Risk Stratification For Cardiovascular Events Research Articles

#1329 Assessing eGFR performance against measured GFR stratifying for ethnicity and albumin: development of the AIM CKD UK study

Abstract Background and Aims Accurate measurement of kidney function using estimated glomerular filtration rate (eGFR) is essential for appropriate risk stratification of cardiovascular events, kidney failure and prescribing medications. The AIM CKD UK study (IRAS 320215) will assess the accuracy of current and novel creatinine-based eGFR equations compared to exogenous filtration marker derived measured GFR (mGFR) for people of different ethnicities in large national cohort. We performed a preliminary analysis from a single centre in AIM CKD UK to inform future data collection and assessed: Method All adults (≥18-years) who had paired mGFR and eGFR tests within 30 days between 2009-2022 were included. Patients with mGFR ≥150 ml/min/1.73 m2, incomplete datasets and previous amputations were excluded. Age, reported ethnicity, biological sex, referral specialty, height, weight, exogenous filtration marker, creatinine and albumin concentration were recorded. eGFR was calculated from creatinine, age and sex using five equations (Fig. 1). Each eGFR equation was compared to mGFR using median bias, precision, 30% accuracy (P30). Agreement was demonstrated with Bland-Altman plots. Results were stratified for time between eGFR-mGFR (≤7 days vs 8-30 days) and albumin concentration; low (<35 g/L) vs normal / high (≥35 g/L). Assessment of equation performance in different ethnicity was also stratified for the three largest ethnicity groups (White, Black and South Asian ethnicity). Data were analysed using software R V4.2.2. Results There were 2623 patients who met the inclusion criteria. Mean age was 54.8 ± 13.1 years, with 57.8% male (N = 1515). The majority of patients were White ethnicity (58.7%; N = 1539). Median mGFR was 77 mL/min/1.73 m2 (IQR 62–91 mL/min/1.73 m2). Median serum creatinine concentration was 74 umol/L (IQR 61–90 umol/L). The CKD-EPI 2009 equation, compared to mGFR, demonstrated a median bias of +12.8 mL/min/1.73 m2, percentage bias of 16.9% and P30 of 68.6%. The Lund-Malmo revised equation performed best with median bias of 2.1 mL/min/1.73 m2 (percentage bias 2.9%) and a P30 of 82.7%. Agreement, with ethnicity stratification is summarised in Table 1. The majority of patients (N = 2439; 93.0%) had paired mGFR-eGFR tests within 7-days. There was no significant difference between the median bias of each group (P = .749). 2610 (99.5%) patients had concurrent albumin tests performed; 183 (7.0%) of these patients had low albumin concentrations. Median bias was significantly higher in this group compared to normal/high albumin for each equation (e.g. Low vs Normal/high albumin median bias for CKD-EPI equation = 20.3 vs 12.5 mL/min/1.73 m2; P <. 001). Conclusion The LM revised and European Kidney Function Consortium equations perform best in this cohort. Limitations include selection bias and retrospective data. Future data analysis for the AIM CKD study can include paired samples within 30 days as there is no significant difference between 0-7 and 8-30 days. The impact of serum albumin on mGFR-eGFR association in a larger cohort stratified for confounding variables, such as liver disease, malignancy and body mass index is required.

Fully automated artificial intelligence-based coronary CT angiography image processing: efficiency, diagnostic capability, and risk stratification.

