Coronary angiography of the ex-situ beating donor heart in a portable organ care system.

OBJECTIVES: To determine safety and feasibility of ex-situ coronary angiography. BACKGROUND: To cater for the perpetually growing demand for heart donors, interest in donation following circulatory death (DCD) has been rekindled. Further pursuit of donor pool expansion has led to eligibility extension to "marginal" donors who are at higher risk of coronary artery disease (CAD). Excluding CAD in potentially eligible DCD donors, for whom ante-mortem angiography is commonly not permitted, is therefore challenging. Ex-situ coronary angiography serves as an ethical and feasible diagnostic tool to assess for preclusive CAD. METHODS: We undertook a systematic review of the published literature and institutional retrospective review of case experience with ex-situ coronary angiography of donor hearts, supported by a portable organ care system. RESULTS: Combined literature and institutional case review yielded nine total cases of ex-situ coronary angiography of donor human hearts plus one experimental porcine model. Of the eight cases of ex-situ coronary angiography performed at our institute, all were conducted without complication or injury to the allograft. Two thirds of reported human cases have proceeded to successful transplantation. CONCLUSIONS: Diagnostic coronary angiography of the ex-situ beating donor heart is safe, feasible, and demonstrates novel clinical utility in mitigating subsequent transplantation of unsuitable allografts. In the setting of suspected coronary atherosclerosis of the donor heart, which may preclude favorable transplantation outcomes, ex-situ coronary angiography should be considered at eligible transplant centers.

Recanalization of an atretic left internal mammary graft after bypass surgery for an anomalous left main coronary artery origin: a case report.

BACKGROUND: The inter-arterial anomalous course of the left main coronary artery (LMCA) originating from the right coronary sinus of Valsalva is a rare, though potentially lethal pathology. Coronary artery bypass grafting is a potential surgical therapy with previously reported success, however, there is concern for the possibility of graft occlusion in the setting of competitive native vessel flow. CASE SUMMARY: A 48-year-old gentleman presented to our facility with a non-ST elevation acute coronary syndrome. A malignant anomalous course of the LMCA was confirmed using invasive coronary angiography and computed tomography (CT). The patient underwent surgical revascularization of the left anterior descending artery with a left internal mammary artery (LIMA) graft, which was found to be atretic on follow-up CT. Seven years later the patient underwent repeat CT imaging, which confirmed recanalization of the previously atretic LIMA. DISCUSSION: We present the first documented case of a patient with spontaneous recanalization of an occluded LIMA following bypass surgery for an inter-arterial anomalous course of the LMCA. We postulate that the dynamic obstruction of the anomalous LMCA led to variable flow dependence on the bypass graft and subsequent atresia of the LIMA, due to the favourable native flow conditions in the absence of significant obstructive coronary disease. The exact mechanism of LIMA recanalization remains unclear, but in our case may have been partly mediated by a small increase in left main plaque.

Takotsubo cardiomyopathy following unintentionally large subcutaneous adrenaline injection: a case report.

INTRODUCTION: Stress cardiomyopathy, also known as takotsubo syndrome, is characterized by transient left ventricular dysfunction not attributable to obstructive epicardial coronary artery disease. Several pathological mechanisms have been proposed, including multivessel coronary artery vasospasm, coronary microcirculatory dysfunction, and excess catecholamine secretion. CASE PRESENTATION: A 68-year-old male presented to our institution for elective surgical removal of a cutaneous basal cell carcinoma on the right side of his face. Within minutes following the administration of local anaesthesia, the patient developed severe hypertension, tachycardia, ST-segment elevation on the electrocardiogram, and non-sustained broad-complex tachycardia. Urgent cardiac catheterization revealed non-obstructive coronary artery disease and left ventriculography demonstrated apical hypokinesia and moderate systolic dysfunction consistent with the takotsubo syndrome. On review of the medications administered, it was noted that an unintentionally large dose of adrenaline (4mg) had been injected subcutaneously with lignocaine. He was monitored in the coronary care and recovered fully with supportive care only. Bisoprolol was initiated on day 1 post procedure. On follow-up one month later, his left ventricular function had normalized. DISCUSSION: Our case report provides direct evidence supporting the pathogenetic role of excess catecholamine secretion in the development of the takotsubo syndrome. A review of the literature reveals that both exogenous catecholamine administration (adrenaline injection in the context of anaphylaxis or infiltrative anaesthesia) and excess endogenous catecholamine (phaechromocytoma) secretion has been associated with the takotsubo syndrome. Local infiltrative anaesthesia with the addition of adrenaline is commonly used as a vasoconstrictor in a wide variety of surgical procedures. To reduce the risk of adverse events, the lowest effective concentration of adrenaline to provide pain control and vasoconstriction is recommended.

