Objectives This study sought to determine the diagnostic accuracy of 64-slice computed tomographic coronary angiography (CTCA) to detect or rule out significant coronary artery disease (CAD). ...Background CTCA is emerging as a noninvasive technique to detect coronary atherosclerosis. Methods We conducted a prospective, multicenter, multivendor study involving 360 symptomatic patients with acute and stable anginal syndromes who were between 50 and 70 years of age and were referred for diagnostic conventional coronary angiography (CCA) from September 2004 through June 2006. All patients underwent a nonenhanced calcium scan and a CTCA, which was compared with CCA. No patients or segments were excluded because of impaired image quality attributable to either coronary motion or calcifications. Patient-, vessel-, and segment-based sensitivities and specificities were calculated to detect or rule out significant CAD, defined as ≥50% lumen diameter reduction. Results The prevalence among patients of having at least 1 significant stenosis was 68%. In a patient-based analysis, the sensitivity for detecting patients with significant CAD was 99% (95% confidence interval CI: 98% to 100%), specificity was 64% (95% CI: 55% to 73%), positive predictive value was 86% (95% CI: 82% to 90%), and negative predictive value was 97% (95% CI: 94% to 100%). In a segment-based analysis, the sensitivity was 88% (95% CI: 85% to 91%), specificity was 90% (95% CI: 89% to 92%), positive predictive value was 47% (95% CI: 44% to 51%), and negative predictive value was 99% (95% CI: 98% to 99%). Conclusions Among patients in whom a decision had already been made to obtain CCA, 64-slice CTCA was reliable for ruling out significant CAD in patients with stable and unstable anginal syndromes. A positive 64-slice CTCA scan often overestimates the severity of atherosclerotic obstructions and requires further testing to guide patient management.
Abstract Background Previous studies suggested that electrical abnormalities precede overt structural disease in arrhythmogenic right ventricular cardiomyopathy (ARVC). Abnormal RV deformation has ...been reported in early ARVC without structural abnormalities. The pathophysiological mechanisms underlying these abnormalities remain unknown. Objectives The authors used imaging and computer simulation to differentiate electrical from mechanical tissue substrates among ARVC clinical stages. Methods ARVC desmosomal mutation carriers (n = 84) were evaluated by electrocardiography (ECG), Holter monitoring, late-enhancement cardiac magnetic resonance imaging, and echocardiographic RV deformation imaging. Subjects were categorized based on the presence of 2010 International Task Force criteria: 1) subclinical stage (n = 21); 2) electrical stage (n = 15); and 3) structural stage (n = 48). Late enhancement was not present in any subclinical or electrical stage subjects. Results Three distinctive characteristic RV longitudinal deformation patterns were identified: type I: normal deformation (n = 12); type II: delayed onset of shortening, reduced systolic peak strain, and mild post-systolic shortening (n = 35); and type III: systolic stretching with large post-systolic shortening (n = 37). A majority (69%) of structural staged mutation carriers were type III, whereas a large proportion of both electrical and subclinical stage subjects (67% and 48%, respectively) were type II. Computer simulations demonstrated that the type II pattern can be explained by a combination of reduced contractility and mildly increased passive myocardial stiffness. This evolved into type III by aggravating both mechanical substrates. Electrical activation delay alone explained none of the patterns. Conclusions Different ARVC stages were characterized by distinct RV deformation patterns, all of which could be reproduced by simulating different degrees of mechanical substrates. Subclinical and electrical staged ARVC subjects already showed signs of local mechanical abnormalities. Our novel approach could lead to earlier disease detection and, thereby, influence current definitions of electrical and subclinical ARVC stages.
The clinical profile of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) patients with late presentation is unknown.
The purpose of this study was to characterize the genotype, ...cardiac phenotype, and long-term outcomes of ARVC/D patients with late presentation (age ≥50 years at diagnosis).
Five hundred two patients with an ARVC/D diagnosis from Johns Hopkins and Utrecht Registries were studied and long-term clinical outcomes ascertained.
