Transcutaneous Exercise Oximetry for Patients With Claudication　- A Retrospective Review of Approximately 5,000 Consecutive Tests Over 15 Years.

BACKGROUND: Exercise transcutaneous oximetry (Ex-tcPO2) is used to argue for the vascular origin of lower limb pain, especially at the proximal level, where the diagnosis of peripheral artery disease can be difficult. This study analyzed the principal indications, mean results, and limitations of Ex-tcPO2, as well as the relationship between the annual number of Ex-tcPO2 tests and internal iliac artery (IIA) revascularizations.Methods and Results:Data from our first 15 years' experience (3,631 patients, 5,080 tests) with Ex-tcPO2 were analyzed retrospectively using the minimal value of the decrease from rest of oxygen pressure (DROPmin). We had 99.7% of expected DROPminresults. The proportion of tests showing isolated proximal unilateral or bilateral ischemia ranged from ~5% to ~20%. A gradual increase with time was observed in both the annual number of Ex-tcPO2 tests (from 0 to ~500 per year) and the annual number of IIA revascularizations performed (from 0 up to 18 per year). At least 85% of patients (77/91) showed function improvement after IIA revascularization. CONCLUSIONS: Ex-tcPO2 (using DROPmin) provides an objective argument for exercise-induced ischemia, bilaterally at the distal and/or proximal level. Using Ex-tcPO2 has improved our diagnostic performance and markedly changed our therapeutic decisions, specifically for proximal claudication. The increased number of Ex-tcPO2 tests is associated with an increased number of IIA revascularizations, although a causal relationship was not proven.

Exercise Transcutaneous Oximetry of the Buttocks　- External Validation With Computed Tomography Angiography.

BACKGROUND: Exercise transcutaneous oximetry (Ex-tcPO2) is a non-invasive test for exercise-induced buttock ischemia. Prior study defined Ex-tcPO2 normal/abnormal cut-offs against arteriography but no external validation was available. The aims of this study were therefore to (1) determine the diagnostic performance of Ex-tcPO2 against CTA; (2) determine the cut-off point for detection of stenosis >75% in arteries toward the hypogastric circulation; and (3) determine the effect of chest profile classification on the diagnostic performance of Ex-tcPO2.Methods and Results:A total of 207 patients referred for Ex-tcPO2 were analyzed. DROP during Ex-tcPO2 was compared with the CTA results. Chest-tcPO2 changes were automatically classified into pre-defined profiles representing normal or abnormal responses. Using DROP <-15 mmHg as a cut-off, Ex-tcPO2 had 80.2% sensitivity, 72.3% specificity, 43.1% PPV, 93.3% NPV and 73.9% accuracy, to detect 1 stenosis >75% in arteries toward the hypogastric circulation. Optimal DROP to detect stenosis was: -15 mmHg. The overall diagnostic performance of Ex-tcPO2 was independent of chest profile classification. CONCLUSIONS: Ex-tcPO2 has satisfactory diagnostic performance to detect arterial stenoses towards the hypogastric circulation. Abnormal chest-tcPO2 profile does not impair the overall diagnostic performance of the test.

Optimisation of movement detection and artifact removal during laser speckle contrast imaging.

INTRODUCTION: Laser speckle contrast imaging (LSCI) allows an easy non-contact monitoring of the cutaneous blood flow (CBF), but is highly sensitive to movement artifacts (ARTm). Subtraction of a signal recorded on an adhesive opaque surface (AOS) close to the area of interest was reported as a mean of reducing noise from the raw skin LSCI (LSCIsk) signal, provided an individual calibration was performed. Assuming that AOS=a·CBF+b·ARTm, an ideal patch should completely block the light reflection due to CBF and thus be insensitive to skin blood flow changes ("a"~0), while keeping a reflection signal amplitude similar to the one from the skin in case of artifact ("b"~1). This ideal AOS has not been determined and may discriminate flow from movements during LSCI recordings. MATERIALS AND METHODS: We tested different AOSs to determine their "a" and "b" parameters in 35 and 34 healthy volunteers, respectively. The AOS surface providing results as close as possible to an ideal AOS, was used for a point-by-point de-noising of post occlusive reactive hyperemia (PORH) on two different days in 15 new subjects. Correlation of raw, smoothed (average smoothing over 1s intervals) and denoised signals was tested through a cross-correlation analysis of the two POHR tests. RESULTS: The optimal "a" and "b" values were obtained with a homemade bilayer adhesive patch (a=0.06±0.05 and b=1.03±0.17) whereas other tested AOS had "a" values ranging from 0.05 to 0.23 and "b" values ranging from 2.69 to 3.82. Using the bilayer adhesive patch the cross-correlation between the two tests of POHR increased from 0.330±0.128 for raw, to 0.461±0.168 for smoothed and 0.649±0.128 for denoised signals respectively (p<0.05 from raw coefficients). CONCLUSION: The home-made bilayer adhesive seems the optimal AOS for the removal of ARTm from the LSCIsk signal while respecting CBF signal. This specific AOS allows for an efficient de-noising of LSCI measurements without the need for individual calibration.

