Brian Fowell Buxton (15/04/1940-20/05/2022)-Outstanding Achievements and Personal Memories.

Brian F. Buxton, one of Australia's greatest cardiac surgeons, died in May 2022, aged 82 years. In June 2022, a memorial celebration of Brian's life was held in Melbourne, Australia, attended by 550 colleagues and friends from many walks of life-not only "medical people" but also friends involved in Brian's sailing and hiking activities. This Special Article includes an introduction from Professor Jayme Bennetts, President of the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS), an abridged version of a memorial address by Professor James Tatoulis and contributions from two other long-term professional colleagues and personal friends of Buxton, Professor Jaishankar Raman and Professor Franklin Rosenfeldt, founding editor of Heart, Lung and Circulation. Buxton was an outstanding and pioneering surgeon, clinical leader, and good friend to many. The Brian F. Buxton Cardiac and Thoracic Aortic Surgery Unit in Melbourne, Australia, is now so named in honour of his outstanding achievements and as a legacy. Vale Brian F. Buxton.

Combined Assessment of Functional and Metabolic Performance of Human Donor Hearts: Possible Application in Donation After Circulatory Death.

BACKGROUND: Donation after circulatory death (DCD) represents an increasing source of organs. However, evaluating the suitability of DCD hearts for transplantation represents a challenge. Contractile function is the ultimate determinant of recovery. We developed a novel technique in an ex vivo rig for the measurement of contractility using intraventricular balloons. We compared this technique with the measurement of lactate metabolism, the current gold standard. METHODS: Human DCD (n = 6) and donation after brain death (n = 6) hearts were preserved by perfusion with a cold oxygenated crystalloid solution for 4 h, transferred to a blood perfusion rig at 37 °C where balloons were inserted into the left (LV) and right (RV) ventricles to measure developed pressure (DP = systolic minus diastolic). Perfusate lactate levels were measured for metabolic assessment. Concordance between LVDP and lactate was assessed during 4 h using cutoffs for LVDP of 70 mm Hg and for lactate of 10 mmol/L. RESULTS: Measurements of contractile function (LVDP) and metabolism (lactate levels) were deemed concordant in 7 hearts with either a high LVDP (mean 100 mm Hg) with low lactate (mean 6.7 mmol/L)) or a low LVDP (15 mm Hg) with high lactate (mean 17.3 mmol/). In the remaining 5 hearts, measurements were deemed discordant: 4 hearts had high LVDP (mean 124 mm Hg), despite high lactate levels 17.3 mmol/L) and 1 had low LVDP (54 mm Hg) but low lactate (6.9 mmol/L). CONCLUSIONS: The intraventricular balloon technique provides useful information regarding contractile recovery of donor hearts that if combined with lactate metabolism has potential application for the evaluation of DCD and marginal donation after brain death hearts before transplant.

Apoptotic Markers in Donor Hearts After Brain Death vs Circulatory Death.

BACKGROUND: Use of donation after circulatory death (DCD) hearts is becoming more prevalent in cardiac transplantation. However, there is no standardized approach to myocardial preservation, and little data exists on ultrastructural changes in DCD hearts. We have previously identified increased proapoptotic and proinflammatory activity in brain dead donor (BDD) hearts that subsequently exhibit primary graft failure and lower levels in DCD left atrial tissue. This study further investigates these markers and correlates them with cardiac function in DCD hearts. METHODS: This prospective study used donor hearts deemed unsuitable for transplant after gaining institutional ethics approval; 11 human hearts were obtained from 5 DCD donors and 6 BDDs. All hearts were preserved by continuous microperfusion for 4 hours with a cold crystalloid solution and then were evaluated on a blood perfusion bench rig. After 4 hours perfusion and working assessment, tissues from all cardiac chambers were stored for later messenger RNA (mRNA) analysis for proapoptotic and proinflammatory markers. RESULTS: Significantly raised levels of caspase-1, BNIP3, and NADPH oxidase mRNA expression were identified in cardiac chambers from BDD hearts compared to DCD hearts, and these differences were exaggerated in older donors. In the pooled analysis, lower expression of caspase-1, NF-κB1, and BNIP3 mRNA correlated with developed pressure at 1 hour after reperfusion in the right ventricle, but not the left. CONCLUSION: Compared to BDD hearts, DCD hearts exhibit less stimulation of proapoptotic cascades and reactive oxygen species, potentially reducing their susceptibility to ischemic reperfusion injury.