To prospectively investigate whether fully automated artificial intelligence (FAAI)-based coronary CT angiography (CCTA) image processing is non-inferior to semi-automated mode in efficiency, diagnostic ability, and risk stratification of coronary artery disease (CAD). Adults with indications for CCTA were prospectively and consecutively enrolled at two hospitals and randomly assigned to either FAAI-based or semi-automated image processing using equipment workstations. Outcome measures were workflow efficiency, diagnostic accuracy for obstructive CAD (≥ 50% stenosis), and cardiovascular events at 2-year follow-up. The endpoints included major adverse cardiovascular events, hospitalization for unstable angina, and recurrence of cardiac symptoms. The non-inferiority margin was 3 percentage difference in diagnostic accuracy and C-index. In total, 1801 subjects (62.7 ± 11.1 years) were included, of whom 893 and 908 were assigned to the FAAI-based and semi-automated modes, respectively. Image processing times were 121.0 ± 18.6 and 433.5 ± 68.4 s, respectively (p<0.001). Scan-to-report release times were 6.4 ± 2.7 and 10.5 ± 3.8 h, respectively (p< 0.001). Of all subjects, 152 and 159 in the FAAI-based and semi-automated modes, respectively, subsequently underwent invasive coronary angiography. The diagnostic accuracies for obstructive CAD were 94.7% (89.9-97.7%) and 94.3% (89.5-97.4%), respectively (difference 0.4%). Of all subjects, 779 and 784 in the FAAI-based and semi-automated modes were followed for 589 ± 182 days, respectively, and the C-statistic for cardiovascular events were 0.75 (0.67 to 0.83) and 0.74 (0.66 to 0.82) (difference 1%). FAAI-based CCTA image processing significantly improves workflow efficiency than semi-automated mode, and is non-inferior in diagnosing obstructive CAD and risk stratification for cardiovascular events. Conventional coronary CT angiography image processing is semi-automated. This observation shows that fully automated artificial intelligence-based image processing greatly improves efficiency, and maintains high diagnostic accuracy and the effectiveness in stratifying patients for cardiovascular events. • Coronary CT angiography (CCTA) relies heavily on high-quality and fast image processing. • Full-automation CCTA image processing is clinically non-inferior to the semi-automated mode. • Full automation can facilitate the application of CCTA in early detection of coronary artery disease.

Development of a Three-Dimensional Carotid Ultrasound Image Segmentation Workflow for Improved Efficiency, Reproducibility and Accuracy in Measuring Vessel Wall and Plaque Volume and Thickness.

Automated segmentation of carotid lumen-intima boundary (LIB) and media-adventitia boundary (MAB) by deep convolutional neural networks (CNN) from three-dimensional ultrasound (3DUS) images has made assessment and monitoring of carotid atherosclerosis more efficient than manual segmentation. However, training of CNN still requires manual segmentation of LIB and MAB. Therefore, there is a need to improve the efficiency of manual segmentation and develop strategies to improve segmentation accuracy by the CNN for serial monitoring of carotid atherosclerosis. One strategy to reduce segmentation time is to increase the interslice distance (ISD) between segmented axial slices of a 3DUS image while maintaining the segmentation reliability. We, for the first time, investigated the effect of ISD on the reproducibility of MAB and LIB segmentations. The intra-observer reproducibility of LIB and MAB segmentations at ISDs of 1 mm and 2 mm was not statistically significantly different, whereas the reproducibility at ISD = 3 mm was statistically lower. Therefore, we conclude that segmentation with an ISD of 2 mm provides sufficient reliability for CNN training. We further proposed training the CNN by the baseline images of the entire cohort of patients for automatic segmentation of the follow-up images acquired for the same cohort. We validated that segmentation with this time-based partitioning approach is more accurate than that produced by patient-based partitioning, especially at the carotid bifurcation. This study forms the basis for an efficient, reproducible, and accurate 3DUS workflow for serial monitoring of carotid atherosclerosis useful in risk stratification of cardiovascular events and in evaluating the efficacy of new treatments.

Relationship Between Endothelial Dysfunction and the Outcomes After Atrial Fibrillation Ablation.

Background Endothelial dysfunction (ED) is associated with cardiovascular events in patients with atrial fibrillation (AF). However, the utility of ED as a prognostic marker after AF ablation supplementary to the CHA2DS2-VASc score is unclear. This study aimed to investigate the relationship between ED and 5-year cardiovascular events in patients undergoing AF ablation. Methods and Results We conducted a prospective cohort study of patients who underwent a first-time AF ablation and for whom the endothelial function was assessed by the peripheral vascular reactive hyperemia index (RHI) before ablation. We defined ED as an RHI of <2.1. Cardiovascular events included strokes, heart failure requiring hospitalization, arteriosclerotic disease requiring treatment, venous thromboses, and ventricular arrhythmias or sudden cardiac death. We compared the 5-year incidence of cardiovascular events after AF ablation between those with and without ED. Among the 1040 patients who were enrolled, 829 (79.7%) had ED, and the RHI value was found to be associated with the CHA2DS2-VASc score (P=0.004). The 5-year incidence of cardiovascular events was higher among patients with ED than those without ED (98 [11.8%] versus 13 [6.2%]; log-rank P=0.014). We found ED to be an independent predictor of cardiovascular events after AF ablation (hazard ratio [HR], 1.91 [95% CI, 1.04-3.50]; P=0.036) along with a CHA2DS2-VASc score of ≥2 (≥3 for women) (HR, 3.68 [95% CI, 1.89-7.15]; P<0.001). Conclusions The prevalence of ED among patients with AF was high. Assessing the endothelial function could enable the risk stratification of cardiovascular events after AF ablation.

