Radial versus femoral access in patients with acute coronary syndromes undergoing invasive management: a randomised multicentre trial.

BACKGROUND It is unclear whether radial compared with femoral access improves outcomes in unselected patients with acute coronary syndromes undergoing invasive management. METHODS We did a randomised, multicentre, superiority trial comparing transradial against transfemoral access in patients with acute coronary syndrome with or without ST-segment elevation myocardial infarction who were about to undergo coronary angiography and percutaneous coronary intervention. Patients were randomly allocated (1:1) to radial or femoral access with a web-based system. The randomisation sequence was computer generated, blocked, and stratified by use of ticagrelor or prasugrel, type of acute coronary syndrome (ST-segment elevation myocardial infarction, troponin positive or negative, non-ST-segment elevation acute coronary syndrome), and anticipated use of immediate percutaneous coronary intervention. Outcome assessors were masked to treatment allocation. The 30-day coprimary outcomes were major adverse cardiovascular events, defined as death, myocardial infarction, or stroke, and net adverse clinical events, defined as major adverse cardiovascular events or Bleeding Academic Research Consortium (BARC) major bleeding unrelated to coronary artery bypass graft surgery. The analysis was by intention to treat. The two-sided α was prespecified at 0·025. The trial is registered at ClinicalTrials.gov, number NCT01433627. FINDINGS We randomly assigned 8404 patients with acute coronary syndrome, with or without ST-segment elevation, to radial (4197) or femoral (4207) access for coronary angiography and percutaneous coronary intervention. 369 (8·8%) patients with radial access had major adverse cardiovascular events, compared with 429 (10·3%) patients with femoral access (rate ratio [RR] 0·85, 95% CI 0·74-0·99; p=0·0307), non-significant at α of 0·025. 410 (9·8%) patients with radial access had net adverse clinical events compared with 486 (11·7%) patients with femoral access (0·83, 95% CI 0·73-0·96; p=0·0092). The difference was driven by BARC major bleeding unrelated to coronary artery bypass graft surgery (1·6% vs 2·3%, RR 0·67, 95% CI 0·49-0·92; p=0·013) and all-cause mortality (1·6% vs 2·2%, RR 0·72, 95% CI 0·53-0·99; p=0·045). INTERPRETATION In patients with acute coronary syndrome undergoing invasive management, radial as compared with femoral access reduces net adverse clinical events, through a reduction in major bleeding and all-cause mortality. FUNDING The Medicines Company and Terumo.

Comparative Effectiveness and Safety of New-Generation Versus Early-Generation Drug-Eluting Stents According to Complexity of Coronary Artery Disease: A Patient-Level Pooled Analysis of 6,081 Patients.

OBJECTIVES The purpose of this study was to compare the 2-year safety and effectiveness of new- versus early-generation drug-eluting stents (DES) according to the severity of coronary artery disease (CAD) as assessed by the SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score. BACKGROUND New-generation DES are considered the standard-of-care in patients with CAD undergoing percutaneous coronary intervention. However, there are few data investigating the effects of new- over early-generation DES according to the anatomic complexity of CAD. METHODS Patient-level data from 4 contemporary, all-comers trials were pooled. The primary device-oriented clinical endpoint was the composite of cardiac death, myocardial infarction, or ischemia-driven target-lesion revascularization (TLR). The principal effectiveness and safety endpoints were TLR and definite stent thrombosis (ST), respectively. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated at 2 years for overall comparisons, as well as stratified for patients with lower (SYNTAX score ≤11) and higher complexity (SYNTAX score >11). RESULTS A total of 6,081 patients were included in the study. New-generation DES (n = 4,554) compared with early-generation DES (n = 1,527) reduced the primary endpoint (HR: 0.75 [95% CI: 0.63 to 0.89]; p = 0.001) without interaction (p = 0.219) between patients with lower (HR: 0.86 [95% CI: 0.64 to 1.16]; p = 0.322) versus higher CAD complexity (HR: 0.68 [95% CI: 0.54 to 0.85]; p = 0.001). In patients with SYNTAX score >11, new-generation DES significantly reduced TLR (HR: 0.36 [95% CI: 0.26 to 0.51]; p < 0.001) and definite ST (HR: 0.28 [95% CI: 0.15 to 0.55]; p < 0.001) to a greater extent than in the low-complexity group (TLR pint = 0.059; ST pint = 0.013). New-generation DES decreased the risk of cardiac mortality in patients with SYNTAX score >11 (HR: 0.45 [95% CI: 0.27 to 0.76]; p = 0.003) but not in patients with SYNTAX score ≤11 (pint = 0.042). CONCLUSIONS New-generation DES improve clinical outcomes compared with early-generation DES, with a greater safety and effectiveness in patients with SYNTAX score >11.

