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Aims: Heart failure (HF) is a chronic and progressive syndrome associated with a poor prognosis. While it may seem intuitive that the risk of adverse outcomes varies across the different stages of HF, an overview of these risks is lacking. This study aims to determine the risk of all‐cause mortality and HF hospitalizations associated with new‐onset HF, chronic HF (CHF), worsening HF (WHF), and advanced HF. Methods and results: We performed a systematic review of observational studies from 2012 to 2022 using five different databases. The primary outcomes were 30‐day and 1‐year all‐cause mortality, as well as 1‐year HF hospitalization. Studies were pooled using random effects meta‐analysis, and mixed‐effects meta‐regression was used to compare the different HF groups. Among the 15 759 studies screened, 66 were included representing 862 046 HF patients. Pooled 30‐day mortality rates did not reveal a significant distinction between hospital‐admitted patients, with rates of 10.13% for new‐onset HF and 8.11% for WHF (p = 0.10). However, the 1‐year mortality risk differed and increased stepwise from CHF to advanced HF, with a rate of 8.47% (95% confidence interval [CI] 7.24–9.89) for CHF, 21.15% (95% CI 17.78–24.95) for new‐onset HF, 26.84% (95% CI 23.74–30.19) for WHF, and 29.74% (95% CI 24.15–36.10) for advanced HF. Readmission rates for HF at 1 year followed a similar trend. Conclusions: Our meta‐analysis of observational studies confirms the different risk for adverse outcomes across the distinct HF stages. Moreover, it emphasizes the negative prognostic value of WHF as the first progressive stage from CHF towards advanced HF. [ABSTRACT FROM AUTHOR]

The prognostic value of SYNTAX score (SS), intravascular ultrasound (IVUS)-derived plaque burden (PB) and near-infrared spectroscopy (NIRS)-derived lipid core burden index(LCBI) for identification of high-risk patients for major adverse cardiovascular events (MACE) has been proven in previous studies. The majority of patients presenting in the cathlab however do not endure MACE over time, and identification of low-risk groups has remained underexposed. This study evaluates the combined prognostic value of SS, PB and LCBI in identifying patients with low MACE risk. This post-hoc analysis combines the ATHEROREMO and IBIS-3 studies and included 798 patients undergoing coronary angiography. Anatomical SS was calculated (N = 617) and ≥40mm non-stenotic segment of a non-target vessel was investigated with IVUS (N = 645) and NIRS (N = 273) to determine PB and maximum 4mm LCBI (LCBI4mm). During five-year follow-up, 191 MACE were observed. Patients with PB ≤70%, LCBI4mm ≤227 (median), or SS ≤8 (median) had lower MACE incidence than their counterparts with higher values. Combined into one model, LCBI4mm ≤227 (adjusted hazard ratio [aHR] 0.49, 95% confidence interval [CI] 0.30–0.78; p-value = 0.003) and SS ≤8 (aHR 0.67, 95%CI 0.48–0.96, p-value = 0.027) were independently associated with (lower) MACE rate, but PB was not. Additionally, negative predictive value (NPV) of this model was high (SS<8: 0.80, PB<70%: 0.77, LCBI4mm<227: 0.79). In this cohort, SS and LCBI4mm proved to be independent predictors of MACE-free survival during five-year follow-up. Combination of SS and LCBI4mm is useful to identify a low-risk population. Furthermore, NPV of SS, PB and LCBI4mm for prediction of MACE is high. [ABSTRACT FROM AUTHOR]

