Women With Spontaneous Coronary Artery Dissection Are at Increased Risk of Iatrogenic Coronary Artery Dissection.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a non-atherosclerotic cause of acute coronary syndrome (ACS) that affects women disproportionately. Previous case series have found that patients with SCAD undergoing cardiac catheterisation have high rates of iatrogenic coronary damage. We formally compared the rate of iatrogenic coronary artery dissection in women with and without SCAD undergoing cardiac catheterisation over a 11-year period. METHODS: Women with SCAD were identified by a search of the cardiac catheterisation database 2007-2017 for the keywords 'SCAD', 'spontaneous coronary artery dissection', 'spontaneous coronary dissection', and 'spontaneous dissection'. For each identified case, the medical record and the coronary angiogram images were reviewed to confirm spontaneous coronary dissection. For cases of recurrent SCAD, duplicates were removed so that each patient was included only once in this analysis. For each identified case of SCAD, a control case was chosen from women aged <70 years, without SCAD, undergoing cardiac catheterisation for an ACS during the same 10-year period. One control case was chosen to match each SCAD patient as closely as possible for age and year of cardiac catheterisation. Iatrogenic coronary dissection was defined as new, proximal, flow limiting coronary artery dissection in a different coronary segment to the presenting spontaneous coronary dissection. RESULTS: Eighty-five (85) cases of women with SCAD were identified. Mean age was not different between SCAD and non-SCAD women (51±11 and 51±10 years, respectively). The SCAD group had lower rates of ST elevation myocardial infarction, lower rises in serum creatine kinase (CK) and troponin levels, lower rates of diabetes and smoking, and far less placement of stents during the procedure than the control group. The rate of additional iatrogenic dissection relating to the cardiac catheterisation procedure was 4 of 85 (4.7%) versus 0 of 85 (0%), p=0.04 in SCAD and control groups, respectively, despite a much lower rate of percutaneous coronary intervention in the SCAD group. No common factors could be identified regarding particular equipment or procedural factors associated with iatrogenic dissection. CONCLUSION: The rate of iatrogenic dissection in women with SCAD during cardiac catheterisation is confirmed to be high and significantly higher than a contemporaneous age-matched group of women without SCAD. This observation likely indicates generalised coronary fragility in this disease, and emphasises the importance of the utmost care in the engagement, injection and intervention involving the coronary arteries in this disease. Development of a non-invasive coronary imaging modality or biomarker able to diagnose SCAD non-invasively would be a great advance in the care of patients with this condition, because it would avoid the need for invasive coronary angiography for diagnosis.

Dilatation of the Ascending Aorta in Turner Syndrome: Influence of Bicuspid Aortic Valve Morphology and Body Composition.

BACKGROUND: Aortic dilatation and bicuspid aortic valve (BAV) are frequent in Turner syndrome (TS). Due to short stature, aortic size index (ASI)-ascending aortic diameter (AD)/body surface area (BSA)-is used to identify aortic dilatation in TS patients. We sought to: 1) describe echocardiographic findings in the largest cohort of Australian women with TS; 2) assess if ASI progresses differently with age in TS BAV compared to non-syndromic BAV; and 3) determine whether adjustment of AD for body composition may be superior to BSA indexation. METHODS: Transthoracic echocardiography (TTE) data were retrospectively collected on 125 women with TS. Body composition was quantified by dual energy X-ray absorptiometry (DXA) in 60 women within 6 months of baseline TTE. Age-matched females with non-syndromic BAV (n=170) were used as controls for TS patients with BAV. RESULTS: Mean age of TS women was 28±16 years, and mean height and BSA were 141.6±21.7 cm and 1.4±0.4 m2, respectively. Mean AD was 2.5±0.8 cm, and ASI 2.0±0.6 cm/m2. Aortic dilatation (ASI >2.0 cm/m2) was present in 42 (34%) patients. Turner syndrome women with BAV (n=34; 27%) had a larger ASI than those with tri-leaflet AV (2.2±0.4 cm/m2 vs. 1.7±0.3 cm/m2, p<0.001). In the pooled BAV cohort, TS patients had a higher baseline ASI (2.2±0.4 cm/m2 vs. 2.1±0.3 cm/m2, p=0.02) and greater increase in ASI with age (0.21 mm/m2/year vs. 0.10 mm/m2/year, p=0.01) compared to non-syndromic BAV patients. DXA fat-free mass (r=0.33, p=0.01) and lean mass (r=0.32, p=0.02) correlated with AD, as did BSA (r=0.62, p<0.001). CONCLUSION: Turner syndrome women with BAV have a greater degree of baseline aortic dilatation and a twofold faster increase in aortic dimension with age when compared to matched women with non-syndromic BAV. Several DXA-derived body composition parameters correlate with aortic size in TS, however BSA appears to be the most robust method of indexation.

