Entire Cardiovascular System Research Articles

Silicon-RosIndolizine fluorophores with shortwave infrared absorption and emission profiles enable in vivo fluorescence imaging.

In vivo fluorescence imaging in the shortwave infrared (SWIR, 1,000-1,700 nm) and extended SWIR (ESWIR, 1,700-2,700 nm) regions has tremendous potential for diagnostic imaging. Although image contrast has been shown to improve as longer wavelengths are accessed, the design and synthesis of organic fluorophores that emit in these regions is challenging. Here we synthesize a series of silicon-RosIndolizine (SiRos) fluorophores that exhibit peak emission wavelengths from 1,300-1,700 nm and emission onsets of 1,800-2,200 nm. We characterize the fluorophores photophysically (both steady-state and time-resolved), electrochemically and computationally using time-dependent density functional theory. Using two of the fluorophores (SiRos1300 and SiRos1550), we formulate nanoemulsions and use them for general systemic circulatory SWIR fluorescence imaging of the cardiovascular system in mice. These studies resulted in high-resolution SWIR images with well-defined vasculature visible throughout the entire circulatory system. This SiRos scaffold establishes design principles for generating long-wavelength emitting SWIR and ESWIR fluorophores.

Mechanistic insights on age-related changes in heart-aorta-brain hemodynamic coupling using a pulse wave model of the entire circulatory system.

Age-related changes in aortic biomechanics can impact the brain by reducing blood flow and increasing pulsatile energy transmission. Clinical studies have shown that impaired cardiac function in patients with heart failure is associated with cognitive impairment. Although previous studies have attempted to elucidate the complex relationship between age-associated aortic stiffening and pulsatility transmission to the cerebral network, they have not adequately addressed the effect of interactions between aortic stiffness and left ventricle (LV) contractility (neither on energy transmission nor on brain perfusion). In this study, we use a well-established and validated one-dimensional blood flow and pulse wave computational model of the circulatory system to address how age-related changes in cardiac function and vasculature affect the underlying mechanisms involved in the LV-aorta-brain hemodynamic coupling. Our results reveal how LV contractility affects pulsatile energy transmission to the brain, even with preserved cardiac output. Our model demonstrates the existence of an optimal heart rate (near the normal human heart rate) that minimizes pulsatile energy transmission to the brain at different contractility levels. Our findings further suggest that the reduction in cerebral blood flow at low levels of LV contractility is more prominent in the setting of age-related aortic stiffening. Maintaining optimal blood flow to the brain requires either an increase in contractility or an increase in heart rate. The former consistently leads to higher pulsatile power transmission, and the latter can either increase or decrease subsequent pulsatile power transmission to the brain.NEW & NOTEWORTHY We investigated the impact of major aging mechanisms of the arterial system and cardiac function on brain hemodynamics. Our findings suggest that aging has a significant impact on heart-aorta-brain coupling through changes in both arterial stiffening and left ventricle (LV) contractility. Understanding the underlying physical mechanisms involved here can potentially be a key step for developing more effective therapeutic strategies that can mitigate the contributions of abnormal LV-arterial coupling toward neurodegenerative diseases and dementia.

Skeletotopy of the caudal vena cava of Yorkshire piglets

The venous system of animals always arouses a certain interest among veterinary specialists. On the one hand, there are issues related to comparative anatomy in different animal species, and on the other hand, there is a practical interest put forward by veterinary surgeons and clinicians. First of all, it is certainly the valve apparatus of this system, which gives reason to believe that the valves of the veins not only direct the movement of blood through the venous vessels, but also contribute to balancing the blood pressure in the entire cardiovascular system. The purpose of our study is to study the skeletotopy of the caudal vena cava of Yorkshire piglets, to give anatomical and topographic characteristics of veins, to carry out morphometry of main collectors. To study the branching of the caudal vena cava of Yorkshire piglets, ten corpses aged 28-30 days of life were obtained, which were delivered from the pig breeding complex to the Department of Animal Anatomy of the St. Petersburg State University of Veterinary Medicine. During the study, such methods as: fine anatomical dissection, vasorentgenography, morphometry, photographing were used. As a result of our study, skeletotopy of the caudal vena cava of Yorkshire piglets with anatomical and topographic characteristics of veins was established and morphometry of the main collectors was performed. The topography of the iliac veins in Yorkshire piglets has certain patterns associated with the conditions of maintenance and movement. No valves were found in the common iliac vein, which ensures the outflow of blood from the parietal and visceral branches. A large number of anastomoses were established between the circumferential deep iliac, gluteal and internal sacral veins.

