Progressive breathlessness in an Afro Caribbean hypertensive subject.

The sensitivity and specificity of structural assessment of the heart by echocardiography in black hypertensive patients presenting with symptoms of heart failure is often incomplete. Cardiovascular magnetic resonance, mainly by virtue of its ability to characterize myocardial tissue composition, may be of value in differentiating some of the common pathologies noninvasively. We present an illustrative case of hypertrophic cardiomyopathy in a British Afro Caribbean hypertensive patient where at least some features of familial amyloidosis were present on screening echocardiography. Cardiovascular magnetic resonance examination of this case established not only the usefulness of this technique, but also highlighted the importance of recognizing the variations and departure from the usual which one associates with hypertrophic cardiomyopathy, so as to arrive at the final diagnosis.

Symptoms in the presence of a giant windsock eustachian valve remnant.

We present the case of a 43 year-old female with an isolated episode of atypical chest pain and an ill-defined cardiac murmur who was coincidentally found to possess a large serpiginious residual embryonic structure in right atrium. Multiple modality imaging was required to confirm this to be a rare giant eustachian valve remnant. The eustachian valve in the fetus directs oxygenated blood towards the foramen ovale. While absent or very small in adult life it rarely persists to any significant degree and must be distinguished from other right atrial shelf anomalies. The true potential of these structures to cause pathological interference with cardiac function or symptoms is unknown due to their rarity.

Risk stratification in cardiovascular disease primary prevention - scoring systems, novel markers, and imaging techniques.

The aim of this paper is to review and discuss current methods of risk stratification for cardiovascular disease (CVD) prevention, emerging biomarkers, and imaging techniques, and their relative merits and limitations. This report is based on discussions that took place among experts in the area during a special CardioVascular Clinical Trialists workshop organized by the European Society of Cardiology Working Group on Cardiovascular Pharmacology and Drug Therapy in September 2009. Classical risk factors such as blood pressure and low-density lipoprotein cholesterol levels remain the cornerstone of risk estimation in primary prevention but their use as a guide to management is limited by several factors: (i) thresholds for drug treatment vary with the available evidence for cost-effectiveness and benefit-to-risk ratios; (ii) assessment may be imprecise; (iii) residual risk may remain, even with effective control of dyslipidemia and hypertension. Novel measures include C-reactive protein, lipoprotein-associated phospholipase A(2) , genetic markers, and markers of subclinical organ damage, for which there are varying levels of evidence. High-resolution ultrasound and magnetic resonance imaging to assess carotid atherosclerotic lesions have potential but require further validation, standardization, and proof of clinical usefulness in the general population. In conclusion, classical risk scoring systems are available and inexpensive but have a number of limitations. Novel risk markers and imaging techniques may have a place in drug development and clinical trial design. However, their additional value above and beyond classical risk factors has yet to be determined for risk-guided therapy in CVD prevention.

Prevention of cardiovascular disease guided by total risk estimations--challenges and opportunities for practical implementation: highlights of a CardioVascular Clinical Trialists (CVCT) Workshop of the ESC Working Group on CardioVascular Pharmacology and Drug Therapy.

This paper presents a summary of the potential practical and economic barriers to implementation of primary prevention of cardiovascular disease guided by total cardiovascular risk estimations in the general population. It also reviews various possible solutions to overcome these barriers. The report is based on discussion among experts in the area at a special CardioVascular Clinical Trialists workshop organized by the European Society of Cardiology Working Group on Cardiovascular Pharmacology and Drug Therapy that took place in September 2009. It includes a review of the evidence in favour of the "treat-to-target" paradigm, as well as potential difficulties with this approach, including the multiple pathological processes present in high-risk patients that may not be adequately addressed by this strategy. The risk-guided therapy approach requires careful definitions of cardiovascular risk and consideration of clinical endpoints as well as the differences between trial and "real-world" populations. Cost-effectiveness presents another issue in scenarios of finite healthcare resources, as does the difficulty of documenting guideline uptake and effectiveness in the primary care setting, where early modification of risk factors may be more beneficial than later attempts to manage established disease. The key to guideline implementation is to improve the quality of risk assessment and demonstrate the association between risk factors, intervention, and reduced event rates. In the future, this may be made possible by means of automated data entry and various other measures. In conclusion, opportunities exist to increase guideline implementation in the primary care setting, with potential benefits for both the general population and healthcare resources.

