A randomized double-blind trial of an interventional device treatment of functional mitral regurgitation in patients with symptomatic congestive heart failure-Trial design of the REDUCE FMR study

The Carillon Mitral Contour System has been studied in 3 nonrandomized trials in patients with symptomatic congestive heart failure and functional mitral regurgitation. The REDUCE FMR study is a uniquely designed, double-blind trial evaluating the impact of the Carillon device on reducing regurgitant volume, as well as assessing the safety and clinical efficacy of this device. Carillon is a coronary sinus-based indirect annuloplasty device. Eligible patients undergo an invasive venogram to assess coronary sinus vein suitability for the Carillon device. If the venous dimensions are suitable, they are randomized on a 3:1 basis to receive a device or not. Patients and assessors are blinded to the treatment assignment. The primary end point is the difference in regurgitant volume at 1 year between the implanted and nonimplanted groups. Other comparisons include clinical parameters such as heart failure hospitalizations, 6-minute walk test, Kansas City Cardiomyopathy Questionnaire (KCCQ), and other echocardiographic parameters. An exercise echo substudy will also be included

Incremental benefit of myocardial contrast to combined dipyridamole-exercise stress echocardiography for the assessment of coronary artery disease

Background-Although assessment of myocardial perfusion by myocardial contrast echocardiography (MCE) is feasible, its incremental benefit to stress echocardiography is not well defined. We examined whether the addition of MCE to combined dipyridamole-exercise echocardiography (DExE) provides incremental benefit for evaluation of coronary artery disease (CAD). Methods and Results-MCE was combined with DExE in 85 patients, 70 of whom were undergoing quantitative coronary angiography and 15 patients with a low probability of CAD. MCE was acquired by low-mechanical-index imaging in 3 apical views after acquisition of standard resting and poststress images. Wall motion, left ventricular opacification, and MCE components of the study were interpreted sequentially, blinded to other data. Significant (>50%) stenoses were present in 43 patients and involved 69 coronary territories. The addition of qualitative MCE improved sensitivity for the detection of CAD (91% versus 74%, P=0.02) and accurate recognition of disease extent (87% versus 65% of territories, P=0.003), with a nonsignificant reduction in specificity. Conclusions-The addition of low-mechanical-index MCE to standard imaging during DExE improves detection of CAD and enables a more accurate determination of disease extent

Myocardial blood volume and perfusion reserve responses to combined dipyridamole and exercise stress: A quantitative approach to contrast stress echocardiography

Background: Qualitative interpretation of myocardial contrast echocardiography (MCE) improves the accuracy of wall-motion analysis for assessment of coronary artery disease (CAD). We examined the feasibility and accuracy of quantitative MCE for diagnosis of CAD. Methods: Dipyridamole/exercise stress MCE (destruction-replenishment protocol with real-time imaging) was performed in 90 patients undergoing quantitative coronary angiography, 48 of whom had significant (> 50%) stenoses. MCE was repeated with exercise alone in 18 patients. Myocardial blood flow (A*beta) was obtained from blood volume (A) and time to refill (beta). Results: Quantification of flow reserve was feasible in 88%. The mean A*beta reserve in the anterior wall was significantly impaired for patients with left anterior descending coronary artery disease (n = 28) compared with those with no disease (1.6 +/- 1.2 vs; 4.0 +/- 2.5, P <=.001). This reflected impaired beta reserve, with no difference in the A reserve. Applying a receiver operating characteristic curve derived cutoff of 2.0 for A*beta reserve, quantitative MCE was 76% sensitive and 71% specific for the diagnosis of significant left anterior descending coronary artery stenosis. Posterior circulation results were similar, with 78% sensitivity and 59% specificity for detection of posterior CAD. Overall, quantitative MCE was similarly sensitive to qualitative approach for diagnosis of CAD (88% vs 93%), but with lower specificity (52% vs 65%, P =.07). In 18 patients restudied with pure exercise stress, the mean myocardial blood flow reserve was less than after combined stress (2.1 +/- 1.6 vs 3.7 +/- 1.9, P =.01). Conclusion: Quantitative MCE is feasible for the diagnosis of CAD with dipyridamole/exercise stress. Dipyridamole prolongs postexercise hyperemia, augmenting the degree of hyperemia at the time of imaging

A comparison of methods for assessing total arterial compliance

There are several methods of assessing total arterial compliance (TAC) based on the two element Windkessel model, which is a ratio of pressure and volume, but the optimal technique is unclear. In this study, three methods of estimating TAC were compared to determine which was the most robust in a large group of patients with and without cardiovascular risk. In all, 320 patients (170 men; age 55 +/- 10) were studied; TAC was determined by the pulse-pressure method (PPM), the area method (AM) and the stroke volume/pulse-pressure method (SVPP). We obtained arterial waveforms using radial applanation tonometry, dimensions using two-dimensional echocardiography and flow data by Doppler. Clinical data, risk factors, echo parameters and TAC by all three methods were then compared. TAC (mlmmHg(-1)) by the PPM was 1.24 +/- 0.51, by the AM 1.84 +/- 0.90 and by the SVPP 1.96 +/- 0.76 (

Measuring regional arterial stiffness in patients with peripheral artery disease: innovative technology.