A 0D-3D multi-scale model of the portal venous system coupled with the entire cardiovascular system applied to predict postsplenectomy hemodynamic metrics.

Splenectomy is a common surgery for portal hypertensive patients with splenomegaly. Although splenectomy is able to effectively relieve the complications of portal hypertension, it also increases the risk of portal venous system thrombosis remarkably. Previous studies demonstrated that the hemodynamic metrics of the portal venous system could be employed in predicting the risk of postsplenectomy thrombosis, and 3D models were utilized to simulate the blood flow in the portal venous system. Aiming to reflect the global effect of splenectomy and better simulate the hemodynamic metrics, in this study, a 0D-3D multi-scale model of the portal venous system coupled with the entire cardiovascular system was constructed based on population-averaged data in combination with patient-specific preoperative clinical measurements. The pre- and postoperative global blood flows as well as the variations were calculated successfully, and the flow field and time-averaged wall shear stress of the portal venous system were simulated. The model-simulated spatial distributions of the hemodynamic metrics in the portal venous system were comparable with the regions suffering from thrombosis after splenectomy. These results imply that the present model could reflect the reallocation of the blood flow in the splanchnic circulation after splenectomy and simulate the hemodynamic metrics of the portal venous system, which would promote the more accurate risk stratification of postsplenectomy thrombosis and improve the patient-specific postoperative management.Clinical Relevance- The computational model developed by the present study provides a feasible scheme for simulating postsplenectomy hemodynamic metrics of the portal venous system more accurately, which would benefit the risk prediction and prophylaxis of portal venous system thrombosis for portal hypertensive patients receiving splenectomy.

Interplay Among Lipoproteins, Endothelial Cells and Platelets

Epidemiological studies have allowed variables related to coagulation to be implicated in the process of atheromatous plaque formation. These include fibrinogen, factors VIII, VII, and von Willebrand, as well as fibrinolytic activity. It is important to note that the reported changes are reversible and there is a reduction in atherosclerotic disease when hyperlipidemia is corrected. The interference that dyslipidemia makes in the hemostasis system is located in three fundamental points: the endothelial cell, platelets and circulating coagulation factors and fibrinolysis. The lumen of the vessels of the entire cardiovascular system is covered by a single layer of juxtaposed endothelial cells, which are in direct contact with the circulating blood. They separate the blood from the subendothelial matrix, where adhesive proteins important for activating coagulation such as collagen, von Willebrand factor and fibronectin are found. The endothelial cell has multiple functions that, as a whole, protect from the activation of coagulation and thrombus formation. The role of hemostasis in the initial phase of atherogenesis is mainly related to platelet activation. They have a lipoprotein cell membrane containing glycoproteins, which function as important receptors for platelet activation represented by the processes of adhesion, shape change, secretion of granules and aggregation for platelet plug formation.

