Derivation and Internal Validation of a Disease-Specific Cardiovascular Risk Prediction Model for Patients With Psoriatic Arthritis and Psoriasis.

OBJECTIVE: To address suboptimal cardiovascular risk prediction in patients with psoriatic disease (PsD), we developed and internally validated a five-year disease-specific cardiovascular risk prediction model. METHODS: We analyzed data from a prospective cohort of participants with PsD without a history of cardiovascular events. Traditional cardiovascular risk factors and PsD-related measures of disease activity were considered as potential predictors. The study outcome included nonfatal and fatal cardiovascular events. A base prediction model included 10 traditional cardiovascular risk factors. Eight PsD-related factors were assessed by adding them to the base model to create expanded models, which were controlled for PsD therapies. Variable selection was performed using Least Absolute Shrinkage and Selection Operator (LASSO) penalized regression with 10-fold cross-validation. Model performance was assessed using measures of discrimination and calibration and measures of sensitivity and specificity. RESULTS: Between 1992 and 2020, 85 of 1,336 participants developed cardiovascular events. Discrimination of the base model (with traditional cardiovascular risk factors alone) was excellent, with an area under the receiver operator characteristic curve (AUC) of 85.5 (95% confidence interval [CI] 81.9-89.1). Optimal models did not select any of the tested disease-specific factors. In a sensitivity analysis, which excluded lipid lowering and antihypertensive treatments, the number of damaged joints was selected in the expanded model. However, this model did not improve risk discrimination compared to the base model (AUC 85.5, 95% CI 82.0-89.1). CONCLUSION: Traditional cardiovascular risk factors alone are effective in predicting cardiovascular risk in patients with PsD. A risk score based on these factors performed well, indicating excellent discrimination and calibration.

Cardiac Magnetic Resonance Imaging T1 and T2 Mapping in Systemic Lupus Erythematosus in Relation to Antimalarial Treatment.

PURPOSE: Patients with systemic lupus erythematosus (SLE) are at risk of cardiac disease including antimalarial-induced cardiomyopathy (AMIC). The purpose of this study is to evaluate cardiac magnetic resonance imaging parametric mapping findings in SLE patients with AMIC and investigate the relationship of T1/T2 mapping to antimalarial (AM) treatment duration. MATERIALS AND METHODS: All patients with SLE who had undergone cardiac magnetic resonance imaging with T1/T2 mapping for evaluation of suspected cardiac disease between 2018 and 2021 were evaluated and compared with healthy controls. To facilitate comparison between scanners, T1/T2 values were converted to a z -score using scanner-specific local reference values. Patients were classified into 3 groups: AMIC, myocarditis, and other (no AMIC or myocarditis). RESULTS: Forty-five SLE patients (47±17 y, 80% female; 8 [18%] with AMIC and 7 [16%] with myocarditis) and 30 healthy controls (39±15 y, 60% female) were included. Patients with AMIC had higher T1 and T2 compared with controls ( z -score 1.1±1.3 vs. 0±0.6, P =0.01 and 1.7±1.1 vs. 0±1.0, P <0.01, respectively) and lower values compared with those with myocarditis (3.7±1.6, P <0.01 and 4.0±2.0, P <0.01, respectively). T1 correlated negatively with AM treatment duration in patients without AMIC or myocarditis ( r =-0.36, P =0.048) and positively in patients with AMIC ( r =0.92, P =0.001). AM treatment duration did not correlate significantly with T1 in patients with myocarditis or with T2 in any group. CONCLUSIONS: The relationship between T1 and AM treatment duration differed between groups. Native T1 decreases with longer treatment in patients without AMIC or myocarditis, possibility due to glycosphingolipid accumulation. In patients with AMIC, increasing T1 with longer treatment could reflect fibrosis.

Cardiac Magnetic Resonance Imaging and Clinical Follow-up in Antimalarial-induced Cardiomyopathy in Patients With Systemic Lupus Erythematosus.

