Major Adverse Cardiovascular Endpoints Research Articles

Association of dipeptidyl peptidase-4 inhibitor initiation at glycated haemoglobin

Therapeutic inertia, hypoglycaemia and poor treatment persistence can lead to glycaemic fluctuation and poor outcomes in type 2 diabetes (T2D). We compared glycated haemoglobin (HbA1c) variability, insulin initiation, severe hypoglycaemia and clinical events in patients with T2D initiated dipeptidyl peptidase-4 inhibitors (DPP4is) at low versus high HbA1c thresholds. Using territory-wide electronic medical records in Hong Kong, we curated a propensity score-matched cohort of patients initiated DPP4i at HbA1c <7.5% versus ≥7.5% in 2007-2019. We expressed the HbA1c variability score (HVS) as a proportion of HbA1c varied by ≥0.5% compared with preceding values. We used the Cox model to compare the risks of insulin initiation and clinical outcomes, adjusted for time-varying variables between the two groups. Mediation analysis estimated the effects of HbA1c variability on outcomes. Among 6874 insulin-naïve patients who initiated DPP4i, 88.7% were treated with metformin and 79.6% with sulphonylureas at baseline (54.9% men; mean age 65.2 ± 11.4 years). After a median follow-up of 4.6 years, compared with the high-threshold plus high-HVS group (≥50%), the low-threshold plus low-HVS (<50%) group had reduced hazard ratios (95% confidence interval) of insulin initiation (0.35, 0.31-0.40), severe hypoglycaemia (0.38, 0.34-0.44), major adverse cardiovascular endpoints (0.76, 0.66-0.88), heart failure (0.42, 0.36-0.49), end-stage kidney disease (0.65, 0.36-0.49) and mortality (0.45, 0.35-0.57). Reduced HbA1c variability explained 31.1%-81.2% of the effect size of DPP4i initiation at HbA1c <7.5% versus ≥7.5% on outcomes. In Chinese patients with T2D, avoiding therapeutic inertia with intensified glycaemic control at HbA1c <7.5% using drugs with low risk of hypoglycaemia and good tolerability, such as DPP4i, delayed insulin treatment, reduced HbA1c variability and improved clinical events.

Association of Variability and Hypertensive Loads in 24-h Blood Pressure With Mortality and Cardiovascular Risk.

Evidence shows that high 24-h blood pressure (BP) variability increases cardiovascular risk. We investigated whether 24-h BP variability relates to mortality and cardiovascular risk due to inherent variability and/or hypertensive loads in 24-h BP. A total of 1,050 participants from the Maracaibo Aging Study (mean age, 66 years; women, 67.2%) underwent 24-h ambulatory BP monitoring and were followed between 2001 and 2016. To evaluate inherent BP variability, we used average real variability (ARV) as it captures variability among consecutive BP readings. 24-h systolic BP load was the proportion (%) of systolic BP readings ≥130 mm Hg during the daytime and ≥110 during the nighttime. Our primary endpoint was total mortality and major adverse cardiovascular endpoints (MACE). Statistics included Cox proportional models. During a median follow-up of 8.3 years, 299 participants died and 210 experienced MACE. Each +2 mm Hg (corresponding to 1-standard deviation) higher 24-h systolic ARV (mean value, 9.0 ± 2.0 mm Hg) was associated with higher hazard ratios (HRs) for mortality by 1.28-fold (95% confidence interval [CI], 1.14-1.43) and for MACE by 1.24-fold (95% CI, 1.08-1.42). Each 30% higher 24-h systolic BP load (median value, 63%) was associated with mortality and MACE with HRs of 1.29 (95% CI, 1.15-1.46) and 1.28 (95% CI, 1.10-1.48); respectively. After models were additionally adjusted by BP level, only ARV was associated with mortality (HR, 1.17; 95% CI, 1.04-1.33) and MACE (HR, 1.16; 95% CI, 1.00-1.34). High ARV and hypertensive loads in 24-h systolic BP were associated with mortality and cardiovascular risk, however, only ARV is associated independently of the BP level.

