Our obsession with normal values

Normal values provide the background for interpretation of quantitative imaging data and thus are essential information for daily routine. Nevertheless, the ways how normal values are obtained, presented, and interpreted, often do not receive the attention they deserve. We review the concepts of normalcy, the implications of typical normal ranges including the types of distribution of normal data, the possibilities to index for confounding biological factors like body surface area, and the limitations of the very concept of normal values, demonstrating that there are no easy statistical solutions for difficult clinical problems

Response to pulmonary arterial hypertension drug therapies in patients with pulmonary arterial hypertension and cardiovascular risk factors.

The age at diagnosis of pulmonary arterial hypertension (PAH) and the prevalence of cardiovascular (CV) risk factors are increasing. We sought to determine whether the response to drug therapy was influenced by CV risk factors in PAH patients. We studied consecutive incident PAH patients (n = 146) between January 1, 2008, and July 15, 2011. Patients were divided into two groups: the PAH-No CV group included patients with no CV risk factors (obesity, systemic hypertension, type 2 diabetes mellitus, permanent atrial fibrillation, mitral and/or aortic valve disease, and coronary artery disease), and the PAH-CV group included patients with at least one. The response to PAH treatment was analyzed in all the patients who received PAH drug therapy. The PAH-No CV group included 43 patients, and the PAH-CV group included 69 patients. Patients in the PAH-No CV group were younger than those in the PAH-CV group (P < 0.0001). In the PAH-No CV group, 16 patients (37%) improved on treatment and 27 (63%) did not improve, compared with 11 (16%) and 58 (84%) in the PAH-CV group, respectively (P = 0.027 after adjustment for age). There was no difference in survival at 30 months (P = 0.218). In conclusion, in addition to older age, CV risk factors may predict a reduced response to PAH drug therapy in patients with PAH

Post-myocardial infarction left ventricular pseudoaneurysm diagnosed incidentally by echocardiography

A 54-year-old male developed a left ventricular pseudoaneurysm (Ps) along the lateral wall of the left ventricle (LV), which was diagnosed incidentally by two-dimensional transthoracic echocardiography (2DTTE) 6 months after an acute myocardial infarction. Color flow imaging (CFI) showed blood flow from the LV into the aneurysmal cavity and invasive coronary angiography revealed sub-occlusion of the circumflex artery. A complementary study using cardiovascular magnetic resonance (CMR) confirmed a dilated left ventricle with depressed ejection fraction, thin dyskinetic anterolateral and inferolateral walls, a Ps adjacent to the lateral wall of the LV contained by the pericardium and blood passing in and out through a small defect in the LV mid-anterolateral wall. Late gadolinium-enhanced imaging demonstrated transmural myocardial infarction in the lateral wall and delayed enhancement of the pericardium, which formed the walls of the Ps. A conservative approach was adopted in this case, optimizing the patient’s heart failure medications, including cardioselective beta-blocker agents, angiotensin-converting enzyme inhibitors, spironolactone and chronic anticoagulation therapy because of a high risk of ischemic stroke in these patients. At the 13-month follow-up, the patient remained stable with New York Heart Association class II heart failure. In conclusion, 2DTTE and CFI seem to be suitable initial methods for diagnosing Ps of the LV, but CMR is an excellent complementary method for characterizing further this cardiac entity. Furthermore, the long-term outcome of patients with Ps of the LV who are treated medically appears to be relatively benign

