Focal dermal hypoplasia (goltz-gorlin syndrome): A new case with a novel variant in the PORCN gene (c.1250T>C:p.F417S) and unusual spinal anomaly.

Focal dermal hypoplasia (FDH; Goltz-Gorlin syndrome; OMIM 305600) is a disorder that features involvement of the skin, skeletal system, and eyes. It is caused by loss-of-function mutations in the PORCN gene. We report a young girl with FDH, microphthalmos associated with colobomatous orbital cyst, dural ectasia and cystic malformation of the spinal cord, and a de novo variant in PORCN. This association has not been previously reported, and based on these observations the phenotypic spectrum of FDH might be broader than previously appreciated. It would be prudent to alter the suggested surveillance for this rare disorder. © 2013 Wiley Periodicals, Inc.

Impact of salt on cardiac differential gene expression and coronary lesion in normotensive mineralocorticoid-treated mice.

We previously reported that excess of deoxycorticosterone-acetate (DOCA)/salt-induced cardiac hypertrophy in the absence of hypertension in one-renin gene mice. This model allows us to study molecular mechanisms of high-salt intake in the development of cardiovascular remodeling, independently of blood pressure in a high mineralocorticoid state. In this study, we compared the effect of 5-wk low- and high-salt intake on cardiovascular remodeling and cardiac differential gene expression in mice receiving the same amount of DOCA. Differential gene and protein expression was measured by high-density cDNA microarray assays, real-time PCR and Western blot analysis in DOCA-high salt (HS) vs. DOCA-low salt (LS) mice. DOCA-HS mice developed cardiac hypertrophy, coronary perivascular fibrosis, and left ventricular dysfunction. Differential gene and protein expression demonstrated that high-salt intake upregulated a subset of genes encoding for proteins involved in inflammation and extracellular matrix remodeling (e.g., Col3a1, Col1a2, Hmox1, and Lcn2). A major subset of downregulated genes encoded for transcription factors, including myeloid differentiation primary response (MyD) genes. Our data provide some evidence that vascular remodeling, fibrosis, and inflammation are important consequences of a high-salt intake in DOCA mice. Our study suggests that among the different pathogenic factors of cardiac and vascular remodeling, such as hypertension and mineralocorticoid excess and sodium intake, the latter is critical for the development of the profibrotic and proinflammatory phenotype observed in the heart of normotensive DOCA-treated mice.

Comparativecost-effectivenessanalyses of cardiacmagneticresonanceimaging versus invasive coronary angiography combined with fractional flow reserve testing to diagnose ischemia in coronary artery disease

Introduction: According to guidelines, patients with coronary artery disease (CAD) should undergo revascularization if myocardial ischemia is present. While coronary angiography (CXA) allows the morphological assessment of CAD, the fractional flow reserve (FFR) has proved to be a complementary invasive test to assess the functional significance of CAD, i.e. to detect ischemia. Perfusion Cardiac Magnetic Resonance (CMR) has turned out to be a robust non-invasive technique to assess myocardial ischemia. The objective: is to compare the cost-effectiveness ratio - defined as the costs per patient correctly diagnosed - of two algorithms used to diagnose hemodynamically significant CAD in relation to the pretest likelihood of CAD: 1) aCMRto assess ischemia before referring positive patients to CXA (CMR + CXA), 2) a CXA in all patients combined with a FFR test in patients with angiographically positive stenoses (CXA + FFR). Methods: The costs, evaluated from the health care system perspective in the Swiss, German, the United Kingdom (UK) and the United States (US) contexts, included public prices of the different tests considered as outpatient procedures, complications' costs and costs induced by diagnosis errors (false negative). The effectiveness criterion wasthe ability to accurately identify apatient with significantCAD.Test performancesused in the model were based on the clinical literature. Using a mathematical model, we compared the cost-effectiveness ratio for both algorithms for hypothetical patient cohorts with different pretest likelihood of CAD. Results: The cost-effectiveness ratio decreased hyperbolically with increasing pretest likelihood of CAD for both strategies. CMR + CXA and CXA + FFR were equally costeffective at a pretest likelihood of CAD of 62% in Switzerland, 67% in Germany, 83% in the UK and 84% in the US with costs of CHF 5'794, Euros 1'472, £ 2'685 and $ 2'126 per patient correctly diagnosed. Below these thresholds, CMR + CXA showed lower costs per patient correctly diagnosed than CXA + FFR. Implications for the health care system/professionals/patients/society These results facilitate decision making for the clinical use of new generations of imaging procedures to detect ischemia. They show to what extent the cost-effectiveness to diagnose CAD depends on the prevalence of the disease.

