score and 36 events. Median follow-up time was 4.9 years. RESULTS: In the OB-CAD cohort the SYNTAX and the Gensini score predicted outcome. Kaplan-Meier curve analysis with the dichotomized Gensini score showed a significant result (p = 0.04) in the NOB-CAD cohort. Cox Regression analysis after adjustment showed a hazard ratio (HR) of 1.33 and p = 0.04 for the Gensini score in the NOB-CAD cohort. Receiver operating characteristic curve (ROC) analysis provided the highest area under the curve (AUC) regarding the outcome for the Gensini score with 0.65 (p = 0.004). Comparing the SYNTAX and Gensini score in this cohort showed improved discrimination of patients with events by the Gensini score (p = 0.02). CONCLUSION: The Gensini score predicted events in patients with ≤50 % diameter lesions. Utilization of this score is useful to define risk in NOB-CAD patients.

Candidate biomarkers in heart failure with reduced and preserved ejection fraction.

CONTEXT: Patients presenting with heart failure symptoms are categorized into heart failure (HF) with reduced and preserved ejection fraction. OBJECTIVE: Aim is to investigate the additional use of candidate biomarkers to characterize patients with either sub-type of HF. METHODS: Literature search was conducted in the electronic databases MEDLINE and Cochrane Central Register of Controlled Trials from inception through November 2014. RESULTS: The results of 47 diseased and general population cohorts were included. CONCLUSION: Current studies could outline the additional use of candidate biomarkers especially GDF-15, MR-proADM and high-sensitive determined troponin, although major outcome studies are still missing.

The utility of pregnancy-associated plasma protein A for determination of prognosis in a cohort of patients with coronary artery disease.

BACKGROUND: Pregnancy-associated plasma protein-A (PAPP-A) is discussed as a biomarker representing unstable plaques in coronary artery disease (CAD). METHODS: In this study 927 patients with CAD (534 with stable angina and 393 with acute coronary syndrome [ACS]) and 217 patients without CAD and measured PAPP-A levels were included. Follow-up for a median of 5 years was documented. RESULTS: Rising quartiles of PAPP-A concentration had a higher cardiovascular mortality in the overall cohort of patients with CAD (p = 0.002) and the cohort with ACS (p = 0.01). Patients with suspected ACS below the LOD for troponin I but elevated PAPP-A levels had an increased cardiovascular mortality. A cut-off of 11.4 IU/l identified patients with a higher mortality during follow-up. CONCLUSION: Rising PAPP-A levels are prognostic in patients with CAD. PAPP-A levels were especially predictive in ACS patients with troponin below 10% CV of the 99 th percentile for cardiovascular mortality.

Risk Factors of Coronary Artery Disease in Secondary Prevention--Results from the AtheroGene--Study.

BACKGROUND: Risk factors are important in cardiovascular (CV) medicine for risk stratification of patients. We aimed to compare the traditional risk factors to clinical variables for the prediction of secondary cardiovascular events. METHODS AND RESULTS: For this study, 3229 patients with known coronary artery disease (CAD) were included. We calculated whether the traditional risk factors, diabetes mellitus, increased LDL/HDL ratio, arterial hypertension and smoking alone and in combination with the clinical variables, ejection fraction, creatinine clearance, multi-vessel disease and CRP concentration predict the outcome cardiovascular death or non-fatal myocardial infarction (N = 432) during the mean follow-up time of 4.2 ± 2.0 years. In this cohort diabetes mellitus was the risk factor with the strongest influence regarding occurrence of secondary events (hazard ratio; HR:1.70, confidence interval; CI 95%: 1.36-2.11; P<0.0001), followed by LDL/HDL ratio and smoking. However, risk stratification is further improved by using additional clinical variables like ejection fraction (HR:3.30 CI 95%:2.51-4.33; P>0.0001) or calculated creatinine clearence (Cockroft-Gault formula) (HR:2.26 CI 95%:1.78-2.89; P<0.0001). Further ameliorating risk stratification from the clinical variables were CRP and multi-vessel disease. The most precise risk prediction was achieved when all clinical variables were added to the CV risk factors. CONCLUSION: Diabetes mellitus has the strongest influence to predict secondary cardiovascular events in patients with known CAD. Risk stratification can further be improved by adding CV risk factors and clinical variables together. Control of risk factors is of paramount importance in patients with known CAD, while clinical variables can further enhance prediction of events.