Early Gastrointestinal Complications From Ventricular Assist Devices is Increased by Non-Pulsatile Flow.

BACKGROUND: Measurements of organ flow and perfusion during cardiopulmonary bypass suggest that perfusion of the splanchnic bed can be impaired by non-pulsatile flow. We postulated that non-pulsatile flow from centrifugal ventricular assist devices might also compromise splanchnic blood flow and cause bowel ischaemia especially in the period of circulatory instability early post-implant. The aim of the present studies was to compare the incidence of gastrointestinal (GI) complications in patients having a non-pulsatile device with the incidence in those having a pulsatile device. METHODS: In a pilot study, the initial 12 patients who received the Ventrassist (Ventracor, Sydney, NSW, Australia) centrifugal, non-pulsatile device during the period from June 2003 to September 2005 at the Alfred Hospital, Melbourne were compared with 11 patients who received a Thoratec (Thoratec, Pleasanton, CA, USA), pulsatile, positive displacement device and the incidence was recorded of GI complications requiring an intervention either surgical, endoscopic or by interventional radiology. This was followed by a larger (full) study of a second cohort of similar ventricular assist device (VAD) patients from January 1992 until December 2012 comparing 53 patients having non-pulsatile devices and 110 having pulsatile devices. RESULTS: In the pilot study, the overall incidence of complications in the non-pulsatile group (67%) was almost double that in the pulsatile group (36%) but the difference was not statistically significant (p = 0.15) because of the small number (n = 23) of participants. In the full study, all GI complications with either device occurred within the first 3 weeks post-implant. In the non-pulsatile patients, there was a higher incidence of GI bleeding, 23% vs 4% (p = 0.002), endoscopies, 24% vs 12% (p = 0.049). More patients with a non-pulsatile flow device had delayed absorption of nasogastric feeds than their pulsatile counterparts, 35% vs 7% (p < 0.0001). Patients with a non-pulsatile flow device had a higher overall rate of gastrointestinal complications than patients had with a pulsatile flow device, 56% vs 20% (p < 0.0001). After correcting for the other predictors, the odds of developing a gastrointestinal complication in the pulsatile group was significantly lower (odds ratio 0.07) than in the non-pulsatile device group (p < 0.0001). CONCLUSIONS: We conclude that the use of non-pulsatile centrifugal VADs compared with pulsatile positive displacement VADs is associated with a higher incidence of both haemorrhagic and ischaemic complications in the gastro-intestinal system especially in the very early post-implant period. Whether these complications could be reduced in centrifugal devices by increasing their pulsatility is not clear and merits further research.

Combining Ubiquinol With a Statin May Benefit Hypercholesterolaemic Patients With Chronic Heart Failure.

Heart failure (HF) is one of the most common causes of death in Western society. Recent results underscore the utility of coenzyme Q10 (CoQ10) addition to standard medications in order to reduce mortality and to improve quality of life and functional capacity in chronic heart failure (CHF). The rationale for CoQ10 supplementation in CHF is two-fold. One is the well-known role of CoQ10 in myocardial bioenergetics, and the second is its antioxidant property. Redox balance is also improved by oral supplementation of CoQ10, and this effect contributes to enhanced endothelium-dependent relaxation. Previous reports have shown that CoQ10 concentration is decreased in myocardial tissue in CHF and by statin therapy, and the greater the CoQ10 deficiency the more severe is the cardiocirculatory impairment. In patients with CHF and hypercholesterolaemia being treated with statins, the combination of CoQ10 with a statin may be useful for two reasons: decreasing skeletal muscle injury and improving myocardial function. Ubiquinol, the active reduced form of CoQ10, presents higher bioavailability than the oxidised form ubiquinone, and should be the preferred form to be added to a statin. The combination ezetimibe/simvastatin may have advantages over single statins. Since ezetimibe reduces absorption of cholesterol and does not affect CoQ10 synthesis in the liver, the impact of this combination on CoQ10 tissue levels will be much less than that of high dose statin monotherapy at any target low density lipoprotein-cholesterol (LDL-C) level to be reached. This consideration makes the ezetimibe/statin combination the ideal LDL-lowering agent to be combined with ubiquinol in CHF patients. However, particular caution is advisable with the use of strategies of extreme lowering of cholesterol that may negatively impact on myocardial function. All in all there is a strong case for considering co-administration of ubiquinol with statin therapy in patients with depressed or borderline myocardial function.

