Orthotopic Heart and Combined Heart Liver Transplantation: the Ultimate Treatment Option for Failing Fontan Physiology.

Purpose of the Review: This is a comprehensive update on failing Fontan physiology and the role of heart and combined heart and liver transplantation in the current era. Recent Findings: Single ventricle physiology encompasses a series of rare congenital cardiac abnormalities that are characterized by absence of or hypoplasia of one ventricle. This effectively results in a single ventricular pumping chamber. These abnormalities are rarely compatible with long-term survival if left without surgical palliation in the first few years of life. Surgical treatment of single ventricle physiology has evolved over the past 60 years and is characterized by numerous creative innovations. These include the development of arteriopulmonary shunts, the evolution of partial cavopulmonary connections, and the eventual development of the "Fontan" operation. Regardless of the type of Fontan modification, the long-term consequences of the Fontan operation are predominantly related to chronic central venous hypertension and the multi-organ consequences thereof. Atrial arrhythmias can further compromise this circulation.Patients with single ventricle physiology represent a special sub-segment of congenital cardiac transplants and are arguably the most challenging patients considered for transplantation. Summary: This review describes in detail the challenges and opportunities of heart and liver transplantation in Fontan patients, as viewed and managed by the experienced team at the Ahmanson/UCLA Adult Congenital Heart Center.

A Novel Negative Pressure Isolation Device for Aerosol Transmissible COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic creates a need to protect health care workers (HCWs) from patients undergoing aerosol-generating procedures which may transmit the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Existing personal containment devices (PCDs) may protect HCWs from respiratory droplets but not from potentially dangerous respiratory-generated aerosols. We describe a new PCD and its aerosol containment capabilities. The device ships flat and folds into a chamber. With its torso drape and protective arm sleeves mounted, it provides contact, droplet, and aerosol isolation during intubation and cardiopulmonary resuscitation (CPR). Significantly improved ergonomics, single-use workflow, and ease of removal distinguish this device from previously published designs.

Prolonged central venous desaturation measured by continuous oximetry is associated with adverse outcomes in pediatric cardiac surgery.

BACKGROUND: The role of continuous central venous oxygen saturation (ScvO2) oximetry during pediatric cardiac surgery for predicting adverse outcomes is not known. Using a recently available continuous ScvO2 oximetry catheter, we examined the association between venous oxygen desaturations and patient outcomes. We hypothesized that central venous oxygen desaturations are associated with adverse clinical outcomes. METHODS: Fifty-four pediatric patients undergoing cardiac surgery were prospectively enrolled in an unblinded observational study. ScvO2 was measured continuously in the operating room and for up to 24 h post-Intensive Care Unit admission. The relationships between ScvO2 desaturations, clinical outcomes, and major adverse events were determined. RESULTS: More than 18 min of venous saturations less than 40% were associated with major adverse events with 100% sensitivity and 97.6% specificity. Significant correlations resulted between the ScvO2 area under the curve less than 40% and creatinine clearance at 12 h in the Intensive Care Unit (r = -0.58), Intensive Care Unit length of stay (r = 0.56), max inotrope use (r = 0.52), inotrope use at 24 h (r = 0.40), inotrope index score (r = 0.39), hospital length of stay (r = 0.36), and length of intubation (r = 0.32). CONCLUSIONS: We demonstrate that ScvO2 desaturations by continuous oximetry are associated with major adverse events in pediatric patients undergoing cardiac surgery. The most significant associations with major adverse events are seen in patients with greater than 18 min of central venous saturations less than 40%. Our results support the further investigation of ScvO2 as a potential target parameter in high-risk pediatric patients to minimize the risk of major adverse events.

Thromboxane A2 receptor and MaxiK-channel intimate interaction supports channel trans-inhibition independent of G-protein activation.

