Comparison of treatment modalities for non-tuberculous mycobacterial cervicofacial lymphadenitis in children.

PURPOSE: We aim to compare the different treatment modalities of non-tuberculous cervicofacial lymphadenitis in children, by means of a retrospective study conducted in the University Hospitals of Leuven of patients treated between 2012 and 2022. METHODS: For this retrospective cohort study, data were collected and pseudonimised from 52 patients with non-tuberculous cervicofacial lymphadenitis, who were treated in our hospital between January 2012 and December 2022, either conservatively, antibiotically, surgically, or with a combination of these options. We only included patients who were considered immunocompetent. All of the included patients were below 10 years at time of treatment. We collected data regarding time to resolution and adverse effects, i.e., skin discoloration, excessive scar formation, fistula formation, persistence of adenopathies after treatment, need for additional treatment, facial nerve paresis/paralysis, or systemic side-effects due to antibiotic treatment. RESULTS: The mean time to resolution (in days) when looking at primary treatments, was shortest in partial excisions (16), followed by complete excisions (19), antibiotic therapy (129), incision and drainage (153), curettage (240), and finally conservative management (280). Taking into account isolated treatments (i.e., both primary and adjuvant), we also observed consistently faster time to resolution in surgical and antibiotic treatments when compared to conservative treatment. Antibiotic therapy (p = 0.003), incision and drainage (p = 0,004) were associated with a significantly higher need for adjuvant treatment. Curettage was associated with a higher incidence of fistula formation (p = 0,006) and higher number of adjuvant treatments (p = 0,002). CONCLUSIONS: This study shows a faster resolution of nontuberculous mycobacterial cervicofacial lymphadenitis in children when treated surgically, more specifically when treated with partial or complete lymph node excision. Antibiotic treatment also leads to faster resolution than conservative management. There was a low rate of complications, and no permanent facial nerve damage was reported.

ECFS standards of care on CFTR-related disorders: Diagnostic criteria of CFTR dysfunction.

The spectrum of disorders involving CFTR (cystic fibrosis transmembrane conductance regulator) dysfunction correlates with a continuous gradient of CFTR function defined by the combination of two allelic CFTR variants. CFTR-related disorders are clinical entities with features of cystic fibrosis (CF) and evidence for presence of CFTR dysfunction but not meeting criteria for diagnosis of CF. Individuals with CFTR-RDs demonstrate a wide range of CFTR activity and are still under-recognized or misclassified. The level of CFTR dysfunction may be measured in vivo (sweat testing, nasal potential difference measurements) and/or by ex vivo tests (intestinal current measurement), or indirectly indicated by CFTR variants, as alteration in sequence of the CFTR gene translates into CFTR dysfunction. CFTR bioassays can aid in the diagnosis of individuals with CF, but we lack parameters to differentiate CF from CFTR-RD. In the era of the CFTR modulators and their potential clinical benefit, it is of utmost importance to diagnose CFTR-RD as unambiguously as possible. We therefore propose the following to define compatible CFTR dysfunction in a person with a suspected diagnosis of CFTR-RD : (1) evidence of CFTR dysfunction in vivo or ex vivo in at least two different CFTR functional test types, or (2) One CFTR variant known to reduce CFTR function and evidence of CFTR dysfunction in vivo or ex vivo in at least two different CFTR functional test types, or (3) Two CFTR variants shown to reduce CFTR function, with at most one CF-causing variant.

Standards of care guidance for sweat testing; phase two of the ECFS quality improvement programme.

More than five decades after the introduction of the quantitative pilocarpine iontophoresis technique, surveys still highlight inconsistencies in the performance and reporting of sweat tests in Europe. The sweat test remains key for the Cystic Fibrosis (CF) diagnostic pathway for all age groups, as it reflects the basic pathophysiological defect in the sweat gland. It is also critical following newborn screening as a confirmatory diagnostic step. Despite its importance, sweat test quality is variable whether performed in the laboratory or as a point of care test. The ECFS DNWG aims to improve sweat test performance, taking into account the barriers and issues identified in the European survey; the previous step in the ECFS sweat test project. This manuscript proposes a grading of sweat test guidance from "acceptable" to "optimal", aiming to pragmatically improve quality while taking into account local situations, especially in resource-limited settings.

TREatment of ATopic eczema (TREAT) Registry Taskforce: protocol for a European safety study of dupilumab and other systemic therapies in patients with atopic eczema.