Anaesthetic induction with etomidate in cardiac surgery: A randomised controlled trial.

BACKGROUND Etomidate is perceived as preserving haemodynamic stability during induction of anaesthesia. It is also associated with adrenocortical dysfunction. The risk/benefit relationship is controversial. OBJECTIVES We tested the hypotheses that single-dose etomidate increases cumulative vasopressor requirement, time to extubation and length of stay in the ICU. DESIGN Double-blind randomised controlled trial. SETTING Bern University Hospital, Switzerland, from November 2006 to December 2009. PATIENTS There were 90 patients undergoing coronary artery bypass grafts (CABG) and 40 patients undergoing mitral valve surgery (MVS). Reasons for noninclusion were known adrenocortical insufficiency, use of etomidate or propofol within 1 week preoperatively, use of glucocorticoids within 6 months preoperatively, severe renal or liver dysfunction, or carotid stenosis. INTERVENTIONS CABG patients were allocated randomly to receive either etomidate 0.15 mg kg with placebo, propofol 1.5 mg kg with placebo or etomidate 0.15 mg kg with hydrocortisone (n = 30 in each arm). Risk stratification (low vs. high) was achieved by block randomisation. MVS patients received either etomidate 0.15 mg kg or propofol 1.5 mg kg (n = 20 in each arm). MAIN OUTCOME MEASURES Cumulative vasopressor requirements, incidence of adrenocortical insufficiency, length of time to extubation and length of stay in ICU. RESULTS Cumulative vasopressor requirements 24 h after induction did not differ between treatments in patients who underwent CABG, whereas more noradrenaline was used in MVS patients following propofol induction (absolute mean difference 5.86 μg kg over 24 h P = 0.047). The incidence of relative adrenocortical insufficiency was higher after etomidate alone than propofol (CABG 83 vs. 37%, P < 0.001; MVS: 95 vs. 35%, P < 0.001). The time to extubation, length of stay in ICU and 30-day mortality did not differ among treatments. Within low and high-risk subgroups, no differences in vasopressor use or outcomes were found. CONCLUSION In elective cardiac surgery, laboratory indicators of etomidate-induced adrenal insufficiency do not translate into increased vasopressor requirement or inferior early outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT 00415701.

Impact of Diabetic Status on Outcomes After Revascularization With Drug-Eluting Stents in Relation to Coronary Artery Disease Complexity: Patient-Level Pooled Analysis of 6081 Patients.

BACKGROUND Diabetes mellitus and angiographic coronary artery disease complexity are intertwined and unfavorably affect prognosis after percutaneous coronary interventions, but their relative impact on long-term outcomes after percutaneous coronary intervention with drug-eluting stents remains controversial. This study determined drug-eluting stents outcomes in relation to diabetic status and coronary artery disease complexity as assessed by the Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) score. METHODS AND RESULTS In a patient-level pooled analysis from 4 all-comers trials, 6081 patients were stratified according to diabetic status and according to the median SYNTAX score ≤11 or >11. The primary end point was major adverse cardiac events, a composite of cardiac death, myocardial infarction, and clinically indicated target lesion revascularization within 2 years. Diabetes mellitus was present in 1310 patients (22%), and new-generation drug-eluting stents were used in 4554 patients (75%). Major adverse cardiac events occurred in 173 diabetics (14.5%) and 436 nondiabetic patients (9.9%; P<0.001). In adjusted Cox regression analyses, SYNTAX score and diabetes mellitus were both associated with the primary end point (P<0.001 and P=0.028, respectively; P for interaction, 0.07). In multivariable analyses, diabetic versus nondiabetic patients had higher risks of major adverse cardiac events (hazard ratio, 1.25; 95% confidence interval, 1.03-1.53; P=0.026) and target lesion revascularization (hazard ratio, 1.54; 95% confidence interval, 1.18-2.01; P=0.002) but similar risks of cardiac death (hazard ratio, 1.41; 95% confidence interval, 0.96-2.07; P=0.08) and myocardial infarction (hazard ratio, 0.89; 95% confidence interval, 0.64-1.22; P=0.45), without significant interaction with SYNTAX score ≤11 or >11 for any of the end points. CONCLUSIONS In this population treated with predominantly new-generation drug-eluting stents, diabetic patients were at increased risk for repeat target-lesion revascularization consistently across the spectrum of disease complexity. The SYNTAX score was an independent predictor of 2-year outcomes but did not modify the respective effect of diabetes mellitus. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00297661, NCT00389220, NCT00617084, and NCT01443104.