Aims: Previous studies have identified candidate circulating microRNAs (circmiRs) as biomarkers for heart failure (HF) using relatively insensitive arrays, validated in small cohorts. The present study used RNA sequencing to identify novel candidate circmiRs and compared these with previously identified circmiRs in a large, prospective cohort of patients with acute HF (AHF).Methods and Results: RNA sequencing of plasma from instrumented pigs was used to identify circmiRs produced by myocardium. Production of known myomiRs and microRNA (miR)-1306-5p was identified. The prognostic values of this and 11 other circmiRs were tested in a prospective cohort of 496 AHF patients, from whom blood samples were collected at up to seven time-points during the study's 1-year follow-up. The primary endpoint was the composite of all-cause mortality and HF rehospitalization. In the prospective AHF cohort, 188 patients reached the primary endpoint, and higher values of repeatedly measured miR-1306-5p were positively associated with risk for reaching the primary endpoint at the same time-point [hazard ratio (HR) 4.69, 95% confidence interval (CI) 2.18-10.06], independent of clinical characteristics and NT-proBNP. Baseline miR-1306-5p did not improve model discrimination/reclassification significantly compared with NT-proBNP. For miR-320a, miR-378a-3p, miR-423-5p and miR-1254, associations with the primary endpoint were present after adjustment for age and sex (HR 1.38, 95% CI 1.12-1.70; HR 1.35, 95% CI 1.04-1.74; HR 1.45, 95% CI 1.10-1.92; HR 1.22, 95% CI 1.00-1.50, respectively). Rates of detection of myomiRs miR-208a-3p and miR-499a-5p were very low.Conclusions: Repeatedly measured miR-1306-5p was positively associated with adverse clinical outcome in AHF, even after multivariable adjustment including NT-proBNP. However, baseline miR-1306-5p did not add significant discriminatory value to NT-proBNP. Low-abundance, heart-enriched myomiRs are often undetectable, which mandates the development of more sensitive assays. [ABSTRACT FROM AUTHOR]

Background: Some aspects of prognosis are not reflected by cumulative survival estimates. These aspects include information on the time already survived by the patient and the patient's survival compared with the general population. Conditional survival (ie, conditional on having survived a certain period of time already) and relative conditional survival (ie, compared with the general population) do incorporate these aspects. We investigated these measures of prognosis in patients undergoing percutaneous coronary intervention.Methods and Results: We studied 17 903 consecutive patients undergoing percutaneous coronary intervention between 2000 and 2014. Cumulative survival was estimated for patients with ST-segment-elevation myocardial infarction (n=5996, 853 deaths), non-ST-segment-elevation myocardial infarction (n=5371, 901 deaths), and stable angina pectoris (n=6536, 965 deaths) in 4 age categories. One-year conditional and relative conditional survival up to 10 years post-percutaneous coronary intervention was calculated. The results demonstrated that 1-year cumulative survival for patients with ST-segment-elevation myocardial infarction aged ≥76 years was 83%. One-year conditional survival, conditional on surviving the first month, was 92% in this group, and relative conditional survival (relative to the general population) was 99%. In younger age categories and in patients with non-ST-segment-elevation myocardial infarction and stable angina pectoris , similar patterns were found albeit less pronounced. Five-year relative conditional rendered similar results.Conclusions: Relative conditional survival provides a comprehensive picture of patient prognosis, particularly for older patients with ST-segment-elevation myocardial infarction. Although, as expected, their cumulative survival is low, once they survive the first month after percutaneous coronary intervention, their prognosis is comparable to that of the general population. Therefore, relative conditional survival estimates provide an important, meaningful addition when discussing prognosis with patients. [ABSTRACT FROM AUTHOR]

Background: Studies on serially measured GDF-15 (growth differentiation factor 15) in acute heart failure (HF) are limited. Moreover, several pathophysiological pathways contribute to HF. Therefore, we aimed to explore the (additional) prognostic value of serially measured GDF-15 using a multi-marker approach to more accurately predict HF risk. Methods: TRIUMPH (Translational Initiative on Unique and Novel Strategies for Management of Patients With Heart Failure) is a prospective cohort of 496 patients with acute HF who were enrolled in 14 hospitals in the Netherlands between 2009 and 2014. Blood sampling was scheduled at 7 moments during 1-year follow-up. GDF-15, NT-proBNP (N-terminal pro-B-type natriuretic peptide), ST2 (suppression of tumorigenicity 2), galectin-3, troponin I, and creatinine were measured in a central laboratory. We associated repeated measurements of these biomarkers with the composite primary end point of all-cause mortality and HF rehospitalization, using multivariable joint modeling. Results: Median age was 74 years, and 37% were women. Median baseline GDF-15 was 4632 pg/mL. The primary end point was reached in 188 (40%) patients. The average estimated GDF-15 level increased weeks before the primary end point was reached. The hazard ratio per 1 SD difference in log-GDF-15 was 2.14 (95% CI, 1.78–2.57) unadjusted, 1.96 (1.49–2.53) after adjustment for clinical confounders and 1.44 (1.05–1.91) when jointly modeled with all biomarkers. The adjusted HRs for NT-proBNP were 2.38 (1.78–3.33) and 1.52 (1.15–2.08), respectively. The multimarker model combining GDF-15, NT-proBNP, and troponin I provided a favorable risk discrimination (area under the curve=0.785). Conclusions: Sequentially measured GDF-15 independently and dynamically predicts risk of adverse outcomes during 1-year follow-up after index admission for acute HF. NT-proBNP remains a robust predictor among potential candidates. Multiple biomarkers should be considered for stratification in clinical practice. Registration: URL: https://www.trialregister.nl/trial/1783; Unique Identifier: NTR1893. (The trial can be found temporarily at https://trialsearch.who.int/Trial2.aspx?TrialID=NTR1893.) [ABSTRACT FROM AUTHOR]

