Moderate and high disease activity levels increase the risk of subclinical atherosclerosis progression in early rheumatoid arthritis: a 5-year prospective study.

OBJECTIVES: To elucidate the association between different disease activity levels over time on long-term vascular outcomes in patients with early rheumatoid arthritis (ERA). METHODS: This was a 5-year prospective study. Patients with consecutive ERA without overt cardiovascular disease (CVD) were recruited to receive 1 year of tight-control treatment followed by standard-of-care management. High-resolution carotid ultrasound was assessed at baseline and year 5. The primary outcome was subclinical atherosclerosis progression (AP+), defined as the occurrence of incident plaque, increased region harbouring plaques and/or maximum carotid intima-media thickness progression ≥0.9 mm at year 5. Inflammatory burden during the follow-up period was represented by the cumulative average Disease Activity Score 28-erythrocyte sedimentation rate (ca-DAS28-ESR). Persistent low disease activity (LDA) or remission state was defined as ca-DAS28-ESR≤3.2. RESULTS: One-hundred and four patients with ERA (age: 52±11 years, 81 (77.9%) female) were included in this analysis. Fifty-two (50%) patients achieved persistent LDA or remission and 42 patients (40.4%) had AP+. Patients in the AP+ group were older and had more traditional cardiovascular risk factors at baseline. Multivariate logistic regression analysis revealed that patients with persistent moderate or high disease activity (ca-DAS28-ESR>3.2) had a significantly increased risk of AP+ (OR 5.05, 95% CI 1.53, 16.64, p=0.008) compared with those who achieved persistent remission. The risk of AP+ was similar in patients who achieved persistent LDA and remission. CONCLUSIONS: Achieving persistent LDA or remission may prevent progression of atherosclerosis in ERA. A treat-to-target approach aiming at sustained LDA or remission may reduce the risk of CVD by preventing AP+.

Deep learning networks in the segmentation of the left atrial appendage in 2D ultrasound: A comparative analysis.

Left atrial appendage (LAA) is the major source of thromboembolism in patients with non-valvular atrial fibrillation. Currently, LAA occlusion can be offered as a treatment for these patients, obstructing the LAA through a percutaneously delivered device. Nevertheless, correct device sizing is a complex task, requiring manual analysis of medical images. This approach is sub-optimal, time-demanding, and highly variable between experts. Different solutions were proposed to improve intervention planning, but, no efficient solution is available to 2D ultrasound, which is the most used imaging modality for intervention planning and guidance. In this work, we studied the performance of recently proposed deep learning methods when applied for the LAA segmentation in 2D ultrasound. For that, it was created a 2D ultrasound database. Then, the performance of different deep learning methods, namely Unet, UnetR, AttUnet, TransAttUnet was assessed. All networks were compared using seven metrics: i) Dice coefficient; ii) Accuracy iii) Recall; iv) Specificity; v) Precision; vi) Hausdorff distance and vii) Average distance error. Overall, the results demonstrate the efficiency of AttUnet and TransAttUnet with dice scores of 88.62% and 89.28%, and accuracy of 88.25% and 86.30%, respectively. The current results demonstrate the feasibility of deep learning methods for LAA segmentation in 2D ultrasound.Clinical relevance- Our results proved the clinical potential of deep neural networks for the LAA anatomical analysis.

Serum Calprotectin Level Is Independently Associated With Carotid Plaque Presence in Patients With Psoriatic Arthritis.

Background: Whether calprotectin could play a role in augmenting cardiovascular (CV) risk in patients with psoriatic arthritis (PsA) remains uncertain. The aim of this study is to elucidate the association between serum calprotectin level and subclinical atherosclerosis in patient with PsA. Method: Seventy-eight PsA patients (age: 52 ± 10 years, 41 [52.6%] male) without CV disease were recruited into this cross-sectional study. Carotid intima-media thickness (cIMT) and the presence of plaque were determined by high-resolution ultrasound. Calprotectin levels in serum were quantified by enzyme-linked immunosorbent assay. The variables associated with the presence of carotid plaque (CP) were selected from the least absolute shrinkage and selection operator (LASSO) regression analysis. Results: 29/78 (37.2%) of patient had carotid plaque (CP+ group). Serum calprotectin level was significantly higher in the CP+ group (CP- group: 564.6 [329.3-910.5] ng/ml; CP+ group: 721.3 [329.3-910.5] ng/ml, P = 0.005). Serum calprotectin level correlated with PsA disease duration (rho = 0.280, P = 0.013) and mean cIMT (rho = 0.249, P = 0.038). Using LASSO regression analysis, the levels of Ln-calprotectin (OR: 3.38, 95% CI [1.37, 9.47]; P = 0.026) and PsA disease duration (OR: 1.09, 95% CI [1.01, 1.18]; P = 0.013) were screened out from a total of 19 variables. The model in predicting the presence of CP was constructed by Ln-calprotectin and PsA disease duration with an area under the receiver-operating characteristic (ROC) curve of 0.744, (95 CI% [0.59, 0.80], P = 0.037). Conclusion: Serum calprotectin level is associated with the presence of CP in PsA. Further studies are required to confirm whether this pathway is associated with CV events in PsA.

