Emerging Biomarkers in Acute Coronary Syndromes - A Pathophysiologic Perspective.

Diagnosis and prognostication in acute coronary syndromes (ACS) is achieved using a combination of clinical factors and biomarkers, notably cardiac troponin and B type natriuretic peptide and its N terminal fragment NT-proBNP. However, there are numerous biomarkers that have been shown to be associated with ACS, with variable incremental utility. This brief review focusses on some promising emerging biomarkers in ACS, discussed according to pathophysiologic mechanism, as well as diagnostic and prognostic utility.

Impact of chronic kidney disease on mortality and cardiovascular outcomes after acute coronary syndrome: A nationwide data linkage study (ANZACS-QI 44).

AIMS: Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease (CVD). We examined the characteristics, management and outcomes of patients with CKD in the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) national registry. METHODS: The cohort comprised New Zealand (NZ) patients with an acute coronary syndrome undergoing coronary angiography between January 2013 and December 2016. Patients were categorized according to their stage of CKD. Outcomes included all-cause and cause-specific mortality and hospitalization with myocardial infarction (MI), stroke and major bleeding. RESULTS: Of the 20 604 patients, 20.3% had normal renal function, with 53.3%, 23.3%, 1.7% and 1.4% having CKD stages 2, 3, 4 and 5 CKD, respectively. Patients with severe CKD were more likely to be Maori or Pacific and live in an area with greater socioeconomic deprivation. Death, recurrent MI or stroke, and major bleeding all increased incrementally with each worsening stage of CKD severity. Compared with those with normal renal function, patients with stage 5 CKD had a much higher all-cause (hazard ratio [HR] 16.41, 95% CI 13.06-20.61), cardiovascular (HR 16.38, 95% CI 12.17-22.04) and non-cardiovascular mortality (HR 13.66 9, 95% CI.56-19.51). In addition, patients with stage 5 CKD were at a higher risk of recurrent MI or stroke (HR 4.73, 95% CI 3.86-5.80) and bleeding (HR 5.84, 95% CI 4.39-7.76). CONCLUSION: CKD was associated with increased mortality and a high incidence of morbidity in patients undergoing coronary angiography in New Zealand. Initiatives to understand and improve outcomes in this group of patients are urgently needed.

Polygenic Risk Scores in Coronary Artery Disease and Atrial Fibrillation.

Coronary artery disease (CAD) and atrial fibrillation (AF) are two highly prevalent cardiovascular disorders that are associated with substantial morbidity and mortality. Conventional clinical risk factors for these disorders may not be identified prior to mid-adult life when pathophysiological processes are already established. A better understanding of the genetic underpinnings of disease should facilitate early detection of individuals at risk and preventative intervention. Single rare variants of large effect size that are causative for CAD, AF, or predisposing factors such as hypertension or hyperlipidaemia, may give rise to familial forms of disease. However, in most individuals, CAD and AF are complex traits in which combinations of genetic and acquired factors play a role. Common genetic variants that affect disease susceptibility have been identified by genome-wide association studies, but the predictive value of any single variant is limited. To address this issue, polygenic risk scores (PRS), comprised of suites of disease-associated common variants have been devised. In CAD and AF, incorporation of PRS into risk stratification algorithms has provided incremental prognostic information to clinical factors alone. The long-term health and economic benefits of PRS-guided clinical management remain to be determined however, and further evidence-based data are required.

Clinical Characteristics and Burden of Risk Factors Among Patients With Early Onset Acute Coronary Syndromes: The ANZACS-QI New Zealand National Cohort (ANZACS-QI 17).