Objective: To investigate relations of several circulating chemokines with extent and phenotype of coronary atherosclerosis and with 1-year clinical outcome. Methods: Intravascular ultrasound virtual histology (IVUS-VH) imaging of a coronary artery was performed in 581 patients. Monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), MIP-1β and regulated upon activation normal T cell expressed and secreted (RANTES) were measured in plasma. Results: Higher MCP-1, MIP-1α and lower RANTES were associated with coronary plaque burden. Higher MCP-1, MIP-1α and lower RANTES were associated with the presence of IVUS-VH-derived thin-cap fibroatheroma lesions. RANTES was associated with major adverse cardiac events. Conclusions: RANTES is a promising biomarker that is inversely associated with coronary plaque burden and vulnerability, as well as with death and acute coronary syndrome. [ABSTRACT FROM AUTHOR]

Aims Acute coronary syndromes (ACS) are mostly caused by plaque rupture. This study aims to investigate the prognostic value of in vivo detection of high-risk coronary plaques by intravascular ultrasound (IVUS) in patients undergoing coronary angiography. Methods and results Between November 2008 and January 2011, IVUS of a non-culprit coronary artery was performed in 581 patients who underwent coronary angiography for ACS (n = 318) or stable angina (n = 263). Primary endpoint was major adverse cardiac events (MACEs) defined as mortality, ACS, or unplanned coronary revascularization. Culprit lesion-related events were not counted. Cumulative Kaplan–Meier incidence of 1-year MACE was 7.8%. The presence of IVUS virtual histology-derived thin-cap fibroatheroma (TCFA) lesions (present 10.8% vs. absent 5.6%; adjusted HR: 1.98, 95% CI: 1.09–3.60; P = 0.026) and lesions with a plaque burden of ≥70% (present 16.2% vs. absent 5.5%; adjusted HR: 2.90, 95% CI: 1.60–5.25; P < 0.001) were independently associated with a higher MACE rate. Thin-cap fibroatheroma lesions were also independently associated with the composite of death or ACS only (present 7.5% vs. absent 3.0%; adjusted HR: 2.51, 95% CI: 1.15–5.49; P = 0.021). Thin-cap fibroatheroma lesions with a plaque burden of ≥70% were associated with a higher MACE rate within (P = 0.011) and after (P < 0.001) 6 months of follow-up, while smaller TCFA lesions were only associated with a higher MACE rate after 6 months (P = 0.033). Conclusion In patients undergoing coronary angiography, the presence of IVUS virtual histology-derived TCFA lesions in a non-culprit coronary artery is strongly and independently predictive for the occurrence of MACE within 1 year, particularly of death and ACS. Thin-cap fibroatheroma lesions with a large plaque burden carry higher risk than small TCFA lesions, especially on the short term. [ABSTRACT FROM PUBLISHER]

Aims Heart failure with normal ejection fraction (HFNEF) is a major and growing public health problem, currently representing half of the heart failure burden. Although many studies have investigated the diagnostic and prognostic value of new biomarkers in heart failure, limited data are available on biomarkers other than natriuretic peptides in HFNEF. We performed a systematic review of epidemiological studies on the associations of biomarkers with the occurrence of HFNEF and with the prognosis of HFNEF patients. Methods and results Biomarkers examined most extensively in HFNEF include biomarkers of myocyte stress, inflammation, and extracellular matrix remodelling. Some biomarkers have been shown to be increased to a different extent in HFNEF compared with heart failure with reduced ejection fraction (HFREF). Several biomarkers, including biomarkers of myocyte stress, inflammation, extracellular matrix remodelling, growth differentiation factor 15 (GDF-15), cystatin C, resistin, and galectin-3, were associated with development of HFNEF and with clinical outcomes of HFNEF patients in terms of morbidity and mortality. Conclusion Several biomarkers, including biomarkers of myocyte stress, inflammation, extracellular matrix remodelling, GDF-15, cystatin C, resistin, and galectin-3, appeared to be promising diagnostic and prognostic tools in patients with HFNEF. Investigation of the incremental diagnostic and prognostic value of these biomarkers, or a combination thereof, over established clinical covariates and imaging techniques in large, prospective studies is warranted. [ABSTRACT FROM PUBLISHER]