Volume status and diuretic therapy in systolic heart failure and the detection of early abnormalities in renal and tubular function.

OBJECTIVES: This study sought to determine the pharmacodynamic effect of modulation of volume status by withdrawal and reinstitution of diuretic treatment on markers of renal and tubular function. BACKGROUND: Decreased renal perfusion and increased congestion are associated with renal dysfunction in patients with heart failure. METHODS: In this study, 30 patients with chronic systolic heart failure in a presumed euvolemic state and on standard oral furosemide therapy (40 to 80 mg) were examined. At baseline, subjects were withdrawn from their loop diuretics. After 72 h, their furosemide regimen was reinstated, and patients were studied again 3 days later. Serum creatinine, atrial and B-type natriuretic peptide, urinary kidney injury molecule (KIM)-1, urinary N-acetyl-beta-D-glucosaminidase (NAG), and serum as well as urinary neutrophil gelatinase-associated lipocalin (NGAL) were determined at various time points. RESULTS: Diuretic withdrawal resulted in increases in atrial and B-type natriuretic peptide (both p < 0.05). Serum creatinine was unaffected. Both urinary KIM-1 (p < 0.001) and NAG (p = 0.010) concentrations rose significantly, after diuretic withdrawal, whereas serum and urinary NGAL were not significantly affected. After reinitiation of furosemide, both urinary KIM-1 and NAG concentrations returned to baseline (both p < 0.05), but NGAL values were unaffected. CONCLUSIONS: Subclinical changes in volume status by diuretic withdrawal and reinstitution are associated with increases and decreases of markers of tubular dysfunction in stable heart failure. Diuretic therapy may favorably affect renal and tubular function by decreasing congestion.

Performing repeated noninvasive bedside measures of volume response to intravenous furosemide in acute pulmonary edema: a feasibility assessment.

Optimizing responses to intravenous furosemide (ivF) in acute pulmonary edema is limited by current insensitive noninvasive means of volume assessment. We conducted a pilot study to assess the feasibility of performing repeated measures of echocardiographic and bioimpedance analysis (BIA) parameters and test their response as noninvasive markers of volume response to ivF. We also aimed to identify the most potentially sensitive markers of this response. Patients receiving ivF for a clinical diagnosis of acute cardiogenic pulmonary edema were studied. Echocardiographic and BIA parameters were measured at 0, 0.5, 1, 2, and 3 h after ivF. Intraobserver variability for each parameter was determined. Thirty-one patients were enrolled who were receiving 40-100 mg of ivF. Transmitral (MV) early peak velocity following Valsalva maneuver and transtricuspid (TV) early peak velocity reduced significantly (P= 0.012 and 0.010, respectively), whereas MV deceleration time increased significantly (P= 0.006) in response to ivF. Short-axis inferior vena cava diameter (SIVC) in expiration and inspiration and SIVC corrected for body surface area in expiration and inspiration reduced significantly following ivF (P= 0.039, 0.020, 0.032, and 0.016, respectively). BIA estimates of extracellular water decreased significantly (P= 0.001), whereas impedance (Z) at currents of 5, 50, 100, and 200 kHz increased following ivF; the changes were significant with all but the last parameter (P < 0.0001, 0.006, 0.010, and 0.051, respectively). Maximal change from baseline for each parameter was greater than its respective intraobserver variability. Performing repeated measures of echocardiographic and BIA parameters is feasible in this unstable group of patients. The above panel of parameters could potentially be used to track volume response to ivF and, thus, to optimize treatment in acute pulmonary edema.

