Remote patient monitoring for chronic heart failure in France: When an innovative funding program (ETAPES) meets an innovative solution (Satelia® Cardio).

Introduction: Remote patient monitoring (RPM) is a telehealth activity to collect and analyze patient health or medical data. Its use has expanded in the past decade and has improved medical outcomes and care management of non-communicable chronic diseases. However, implementation of RPM into routine clinical activities has been limited. The objective of this study was to describe the French funding program for RPM (known as ETAPES) and one of the RPM solution providers (Satelia®) dedicated to chronic heart failure (CHF). Methods: A descriptive assessment of both the ETAPES funding program and Satelia® RPM solution was conducted. Data were collected from official legal documents and information that was publicly available online from the French Ministry of Health. Results and Discussion: ETAPES was formally created in 2016 based on previous legislation pertaining to the national health insurance funding strategy. However, it only started to operate in 2018. Patients with CHF were only eligible if they were at medium or high risk of re-hospitalization with a New York Heart Association (NYHA) score superior or equal to two and a BNP>100 pg/ml or NT pro BNP>1000 pg/ml. Medical monitoring was supported through the therapeutic education of a patient on the RPM model of care with a minimum of three training sessions during the first six months. The use of Satelia® Cardio is noteworthy since it relies only on symptomatic monitoring through which the patient manually reports their information by answering a simple questionnaire on a regular basis and does not rely on any connected devices. Conclusion: Innovative funding programs and solutions for RPM need real-world evaluation in the future.

Rho GTPases and the control of the oxidative burst in polymorphonuclear leukocytes.

Stimulation of quiescent leukocytes activates the NADPH oxidase, a membrane-associated enzyme system that generates superoxide and other reactive oxygen species (ROS) that are used to kill bacteria within the phagosome. This chapter describes this multicomponent NADPH oxidase system, one of the first cellular systems shown to be directly regulated by Rac GTPases. We present current models of NADPH oxidase regulation by Rac2 and describe how Rac2 activation controls the timing of ROS production in adherent neutrophils. The antagonistic role that Cdc42 plays as a competitor of Rac2 for binding to the cytochrome component of the NADPH oxidase is discussed as a possible mechanism for tonic regulation of ROS production during the formation of the phagosome. Finally, we briefly depict mechanisms by which invasive bacteria can alter (inhibit) NADPH oxidase function, focusing on the effects of invasive bacteria on components and assembly of the NADPH oxidase.

Influences of lovastatin administration on the respiratory burst of leukocytes and the phosphorylation potential of mitochondria in guinea pigs.

Lovastatin, a cholesterol-lowering drug, decreased plasma cholesterol and cardiac tissue coenzyme Q10 levels in guinea pigs given 20 mg per kg body weight twice a day. Plasma cholesterol levels were reduced 40% in animals 2 to 4 months of age and 61% in animals 2 years of age. Coenzyme Q10 values in cardiac muscle and cardiac mitochondria of the treated, older group were decreased 31% and 37%, respectively. A significant decrease was not observed in coenzyme Q10 levels of the younger animal group. The potential to phosphorylate ADP to ATP driven by pyruvate-malate and succinate oxidation was decreased 43% and 45%, respectively, for cardiac mitochondria from the treated, 2-year-old animals. A decrease in phosphorylation potential was not observed for the younger group. The respiratory burst of leukocytes isolated from the intraperitoneal cavities of the treated, older animals was decreased 67%, while leukocytes isolated directly from their blood was decreased 76% (Diebold, B., Bhagavan, N. and Guillory, R. (1991) FASEB J. 5, A1203). In contrast to the intact leukocytes, the superoxide production of the cell-free systems prepared from leukocytes isolated from treated and untreated animals did not differ significantly. These observations suggest that in vivo lovastatin may not directly affect the leukocyte superoxide generating system, but may influence it indirectly possibly by modifying the lipid content of the membrane.

Potential drug targets: small GTPases that regulate leukocyte function.

Leukocytes are not only important mediators of innate immunity, but they also induce and perpetuate inflammatory responses that are harmful to the host. Although inflammatory mediators activate leukocytes through a common heterotrimeric G protein (Gi) signalling intermediate, many downstream inflammatory functions are regulated by distinct small GTPases, which suggests that pharmacological modulation of small GTPase activity would be useful in developing specific anti-inflammatory therapies. The recent identification of multiple small GTPase effectors, the recognition of the role of GTPase regulatory proteins in directing downstream signalling from small GTPases, and detailed structural information on the GTPases themselves suggests new possibilities for the development of effective and selective anti-inflammatory drugs.