BACKGROUND: Cardiovascular (CV) risk factor profiles of people experiencing acute coronary syndromes (ACS) vary with age, and in New Zealand (NZ), Maori and people of Pacific Island descent typically present with ACS at a younger age. We aimed to explore age- and ethnicity-related differences in CV risk factors in a large NZ cohort with first-time ACS. METHODS: The All NZ Acute Coronary Syndrome Quality Improvement program (ANZACS-QI) registry collects comprehensive data for patients admitted with ACS at NZ hospitals. This analysis includes patients with no prior atherosclerotic CV disease enrolled from 1 July, 2012 to 30 June, 2015. RESULTS: 14,190 patients had confirmed ACS, 8493 (60%) patients with no prior CVD comprised the study cohort. The mean age was 64 years, 25% were aged <55years, and 66% were male. Those aged <55years were more likely than older patients to be current smokers (48% vs 19%), have higher body mass index (BMI) (48% vs 34% with BMI≥30kg/m2), and higher total cholesterol:HDL ratios (≥4.0, 70% vs 50%), all p<0.001. Sixteen per cent of those <55years had diabetes; these patients often had a BMI≥30kg/m2 (67%) and higher median HbA1c than older patients with diabetes (69mmol/mol vs 55mmol/mol). Maori and people of Pacific Island descent were overrepresented in the younger age group; these patients had a very high risk factor burden. CONCLUSIONS: A quarter of NZ patients admitted to hospital with a first-time CV disease event are aged <55years. Younger patients have a very high risk factor burden: half are current smokers, half have a BMI≥30kg/m2, and 16% have diabetes.

Call to action-the urgent need for a heart health plan in New Zealand.

Cardiovascular diseases are responsible for almost 10,000 deaths annually in Aotearoa New Zealand. Almost a quarter of these are avoidable, increasing to half of all cardiovascular deaths for Maori and Pacific people. Health system reforms are an opportunity to set clear ambitious goals for improved heart health. This has been done for smoking, a cancer plan, mental health and diabetes among other health conditions. Given the scale of avoidable heart disease and avoidable heart health inequity, much of it due to people simply not accessing existing treatment options, there is no excuse not to deliver a national heart health action plan and we urge health policy makers to put it on the agenda.

Correcting bias in cardiac geometries derived from multimodal images using spatiotemporal mapping.

Cardiovascular imaging studies provide a multitude of structural and functional data to better understand disease mechanisms. While pooling data across studies enables more powerful and broader applications, performing quantitative comparisons across datasets with varying acquisition or analysis methods is problematic due to inherent measurement biases specific to each protocol. We show how dynamic time warping and partial least squares regression can be applied to effectively map between left ventricular geometries derived from different imaging modalities and analysis protocols to account for such differences. To demonstrate this method, paired real-time 3D echocardiography (3DE) and cardiac magnetic resonance (CMR) sequences from 138 subjects were used to construct a mapping function between the two modalities to correct for biases in left ventricular clinical cardiac indices, as well as regional shape. Leave-one-out cross-validation revealed a significant reduction in mean bias, narrower limits of agreement, and higher intraclass correlation coefficients for all functional indices between CMR and 3DE geometries after spatiotemporal mapping. Meanwhile, average root mean squared errors between surface coordinates of 3DE and CMR geometries across the cardiac cycle decreased from 7 ± 1 to 4 ± 1 mm for the total study population. Our generalised method for mapping between time-varying cardiac geometries obtained using different acquisition and analysis protocols enables the pooling of data between modalities and the potential for smaller studies to leverage large population databases for quantitative comparisons.

Prognostic modelling of clinical outcomes after first-time acute coronary syndrome in New Zealand.