S-09-5: EPIDEMIOLOGY AND CARDIOMETABOLIC DISORDERS - UPDATE OF SGKT2-IS RCT META-ANALYSIS

Diabetes and hypertension are chronic diseases. They often coincide in the same patients and enhance the risk of cardiovascular and renal complications in a multiplicative manner. As one of the main regulators in glucose homeostasis, sodium glucose cotransporter 2 (SGLT2) is expressed in the proximal tubule of the nephron and facilitates glucose reabsorption from glomerulus along the nephron. Based on this function, several SGLT2 inhibitors (SGLT2i) were developed as a novel class of antidiabetic drugs, including empagliflozin, dapagliflozin, catagliflozin, ertugliflozin, and sotagliflozin. By far, totaled 10 RCTs involving 68,916 patients have been performed that tested the long-term outcomes associated with SGLT2i use. In five RCTs where all the patients enrolled had heart failure history (n = 21947), 87.9% were hypertensive and 76.3% were diabetic. Following a median of 0.8 to 2.3 years of treatment, HRs were 0.72 (0.67, 0.78) for first hospitalization for heart failure, 0.87 (0.79, 0.95) for cardiovascular death, and 0.92 (0.86, 0.99) for all-cause death. In another meta-analysis on five RCTs (n = 43467) that mainly recruited type 2 diabetic patients with uncontrolled hyperglycemia, more than 87% were hypertensive. After a median of 1.5 to 4.2 years of follow up, HRs were 0.87 (0.82, 0.93) for major adverse cardiovascular endpoints (MACE), 0.68 (0.62, 0.75) for heart failure, 0.82 (0.72, 0.93) for cardiovascular death, 0.87 (0.79, 0.96) for myocardial infarction, and 0.61 (0.56, 0.67) for worsening chronic kidney disease. The risk of heart failure and chronic kidney disease, but not MACE, decreased with more blood pressure lowering. Nevertheless, stricter glycemic control was associated with higher heart failure risk, but unrelated to MACE or chronic kidney disease. When dissecting the dosage effects of catagliflozin on lipid profiles, the results of a meta-analysis using 12 RCTs indicated that canagliflozin 100 mg or 300 mg significantly reduced systolic and diastolic blood pressure, but increased LDL and HDL cholesterol in a dose-dependent effect. Taken together, SGLT2i could reduce cardiovascular risk in diabetic and non-diabetic patients. The impact of SGLT2i on metabolic traits needs further investigation.

Incidence, Predictive Factors and Long-Term Clinical Impact of Left Ventricular Remodeling According to the Completeness of Revascularization in Patients with ST-Elevation Myocardial Infarction and Multivessel Disease.

In this study, we identified several factors related to left ventricular remodeling (LVR) and examined the impact of LVR on the prognosis of patients with ST-elevated myocardial infarction and multivessel disease treated with complete (CR) or incomplete (IR) revascularization. LVR was defined as an LV end-diastolic diameter &gt;55 mm. A total of 262 patients without LVR at presentation were followed up with echocardiography between 1 month and 1 year. The primary outcome was a composite of all-cause death (AD), MI, and heart failure (HF), referred to as a major adverse cardiovascular endpoint (MACE). Then, each variable was analyzed as a secondary outcome. Follow-up echocardiography identified 26 patients (9.9%) with LVR. LVR was associated with an initial LV ejection fraction &lt;50%, Killip 3 disease at presentation, and a peak troponin I level &gt;70 mg/dL. Survival analysis showed an association between LVR and adverse outcomes only in the IR group, in which the adjusted hazard ratio (HR) was increased for the MACE (HR = 3.22, 95% confidence interval (CI) = 1.19-8.71, p = 0.002) and HF (HR = 21.37, 95% CI = 4.47-102.09, p&lt; 0.001), but not for the CR group. In STEMI with MVD, LVR within the first year after percutaneous coronary intervention was associated with worse outcomes in the IR but not the CR group.

Comparison of Predictive Ability of Arterial Stiffness Parameters Including Cardio-Ankle Vascular Index, Pulse Wave Velocity and Cardio-Ankle Vascular Index0.

Cardio-ankle vascular index (CAVI) was developed to reflect the stiffness of the arterial tree from the aortic origin to the ankle. This arterial stiffness parameter is useful for assessing the severity of cardiovascular disease (CVD) and its risk. However, compared to pulse wave velocity (PWV), the conventional gold standard of arterial stiffness parameter, there has been a concern regarding CAVI that there are fewer longitudinal studies for CVD. Furthermore, the accuracy of CAVI for atherosclerotic diseases compared to other parameters has not been well validated. This review article aims to summarize recent findings to clarify the predictive ability of CAVI in longitudinal studies. First, several large longitudinal studies have found that not only baseline CAVI but also CAVI changes during the observation period predict cardiovascular events. Second, CAVI may have superior discriminatory power for all-cause mortality and major adverse cardiovascular endpoints compared to PWV. Furthermore, one large longitudinal study found CAVI to be a stronger predictor for renal function decline compared to PWV as well as CAVI0, a variant of CAVI that mathematically excludes BP dependence. Additionally, CAVI shows the properties that allow the elucidation of specific hemodynamics in aortic valve disease or hypovolemia. In conclusion, CAVI may be a modifiable arterial stiffness parameter not only for predicting and preventing atherosclerotic diseases but also for elucidating specific hemodynamic pathophysiology.