New diagnostic criteria for diabetes and coronary artery disease: insights from an angiographic study.

OBJECTIVES: The goal of this research was to study coronary atherosclerosis in patients with type 2 diabetes compared with patients without diabetes according to the new definition of diabetes advocated by the American Diabetes Association in 1997. BACKGROUND: Patients with diabetes (fasting plasma glucose above 7.0 mM/L) have a higher risk of cardiovascular death. The correlation with the pattern and severity of their coronary atherosclerosis, especially in the new patients with "mild" diabetes (7.0 mM/L < or = fasting plasma glucose < 7.8 mM/L), remains unclear. METHODS: A cohort of 466 patients undergoing coronary angiography but free of any previous infarction, coronary intervention and insulin therapy were prospectively recruited. Ninety-three had diabetes (fasting plasma glucose > 7.0 mM/L or hypoglycemic oral treatment). Five angiographic indexes were calculated to describe severity and extent of coronary atherosclerosis. RESULTS: Overall, patients with diabetes had more diffuse coronary atherosclerosis, a greater prevalence of mild, moderate and severe stenoses and a two-fold higher occlusion rate than patients without diabetes, even after adjustment for age, gender, body mass index, hypertension, lipid parameters, smoking, family history of cardiovascular events and ischemic symptoms. Patients with "mild diabetes" had a coronary atherosclerosis pattern more similar to patients with normal fasting plasma glucose than to patients formerly defined as diabetic according to the World Health Organization criteria, except that they had a higher prevalence of <50% stenoses. CONCLUSIONS: In patients with type 2 diabetes, those with 7.0 mM/L < or = fasting plasma glucose < 7.7 mM/L have a slightly greater prevalence of mildly severe lesions that may partly explain their higher cardiovascular event rate.

Pulsatile diameter and elastic modulus of the aortic arch in essential hypertension: a noninvasive study.

A noninvasive evaluation of the aortic arch diameter was performed in 16 subjects with sustained essential hypertension and in 15 normal subjects of similar age, gender and body surface area. In all subjects, measurements were obtained of brachial mean arterial pressure and pulse pressure, cardiac mass (judged on echocardiography) and carotid-femoral pulse wave velocity together with ultrasound determinations of aortic arch diastolic and systolic diameter (suprasternal window). For each subject, pulsatile change in aortic diameter, strain and aortic arch elastic modulus were calculated. Compared with normal subjects, the hypertensive subjects showed an increase in aortic arch diameter (diastolic diameter 29.6 +/- 1.0 versus 25.4 +/- 1.0 mm, p less than 0.01), in elastic modulus (1.071 +/- 0.131 versus 0.526 +/- 0.045 10(5) N.m-2, p less than 0.001) and pulse wave velocity (11.8 +/- 0.5 versus 8.9 +/- 0.3 m/s, p less than 0.001). In the study group, a positive correlation was observed between diastolic aortic arch diameter and mean arterial pressure (r = 0.54, p less than 0.01) and between elastic modulus and cardiac mass (r = 0.60, p less than 0.01). Elastic modulus and age were positively correlated (r = 0.73, p less than 0.01) in hypertensive but not in normal subjects (r = 0.08, NS). This study is the first to demonstrate noninvasively that both the aortic arch diameter and the elastic modulus are increased in patients with sustained uncomplicated essential hypertension. These findings suggest that the increase in elastic modulus could influence the development of cardiac hypertrophy, and that both age and blood pressure act independently as factors that alter the arterial wall of subjects with sustained essential hypertension.

Geometric features of coronary artery lesions favoring acute occlusion and myocardial infarction: a quantitative angiographic study.