Prediction of cardiovascular events using myocardial strain ratio derived from 13N-ammonia positron emission tomography.

Myocardial flow reserve (MFR), derived from ammonia N-13 positron emission tomography (NH3-PET), can predict the prognosis of patients with various heart diseases. We aimed to investigate whether myocardial strain ratio (MSR) was useful in predicting MACE and allowed for further risk stratification of cardiovascular events in patients with ischemic heart disease (IHD) in addition to MFR. Ninety-five patients underwent NH3-PET because of IHD. MFR was determined as the ratio of hyperemic to resting myocardial blood flow (MBF). MSR was defined as the ratio of strains at stress and rest. The endpoint was major adverse cardiac events (MACE), including all-cause death, acute coronary syndrome, heart failure hospitalization, and revascularization. The ability to predict MACE was assessed using receiver operating characteristic (ROC) analysis, and the predictability of ME was analyzed using Kaplan-Meier analysis. The Cox proportional hazards regression model was used to calculate the hazard ratio (HR) with 95% confidence interval (CI). The ROC curve analysis demonstrated a cutoff of 0.93 for MACE with MSR (sensitivity and specificity of 77% and 71%, respectively). Patients with MSR < 0.93 displayed a significantly higher MACE rate than those with MSR ≥ 0.93 (p = 0.0036). The Cox proportional hazards regression analysis indicated that MSR was an independent marker that could predict MACE in imaging and clinical parameters (HR, 7.32; 95% CI: 1.59-33.7, p = 0.011). MSR was an independent predictor of MACE and was useful for further risk stratification in IHD. MSR has the potential for a new indicator of revascularization in patients with IHD. • We hypothesized that combining myocardial flow reserve (MFR) with the myocardial strain ratio (MSR) obtained by applying the feature-tracking technique to ammonia N-13 PET would make it predictive of major adverse cardiac events (MACE) compared to MFR alone. • MSR was an independent predictor of MACE, allowing for further risk stratification in addition to MFR in patients with ischemic heart disease. • MSR is a potential new indicator of revascularization.

Association of High-Sensitivity Troponin I with Cardiac and Cerebrovascular Events in Patient after Ischemic Stroke

Introduction: Early recognition and risk stratification of cardiovascular events are necessary in patients after ischemic stroke. Recent evidence suggests that elevated high-sensitive cardiac troponin is a predictor of mortality and vascular events. Therefore, we aimed to explore the prognostic role of high-sensitive cardiac troponin I (hs-TnI) on mortality and cardiovascular outcomes in patients after ischemic stroke. Methods: From August 2014 to July 2017, 1,506 patients with acute ischemic stroke were pulled consecutively in a retrospective single-center registry. Of these, 1,019 patients were selected and classified into the elevated or non-elevated hs-TnI groups according to hs-TnI level of 99th percentile upper reference limit (URL) at the time of admission for ischemic stroke. The primary outcome was a major adverse cardiac and cerebrovascular event (MACCE) during follow-up. Results: Among 1,019 patients, 708 patients were non-elevated hs-TnI group (<99th percentile URL of hs-TnI) and 311 patients were elevated hs-TnI group (≥99th percentile URL of hs-TnI). The median follow-up period was 22.5 (interquartile range 5.0–38.8) months. In a multivariable Cox regression model, the elevated hs-TnI group has a higher risk of MACCE (adjusted hazard ratio [HR]: 3.12; 95% confidence interval [CI]: 2.33–4.17; p < 0.01), all-cause mortality (adjusted HR: 4.15; 95% CI: 2.47–6.99; p < 0.01) and readmission caused by coronary revascularization (adjusted HR: 3.12; 95% CI: 1.41–6.90; p < 0.01), heart failure (adjusted HR: 2.76; 95% CI: 1.38–5.51; p < 0.01), and stroke (adjusted HR: 1.73; 95% CI: 1.07–2.78; p = 0.02) compared with the non-elevated hs-TnI group. Conclusions: Elevated hs-TnI is independently associated with higher mortality and cardiac and cerebrovascular events in patients with ischemic stroke and may serve as a valuable prognostic factor in management after ischemic stroke.

Blood Flow Turbulence Quantification of Carotid Artery With a High-Frame Rate Vector Flow Imaging.