Clinical Outcome in Cardiac Resynchronization Therapy (CRT) Functional Responders. Introduction : We evaluated clinical outcome and incidence of (in)appropriate shocks in consecutive chronic heart failure (CHF) patients treated with CRT with a defibrillator (CRT-D) according to functional response status. Furthermore, we investigated which factors predict such functional response. Methods and Results : In a large teaching hospital, 179 consecutive CHF patients received CRT-D in 2005-2010. Patients were considered functional responders if left ventricular ejection fraction (LVEF) increased to ≥35% postimplantation. Analysis was performed on 142 patients, who had CRT-D as primary prevention, complete data and a baseline LVEF <35%. Endpoints consisted of all-cause mortality, heart failure (HF) hospitalizations, appropriate shocks and inappropriate shocks. Median follow-up was 3.0 years (interquartile range [IQR] 1.6-4.4) and median baseline LVEF was 20% (IQR 18-25%). The functional response-group consisted of 42 patients. In this group no patients died, none were hospitalized for HF, none received appropriate shocks and 3 patients (7.1%) received ≥1 inappropriate shocks. In comparison, the functional nonresponse group consisted of 100 patients, of whom 22 (22%) died (P = 0.003), 17 (17%) were hospitalized for HF (P = 0.007), 17 (17%) had ≥1 appropriate shocks (P = 0.003) and 8 (8.1%) received ≥1 inappropriate shocks (P = 0.78). Multivariable analysis showed that left bundle branch block (LBBB), QRS duration ≥150 milliseconds and no need for diuretics at baseline are independent predictors of functional response. Conclusion : Functional responders to CRT have a good prognosis and rarely need ICD therapy. LBBB, QRS duration ≥150 milliseconds and lack of chronic diuretic use predict functional response. (J Cardiovasc Electrophysiol, Vol. 24, pp. 316-322, March 2013) [ABSTRACT FROM AUTHOR]

Background: It has been shown that intravascular ultrasound (IVUS) and radiofrequency (RF-)IVUS can detect high-risk coronary plaque characteristics.Objectives: The authors studied the long-term prognostic value of (RF-)IVUS-derived plaque characteristics in patients with coronary artery disease (CAD) undergoing coronary angiography.Methods: From 2008 to 2011, (RF-)IVUS was performed in 1 nonstenotic segment of a nonculprit coronary artery in 581 patients undergoing coronary angiography for acute coronary syndrome (ACS) or stable angina. The pre-defined primary endpoint was major adverse cardiovascular events (MACE), defined as the composite of all-cause death, nonfatal ACS, or unplanned revascularization. Hazard ratios (HRs) were adjusted for age, sex, and clinical risk factors.Results: During a median follow-up of 4.7 years, 152 patients (26.2%) had MACE. The presence of a lesion with a minimal luminal area ≤4.0 mm2 was independently associated with MACE (HR: 1.49; 95% CI: 1.07 to 2.08; p = 0.020), whereas the presence of a thin-cap fibroatheroma lesion or a lesion with a plaque burden ≥70% on its own were not. Results were comparable when the composite endpoint included cardiac death instead of all-cause death. The presence of a lesion with a plaque burden of ≥70% was independently associated with the composite endpoint of cardiac death, nonfatal ACS, or unplanned revascularization after exclusion of culprit lesion-related events (HR: 1.66; 95% CI: 1.06 to 2.58; p = 0.026). Likewise, each 10-U increase in segmental plaque burden was independently associated with a 26% increase in risk of this composite endpoint (HR: 1.26 per 10-U increase; 95% CI: 1.03 to 1.52; p = 0.022).Conclusions: IVUS-derived small luminal area and large plaque burden, and not RF-IVUS-derived compositional plaque features on their own, predict adverse cardiovascular outcome during long-term follow-up in patients with CAD. (The European Collaborative Project on Inflammation and Vascular Wall Remodeling in Atherosclerosis-Intravascular Ultrasound Study [AtheroRemoIVUS]; NCT01789411). [ABSTRACT FROM AUTHOR]