Markers of thrombosis and hemostasis in acute coronary syndromes: relationship to increased heart rate and reduced heart-rate variability.

BACKGROUND: Acute coronary syndromes (ACS) are characterized by abnormal heart-rate variability (HRV) and biomarkers of endothelial damage and thrombosis. HYPOTHESIS: We hypothesized an association between these factors in patients with ACS. METHODS: We studied 99 patients with ACS measuring HRV and plasma markers of endothelial damage/dysfunction (von Willebrand factor, vWF) and thrombosis/hemostasis (soluble P-selectin (s-Psel); CD(40)-ligand (CD(40)-L); D-dimer). HRV and plasma indices were compared to age- and gender-matched controls. Measures were repeated at 4 months in a subset. vWF, s-Psel and D-Dimer levels were raised compared to control. RESULTS: HRV indices were reduced (mean RR, SDNN, SDNNi, RMSSD, Triangular index, LF and HF). There were weak correlations between mean RR and s-Psel (R = - 0.234, p = 0.023) and D-dimer (R = - 0.219, p = 0.041). At 4-month follow-up, significant correlations were between mean RR and CD(40)L (R = - 0.414, p = 0.008) and D-dimer (R = - 0.363, p = 0.012). On multivariate logistic regression analysis statin use (p = 0.046) was the only independent predictor of acute s-Psel levels. Age (p = 0.004) and mean RR interval (p = 0.01) were independent predictors of D-dimer levels at follow-up. CONCLUSIONS: Abnormal HRV is associated with markers of hemostasis and thrombosis in ACS, and present both in the acute and rehabilitation phases.

Generalized obesity but not that characterized by raised waist-hip ratio is associated with increased perceived breathlessness during treadmill exercise testing.

The management of obesity is linked to defining its impact on exercise. One impact of obesity in coronary disease care is in the quantification of exercise limitation by treadmill protocols. In this study, we considered the impact of obesity as definition by body mass index (BMI) or waist-hip ratio (WHR) on perceived exercise limiting symptoms, which are accepted and valuable targets for drug or lifestyle modification. We gathered morphometric data prospectively using bioimpedance (Bodystat Quadscan 3000), BMI, and WHR in 228 unselected cardiac patients attending for diagnostic Bruce treadmill tests. The patients were categorized as obese (BMI >30 kg/m(2)), overweight (BMI 25.0-29.9 kg/m(2)), or normal weight (BMI <25 kg/m(2)). A quantitative visual analog scale (10 cm) of perceived breathlessness was defined by the subjects at the end of each stage along with standard exercise data. In total, 188 patients were included for the final analysis excluding 12 patients with severe LV dysfunction and 10 patients with severe inducible ischemia necessitating an early termination of the test. There was no difference by obesity indices in the distribution of reasons for stopping the test (elective arrhythmia, inducible ischemia, or intolerable functional symptoms). Perceived symptom score on the visual analog scale were persistently higher at the end of stages 1, 2, and 3 of the Bruce protocol in obese individuals as compared with overweight and normal weight subjects. (P= 0.034, 0.003, and 0.042, respectively). Perceived symptoms during exercise when assessed by WHR did not show any statistical difference in severity. Generalized obesity associated with a high BMI is associated with increased perceived breathlessness during standard exercise testing regardless of ischemia or known left ventricular systolic function. This clearly indicates that perceived breathlessness does not correlate with obesity as defined by WHR, which is known to be a more sensitive marker of coronary disease. Therapeutic interventions in obesity should take into account the frame of reference of definition of obesity.

Evolution in cardiovascular care: highlights and observations from the ESC Congress 2008.

The European Society of Cardiology (ESC) in Munich represents the second of the three major annual international cardiovascular meetings. The East European involvement in this meeting (in terms of numbers of delegates, if not presentations) continues to emerge, while the representation from North America, Australasia and the Far East represents an increasing proportion. Of note, the cardiovascular nursing representation is much greater than that of 10 years ago, while the basic science presentations may be less noticeable. The format of the meeting has shifted significantly towards plenary clinical commentaries with limited discussion rather than presentations by individuals or groups. In my opinion, the quality of some debate is marginal. Occasionally, a small number of internationally known speakers appear to move effortlessly between multiple presentations in plenary sessions to industry stands all in 1 day!