Antimalarial-induced cardiomyopathy is under-recognized in clinical practice and there is limited data on the evolution of cardiac imaging abnormalities after cessation of anti-malarial therapy. In this case series of 9 patients with antimalarial-induced cardiomyopathy, follow-up cardiac magnetic resonance imaging demonstrated interval increase in late gadolinium enhancement extent in 89% of patients and interval decrease in left ventricular ejection fraction in all, despite cessation of anti-malarial therapy. Progression of cardiac abnormalities despite cessation of therapy underscores the important role of imaging in the early recognition of antimalarial-related treatment changes.

Statin Use for Primary Cardiovascular Disease Prevention Is Low in Inflammatory Arthritis.

BACKGROUND: Patients with inflammatory arthritis (IA) are at high risk for atherosclerotic cardiovascular disease (ASCVD), yet management of dyslipidemia is infrequently prioritized. We applied Canadian dyslipidemia guidelines to determine how many patients with IA would be eligible for primary prevention with statins. METHODS: We conducted a cross-sectional study of patients with IA in a cardio-rheumatology clinic, with no known CVD and without statin therapy at cohort entry. We stratified patients by Framingham Risk Score (FRS) and summarized the proportion meeting guideline statin-indicated criteria. Multivariable logistic regression analyses determined the association of variables with statin indication after adjustment for age, sex, traditional ASCVD risk factors, and arthritis characteristics. RESULTS: Among 302 patients, most had rheumatoid arthritis (59%). Mean age was 58 years, and 71% were female. Overall, 50% of the cohort was eligible for statin therapy. The majority was low FRS risk category (68%), and the most frequent qualifier for statins was elevated apolipoprotein B (ApoB) levels or low-density lipoprotein cholesterol (LDL-c) levels. In the intermediate FRS group, 91% met criteria for statin therapy based on the presence of a coronary artery calcification (CAC) score > 0 or an elevated high-sensitivity C-reactive protein. Male sex, hypertension, elevated ApoB, and a CAC score > 0 were the factors most strongly associated with indication for statin therapy. CONCLUSIONS: Statin therapy is suboptimal in IA despite a significant number of patients meeting indication based on lipoprotein thresholds or CAC scores. Understanding the barriers and potential facilitators of implementing and interpreting these CVD screening tools in IA is needed.

Visual Ordinal Scoring of Coronary Artery Calcium on Contrast-Enhanced and Noncontrast Chest CT: A Retrospective Study of Diagnostic Performance and Prognostic Utility.

BACKGROUND. Current guidelines recommend visual evaluation of coronary artery calcium (CAC) on all nongated noncontrast chest CT examinations. However, chest CT examinations are often performed with contrast material administration. OBJECTIVE. The purpose of our study was to evaluate diagnostic performance, prognostic utility, and interobserver agreement of visual CAC assessment on chest CT performed for other indications. METHODS. This retrospective study included 260 patients (158 men, 102 women; mean age, 60 ± 11 [SD] years) who underwent both nongated chest CT (contrast-enhanced in 116 patients; noncontrast in 144 patients) and cardiac calcium score CT within a 12-month interval. A cardiothoracic radiologist visually assessed CAC on chest CT using an ordinal scale (absent, mild, moderate, or severe). Cardiac CT Agatston calcium scores were quantified according to established guidelines and were categorized as CAC absent (0), mild CAC (1-99), moderate CAC (100-299), or severe CAC (≥ 300). The diagnostic performance of chest CT for the presence of CAC was assessed using cardiac CT as the reference standard. Major adverse cardiac events (MACE) were assessed as a composite of cardiovascular death and myocardial infarction and were evaluated using Cox proportional hazards models. A second cardiothoracic radiologist performed visual CAC assessments in a random subset of 50 chest CT examinations to assess interob-server agreement. RESULTS. For the presence of any CAC on cardiac CT, contrast-enhanced and non-contrast chest CT had sensitivity of 83% (62/75) and 89% (85/95) (p = .20) and specificity of 100% (41/41) and 100% (49/49) (p = .99). CAC present on cardiac CT was misclassified as absent on 13 contrast-enhanced and 10 noncontrast chest CT examinations; Agatston score was less than 30 in all such patients, and none experienced any MACE. The visual ordinal CAC score was associated with MACE for contrast-enhanced chest CT (hazard ratio [HR] = 4.5 [95% CI, 1.2-16.4], p = .02) and noncontrast chest CT (HR = 3.4 [95% CI, 1.5-7.8], p = .003). Interobserver agreement was excellent for contrast-enhanced (κ = 0.89) and noncontrast (κ = 0.95) chest CT. CONCLUSION. Visual ordinal CAC assessment on both contrast-enhanced and non-contrast chest CT has high diagnostic performance, prognostic utility, and interobserver agreement. CLINICAL IMPACT. Routine reporting of CAC on all chest CT examinations regardless of clinical indication and contrast material administration could identify a large number of patients with previously unknown CAC who might benefit from preventive treatment.