P80: Adding Intra-Aortic Balloon Pump Counter-Pulsation To Vasodilator Therapy Results In Better Organ Perfusion In Patients With Biventricular Heart Failure Awaiting A Heart Transplant

Background: Significant right ventricular dysfunction with elevated central venous pressure is associated with poor survival in heart failure patients with reduced ejection fraction (HFrEF). Heart transplant is often the only option for this group of patients, as they are not candidates for left ventricular assist device therapy. Medical management of HFrEF involves lowering the systemic afterload with vasodilators. While this therapy is very effective in isolated left ventricular dysfunction, in patients with biventricular dysfunction and high venous pressure, vasodilation can lead to low organ perfusion pressure, resulting in organ dysfunction. Organ perfusion pressure is calculated as the difference between mean arterial pressure and central venous pressure. We hypothesized that combining intra-aortic balloon pump (IABP) counter-pulsation with vasodilator therapy might be a good clinical option for stabilizing these patients while awaiting a heart transplant. Methods: To understand the hemodynamics of vasodilator and IABP therapy in biventricular heart failure, we used a closed-loop multiscale model of the entire cardiovascular system, including a one-dimensional model of the arterial tree coupled with a lumped model of the heart and IABP counter-pulsation. In addition, a baroreceptor model was also used to capture the physiological changes secondary to ventricular dysfunction realistically. Results: Our mathematical model accurately captures the features of the aortic pressure waveform with IABP support (Figure 1) and the hemodynamic consequences of the onset of right ventricular dysfunction (Table 1). Biventricular dysfunction leads to lower cardiac output and organ perfusion pressure when compared with isolated left ventricular dysfunction. Vasodilation during biventricular dysfunction increases the cardiac output but reduces the organ perfusion pressure further. IABP counter-pulsation increases cardiac output along with higher mean arterial pressure and hence higher organ perfusion pressure. The best results are seen when vasodilators are used in conjunction with IABP, where a “sweet spot” of maximal increase in cardiac output with the best possible organ perfusion pressure is obtained, and this combined additive effect of IABP counter-pulsation and vasodilation is also reflected across the renal vasculature (Table 1). Conclusion: Vasodilation with high venous pressure can lead to low organ perfusion pressure and consequent organ dysfunction. Fine-tuning IABP counter-pulsation and vasodilator seems to confer a substantial hemodynamic benefit in this setting.Figure 1. Simulated aortic pressure waveform with IABP support

A Literature Review on the Anesthetic Management of Pulmonary Arterial Hypertension in Non-cardiothoracic Surgery.

Pulmonary hypertension (PH) is characterized by narrowing small pulmonary arteries, escalating pulmonary vascular resistance, and affecting the entire cardiovascular system. Pulmonary arterial hypertension (PAH) represents a subgroup of PH and typically affects one in 20,000 individuals. When treating individuals with PAH for non-cardiothoracic surgery, anesthetic management strategies should be tailored to the individual's specific needs. This literature review assessed the anesthetic management of PAH in non-cardiothoracic surgery. Electronic databases such as PubMed, ScienceDirect, Ovid Medical Literature Analysis and Retrieval System Online (MEDLINE), Cochrane, and Google Scholar were searched using relevant keywords related to PAH, noncardiac surgery, and anesthesia. Reference lists and author names were also investigated. The articles that met the inclusion criteria provided evidence suggesting that preoperative assessment should be comprehensive, hemodynamic goals should be established, anesthesia providers should be familiar with the underlying pathology, and cross-consultations between surgeons and anesthesia providers are essential for achieving satisfactory outcomes. Furthermore, patient care should extend beyond the surgical procedure into postoperative recovery in the post-anesthesia care unit (PACU) or intensive care unit (ICU) setting. In conclusion, it is vital for anesthetic management strategies to accommodate the unique needs of PAH patients to optimize their safety during perioperative care.