Statin-Associated Cardiomyopathy Responds to Statin Withdrawal and Administration of Coenzyme Q10.

CONTEXT: Heart failure (HF) is rapidly increasing in incidence and is often present in patients receiving long-term statin therapy. OBJECTIVE: To test whether or not patients with HF on long-term statin therapy respond to discontinuation of statin therapy and initiation of coenzyme Q10 (CoQ10) supplementation. DESIGN: We prospectively identified patients receiving long-term statin therapy in whom HF developed in the absence of any identifiable cause. Treatment consisted of simultaneous statin therapy discontinuation and CoQ10 supplementation (average dosage = 300 mg/d). MAIN OUTCOME MEASURES: Baseline and follow-up physical examination findings, symptom scores, echocardiograms, and plasma CoQ10 and cholesterol levels. RESULTS: Of 142 identified patients with HF, 94% presented with preserved ejection fraction (EF) and 6% presented with reduced EF (< 50%). After a mean follow-up of 2.8 years, New York Heart Association class 1 increased from 8% to 79% (p < 0.0001). In patients with preserved EF, 34% had normalization of diastolic function and 25% showed improvement (p < 0.0001). In patients with reduced EF at baseline, the EF improved from a mean of 35% to 47% (p = 0.02). Statin-attributable symptoms including fatigue, muscle weakness, myalgias, memory loss, and peripheral neuropathy improved (p < 0.01). The 1-year mortality was 0%, and the 3-year mortality was 3%. CONCLUSION: In patients receiving long-term statin therapy, statin-associated cardiomyopathy may develop that responds safely to statin treatment discontinuation and CoQ10 supplementation. Statin-associated cardiomyopathy may be a contributing factor to the current increasing prevalence of HF with preserved EF.

CoQ10 and Cognition a Review and Study Protocol for a 90-Day Randomized Controlled Trial Investigating the Cognitive Effects of Ubiquinol in the Healthy Elderly.

Introduction: With an aging population there is an important need for the development of effective treatments for the amelioration of cognitive decline. Multiple mechanisms underlie age-related cognitive decline including cerebrovascular disease, oxidative stress, reduced antioxidant capacity and mitochondrial dysfunction. CoQ10 is a novel treatment which has the potential to improve brain function in healthy elderly populations due to established beneficial effects on mitochondrial function, vascular function and oxidative stress. Methods and Analysis: We describe the protocol for a 90-day randomized controlled trial which examines the efficacy of Ubiquinol (200 mg/day) vs. placebo for the amelioration of cognitive decline in a healthy (non-demented) elderly sample, aged 60 years and over. The primary outcome is the effect of Ubiquinol at 90 days compared to baseline on CogTrack composite measures of cognition. Additional cognitive measures, as well as measures of cardiovascular function, oxidative stress, liver function and mood will also be monitored across 30-, 60- and 90- day time points. Data analyses will involve repeated measures analysis of variance (ANOVA). Discussion: This study will be the first of its kind to provide important clinical and mechanistic data regarding the efficacy of Ubiquinol as a treatment for age-related cognitive decline in the healthy elderly with important implications for productivity and quality of life within this age group. Clinical Trial Registration: The trial has been registered with the Australian and New Zealand Clinical Trials Registry (ANZCTRN12618001841268).

Evidence and mechanisms for statin-induced cognitive decline.