Association of Cardiac Biomarkers With Cardiovascular Outcomes in Patients With Psoriatic Arthritis and Psoriasis: A Longitudinal Cohort Study.

OBJECTIVE: In patients with psoriatic disease (PsD), we determined whether cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were associated with carotid plaque burden and the development of cardiovascular events independent of the Framingham Risk Score (FRS). METHODS: Among 1,000 patients with PsD, carotid total plaque area (TPA) was measured in 358 participants at baseline. Cardiac troponin I and NT-proBNP were measured using automated clinical assays. The association between cardiac biomarkers and carotid atherosclerosis was assessed by multivariable regression after adjusting for cardiovascular risk factors. Improvement in the prediction of cardiovascular events beyond the FRS was tested using measures of risk discrimination and reclassification. RESULTS: In univariate analyses, cTnI (ß coefficient 0.52 [95% confidence interval (95% CI) 0.3, 0.74], P < 0.001) and NT-proBNP (ß coefficient 0.24 [95% CI 0.1, 0.39], P < 0.001) were associated with TPA. After adjusting for cardiovascular risk factors, the association remained statistically significant for cTnI (adjusted ß coefficient 0.21 [95% CI 0, 0.41], P = 0.047) but not for NT-proBNP (P = 0.21). Among the 1,000 patients with PsD assessed for cardiovascular risk prediction, 64 patients had incident cardiovascular events. When comparing a base model (with the FRS alone) to expanded models (with the FRS plus cardiac biomarkers), there was no improvement in predictive performance. CONCLUSION: In patients with PsD, cTnI may reflect the burden of atherosclerosis, independent of traditional cardiovascular risk factors. Cardiac troponin I and NT-proBNP are associated with incident cardiovascular events independent of the FRS, but further study of their role in cardiovascular risk stratification is warranted.

Incidence of and Risk Factors for Heart Failure in Patients With Psoriatic Disease: A Cohort Study.

