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.

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.

Multicentre double-blind randomized controlled trial of perhexiline as a metabolic modulator to augment myocardial protection in patients with left ventricular hypertrophy undergoing cardiac surgery.

OBJECTIVES: Patients undergoing cardiac surgery require adequate myocardial protection. Manipulating myocardial metabolism may improve the extent of myocardial protection. Perhexiline has been shown to be an effective anti-anginal agent due to its metabolic modulation properties by inhibiting the uptake of free fatty acids into the mitochondrion, and thereby promoting a more efficient carbohydrate-driven myocardial metabolism. Metabolic modulation may augment myocardial protection, particularly in patients with left ventricular hypertrophy (LVH) known to have a deranged metabolic state and are at risk of poor postoperative outcomes. This study aimed to evaluate the role of perhexiline as an adjunct in myocardial protection in patients with LVH secondary to aortic stenosis (AS), undergoing an aortic valve replacement (AVR). METHODS: In a multicentre double-blind randomized controlled trial of patients with AS undergoing AVR ± coronary artery bypass graft surgery, patients were randomized to preoperative oral therapy with either perhexiline or placebo. The primary end point was incidence of inotrope use to improve haemodynamic performance due to a low cardiac output state during the first 6 h of reperfusion, judged by a blinded end points committee. Secondary outcome measures included haemodynamic measurements, electrocardiographic and biochemical markers of new myocardial injury and clinical safety outcome measures. RESULTS: The trial was halted early on the advice of the Data Safety and Monitoring Board. Sixty-two patients were randomized to perhexiline and 65 to placebo. Of these, 112 (54 perhexiline and 48 placebo) patients received the intervention, remained in the trial at the time of the operation and were analysed. Of 110 patients who achieved the primary end point, 30 patients (16 perhexiline and 14 placebo) had inotropes started appropriately; there was no difference in the incidence of inotrope usage OR of 1.65 [confidence interval (CI): 0.67-4.06] P = 0.28. There was no difference in myocardial injury as evidenced by electrocardiogram odds ratio (OR) of 0.36 (CI: 0.07-1.97) P = 0.24 or postoperative troponin release. Gross secondary outcome measures were comparable between the groups. CONCLUSIONS: Perhexiline as a metabolic modulator to enhance standard myocardial protection does not provide an additional benefit in haemodynamic performance or attenuate myocardial injury in the hypertrophied heart secondary to AS. The role of perhexiline in cardiac surgery is limited.

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.

A perilous course following myocardial infarction: ischaemic ventricular septal defect in a transplanted heart.

Coronary artery disease in the donor heart is an established cause of early graft failure. However, identification of this before implantation is difficult. Cardiogenic shock associated with significant myocardial infarction during the early postoperative period is rare. Here, we report a case of a 42-year-old man who presented acutely with cardiogenic shock; he was supported by short-term extracorporeal support as a bridge to transplantation. Following successful orthotopic heart transplantation, he sustained coronary artery atheromatous plaque rupture, resulting in acute coronary artery occlusion, and subsequently developed an ischaemic ventricular septal defect on the third postoperative day.

Current results of endovascular repair of thoraco-abdominal aneurysms†.

OBJECTIVES: Fenestrated and branch endografts represent a totally endovascular solution for high-risk patients with atherosclerotic thoraco-abdominal aortic aneurysms (TAAAs). This study reports the early outcome of endovascular TAAA repair. METHODS: Interrogation of a prospective database of consecutive patients who underwent endovascular repair (EVAR) for TAAA between June 2007 and October 2012. RESULTS: Sixty-two high-risk patients (55 men; median age 72, range 54-84 years) underwent fenestrated (n = 39) or branch (n = 23) EVAR for non-ruptured TAAA [extent I-III (n = 26) and IV (n = 36)]. Twenty patients had undergone 22 previous aortic procedures. A total of 221 target vessels (coeliac 50, superior mesenteric 61, renal 106, left subclavian 1 and hypogastric 3) were preserved with scallops (n = 17), fenestrations (n = 140) or branches (n = 62) and 201 of these vessels were stent-grafted (coeliac 34, superior mesenteric 58, renal 105, left subclavian 1 and hypogastric 3). The 30-day mortality was 1.6% (n = 1) and one further patient died on postoperative day 62 from respiratory complications. Spinal cord injury (SCI) developed in 5 (8%) patients (3 women and 2 men). Two patients required temporary renal replacement therapy and a further two commenced planned postoperative dialysis. CONCLUSIONS: In high-risk patients with TAAA, fenestrated and branch EVAR is associated with low early mortality and requirement for renal support, but the risk of SCI is not insignificant despite the use of cerebrospinal fluid drainage and blood pressure manipulation. Our current practice is to stage the repair of extent I-III aneurysms and this has significantly reduced the incidence of SCI.

