Pathophysiology of severe primary graft dysfunction in orthotopic heart transplantation.

BACKGROUND: A series of insults on the donor heart result in pathophysiological changes that manifest as primary graft dysfunction (PGD) post-orthotopic heart transplantation. The objectives of this study were: (i) describe the pathophysiology of severe PGD using an established cardiovascular model; and (ii) the evolution of the pathophysiology during recovery from severe PGD. METHODS: Hemodynamic data from 20 consecutive patients with severe PGD (need for mechanical circulatory support, MCS) at baseline (T0), 6 h (T6) and "recovery" (explant of support), and 20 consecutive patients without severe PGD were used to model the pathophysiology using the cardiovascular model described by Burkhoff and Dickstein. RESULTS: There was a progressive (from T0 to T6) up- and leftward shift in the diastolic pressure-volume relationship, especially of the right ventricle (RV), resulting in reduced capacitance. RV end-systolic elastance (Ees) was significantly elevated in severe PGD but preload-recruitable stroke work (PRSW) was significantly lower compared to patients without severe PGD. "Recovery" (after liberation from MCS) was associated with improvement in RV Ees, chamber capacitance and PRSW, although they remained significantly lower than patients without severe PGD. CONCLUSION: Severe PGD of the dominant right heart failure phenotype is characterized by reduced chamber capacitance, increased "stiffness" and impaired contractility. Complete normalization was not required for successful weaning of MCS.

Health-related quality of life, uncertainty and coping strategies in solid organ transplant recipients during shielding for the COVID-19 pandemic.

Strict isolation of vulnerable individuals has been a strategy implemented by authorities to protect people from COVID-19. Our objective was to investigate health-related quality of life (HRQoL), uncertainty and coping behaviours in solid organ transplant (SOT) recipients during the COVID-19 pandemic. A cross-sectional survey of adult SOT recipients undergoing follow-up at our institution was performed. Perceived health status, uncertainty and coping strategies were assessed using the EQ-5D-5L, Short-form Mishel Uncertainty in Illness Scale (SF-MUIS) and Brief Cope, respectively. Interactions with COVID-19 risk perception, access to health care, demographic and clinical variables were assessed. The survey was completed by 826 of 3839 (21.5%) invited participants. Overall, low levels of uncertainty in illness were reported, and acceptance was the major coping strategy (92%). Coping by acceptance, feeling protected, self-perceived susceptibility to COVID-19 were associated with lower levels of uncertainty. Health status index scores were significantly lower for those with mental health illness, compromised access to health care, a perceived high risk of severe COVID-19 infection and higher levels of uncertainty. A history of mental health illness, risk perceptions, restricted healthcare access, uncertainty and coping strategies was associated with poorer HRQoL in SOT recipients during strict isolation. These findings may allow identification of strategies to improve HRQoL in SOT recipients during the pandemic.

Cardiac Power Output Index and Severe Primary Graft Dysfunction After Heart Transplantation.

OBJECTIVES: To evaluate the value of cardiac power output index (CPOi) in predicting severe primary graft dysfunction (PGD) after heart transplantation (defined as mechanical circulatory support [MCS] and/or mortality <30 days after transplant). DESIGN: Observational cohort study. SETTING: A heart transplant center in the United Kingdom. PARTICIPANTS: Consecutive patients who underwent heart transplantation from January 2014 to December 2019 (n = 160). Twenty patients were excluded, as MCS was instituted immediately after transplant. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hemodynamic data on return to the intensive care unit (time 0, T0) and at 6 hours (T6) were collected to calculate CPOi at both points in 140 consecutive patients-22 patients developed severe PGD. The CPOi at T0 correlated with donor-recipient predicted heart mass and inversely with inotrope score. Patients who developed severe PGD had significantly lower CPOi at T0 and T6. The areas under the receiver operating characteristic curve for CPOi at T0 and T6 for the development of severe PGD were 0.90 and 0.92, respectively. Adjusting for vasoactive-inotrope score did not improve discrimination. The probability of severe PGD if CPOi at T0 <0.34 W/m2 and T6 <0.33 W/m2 was 79%, but was only 2% if both CPOi at T0 and T6 were >0.34 W/m2 and >0.33 W/m2, respectively. After adjusting for baseline differences, CPOi at T6 (odds ratio 0.78; 95% CI 0.67-0.91, p = .001) was significantly associated with severe PGD. CONCLUSION: Low CPOi at T0 is associated with severe PGD. Serial assessment of CPOi increases the diagnostic probability of severe PGD.