1D-model of the human liver circulatory system

Background and objectiveBlood flow rate and pressure can be measured in vivo by invasive and non-invasive techniques in the large vessels of the hepatic vasculature, but it is not possible to do so along the entire liver circulatory system. Here, we develop a novel 1D model of the liver circulatory system to obtain the hemodynamic signals from macrocirculation to microcirculation with a very low computational cost. MethodsThe model considers structurally well-defined elements that constitute the entire hepatic circulatory system, the hemodynamics (the temporal-dependence of the blood flow rate and pressure), and the elasticity of the vessel walls. ResultsUsing flow rate signals from in vivo measurements as inputs in the model, we obtain pressure signals within their physiological range of values. Furthermore, the model allows to get and analyze the blood flow rate and pressure signals along any vessel of the hepatic vasculature. The impact of the elasticity of the different model components on the inlet pressures is also tested. ConclusionsA 1D model of the entire blood vascular system of the human liver is presented for the first time. The model allows to obtain the hemodynamic signals along the hepatic vasculature at a low computational cost. The amplitude and shape of the flow and pressure signals has hardly been studied in the small liver vessels. In this sense, the proposed model is a useful non-invasive exploration tool of the characteristics of the hemodynamic signals. In contrast to models that partially address the hepatic vasculature or those using an electrical analogy, the model presented here is made entirely of structurally well-defined elements. Future works will allow to directly emulate structural vascular alterations due to hepatic diseases and studying their impact on pressure and blood flow signals at key locations of the vasculature.

A multiscale approach reveals elaborate circulatory system and intermittent heartbeat in velvet worms (Onychophora)

An antagonistic hemolymph-muscular system is essential for soft-bodied invertebrates. Many ecdysozoans (molting animals) possess neither a heart nor a vascular or circulatory system, whereas most arthropods exhibit a well-developed circulatory system. How did this system evolve and how was it subsequently modified in panarthropod lineages? As the closest relatives of arthropods and tardigrades, onychophorans (velvet worms) represent a key group for addressing this question. We therefore analyzed the entire circulatory system of the peripatopsid Euperipatoides rowelli and discovered a surprisingly elaborate organization. Our findings suggest that the last common ancestor of Onychophora and Arthropoda most likely possessed an open vascular system, a posteriorly closed heart with segmental ostia, a pericardial sinus filled with nephrocytes and an impermeable pericardial septum, whereas the evolutionary origin of plical and pericardial channels is unclear. Our study further revealed an intermittent heartbeat—regular breaks of rhythmic, peristaltic contractions of the heart—in velvet worms, which might stimulate similar investigations in arthropods.

Fast and robust parameter estimation with uncertainty quantification for the cardiac function

Background and objectivesParameter estimation and uncertainty quantification are crucial in computational cardiology, as they enable the construction of digital twins that faithfully replicate the behavior of physical patients. Many model parameters regarding cardiac electromechanics and cardiovascular hemodynamics need to be robustly fitted by starting from a few, possibly non-invasive, noisy observations. Moreover, short execution times and a small amount of computational resources are required for the effective clinical translation. MethodsIn the framework of Bayesian statistics, we combine Maximum a Posteriori estimation and Hamiltonian Monte Carlo to find an approximation of model parameters and their posterior distributions. Fast simulations and minimal memory requirements are achieved by using an accurate and geometry-specific Artificial Neural Network surrogate model for the cardiac function, matrix–free methods, automatic differentiation and automatic vectorization. Furthermore, we account for the surrogate modeling error and measurement error. ResultsWe perform three different in silico test cases, ranging from the ventricular function to the entire cardiocirculatory system, involving whole-heart mechanics, arterial and venous hemodynamics. By employing a single central processing unit on a standard laptop, we attain highly accurate estimations for all model parameters in short computational times. Furthermore, we obtain posterior distributions that contain the true values inside the 90% credibility regions. ConclusionsMany model parameters regarding the entire cardiovascular system can be fastly and robustly identified with minimal hardware requirements. This can be achieved when a small amount of non-invasive data is available and when high levels of signal-to-noise ratio are present in the quantities of interest. With these features, our approach meets the requirements for clinical exploitation, while being compliant with Green Computing practices.

Murine endothelial serine palmitoyltransferase 1 (SPTLC1) is required for vascular development and systemic sphingolipid homeostasis.

