Differentiation of athlete's heart from pathological forms of cardiac hypertrophy by means of geometric indices derived from cardiovascular magnetic resonance.

PURPOSE: Determination of the underlying etiology of left ventricular hypertrophy (LVH) is a common, challenging, and critical clinical problem. The authors aimed to test whether pathological LVH, such as occurs in hypertrophic cardiomyopathy (HCM), hypertensive heart disease, or aortic stenosis, and physiological LVH in athletes, can be distinguished by means of left ventricular volume and geometric indices, derived from cardiovascular magnetic resonance imaging. METHODS: A total of 120 subjects were studied on a 1.5 Tesla MR (Sonata, Siemens Medical Solutions, Erlangen, Germany) scanner, comprising healthy volunteers (18), competitive athletes (25), patients with HCM (35), aortic stenosis (24), and hypertensive heart disease (18). Left ventricular mass index, ejection fraction, end-diastolic, end-systolic and stroke volume index, diastolic wall thickness, wall thickness ratio and diastolic and systolic wall-to-volume ratios were determined. RESULTS: Left ventricular (LV) mass indices were similar for all forms of LVH (p > 0.05), which were at least 35% higher than those obtained in healthy volunteers (p < 0.05). Multiple logistic regression showed that the percentage of correctly predicted diagnoses was 100% for athlete's heart, 80% for hypertrophic cardiomyopathy, 54% for aortic stenosis, and 22% for hypertensive heart disease. Using a receiver operating curve-determined cut-off value for diastolic wall-to-volume ratio of less than 0.15 mm x m2 x ml(-1), athletes' hearts could be differentiated from all forms of pathological cardiac hypertrophy with 99% specificity. CONCLUSIONS: Athlete's heart can be reliably distinguished from all forms of pathological cardiac hypertrophy using CMR-derived LV volume and geometric indices, but pathological forms of LVH present with overlapping cardiac hypertrophy phenotypes. This capability of CMR should be of high clinical value.     

Effect of Aspiration Thrombectomy on Microvascular Obstruction in NSTEMI Patients : The TATORT-NSTEMI Trial

Background

Aspiration thrombectomy in ST-segment elevation myocardial infarction is recommended by current guidelines based on several randomized trials. There are no trials assessing thrombectomy in non–ST-segment elevation myocardial infarction (NSTEMI) patients.

Objectives

The TATORT-NSTEMI (Thrombus Aspiration in Thrombus Containing Culprit Lesions in Non–ST-Elevation Myocardial Infarction) trial sought to assess the effect of aspiration thrombectomy on microvascular injury in patients with NSTEMI compared with standard percutaneous coronary intervention (PCI).

Methods

This prospective, controlled, multicenter study randomized 440 patients to adjunctive thrombectomy (n = 221) compared with conventional PCI (n = 219) in NSTEMI patients with thrombus-containing lesions. The primary endpoint of the extent of microvascular obstruction (MO) in the percentage of left ventricular mass (%LV) was assessed by cardiac magnetic resonance imaging within 4 days. Secondary endpoints included infarct size, myocardial salvage index, and angiographic parameters including myocardial blush grade and Thrombolysis In Myocardial Infarction flow grade. The combined clinical endpoint consisted of death, reinfarction, target vessel revascularization, and new congestive heart failure within 6 months.

Results

The primary endpoint of MO was not different between the thrombectomy and the standard PCI group with 2.0%LV (interquartile range [IQR]: 0.8 to 4.1) versus 1.4%LV (IQR: 0.7 to 2.6) (p = 0.17). Similarly, no significant differences were observed for infarct size (8.6%LV; IQR: 4.0 to 14.7 vs. 7.4%LV; IQR: 4.1 to 13.1; p = 0.46), myocardial salvage index (63.3; IQR: 35.4 to 87.2 vs. 65.6; IQR: 46.9 to 82.6; p = 0.45), or angiographic parameters such as blush grade (p = 0.63) and Thrombolysis In Myocardial Infarction flow grade (p = 0.66). Clinical follow-up at 6 months revealed no differences in the combined clinical endpoints (p = 0.22).

Conclusions

Aspiration thrombectomy in conjunction with PCI in NSTEMI with a thrombus-containing lesion does not lead to a reduction in MO. (Thrombus Aspiration in Thrombus Containing Culprit Lesions in Non-ST-Elevation Myocardial Infarction [TATORT-NSTEMI]; NCT01612312).     