Late presentation was seen in 104 patients (21%; 38% PKP2 carriers); 3% were ≥65 years at diagnosis. Sustained ventricular tachycardia was the major (43%) mode of presentation in patients with late presentation, whereas cardiac syncope was infrequent (P <.001). Those with late presentation were significantly less likely to harbor a known pathogenic mutation (53%; P = .005), have less precordial T-wave repolarization changes (P <.001), and have lower ventricular ectopy burden (P = .026). Over median 6-year follow-up, 68 patients with late presentation (65%) experienced sustained ventricular arrhythmias, with similar arrhythmia-free survival at 5-year follow up (P = .48). Left ventricular dysfunction and heart failure were seen in 24 (32%) and 15 patients (14%), respectively, without need for cardiac transplantation. In the late presentation cohort, male sex, pathogenic mutation, right ventricular structural disease, lack of family history, and electrophysiologic study inducibility were associated with increased arrhythmic risk.
One-fifth of all ARVC/D patients present after age 50 years, often with sustained ventricular tachycardia, and are less likely to have prior syncope, ECG changes, ventricular ectopy, or identifiable pathogenic mutation. In ARVC/D, late presentation does not confer a benign prognosis and is associated with high arrhythmic risk.
The overt stage of arrhythmogenic right ventricular (RV) dysplasia/cardiomyopathy (ARVD/C) is preceded by a concealed stage with minor or no signs of disease. However, sudden death may occur in this ...early phase. Deformation imaging may contribute to early diagnosis. The aims of this study were to compare the diagnostic accuracy of the conventional (1994) versus the recently published (2010) new echocardiographic criteria for ARVD/C and to evaluate the additional value of echocardiographic tissue deformation imaging to detect subclinical RV functional abnormalities in asymptomatic carriers of pathogenic ARVD/C mutations.
Fourteen asymptomatic first-degree relatives of ARVD/C probands (the ARVD/C-r group; mean age, 38.0 ± 13.2 years) with a pathogenic plakophilin-2 mutation and a group of age-matched controls (n = 56; mean age, 38.2 ± 12.7 years) were included at a 1:4 ratio. A complete echocardiographic evaluation (dimensions, global systolic parameters, and visual assessment and deformation imaging of the RV free wall including Doppler tissue imaging and two-dimensional strain echocardiography) was obtained. Peak systolic strain less negative than -18% and/or postsystolic shortening (postsystolic index > 15%) in any RV segment was considered abnormal.
RV dimensions in the ARVD/C-r group were similar to those in controls (RV outflow tract, 15.4 ± 2.9 vs 14.4 ± 1.9 mm/m(2), P = NS; RV inflow tract, 18.6 ± 2.6 vs 19.1 ± 2.6 mm/m(2), P = NS), and global systolic parameters were moderately reduced (tricuspid annular plane systolic excursion, 20.0 ± 3.2 vs 23.9 ± 2.8 mm, P = .001; RV fractional area change, 40.3 ± 8.4 vs 40.6 ± 7.1, P = NS). According to task force criteria, 57% of the ARVD/C-r group and 29% of controls were classified as abnormal when applying the 1994 criteria and 29% and 4% when applying the 2010 criteria, respectively. Doppler tissue imaging and two-dimensional strain deformation (and strain rate) values were reduced in the ARVD/C-r group in the basal and mid RV segments compared with controls (P < .001). In the ARVD/C-r group, peak systolic strain less negative than -18% was seen in six patients (43%), postsystolic strain in nine (64%), and either abnormality in 10 (71%), almost exclusively in the basal segment; these findings were observed in none of the controls.
The 2010 criteria for ARVD/C improve specificity, whereas sensitivity is significantly reduced in this asymptomatic population. In contrast, echocardiographic deformation imaging detects functional abnormalities in the subtricuspid region in 71% of asymptomatic carriers of a pathogenic plakophilin-2 mutation, while regional deformation was normal in all control subjects, indicating superiority of both sensitivity and specificity with these new modalities.