To assess the feasibility and performance of Turbulence (Tur) index as a quantitative tool for carotid artery flow turbulence; to detect and compare the blood flow patterns of common carotid artery (CCA) and carotid bulb (CB) at different ages and cardiac phases in healthy adults, and thus interpret the evolvement of etiology difference between CCA and CB. Carotid flow characteristics of 40 healthy volunteers were evaluated quantitatively by a high-frame rate vector flow imaging. Three types of flow patterns were defined depending on the distributive range of complex flow during systole in CB. Comparison of mean Tur value in CCA and CB at different age groups and cardiac phases was performed. And the correlation between Tur value and the diameter ratio of proximal internal carotid artery to common carotid artery (DRpro-ica/cca) was tested. Mean Tur values in CB were remarkably higher than that in CCA, whether during systole or diastole (P < .001). Meanwhile Tur values in CB during systole were significantly higher than that during diastole (P < .001). Flow complexity of CB showed variations among 40 participants especially in systole, whereas the flow pattern of CCA was relatively consistent. Mean Tur values were positively correlated with DRpro-ica/cca in CB (ρ=0.69, P < .05). V Flow imaging provided a reliable method-Tur, for quantitative analysis of carotid blood flow. It had potential to be further applied in distinguishing complex hemodynamic characteristics in high-risk people of carotid diseases for the risk stratification of cardiovascular events.

Essen score in the prediction of cerebrovascular events compared with cardiovascular events after ischaemic stroke or transient ischaemic attack: a nationwide registry analysis.

BACKGROUNDThe Essen risk score improves stratification of patients with acute ischemic stroke by early stroke recurrence. Recent study showed it could also predict myocardial infarction (MI). This study aimed to compare the Essen score’s ability to predict cerebrovascular events with compared cardiovascular events.METHODSWe included patients with acute ischaemic stroke or transient ischaemic attack within seven days from the Third China National Stroke Registry. One-year cumulative event rates of combined vascular events (a composite of MI, stroke recurrence or vascular death) and cardiac events (a composite of MI, heart failure or cardiac death) was estimated using the Kaplan-Meier method. The predictive value of the Essen score was assessed with C-statistics. In multivariate Cox regression analyses, we assessed whether Essen score, etiological subtype and imaging parameters were associated with outcomes.RESULTSOf 13,012 patients were included, the cumulative one-year event rates were 10.03% for combined vascular events and 0.77% for cardiac events, respectively. Compared with those with an Essen score < 3, patients with an Essen score ≥ 3 were more likely to have a subsequent combined vascular event [hazard ratio (HR) = 1.39, 95% CI: 1.24−1.55] and cardiac events (HR = 2.30, 95% CI: 1.53−3.44). The score tended to be more predictive of the risk of MI (C-statistic = 0.63, 95% CI: 0.55−0.71) and cardiac events (C-statistic = 0.62, 95% CI: 0.56−0.67) than stroke recurrence (C-statistic = 0.55, 95% CI: 0.54−0.57) and combined vascular events (C-statistic = 0.56, 95% CI: 0.54−0.57). In multivariable analysis after adjusted Essen score, patients with multiple acute infarctions or single acute infarctions and large artery atherosclerosis subtype were independently associated with an increased risk of combined vascular events. While the cardioembolism subtype was associated with an increased risk of cardiac events.CONCLUSIONSThe Essen score is potentially more suitable for risk stratification of cardiovascular events than cerebrovascular events. Moreover, future predictive tools should take brain imaging findings and cause of stroke into consideration.

Rationale and design of the HINODE study: Heart failure indication and sudden cardiac death prevention trial Japan.

BackgroundRandomized trials in Western countries have provided evidence that prophylactic implantable cardioverter‐defibrillator (ICD) therapy reduces mortality in heart failure (HF) patients with reduced left ventricular ejection fraction. However, the risk of life‐threatening ventricular arrhythmias in Japanese HF patients sharing similar risk factors is still unknown.MethodsThe Heart Failure Indication and Sudden Cardiac Death Prevention Trial Japan trial (NCT03185832) is a prospective, multicenter registry designed to collect data on ventricular arrhythmia, HF events, and mortality in Japanese HF patients. Japanese patients with HF and 2‐5 predefined risk factors who were indicated for cardiac device implantation based on European Society of Cardiology guidelines were enrolled in four treatment arms: implantable cardioverter‐defibrillator (ICD), cardiac resynchronization therapy defibrillator (CRT‐D), HF pacing (PA; Pacemaker and cardiac resynchronization pacemaker), and nondevice (ND) cohorts and followed for a minimum of 12 months. Since it is anticipated that some baseline patient characteristics and risk factors will differ significantly from those reported in predominantly Western populations, event rates will be compared to a propensity‐matched population from the MADIT RIT trial. Primary endpoints are composite rates of first appropriately treated ventricular arrhythmias (VA) or/and life‐threatening VA symptoms for the ICD and CRT‐D cohorts. For nondevice and PA cohorts, the primary outcome is all‐cause mortality.ConclusionsThe Heart Failure Indication and Sudden Cardiac Death Prevention Trial Japan is a large prospective multicenter registry with defined device treatment cohorts and will provide data for risk stratification for cardiovascular events in Japanese HF patients.