Prospective gated 64 slice computed tomography in assessment of coronary artery disease: A single center experience and relationship of body mass index to outcomes

Coronary artery disease (CAD) is the most common cause of morbidity and mortality in the United States. While Coronary Angiography (CA) is the gold standard test to investigate coronary artery disease, Prospective gated-64 Slice Computed Tomography (Prosp-64CT) is a new non-invasive technology that uses the 64Slice computed tomography (64CT) with electrocardiographic gating to investigate coronary artery disease. The aim of the current study was to investigate the role of Body Mass Index (BMI) as a factor affecting occurrence of CA after a Prosp-64CT, as well as the quality of the Prosp-64CT. Demographic and clinical characteristics of the study population were described. A secondary analysis of data on patients who underwent a Prosp-64CT for evaluation of coronary artery disease was performed. Seventy seven patients who underwent Prosp-64CT for evaluation for coronary artery disease were included. Fifteen patients were excluded because they had missing data regarding BMI, quality of the Prosp-64CT or CA. Thus, a total of 62 patients were included in the final analysis. The mean age was 56.2 years. The mean BMI was 31.3 kg/m 2. Eight (13%) patients underwent a CA within one month of Prosp-64CT. Eight (13%) patients had a poor quality Prosp-64CT. There was significant association of higher BMI as a factor for occurrence of CA post Prosp-64CT (P<0.05). There was a trend, but no statistical significance was observed for the association of being obese and occurrence of CA (P=0.06). BMI, as well as obesity, were not found to be significantly associated with poor quality of Prosp-64CT (P=0.19 and P=0.76, respectively). In conclusion, BMI was significantly associated with occurrence of CA within one month of Prosp-64CT. Thus, in patients with a higher BMI, diagnostic investigation with both tests could be avoided; rather, only a CA could be performed. However, the relationship of BMI to quality of Prosp-64CT needs to be further investigated since the sample size of the current study was small.^

A case-comparison study of weight fluctuations during young adulthood and coronary artery disease during middle age

The hypothesis that large fluctuations in weight during young adulthood are associated with the degree of coronary artery disease was investigated by comparing patterns of weight change of patients with angiographically defined diseased or normal arteries. Participants (n = 823) were selected from men and women aged 40-74 years who had undergone angiography at North Carolina Baptist Hospital during 1987-88. Weight history from age 20 to 40 was assessed with a mailed questionnaire. Per cent prevalence of "yo-yo dieting" adjusted for age, race, and coronary disease risk factors in patients who had 0, 1, 2, 3, or more than 3 diseased arteries was 8.6, 8.8, 3.7, 5.6 and 7.1 per cent respectively (p = 0.313). These results do not support the research hypothesis. However, since the results may have been confound by neuroticism, they should not be interpreted as strong evidence against this hypothesis. ^

Vascular engineering for bypass surgery

Since the introduction of synthetic vascular grafts in the 1960s, only two-stage endothelial cell seeding has demonstrated any significant improvement over conventional vascular grafts, and its benefits have yet to be demonstrated on a large scale. Tissue engineering is a rapidly expanding field with great potential, but efforts to construct tissue-engineered arterial grafts have, to date, yielded little clinical success. This review explores the latest approaches to the construction of a superior vascular graft, along with its potential for use in the clinic in the future.