Retrospective Study of Appropriate Primary Prevention in Postmenopausal Women Presenting with a Major Adverse Cardiovascular Endpoint (MACE)

Background: Postmenopausal women may be at an increased risk for cardiovascular events. The postmenopausal transition represents a key time for implementation of preventative strategies to reduce the risk of cardiovascular disease. The objective of this study was to evaluate the appropriate use of primary prophylaxis of cardiovascular disease in this population and to determine if an opportunity exists for improvement in primary prevention prescribing. Methods: A single-center, retrospective study was conducted of postmenopausal women aged 45–60 years between 1 October 2019 and 30 April 2021 with a diagnosis of a new major adverse cardiovascular event (MACE). This study was approved by the University at Buffalo Institutional Review Board. Results: After application of inclusion and exclusion criteria, 231 patients were included and analyzed. Median age was 55 years; 66.6% white; median body mass index was 30.11 kg/m2; 30.3% history of diabetes; 51.1% current smokers; 82.3% with a primary care provider (PCP); 97.6% insured. Patients with diabetes, current smokers, and those without a PCP were more likely to have inappropriate primary prevention use than patients without diabetes, non-smokers, and with a PCP, respectively (78.7% vs. 51.3%, p = 0.0002; 57.6% vs. 42.4%, p = 0.0177; 73.7% vs. 56.0%, p = 0.0474). Specifically, current smokers, and those with diabetes had significantly more inappropriate use of aspirin and statins for primary prevention than non-smokers and patients without diabetes. Conclusions: This study observed the use of appropriate primary prevention therapies in postmenopausal women and found that an opportunity may exist to improve prescribing appropriate primary prevention therapies for certain groups, most notably in postmenopausal women with diabetes, smokers, uninsured, and those without a PCP.

Minor perturbations of thyroid homeostasis and major cardiovascular endpoints-Physiological mechanisms and clinical evidence.

It is well established that thyroid dysfunction is linked to an increased risk of cardiovascular morbidity and mortality. The pleiotropic action of thyroid hormones strongly impacts the cardiovascular system and affects both the generation of the normal heart rhythm and arrhythmia. A meta-analysis of published evidence suggests a positive association of FT4 concentration with major adverse cardiovascular end points (MACE), but this association only partially extends to TSH. The risk for cardiovascular death is increased in both subclinical hypothyroidism and subclinical thyrotoxicosis. Several published studies found associations of TSH and FT4 concentrations, respectively, with major cardiovascular endpoints. Both reduced and elevated TSH concentrations predict the cardiovascular risk, and this association extends to TSH gradients within the reference range. Likewise, increased FT4 concentrations, but high-normal FT4 within its reference range as well, herald a poor outcome. These observations translate to a monotonic and sensitive effect of FT4 and a U-shaped relationship between TSH and cardiovascular risk. Up to now, the pathophysiological mechanism of this complex pattern of association is poorly understood. Integrating the available evidence suggests a dual etiology of elevated FT4 concentration, comprising both ensuing primary hypothyroidism and a raised set point of thyroid function, e. g. in the context of psychiatric disease, chronic stress and type 2 allostatic load. Addressing the association between thyroid homeostasis and cardiovascular diseases from a systems perspective could pave the way to new directions of research and a more personalized approach to the treatment of patients with cardiovascular risk.

Significance of indeterminate and abnormal stress electrocardiography despite normal imaging in patients with suspected coronary artery disease – An analysis of the PROMISE trial

BackgroundAbnormal and indeterminate electrocardiographic (ECG) changes during cardiac stress imaging are not uncommon. While the prognostic importance of abnormal ECG despite normal imaging has been previously studied, prognosis of indeterminate stress ECG changes is uncertain. MethodsWe studied the prognostic value of stress ECG changes in symptomatic patients without known CAD and normal stress imaging from the PROMISE trial. Patients with normal ECG (concordant), indeterminate ECG and abnormal ECG (discordant) were identified among those with negative exercise imaging stress test (EIST) and negative vasodilator nuclear stress test (PIST). Outcomes of interest were major adverse cardiovascular endpoint (MACE, including all-cause mortality, myocardial infarction, and unstable angina hospitalization) and likelihood of coronary revascularization. ResultsIn EIST, indeterminate stress ECG [1.1% vs. 0.2% adjusted hazard ratio (aHR) 4.2, (95% CI 1.11–15.6), p = 0.034] and discordant ECG [7.2% vs. 0.2% adjusted hazard ratio (aHR) 27.6, (95% CI 9.6–79.8), p < 0.0001] were associated with increased likelihood of revascularization compared to normal stress ECG. Similar findings were observed with PIST [indeterminate vs concordant [1.7% vs. 0.5% adjusted hazard ratio (aHR) 5.9, (95% CI 1.1–31.7), p = 0.041; discordant vs concordant 15.4% vs. 0.5% adjusted hazard ratio (aHR) 24.2, (95% CI 4.6–127.7), p = 0.0002]. MACE rates were similar between ECG subgroups, in both EIST and PIST. ConclusionIn symptomatic patients without known CAD undergoing stress imaging, indeterminate and discordant ECG changes results may indicate presence of obstructive CAD despite normal imaging results and predict increased likelihood of coronary revascularization despite no significant difference in MACE.