INTRODUCTION: Statin drugs have become the most highly prescribed drugs for cardiovascular disease. However, there is disagreement as to the existence of adverse effects of statin administration on cognitive function. Therefore, it is important to better understand the effects of statins on cognition and possible mechanisms of these effects. Areas covered: We analyzed relevant studies of the relationship between cognitive performance and statin and usage. We included articles published between 2018 and 1992. We identified three randomized trials, one observational study and 66 case reports that provided credible evidence of statin-induced cognitive impairment. We also identified seven randomized trials and two observational studies reporting no significant evidence of statin-induced cognitive impairment. Expert opinion: We found methodological differences that may have contributed to the divergence of these results. Evaluation of all these studies indicated that statin-associated cognitive decline is a real entity. Likely mechanisms to explain the adverse effects include 1. Reduction of synthesis of coenzyme Q10 with consequent increasing oxidative stress and reduction of cerebral energy production; 2. Depletion of central nervous system myelin by inhibition of cholesterol synthesis. We conclude that statin-induced cognitive decline does exist, needs to be better recognized and requires more studies of prevention and treatment.

Effect of coenzyme Q10 in Europeans with chronic heart failure: A sub-group analysis of the Q-SYMBIO randomized double-blind trial.

BACKGROUND: Geographical differences in patient characteristics, management and outcomes in heart failure (HF) trials are well recognized. The aim of this study was to assess the consistency of the treat- ment effect of coenzyme Q10 (CoQ10) in the European sub-population of Q-SYMBIO, a randomized double-blind multinational trial of treatment with CoQ10, in addition to standard therapy in chronic HF. METHODS: Patients with moderate to severe HF were randomized to CoQ10 300 mg daily or placebo in addition to standard therapy. At 3 months the primary short-term endpoints were changes in New York Heart Association (NYHA) functional classification, 6-min walk test, and levels of N-terminal pro-B type natriuretic peptide. At 2 years the primary long-term endpoint was major adverse cardiovascular events (MACE). RESULTS: There were no significant changes in short-term endpoints. The primary long-term endpoint of MACE was reached by significantly fewer patients in the CoQ10 group (n = 10, 9%) compared to the placebo group (n = 33, 27%, p = 0.001). The following secondary endpoints were significantly improved in the CoQ10 group compared with the placebo group: all-cause and cardiovascular mortality, NYHA classification and left ventricular ejection fraction (LVEF). In the European sub-population, when compared to the whole group, there was greater adherence to guideline directed therapy and similar results for short- and long-term endpoints. A new finding revealed a significant improvement in LVEF. CONCLUSIONS: The therapeutic efficacy of CoQ10 demonstrated in the Q-SYMBIO study was confirmed in the European sub-population in terms of safely reducing MACE, all-cause mortality, cardiovascular mortality, hospitalization and improvement of symptoms.

On-Pump Beating Heart Versus Conventional Coronary Artery Bypass Grafting Early After Myocardial Infarction: A Propensity-Score Matched Analysis From the ANZSCTS Database.

BACKGROUND: Coronary artery bypass grafting (CABG) performed early after acute myocardial infarction (AMI) carries a high risk of mortality. By avoiding cardioplegic arrest and aortic cross-clamping, on-pump beating heart CABG (ONBEAT) may benefit patients requiring urgent or emergency revascularisation in the setting of AMI. We evaluated the early and long-term outcomes of ONBEAT versus conventional CABG (ONSTOP) utilising the ANZSCTS National Cardiac Surgery Database. METHODS: Between 2001 and 2015, 5,851 patients underwent non-elective on-pump CABG within 7 days of AMI. Of these, 77 patients (1.3%) underwent ONBEAT and 5774 (98.7%) underwent ONSTOP surgery. Propensity-score matching (with a 1:2 matching ratio) was performed for risk adjustment. Survival data were obtained from the National Death Index. RESULTS: Before matching, the unadjusted 30-day mortality was ONBEAT: 9/77 (11.7%) vs. ONSTOP: 256/5,774 (4.4%), p<0.001. Preoperative factors independently associated with the ONBEAT were: septuagenarian age, peripheral vascular disease, redo surgery, cardiogenic shock, emergency surgery and single-vessel disease. After propensity-score matching, 30-day mortality was similar (ONBEAT: 9/77 (11.7%) vs. ONSTOP: 16/154 (10.4%), p=0.85), as was the rate of major adverse cardiac and cerebrovascular events (ONBEAT: 17/77 (22.1%) vs. ONSTOP: 38/154 (24.7%), p=0.84). ONBEAT patients received fewer distal anastomoses and were more likely to have incomplete revascularisation (ONBEAT: 15/77 (19.5%) vs. ONSTOP: 15/154, (9.7%), p=0.03). Despite this, 12-year survival was comparable (ONBEAT: 64.8% (95% CI 39.4-82.4%) vs. ONSTOP: 63.6% (95% CI 50.5, 74.3%), p=0.89). CONCLUSIONS: ONBEAT can be performed safely in high-risk patients requiring CABG early after AMI with similar short and long-term survival compared to ONSTOP.