This study aimed to identify heart failure (HF) subphenotypes using 92 repeatedly measured circulating proteins in 250 patients with heart failure with reduced ejection fraction, and to investigate their clinical characteristics and prognosis. Clinical data and blood samples were collected tri-monthly until the primary endpoint (PEP) or censoring occurred, with a maximum of 11 visits. The Olink Cardiovascular III panel was measured in baseline samples and the last two samples before the PEP (in 66 PEP cases), or the last sample before censoring (in 184 PEP-free patients). The PEP comprised cardiovascular death, heart transplantation, Left Ventricular Assist Device implantation, and hospitalization for HF. Cluster analysis was performed on individual biomarker trajectories to identify subphenotypes. Then biomarker profiles and clinical characteristics were investigated, and survival analysis was conducted. Clustering revealed three clinically diverse subphenotypes. Cluster 3 was older, with a longer duration of, and more advanced HF, and most comorbidities. Cluster 2 showed increasing levels over time of most biomarkers. In cluster 3, there were elevated baseline levels and increasing levels over time of 16 remaining biomarkers. Median follow-up was 2.2 (1.4–2.5) years. Cluster 3 had a significantly poorer prognosis compared to cluster 1 (adjusted event-free survival time ratio 0.25 (95%CI:0.12–0.50), p < 0.001). Repeated measurements clusters showed incremental prognostic value compared to clusters using single measurements, or clinical characteristics only. Clustering based on repeated biomarker measurements revealed three clinically diverse subphenotypes, of which one has a significantly worse prognosis, therefore contributing to improved (individualized) prognostication. • We repeatedly measured 92 circulating proteins in 250 ambulant patients with HFrEF. • Clustering of individual biomarker trajectories identified 3 HFrEF subphenotypes. • Subphenotypes were clinically diverse and associated with adverse events. • Thus temporal biomarker pattern subphenotypes may aid in personalized prognostication. [ABSTRACT FROM AUTHOR]

Background and Aims Previous lipidomics analyses have demonstrated that several lipid molecules in plasma are associated with fatal outcome in patients with coronary artery disease (CAD). This study aims to investigate the associations of previously identified high risk lipid molecules in plasma with coronary plaque characteristics derived from intravascular ultrasound virtual histology (IVUS-VH) imaging, with coronary lipid core burden index (LCBI) on near-infrared spectroscopy (NIRS), and with one year cardiovascular outcome in patients with CAD. Methods Between 2008 and 2011, IVUS-VH imaging of a non-culprit coronary artery was performed in 581 patients who underwent coronary angiography for acute coronary syndrome (ACS) or stable CAD. NIRS imaging was additionally performed in 191 patients. Plasma concentrations of molecular lipids were measured with mass spectrometry. Results Several cholesteryl ester, ceramide and lactosylceramide species and ceramide ratios were associated with vulnerable plaque characteristics on IVUS-VH and NIRS imaging and with 1-year major adverse cardiac events (MACE, defined as all-cause mortality, ACS and unplanned coronary revascularization). In particular, ceramide d18:1/16:0 was consistently associated with higher necrotic core fraction on IVUS-VH (p = 0.001), higher LCBI (p = 0.024) on NIRS and higher MACE rate (adjusted HR 1.79 per standard deviation increase in log-transformed lipid concentration, 95%CI 1.24–2.59, p = 0.002). Conclusion Several molecular lipid species, and particularly ceramide(d18:1/16:0), are associated with the fraction of necrotic core tissue and lipid core burden in coronary atherosclerosis, and are predictive for 1-year clinical outcome after coronary angiography. These molecular lipids may improve risk stratification in CAD and may also be interesting therapeutic targets for the treatment of atherosclerotic disease. [ABSTRACT FROM AUTHOR]

