Appropriate use criteria for optical coherence tomography guidance in percutaneous coronary interventions : Recommendations of the working group of interventional cardiology of the Netherlands Society of Cardiology.

INTRODUCTION: Optical coherence tomography (OCT) enables detailed imaging of the coronary wall, lumen and intracoronary implanted devices. Responding to the lack of specific appropriate use criteria (AUC) for this technique, we conducted a literature review and a procedure for appropriate use criteria. METHODS: Twenty-one of all 184 members of the Dutch Working Group on Interventional Cardiology agreed to evaluate 49 pre-specified cases. During a meeting, factual indications were established whereupon members individually rated indications on a 9-point scale, with the opportunity to substantiate their scoring. RESULTS: Twenty-six indications were rated 'Appropriate', eighteen indications 'May be appropriate', and five 'Rarely appropriate'. Use of OCT was unanimously considered 'Appropriate' in stent thrombosis, and 'Appropriate' for guidance in PCI, especially in distal left main coronary artery and proximal left anterior descending coronary artery, unexplained angiographic abnormalities, and use of bioresorbable vascular scaffold (BVS). OCT was considered 'Rarely Appropriate' on top of fractional flow reserve (FFR) for treatment indication, assessment of strut coverage, bypass anastomoses or assessment of proximal left main coronary artery. CONCLUSIONS: The use of OCT in stent thrombosis is unanimously considered 'Appropriate' by these experts. Varying degrees of consensus exists on the appropriate use of OCT in other settings.

The impact of patient-reported frailty on cardiovascular outcomes in elderly patients after non-ST-acute coronary syndrome.

BACKGROUND: As life expectancy increases, the population of older individuals with coronary artery disease and frailty is growing. We aimed to assess the impact of patient-reported frailty on the treatment and prognosis of elderly early survivors of non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: Frailty data were obtained from two prospective trials, POPular Age and the POPular Age Registry, which both assessed elderly NSTE-ACS patients. Frailty was assessed one month after admission with the Groningen Frailty Indicator (GFI) and was defined as a GFI-score of 4 or higher. In these early survivors of NSTE-ACS, we assessed differences in treatment and 1-year outcomes between frail and non-frail patients, considering major adverse cardiovascular events (MACE, including cardiovascular mortality, myocardial infarction, and stroke) and major bleeding. RESULTS: The total study population consisted of 2192 NSTE-ACS patients, aged ≥70 years. The GFI-score was available in 1320 patients (79 ± 5 years, 37% women), of whom 712 (54%) were considered frail. Frail patients were at higher risk for MACE than non-frail patients (9.7% vs. 5.1%, adjusted hazard ratio [HR] 1.57, 95% confidence interval [CI] 1.01-2.43, p = 0.04), but not for major bleeding (3.7% vs. 2.8%, adjusted HR 1.23, 95% CI 0.65-2.32, p = 0.53). Cubic spline analysis showed a gradual increase of the risk for clinical outcomes with higher GFI-scores. CONCLUSIONS: In elderly NSTE-ACS patients who survived 1-month follow-up, patient-reported frailty was independently associated with a higher risk for 1-year MACE, but not with major bleeding. These findings emphasize the importance of frailty screening for risk stratification in elderly NSTE-ACS patients.

Pharmaco-invasive therapy: Early implementation of statins and proprotein convertase subtilisin/kexin type 9 inhibitors after acute coronary syndrome.

Elevated LDL-cholesterol (LDL-C) plays a major role in atheroma formation and inflammation. Medical therapy to lower elevated LDL-C is the cornerstone for reducing the progression of atherosclerotic cardiovascular disease. Statin therapy, and more recently, other drugs such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, have proven efficacy in long-term lowering of LDL-C and therefore diminish cardiovascular risk. During an acute coronary syndrome (ACS), a systemic inflammatory response can destabilize other non-culprit atherosclerotic plaques. Patients with these vulnerable plaques are at high risk of experiencing recurrent cardiovascular events in the first few years post-ACS. Initiating intensive LDL-C lowering therapy in these patients with statins or PCSK9 inhibitors can be beneficial via several pathways. High-intensity statin therapy can reduce inflammation by directly lowering LDL-C, but also through its pleiotropic effects. PCSK9 inhibitors can directly lower LDL-C to recommended guideline thresholds, and could have additional effects on inflammation and plaque stability. We discuss the potential role of early implementation of statins combined with PCSK9 inhibitors to influence these cascades and to mediate the associated cardiovascular risk, over and above the well-known long-term beneficial effects of chronic LDL-C lowering.

Intensive management of hyperglycaemia in acute coronary syndromes. Study design and rationale of the BIOMArCS 2 glucose trial.

