Real-world performance and accuracy of stress echocardiography: the EVAREST observational multi-centre study.

AIMS: Stress echocardiography is widely used to identify obstructive coronary artery disease (CAD). High accuracy is reported in expert hands but is dependent on operator training and image quality. The EVAREST study provides UK-wide data to evaluate real-world performance and accuracy of stress echocardiography. METHODS AND RESULTS: Participants undergoing stress echocardiography for CAD were recruited from 31 hospitals. Participants were followed up through health records which underwent expert adjudication. Cardiac outcome was defined as anatomically or functionally significant stenosis on angiography, revascularization, medical management of ischaemia, acute coronary syndrome, or cardiac-related death within 6 months. A total of 5131 patients (55% male) participated with a median age of 65 years (interquartile range 57-74). 72.9% of studies used dobutamine and 68.5% were contrast studies. Inducible ischaemia was present in 19.3% of scans. Sensitivity and specificity for prediction of a cardiac outcome were 95.4% and 96.0%, respectively, with an accuracy of 95.9%. Sub-group analysis revealed high levels of predictive accuracy across a wide range of patient and protocol sub-groups, with the presence of a resting regional wall motion abnormalitiy significantly reducing the performance of both dobutamine (P < 0.01) and exercise (P < 0.05) stress echocardiography. Overall accuracy remained consistently high across all participating hospitals. CONCLUSION: Stress echocardiography has high accuracy across UK-based hospitals and thus indicates stress echocardiography is being delivered effectively in real-world practice, reinforcing its role as a first-line investigation in the assessment of patients with stable chest pain.

COVID-19 myopericarditis with cardiac tamponade in the absence of respiratory symptoms: a case report.

BACKGROUND: Previous reports have shown various cardiac complications to be associated with COVID-19 including: myocardial infarction, microembolic complications, myocardial injury, arrythmia, heart failure, coronary vasospasm, non-ischemic cardiomyopathy, stress (Takotsubo) cardiomyopathy, pericarditis and myocarditis. These COVID-19 cardiac complications were associated with respiratory symptoms. However, our case illustrates that COVID-19 myopericarditis with cardiac tamponade can present without respiratory symptoms. CASE PRESENTATION: A 58-year-old Caucasian British woman was admitted with fever, diarrhoea and vomiting. She developed cardiogenic shock and Transthoracic echocardiogram (TTE) found a pericardial effusion with evidence of cardiac tamponade. A nasopharyngeal swab showed a COVID-19 positive result, despite no respiratory symptoms on presentation. A pericardial drain was inserted and vasopressor support required on intensive treatment unit (ITU). The drain was removed as she improved, an antibiotic course was given and she was discharged on day 12. CONCLUSIONS: Our case demonstrates that patients without respiratory symptoms could have COVID-19 and develop cardiac complications. These findings can aid timely diagnosis of potentially life-threatening COVID-19 myopericarditis with cardiac tamponade.

Uncomplicated obesity is associated with abnormal aortic function assessed by cardiovascular magnetic resonance.

AIMS: Obese subjects with insulin resistance and hypertension have abnormal aortic elastic function, which may predispose them to the development of left ventricular dysfunction. We hypothesised that obesity, uncomplicated by other cardiovascular risk factors, is independently associated with aortic function. METHODS AND RESULTS: We used magnetic resonance imaging to measure aortic compliance, distensibility and stiffness index in 27 obese subjects (BMI 33 kg/m2) without insulin resistance and with normal cholesterol and blood pressure, and 12 controls (BMI 23 kg/m2). Obesity was associated with reduced aortic compliance (0.9 +/- 0.1 vs. 1.5 +/- 0.2 mm2/mmHg in controls, p < 0.02) and distensibility (3.3 +/- 0.01 vs. 5.6 +/- 0.01 mmHg-1 x 10-3, p < 0.02), as well as higher stiffness index (3.4 +/- 0.3 vs. 2.1 +/- 0.1, p < 0.02). Body mass index and fat mass were negatively correlated with aortic function. Leptin was higher in obesity (8.9 +/- 0.6 vs. 4.7 +/- 0.6 ng/ml, p < 0.001) and also correlated with aortic measures. In multiple regression models, fat mass, leptin and body mass index were independent predictors of aortic function. CONCLUSION: Aortic elastic function is abnormal in obese subjects without other cardiovascular risk factors. These findings highlight the independent importance of obesity in the development of cardiovascular disease.