Influence of individual proton pump inhibitors on clinical outcomes in patients receiving clopidogrel following percutaneous coronary intervention.

Background:Data are conflicting on whether proton pump inhibitors (PPIs) diminish the efficacy of clopidogrel. We investigated individual PPIs and adverse cardiovascular events in postpercutaneous coronary intervention (PCI) patients on dual antiplatelet therapy with clopidogrel.Methods:We searched Ovid-MEDLINE, EMBASE, and Cochrane from inception to March 2020 to identify studies that evaluated the efficacy and safety of clopidogrel added PPIs versus clopidogrel only in post-PCI patient. We extracted data from 28 studies for major adverse cardiovascular endpoints (MACE), myocardial infarction (MI), cardiovascular death, and gastrointestinal bleeding. Risk ratios (RR) and hazard ratios (HR) were pooled separately.Results:Data were extracted on 131,412 patients from the 28 studies included. Concomitant use of PPI with clopidogrel was associated with increased risk of MACE (RR 1.30; 95% confidence interval [CI] 1.15–1.48; P < .001) and MI (RR 1.43; 95% CI 1.25–1.64; P < .001). Random-effects meta-analyses with individual PPIs demonstrated an increased risk of MACE in those taking pantoprazole (RR 1.31; 95% CI 1.07–1.61, P = .01) or lansoprazole (RR 1.35; 95% CI 1.19–1.54, P < .0001) compared with patients not on PPIs. Likewise, in adjusted analyses, the pooled HR of adjusted events for MACEs showed that the increased risk of MACEs was similar for 4 classes of PPIs but not for rabeprazole (HR: 1.32; 95% CI 0.69–2.53, P = .40).Conclusion:The post-PCI patients on dual antiplatelet therapy with clopidogrel in the PPI group were associated with higher risk of MACE and MI. Although the results for rabeprazole were not robust, it was the only PPI that did not yield a significantly increased risk of MACE.

Cost-Effectiveness and Safety of Same-Day Discharge after Elective Percutaneous Coronary Intervention

Objectives: We sought to investigate the rates of same-day discharge (SDD) post elective percutaneous coronary intervention (PCI) at our institution and review its safety by examining clinical outcomes. We also performed an economic analysis evaluating our hospital’s cost data for SDD following PCI. Methods: Patients undergoing elective PCI at St George Hospital, Australia, from January 2017 to December 2019 were evaluated. Primary outcomes included 7-day major adverse cardiovascular endpoints (MACEs) and readmission to hospital within 30 days. Results: Among 502 patients who underwent elective PCI, 421 patients (83.8%) were managed with SDD. There was one case of acute stent thrombosis and one case of coronary wire-induced perforation requiring a pericardial drain that occurred following elective PCI with SDD (0.54%). Unplanned cardiac re-hospitalisation at 30 days following elective PCI was 5.2%. SDD after elective PCI was associated with a healthcare cost saving of AUD 4817 per case. Conclusion: SDD following elective PCI was demonstrated to be a safe and effective strategy that was also associated with significant cost savings. SDD following elective PCI warrants more widespread use as it lowers healthcare costs, has equivalent patient outcomes and improves patient satisfaction.

Safety and Cost Implications of Same-Day Discharge Following Elective Percutaneous Closure of Patent Foramen Ovale and Atrial Septal Defects in Australia

Background: Percutaneous closure of patent foramen ovale (PFO) and atrial septal defects (ASD) is being more commonly performed due to changes in international guidelines supporting its use. This study was performed to determine the clinical outcomes, safety and cost implications of same-day discharge (SDD) following such procedures and place this in an Australian context. Methods: This was a retrospective, observational study of patients undergoing elective percutaneous PFO or ASD closure at St. George Hospital, Australia between January 2011 and January 2020. Primary outcomes included 30-day major adverse cardiovascular endpoints (MACE) and readmission to hospital within 30 days. Results: Twenty-four patients were included in the primary analysis. Ten (41.7%) patients underwent elective ASD closure while 14 (58.3%) underwent PFO closure. Among the 24 patients who underwent elective percutaneous closure of structural heart disease, 23 patients (95.8%) were managed with SDD. There were no MACE outcomes at 30 days. No patients were re-admitted to hospital at 30 days following these procedures. When compared to overnight admission to hospital post-elective percutaneous structural heart condition closure, SDD yielded a cost saving of AUD 5999 per case. Conclusion: SDD following elective percutaneous closure of ASD and PFO was demonstrated to be a safe and effective strategy for managing patients. With more widespread use, it can lead to significant cost savings for hospitals without compromising patient care.