Common variants associated with plasma triglycerides and risk for coronary artery disease.

Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 × 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

Contribution of major cardiovascular risk factors to familial premature coronary artery disease: the GENECARD project.

OBJECTIVES: This study was designed to assess the prevalence of major cardiovascular risk factors in familial premature coronary artery disease (P-CAD), affecting two or more siblings within one sibship. BACKGROUND: Premature CAD has a genetic component. It remains to be established whether familial P-CAD is due to genes acting independently from major cardiovascular risk factors. METHODS: We recruited 213 P-CAD survivors from 103 sibships diagnosed before age <or=50 (men) or <or=55 (women) years old. Hypertension, hypercholesterolemia, obesity, and smoking were documented at the time of the event in 163 patients (145 men and 18 women). Each patient was compared with two individuals of the same age and gender, diagnosed with sporadic (nonfamilial) P-CAD, and three individuals randomly sampled from the general population. RESULTS: Compared with the general population, patients with sporadic P-CAD had a higher prevalence of hypertension (29% vs. 14%, p < 0.001), hypercholesterolemia (54% vs. 33%, p < 0.001), obesity (20% vs. 13%, p < 0.01), and smoking (76% vs. 39%, p < 0.001). These risk factors were equally or even more prevalent in patients with familial P-CAD (43% [p < 0.05 vs. sporadic P-CAD], 58% [p = 0.07], 21% and 72%, respectively). Overall, only 7 (4%) of 163 of patients with familial P-CAD and 22 (7%) of 326 of patients with sporadic P-CAD had none of these conditions, as compared with 167 (34%) of 489 patients in the general population. CONCLUSIONS: Classic, remediable risk factors are highly prevalent in patients with familial P-CAD. Accordingly, a major contribution of genes acting in the absence of these risk factors is unlikely.

High prevalence of unsuspected abdominal aortic aneurysms in patients hospitalised for surgical coronary revascularisation.

OBJECTIVES: Prevalence of abdominal aortic aneurysms (AAA) is not exactly known among patients with coronary artery disease (CAD) who are considered for surgical revascularisation. We evaluated the value of screening AAA among coronary patients admitted in our cardiovascular surgery unit. METHODS: Over a 24-month period, an abdominal echography was proposed to male patients aged 60 or more while hospitalised for surgical coronary revascularisation. Patients with previous investigation of the aorta were excluded. The aorta was considered aneurysmal when the anterior-posterior diameter was of 30 mm or more. RESULTS: Three hundred and ninety-five consecutive patients all accepted a proposed abdominal echographic screening for AAA. Forty unsuspected AAA were detected (10.1%). The mean diameter was 38.9 +/- 1.3 mm. Four AAA were larger than 50 mm and considered for surgery after the CABG procedure. Surveillance was proposed to the other 36, especially the 10 patients with an AAA larger than 40 mm. Patients with AAA were significantly older than those without AAA (71.3 +/- 0.8 vs. 69.4 +/- 0.3 years, P<0.05). Smoking history (P<0.05) and hypertension (P<0.05) were also associated more frequently with AAA. More than 16% of the patients being smokers and suffering hypertension presented with unsuspected AAA. CONCLUSIONS: In-hospital screening of AAA is very efficient among patients with coronary artery disease. Therefore, patients with CAD may be considered for routine AAA screening.

Right coronary artery flow velocity and volume assessment with spiral K-space sampled breathhold velocity-encoded MRI at 3 tesla: accuracy and reproducibility.

PURPOSE: To evaluate accuracy and reproducibility of flow velocity and volume measurements in a phantom and in human coronary arteries using breathhold velocity-encoded (VE) MRI with spiral k-space sampling at 3 Tesla. MATERIALS AND METHODS: Flow velocity assessment was performed using VE MRI with spiral k-space sampling. Accuracy of VE MRI was tested in vitro at five constant flow rates. Reproducibility was investigated in 19 healthy subjects (mean age 25.4 +/- 1.2 years, 11 men) by repeated acquisition in the right coronary artery (RCA). RESULTS: MRI-measured flow rates correlated strongly with volumetric collection (Pearson correlation r = 0.99; P < 0.01). Due to limited sample resolution, VE MRI overestimated the flow rate by 47% on average when nonconstricted region-of-interest segmentation was used. Using constricted region-of-interest segmentation with lumen size equal to ground-truth luminal size, less than 13% error in flow rate was found. In vivo RCA flow velocity assessment was successful in 82% of the applied studies. High interscan, intra- and inter-observer agreement was found for almost all indices describing coronary flow velocity. Reproducibility for repeated acquisitions varied by less than 16% for peak velocity values and by less than 24% for flow volumes. CONCLUSION: 3T breathhold VE MRI with spiral k-space sampling enables accurate and reproducible assessment of RCA flow velocity.