Large conductance voltage- and calcium-activated potassium channels (MaxiK, BK(Ca)) are well known for sustaining cerebral and coronary arterial tone and for their linkage to vasodilator ß-adrenergic receptors. However, how MaxiK channels are linked to counterbalancing vasoconstrictor receptors is unknown. Here, we show that vasopressive thromboxane A2 receptors (TP) can intimately couple with and inhibit MaxiK channels. Activation of the receptor with its agonist trans-inhibits MaxiK independently of G-protein activation. This unconventional mechanism is supported by independent lines of evidence: (i) inhibition of MaxiK current by thromboxane A2 mimetic, U46619, occurs even when G-protein activity is suppressed; (ii) MaxiK and TP physically associate and display a high degree of proximity; and (iii) Förster resonance energy transfer occurs between fluorescently labeled MaxiK and TP, supporting a direct interaction. The molecular mechanism of MaxiK-TP intimate interaction involves the receptor's first intracellular loop and C terminus, and it entails the voltage-sensing conduction cassette of MaxiK channel. Further, physiological evidence of MaxiK-TP physical interaction is given in human coronaries and rat aorta, and by confirming TP role (with antagonist SQ29,548) in the U46619-induced MaxiK inhibition in human coronaries. We propose that vasoconstrictor TP receptor and MaxiK-channel direct interaction facilitates G-protein-independent TP to MaxiK trans-inhibition, which would promote vasoconstriction.

Inhaled nitric oxide in the preoperative evaluation of pulmonary hypertension in heart transplant candidates.

OBJECTIVE: The goal of this study was to evaluate the efficacy of 100% oxygen and inhaled nitric oxide (iNO) in decreasing pulmonary vascular resistance (PVR) and transpulmonary gradient (TPG) in dilated cardiomyopathy patients being evaluated for orthotopic heart transplantation (OHT); who, despite maximal intravenous (IV) dilator therapy, had persistent moderate-to-severe pulmonary hypertension. DESIGN: A prospective nonrandomized clinical study. SETTING: University hospital, major transplant center. PARTICIPANTS: Twenty-one adult patients undergoing OHT evaluation. INTERVENTIONS: One hundred percent oxygen and iNO at 20 and 40 ppm were sequentially administered to the patients once they were optimized with IV vasodilators and inotropes. MEASUREMENTS AND MAIN RESULTS: Although no significant change was noted with oxygen, iNO 20 ppm reduced the mean pulmonary artery pressure (44.1 +/- 1.7 to 38.6 +/- 1.8 mmHg, p < 0.05), PVR index (823 +/- 47 to 621 +/- 55 dyne/s/m(2)/cm(5), p < 0.05), TPG (22.4 +/- 1.4 to 17.0 +/- 1.5 mmHg, p < 0.05), and right ventricular stroke work index (14.7 +/- 1.2 to 11.1 +/- 1.2 g . m/m(2)/beat, p < 0.05). In 13 of 21 patients, PVR decreased by greater than 25% after iNO therapy. Nine of these patients had PVR and TPG decrease to levels considered acceptable for OHT listing. CONCLUSIONS: iNO can further improve right ventricular hemodynamics even after presumed optimization with IV vasodilators and serves as a test of PVR reversibility during the preoperative assessment of OHT candidates.

Functional and molecular evidence of MaxiK channel beta1 subunit decrease with coronary artery ageing in the rat.

Large-conductance, voltage- and Ca2+ -activated K+ channels (MaxiK, BK) are key regulators of vascular tone. Vascular MaxiK are formed by the pore-forming alpha subunit and the modulatory beta1 subunit, which imprints unique kinetics, Ca2+/voltage sensitivities and pharmacology to the channel. As age progresses, alpha subunit functional expression and protein levels diminish in coronary myocytes. However, whether ageing modifies beta1 subunit expression or the mechanism of alpha subunit reduction is unknown. Thus, we examined functional and pharmacological characteristics of MaxiK, as well as alpha and beta1 transcript levels in coronary myocytes from young and old F344 rats. The mechanism of age-dependent alpha subunit protein reduction involves its transcript downregulation. A corresponding loss of beta1 transcripts was also detected in old myocytes, suggesting a proportional age-dependent decrease of beta1 to alpha subunit protein. Indeed, MaxiK channel properties, defined by coassembly of beta1 and alpha subunits, were equivalent in young versus old, for example in terms of (i) activation kinetics, (ii) sensitivity to Ca2+ levels > 1 microm (iii) dehydrosoyasaponin-I-induced activation, and (iv) iberiotoxin blockade. Consistent with less MaxiK expression/function in older myocytes, the ability of iberiotoxin to contract coronary rings was reduced approximately 50% with ageing confirming our previous findings. 5-Hydroxytryptamine (5-HT) contractile efficacy was reduced by iberiotoxin pretreatment in young > old coronary arteries (explained by larger iberiotoxin-induced contraction and decreased dynamic range for 5-HT contraction in young versus old) with no apparent differences in nitroglycerine-induced relaxation. We propose that the age-related MaxiK reduction involves a parallel decrease of alpha and beta1 functional expression via a transcript downregulatory mechanism; a major impact on basal and possibly stimulated coronary contraction may contribute to altered coronary flow regulation and coronary morbidity in the elderly.