Endovascular Repair of Acute Thoraco-abdominal Aortic Aneurysms.

OBJECTIVES: The outcome of endovascular repair (EVAR) for acute thoraco-abdominal aortic aneurysm (TAAA) is reported and the applicability of the t-Branch off the shelf (OTS) device is determined. METHODS: Interrogation of a prospectively maintained database identified all patients who underwent EVAR for acute TAAA between September 2012 (when the first non-elective t-Branch case was performed) and November 2015. Early and medium-term outcomes were analysed. Survival and re-intervention-free survival were calculated by Kaplan-Meier analysis. RESULTS: A total of 39 patients (27 men; mean ± SD age, 72 ± 8 years) were treated for acute symptomatic (n = 29) or ruptured (n = 10) TAAA (20 anatomical extent I-III, 19 extent IV). Fourteen patients had mycotic aneurysms. The mean aneurysm diameter was 80 ± 20 mm. The mean ± SD follow-up was 21.4 ± 15.4 months. Surgeon modified fenestrated EVAR was used in 24 patients, chimney/periscope EVAR in two, and t-Branch in 13 (33%) patients. Aortic coverage was greater than 40 mm above the coeliac axis in all patients. A total of 127 target vessels (TVs) were preserved (mean 3.3 per patient) and two occluded within 30 days. The 30 day mortality was 26%. Four (10%) patients developed spinal cord ischaemia (SCI): two with paraplegia died within 30 days, and two with paraparesis recovered completely with blood pressure manipulation and cerebrospinal fluid drainage. Estimated overall survival (±SD) at 12 and 24 months was 71.8 ± 7.2% and 63.2 ± 7.9%, respectively. Estimated freedom from re-intervention at 12 and 24 months was 93 ± 4.8% and 85.3 ± 6.8%, respectively. CONCLUSIONS: EVAR for acute TAAA is associated with acceptable early and mid-term results in patients who have no other treatment options. Only one third of these patients were suitable for the t-Branch device, indicating that further advances in device design are required to treat the majority of acute TAAA patients with commercially available OTS technology.

The Physiology of Continuous-Flow Left Ventricular Assist Devices.

The use of left ventricular assist devices (LVADs) has increased significantly over the past few years, in part because heart transplant activity has plateaued, but also because of the improving clinical outcomes with contemporary continuous-flow LVAD. As such, there is now a growing population of patients with continuous-flow LVADs. Management of these patients is complicated by the altered circulatory physiology, because continuous-flow LVADs provide a parallel circulation from the heart to the aorta, which interacts with the native left heart (systemic) circulation with consequent effects on the right heart circulation. In addition, the displayed pump parameters can mislead the unwary clinician. An understanding of LVAD physiology can guide clinicians in the management of patients with LVADs. This review describes the basic design of axial and centrifugal continuous-flow LVADs, the functional anatomy and physiology of continuous-flow LVADs, and the interaction between the heart and the LVAD. leading to a discussion about the interpretation of the pump parameters in clinical practice.

Extracorporeal Life Support: Physiological Concepts and Clinical Outcomes.

Extracorporeal life support (ECLS) describes a system that involves drainage from the venous circulation and return via an oxygenator into the arterial circulation (veno-arterial extracorporeal membrane oxygenation). ECLS provides effective cardiopulmonary support, but the parallel circulation has complex effects on the systemic and pulmonary circulatory physiology. An understanding of the physiological changes is fundamental to the management of ECLS. In this review, the key physiological concepts and the implications on the clinical management of ECLS are discussed. In addition, the clinical outcomes associated with ECLS in cardiogenic shock are systematically reviewed. The paucity of clinical trials on ECLS highlights the need for randomized trials to guide the selection of patients.

Sprint interval and moderate-intensity continuous training have equal benefits on aerobic capacity, insulin sensitivity, muscle capillarisation and endothelial eNOS/NAD(P)Hoxidase protein ratio in obese men.