Update on surgical repair in functional mitral regurgitation.

BACKGROUND: Functional mitral regurgitation (FMR) is common in patients with myocardial infarction or dilated cardiomyopathy, and portends a poor prognosis despite guideline-directed medical therapy (GDMT). Surgical or transcatheter mitral repair for FMR from recent randomized clinical trials showed disappointing or conflicting results. AIMS: To provide an update on the role of surgical repair in the management of FMR. MATERIALS AND METHODS: A literature search was conducted utilizing PubMed, Ovid, Web of Science, Embase, and Cochrane Library. The search terms included secondary/FMR, ischemic mitral regurgitation, mitral repair, mitral replacement, mitral annuloplasty, transcatheter mitral repair, and percutaneous mitral repair. Randomized clinical trials over the past decade were the particular focus of the current review. RESULTS: Recent data underlined the complexity and poor prognosis of FMR. GDMT and cardiac resynchronization, when indicated, should always be applied. Accurate assessment of the interplay between ventricular geometry and mitral valve function is essential to differentiate proportionate FMR from the disproportionate subgroup, which could be helpful in selecting appropriate transcatheter intervention strategies. Surgical repair, most commonly performed with an undersized ring annuloplasty, remains controversial. Adjunctive valvular or subvalvular repair techniques are evolving and may produce improved results in selected FMR patients. CONCLUSION: FMR resulted from complex valve-ventricular interaction and remodeling. Distinguishing proportionate FMR from disproportionate FMR is important in exploring their underlying mechanisms and to guide medical treatment with surgical or transcatheter interventions. Further studies are warranted to confirm the clinical benefit of appropriate surgical repair in selected FMR patients.

Comparison of carotid artery ultrasound and Framingham risk score for discriminating coronary artery disease in patients with psoriatic arthritis.

OBJECTIVES: This study aimed to assess the performance of carotid ultrasound (US) parameters alone or in combination with Framingham Risk Score (FRS) in discriminating patients with psoriatic arthritis (PsA) with and without coronary artery disease (CAD). METHODS: Ninety-one patients with PsA (56 males; age: 50±11 years, disease duration: 9.4±9.2 years) without overt cardiovascular (CV) diseases were recruited. Carotid intima-media thickness (cIMT), the presence of plaque and total plaque area (TPA) was determined by high-resolution US. CAD was defined as the presence of any coronary plaque on coronary CT angiography (CCTA). Obstructive-CAD (O-CAD) was defined as >50% stenosis of the lumen. RESULTS: Thirty-five (38%) patients had carotid plaque. Fifty-four (59%) patients had CAD (CAD+) and 9 (10%) patients had O-CAD (O-CAD+). No significant associations between the presence of carotid plaque and CAD were found. However, cIMT and TPA were higher in both the CAD+ and O-CAD+ group compared with the CAD- or O-CAD- groups, respectively. Multivariate logistic regression analysis revealed that mean cIMT was an independent explanatory variable associated with CAD and O-CAD, while maximum cIMT and TPA were independent explanatory variables associated with O-CAD after adjusting for covariates. The optimal cut-offs for detecting the presence of CAD were FRS >5% and mean cIMT at 0.62 mm (AUC: 0.71; sensitivity: 67%; specificity: 76%), while the optimal cut-offs for detecting the presence of O-CAD were FRS >10% in combination with mean cIMT at 0.73 mm (AUC: 0.71; sensitivity: 56%; specificity: 85%). CONCLUSION: US parameters including cIMT and TPA may be considered in addition to FRS for CV risk stratification in patients with PsA.

Screening for Fabry Disease in patients with unexplained left ventricular hypertrophy.