The role of intravascular ultrasound in percutaneous coronary intervention of complex coronary lesions.

Intravascular ultrasound (IVUS) is a catheter-based coronary imaging technique. It utilises the emission & subsequent detection of reflected high frequency (30-60 MHz) sound waves to create high resolution, cross-sectional images of the coronary artery. IVUS has been the cornerstone of intracoronary imaging for more than two decades. When compared to the invasive coronary angiogram which studies only the silhouette of the contrast-filled artery lumen, IVUS also crucially images the vessel wall. Because of this capability, IVUS has greatly facilitated understanding of the coronary atherosclerosis process. Such insights from IVUS reveal how commonly and extensively plain angiography underestimates the true extent of coronary plaque, the characteristics of plaques prone to rupture and cause acute coronary syndromes (lipid rich, thin cap atheroma), and a realisation of the widespread occurrence of vessel remodelling in response to atherosclerosis. Similarly, IVUS has historically provided salutary mechanistic insights that have guided many of the incremental advances in the techniques of percutaneous coronary intervention (PCI). Examples include mechanisms of in-stent restenosis, and the importance of high-pressure post-dilatation of stents to ensure adequate stent apposition and thereby reduce the occurrence of stent thrombosis. IVUS also greatly facilitates the choice of correct diameter and length of stent to implant. Overall, a compelling body of evidence indicates that use of intravascular ultrasound in PCI helps to achieve optimal technical results and to mitigate the risk of adverse cardiac events. In this review, the role of intravascular ultrasound as an adjunct to PCI in complex coronary lesions is explored. The complex coronary situations discussed are the left main stem, ostial stenoses, bifurcation stenoses, thrombotic lesions, the chronically occluded coronary artery, and calcified coronary artery disease. By thorough review of the available evidence, we establish that the advantages of IVUS guidance are particularly evident in each of these complex CAD subsets. In particular, some consider the use of IVUS to be almost mandatory in left main PCI. A comparison with other intracoronary imaging techniques is also explored.

Publisher Correction: The role of cardiac transcription factor NKX2-5 in regulating the human cardiac miRNAome.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The role of cardiac transcription factor NKX2-5 in regulating the human cardiac miRNAome.

MicroRNAs (miRNAs) are translational regulatory molecules with recognised roles in heart development and disease. Therefore, it is important to define the human miRNA expression profile in cardiac progenitors and early-differentiated cardiomyocytes and to determine whether critical cardiac transcription factors such as NKX2-5 regulate miRNA expression. We used an NKX2-5eGFP/w reporter line to isolate both cardiac committed mesoderm and cardiomyocytes. We identified 11 miRNAs that were differentially expressed in NKX2-5 -expressing cardiac mesoderm compared to non-cardiac mesoderm. Subsequent profiling revealed that the canonical myogenic miRNAs including MIR1-1, MIR133A1 and MIR208A were enriched in cardiomyocytes. Strikingly, deletion of NKX2-5 did not result in gross changes in the cardiac miRNA profile, either at committed mesoderm or cardiomyocyte stages. Thus, in early human cardiomyocyte commitment and differentiation, the cardiac myogenic miRNA program is predominantly regulated independently of the highly conserved NKX2-5 -dependant gene regulatory network.

SIRPA, VCAM1 and CD34 identify discrete lineages during early human cardiovascular development.

