Heart Failure: Will There be Any light at the End of the Tunnel with Stem Cell Therapy?

Cardiac regeneration using stem cells emerges as a noveltreatment option for heart failure. Clinical applications havereported encouraging but modest favorable results, concerningcardiac functional recovery. However, many issues need clarification.The most appropriate cell type, the optimal number ofinjected cells and time for cell delivery, as well as the mode ofcell function remain to be elucidated. Furthermore, ways to improve cell survival and long term engraftment are being sought, in an effort to enhance the regenerative capability of the cells. A substantial amount of basic, translational and clinical research is still needed, in order to take advantage of the full therapeuticpotential of stem cell treatments for heart failure

Persistent Left Superior Vena Cava With Absent Right Superior Vena Cava

We report the case of a 52-year-old patient who referred to our hospital with the indication for a pacemaker implantation. The attempt to implant the pacemaker lead through the right subclavian vein revealed an unusual course of the lead. The phlebography through the right subclavian vein revealed the presence of a persistent left superior vena cava and the absence of right superior vena cava

Perfusion defect size predicts engraftment but not early retention of intra-myocardially injected cardiosphere-derived cells after acute myocardial infarction

Therapeutic cell retention and engraftment are critical for myocardial regeneration. Underlying mechanisms, including the role of tissue perfusion, are not well understood. In Wistar Kyoto rats, syngeneic cardiosphere-derived cells (CDCs) were injected intramyocardially, after experimental myocardial infarction. CDCs were labeled with [18F]-FDG (n = 7), for quantification of 1-h retention, or with sodium-iodide-symporter gene (NIS; n = 8), for detection of 24-h engraftment by reporter imaging. Perfusion was imaged simultaneously. Infarct size was 37 ± 9 and 38 ± 9% of LV in FDG and NIS groups. Cell signal was located in the infarct border zone in all animals. No significant relationship was observed between infarct size and 1-h CDC retention (r = −0.65; P = 0.11). However, infarct size correlated significantly with 24-h engraftment (r = 0.75; P = 0.03). Residual perfusion at the injection site was not related to cell retention/engraftment. Larger infarcts are associated with improved CDC engraftment. This observation encourages further investigation of microenvironmental conditions after ischemic damage and their role in therapeutic cell survival

Cardiac Allograft Vasculopathy in Redo-transplants: Is it More or Less the Same the Second Time Around?

Purpose: Cardiac allograft vasculopathy (CAV) continues to hinder the long-term success of heart transplant recipients.  Redo-transplantation is currently the only definitive treatment for advanced CAV. We examined whether these patients are at similar CAV-risk with the second transplantMethods: Heart recipients from 1985 to 2011 at the UTAH program were included in the study and those with CAV as an indication for redo-transplantation were identified. CAV diagnosis was made by coronary angiography and based on the 2010 ISHLT standardized nomenclature for CAV. Patient demographics, rejection history, and CAV incidence were analyzed. Results: Of the 1,169 eligible patients, 135 (11.5%) developed CAV post their first transplant; 78 cases within 10 years and 54 beyond 10 years. The mean time to CAV was 6.58 years. Of the 135 patients who developed CAV, only 21 (15.5%) ended up requiring a redo-transplant. Of the 21 retransplanted patients, 4 (19.0%) developed CAV again; 2 patients within 10 years and 2 patients beyond 10 years indicating a similar risk for CAV occurrence for first and redo-transplant. Conclusions: Our results indicate that CAV is as likely to develop in redo-transplants despite recent advances in immunosuppression and the standardized use of lipid-lowering agents. Although outcomes in redo-transplantation for the indication of CAV are favorable, efforts to better understand and minimize CAV are needed, especially in the face of scarce donor organs

The evolving field of nonpharmacological therapies to improve functional capacity in chronic heart failure

Clinical investigations in chronic heart failure (HF) have been increasingly including endpoints related to functional and exercise capacity. Noninvasive ventilation support (NIVS) constitutes a therapeutic option that could improve several markers of cardiovascular performance and functional capacity along with improvements in HF symptoms such as dyspnea. NIVS with bilevel positive airway pressure (BiPAP) is a therapeutic option that can be better tolerated by patients than continuous positive airway pressure (cPAP) and potentially improve the adherence of patients with HF to NIVS. Future investigations should improve our understanding as to how to select patients with HF most amenable to respond favorably, elucidate the frequency and duration of NIVS session required to maintain the observed short-term beneficial effects for a long period of time, and shed additional light on the mechanisms associated with these benefits. In summary, NIVS appears to be a promising nonpharmacological therapy to improve exercise capacity and quality of life in chronic HF