547 Same Day Discharge Following Percutaneous Closure of Structural Heart Conditions: A Novel and Safe Approach for Patient Management

Percutaneous closure of patent foramen ovale (PFO) and atrial septal defects (ASD) has become more commonly performed due to recent changes in international guidelines supporting its use. The safety and effectiveness of same day discharge (SDD) home for outpatients who present electively for such procedures has not been examined. We sought to retrospectively investigate the rates of SDD at our institution and review its safety by examining clinical outcomes following elective percutaneous PFO or ASD closure. We also performed an economic analysis evaluating our hospital’s cost data for SDD following these procedures. Patients undergoing elective percutaneous PFO, ASD or PDA closure at St George Hospital, Australia, from January 2011 to January 2020 were evaluated. Primary outcomes included 7-day major adverse cardiovascular endpoints (MACE) and readmission to hospital within 30 days. 24 patients were included in the primary analysis. 10 (41.7%) patients underwent elective ASD closure while 14 (58.3%) underwent PFO closure. Among 24 patients who underwent elective percutaneous closure of structural heart disease, 23 patients (95.8%) were managed with SDD. There were no MACE outcomes at 30 days. No patients were re-admitted to hospital at 30 days following these procedures. When compared to overnight admission to hospital post elective percutaneous structural heart condition closure, SDD yielded a cost saving of $4,817 per case. SDD following elective percutaneous structural heart condition closure was demonstrated to be a safe and effective strategy for managing patients that was also associated with significant cost savings to hospitals.

Hypertension Development, Management, and Cardiovascular Events Following Ibrutinib Initiation for Hematologic Malignancies

BackgroundIbrutinib (IB), a nonselective Bruton's tyrosine kinase inhibitor, is associated with significantly improved disease control rates, progression free, and overall survival in several B-cell malignancies. Yet, IB's nonselective actions may result in a number of unintended adverse effects and complications that can lead to drug discontinuation. New or worsening hypertension (HTN) has been reported in 10-29% of those receiving IB within clinical trials. However, recent observational data suggest that this rate may be much higher in clinical practice and resistant to treatment. The management of IB-related HTN has not been previously well described. Furthermore, the relationship between IB-associated HTN and serious cardiovascular (CV) complications is unknown. Therefore, we sought to characterize the incidence, risk factors, management, and CV complications associated with IB-related HTN across long-term follow-up.MethodsWe performed a retrospective, single-center cohort study of all consecutive adult patients treated with IB for a hematologic malignancy from 2009-2016. Patient demographics, blood pressure (BP), antihypertensive therapy, cancer variables, and CV complications were collected throughout the duration of IB therapy. HTN was defined as systolic BP of ≥ 130 mmHg on 2 separate visits within 3 months. Worsened HTN was defined as an increase in HTN grade by Common Terminology Criteria for Adverse Events (CTCAE) or an increase an antihypertensive therapy. The composite of major adverse CV endpoint (MACE), including atrial fibrillation, ventricular arrhythmia, myocardial infarction, cerebrovascular accident, heart failure, and CV death, as stratified by HTN status was assessed. Univariate and multivariate Fine and Gray regression analyses accounting for competing risks of death and IB-discontinuation were preformed to determine the association between baseline covariates and outcomes, and survival analysis techniques were used to estimate the cumulative incidence of events. To assess whether any antihypertensive agent(s) was more effective in preventing IB-related HTN, the use of these agents at baseline was assessed by class, as protective factors against worsened HTN.ResultsOverall, 562 patients treated with IB were identified, a majority of which had CLL (73%) and were male (70%); mean age 64 ± 11 years. Sixty-two percent had preexisting HTN at the time of starting IB with 35% requiring at least one antihypertensive medication. During follow-up, 440 (78%) developed new or worsening HTN (figure 1A), with a mean increase in systolic BP of 5.2 mmHg (± 20.7). In those without baseline HTN, 72% developed new HTN while on IB, with a mean increase in systolic BP of 13.4 mmHg (± 20.1). Among patients with preexisting HTN, 82% saw worsening of their BP (mean increase in systolic BP of 4.1 mmHg (± 21.4)), including increased CTCAE grade in 77% and new antihypertensive medications in 46% of patients. Estrogen/progestin use [HR 3.47, 95% CI (1.25-9.64)] and history of diabetes [HR 1.66, 95% CI (1.03-2.66)] were risk factors for new, but not worsened HTN on multivariable analysis. MACE occurred in 19.1% of patients with new or worsened HTN, compared to 8.2% of patients with no HTN (figure 1B). In a multivariable model containing traditional HTN risk factors, new or worsened HTN was not significantly associated with MACE [HR 1.98, 95% CI (0.74-5.31)]. No specific class of antihypertensive agent was associated with the prevention of worsened HTN.ConclusionIn this retrospective study, IB-therapy was associated with a substantial increase in the incidence and severity of HTN. Further research into the mechanisms, early detection strategies, optimal management, and clinical impacts of this complication are needed. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Endothelial function predicts 1-year adverse clinical outcome in patients hospitalized in the emergency department chest pain unit

