Independent Predictors Of Clinical Events Research Articles

Long-Term Outcomes in Patients With Relatively High His-Bundle Capture Threshold After Permanent His-Bundle Pacing - A Multicenter Clinical Study.

Outcomes in patients with relatively high His-bundle (HB) capture thresholds at implantation are unknown. This study aimed to compare changes in the HB capture threshold and prognosis between patients with a relatively high threshold and those with a low threshold. Forty-nine patients who underwent permanent HB pacing (HBP) were divided into two groups: low (<1.25 V at 1.0 ms; n=35) and high (1.25-2.49 V; n=14) baseline HB capture threshold groups. The HB capture threshold was evaluated at implantation, and after 1 week, 1, 3, and 6 months, and every 6 months thereafter. HB capture threshold rise was defined as threshold rise ≥1.0 V at 1.0 ms compared with implantation measures. We compared outcomes between the groups. During a mean follow-up period of 34.6 months, the high-threshold group showed a trend toward a higher incidence of HB capture threshold of ≥2.5 V (50% vs. 14%; P=0.023), HBP abandonment (29% vs. 8.6%; P=0.091), lead revision (21% vs. 2.9%; P=0.065), and clinical events (all-cause death, heart failure hospitalization, and new-onset or progression of atrial fibrillation; 50% vs. 23%; P=0.089) than the low-threshold group. A baseline HB capture threshold of ≥1.25V was an independent predictor of clinical events. A relatively high HB capture threshold is associated with increased risk of HBP abandonment, lead revision, and poor clinical outcomes.

Angiography-derived radial wall strain as a predictor of myocardial ischemia, high-risk plaque, and outcomes

Abstract Background Angiography-derived radial wall strain (RWS) is a novel method to assess the biomechanical characteristics of the underlying plaque. There is limited data regarding how the biomechanical attributes of atherosclerotic lesions relate to their physiologic and morphological attributes. Purpose This study aimed to investigate the association of RWS with myocardial ischemia and high-risk plaque, and their prognostic implication. Methods From the international CCTA-FFR registry, 484 deferred vessels underwent RWS analysis. Angiography-derived RWS was defined as relative changes of lumen diameter within the cardiac cycle, expressed as a percentage of the largest lumen diameter. Plaque characteristics were assessed in a coronary CT angiography core laboratory and high-risk plaque was defined as 3 or more high-risk plaque characteristics (HRPC) including minimum lumen area &amp;lt;4.0 mm2, plaque burden ≥70%, low-attenuation plaque, and positive remodeling. Functional significance of coronary lesion was assessed by invasively measured fractional flow reserve (FFR). The primary outcome was vessel-oriented composite outcome (VOCO), a composite of cardiac death, target vessel myocardial infarction, or target vessel revascularization at 5 years. All clinical outcomes were adjudicated by an independent clinical event committee. Results The mean FFR was 0.89±0.07, and that for maximum RWS (RWSmax) was 11.2±2.5%. RWS proportionally increased along with the decrease in FFR values, and the increase in the number of HRPC (Both p-for-trend &amp;lt;0.001). The proportion of vessels with FFR ≤0.80 and that of vessels with high-risk plaque increased in the order of RWSmax quartile group (Both p-for-trend &amp;lt;0.001) and these associations maintained after the adjustment of clinical characteristics (adjusted odds ratio [OR] 1.31, p value &amp;lt;0.001 for FFR ≤0.80; adjusted OR 1.24, p value &amp;lt;0.001 for high-risk plaque) and angiographic parameters (adjusted OR 1.24, p value &amp;lt;0.001 for FFR ≤0.80; adjusted OR 1.14, p value 0.012 for high-risk plaque). High RWSmax (&amp;gt;14.2%, optimal cut-off value for VOCO) was an independent predictor for VOCO after adjusting for diabetes and % diameter stenosis, FFR ≤0.8, or high-risk plaque (Figure 1). In a mediation analysis, RWS showed an independent effect from lesion-specific ischemia or high-risk morphological attributes in defining prognosis (Figure 2). Conclusion(s) Angiography-derived RWS was closely related to coronary physiologic and plaque morphological attributes, but was an independent predictor of clinical events. This novel index can provide additional prognostic implications over physiological severity or plaque characteristics in patients with coronary artery disease.Prognostic implications of high RWSMediation analysis

Prognostic Values of Fractional Flow Reserve Based on Clinical Outcomes in Patients on Chronic Hemodialysis