The Relationship of Left Ventricular Trabeculation to Ventricular Function and Structure Over a 9.5-Year Follow-Up : The MESA Study

Background

Left ventricular (LV) trabeculation is highly variable among individuals and is increased in some diseases (e.g., congenital heart disease or cardiomyopathies), but its significance in population-representative individuals is unknown.

Objectives

The goal of this study was to determine if excessive LV trabeculation in population-representative individuals is associated with preceding changes in cardiac volumes and function.

Methods

For technical reasons, the extent of trabeculation, which is expressed as the ratio of noncompacted to compacted (NC/C) myocardium, was measured on cardiac magnetic resonance (CMR) long-axis cine images in 2,742 participants in the MESA (Multi-Ethnic Study of Atherosclerosis) (mean age 68.7 years; 52.3% women; 56.4% with hypertension; 16.8% with diabetes) at examination 5. These were considered in quintiles of trabeculation extent; the NC/C ratio of quintile 5 was 2.46 to 5.41. We determined the relationship between the maximal NC/C ratio and the preceding change (9.5 years between examinations 1 and 5) in end-systolic volume indexed (ESVi) to body surface area. Secondary analyses assessed the associations between the maximal NC/C ratio and preceding changes in end-diastolic volume indexed (EDVi) to body surface area and the ejection fraction (EF).

Results

Over 9.5 years, the ESVi decreased by 1.3 ml/m², the EDVi decreased by 5.1 ml/m², and the EF decreased by 0.6% (p < 0.0001). Even in subjects with excessive trabeculation, there were no clinically relevant differences in LV volumes and systolic function changes among the quintiles of trabeculation extent.

Conclusions

Greater extent of, and even excessive, LV trabeculation measured in end-diastole in asymptomatic population-representative individuals appeared benign and was not associated with deterioration in LV volumes or function during an almost 10-year period.     

Impact of the operator's experience on value of high-resolution transabdominal ultrasound in the diagnosis of choledocholithiasis: a prospective comparison using endoscopic retrograde cholangiography as the gold standard

OBJECTIVE: Transabdominal ultrasound (US) is the most frequently used imaging method for the diagnosis of choledocholithiasis. The aim of this prospective study was to evaluate the diagnostic accuracy of high-resolution US in the diagnosis of common bile duct stones depending on the operator's experience and in comparison with endoscopic retrograde cholangiography (ERC) as the gold standard. MATERIAL AND METHODS: From April 2003 through November 2004, 126 patients referred because of clinically and biochemically suspected common bile duct stones were included in the study. Two patients were excluded because they refused to undergo ERC. Consequently, the study comprised 124 patients (86 F, 38 M, mean age 63.2 years, range 21-91 years). High-resolution US was performed (2-5 MHz sector scanner; Siemens Elegra, Erlangen, Germany) by operators who were unaware of the results of other imaging procedures. The definitive diagnosis was established by means of ERC. RESULTS: Thirty-five out of 124 patients were investigated by experienced examiners. Twenty-seven of 35 patients (77%) were found to have stones at ERC. Bile duct stones were correctly found by US in 22 out of 27 patients (sensitivity 82%, 95% CI: 63-92). Of the 8 patients without stones at ERC, one false-positive diagnosis was made with US (specificity 88%, 95% CI: 53-98). Correct diagnoses were made in 29 out of 35 (accuracy 83%, 95% CI: 67-92) patients investigated by experienced examiners. Eighty-nine out of 124 patients were investigated by less-experienced examiners. Fifty-four of 89 patients (61%) were found to have stones at ERC. Choledocholithiasis was found correctly in only 25 out of 54 patients (sensitivity 46%, 95% CI: 34-59). Of the 35 patients without stones at ERC, three false-positive diagnoses were made with US (specificity 91%, 95% CI: 78-97). In conclusion, correct diagnoses were observed in 57 of 89 patients (accuracy 64%, 95% CI: 54-73) investigated by less-experienced examiners (p<0.05 in comparison with the results of experienced examiners). CONCLUSIONS: High-resolution US carried out by experienced examiners has a high diagnostic accuracy in the diagnosis of choledocholithiasis. Therefore, good training and continued experience are prerequisites for successful sonographic detection of bile duct stones using US. Under these conditions, further expensive and invasive methods such as ERC, magnetic resonance cholangiopancreatography and endoscopic ultrasonography may not be necessary in cases with a clear sonographic diagnosis.     

Myeloid-related protein 8/14 complex is released by monocytes and granulocytes at the site of coronary occlusion: a novel, early, and sensitive marker of acute coronary syndromes.