Pulse contour analysis for cardiac output monitoring in cardiac surgery for congenital heart disease.

UNLABELLED: Conventional methods of cardiac output monitoring using pulmonary artery catheters may not be feasible in patients with congenital heart disease because of patients' small size or aberrant anatomy. We studied the accuracy of a new device, which uses pulse contour analysis to measure continuous cardiac output, in children and adults undergoing congenital heart surgery. Sixteen patients, median ages 7 yr old, were included in this prospective study. One-hundred-ninety-one data points were obtained in the pre- and postcardiopulmonary bypass periods and in the first 12 h after intensive care unit admission. We evaluated the relationship between cardiac index (CI) derived from transpulmonary thermodilution (TDCI) and CI derived from pulse contour analysis (PCCI). Bias and limits of agreement between TDCI and PCCI over all time periods were 0.1 +/- 1.94, indicating a wide dispersion of the data. Coefficient of correlation (r) between the TDCI and PCCI was 0.7. Although in previous studies, PCCI has been suggested to be accurate in adult cardiac surgery, we found it to be less reliable in our study patients, even after shunt correction. The relationships of the volume and pressure based measures of preload, intrathoracic blood volume index (ITBI), and central venous pressure with CI were also investigated. After repair, correlation (r) between PCCI or TDCI and ITBI (0.56 and 0.71, respectively) was better than that between PCCI or TDCI and CVP (0.16 and 0.11, respectively), indicating greater validity of ITBI as a measure of preload. IMPLICATIONS: Our results suggest that the pulse contour analysis cardiac output (CO) monitoring in patients undergoing congenital heart surgery may not provide as accurate or reliable measures of CO as previously suggested. The volume-based variable of preload intrathoracic blood volume index (ITBI) has better correlation with cardiac index (CI) than the central venous pressure, suggesting that ITBI may be a better indicator of preload.

Aging, ion channel expression, and vascular function.

Cardiovascular disease remains the leading cause of death in the United States, and aging is one of the main risk factors for its development. Coronary arteries nurture the heart, but as age progresses, they suffer changes that make them stiffer, thicker, and with higher spontaneous contractile activity. Even in the absence of pathological atherosclerotic lesions, these changes make the coronary arteries at risk for vasospasm and the individual at risk for myocardial ischemia and heart failure. Thus, knowledge of the molecular mechanisms involved in the vascular physiology, disease, and aging of the coronary circulation is required to develop strategies to preserve the quality of life of an increasingly aging population. One of the key factors that regulate coronary arterial tone is the activity of K+ channels in the vascular smooth muscle cells (SMCs). In particular, voltage-dependent and Ca(2+)-activated K+ (BKCa) channels, which are abundant in the coronary SMCs, are targets of vasoconstrictors and vasorelaxants, and play a key role in determining arterial tone and diameter. Aging induces a reduction in the density of the alpha-subunit of BKCa channels in coronary smooth muscle, lowers baseline endothelial release of the relaxant nitric oxide (NO), and increases the response to endothelial constrictor factors and K+. Thus, aging induces the remodeling of important proteins involved in the excitability and contractility of the coronary circulation. Altogether, these changes increase the risk of coronary artery vasospasm, myocardial ischemia, and infarct in the elderly.