Recurrent contrast-induced encephalopathy following coronary angiography.

Contrast-induced encephalopathy (CIE) is an acute and reversible neurological disturbance associated with the intra-arterial administration of iodinated contrast medium during cardiac catheterisation. It may manifest with encephalopathy, motor and sensory disturbances; vision disturbances, including cortical blindness, ophthalmoplegia, aphasia; and seizures. Disruption of the blood-brain barrier and direct neuronal toxicity are believed to be implicated in the pathophysiology of the syndrome. Symptoms appear soon after contrast administration and resolve completely within 24-48 h. Risk factors may include hypertension, diabetes mellitus, renal impairment, the administration of large volumes of iodinated contrast, percutaneous coronary intervention or selective angiography of internal mammary grafts and previous adverse reaction to iodinated contrast. On cerebral imaging, CIE may mimic subarachnoid haemorrhage or cerebral ischaemia, but imaging may be normal. Prognosis is excellent with supportive management alone. CIE may recur, but re-challenge with iodinated contrast without adverse effects has been documented. CIE is a diagnosis of exclusion and is an important clinical entity to consider in the differential diagnosis of stroke following cardiac catheterisation. Physicians should be aware of it and consider it prior to initiating thrombolysis.

Contrast-induced encephalopathy following cardiac catheterization.

OBJECTIVES: To describe the epidemiology, pathophysiology, clinical presentation, and management of contrast-induced encephalopathy (CIE) following cardiac catheterization. BACKGROUND: CIE is an acute, reversible neurological disturbance directly attributable to the intra-arterial administration of iodinated contrast medium. METHODS: The PubMed database was searched and all cases in the literature were retrieved and reviewed. RESULTS: 52 reports of CIE following cardiac catheterization were found. Encephalopathy, motor and sensory disturbances, vision disturbance, opthalmoplegia, aphasia, and seizures have been reported. Transient cortical blindness is the most commonly reported neurological syndrome, occurring in approximately 50% of cases. The putative mechanism involves disruption of the blood brain barrier and direct neuronal injury. Contrast-induced transient vasoconstriction has also been implicated. Symptoms typically appear within minutes to hours of contrast administration and resolve entirely within 24-48 hr. Risk factors may include hypertension, diabetes mellitus, renal impairment, the administration of large volumes of iodinated contrast, percutaneous coronary intervention or selective angiography of internal mammary grafts, and previous adverse reaction to iodinated contrast. Characteristic findings on cerebral imaging include cortical and sub-cortical contrast enhancement on computed tomography (CT). Imaging findings in CIE may mimic subarachnoid hemorrhage or cerebral ischemia; the Hounsfield scale on CT and the apparent diffusion coefficient on magnetic resonance imaging (MRI) are useful imaging tools in distinguishing these entities. In some cases, brain imaging is normal. Prognosis is excellent with supportive management alone. CIE tends to recur, although re-challenge with iodinated contrast without adverse effects has been documented. CONCLUSIONS: CIE is an important clinical entity to consider in the differential diagnosis of stroke following cardiac catheterization. Given that prognosis is excellent with supportive management only, physicians should be aware of it, and consider it prior to initiating thrombolysis. © 2016 Wiley Periodicals, Inc.

Early graft failure complicating coronary artery bypass surgery for anomalous left coronary artery from the right coronary sinus.