Fabry Disease (FD) is a systemic disorder that can result in cardiovascular, renal, and neurovascular disease leading to reduced life expectancy. FD should be considered in the differential of all patients with unexplained left ventricular hypertrophy (LVH). We therefore performed a prospective screening study in Edmonton and Hong Kong using Dried Blood Spot (DBS) testing on patients with undiagnosed LVH. Participants found to have unexplained LVH on echocardiography were invited to participate and subsequently subjected to DBS testing. DBS testing was used to measure α-galactosidase (α-GAL) enzyme activity and for mutation analysis of the α-galactosidase (GLA) gene, both of which are required to make a diagnosis of FD. DBS testing was performed as a screening tool on patients (n = 266) in Edmonton and Hong Kong, allowing for detection of five patients with FD (2% prevalence of FD) and one patient with hydroxychloroquine-induced phenocopy. Left ventricular mass index (LVMI) by GLA genotype showed a higher LVMI in patients with IVS4 + 919G > A mutations compared to those without the mutation. Two patients were initiated on ERT and hydroxychloroquine was discontinued in the patient with a phenocopy of FD. Overall, we detected FD in 2% of our screening cohort using DBS testing as an effective and easy to administer screening tool in patients with unexplained LVH. Utilizing DBS testing to screen for FD in patients with otherwise undiagnosed LVH is clinically important due to the availability of effective therapies and the value of cascade screening in extended families.

Short term clinical outcomes and analysis of risk factors for pacemaker implantation: a single center experience of self-expandable TAVI valves.

OBJECTIVES: Transcatheter aortic valve implantation is a recognized treatment for patients with severe aortic stenosis at all risk groups. However, permanent pacemaker rates remain high for self expandable transcatheter valves and permanent pacemaker implantation has been associated with increased morbidity. In this analysis we aim to evaluate short term clinical outcomes post self expandable transcatheter aortic valve implantation and determine risk factors for permanent pacemaker implantation. METHODS: 88 patients with severe aortic stenosis with transcatheter aortic valve implantation performed between the year 2016-2018 were retrospectively analyzed. Outcomes of interest included 1- year all cause mortality, 30-day major adverse cardiovascular events, permanent pacemaker and paravalvular leak rates. Survival analysis was performed with Kaplan Meier analysis and risk factors for survival and permanent pacemaker rates were identified with log rank test and regression analysis. RESULTS: The mean age of the cohort was 80.3 +/- 6.9 years. The mean STS score was 9.25. The 30 day all-cause mortality was 5.7% and 1-year all cause mortality was 16.7%. 80 patients had transfemoral transcatheter aortic valve implantation, and a majority of the patients (85.2%) were implanted with Corevalve Evolut R device. The device success rate was 88.6%. Multivariate analysis identified concomitant severe coronary artery disease (OR = 18.2 +/- 0.9; P = 0.002), pre transcatheter aortic valve implantation atrial fibrillation (OR = 8.6 +/- 0.91; P = 0.02) and post procedural disabling stroke (OR = 32.6 +/- 1.35; P = 0.01) as risk factors for 1-year mortality. The 30-day pacemaker rate was 17.6%. The presence of right bundle branch block (OR 11.1 +/- 0.86; P = 0.005), non-coronary cusp implantation depth (OR = 1.34 +/- 0.15; P = 0.05) and a non coronary cusp implantation depth / membranous septal length ratio of more than 50% were associated with post procedural pacemaker implantation (OR = 29.9 +/- 1.72; P = 0.05). Among the 15 patients with post procedural pacemaker implantation, 40% were found to be non-pacemaker dependent at 1 year. CONCLUSION: Short term outcomes of transcatheter aortic valve implantation in severe aortic stenosis patients are promising. Pacemaker rates remain high. More studies are needed to evaluate the factors that influence pacemaker rates and dependence to further improve transcatheter aortic valve implantation outcomes.

Treat to target and prevention of subclinical atherosclerosis in psoriatic arthritis-which target should we choose?

OBJECTIVE: PsA patients who achieved sustained minimal disease activity (sMDA) had less subclinical atherosclerosis progression. The vascular effects of achieving other potential treatment targets, including the PsA Disease Activity Score (PASDAS) and the Disease Activity in PsA (DAPSA) score, remained uncertain. This study aimed to compare the vascular effects of achieving different treatment targets in PsA patients. METHOD: This is a post hoc analysis of a 2 year treat-to-target study aimed at MDA. A total of 101 consecutive PsA patients without overt cardiovascular disease were recruited. High-resolution carotid ultrasound and arterial stiffness markers were assessed annually. Low disease activity (LDA) was defined as MDA, DAPSA ≤14 or PASDAS ≤3.2. Sustained disease control was defined as achieving these targets at each visit from month 12 until month 24. RESULTS: Ninety patients [52 male (57.8%), age 50 years (s.d. 11)] who completed 24 months of follow-up were included in this analysis. A total of 44%, 48% and 45% of patients achieved sustained DAPSA LDA (sDAPDA-LDA), sustained PASDAS LDA (sPASDAS-LDA) and sMDA, respectively. Patients who achieved sMDA had significantly less progression of carotid intima-media thickness than those who did not (P = 0.031). Using multivariate analysis, achieving sMDA and sPASDAS-LDA had a protective effect on plaque progression, less increase in total plaque area, reduced mean intima-media thickness and reduced augmentation index after adjusting for covariates. In contrast, no significant differences in the progression of vascular parameters were demonstrated between patients who did or did not achieve sDAPSA-LDA. CONCLUSION: Achieving sMDA/sDASPAS-LDA, but not sDAPSA-LDA, was associated with a protective effect in subclinical atherosclerosis and arterial stiffness progression. A multidimensional domain of disease control might be better in minimizing cardiovascular risk in PsA.