BACKGROUND: A long-term prospective observational safety study is essential to characterize fully the safety profile of systemic immunomodulating therapies for patients with atopic eczema. The TREatment of ATopic eczema (TREAT) Registry Taskforce offers a large platform to conduct such research using national registries that collect the same data using a predefined core dataset. OBJECTIVES: To present a protocol for a safety study comparing dupilumab with other systemic immunomodulating therapies in children and adults with moderate-to-severe atopic eczema, to assess the long-term safety risk of these therapies in a routine clinical care setting. METHODS: We describe a registry-embedded international observational prospective cohort study. Adult and paediatric patients who start treatment with dupilumab or another systemic immunomodulating agent for their atopic eczema will be included. The primary end point is the incidence of malignancies (excluding nonmelanoma skin cancer) compared between the treatment groups. Secondary end points include other serious adverse events and adverse events of special interest, such as eye disorders and eosinophilia. CONCLUSIONS: This protocol delineates a safety study for dupilumab in adult and paediatric patients with atopic eczema, using a standardized methodological approach across several national registries. The protocol could also be used for other novel systemic immunomodulating therapies, and could provide licensing and reimbursement authorities, pharmaceutical companies and clinicians with safety evidence from a routine clinical care setting. What's already known about this topic? There is a need for long-term data on the safety of systemic immunomodulating therapies in patients with atopic eczema. Regulatory bodies, such as the European Medicines Agency, increasingly stipulate the collection of such data as part of the licensing agreement for new treatments, to assess the new agent's long-term safety profile against established therapies. Large numbers of patients with a long duration of follow-up are necessary in order to detect rare events like malignancies. What does this study add? The TREAT Registry Taskforce offers a platform to conduct such research with a network of multiple national atopic eczema research registries. We present a protocol for an investigator-initiated multicentre safety study comparing dupilumab with other systemic immunomodulating therapies in adults and subsequently adolescents and children with moderate-to-severe atopic eczema. This protocol can be used as a framework for similar studies for other novel systemic immunomodulating therapies across both adult and paediatric populations.

Biological variability of the sweat chloride in diagnostic sweat tests: A retrospective analysis.

BACKGROUND: The sweat test is the current gold standard for the diagnosis of cystic fibrosis (CF). CF is unlikely when sweat chloride (Clsw) is lower than 30mmol/L, Clsw>60 is suggestive of CF, with intermediate values between 30 and 60mmol/L. To correctly interpret a sweat chloride value, the biological variability of the sweat chloride has to be known. METHODS: Sweat tests performed in two centers using the classic Gibson and Cooke method were retrospectively reviewed (n=5904). Within test variability of Clsw was measured by comparing results from right and left arm collected on the same day. Between test variability was calculated from subjects with sweat tests performed on more than one occasion. RESULTS: Within test variability of Clsw calculated in 1022 subjects was low with differences between -3.2 (p5) and +3.6mmol/L (p95). Results from left and right arm were classified differently in only 3 subjects. Between test variability of Clsw in 197 subjects was larger, with differences between -18.2mmol/L (p5) and +14.1mmol/L (p95) between repeat tests. Changes in diagnostic conclusion were seen in 55/197 subjects, the most frequent being changing from indeterminate to 'CF unlikely' range (48/102). CONCLUSION: Variability of sweat chloride is substantial, with frequent changes in diagnostic conclusion, especially in the intermediate range.

Variability of sweat chloride concentration in subjects with cystic fibrosis and G551D mutations.

INTRODUCTION: Sweat chloride concentration, a biomarker of CFTR function, is an appropriate outcome parameter in clinical trials aimed at correcting the basic CF defect. Although there is consensus on a cut-off value to diagnose CF, we have only limited information on the within subject variability of sweat chloride over time. Such information would be useful for sample size calculations in clinical trials. Therefore, we retrospectively analyzed repeated sweat chloride values obtained in patients with G551D mutation(s) assigned to placebo in an ivacaftor interventional trial. METHODS: In subjects with G551D at least 12years of age, a pilocarpine sweat test using Macroduct collector was taken on both arms at 8 time points over 48weeks. We explored 1062 pilocarpine sweat test values obtained in 78 placebo patients of the VX08-770-102 trial. RESULTS: Mean overall sweat chloride value (all patients, all tests, n=1062) was 100.8mmol/L (SD 12.7mmol/L). Using a multilevel mixed model, the between-subject standard deviation (SD) for sweat chloride was 8.9mmol/L (95% CI 7.4-10.6) and within-subject SD was 8.1mmol/L (95% CI 7.5-8.7). Limits of repeatability for repeat measurements were -19.7 to +21.6mmol/L using values from one arm, and -13.3 to 11.8mmol/L using mean of values obtained at 4 test occasions. Sample size calculations showed that the minimal treatment effect on sweat chloride concentration that can be demonstrated for a group of 5 patients is around 15mmol/L, using a cross-over design and combinations of 4 tests for each phase of the trial. CONCLUSION: Although the sweat test is considered a robust measure, sweat chloride measurements in patients with CF and a G551D mutation had an inherent biological variability that is higher than commonly considered. Further analyses of placebo group data are crucial to learn more about the natural variability of this outcome parameter.

