Graves’ Disease and Cardiac Complications

Graves’ disease is an autoimmune thyroid disease and a common cause of hyperthyroidism. Thyroid hormones have multiple adverse effect on cardiovascular system through many direct and indirect mechanisms. They increases heart rate, cardiac contractility, systolic and mean pulmonary artery pressure, cardiac output, diastolic relaxation, and myocardial oxygen consumption, whereas decrease systemic vascular resistance and diastolic pressure. All these hemodynamic changes in cardiovascular system can eventually lead to heart failure, tachyarrhythmias, systemic and pulmonary hypertension, if left untreated. Cardiovascular complications of Graves’ disease are frequent and important cause of increased morbidity and mortality. This chapter reviews the cardiovascular complications of Graves’ hyperthyroidism with underlying mechanisms and treatment.

Development of an automated closed-loop β-blocker delivery system to stably reduce myocardial oxygen consumption without inducing circulatory collapse in a canine heart failure model: a proof of concept study

Beta-blockers are well known to reduce myocardial oxygen consumption (MVO2) and improve the prognosis of heart failure (HF) patients. However, its negative chronotropic and inotropic effects limit their use in the acute phase of HF due to the risk of circulatory collapse. In this study, as a first step for a safe β-blocker administration strategy, we aimed to develop and evaluate the feasibility of an automated β-blocker administration system. We developed a system to monitor arterial pressure (AP), left atrial pressure (PLA), right atrial pressure, and cardiac output. Using negative feedback of hemodynamics, the system controls AP and PLA by administering landiolol (an ultra-short-acting β-blocker), dextran, and furosemide. We applied the system for 60 min to 6 mongrel dogs with rapid pacing-induced HF. In all dogs, the system automatically adjusted the doses of the drugs. Mean AP and mean PLA were controlled within the acceptable ranges (AP within 5 mmHg below target; PLA within 2 mmHg above target) more than 95% of the time. Median absolute performance error was small for AP [median (interquartile range), 3.1% (2.2–3.8)] and PLA [3.6% (2.2–5.7)]. The system decreased MVO2 and PLA significantly. We demonstrated the feasibility of an automated β-blocker administration system in a canine model of acute HF. The system controlled AP and PLA to avoid circulatory collapse, and reduced MVO2 significantly. As the system can help the management of patients with HF, further validations in larger samples and development for clinical applications are warranted.

A novel intra-ventricular assist device enhances cardiac performance in normal and acutely failing isolated porcine hearts

Background: We recently demonstrated that a novel intra-ventricular membrane pump (IVMP) was able to increase the pump function of isolated beating porcine hearts. In follow-up, we now investigated the impact of the IVMP on myocardial oxygen consumption and total mechanical efficiency (TME) and assessed the effect of IVMP-support in acutely failing hearts. Methods: In 10 ex vivo beating porcine hearts, we studied hemodynamic parameters, as well as arterial and coronary venous oxygen content. We assessed cardiac power (CP), myocardial oxygen consumption (MVO2), and TME (CP divided by MVO2) under baseline conditions and during IVMP-support. Additionally, five isolated hearts were subjected to global hypoxia to investigate the effects of IVMP-support on CP under conditions of acute heart failure. Results: Under physiological conditions, baseline CP was 0.36 ± 0.10 W, which increased to 0.65 ± 0.16 W during IVMP-support (increase of 85% ± 24, p < 0.001). This was accompanied by an increase in MVO2 from 18.6 ± 6.2 ml/min at baseline, to 22.3 ± 5.0 ml/min during IVMP-support (+26 ± 31%, p = 0.005). As a result, TME (%) increased from 5.9 ± 1.2 to 8.8 ± 1.8 (50 ± 22% increase, p < 0.001). Acute hypoxia-induced cardiac pump failure reduced CP by 35 ± 6%, which was fully restored to baseline levels during IVMP-support in all hearts. Conclusion: IVMP-support improved mechanical efficiency under physiological conditions, as the marked increase in cardiac performance only resulted in a modest increase in oxygen consumption. Moreover, the IVMP rapidly restored cardiac performance under conditions of acute pump failure. These observations warrant further study, to evaluate the effects of IVMP-support in in vivo animal models of acute cardiac pump failure.