Serine palmitoyl transferase (SPT), the rate-limiting enzyme in the de novo synthesis of sphingolipids (SL), is needed for embryonic development, physiological homeostasis, and response to stress. The functions of de novo SL synthesis in vascular endothelial cells (EC), which line the entire circulatory system, are not well understood. Here, we show that the de novo SL synthesis in EC not only regulates vascular development but also maintains circulatory and peripheral organ SL levels. Mice with an endothelial-specific gene knockout of SPTLC1 (Sptlc1 ECKO), an essential subunit of the SPT complex, exhibited reduced EC proliferation and tip/stalk cell differentiation, resulting in delayed retinal vascular development. In addition, Sptlc1 ECKO mice had reduced retinal neovascularization in the oxygen-induced retinopathy model. Mechanistic studies suggest that EC SL produced from the de novo pathway are needed for lipid raft formation and efficient VEGF signaling. Post-natal deletion of the EC Sptlc1 also showed rapid reduction of several SL metabolites in plasma, red blood cells, and peripheral organs (lung and liver) but not in the retina, part of the central nervous system (CNS). In the liver, EC de novo SL synthesis was important for acetaminophen-induced rapid ceramide elevation and hepatotoxicity. These results suggest that EC-derived SL metabolites are in constant flux between the vasculature, circulatory elements, and parenchymal cells of non-CNS organs. Taken together, our data point to the central role of the endothelial SL biosynthesis in maintaining vascular development, neovascular proliferation, non-CNS tissue metabolic homeostasis, and hepatocyte response to stress.

A review study of fetal circulatory models to develop a digital twin of a fetus in a perinatal life support system.

BackgroundPreterm birth is the main cause of neonatal deaths with increasing mortality and morbidity rates with decreasing GA at time of birth. Currently, premature infants are treated in neonatal intensive care units to support further development. However, the organs of, especially, extremely premature infants (born before 28 weeks of GA) are not mature enough to function optimally outside the womb. This is seen as the main cause of the high morbidity and mortality rates in this group. A liquid-filled incubator, a so-called PLS system, could potentially improve these numbers for extremely premature infants, since this system is designed to mimic the environment of the natural womb. To support the development and implementation of such a complex system and to interpret vital signals of the fetus during a PLS system operation, a digital twin is proposed. This mathematical model is connected with a manikin representing the digital and physical twin of the real-life PLS system. Before developing a digital twin of a fetus in a PLS system, its functional and technical requirements are defined and existing mathematical models are evaluated.Method and resultsThis review summarizes existing 0D and 1D fetal circulatory models that potentially could be (partly) adopted for integration in a digital twin of a fetus in a PLS system based on predefined requirements. The 0D models typically describe hemodynamics and/or oxygen transport during specific events, such as the transition from fetus to neonate. Furthermore, these models can be used to find hemodynamic differences between healthy and pathological physiological states. Rather than giving a global description of an entire cardiovascular system, some studies focus on specific organs or vessels. In order to analyze pressure and flow wave profiles in the cardiovascular system, transmission line or 1D models are used. As for now, these models do not include oxygen transport.ConclusionThis study shows that none of the models identified in literature meet all the requirements relevant for a digital twin of a fetus in a PLS system. Nevertheless, it does show the potential to develop this digital twin by integrating (parts) of models into a single model.

Uncertainty quantification in cerebral circulation simulations focusing on the collateral flow: Surrogate model approach with machine learning.