The Real-World Cost-Effectiveness of Coronary Artery Bypass Surgery Versus Stenting in High-Risk Patients: Propensity Score-Matched Analysis of a Single-Centre Experience.

BACKGROUND: There are limited economic evaluations comparing coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for multi-vessel coronary artery disease (MVCAD) in contemporary, routine clinical practice. OBJECTIVE: The aim was to perform a cost-effectiveness analysis comparing CABG and PCI in patients with MVCAD, from the perspective of the Australian public hospital payer, using observational data sources. METHODS: Clinical data from the Melbourne Interventional Group (MIG) and the Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) registries were analysed for 1022 CABG (treatment) and 978 PCI (comparator) procedures performed between June 2009 and December 2013. Clinical records were linked to same-hospital admissions and national death index (NDI) data. The incremental cost-effectiveness ratios (ICERs) per major adverse cardiac and cerebrovascular event (MACCE) avoided were evaluated. The propensity score bin bootstrap (PSBB) approach was used to validate base-case results. RESULTS: At mean follow-up of 2.7 years, CABG compared with PCI was associated with increased costs and greater all-cause mortality, but a significantly lower rate of MACCE. An ICER of $55,255 (Australian dollars)/MACCE avoided was observed for the overall cohort. The ICER varied across comparisons against bare metal stents (ICER $25,815/MACCE avoided), all drug-eluting stents (DES) ($56,861), second-generation DES ($42,925), and third-generation of DES ($88,535). Moderate-to-low ICERs were apparent for high-risk subgroups, including those with chronic kidney disease ($62,299), diabetes ($42,819), history of myocardial infarction ($30,431), left main coronary artery disease ($38,864), and heart failure ($36,966). CONCLUSIONS: At early follow-up, high-risk subgroups had lower ICERs than the overall cohort when CABG was compared with PCI. A personalised, multidisciplinary approach to treatment of patients may enhance cost containment, as well as improving clinical outcomes following revascularisation strategies.

Prevalence of Zinc Deficiency in Cardiac Surgery Patients.

BACKGROUND: The aim of this study was to define the status of preoperative zinc levels in patients with heart disease presenting for cardiac surgery and to identify any predictors for and any clinical consequences of low zinc levels. METHODS: Adult patients presenting for elective surgery, either coronary artery bypass graft surgery and/or valve replacement, provided a fasting blood sample on the day of admission for surgery. Plasma and erythrocyte zinc levels were analysed and the levels correlated with the patient's characteristics and clinical outcomes. RESULTS: Of 56 patients 53% (n=30) had abnormally low plasma zinc levels (<12µmol/L) and 5.5% (n=3) had abnormally low erythrocyte zinc levels (<160µmol/L), indicative of deficiency. There were significant associations between lower plasma zinc levels and the presence of hypertension (p=0.02), hypercholesteraemia (p=0.02) and higher body mass index (BMI) (p=0.034) but no effect on major postoperative clinical outcomes. CONCLUSIONS: This small study shows that zinc deficiency is common in cardiac surgery patients, especially in the presence of hypertension, hypercholesterolaemia or obesity. The effects of zinc deficiency in cardiac surgery need to be further investigated.

A novel combination technique of cold crystalloid perfusion but not cold storage facilitates transplantation of canine hearts donated after circulatory death.