A targeting microbubble for ultrasound molecular imaging

Microbubbles conjugated with targeting ligands are used as contrast agents for ultrasound molecular imaging. However, they often contain immunogenic (strept)avidin, which impedes application in humans. Although targeting bubbles not employing the biotin-(strept)avidin conjugation chemistry have been explored, only a few reached the stage of ultrasound imaging in vivo, none were reported/evaluated to show all three of the following properties desired for clinical applications: (i) low degree of non-specific bubble retention in more than one non-reticuloendothelial tissue; (ii) effective for real-time imaging; and (iii) effective for acoustic quantification of molecular targets to a high degree of quantification. Furthermore, disclosures of the compositions and methodologies enabling reproduction of the bubbles are often withheld.To develop and evaluate a targeting microbubble based on maleimide-thiol conjugation chemistry for ultrasound molecular imaging.Microbubbles with a previously unreported generic (non-targeting components) composition were grafted with anti-E-selectin F(ab')2 using maleimide-thiol conjugation, to produce E-selectin targeting microbubbles. The resulting targeting bubbles showed high specificity to E-selectin in vitro and in vivo. Non-specific bubble retention was minimal in at least three non-reticuloendothelial tissues with inflammation (mouse heart, kidneys, cremaster). The bubbles were effective for real-time ultrasound imaging of E-selectin expression in the inflamed mouse heart and kidneys, using a clinical ultrasound scanner. The acoustic signal intensity of the targeted bubbles retained in the heart correlated strongly with the level of E-selectin expression (|r|≥0.8), demonstrating a high degree of non-invasive molecular quantification.Targeting microbubbles for ultrasound molecular imaging, based on maleimide-thiol conjugation chemistry and the generic composition described, may possess properties (i)-(iii) desired for clinical applications

The association of ferritin with cardiovascular and all-cause mortality in community-dwellers: The English longitudinal study of ageing

Background: Ferritin constitutes a sensitive iron-storage index and multi-functional protein. Evidence on its association with mortality in general population is scarce and conflicting. We investigated the sex-specific associations of ferritin levels with all-cause and cardiovascular mortality in a population-based cohort. Methods: Data came from the English Longitudinal Study of Ageing and the national mortality registry. The sample comprised 5,471 participants aged ≥52 years. Blood concentration of ferritin was measured at baseline in 2004–05. Sex-specific Cox proportional hazards models were estimated with adjustment for age, major chronic diseases, marital status, educational attainment, total net household wealth, anemia, inflammatory markers, body mass index, smoking, and physical activity. Stratified analyses by chronic disease status were also performed. Results: We categorized ferritin in sex-specific quartiles. In men, we used, the following categorization: lowest (2-69ng/ml), second lowest (70-118ng/ml), second highest (reference category) (119-193ng/ml) and highest (194-598ng/ml) ferritin quartiles. In women, ferritin was categorized as follows: lowest (2-44ng/ml), second lowest (45-73ng/ml), second highest (reference category) (74-115ng/ml) and highest (116-341ng/ml) ferritin quartiles. 841 deaths of which 262 cardiovascular disease-related were recorded over a mean follow-up time of 7.7 years. Risk for all-cause mortality was found increased in men with hyperferritinemia (194-598ng/ml) and no history of major chronic diseases compared with the reference group [fully-adjusted HR: 1.49 (95%CI 1.03–2.16)]. Among women, those in the lowest ferritin quartile (2-44ng/ml) had increased risk for all-cause mortality [fully-adjusted HR: 1.59 (95%CI 1.18–2.13)] compared with the reference group after adjustment for all covariates. Regarding cardiovascular mortality, we observed a positive association with ferritin levels in men, which was blunted after adjustment for inflammatory markers and lifestyle parameters. Men with no major chronic diseases who were in the highest ferritin quartile had a significantly increased risk of cardiovascular mortality. No association between ferritin levels and cardiovascular mortality was detected in women. Conclusion: Circulating ferritin levels showed sex-specific prognostic patterns. High ferritin levels in men with no major chronic disease and low ferritin levels in all women were associated with increased all-cause mortality after adjusting for covariates. High ferritin levels in men with no major chronic diseases were also independently associated with an increased risk of cardiovascular mortality. Future research is needed to clarify the prognostic role of ferritin

Evolution of subclinical myocardial dysfunction detected by two-dimensional and three-dimensional speckle tracking in asymptomatic type 1 diabetic patients: a long-term follow-up study

