Regenerative therapies in young hearts with structural or congenital heart disease

Michel‐Behnke, Ina; Pávó, Imre; Recla, Sabine; Khalil, Markus; Jux, Christian; Schranz, Dietmar

doi:10.21037/tp.2019.03.01

Cited by 8 publications

(5 citation statements)

References 59 publications

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“…On the other hand, this failure might be due to a reduced regenerative myocardial capacity, which is known to correlate negatively with patients' age ( 33 ). Currently, two models describe that human infants and children generate new cardiomyocytes, with cardiomyocyte generation being highest in infancy, and declining to a relative stagnation in adults, with very low but measurable levels after 20 years of life ( 34 – 37 ).…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Artery Banding for Ventricular Rehabilitation in Infants With Dilated Cardiomyopathy: Early Results in a Single-Center Experience

et al. 2020

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Background: Pulmonary artery banding (PAB) is reported as an innovative strategy for children with end-stage heart failure (ESHF) to bridge to transplantation or recovery. We report our early experience with PAB to evaluate outcomes, indications, and limitations. Materials and Methods: This is a single-center prospective clinical study, including infants and children admitted for ESHF owing to dilated cardiomyopathy (DCM) with preserved right ventricular function after failure of maximal conventional therapy. All patients underwent perioperative anticongestive medical therapy with ACE inhibitor, beta blocker, and spironolactone. Post-operatively, all patients underwent echocardiographic follow-up to assess myocardial recovery. Results: We selected five patients (four males) who underwent PAB at a median age of 8.6 months (range 3.9-42.2 months), with preoperative ejection fraction (EF) < 30%. Sternal closure was delayed in all. One patient did not improve after PAB and underwent Berlin Heart implantation after 33 days, followed by heart transplant after 13 months. Four patients were discharged home on full anticongestive therapy. However, 2 months after discharge, one patient experienced severe acute heart failure secondary to pneumonia, which required mechanical circulatory support, and the patient underwent a successful heart transplant after 21 days. The remaining three patients are doing well at home, 22.4, 16.9, and 15.4 months after PAB. They all underwent elective percutaneous de-banding, 18.5, 4.8, and 10.7 months after PAB. EF increased from 17.7 ± 8.5% to 63.3 ± 7.6% (p = 0.03), and they have all been delisted. Conclusion: Use of PAB may be an effective alternative to mechanical support in selected infants for bridging to transplant or recovery. Better results seem to occur in patients aged < 12 months. Further experience and research are required to identify responders and non-responders to this approach.

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Section: Discussionmentioning

confidence: 99%

Pulmonary Artery Banding for Ventricular Rehabilitation in Infants With Dilated Cardiomyopathy: Early Results in a Single-Center Experience

et al. 2020

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“…This differential disease pathogenesis during heart failure progression may reflect distinct disease mechanisms between adult and pediatric DCMs and also suggest that cell therapy may be appropriate for children with DCM (22). Recent progress in clinical studies has raised pivotal questions with respect to the optimized cell dose and delivery modality for pediatric DCM (27). Whether cell infusion with interrupted coronary flow is necessary for therapeutic efficacy remains uncertain but has been shown to increase the risks of adverse coronary events.…”

Section: Mir-146a-5p Inhibits Inflammatory Responses In Human Cardiommentioning

confidence: 99%

Cardiosphere-derived exosomal microRNAs for myocardial repair in pediatric dilated cardiomyopathy

et al. 2020

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Although cardiosphere-derived cells (CDCs) improve cardiac function and outcomes in patients with single ventricle physiology, little is known about their safety and therapeutic benefit in children with dilated cardiomyopathy (DCM). We aimed to determine the safety and efficacy of CDCs in a porcine model of DCM and translate the preclinical results into this patient population. A swine model of DCM using intracoronary injection of microspheres created cardiac dysfunction. Forty pigs were randomized as preclinical validation of the delivery method and CDC doses, and CDC-secreted exosome (CDCex)–mediated cardiac repair was analyzed. A phase 1 safety cohort enrolled five pediatric patients with DCM and reduced ejection fraction to receive CDC infusion. The primary endpoint was to assess safety, and the secondary outcome measure was change in cardiac function. Improved cardiac function and reduced myocardial fibrosis were noted in animals treated with CDCs compared with placebo. These functional benefits were mediated via CDCex that were highly enriched with proangiogenic and cardioprotective microRNAs (miRNAs), whereas isolated CDCex did not recapitulate these reparative effects. One-year follow-up of safety lead-in stage was completed with favorable profile and preliminary efficacy outcomes. Increased CDCex-derived miR-146a-5p expression was associated with the reduction in myocardial fibrosis via suppression of proinflammatory cytokines and transcripts. Collectively, intracoronary CDC administration is safe and improves cardiac function through CDCex in a porcine model of DCM. The safety lead-in results in patients provide a translational framework for further studies of randomized trials and CDCex-derived miRNAs as potential paracrine mediators underlying this therapeutic strategy.

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“…Restored ventricular electromechanical synchrony, increased LV ejection fraction are associated with clinical improvement at rest and during exercise. The interplay of endogenous stimulating and inhibiting mechanisms might be responsible for PAB induced repair particularly in infants and young children with DCM; the PAB-induced interplay of well-known and unknown molecular parameters seem to work like an epigenetic factor for re-balancing cardiac function and reparation; provided, that the prospectively stressed heart is additionally flanked by heart protecting drugs (48). The surgical risk of PAB placement in infancy is relatively low.…”

Section: Pulmonary Artery Banding (Pab) In Lv-dcmmentioning

confidence: 99%

Heart failure therapy based on interventricular mechanics and cardio-vascular communications

Schranz

Akintuerk

Esmaeili

et al. 2021

Cardiovasc Diagn Ther

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The heart should not be divided in right and left, whether in health nor in disease. However, the morphological and functional differences between the right and left ventricle should be known and the impact of the ventricle's position considered. Further, the parameters beyond heart rate, contractility, pre-and afterload guaranteeing a sufficient systemic cardiac output have to be integrated in therapeutic measures; preferentially the influence of interventricular mechanics. Despite of recent developments of specific drug therapies, heart failure is associated with a high rate of morbidity and mortality in children.During the progression of heart failure, pulmonary vascular disease is the consequence or the reason for further failing. Clinical symptoms are associated with congestion and low cardiac output at rest or exercise.Improved understanding of the pathophysiological mechanisms particularly of ventricular failure has resulted in the development of innovative therapies that target atrial/ventricular/arterial interactions. Recent advances in interventional and surgical approaches provide promising new strategies to deal with right and left ventricular deterioration. These techniques may delay listing for heart and (heart-)lung transplantation or even make redundant in individual cases. The beneficial effects of these ventricular interaction strategies are mainly based on the mechanics of the interventricular septum and improvement of systolic and diastolic ventricular performance.

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Regenerative therapies in young hearts with structural or congenital heart disease

Cited by 8 publications

References 59 publications

Pulmonary Artery Banding for Ventricular Rehabilitation in Infants With Dilated Cardiomyopathy: Early Results in a Single-Center Experience

Pulmonary Artery Banding for Ventricular Rehabilitation in Infants With Dilated Cardiomyopathy: Early Results in a Single-Center Experience

Cardiosphere-derived exosomal microRNAs for myocardial repair in pediatric dilated cardiomyopathy

Heart failure therapy based on interventricular mechanics and cardio-vascular communications

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