Comparison of two devices for measuring exercise transcutaneous oxygen pressures in patients with claudication.

BACKGROUND: We aimed at estimating the agreement between the Medicap" (photo-optical) and Radiometer• (electrochemical) sensors during exercise transcutaneous oxygen pressure ( tcp02) tests. Our hypothesis was that although absolute starting values (tcp02rest: mean over 2 minutes) might)e different, tcpOTchanges over time and the minimal value of the decrease from rest of oxygen pressure (DROPmin) results at exercise shall be concordant between the two systems. taneously, one of each system on the chest, on each buttock and on each calf. RESULTS: Seventeen Medicap" probes disconnected during the tests. tcp02rest and DROPmin values were higher with Medicap• than with Radiometer•, by 13.7 ± 17.1mmHg and 3.4 ± 11.7 mmHg, respectively. Despite the differences in absolute starting values, changes over time were similar between the two systems. The concordance between the two systems was approximately 70% for classification of test results from DROPmin. CONCLUSIONS: Photo-optical sensors are promising alternatives to electro-chemical sensors for exercise oximetry, provided that miniaturization and weight reduction of the new sensors are possible. PATIENTS AND METHODS: Forty seven patients with arterial claudication ( 65 ± 7 years) performed a treadmill test with 5 probes each of the electro-chemical and photo-optical devices simul-

Improvement of cardiac diastolic function by long-term centrally mediated sympathetic inhibition in one-kidney, one-clip hypertensive rabbits.

BACKGROUND: Hypertension is associated with left ventricular hypertrophy (LVH) and diastolic dysfunction. The sympathetic nervous system (SNS) is strongly implicated in these alterations. The possible beneficial effect of a centrally mediated sympathetic inhibition on the diastolic function in severe hypertension has never been studied. We have evaluated the cardiac effects (remodeling, diastolic and systolic functions) of a long-term treatment with a centrally acting drug, rilmenidine, in a model of severe renovascular hypertension. METHODS: One-kidney, one-clip (1K,1C) Goldblatt hypertensive rabbits were randomized in two groups, one receiving rilmenidine (5 mg/kg/day) for 6 weeks and the other treated with vehicle only. Hemodynamic effects and left ventricular (LV) remodeling were evaluated by serial tail cuff pressure measurements, and echocardiography every 15 days. These measurements were followed up with invasive hemodynamic measurements and histological analysis. RESULTS: Rilmenidine induced a decrease of 8% in blood pressure, a significant bradycardia (19% at 6 weeks after treatment) and an 18% reduction in LV mass, without reduction of ejection fraction (EF). These effects were accompanied by an improvement of the diastolic function, as shown by isovolumic relaxation time and decrease in Tau index, an E/A ratio reversion, and an Ea velocity increase. Moreover, reduction in the atrial (A) and atrial reverse (Ar) velocities, without any effect on LV filling pressures, was observed. CONCLUSIONS: In 1K,1C Goldblatt rabbits, which mimic most of the characteristics of human hypertensive cardiopathy, we have shown, for the first time, that a central inhibition of the SNS rapidly reverses cardiac hypertrophy and problems associated with primary LV relaxation, without negative inotropic action.

Vasodilator response to galvanic current stimulation of the skin accurately detects acetylsalicylic acid intake: A study in 400 vascular patients.

BACKGROUND AND AIMS: The first cause of low-dose acetylsalicylic-acid (ASA) inefficacy is poor adherence to treatment. No non-invasive technique is available to assess ASA intake. Current-induced vasodilation (CIV) was found abolished in healthy volunteers after low-dose ASA intake. We tested clinical characteristics, treatments, and comorbid conditions influencing CIV amplitude in vascular patients. METHODS: CIV was tested in 400 patients (277 males and 123 females, aged 65.4 ±â€¯13.4 years). We focused on clinical characteristics, treatments, and comorbid conditions as covariates of CIV amplitude. We studied the CIV amplitude to covariate relationships with multivariate linear regression and receiver operating characteristics (ROC). RESULTS: The multivariate linear model determined that ASA intake within the last 48 h and the interaction between ASA intake and body mass index (BMI) were the sole covariates associated with CIV amplitude. For the whole population, the area under the ROC curve (AUC) for CIV to predict ASA intake was 0.853 [95% confidence interval (CI): 0.814-0.892]. Considering separately the areas observed for non-obese (BMI ≤30, n = 303) and obese (BMI>30, n = 93) patients, the AUC [95% CI] was 0.873 [0.832-0.915] and 0.776 [0.675-0.878], respectively (p = 0.083). CONCLUSIONS: ASA is the only drug that affects the amplitude of CIV response observed after galvanic current application to the skin of vascular patients. CIV depends on BMI but not age or gender. As such, CIV appears to be a potential objective marker of ASA intake and could facilitate future non-invasive assessments of adherence to ASA treatment.