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.

Evidence, lack of evidence, controversy, and debate in the provision and performance of the surgery of acute type A aortic dissection.

Acute type A aortic dissection is a lethal condition requiring emergency surgery. It has diverse presentations, and the diagnosis can be missed or delayed. Once diagnosed, decisions with regard to initial management, transfer, appropriateness of surgery, timing of operation, and intervention for malperfusion complications are necessary. The goals of surgery are to save life by prevention of pericardial tamponade or intra-pericardial aortic rupture, to resect the primary entry tear, to correct or prevent any malperfusion and aortic valve regurgitation, and if possible to prevent late dissection-related complications in the proximal and downstream aorta. No randomized trials of treatment or techniques have ever been performed, and novel therapies-particularly with regard to extent of surgery-are being devised and implemented, but their role needs to be defined. Overall, except in highly specialized centers, surgical outcomes might be static, and there is abundant room for improvement. By highlighting difficulties and controversies in diagnosis, patient selection, and surgical therapy, our over-arching goal should be to enfranchise more patients for treatment and improve surgical outcomes.

Endocrine changes in brain death and transplantation.

Following brain death (BD) many hormonal changes occur. These include an increase and then a fall in the levels of circulating catecholamines, reduced levels of anti-diuretic hormone and cortisol as well as alterations in the hypothalamic-pituitary thyroid axis consistent with the non-thyroidal illness syndrome. In an era when the numbers of potential recipients listed for transplantation are greater than the number of donors, with an increasing donor age, a detailed knowledge of the endocrine changes and pathophysiological consequences of these is essential to optimise the management of the brain-stem dead organ donor. There still remains significant debate as to whether hormone replacement therapy to correct the observed changes is beneficial.

Recommendations for haemodynamic and neurological monitoring in repair of acute type a aortic dissection.

During treatment of acute type A aortic dissection there is potential for both pre- and intra-operative malperfusion. There are a number of monitoring strategies that may allow for earlier detection of potentially catastrophic malperfusion (particularly cerebral malperfusion) phenomena available for the anaesthetist and surgeon. This review article sets out to discuss the benefits of the current standard monitoring techniques available as well as desirable/experimental techniques which may serve as adjuncts in the monitoring of these complex patients.

Which troponometric best predicts midterm outcome after coronary artery bypass graft surgery?

BACKGROUND: Various troponin I measurements (troponometrics) have been used as surrogate markers of patient outcome after coronary artery bypass grafting (CABG). Our aim was to define the postoperative troponometric best able to predict in-hospital and late mortality. METHODS: In 440 patients (seen from January 2000 to September 2004) undergoing isolated on-pump CABG with standardized anesthesia, perfusion, cardioplegia, and postoperative care, we followed all-cause mortality (census June 2009, 100% complete). Subjects underwent troponin I (cardiac troponin I [cTnI]) estimation at baseline and 6, 12, 24, 48, and 72 hours postoperatively, and individual time-point cTnI (T6, T12, T24, T48, T72), peak cTnI (Cmax), increase in cTnI between 6 and 12 hours (T↑6-12) and 6 and 24 hours (T↑6-24), cumulative area under the curve cTnI (CAUC24, CAUC48, and CAUC72), and cTnI≥13 ng·mL(-1) at any time point were each analyzed using univariate and multivariable Cox models to identify the probability of in-hospital and late death. Logistic EuroSCOREs and calculated creatinine clearance (CrCl) were also included. The Akaike information criterion (AIC) was used to determine goodness of fit. RESULTS: There were 62 of 440 deaths after a median (interquartile range) follow-up period of 7.0 (5.7 to 8.1) years. Univariate Cox analysis demonstrated T12, T24, T48, T72, T↑6-12, T↑6-24, standardized CAUC24, CAUC48, and CAUC72 each to be predictors of midterm mortality. On Cox multivariable analysis in models incorporating both logistic EuroSCOREs and CrCl, both T72 (hazard ratio [HR], 95% confidence interval [CI], 1.10 [1.06 to 1.14]; p<0.001) and CAUC72 (1.45 [1.26 to 1.62], p<0.001) were identified as independent predictors of mortality. Of these, CAUC72 was superior based on the lowest AIC. CONCLUSIONS: In myocardial protection studies, serial troponin I data should be collected until 72 hours postoperatively to calculate CAUC72, as this troponometric best predicts midterm mortality.