BackgroundEndothelial function is a marker for cardiovascular risk. Thus, abnormal endothelial function may be associated with adverse 1-year outcome in patients presenting to the emergency department chest pain unit (CPU). MethodsFollowing endothelial function testing, using EndoPAT 2000 in 300 consecutive subjects with chest pain and no history of coronary artery disease (CAD) presenting to CPU, patients underwent coronary computerized tomographic angiography (CCTA) or single-photon emission computed tomography according to availability. ResultsMean 10-year Framingham risk score (FRS) was 6.6±5.9%, median reactive hyperemia index (RHI) as a measure of endothelial function 2.08 and mean was 2.0±0.4. During a 1-year follow-up, the 20 (6.6%) patients who developed major adverse cardiovascular end-points (MACE), including all-cause mortality, non-fatal myocardial infarction, hospitalization for heart failure or angina pectoris, stroke, coronary artery bypass grafting and percutaneous coronary interventions, had higher 10-year FRS (10.5±8.2% vs 6.3±5.7%; p<0.001), lower baseline RHI (1.43±0.41 vs 2.10±0.44; p<0.001) and a greater extent of coronary atherosclerosis lesions (70% vs 3.9%, p<0.001) in the CPU CCTA, compared to those without MACE. RHI≤the median was associated with higher 1-year MACE (13% vs 0.7%, p<0.001) compared to RHI>the median. Multivariate analysis demonstrated that RHI≤the median is an independent predictor of coronary atherosclerosis lesions in the CPU CCTA (OR 5.98, 95% CI 03.29-10.88; p<0.001) and 1-year MACE (OR 15.207, 95% CI 2.00-115.33; p<0.01). ConclusionsOur findings suggest that non-invasive endothelial function testing may have clinical utility in triaging patients in the CPU and in predicting 1-year MACE.

NEW ONSET ATRIAL FIBRILLATION IN ACUTE CORONARY SYNDROME: FINDINGS FROM THE GRACE ECG SUBSTUDY

Atrial fibrillation (AF) is a frequent complication of acute coronary syndrome (ACS) and is associated with an increased risk of in-hospital and long-term mortality. Yet, many studies lack recurrent electrocardiographic (ECG) assessments in hospital and core-lab verification of AF, which is important for accurate prognostication. The purpose of this study was to determine whether patients presenting with ACS who developed new-onset AF had an increased risk of death or a composite major adverse cardiovascular endpoint (MACE) of death, myocardial (re)infarction (MI), or stroke when compared to patients with and without prior AF.

Prognostic value of high sensitivity troponin T after ST-segment elevation myocardial infarction in the era of cardiac magnetic resonance imaging.

To determine if high sensitivity troponin T (hs-TnT) measurements performed during the 'plateau phase' of troponin release (≥48 h) following ST-segment elevation myocardial infarction (STEMI) can predict major adverse cardiovascular endpoints (MACE), and to evaluate its prognostic value compared with cardiac magnetic resonance imaging (CMRI) parameters. We prospectively recruited 201 first presentation STEMI patients. Serial hs-TnT levels were measured at admission, peak (highest), 24, 48 and 72 h. CMRI and transthoracic echocardiography were performed (4 days median) post-STEMI, evaluating infarct scar characteristics and left ventricular ejection fraction (LVEF). Associations were determined between hs-TnT levels and CMRI parameters early after STEMI with MACE (comprising mortality, re-infarction, new or worsening of heart failure, cerebrovascular accident, and sustained ventricular arrhythmias) at medium-term follow-up. After 602 days (median), 33 (17%) patients had MACE. Upper tertile hs-TnT levels at 48 and 72 h were associated with MACE (Kaplan-Meier P = 0.002 and P = 0.012, respectively). Multivariate Cox analyses, incorporating diabetes, CMRI scar size, LVEF and hs-TnT levels (applied at a single hs-TnT time point) showed that 48 and 72 h hs-TnT levels were independent predictors for MACE (HR = 1.20, P = 0.002, and HR = 1.21, P = 0.035 respectively). Measurement of hs-TnT in the plateau phase after STEMI is an inexpensive method of prognostic risk assessment.

