Polymer-based or polymer-free stents in patients at high bleeding risk

BACKGROUND Polymer-free drug-coated stents provide superior clinical outcomes to bare-metal stents in patients at high bleeding risk who undergo percutaneous coronary intervention (PCI) and are treated with 1 month of dual antiplatelet therapy. Data on the use of polymer-based drug-eluting stents, as compared with polymer-free drug-coated stents, in such patients are limited. METHODS In an international, randomized, single-blind trial, we compared polymer-based zotarolimus-eluting stents with polymer-free umirolimus­coated stents in patients at high bleeding risk. After PCI, patients were treated with 1 month of dual antiplatelet therapy, followed by single antiplatelet therapy. The primary outcome was a safety composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year. The principal secondary outcome was target-lesion failure, an effectiveness composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. Both outcomes were powered for noninferiority. RESULTS A total of 1996 patients at high bleeding risk were randomly assigned in a 1:1 ratio to receive zotarolimus-eluting stents (1003 patients) or polymer-free drugcoated stents (993 patients). At 1 year, the primary outcome was observed in 169 of 988 patients (17.1%) in the zotarolimus-eluting stent group and in 164 of 969 (16.9%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% confidence interval [CI], 3.5; noninferiority margin, 4.1; P=0.01 for noninferiority). The principal secondary outcome was observed in 174 patients (17.6%) in the zotarolimus-eluting stent group and in 169 (17.4%) in the polymer-free drug-coated stent group (risk difference, 0.2 percentage points; upper boundary of the one-sided 97.5% CI, 3.5; noninferiority margin, 4.4; P=0.007 for noninferiority). CONCLUSIONS Among patients at high bleeding risk who received 1 month of dual antiplatelet therapy after PCI, use of polymer-based zotarolimus-eluting stents was noninferior to use of polymer-free drug-coated stents with regard to safety and effectiveness composite outcomes. (Funded by Medtronic; ONYX ONE ClinicalTrials.gov number, NCT03344653.). (AU)

Quantitative description of the 3D regional mechanics of the left atrium using cardiac magnetic resonance imaging.

The left atrium (LA) plays an important role in the maintenance of hemodynamic and electrical stability of the heart. One of the conditions altering the atrial mechanical function is atrial fibrillation (AF), leading to an increased thromboembolic risk due to impaired mechanical function. Preserving the regions of the LA that contribute the greatest to atrial mechanical function during curative strategies for AF is important. The purpose of this study is to introduce a novel method of regional assessment of mechanical function of the LA. We used cardiac MRI to reconstruct the 3D geometry of the LA in nine control and nine patients with paroxysmal atrial fibrillation (PAF). Regional mechanical function of the LA in pre-defined segments of the atrium was calculated using regional ejection fraction and wall velocity. We found significantly greater mechanical function in anterior, septal and lateral segments as opposed to roof and posterior segments, as well as a significant decrease of mechanical function in the PAF group. We suggest that in order to minimize the impact of the AF treatment on global atrial mechanical function, damage related to therapeutic intervention, such as catheter ablation, in those areas should be minimized.

Percutaneous renal denervation and the second generation EnligHTN System.

Hypertension remains a major public health burden despite the plethora of therapeutic agents available for this disorder, compelling innovation of alternate therapies including interventional approaches where necessary. The kidney is a major player in the pathophysiology of this disease with increased sympathetic activity being the key factor in the initiation and maintenance of drug resistant hypertension in many patients. Thus renal denervation targeted at decreasing sympathetic drive is becoming the apparent choice in carefully selected patients with resistant hypertension who have exhausted all medical options. The Symplicity and EnligHTN trials using first and second generation catheters respectively have demonstrated that renal sympathetic denervation results in significant blood pressure reduction. The initial renal denervation catheter used in the Symplicity trial was a single electrode system. Refinement of this process has led to the EnligHTN catheter's design. This is a multielectrode self-expanding nitinol basket that allows the positioning of the thermal injury pattern to be pre-specified and in theory lead to better positioning of the lesions. We present a review of the premise behind renal artery denervation, discuss the data and early technologies focusing on the characteristics and utility of the first multielectrode renal denervation device, the EnligHTN renal denervation catheter.