KEY POINTS: Skeletal muscle capillary density and vasoreactivity are reduced in obesity, due to reduced nitric oxide bioavailability. Sprint interval training (SIT) has been proposed as a time efficient alternative to moderate-intensity continuous training (MICT), but its effect on the skeletal muscle microvasculature has not been studied in obese individuals. We observed that SIT and MICT led to equal increases in capillarisation and endothelial eNOS content, while reducing endothelial NOX2 content in microvessels of young obese men. We conclude that SIT is equally effective at improving skeletal muscle capillarisation and endothelial enzyme balance, while being a time efficient alternative to traditional MICT. ABSTRACT: Sprint interval training (SIT) has been proposed as a time efficient alternative to moderate-intensity continuous training (MICT), leading to similar improvements in skeletal muscle capillary density and microvascular function in young healthy humans. In this study we made the first comparisons of the muscle microvascular response to SIT and MICT in an obese population. Sixteen young obese men (age 25 ± 1 years, BMI 34.8 ± 0.9 kg m(-2) ) were randomly assigned to 4 weeks of MICT (40-60 min cycling at ∼65% V̇O2 peak , 5 times per week) or constant load SIT (4-7 constant workload intervals of 200% Wmax 3 times per week). Muscle biopsies were taken before and after training from the m. vastus lateralis to measure muscle microvascular endothelial eNOS content, eNOS serine(1177) phosphorylation, NOX2 content and capillarisation using quantitative immunofluorescence microscopy. Maximal aerobic capacity (V̇O2 peak ), whole body insulin sensitivity and arterial stiffness were also assessed. SIT and MICT increased skeletal muscle microvascular eNOS content and eNOS ser(1177) phosphorylation in terminal arterioles and capillaries (P < 0.05), but the latter effect was eliminated when normalised to eNOS content (P = 0.217). SIT and MICT also reduced microvascular endothelial NOX2 content (P < 0.05) and both increased capillary density and capillary-fibre perimeter exchange index (P < 0.05). In parallel, SIT and MICT increased V̇O2 peak (P < 0.05) and whole body insulin sensitivity (P < 0.05), and reduced central artery stiffness (P < 0.05). As no significant differences were observed between SIT and MICT it is concluded that SIT is a time efficient alternative to MICT to improve aerobic capacity, insulin sensitivity and muscle capillarisation and endothelial eNOS/NAD(P)Hoxidase protein ratio in young obese men.

Effect of resistance training on microvascular density and eNOS content in skeletal muscle of sedentary men.

OBJECTIVE: The effects of RT on muscle mass, strength, and insulin sensitivity are well established, but the underlying mechanisms are only partially understood. The main aim of this study was to investigate whether RT induces changes in endothelial enzymes of the muscle microvasculature, which would increase NO bioavailability and could contribute to improved insulin sensitivity. METHODS: Eight previously sedentary males (age 20 ± 0.4 years, BMI 24.5 ± 0.9 kg/m(2) ) completed six weeks of RT 3x/week. Muscle biopsies were taken from the m. vastus lateralis and microvascular density; and endothelial-specific eNOS content, eNOS Ser(1177) phosphorylation, and NOX2 content were assessed pre- and post-RT using quantitative immunofluorescence microscopy. Whole-body insulin sensitivity (measured as Matsuda Index), microvascular Kf (functional measure of the total available endothelial surface area), and arterial stiffness (AIx, central, and pPWV) were also measured. RESULTS: Measures of microvascular density, microvascular Kf , microvascular eNOS content, basal eNOS phosphorylation, and endothelial NOX2 content did not change from pre-RT to post-RT. RT increased insulin sensitivity (p < 0.05) and reduced resting blood pressure and AIx (p < 0.05), but did not change central or pPWV. CONCLUSIONS: RT did not change any measure of muscle microvascular structure or function.

Sprint interval and endurance training are equally effective in increasing muscle microvascular density and eNOS content in sedentary males.