Background We sought to assess the long-term evolution of left ventricular (LV) function using two-dimensional (2D) and three-dimensional (3D) speckle tracking echocardiography (STE) for the detection of preclinical diabetic cardiomyopathy, in asymptomatic type 1 diabetic patients, over a 6-year follow-up. Design and methods Sixty-six asymptomatic type 1 diabetic patients with no cardiovascular risk factors were compared to 26 matched healthy controls. Conventional, 2D and 3D-STE were performed at baseline. A subgroup of 14 patients underwent a 6-year follow-up evaluation. Results At baseline, diabetic patients had similar LV ejection fraction (60 vs 61%; P = NS), but impaired longitudinal function, as assessed by 2D-global longitudinal strain (GLS) (−18.9 ± 2 vs −20.5 ± 2; P = 0.0002) and 3D-GLS (−17.5 ± 2 vs −19 ± 2; P = 0.003). At follow-up, diabetic patients had worsened longitudinal function compared to baseline (2D-GLS: −18.4 ± 1 vs −19.2 ± 1; P = 0.03). Global circumferential (GCS) and radial (GRS) strains were unchanged at baseline and during follow-up. Metabolic status did not correlate with GLS, whereas GCS and GRS showed a good correlation, suggestive of a compensatory increase of circumferential and radial functions in advanced stages of the disease – long-term diabetes (GCS: −26 ± 3 vs −23.3 ± 3; P = 0.008) and in the presence of microvascular complications (GRS: 38.8 ± 9 vs 34.3 ± 8; P = 0.04). Conclusions Subclinical myocardial dysfunction can be detected by 2D and 3D-STE in type 1 diabetic patients, independently of any other cardiovascular risk factors. Diabetic cardiomyopathy progression was suggested by a mild decrease in longitudinal function at the follow-up, but did not extend to a clinical expression of the disease, as no death or over heart failure was reported

The use of pocket-size imaging devices: a position statement of the European Association of Echocardiography.

Pocket-size imaging devices are a completely new type of echo machines which have recently reached the market. They are very cheap, smartphone-size hand-held echo machines with limited technical capabilities. The aim of this European Association of Echocardiography (EAE) position paper is to provide recommendations on the use of pocket-size imaging devices in the clinical arena by profiling the educational needs of potential users other than cardiologists experts in echo. EAE recommendations about pocket-size imaging devices can be summarized in: (1) pocket-size imaging devices do not provide a complete diagnostic echocardiographic examination. The range of indications for their use is therefore limited. (2) Imaging assessment with pocket-size imaging devices should be reported as part of the physical examination of the patient. Image data should be stored according to the applicable national rules for technical examinations. (3) With the exception of cardiologists who are certified for transthoracic echocardiography according to national legislation, specific training and certification is recommended for all users. The certification should be limited to the clinical questions that can potentially be answered by pocket-size devices. (4) The patient has to be informed that an examination with the current generation of pocket-size imaging devices does not replace a complete echocardiogram.Peer reviewe

Pregnancy outcomes in women with aortic coarctation

OBJECTIVE Pregnancy in women with aortic coarctation (CoA) has an estimated moderately increased risk (mWHO II-III) of adverse cardiovascular, obstetric or fetal events, but prospective data to validate this risk classification are scarce. We examined pregnancy outcomes and identified associations with adverse outcomes. METHODS Pregnancies in women with CoA were selected from the worldwide prospective Registry of Pregnancy and Cardiac Disease (ROPAC, n=303 out of 5739), part of the European Society of Cardiology EURObservational Research Programme. The frequency of and associations with major adverse cardiac events (MACE) and hypertensive disorders (pregnancy-induced hypertension, (pre-)eclampsia or haemolysis, elevated liver enzymes and low platelets syndrome) were analysed. RESULTS Of 303 pregnancies (mean age 30 years, pregnancy duration 39 weeks), 9.6% involved unrepaired CoA and 27.1% were in women with pre-existing hypertension. No maternal deaths or aortic dissections occurred. MACE occurred in 13 pregnancies (4.3%), of which 10 cases were of heart failure (3.3%). Univariable associations with MACE included prepregnancy clinical signs of heart failure (OR 31.8, 95% CI 6.8 to 147.7), left ventricular ejection fraction 1 (OR 11.4, 95% CI 3.6 to 36.3) and cardiac medication use (OR 4.9, 95% CI 1.3 to 18.3). Hypertensive disorders of pregnancy occurred in 16 (5.3%), cardiac medication use being their only predictor (OR 3.2, 95% CI 1.1 to 9.6). Premature births were 9.1%, caesarean section was performed in 49.7% of pregnancies. Of 4 neonatal deaths, 3 were after spontaneous extreme preterm birth. CONCLUSIONS The ROPAC data show low MACE and hypertensive disorder rates during pregnancy in women with CoA, suggesting pregnancy to be more safe and better tolerated than previously appreciated