[New tools in cystic fibrosis]. / Nouvelles techniques d'évaluation dans la mucoviscidose.

The use of 3 novel tools available for the diagnosis and treatment in cystic fibrosis are described here. 1) The lung clearance index is a sensitive method which can detect functional impairment in the first months after birth. 2) Detailed morphological analyses of the lung can be performed with the new MRI sequences, without any contrast medium or risk of radiation. The analysis of functional MRI data (perfusion, diffusion, ventilation, inflammation) will be possible, and these data will be correlated to morphological data. The exploration of other organs such as the sinuses, liver and abdomen during the same examination represents another definite advantage. 3) Organoïds are a good example of personalized medicine. This tool explores CFTR function and treatment response in each of the 2000 or so known CFTR mutations. These tests are limited to specialized centers, mostly within a research context. However, their generalization after standardization is expected in the near future.

Value of allohaemagglutinins in the diagnosis of a polysaccharide antibody deficiency.

Polysaccharide antibody deficiency is characterized by a poor or absent antibody response after vaccination with an unconjugated pneumococcal polysaccharide vaccine. Allohaemagglutinins (AHA) are antibodies to A or B polysaccharide antigens on the red blood cells, and are often used as an additional or alternative measure to assess the polysaccharide antibody response. However, few studies have been conducted to establish the clinical significance of AHA. To investigate the value of AHA to diagnose a polysaccharide antibody deficiency, pneumococcal polysaccharide antibody titres and AHA were studied retrospectively in 180 subjects in whom both tests had been performed. Receiver operating characteristic curves for AHA versus the pneumococcal vaccine response as a marker for the anti-polysaccharide immune response revealed an area under the curve between 0·5 and 0·573. Sensitivity and specificity of AHA to detect a polysaccharide antibody deficiency, as diagnosed by vaccination response, were low (calculated for cut-off 1/4-1/32). In subjects with only low pneumococcal antibody response, the prevalence of bronchiectasis was significantly higher than in subjects with only low AHA (45·5 and 1·3%, respectively) or normal pneumococcal antibody response and AHA (2·4%). A logistic regression model showed that low pneumococcal antibody response but not AHA was associated with bronchiectasis (odds ratio 46·2). The results of this study do not support the routine use of AHA to assess the polysaccharide antibody response in patients with suspected immunodeficiency, but more studies are warranted to clarify the subject further.

Comparison of two treatment regimens for eradication of Pseudomonas aeruginosa infection in children with cystic fibrosis.

UNLABELLED: In patients with cystic fibrosis (CF), treatment of new Pseudomonas aeruginosa (Pa) infection postpones the occurrence of chronic infection, but the best eradication regimen is unknown . AIM OF THE STUDY: Compare 2 Pa eradication regimens in children with new Pa infection. METHODS: Children with CF (0-18 years) and a new isolation of Pa from sputum, cough swab or BAL were randomized to treatment with tobramycin inhalation solution for 28 days (TIS) or inhaled sodiumcolistimethate (2×2millU/day) plus oral ciprofloxacin (30 mg/kg/day) for 3 months (CC). Airway cultures were taken for 6 consecutive months, then every 3 months. The primary outcome was Pa eradication at the end of treatment. Secondary outcome parameters were: time to Pa relapse from end of treatment, total and Pa specific IgG, FEV(1), BMI and Pa status at 2year follow-up. RESULTS: 58 patients with new Pa isolation were randomized. Their median age was 9 years (IQR 4.7-13.1) and their median FEV(1) 98% predicted (IQR 87-107). Eighteen treatments concerned the first Pa isolation 'ever' (TIS: 8; CC: 10). For the remaining, median time since previous Pa was 19 months (IQR 9-41). Eradication at end of treatment was similar for both treatments: 26/29 CC and 23/29 in TOBI treated patients (p=0.47). Median time to recurrence of Pa was 9 months (95% CI 0.0-19.0) for CC and 5 months (95% CI 1.7-8.3) for TIS (p=0.608). After 1 year, the 2 groups did not differ in change in total and Pa specific IgG, FEV(1) and BMI. After 2 years, 10% of patients had chronic Pa infection. CONCLUSION: In children with CF and new Pa infection, inhalation of TIS (28 days) or CC (3 months) resulted in similar eradication success at the end of treatment (80 and 90% respectively) and similar clinical evolution during the first 2 years of follow-up.