Sprint interval training (SIT) has been proposed as a time efficient alternative to endurance training (ET) for increasing skeletal muscle oxidative capacity and improving certain cardiovascular functions. In this study we sought to make the first comparisons of the structural and endothelial enzymatic changes in skeletal muscle microvessels in response to ET and SIT. Sixteen young sedentary males (age 21 ± SEM 0.7 years, BMI 23.8 ± SEM 0.7 kg m(-2)) were randomly assigned to 6 weeks of ET (40-60 min cycling at ∼65% , 5 times per week) or SIT (4-6 Wingate tests, 3 times per week). Muscle biopsies were taken from the m. vastus lateralis before and following 60 min cycling at 65% to measure muscle microvascular endothelial eNOS content, eNOS serine(1177) phosphorylation, NOX2 content and capillarisation using quantitative immunofluorescence microscopy. Whole body insulin sensitivity, arterial stiffness and blood pressure were also assessed. ET and SIT increased skeletal muscle microvascular eNOS content (ET 14%; P < 0.05, SIT 36%; P < 0.05), with a significantly greater increase observed following SIT (P < 0.05). Sixty minutes of moderate intensity exercise increased eNOS ser(1177) phosphorylation in all instances (P < 0.05), but basal and post-exercise eNOS ser(1177) phosphorylation was lower following both training modes. All microscopy measures of skeletal muscle capillarisation (P < 0.05) were increased with SIT or ET, while neither endothelial nor sarcolemmal NOX2 was changed. Both training modes reduced aortic stiffness and increased whole body insulin sensitivity (P < 0.05). In conclusion, in sedentary males SIT and ET are effective in improving muscle microvascular density and eNOS protein content.

Interleukin-36 is vasculoprotective in both sexes despite sex-specific changes in the coronary microcirculation response to IR injury.

Aims: Risks and outcomes of myocardial infarction (MI) are different between men and women and some studies have demonstrated that the latter have a higher risk of mortality. Whilst there are many reasons for this, it may also partially be linked to stronger innate and adaptive immune responses mounted by females compared to males. However, little is known about how sex impacts the coronary microvessels, the site where inflammatory processes take place, after an MI. Intravital and laser speckle microscopy was used to image coronary microvessels and ventricular perfusion in vivo in response to myocardial ischaemia-reperfusion (IR) injury in male and female mice. Interleukin-36 (IL-36) is the latest addition to the IL-1 superfamily of pro-inflammatory cytokines and has recently been shown to mediate inflammation in a number of non-cardiovascular diseases. Its role in mediating potential sex-related microcirculatiory pertubations in the heart are unknown. Therefore, the vasculoprotective efficacy of an IL-36 receptor antagonist (IL-36Ra) was also investigated. Methods and results: Immunostaining and flow cytometry demonstrated higher expression of IL-36 and its receptor in female hearts, an observation confirmed in human samples. Intravital imaging of the anaesthetised mouse beating heart identified significantly greater neutrophil recruitment in female hearts, but a greater burden of thrombotic disease in male hearts. Male mice had reduced functional capillary density and were unable to restore perfusion to baseline values as effectively as females. However, female mice had significantly larger infarcts. Interestingly, IL-36Ra decreased inflammation, improved perfusion, and reduced infarct size in both sexes despite increasing platelet presence in male hearts. Mechanistically, this was explained by IL-36Ra attenuating endothelial oxidative damage and VCAM-1 expression. Importantly, IL-36Ra administration during ischaemia was critical for vasculoprotection to be realised. Conclusion: This novel study identified notable sex-related differences in the coronary microcirculatory response to myocardial IR injury which may explain why some studies have noted poorer outcomes in women after MI. Whilst contemporary MI treatment focuses on anti-platelet strategies, the heightened presence of neutrophils in female IR injured coronary microvessels necessitates the development of an effective anti-inflammatory approach for treating female patients. We also emphasise the importance of early intervention during the ischaemic period in order to maximise therapeutic effectiveness.

Glucose-insulin-potassium reduces the incidence of low cardiac output episodes after aortic valve replacement for aortic stenosis in patients with left ventricular hypertrophy: results from the Hypertrophy, Insulin, Glucose, and Electrolytes (HINGE) trial.