Anomalous left coronary artery from the right sinus is a recognized cause of myocardial ischemia, ventricular arrhythmia, and sudden cardiac death. The optimal management remains controversial with potential options including coronary artery bypass grafting with or without native vessel ligation, coronary artery re-implantation, and surgical un-roofing. In the case presented, bypass grafting of an anomalous left coronary artery was complicated by early graft failure due to competitive flow from the native vessel. .

Equivalent lipid oxidation profiles in advanced atherosclerotic lesions of carotid endarterectomy plaques obtained from symptomatic type 2 diabetic and nondiabetic subjects.

Type 2 diabetes (T2D) increases the risk for cardiovascular disease and is thought to be associated with increased oxidative stress, a contributor to atherogenesis. Surprisingly, however, there is little direct evidence that T2D-associated oxidative stress results in increased lipid oxidation and/or decreased antioxidant capacity in human atherosclerotic lesions. The aim of this study was to measure vascular lipid oxidation and antioxidants in T2D. The arterial content of oxidized lipid and antioxidants in carotid endarterectomy specimens obtained from diabetic and normoglycemic patients was determined using high-performance liquid chromatography (HPLC), stable isotope dilution gas chromatography-mass spectrometry (GC/MS), and gas-liquid chromatography techniques. The concentrations of hydroxyoctadecanoic acid, F(2)-isoprostanes, and 7-ketocholesterol, as well as alpha-tocopherol, ascorbate, and urate were not different in the two patient groups, whether expressed per unit protein or as a ratio per parent compound. Unexpectedly, a significant decrease in the level of arterial lipid hydroperoxide was found in diabetic patients. Our results do not support the notion that advanced atherosclerotic lesions from T2D patients contain more oxidized lipids than corresponding lesions from nondiabetic subjects.

The Carotid Revascularization Endarterectomy versus Stenting Trial: credentialing of interventionalists and final results of lead-in phase.

The success of carotid artery stenting in preventing stroke requires a low risk of periprocedural stroke and death. A comprehensive training and credentialing process was prerequisite to the randomized Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) to assemble a competent team of interventionalists with low periprocedural event rates. Interventionalists submitted cases to a multidisciplinary Interventional Management Committee. This committee evaluated 427 applicants. Of these, 238 (56%) were selected to participate in the training program and the lead-in phase, 73 (17%) who had clinical registry experience and satisfactory results with the devices used in CREST were exempt from training and were approved for the randomized phase, and 116 (27%) did not qualify for training. At 30 days in the lead-in study, stroke, myocardial infarction, or death occurred in 6.1% of symptomatic subjects and 4.8% of asymptomatic subjects. Stroke or death occurred in 5.8% of symptomatic subjects and 3.8% of asymptomatic subjects. Outcomes were better for younger subjects and varied by operator training. Based on experience, training, and lead-in results, the Interventional Management Committee selected 224 interventionalists to participate in the randomized phase of CREST. We believe that the credentialing and training of interventionalists participating in CREST have been the most rigorous reported to date for any randomized trial evaluating endovascular treatments. The study identified competent operators, which ensured that the randomized trial results fairly contrasted outcomes between endarterectomy and stenting.

Endothelial dysfunction and restenosis following percutaneous coronary intervention.

BACKGROUND: Restenosis remains an important limitation of PCI. Although local factors such as small vessel diameter and systemic factors such as diabetes explain some of its incidence, it nevertheless also occurs in low-risk patients. We hypothesize that endothelial dysfunction may be an independent risk factor in some of these cases. METHODS: 20 patients who had previously undergone PCI were studied at cardiac catheterization (10 with restenotic lesions were matched to 10 without restenosis). Infusion of multiple concentrations of acetylcholine (ACh) and nitroglycerine (GTN) were made via a 3F infusion catheter into the target artery. Following infusion, changes in diameter of segments proximal and distal to the PCI site were measured. RESULTS: There was a significant impairment in endothelium-dependent dilatation at the maximal dose of acetylcholine in those with restenosis compared to those without restenosis, both proximal and distal to the stented area (proximal; 11.5+/-7.0% versus -20.9+/-9.0% p<0.001, distal; 12.0+/-3.1% versus -17.8+/-8.1% p<0.001), but there was no difference in the response to GTN. There was a significant correlation between the endothelium-dependent dilatation response and the percent restenosis (r=-0.65, p=0.003). CONCLUSIONS: Coronary endothelium-dependent dilatation is reduced in subjects with restenosis in arterial segments separate from the stented lesion. This supports a hypothesis that endothelial dysfunction contributes to the development of restenosis, following percutaneous coronary intervention.