The fractional flow reserve (FFR) cut-off values of 0.75 or 0.8 have been widely used; however, whether they apply to patients on hemodialysis remains unknown. We aimed to investigate the cut-off value of FFR associated with clinical outcomes in patients on hemodialysis. Using the Japanese multicenter registry, we analyzed data of patients on hemodialysis with measured FFR between January 2010 and December 2016. Survival classification and regression tree analysis for the composite primary outcome of cardiovascular mortality, myocardial infarction, and target vessel revascularization revealed a threshold FFR of 0.83. Multivariate Cox regression analyses were performed for the clinical outcomes. Additionally, the primary outcome was analyzed using propensity score matching by dividing the patients into complete and incomplete revascularization groups according to the presence of residual lesions with an FFR of ≤0.83 after the intervention. Of the 212 included patients, 112 (52.8%) had lesions with an FFR of ≤0.83. After adjusting for confounders, an FFR of ≤0.83 was associated with a higher risk for the primary outcome (adjusted hazard ratio 2.01, 95% confidence interval 1.11 to 3.66, p=0.021). Propensity score matching showed that complete revascularization for lesions with an FFR of ≤0.83 was associated with a reduced risk for the primary outcome compared with incomplete revascularization (hazard ratio 0.38, 95% confidence interval 0.20 to 0.71, log-rank p=0.0016). In conclusion, an FFR of ≤0.83 was an independent predictor of clinical events in patients on hemodialysis. Furthermore, complete revascularization was associated with better clinical outcomes. Thus, this population may require a distinct FFR cut-off value.

Early optical coherence tomography evaluation of donor-transmitted atherosclerosis and cardiac allograft vasculopathy: insights from a prospective, single-center study

The impact of donor transmitted atherosclerosis as assessed by intravascular ultrasound on development and progression of cardiac allograft vasculopathy (CAV) after heart transplantation (HT) remains poorly defined in contemporary practice. In this exploratory analysis, we sought to assess the prognostic role of early qualitative assessment of donor artery morphology using optical coherence tomography (OCT) as a more sensitive imaging modality. HT recipients were prospectively enrolled for baseline OCT imaging of the left anterior descending coronary artery. OCT findings were classified as normal, homogeneous intimal thickening, and advanced plaque characteristics. The endpoint was a composite of cardiac death, myocardial infarction, or new angiographically detectable CAV stratified by the International Society of Heart and Lung Transplantation criteria up to 4 years of follow-up. A total of 35 patients underwent baseline OCT of whom 51.4% had normal OCT, 14.3% had homogenous plaque, and 34.3% had advanced characteristics. There were no significant differences in baseline demographics between patients with and without normal morphology. During a mean follow-up of 3.3±0.4 years, the endpoint occurred in 11 patients including 1 death, 7 CAV1, 3 CAV2, and 1 CAV3. Kaplan-Meier analysis revealed a significantly higher event rate in patients with advanced characteristics (log-rank p=0.010). In multivariate analysis, OCT-based plaque morphology was an independent predictor of clinical events (adjusted hazard ratio 4.57, 95% confidence interval 1.50-13.92, p=0.008) while maximal intimal thickness ≥0.5mm was not. Early qualitative OCT assessment of donor coronary artery morphology appears to be a reliable marker for predicting future cardiovascular events in HT recipients. Our findings warrant more careful study in a larger cohort.

Prognostic impact of atrial fibrillation under oral anticoagulation therapy in patients with type B acute aortic dissection

Abstract Background Patients with acute aortic dissection (AAD) sometimes are complicated with atrial fibrillation (AF). However, the impact of AF and the use of oral anticoagulation (OAC) on the prognosis of AAD remains unclear. In this study, we evaluated the prognostic impact of AF and OAC therapy in patients with type B AAD. Methods Consecutive patients diagnosed with type B AAD between January 2010 and December 2020 in our university hospital were retrospectively analyzed. All patients were divided into 2 groups based on the concomitance with or without AF. The primary endpoint was set as major adverse cardiovascular events (MACEs), including all-cause death, enlargement of aortic diameter, aortic ruptures, and cerebral infarction. Kaplan-Meier survival curves were constructed, and Cox proportional hazards analysis was performed to identify independent predictors of clinical events at 1 year. Results A total of 146 patients diagnosed with type B AAD were enrolled, with a mean age of 66±12 years, and 81% of male. Thirty-two patients (22%) experienced MACEs during 272±142 days-observation. Concomitant AF was observed in 27 patients (18%). In the Kaplan-Meier curve analysis, the patients with AF showed significantly higher events than those without AF (log-lank p&amp;lt;0.001). In the multivariate Cox proportional hazards models, presence of AF (HR: 2.402, 95% CI: 1.099–4.978 p=0.029), maximum descending aorta diameter (HR: 1.0366, 95% CI: 1.005–1.064 p=0.023), and age&amp;gt;75 years (HR: 2.635, 95% CI: 1.268–5.388 p=0.011) were independent predictors of MACEs. Regarding OAC in patients with AF, Kaplan-Meier analysis showed that usage of OAC was associated with a higher incidence of MACEs than those without (log-rank, p=0.036) Conclusion Presence of AF, enlargement of descending aorta diameter, and age were independent predictors of future MACEs in patients with type B AAD. Additionally, usage of OAC is associated with MACEs in patients with type B AAD complicated with AF. Funding Acknowledgement Type of funding sources: None.

