An Extremely Rare Congenital Muscle Bundle Crossing the Right Atrial Cavity.

Muscle bundles in the right atrium are an extremely rare congenital anomaly. We report the case of a patient with 2 atrial septal defects and a large muscle bundle crossing the right atrium. Only 3 comparable cases have previously been published. (Level of Difficulty: Intermediate.).

Colchicine in Patients With Coronary Artery Disease: A Systematic Review and Meta-Analysis of Randomized Trials.

Background Inflammation plays a pivotal role in coronary artery disease (CAD). The anti-inflammatory drug colchicine seems to reduce ischemic events in patients with CAD. So far there is equipoise about its safety and impact on mortality. Methods and Results To evaluate the utility of colchicine in patients with acute and chronic CAD, we performed a systematic review and meta-analysis. MEDLINE, EMBASE, Cochrane CENTRAL and conference abstracts were searched from January 1975 to October 2020. Randomized trials assessing colchicine compared with placebo/standard therapy in patients with CAD were included. Data were combined using random-effects models. The reliability of the available data was tested using trial sequential analyses . Of 3108 citations, 13 randomized trials (n=13 125) were included. Colchicine versus placebo/standard therapy in patients with CAD reduced risk of myocardial infarction (odds ratio [OR] 0.64; 95% CI, 0.46-0.90; P=0.01; I2 41%) and stroke/transient ischemic attack (OR 0.50; 95% CI, 0.31-0.81; P=0.005; I2 0%). But treatment with colchicine compared with placebo/standard therapy had no influence on all-cause and cardiovascular mortality (OR 0.96; 95% CI, 0.65-1.41; P=0.83; I2 24%; and OR 0.82; 95% CI, 0.55-1.22; P=0.45; I2 0%, respectively). Colchicine increased the risk for gastrointestinal side effects (P<0.001). According to trial sequential analyses, there is only sufficient evidence for a myocardial infarction risk reduction with colchicine. Conclusions Among patients with CAD, colchicine reduces the risk of myocardial infarction and stroke, but has a higher rate of gastrointestinal upset with no influence on all-cause mortality.

Efficacy of Ranolazine for Treatment of Coronary Microvascular Dysfunction-A Systematic Review and Meta-analysis of Randomized Trials.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a common cause of angina and exercise intolerance in patients without obstructive coronary artery disease. The efficacy of ranolazine, a late sodium channel blocker, in patients with symptomatic obstructive coronary artery disease is well established. To evaluate the efficacy of ranolazine in CMD, we performed a systematic review and meta-analysis of randomized studies. METHODS: MEDLINE, EMBASE, Cochrane CENTRAL, and conference abstracts were searched from January 1975 to March 2020. Randomized trials evaluating ranolazine in patients with CMD were screened. Two reviewers independently extracted data and assessed study quality. End points of interest included a change in angina measured by the Seattle Angina Questionnaire (SAQ), coronary flow reserve (CFR), and clinical outcomes. Data were combined using random-effects models. RESULTS: Of 836 citations, 6 randomized studies (318 patients) were included. Median follow-up was 4 weeks. When pooling the 6 trials analyzing ranolazine, we found that patients treated with ranolazine had a higher SAQ value regarding physical functioning (mean difference, 6.42; 95% confidence interval [CI], 2.41; 10.42) quality of life (10.07; 95% CI, 3.4; 16.74), and angina stability (20.14; 95% CI, 10.12; 30.17), as well as improved CFR (0.27; 95% CI, 0.09; 0.45) compared with placebo/control therapy. A high heterogeneity was observed (range I 2, 30%-84%). CONCLUSIONS: In CMD, ranolazine may be associated with improvements in CFR and some of the SAQ domains, including angina stability, physical functioning, and quality of life. However, it does not seem to beneficially impact angina frequency and treatment satisfaction. It is also unknown if it improves prognosis of afflicted patients.