Is soluble CD40 ligand a mediator of angiogenesis in patients with coronary artery disease?

BACKGROUND: In cardiovascular disease, soluble CD40 ligand (sCD40L) has been associated with an adverse prognosis. Angiogenesis has been implicated in the progression of coronary artery disease (CAD) and sCD40L has pro-angiogenic effects in vitro. Angiogenesis itself is regulated by many mediators, such as vascular endothelial growth factor (VEGF) and the angiopoietins (Ang). Ang-1 promotes vascular maturation whilst Ang-2 destabilises the blood vessel and permits vascular growth with VEGF. Hence, selective elevation of VEGF and Ang-2 suggest a state of vascular plasticity and increased angiogenesis. We hypothesised raised plasma levels of VEGF and Ang-2, but not Ang-1, and correlations with raised sCD40L levels and CAD severity/collateralisation in patients with CAD. METHODS: We recruited 153 patients attending diagnostic angiography for CAD and 47 healthy controls. Patients with previous revascularisation or unequivocally normal angiograms were excluded. The coronary atheroma score (CAS) and coronary stenosis score (CSS), and the presence of collaterals, were assessed by 2 blinded observers. Plasma sCD40L, VEGF, Ang-1 and -2 levels were measured by ELISA. RESULTS: Plasma levels of sCD40L, VEGF and Ang-2, but not Ang-1, were higher in CAD patients compared to controls. Both plasma VEGF (r=0.526, p<0.001) and Ang-2 (r=0.429, p<0.001) were correlated with sCD40L, but not with CAS, CSS or collateralisation. On stepwise multivariate regression analysis, plasma sCD40L was an independent predictor of plasma VEGF (p=0.002), and Ang-2 (p<0.001) levels. CONCLUSION: These data suggest abnormal indices of angiogenesis in CAD, which may be associated with increased CD40-CD40L interactions in patients with CAD. Plasma sCD40L, VEGF and Ang-2 levels were not correlated to angiographic CAD/collateralisation.

Multiple microvessels extending from the coronary arteries to the left ventricle in a middle aged female presenting with ischaemic chest pain: a case report.

Possible ischaemic chest pain presentations are exceedingly common. Angiographic triage of clinical, electrocardiographic or biomarker positive presentations is increasingly feasible with the expansion of cardiac catheterization facilities. This management pattern often extends to problem patients with negative biomarker screens whose symptoms appear unstable. With invasive triage even very rare congenital or developmental coronary anomalies will be more frequently recognized although their relationship to ischaemia can be confounded by association. In this a case we report a woman with widespread direct coro-ventricular micro-channel formation across the heart and an ischaemic presentation, despite angiographically normal epicoronary vessels. This pattern, while very rare, needs to be recognized as one possible phenotype in this very common clinical presentation.

Indices of angiogenesis, platelet activation, and endothelial damage/dysfunction in relation to ethnicity and coronary artery disease: differences in central versus peripheral levels.

BACKGROUND: We hypothesized that indices of angiogenesis (vascular endothelial growth factor (VEGF), angiopoietins (Ang-1 and -2), platelet activation (soluble P-selectin)) and endothelial damage/dysfunction (von Willebrand factor (vWf)) would be more deranged in South Asians than in white Europeans when measured within the coronary sinus or coronary artery per se (that is, intracardiac sampling of blood supplying and draining the heart), as compared to measurements from the peripheral venous system. METHODS: To test this hypothesis, we performed a cross-sectional study of 87 subjects undergoing cardiac catheterization, where 43 were South Asian and 44 were white European. RESULTS: South Asian participants were younger (P = 0.01) but had a lower rate of self-reported smoking (P = 0.01). The extent of coronary atherosclerosis, assessed using presence of lesions > 50%, number of vessels diseased and Gensini score, was comparable between the two ethnic groups (all P = NS). When samples were analysed from the coronary circulation or the femoral vein in relation to South Asian and white European ethnicity, there were no significant differences in the levels of VEGF, angiopoietins 1 and 2, soluble P-selectin and vWf levels between the two ethnic groups. CONCLUSION: Indices of angiogenesis, platelet activation, and endothelial damage/dysfunction are comparable in South Asians and their white European counterparts. Our results suggest that their pathophysiological roles may be comparable in South Asians and white Europeans in the context of coronary artery disease.