Metabolic modulation with perhexiline in chronic heart failure: a randomized, controlled trial of short-term use of a novel treatment.

BACKGROUND: Chronic heart failure (CHF) is a major cause of morbidity and mortality that requires a novel approach to therapy. Perhexiline is an antianginal drug that augments glucose metabolism by blocking muscle mitochondrial free fatty acid uptake, thereby increasing metabolic efficiency. We assessed the effects of perhexiline treatment in CHF patients. METHODS AND RESULTS: In a double-blind fashion, we randomly assigned patients with optimally medicated CHF to either perhexiline (n=28) or placebo (n=28). The primary end point was peak exercise oxygen consumption (VO2max), an important prognostic marker. In addition, the effect of perhexiline on myocardial function and quality of life was assessed. Quantitative stress echocardiography with tissue Doppler measurements was used to assess regional myocardial function in patients with ischemic CHF. 31P magnetic resonance spectroscopy was used to assess the effect of perhexiline on skeletal muscle energetics in patients with nonischemic CHF. Treatment with perhexiline led to significant improvements in VO2max (16.1+/-0.6 to 18.8+/-1.1 mL . kg(-1) . min(-1); P<0.001), quality of life (Minnesota score reduction from 45+/-5 to 34+/-5; P=0.04), and left ventricular ejection fraction (24+/-1% to 34+/-2%; P<0.001). Perhexiline treatment also increased resting and peak dobutamine stress regional myocardial function (by 15% and 24%, respectively) and normalized skeletal muscle phosphocreatine recovery after exercise. There were no adverse effects during the treatment period. CONCLUSIONS: In patients with CHF, metabolic modulation with perhexiline improved VO2max, left ventricular ejection fraction, symptoms, resting and peak stress myocardial function, and skeletal muscle energetics. Perhexiline may therefore represent a novel treatment for CHF with a good safety profile, provided that the dosage is adjusted according to plasma levels.

Abnormal cardiac and skeletal muscle energy metabolism in patients with type 2 diabetes.

BACKGROUND: It is well known that patients with type 2 diabetes have increased risk of cardiovascular disease, but it is not known whether they have underlying abnormalities in cardiac or skeletal muscle high-energy phosphate metabolism. METHODS AND RESULTS: We studied 21 patients with type 2 diabetes with no evidence of coronary artery disease or impaired cardiac function, as determined by echocardiography, and 15 age-, sex-, and body mass index-matched control subjects. Cardiac high-energy phosphate metabolites were measured at rest using 31P nuclear magnetic resonance spectroscopy (MRS). Skeletal muscle high-energy phosphate metabolites, intracellular pH, and oxygenation were measured using 31P MRS and near infrared spectrophotometry, respectively, before, during, and after exercise. Although their cardiac morphology, mass, and function appeared to be normal, the patients with diabetes had significantly lower phosphocreatine (PCr)/ATP ratios, at 1.50+/-0.11, than the healthy volunteers, at 2.30+/-0.12. The cardiac PCr/ATP ratios correlated negatively with the fasting plasma free fatty acid concentrations. Although skeletal muscle energetics and pH were normal at rest, PCr loss and pH decrease were significantly faster during exercise in the patients with diabetes, who had lower exercise tolerance. After exercise, PCr recovery was slower in the patients with diabetes and correlated with tissue reoxygenation times. The exercise times correlated negatively with the deoxygenation rates and the hemoglobin (Hb)A1c levels and the reoxygenation times correlated positively with the HbA1c levels. CONCLUSIONS: Type 2 diabetic patients with apparently normal cardiac function have impaired myocardial and skeletal muscle energy metabolism related to changes in circulating metabolic substrates.