Collateral circulation in the circle of Willis (CoW), closely associated with disease mechanisms and treatment outcomes, can be effectively investigated using one-dimensional-zero-dimensional hemodynamic simulations. As the entire cardiovascular system is considered in the simulation, it captures the systemic effects of local arterial changes, thus reproducing collateral circulation that reflects biological phenomena. The simulation facilitates rapid assessment of clinically relevant hemodynamic quantities under patient-specific conditions by incorporating clinical data. During patient-specific simulations, the impact of clinical data uncertainty on the simulated quantities should be quantified to obtain reliable results. However, as uncertainty quantification (UQ) is time-consuming and computationally expensive, its implementation in time-sensitive clinical applications is considered impractical. Therefore, we constructed a surrogate model based on machine learning using simulation data. The model accurately predicts the flow rate and pressure in the CoW in a few milliseconds. This reduced computation time enables the UQ execution with 100 000 predictions in a few minutes on a single CPU core and in less than a minute on a GPU. We performed UQ to predict the risk of cerebral hyperperfusion (CH), a life-threatening condition that can occur after carotid artery stenosis surgery if collateral circulation fails to function appropriately. We predicted the statistics of the postoperative flow rate increase in the CoW, which is a measure of CH, considering the uncertainties of arterial diameters, stenosis parameters, and flow rates measured using the patients' clinical data. A sensitivity analysis was performed to clarify the impact of each uncertain parameter on the flow rate increase. Results indicated that CH occurred when two conditions were satisfied simultaneously: severe stenosis and when arteries of small diameter serve as the collateral pathway to the cerebral artery on the stenosis side. These findings elucidate the biological aspects of cerebral circulation in terms of the relationship between collateral flow and CH.

THE RELEVANCE OF CLINICAL PATHOLOGY LABORATORIES IN THE MANAGEMENT OF ACUTE MYOCARDIAL INFARCTION: A REVIEW

Acute myocardial infarction (AMI) impairs the myocardium ability to pump blood. If this condition is not reversed in time, it will compromise the entire cardiovascular system, which in turn can lead to the collapse of all other physiological systems. Therefore, for the rapid and correct management of this condition the role played by the clinical pathology laboratory (CPL) is crucial due to its rapid response in the quantification of cardiac biomarkers. Through the measurements realized in CPL, it is possible to not only diagnose myocardial injury but also evaluate the injury size, establish a prognostic, or estimate the risk of re-infarction. Currently, the data provided by CPL to the clinician is increasingly accurate and robust, which is only possible due to the evolution that has been made in this field during the last three decades. Therefore, the major objective of this review is to emphasize the relevance that CPL has in the management of AMI patients.

Potential of Medical Management to Mitigate Suction Events in Ventricular Assist Device Patients.

Ventricular suction is a common adverse event in ventricular assist device (VAD) patients and can be due to multiple underlying causes. The aim of this study is to analyze the potential of different therapeutic interventions to mitigate suction events induced by different pathophysiological conditions. To do so, a suction module was embedded in a cardiovascular hybrid (hydraulic-computational) simulator reproducing the entire cardiovascular system. An HVAD system (Medtronic) was connected between a compliant ventricular apex and a simulated aorta. Starting from a patient profile with severe dilated cardiomyopathy, four different pathophysiological conditions leading to suction were simulated: hypovolemia (blood volume: -900 ml), right ventricular failure (contractility -70%), hypotension (systemic vascular resistance: 8.3 Wood Units), and tachycardia (heart rate:185 bpm). Different therapeutic interventions such as volume infusion, ventricular contractility increase, vasoconstriction, heart rate increase, and pump speed reduction were simulated. Their effects were compared in terms of general hemodynamics and suction mitigation. Each intervention elicited a different effect on the hemodynamics for every pathophysiological condition. Pump speed reduction mitigated suction but did not ameliorate the hemodynamics. Administering volume and inducing a systemic vasoconstriction were the most efficient interventions in both improving the hemodynamics and mitigating suction. When simulating volume infusion, the cardiac powers increased, respectively, by 38%, 25%, 42%, and 43% in the case of hypovolemia, right ventricular failure, hypotension, and tachycardia. Finally, a management algorithm is proposed to identify a therapeutic intervention suited for the underlying physiologic condition causing suction.