Effect of Achieving Minimal Disease Activity on the Progression of Subclinical Atherosclerosis and Arterial Stiffness: A Prospective Cohort Study in Psoriatic Arthritis.

OBJECTIVE: To investigate the effects of achieving minimal disease activity (MDA) on the progression of subclinical atherosclerosis and arterial stiffness in patients with psoriatic arthritis (PsA). METHODS: A total of 101 consecutive patients with PsA were recruited for this prospective cohort study. All patients received protocolized treatment targeting MDA for a period of 2 years. High-resolution carotid ultrasound and arterial stiffness markers were assessed annually. The primary outcome measure was the effect of achieving MDA at 12 months (MDA group) on the progression of subclinical atherosclerosis over a period of 24 months. Secondary objectives were to compare the changes in arterial stiffness markers over 24 months between the MDA and non-MDA groups, as well as the changes in subclinical atherosclerosis and arterial stiffness markers in patients who achieved MDA at each visit from month 12 through month 24 (sustained MDA [sMDA]). RESULTS: Ninety PsA patients (mean ± SD age 50 ± 11 years, 58% male [n = 52]) who completed 24 months of follow-up were included in this analysis. Fifty-seven patients (63%) had achieved MDA at 12 months. Subclinical atherosclerosis and arterial stiffness outcomes were similar between the MDA and non-MDA groups. Forty-one patients (46%) achieved sMDA. As shown by multivariate analysis, achieving sMDA had a protective effect on plaque progression (odds ratio 0.273 [95% confidence interval 0.088-0.846], P = 0.024), and less of an increase in total plaque area, mean intima-media thickness, and augmentation index values after adjustment for covariates. CONCLUSION: Our results support the recommendation that once MDA is achieved, it should ideally be maintained for a prolonged period in order to prevent progression of carotid atherosclerosis and arterial stiffness in patients with PsA.

Junior medical student performed focused cardiac ultrasound after brief training to detect significant valvular heart disease.

BACKGROUND: Focused cardiac ultrasound (FOCUS) examination using a portable device is increasingly used for bedside diagnosis of cardiovascular diseases. This is a 4-week pilot project aiming to teach medical students to perform FOCUS to detect valvular heart lesions. METHODS: Patients undergoing routine transthoracic echocardiography (TTE) were recruited by third year medical students who performed physical examination (PE) and FOCUS after 6-hour training to detect significant (moderate-to-severe) valvular lesions. Performance of FOCUS and PE was compared to TTE as reference using kappa statistics. RESULTS: 10 medical students performed 212 PE and FOCUS on 107 patients with mean age 63.7 ±â€¯14.9 years. TTE detected 126 significant valvular lesions of which FOCUS correctly identified 54 lesions (κ = 0.45) compared to 32 lesions by PE (κ = 0.28, p < 0.01). FOCUS was better than PE in identifying mitral stenosis (κ = 0.51 vs. 0.17), aortic stenosis (κ = 0.45 vs. 0.16) and tricuspid regurgitation (κ = 0.39 vs. 0.09, all p < 0.01). Students became more proficient in performing FOCUS examination with time. CONCLUSIONS: Teaching junior medical students to perform and interpret FOCUS was feasible after brief training and better than PE in detecting significant valvular lesions. Further studies are warranted to determine the utility of incorporating this new technology into mainstream medical training.

Heart Failure and Frailty in the Community-Living Elderly Population: What the UFO Study Will Tell Us.