Platelet activation in coronary artery disease: intracardiac vs peripheral venous levels and the effects of angioplasty.

BACKGROUND: Platelet activation and aggregation play a key role in coronary artery disease, with antiplatelet therapies leading to improved clinical outcomes. Limited data exist as to whether peripheral venous blood measurements of platelet physical indexes (eg, platelet count, volume, and granularity) and soluble markers of platelet activation (eg, P-selectin [sP-sel] and CD40 ligand [CD40L]) reflect the local (intracardiac) coronary environment. Furthermore, how percutaneous coronary interventions (PCIs) affect levels of peripheral/cardiac platelet indexes is unclear. METHODS: Blood samples were sequentially acquired from the coronary os, aortic root, coronary sinus, and the femoral vein, and where relevant, pre-PCI and post-PCI. Eighty-seven patients undergoing coronary angiography were recruited (mean [+/-SD] age, 59.8+/-10.8 years; 54 men [62%]), of whom 36 proceeded to PCI. Platelet physical indexes and plasma sP-sel and CD40L levels were measured (by enzyme-linked immunosorbent assay). RESULTS: At baseline, no intracardiac vs peripheral differences were noted in sP sel levels, while CD40L levels were elevated in the aorta compared to the coronary sinus and femoral venous. The mean platelet count (MPC) was similar at all four sites, but within the coronary sinus blood, mean platelet volume (MPV) was significantly lower and mean platelet granularity (MPG) was higher when compared to arterial levels. Though aortic and femoral levels of sP-sel were raised following PCI, transcardiac gradients of plasma sP-sel levels were unaffected. PCI was associated with lower CD40L, MPC, and MPV levels but with a higher MPG level in all sampling sites. CONCLUSIONS: sP-sel levels measured peripherally reflect the cardiac environment, unlike CD40L, MPC, MPV, and MPG. PCI leads to further platelet activation (raised sP-sel) despite aggressive antiplatelet therapy.

Comparative dose titration responses to the introduction of bisoprolol or carvedilol in stable chronic systolic heart failure.

INTRODUCTION: Several beta blocking drugs (BB) reduce mortality in systolic heart failure (LVSD). We have compared the initial response to introduction of carvedilol and bisoprolol during the standard dose titration protocols for each drug. METHODS: Approximately 31 unselected patients with stable LVSD were randomised to either carvedilol or bisoprolol measuring blood pressure, heart rate responses and both time and frequency domain heart rate variability (HRV). RESULTS: One subject died; five withdrew due to intolerable BB related side effects. Carvedilol (n = 13) and bisoprolol (n = 12) attained similar maximal heart rate reduction and induced comparable falls in systolic and diastolic blood pressure. Higher carvedilol doses were associated with lower blood pressure compared to baseline. Individual time domain HRV indices remained unchanged over the initial titration period. Significant increases in triangular Index (TI) were seen with both BB. Carvedilol demonstrated greater (but non-significant) rises in TI compared to Bisoprolol. CONCLUSIONS: In this study we found similar degrees and rate of onset of HR, HRV and BP response to both carvedilol and bisoprolol in treated LVSD patients. Carvedilol appears to show superior HRV rises compared to bisoprolol during initial titration. Any significant increases in HRV attributable to carvedilol compared to bisoprolol may emerge over a longer treatment interval in LVSD.