A simplified method of stabilization and hemostasis for minimally invasive coronary artery bypass.

We describe a simple method to achieve both hemostasis and stabilization of the left anterior descending coronary artery during minimally invasive coronary artery bypass grafting. This technique allows the surgeon to perform a precise anastomosis of the left internal mammary artery to the target vessel on a beating heart.

Noninvasive visualization of coronary artery endothelial function in healthy subjects and in patients with coronary artery disease.

OBJECTIVES: The goal was to test 2 hypotheses: first, that coronary endothelial function can be measured noninvasively and abnormal function detected using clinical 3.0-T magnetic resonance imaging (MRI); and second, that the extent of local coronary artery disease (CAD), in a given patient, is related to the degree of local abnormal coronary endothelial function. BACKGROUND: Abnormal endothelial function mediates the initiation and progression of atherosclerosis and predicts cardiovascular events. However, direct measures of coronary endothelial function have required invasive assessment. METHODS: The MRI was performed in 20 healthy adults and 17 patients with CAD. Cross-sectional coronary area and blood flow were quantified before and during isometric handgrip exercise, an endothelial-dependent stressor. In 10 severe, single-vessel CAD patients, paired endothelial function was measured in the artery with severe stenosis and the contralateral artery with minimal disease. RESULTS: In healthy adults, coronary arteries dilated and flow increased with stress. In CAD patients, coronary artery area and blood flow decreased with stress (both p </= 0.02). In the paired study, coronary artery area and blood flow failed to increase during exercise in the mildly diseased vessel, but both area (p = 0.01) and blood flow (p = 0.02) decreased significantly in the severely diseased, contralateral artery. CONCLUSIONS: Endothelial-dependent coronary artery dilation and increased blood flow in healthy subjects, and their absence in CAD patients, can now be directly visualized and quantified noninvasively. Local coronary endothelial function differs between severely and mildly diseased arteries in a given CAD patient. This novel, safe method may offer new insights regarding the importance of local coronary endothelial function and improved risk stratification in patients at risk for and with known CAD.

Contrast agent-enhanced, free-breathing, three-dimensional coronary magnetic resonance angiography.

For free-breathing, high-resolution, three-dimensional coronary magnetic resonance angiography (MRA), the use of intravascular contrast agents may be helpful for contrast enhancement between coronary blood and myocardium. In six patients, 0.1 mmol/kg of the intravascular contrast agent MS-325/AngioMARK was given intravenously followed by double-oblique, free-breathing, three-dimensional inversion-recovery coronary MRA with real-time navigator gating and motion correction. Contrast-enhanced, three-dimensional coronary MRA images were compared with images obtained with a T2 prepulse (T2Prep) without exogenous contrast. The contrast-enhanced images demonstrated a 69% improvement in the contrast-to-noise ratio (6.6 +/- 1.1 vs. 11.1 +/- 2.5; P < 0.01) compared with the T2Prep approach. By using the intravascular agent, extensive portions (> 80 mm) of the native left and right coronary system could be displayed consistently with sub-millimeter in-plane resolution. The intravascular contrast agent, MS-325/AngioMARK, leads to a considerable enhancement of the blood/muscle contrast for coronary MRA compared with T2Prep techniques. The clinical value of the agent remains to be defined in a larger patient series. J. Magn. Reson. Imaging 1999;10:790-799.

Acute aortic dissection with carotid and coronary malperfusion: from imaging to pathology.

Postmortem imaging, including postmortem computed tomography angiography, has become an integral tool in forensic investigation in recent years. A relatively new technique, multiphase postmortem computed tomography angiography, allows detailed visualization of the vascular system and makes it possible to evaluate the dynamic perfusion of aortic branches, including the coronary arteries. Here, we report a case of aortic dissection involving the ascending aorta (type A) with coronary and carotid malperfusion. This case illustrates the complementary use of many of the diagnostic tools that are now available in forensic practice, from imaging to conventional autopsy to pathologic techniques such as immunohistochemistry.

Feasibility and effectiveness of using coronary stents in the treatment of hepatic artery stenoses after orthotopic liver transplantation: preliminary report.

OBJECTIVE: Our aim is to evaluate the feasibility, efficacy, and patency of using coronary stents for the treatment of hepatic artery stenosis after liver transplantation. CONCLUSION: Hepatic artery stenosis after liver transplantation can be treated using coronary stents. The low rate of complication, high technical success, and 1-year patency rates are encouraging.