Plasma N-terminal pro-B-type natriuretic peptide in the detection of aortic valve stenosis.

BACKGROUND: Systolic murmur suggestive of aortic valve origin is a common accidental finding, particularly in the elderly. Usually, it is due to aortic stenosis (AS) or aortic sclerosis (ASc). Currently, echocardiography is used to differentiate AS from ASc. Plasma N-terminal (NT)-prohormone BNP (NT-proBNP) is known to correlate with the severity of AS. We assessed whether NT-proBNP separates AS from ASc. METHODS: The study population consisted of three groups: AS (n = 87, age 77 ± 7 years), ASc (n = 76, age 72 ± 10 years), and healthy controls (n = 101, age 55 ± 10 years). All subjects underwent transthoracic echocardiography and measurement of plasma NT-proBNP. Patients with diseases known to increase NT-proBNP were excluded. RESULTS: The crude plasma NT-proBNP (median; IQR) in AS patients (413; 165-1055 ng/l) was significantly higher compared to ASc patients (96; 53-237 ng/l, p < 0.001) and healthy controls (50; 29-76 ng/l, p < 0.001). After adjusting for the confounding factors (age, coronary artery disease, renal function and diastolic blood pressure), plasma NT-proBNP remained significantly higher in AS patients as compared to ASc (p < 0.002) and controls (p < 0.0001). In the receiver-operating characteristic curve for NT-proBNP to identify AS from ASc and controls, the area under the curve was 0.878 with optimal cutoff of 115 ng/l. In addition, using 115 ng/l to separate AS from ASc yielded sensitivity of 0.885, and negative predictive value of 0.808. CONCLUSIONS: NT-proBNP was sensitive to identify AS and useful to rule out AS in patients with systolic murmur in the left ventricular outflow tract provided the patient does not have coexisting disease known to impact NT-proBNP.

Heparin does not improve myocardial glucose metabolism suppression in [18 F]FDG PET/CT in patients with low ß-hydroxybutyrate level.

BACKGROUND: Inadequate myocardial glucose metabolism suppression (GMS) can hamper interpretation of cardiac [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET/CT). Use of ß-hydroxybutyrate (BHB) measurement before [18F]FDG injection has been proposed for predicting adequate GMS. However, limited information is available on BHB measurement in guiding preparations for [18F]FDG-PET/CT. The purpose of this study was to evaluate if point-of-care measured BHB is useful in guiding heparin premedication for cardiac [18F]FDG-PET/CT. RESULTS: 155 patients (82 male) had followed a high-fat, low-carbohydrate diet and fasted for at least twelve hours. For the first 63 patients, BHB was measured, but it was not used to guide premedication. For the subsequent 92 patients, heparin 50 IU/kg was injected intravenously 15-20 min before [18F]FDG injection if the BHB level was low (< 0.35 mmol/l). Cardiac [18F]FDG uptake pattern was evaluated visually and [18F]FDG uptake in the myocardium and blood pool were measured. Median BHB level was 0.4 (range 0.1-5.8) mmol/l. Eighty-eight patients (57%) reached a BHB level higher than 0.35 mmol/l. 112 patients (72%) had adequate GMS. In the high BHB group, 74 patients (84%) had adequate GMS, whereas of those with low BHB, only 38 (57%) had adequate GMS (p < 0.001). In the low BHB group, the prevalence of inadequate GMS was comparable in patients with and without heparin (44% vs. 42%, p = 0.875). CONCLUSIONS: While high BHB predicts adequate GMS, unfractionated heparin does not improve GMS in patients with low BHB.

30-Year Trends in the Incidence, Characteristics, and Outcome of Cardiac Sarcoidosis in a Nationwide Cohort.