Principais fatores de risco em cães com insuficiência cardíaca congestiva diagnosticada por parâmetros ecocardiográficos

Nowadays, congestive heart failure is one of the major complications of heart disease in small animals, which is characterized by a clinical condition in which the heart is unable to eject the blood efficiently. At long term, some compensatory mechanisms it will eventually become detrimental and, mainly, due to the congestion caused by it. In dogs, the main cause of CHF is chronic mitral valve degeneration, it is responsible for the degeneration of collagen present in the mitral valve structure that will have detrimental consequences on the entire circulatory system. The aim of the present study was to perform a retrospective study of 498 echocardiographic reports collected at a veterinary cardiology service of the Bauru region, from January 2017 to June 2019. Two groups were formed according to the Doppler echocardiographic alterations found, one that included animals with characteristics of congestive heart failure (CHF), and the other formed by non-CHF patients. Of the total number of animals evaluated, 61 were classified as affected by congestive heart failure and after classification, it was considered the main epidemiological factors (race, sex and age) of animals belonging to this group. Small breed animals were overrepresented and also elderly animals, with no apparent sexual predisposition. In addition, animals with CHF presented higher values when compared to animals without CHF of LA/Ao ratio (2.31 ± 0.30 vs. 1.46 ± 0.35), E/IRTV ratio (2.96 ± 0.39 vs. 1.16 ± 0.43) and E-wave velocity (1.45 m/s ± 0.18 vs. 0.75 m/s ± 0.22) on echocardiographic examination.

A computational analysis of atrial fibrillation effects on coronary perfusion across the different myocardial layers

Patients with atrial fibrillation (AF) may present ischemic chest pain in the absence of classical obstructive coronary disease. Among the possible causes, the direct hemodynamic effect exerted by the irregular arrhythmia has not been studied in detail. We performed a computational fluid dynamics analysis by means of a 1D-0D multiscale model of the entire human cardiovascular system, enriched by a detailed mathematical modeling of the coronary arteries and their downstream distal microcirculatory districts (subepicardial, midwall and subendocardial layers). Three mean ventricular rates were simulated (75, 100, 125 bpm) in both sinus rhythm (SR) and atrial fibrillation, and an inter-layer and inter-frequency analysis was conducted focusing on the ratio between mean beat-to-beat blood flow in AF compared to SR. Our results show that AF exerts direct hemodynamic consequences on the coronary microcirculation, causing a reduction in microvascular coronary flow particularly at higher ventricular rates; the most prominent reduction was seen in the subendocardial layers perfused by left coronary arteries (left anterior descending and left circumflex arteries).

Protective Effects and Therapeutics of Ginsenosides for Improving Endothelial Dysfunction: From Therapeutic Potentials, Pharmaceutical Developments to Clinical Trials.

The endothelium covers the internal lumen of the entire circulatory system and plays an important modulatory role in vascular homeostasis. Endothelium dysfunction, characterized by a vasoconstrictive, pro-inflammatory, and pro-coagulant state, usually manifests as a significant pathological process of vascular diseases, including hypertension, atherosclerosis (AS), stroke, diabetes mellitus, coronary artery disease, and cancer. Therefore, there is an urgent necessity to seek promising therapeutic drugs or remedies to ameliorate endothelial dysfunction-induced vascular ailments and complications. Recently, much attention has been attached to ginsenosides, the most significant active components of ginseng, which have always been referred to as "all-healing" and widely used for its extensively medicinal value. Surprisingly, ginsenosides have diverse biological activity which might be related to inflammation, apoptosis, oxidative stress, and angiogenesis. In this review, a brief introduction about endothelial dysfunction and ginsenosides was demonstrated, and the emphasis was put on summarizing multi-faceted pharmacological effects and underlying molecular mechanisms of ginsenosides on the endothelium, including vasorelaxation, anti-oxidation, anti-inflammation, and angio-modulation. Beyond that, nanotechnology to improve efficacy and the existing clinical trials of ginsenosides were concluded. Hopefully, our work will give suggestions for promoting clinical application of traditional Chinese medicine, e.g.,hypertension, AS, diabetes, ischemic stroke, and cancer. This review provides a comprehensive base of knowledge for ginsenosides to prevention and treatment of vascular injury- related diseases with clinical significance.