In vivo imaging of vulnerable plaque with intravascular modalities: its advantages and limitations.

In vivo imaging of plaque instability has been considered to have a great potential to predict future coronary events and evaluate the stabilization effect of novel anti-atherosclerotic medical therapies. Currently, there are several intravascular imaging modalities which enable to visualize plaque components associated with its vulnerability. These include virtual histology intravascular ultrasound (VH-IVUS), integrated backscatter IVUS (IB-IVUS), optical coherence tomography (OCT), near-infrared spectroscopy and coronary angioscopy. Recent studies have shown that these tools are applicable for risk stratification of cardiovascular events as well as drug efficacy assessment. However, several limitation exists in each modality. The current review paper will outline advantages and limitation of VH-IVUS, IB-IVUS, OCT, NIRS and coronary angioscopy imaging.

Impact of the Fibrosis-4 Index on Risk Stratification of Cardiovascular Events and Mortality in Patients with Atrial Fibrillation: Findings from a Japanese Multicenter Registry.

Background: Liver diseases drive the development and progression of atrial fibrillation (AF). The Fibrosis-4 (FIB4) index is a non-invasive scoring method for detecting liver fibrosis, but the prognostic impact of using it for AF patients is still unknown. Herein, we evaluated using the FIB4 index as a risk assessment tool for cardiovascular events and mortality in patients with AF. Methods: We performed a post-hoc analysis of a prospective, observational multicenter study. A total of 3067 patients enrolled in a multicenter Japanese registry were grouped as first tertile (FIB4 index < 1.75, n = 1022), second tertile (1.75 ≤ FIB4 index < 2.51, n = 1022), and third tertile (FIB4 index ≥ 2.51, n = 1023). Results: The third tertile had statistically significant results: older age, lower body mass index, increased heart failure prevalence, and lower clearances of hemoglobin and creatinine (all p < 0.05). During the follow-up period, incidences of major bleeding, cardiovascular events, and all-cause mortality were significantly higher for the third tertile (all p < 0.05). After multivariate adjustment, the third tertile associated independently with cardiovascular events (HR 1.72; 95% CI 1.31–2.25) and all-cause mortality (HR 1.43; 95% CI 1.06–1.95). Adding the FIB4 index to a baseline model with CHA2DS2-VASc score improved the prediction of cardiovascular events and all-cause mortality, as shown by the significant increase in the C-statistic (all p < 0.05), net reclassification improvement (all p < 0.001), and integrated discrimination improvement (all p < 0.001). A FIB4 index ≥ 2.51 most strongly associated with cardiovascular events and all-cause mortality in AF patients with high CHADS2 scores (all p < 0.001). Conclusions: The FIB4 index is independently associated with risks of cardiovascular events and all-cause mortality in AF patients.

The Challenges With the Cardiac Evaluation of Liver and Kidney Transplant Candidates.

Cardiovascular events are among the leading cause of mortality in kidney and liver transplant recipients. Thus, screening for cardiovascular disease and risk stratification for cardiovascular events constitute an important part of the pretransplant evaluation. In this review, we first summarize current guidelines in the cardiac risk assessment of kidney and liver transplant candidates. We then elaborate on the limitations of these guidelines, summarize the current knowledge gaps, and narrow down a spectrum of 6 themes that serve as challenges to research and practice development. This spectrum pertains to understanding the disease itself, which is challenging due to the altered cardiac physiology in these patients and current guidelines that do not adequately account for nonischemic diseases and events. We then describe the challenges in assessing these patients, their symptoms, and individualizing their risk of cardiovascular events with a special consideration for nontraditional risk factors. We also explore the limitations of the current and novel diagnostic tests and the lack of evidence of therapeutic efficacy in intervening in patients with asymptomatic disease. The transplant procedure itself can be a potential modifiable risk factor for cardiovascular events, that is, surgical technique, type of donor, and induction immunosuppression. Lastly, we describe the potential issues with the current literature when defining cardiac diseases and events across different studies and shortcomings of extrapolating data from the nontransplant literature. We conclude by proposing research and practice implications of our discussion and that there is a need for evidence to guide the revision of current guidelines.