BACKGROUND: Donation after circulatory death (DCD) represents a potential new source of hearts to increase the donor pool. We showed previously that DCD hearts in Greyhound dogs could be resuscitated and preserved by continuous cold crystalloid perfusion but not by cold static storage and could demonstrate excellent contractile and metabolic function on an in vitro system. In the current study, we demonstrate that resuscitated DCD hearts are transplantable. METHODS: Donor Greyhound dogs (n = 12) were divided into perfusion (n = 8) and cold static storage (n = 4) groups. General anesthesia was induced and ventilation ceased for 30 minutes to achieve circulatory death. Donor cardiectomy was performed, and for 4 hours the heart was preserved by controlled reperfusion, followed by continuous cold perfusion with an oxygenated crystalloid perfusate or by static cold storage, after which orthotopic heart transplantation was performed. Recovery was assessed over 4 hours by hemodynamic monitoring. RESULTS: During cold perfusion, hearts showed continuous oxygen consumption and low lactate levels, indicating aerobic metabolism. The 8 dogs in the perfusion group were weaned off bypass, and 4 hours after bypass produced cardiac output of 4.73 ± 0.51 liters/min, left ventricular power of 7.63 ± 1.32 J/s, right ventricular power of 1.40 ± 0.43 J/s, and left ventricular fractional area shortening of 39.1% ± 5.2%, all comparable to pre-transplant values. In the cold storage group, 3 of 4 animals could not be weaned from cardiopulmonary bypass, and the fourth exhibited low-level function. CONCLUSIONS: Cold crystalloid perfusion, but not cold static storage, can resuscitate and preserve the DCD donor heart in a canine model of heart transplantation, thus rendering it transplantable. Controlled reperfusion and cold crystalloid perfusion have potential for clinical application in DCD transplantation.

Relationships Among Cognitive Function and Cerebral Blood Flow, Oxidative Stress, and Inflammation in Older Heart Failure Patients.

BACKGROUND: The mechanisms for cognitive impairment in heart failure (HF) are unclear. We investigated the relative contributions of cerebral blood flow velocity (BFV), oxidative stress, and inflammation to HF-associated cognitive impairment. METHODS AND RESULTS: Thirty-six HF patients (≥60 years) and 40 healthy controls (68 ± 7 vs 67 ± 5 years, P > .05; 69% vs 50% male, P > .05) completed the Cognitive Drug Research computerized assessment battery and Stroop tasks. Common carotid (CCA) and middle cerebral arterial BFV were obtained by transcranial Doppler. Blood samples were collected for oxidant (diacron-reactive oxygen metabolites; F2-isoprostanes), antioxidant (coenzyme Q10; CoQ10), and inflammatory markers (high-sensitivity C-reactive protein). Compared with controls, patients exhibited impaired attention (Cognitive Drug Research's Power of Attention domain, congruent Stroop) and executive function (incongruent Stroop). Multiple regression modeling showed that CCA-BFV and CoQ10 but not group predicted performance on attention and executive function. Additionally, in HF patients, CCA-BFV and CoQ10 (ß = -0.34 vs ß = -0.35) were significant predictors of attention, and CCA-BFV (ß = -0.34) was a predictor of executive function. CONCLUSIONS: Power of Attention and executive function is impaired in older HF patients, and reduced CCA-BFV and CoQ10 are associated with worse cognition. Interventions addressing these mechanisms may improve cognition in older HF patients.

Cold Crystalloid Perfusion Provides Cardiac Preservation Superior to Cold Storage for Donation After Circulatory Death.

BACKGROUND: We previously showed that donation after circulatory death (DCD) canine hearts can be resuscitated if perfused with warm blood. However, clinical application of this technique is complex and difficult. We have developed a simplified system of cold crystalloid perfusion and compared it with standard cold storage for DCD heart preservation. METHODS: Anesthetized greyhounds underwent 30 minutes DCD by withdrawal of ventilation followed by assignment to either 4 hours of perfusion (n = 6) or cold storage (n = 7). Nonpreserved hearts (n = 5) served as a normal reference group. Perfusion hearts were reperfused with a protective solution then perfused for 4 hours with a novel oxygenated, nutrient-containing solution at 20 mL/min at 4°C to 10°C. Cold storage hearts were flushed with St Thomas' cardioplegic solution and stored in ice. After preservation, the recovery of the hearts was assessed on a blood-perfused working heart rig. RESULTS: During preservation, perfusion hearts consumed oxygen (0.09 ± 0.01 mL/100 g per minute) and showed decreasing lactate production in the perfusate (initial: 0.031 ± 0.004 vs final: 0.007 ± 0.002 mmol/min; P = 0.001). After preservation, compared to cold storage hearts, perfusion hearts had higher cardiac output (P = 0.004), LV dP/dt max (P = 0.003) and myocardial oxygen efficiency (P = 0.01), with lower blood perfusate lactate (P = 0.007). Hemodynamic values of perfused hearts reached 60% or more those in the normal reference group. CONCLUSIONS: Continuous cold crystalloid perfusion in a canine model of DCD: (1) facilitates aerobic metabolism and resuscitates the DCD heart, (2) provides functional and metabolic recovery superior to cold storage, (3) shows promise for improved clinical preservation of DCD and marginal donor hearts.