OBJECTIVE: The Multi-Ethnic New Zealand Study of Acute Coronary Syndromes (MENZACS) was established to investigate the drivers of secondary events after first-time acute coronary syndrome (ACS), including addressing inequitable outcomes by ethnicity. Herein, the first clinical outcomes and prognostic modelling approach are reported. METHODS: First, in 28 176 New Zealanders with first-time ACS from a national registry, a clinical summary score for predicting 1-year death/cardiovascular readmission was created using Cox regression of 20 clinical variables. This score was then calculated in the 2015 participant MENZACS study to represent clinical risk. In MENZACS, Cox regression was used to assess N-terminal pro-B-type natriuretic peptide (NT-proBNP) as a prognostic marker for death/cardiovascular readmission in four models, adjusting for (1) age and sex; (2) age, sex, ethnicity; (3) clinical summary score; (4) clinical summary score and ethnicity. RESULTS: Of the 2015 MENZACS participants (mean age 61 years, 79% male, 73% European, 14% Maori, 5% Pacific people), 2003 were alive at discharge. Of the 2003, 416 (20.8%) experienced all-cause death/cardiovascular readmission over a median of 3.5 years. In a simple model, age, male sex, Maori ethnicity and NT-proBNP levels were significant predictors of outcome. After adjustment for the clinical summary score, which includes age and sex, NT-proBNP and ethnicity were no longer statistically significant: log2(NT-proBNP) hazard ratio (HR) 1.03, 95% confidence interval (95% CI) 0.98 to 1.08, p=0.305; Maori ethnicity HR 1.26, 95% CI 0.97 to 1.62, p=0.084. CONCLUSIONS: In 2015 patients with first-time ACS, recurrent events were common (20.8%). Increasing NT-proBNP levels and Maori ethnicity were predictors of death/cardiovascular readmission, but not after adjustment for the 20 clinical risk factors represented by the clinical summary score. TRIAL REGISTRATION NUMBER: ACTRN12615000676516.

MITEA: A dataset for machine learning segmentation of the left ventricle in 3D echocardiography using subject-specific labels from cardiac magnetic resonance imaging.

Segmentation of the left ventricle (LV) in echocardiography is an important task for the quantification of volume and mass in heart disease. Continuing advances in echocardiography have extended imaging capabilities into the 3D domain, subsequently overcoming the geometric assumptions associated with conventional 2D acquisitions. Nevertheless, the analysis of 3D echocardiography (3DE) poses several challenges associated with limited spatial resolution, poor contrast-to-noise ratio, complex noise characteristics, and image anisotropy. To develop automated methods for 3DE analysis, a sufficiently large, labeled dataset is typically required. However, ground truth segmentations have historically been difficult to obtain due to the high inter-observer variability associated with manual analysis. We address this lack of expert consensus by registering labels derived from higher-resolution subject-specific cardiac magnetic resonance (CMR) images, producing 536 annotated 3DE images from 143 human subjects (10 of which were excluded). This heterogeneous population consists of healthy controls and patients with cardiac disease, across a range of demographics. To demonstrate the utility of such a dataset, a state-of-the-art, self-configuring deep learning network for semantic segmentation was employed for automated 3DE analysis. Using the proposed dataset for training, the network produced measurement biases of -9 ± 16 ml, -1 ± 10 ml, -2 ± 5 %, and 5 ± 23 g, for end-diastolic volume, end-systolic volume, ejection fraction, and mass, respectively, outperforming an expert human observer in terms of accuracy as well as scan-rescan reproducibility. As part of the Cardiac Atlas Project, we present here a large, publicly available 3DE dataset with ground truth labels that leverage the higher resolution and contrast of CMR, to provide a new benchmark for automated 3DE analysis. Such an approach not only reduces the effect of observer-specific bias present in manual 3DE annotations, but also enables the development of analysis techniques which exhibit better agreement with CMR compared to conventional methods. This represents an important step for enabling more efficient and accurate diagnostic and prognostic information to be obtained from echocardiography.

Left ventricular systolic and diastolic function assessed by tissue Doppler imaging and outcome in asymptomatic aortic stenosis.