OBJECTIVES: We sought to identify the angiographic predictors of a future infarction, to study their interaction with time to infarction, patient risk factors and medications, and to evaluate their clinical utility for risk stratification. BACKGROUND: Identification of coronary lesions at risk of acute occlusion remains challenging. Stenosis severity is poorly predictive but other stenosis descriptors might be better predictors. METHODS: Eighty-four patients with an acute myocardial infarction and a coronary angiogram performed within the preceding 36 months (baseline angiogram), and after infarction were selected. All coronary stenoses (from 10% to 95% lumen diameter reduction) at baseline angiogram were analyzed by computer-assisted quantification. Each of the 84 lesions responsible for the infarction (culprit) was compared with the nonculprit stenoses (controls) in the same patient. RESULTS: Culprit lesions were more symmetrical (symmetry index +15%; p < 0.001), had steeper outflow angles (maximal angle +4 degrees; p < 0.001), were more severe (percent stenosis +5%; p = 0.001) and longer (+ 1.5 mm, p = 0.01) than controls. The symmetry index and the outflow angles were the two independent predictors of infarction at three-year follow-up. Stenosis severity predicted only infarctions occurring within 1 year after angiography. In moderately severe stenoses (40% to 70% stenosis), stratification using the symmetry index and outflow angles accurately predicted lesions remaining free of occlusion and infarction at three-year follow-up. CONCLUSIONS: Better characterization of stenosis geometry might help to understand the pathophysiologic mechanisms triggering coronary occlusion and to stratify patients for improved care.

Assessment of left ventricular contraction by parametric analysis of main motion (PAMM): theory and application for echocardiography.

The computerized study of the regional contraction of the left ventricle has undergone numerous developments, particularly in relation to echocardiography. A new method, parametric analysis of main motion (PAMM), is proposed in order to synthesize the information contained in a cine loop of images in parametric images. PAMM determines, for the intensity variation time curves (IVTC) observed in each pixel, two amplitude coefficients characterizing the continuous component and the alternating component; the variable component is generated from a mother curve by introducing a time shift coefficient and a scale coefficient. Two approaches, a PAMM data driven and a PAMM model driven (simpler and faster), are proposed. On the basis of the four coefficients, an amplitude image and an image of mean contraction time are synthesized and interpreted by a cardiologist. In all cases, both PAMM methods allow better IVTC adjustment than the other methods of parametric imaging used in echocardiography. A preliminary database comprising 70 segments is scored and compared with the visual analysis, taken from a consensus of two expert interpreters. The levels of absolute and relative concordance are 79% and 97%. PAMM model driven is a promising method for the rapid detection of abnormalities in left ventricle contraction.

[1/1 nodo-ventricular conduction atrial flutter with amiodarone]. / Flutter atrial à conduction nodovenhiculaire 1/1 sous amiodarone.

1/1 atrial flutter is a regularly described complication of class I anti-arrhythmics. It is, however, very rarely encountered with class III anti-arrhythmics because prolongation of the atrio-ventricular node refractory period prevents 1/1 nodo-ventricular conduction. There have only been seven cases of 1/1 atrial flutter with amiodarone reported in the literature. Here we describe a new case of 1/1 atrial flutter with amiodarone. Our case clearly illustrates not only the different pro-arrhythmic effects of amiodarone (prolongation of the flutter cycle, and infra-Hissian block) but also the pathophysiological mechanisms possible with 1/1 conduction (prolongation of the flutter cycle, considerable permeability of the AV node). It demonstrates the difficulties of diagnosing such a rhythm disturbance, and that it is sometimes poorly tolerated, as well as underlining the importance of early diagnosis (in this case by oesophageal recording). Preventive treatment of 1/1 flutter can include amiodarone, digitalis, a betablocker or a bradycardic calcium inhibitor.

Combined effects of blood pressure and body mass index on left ventricular structure in middle-aged males: cross-sectional and 2-year longitudinal results.