The study of human cardiogenesis would benefit from a detailed cell lineage fate map akin to that established for the haematopoietic lineages. Here we sought to define cell lineage relationships based on the expression of NKX2-5 and the cell surface markers VCAM1, SIRPA and CD34 during human cardiovascular development. Expression of NKX2-5(GFP) was used to identify cardiac progenitors and cardiomyocytes generated during the differentiation of NKX2-5(GFP/w) human embryonic stem cells (hESCs). Cardiovascular cell lineages sub-fractionated on the basis of SIRPA, VCAM1 and CD34 expression were assayed for differentiation potential and gene expression. The NKX2-5(pos)CD34(pos) population gave rise to endothelial cells that rapidly lost NKX2-5 expression in culture. Conversely, NKX2-5 expression was maintained in myocardial committed cells, which progressed from being NKX2-5(pos)SIRPA(pos) to NKX2-5(pos)SIRPA(pos)VCAM1(pos). Up-regulation of VCAM1 was accompanied by the expression of myofilament markers and reduced clonal capacity, implying a restriction of cell fate potential. Combinatorial expression of NKX2-5, SIRPA, VCAM1 and CD34 can be used to define discrete stages of cardiovascular cell lineage differentiation. These markers identify specific stages of cardiomyocyte and endothelial lineage commitment and, thus provide a scaffold for establishing a fate map of early human cardiogenesis.

Intrinsic cardiac origin of human cardiosphere-derived cells.

AIMS: Cardiosphere-derived cells (CDCs) are in clinical development as a regenerative cell product which can be expanded ex vivo from patient cardiac biopsies. Cardiosphere-derived cells are clonogenic, exhibit multilineage differentiation, and exert functional benefits in preclinical models of heart failure. The origin of CDCs remains unclear: are these cells endogenous to the heart, or do they arise from cells that populate the heart via blood-borne seeding? METHODS AND RESULTS: Right ventricular endomyocardial biopsies were obtained from cardiac transplant recipients (n = 10, age 57 ± 15 years), and CDCs expanded from each biopsy. Donor-recipient mismatches were used to probe the origin of CDCs in three complementary ways. First, DNA analysis of short-tandem nucleotide repeats (STRs) was performed on genomic DNA from donor and recipient, then compared with the STR pattern of CDCs. Second, in two cases where the donor was male and the recipient female, CDCs were examined for the presence of X and Y chromosomes by fluorescence in situ hybridization. Finally, in two cases, quantitative PCR (qPCR) was performed for individual-specific polymorphisms of a major histocompatability locus to quantify the contribution of recipient cells to CDCs. In no case was recipient DNA detectable in the CDCs by STR analysis. In the two cases in which a female patient had received a male heart, all CDCs examined had an X and Y chromosome, similarly indicating exclusively donor origin. Likewise, qPCR on CDCs did not detect any recipient DNA. CONCLUSION: Cardiosphere-derived cells are of endogenous cardiac origin, with no detectable contribution from extra-cardiac seeding.

Adherence to hypoglycaemic medication among people with type 2 diabetes in primary care.

AIMS: To assess levels and correlates of adherence to hypoglycaemic medication among patients offered organised general practice diabetes care. METHODS: 60 patients prescribed oral hypoglycaemic medication were recruited to a two-month prospective study. Prescribed doses taken and days on which the prescribed number of doses was taken were measured by MEMS (Medication Event Monitoring System). RESULTS: Overall 99.1% of prescribed doses were taken (median, IQR: 96.8-100%), this was inversely correlated with daily dose frequency (Spearman's rho=0.37, p=0.004). Only 4 patients (6.7%) took less than 90% of prescribed doses. The prescribed dose was taken on 96.4% of days (median, IQR: 89.1-98.2%), this was correlated with age (rho=0.26, p=0.047) and inversely correlated with HbA(1c) levels (rho=-0.29, p=0.02) and daily dose frequency (rho=-0.33, p=0.009). Adherence to metformin was less than to other hypoglycaemic medication (Z=-3.48, p=0.0005). CONCLUSIONS: A dispensing practice with a well-run diabetes service can support high rates of adherence to hypoglycaemic medication. Before changing medication, low adherence might be considered as a possible cause of progressive hyperglycaemia, particularly among patients prescribed metformin more than once a day. Selective monitoring with MEMS may have a clinical as well as a research role in such people.

Plasma lipidomic analysis of stable and unstable coronary artery disease.