AIMS: We investigated whether myeloid-related protein 8/14 complex (MRP8/14) expressed by infiltrating monocytes and granulocytes may represent a mediator and early biomarker of acute coronary syndromes (ACS). METHODS AND RESULTS: Immunohistochemistry of coronary thrombi was done in 41 ACS patients. Subsequently, levels of MRP8/14 were assessed systemically in 75 patients with ACS and culprit lesions, with stable coronary artery disease (CAD), or with normal coronary arteries. In a subset of patients, MRP8/14 was measured systemically and at the site of coronary occlusion. Macrophages and granulocytes, but not platelets stained positive for MRP8/14 in 76% of 41 thrombi patients. In ACS, local MRP8/14 levels [22.0 (16.2-41.5) mg/L] were increased when compared with systemic levels [13.4 (8.1-14.7) mg/L, P = 0.03]. Systemic levels of MRP8/14 were markedly elevated [15.1 (12.1-21.8) mg/L, P = 0.001] in ACS when compared with stable CAD [4.6 (3.5-7.1) mg/L] or normals [4.8 (4.0-6.3) mg/L]. Using a cut-off level of 8 mg/L, MRP8/14 but not myoglobin or troponin, identified ACS presenting within 3 h from symptom onset. CONCLUSION: In ACS, MRP8/14 is markedly expressed at the site of coronary occlusion by invading phagocytes. The occurrence of elevated MRP8/14 in the systemic circulation prior to markers of myocardial necrosis makes it a prime candidate for the detection of unstable plaques and management of ACS.     

Microparticles as mediators of cellular cross-talk in inflammatory disease

Microparticles are a heterogeneous population of membrane-coated vesicles which can be released from virtually all cell types during activation or apoptosis. Release occurs from the cell surface in an exogenous budding process involving local rearrangement of the cytoskeleton. Given their origin, these particles can be identified by staining for cell surface markers and annexin V. As shown in in vitro studies, microparticles may represent a novel subcellular element for intercellular communication in inflammation. Thus, microparticles can transfer chemokine receptors and arachidonic acid between cells, activate complement, promote leukocyte rolling and stimulate the release of pro-inflammatory mediators. Under certain conditions, however, microparticles may also exert anti-inflammatory properties by inducing immune cell apoptosis and the production of anti-inflammatory mediators. Microparticles may play an important role in the pathogenesis of rheumatologic diseases as evidenced by their elevation in diseases such as systemic sclerosis (SSc), systemic vasculitis and antiphospholipid antibody syndrome and correlation with clinical events. A role in inflammatory arthritis is suggested by the finding that leukocyte-derived microparticles induce the production of matrix metalloproteinases and cytokines by synovial fibroblasts. Together, these findings point to novel signaling pathways of cellular cross-talk that may operate along the spectrum of soluble cytokines and mediators of direct cell–cell contact.     

VEGF-PLCgamma1 pathway controls cardiac contractility in the embryonic heart

The strength of the heart beat can accommodate in seconds to changes in blood pressure or flow. The mechanism for such homeostatic adaptation is unknown. We sought the cause of poor contractility in the heart of the embryonic zebrafish with the mutation dead beat. We find through cloning that this is due to a mutation in the phospholipase C gamma1 (plcgamma1) gene. In mutant embryos, contractile function can be restored by PLCgamma1 expression directed selectively to cardiac myocytes. In other situations, PLCgamma1 is known to transduce the signal from vascular endothelial growth factor (VEGF), and we show here that abrogation of VEGF also interferes with cardiac contractility. Somewhat unexpectedly, FLT-1 is the responsible VEGF receptor. We show that the same system functions in the rat. Blockage of VEGF-PLCgamma1 signaling decreases calcium transients in rat ventricular cardiomyocytes, whereas VEGF imposes a positive inotropic effect on cardiomyocytes by increasing calcium transients. Thus, the muscle of the heart uses the VEGF-PLCgamma1 cascade to control the strength of the heart beat. We speculate that this paracrine system may contribute to normal and pathological regulation of cardiac contractility.     