AIMS: Left ventricular (LV) hypertrophy and abnormal non-invasive measures of LV diastolic function are common in patients with severe aortic stenosis (AS) but their prognostic importance is uncertain. This study aimed to determine whether tissue Doppler measures of LV systolic and/or diastolic function or echocardiographic LV hypertrophy are useful for risk stratifying asymptomatic patients with severe calcific AS. METHODS AND RESULTS: One hundred and eighty-three initially asymptomatic patients with moderate or severe AS (valve area mean 0.96 ± SD 0.3 cm(2)) and a normal LV ejection fraction were followed for median 31 (IQR 14-40) months. Peak systolic (S') and diastolic (E') mitral annular velocities and LV mass were measured by echocardiography at baseline and during follow-up. During follow-up 106 (58%) patients suffered symptomatic deterioration, including three sudden deaths and one resuscitated cardiac arrest. Peak aortic velocity (for 0.5 m/s increase HR = 1.43, 95% CI 1.25, 1.64, P < 0.0001) and aortic valve area (-0.1 cm(2)/m(2) HR = 1.23, 95% CI 1.12, 1.35, P = 0.004) at baseline were most strongly associated with symptomatic deterioration. After peak aortic velocity adjustment neither LV mass index nor any measure of LV systolic or diastolic function was associated with symptomatic deterioration (P > 0.2 for all). CONCLUSION: In patients with calcific AS who have a normal LV ejection fraction the severity of stenosis is the most important correlate of symptomatic deterioration. Tissue Doppler measures of LV systolic and diastolic function and LV mass provide limited predictive information after accounting for the severity of stenosis.

Acute coronary syndrome registry enrolment status: differences in patient characteristics and outcomes and implications for registry data use (ANZACS-QI 36).

AIMS: Clinical registry-derived data are widely used to represent patient populations. In New Zealand (NZ), a national registry-the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry-aims to include all patients undergoing coronary angiography; other acute coronary syndrome (ACS) patients are also registered but without complete capture. This study compares national hospitalization data of all first-time ACS admissions in NZ with patients in the ANZACS-QI registry, to investigate the use of clinical registry-derived data in research and in assessing clinical care. METHODS AND RESULTS: Patients admitted with first-time ACS in the NZ National Hospitalisation Dataset between 1 January 2015 and 31 December 2016 were included. Clinical characteristics and time to 12-month clinical outcomes were compared between patients captured and not-captured in the registry. A total of 16 569 patients were admitted with first-time ACS, median age 69 years, 61% male; 60% (n = 9918) were enrolled in ANZACS-QI. Registry-captured patients were younger, more often male, and with a lower comorbidity burden than non-captured patients. Overall, 16% patients died within 12 months, 15% experienced a non-fatal cardiovascular (CV) readmission, and 28% either died or were readmitted. Patients not captured in the registry were more than twice as likely to have experienced death or a non-fatal CV readmission within 12 months as captured patients. CONCLUSIONS: First-time ACS patients captured in the ANZACS-QI registry had very different clinical characteristics and outcomes than those not captured. Cardiovascular registry-derived data are dependent on registry design and may not be representative of the wider patient population; this must be considered when using registry-derived data.

Outcomes for working age patients after first-time acute coronary syndrome - ANZACS-QI 35.

BACKGROUND: Acute coronary syndrome (ACS) events and the ongoing burden of disease can have a significant impact on the subsequent life-course of working age people. METHODS: We report 12-month clinical outcomes for 10,822 patients hospitalized with first-time ACS between 2015-2016 and enrolled in the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry, with a focus on people of working age (defined as <65 years). RESULTS: Nearly half (48%) of first-time ACS occurred in people of working age. Compared to those >65 years, these patients had a high burden of cardiovascular risk factors, and were more likely to be male (75% vs 60%), to be of non-European ethnicity (36% vs 15%), and to be living in areas of high deprivation. Subsequent clinical events were common in the younger patients, with 15% dying or being readmitted for cardiovascular causes within 12 months despite high rates of angiography (96%), revascularization (74%) and evidence-based medical therapy at the time of the index ACS event. CONCLUSIONS: The high risk factor burden and subsequent high rate of clinical events in working age patients reinforces the need for a longer-term focus on strategies to improve clinical outcomes following first-time ACS.

Systematic Comparison of Left Ventricular Geometry Between 3D-Echocardiography and Cardiac Magnetic Resonance Imaging.

