Renal Function in Relation to Cardiac 123I-MIBG Scintigraphy in Patients with Chronic Heart Failure

The aim of this study was to explore if estimates of renal function could explain variability of 123I-metaiodobenzylguanidine (123I-MIBG) assessed myocardial sympathetic activity. Furthermore estimates of renal function were compared to 123I-MIBG as predictors of cardiac death in chronic heart failure (CHF). Semi-quantitative parameters of 123I-MIBG myocardial uptake and washout were calculated using early heart/mediastinum ratio (H/M), late H/M and washout. Renal function was calculated as estimated Creatinine Clearance (e-CC) and as estimated Glomerular Filtration Rate (e-GFR). Thirty-nine patients with CHF (24 males; age: 64.4 ± 10.5 years; NYHA II/III/IV: 17/20/2; LVEF: 24.0 ± 11.5%) were studied. Variability in any of the semi-quantitative 123I-MIBG myocardial parameters could not be explained by e-CC or e-GFR. During follow-up (60 ± 37 months) there were 6 cardiac deaths. Cox proportional hazard regression analysis showed that late H/M was the only independent predictor for cardiac death (Chi-square 3.2, regression coefficient: −4.095; standard error: 2.063; hazard ratio: 0.17 [95% CI: 0.000–0.950]). Addition of estimates of renal function did not significantly change the Chi-square of the model. Semi-quantitative 123I-MIBG myocardial parameters are independent of estimates of renal function. In addition, cardiac sympathetic innervation assessed by 123I-MIBG scintigraphy seems to be superior to renal function in the prediction of cardiac death in CHF patients

Patients' preferences for secondary prevention following a coronary event

Objective:Despite clear evidence on the effectiveness of secondary prevention, patients with coronary artery disease frequently fail to reach guideline-based risk factor targets. Integrating patients’ preferences into treatment decisions has been recommended to reduce this gap. However, this requires knowledge about patient treatment preferences. Therefore, through a survey study, we aimed to explore which risk factors patients self-perceived, prioritised for improvement, and needed support with after a recent hospitalisation for coronary heart disease. Methods: A digital questionnaire was presented to patients &gt; 18 years recently discharged (≤3 months) from an acute coronary care unit in the Netherlands (Europe). Patients could select from eight cardiovascular risk factors that they (1) self-perceived, (2) prioritised for improvement, and (3) needed support to improve. Patients’ perceived risk factors were compared to those documented in the medical records. Results: Respondents (N = 254, 26 % women), mean age 64 (SD 10) years, identified ‘physical inactivity’ more frequently than their medical records (140 patients vs. 91 records, p &lt; 0.001), while three other risk factors were reported with equal and four with lower frequency. ‘Physical inactivity’, ‘overweight’ and ‘stress’ were most frequently prioritised for improvement (82 %, 88 % and 78 %) and professional support (64 %, 50 % and 58 %), with 87 % preferring lifestyle optimisation if this would reduce drug use. Conclusions: Patients with a recent coronary event show significant disparities in identifying risk factors compared to their medical records. They tend to prefer improving lifestyle- over drug-modifiable risk factors, particularly physical inactivity, overweight and stress, and indicate the need for support in improving these factors.</p

Lipoprotein(a) has no major impact on calcification activity in patients with mild to moderate aortic valve stenosis