CFTR biomarkers: time for promotion to surrogate end-point.

In patients with cystic fibrosis, cystic fibrosis transmembrane conductance regulator (CFTR) biomarkers, such as sweat chloride concentration and/or nasal potential difference, are used as end-points of efficacy in phase-III clinical trials with the disease modifying drugs ivacaftor (VX-770), VX809 and ataluren. The aim of this project was to review the literature on reliability, validity and responsiveness of nasal potential difference, sweat chloride and intestinal current measurement in patients with cystic fibrosis. Data on clinimetric properties were collected for each biomarker and reviewed by an international team of experts. Data on reliability, validity and responsiveness were tabulated. In addition, narrative answers to four key questions were discussed and agreed by the team of experts. The data collected demonstrated the reliability, validity and responsiveness of nasal potential difference. Fewer data were found on reliability of sweat chloride concentration; however, validity and responsiveness were demonstrated. Validity was demonstrated for intestinal current measurement, but further information is required on reliability and responsiveness. For all three end-points, normal values were collected and further research requirements were proposed. This body of work adds useful information to support the promotion of CFTR biomarkers to surrogate end-points and to guide further research in the area.

New clinical diagnostic procedures for cystic fibrosis in Europe.

In the majority of cases, there is no difficulty in diagnosing Cystic Fibrosis (CF). However, there may be wide variation in signs and symptoms between individuals which encourage the scientific community to constantly improve the diagnostic tests available and develop better methods to come to a final diagnosis in patients with milder phenotypes. This paper is the result of discussions held at meetings of the European Cystic Fibrosis Society Diagnostic Network supported by EuroCareCF. CFTR bioassays in the nasal epithelium (nasal potential difference measurements) and the rectal mucosa (intestinal current measurements) are discussed in detail including efforts to standardize the techniques across Europe. New approaches to evaluate the sweat gland, future of genetic testing and methods on the horizon like CFTR expression in human leucocytes and erythrocytes are discussed briefly.

Change in IgG and evolution of lung function in children with cystic fibrosis.

Reports from the seventies and eighties have shown that cystic fibrosis (CF) patients with severe lung disease have high levels of IgG and that this is associated with worse prognosis. We decided to explore IgG level as a possible outcome parameter for lung disease severity in a cohort of pediatric CF patients treated according to current standards of care. Seventy three CF children older than 5 years (and max 15 years old at the initial evaluation) attending the same CF center were followed during a period of 4 years. Data collection included spirometry, height, weight, sputum cultures and total IgG. Median age at the start was 10 years. IgG z scores<2 SD were seen in 2.7% of patients in 2004 and 2008. Twelve patients (16%) had an IgG>2 SD in 2004 and this number increased to 18 (25%) in 2008. IgG z-scores were inversely correlated with FEV(1)% predicted (r=-0.323 in 2004; p<.001). In longitudinal evaluation, changes in IgG z-score correlate inversely with changes in FEV(1)% predicted (r=-0.498; p<.001). We can conclude that even for CF patients treated according to current standards IgG z-score increases with age and is correlated with a decline in FEV(1).

Inhaled corticosteroids and lower lung function decline in young children with cystic fibrosis.

A recent American registry analysis in cystic fibrosis (CF) children showed less lung function decline after starting inhaled corticosteroid (ICS) use. We therefore examined the influence of ICS treatment on lung function in Belgian CF patients. Data from patients ≥ 6 yrs of age were eligible, provided entries on lung function, height and ICS use were available in two consecutive years. Data after oral steroid use or transplant were excluded. 852 subjects contributed data with 2,976 data pairs analysed, 44.9% concerning years of ICS use. Yearly % predicted decline in forced expiratory volume in 1 s (FEV1) was 1.07% lower during ICS use (p = 0.001). Subgroup analysis for age revealed that the lower FEV1 decline rate during ICS use was only statistically significant in children 6-12 yrs of age (2.56%; p = 0.0003). Baseline FEV(1) was lower by 5.89% (p < 0.0001) in ICS users for all age groups combined, but there was no difference in baseline lung function in the children 6-12 yrs of age. In 6-12-yr-old children with CF, baseline lung function was similar in ICS users and nonusers, but annualised FEV1 decline was 2.56% pred lower in ICS users. Our data therefore support recent American findings.