The routine measurement of pulse wave velocity (PWV) made the non-invasive evaluation of aortic stiffness a reality both in clinical practice and in research settings. These routine measurements also revealed that this stiffness accurately reflects aortic calcium content1. Theoretically, the measurement of PWV is easy: it is sufficient to detect the pulse wave in two body districts and then calculate the velocity using the transit time. Many methods are currently available to take these measurements (Table 1). Those methods based on applanation tonometry (i.e., methods using a micromanometer-tipped probe applanating the artery. This produces a signal approximating the instantaneous arterial pressure2) are traditionally considered to be the gold standard3. Applanation tonometry, in particular, the use of the SphygmoCor system (AtCor Medical, Sidney, Australia) applied to large-scale studies showed that regional arterial stiffness expressed as the carotid-femoral PWV is correlated with cardiovascular outcomes and with cardiovascular risk in general (Figure 1). Apart from the training required and the fact that the procedure is largely dependent on the operator, the main problem with applanation tonometry is that waves obtained at arterial and femoral sites are recorded sequentially, not simultaneously, and must be related to each other by means of electrocardiographic tracings (the so-called foot-to-foot method). Relating the waves requires that no physiological variations occur between the two measurements. Given that the carotid and femoral waveforms are recorded sequentially, any variability in the heart rate or blood pressure may confound the readings. Consequently, both expert consensus documents4 and all scientific articles on PWV enumerate a list of recommendations, which are time-consuming and partially out of the researcher\u2019s control, to be strictly observed during measurement. The piezoelectronic system (Complior, Colson, Les Lilas, France) is electrocardiogram independent and allows the simultaneous recording of carotid and femoral waves. Therefore, this system is potentially less error prone. Many large-scale studies have been performed with the Complior device, demonstrating the predictive value of PWV in an epidemiological setting4. Ultrasound methods also allow the simultaneous measurement of pulse waves at the carotid and femoral sites4, but these methods are demanding, strongly operator-dependent and not easy to use in large-scale epidemiological studies, for instance, in population-based studies. More recently, thanks to technological progress, the market started to prioritize ease of use in addition to reliability. As a consequence, user-friendly and patient-friendly devices have appeared. It is only natural that those devices would take measurements at two sites simultaneously. The oscillometric method based on two cuffs, one placed on the neck and the other on the thigh, appears to be sufficiently easy to perform to suggest its use in large-scale studies. Its main advantage is that it does not require a long training period and has little operator dependence. Furthermore, the measurement can be performed faster, and the simultaneous carotid and femoral recordings make the observations more reliable and less dependent on the physiological stability of the subject. Two oscillometric devices, the Vicorder5-7 (Skidmore Medical, Bristol, UK) and the Arteriograph8 (TensioMed, Budapest, Hungary), have been validated in different samples, demonstrating a good intra- and inter-observer repeatability and good agreement with applanation tonometry. One study comparing the Vicorder and the SphygmoCor in a subset of patients with peripheral artery disease, by Shahin et al., appears on page XXX of this issue of Hypertension Research9. To be more precise, the values obtained with the Vicorder and those obtained with the SphygmoCor are not exactly the same, the former being generally lower than the latter. This difference seems to be due predominantly to a difference in the measured transit time, a difference that is attributable to the presence of a thigh cuff, making the femoral recording point distal to the inguinal canal, which is the reference point for the SphygmoCor5,7. The effects of this difference can be minimized by adjusting for the additional femoral artery segment when applying the multivariate algorithms 7. Other authors attribute the imperfect agreement between the Vicorder and the SphygmoCor to more tangible factors. First, the SphygmoCor uses the systolic upstroke to detect the pressure wave, whereas oscillometric devices detect the time point of maximal pressure, a point that can differ from site to site6. Theoretically, the SphygmoCor is therefore independent of pressure variations during the hemodynamic cycle and might be expected to show better reproducibility6. Nevertheless, the SphygmoCor algorithms also take into account the humeral blood pressure. Furthermore, to be pedantic, these authors found higher values for PWV with the Vicorder than with the SphygmoCor6, whereas all the other researchers tendentially found lower values with the former than with the latter7,9. This discrepancy leaves the question open10. The study by Shahin et al9 was performed with patients with peripheral artery disease, a condition that is of increasing interest because of its high prevalence in the general population but is generally neglected in angiological studies. This disease is often considered an exclusion criterion. The presence of a stenosis could, in fact, be deceptive. The question as to whether PWV can be reliably measured in such subjects using a simple non-invasive device despite atherosclerotic plaques in the lower limbs\u2014or whether, on the contrary, these measurements are hampered by technical limits\u2014has been unanswered until now. In our experience, carotid-femoral PWV is 30% higher in subjects with peripheral artery disease (Figure 2), a difference that could be due either to a higher systemic wall stiffness or to misleading plaque-dependent local turbulence under the detector. Shahin et al. demonstrated that, although the Vicorder offers results comparable to those of the gold standard in terms of PWV, its use in arteriopathic subjects was easier and its results less dependent on local stenosis, thus opening the road to the epidemiological evaluation of patients with peripheral artery disease. Other studies addressing this topic in larger groups of subjects are necessary