Citations

Sinus venosus defect (SVD) is a deficiency in the sinus venosus portion of the atrium, often associated with partial anomalous pulmonary venous connections. In patients with vein of Galen malformation (VGAM), SVD provides a unique challenge with respect to embolization treatment. In our case, the child had percutaneous device closure of the SVD prior to VGAM embolization. Nine years later, he required surgical removal of the SVD device and Warden procedure due to progressive right-sided cardiac enlargement.

Key PointsCoexisting psychiatric comorbidities are associated with greater increased health care utilization and cost of care in patients with MM. Clinical complications of MM are seen more frequently in patients with coexisting psychiatric conditions.

AbstractBACKGROUNDIncreased cardiac troponin I or T detected by high-sensitivity assays (hs-cTnI or hs-cTnT) confers an increased risk of adverse prognosis. We determined whether patients presenting with putatively normal, detectable cTn concentrations [> limit of detection and < upper reference limit (URL)] have increased risk of major adverse cardiovascular events (MACE) or all-cause mortality.METHODSA prospective 5-year follow-up of patients recruited in the emergency department with possible acute coronary syndrome (ACS) and cTn concentrations measured with hs-cTnI (Abbott) and hs-cTnT (Roche) assays. Cox regression models were generated with adjustment for covariates in those without MACE on presentation. Hazard ratios (HRs) for hs-cTn were calculated relative to the HRs at the median concentration.RESULTSOf 1113 patients, 836 were without presentation MACE. Of these, 138 incurred a MACE and 169 died during a median 5.8-year follow-up. HRs for MACE at the URLs were 2.3 (95% CI, 1.7–3.2) for hs-cTnI and 1.8 (95% CI, 1.3–2.4) for hs-cTnT. Corresponding HRs for mortality were 1.7 (95% CI, 1.2–2.2) for hs-cTnI and 2.3 (95 % CI, 1.7–3.1) for hs-cTnT. The HR for MACE increased with increasing hs-cTn concentration similarly for both assays, but the HR for mortality increased at approximately twice the rate for hs-cTnT than hs-cTnI. Patients with hs-cTnI ≥10 ng/L or hs-cTnT ≥16 ng/L had the same percentage of MACE at 5-year follow-up (33%) as patients with presentation MACE.CONCLUSIONSMany patients with ACS ruled out and putatively normal but detectable hs-cTnI concentrations are at similar long-term risk as those with MACE. hs-cTnT concentrations are more strongly associated with 5-year mortality than hs-cTnI.

Background: Copeptin in combination with troponin has been shown to have incremental value for the early rule-out of myocardial infarction, but its performance in Black patients specifically has never been examined. In light of a potential for wider use, data on copeptin in different relevant cohorts are needed. This is the first study to determine whether copeptin is equally effective at ruling out myocardial infarction in Black and Caucasian races. Methods: This analysis of the CHOPIN trial included 792 Black and 1075 Caucasian patients who presented to the emergency department with chest pain and had troponin-I and copeptin levels drawn. Results: One hundred and forty-nine patients were diagnosed with myocardial infarction (54 Black and 95 Caucasian). The negative predictive value of copeptin at a cut-off of 14 pmol/l (as in the CHOPIN study) for myocardial infarction was higher in Blacks (98.0%, 95% confidence interval (CI) 96.2–99.1%) than Caucasians (94.1%, 95% CI 92.1–95.7%). The sensitivity at 14 pmol/l was higher in Blacks (83.3%, 95% CI 70.7–92.1%) than Caucasians (53.7%, 95% CI 43.2–64.0%). After controlling for age, hypertension, heart failure, chronic kidney disease and body mass index in a logistic regression model, the interaction term had a P value of 0.03. A cut-off of 6 pmol/l showed similar sensitivity in Caucasians as 14 pmol/l in Blacks. Conclusions: This is the first study to identify a difference in the performance of copeptin to rule out myocardial infarction between Blacks and Caucasians, with increased negative predictive value and sensitivity in the Black population at a cut-off of 14 pmol/l. This also holds true for non-ST-segment elevation myocardial infarction and, although numbers were small, similar trends exist in the normal troponin population. This may have significant implications for early rule-out strategies using copeptin.

The increase in interstitial potassium (K+) during muscle contractions is thought to be a vasodilatory signal that contributes to exercise hyperemia. To determine the role of extracellular K+in exercise hyperemia, we perfused skeletal muscle with K+before contractions, such that the effect of any endogenously-released K+would be minimized. We tested the hypothesis that local, intra-arterial infusion of potassium chloride (KCl) at rest would impair vasodilation in response to subsequent rhythmic handgrip exercise in humans. In 11 young adults, we determined forearm blood flow (FBF) (Doppler ultrasound) and forearm vascular conductance (FVC) (FBF/mean arterial pressure) during 4 min of rhythmic handgrip exercise at 10% of maximal voluntary contraction during 1) control conditions, 2) infusion of KCl before the initiation of exercise, and 3) infusion of sodium nitroprusside (SNP) as a control vasodilator. Infusion of KCl or SNP elevated resting FVC similarly before the onset of exercise (control: 39 ± 6 vs. KCl: 81 ± 12 and SNP: 82 ± 13 ml·min−1·100 mmHg−1; both P < 0.05 vs. control). Infusion of KCl at rest diminished the hyperemic (ΔFBF) and vasodilatory (ΔFVC) response to subsequent exercise by 22 ± 5% and 30 ± 5%, respectively (both P < 0.05 vs. control), whereas SNP did not affect the change in FBF ( P = 0.74 vs. control) or FVC ( P = 0.61 vs. control) from rest to steady-state exercise. These findings implicate the K+ion as an essential vasodilator substance contributing to exercise hyperemia in humans.NEW & NOTEWORTHY Our findings support a significant and obligatory role for potassium signaling in the local vasodilatory and hyperemic response to exercise in humans.

Abstract Background Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10−8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. Methods We conducted a GWAS in European descent CRC cases and control subjects using a discovery–replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10−8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. Results The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10−8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. Conclusions This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.