Assessment of statistical change criteria used to define significant change in neuropsychological test performance following cardiac surgery

Objective: This paper compares four techniques used to assess change in neuropsychological test scores before and after coronary artery bypass graft surgery (CABG), and includes a rationale for the classification of a patient as overall impaired. Methods: A total of 55 patients were tested before and after surgery on the MicroCog neuropsychological test battery. A matched control group underwent the same testing regime to generate test–retest reliabilities and practice effects. Two techniques designed to assess statistical change were used: the Reliable Change Index (RCI), modified for practice, and the Standardised Regression-based (SRB) technique. These were compared against two fixed cutoff techniques (standard deviation and 20% change methods). Results: The incidence of decline across test scores varied markedly depending on which technique was used to describe change. The SRB method identified more patients as declined on most measures. In comparison, the two fixed cutoff techniques displayed relatively reduced sensitivity in the detection of change. Conclusions: Overall change in an individual can be described provided the investigators choose a rational cutoff based on likely spread of scores due to chance. A cutoff value of ≥20% of test scores used provided acceptable probability based on the number of tests commonly encountered. Investigators must also choose a test battery that minimises shared variance among test scores.

Endothelin A receptor localization in the internal mammary artery

Introduction: The vasoconstricting peptide endothelin-1 (ET-1) binds two G-protein-coupled receptor subtypes, the Endothelin A (ETA) and Endothelin B (ETB) receptors. The ETB receptor subtype has been predominantly localised to the arterial and venous endothelial cells both in-vivo and in culture. Stimulation of ET-1 through this receptor subtype can modulate the expression of endothelial nitric oxide and accelerate endothelial cell wound healing. In comparison the ETA receptor is abundantly expressed in medial vascular smooth muscle cells and mediates the vasoconstrictor action of ET-1 and is thought to play a key role in angiogenesis. Aims: To determine the levels of ETA receptor expression and localisation in the internal mammary artery (IMA). Methods: Twenty-four IMA sections were examined from patients undergoing coronary artery bypass (CABG) surgery (5F; 19M; mean age 67 years). And 14 organ donor IMA specimens were used as controls (7M; 7F; mean age 45 years. The tissue was fixed in formalin and processed for histology. Immunohistochemistry was performed on cross-sections of the left distal IMA to assess the areas of ETA receptor staining. The percentage are of ETA receptor staining in the media was calculated using image analysis software connected to an optical microscope and semiquantitative assessment was used to grade staining intensity, that is, mild (+), moderate (++) and strong (+++). Results: ETA receptor staining was significantly elevated in the media of the CABG specimens compared with the donor controls (46.88+/11.52% Vs 18.58+/7.65%, P = .0001). Interestingly, the endothelium (++) of the IMA, as well as the small microvessels in the adventitia (+++) stained positive for ETA receptor expression. Without using a haematoxylin counterstain, the nuclei of the cell stained more intensely (+++) with respect to the cytoplasm in both the medial smooth muscle (++) and endothelial cells (++). Fibroblasts in the medial adventitia junction were also positive for ETA receptor expression (+++). Further, this receptor subtype was also strongly expressed by inflammatory cells (monocytes and macrophages). Conclusions: These results demonstrate that the ETA receptor expression is increased in the medial SMC layer of the CABG IMA specimens and also present in the endothelium, vasa vasorum, fibroblasts and inflammatory cell types. Thus it is possible that in addition to affecting vascular tone, ET-1 may play an important role in IMA remodelling.

Sternal wound dehiscence from intense coughing in a cardiac surgery patient: could it be prevented?

This case report is on a obese patient who underwent a coronary artery bypass. The immediate postoperative phase, on the 8th day, was characterized by sternal dehiscence with diastasis, from intense coughing. At present, for obese patients there are not any guidelines aimed to prevent the sternal diastasis. The use of a sternum support vest after median sternotomy could be a valuable tool in the postoperative care of our patients, in order to avoid chest wall hyperexpansion and to prevent sternal wound dehiscence and diastasis.