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.

Does modifying electrode placement of the 12 lead ECG matter in healthy subjects?

BACKGROUND: Limb electrodes for the 12 lead ECG are routinely placed on the torso during exercise stress testing or when limbs are clinically inaccessible. It is unclear whether such electrode modification produces ECG changes in healthy male or female subjects that are clinically important according to the 2009 AHA, ACCF, HRS guidelines. We therefore measured whether ECG modification produced clinically important or false positive ECG changes e.g., appearance of Q waves in leads V(1-3), ST changes greater than 0.1 mV, T wave changes greater than 0.5 mV (frontal plane) or 1 mV (transverse plane), QRS axis shifts or alterations to QTc/P-R/QRS intervals. METHODS: The 12 lead ECG was measured in 18 healthy and semi-recumbent subjects using the standard and Takuma modified limb placements. RESULTS: In the frontal plane we demonstrate that the modification of limb electrode placement produces small Q, R and T wave amplitude and QRS axis changes that are statistically but not clinically significant. In the transverse plane it produces no statistically or clinically significant changes in the ECG or in ST segment morphology, P-R, QRS or QTc intervals. CONCLUSIONS: We provide better and more robust evidence that routine modification of limb electrode placement produces only minor changes to the ECG waveform in healthy subjects. These are not clinically significant according to the 2009 guidelines and thus have no effect on the clinical specificity of the 12 lead ECG.

Biomarkers in acute aortic dissection and other aortic syndromes.

Acute aortic syndromes have an incidence of >30 per million per annum and a high mortality without definitive treatment. Survival may relate to the speed of diagnosis. Although pain is the most common symptom, there is a large fraction of patients in whom the diagnosis may be mistaken or overlooked. Currently, a high index of clinical suspicion is the chief prompt that diverts a patient into a definitive algorithm of imaging investigations. Although there is no point-of-care biochemical test that can be reliably used to positively identify dissection, biomarkers are available that could accelerate the diagnostic pathway and thereby expedite treatment.

N-terminal pro-brain-type natriuretic peptide: a biochemical surrogate of cardiac function in the potential heart donor.