Aims: Left ventricular (LV) volumes estimated using three-dimensional echocardiography (3D-echo) have been reported to be smaller than those measured using cardiac magnetic resonance (CMR) imaging, but the underlying causes are not well-understood. We investigated differences in regional LV anatomy derived from these modalities and related subsequent findings to image characteristics. Methods and Results: Seventy participants (18 patients and 52 healthy participants) were imaged with 3D-echo and CMR (<1 h apart). Three-dimensional left ventricular models were constructed at end-diastole (ED) and end-systole (ES) from both modalities using previously validated software, enabling the fusion of CMR with 3D-echo by rigid registration. Regional differences were evaluated as mean surface distances for each of the 17 American Heart Association segments, and by comparing contours superimposed on images from each modality. In comparison to CMR-derived models, 3D-echo models underestimated LV end-diastolic volume (EDV) by -16 ± 22, -1 ± 25, and -18 ± 24 ml across three independent analysis methods. Average surface distance errors were largest in the basal-anterolateral segment (11-15 mm) and smallest in the mid-inferoseptal segment (6 mm). Larger errors were associated with signal dropout in anterior regions and the appearance of trabeculae at the lateral wall. Conclusions: Fusion of CMR and 3D-echo provides insight into the causes of volume underestimation by 3D-echo. Systematic signal dropout and differences in appearances of trabeculae lead to discrepancies in the delineation of LV geometry at anterior and lateral regions. A better understanding of error sources across modalities may improve correlation of clinical indices between 3D-echo and CMR.

Fundamental Heart Sound Classification using the Continuous Wavelet Transform and Convolutional Neural Networks.

Correct identification of the fundamental heart sounds is an important step in identifying the heart cycle stages. Heart valve pathologies can cause abnormal heart sounds or extra sounds, and an important distinguishing feature between different pathologies is the timing of these extra sounds in the heart cycle. In the design of an understandable heart sound analysis system, heart sound segmentation is an indispensable step. In this study classification of the fundamental heart sounds using continuous wavelet transform (CWT) scalograms and convolutional neural networks (CNN) is investigated. Classification between the first and second heart sound of scalograms produced by the Morse analytic wavelet was compared for CNN, support vector machine (SVM), and knearest neighbours (kNN) classifiers. Samples of the first and second heart sound were extracted from a publicly available dataset of normal and abnormal heart sound recordings, and magnitude scalograms were calculated for each sample. These scalograms were used to train and test CNNs. Classification using features extracted from a fully connected layer of the network was compared with linear binary pattern features. The CNN achieved an average classification accuracy of 86% when distinguishing between the first and second heart sound. Features extracted from the CNN and classified using a SVM achieved similar results (85.9%). Classification of the CNN features outperformed LBP features using both SVM and kNN classifiers. The results indicate that there is significant potential for the use of CWT and CNN in the analysis of heart sounds.

Long-Term Outcomes of the Mosaic Bioprosthesis.

BACKGROUND: The Mosaic bioprosthesis is a third-generation stented porcine bioprosthesis. This study was performed to evaluate long-term survival and durability associated with this device. METHODS: A total of 1,029 patients (797 aortic valve replacements, 232 mitral valve replacements) previously enrolled at 6 centers as part of the original regulatory study were included. We evaluated freedom from death, valve-related reoperation, and explant due to structural valve deterioration (SVD), and compared these outcomes by age (<60 and ≥60 years) at the time of implant. RESULTS: Cumulative follow-up was 7021.2 patient-years in the aortic cohort and 1969.5 patient-years in the mitral cohort. Mean age was 69.5 ± 8.6 and 67.9 ± 10.5 years; 66% and 48% were male, respectively. In the aortic cohort at 17 years, freedom from death was 54.0% in patients younger than 60 years and 24.0% in patients aged 60 years and older (p < 0.01); freedom from reoperation was 36.4% and 81.2%, respectively (p < 0.01); and freedom from explant due to SVD was 47.5% and 89.1% (p < 0.01). At 16 years in the mitral cohort, freedom from death was 67.6% and 20.6% (p < 0.01); freedom from reoperation was 51.3% versus 77.9% (p = 0.04); and freedom from explant due to SVD was 65.2% versus 83.8% (p = 0.23). CONCLUSIONS: This study demonstrates acceptable long-term rates of death, reoperation, and explant due to SVD with the Mosaic bioprosthesis implanted in either the aortic or mitral position. Freedom from explant due to SVD was lower in patients younger than 60 years in the aortic cohort at 17 years, but it was not significantly different between patients younger than 60 years or 60 years and older in the mitral cohort at 16 years.