Patients' satisfaction and quality of life in coronary artery disease

OBJECTIVES: To assess satisfaction of survivors of coronary artery diseases (CAD) with healthcare services and to determine whether specific components of standard health-related quality of life (HRQL) assessment tools might identify areas of satisfaction and dissatisfaction. METHOD: A specific tool developed to provide a comprehensive assessment of healthcare needs was administered concomitantly with generic and specific HRQL instruments, on 242 patients with CAD, admitted to an acute coronary unit during a single year. RESULTS: 92.5% of patients confirmed their trust in and satisfaction with the care given by their General Practitioner; even so, one third experienced difficulty getting an appointment and a quarter wanted more time for each consultation or prompt referral to a specialist when needed. Around a third expressed dissatisfaction with advice from the practice nurse or hospital consultant. Overall 54% were highly satisfied with services, 33% moderately satisfied and 13% dissatisfied.Cronbach's alpha was 0.87; the corrected total-item correlation ranged between 0.55-0.75, with trivial 'floor' score and low 'ceiling' effect. Several domains in all three HRQL tools correlated with items relating to satisfaction. The Seattle Angina Questionnaire Treatment Score correlated significantly with all satisfaction items and with the global satisfaction score. CONCLUSION: Cardiac patients' demanded better services and advice from, and more time with, health professionals and easier surgery access. The satisfaction tool showed acceptable psychometric properties. In this patient group, disease-specific HRQL tools seem more appropriate than generic tools for surveys of patient satisfaction

Application of data mining techniques in the prediction of coronary artery disease : use of anaesthesia time-series and patient risk factor data

The high morbidity and mortality associated with atherosclerotic coronary vascular disease (CVD) and its complications are being lessened by the increased knowledge of risk factors, effective preventative measures and proven therapeutic interventions. However, significant CVD morbidity remains and sudden cardiac death continues to be a presenting feature for some subsequently diagnosed with CVD. Coronary vascular disease is also the leading cause of anaesthesia related complications. Stress electrocardiography/exercise testing is predictive of 10 year risk of CVD events and the cardiovascular variables used to score this test are monitored peri-operatively. Similar physiological time-series datasets are being subjected to data mining methods for the prediction of medical diagnoses and outcomes. This study aims to find predictors of CVD using anaesthesia time-series data and patient risk factor data. Several pre-processing and predictive data mining methods are applied to this data. Physiological time-series data related to anaesthetic procedures are subjected to pre-processing methods for removal of outliers, calculation of moving averages as well as data summarisation and data abstraction methods. Feature selection methods of both wrapper and filter types are applied to derived physiological time-series variable sets alone and to the same variables combined with risk factor variables. The ability of these methods to identify subsets of highly correlated but non-redundant variables is assessed. The major dataset is derived from the entire anaesthesia population and subsets of this population are considered to be at increased anaesthesia risk based on their need for more intensive monitoring (invasive haemodynamic monitoring and additional ECG leads). Because of the unbalanced class distribution in the data, majority class under-sampling and Kappa statistic together with misclassification rate and area under the ROC curve (AUC) are used for evaluation of models generated using different prediction algorithms. The performance based on models derived from feature reduced datasets reveal the filter method, Cfs subset evaluation, to be most consistently effective although Consistency derived subsets tended to slightly increased accuracy but markedly increased complexity. The use of misclassification rate (MR) for model performance evaluation is influenced by class distribution. This could be eliminated by consideration of the AUC or Kappa statistic as well by evaluation of subsets with under-sampled majority class. The noise and outlier removal pre-processing methods produced models with MR ranging from 10.69 to 12.62 with the lowest value being for data from which both outliers and noise were removed (MR 10.69). For the raw time-series dataset, MR is 12.34. Feature selection results in reduction in MR to 9.8 to 10.16 with time segmented summary data (dataset F) MR being 9.8 and raw time-series summary data (dataset A) being 9.92. However, for all time-series only based datasets, the complexity is high. For most pre-processing methods, Cfs could identify a subset of correlated and non-redundant variables from the time-series alone datasets but models derived from these subsets are of one leaf only. MR values are consistent with class distribution in the subset folds evaluated in the n-cross validation method. For models based on Cfs selected time-series derived and risk factor (RF) variables, the MR ranges from 8.83 to 10.36 with dataset RF_A (raw time-series data and RF) being 8.85 and dataset RF_F (time segmented time-series variables and RF) being 9.09. The models based on counts of outliers and counts of data points outside normal range (Dataset RF_E) and derived variables based on time series transformed using Symbolic Aggregate Approximation (SAX) with associated time-series pattern cluster membership (Dataset RF_ G) perform the least well with MR of 10.25 and 10.36 respectively. For coronary vascular disease prediction, nearest neighbour (NNge) and the support vector machine based method, SMO, have the highest MR of 10.1 and 10.28 while logistic regression (LR) and the decision tree (DT) method, J48, have MR of 8.85 and 9.0 respectively. DT rules are most comprehensible and clinically relevant. The predictive accuracy increase achieved by addition of risk factor variables to time-series variable based models is significant. The addition of time-series derived variables to models based on risk factor variables alone is associated with a trend to improved performance. Data mining of feature reduced, anaesthesia time-series variables together with risk factor variables can produce compact and moderately accurate models able to predict coronary vascular disease. Decision tree analysis of time-series data combined with risk factor variables yields rules which are more accurate than models based on time-series data alone. The limited additional value provided by electrocardiographic variables when compared to use of risk factors alone is similar to recent suggestions that exercise electrocardiography (exECG) under standardised conditions has limited additional diagnostic value over risk factor analysis and symptom pattern. The effect of the pre-processing used in this study had limited effect when time-series variables and risk factor variables are used as model input. In the absence of risk factor input, the use of time-series variables after outlier removal and time series variables based on physiological variable values’ being outside the accepted normal range is associated with some improvement in model performance.