OBJECTIVE: To assess the incidence and risk factors for heart failure in patients with psoriatic disease and to describe their electrocardiographic and echocardiographic findings. METHODS: A cohort analysis was conducted involving patients with psoriatic disease followed prospectively from 1978 to 2018. Participants were assessed according to a standard protocol every 6 to 12 months. The primary outcome was the time to first event of heart failure, further classified into ischemic and nonischemic heart failure (secondary outcomes). The association between cardiovascular risk factors, measures of disease activity, and heart failure events was assessed using Cox proportional hazards regression. Electrocardiographic and echocardiographic findings associated with heart failure events were described. RESULTS: A total of 1,994 patients with psoriatic disease were analyzed, with 64 incident heart failure events (38 ischemic, 26 nonischemic). The incidence rate of first heart failure event was 2.85 per 1,000 patient-years. In all events, the most common electrocardiographic findings were atrial fibrillation (22%) and bundle branch blocks (29%). Echocardiogram revealed 37% reduced ejection fraction and 63% preserved ejection fraction. In multivariable analysis, independent risk factors for all heart failure events were ischemic heart disease, adjusted mean tender joint count, adjusted mean swollen joint count, adjusted mean erythrocyte sedimentation rate, adjusted mean C-reactive protein level, and physical function (by Health Assessment Questionnaire) (all P < 0.05). Minimal disease activity state was protective for all heart failure (P < 0.05). CONCLUSION: Increased risk of heart failure is associated with a combination of known cardiovascular risk factors and measures of disease activity, particularly in nonischemic heart failure. The effect of inflammation on heart failure may be partially independent of atherosclerotic disease.

Targeted metabolomic profiling and prediction of cardiovascular events: a prospective study of patients with psoriatic arthritis and psoriasis.

OBJECTIVE: In patients with psoriatic disease (PsD), we sought serum metabolites associated with cardiovascular (CV) events and investigated whether they could improve CV risk prediction beyond traditional risk factors and the Framingham Risk Score (FRS). METHODS: Nuclear magnetic resonance metabolomics identified biomarkers for incident CV events in patients with PsD. The association of each metabolite with incident CV events was analysed using Cox proportional hazards regression models first adjusted for age and sex, and subsequently for traditional CV risk factors. Variable selection was performed using penalisation with boosting after adjusting for age and sex, and the FRS. RESULTS: Among 977 patients with PsD, 70 patients had incident CV events. In Cox regression models adjusted for CV risk factors, alanine, tyrosine, degree of unsaturation of fatty acids and high-density lipoprotein particles were associated with decreased CV risk. Glycoprotein acetyls, apolipoprotein B and cholesterol remnants were associated with increased CV risk. The age-adjusted and sex-adjusted expanded model with 13 metabolites significantly improved prediction of CV events beyond the model with age and sex alone, with an area under the receiver operator characteristic curve (AUC) of 79.9 versus 72.6, respectively (p=0.02). Compared with the FRS alone (AUC=73.9), the FRS-adjusted expanded model with 11 metabolites (AUC=75.0, p=0.72) did not improve CV risk discrimination. CONCLUSIONS: We identify novel metabolites associated with the development of CV events in patients with PsD. Further study of their underlying causal role may clarify important pathways leading to CV events in this population.

Value of Carotid Ultrasound in Cardiovascular Risk Stratification in Patients With Psoriatic Disease.

OBJECTIVE: This study aimed to assess whether subclinical atherosclerosis, as evaluated by carotid ultrasound, could predict incident cardiovascular events (CVEs) in patients with psoriatic disease (PsD) and determine whether incorporation of imaging data could improve CV risk prediction by the Framingham Risk Score (FRS). METHODS: In this cohort analysis, patients with PsD underwent ultrasound assessment of the carotid arteries at baseline. The extent of atherosclerosis was assessed using carotid intima-media thickness (CIMT) and total plaque area (TPA). Incident CVEs (new or recurrent) that occurred following the ultrasound assessment were identified. The association between measures of carotid atherosclerosis and the risk of developing an incident CVE was evaluated using Cox proportional hazards models, with adjustment for the FRS. RESULTS: In total, 559 patients with PsD were assessed, of whom 23 had incident CVEs ascertained. The calculated rate of developing a first CVE during the study period was 1.11 events per 100 patient-years (95% confidence interval [95% CI] 0.74-1.67). When analyzed separately in Cox proportional hazards models that were controlled for the FRS, the TPA (hazard ratio [HR] 3.74, 95% CI 1.55-8.85; P = 0.003), mean CIMT (HR 1.21, 95% CI 1.03-1.42; P = 0.02), maximal CIMT (HR 1.11, 95% CI 1.01-1.22; P = 0.03), and high TPA category (HR 3.25, 95% CI 1.18-8.95; P = 0.02) were each predictive of incident CVEs in patients with PsD. CONCLUSION: The burden of carotid atherosclerosis is associated with an increased risk of developing future CVEs. Combining vascular imaging data with information on traditional CV risk factors could improve the accuracy of CV risk stratification in patients with PsD.