Ankle brachial index is equally predictive of exercise-induced limb ischemia in diabetic and non-diabetic patients with walking limitation.

BACKGROUND: In diabetic patients, arterial stiffness may impair compressibility of vessels and result in higher ankle to brachial index (ABI) than in non-diabetic subjects. METHODS: We studied 1972 non-diabetic and 601 diabetic patients, with suspected peripheral artery disease, Exercise transcutaneous oxygen pressure (Ex-tcpO2), expressed in DROP index (limb tcpO2 change minus chest tcpO2 change), is insensitive to arterial stiffness and can estimate exercise-induced regional blood flow impairment (RBFI). A minimal DROP <-15 mm Hg indicates the presence of RBFI (positive test). ABI was simplified to a category variable (ABIc) by rounding ABI to the closest first decimal. RESULTS: In the ABIc range 0.4 to 1.1 linear regression for mean DROP values were: y = 34 x - 53; (R2 = 0.211) and y = 33 x - 52; (R2 = 0.186) in diabetic and Non-diabetic patients, respectively. Both Db and non-D patients showed a high proportion of positive Ex-tcpO2 tests for ABIc in the normal range (ABIc: 1.0 and over) from 27.1 to up to 58%. More than half of patients with borderline ABI (ABIc = 0.9) had RBFI during exercise. it was 65.6% in diabetic and 58.5% non-diabetic patients. CONCLUSIONS: Resting ABI was not a better predictor of exercise-induced RBFI in non-Db than in Diabetic patients. Our results highlights the interest of still measuring resting-ABI in diabetic patients to argue for the vascular origin of exertional limb pain, but also of performing exercise tests in patients with walking impairment.

Exercise transcutaneous oximetry significantly modifies the diagnostic hypotheses and impacts scheduled investigations or treatments of patients with exertional limb pain.

INTRODUCTION: In lower extremity peripheral artery disease (PAD), transcutaneous oximetry at exercise (Ex-TcpO2) has been largely validated in research practice, but evidence of routine practice in various vascular laboratories is missing. We hypothesized that Ex-TcPO2 would change the diagnosis hypotheses, investigations and treatments for patients referred for exertional limb pain. MATERIAL & METHODS: A multicenter prospective trial was conducted in nine different referral centers. Investigators performed Ex-TcpO2 and recorded investigations and treatments already scheduled for the patient. We encoded referral physician's diagnostic hypothesis. Before Ex-TcpO2, vascular physicians were asked to give their diagnosis hypotheses. A minimal decrease from rest of oxygen pressure (DROP)

Recurrent Isolated Neonatal Hemolytic Anemia: Think About Glutathione Synthetase Deficiency.

Hemolytic anemia (HA) of the newborn should be considered in cases of rapidly developing, severe, or persistent hyperbilirubinemia. Several causes of corpuscular hemolysis have been described, among which red blood cell enzyme defects are of particular concern. We report a rare case of red blood cell enzyme defect in a male infant, who presented during his first months of life with recurrent and isolated neonatal hemolysis. All main causes were ruled out. At 6.5 months of age, the patient presented with gastroenteritis requiring hospitalization; fortuitously, urine organic acid chromatography revealed a large peak of 5-oxoproline. Before the association between HA and 5-oxoprolinuria was noted, glutathione synthetase deficiency was suspected and confirmed by a low glutathione synthetase concentration and a collapse of glutathione synthetase activity in erythrocytes. Moreover, molecular diagnosis revealed 2 mutations in the glutathione synthetase gene: a previously reported missense mutation (c.[656A>G]; p.[Asp219Gly]) and a mutation not yet described in the binding site of the enzyme (c.[902T>C]; p.[Leu301Pro]). However, 15 days later, a control sample revealed no signs of 5-oxoprolinuria and the clinical history discovered administration of acetaminophen in the 48 hours before hospitalization. Thus, in this patient, acetaminophen exposure allowed the diagnosis of a mild form of glutathione synthetase deficiency, characterized by isolated HA. Early diagnosis is important because treatment with bicarbonate, vitamins C and E, and elimination of trigger factors are recommended to improve long-term outcomes. Glutathione synthetase deficiency should be screened for in cases of unexplained newborn HA.