Clinical Impact of Irregular Protrusion Angle After Coronary Stenting at Culprit Lesions With ST-Elevation Myocardial Infarction - An Intravascular Optical Coherence Tomography Study.

Background: A recent optical coherence tomography (OCT) registry showed that the presence of irregular protrusion (IP) after coronary stenting was a predictor of worse 1-year cardiovascular events. This study evaluated the clinical impact of OCT-detected IP after coronary stenting at ST-elevation myocardial infarction (STEMI) culprit lesions.Methods and Results: In all, 139 consecutive STEMI patients with OCT-detected IP after stenting were analyzed retrospectively. The maximum IP angles were measured and patients with IP were divided into 2 groups (large IP, maximum IP angle ≥180°; small IP, 0°<angle<180°). The primary endpoints were cardiac death, target vessel myocardial infarction, target lesion revascularization, and stent thrombosis at 1 year after the index percutaneous coronary intervention (PCI). Of STEMI patients with IP, 51.8% had large IP. The incidence of the primary endpoints higher was higher in the large than small IP group (12.5% vs. 1.5%, respectively; P=0.018). The occurrence of plaque rupture was an independent predictor of large IP (odds ratio 4.58; 95% confidential interval 1.86–11.27; P=0.001).Conclusions: Maximum IP angle ≥180° was an independent predictor of clinical events in STEMI patients with IP.

Diffuse Myocardial Fibrosis and Diastolic Function in Aortic Stenosis

ObjectivesThe aim of this study was to investigate the relationship between extracellular volume fraction (ECV), a noninvasive parameter that quantifies the degree of diffuse myocardial fibrosis on cardiac magnetic resonance (CMR), and left ventricular diastolic dysfunction (LVDD) in patients with aortic stenosis (AS). BackgroundMyocardial fibrosis on invasive myocardial biopsy is associated with LVDD. However, there is a paucity of data on the association between noninvasively quantified diffuse myocardial fibrosis and the degree of LVDD and how these are related to symptoms and long-term prognosis in patients with AS. MethodsPatients with moderate or severe AS (n = 191; mean age 68.4 years) and 30 control subjects without cardiovascular risk factors underwent CMR. LVDD grade was evaluated using echocardiography according to the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines. Clinical outcomes were defined as a composite of all-cause mortality or hospitalization for heart failure aggravation. ResultsPatients in higher ECV quintiles had a significantly higher prevalence of LVDD. Higher ECV was particularly associated with decreased myocardial relaxation (septal e′ <7 cm/s) and increased LV filling pressure (E/e′ ratio ≥15). Although both impaired diastolic function and higher ECV were significantly associated with a worse degree of dyspnea, patients with higher ECV showed greater dyspnea within the same grade of LVDD. During a median follow-up period of 5.6 years, 37 clinical events occurred. Increased ECV, as well as lower septal e′ and higher E/septal e′ ratio, were independent predictors of clinical events, irrespective of age, AS severity, aortic valve replacement, and left ventricular (LV) ejection fraction. ECV provided incremental prognostic value on top of clinical factors and LV systolic and diastolic function. ConclusionsDiffuse myocardial fibrosis, assessed using ECV on CMR, was associated with LVDD in patients with AS, but both ECV and LV diastolic function parameters provided a complementary explanation for dyspnea and clinical outcomes. Concomitant assessment of both LVDD and diffuse myocardial fibrosis may further identify patients with AS with greater symptoms and worse prognosis.

Impact of disproportionate secondary mitral regurgitation in patients undergoing edge-to-edge percutaneous mitral valve repair.

The aim of this study was to evaluate the prognostic role of echocardiographic parameters assessing secondary mitral regurgitation (SMR) severity and left ventricular dimension, including proportionate versus disproportionate SMR, in MitraClip recipients. We analysed 137 patients undergoing MitraClip implantation for SMR at three centres. SMR was classified as proportionate or disproportionate based on the median value of the ratio between effective regurgitant orifice area (EROA) and left ventricular end-diastolic volume (LVEDV). The primary endpoint was a composite of cardiovascular mortality and heart failure hospitalisation at two-year follow-up. Mean age was 70±10 years, 80% were male, and median EuroSCORE II was 5.7%. No differences were observed in the disproportionate compared to the proportionate group except for a more severe NYHA class and their expected higher EROA and lower LVEDV. Number of clips deployed, device success and procedural success were similar between the two groups. Residual mitral regurgitation (MR) >1+ at 30 days was more common among patients with an EROA >0.42 cm2 compared to those with an EROA ≤0.42 cm2 (81.3% vs 58%; p=0.004). The relative risk of the primary endpoint was independent from any echocardiographic parameter, including the presence of disproportionate SMR. The only independent predictors of clinical events were EuroSCORE II >8%, NYHA class and residual MR >1+ at 30 days. Echocardiographic parameters, including the EROA/LVEDV ratio, do not have independent prognostic value in patients undergoing MitraClip implantation. High surgical risk, advanced symptoms and non-optimal MR reduction increase the relative risk of two-year clinical events.