Modalities of Left Ventricle Decompression during VA-ECMO Therapy

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is used to sustain circulatory and respiratory support in patients with severe cardiogenic shock or refractory cardiac arrest. Although VA-ECMO allows adequate perfusion of end-organs, it may have detrimental effects on myocardial recovery. Hemodynamic consequences on the left ventricle, such as the increase of afterload, end-diastolic pressure and volume, can lead to left ventricular (LV) distention, increase of myocardial oxygen consumption and delayed LV function recovery. LV distention occurs in almost 50% of patients supported with VA-ECMO and is associated with an increase in morbidity and mortality. Thus, recognizing, preventing and treating LV distention is key in the management of these patients. In this review, we aim to discuss the pathophysiology of LV distention and to describe the strategies to unload the LV in patients supported with VA-ECMO.

Myocardial oxygen consumption during histidine-tryptophan-ketoglutarate cardioplegia in young human hearts

OBJECTIVES Energy demand and supply need to be balanced to preserve myocardial function during paediatric cardiac surgery. After a latent aerobic period, cardiac cells try to maintain energy production by anaerobic metabolism and by extracting oxygen from the given cardioplegic solution. Myocardial oxygen consumption (MVO2) changes gradually during the administration of cardioplegia. METHODS MVO2 was measured during cardioplegic perfusion in patients younger than 6 months of age (group N: neonates; group I: infants), with a body weight less than 10 kg. Histidine-tryptophan-ketoglutarate crystalloid solution was used for myocardial protection and was administered during a 5-min interval. To measure pO2 values during cardioplegic arrest, a sample of the cardioplegic fluid was taken from the inflow line before infusion. Three fluid samples were taken from the coronary venous effluent 1, 3 and 5 min after the onset of cardioplegia administration. MVO2 was calculated using the Fick principle. RESULTS The mean age of group N was 0.2 ± 0.09 versus 4.5 ± 1.1 months in group I. The mean weight was 3.1 ± 0.2 versus 5.7 ± 1.6 kg, respectively. MVO2 decreased similarly in both groups (min 1: 0.16 ± 0.07 vs 0.36 ± 0.1 ml/min; min 3: 0.08 ± 0.04 vs 0.17 ± 0.09 ml/min; min 5: 0.05 ± 0.04 vs 0.07 ± 0.05 ml/min). CONCLUSIONS We studied MVO2 alterations after aortic cross-clamping and during delivery of cardioplegia in neonates and infants undergoing cardiac surgery. Extended cardioplegic perfusion significantly reduces energy turnover in hearts because the balance procedures are both volume- and above all time-dependent. A reduction in MVO2 indicates the necessity of a prolonged cardioplegic perfusion time to achieve optimized myocardial protection.

Development of an Automated Drug Delivery System for an Ultra-Short-acting β-Blocker, Landiolol, to Stably Reduce Myocardial Oxygen Consumption without Inducing Circulatory Collapse in a Canine Heart Failure Model