OBJECTIVE: To compare the 2-year longitudinal with the cross-sectional relationships of blood pressure and body mass index with echocardiographic left ventricular measurements in middle-aged males with no history of cardiovascular disease or hypertension. METHODS: M-mode echocardiograms of adequate quality were obtained at initial and 2-year follow-up examinations in 177 subjects. Measurements of left ventricular wall thickness and internal dimensions were made, and estimates of left ventricular mass/height were calculated. Longitudinal changes in left ventricular measurements and risk factors were computed as the differences between the follow-up and initial values. RESULTS: Systolic blood pressure (SBP) was significantly associated with left ventricular mass/height and wall thickness in cross-sectional and in longitudinal analyses. Similar results were observed after adjusting for age, body mass index, sport activity and heart rate. Although body mass index was strongly related to left ventricular mass/height, wall thickness and internal dimension in the cross-sectional study, no significant associations were observed between changes in body mass index and in left ventricular measurements. CONCLUSIONS: The present study emphasizes the differential effects of spontaneous changes in blood pressure and body mass index on the evolution of the left ventricular mass in middle-aged males. Spontaneous changes in SBP during the 2-year follow-up period were associated with rapid changes in left ventricular structure. The 2-year period might not have been sufficient for body mass index to induce changes in left ventricular structure. The duration and amplitude of body weight changes which entail changes in left ventricular mass remain to be determined by further longitudinal investigations.

Determinants of right ventricular pressure in mild hypertension.

OBJECTIVE: Doppler echocardiography was used to define reference values and determinants of tricuspid regurgitation peak velocity (TRV) in hypertensive patients. A TRV value > 2.5 m/s is the threshold usually defining abnormal right ventricular systolic pressure. DESIGN AND PATIENTS: Doppler echocardiography was performed in 320 consecutive uncomplicated hypertensive patients, without overt pulmonary or heart disease. Doppler echocardiography included LV mass measurement, LV inflow and pulmonary venous flow analysis, LV systolic function and TRV measurements. RESULTS: Among 320 patients, 255 had normal TRV < 2.5 m/s and 65 had elevated TRV > or = 2.5 m/s. Compared with the normal TRV group, the elevated TRV group was older (60 versus 50 years, P < 0.0001), systolic blood pressure was higher (156 versus 151 mmHg, P = 0.02) and antihypertensive therapy was more frequent (68 versus 51%, P = 0.02); indexed LV mass was higher (45.4 versus 40.6 g/m2.7, P = 0.001), pulmonary D wave peak velocity was higher (42 versus 38 cm/s, P = 0.03). In univariate analysis, age was the most predictive variable of TRV (r = 0.36). In multivariate analysis, three variables were independently related to TRV: age, LV mass, pulmonary D wave (multiple r = 0.47). CONCLUSION: In mild hypertension, TRV is independently related to age, and to a lesser extent, to LV morphology and LV filling pressure. In clinical practice, age should be taken into account to interpret TRV.

Comparison of arbutamine and exercise echocardiography in diagnosing myocardial ischemia.

Arbutamine is a new catecholamine designed for use as a pharmacologic stress agent. This study compared the sensitivity of arbutamine with symptom-limited exercise to induce echocardiographic signs of ischemia. Arbutamine was administered by a computerized closed-loop delivery system that controls the infusion rate of arbutamine toward a predefined rate of heart rate increase and maximum heart rate limit. Beta blockers were stopped > or = 48 hours before both tests. Stress was stopped for intolerable symptoms, or clinical, electrocardiographic or echocardiographic signs of ischemia (new or worsening wall motion abnormality), target heart rate (> or = 85% age predicted maximum heart rate), or plateau of heart rate response. Thirty-seven patients were entered into the study (35 arbutamine and exercise, 1 arbutamine only, 1 exercise only), of which 30 had angiographic evidence of coronary artery disease (> or = 50% lumen diameter narrowing). Rate-pressure product increased significantly in response to both stress modalities (p < 0.001) and was significantly greater with exercise (11,308 +/- 2,443) than with arbutamine (9,486 +/- 2,479, p < 0.001). The time to maximum heart rate was longer during arbutamine stress echocardiography than during exercise testing (17.3 +/- 9.4 versus 9.3 +/- 4.2 minutes, respectively, p < 0.001). There were more patients with interpretable echo data for arbutamine (82%) than for exercise (67%). Sensitivity for recognition of myocardial ischemia was 94% (95% confidence interval 70% to 100%) and 88% (95% confidence interval 62% to 98%), respectively. The most frequent adverse events during arbutamine (n = 36) were dyspnea (5.6%) and tremor (5.6%). Two arbutamine stress tests were discontinued due to arrhythmias: 1 patient had premature atrial and ventricular beats, and the other had premature atrial contractions and atrial fibrillation. Arrhythmias were well tolerated and resolved without sequelae. In conclusion, the sensitivity of arbutamine to induce echocardiographic signs of ischemia was similar to that of exercise despite a lower rate-pressure product. Arbutamine was well tolerated and provides a reliable alternative to exercise echocardiography.