BACKGROUND: Patients undergoing aortic valve replacement for critical aortic stenosis often have significant left ventricular hypertrophy. Left ventricular hypertrophy has been identified as an independent predictor of poor outcome after aortic valve replacement as a result of a combination of maladaptive myocardial changes and inadequate myocardial protection at the time of surgery. Glucose-insulin-potassium (GIK) is a potentially useful adjunct to myocardial protection. This study was designed to evaluate the effects of GIK infusion in patients undergoing aortic valve replacement surgery. METHODS AND RESULTS: Patients undergoing aortic valve replacement for aortic stenosis with evidence of left ventricular hypertrophy were randomly assigned to GIK or placebo. The trial was double-blind and conducted at a single center. The primary outcome was the incidence of low cardiac output syndrome. Left ventricular biopsies were analyzed to assess changes in 5' adenosine monophosphate-activated protein kinase (AMPK), Akt phosphorylation, and protein O-linked ß-N-acetylglucosamination (O-GlcNAcylation). Over a 4-year period, 217 patients were randomized (107 control, 110 GIK). GIK treatment was associated with a significant reduction in the incidence of low cardiac output state (odds ratio, 0.22; 95% confidence interval, 0.10 to 0.47; P=0.0001) and a significant reduction in inotrope use 6 to 12 hours postoperatively (odds ratio, 0.30; 95% confidence interval, 0.15 to 0.60; P=0.0007). These changes were associated with a substantial increase in AMPK and Akt phosphorylation and a significant increase in the O-GlcNAcylation of selected protein bands. CONCLUSIONS: Perioperative treatment with GIK was associated with a significant reduction in the incidence of low cardiac output state and the need for inotropic support. This benefit was associated with increased signaling protein phosphorylation and O-GlcNAcylation. Multicenter studies and late follow-up will determine whether routine use of GIK improves patient prognosis.

Outcomes of temporary mechanical circulatory support in cardiogenic shock due to end-stage heart failure.

Background: There are few reports of mechanical circulatory support (MCS) in patients with cardiogenic shock (CS) due to end-stage heart failure (ESHF). We evaluated our institutional MCS strategy and compared the outcomes of INTERMACS 1 and 2 patients with CS due to ESHF. Methods: Retrospective analysis of prospectively collected data (November 2014 to July 2019) from a single centre. ESHF was defined by a diagnosis of HF prior to presentation with CS. Other causes of CS (eg: acute myocardial infarction) were excluded. We compared the clinical course, complications and 90-day survival of patients with CS due to ESHF in INTERMACS profile 1 and 2. Results: We included 60 consecutive patients with CS due to ESHF Differences in baseline characteristics were consistent with the INTERMACS profiles. The duration of MCS was similar between INTERMACS 1 and 2 patients (14 (10-33) vs 15 (7-23) days, p = 0.439). There was no significant difference in the number of patients with complications that required intervention. Compared to INTERMACS 2, INTERMACS 1 patients had more organ dysfunction on support and significant lower 90-day survival (66% vs 34%, p = 0.016). Conclusion: Our temporary MCS strategy, including earlier intervention in patients with CS due to ESHF at INTERMACS 2 was associated with less organ dysfunction and better 90-day survival compared to INTERMACS 1 patients.

Delayed presentation of a traumatic descending thoracic aorta aneurysm as an aorto-oesophageal fistula.

Aorto-oesophageal fistula is a rarely described but life-threatening complication presenting with upper gastrointestinal haemorrhage. We present a case of a 58-year-old gentleman who presented to a peripheral hospital with a short duration of haematemesis and melaena and recent onset symptoms of dysphagia. This gentleman had a past medical history of alcohol excess and a history of trauma following a road traffic accident 38 years ago. Initial computer tomography scan demonstrated a large saccular aneurysm arising from the descending thoracic aorta adjacent to the oesophagus. The patient underwent radiological stenting of the large aneurysm with thoracic endovascular aortic replacement procedure. Follow-up computerized tomography (CT) angiography demonstrated satisfactory appearances of the thoracic aortic stent graft with no evidence of endo-leak. The triad of dysphagia, occult gastrointestinal blood loss and CT findings of a large aneurysm should prompt diagnosis or aorto-oesophageal fistula until proven otherwise.

Hypocapnia Alone Fails to Provoke Important Electrocardiogram Changes in Coronary Artery Diseased Patients.