Abnormal Cardiac Biomarkers in Patients with Systemic Lupus Erythematosus and No Prior Heart Disease: A Consequence of Antimalarials?

OBJECTIVE: Cardiac involvement in systemic lupus erythematosus (SLE) is often undiagnosed in its early phases. Specific heart biomarkers may identify patients at risk. We sought to investigate the prevalence and associated factors for such biomarkers in SLE. METHODS: Brain natriuretic peptide (BNP) and cardiac troponin I (cTnI) were measured simultaneously in 151 consecutive patients with no history of heart disease or pulmonary arterial hypertension (PAH). None had electrocardiographic abnormalities suggestive of acute coronary syndrome. Cross-sectional comparisons and logistic regression analyses were performed. Patients with abnormal biomarkers were investigated to delineate the specific cause. RESULTS: Sixteen patients (16/151, 10.6%) had elevated BNP, and 9 of them also had abnormal cTnI. Compared to subjects with normal biomarkers, they were older, had longer disease and antimalarial (AM) use duration, and more frequently persistent creatine phosphokinase (CPK) elevation. Multivariable regression analysis showed prolonged AM treatment (> 5.6 yrs) and persistent CPK elevation to be important predictors for elevated cardiac biomarkers. Six patients were diagnosed with definite (based on endomyocardial biopsy, n = 2) or possible (based on cardiac magnetic resonance after exclusion of other causes) AM-induced cardiomyopathy (AMIC); all had both BNP and cTnI elevated. Alternative causes were identified in 5, while no definitive diagnosis could be made in the remaining patients. CONCLUSION: About 10% of patients with SLE had elevated myocardial biomarkers, in the absence of prior cardiac disease or PAH. One-third of them were diagnosed with AMIC. Prolonged AM therapy and persistent CPK elevation conferred an increased risk for abnormal BNP and cTnI, which might predict AMIC.

Antimalarial-induced Cardiomyopathy in Systemic Lupus Erythematosus: As Rare as Considered?

OBJECTIVE: Antimalarials (AM) are recommended for all systemic lupus erythematosus (SLE) patients without specific contraindications. Their main adverse effect is retinal damage; however, heart disease has been described in isolated cases. The aim of our study is to describe 8 patients with AM-induced cardiomyopathy (AMIC) in a defined SLE cohort. METHODS: Patients attending the Toronto Lupus Clinic and diagnosed with definite (based on endomyocardial biopsy; EMB) and possible AMIC were included [based on cardiac magnetic resonance imaging (cMRI) and other investigations]. RESULTS: Eight female patients (median age 62.5 yrs, disease duration 35 yrs, AM use duration 22 yrs) were diagnosed with AMIC in the past 2 years. Diagnosis was based on EMB in 3 (extensive cardiomyocyte vacuolation, intracytoplasmic myelinoid, and curvilinear bodies). In 4 patients, cMRI was highly suggestive of AMIC (ventricular hypertrophy and/or atrial enlargement and late gadolinium enhancement in a nonvascular pattern). Another patient was diagnosed with complete atrioventricular block, left ventricular and septal hypertrophy, along with concomitant ocular toxicity. All patients had abnormal cardiac troponin I (cTnI) and brain natriuretic peptide (BNP), whereas 7/8 also had chronically elevated creatine phosphokinase. During followup, 1 patient died from refractory heart failure. In the remaining patients, hypertrophy regression and a steady decrease of heart biomarkers were observed after AM cessation. CONCLUSION: Once considered extremely rare, AMIC seems to be underrecognized, probably because of the false attribution of heart failure or hypertrophy to other causes. Certain biomarkers (cTnI, BNP) and imaging findings may lead to early diagnosis and enhance survival.

