Review on Mechanical Support and Cell-Based Therapies for the Prevention and Recovery of the Failed Fontan-Kreutzer Circulation

Though the current staged surgical strategy for palliation of single ventricle heart disease, culminating in a Fontan circulation, has increased short-term survival, mounting evidence has shown that the single ventricle, especially a morphologic right ventricle (RV), is inadequate for long-term circulatory support. In addition to high rates of ventricular failure, high central venous pressures (CVP) lead to liver fibrosis or cirrhosis, lymphatic dysfunction, kidney failure, and other comorbidities. In this review, we discuss the complications seen with Fontan physiology, including causes of ventricular and multi-organ failure. We then evaluate the clinical use, results, and limitations of long-term mechanical assist devices intended to reduce RV work and high CVP, as well as biological therapies for failed Fontan circulations. Finally, we discuss experimental tissue engineering solutions designed to prevent Fontan circulation failure and evaluate knowledge gaps and needed technology development to realize a more robust single ventricle therapy.

TIVA for ECMO and VAD

In recent decades, the use of temporary and permanent use of mechanical assist devices is on the rise for patients with end-stage cardiac failure. These support strategies hold inherently different risks in the face of noncardiac critical illness and require multidisciplinary treatment strategies. The main issues with all mechanical devices whether extracorporeal membrane oxygenation (ECMO) or ventricular assist device (VAD), are related to thrombosis, anticoagulation, infection, avoiding hypertension and thus use of intravenous drugs, which requires intense monitoring, to circumvent further renal, ischemic or neurological injury and prevent complication.

Endothelial shear stress enhancements: a potential solution for critically ill Covid-19 patients

Most critically ill Covid-19 patients succumb to multiple organ failure and/or sudden cardiac arrest (SCA) as a result of comorbid endothelial dysfunction disorders which had probably aggravated by conventional mechanical assist devices. Even worse, mechanical ventilators prevent the respiratory pump from performing its crucial function as a potential generator of endothelial shear stress (ESS) which controls microcirculation and hemodynamics since birth. The purpose of this work is to bring our experience with ESS enhancement and pulmonary vascular resistance (PVR) management as a potential therapeutic solution in acute respiratory distress syndrome (ARDS). We propose a non-invasive device composed of thoracic and infradiaphragmatic compartments that will be pulsated in an alternating frequency (20/40 bpm) with low-pressure pneumatic generator (0.1–0.5 bar). Oxygen supply, nasogastric with, or without endotracheal tubes are considered.

Endothelial Shear Stress Enhancements: A Potential Solution for Critically Ill Covid-19 Patients

Rationale: Most critically ill Covid-19 patients succumb to multiple organ failure and / or cardiac arrest as a result of comorbid endothelial dysfunction disorders which had probably aggravated by conventional mechanical assist devices. Even worse, mechanical ventilators prevent the respiratory pump from performing its crucial function as a potential generator of endothelial shear stress (ESS) which controls microcirculation and hemodynamics since birth. The purpose of this work is to bring our experience with ESS enhancement and pulmonary vascular resistance (PVR) management as a potential therapeutic solution in acute respiratory distress syndrome (ARDS). We propose a noninvasive device composed of thoracic and infradiaphragmatic compartments that will be pulsated in an alternating frequency (20/40 bpm) with low-pressure pneumatic generator (0.1-0.5 bar). Oxygen supply, nasogastric ± endotracheal tubes are considered. Proof-of-concept: prototypes were tested in pediatric models of refractory cardiac arrest (≥20min), showed restoration of hemodynamics (BP≥100 mm Hg) and urine output, regardless of heartbeats, pharmacological supports and mechanical ventilation. Conclusions ESS enhancement represents a more effective treatment to increase tissue oxygenation and improve hemodynamic in ARDS. A cost-effective method which could be induced with a non-invasive pulsatile device adaptable to cardiopulmonary-circulatory biophysics to maintain a fully functional respiratory pump and avoid confrontation of the opposite hydraulic circuits.

Aetiology and outcomes of severe right ventricular dysfunction

Aims Right ventricular dysfunction (RVD) is an important determinant of functional status and survival in various diseases states. Data are sparse on the epidemiology and outcome of patients with severe RVD. This study examined the characteristics, aetiology, and survival of patients with severe RVD. Methods and results Retrospective study of consecutive patients with severe RVD diagnosed by transthoracic echocardiography (TTE) between 2011 and 2015 in a single tertiary referral institution. Patients with prior cardiac surgery, mechanical assist devices, and congenital heart disease were excluded. Primary endpoint was all-cause mortality. In 64 728 patients undergoing TTE, the prevalence of ≥mild RVD was 21%. This study focused on the cohort of 1299 (4%) patients with severe RVD; age 64 ± 16 years; 61% male. The most common causes of severe RVD were left-sided heart diseases (46%), pulmonary thromboembolic disease (18%), chronic lung disease/hypoxia (CLD; 17%), and pulmonary arterial hypertension (PAH; 11%). After 2 ± 2 years of follow-up, 701 deaths occurred, 66% within the first year of diagnosis. The overall probability of survival at 1- and 5 years for the entire cohort were 61% [95% confidence interval (CI) 58–64%] and 35% (95% CI 31–38%), respectively. In left-sided heart diseases, 1- and 5-year survival rates were 61% (95% CI 57–65%) and 33% (95% CI 28–37%), respectively; vs. 76% (95% CI 68–82%) and 50% (95% CI 40–59%) in PAH, vs. 71% (95% CI 64–76%) and 49% (95% CI 41–58%) in thromboembolic diseases, vs. 42% (95% CI 35–49%) and 8% (95% CI 4–15%) in CLD (log-rank P < 0.0001). Presence of ≥moderate tricuspid regurgitation portended worse survival in severe RVD. Conclusion One-year mortality of patients with severe RVD was high (∼40%) and dependent on the aetiology of RVD. Left-sided heart diseases is the most common cause of severe RVD but prognosis was worst in CLD.