Prognostic value of three-dimensional echocardiographic right ventricular ejection fraction in patients with pulmonary arterial hypertension.

BackgroundRight ventricular (RV) function is an independent predictor of clinical outcomes in patients with pulmonary arterial hypertension (PAH). However, it remains controversial which RV parameter should be measured as an appropriate index for the treatment of PAH. The aim of this study was to identify the most useful parameter that correlates with hemodynamics and predicts clinical outcomes in PAH.ResultsMost of the clinical and echocardiographic RV parameters were significantly correlated with pulmonary vascular resistance (PVR) as well as mean pulmonary arterial pressure (mPAP). Among these, three dimensional right ventricular ejection fraction (3DRVEF) showed the strongest hemodynamic correlation, followed by 6-minute walk distance. Receiver operating characteristic analysis of association with cardiac events including death, hospitalization, and intervention revealed a greater area under the curve for 3DRVEF than for mPAP (0.78 vs. 0.74). Kaplan-Meier analysis showed that patients with 3DRVEF less than 38% had significantly shorter event-free survival than those with greater than 38% (P = 0.0007). Finally, the Cox proportional hazards analysis revealed that 3DRVEF, but not mPAP, was an independent predictor of clinical events in PAH.Materials and MethodsEighty-six consecutive patients were enrolled in this study. RV hemodynamic parameters were measured by right heart catheterization (RHC). RV function was assessed using two-dimensional speckle-tracking echocardiography and three-dimensional transthoracic echocardiography (3DTTE) to evaluate RV free wall global strain (RVFS) and RVEF.ConclusionsRVEF measured by 3DTTE could be a useful parameter for noninvasively assessing RV hemodynamics and predicting the clinical outcomes in PAH patients.

Impact of preprocedural atrial fibrillation on immediate and long-term outcomes after successful percutaneous mitral valvuloplasty of significant mitral stenosis

Optimal time to perform percutaneous mitral valvuloplasty (PMV) for patients with significant mitral stenosis (MS) and atrial fibrillation (AF) remains controversial. We sought to identify prognostic factors and evaluate long-term clinical outcomes after PMV of 77 consecutive patients with MS with a mitral valve area (MVA) <1.5 cm2. According to baseline heart rhythm, these patients were divided into sinus rhythm (SR; n = 24) and AF (n = 53) groups. The study endpoint was defined as a composite of all-cause mortality, admission for heart failure, mitral valve surgery, repeated PMV, and major cerebral vascular accident during follow-up. After successful PMV, there was no significant difference between the two groups in post-MVA and post-mitral mean pressure gradient. However, the New York Heart Association Functional Classification post-procedure was worse in the AF group (p < 0.01). In the AF group, event-free survival during follow-up was significantly lower compared with that of the SR group (p = 0.016). Independent predictors of clinical events were AF [hazard ratio (HR), 2.73; 95 % confidence interval (CI), 1.04–9.36; p = 0.03] and pulmonary artery systolic pressure (HR 2.57; 95 % CI 1.18–5.47; p = 0.017). Patients with AF at baseline were significantly associated with worse symptoms and higher event rates after successful PMV compared with those with SR. The clinical benefit of PMV may be considered for patients with MVA <1.5 cm2 before the onset of AF.

Early and midterm outcomes of bioresorbable vascular scaffolds for ostial coronary lesions: insights from the GHOST-EU registry.