The evolving field of nonpharmacological therapies to improve functional capacity in chronic heart failure

Clinical investigations in chronic heart failure (HF) have been increasingly including endpoints related to functional and exercise capacity. Noninvasive ventilation support (NIVS) constitutes a therapeutic option that could improve several markers of cardiovascular performance and functional capacity along with improvements in HF symptoms such as dyspnea. NIVS with bilevel positive airway pressure (BiPAP) is a therapeutic option that can be better tolerated by patients than continuous positive airway pressure (cPAP) and potentially improve the adherence of patients with HF to NIVS. Future investigations should improve our understanding as to how to select patients with HF most amenable to respond favorably, elucidate the frequency and duration of NIVS session required to maintain the observed short-term beneficial effects for a long period of time, and shed additional light on the mechanisms associated with these benefits. In summary, NIVS appears to be a promising nonpharmacological therapy to improve exercise capacity and quality of life in chronic HF. (C) 2018 Hellenic Society of Cardiology. Publishing services by Elsevier B.V

A combined cellular and surgical ventricular reconstruction therapeutic approach produces attenuation of remodeling in infarcted rats

Background: Left ventricular reconstruction (LVR) has been shown to provide transient benefits to the LV structure and function of infarcted hearts; however, long-term results have been disappointing as LVR-induced benefits are typically not sustained. We hypothesized that administration of cardiosphere-derived cells (CDCs), which promote myocardial repair and regeneration, may result in long-term preservation of the beneficial effects of LVR in ischemic cardiomyopathy. Methods: Wistar Kyoto rats underwent myocardial infarction (MI) and two weeks later were randomized into 3 groups: in Group 1 (n=9), LVR was performed by plication of the infarcted apex and CDCs were injected in the infarct border zone (IBZ); group 2 animals (n=9) underwent LVR and received vehicle solution in the IBZ; and Group 3 animals (n=10) were injected with vehicle solution in the IBZ without undergoing LVR. Echocardiograms were performed at baseline, 4 days post-apex plication, and at 3 months post-MI. Results: At baseline, all animal groups had a comparable LVEF, LV end-diastolic volume (EDV) and LV end-systolic volume (ESV). Four days post-LV apex plication, Group 1 and Group 2 animals exhibited comparable significant improvement in EF and comparable significant reduction in LVEDV and LVESV. Three months post-MI, Group 1 animals had a decreased LVEDV, decreased LVESV, less impaired CS, increased peak systolic torsion and increased EF compared to animals in Groups 2 and 3. Conclusion: In infarcted rat hearts, intramyocardial delivery of CDCs in conjunction with LVR resulted in significant and sustained amelioration of LV remodeling and improvement in LV function compared to LVR alone. (C) 2016 Hellenic Society of Cardiology. Publishing services by Elsevier B.V

The <i>Han:SPRD</i> Rat: A Preclinical Model of Polycystic Kidney Disease

Autosomal Dominant Polycystic Kidney Disease (ADPKD) stands as the most prevalent hereditary renal disorder in humans, ultimately culminating in end-stage kidney disease. Animal models carrying mutations associated with polycystic kidney disease have played an important role in the advancement of ADPKD research. The Han:SPRD rat model, carrying an R823W mutation in the Anks6 gene, is characterized by cyst formation and kidney enlargement. The mutated protein, named Samcystin, is localized in cilia of tubular epithelial cells and seems to be involved in cystogenesis. The homozygous Anks6 mutation leads to end-stage renal disease and death, making it a critical factor in kidney development and function. This review explores the utility of the Han:SPRD rat model, highlighting its phenotypic similarity to human ADPKD. Specifically, we discuss its role in preclinical trials and its importance for investigating the pathogenesis of the disease and developing new therapeutic approaches

LVAD as a Bridge to Remission from Advanced Heart Failure: Current Data and Opportunities for Improvement

Left ventricular assist devices (LVADs) are an established treatment modality for advanced heart failure (HF). It has been shown that through volume and pressure unloading they can lead to significant functional and structural cardiac improvement, allowing LVAD support withdrawal in a subset of patients. In the first part of this review, we discuss the historical background, current evidence on the incidence and assessment of LVAD-mediated cardiac recovery, and out-comes including quality of life after LVAD support withdrawal. In the second part, we discuss current and future opportunities to promote LVAD-mediated reverse remodeling and improve our pathophysiological understanding of HF and recovery for the benefit of the greater HF population