Digital devices for teaching cardiac auscultation - a randomized pilot study.

BACKGROUND: Competent cardiac auscultation is a declining skill. Digital stethoscopes and hand-held echocardiography (HHE) are modern devices which may improve the accuracy of heart murmur recognition and diagnosis. Their incremental value compared to conventional examination has not been evaluated in depth. OBJECTIVES: Our aim was to quantify the utility of digital stethoscopes and HHE as teaching aids to improve medical students' diagnostic accuracy in the evaluation of heart murmurs using a novel clinically weighted scoring system. DESIGN: This pilot study involved eight medical students and eight patients with heart murmurs. Four patients were examined at 2 sessions, 1 week apart. Medical students were randomised into two groups: the 'intervention group' examined patients with a standard and digital stethoscope, and then received demonstration of the valvular lesion with HHE to illustrate the diagnosis. The 'control group' used a standard stethoscope only and were taught using traditional methods. Students' scores were compared to a 'gold standard' derived from a consensus of auscultation findings of three cardiologists. RESULTS: Overall the mean percent correct of total possible score was 65.4% (SD8.4). Using a mixed models ANOVA approach to repeated measures, the mean [95% CI] increase from training to validation period for the control group was 2.5% [-11.5, 16.5] P(Tukey) = 0.95 and 15.8% [1.7,29.8] P(Tukey) = 0.027 for the intervention group. Between the validation and training sessions for both groups, there was an increase of 9.1% [1.82, 16.4] in scores (p = 0.018). The mean [95% CI] difference in scores of the control and intervention groups was 1.9% [-5.4, 9.2] (p = 0.59). The Cohen's effect size estimate was 0.9. CONCLUSION: Digital stethoscopes and hand-held echo may be useful devices for teaching cardiac auscultation. This pilot study provides a novel study design, a heart murmur grading system, and data that will help develop definitive studies to assess new teaching techniques for cardiac auscultation using digital technology.

Extra-aortic balloon counterpulsation: an intraoperative feasibility study.

BACKGROUND: Current methods of counterpulsation or ventricular assistance have significant vascular and limb complications. The aim of this study was to determine the safety and performance of a new method of non-blood-contacting counterpulsation using an inflatable cuff around the ascending aorta (extra-aortic balloon [EAB]). METHODS AND RESULTS: In 6 patients undergoing first time off-pump coronary bypass surgery via sternotomy, the EAB was secured around the ascending aorta and attached to a standard counterpulsation console. At baseline and with 1:2 and 1:1 augmentation, hemodynamic and echocardiographic parameters of ventricular function and coronary flow were measured. High-intensity transient signals were measured using transcutaneous Doppler over the right common carotid artery. No complications occurred. With EAB there was no significant change in heart rate or blood pressure and no increase in high-intensity transient signals. There was a 67% increase in diastolic coronary blood flow (mean left-main diastolic velocity time integral 15.3 cm unassisted versus 25.1 cm assisted, P<0.05). Measurements with transesophageal echocardiography at baseline and with 1:1 counterpulsation demonstrated a 6% reduction in end-diastolic area (P=NS), a 16% reduction in end-systolic area (P<0.01), a 31% reduction in left ventricular wall stress (P<0.05), and a 13% improvement in fractional area change (P<0.005). CONCLUSIONS: EAB counterpulsation augments coronary flow and reduces left ventricular afterload. Further testing is warranted to assess the use of the EAB for chronic non-blood-contacting support of the failing heart.