We aimed to investigate the outcomes of bioresorbable vascular scaffolds (BVS) in coronary ostial lesions. Ostial lesions represent a challenging angiographic subset, with higher event rates compared with non-ostial lesions. BVS might be associated with advantages over the long term, but their safety in this setting remains to be explored. Procedural and 12-month follow-up data from consecutive patients treated with BVS for lesions located at the ostium of the right (RCA), left anterior (LAD) or circumflex (LCX) coronary in 11 European centres were collected. The primary device-oriented endpoint was defined as a combination of cardiovascular death, target vessel myocardial infarction or target lesion revascularisation. The database included a total of 1,549 lesions in 1,304 patients with a mean age of 62±11years. There were 90 ostial lesions (5.8%) in 84 patients (6.4%) located at the ostial RCA (14; 16%), LCX (29; 32%), or LAD (47; 52%). Patients presenting with ostial lesions did not differ from the remaining cohort except for a higher incidence of prior revascularisation. Predilation was performed in 97% of the lesions (vs. 96% in non-ostial, p=0.618), post-dilation in 43% (versus 58% in the non-ostial group, p=0.008). At quantitative coronary angiography, treatment of ostial lesions was associated with higher residual stenosis (30% [23-41] vs. 26% [20-37], p=0.035), but no difference in minimum lumen diameter existed (p=0.447). Follow-up data were available at 385 [362-465] days. The 12-month Kaplan-Meier estimated rates of scaffold thrombosis were 4.9% and 2.0% (ostial and non-ostial lesion groups, respectively, log-rank p=0.005). The device-oriented composite endpoint occurred, respectively, in 12.6% and 4.6% at 12 months (log-rank p=0.001). Treatment of ostial lesions was an independent predictor of this endpoint (p=0.0025, HR 2.65 [1.41-4.97]). In combination with a suboptimal implantation technique, treatment of coronary ostial lesions was an independent predictor of clinical events in a cohort of patients treated with BVS.

Incremental Prognostic Value of Brachial-Ankle Pulse Wave Velocity to Single-Photon Emission Computed Tomography in Patients with Suspected Coronary Artery Disease.

Arterial stiffness assessed by brachial-ankle pulse wave velocity (baPWV) is predictive of cardiovascular events. This study was designed to investigate whether baPWV has an additional prognostic value to single-photon emission computed tomography (SPECT) in patients with suspected coronary artery disease (CAD). A total of 350 subjects (age, 66.2 ± 10.5 years, 53.4% male) with suspected CAD undergoing myocardial SPECT and baPWV within 30 days were retrospectively analyzed. Cardiovascular events, including cardiovascular death, acute coronary syndrome and ischemic stroke, were assessed. Both fixed and reversible perfusion defects on SPECT were considered abnormal myocardial perfusion imaging (MPI) findings. During the median follow-up period of 441 days (interquartile range 169-719 days), cardiovascular events occurred in 21 patients (6.0%). In multivariable Cox regression analysis, abnormal MPI [hazard ratio (HR), 2.67; 95% confidence interval (CI), 1.21-10.37; p=0.024] and high baPWV (≥ 1,790 cm/s) (HR, 2.03; 95% CI, 1.08-6.38; p=0.007) were independent predictors of clinical events even after adjusting for possible confounders. Also, high baPWV had an incremental prognostic value to traditional risk factors and abnormal MPI in predicting cardiovascular events (overall Chi-square, from 24.08 to 27.42; p ＜ 0.001). Kaplan-Meier survival curves stratified by baPWV and MPI proved significantly improved prediction of cardiovascular events (log-rank p=0.001). baPWV has an incremental prognostic value to traditional risk factors and MPI. Therefore, baPWV can be used to identify subjects at higher risk of cardiovascular events in patients undergoing SPECT.

Abstract 11514: Adverse Events in Patients With Rheumatic Mitral Valve Disease in Sinus Rhythm

Introduction: Patients with rheumatic mitral stenosis (RMS) and atrial fibrillation (AF) have revealed a high incidence of systemic embolism. Current guidelines do not recommend anticoagulation in patient with RMS and sinus rhythm. Hypothesis: The predictors of clinical events may facilitate adverse outcome in RMS patients with sinus rhythm. Methods: A total 1,019 patients who diagnosed with RMS were evaluated retrospectively between March 2003 and June 2013. Of these, patients with past or present AF (n = 447), who used anticoagulants or had prior thromboembolism (n = 154), or who performed mitral valve replacement within 9-month after diagnosis (n = 125) were excluded. A total of 293 patients were included. The clinical events were defined as all cause death and systemic embolism. Results: During the mean follow-up period of 68.2 ± 36.6 months, clinical events were developed in twenty-one patients (7.2%; embolism 12, all cause death 9) with 2.1% of average annual event rate. In the Cox-proportional hazard regression analysis, age was independent predictor of clinical events (HR 1.07 (95% CI 1.01-1.13), p = 0.026) after adjustment of confounding factors. LA dimension ≥ 47 mm showed borderline significance to predict events (HR 2.45 (95% CI 0.98 - 6.15), p = 0.057). Mitral valve area was not associated with events. In middle and old aged group (age ≥ 50), LA dimension ≥ 47 mm was a good prognosticator (HR 2.97 (95% CI 1.05 - 8.36), p = 0.040). During follow-up, sixty patients (20.5%) were developed AF with 3.5% annual event rate. LA dimension ≥ 47 mm was an independent predictor of composite all events including clinical events and development of AF. Conclusions: New onset AF was frequently developed in patients with RMS and sinus rhythm. Because of high risk of embolism of valvular AF, we need careful follow up in these patients group. In middle and old age group, enlarged LA dimension was closely related with all cause death or systemic embolism.