OBJECTIVE: Traditional risk factors for coronary artery disease (CAD) fail to adequately distinguish patients who have atherosclerotic plaques susceptible to instability from those who have more benign forms. Using plasma lipid profiling, this study aimed to provide insight into disease pathogenesis and evaluate the potential of lipid profiles to assess risk of future plaque instability. METHODS AND RESULTS: Plasma lipid profiles containing 305 lipids were measured on 220 individuals (matched healthy controls, n=80; stable angina, n=60; unstable coronary syndrome, n=80) using electrospray-ionisation tandem mass spectrometry. ReliefF feature selection coupled with an L2-regularized logistic regression based classifier was used to create multivariate classification models which were verified via 3-fold cross-validation (1000 repeats). Models incorporating both lipids and traditional risk factors provided improved classification of unstable CAD from stable CAD (C-statistic=0.875, 95% CI 0.874-0.877) compared with models containing only traditional risk factors (C-statistic=0.796, 95% CI 0.795-0.798). Many of the lipids identified as discriminatory for unstable CAD displayed an association with disease acuity (severity), suggesting that they are antecedents to the onset of acute coronary syndrome. CONCLUSION: Plasma lipid profiling may contribute to a new approach to risk stratification for unstable CAD.

Intramyocardial injection of autologous cardiospheres or cardiosphere-derived cells preserves function and minimizes adverse ventricular remodeling in pigs with heart failure post-myocardial infarction.

OBJECTIVES: The purpose of this study was to test the safety and efficacy of direct injection of cardiosphere-derived cells (CDCs) and their 3-dimensional precursors, cardiospheres, for cellular cardiomyoplasty in a mini-pig model of heart failure after myocardial infarction. BACKGROUND: Intracoronary administration of CDCs has been demonstrated to reduce infarct size and improve hemodynamic indexes in the mini-pig model, but intramyocardial injection of CDCs or cardiospheres has not been assessed in large animals. METHODS: Autologous cardiospheres or CDCs grown from endomyocardial biopsies were injected through thoracotomy 4 weeks after anteroseptal myocardial infarction. Engraftment optimization with luciferase-labeled CDCs guided the choice of cell dose (0.5 million cells/site) and target tissue (20 peri-infarct sites). Pigs were randomly allocated to placebo (n = 11), cardiospheres (n = 8), or CDCs (n = 10). Functional data were acquired before injection and again 8 weeks later, after which organs were harvested for histopathology. RESULTS: Beyond the immediate perioperative period, all animals survived to protocol completion. Ejection fraction was equivalent at baseline, but at 8 weeks was higher than placebo in both of the cell-treated groups (placebo vs. CDC, p = 0.01; placebo vs. cardiospheres, p = 0.01). Echocardiographic and hemodynamic indexes of efficacy improved disproportionately with cardiospheres; likewise, adverse remodeling was more attenuated with cardiospheres than with CDCs. Provocative electrophysiologic testing showed no differences among groups, and no tumors were found. CONCLUSIONS: Dosage-optimized direct injection of cardiospheres or CDCs is safe and effective in preserving ventricular function in porcine ischemic cardiomyopathy. Although CDCs and cardiospheres have equivalent effects on left ventricular ejection fraction, cardiospheres are superior in improving hemodynamics and regional function, and in attenuating ventricular remodeling.

Predictive accuracy of SYNTAX score for predicting long-term outcomes of unprotected left main coronary artery revascularization.

The American College of Cardiology/American Heart Association recently updated recommendations for percutaneous coronary intervention (PCI) of unprotected left main coronary artery (ULMCA) disease from class III to II(b) according to the results of the SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) trial. The SYNTAX score is an angiographic tool using solely the coronary anatomy. We studied the effect of co-morbidities (Parsonnet's score) on the ability of the SYNTAX score to predict long-term outcomes in patients with ULMCA disease treated by revascularization. A total of 328 patients underwent revascularization of ULMCA from April 2003 to February 2007. Of the 328 patients, 120 underwent PCI (median follow-up 973 days) and 208 underwent coronary artery bypass grafting (CABG) (median follow-up 1,298 days). The ability of the SYNTAX score to predict outcomes was assessed using the Cox proportional hazards model. The outcomes between the PCI and CABG groups were compared by propensity analysis. The median SYNTAX score was 26 in the PCI and 28 in the CABG group (p = 0.5). In the PCI group, greater quartiles were associated with worse survival (62.1% at SYNTAX score of ≥36 vs 82.4% at SYNTAX score of <36, p = 0.03) and all-cause mortality, myocardial infarction, cerebrovascular events, and target vessel revascularization-free (MACCE) survival (47.7%, SYNTAX score ≥20 vs 76.6%, SYNTAX score <20, p = 0.02). Using the Parsonnet score as a covariate, the SYNTAX score continued to be an independent predictor of MACCE and demonstrated a trend toward predicting mortality in the PCI group. In contrast, the SYNTAX score did not predict the outcomes for the CABG group. No difference was found in mortality between the PCI and CABG groups for ULMCA disease, regardless of coronary complexity; although greater SYNTAX scores were associated with increased MACCE rates with PCI compared to CABG. Both the coronary anatomy (SYNTAX score) and co-morbidities (Parsonnet's score) predicted long-term outcomes for PCI of ULMCA disease. In contrast, the SYNTAX score did not predict the outcomes after CABG. In conclusion, the ideal scoring system to guide an appropriate revascularization decision for ULMCA disease should take into account both the coronary anatomy and the co-morbidities.