BACKGROUND: There is still an urgent clinical need to develop non-invasive diagnostic tests for early ischemic heart disease because, once angina occurs, it is too late. Hypocapnia has long been known to cause coronary artery vasoconstriction. Some new cardiology tests are accompanied by the claim that they must have potential diagnostic value if hypocapnia enhances their cardiac effects in healthy subjects. But no previous study has tested whether hypocapnia produces bigger cardiac effects in patients with angina than in healthy subjects. METHODS: Severe hypocapnia (a PetCO2 level of 20 mmHg) lasting >15 min was mechanically induced by facemask, while conscious and unmedicated, in 18 healthy subjects and in 10 patients with angina and angiographically confirmed coronary artery disease, awaiting by-pass surgery. Each participant was their own control in normocapnia (where CO2 was added to the inspirate) and the order of normocapnia and hypocapnia was randomized. Twelve lead electrocardiograms (ECG) were recorded and automated measurements were made on all ECG waveforms averaged over >120 beats. 2D echocardiography was also performed on healthy subjects. RESULTS: In the 18 healthy subjects, we confirm that severe hypocapnia (a mean PetCO2 of 20 ± 0 mmHg, P < 0.0001) consistently increased the mean T wave amplitude in leads V1-V3, but by only 31% (P < 0.01), 15% (P < 0.001) and 11% (P < 0.05), respectively. Hypocapnia produced no other significant effects (p > 0.05) on their electro- or echocardiogram. All 10 angina patients tolerated the mechanical hyperventilation well, with minimal discomfort. Hypocpania caused a similar increase in V1 (by 39%, P < 0.05 vs. baseline, but P > 0.05 vs. healthy controls) and did not induce angina. Its effects were no greater in patients who did not take ß-blockers, or did not take organic nitrates, or had the worst Canadian Cardiovascular Society scores. CONCLUSION: Non-invasive mechanical hyperventilation while awake and unmedicated is safe and acceptable, even to patients with angina. Using it to produce severe and prolonged hypocapnia alone does produce significant ECG changes in angina patients. But its potential diagnostic value for identifying patients with coronary stenosis requires further evaluation.

How does glucose insulin potassium improve hemodynamic performance? Evidence for altered expression of beta-adrenoreceptor and calcium handling genes.

BACKGROUND: Glucose insulin potassium (GIK) improves hemodynamic performance after coronary artery surgery (CABG). We investigated whether this is associated with changes in gene expression of beta1-adrenergic receptor (ADRB1) or other calcium handling proteins. METHODS AND RESULTS: During a randomized double-blind placebo-controlled trial, 48 patients undergoing on-pump CABG, allocated to receive pre-ischemic placebo (5% dextrose) or GIK (40% dextrose, K+ 100 mmol.L(-1), insulin 70 u.L(-1); 0.75 mL.kg(-1).h(-1)) continued for 6 hours after the removal of the aortic cross-clamp (AXC), underwent left ventricular biopsy for analysis of specific mRNAs immediately before AXC, before release of AXC, and 10 minutes after reperfusion (placebo n=24, GIK n=24). GIK or placebo was infused for a mean of 79+/-21 minutes or 79+/-18 minutes pre-ischemia respectively. Serial hemodynamic measurements were performed. Biopsy samples were snap-frozen and stored at -80 degrees C, mRNA was extracted and TaqMan real-time polymerase chain reaction was performed to investigate expression of ADRB1, sarcoplasmic reticulum Ca-ATPase (SERCA2a), and phospholamban (PLB). GIK significantly increased cardiac index versus placebo (P=0.037). TaqMan reverse-transcriptase polymerase chain reaction showed significantly greater ADRB1 mRNA expression at all time points (4.9-fold, 7.4-fold, and 15.6-fold increase, respectively; P<0.001), significantly greater SERCA2a mRNA expression after reperfusion (13.2-fold; P<0.001), and increased PLB mRNA expression at pre-ischemia and reperfusion (P<0.001 for both time-points) in GIK groups versus placebo. CONCLUSIONS: The beneficial hemodynamic effects of GIK therapy are associated with increased ADRB1 and SERCA2a mRNA expression. Further work is therefore warranted to investigate these mRNA effects at the protein level.

Glucose-insulin-potassium and tri-iodothyronine individually improve hemodynamic performance and are associated with reduced troponin I release after on-pump coronary artery bypass grafting.

BACKGROUND: Both glucose-insulin-potassium (GIK) and tri-iodothyronine (T3) may improve cardiovascular performance after coronary artery surgery (CABG) but their effects have not been directly compared and the effects of combined treatment are unknown. METHODS AND RESULTS: In 2 consecutive randomized double-blind placebo-controlled trials, in patients undergoing first time isolated on-pump CABG between January 2000 and September 2004, 440 patients were recruited and randomized to either placebo (5% dextrose) (n=160), GIK (40% dextrose, K+ 100 mmol.L(-1), insulin 70 u.L(-1)) (0.75 mL.kg(-1) h(-1)) (n=157), T3 (0.8 microg.kg(-1) followed by 0.113 microg.kg(-1) h(-1)) (n=63) or GIK+T3 (n=60). GIK/placebo therapy was administered from start of operation until 6 hours after removal of aortic cross-clamp (AXC) and T3/placebo was administered for a 6-hour period from removal of AXC. Serial hemodynamic measurements were taken up to 12 hours after removal of AXC and troponin I (cTnI) levels were assayed to 72 hours. Cardiac index (CI) was significantly increased in both the GIK and GIK/T3 group in the first 6 hours compared with placebo (P<0.001 for both) and T3 therapy (P=0.009 and 0.029, respectively). T3 therapy increased CI versus placebo between 6 and 12 hours after AXC removal (P=0.01) but combination therapy did not. Release of cTnI was lower in all treatment groups at 6 and 12 hours after removal of AXC. CONCLUSIONS: Treatment with GIK, T3, and GIK/T3 improves hemodynamic performance and results in reduced cTnI release in patients undergoing on-pump CABG surgery. Combination therapy does not provide added hemodynamic effect.