Relation of Myocardial Systolic Mechanics to Serum Ferritin Level as a Prognosticator in Thalassemia Patients Undergoing Repeated Transfusion

Myocardial iron overload leading to congestive heart failure (HF) or arrhythmias is a recognized complication in thalassemia patients undergoing chronic blood transfusion. The relationship between myocardial iron load, subclinical systolic dysfunction, and clinical events remains less well known. We studied a total of 77 subjects, comprising 37 thalassemia patients (mean age: 24.2 ± 5.5 years) with a history of repeated blood transfusions, in addition to 40 age- and gender-matched controls (mean age: 24 ± 4.5 years). Serum ferritin levels were checked in all subjects, as well as semiautomated quantification of left ventricular (LV) longitudinal, circumferential, and radial deformations assessed by two-dimensional (2D) speckle tracking analysis. Compared with the control group, thalassemia patients showed significantly larger LV mass index and lower myocardial deformations (P < 0.05), but left ventricular ejection fraction (LVEF) did not differ significantly (P = 0.233). There was a significant linear correlation between serum ferritin level and longitudinal (r = 0.44, P = 0.0078) and radial strain (r = -0.46, P = 0.0051), with optimal cutoff provided to be -15.48%, -21.31%, and 26.67% for longitudinal, circumferential, and radial strain in predicting clinical events, respectively. During a median of 802.5 days follow-up, 11 clinical composites (HF incidence, ventricular tachyarrhythmia, and death) occurred (N = 9 subjects); subjects with composites had significantly reduced longitudinal and radial strain compared to those without (both P < 0.05). After adjusting for age, sex, serum ferritin level, and LV mass index, a worsening of longitudinal strain remained as an independent predictor of clinical events and death (HR: 6.05, P = 0.033). Subclinical systolic dysfunction appears more likely in thalassemia subjects with a history of repeated blood transfusions, which further correlated with serum ferritin levels. In addition, worsening LV myocardial deformation parameters may play an independent role in predicting clinical outcomes beyond traditional measures in this population.

Left Atrial and Left Ventricular Diastolic Function in Chronic Chagas Disease

Left atrial (LA) and left ventricular (LV) diastolic function analysis can yield new strategies to recognize early cardiac involvement and prognostic indicators in Chagas disease. Patients with Chagas disease with the indeterminate (n= 69) or with the cardiac form (32 with changes limited to electrocardiography [stage A], 25 with changes in LV systolic function but no heart failure [HF; stage B], and 26 with HF) underwent evaluation of LV diastolic function (mitral inflow, pulmonary vein flow, color M-mode echocardiography, and tissue Doppler analysis), and LA function by three-dimensional echocardiography and strain analysis and were prospectively followed for the occurrence of clinical events. Echocardiograms were also obtained from 32 controls. LV diastolic dysfunction was gradually more prevalent and severe across groups from patients with the indeterminate form of Chagas disease to patients with HF. Tissue Doppler was the best tool to demonstrate the worsening of LV diastolic function across the groups (E' velocity: controls, 12.6 ± 2.3 cm/sec; patients with the indeterminate form, 12.1 ± 3.1 cm/sec; stage A, 10.3 ± 2.9 cm/sec; stage B, 8.3 ± 2.8cm/sec; patients with HF, 5.6 ± 1.9; P < .0001). Although maximum LA volume was increased only in patients with HF, minimum LA volume (controls, 8 ± 2 mL/m(2); patients with the indeterminate form, 8 ± 2 mL/m(2); stage A, 9 ± 3 mL/m(2); stage B, 11 ± 4 mL/m(2); patients with HF, 27 ± 17 mL/m(2); P < .0001) and precontraction LA volume (controls, 11 ± 3 mL/m(2); patients with the indeterminate form, 12 ± 3 mL/m(2); stage A, 13 ± 4mL/m(2); stage B, 16 ± 5 mL/m(2); patients with HF, 32 ± 19 mL/m(2); P < .0001) were increased in all cardiac form groups. LA conductive function was depressed in all cardiac form groups, while LA contractile function was depressed only in patients with HF. Cox proportional-hazards regression analysis revealed that end-systolic LV diameter (hazard ratio, 1.6; 95% confidence interval, 0.9-2.8; P= .09), E' velocity (hazard ratio, 0.5; 95% confidence interval, 0.3-0.8; P= .001), and peak negative global LA strain (hazard ratio, 1.21; 95% confidence interval, 1.02-1.4; P= .03), were independent predictors of clinical events. LV diastolic dysfunction was found in all forms of chronic Chagas disease, including those without LV systolic dysfunction. LV diastolic dysfunction may contribute to changes in LA volume and conductive function found in early stages of the cardiac form. Both LV diastolic function and LA contractile function were independent predictors of clinical events.

