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.

Utility of mesenchymal stromal cells for myocardial infarction. Transitioning from bench to bedside.

Amongst experimental therapies being evaluated for myocardial infarction (MI), the field of cellular cardiomyoplasty still provokes much excitement, well into its second decade of investigation. Mesenchymal stromal/stem cells (MSCs) have held a particularly enduring place as one of the mainstays of adult-derived stem cell research in cardiovascular disease. These rare, non-hematopoietic cells are natively present throughout different postnatal tissues, most famously bone marrow, where they typically participate in perivascular stem cell niches and play key supportive and trophic roles. Their application for exogenous stem cell delivery is made attractive by their ease of isolation, proclivity for ex vivo expansion and potential for allogeneic use. There is now a remarkable wealth of in vitro and animal-based evidence attesting to the ability of MSCs to safely augment cardiac repair post-MI through pleiotropic mechanisms that continue to be delineated and in turn, optimised. However, despite such preclinical promise and the encouraging results of preliminary experience in human patients, the broader translation of MSCs to the clinical cardiovascular realm requires much more refinement to overcome fundamental limitations, not to mention rigorous validation to resolve lingering areas of uncertainty. Here we review the basic biological properties that have made MSCs so widely investigated for cardiovascular repair, discuss the preclinical evidence for their efficacy and purported mechanisms of action and consider the practicalities and evidence for their use in human patients with MI and cardiomyopathy.

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.

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.

Evidence-based management of heart failure in clinical practice: a review of device-based therapy use.

BACKGROUND: Heart failure is a growing health issue and is associated with significant mortality risk. Device therapy is efficacious in preventing sudden death in patients with heart failure; however, this evidence comes from rigorous clinical trials. It is unclear how device therapy is utilized in 'real-world' practice. The primary objective was to characterize patterns of device use in patients with heart failure at risk of sudden death and to identify barriers to guideline-driven prescription of implantable cardioverter-defibrillators. METHODS: We report a cross-sectional study of patients attending general cardiology clinic over a 3-month period. RESULTS: Of 1003 consecutive patients attending the cardiology clinic, 176 had heart failure. Of these, 66 were potentially eligible for device therapy, but only 16 of these had actually undergone device implantation. Potentially eligible non-recipients were older (P < 0.001), more likely to have ischaemic cardiomyopathy (P= 0.002), less likely to be prescribed spironolactone (P= 0.005) or warfarin (P= 0.02), and less likely to have a widened QRS > 120 ms (P= 0.005). There was a high prevalence of underuse of evidence-based pharmacotherapies among patients with heart failure. CONCLUSION: There is substantial underuse of device therapy in patients with heart failure. Strikingly, whereas patients with symptoms of heart failure were more likely to receive a device, those being managed for ischaemic heart disease were not. There is also a high prevalence of failure to prescribe evidence-based pharmacotherapy in a tertiary hospital general cardiology clinic. This may be explained in part by the lack of a patient database to record treatment contraindications and to alert clinicians to possible gaps in patient therapy.