OBJECTIVE: To assess whether patients with aortic valve stenosis (AS) with elevated lipoprotein(a) (Lp(a)) are characterised by increased valvular calcification activity compared with those with low Lp(a). METHODS: We performed (18)F-sodium fluoride ((18)F-NaF) positron emission tomography/CT in patients with mild to moderate AS (peak aortic jet velocity between 2 and 4 m/s) and high versus low Lp(a) (>50 mg/dL vs <50 mg/dL, respectively). Subjects were matched according to age, gender, peak aortic jet velocity and valve morphology. We used a target to background ratio with the most diseased segment approach to compare (18)F-NaF uptake. RESULTS: 52 individuals (26 matched pairs) were included in the analysis. The mean age was 66.4±5.5 years, 44 (84.6%) were men, and the mean aortic valve velocity was 2.80±0.49 m/s. The median Lp(a) was 79 (64–117) mg/dL and 7 (5–11) mg/dL in the high and low Lp(a) groups, respectively. Systolic blood pressure and low-density-lipoprotein cholesterol (corrected for Lp(a)) were significantly higher in the low Lp(a) group (141±12 mm Hg vs 128±12 mm Hg, 2.5±1.1 mmol/L vs 1.9±0.8 mmol/L). We found no difference in valvular (18)F-NaF uptake between the high and low Lp(a) groups (3.02±1.26 vs 3.05±0.96, p=0.902). Linear regression analysis showed valvular calcium score to be the only significant determinant of valvular (18)F-NaF uptake (β=0.63; 95% CI 0.38 to 0.88 per 1000 Agatston unit increase, p<0.001). Lp(a) was not associated with (18)F-NaF uptake (β=0.17; 95% CI −0.44 to 0.88, p=0.305 for the high Lp(a) group). CONCLUSION: Among patients with mild to moderate AS, calcification activity is predominantly determined by established calcium burden. The results do not support our hypothesis that Lp(a) is associated with valvular (18)F-NaF uptake

Plasma proteomic patterns show sex differences in early concentric left ventricular remodeling

BACKGROUND: Concentric remodeling (cRM) can precede heart failure with preserved ejection fraction (HFpEF), a condition prevalent in women. METHODS: Patients (n=60 593, 54.2% women) visiting outpatient clinics of Cardiology Centers of the Netherlands were analyzed for cRM, HFpEF development, and mortality risk. We studied risk factors for relative wall thickness both sex-stratified and in women and men combined. Biomarker profiling was performed (4534 plasma proteins) in a substudy involving 557 patients (65.4% women) to identify pathways involved in cRM. RESULTS: cRM was present in 23.5% of women and 27.6% of men and associated with developing HFpEF (HR, 2.15 [95% CI, 1.51-2.99]) and mortality risk (HR, 1.09 [95% CI, 1.00-1.19]) in both sexes. Age, heart rate, and hypertension were statistically significantly stronger risk factors for relative wall thickness in women than men. Higher circulating levels of IFNA5 (interferon alpha-5) were associated with higher relative wall thickness in women only. Pathway analysis revealed differential pathway activation by sex and increased expression of inflammatory pathways in women. CONCLUSIONS: cRM is prevalent in approximately 1 in 4 women and men visiting outpatient cardiology clinics and associated with HFpEF development and mortality risk in both sexes. Known risk factors for cRM were more strongly associated in women than men. Proteomic analysis revealed inflammatory pathway activation in women, with a central role for IFNA5. Differential biologic pathway activation by sex in cRM may contribute to the female predominance of HFpEF and holds promise for identification of new therapeutic avenues for prevention and treatment of HFpEF. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT001747

Outcomes in patients with a first episode of chest pain undergoing early coronary CT imaging

OBJECTIVES: To investigate the impact of a CT-first strategy on all-cause and cardiovascular mortality in patients presenting with chest pain in outpatient cardiology clinics. METHODS: Patients with a first presentation of suspected angina pectoris were identified and their data linked to the registrations of Statistics Netherlands for information on mortality. The linked database consisted of 33 068 patients. CT-first patients were defined as patients with a CT calcium score and coronary CT angiography, within 6 weeks after their initial visit. Propensity score matching (1:5) was used to match patients with and without a CT-first strategy. After matching, 12 545 patients were included of which 2308 CT-first patients and 10 237 patients that underwent usual care. RESULTS: Mean age was 57 years, 56.3% were women and median follow-up was 4.9 years. All-cause mortality was significantly lower in CT-first patients (n=43, 1.9%) compared with patients without CT (n=363, 3.5%) (HR: 0.51, 95% CI 0.37 to 0.70). Furthermore, CT-first patients were more likely to receive cardiovascular preventative and antianginal medication (aspirin: 44.9% vs 27.1%, statins: 48.7% vs 30.3%, beta-blockers: 37.8% vs 25.5%, in CT-first and without CT-first patients, respectively) and to undergo downstream diagnostics and interventions (coronary interventions: 8.5% vs 5.7%, coronary angiography: 16.2% vs 10.6% in CT-first and without CT-first patients, respectively). CONCLUSIONS: In a real-world regular care database, a CT-first strategy in patients suspected of angina pectoris was associated with a lowering of all-cause mortality