Ventriculo-vascular coupling index in asymptomatic mild to moderate aortic stenosis: an important prognostic indicator

Purpose: Valve area and global hemodynamic load are important predictors of adverse outcome in moderate to severe aortic stenosis (AS). However, only limited data have been available to provide risk stratification. We evaluated whether ventriculo-vascular coupling index (VVCI) can be used as a prognosticator reflecting systemic hemodynamic load. Methods: A total of 848 consecutive asymptomatic patients (mean age, 71±12) with mild to moderate AS (jet velocity >2.0 m/s) were retrospectively analyzed. We excluded the patients who have aortic valve area <1.0 cm2 or ejection fraction <50%. Cardiovascular death, aortic valve replacement and admission for heart failure were regarded as clinical events. Results: During mean follow up duration of 23±21 months, 40 patients were died from cardiovascular cause, 25 patients experienced aortic valve replacement and 31 patients were admitted with heart failure. Estimated event-free survival was 93.0±1.0% at 1 year, 86.0±1.6% at 3 years and 75.7±3.0% at 5 years. In multivariate Cox regression analysis, VVCI turned out to be the most powerful predictor of clinical events (adjusted HR 5.39, [95% CI 1.85-15.66], P=0.002). The patients with higher VVCI (≥0.41; the best cut-off value in ROC analysis) experienced clinical events more frequently (8.3% vs. 16.6%; OR 2.2 [95% CI 1.40-3.43], P<0.001). Normal or low BMI (adjusted HR 0.89 [95% CI 0.82-0.96], P=0.003), low hemoglobin (adjusted HR 0.87 [95% CI 0.77-0.99], P=0.037) and high peak aortic jet velocity (adjusted HR 1.76 [95% CI 1.18-2.62], P=0.006) were also independent predictor of outcome. ![Figure][1] Kaplan-Meier event-free survival curves Conclusion: In addition to conventional parameters, VVCI, BMI and hemoglobin are also powerful independent predictors of clinical events in asymptomatic mild to moderate AS. [1]: pending:yes

Levels of von Willebrand factor antigen and von Willebrand factor cleaving protease (ADAMTS13) activity predict clinical events in chronic heart failure

Decreased activity of ADAMTS13, the von Willebrand factor (VWF) cleaving protease, was recently reported in cardiovascular diseases and in hepatic failure. Chronic heart failure (CHF) is characterised by abnormalities of left ventricular function accompanied by the failure of the liver and dysregulation of endothelial activation. Therefore, the aim of our study was to measure ADAMTS13 activity in CHF, and determine the prognostic value of VWF and ADAMTS13 on major clinical events in CHF. ADAMTS13 activity (measured by FRETS-VWF73 substrate) was decreased in CHF (n = 152, left ventricular ejection fraction <45%), and it correlated negatively with B-type natriuretic peptide (BNP) NYHA (New York Heart Association) classes, markers of synthetic capacity of the liver and endothelial dysfunction (all p < 0.005). Both, high VWF:Ag levels (hazard ratio [HR] 1.52, 95% confidence interval [CI] 1.189-1.943), and low ADAMTS13/VWF:Ag ratios (HR 0.70, 95% CI 0.58-0.84) independently and significantly predicted short-term (1 year follow-up) clinical adverse events in heart failure (HF). Decreased activity of ADAMTS13 with concomitant high VWF:Ag levels is a significant independent predictor of clinical events in CHF. The levels of the two molecules may integrate the impaired synthetic capacity of the liver and the disturbed endothelial regulation and can therefore be a useful tool to predict clinical events in CHF.

Abstract 569: NT-proBNP is an Important Independent Predictor of Clinical Events after Primary PCI for STEMI