The effect of left ventricular assist device therapy in patients with heart failure and mixed pulmonary hypertension.

BACKGROUND: Diastolic pressure gradient (DPG) of ≥7 mmHg has been proposed to distinguish mixed pulmonary hypertension from isolated post-capillary pulmonary hypertension in heart failure (HF). We evaluated the changes in pulmonary hemodynamics with left ventricular assist devices (LVADs) in patients with DPG of ≥7 or <7 mmHg, and effects on peak oxygen uptake (VO2) in patients with advanced HF. METHODS: Pre- and post-LVAD implant pulmonary hemodynamics (including right atrial (RA) pressures, DPG, pulmonary vascular resistance (PVR), pulmonary capacitance (PCap) and cardiac output), echocardiography, cardiopulmonary exercise test were measured in 38 consecutive patients. RESULTS: Ten of 38 patients had baseline DPG ≥7 mmHg. There were no significant difference in baseline characteristics, peak VO2 and ventilation slope, but PVR were higher, and PCap lower in patients with DPG ≥7 mmHg. Pulmonary artery pressures improved in all patients, but PVR and DPG remained higher and PCap lower in patients with baseline DPG ≥7 mmHg after a median follow-up of 181 (IQR 153-193) days. Peak VO2 increased and ventilation slope reduced post-LVAD, and these improvements were comparable between groups. Only RA pressure reduction and exercise increase in heart rate were significant predictors of peak VO2 increase on multivariate analysis. CONCLUSIONS: Baseline DPG of ≥7 mmHg compared to DPG <7 mmHg have persistently lower PCap and higher PVR post-LVAD, but the increase in peak VO2 was comparable despite these residual pulmonary vascular abnormalities. The improvement in peak VO2 was related to reduction in right atrial pressure and exercise increase in heart rate.

Open aortic arch replacement in high-risk patients: the gold standard.

OBJECTIVES: Open total aortic arch replacement (TAR) in high-risk patients is considered by some to be associated with a prohibitively perioperative risk. Recent reports describe hybrid techniques to treat this group. We reviewed our outcomes of open surgery in a 'high-risk' group of patients. METHODS: All patients who underwent open TAR between 2000 and 2013 were identified from our prospectively maintained database. Patients comparable with the ones who underwent hybrid repair in previous studies (logistic EuroSCORE between 20 and 60 without intervention on the aortic root or on the mitral/tricuspid valve) were selected for analysis. RESULTS: Fifty-eight patients were identified. Median logistic EuroSCORE was 27.4 (range 20-57) and median age was 76 years (34.5% male). There were 11 resternotomies (18.9%) and 20 procedures were urgent/emergency (34.5%). Preoperative comorbidities included chronic obstructive pulmonary disease (31%), coronary artery disease (22.4%), peripheral vascular disease (48.3%), previous stroke (5.2%), previous myocardial infarction (3.4%) and left ventricular dysfunction (12%). Concomitant procedures included aortic valve replacement/resuspension (58.7%), coronary artery bypass grafting (22.4%), open descending aorta replacement (10.3%) and frozen elephant trunk (19%). Overall in-hospital mortality, permanent stroke and spinal cord injury rate were 6.9, 1.7 and 0%, respectively. There were no deaths or stroke in the elective group. One-year, 5-year and 10-year estimates of survival were 82.7, 70.0 and 37.8%, respectively. CONCLUSIONS: Open TAR can be performed with low mortality and morbidity and excellent long-term results even in high-risk patients. Total endovascular repair may represent an option for patients not suitable for open surgery.