Use of nebulized amphotericin B in the treatment of allergic bronchopulmonary aspergillosis in cystic fibrosis.

Background. Systemic steroids and adjunctive antifungal therapy are the cornerstone in treating allergic bronchopulmonary aspergillosis (ABPA) in the context of CF. Aim. Evaluate the use of inhaled amphotericin B (iAMB) as antifungal agent in this context. Methods. Report of 7 CF patients with recurrent or difficult to treat ABPA and failure to taper systemic corticosteroids treated with AMB deoxycholate (AMB-d) (Fungizone 25 mg 3× a week) or AMB lipid complex (ABLC) (Abelcet 50 mg twice weekly). Successful therapy was defined as steroid withdrawal without ABPA relapse within 12 months. Results. Therapy was successful in 6 of 7 patients treated with iAMB. In 5/6, lung function improved. The patient with treatment failure has concomitant MAC lung infection. Conclusion. Inhaled AMB may be an alternative to commonly used adjunctive antifungal therapy in the treatment of ABPA. More data are needed on safety and efficacy.

Preserved hyperaemic response in supraclavicular ultrasonography demonstrates function on demand of the LIMA to LAD string sign graft after CABG.

AIM: To correlate supraclavicular ultrasonography with angiographically patent and string sign left internal mammary artery (LIMA) to left anterior descending artery (LAD) grafts. METHODS: Sixteen patients with a single LIMA anastomosis to the LAD were prospectively entered in a follow-up study. The supraclavicular ultrasonography of the LIMA origin was studied preoperatively and at 5.3+/-3.6 months and 1.7+/-0.4 year postoperatively. At the late postoperative ultrasonography electrocardiographically controlled hyperemic response was also studied for 6 min. Control angiography was performed at 1.5+/-0.8 year. Differences within groups were tested with a paired t-test and between groups with an unpaired t-test. RESULTS: Control angiography showed in 13 patients (group I) a patent LIMA graft and in 3 patients (group II) a string sign LIMA graft. Preoperative blood velocities were not significantly different between groups. Postoperatively, both groups revealed higher diastolic and lower systolic blood velocities compared to preoperative values. The blood velocities at rest did not change in group I and all velocities decreased in group II in time postoperatively. The blood velocities in maximal hyperemic response increased significantly within the groups and were not significantly different between the groups. No ischemia could be detected electrocardiographically during hyperemic response and no patient presented angina. CONCLUSIONS: Both groups showed a shift towards coronary type diastolic blood velocities at rest and at hyperaemic response. Significant hyperemic response was also present in string sign LIMA grafts and demonstrates response capacity to increased myocardial oxygen demand.

Postoperative changes in duplex ultrasound velocity characteristics in the nonmobilized right internal mammary artery in patients with left internal mammary artery bypass grafting.

The internal mammary artery (IMA) is the conduit of choice in coronary revascularization because of its long-term patency. We analyzed the effect of left internal mammary artery (LIMA) harvesting on sternal perfusion. Diameters and velocity parameters of the nonmobilized right internal mammary artery (RIMA) were noninvasively analyzed with duplex ultrasound in 41 patients with LIMA myocardial revascularization pre- (2.6 +/- 5 days) and postoperatively (4.9 +/- 3.9 months). Data of 41 patients were analyzed; 38 patients underwent all examinations with adequate supraclavicular signals. The proximal RIMA diameter and all velocity parameters increased significantly at follow-up (3.1 +/- 0.6 vs. 3.2 +/- 0.5 mm, p = 0.03; diastolic peak velocity [DPV] 15 +/- 7 vs. 27 +/- 9 cm/sec, p < 0.0001; systolic peak velocity [SPV] 90 +/- 24 vs. 105 +/- 29 cm/sec, p < 0.02). This was more pronounced for the diastolic parameters and for all parameters in the proximal part of the RIMA than in the distal part (DPV 11.9 +/- 10.1 vs. 9.5 +/- 10.2 cm/sec, p = NS; SPV 14.9 +/- 33.9 vs. 7.4 +/- 26.0 cm/sec, p = NS). With longer time intervals of follow-up the increase in all diastolic velocity parameters became less pronounced. As demonstrated in the RIMA velocity parameters, patients with skeletonized LIMA grafts (n = 4) had significantly more flow, suggesting hyperemic flow, than patients with pedicled LIMA grafts (n = 34). Only in diastolic velocity integral (DVI) and systolic/diastolic velocity ratio (SDVRA) were there significant differences between diabetics (n = 9) and nondiabetics (n = 29) and only in DVI between female, (n = 8) and male (n = 30) patients. This study indicates that duplex ultrasound is a useful tool for noninvasive RIMA follow-up in LIMA myocardial revascularization.