CONTEXTE: La dysfonction microvasculaire coronaire (DMC) est une cause courante d'angine et d'intolérance à l'effort chez les patients sans coronaropathie obstructive. L'efficacité de la ranolazine, un bloqueur des canaux sodiques tardifs, chez les patients atteints d'une coronaropathie obstructive symptomatique est bien établie. Pour évaluer l'efficacité de la ranolazine dans le traitement de la DMC, nous avons effectué une revue systématique et méta-analyse d'études à répartition aléatoire. MÉTHODOLOGIE: MEDLINE, EMBASE, Cochrane CENTRAL et les résumés de congrès ont fait l'objet d'une recherche pour la période allant de janvier 1975 à mars 2020. Les essais à répartition aléatoire sur l'emploi de la ranolazine chez des patients atteints de DMC ont été criblés. Deux examinateurs ont, de manière indépendante, extrait les données et évalué la qualité des études. Les paramètres d'intérêt étaient une variation de l'angine mesurée à l'aide du questionnaire SAQ (Seattle Angina Questionnaire), la réserve coronaire et les issues cliniques. Les données ont été combinées avec des modèles à effets aléatoires. RÉSULTATS: Parmi 836 références, six études à répartition aléatoire (318 patients) ont été retenues. La durée médiane de suivi était de quatre semaines. Après avoir regroupé les données des six essais sur la ranolazine, nous avons constaté que les patients traités par la ranolazine avaient un score SAQ plus élevé en ce qui a trait au fonctionnement physique (différence moyenne : 6,42; intervalle de confiance [IC] à 95 % : 2,41 à 10,42), à la qualité de vie (10,07; IC à 95 % : 3,4 à 16,74) et à la stabilité de l'angine (20,14; IC à 95 % : 10,12 à 30,17), de même qu'une réserve coronaire améliorée (0,27; IC à 95 % : 0,09 à 0,45) comparativement aux patients ayant reçu un placebo/traitement témoin. Une forte hétérogénéité a été observée (plage des I 2 : 30 à 84 %). CONCLUSIONS: Dans les cas de DMC, la ranolazine est associée à des améliorations de la réserve coronaire et de certains des domaines du questionnaire SAQ, dont la stabilité de l'angine, le fonctionnement physique et la qualité de vie. Toutefois, elle ne semble pas avoir d'effet bénéfique sur la fréquence de l'angine et la satisfaction à l'égard du traitement. On ne sait pas non plus si elle améliore le pronostic des patients touchés.

"Exercise induced asthma" is not always asthma.

A 25 year old woman was referred to our center for further evaluation of an exercise-induced dyspnea. Moreover, the patient suffered from hoarseness and recurrent sinusitis and otitis. After initially finding nothing suspicious, a spiro-ergometry was performed. Interestingly, we saw a relevant limitation of the inspiratory flow-volume curve under maximal exercise load. Further evaluation (in particular the bronchoscopy and the resulting biopsies) led us to the final diagnosis of a granulomatosis with polyangiitis. After 4 weeks of an established therapy regime with prednisone and rituximab the prior detected subglottic stenosis and the inspiratory flow-volume curve limitation could no longer detected. We describe a rare differential diagnosis of an exercise-induced asthma and we underline the importance of a multimodal therapy concept. We highlight the critical nature of the flow-volume curve in spiro-ergometry under maximal exercise load. We recommend frequent follow-up control visits to monitor the subglottic stenosis.

Relationships of Measured and Genetically Determined Height With the Cardiac Conduction System in Healthy Adults.

BACKGROUND: Increasing height is an independent risk factor for atrial fibrillation, but the underlying mechanisms are unknown. We hypothesized that height-related differences in electric conduction could be potential mediators of this relationship. METHODS AND RESULTS: We enrolled 2149 adults aged 25 to 41 years from the general population. Height was directly measured, and a resting 12-lead ECG obtained under standardized conditions. Multivariable linear regression models were used to evaluate the association between measured height and ECG parameters. Mendelian randomization analyses were then performed using 655 independent height-associated genetic variants previously identified in the GIANT consortium. Median age was 37 years, and median height was 1.71 m. Median PR interval, QRS duration, and QTc interval were 156, 88, and 402 ms, respectively. After multivariable adjustment, ß-coefficients (95% confidence intervals) per 10 cm increase in measured height were 4.17 (2.65-5.69; P<0.0001) for PR interval and 2.06 (1.54-2.58; P<0.0001) for QRS duration. Height was not associated with QTc interval or the Sokolow-Lyon index. An increase of 10 cm in genetically determined height was associated with increases of 4.33 ms (0.76-7.96; P=0.02) in PR interval and 2.57 ms (1.33-3.83; P<0.0001) in QRS duration but was not related to QTc interval or Sokolow-Lyon index. CONCLUSIONS: In this large population-based study, we found significant associations of measured and genetically determined height with PR interval and QRS duration. Our findings suggest that adult height is a marker of altered cardiac conduction and that these relationships may be causal.

Relationships of iron metabolism with insulin resistance and glucose levels in young and healthy adults.

AIMS: Several biomarkers within the iron metabolism pathway have been related to the occurrence of diabetes mellitus, but underlying mechanisms are unknown. The aim of our study was to investigate the differential relationships of iron metabolism with a broad range of diabetes markers in young and healthy adults. DESIGN: 2160 participants aged 25 to 41years were enrolled in a population-based study. Established cardiovascular disease, diabetes or a body mass index >35kg/m(2) were exclusion criteria. Multivariable linear regression models were built to assess the associations of ferritin and transferrin saturation (TSAT) with blood levels of glucagon-like peptide-1 (GLP-1), insulin, homeostatic model assessment-insulin resistance (HOMA-IR), fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). RESULTS: Median (interquartile range) age was 37 (31, 40) years. In multivariable linear regression analyses, ß-coefficients (95% confidence intervals) per 1-SD increase in ferritin were 0.04 (0.02; 0.07, p=0.0008) for GLP-1, 0.06 (0.04; 0.08, p<0.0001) for insulin, 0.07 (0.04; 0.09, p<0.0001) for HOMA-IR, 0.004 (-0.00; 0.01, p=0.07) for FPG and -0.003 (-0.01; -0.00, p=0.07) for HbA1c. ß-coefficients (95% CI) per 1-SD increase in TSAT were -0.07 (-0.09; -0.05, p<0.0001) for GLP-1, -0.06 (-0.08; -0.04, p<0.0001) for insulin, -0.07(-0.09; -0.05, p<0.0001) for HOMA-IR, -0.01 (-0.01; -0.00, p<0.0001) for FPG and -0.01 (-0.01; -0.00, p=0.0004) for HbA1c. CONCLUSIONS: Markers of insulin resistance are strongly related with markers of iron metabolism in healthy subjects. These relationships were inconsistent and weaker for short-term and long-term glucose levels. These results may provide insights in the relationships between iron metabolism and diabetes occurrence.