C-Reactive Protein and Its Structural Isoforms: An Evolutionary Conserved Marker and Central Player in Inflammatory Diseases and Beyond.

C-reactive protein (CRP) is an evolutionary highly conserved member of the pentraxin superfamily of proteins. CRP is widely used as a marker of inflammation, infection and for risk stratification of cardiovascular events. However, there is now a large body of evidence, that continues to evolve, detailing that CRP directly mediates inflammatory reactions and the innate immune response in the context of localised tissue injury. These data support the concept that the pentameric conformation of CRP dissociates into pro-inflammatory CRP isoforms termed pCRP* and monomeric CRP. These pro-inflammatory CRP isoforms undergo conformational changes that facilitate complement binding and immune cell activation and therefore demonstrate the ability to trigger complement activation, activate platelets, monocytes and endothelial cells. The dissociation of pCRP occurs on the surface of necrotic, apoptotic, and ischaemic cells, regular β-sheet structures such as β-amyloid, the membranes of activated cells (e.g., platelets, monocytes, and endothelial cells), and/or the surface of microparticles, the latter by binding to phosphocholine. Therefore, the deposition and localisation of these pro-inflammatory isoforms of CRP have been demonstrated to amplify inflammation and tissue damage in a broad range of clinical conditions including ischaemia/reperfusion injury, Alzheimer's disease, age-related macular degeneration and immune thrombocytopaenia. Given the potentially broad relevance of CRP to disease pathology, the development of inhibitors of CRP remains an area of active investigation, which may pave the way for novel therapeutics for a diverse range of inflammatory diseases.

4312Left ventricular systolic function in patients with systemic lupus erythematosus and its association with cardiovascular events

Abstract Introduction Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that may involve the cardiovascular system. Diagnosis of cardiac involvement, particularly at an early stage, represents challenge since symptoms in SLE patients are often atypical and current diagnostic tools are characterized by a low sensitivity to detect myocardial dysfunction. Purpose of this study was to assess left ventricular (LV) systolic function in a large cohort of SLE patients in comparison with a control group of healthy subjects and using standard echocardiographic measures and global longitudinal strain (GLS) by 2D speckle tracking analysis. Furthermore, the association between echocardiographic parameters and the occurrence of cardiovascular events was tested. Methods A total of 102 patients (87% female, 42±15 years) were analysed including echocardiography at the time of their first visit. All patients fulfilled the American College of Rheumatology (ACR 1997) and The Systemic Lupus Erythematosus International Collaborating Clinics (SLICC 2012) classification criteria for SLE. During follow-up, cardiovascular events included cerebrovascular accident or transient ischemic attack, pulmonary embolism, coronary artery interventions, hospitalisations for heart failure and development of supraventricular arrhythmias. The control group consisted of 50 age- and gender-matched healthy subjects. Results Prevalence of comorbidities, such as hypertension (8%), hypercholesterolemia (4%) and diabetes mellitus (2%) was relatively low in SLE patients. In comparison with the control group, SLE patients were characterized by worse LV systolic function as measured by LV ejection fraction (51±6% vs 62±6%, p&lt;0.001) and by LV GLS (−15±3% vs −19±2%, p&lt;0.001), as well as worse LV diastolic function (e' septal: SLE 9±2 cm/s vs 10±2 cm/s healthy controls, p=0.020; E/e': SLE 8±3 vs 7±2 healthy controls, p&lt;0.001; TR velocity: SLE 2±0.6 m/s vs 1.6±0.5 m/s healthy controls, p=0.020). During a median follow up of 11 years (Interquartile range: 4–19 years), 43 (42%) patients developed cardiovascular events. Kaplan-Meier curves show that SLE patients with more impaired GLS (based on the median value of −15%) experienced higher cumulative rates of cardiovascular events as compared to patients with GLS ≤−15% (Chi-square 7.197; Log rank p=0.007). On uni- and multivariate Cox-regression models, LV GLS demonstrated significant association with cardiovascular events (HR: 2.229; 95% CI: 1.024–4.853; p=0.043), together with age (HR: 1.043; 95% CI: 1.017–1.069; p=0.014) after correcting for LV mass index and e'; in turn, LV ejection fraction was not significantly associated with cardiovascular events. LV GLS in SLE patients Conclusions In SLE patients, LV systolic function as measured by GLS is significantly impaired and independently associated with cardiovascular events. Incorporation of LV GLS in the early assessment of these patients may significantly improve risk-stratification for cardiovascular events.