Anatomy and Physiology of Left Ventricular Suction Induced by Rotary Blood Pumps.

This study in five large greyhound dogs implanted with a VentrAssist left ventricular assist device focused on identification of the precise site and physiological changes induced by or underlying the complication of left ventricular suction. Pressure sensors were placed in left and right atria, proximal and distal left ventricle, and proximal aorta while dual perivascular and tubing ultrasonic flow meters measured blood flow in the aortic root and pump outlet cannula. When suction occurred, end-systolic pressure gradients between proximal and distal regions of the left ventricle on the order of 40-160 mm Hg indicated an occlusive process of variable intensity in the distal ventricle. A variable negative flow difference between end systole and end diastole (0.5-3.4 L/min) was observed. This was presumably mediated by variable apposition of the free and septal walls of the ventricle at the pump inlet cannula orifice which lasted approximately 100 ms. This apposition, by inducing an end-systolic flow deficit, terminated the suction process by relieving the imbalance between pump requirement and delivery from the right ventricle. Immediately preceding this event, however, unnaturally low end-systolic pressures occurred in the left atrium and proximal left ventricle which in four dogs lasted for 80-120 ms. In one dog, however, this collapse progressed to a new level and remained at approximately -5 mm Hg across four heart beats at which point suction was relieved by manual reduction in pump speed. Because these pressures were associated with a pulmonary capillary wedge pressure of -5 mm Hg as well, they indicate total collapse of the entire pulmonary venous system, left atrium, and left ventricle which persisted until pump flow requirement was relieved by reducing pump speed. We suggest that this collapse caused the whole vascular region from pulmonary capillaries to distal left ventricle to behave as a Starling resistance which further reduced right ventricular output thus contributing to a major reduction in pump flow. We contend that similar complications of manual speed control also occur in the human subject and remain a major unsolved problem in the clinical management of patients implanted with rotary blood pumps.

In vivo irreversible electroporation kidney ablation: experimentally correlated numerical models.

Irreversible electroporation (IRE) ablation uses brief electric pulses to kill a volume of tissue without damaging the structures contraindicated for surgical resection or thermal ablation, including blood vessels and ureters. IRE offers a targeted nephron-sparing approach for treating kidney tumors, but the relevant organ-specific electrical properties and cellular susceptibility to IRE electric pulses remain to be characterized. Here, a pulse protocol of 100 electric pulses, each 100 µs long, is delivered at 1 pulse/s to canine kidneys at three different voltage-to-distance ratios while measuring intrapulse current, completed 6 h before humane euthanasia. Numerical models were correlated with lesions and electrical measurements to determine electrical conductivity behavior and lethal electric field threshold. Three methods for modeling tissue response to the pulses were investigated (static, linear dynamic, and asymmetrical sigmoid dynamic), where the asymmetrical sigmoid dynamic conductivity function most accurately and precisely matched lesion dimensions, with a lethal electric field threshold of 575 ± 67 V/cm for the protocols used. The linear dynamic model also attains accurate predictions with a simpler function. These findings can aid renal IRE treatment planning under varying electrode geometries and pulse strengths. Histology showed a wholly necrotic core lesion at the highest electric fields, surrounded by a transitional perimeter of differential tissue viability dependent on renal structure.

The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial.