OBJECTIVES: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is elevated in subarachnoid haemorrhage, brainstem death (BSD) and heart failure. We examined the relationship between NT-proBNP and cardiac functional status after BSD and left ventricular (LV) BNP precursor gene expression. METHODS: We assayed NT-proBNP in the serum of potential heart donors investigated with pulmonary artery flotation catheters, transthoracic echocardiography and cardiac troponin (cTn) I and T. After 6.9 h of optimisation, haemodynamic studies were repeated to determine haemodynamic functional suitability for transplantation. Median (interquartile range (IQR)) NT-proBNP levels are reported according to initially measured dichotomised pulmonary capillary wedge pressure (PCWP), cardiac index (CI), indexed cardiac power output (CPOi), left ventricular ejection fraction (LVEF), wall motion score (WMS), extravascular lung water index (EVLWI), cTnT and cTnI and end-management functional suitability. LV biopsies were snap-frozen, mRNA extracted and reverse-transcribed, allowing performance of Taqman real-time polymerase chain reaction assays of mRNA-BNP precursor. RESULTS: There were 79 subjects. Median NT-proBNP was 121 pg ml(-1) (range 5-4139) and levels correlated with time from coning (p<0.01, r=-0.379). Higher NT-proBNP was found in donors with PCWP >14 mmHg; 504 (120-1544) versus 101 (38-285); p=0.01; CI <2.4 l min(-1) m(-2) 410 (123-1511) versus 95 (37-264); p=0.001; CPOi <0.5 Wm(-2) 256 (78-694) versus 105 (37-315); p=0.02; LVEF <50% 231 (75-499) versus 72 (36-177); p=0.04; WMS >2; 343 (80-673) versus 99 (37-236); p=0.01; cTnT >0.1 microg ml(-1) 499 (127-967) versus 80 (36-173); p<0.001 and cTnI >1 mg ml(-1) 410 (97-684) versus 88 (36-190); p<0.01 and in hearts functionally unsuitable at end-optimisation; 189 (74-522) versus 85 (39-243); p=0.02. Hearts functionally suitable for transplantation expressed significantly less mRNA encoding for BNP precursor (0.19-fold; p=0.01). CONCLUSION: During or after BSD, NT-proBNP is released and the heart is a likely source. Higher NT-proBNP levels are associated with donor heart dysfunction and a failure to achieve haemodynamic functional suitability criteria. This supports the hypothesis that biomarkers, including NT-proBNP, may be useful in donor heart assessment.

The effects of acute triiodothyronine therapy on myocardial gene expression in brain stem dead cardiac donors.

CONTEXT: After brain stem death (BSD), a low T(3) state is common, and T(3) supplementation has been advocated to improve heart function and yield for transplantation. OBJECTIVES: The aim of the study was to assess the effects of T(3) on expression of mRNAs encoding T(3)-responsive genes in the post-BSD human heart. DESIGN: Within a prospective double-blind trial, potential BSD cardiac donors undergoing hemodynamic optimization were randomized to T(3) (0.8 microg . kg(-1) bolus; infusion 0.113 microg . kg(-1) . h(-1)) or placebo (5% dextrose) for up to 6 h. Left ventricular biopsies were obtained at end-assessment from 30 donors (T(3); n=16). TaqMan real-time PCR was performed to investigate mRNA expression of the voltage-gated potassium channel Kv1.5, beta-1 adrenergic receptor (ADRB1), sarcoplasmic reticulum calcium ATPase type 2a (SERCA2a), and phospholamban (PLB). RESULTS: Time between diagnosis of BSD and donor management was 13.2 h (range, 9.7-16.8 h). T(3) donors were managed for 7.6 (6.9-8.3) h. Median serum free T(3) (fT3) at baseline was 2.9 (2.3-3.8) pmol . liter(-1) (reference range, 3.3-7.5 pmol . liter(-1)). At baseline, 19 of 30 (56.7%) had low serum fT3, and T(3) treatment increased fT3 to supraphysiological levels (P < 0.001). Expression of mRNAs encoding Kv1.5 and SERCA2a was increased 1.99-fold and 1.51-fold (P = 0.015 and 0.043). There was no significant change in the expression of mRNAs encoding ADRB1 and PLB. Treatment with T(3) did not improve hemodynamic function compared with placebo. CONCLUSIONS: Acute administration of T(3) in the BSD cardiac donor reverses the low T(3) state and increases expression of the mRNAs encoding Kv1.5 and SERCA2a, but not ADRB1 or PLB and is not associated with any improvement in hemodynamic performance.

Thyroid hormone in cardiac surgery.

Thyroid hormone has a wide range of cardiovascular effects which are mediated at both genomic and non-genomic levels. As a stress response to surgery, the non-thyroidal illness syndrome or euthyroid sick syndrome occurs in the post-operative period following cardiac surgery. There remains debate about the potential benefits of the treatment of the non-thyroidal illness syndrome in this setting with acute thyroid hormone supplementation. This review article sets out to discuss the potential benefits of thyroid hormone supplementation and the results from trials relating to both adult and paediatric cardiac surgical population as well as in the setting of brain stem death to optimise the potential cardiac donor.