Risk Stratification of Cardiovascular Events in Very Elderly Patients with Known or Suspected Coronary Artery Disease Who Had Normal Single-photon Emission Computed Tomographic Myocardial Perfusion Imaging Findings

Objective We aimed to stratify the risk of major cardiovascular (MCV) events in Japanese patients with known or suspected coronary artery disease (CAD) who had normal single-photon emission computed tomographic myocardial perfusion imaging (SPECT MPI) findings and to compare the risk by generation. Methods This was a retrospective study. The composite endpoint was the occurrence of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. Patients The study subjects were 2,035 patients with normal SPECT MPI findings at baseline who had been followed up to confirm their prognosis for 3 years. The patients were categorized into 3 age groups: very elderly (≥80 years old, n=311), elderly (65-79 years old, n=1,097), and younger (<65 years old, n=542). Results During the follow-up, 68 patients experienced MCV events: cardiovascular death (n=29), non-fatal myocardial infarction (n=15), and non-fatal stroke (n=24). The MCV event rate was significantly higher in very elderly patients than in other patients. Multivariate predictors were age categories, the estimated glomerular filtration rate, atrial fibrillation, and stress left ventricular ejection fraction. The MCV event rate was 6.1% in very elderly patients. However, the MCV event rate in those with normal cardiac and renal functions without atrial fibrillation was 3.3%, which was similar to that in elderly and younger patients. Conclusion The MCV event rate was high in very elderly patients despite their normal SPECT MPI findings at baseline. Therefore, very elderly patients with multivariate risks should be carefully followed to avoid a poor prognosis.

Short-term blood pressure variability outweighs average 24-h blood pressure in the prediction of cardiovascular events in hypertension of the young.

The association of short-term blood pressure (BP) variability (BPV) with cardiovascular events (CVEs) is controversial. Aim of this study was to investigate whether BPV measured as weighted 24-h SD was associated with CVE in a prospective cohort study of young patients screened for stage 1 hypertension. We performed 24-h ambulatory BP monitoring in 1206 participants aged 33.1 ± 8.5 years, untreated at baseline examination. Participants were divided into two categories with low (<12.8 mmHg) or high (≥12.8 mmHg) SBPV. Hazard ratios for CVE associated with BPV expressed either as continuous or categorical variable were computed from multivariable Cox models. During 15.4 ± 7.4 years of follow-up there were 69 fatal and nonfatal CVE. In multivariable Cox models, high SBPV was an independent predictors of CVE [2.75 (1.65-4.58); P = 0.0001] and of coronary events [3.84 (2.01-7.35), P < 0.0001]. Inclusion in the model of development of hypertension requiring treatment during the follow-up, did not reduce the strength of the associations. Addition of SBPV to fully adjusted models had significant impact on risk reclassification and integrated discrimination (relative integrated discrimination improvement for BPV as continuous variable: 13.5%, P = 0.045, and for BPV as categorical variable: 26.6%, P = 0.001). When the coefficient of variation was used as BPV metric similar results were obtained. Of note, in all Cox models average 24-h BP was no longer an independent predictor of outcome after BPV was included. Short-term BPV adds to the risk stratification for cardiovascular events in young-to-middle-age patients screened for stage 1 hypertension over and above traditional 24-h ambulatory monitoring indexes.

Rationale, design, and endpoints of the ‘DEvice-Detected CArdiac Tachyarrhythmic Events and Sleep-disordered Breathing (DEDiCATES)’ study: Prospective multicenter observational study of device-detected tachyarrhythmia and sleep-disordered breathing

BackgroundFew studies have investigated the prognostic value of cardiac implantable electronic device (CIED)-detection of sleep-disordered breathing (SDB) for risk stratification of cardiovascular events. In the Device-Detected CArdiac Tachyarrhythmic events and Sleep-disordered breathing (DEDiCATES) study, we aim to determine whether device-detected SDB events are associated with increased risk of cardiac arrhythmias or other cardiovascular outcomes. Methods and designSix-hundred patients (300 patients with low-voltage pacing devices and 300 with high-voltage defibrillator devices) who have dual chamber CIEDs with AP Scan™ function (Boston Scientific Inc., Marlborough, MA, USA) are planned to be enrolled in this study. AP Scan reports the average number of sleep disturbance events per hour per night in the form of a Respiratory Disturbance Index (RDI). The daily RDI values are to be used for quantitative measurement of the severity and burden of SDB. CIED-detected atrial high rate episodes (AHREs) and clinical atrial tachyarrhythmia will be assessed as the primary outcomes over a follow-up period of 2 years. Correlations between CIED-detected SDB and AHRE burdens will be analyzed. The secondary outcomes are CIED-detected or clinical ventricular arrhythmic events, stroke, heart failure hospitalization, mortality, and quality of life. ConclusionThis study will determine the prognostic value of automated diagnostic function of CIED for SDB, which will help to improve the cardiovascular prognoses of CIED patients by enabling convenient and accurate assessments of SDB events.