BACKGROUND: Elevated admission plasma glucose is associated with increased mortality in patients who are admitted with an acute coronary syndrome. This may be mediated by increased inflammation, apoptosis and coagulation, and by a disturbed endothelial function that can be found in hyperglycaemic patients. Insulin has several characteristics that may potentially counteract these mechanisms. METHODS: The BIOMArCS programme is a multi-centre initiative and currently consists of three different studies. The effects of acute coronary syndrome on acute biomarkers washout are studied in the BIOMArCS pilot and the value of biomarkers in predicting upcoming acute coronary syndrome events is studied in BIOMArCS 1. The third study (BIOMArCS 2 glucose), which will be presented here, investigates the effectiveness and safety of intensive glucose level control compared with conventional glucose management in patients with acute coronary syndrome and an admission plasma glucose of 7.8-16 mmol/l. In BIOMArCS 2 glucose, a total of 300 patients without insulin-treated diabetes mellitus will be randomized in a 1:1 ratio to either intensive or conventional glucose management on top of standard medical care. The primary endpoint is infarct size as expressed by the cardiac troponin T level 72 h after admission. To study the metabolic effects of insulin administration, we will investigate biomarker washout patterns of various metabolic mechanisms up to 7 days after admission. These markers will address inflammation, oxidative stress, hypercoagulability, endothelial activation and vasodilatation. IMPLICATIONS: Current acute coronary syndrome guidelines lack a clear strategy for hyperglycaemia treatment. This study will extend our knowledge on this matter as it may clarify mechanisms and generate hypotheses of if and how myocardial infarct size may be limited by glucose management at admission.

Release of growth-differentiation factor 15 and associations with cardiac function in adult patients with congenital heart disease.

BACKGROUND: Growth-differentiation factor-15 (GDF-15), a cytokine with broad cardiac and non-cardiac activity, has diagnostic and prognostic value in various diseases, including heart failure. We aimed to investigate the release of GDF-15 in adults with congenital heart disease (ConHD), and assess the association with cardiac function and functional capacity. METHODS: A total of 587 consecutive adults with ConHD (median age 33 [IQR 25-41] years, 59% men, and 90% NYHA I) underwent electrocardiography, echocardiography, venepuncture and were seen by a cardiologist. A subset of 143 patients underwent bicycle ergometry on the same day. RESULTS: Median plasma GDF-15 was 618 [IQR 487-867] ng/L. In 87 patients (15%), GDF-15 was above the reference value of normal (1109 ng/L). GDF-15 levels were higher in older patients (r=0.367, p<0.001). GDF-15 was higher in patients with elevated pulmonary pressure (median 1114 [IQR 796-2320 ng/L) than in patients with normal pulmonary pressure (median 606 [IQR 481-826] ng/L, p<0.001). GDF-15 correlated positively with NT-proBNP (r=0.445, p<0.001). In multivariate analysis adjusting for age, sex, and NT-proBNP, hs-TnT and hs-CRP, GDF-15 above the reference value was associated with NYHA class (odds ratio for NYHA≥II: 3.5 [95% CI 1.8-6.8], p<0.001), and decreased exercise capacity (odds ratio for workload >85%:0.2 [95% CI 0.06-0.8], p=0.018), but not with systolic ventricular function or ECG rhythm. CONCLUSIONS: GDF-15 is elevated in a substantial number of patients and higher in those with elevated pulmonary pressures, regardless of underlying congenital diagnosis. GDF-15 is associated with NYHA class, NT-proBNP and exercise capacity, suggesting the marker has diagnostic and potential prognostic value in adults with ConHD.

Multimarker risk model containing troponin-T, interleukin 10, myeloperoxidase and placental growth factor predicts long-term cardiovascular risk after non-ST-segment elevation acute coronary syndrome.

OBJECTIVE: To evaluate the predictive value of seven biomarkers, which individually have been shown to be independent predictors, for use in a combined multimarker model for long-term cardiovascular outcome after non-ST-segment elevation acute coronary syndrome (NSTEACS). DESIGN AND SETTING: Levels of high-sensitivity C-reactive protein (hsCRP), myeloperoxidase, pregnancy-associated plasma protein A, placental growth factor (PlGF), soluble CD40 ligand (sCD40L), interleukin 10 (IL-10) and troponin-T (TnT) were determined in patients enrolled in the CAPTURE trial. Cox proportional hazard regression analyses were applied to evaluate the relation between biomarkers and the occurrence of all-cause mortality or non-fatal myocardial infarction (MI). PATIENTS: 1090 patients with NSTEACS. MAIN OUTCOME MEASURE: All-cause mortality and non-fatal MI during a median follow-up of 4 years. RESULTS: The composite endpoint was reached by 15.3% of patients. Admission levels of TnT >0.01 µg/l (adjusted HR 1.8), IL-10 <3.5 ng/l (1.7), myeloperoxidase >350 µg/l (1.5) and PlGF >27 ng/l (1.9) remained significant predictors for the incidence of all-cause mortality or non-fatal MI after multivariable adjustment for other biomarkers and clinical characteristics, whereas hsCRP, pregnancy-associated plasma protein A and sCD40L were only associated with the endpoint in univariate analysis. A multimarker model consisting of TnT, IL-10, myeloperoxidase and PlGF predicted 4-year event rates that varied between 6.0% (all markers normal) and 35.8% (three or more biomarkers abnormal). CONCLUSION: In patients with NSTEACS, biomarkers characterising distinct aspects of the underlying atherosclerotic process and myocardial damage of the initial cardiac event can assist in predicting long-term adverse cardiac outcomes. The use of combinations of selected biomarkers adds incremental predictive value to further risk stratification in an otherwise seemingly homogeneous NSTEACS population.