Objectives This study sought to evaluate the vascular risk of low high-density lipoprotein-cholesterol (HDL-C) in relation to the use and intensity of lipid-lowering medication in patients with ...clinically manifest vascular diseases. Background Low levels of HDL-C are associated with an increased risk for vascular diseases and may contribute to residual vascular risk in patients already treated for other risk factors. However, post-hoc analyses from statin trials indicate that the vascular risk associated with low HDL-C may be low or even absent in patients using intensive statin therapy. Methods We performed a prospective cohort study of 6,111 patients with manifest vascular disease. Cox proportional hazards models were used to evaluate the risk of HDL-C on vascular events in patients using no, usual dose, or intensive lipid-lowering therapy. Results New vascular events (myocardial infarction, stroke, or vascular death) occurred in 874 subjects during a median follow-up of 5.4 years (interquartile range: 2.9 to 8.6 years). In patients not using lipid-lowering medication at baseline (n = 2,153), a 0.1 mmol/l increase in HDL-C was associated with a 5% reduced risk for all vascular events (hazard ratio HR: 0.95; 95% confidence interval CI: 0.92 to 0.99). In patients on usual dose lipid-lowering medication (n = 1,910) there was a 6% reduced risk (HR: 0.94; 95% CI: 0.90 to 0.98). However, in patients using intensive lipid-lowering treatment (n = 2,046), HDL-C was not associated with recurrent vascular events (HR: 1.02; 95% CI: 0.98 to 1.07) irrespective of low-density lipoprotein cholesterol level. Conclusions In patients with clinically manifest vascular disease using no or usual dose lipid-lowering medication, low plasma HDL-C levels are related to increased vascular risk, whereas in patients using intensive lipid-lowering medication, HDL-C levels are not related to vascular risk.
Among studies describing the phenotype of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), significant discrepancy exists regarding the extent and impact of left ventricular (LV) ...involvement. The capability of conventional and new quantitative echocardiographic techniques to accurately detect LV involvement in ARVD/C remains unknown. The aim of this study was to test the hypothesis that accurate detection of LV involvement on echocardiography identifies patients at additional risk for cardiac events during follow-up.
Thirty-eight patients with ARVD/C, 16 pathogenic mutation-positive relatives, and 55 healthy control subjects were prospectively enrolled. Conventional echocardiography with additional deformation imaging was performed in all subjects to detect LV involvement. In a subgroup (n = 27), cardiac magnetic resonance imaging was performed with late enhancement. All patients and relatives were prospectively followed for events (sustained ventricular tachycardia, appropriate implantable cardioverter-defibrillator intervention, sudden cardiac death, and heart transplantation).
Conventional echocardiography detected LV involvement in 32% of patients with ARVD/C and in none of the relatives. Deformation imaging revealed LV involvement in 68% of patients with ARVD/C and 25% of relatives and was correlated closely with late enhancement on cardiac magnetic resonance imaging. During a mean follow-up period of 5.9 ± 2.3 years, 20 patients with ARVD/C (53%) experienced events, and no events occurred in the relatives. LV involvement detected by deformation imaging (hazard ratio, 4.9; 95% CI, 1.7-14.2) and right ventricular outflow tract enlargement (hazard ratio, 1.2; 95% CI, 1.1-1.3) were the only independent predictors of outcomes.
Deformation imaging detected a high incidence of LV involvement in patients with ARVD/C and their relatives. Compared with conventional echocardiography, deformation imaging is superior in detecting minor LV involvement. LV involvement and an enlarged right ventricular outflow tract are independent prognostic markers of outcomes.
...the authors combined patients who met the TFC (>=4 diagnostic points) with patients who had only 3 diagnostic points. Structural abnormalities in children with ARVD/C are often mild, and involve ...focal subtricuspid dyskinesia with preserved global function rather than severe RV enlargement.
Image guidance to assist left ventricular (LV) lead placement may improve outcome after cardiac resynchronization therapy (CRT), but previous approaches and results varied greatly, and multicenter ...feasibility is lacking altogether.
We sought to investigate the multicenter feasibility of image guidance for periprocedural assistance of LV lead placement for CRT.
In 30 patients from 3 hospitals, cardiac magnetic resonance imaging was performed within 3 months prior to CRT to identify myocardial scar and late mechanical activation (LMA). LMA was determined using radial strain, plotted over time. Segments without scar but clear LMA were classified as optimal for LV lead placement, according to an accurate 36-segment model of the whole heart. LV leads were navigated using image overlay with periprocedural fluoroscopy. After 6 months, volumetric response and super-response were defined as ≥15% or ≥30% reduction in LV end-systolic volume, respectively.