SST2 as a new biomarker of CKD induced cardiac remodeling – Impact on risk prediction

Heart failure is the most frequent cardiac complication of chronic kidney disease (CKD). Biomarkers can help identifying high-risk patients. Natriuretic peptides are largely used for monitoring patients with cardiac failure, but are highly dependent of GFR. Soluble suppressor of tumorigenicity 2 (sST2) is identified in risk stratification of cardiovascular events (CVE) in heart failure. Furthermore, sST2 could be included in a bioclinical score to stratify mortality risk. The aim of this study is to evaluate the interest of circulating sST2 level in heart dysfunction, the bioclinical score to predict risk of composite outcome (major adverse coronary events) as well as mortality prediction for CKD patients. A retrospective study was carried out on 214 patients enrolled from 2004 to 2015 at Montpellier University Hospital. sST2 was measured with Presage ST2 ® kit. CKD status was defined by the CKD-epi equation to estimate GFR. Indices of cardiac parameters were performed by cardiac echography. No patient had reduced ejection fraction. 109 patients had left ventricular hypertrophy, and 181 had diastolic dysfunction, with structural, functional abnormalities or both. sST2 is independent of age and eGFR ( P = 0.44, r = 0.05 and P = 0.3, r = 0.07, respectively). Regarding echocardiogram data, sST2 is correlated with left ventricular mass index ( P = 0.02, r = 0.16), left atrial diameter ( P = 0.04, r = 0.14) and volume index ( P = 0.05, r = 0.13) and). sST2 alone does not change risk prediction of death and/or CVE compared to cardiac biomarkers. Included in a bio-clinical score sST2 has added value and better stratifies the risk of CVE and/or death in CKD patients. sST2 is associated with cardiac remodeling independently of eGFR, unlike other cardiac biomarkers (hs-cTnT and NT-proBNP). Included in a bioclinical score, it allows a better risk stratification of death and/or CVE in early stages of CKD patients.

Assessment of Leukocyte Telomere Length as an Indicator of Biological Age for Risk Stratification of Cardiovascular Events: A Meta-Analysis

Background: Chronological age is the most common risk factor for atrial fibrillation (AF). Telomere length is a marker of biological age. The association between biological age and AF, AF risk factors, and cardiovascular events is not well established.

Prognostic Impact of Diastolic Wall Strain in Patients at Risk for Heart Failure.

Diastolic wall strain (DWS) is based on the linear elastic theory, according to which decreased wall thinning during diastole reflects reduced left ventricular compliance and thus increased diastolic stiffness. Increased diastolic stiffness as assessed by DWS is associated with a worse prognosis in patients who have heart failure (HF) with preserved ejection fraction. However, there are no data about the prognostic value of DWS derived by M-mode echocardiography in patients at risk for HF. We retrospectively enrolled 1829 consecutive patients without prior HF who were hospitalized for cardiovascular (CV) diseases in our hospital between 2005 and 2012. Patients were divided into two groups stratified by DWS (median value 0.34). The study endpoint was the composite of major adverse cardiovascular events (MACE), including all-cause death, myocardial infarction, stroke, and hospitalization for HF. Over a 4.2-year median follow-up, adverse events were observed in 322 patients (17.6%). In Kaplan-Meier analysis, patients with low DWS (≤ 0.34, n = 915) showed worse prognoses than those with high DWS (> 0.34, n = 914) (MACE incidence 39.4% versus 31.9%, P = 0.011). In multivariate Cox proportional hazards analysis after the adjustment for age, sex, and echocardiographic parameters, low DWS (≤ 0.34) was significantly associated with the incidence of MACE (hazard ratio: 1.26, 95% confidence interval: 1.01-1.59; P = 0 .045). In patients without prior HF, DWS is an independent predictor of MACE. Simple assessment of DWS might improve risk stratification for CV events in those patients.