Two-dimensional speckle tracking echocardiography prognostic parameters in patients after acute myocardial infarction.

The aim of the study was to evaluate the left ventricle (LV) function with speckle tracking echocardiography (STE) and to assess its relation to prognosis in patients after acute myocardial infarction (AMI). Sixty-three patients (F/M = 16/47 pts; 62.33 ± 11.85 years old) with AMI (NSTEMI/STEMI 24/39 pts) and successful percutaneous coronary intervention (PCI) with stent implantation (thrombolysis in myocardial infarction; TIMI 3 flow) were enrolled in this study. All patients underwent baseline two-dimensional conventional echocardiography and STE 3 days (baseline) and 30 days after PCI. All patients were followed up for cardiovascular clinical endpoints, major adverse cardiovascular endpoint (MACE), and functional status (Canadian Cardiovascular Society and New York Heart Association). During the follow-up (31.9 ± 5.1 months), there were 3 cardiovascular deaths, 15 patients had AMI, 2 patients had cerebral infarction, 24 patients reached the MACE. Baseline LV torsion (P = 0.035), but none of the other strain parameters were associated with the time to first unplanned cardiovascular hospitalization. Univariate analysis showed that baseline longitudinal two-chamber and four-chamber strain (sLa2 0 and sLa4 0) and the same parameters obtained 30 days after the AMI together with transverse four-chamber strain (sLa2 30, sLa4 30, and sTa4 30) were significantly associated with combined endpoint (MACE). The strongest association in the univariate analysis was found for the baseline sLa2. However, in multivariable analysis only a left ventricular remodeling (LVR - 27% pts) was significantly associated with MACE and strain parameters were not associated with the combined endpoint. The assessment of LV function with STE may improve cardiovascular risk prediction in postmyocardial infarction patients.

The prognostic value of discharge heart rate in patients with impaired left ventricular function after acute myocardial infarction

Objectives: Heart rate (HR) has demonstrated to be a prognostic value in AMI patients. However, it is unclear whether HR is still secure regardless of left ventricular (LV) function. We investigated the association between clinical prognosis and discharge HR in acute myocardial infarction (AMI) patients who were stratified by LV function. Methods: A total of 1175 AMI patients who underwent PCI, except for in-hospital death, were analyzed from ICAS (Ibaraki Cardiovascular Assessment Study) multi-center registry. Analyzed subjects were divided by resting HR at discharge (quartiles) and LV ejection fraction (≥50% or <50%). Major adverse cardiovascular endpoint (MACE) was defined as a composite endpoint of all-cause mortality, myocardial infarction, stroke, or heart failure. Results: MACE was observed in 131 patients (11%) during median follow-up period of 496 days, and there was a stepwise increase in MACE with increasing HR. Among the groups with impaired LV function, high HR was significantly associated with increased risk of MACE (3.4- and 5.2-fold, for HR quartiles 3 [68-75 bpm] and quartile 4 [>75bpm], respectively). Multivariate Cox regression analysis showed that discharge HR remained to be an independent predictor of MACE (hazard ratio [every increase of 5 bpm]:1.10, 95% confidence interval:1.04-1.18, p=0.003). ![Figure][1] Figure 1 Conclusion: Resting HR at discharge was a significant predictor of MACE after AMI, especially in the patients with impaired LV function. [1]: pending:yes

How low can we go: high-sensitivity troponin T in patients presenting with chest pain