Increased expression of renal neutral endopeptidase in severe heart failure.

The enzyme neutral endopeptidase (NEP; EC 3.4.24.11) cleaves several vasoactive peptides such as the atrial natriuretic peptide (ANP). ANP is a hormone of cardiac origin with diuretic and natriuretic actions. Despite elevated circulating levels of ANP, congestive heart failure (CHF) is characterized by progressive sodium and water retention. In order to elucidate the loss of natriuretic and diuretic properties of ANP in CHF we analyzed activity, protein concentrations, mRNA and immunostaining of NEP in kidneys of different models of severe CHF in the rat.CHF was induced by either aortocaval shunt, aortic banding or myocardial infarction in the rat. All models were defined by increased left ventricular end-diastolic pressure and decreased contractility. The diminished effectiveness of ANP was reflected by reduced cGMP/ANP ratio in animals with shunt or infarction. Renal NEP activity was increased in rats with aortocaval shunt (203 +/- 7%, p < 0.001), aortic banding (184 +/- 11%, p < 0.001) and infarction (149 +/- 10%, p < 0.005). Western blot analysis revealed a significant increase in renal NEP protein content in two models of CHF (shunt: 214 +/- 57%, p < 0.05; infarction: 310 +/- 53 %, p < 0.01). The elevated protein expression was paralleled by a threefold increase in renal NEP-mRNA level in the infarction model. The increased renal NEP protein expression and activity may lead to enhanced degradation of ANP and may contribute to the decreased renal response to ANP in heart failure. Thus, the capacity to counteract sodium and water retention, would be diminished. The increased renal NEP activity may therefore be a hitherto unknown factor in the progression of CHF.

Congenital partial absence of the left pericardium associated with tricuspid regurgitation.

We report the case of a 47-year-old man who presented with several episodes of left precordial pain, one of which had been severe, but was unrelated to exertion or posture. Transthoracic echocardiography and cardiovascular magnetic resonance showed evidence of congenital partial absence of the left pericardium and severe tricuspid regurgitation. Both diagnoses were confirmed at surgery when the pericardial defect was repaired and the tricuspid valve was replaced at the same operation. He went on to make a good recovery.

Haemoglobin and flow-mediated vasodilation.

A low [Hb] (Hb concentration) is out-balanced by peripheral vasodilation via mechanisms that are incompletely understood. Peripheral vasodilation is influenced by NO (nitric oxide) released from vascular endothelium in response to increased vessel wall shear stress, and absorption by Hb is the main mechanism by which the bioactivity of NO is disarmed. Thus we propose that graded NO absorption is the mechanism through which a low [Hb] is related to peripheral vasodilation. In the present study, we examined the relationship between [Hb] and FMD (flow-mediated vasodilation; 5 min of cuff ischaemia) of the radial and brachial arteries in 33 normal subjects and in 13 patients with Type II diabetes, known to have impaired NO-mediated vasodilation. The smaller radial artery provided the more sensitive test, as it had a 2-fold larger FMD than the brachial artery (22+/-18% compared with 9+/-18% respectively, in normal subjects; means+/-S.D., P<0.05). FMD of the radial artery had a negative correlation with [Hb] (r(2)=-0.66, P<0.05; n=27). In subjects with [Hb] below and above the median of 14.1 g/dl, the radial artery FMD was 30+/-22% compared with 13+/-12% respectively (P<0.05). In diabetic patients, FMD was lower and a co-variation with [Hb] could not be established. Thus, in normal subjects, NO-mediated endothelium-related vasodilation at least partly out-balanced the 'added burden' of a low [Hb] during post-ischaemic reperfusion.