Cardiac magnetic resonance, transthoracic and transoesophageal echocardiography: a comparison of in vivo assessment of ventricular function in rats.

In vivo assessment of ventricular function in rodents has largely been restricted to transthoracic echocardiography (TTE). However 1.5 T cardiac magnetic resonance (CMR) and transoesophageal echocardiography (TOE) have emerged as possible alternatives. Yet, to date, no study has systematically assessed these three imaging modalities in determining ejection fraction (EF) in rats. Twenty rats underwent imaging four weeks after surgically-induced myocardial infarction. CMR was performed on a 1.5 T scanner, TTE was conducted using a 9.2 MHz transducer and TOE was performed with a 10 MHz intracardiac echo catheter. Correlation between the three techniques for EF determination and analysis reproducibility was assessed. Moderate-strong correlation was observed between the three modalities; the greatest between CMR and TOE (intraclass correlation coefficient (ICC) = 0.89), followed by TOE and TTE (ICC = 0.70) and CMR and TTE (ICC = 0.63). Intra- and inter-observer variations were excellent with CMR (ICC = 0.99 and 0.98 respectively), very good with TTE (0.90 and 0.89) and TOE (0.87 and 0.84). Each modality is a viable option for evaluating ventricular function in rats, however the high image quality and excellent reproducibility of CMR offers distinct advantages even at 1.5 T with conventional coils and software.

Multivessel coronary artery spasm.

Coronary spasm is increasingly recognised as an important aetiological mechanism causing myocardial ischaemia. Occasionally cases present with evidence of ST segment elevation myocardial infarction, usually secondary to spasm confined to a solitary coronary artery. We present the rare and life-threatening case of severe coronary spasm afflicting all three major epicardial arteries simultaneously. It describes the difficult emergency scenario and ongoing management dilemmas encountered by physicians confronted with multivessel coronary spasm. Moreover we discuss the malignant prognosis associated with this ailment and describe the potential insights provided by cardiac magnetic resonance imaging that might identify those at greatest risk after the index event.

Enrichment for STRO-1 expression enhances the cardiovascular paracrine activity of human bone marrow-derived mesenchymal cell populations.

The cardiovascular therapeutic potential of bone marrow mesenchymal stromal/stem cells (MSC) is largely mediated by paracrine effects. Traditional preparation of MSC has involved plastic adherence-isolation. In contrast, prospective immunoselection aims to improve cell isolation by enriching for mesenchymal precursor cells (MPC) at higher purity. This study compared the biological characteristics and cardiovascular trophic activity of plastic adherence-isolated MSC (PA-MSC) and MPC prepared from the same human donors by immunoselection for stromal precursor antigen-1 (STRO-1). Compared to PA-MSC, STRO-1-MPC displayed greater (1) clonogenicity, (2) proliferative capacity, (3) multilineage differentiation potential, and (4) mRNA expression of mesenchymal stem cell-related transcripts. In vitro assays demonstrated that conditioned medium from STRO-1-MPC had greater paracrine activity than PA-MSC, with respect to cardiac cell proliferation and migration and endothelial cell migration and tube formation. In keeping with this, STRO-1-MPC exhibited higher gene and protein expression of CXCL12 and HGF. Inhibition of these cytokines attenuated endothelial tube formation and cardiac cell proliferation, respectively. Paracrine responses were enhanced by using supernatant from STRO-1(Bright) MPC and diminished with STRO-1(Dim) conditioned medium. Together, these findings indicate that prospective isolation gives rise to mesenchymal progeny that maintain a higher proportion of immature precursor cells compared to traditional plastic adherence-isolation. Enrichment for STRO-1 is also accompanied by increased expression of cardiovascular-relevant cytokines and enhanced trophic activity. Immunoselection thus provides a strategy for improving the cardiovascular reparative potential of mesenchymal cells.

Gross echocardiographic underestimation of mitral valve calcification--a near fatal experience.