Vascular time-activity variation in patients undergoing 123I-MIBG myocardial scintigraphy: implications for quantification of cardiac and mediastinal uptake

For the quantification of cardiac (123)I-metaiodobenzylguanidine (MIBG) uptake, the mediastinum is commonly used as a reference region reflecting nonspecific background activity. However, variations in the quantity of vascular structures in the mediastinum and the rate of renal clearance of (123)I-MIBG from the blood pool may contribute to increased interindividual variation in uptake. This study examined the relationship between changes in heart (H) and mediastinal (M) counts and the change in vascular (123)I-MIBG activity, including the effect of renal function. Fifty-one subjects with ischemic heart disease underwent early (15 min) and late (4 h) anterior planar images of the chest following injection of (123)I-MIBG. Vascular (123)I-MIBG activity was determined from venous blood samples obtained at 2 min, 15 min, 35 min, and 4 h post-injection. From the vascular clearance curve of each subject, the mean blood counts/min per ml at the time of each acquisition and the slope of the clearance curve were determined. Renal function was expressed as the estimated creatinine clearance (e-CC) and the estimated glomerular filtration rate (e-GFR). Relations between H and M region of interest (ROI) counts/pixel, vascular activity, and renal function were then examined using linear regression. Changes in ROI activity ratios between early and late planar images could not be explained by blood activity, the slope of the vascular clearance curves, or estimates of renal function. At most 3% of the variation in image counts could be explained by changes in vascular activity (p = 0.104). The e-CC and e-GFR could at best explain approximately 1.5% of the variation in the slopes of the vascular clearance curve (p = 0.194). The change in measured H and M counts between early and late planar (123)I-MIBG images is unrelated to intravascular levels of the radiopharmaceutical. This suggests that changes in M counts are primarily due to decrease in soft tissue activity and scatter from the adjacent lung

Impact of mediastinal, liver and lung 123I-metaiodobenzylguanidine (123I-MIBG) washout on calculated 123I-MIBG myocardial washout

PURPOSE: In planar (123)I-metaiodobenzylguanidine ((123)I-MIBG) myocardial imaging mediastinum (M) activity is often used as a background correction in calculating "washout" (WO). However, the most likely sources for counts that might produce errors in estimating myocardial (Myo) activity are lung (Lu) and liver (Li), which typically have higher counts/pixel (cpp) than M. The present study investigated the relationship between changes in Lu, Li and Myo activity between early and late planar (123)I-MIBG images, with comparison to M as the best estimator of non-specific background activity. METHODS: Studies on 98 subjects with both early (e) and late (l) planar (123)I-MIBG images were analysed. There were 68 subjects with chronic heart failure (CHF), 14 with hypertension (HTN) but no known heart disease and 16 controls (C). For each image, regions of interest (ROIs) were drawn: an irregular whole Myo, Lu, upper M and Li. For each ROI, WO was calculated as [(cpp(e)-cpp(l:decay corrected))/cpp(e)]x100%. RESULTS: Multivariable forward stepwise regression analysis showed that overall a significant proportion of the variation in Myo WO could be explained by a model containing M WO and Lu WO (37%, p < 0.001). Only in controls was M WO the sole variable explaining a significant proportion of the variation in Myo WO (27%, p = 0.023). CONCLUSION: Although increased Myo WO in CHF subjects reflects disease severity, part of the count differences measured on planar (123)I-MIBG myocardial images likely reflects changes in the adjacent and surrounding Lu tissue. The results for the controls suggest that this is the only group where a mediastinum correction alone may be appropriate for cardiac WO calculation