Acute myocardial infarction with ST-segment elevation (STEMI) remains a major global public health issue. Despite advances in therapy, patients remain at risk for death, repeat myocardial infarction (MI) shock and heart failure (HF). Novel markers that predict those at risk are needed. We studied 903 STEMI patients in The Assessment of Pexelizumab in Acute Myocardial Infarction trial (which enrolled STEMI patients presenting &lt; 6 hrs of symptom onset who were to undergo primary PCI) in a case-control design (cases selected based on the trial’s primary composite outcome - death, shock or HF - and matched on age, gender and infarct location to controls). NT-proBNP (pg/ml) was measured at randomization and 24 hrs. Outcomes (individually and the composite) of death, shock, and HF at 90 days were examined by quartiles of NT-proBNP. A CART model was used to categorize adjusted risk. NT-proBNP was higher in patients who had events. Patients with higher NT-proBNP levels at baseline (median symptom onset to randomization 2.7 hrs) and 24 hrs had more events (composite p&lt;0.001; death p&lt;0.0001; HF p&lt;0.0001; shock p=0.05) - See figure . Using the CART model (adjusted for age, gender and infarct location), baseline Killip class and NT-proBNP could further subcategorize patients into 90 day mortality categories 4%, 10%, 30%, and 53%. In fact, only 4 patients (1%) with a 24 hour NT-proBNP &lt;999 pg/ml had any event in the next 90 days. Although the overall prognosis in STEMI patients undergoing primary PCI is good, NT-proBNP performed early and at 24 hrs provides important prognostic information for predicting negative outcomes i.e. shock, heart failure and death. Figure. Kaplan-Meier curve for the primary composite outcome stratified by baseline NT-proBNP (a), or 24 hour NT-proBNP (b).

Usefulness of N-Terminal Pro–Brain Natriuretic Peptide and Brain Natriuretic Peptide to Predict Cardiovascular Outcomes in Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction

More than 40% of patients hospitalized with heart failure have preserved left ventricular ejection fraction (HF-PLVEF) and are at high risk for cardiovascular (CV) events. The purpose of this study was to determine the value of N-terminal pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) in predicting CV outcomes in patients with HF-PLVEF. Participants with an ejection fraction >40% in the prospective CHARM Echocardiographic Substudy were included in this analysis. Plasma NT-proBNP levels were measured, and 2 cut-offs were selected prospectively at 300 pg/ml and 600 pg/ml. BNP cut-off was set at 100 pg/ml. Clinical characteristics were recorded, and systolic and diastolic function were evaluated by echocardiography. The primary substudy outcome was the composite of CV mortality, hospitalization for heart failure, and myocardial infarction or stroke. A total of 181 patients were included, and there were 17 primary CV events (9.4%) during a median follow-up time of 524 days. In a model including clinical characteristics, echocardiographic measures, and BNP or NT-proBNP, the composite CV event outcome was best predicted by NT-proBNP >300 pg/ml (hazard ratio 5.8, 95% confidence intervals [CI] 1.3 to 26.4, p = 0.02) and moderate or severe diastolic dysfunction on echocardiography. When NT-proBNP >600 pg/ml was used in the model, it was the sole independent predictor of primary CV events (hazard ratio 8.0, 95% CI 2.6 to 24.8, p = 0.0003) as was BNP >100 pg/ml (hazard ratio 3.1, 95% CI 1.2 to 8.2, p = 0.02) in the BNP model. In conclusion, both elevated NT-proBNP and BNP are strong independent predictors of clinical events in patients with HF-PLVEF.

Severe Left Ventricular Dyssynchrony Is Associated With Poor Prognosis in Patients With Moderate Systolic Heart Failure Undergoing Coronary Artery Bypass Grafting

The objective of the present study was to assess the relationship between the presence of left ventricular (LV) dyssynchrony and clinical outcome in patients with moderate systolic heart failure undergoing coronary artery bypass graft (CABG) surgery. The presence of LV dyssynchrony is associated with poor prognosis in patients with LV dysfunction. The study consisted of 215 consecutive patients with ischemic cardiomyopathy and dyspnea (age 65 +/- 9 years, 81% male) undergoing CABG. Dyssynchrony was calculated by tissue Doppler imaging from regional time intervals in basal LV segments before and 1 month after CABG. Myocardial viability was assessed using single-photon emission computed tomography (SPECT) before CABG. Twenty-five patients (11.6%) died within 30 days (in-hospital mortality) of CABG. The presence of pre-CABG dyssynchrony > or =119 ms had the highest predictive accuracy for in-hospital mortality, with a sensitivity of 84% and a specificity of 71%. During the median follow-up period of 359 days (interquartile range 219 to 561), an additional 19 patients (10.3%) died and 34 patients (18.5%) were hospitalized for worsening heart failure. At Cox regression analysis, post-CABG dyssynchrony > or =72 ms and > or =5 viable segments were identified as independent predictors of clinical events, with a hazard ratio (HR) of 5.02, 95% confidence interval (CI) 2.57 to 10.02 (p < 0.001), and an HR of 0.63, 95% CI 0.55 to 0.75 (p < 0.001), respectively. Patients without post-CABG dyssynchrony and with viable myocardium had excellent prognosis compared with patients with severe post-CABG dyssynchrony and nonviable myocardium (event rate 3% vs. 64%; p < 0.001). The presence of severe LV dyssynchrony is associated with poor clinical outcomes despite revascularization. These results advocate a routine assessment of both LV dyssynchrony and viability to predict outcome in systolic heart failure patients undergoing CABG surgery.