Background: Cardiac sarcoidosis (CS) is a rare but potentially fatal inflammatory cardiomyopathy. Objectives: The authors studied temporal changes in the incidence, characteristics, and outcome of CS. Methods: A retrospective analysis was made of a 30-year nationwide cohort of CS. Results: The cohort comprised 511 patients with a median age of 52 years and female preponderance (69%). Altogether 77, 166, and 268 cases of CS were diagnosed in years 1988 to 2009, 2010 to 2014, and 2015 to 2019, respectively; the 5-year count of 2015 to 2019 was 134-fold the count of 1990 to 1994 (268/2) and 18-fold the count of 2000 to 2004 (268/15). Prior to 2010, compared with the later periods, CS presented more often with ventricular tachycardia/fibrillation (prevalence 36% vs 19% in 2010-2014 and 11% in 2015-2019, P < 0.001), left ventricular ejection fraction <50% (49%, 35%, and 31%; P = 0.010), and elevation of natriuretic peptides (87%, 57%, and 49%; P < 0.001). On magnetic resonance imaging, late gadolinium enhancement involved a median of 15% (IQR: 11%-22%) of left ventricular mass in studies of 1988 to 2009 (n = 16), 15% (IQR: 9%-22%) in studies of 2010 to 2014 (n = 87), and 11% (IQR: 5%-19%) in studies of 2015 to 2019 (n = 150) (P = 0.031). The respective 5-year incidences of the composite of death, heart transplantation, left ventricular-assisted device implantation, or ventricular tachyarrhythmia were 40% (95% CI: 29%-51%), 32% (95% CI: 25%-39%), and 23% (95% CI: 16%-30%) (P = 0.002). The prognostic trend disappeared after adjustment for differences in the presenting phenotype. Conclusions: Diagnoses of incident CS have increased exponentially in Finland. Concurrently, the phenotype has turned milder and prognosis better, suggesting detection of CS at an earlier stage of its course.

Biallelic loss-of-function in NRAP is a cause of recessive dilated cardiomyopathy.

BACKGROUND: Familial dilated cardiomyopathy (DCM) is typically a monogenic disorder with dominant inheritance. Although over 40 genes have been linked to DCM, more than half of the patients undergoing comprehensive genetic testing are left without molecular diagnosis. Recently, biallelic protein-truncating variants (PTVs) in the nebulin-related anchoring protein gene (NRAP) were identified in a few patients with sporadic DCM. METHODS AND RESULTS: We determined the frequency of rare NRAP variants in a cohort of DCM patients and control patients to further evaluate role of this gene in cardiomyopathies. A retrospective analysis of our internal variant database consisting of 31,639 individuals who underwent genetic testing (either panel or direct exome sequencing) was performed. The DCM group included 577 patients with either a confirmed or suspected DCM diagnosis. A control cohort of 31,062 individuals, including 25,912 individuals with non-cardiac (control group) and 5,150 with non-DCM cardiac indications (Non-DCM cardiac group). Biallelic (n = 6) or two (n = 5) NRAP variants (two PTVs or PTV+missense) were identified in 11 unrelated probands with DCM (1.9%) but none of the controls. None of the 11 probands had an alternative molecular diagnosis. Family member testing supports co-segregation. Biallelic or potentially biallelic NRAP variants were enriched in DCM vs. controls (OR 1052, p<0.0001). Based on the frequency of NRAP PTVs in the gnomAD reference population, and predicting full penetrance, biallelic NRAP variants could explain 0.25%-2.46% of all DCM cases. CONCLUSION: Loss-of-function in NRAP is a cause for autosomal recessive dilated cardiomyopathy, supporting its inclusion in comprehensive genetic testing.

Range margin shifts of birds revisited - the role of spatiotemporally varying survey effort.

Global climate warming is predicted to lead to global and regional changes in the distribution of organisms. One influential approach to test this prediction using temporally repeated mapping surveys of organisms was suggested in a seminal paper by Thomas & Lennon (1999, Nature). The Thomas & Lennon approach corrects observed changes in the range margin for changes in the range size, and thus potentially controls for other broad-scale environmental changes between surveys, however the approach does not necessarily account for potential biases in sampling effort. To verify whether the issue of variation in sampling effort affects empirical estimates of shifts in range margin, we reanalyzed all three published studies exploring range margin changes of breeding birds in Great Britain (GB), Finland, and New York State (NY). Accounting for changes in survey effort on range margins lowered the estimated shift for breeding birds in New York, but the shift remained statistically significant. For Great Britain and Finland, for which no direct estimate of survey effort is available, we used species richness (a strong correlate of survey effort in New York) as a proxy and found that in both cases the estimated shift in range margin was significantly reduced and became nonsignificant. To understand how robust the approach is to sampling biases, we use a simulation model to show that the Thomas & Lennon approach is, under certain conditions, sensitive to changes in detection probability (probability to detect true occupancy) which in turn may be affected by changes in surveying effort between surveys. We thus found evidence that temporal changes in the distribution of breeding birds based on repeated mapping surveys may be inflated by changes in survey effort along range boundaries. We discuss possible approaches to deal with this issue in the analysis and design of national or regional surveys.