Impact of statins based on high-risk plaque features on coronary plaque progression in mild stenosis lesions: results from the PARADIGM study.

AIMS: To investigate the impact of statins on plaque progression according to high-risk coronary atherosclerotic plaque (HRP) features and to identify predictive factors for rapid plaque progression in mild coronary artery disease (CAD) using serial coronary computed tomography angiography (CCTA). METHODS AND RESULTS: We analyzed mild stenosis (25-49%) CAD, totaling 1432 lesions from 613 patients (mean age, 62.2 years, 63.9% male) and who underwent serial CCTA at a ≥2 year inter-scan interval using the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging (NCT02803411) registry. The median inter-scan period was 3.5 ± 1.4 years; plaques were quantitatively assessed for annualized percent atheroma volume (PAV) and compositional plaque volume changes according to HRP features, and the rapid plaque progression was defined by the ≥90th percentile annual PAV. In mild stenotic lesions with ≥2 HRPs, statin therapy showed a 37% reduction in annual PAV (0.97 ± 2.02 vs. 1.55 ± 2.22, P = 0.038) with decreased necrotic core volume and increased dense calcium volume compared to non-statin recipient mild lesions. The key factors for rapid plaque progression were ≥2 HRPs [hazard ratio (HR), 1.89; 95% confidence interval (CI), 1.02-3.49; P = 0.042], current smoking (HR, 1.69; 95% CI 1.09-2.57; P = 0.017), and diabetes (HR, 1.55; 95% CI, 1.07-2.22; P = 0.020). CONCLUSION: In mild CAD, statin treatment reduced plaque progression, particularly in lesions with a higher number of HRP features, which was also a strong predictor of rapid plaque progression. Therefore, aggressive statin therapy might be needed even in mild CAD with higher HRPs. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02803411.

Independent association of serum uric acid levels with arterial stiffness in the absence of established cardiovascular disorders.

BACKGROUND: The impact of serum uric acid (SUA) on atherosclerosis has been suspected to be epiphenomenal owing to its close relationship with metabolic abnormalities. The aim of the present study was to evaluate the association between SUA levels and arterial stiffness in the absence of established cardiovascular (CV) disorders. METHODS: The relationship between SUA levels and brachial-ankle pulse wave velocity (baPWV) was examined in 353 asymptomatic adults (57 ± 8 years, 11.9% men) without established CV disorders defined as systolic blood pressure (BP) ≥140 mmHg or diastolic BP ≥ 90 mmHg; total cholesterol ≥240 mg/dL; low-density lipoprotein cholesterol ≥160 mg/dL; high-density lipoprotein cholesterol <40 mg/dL; fasting glucose ≥126 mg/dL; body mass index ≥25.0 kg/m2 ; current smoking; and history of medication for hypertension, diabetes, and dyslipidemia. Subjects were stratified into four groups based on the quartiles of their SUA levels. RESULTS: Mean baPWV was significantly different in all groups: group I, 1320 ± 195 cm/s; group II, 1336 ± 195 cm/s; group III, 1404 ± 199 cm/s; and group IV, 1483 ± 248 cm/s (P < .001). SUA levels were significantly correlated with baPWV (r = .364) (P < .001). Multivariate linear regression analysis showed that SUA (ß: 32.93; 95% confidence interval [CI]: 18.99-54.87), together with age (ß: 11.44; 95% CI: 9.36-13.53) and systolic BP (ß: 8.98; 95% CI: 6.80-11.16), was significantly associated with baPWV (P < .001). CONCLUSIONS: High SUA levels have an independent association with increased arterial stiffness even in subjects without established CV disorders.

Increasing incidence of macular edema in excessive morning blood pressure surge in patients with retinal vein occlusion.