Meta-analysis of incidence, clinical characteristics and implications of stent fracture.

A meta-analysis of published studies was conducted to evaluate the incidence, predictors, and clinical outcomes of stent fractures. Eight studies with 108 stent fractures in 5,321 patients were analyzed using the Bayesian method. Study end points included in-stent restenosis (ISR) and target lesion revascularization (TLR). The mean incidence of stent fracture per patient was 4.0% (95% confidence interval 0.4% to 16.3%). All cases, except 1, were reported with sirolimus-eluting stents. The incidence of stent fracture was 30.4% in the left anterior descending coronary artery, 10.9% in the left circumflex coronary artery, 56.4% in the right coronary artery, < 0.01% in the left main coronary artery, and 1.7% in saphenous vein grafts. The probability of stent fracture was significantly higher in the right coronary artery than in the left anterior descending and left circumflex lesions (p < 0.01). Left main stents were less likely to fracture compared to those in all other vessels (p < 0.01). The probability of stent fracture was significantly increased in overlapping stents (7.5% vs 2.1%, p = 0.01) and long stents (46 vs 32.5 mm, p < 0.01). Lesions with stent fractures had higher rates of ISR (38% vs 8.2%, p < 0.01) and TLR (17% vs 5.6%, p < 0.01). Conversely, the probability of stent fractures was higher in patients with ISR (12.8% vs 2.1%, p < 0.01) and TLR (8.8% vs 2.7%, p < 0.01). In conclusion, although not always associated with clinical sequelae, the probability of ISR and TLR is increased with stent fracture. Conversely, the probability of stent fractures is increased in lesions with ISR or TLR, thus raising the need for surveillance and management guidelines for at-risk patients.

A meta-analysis of 3,773 patients treated with percutaneous coronary intervention or surgery for unprotected left main coronary artery stenosis.

OBJECTIVES: This study sought to understand the total weight of evidence regarding outcomes in coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in unprotected left main coronary artery (ULMCA) stenosis. BACKGROUND: Following a diagnosis of significant ULMCA stenosis in an individual that is a candidate for surgery, CABG is recommended by the American College of Cardiology/American Heart Association guidelines, whereas PCI is not recommended (Class III). METHODS: Databases were searched for clinical studies that reported outcomes after PCI and CABG for the treatment of ULMCA stenosis. Ten studies were identified that included a total of 3,773 patients. RESULTS: Meta-analysis showed that death, myocardial infarction, and stroke (major adverse cardiovascular or cerebrovascular events) were similar in the PCI- and CABG-treated patients at 1 year (odds ratio [OR]: 0.84 [95% confidence interval: 0.57 to 1.22]), 2 years (OR: 1.25 [95% CI: 0.81 to 1.94]), and 3 years (OR: 1.16 [95% CI: 0.68 to 1.98]). Target vessel revascularization was significantly higher in the PCI group at 1 year (OR: 4.36 [95% CI: 2.60 to 7.32]), 2 years (OR: 4.20 [95% CI: 2.21 to 7.97]), and 3 years (OR: 3.30 [95% CI: 0.96 to 11.33]). There was no difference in mortality in PCI- versus CABG-treated patients at 1 year (OR: 1.00 [95% CI: 0.70 to 1.41]), 2 years (OR: 1.27 [95% CI: 0.83 to 1.94]), and 3 years (OR: 1.11 [95% CI: 0.66 to 1.86]). CONCLUSIONS: Our analysis reveals no difference in mortality or major adverse cardiovascular or cerebrovascular events, for up to 3 years, between PCI and CABG for the treatment of ULMCA stenosis. However, PCI patients had a significantly higher risk of target vessel revascularization. In selected patients with ULMCA stenosis, PCI is emerging as an acceptable option.