OBJECTIVES: This randomized controlled multicenter trial evaluated coenzyme Q10 (CoQ10) as adjunctive treatment in chronic heart failure (HF). BACKGROUND: CoQ10 is an essential cofactor for energy production and is also a powerful antioxidant. A low level of myocardial CoQ10 is related to the severity of HF. Previous randomized controlled trials of CoQ10 in HF were underpowered to address major clinical endpoints. METHODS: Patients with moderate to severe HF were randomly assigned in a 2-year prospective trial to either CoQ10 100 mg 3 times daily or placebo, in addition to standard therapy. The primary short-term endpoints at 16 weeks were changes in New York Heart Association (NYHA) functional classification, 6-min walk test, and levels of N-terminal pro-B type natriuretic peptide. The primary long-term endpoint at 2 years was composite major adverse cardiovascular events as determined by a time to first event analysis. RESULTS: A total of 420 patients were enrolled. There were no significant changes in short-term endpoints. The primary long-term endpoint was reached by 15% of the patients in the CoQ10 group versus 26% in the placebo group (hazard ratio: 0.50; 95% confidence interval: 0.32 to 0.80; p = 0.003) by intention-to-treat analysis. The following secondary endpoints were significantly lower in the CoQ10 group compared with the placebo group: cardiovascular mortality (9% vs. 16%, p = 0.026), all-cause mortality (10% vs. 18%, p = 0.018), and incidence of hospital stays for HF (p = 0.033). In addition, a significant improvement of NYHA class was found in the CoQ10 group after 2 years (p = 0.028). CONCLUSIONS: Long-term CoQ10 treatment of patients with chronic HF is safe, improves symptoms, and reduces major adverse cardiovascular events. (Coenzyme Q10 as adjunctive treatment of chronic heart failure: a randomised, double-blind, multicentre trial with focus on SYMptoms, BIomarker status [Brain-Natriuretic Peptide (BNP)], and long-term Outcome [hospitalisations/mortality]; ISRCTN94506234).

Prevalence of vitamin D deficiency prior to cardiothoracic surgery.

BACKGROUND: Vitamin D deficiency is one of the most common chronic medical conditions in the world and also prevalent in Australia. A growing body of evidence suggests that low vitamin D also has adverse effects on cardiovascular health, including coronary risk factors and adverse cardiovascular outcomes such as myocardial infarction, cardiac failure and stroke. There is some evidence suggesting that a greater proportion of people with cardiovascular disease have low vitamin D compared to the general population. We examined the prevalence of vitamin D deficiency and insufficiency in elective cardiothoracic surgical patients presenting to the Alfred Hospital in Melbourne, Australia and compared this to recent Victorian statistics for people of the same age group. METHODS: Consecutive adult elective cardiothoracic surgical patients listed for either coronary artery bypass graft surgery or heart valve repair or replacement surgery attending The Alfred Hospital, Melbourne between July 2011 and October 2012 were invited to participate. This ensured that patients were enrolled over all four seasons. Fasting serum samples were taken on the day of surgery, immediately after admission. Eighty volunteers participated in the study. Of the group, 40% were due to have coronary artery bypass graft surgery, 35% valve surgery and 25% a combination of the two; 74% reported having hypertension, 69% hyperlipidaemia, 26% diabetes and 39% had a BMI >30 kg/m(2). RESULTS: Test results revealed that 92.5% of patients had Vitamin D levels < 75 nmol/L, 67.5% had levels < 60 nmol/L, 52.5% had levels between 30-59 nmol/L and 15% had levels < 30 nmol/L. Inadequate vitamin D levels were found in 80% of obese patients (BMI > 30 kg/m(2)) compared to 59% of non-obese patients. CONCLUSIONS: Based on our small screening study, a substantial proportion of elective cardiothoracic surgical patients have less than optimal serum vitamin D3 levels prior to surgery. We found two-thirds of patients had serum vitamin D levels below 60 nmol/L, placing them at higher risk of falls. This finding is of concern as these patients would have received multiple consultations with various medical practitioners prior to hospital admission and yet their inadequate vitamin D status remained. Failing to identify patients with low vitamin D and correcting it with supplementation places older adults at unnecessary risk, especially of falls, which are associated with a high risk of mortality. In an ageing population with CVD, vitamin D status needs to be assessed and any inadequacy corrected. Whether low vitamin D status prior to cardiac surgery affects post-surgery outcomes, is another issue which deserves future investigation.