Morning blood pressure surge (MBPS) had been known to be associated with hypertensive target organ injury and vascular events. Retinal vein occlusion (RVO) is also known to be related with underlying cardiovascular risk factors. This study investigated the effect of MBPS on patients with RVO. In total, 76 patients with RVO who had undergone systemic cardiovascular examination including a 24-hour ambulatory blood pressure monitoring, carotid artery intima media thickness, and pulse wave velocity were evaluated between January 2015 and February 2019. The MBPS was calculated as follows: mean systolic blood pressure measured over two hours after awakening minus mean systolic blood pressure measured during the one hour that included the lowest sleep blood pressure. Macular edema was significantly more prevalent in the MBPS group compared with the non-MBPS group. After adjusting for confounding factors, multivariate regression analyses revealed that MBPS independently predicted macular edema in patients with RVO [Odds ratio 4.75, 95% confidence interval 1.136-16.6, p = 0.015]. In conclusion, evaluating blood pressure patterns, especially MBPS, using 24-hour ambulatory blood pressure monitoring may be useful for assessing and predicting ophthalmologic outcome and may facilitate better blood pressure control in patients with RVO.

Association of High-Density Calcified 1K Plaque With Risk of Acute Coronary Syndrome.

Importance: Plaque morphologic measures on coronary computed tomography angiography (CCTA) have been associated with future acute coronary syndrome (ACS). However, the evolution of calcified coronary plaques by noninvasive imaging is not known. Objective: To ascertain whether the increasing density in calcified coronary plaque is associated with risk for ACS. Design, Setting, and Participants: This multicenter case-control cohort study included individuals enrolled in ICONIC (Incident Coronary Syndromes Identified by Computed Tomography), a nested case-control study of patients drawn from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry, which included 13 study sites in 8 countries. Patients who experienced core laboratory-verified ACS after baseline CCTA (n = 189) and control individuals who did not experience ACS after baseline CCTA (n = 189) were included. Patients and controls were matched 1:1 by propensity scores for age; male sex; presence of hypertension, hyperlipidemia, and diabetes; family history of premature coronary artery disease (CAD); current smoking status; and CAD severity. Data were analyzed from November 2018 to March 2019. Exposures: Whole-heart atherosclerotic plaque volume was quantitated from all coronary vessels and their branches. For patients who underwent invasive angiography at the time of ACS, culprit lesions were coregistered to baseline CCTA lesions by a blinded independent reader. Low-density plaque was defined as having less than 130 Hounsfield units (HU); calcified plaque, as having more than 350 HU and subcategorized on a voxel-level basis into 3 strata: 351 to 700 HU, 701 to 1000 HU, and more than 1000 HU (termed 1K plaque). Main Outcomes and Measures: Association between calcium density and future ACS risk. Results: A total of 189 patients and 189 matched controls (mean [SD] age of 59.9 [9.8] years; 247 [65.3%] were male) were included in the analysis and were monitored during a mean (SD) follow-up period of 3.9 (2.5) years. The overall mean (SD) calcified plaque volume (>350 HU) was similar between patients and controls (76.4 [101.6] mm3 vs 99.0 [156.1] mm3; P = .32), but patients who experienced ACS exhibited less 1K plaque (>1000 HU) compared with controls (3.9 [8.3] mm3 vs 9.4 [23.2] mm3; P = .02). Individuals within the highest quartile of 1K plaque exhibited less low-density plaque, as a percentage of total plaque, when compared with patients within the lower 3 quartiles (12.6% [10.4%] vs 24.9% [20.6%]; P < .001). For 93 culprit precursor lesions detected by CCTA, the volume of 1K plaque was lower compared with the maximally stenotic lesion in controls (2.6 [7.2] mm3 vs 7.6 [20.3] mm3; P = .01). The per-patient and per-lesion results were similar between the 2 groups when restricted to myocardial infarction cases. Conclusions and Relevance: Results of this study suggest that, on a per-patient and per-lesion basis, 1K plaque was associated with a lower risk for future ACS and that measurement of 1K plaque may improve risk stratification beyond plaque burden.

Preclinical Evaluation of a Noncontact Simultaneous Monitoring Method for Respiration and Carotid Pulsation Using Impulse-Radio Ultra-Wideband Radar.