Acute severe mitral regurgitation is a feared complication following percutaneous balloon mitral valvuloplasty (PBMV) for the treatment of severe mitral stenosis, contributing to the 1% peri-procedural mortality rate of this procedure. Whilst there is an extensive experience with the use of the Wilkins echocardiographic score to assess patient suitability and predict long-term clinical outcomes following PBMV, catastrophic severe acute mitral regurgitation, such as that described in our patient, is a remarkably rare occurrence following PBMV in patients with favourable Wilkins echocardiographic criteria. We highlight a case of the gross underestimation of the degree of valvular calcification using trans-oesophageal echocardiography, when compared to the findings at surgery, which contributed to our patients' life-threatening mitral regurgitation following the first balloon inflation. We advocate further research into the utility of multi-detector computed tomography (MDCT) imaging for the adjunctive pre-procedural assessment of the degree mitral calcification in order to further minimise the risk of peri-procedural complications associated with PBMV. This would be particularly suitable in the elderly population who normally have greater degrees of valvular calcification that may be underestimated with echocardiography alone.

Non-invasive assessment of saphenous vein graft patency in asymptomatic patients.

The development and progression of atherosclerotic disease in saphenous vein grafts (SVGs) following coronary artery bypass surgery (CABG) are often without symptoms. Four-slice CT is a non-invasive imaging technique reliable for assessing SVG patency. This study utilised CT to assess temporal progression of patency in asymptomatic patients. A four-slice CT scanner was used employing standard techniques. Analysis of the reconstructed images was performed offline by two experienced operators blinded to patient details. The primary aim was vein graft patency. 130 asymptomatic subjects were studied. The mean time from CABG was 7.3 years (range, 15 days to 21 years 9 months; standard deviation (SD), 4.4 years). 294 of the 305 SVGs were suitable for assessment of patency. The overall occlusion rate for assessable grafts was 23.5%. Occlusion rates for grafts <1 year old was 12.5% (2/16), 20.7% (42/203) for grafts 1-10 years old, and 33.3% (25/75) for grafts >10 years old. In conclusion, significant occlusion of SVGs occurs early after CABG in asymptomatic patients. Four-slice CT has the potential for the non-invasive assessment of individuals after surgery.

Giant saphenous vein graft pseudoaneurysm rupture presenting with cardiac tamponade.

Saphenous vein graft aneurysms are a rare but potentially fatal complication following coronary artery bypass graft (CABG) surgery, with a wide variation in clinical presentations ranging from recurrent atypical chest pain to sudden cardiac death. Although uncommon, the diagnosis should be considered in all patients presenting with a hilar or mediastinal mass following CABG, as timely treatment may avert potentially fatal aneurysm rupture and death. We report a rare case of a giant vein graft pseudoaneurysm rupture causing cardiac tamponade.

Serial magnetic resonance imaging correlates with neurological outcome in an experimental model of spinal cord ischemia.

BACKGROUND: Paraplegia complicating surgical thoracoabdominal aneurysm (TAA) repair remains an unpredictable and poorly understood phenomenon. The ability to identify patients at increased risk of delayed paraplegia before the process becomes irreversible could allow early interventions to attenuate this risk. METHODS: In a rabbit model of infra-renal spinal cord ischemia, serial T2 weighted (T2W) magnetic resonance (MR) imaging was performed 2- and 8 h after the ischemic insult with changes correlated with clinical outcome. Using the axial T2W images, signal intensity measurements of the lateral horns of the spinal cord were acquired, both above (that is, thoracolumbar cord) and below (that is, lumbar cord) the renal arteries. This ratio (lumbar/thoracolumbar cord signal intensity) was evaluated and compared between groups. RESULTS: No changes were seen in the signal intensity of rabbits that remained neurologically intact. Rabbits with delayed paralysis showed a significant (P<0.01) decrease in signal intensity ratio at 2 h (1.13+/-0.03), while a significant (P<0.01) increase was noted in those rabbits with immediate persistent paralysis (1.43+/-0.04). There was a significant (P<0.01) increase in the signal intensity ratios at 2 h in the delayed paralysis group (1.55+/-0.14), with a further significant (P<0.01) increase at 8 h in the immediate persistent paralysis group (1.76+/-0.07). CONCLUSIONS: Findings on MR imaging can differentiate clinical outcomes in this experimental model of spinal cord ischemia. While further studies are required, MR could be useful in predicting which patients are at risk for delayed paraplegia after TAA repair.