Antioxidants protect from atherosclerosis by a heme oxygenase-1 pathway that is independent of free radical scavenging.

Oxidative stress is implicated in atherogenesis, yet most clinical trials with antioxidants, particularly vitamin E, have failed to protect against atherosclerotic diseases. A striking exception is probucol, which retards atherosclerosis in carotid arteries and restenosis of coronary arteries after angioplasty. Because probucol has in vitro cellular-protective effects independent of inhibiting lipid oxidation, we investigated the mode of action of probucol in vivo. We used three models of vascular disease: apolipoprotein E-deficient mice, a model of atherosclerosis; rabbit aortic balloon injury, a model of restenosis; and carotid injury in obese Zucker rats, a model of type 2 diabetes. Unexpectedly, we observed that the phenol moieties of probucol were insufficient, whereas its sulphur atoms were required for protection. Probucol and its sulphur-containing metabolite, but not a sulphur-free phenolic analogue, protected via cell-specific effects on inhibiting macrophage accumulation, stimulating reendothelialization, and inhibiting vascular smooth muscle cell proliferation. These processes were mediated via induction of heme oxygenase-1 (HO-1), an activity not shared by vitamin E. Our findings identify HO-1 as the molecular target of probucol. They indicate 2-electron rather than radical (1-electron) oxidants as important contributors to atherogenesis, and point to novel lead compounds for therapeutic intervention against atherosclerotic diseases.

Probucol inhibits in-stent thrombosis and neointimal hyperplasia by promoting re-endothelialization.

BACKGROUND: Evidence suggests that delayed re-endothelialization is responsible for in-stent thrombosis. Probucol inhibits neointimal thickening in animals via enhanced re-endothelialization and is the only oral drug that consistently inhibits restenosis after coronary angioplasty in humans. Here, we examined the effects of probucol on re-endothelialization and neointimal formation in a stent model. METHODS AND RESULTS: New Zealand White rabbits were fed a hypercholesterolemic diet with probucol (1%) or without (control) (n=11 each) for 6 weeks. At 2 weeks, endothelial denudation and stenting of the iliac artery was performed. Iliac arteries were harvested at week 6, and stented segments sectioned and analyzed. Compared with control, probucol increased in-stent re-endothelialization (74+/-6% in controls versus 93+/-3% in probucol-treated; P=0.008), and decreased average luminal stenosis (58+/-27 versus 31+/-16%; P=0.01) and stent depth (619+/-310 versus 314+/-158 microm; P=0.009). Compared with control, probucol also decreased accumulation of macrophages in the neointima. Furthermore, none of the probucol-treated rabbits had in-stent thrombosis, whereas four of eleven control rabbits showed thrombosis (P=0.04). CONCLUSIONS: Probucol demonstrates anti-restenotic and appears to have anti-thrombotic properties that are likely related to its ability to promote in-stent re-endothelialization.

Endothelial dysfunction as a predictor of acute coronary syndromes.

Endothelial dysfunction is a key early event in atherogenesis and is integral in the onset of acute coronary syndromes. Disruption of the normal endothelial functions leads to loss of vasomotor control, reduced production of nitric oxide, formation of a procoagulant surface, and promotion of inflammation. These events may lead to destabilization of atherosclerotic plaques and the onset of acute coronary syndromes. There are several direct and indirect ways of assessing endothelial dysfunction in vivo. Several of these measures of endothelial dysfunction have been shown to correlate with increased risk of adverse cardiovascular outcomes.