There has been the possibility for respiration and carotid pulsation to be simultaneously monitored from a distance using impulse-radio ultra-wideband (IR-UWB) radar. Therefore, we investigated the validity of simultaneous respiratory rates (RR), pulse rates (PR) and R-R interval measurement using IR-UWB radar. We included 19 patients with a normal sinus rhythm (NSR) and 14 patients with persistent atrial fibrillation (PeAF). The RR, PR, R-R interval and rhythm were obtained simultaneously from the right carotid artery area in a supine position and under normal breathing conditions using IR-UWB radar. There was excellent agreement between the RR obtained by IR-UWB radar and that manually counted by a physician (intraclass correlation coefficient [ICC] 0.852). In the NSR group, there was excellent agreement between the PR (ICC 0.985), average R-R interval (ICC 0.999), and individual R-R interval (ICC 0.910) measured by IR-UWB radar and electrocardiography. In the PeAF group, PR (ICC 0.930), average R-R interval (ICC 0.957) and individual R-R interval (ICC 0.701) also agreed well between the two methods. These results demonstrate that IR-UWB radar can simultaneously monitor respiration, carotid pulse and heart rhythm with high precision and may thus be utilized as a noncontact continuous vital sign monitoring in clinical practice.

Sick Sinus Syndrome After the Maze Procedure Performed Concomitantly With Mitral Valve Surgery.

Background To characterize the development of sick sinus syndrome ( SSS ) after the additive maze procedure ( MP ) during mitral valve surgery. Methods and Results Follow-up data (median, 3.6 years) of 750 patients with a prevalence of rheumatic cause of 57.6% were analyzed. SSS occurred in 35 patients with a time-dependent increase: the incidence rates at 1, 2, and 4 years after surgery were 2.9%, 3.7%, and 4.3%, respectively. The additive MP showed higher risks of SSS development (hazard ratio, 7.44; 95% confidence interval, 3.45-16.05; P<0.001) and pacemaker implantation (hazard ratio, 3.61; 95% confidence interval, 1.95-6.67; P<0.001). Patients who developed SSS showed higher 4-year rates of clinical events (death, stroke, and hospital admission) (67.5±8.5% versus 33.0±1.9%; P<0.001). After adjustment for age and preoperative peak systolic pulmonary artery pressure, the lesion extent (biatrial versus left atrial MP ), not the underlying cause (rheumatic versus nonrheumatic), was independently associated with SSS development (hazard ratio, 3.58; 95% confidence interval, 1.08-11.86; P=0.037). The adverse effect of the biatrial MP was confirmed in patients with trivial or mild preoperative tricuspid regurgitation showing higher SSS incidence (4.6±1.4% versus 1.0±0.7%; P=0.023), not in those with moderate-to-severe tricuspid regurgitation (6.8±1.7% versus 3.8±3.8%; P=0.337). Recurrence of atrial fibrillation was not associated with the lesion extent of the MP . Conclusions After the additive MP , the ongoing risk of SSS development should be acknowledged irrespective of the underlying cause. Considering additive risk of biatrial MP with similar atrial fibrillation recurrence rate, minimizing lesion extent is warranted.

Initial surgery versus conservative management of symptomatic severe mitral regurgitation in the elderly.

OBJECTIVE: In elderly patients, the benefit of surgical correction of severe mitral regurgitation (MR) may not be greater than the operative risk. This study sought to compare the long-term clinical outcomes between initial surgery and conservative management in elderly patients (≥70 years of age) with severe MR. METHODS: We prospectively evaluated 157 consecutive patients (75 men, 74±4 years of age) with severe degenerative MR and mild symptoms. Mitral valve surgery was performed on 79 (initial surgery group), whereas the conservative strategy was chosen for 78 patients (conservative management group). We compared the overall and cardiac mortality and cardiac event between strategies in the overall and propensity-matched cohort (46 pairs). RESULTS: During the median follow-up of 5.4 years, overall death occurred less in the initial surgery group (16 vs 37 patients). This group showed reduced cardiac mortality (HR 0.31; 95% CI 0.13 to 0.73; p=0.007), overall mortality (HR 0.39; 95% CI 0.21 to 0.74; p=0.004) and cardiac event (HR 0.26; 95% CI 0.13 to 0.53; p<0.001). A significant reduction in cardiac mortality (HR 0.18; 95% CI 0.05 to 0.63; p=0.007), overall mortality (HR 0.36; 95% CI 0.15 to 0.86; p=0.022) and cardiac event (HR 0.20; 95% CI 0.07 to 0.52; p=0.001) in the initial surgery group was also observed in the propensity-matched cohort. CONCLUSIONS: In elderly patients with severe degenerative MR and mild symptoms, initial surgical strategy was associated with significant long-term reductions in cardiac and overall mortality compared with conservative management.

