In-field use of I-VED electrical impedance sensor for assessing post-dive decompression stress in humans.

Purpose: Ultrasound imaging is commonly used in decompression research to assess venous gas emboli (VGE) post-dive, with higher loads associated with increased decompression sickness risk. This work examines, for the first time in humans, the performance of a novel electrical impedance spectroscopy technology (I-VED), on possible detection of post-dive bubbles presence and arterial endothelial dysfunction that may be used as markers of decompression stress. Methods: I-VED signals were recorded in scuba divers who performed standardized pool dives before and at set time points after their dives at 35-minute intervals for about two hours. Two distinct frequency components of the obtained signals, Low-Pass Frequency-LPF: 0-0.5 Hz and Band-Pass Frequency-BPF: 0.5-10 Hz, are extracted and respectively compared to VGE presence and known flow-mediated dilation trends for the same dive profile for endothelial dysfunction. Results: Subjects with VGE counts above the median for all subjects were found to have an elevated average LPF compared to subjects with lower VGE counts, although this was not statistically significant (p=0.06), as well as significantly decreased BPF standard deviation post-dive compared to pre-dive (p=0.008). Conclusions: I-VED was used for the first time in humans and operated to provide qualitative in-vivo electrical impedance measurements that may contribute to the assessment of decompression stress. Compared to ultrasound imaging, the proposed method is less expensive, not operator-dependent and compatible with continuous monitoring and application of multiple probes. This study provided preliminary insights; further calibration and validation are necessary to determine I-VED sensitivity and specificity.

Cell-Derived Microparticles and Acute Coronary Syndromes: Is there a Predictive Role for Microparticles?

BACKGROUND: Despite the recent advances in the treatment of Acute Coronary Syndromes (ACS), patients with ACS are still exposed to an increased risk for adverse cardiovascular events, while their prognosis is difficult to determine. Experimental and clinical studies have shown that cell-derived Microparticles (MPs) are associated with the underlying pathophysiological processes that are responsible for atherogenesis and may be causally implicated in the induction of atherothrombosis. OBJECTIVE: In the present article, we aimed to review the available evidence regarding the predictive role of MPs in patients with ACS. RESULTS: Evidence suggests that endothelial MPs are associated with future adverse cardiovascular events in patients with ACS. Platelet-derived MPs have been excessively studied, since they have been found to trigger the coagulation cascade; however, their role as predictors of future cardiovascular events remains debatable. The role of red blood cell-derived MPs is more intriguing; they have been proposed as markers of ongoing thrombosis in patients with ACS, while previous studies have shown that they have anti-coagulant properties in healthy individuals. Leukocyte-derived MPs may also have a predictive role, although the studies regarding these are still limited. Last but not least, it was an interesting discovery that circulating MPs can provide information regarding the angiographic lesions in patients with ACS. CONCLUSION: The concept of MPs as potential circulating biomarkers in patients with ACS holds much promise. However, large-scale clinical studies are required to evaluate whether the measurement of plasma MPs could be of clinical significance and, thus, dictate a more aggressive treatment strategy in patients with high levels of circulating MPs.

Incremental Prognostic Value of Stress Echocardiography With Carotid Ultrasound for Suspected CAD.

OBJECTIVES: This study hypothesized that ischemia and atherosclerosis assessment by ultrasound (US) may provide incremental prognostic information in patients with new-onset chest pain who do not have coronary artery disease (CAD). BACKGROUND: The clinical significance of atherosclerosis assessment by carotid US in patients undergoing stress echocardiography (SE) in such patients is unknown. METHODS: Consecutive patients with suspected angina but no history of CAD underwent simultaneous SE and US prospectively to assess myocardial ischemia and carotid plaque burden (CPB), respectively. Patients were followed up for major adverse events (MAEs)-all-cause mortality, nonfatal myocardial infarction, and unplanned coronary revascularization. RESULTS: Of 591 recruited patients, 580 (men, 46%; mean age 59 ± 11 years) patients were available for follow-up. SE demonstrated myocardial ischemia in 12%, but prevalence of carotid plaques was 59%. During a mean follow-up of 1,117 ± 361 days, 40 first MAEs occurred. In the multivariable regression model, pre-test probability (PTP) of CAD (p = 0.001), abnormal SE (p < 0.0001), and CPB (p < 0.0001) predicted MAEs. MAE rates per year increased from 0.9% versus 1.97% versus 4.3% versus 9.7% in patients with no carotid plaque and normal SE versus patients who had plaque and normal SE versus those with no plaque and abnormal SE versus patients with plaque and abnormal SE, respectively (p < 0.0001). In hierarchical analysis, plaque burden provided incremental prognostic value over PTP of CAD and SE; likewise, SE was incremental to PTP-CAD and CPB (p < 0.0001 for both). CONCLUSIONS: In patients with suspected stable angina without known CAD, simultaneous SE (for ischemia) and US (for atherosclerosis) provided incremental prognostic value.