The value of CT cardiac angiography and CT calcium score testing in a modern cardiology service in New Zealand: a report of a single centre eight-year experience from 5,237 outpatient procedures.

BACKGROUND: Computed tomographic (CT) cardiac angiography is of increasing value in several areas of patient management in cardiology. We assessed the ability of CT cardiac angiography to effectively 'rule out' severe coronary stenoses in patients presenting with 'atypical' symptoms and/or an equivocal stress test, which offers a new approach to the management of coronary artery disease. We also examined the use of the CT calcium score test in cardiovascular (CVS) risk assessment. METHODS: From a large single centre (Mercy Hospital) in Auckland, using a prospectively acquired, comprehensive database, we audited the entire eight-year experience of 5,169 patients (7/8/06 to 31/1/14) who underwent 5,237 64-slice computed tomographic (CT) cardiac angiogram or CT calcium score tests (GE Lightspeed scanner). RESULTS: From 5,169 patients there were 5,237 CT procedures. The mean patient age was 57 (SD 10) years; 42% patients were female. Of the 3,603 (69%) full CT cardiac angiogram scans, 3,509 (67%) included a calcium score test. One thousand four hundred and eighty-three (28%) of scans were a calcium score test only. Of the 3,603 (69%) full CT cardiac angiogram scans, it was possible to 'rule out' significant coronary atheroma (stenosis ≥50%) in 2,947 (82%) of these procedures. Of the 4,903 (94%) patients who had a CT calcium score test, in whom we could calculate the NZ Framingham-based CVS risk, it was possible to reassign 532 (22%) of these patients who were previously thought to be at 'low risk' to be at a higher CVS risk. CONCLUSION: CT cardiac angiography has become established in the modern management of cardiology patients. It has particular value as a tool to 'rule out' severe coronary stenoses, and as a tool to give a more accurate assessment of CVS risk. It adds significant value to the care of many patients within an established cardiology practice.

Increased plasma natriuretic peptide levels reflect symptom onset in aortic stenosis.

BACKGROUND: The onset of symptoms is a critical point in the natural history of aortic stenosis and the cardinal indication for valve replacement. This study assessed the associations between natriuretic peptide levels, disease severity, and cardiac symptoms in aortic stenosis. METHODS AND RESULTS: Seventy-four patients with isolated aortic stenosis underwent independent assessment of symptoms, transthoracic echocardiography, and measurement of plasma levels of atrial natriuretic peptide, brain natriuretic peptide (BNP), and N-BNP. Natriuretic peptide levels were also measured in 100 clinically normal control subjects. The aortic valve area was smaller in symptomatic patients (n=45) than in asymptomatic patients (n=29; mean, 0.71+/-0.23 cm2 and 0.99+/-0.31 cm2, respectively; P<0.0001). Plasma natriuretic peptide levels were higher in symptomatic patients than in asymptomatic patients (for N-BNP: median, 112 versus 33 pmol/L; interquartile range, 70 to 193 versus 16 to 58 pmol/L, respectively; P=0.0002). After adjustment for age, sex, serum creatinine, aortic valve area, and left ventricular ejection fraction, N-BNP levels were 1.74 times higher (95% confidence interval, 1.12 to 2.69) for symptomatic than asymptomatic patients with aortic stenosis (P=0.014). Natriuretic peptide levels increased with the New York Heart Association class (for N-BNP median values were 13, 34, 105, and 202 pmol/L for normal control subjects, class I, class II, and class III/IV patients, respectively; interquartile ranges for the same patients were 8 to 21, 16 to 58, 57 to 159, and 87 to 394 pmol/L; P<0.0001). Similar associations were observed for BNP and atrial natriuretic peptide. CONCLUSIONS: Plasma natriuretic peptide levels are elevated in symptomatic patients with aortic stenosis. Measurement of natriuretic peptides may complement clinical and echocardiographic evaluation of patients with aortic stenosis.