Background: Beta-blockers are well known to reduce myocardial oxygen consumption (MVO2) and improve the prognosis of heart failure (HF) patients. Although the use of β-blockers in the acute phase of HF can be expected to be beneficial, the negative chronotropic and inotropic effects limit their use due to the risk of circulatory collapse (cardiogenic shock, and/or pulmonary congestion). A safe method to administer β-blockers in the acute phase of HF is in great need. In this study, we developed an automated drug delivery system that controls the infusion of landiolol, an ultra-short-acting β-blocker, while preventing circulatory collapse. Method: We designed a system that simultaneously regulates cardiac function and volume status to control haemodynamics. The system monitors arterial pressure (AP), left atrial pressure (PLA), right atrial pressure, and cardiac output. Using negative feedback of haemodynamics, the system controls mean AP and mean PLA by administering landiolol, dextran, and furosemide. We applied the system for 60 min to 5 mongrel dogs with rapid pacing-induced HF, and assessed haemodynamics, MVO2 and lactate.Results: In all dogs, the system successfully adjusted delivery of the drugs resulting in accurate control of mean AP and mean PLA. From 15 to 60 min after the system was activated, median of absolute performance error (index of precision of control) was small for mean AP (median [interquartile range], 2.5 [2.1 – 3.7] %) and mean PLA (4.1 [1.8 – 6.2] %). Although the system decreased mean AP compared to baseline, mean and systolic AP were maintained not lower than 70 and 100 mmHg, respectively, and lactate did not increase. Furthermore, the system significantly decreased PLA and MVO2 (3.6 [3.3 – 4.0] to 2.7 [2.5 – 3.3] ml·min-1·100 g left ventricular weight-1) compared to baseline. Consequently, the automated drug delivery system successfully reduced MVO2 without inducing circulatory collapse.Conclusion: We developed an automated landiolol delivery system that achieved safe administration of landiolol in a canine model of acute HF. The system controlled AP and PLA accurately and stably, and reduced MVO2. With further development for clinical application, the automated drug delivery system may be the key tool to improve management of patients with HF.

Effect of voluntary breathing exercises on stable coronary artery disease in heart rate variability and rate-pressure product: a study protocol for a single blind, prospective randomized controlled trial

Background: At present, China has more than 11 million patients with stable coronary heart disease, becoming a major public health problem. The pathological changes of coronary heart disease can lead to dysfunction of cardiac autonomic nervous system, which increases the risk of complications such as malignant arrhythmia (ventricular flutter, ventricular fibrillation, etc.), heart rate, systolic blood pressure, and rate-pressure-product (RPP), which is highly correlated with myocardial oxygen consumption and indirectly reflects myocardial blood supply and oxygen consumption. Although the guidelines recommend that such patients take drugs to reduce heart rate and myocardial oxygen consumption, the clinical control of heart rate is still not ideal. Thus, in this trial, we will use voluntary breathing exercises as the strategy of exercise rehabilitation patients with Stable coronary artery disease（SCAD）, in order to increase the vagus nerve activity and/or reduce the sympathetic nervous activity, help maintain or rebuild the balance of plant nerve system, improve the time domain index of heart rate variability, reduce the burden on the heart, relieve patients' anxiety and other negative emotions. Methods: This is a 6 months single-blind, randomized controlled clinical trial that will be conducted in the First Affiliated Hospital of Soochow University. 140 patients who fill out the Informed Consent Form are registered and randomized 1:1 into the Voluntary Breathing Exercises（VBE）-based clinical trial monitoring group (n = 70) or the Routine follow-up group (n = 70). The VBE-based clinical trial monitoring group is given VBE training on the basis of conventional treatment and health education, while the control group received conventional health education and follow-up. The primary outcome will be measured heart rate variability(HRV) and rate-pressure product (RPP). Secondary outcomes will include changes in self-rating anxiety ccale (SAS), total cholesterol(TC),triglyceride(TG), high density lipoprotein (HDL-C),low density lipoprotein(LDL-C), weight and body mass index (BMI). Discussion: This trial will carry out scientific respiratory exercise for patients with stable coronary heart disease, which belongs to the category of active secondary prevention for patients, and changes from remedial to pre-protective. VBE is easy to operate, and is not limited by time and place. It is very important and meaningful to carry out VBE for patients with SCAD. This study will provide considerable evidence for further large-scale trials and alternative strategies for the rehabilitation nursing of patients with SCAD. Trial registration: This study is registered at Chinese Clinical Trials Registry.gov, ID:1900024043.Registered on 23 June 2019. Keywords: Breathing, Stable coronary artery disease, Heart rate variability, Blood pressure , Myocardial oxygen consumption