Abstract #1088796: Non-Ischemic Cardiomyopathy in Setting of Functional Hypoparathyroidism Secondary to Hypomagnesemia

Magnesium (Mg) is involved in many biochemical reactions and low levels can have negative effects on the entire cardiovascular system. These can occur directly or indirectly via dysfunction in calcium homeostasis. We present a case of severe hypomagnesemia leading to functional hypoparathyroidism in the setting of newly diagnosed cardiomyopathy (CMO) and the importance of aggressive electrolyte repletion as a mainstay in the management of heart failure. 71 year-old male with history of squamous cell lung cancer status post cisplatin-based chemoradiation, CKD, DM2, and GERD presented with dyspnea on exertion and recurrent hypocalcemia. Two months prior, he was diagnosed with non-ischemic CMO with ejection fraction (EF) of 10% in the setting of TSH >100. On admission, he had Mg 0.5 mg/dL (1.6-2.5 mg/dL), calcium (Ca) 6.9 mg/dL (8.4-10.4 mg/dL), ionized calcium (iCa) 3.0 mg/dL (4.4-5.4 mg/dL), phosphorous 5.4 (2.5-4.5 mg/dL) and inappropriately normal parathyroid hormone (PTH) of 50 pg/mL (15-65 pg/mL). Since prior admission TSH and free T4 had improved to 26.96 and 1.3, respectively after adding levothyroxine. On exam, he had tachycardia, bilateral rhonchi, and pitting edema in the lower extremities. NT-BNP was 16,474 and EKG showed sinus tachycardia with lateral T-wave inversions. Chvostek sign was negative, with no perioral numbness or paresthesia. Electrolytes were repleted aggressively. He was discharged on oral Ca and Mg supplements in addition to heart failure medical therapy. Labs on discharge showed improvement in Mg to 2.0 mg/dL, iCa 3.8 mg/dL, phosphorous 3.3 mg/dL, and PTH of 89 pg/mL. Seven months later, his EF% doubled on echocardiogram. Follow up EF% did not recover further despite euthyroidism due to noncompliance with Ca and Mg supplements. Hypomagnesemia is a potential cause of CMO and medications are a significant risk factor that must be considered. Our patient was exposed to cisplatin, chronic PPI use and loop diuretics, which can all chronically decrease Mg stores in the body. Low Mg leads to defects in cyclic AMP generation in the parathyroid gland, which causes decreased PTH secretion and low Ca. This is evidenced by the inappropriately normal PTH in our patient despite low Ca levels. Of note, he had history of hypothyroidism but low EF persisted despite appropriate repletion and normalization of T4 levels. Previous cases have reported hypocalcemia-induced CMO, but few have described the hypomagnesemia as an underlying cause of this finding. This case underlines the importance of monitoring and repletion of Mg and Ca in addition to goal-directed medical therapy for optimized heart failure management.

How I treat cardiovascular complications in patients with lymphoid malignancies

AbstractThe prognosis of several lymphoid malignancies has improved through development of novel therapies, combination with traditional chemotherapies, and delineation of appropriate therapeutic sequencing. Toxicities that are arising because of prolonged or multiple sequential therapeutic interventions are becoming increasingly impactful. Among the broad spectrum of complications that patients with lymphoid malignancies may experience, cardiovascular toxicities are significant in terms of morbidity and mortality. The entire cardiovascular system can be affected, but cardiomyopathy, heart failure, and arrhythmias remain of greatest concerns with the use of anthracyclines, hematopoietic stem cell transplantation, and radiation therapy in patients with lymphoid malignancies. These aspects will be covered in this article within the framework of case-based discussions. Key to the management of cardiovascular complications in patients with lymphoid malignancies is awareness and preparedness across the cancer continuum. Baseline risk stratification helps to direct surveillance and early intervention efforts before, during, and after cancer therapy, which are paramount for the best possible outcomes. Along these lines, the overall goal is to enable the best possible therapies for lymphoid malignancies without the complications of clinically significant cardiovascular events.