Noninvasive assessment of aortocoronary bypass graft patency using pulsed Doppler echocardiography.

To evaluate noninvasively aortocoronary bypass graft patency, pulsed Doppler echocardiography was performed at the time of postoperative coronary angiography in 120 consecutive patients. Ultrasonic examination of 163 vein grafts was possible. One hundred twenty-seven patent and 14 occluded grafts were correctly identified. Eleven patent grafts could not be recorded, and 11 occluded grafts were falsely diagnosed as patent. The method had an overall sensitivity of 92% and a specificity of 56%. This high sensitivity level may be increased to almost 100% by enhanced technical skill and experience. The low specificity level, although the method must be tested in a larger number of bypass grafts, stresses the importance of correctly identifying other sources of diastolic blood flow. Diastolic flows from the superior vena cava, internal mammary veins, tricuspid valve, mitral valve and right ventricle may be eliminated by careful adjustment of the depth, site and size of the pulsed Doppler electronic sampling gate. Standard echocardiographic landmarks for avoiding confusion with the coronary arteries are also described.

Doppler-derived pulmonary arterial systolic pressure in patients with known systemic arterial pressures.

In the present study, we evaluated Doppler-derived systolic pulmonary artery pressure in 476 hypertensive patients. Clinical interpretation of systolic pulmonary arterial pressure should take into account age, body size, and systolic blood pressure values.

Relations between Doppler tracings of pulmonary regurgitation and invasive hemodynamics in acute right ventricular infarction complicating inferior wall left ventricular infarction.

To test the hypothesis that flow characteristics from pulmonary regurgitation (PR) can predict right ventricular (RV) involvement in patients with inferior wall acute myocardial infarction, we prospectively recorded continuous-wave Doppler tracings and right-sided cardiac hemodynamics in 48 consecutive patients with inferior wall acute myocardial infarction and PR. Right heart hemodynamics enabled the identification of 29 patients with (group 1) and 19 without (group 2) RV involvement. In patients with RV involvement, the pulmonary regurgitant flow pattern was characterized by a rapid rise in flow velocity to a peak level followed by an abrupt deceleration in mid-diastole, whereas in patients without RV involvement, the deceleration in mid-diastole was gradual. The pressure half-time of PR (PHTPR) and the lowest mid-diastolic to peak early diastolic velocity ratio were significantly lower in group 1 than in group 2 (91 +/- 31 vs 214 +/- 57 ms [p < 0.001], 0.35 +/- 0.08 vs 0.59 +/- 0.13 [p < 0.001], respectively). The best diagnostic accuracy (95%) was obtained with cut-off values of PHTPR < or = 150 ms and the lowest mid-diastolic to peak early diastolic velocity ratio < or = 0.5: sensitivity 100%, specificity 89%, positive predictive value 94%, and negative predictive value 100%. Using multiple logistic regression analysis, we found that PHTPR was the strongest predictor of RV involvement. Thus, these parameters, derived from pulmonary regurgitant tracings, are useful in the noninvasive bedside diagnosis of RV infarction.

Relation between severity of coronary artery disease, left ventricular function and myocardial infarction, and influence of the ACE I/D gene polymorphism.

Left ventricular (LV) systolic function is partly determined by severity of coronary artery disease and is improved by angiotensin-converting enzyme (ACE) inhibition, at least in post-infarct patients. Because the ACE insertion/deletion (I/D) gene polymorphism is associated with circulating and tissue ACE activity, we sought to evaluate the role of this genetic variant on LV function in patients studied with coronary angiography, taking into account coronary vessel anatomy and history of infarction. Coronary artery disease extent scores, coronary artery patency, and LV ejection fraction were assessed in 400 consecutive Caucasian patients referred for established or suspected ischemic heart disease. A previous infarction had occurred in 141 patients an average of 3.7 years before the study. The ACE DD genotype, compared with the ACE ID/II genotype, was associated with a 2.7% higher ejection fraction in noninfarct patients (p = 0.047) but a 5.0% lower ejection fraction in post-infarct patients (p = 0.047). An interaction effect between the ACE I/D gene polymorphism, the infarction status, and LV ejection fraction was observed in the whole population (p = 0.003), in patients with no disease and 1-, 2-, and 3-vessel diseases (p = 0.03 and p = 0.06, respectively), and in those with chronically occluded coronary vessels (p = 0.02). The influence of the ACE I/D gene polymorphism on LV function is modulated by infarction status and coronary anatomy.