Plasma Proteomic Patterns Show Sex Differences in Early Concentric Left Ventricular Remodeling

BACKGROUND: Concentric remodeling (cRM) can precede heart failure with preserved ejection fraction (HFpEF), a condition prevalent in women. METHODS: Patients (n=60 593, 54.2% women) visiting outpatient clinics of Cardiology Centers of the Netherlands were analyzed for cRM, HFpEF development, and mortality risk. We studied risk factors for relative wall thickness both sex-stratified and in women and men combined. Biomarker profiling was performed (4534 plasma proteins) in a substudy involving 557 patients (65.4% women) to identify pathways involved in cRM. RESULTS: cRM was present in 23.5% of women and 27.6% of men and associated with developing HFpEF (HR, 2.15 [95% CI, 1.51-2.99]) and mortality risk (HR, 1.09 [95% CI, 1.00-1.19]) in both sexes. Age, heart rate, and hypertension were statistically significantly stronger risk factors for relative wall thickness in women than men. Higher circulating levels of IFNA5 (interferon alpha-5) were associated with higher relative wall thickness in women only. Pathway analysis revealed differential pathway activation by sex and increased expression of inflammatory pathways in women. CONCLUSIONS: cRM is prevalent in approximately 1 in 4 women and men visiting outpatient cardiology clinics and associated with HFpEF development and mortality risk in both sexes. Known risk factors for cRM were more strongly associated in women than men. Proteomic analysis revealed inflammatory pathway activation in women, with a central role for IFNA5. Differential biologic pathway activation by sex in cRM may contribute to the female predominance of HFpEF and holds promise for identification of new therapeutic avenues for prevention and treatment of HFpEF. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT001747

Development of a Pipeline for Adverse Drug Reaction Identification in Clinical Notes: Word Embedding Models and String Matching

BACKGROUND: Knowledge about adverse drug reactions (ADRs) in the population is limited because of underreporting, which hampers surveillance and assessment of drug safety. Therefore, gathering accurate information that can be retrieved from clinical notes about the incidence of ADRs is of great relevance. However, manual labeling of these notes is time-consuming, and automatization can improve the use of free-text clinical notes for the identification of ADRs. Furthermore, tools for language processing in languages other than English are not widely available. OBJECTIVE: The aim of this study is to design and evaluate a method for automatic extraction of medication and Adverse Drug Reaction Identification in Clinical Notes (ADRIN). METHODS: Dutch free-text clinical notes (N=277,398) and medication registrations (N=499,435) from the Cardiology Centers of the Netherlands database were used. All clinical notes were used to develop word embedding models. Vector representations of word embedding models and string matching with a medical dictionary (Medical Dictionary for Regulatory Activities [MedDRA]) were used for identification of ADRs and medication in a test set of clinical notes that were manually labeled. Several settings, including search area and punctuation, could be adjusted in the prototype to evaluate the optimal version of the prototype. RESULTS: The ADRIN method was evaluated using a test set of 988 clinical notes written on the stop date of a drug. Multiple versions of the prototype were evaluated for a variety of tasks. Binary classification of ADR presence achieved the highest accuracy of 0.84. Reduced search area and inclusion of punctuation improved performance, whereas incorporation of the MedDRA did not improve the performance of the pipeline. CONCLUSIONS: The ADRIN method and prototype are effective in recognizing ADRs in Dutch clinical notes from cardiac diagnostic screening centers. Surprisingly, incorporation of the MedDRA did not result in improved identification on top of word embedding models. The implementation of the ADRIN tool may help increase the identification of ADRs, resulting in better care and saving substantial health care costs