Long term evolution of magnetic resonance imaging characteristics in a case of atypical left lateral wall hypertrophic cardiomyopathy

We are reporting a long-time magnetic resonance imaging (MRI) follow-up in a rare case of cardiac left lateral wall hypertrophy. Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disorder and a significant cause of sudden cardiac death. Cardiac magnetic resonance (CMR) imaging can be a valuable tool for assessment of detailed information on size, localization, and tissue characteristics of hypertrophied myocardium. However, there is still little knowledge of long-term evolution of HCM as visualized by magnetic resonance imaging. Recently, our group reported a case of left lateral wall HCM as a rare variant of the more common forms, such as septal HCM, or apical HCM. As we now retrieved an old cardiac MRI acquired in this patient more than 20 years ago, we are able to provide the thrilling experience of an ultra-long MRI follow-up presentation in this rare case of left lateral wall hypertrophy. Furthermore, this case outlines the tremendous improvements in imaging quality within the last two decades of CMR imaging.     

Pedicle screw placement accuracy in thoracic and lumbar spinal surgery with a patient-matched targeting guide: a cadaveric study

Purpose

Pedicle screw placement is an increasingly common procedure for the correction of spine degenerative disease, deformity and trauma. However, screw placement is demanding, with complications resulting from inaccurate screw placement. While several different techniques have been developed to improve accuracy, they all have their limitations.

Methods

We examined the MySpine (Medacta International SA, Castel San Pietro, CH) patient-matched pedicle targeting guide in three cadaveric spine specimens operated on by three surgeons. A three-dimensional (3D) preoperative plan was constructed from spinal computed tomography scans, from which individualised guides were developed for the placement of Medacta Unconstrained Screw Technology pedicle screws. Following screw placement, the 3D positioning of the screws was compared to the preoperative plan against a series of pre-defined criteria.

Results

Of 46 inserted screws eligible for assessment, 91.3 % were fully inside the pedicle. There were no cases of Grade B (2–4 mm) or C (>4 mm) pedicle perforation. The mean deviation between the planned and actual screw position at the midpoint of the pedicle was 0.70 mm, the mean horizontal deviation was 0.60 mm and the mean vertical deviation was 0.77 mm. The mean angular deviation in the sagittal plane was 1.74°, versus 1.32° in the transverse plane. The mean deviation in screw depth was 1.55 mm. On all measures, the accuracy of screw placement was within the predefined criteria.

Conclusions

Our cadaver study indicates that pedicle screw placement with the system is accurate and should be investigated in larger in vitro and in vivo studies.

     

Platelet-derived HMGB1 is a critical mediator of thrombosis

Thrombosis and inflammation are intricately linked in several major clinical disorders, including disseminated intravascular coagulation and acute ischemic events. The damage-associated molecular pattern molecule high-mobility group box 1 (HMGB1) is upregulated by activated platelets in multiple inflammatory diseases; however, the contribution of platelet-derived HMGB1 in thrombosis remains unexplored. Here, we generated transgenic mice with platelet-specific ablation of HMGB1 and determined that platelet-derived HMGB1 is a critical mediator of thrombosis. Mice lacking HMGB1 in platelets exhibited increased bleeding times as well as reduced thrombus formation, platelet aggregation, inflammation, and organ damage during experimental trauma/hemorrhagic shock. Platelets were the major source of HMGB1 within thrombi. In trauma patients, HMGB1 expression on the surface of circulating platelets was markedly upregulated. Moreover, evaluation of isolated platelets revealed that HMGB1 is critical for regulating platelet activation, granule secretion, adhesion, and spreading. These effects were mediated via TLR4- and MyD88-dependent recruitment of platelet guanylyl cyclase (GC) toward the plasma membrane, followed by MyD88/GC complex formation and activation of the cGMP-dependent protein kinase I (cGKI). Thus, we establish platelet-derived HMGB1 as an important mediator of thrombosis and identify a HMGB1-driven link between MyD88 and GC/cGKI in platelets. Additionally, these findings suggest a potential therapeutic target for patients sustaining trauma and other inflammatory disorders associated with abnormal coagulation.     

Resistenz gegenüber Plättchenfunktionshemmern: ein reales klinisches Problem

The benefit of dual antiplatelet therapy with acetylsalicylic acid and clopidogrel in cardiovascular risk patients has been documented by several studies. Patients undergoing coronary interventions are in jeopardy of periinterventional thrombotic complications, and stent thrombosis, although a rare event, is still a serious problem, especially in the era of drug-eluting stents. Recently, there is a growing body of evidence that response to antiplatelet therapy is a clinically important entity and subjects presenting a low response to conventional antiplatelet substances are at increased risk for atherothrombotic events. Thereby, aspirin and clopidogrel resistance have been considered a multifactorial phenomenon underlying factors ranging from nonadherence of patients to antiplatelet therapy to demographic characteristics (age, diabetes, renal failure, etc.), acute coronary syndromes as well as genetic polymorphisms involving platelet glycoproteins and cytochrome P450 isoenzymes. The introduction of point-of-care platelet function tests into clinical routine is a still ongoing process, partly because of missing common definitions of resistance, partly due to different laboratory methods that prevent transferability of results. However, first approaches of an adoption of antiplatelet therapy guided by platelet function analysis provide promising results that an individualized antiplatelet strategy might help to improve platelet inhibition in cardiovascular patients. If this will improve clinical outcome has to be evaluated in upcoming studies. The aim of the present article is to give a review about the clinical relevance of resistance to antiplatelet therapy and alternative treatment options.     