Comparison of Results of Tricuspid Valve Repair Versus Replacement for Severe Functional Tricuspid Regurgitation.

The optimal decision regarding whether to repair or replace the tricuspid valve (TV) remains controversial in patients with very severe functional tricuspid regurgitation (TR). We sought to compare clinical outcomes of TV repair versus replacement for very severe TR associated with severe TV tethering. We included 96 consecutive patients (20 men, 58 ± 11 years of age) who had both severe tethering of TV and very severe functional TR and consequently underwent TV surgery during left-sided valve surgery. TV repair was performed on 79 patients (repair group), whereas 17 patients underwent TV replacement (replacement group). The primary end point of the study was defined as the composite of operative mortality, cardiac death, repeat TV surgery, and hospitalization due to congestive heart failure during follow-up. The 2 groups had similar baseline clinical, echocardiographic, and operative characteristics, but operative mortality was significantly higher in the replacement group than in the repair group (p = 0.008). During a median follow-up of 87 months, 19 patients (24%) in the repair group and 8 (47%) in the replacement group attained the composite end point, and TV replacement was independently associated with end points in the Cox proportional hazards analysis after adjustment with propensity score (hazard ratio 4.033, 95% CI 1.470 to 11.071; p = 0.007). In conclusion, compared with TV repair, replacement was associated with higher operative mortality and worse long-term clinical outcomes in patients with very severe functional TR. Repair should be the preferred surgical option even for severe TR associated with more advanced tethering and right ventricular dilatation.

Clinical Implications of Three-Dimensional Real-Time Color Doppler Transthoracic Echocardiography in Quantifying Mitral Regurgitation: A Comparison with Conventional Two-Dimensional Methods.

BACKGROUND: Automatic quantification of real-time three-dimensional (3D) full-volume color Doppler transthoracic echocardiography (FVCD) has been proposed as a feasible and accurate method for quantifying MR. We aimed to explore the clinical implications of real-time 3D-FVCD for mitral regurgitation (MR) with various clinical manifestations, in comparison with the conventional two-dimensional (2D) proximal isovelocity surface area (PISA) and volumetric method and cardiac magnetic resonance imaging (CMR) methods. METHODS: A total 186 patients with MR were enrolled prospectively. Based on exclusion criteria and image quality review, 152 patients were included in the final analysis for 3D-FVCD and 2D transthoracic echocardiography. Among them, 37 patients underwent subsequent CMR for the validation of 3D-FVCD. RESULTS: MR volume from 3D-FVCD demonstrated a better agreement (r = 0.94) with CMR than 2D-PISA or the 2D volumetric method (VM; r = 0.87 vs 0.56). Overall, 2D methods underestimated MR when compared with 3D-FVCD (35.4 ± 28.4 mL for 2D-VM vs 43.8 ± 24.6 mL for 2D-PISA vs 64.6 ± 35.1 mL for 3D-FVCD; P < .001). In subgroup analysis, multijet MR (odds ratio [OR], 6.30; 95% CI, 2.52-15.72) and dilated left ventricular end-systolic diameter ≥40 mm (OR, 2.90; 95% CI, 1.12-7.50) were predictors of significant difference in MR volume (>30 mL for primary MR and >15 mL for secondary MR) between 2D-PISA and 3D-FVCD. In identifying surgical candidates, patients with multijet MR (OR, 4.53, 95% CI, 1.99-10.35) demonstrated a higher risk of discrepancy between 2D-PISA and 3D-FVCD, which were consistent in both primary and secondary MR, respectively. CONCLUSIONS: MR quantification with 3D-FVCD showed better correlation and agreement than conventional 2D methods. MR was underestimated by 2D methods, especially in multijet and dilated left ventricle. Multijet MR demonstrated higher risk of discrepancy for the identification of surgical candidate, regardless of MR etiology.

Association of Thoracic Aorta Calcium Score With Left Ventricular Hypertrophy and Clinical Outcomes in Patients With Severe Aortic Stenosis After Aortic Valve Replacement.