New drugs for the treatment of coronary artery syndromes

Background: Acute coronary syndromes are a major cause of mortality and morbidity. Objectives/Methods: The objective of this evaluation is to review the clinical trials of two new drugs being developed for the treatment of acute coronary syndromes. The first drug is the anti-coagulant otamixaban, and the trial compared otamixaban with unfractionated heparin and eptifibatide in acute coronary syndromes. The second drug is the anti-platelet ticagrelor, and the trial compared ticagrelor with clopidogrel in acute coronary syndromes. Results: In the SEPIA-ACS1 TIMI 42 trial, the primary efficacy endpoint occurred in 6.2% of subjects treated with unfractionated heparin and eptifibatide, and to a significantly lesser extent with otamixaban. In the PLATO trial, the primary efficacy endpoint had occurred less in the ticagrelor group (9.8%) than in the clopidogrel group (11.7%) at 12 months. Conclusions: Two new drugs for acute coronary syndromes, otamixaban and ticagrelor, have recently been shown to have benefits in subjects undergoing percutaneous interventions compared to the present standard regimens for this condition.

Human atrial beta1L-adrenoceptor but not beta3-adrenoceptor activation increases force and Ca2+ current at physiological temperature

BACKGROUND AND PURPOSE It has been proposed that BRL37344, SR58611 and CGP12177 activate b3-adrenoceptors in human atrium to increase contractility and L-type Ca2+ current (ICa-L). b3-adrenoceptor agonists are potentially beneficial for the treatment of a variety of diseases but concomitant cardiostimulation would be potentially harmful. It has also been proposed that (-)-CGP12177 activates the low affinity binding site of the b1-adrenoceptor in human atrium. We therefore used BRL37344, SR58611 and (-)-CGP12177 with selective b-adrenoceptor subtype antagonists to clarify cardiostimulant b-adrenoceptor subtypes in human atrium. EXPERIMENTAL APPROACH Human right atrium was obtained from patients without heart failure undergoing coronary artery bypass or valve surgery. Cardiomyocytes were prepared to test BRL37344, SR58611 and CGP12177 effects on ICa-L. Contractile effects were determined on right atrial trabeculae. KEY RESULTS BRL37344 increased force which was antagonized by blockade of b1- and b2-adrenoceptors but not by blockade of b3-adrenoceptors with b3-adrenoceptor-selective L-748,337 (1 mM). The b3-adrenoceptor agonist SR58611 (1 nM–10 mM) did not affect atrial force. BRL37344 and SR58611 did not increase ICa-L at 37°C, but did at 24°C which was prevented by L-748,337. (-)-CGP12177 increased force and ICa-L at both 24°C and 37°C which was prevented by (-)-bupranolol (1–10 mM), but not L-748,337. CONCLUSIONS AND IMPLICATIONS We conclude that the inotropic responses to BRL37344 are mediated through b1- and b2-adrenoceptors. The inotropic and ICa-L responses to (-)-CGP12177 are mediated through the low affinity site b1L-adrenoceptor of the b1-adrenoceptor. b3-adrenoceptor-mediated increases in ICa-L are restricted to low temperatures. Human atrial b3-adrenoceptors do not change contractility and ICa-L at physiological temperature.