Vessel Fractional Flow Reserve (vFFR) as assessed by three-dimensional quantitative coronary angiography has high correlation with pressure wire-based fractional flow reserve in both a pre- and post-PCI setting. The present study aims to assess the prognostic value of post-PCI vFFR on the incidence of target vessel failure (TVF), a composite endpoint of cardiac death, target vessel myocardial infarction and target vessel revascularization (TVR) at 5-year follow up. Post-PCI vFFR was calculated after routine PCI in a total of 748 patients (832 vessels) with available orthogonal angiographic projections of the stented segment. Median age was 65 (IQR 55–74) years, 18.2% were diabetic, and 29.1% presented with stable angina. Median post-PCI vFFR was 0.91 (IQR 0.86–0.95). Vessels were categorized into tertiles based on post-PCI vFFR: low (vFFR <0.88), middle (vFFR 0.88–0.93), and upper (vFFR ≥0.94). Vessels in the lower and middle tertile were more often LADs and had smaller stent diameters (p <0.001). Vessels in the lower and middle tertile had a higher risk of TVF as compared to vessels in the upper tertile (24.6% and 21.5% vs. 17.1%; adjusted HR 1.84 (95%CI 1.15–2.95), p = 0.011, and 1.58 (95%CI 1.02–2.45), p = 0.040) at 5-years follow-up. Additionally, vessels in the lower tertile had higher rates of TVR as compared to vessels in the higher tertile (12.6% vs. 6.5%, adjusted HR 1.93 (95%CI 1.06–3.53), p = 0.033). Lower post-PCI vFFR values are associated with a significantly increased risk of TVF and TVR at 5-years follow-up. • Suboptimal post-PCI FFR is related to an increased risk of cardiovascular events. • vFFR, an angiography-derived FFR index, correlates strongly with invasive FFR. • Lower post-PCI vFFR values were found more often in LAD vessels and smaller stents. • Lower post-PCI vFFR values had higher rates of target vessel failure at 5-years. • Post-PCI vFFR might identify those who require additional post-PCI optimization. [ABSTRACT FROM AUTHOR]

Background: The clinical outcomes of noncompaction cardiomyopathy (NCCM) range from asymptomatic to heart failure, arrhythmias, and sudden cardiac death. Genetics play an important role in NCCM.Objectives: This study investigated the correlations among genetics, clinical features, and outcomes in adults and children diagnosed with NCCM.Methods: A retrospective multicenter study from 4 cardiogenetic centers in the Netherlands classified 327 unrelated NCCM patients into 3 categories: 1) genetic, with a mutation in 32% (81 adults; 23 children) of patients; 2) probably genetic, familial cardiomyopathy without a mutation in 16% (45 adults; 8 children) of patients; or 3) sporadic, no family history, without mutation in 52% (149 adults; 21 children) of patients. Clinical features and major adverse cardiac events (MACE) during follow-up were compared across the children and adults.Results: MYH7, MYBPC3, and TTN mutations were the most common mutations (71%) found in genetic NCCM. The risk of having reduced left ventricular (LV) systolic dysfunction was higher for genetic patients compared with the probably genetic and sporadic cases (p = 0.024), with the highest risk in patients with multiple mutations and TTN mutations. Mutations were more frequent in children (p = 0.04) and were associated with MACE (p = 0.025). Adults were more likely to have sporadic NCCM. High risk for cardiac events in children and adults was related to LV systolic dysfunction in mutation carriers, but not in sporadic cases. Patients with MYH7 mutations had low risk for MACE (p = 0.03).Conclusions: NCCM is a heterogeneous condition, and genetic stratification has a role in clinical care. Distinguishing genetic from nongenetic NCCM complements prediction of outcome and may lead to management and follow-up tailored to genetic status. [ABSTRACT FROM AUTHOR]

Background and aims Experimental studies have suggested that proprotein convertase substilisin/kexin type 9 (PCSK9) might directly promote inflammatory processes contributing to atherosclerosis by mechanisms independent of low-density lipoprotein (LDL) cholesterol levels. This study aims to investigate the association between serum PCSK9 levels and the fraction and amount of necrotic core tissue in coronary atherosclerotic plaque, as assessed by intravascular ultrasound virtual histology (IVUS-VH) imaging. Methods Between 2008 and 2011, IVUS-VH imaging of a non-culprit coronary artery was performed in 581 patients who underwent coronary angiography for acute coronary syndrome (ACS) or stable angina. PCSK9 concentrations were measured in serum samples that were drawn prior to coronary angiography. None of the patients received PCSK9 inhibitors. Results After adjustment for established cardiac risk factors, statin use and serum LDL cholesterol, serum PCSK9 levels were linearly associated with the fraction of plaque consisting of necrotic core tissue (β = 1.24% increase per 100 μg/L increase in PCKS9, 95%CI 0.55–1.94, p = 0.001) and with the absolute volume of necrotic core tissue (β = 0.09, 95%CI 0.01–0.18, p = 0.033), but were not significantly associated with plaque burden (p = 0.11), plaque volume (p = 0.22) or the presence of IVUS-VH-derived thin-cap fibroatheroma lesions (p = 1.0). Conclusion Serum PCSK9 levels were linearly associated with the fraction and amount of necrotic core tissue in coronary atherosclerosis, independently of serum LDL cholesterol levels and statin use. Therefore, PCSK9 may be an interesting therapeutic target for the treatment of atherosclerotic disease beyond LDL cholesterol regulation. [ABSTRACT FROM AUTHOR]