Relative clinical and economic impact of exercise echocardiography vs. exercise electrocardiography, as first line investigation in patients without known coronary artery disease and new stable angina: a randomized prospective study.

AIMS: Exercise electrocardiography (ExECG) is widely used in suspected stable angina (SA) as the initial test for the evaluation of coronary artery disease (CAD). We hypothesized that exercise stress echo (ESE) would be efficacious with cost advantage over ExECG when utilized as the initial test. METHODS AND RESULTS: Consecutive patients with suspected SA, without known CAD were randomized into ExECG or ESE. Patients with positive tests were offered coronary angiography (CA) and with inconclusive tests were referred for further investigations. All patients were followed-up for cardiac events (death, myocardial infarction, and unplanned revascularization). Cost to diagnosis of CAD was calculated by adding the cost of all investigations, up to and including CA. In the 194 and 191 patients in the ExECG vs. ESE groups, respectively, pre-test probability of CAD was similar (34 ± 23 vs. 35 ± 25%, P = 0.6). Results of ExECG were: 108 (55.7%) negative, 14 (7.2%) positive, 72 (37.1%) inconclusive and of ESE were 181 (94.8%) negative, 9 (4.7%) positive, 1 (0.5%) inconclusive, respectively. Patients with obstructive CAD following positive ESE vs. Ex ECG were 9/9 vs. 9/14, respectively (P = 0.04). Cost to diagnosis of CAD was £266 for ESE vs. £327 for ExECG (P = 0.005). Over a mean follow-up period of 21 ± 5 months, event rates were similar between the two groups. CONCLUSION: In this first randomized study, ESE was more efficacious and demonstrated superior cost-saving, compared with ExECG when used as the initial investigation for the evaluation of CAD in patients with new-onset suspected SA without known CAD.

Novel Anti-Platelets in Stable Coronary Artery Disease.

BACKGROUND: Apart from the acute thrombotic complications that lead to acute coronary syndromes (ACS), platelet activation also plays an important role in the initiation and progression of atherosclerosis. In addition, it is speculated that anti-platelet therapy can be beneficial for patients with stable coronary artery disease (CAD). Of note, patients on optimal anti-platelet treatment still experience thrombotic events, whereas complications, such as bleeding, cannot be ignored. In this light, novel antiplatelet regimens have been used to minimize the residual platelet activation without compromising normal haemostasis. METHODS: We performed a thorough search of the literature in order to review the beneficial role of novel antiplatelets in patients with stable CAD. We have also focused on studies that examine the effect of these drugs on platelet reactivity as well as on cardiovascular outcomes. CONCLUSION: Specific agents, such as vorapaxar and cilostazol, have been found to reduce platelet reactivity as well as to improve patients' prognosis. Of note, the use of novel antiplatelets is of clinical importance in patients with increased thrombotic status and in those with resistance to classic antiplatelets. However, the available data on most of the novel antiplatelets are mainly derived from studies including ACS patients undergoing angioplasty Therefore, large randomized controlled studies are required to evaluate the clinical benefit of novel antiplatelets in patients with stable CAD.

The clinical impact of contemporary stress echocardiography in morbid obesity for the assessment of coronary artery disease.