BACKGROUND: Substantial aortic calcification is known to be associated with aortic stiffening and subsequent left ventricular (LV) hypertrophy. This study examined whether the thoracic aorta calcium score (TACS) is related to LV hypertrophy and whether it leads to an adverse prognosis in patients with severe aortic stenosis (AS) after aortic valve replacement (AVR). METHODS: We retrospectively reviewed 47 patients (mean age, 64 ± 11 years) with isolated severe AS who underwent noncontrast computed tomography of the entire thoracic aorta and who received AVR. TACS was quantified using the volume method with values becoming log transformed (log[TACS+1]). Transthoracic echocardiography was performed before and 1 year after the operation. RESULTS: Preoperative LV mass index (LVMI) displayed significant positive correlations with male gender (r = 0.430, p = 0.010) and log(TACS+1) (r = 0.556, p = 0.003). In multivariate linear regression analysis, only log(TACS+1) was independently associated with LVMI, even after adjusting for age, gender, transaortic mean pressure gradient, and coronary or valve calcium score. Independent determinants for postoperative LVMI included log(TACS+1) and preoperative LVMI after 1 year of follow-up echocardiography, adjusting for age, gender, indexed effective orifice area, and coronary or valve calcium score. During a median follow-up period of 54 months after AVR, there were 10 events (21%), which included 4 deaths from all-causes, 3 strokes, 2 inpatient admissions for heart failure, and 1 myocardial infarction. The event-free survival rate was significantly lower for patients with TACS of 2,257 mm3 or higher compared with those whose TACS was lower than 2,257 mm3 (log-rank p < 0.001). CONCLUSIONS: High TACS was associated with increased LVMI among patients with severe AS. Further, high TACS usefully predicted less regression of LVMI and poor clinical outcomes after AVR. TACS may serve as a useful proxy for predicting LV remodeling and adverse prognosis in patients with severe AS undergoing AVR.

Fabry Disease Presenting with Hypertrophic Cardiomyopathy and Tricuspid Regurgitation.

A 71-year-old female who was diagnosed with nonobstructive hypertrophic cardiomyopathy since 1999 presented with dyspnea and severe edema on both legs. For the management of her symptom, cardiac surgery including tricuspid annuloplasty, Maze operation and right atrial reduction plasty was performed. During follow-up after cardiac surgery, a plasma α-galactosidase activity was checked for the screening of Fabry disease and the result was around lower normal limit. DNA analysis was implemented for confirmation and it revealed a heterozygote α-galactosidase mutation at exon 6 [c.901C>T (p.Arg301Ter)]. This case suggests that Fabry disease might be easily undetected, and clinical suspicion is critical.

Is metabolic syndrome predictive of prevalence, extent, and risk of coronary artery disease beyond its components? Results from the multinational coronary CT angiography evaluation for clinical outcome: an international multicenter registry (CONFIRM).

Although metabolic syndrome is associated with increased risk of cardiovascular disease and events, its added prognostic value beyond its components remains unknown. This study compared the prevalence, severity of coronary artery disease (CAD), and prognosis of patients with metabolic syndrome to those with individual metabolic syndrome components. The study cohort consisted of 27125 consecutive individuals who underwent ≥ 64-detector row coronary CT angiography (CCTA) at 12 centers from 2003 to 2009. Metabolic syndrome was defined as per NCEP/ATP III criteria. Metabolic syndrome patients (n = 690) were matched 1:1:1 to those with 1 component (n = 690) and 2 components (n = 690) of metabolic syndrome for age, sex, smoking status, and family history of premature CAD using propensity scoring. Major adverse cardiac events (MACE) were defined by a composite of myocardial infarction (MI), acute coronary syndrome, mortality and late target vessel revascularization. Patients with 1 component of metabolic syndrome manifested lower rates of obstructive 1-, 2-, and 3-vessel/left main disease compared to metabolic syndrome patients (9.4% vs 13.8%, 2.6% vs 4.5%, and 1.0% vs 2.3%, respectively; p < 0.05), while those with 2 components did not (10.5% vs 13.8%, 2.8% vs 4.5% and 1.3% vs 2.3%, respectively; p > 0.05). At 2.5 years, metabolic syndrome patients experienced a higher rate of MACE compared to patients with 1 component (4.4% vs 1.6%; p = 0.002), while no difference observed compared to individuals with 2 components (4.4% vs 3.2% p = 0.25) of metabolic syndrome. In conclusion, Metabolic syndrome patients have significantly greater prevalence, severity, and prognosis of CAD compared to patients with 1 but not 2 components of metabolic syndrome.