Objective Previous studies have suggested positive associations between periodontal infection and cardiovascular disease. We aimed to investigate the associations of circulating antibodies against periodontal pathogens with 1-year cardiovascular outcome, as well as the extent of coronary atherosclerosis, plaque vulnerability and lesion remodeling on intravascular ultrasound (IVUS) imaging. Methods Between 2008 and 2011, radiofrequency IVUS imaging of a non-culprit coronary artery was performed in 581 patients who underwent coronary angiography. Immunoglobulin G (IgG) and A (IgA) against Porphyromonas gingivalis , Aggregatibacter actinomycetemcomitans , Tannerella forsythia and Prevotella intermedia were measured in plasma. Results None of the antibody levels were associated with coronary plaque burden, radiofreqeuncy-IVUS-derived thin-cap fibroatheroma lesion morphology or 1-year incidence of major adverse cardiac events (MACE), which included all-cause mortality, acute coronary syndrome and unplanned coronary revascularization. IgA against A. actinomycetemcomitans , T. forsythia and P. intermedia were inversely associated with extent of positive lesion remodeling (OR for highest versus lowest tertile 0.55, 95%CI 0.35–0.88, p = 0.012; 0.53, 95%CI 0.32–0.87, p = 0.012; and 0.64, 95%CI 0.40–1.02, p = 0.061, respectively). In diabetic patients specifically, IgG against P. gingivalis tended to be associated with coronary plaque burden ( p = 0.080), while IgA against P. gingivalis tended to be associated with incident MACE ( p = 0.060). Conclusion Plasma IgG and IgA against major periodontal pathogens were not associated with the extent of coronary atherosclerosis (with the exception of a trend in diabetics) nor with coronary plaque vulnerability. IgA against periodontal pathogens were inversely associated with extent of coronary remodeling. Altogether, these results do not add evidence for a substantial role of systemic exposure to periodontal pathogens in coronary artery disease. [ABSTRACT FROM AUTHOR]

Abstract: Background: Little evidence is available on the optimal sequence of intra-aortic balloon pump (IABP) support initiation and primary percutaneous coronary intervention (PCI) in patients who present with cardiogenic shock from ST-elevation myocardial infarction (STEMI). The aim of this study was to evaluate the order of IABP insertion and primary PCI and its association with infarct size and mortality. Methods: A series of 173 consecutive patients admitted with cardiogenic shock from STEMI and treated with primary PCI and IABP between 2000 and 2009 were included. The order of IABP insertion and primary PCI was left at the discretion of the interventional cardiologist. Results: All baseline characteristics were similar in patients who first received IABP (n=87) and patients who received IABP directly after PCI (n=86). In these two groups, cumulative 30-day mortality was 44% and 37% respectively (p=0.39). Median peak serum creatine kinase (CK) concentrations were 5692U/l and 4034U/l respectively (p=0.048). In multivariable analysis, IABP insertion before PCI was independently associated with higher CK levels (p=0.046). In patients who survived 30days, IABP insertion before PCI was not associated with late mortality evaluated at five years of follow-up (HR1.5, 95% CI 0.7–3.3; p=0.34). Conclusions: Early IABP insertion before primary PCI might be associated with higher peak CK levels, indicating a larger infarct size. A possible explanation may be the increased reperfusion delay. Our study suggests that early reperfusion could have priority over routine early IABP insertion in STEMI patients with cardiogenic shock. Randomized studies are needed to determine the optimal timing of IABP insertion relative to primary PCI. [Copyright &y& Elsevier]