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

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

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

Clinical performance and radiation dosimetry of no-carrier-added vs carrier-added 123I-metaiodobenzylguanidine (MIBG) for the assessment of cardiac sympathetic nerve activity

Purpose We hypothesized that assessment of myocardial sympathetic activity with no-carrier-added (nca) I-123-metaiodobenzylguanidine (MIBG) compared to carrier-added (ca) I-123-MIBG would lead to an improvement of clinical performance without major differences in radiation dosimetry. Methods In nine healthy volunteers, 15 min and 4 h planar thoracic scintigrams and conjugate whole-body scans were performed up to 48 h following intravenous injection of 185 MBq I-123-MIBG. The subjects were given both nca and ca I-123-MIBG. Early heart/mediastinal ratios (H/M), late H/M ratios and myocardial washout were calculated. The fraction of administered activity in ten source organs was quantified from the attenuation-corrected geometric mean counts in conjugate views. Radiation-absorbed doses were estimated with OLINDA/EXM software. Results Both early and late H/M were higher for nca I-123-MIBG (ca I-123-MIBG early H/M 2.46 +/- 0.15 vs nca I-123-MIBG 2.84 +/- 0.15, p = 0.001 and ca I-123-MIBG late H/M 2.69 +/- 0.14 vs nca I-123-MIBG 3.34 +/- 0.18, p = 0.002). Myocardial washout showed a longer retention time for nca I-123-MIBG (p <0.001). The effective dose equivalent (adult male model) for nca I-123-MIBG was similar to that for ca I-123-MIBG (0.025 +/- 0.002 mSv/MBq vs 0.026 +/- 0.002 mSv/MBq, p = 0.055, respectively). Conclusion No-carrier-added I-123-MIBG yields a higher relative myocardial uptake and is associated with a higher myocardial retention. This difference between nca I-123-MIBG and ca I-123-MIBG in myocardial uptake did not result in major differences in estimated absorbed doses. Therefore, nca I-123-MIBG is to be preferred over ca I-123-MIBG for the assessment of cardiac sympathetic activit

Normal values and within-subject variability of cardiac I-123 MIBG scintigraphy in healthy individuals: implications for clinical studies

Although several myocardial iodine 123 metaiodobenzylguanidine (MIBG) indices are increasingly used to detect alterations in myocardial sympathetic activity in various forms of cardiac pathology, published measurements of normal values and within-subject variability are lacking. Twenty-five healthy volunteers underwent planar and single photon emission computed tomography (SPECT) imaging. Heart-mediastinum ratio (H/M) and myocardial washout were calculated from planar images comparing three different methods for the assessment of myocardial activity: (1) global region over the myocardium (cavity included), (2) global region over the myocardium (cavity excluded), and (3) fixed small myocardial region. Segmental (relative) uptake and washout were assessed by SPECT. For all MIBG indices, the interindividual variation was the lowest for methods 1 and 2. In SPECT this variation was low for relative segmental uptake compared with washout. In 9 subjects a second MIBG scintigraphy was performed after 3 months. The within-subject variability of H/M and washout assessed by planar methods 1 and 2 was 5%, whereas it was approximately 9% for planar method 3. For relative segmental uptake from SPECT, this variability was 5%. MIBG H/M (planar) and relative segmental uptake (SPECT) show a low interindividual and within-subject variability. This enables the detection of small (regional) variations in myocardial sympathetic nervous function, especially to monitor the effect of therapeutic interventions in patients with various cardiac disease

Ventricular mechanical dyssynchrony and resynchronization therapy in heart failure: a new indication for Fourier analysis of gated blood-pool radionuclide ventriculography

In patients with decreased left ventricular ejection fraction and conduction disease, ventricular mechanical dyssynchrony has been demonstrated. To date, resynchronization by biventricular pacing is increasingly used since it improves ventricular function and exercise capacity in patients with heart failure. To optimize and evaluate the effect of resynchronization therapy and to identify patients who may benefit from biventricular pacing the assessment of left ventricular synchronicity is essential. Therefore, a non-invasive and reproducible technique to obtain information on ventricular synchrony is clinically valuable. In this review, the technical background and the role of phase analysis of gated blood-pool nuclear ventriculography in the assessment of ventricular mechanical synchrony, especially in heart failure patients subjected to biventricular pacing, will be discusse

Risk of aerosol transmission of SARS-CoV-2 in a clinical cardiology setting

Cardiac exercise stress testing (CEST) is an important diagnostic tool in daily cardiology practice. However, during intense physical activity microdroplet aerosols, potentially containing SARS-CoV-2 particles, can persist in a room for a long time. This poses a potential infection risk for the medical staff involved in CEST, as well as for the patients entering the same room afterwards. We measured aerosol generation and persistence, to perform a risk assessment for SARS-CoV-2 transmission through aerosols during CEST. We find that during CEST, the aerosol levels remain low enough that SARS-CoV-2 transmission through aerosols is unlikely, with the room ventilation system producing 14 air changes per hour. A simple measurement of CO2 concentration gives a good indication of the ventilation quality