OBJECTIVE: Non-invasive cardiac imaging may suffer from poor image quality in morbidly obese individuals. This study aimed to determine the clinical value of contemporary stress echocardiography (SE) in morbidly obese patients referred for assessment of suspected coronary artery disease (CAD). METHODS: This prospective, multicentre observational study was conducted in two district hospitals and one tertiary centre in London, UK. Individuals with body mass index ≥35 kg/m(2) referred for SE were evaluated. The percentage of patients with obstructive CAD on coronary angiography, following abnormal SE, was assessed. Patient outcomes were determined with follow-up for the composite end-point of all-cause mortality, myocardial infarction and late revascularisation. RESULTS: Over a 13-month period, 209 morbidly obese patients underwent SE, and contrast agent was used in 96% of patients. A diagnostic result was obtained in 200/209 (96%) patients. Of 32 (15%) patients with inducible ischaemia, 25 underwent angiography, 22 (88%) had corresponding significant CAD and, of these, 16 (77%) underwent revascularisation. Conversely, only 2/157 patients (1.3%) with normal SE underwent angiography, and none underwent revascularisation. Over a mean follow-up period of 17.8±5.4 months, there were nine events. The annualised cardiac event rate after a normal SE was 0.95%. Events were more frequent in patients with inducible ischaemia versus those without ischaemia (5/32 (15.6%) vs 4/153 (2.6%); p=0.002). Ejection fraction <50% (HR 9.5; 95% CI 2.4 to 38.0; p=0.002) and inducible ischaemia (HR 9.4; 95% CI 2.5 to 35.8; p=0.001) were predictors of outcome on univariable Cox regression analysis. CONCLUSIONS: Contemporary SE has excellent feasibility and positive predictive value and resulted in appropriate risk stratification of symptomatic patients with significant obesity. A normal SE portends an excellent outcome over the short-intermediate term in this high-risk patient population.

Relative diagnostic, prognostic and economic value of stress echocardiography versus exercise electrocardiography as initial investigation for the detection of coronary artery disease in patients with new onset suspected angina.

OBJECTIVES: We hypothesised that stress echocardiography (SE), may be superior to exercise ECG (ExECG), for predicting CAD and outcome, and cost-beneficial, when performed as initial investigation in newly suspected angina. METHODS: All patients seen in 2011, with suspected angina, no history of CAD, pre-test likelihood of CAD of > 10% and who underwent SE or ExECG as first line were identified retrospectively. Cost to diagnosis was calculated by adding the cost of all tests, up to and including coronary angiography (CA), on an intention-to-treat basis. Follow-up data on cardiac death and myocardial infarction (MI) were collected, 26 months after the presentation of the last study patient. RESULTS: A total of 456 patients underwent ExECG (224 (49%) negative, 93 (20%) positive, 139 (31%) inconclusive) and 241 underwent SE (200 (83%) negative, 35 (15%) positive, 6 (2%) inconclusive) as first line. In patients subsequently undergoing CA, CAD was present in 46% (37/80) of patients with positive ExECG vs. 72% (23/32) patients with positive SE (p = 0.01). Mean cost to diagnosis was £456 for the ExECG vs. £360 for the SE group (p = 0.002). Over a mean follow-up period of 31 ± 5 months, cardiac events were 2% each in negative SE vs. negative ExECG (p = 0.9). CONCLUSIONS: SE is superior to ExECG for prediction of CAD and is cost-beneficial when used as initial test in patients with no history of CAD presenting with suspected angina.

Role of simultaneous carotid ultrasound in patients undergoing stress echocardiography for assessment of chest pain with no previous history of coronary artery disease.

BACKGROUND: We prospectively explored prevalence of carotid disease (CD), its independent association with coronary artery disease (CAD) and outcome as well as potential impact on management, in patients undergoing stress echocardiography (SE) for new onset chest pain without known CAD. METHODS: Accordingly, 591 consecutive patients referred for SE underwent carotid ultrasound. Carotid disease was defined as carotid intima-media thickness (C-IMT) >75th percentile for age and sex and/or presence of plaque. RESULTS: Myocardial ischemia was demonstrated in only a minority (11%), but there was a high prevalence of CD (70%). Incidence of CD was similar in patients with and without ischemia (76% versus 69%, P = .26). Carotid data led to reclassification of Framingham risk score categories in 65% of patients as well as more than a third of negative SE patients potentially benefitting from primary prevention therapy. Of the 83 patients undergoing coronary arteriography, 59 (71%) demonstrated coronary atherosclerosis (any atheroma) and 33 (40%) CAD. Positive predictive value of SE for CAD was 56%, but presence of carotid plaque improved it to 70%. Although both CD and plaque showed association with CAD and revascularization, after adjustment for conventional risk factors, only carotid plaque maintained significant association (P = .024 and P = .023, respectively). CONCLUSIONS: There is significantly higher prevalence of CD compared with myocardial ischemia in patients undergoing SE and carotid ultrasound for suspected CAD. This can lead to significant Framingham risk score reclassification with important primary prevention implications. Carotid plaque is superior to clinical assessment for the prediction of CAD and improves positive predictive value of SE for CAD in these patients.