Polymorphism of platelet glycoprotein IIb and risk of thrombosis and restenosis after coronary stent placement

Both glycoprotein (GP) IIb and IIIa of platelet fibrinogen receptor are polymorphic proteins. Unlike GPIIIa, there is little information about the clinical significance of the GPIIb polymorphism. We designed this prospective study to assess whether patients with the human platelet antigen (HPA)-3 polymorphism of GPIIb are more susceptible to developing thrombosis and restenosis after coronary stent placement. We included 2,178 consecutive patients with coronary artery disease who underwent intracoronary stent implantation, 789 (36.2%) with HPA-3a/a, 1,023 (47.0%) with HPA-3a/b, and 366 (16.8%) with HPA-3b/b genotype. The incidence of stent thrombosis was 1.7% in HPA-3a/a, 1.7% in HPA-3a/b, and 1.6% in HPA-3b/b patients (p = 0.999). The incidence of stent restenosis was 37.3% in HPA-3a/a, 36.2% in HPA-3a/b, and 34.6% in HPA-3b/b patients (p = 0.724). Event-free survival 1 year after stent placement was 76.1% for HPA-3a/a, 76.5% for HPA-3a/b, and 76.4% for HPA-3b/b patients (p = 0.968). We conclude that the HPA-3 polymorphism of platelet GPIIb is not associated with an increase in the risk of thrombosis and restenosis over 1 year after coronary stent placement. These data indicate that unlike the HPA-1 polymorphism of GPIIIa, the HPA-3 polymorphism of GPIIb may not serve as a useful genetic marker for the risk assessment of patients treated with intracoronary stenting.     

Adenosine stress first pass perfusion for the detection of coronary artery disease in patients with aortic stenosis: a feasibility study

Purpose: Detection of coronary artery disease (CAD) with magnetic resonance imaging (MRI) using adenosine stress first pass perfusion in patients with aortic stenosis in comparison with invasive angiography. Twenty-three consecutive patients (15 male, mean age 68 ± 12 years) with relevant aortic stenosis (aortic valve area 0.90 ± 0.41 cm2) were examined by MRI (1.5 T, Philips Intera CV™). Contrast-enhanced first pass perfusion was performed with adenosine stress (140 μg/kg/min) and under rest conditions. The results were compared with invasive coronary angiography with regard to the presence of a relevant coronary artery stenosis (>70%). Three of 23 patients (13%) had contraindications for adenosine administration (one patient with atrioventricular block, two patients with mild claustrophobia). In the remaining 20 patients, adenosine stress perfusion could be performed without any complications. CAD was correctly detected in eight patients and correctly ruled out in 10 of 12 patients. False-positive results were seen in two patients with severe myocardial hypertrophy. Sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 80%, 83%, and 100%, respectively. Adenosine stress perfusion can be performed without complications even in patients with high grade aortic stenosis. MRI is helpful to detect and rule out significant CAD in these patients. Severe myocardial hypertrophy may lead to false-positive results. Our initial results indicate that due to a high negative predictive value pre-operative invasive coronary angiography might probably be waived in patients without perfusion defects in stress MRI.     

Contribution of cyclooxygenase-1 to thromboxane formation, platelet-vessel wall interactions and atherosclerosis in the ApoE null mouse

ObjectiveProstaglandin and thromboxane (TXA₂) generation is increased in atherosclerosis. Studies with selective inhibitors attribute the enhanced prostacyclin (PGI₂) generation to both cyclooxygenase-1 (COX-1) and COX-2 whereas the increased TXA₂ generation reflects platelet COX-1 expression. However, TXA₂ formation remains elevated in patients with cardiovascular disease on doses of aspirin that fully suppress platelet COX-1, suggesting other tissue sources for TXA₂ formation. Disruption of the thromboxane receptor gene suppresses the development of atherosclerosis. Notwithstanding this, the role of COX-1 in atherosclerosis is unclear, as it is widely distributed and contributes to a number of products, including those that potentially contribute to the resolution of inflammation.Methods and resultsWe examined the role of COX-1 on prostaglandin generation, development of atherosclerosis and platelet–vessel wall interactions in the apoE^?/? murine model by disrupting the COX-1 gene. ApoE^?/?/COX-1^+/+, ApoE^?/?/COX-1^+/? and ApoE^?/?/COX-1^?/?, were administered a 1% cholesterol diet for 8 weeks. Stable urinary metabolites of PGI₂ and TXA₂, which were markedly increased in the ApoE^?/?/COX-1^+/+ were reduced by disruption of COX-1. Deletion of one or both copies of the COX-1 gene suppressed lesion formation. Assessment of platelet–vessel wall interactions by intravital microscopy showed a significant decrease in firm adhesion of platelets in the apoE/COX-1 double knockout (DKO).ConclusionCOX-1 contributes to the enhanced formation of both PGI₂ and TXA₂ in atherosclerosis, and to the development of the disease. Non-platelet sources of COX-1 and TXA₂ that are inaccessible to standard doses of aspirin may contribute to the development of atherosclerosis.