Periprocedural image guidance was successfully performed in all CRT patients (age 66 ± 10 years; 59% men, 62% with nonischemic cardiomyopathy, 69% with left bundle branch block). LV leads were placed as follows: within (14%), adjacent (62%), or remote (24%) from the predefined target. According to the conventional 18-segment model, a remote position occurred only once (3%). On average, 86% of patients demonstrated a volumetric response (mean LV end-systolic volume reduction 36 ± 29%), and 66% of all patients were super-responders.
On-screen image guidance for LV lead placement in CRT was feasible in a multicenter setting. Efficacy will be further investigated in the randomized controlled ADVISE (Advanced Image Supported Lead Placement in Cardiac Resynchronization Therapy) trial (NCT05053568).
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Obesity is related to left ventricular hypertrophy (LVH). Whether LVH on electrocardiography (ECG-LVH) is a result of increased cardiac electrical activity or due to increased left ventricular mass ...(LVM) remains to be determined. The aims of the present study were to investigate the relation between obesity and ECG-LVH and LVM by magnetic resonance imaging (MRI-LVM) in patients with hypertension and to investigate the relation of insulin resistance (IR) and LVH. Patients with hypertension (n = 421) were evaluated using Sokolow-Lyon voltage, Cornell voltage, and cardiac magnetic resonance imaging. Waist circumference was used as a measure of abdominal obesity. Linear regression analysis revealed an inverse relation (adjusted β = −0.02, 95% confidence interval −0.02 to −0.01) between waist circumference and Sokolow-Lyon voltage, indicating a decrease of 0.02 mV per 1-cm increase in waist circumference. There was a positive relation between waist circumference and MRI-LVM (β = 0.49, 95% confidence interval 0.32 to 0.67). Patients in the highest quartile of LVM had a worse metabolic profile than patients with the Sokolow-Lyon voltage criterion. The relations of IR with ECG-LVH and MRI-LVM were similar to those of waist circumference in relation to ECG-LVH and MRI-LVM. In conclusion, there is an inverse relation between waist circumference and ECG-LVH and a positive relation between waist circumference and MRI-LVM. This study indicates that obesity has a different relation to voltage criteria for LVH compared to anatomic criteria for LVH, supporting the hypothesis that IR decreases electrocardiographic voltages, despite an increase in MRI-LVM. The clinical implication is that especially in patients with IR, Sokolow-Lyon voltage is low in contrast to high MRI-LVM.
Abstract Background Studies have shown that red cell distribution width (RDW) is related to outcome in chronic heart failure (CHF). The pathophysiological process is unknown. We studied the ...relationship between RDW and erythropoietin (EPO) resistance, and related factors such as erythropoietic activity, functional iron availability and hepcidin. Methods and Results In the Mechanisms of Erythropoietin Action in the Cardiorenal Syndrome (EPOCARES) study, which investigates the role of EPO in 54 iron-supplemented anemic patients with CHF and chronic kidney disease (CKD) (n = 35 treated with 50 IU/kg/wk Epopoetin beta, n = 19 control), RDW was not associated with EPO resistance. We defined EPO resistance by EPO levels ( r = 0.12, P = .42), the observed/predicted log EPO ratio ( r = 0.12, P = .42), the increase in reticulocytes after 2 weeks of EPO treatment ( r = −0.18, P = .31), and the increase of hemoglobin after 6 months of EPO treatment ( r = 0.26, P = .35). However, RDW was negatively correlated with functional iron availability (reticulocyte hemoglobin content, r = −0.48, P < .001, and transferrin saturation, r = −0.39, P = .005) and positively with erythropoietic activity (soluble transferrin receptor, r = 0.48, P < .001, immature reticulocyte fraction, r = 0.36, P = .01) and positively with interleukin-6 ( r = 0.48, P < .001). No correlation existed between hepcidin-25 and RDW. Conclusions EPO resistance was not associated with RDW. RDW was associated with functional iron availability, erythropoietic activity, and interleukin-6 in anemic patients with CHF and CKD.
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