For the last 10–15 years, troponin measurement has played a central role in the diagnosis of acute myocardial infarction (AMI). This has been most recently confirmed in the universal definition of AMI published by the Joint ESC/ACCF/ AHA/WHF Task Force for the Redefinition of Myocardial Infarction in 2007. This definition of AMI requires the detection of a rise and fall of a cardiac biomarker (preferably troponin) above the 99th percentile of a reference population together with evidence of ischaemia (either as clinical symptoms, electrocardiogram changes or imaging evidence showing loss of viable myocardium). The emphasis on the 99th percentile as the cut-off point comes from evidence obtained using older assays where any measurable troponin increase was associated with worse outcomes. In population studies using the troponin T assay, less than 1% of the population had detectable troponin T concentrations, and these were associated with cardiac abnormalities. The first generation of troponin assays were already superior to the old creatine kinase MB assays and the second-generation troponin assays improved diagnostic sensitivity compared with the first generation. However, only recently an assay (Roche troponin T hs assay) has become available that can consistently measure troponin T in about 50–80% of the normal population. Furthermore, this assay provides increased precision at the 99th percentile. While 10% coefficient of variation (CV) was requested by the original working party at the 99th percentile, none of the troponin assays of the time could provide this. More recently we realized that a 10% CV at this concentration is probably not required and it might be reasonable to accept a functional sensitivity similar to the endocrine assays of about 20%. So, what are the real advantages of newer, more sensitive assays for troponin, if not the improved precision at decision cut-off points? These new high-sensitivity assays give us the opportunity to further refine our diagnostic armamentarium and possibly to improve the diagnostic potential of the assay. Apart from the analytical performance of new assays, it is the clinical evaluation that becomes crucial in trying to judge whether these new assays are real advances. In this edition, two studies look at the performance of the new high-sensitivity troponin T assay in patients presenting with chest pain to a teaching hospital in New Zealand and being evaluated for AMI. These timely papers extend previous studies published in 2009. The first article from Aldous et al. investigates the performance of the high-sensitivity troponin T assay for the early detection of AMI. The sample is fairly small (332 patients out of a total number of about 1500 patients presenting to the Emergency Department) and the incidence of AMI is very high (33%). The New Zealand study confirms earlier studies in a European patient population, showing that the highsensitivity troponin T assay is equivalent to secondgeneration troponin I assays and superior to older style (4th generation) troponin T assays in the diagnostic accuracy for AMI. While the high-sensitivity troponin T assay has a somewhat higher sensitivity for AMI at admission, optimal sensitivity is only achieved about 4–6 h after symptom onset. The gold standard for the diagnosis of AMI was based on older style troponin assays in the European studies, while in this present study an improved second-generation troponin I assay was used. As the investigated troponin I assay was very similar to the assay originally used to make the diagnosis, a positive bias towards the conventional troponin I assay in this study is possible. The second study by Aldous et al. adds significant additional information as it investigates patient outcomes over the next two years. The authors followed up 332 patients with suspected acute coronary syndrome that were investigated between November 2006 and April 2007. Over the following two years, future cardiovascular events (MACE – major adverse cardiovascular endpoint – a composite of cardiovascular death, non-fatal myocardial infarction and revascularization) were measured. Sixty-eight patients experienced a MACE between discharge and two years later. Again, the high-sensitivity troponin T assay was better than the fourth-generation troponin T assay as assessed by receiver operating characteristic curve, but was not noticeably different from the secondgeneration troponin I assay. However, additional information could be obtained from the high-sensitivity troponin T assay in the stratification of patients for future risk.With both the high-sensitivity troponin T and the second-generation troponin I assay, patients with troponin concentrations above the 99th percentile had about a 33% risk of a MACE. Interestingly, with the troponin I assay patients with detectable troponin concentrations

Serum Fetuin-A Levels Are Associated with Vascular Calcifications and Predict Cardiovascular Events in Renal Transplant Recipients

Vascular calcifications predict cardiovascular disease, the major cause of death in renal transplant recipients (RTRs). We studied the determinants of fetuin-A, a potent circulating calcification inhibitor encoded by the AHSG gene, and tested its association with vascular calcifications and long-term survival and cardiovascular events (CVEs) in RTRs. Two hundred seventy-seven prevalent RTRs from a single center were included. CVEs and deaths were prospectively recorded during a 5-year follow-up. Independent determinants of lower serum fetuin-A levels were lower plasma cholesterol, the AHSG rs4918 G allele, and history of smoking. Low serum fetuin-A level was a determinant of aortic calcifications (assessed using spiral CT). Low fetuin-A levels (≤0.47 g/L, first quintile) were independently associated with CVEs and deaths (hazard ratio=1.83; 95% confidence interval, 1.07 to 3.04). The association was confirmed for all-cause mortality, and the major adverse cardiovascular endpoints were analyzed separately. Patients with low fetuin-A and high high-sensitivity C-reactive protein (>4.36 mg/L, fourth quintile) levels had a 3.5-fold increased risk of all-cause mortality and CVEs. In the presence of inflammation, CVE-free survival was influenced by common variants in the AHSG gene. These data show that low fetuin-A levels are independently associated with aortic calcifications and a higher risk of CVEs and mortality. They support fetuin-A as a circulating biomarker able to identify RTRs at risk for vascular calcifications and CVEs.