High prevalence of known and unknown pulmonary diseases in patients with claudication during exercise oximetry: A retrospective analysis.

The prevalence of pulmonary disease in patients with peripheral artery disease (PAD) has not been extensively studied. Recent evidence has shown that ∼20% of the patients have an atypical chest transcutaneous oxygen pressure (TcpO2) pattern during exercise, which suggests walking-induced hypoxemia. The main objectives of this study were to: (1) describe in a retrospective way the characteristics of the patients suffering from claudication, who attended a treadmill testing in our laboratory, (2) assess the prevalence of known or unknown pulmonary disease. The second aim of this study was to evaluate the impact of the therapeutic interventions on the walking capacities, after treatment, of the eventually detected pulmonary disorders.We retrospectively analyzed 1482 exercise TcpO2 test results. Patients that had no history of pulmonary disease, but either reported severe dyspnea or showed atypical profiles on their chest exercise-TcpO2, were advised to refer to the department of pneumology for additional investigations.In addition to the 166 patients with a history of pulmonary disease, 158 patients were suspected of unknown pulmonary disease from the result of their TcpO2 test. Many patients (n = 99/158, 62.7%) did not attend a pulmonologist visit. A pulmonary disease was established in 55 (93.2%) of the other 59 patients. Obstructive sleep apnea syndrome (OSAS) was the one and only diagnosis retained in 42/59 patients (71.2%). Among the 47 patients who had a second evaluation of their walking capacity on treadmill, 38 had treatment of the pulmonary disease found, vascular surgery treatment or a severe restricted diet, 9 had no treatment. Only the "treated" group showed a significant improvement in the maximal walking distance on treadmill between the 2 evaluations, 313 ±â€Š251 m to 433 ±â€Š317 m (P = 0.03).This retrospective pilot study underlines the high prevalence of both known and unknown pulmonary disease in patients whose primary complaint was lower limb claudication. Systematic screening and treatment of pulmonary disease in patients with claudication might be justified, to improve walking ability of such patients and possibly reduce or delay the requirement for revascularization. Prospective studies are required to confirm these preliminary results.

Multiprobe devices for exercise transcutaneous oxymetry in patients complaining claudication: interest and limits of unusual probe positions.

BACKGROUND: Exercise transcutaneous oximetry (PtcO2) can argue for a vascular origin of exercise-related pain in atypical unusual localizations, such as lumbar, thigh or foot pain. We used five probes as a standard for treadmill PtcO2 tests. Recent commercially available devices now include up to eight probes. We aimed at analyzing the potential interest of positioning a 6th probe on the area of unusual localization during exercise PtcO2 tests. METHODS: We retrospectively analyzed our data with a 6-probes device, using as a standard: one probe on the chest, one on each buttock and one on each calf. The sixth probe was positioned either: in the lumbar median position (N.=342), on the anterior lower part of the thigh (N.=391) or on the dorsum of the foot (N.=155) in patients complaining exercise-induced pain including the back, thigh or foot respectively. Results on the sixth probe at the limb were compared to result of the standard adjacent probe. A positive test (abnormal result) was defined as a minimal value of the DROP-index lower than minus 15 mmHg. RESULTS: Prevalence of positive results on the 6th probe with negative results on the adjacent standard probe was 2.3% at the lumbar site, 3.8% at the thigh and 12.3% at the foot level. CONCLUSIONS: Atypical localizations are rarely but sometimes associated to isolated positive exercise PtcO2 results and may justify the use of more than five probes in some patients, specifically for foot pain.

Echocardiography in conscious 1K,1C Goldblatt rabbits reveals typical features of human hypertensive ventricular diastolic dysfunction.

Diastolic dysfunction is a major component of hypertensive cardiomyopathy contributing to a progressive evolution towards overt heart failure. To establish an experimental model that could mimic the human clinical pattern, we standardized the surgery in one-kidney, one-clip Goldblatt (1K,1C) rabbits and characterized their hypertensive cardiopathy by echocardiography. Five weeks after placement of a stenotic string around the left renal artery and removal of the right kidney, arterial pressure was measured and an echocardiography performed in conscious animals. An hypertrophic cardiopathy associated with hypertension and a primary trouble of the LV relaxation was observed. This trouble was characterized by a reversion of E/A and Ea/Aa ratios and an increase of the isovolumic relaxation time and Tau index, without augmentation of left ventricular filling pressures. We show for the first time, in this experimental model, a diastolic dysfunction pattern close to the human one. Moreover, echocardiography in a conscious state gives the opportunity to use this model for future chronic pharmacological studies.