Left atrial volume index as a predictor for persistent left ventricular dysfunction after aortic valve surgery in patients with chronic aortic regurgitation: the role of early postoperative echocardiography.

BACKGROUND: This study aimed to explore whether echocardiographic measurements during the early postoperative period can predict persistent left ventricular systolic dysfunction (LVSD) after aortic valve surgery in patients with chronic aortic regurgitation (AR). METHODS: We prospectively recruited 54 patients (59 ± 12 years) with isolated chronic severe AR who subsequently underwent aortic valve surgery. Standard transthoracic echocardiography was performed before the operation, during the early postoperative period (≤2 weeks), and then 1 year after the surgery. RESULTS: Twelve patients with preoperative LVSD demonstrated LVSD at early after the surgery. Of the 42 patients without LVSD at preoperative echocardiography, 15 patients (36%) developed early postoperative LVSD after surgical correction. All 27 patients without LVSD at early postoperative echocardiography maintained LV function at 1 year after surgery. In the other 27 patients with postoperative LVSD, 17 patients recovered from LVSD and 10 patients did not at 1 year after surgery. Multiple logistic analysis demonstrated that postoperative left atrial volume index (LAVI) was the only independent predictor for persistent LVSD at 1 year after surgery in patients with postoperative LVSD (OR 1.180, 95% CI, 1.003-1.390, P = 0.046). The optimal LAVI cutoff value (>34.9 mL/m(2) ) had a sensitivity of 80% and a specificity of 88% for the prediction of persistent LVSD. CONCLUSION: Prevalence of early postoperative LVSD was relatively high, even in the patients without LVSD at preoperative echocardiography. Postoperative LAVI could be useful to predict persistent LVSD after aortic valve surgery in patients with early postoperative LVSD.

Correlation between coronary artery calcium score and aortic diameter in a high-risk population of elderly male hypertensive patients.

BACKGROUND: Studies on the relationship between coronary artery calcium and aortic diameter are scarce. The aim of the current study was to evaluate the correlation between coronary artery calcium score (CACS) and maximal thoracic and abdominal aortic diameters in a population of elderly (>65 years) male hypertensive patients at high risk for coronary artery disease. PATIENTS AND METHODS: From June 2012 to April 2013, we prospectively enrolled 393 male hypertensive patients older than 65 years of age who had no history of aortic aneurysm. Coronary artery calcium and maximal diameters of the ascending thoracic aorta (ATAmax), descending thoracic aorta (DTAmax), and abdominal aorta (AAmax) were measured using noncontrast computed tomography imaging. Aortic diameters are indexed to body surface area (BSA). Participants were divided into five groups according to CACS (0, 1-10, 10-100, 100-400, and >400). RESULTS: The mean ATAmax/BSA, DTAmax/BSA, and AAmax/BSA were 22.0±2.7, 16.3±1.9, and 13.0±2.9 mm, respectively. On multivariate analysis, ATAmax/BSA was associated independently with age, diabetes, and history of aortic valve replacement (all P<0.001). DTAmax/BSA was associated independently with age (P<0.001). However, there were no significant correlations between thoracic aorta diameter and CACS. In contrast, AAmax/BSA was associated independently with CACS as well as age and history of smoking (P=0.014, 0.003, and 0.019, respectively). Abdominal aortic aneurysm (>30 mm) was more prevalent in patients with a CACS of 400 or more compared with the others (14 vs. 3%, P<0.001). CONCLUSION: CACS was associated with increased abdominal aorta diameter, but not with thoracic aorta diameter. Therefore, screening for an abdominal aortic aneurysm is warranted in patients with a high risk of coronary artery disease and a high CACS. However, the necessity for thoracic aortic aneurysm screening is not clear in these patients.