Quality of life and NYHA class 30 years after mechanical aortic valve replacement.

OBJECTIVE: (1) To evaluate the quality of life (QoL) scores, assessed with SF36 and EuroQol (EQ-5D), of long term survivors after mechanical aortic valve replacement (mAVR); (2) to study the association of QoL with NYHA score, number of major bleeding and thrombo-embolic events and follow-up time; (3) to compare QoL scores of long term mAVR survivors with QoL scores of other populations. METHODS: In total 312 patients had a mAVR between 1964 and 1974 at St. Antonius Hospital Nieuwegein (NL). Mean age at operation was 41 (sd=12). Mean postoperative NYHA class at 1-year follow-up was 1.7 (sd=0.7). In 2001 the survivors (n=78; 25%) were followed-up for late events, NYHA class and QoL scores. 69 patients (93%) returned completed questionnaires. RESULTS: Mean duration of follow-up was 30 years (sd=1.8). Mean age of responders was 65 years (sd=10, range 47-93). In 2001, NYHA class of responders was 2 (sd=0.9). The mean (sd) SF36 scores for responders were: 64 (29) for physical function, 64 (29) for role-physical, 80 (30) for bodily pain, 55 (25) for general health, 63 (23) for vitality, 73 (29) for social functioning, 70 (38) for role-emotional, 76 (18) for mental health. The mean EQ-5D score of responders was: 61 (13). These SF36 and EQ-5D scores are comparable to those of other populations (e.g. cancer, diabetes type-2, migraine, chronic liver disease and iliac artery occlusive disease and Dutch general population). For responders a moderate to high association of SF36 and EQ-5D scores and their NYHA scores (R2=0.36) was found. The number of major bleeding events, age, sex and survival time were not related to QoL. CONCLUSION: At long term follow-up (mean 30 years) of patients who had mAVR, QoL was relatively high; it was moderately to highly associated with their NYHA class; bleeding and thromboembolic events seem to be of little importance for the QoL at long term follow-up. QoL at long term follow-up of patients who had mAVR is comparable to other cross sectional designed studies with short term follow-up and other population.

Differences in LIMA Doppler characteristics for different LAD perfusion areas.

OBJECTIVES: To correlate supraclavicular left internal mammary artery (LIMA) to left anterior descending artery (LAD) area Doppler characteristics with angiographically perfused area. METHODS: Sixty patients (50 male, mean age 62+/-7.3 years) with LIMA to LAD area grafting were prospectively entered in a follow up study. Supraclavicular echo Doppler of the LIMA was studied at the LIMA origin preoperatively, and at 4.8+/-3.8 months and 1.8+/-0.9 years postoperatively. The potential area to be revascularized judged from preoperative angiography was called the 'target' area. Control angiography (native and LIMA) was done at 1.5+/-0.9 years. The perfused area % was classified into group I < or =17.0% (n=16), group II >17.0% and <22.50% (n=17), and group III > or =22.50% (n=18) and related to LIMA Doppler characteristics. Multivariate linear regression analyses (MLRA) were performed to assess the relations between Doppler variables and the perfused area, target area and ratio of perfused/target area. RESULTS: At MLRA perfused area was significantly related to the natural logarithm of diastolic peak velocity (DPV) (P=0.013) and diastolic mean velocity (P=0.048) and the ratio only to the degree of LAD stenosis (P=0.004). In hyperaemic response maximal DPV (DPV max) showed significant correlation to the perfused area (P=0.005) as well as to the ratio (P=0.017). When analyzing the additive power of both investigations, only DPV max (P=0.005) correlated significantly to the perfused area and for the ratio only the degree of stenosis of the LAD emerged as significant (P=0.004). CONCLUSIONS: At MLRA the diastolic flow pattern at rest and the maximal DPV in hyperaemic response correlated significantly with the LIMA run-off area whereas the last variable is the strongest predictor of the LIMA run-off area.