N-Acetyltransferase (NAT) 2 acetylator status and age of tumour onset in patients with sporadic and familial, microsatellite stable (MSS) colorectal cancer

Introduction N-Acetyltransferase (NAT) 2 is an important enzyme involved in the metabolism of different xenobiotics, including potential carcinogens. Allelic variants of the NAT2 gene are determined by a pattern of single nucleotide polymorphisms (SNPs) resulting in slow (SA), intermediate (IA) or rapid acetylator (RA) phenotypes and causing the individual differences in the NAT2 metabolic capacity. To clarify the potential modifying role of the NAT2 acetylator status in microsatellite stable (MSS) colorectal cancer (CRC), we studied 140 patients with sporadic CRC (group 1) and 69 patients with CRC who met at least one criterion of the revised Bethesda guidelines (group 2). Observations We did not observe any significant difference in the NAT2 acetylator status frequency between patients in both groups and 100 healthy controls (P=0.486). Regardless of a younger median age of tumour onset (AO) of 41 years in group 2 patients compared to 64 years in group 1 patients, no significant difference in AO was found between RA and SA status patients in both groups. The median AO in group 1 was 65 years in patients with RA and 63 years with SA status (P=0.065). The median AO in group 2 was 40 years in patients with RA and 42 years with SA status (P=0.814). Multivariate Cox regression analysis revealed that neither the NAT2 acetylator status (P=0.064 and 0.810, respectively) nor the gender (P=0.165 and 0.918, respectively) was a risk factor for the AO in both groups. These data do not support the hypothesis that the NAT2 acetylatorship acts as a modifying factor on the AO in sporadic and familial, microsatellite stable CRC.     

Muscle-Activation Onset Times With Shoes and Foot Orthoses in Participants With Chronic Ankle Instability

Context

Participants with chronic ankle instability (CAI) use an altered neuromuscular strategy to shift weight from double-legged to single-legged stance. Shoes and foot orthoses may influence these muscle-activation patterns.

Objective

To evaluate the influence of shoes and foot orthoses on onset times of lower extremity muscle activity in participants with CAI during the transition from double-legged to single-legged stance.

Design

Cross-sectional study.

Setting

Musculoskeletal laboratory.

Patients or Other Participants

A total of 15 people (9 men, 6 women; age = 21.8 ± 3.0 years, height = 177.7 ± 9.6 cm, mass = 72.0 ± 14.6 kg) who had CAI and wore foot orthoses were recruited.

Intervention(s)

A transition task from double-legged to single-legged stance was performed with eyes open and with eyes closed. Both limbs were tested in 4 experimental conditions: (1) barefoot (BF), (2) shoes only, (3) shoes with standard foot orthoses, and (4) shoes with custom foot orthoses (SCFO).

Main Outcome Measure(s)

The onset of activity of 9 lower extremity muscles was recorded using surface electromyography and a single force plate.

Results

Based on a full-factorial (condition, region, limb, vision) linear model for repeated measures, we found a condition effect (F_3,91.8 = 9.39, P < .001). Differences among experimental conditions did not depend on limb or vision condition. Based on a 2-way (condition, muscle) linear model within each region (ankle, knee, hip), earlier muscle-activation onset times were observed in the SCFO than in the BF condition for the peroneus longus (P < .001), tibialis anterior (P = .003), vastus medialis obliquus (P = .04), and vastus lateralis (P = .005). Furthermore, the peroneus longus was activated earlier in the shoes-only (P = .02) and shoes-with-standard-foot-orthoses (P = .03) conditions than in the BF condition. No differences were observed for the hip muscles.

Conclusions

Earlier onset of muscle activity was most apparent in the SCFO condition for ankle and knee muscles but not for hip muscles during the transition from double-legged to single-legged stance. These findings might help clinicians understand how shoes and foot orthoses can influence neuromuscular control in participants with CAI.Key Words: footwear, insoles, ankle sprains, neuromuscular system, electromyography

Key Points

• Shoes and foot orthoses accelerated muscle-activation onset times of the ankle and knee but not the hip in participants with chronic ankle instability.
• Earlier muscle-activation onset times were most prominent in the shoes-with-custom-foot-orthoses condition.
• At the ankle, the muscle-activation onset time of the peroneus longus was earlier in the shoes-only, shoes-with-standard-foot-orthoses, and shoes-with-custom-foot-orthoses conditions than in the barefoot condition, and the muscle-activation onset time of the tibialis anterior was earlier in the shoes-with-custom-foot-orthoses condition than in the barefoot condition.
• At the knee, the muscle-activation onset times of the vastus medialis obliquus and vastus lateralis were earlier in the shoes-with-custom-foot-orthoses condition than in the barefoot condition.
• The results may help clinicians understand how shoes and foot orthoses can influence neuromuscular control of the lower extremity in participants with chronic ankle instability.