New paradigms of myocardial regeneration post-infarction: tissue preservation, cell environment, and pluripotent cell sources.

Meta-analyses of intracoronary autologous bone marrow cell infusion in patients with acute myocardial infarction establish the procedure as safe. Nonetheless, the typical small increase in ejection fraction is of uncertain clinical significance, with little if any evidence of myocardial regeneration. In this paper, we describe 3 new paradigms of myocardial preservation and regeneration that provide reasonable hope that the goal of myocardial rejuvenation can be achieved. The first paradigm is that substantial preservation of myocardium is possible even during the period of coronary occlusion and immediate reperfusion, before interventions aimed at myocardial regeneration. The factors that induce myocardial preservation may also create an environment more receptive to subsequent myocardial regeneration. The second paradigm is that the local environment may regulate the behavior of cells in the ischemic/infarct region. For instance, adult cells may be induced to re-enter the cell cycle and proliferate with appropriate environmental modification. The final paradigm is that autologous cardiac stem cells or induced pluripotent stem cells can create new myocytes and myocardium. Taken together, these new ideas, each still to be proven, suggest that the goal of regenerating functioning new myocardium can still be achieved.

Compliance mismatch between stenotic and distal reference segment is associated with coronary artery disease instability.

OBJECTIVE: Inflammation and structural factors such as a thin fibrous cap, positive remodeling and large lipid pool have been established as factors associated with coronary plaque instability. This study aimed to investigate the hypothesis that the differential in coronary artery compliance between stenotic and adjacent arterial segments is another factor associated with unstable coronary disease. METHODS: Forty-one patients undergoing a percutaneous coronary intervention were classified as unstable coronary syndrome (n=19) or stable angina (n=22). Intravascular ultrasound was used to assess external elastic lamina (EEL) cross-sectional area at diastole and systole. Aortic pressure was determined from the coronary guiding catheter. Coronary cross-sectional compliance (C) was calculated as the quotient of systolic-to-diastolic area differential and pulse pressure. C was measured within the stenosis and the adjacent reference segments. RESULTS: EEL cross-sectional area was greater in systole than in diastole in the reference segments, but did not differ within the lesion site. C was greater in the distal reference than the stenotic segments (7.7+/-13.1 vs. 0.0+/-12.3mm(2)mmHg(-1)x10(3), p=0.003). When dichotomized by clinical presentation, the distal-to-stenosis compliance difference was only significant in the unstable coronary syndrome group (stable: distal 4.1+/-13.3 vs. stenosis -0.3+/-13.2mm(2)mmHg(-1)x10(3), ANOVA p=0.48; unstable: distal 11.9+/-11.9 vs. stenosis 0.1+/-11.6mm(2)mmHg(-1)x10(3), ANOVA p=0.006, distal-to-stenosis difference p=0.001). CONCLUSIONS: A difference between stenotic and distal reference segment coronary compliance was evident in unstable, but not stable coronary artery disease patients. Coronary compliance differential would increase cyclical forces in the plaque shoulder region, which may contribute to plaque disruption.

Apical ballooning syndrome during treatment with a vascular endothelial growth factor receptor antagonist.

Apical ballooning syndrome (ABS) describes acute regional myocardial dysfunction and has a strong association with emotional stress and female sex. Whilst catecholamine excess has been described in this condition, the precise etiology remains elusive. We report the atypical case of a 61 year old male who developed ABS in the absence of a clear precipitant. His concurrent treatment with a vascular endothelial growth factor (VEGF) receptor antagonist may provide an insight into the pathogenesis of this enigmatic condition. We present a biologically plausible explanation as to why VEGF antagonism may have an important role through its modulation of nitric oxide and catecholamine effects. This hypothesis may also provide an important insight into the cardiovascular toxicities associated with this class of drug. In addition, we report the success of treatment with a beta blocker in ABS complicated by a severe left ventricular outflow tract obstruction.