Effect of isolated left bundle-branch block on biventricular volumes and ejection fraction: a cardiovascular magnetic resonance assessment.

BACKGROUND: Left bundle branch block (LBBB) is associated with abnormal left ventricular (LV) contraction, and is frequently associated with co-morbid cardiovascular disease, but the effect of an isolated (i.e. in the absence of cardiovascular dissease) LBBB on biventricular volumes and ejection fraction (EF) is not well characterized. The objective of this study was to compare LV and right ventricular (RV) volumes and EF in adults with an isolated LBBB to matched healthy controls and to population-derived normative values, using cardiovascular magnetic resonance (CMR) imaging. METHODS: We reviewed our clinical echocardiography database and the Framingham Heart Study Offspring cohort CMR database to identify adults with an isolated LBBB. Age-, sex-, hypertension-status, and body-surface area (BSA)-matched controls were identified from the Offspring cohort. All study subjects were scanned using the same CMR hardware and imaging sequence. Isolated-LBBB cases were compared with matched controls using Wilcoxon paired signed-rank test, and to normative reference values via Z-score. RESULTS: Isolated-LBBB subjects (n = 18, 10F) ranged in age from 37 to 82 years. An isolated LBBB was associated with larger LV end-diastolic and end-systolic volumes (both p < 0.01) and lower LVEF (56+/- 7% vs. 68+/- 6%; p <0.001) with similar myocardial contraction fraction. LVEF in isolated LBBB was nearly two standard deviations (Z = - 1.95) below mean sex and age-matched group values. LV stroke volume, cardiac output, and mass, and all RV parameters were similar (p = NS) between the groups. CONCLUSIONS: Adults with an isolated LBBB have greater LV volumes and markedly reduced LVEF, despite the absence of overt cardiovascular disease. These data may be useful toward the clinical interpretation of imaging studies performed on patients with an isolated LBBB.

Relationship between native papillary muscle T1 time and severity of functional mitral regurgitation in patients with non-ischemic dilated cardiomyopathy.

BACKGROUND: Functional mitral regurgitation is one of the severe complications of non-ischemic dilated cardiomyopathy (DCM). Non-contrast native T1 mapping has emerged as a non-invasive method to evaluate myocardial fibrosis. We sought to evaluate the potential relationship between papillary muscle T1 time and mitral regurgitation in DCM patients. METHODS: Forty DCM patients (55 ± 13 years) and 20 healthy adult control subjects (54 ± 13 years) were studied. Native T1 mapping was performed using a slice interleaved T1 mapping sequence (STONE) which enables acquisition of 5 slices in the short-axis plane within a 90 s free-breathing scan. We measured papillary muscle diameter, length and shortening. DCM patients were allocated into 2 groups based on the presence or absence of functional mitral regurgitation. RESULTS: Papillary muscle T1 time was significantly elevated in DCM patients with mitral regurgitation (n = 22) in comparison to those without mitral regurgitation (n = 18) (anterior papillary muscle: 1127 ± 36 msec vs 1063 ± 16 msec, p < 0.05; posterior papillary muscle: 1124 ± 30 msec vs 1062 ± 19 msec, p < 0.05), but LV T1 time was similar (1129 ± 38 msec vs 1134 ± 58 msec, p = 0.93). Multivariate linear regression analysis showed that papillary muscle native T1 time (ß = 0.10, 95 % CI: 0.05-0.17, p < 0.05) is significantly correlated with mitral regurgitant fraction. Elevated papillary muscle T1 time was associated with larger diameter, longer length and decreased papillary muscle shortening (all p values <0.05). CONCLUSIONS: In DCM, papillary muscle native T1 time is significantly elevated and related to mitral regurgitant fraction.