Relationship of N-Terminal fragment of Pro-B-Type Natriuretic Peptide and copeptin with erythrocytes-related parameters: A population-based study.

BACKGROUND: Plasma levels of natriuretic peptides (NP) have been inversely related to hemoglobin (Hb) concentration in prior studies. However, the mechanism underlying this association remains unclear. We aimed to obtain further insights into potential mechanisms for this correlation in a cohort of healthy adults. METHODS: A population-based study was performed among 2113 healthy adults aged 25-41years. Relationships of N-Terminal fragment of Pro-B-Type Natriuretic Peptide (NT-proBNP) or copeptin with volume-dependent (Hb, hematocrit (Hct), erythrocyte count (EC), mean corpuscular Hb concentration (MCHC)) and volume-independent (mean corpuscular volume (MCV), mean corpuscular Hb (MCH)) erythrocyte-related parameters were assessed using sex-specific multivariable linear regression analyses. RESULTS: The median age was 36.7years. Median NT-proBNP (ng/L) levels were 49.5 and 20 among women and men, respectively (p<0.0001). Mean (standard deviation) Hb (g/L) levels were 130.1(9.1) and 149.7(8.6) among women and men, respectively (p<0.0001). Among men, multivariable adjusted ß-coefficients (95% confidence interval) for NT-proBNP were -1.68 (-2.36; -1.01), p<0.0001 for Hb; -0.38 (-0.57; -0.20), p<0.0001 for Hct; -0.06 (-0.09; -0.04), p<0.0001 for EC; -0.78 (-1.50; -0.07), p=0.03 for MCHC; 0.26 (-0.04; 0.56), p=0.09 for MCV; and 0.03 (-0.08; 0.14), p=0.61 for MCH. For copeptin, these relationships were 1.36 (0.39; 2.32), p=0.006; 0.41 (0.15; 0.68), p=0.002; 0.06 (0.02; 0.09), p=0.002; -0.17 (-1.19; 0.86), p=0.75; -0.12 (-0.55; 0.31), p=0.58 and -0.05 (-0.21; 0.10), p=0.52. Similar results were observed among women. CONCLUSIONS: We found significant relationships of NT-proBNP and copeptin with volume-dependent but not volume-independent erythrocyte-related parameters, suggesting that hemodilution may at least in part explain these associations.

The interrelationships of birthweight, inflammation and body composition in healthy adults.

BACKGROUND: Lower birthweight is associated with an increased risk of cardiovascular diseases and diabetes. We hypothesized that inflammation and body fat may be potential mediators for these inverse relationships. MATERIALS AND METHODS: Healthy adults aged 25-41 years were enrolled in a prospective population-based cohort study in the Principality of Liechtenstein. Main exclusion criteria were diabetes, overt cardiovascular disease or a body mass index > 35 kg/m(2) . Birthweight was self-reported by the study participants. White blood cell (WBC) count and high-sensitivity C-reactive protein (hs-CRP) levels were assayed from fresh blood samples. Body composition was determined by bioelectrical impedance analysis. Multivariable linear regression models were constructed to assess the relationships between birthweight, inflammation and body composition. RESULTS: Our sample consisted of 1774 participants (53·4% females) with a median age of 37 years. Median birthweight was 3355 g. In multivariable models, we found an inverse relationship of birthweight with hs-CRP levels (ß -0·010 (95% CI -0·02; -0·002), P = 0·01) and WBC count (ß -0·002 (95% CI -0·004; -0·0002), P = 0·03). Additional adjustment for body fat mass attenuated these relationships (ß -0·008 (95% CI -0·02; 0·0003), P = 0·06 for hs-CRP levels and (ß -0·002 (95% CI -0·004; 0·0006), P = 0·16 for WBC count. Body fat mass itself was strongly associated with birthweight (ß -0·06 (95% CI -0·10; -0·03), P < 0·0001). CONCLUSION: Birthweight is inversely associated with inflammation in adulthood. This relationship may be mediated by an elevated body fat mass among individuals with lower birthweight.