Noninvasive estimation of systolic pulmonary artery pressure using Doppler echocardiography in patients with chronic obstructive pulmonary disease.

In patients with acquired or congenital heart diseases, the systolic pulmonary artery pressure (PAPs) can be predicted using continuous-wave Doppler ultrasound (CWD) measurement of the peak velocity of a tricuspid regurgitation (TR) jet. The aim of this study was to determine whether CWD could be used to accurately estimate PAP in patients with chronic obstructive pulmonary disease (COPD). In 41 patients with stable COPD, we prospectively performed CWD and right heart catheterization. The mean value of PAPs for the entire group was 38.5 +/- 14.9 mm Hg. Pulmonary arterial hypertension (PAPs greater than or equal to 35 mm Hg) occurred in 51 percent (21/41) of patients. Doppler estimation of PAP was impossible in 34 percent (14/41) because of poor signal quality (n = 3), absence of Doppler-detected TR (n = 8), and inadequate TR Doppler signal (n = 3). The PAP could be estimated in 66 percent (27/41) of patients. A statistically significant correlation was found between the Doppler-estimated PAP and the catheter-measured PAPs (r = 0.65; p less than 0.001; SEE = 9 mm Hg). Therefore, CWD appears to be useful for the noninvasive estimation of PAP in patients with COPD. However, this method is associated with two limitations: (1) the high percentage of patients in whom the PAP cannot be estimated by CWD, mainly because of the absence of Doppler-detected TR, and (2) the high value of the standard error of the estimate. The combination of CWD with other Doppler methods should increase the feasibility and accuracy of Doppler echography for the prediction of PAP in patients with COPD.

Diagnostic and therapeutic implications of transesophageal echocardiography in medical ICU patients with unexplained shock, hypoxemia, or suspected endocarditis.

OBJECTIVE: To evaluate the diagnostic and therapeutic implications of transesophageal echocardiography (TEE) in intensive care patients. DESIGN: Comparative study. SETTING: A 10-bed general intensive care unit. PATIENTS: Between 1 January 1992 and 31 May 1993, 61 patients prospectively identified with shock (n = 14), severe, unexplained hypoxemia (Partial pressure of oxygen in arterial blood/fractional inspired oxygen < 200) (n = 31), or suspected endocarditis (n = 16) underwent a TEE examination to supplement transthoracic echocardiography (TTE) examination. INTERVENTIONS: The results of each TEE examination were compared with the clinical findings and TTE data. TEE examinations were classified as follows: 0, TEE results were similar to TTE results; 00, TEE examination resulted in exclusion of suspected abnormalities; 1, TEE revealed a new but minor diagnosis compared to the TTE diagnosis; 2, TEE revealed a new major diagnosis not requiring a change of treatment; 3, TEE results revealed a new major diagnosis requiring an immediate change of treatment. RESULTS: Intraobserver reliability of the TEE classification was confirmed by a 100% concordance and interobserver reliability was evaluated as an 84% concordance. Results of the TEE classification were: class 0, n = 21 (34%); class 00, n = 13 (21%); class 1, n = 7 (12%); class 2, n = 8 (13%); class 3, n = 12 (20%). Therapeutic implications of TEE in class 3 patients were cardiac surgery in 5 patients (2 cases of acute mitral regurgitation, 2 valvular abscesses, and 1 hematoma compressing the left atrium), discontinuation of positive end-expiratory pressure in 1 ventilated patient with an atrial septal defect, weaning off mechanical ventilation in 1 patient with an atrial septal defect, prescription of antimicrobial therapy in 3 patients with endocarditis, and prescription of anticoagulant therapy in 2 patients with left atrial thrombus. No difficulty inserting the transducer was observed in any of the 61 patients studied. The only noteworthy complication was a case of spontaneously resolving atrial fibrillation. CONCLUSION: TEE is safe and well tolerated and is useful in the management of patients in the intensive care unit with shock, unexplained and severe hypoxemia, or suspected endocarditis when TTE is inconclusive.