Heart failure and frailty are clinical syndromes that present with overlapping phenotypic characteristics. Importantly, their co-presence is associated with increased mortality and morbidity. While mechanical and electrical device therapies for heart failure are vital for select patients with advanced stage disease, the majority of patients and especially those with undiagnosed heart failure would benefit from early disease detection and prompt initiation of guideline-directed medical therapies. In this article, we review the problematic interactions between heart failure and frailty, introduce a focused cardiac screening program for community-living elderly initiated by a mobile communication device app leading to the Undiagnosed heart Failure in frail Older individuals (UFO) study, and discuss how the knowledge of pre-frailty and frailty status could be exploited for the detection of previously undiagnosed heart failure or advanced cardiac disease. The widespread use of mobile devices coupled with increasing availability of novel, effective medical and minimally invasive therapies have incentivized new approaches to heart failure case finding and disease management.

Experimental validation of robot-assisted cardiovascular catheterization: model-based versus model-free control.

PURPOSE: In cardiac electrophysiology, a long and flexible catheter is delivered to a cardiac chamber for the treatment of arrhythmias. Although several robot-assisted platforms have been commercialized, the disorientation in tele-operation is still not well solved. We propose a validation platform for robot-assisted cardiac EP catheterization, integrating a customized MR Safe robot, a standard clinically used EP catheter, and a human-robot interface. Both model-based and model-free control methods are implemented in the platform for quantitative evaluation and comparison. METHODS: The model-based and model-free control methods were validated by subject test (ten participants), in which the subjects have to perform a simulated radiofrequency ablation task using both methods. A virtual endoscopic view of the catheter is also provided to enhance hand-to-eye coordination. Assessment indices for targeting accuracy and efficiency were acquired for the evaluation. RESULTS: (1) Accuracy: The average distance measured from catheter tip to the closest lesion target during ablation of model-free method was 19.1% shorter than that of model-based control. (2) Efficiency: The model-free control reduced the total missed targets by 35.8% and the maximum continuously missed targets by 46.2%, both indices corresponded to a low p value ([Formula: see text]). CONCLUSION: The model-free method performed better in terms of both accuracy and efficiency, indicating the model-free control could adapt to soft interaction with environment, as compared with the model-based control that does not consider contacts.

Electrophysiological Mechanisms of Gastrointestinal Arrhythmogenesis: Lessons from the Heart.

Disruptions in the orderly activation and recovery of electrical excitation traveling through the heart and the gastrointestinal (GI) tract can lead to arrhythmogenesis. For example, cardiac arrhythmias predispose to thromboembolic events resulting in cerebrovascular accidents and myocardial infarction, and to sudden cardiac death. By contrast, arrhythmias in the GI tract are usually not life-threatening and much less well characterized. However, they have been implicated in the pathogenesis of a number of GI motility disorders, including gastroparesis, dyspepsia, irritable bowel syndrome, mesenteric ischaemia, Hirschsprung disease, slow transit constipation, all of which are associated with significant morbidity. Both cardiac and gastrointestinal arrhythmias can broadly be divided into non-reentrant and reentrant activity. The aim of this paper is to compare and contrast the mechanisms underlying arrhythmogenesis in both systems to provide insight into the pathogenesis of GI motility disorders and potential molecular targets for future therapy.

Introducing Final-Year Medical Students to Pocket-Sized Ultrasound Imaging: Teaching Transthoracic Echocardiography on a 2-Week Anesthesia Rotation.

PROBLEM: The availability of less expensive and smaller ultrasound machines has enabled the use of ultrasound in virtually all major medical/surgical disciplines. Some medical schools have incorporated point-of-care ultrasound training into their undergraduate curriculum, whereas many postgraduate programs have made ultrasound training a standard. The Chinese University of Hong Kong has charged its Department of Anaesthesia and Intensive Care to spearhead the introduction of ultrasound into the final-year medical curriculum by introducing handheld transthoracic echocardiography as part of perioperative assessment. INTERVENTION: All 133 final-year students completed a 2-week anesthesia rotation, which began with a half-day session consisting of a lecture and hands-on practice session during which they learned 9 basic transthoracic echocardiography views using 4 basic ultrasound probe positions. CONTEXT: Each student was required to perform a transthoracic echocardiography-examine under supervision of 1 patient/week for 2 weeks, and their results were compared against that of the supervisor's. Most patients were elective cardiac surgery patients. One long question on transthoracic echocardiography was included in their end-of-year surgery examination paper. Students provided feedback on their experience. OUTCOME: Most students learned the basic transthoracic echocardiography views fairly efficiently and had variable, though generally favorable, success rates in identifying obvious cardiac anomalies, including use of color Doppler. A few common mistakes were identified but were easily correctable. Logistics for mobilizing enough bedside supervision were challenging. Students reported positive feedback on the teaching initiative. LESSONS LEARNED: We were able to execute a successful short training course on transthoracic echocardiography during the final-year medical degree anesthesia rotation. Our initiative may set an example for other clinical departments to design similar courses pertinent to their specialties and syllabuses.