Lateral ankle sprains are estimated to account for approximately 15% of all sport injuries.¹ Even more concerning than the initial ankle sprain is the large proportion of patients with residual symptoms and recurrent ankle sprains for months to years after the initial injury.² The occurrence of repetitive ankle sprains and the feeling of the ankle “giving way” with slight or no perturbation has been defined as chronic ankle instability (CAI).³The transition task from double-legged to single-legged stance during barefoot (BF) conditions has been shown to discriminate between uninjured participants and participants with CAI. Researchers have reported that muscle-activation onset times typically were delayed^4,5 and postural stability was impaired⁶ in participants with CAI, indicating the use of another strategy to shift weight from double-legged to single-legged stance. However, it is unclear whether findings from BF tests represent typical daily situations when shoes, and for some persons foot orthoses, are often worn.The human foot is the first point of contact between the body and a supporting surface. The cutaneous mechanoreceptors on the planar surface of the foot are an important source of sensory information,⁷ which is considered essential for achieving and maintaining functional joint stability.⁸ Shoes and foot orthoses act as an interface between the body and a supporting surface and can influence the sensory feedback from these mechanoreceptors by increasing the contact area between the foot and the supporting surface.^7,9 Furthermore, the small kinematic alterations of the rear foot and tibia that have been described with the use of shoes and foot orthoses¹⁰ may put the ankle joint in a more neutral position, thereby improving the capacity of the ankle mechanoreceptors to provide more accurate proprioceptive input toward the central nervous system.¹¹ Changing the sensory input to these mechanisms consequently would change the motor output.⁷Evidence is increasing that shoes and foot orthoses can influence lower extremity muscle activation.^10,12–14 Dingenen et al¹⁴ were the first investigators to measure the influence of shoes and foot orthoses on muscle-activation onset times of the entire lower extremity in uninjured participants during the transition from double-legged to single-legged stance. Their results showed that shoes and foot orthoses can accelerate muscle-activation onset times of the peroneus longus. No differences were reported in more proximal muscles. Recently, researchers have suggested that future investigators should be focused on the influence of shoes and foot orthoses on neuromuscular control, especially in participants with injuries, such as CAI,^10,13,14 to increase our understanding of how positive clinical outcomes from the use of shoes and foot orthoses can be achieved.¹¹ Altering or improving proprioceptive information and muscle-activation patterns in participants with CAI would be clinically beneficial, given that their proprioceptive and neuromuscular deficits have been described.¹⁵To our knowledge, no investigators have focused on the influence of shoes and foot orthoses on muscle-activation onset times of the entire lower extremity in participants with CAI during the transition from double-legged to single-legged stance. Therefore, the purpose of our study was to evaluate the influence of shoes and foot orthoses on muscle-activation onset times during the transition from double-legged to single-legged stance in participants with CAI. Based on the proposed effects of shoes and foot orthoses on lower extremity neuromuscular control, we hypothesized that shoes and foot orthoses would accelerate muscle-activation onset times compared with a BF condition.     

Variants in RUNX3 Contribute to Susceptibility to Psoriatic Arthritis,Exhibiting Further Common Ground With Ankylosing Spondylitis

Objective

Psoriatic arthritis (PsA) is a common inflammatory joint disease distinct from other chronic arthritides and frequently accompanied by psoriasis vulgaris. In a first genome‐wide association study (GWAS), we were able to identify several genetic risk factors. However, even combined with previously identified factors, the genetic contribution to disease was not fully explained. Therefore, we undertook this study to investigate further 17 loci from our GWAS that did not reach genome‐wide significance levels of association in the initial analysis.

Methods

Twenty‐one of 22 single‐nucleotide polymorphisms were successfully genotyped in independent cohorts of 1,398 PsA patients and 6,389 controls and in a group of 964 German patients with psoriasis vulgaris.

Results

Association with a RUNX3 variant, rs4649038, was replicated in independent patients and controls and resulted in a combined P value of 1.40 × 10⁻⁸ by Cochran‐Mantel‐Haenszel test and an odds ratio (OR) of 1.24 (95% confidence interval [95% CI] 1.15–1.33). Further analyses based on linkage disequilibrium (LD) at RUNX3 refined the most significant association to an LD block located in the first intron of one isoform. Weaker evidence for association was detected in German patients with psoriasis vulgaris (P = 5.89 × 10⁻²; OR 1.13 [95% CI 1.00–1.28]), indicating a role in the skin manifestations of psoriasis.

Conclusion

Our analyses identified variants in RUNX3 as susceptibility factors for PsA. RUNX3 has already been implicated in susceptibility to ankylosing spondylitis, another spondyloarthritis, although its risk allele is independent from the one for PsA. RUNX‐3 is involved in CD8+ T lymphocyte differentiation and is therefore a good candidate for involvement in PsA and psoriasis vulgaris as T cell–mediated diseases.