Atrial septal defect becoming clinically evident after cardiac surgery for annuloaortic ectasia: a case report.

Background: Right ventricular volume overload is the key finding in a patient with previously undiagnosed atrial septal defect (ASD). Case summary: A 68-year-old female was referred to our hospital due to progressive pulmonary artery dilatation observed on her chest X-ray. Echocardiography revealed a secundum ASD with right ventricular dilatation. She had undergone aortic root replacement and aortic valve replacement for annuloaortic ectasia and aortic insufficiency 12 years prior to the diagnosis. She was also diagnosed with Marfan syndrome, which was supported by family histories. Computed tomography did not show a secundum ASD before the surgery. We finally closed the secundum ASD with catheter closure device. Discussion: Ascending aneurysm might mask the presence of secundum ASD. Monitoring the change in pulmonary artery dilatation overtime is useful for the diagnosing secundum ASD.

Segmental analysis of aortic basal ring dimensions in normal and dilated tricuspid aortic roots.

OBJECTIVES: In patients with aortic root aneurysm, the aortic basal ring is frequently dilated. It has been speculated that the muscular part of the basal ring dilates most. The purpose of this study was to analyse the segmental dilatation of the basal ring, comparing normal and dilated roots in patients with tricuspid aortic valves. METHODS: Retrospective analysis of computed tomography studies in patients with normal and dilated aortic roots was performed. Lengths of segments of the basal ring corresponding to each of the 3 sinuses, and to the muscular and fibrous parts were measured. Fractions of these segments relative to the total basal ring perimeter were calculated. RESULTS: We analysed 152 normal and 126 dilated aortic roots and 86 propensity-matched pairs. Basal ring dilatation was present in all segments of dilated aortic roots with subtle differences between the segments corresponding to the 3 sinuses. The muscular part of the basal ring dilated proportionately to its fibrous part, with no difference in fractions of measured muscular part in normal and dilated roots [42.2% (interquartile range 4.3%) vs 42.1% (interquartile range 6.3%)]. CONCLUSIONS: Basal ring dilatation was present in all segments corresponding to the 3 sinuses in dilated aortic roots. Both muscular and fibrous parts dilated equally, supporting the need to stabilize the entire basal ring when performing aortic valve repair surgery.

Is Osteogenesis Imperfecta Associated with Cardiovascular Abnormalities? A Systematic Review of the Literature.

Osteogenesis imperfecta (OI) is a rare genetic disorder caused by abnormal collagen type I production. While OI is primarily characterized by bone fragility and deformities, patients also have extraskeletal manifestations, including an increased risk of cardiovascular disease. This review provides a comprehensive overview of the literature on cardiovascular diseases in OI patients in order to raise awareness of this understudied clinical aspect of OI and support clinical guidelines. In accordance with the PRISMA guidelines, a systematic literature search in PubMed, Embase, Web of Science and Scopus was conducted that included articles from the inception of these databases to April 2023. Valvular disease, heart failure, atrial fibrillation, and hypertension appear to be more prevalent in OI than in control individuals. Moreover, a larger aortic root was observed in OI compared to controls. Various cardiovascular diseases appear to be more prevalent in OI than in controls. These cardiovascular abnormalities are observed in all types of OI and at all ages, including young children. As there are insufficient longitudinal studies, it is unknown whether these abnormalities are progressive in nature in OI patients. Based on these findings, we would recommend referring individuals with OI to a cardiologist with a low-threshold.

Clinical effectiveness of valve-sparing aortic root replacement in the treatment of patients with dilated aortic root after operation for tetralogy of Fallot / 中国胸心血管外科临床杂志

@#Objective     To evaluate the clinical effectiveness of valve-sparing aortic root replacement (VSARR) in the treatment of patients with dilated aortic root after operation for tetralogy of Fallot (TOF). Methods     A retrospective analysis was conducted on clinical data of TOF patients with aortic root dilation who underwent VSARR in our hospital from 2016 to 2022. Results     Finally 14 patients were collected, including 8 males and 6 females, with a median age of 22 years ranging from 12-48 years. Among them, 5 patients had severe aortic valve regurgitation, 4 moderate regurgitation, and 5 mild or no regurgitation. Six patients had sinus of valsalva dilation, and 8 significant dilation of the ascending aorta. One patient had residual shunt due to ventricular septal defect, and 9 severe pulmonary valve regurgitation. The David procedure was performed in 10 patients, Yacoub procedure in 2 patients, and Florida sleeve in 2 patients. There was no perioperative mortality in the group. The median follow-up time was 2.9 years (ranging from 0.4 to 6.0 years). One patient had mild aortic valve regurgitation, and the rest had minimal or no regurgitation. One patient had mild stenosis of the left ventricular outflow tract, and the rest patients had no obvious stenosis. Conclusion     VSARR is a satisfactory treatment for aortic root dilation in patients with TOF, with no significant increase in the incidence of left ventricular outflow tract stenosis or aortic regurgitation during mid-term follow-up.

Echocardiographic Phenotypes of Subclinical Organ Damage: Clinical and Prognostic Value in the General Population. Findings from the Pamela Study.

Subclinical alterations in cardiac structure and function include a variety of abnormal phenotypes of established adverse prognostic significance such as left ventricular hypertrophy (LVH), alterations of LV geometry, left atrial (LA) enlargement, and aortic root (AR) dilatation. The excess cardiovascular (CV) risk associated with these phenotypes has been consistently demonstrated in different clinical settings such in patients with systemic hypertension, coronary heart disease, diabetes mellitus, chronic kidney disease, heart failure and in geneal population samples. The Pressioni Monitorate e Loro Associazioni (PAMELA), a longitudinal population-based study originally designed to assess the normality values, prognostic significance of office, home and 24-hour blood pressure, including among the many clinical and laboratory variables the collection of echocardiographic data, allowed to gather important information on the clinical prognostic significance of subclinical cardiac damage during a long follow-up period. This article summarizes the original findings provided by the PAMELA study on the clinical correlates and prognostic significance of echocardiographic markers of subclinical organa damage namely LVH, left atrial enlargement (LA) and AR dilatation at the community level.

Early-onset Marfan syndrome with a novel missense mutation: A case report.

Early-onset Marfan syndrome (eoMFS) progresses rapidly, starting during the neonatal period, causes severe clinical disease, and has a poor prognosis. The genetic abnormality associated with eoMFS is located in a so-called critical neonatal region in exons 25-26 of the fibrillin-1 (FBN1) gene. A female neonate was delivered by emergency cesarean section at 37 weeks gestation due to fetal distress with bradycardia, cyanosis, and no spontaneous breathing. On examination, the patient had multiple musculoskeletal deformities, including loose redundant skin, arachnodactyly, flat soles, and joint contractures. Echocardiography showed poor cardiac contractility with multiple valvular abnormalities. She died 13 h after birth. We identified a novel missense variant c.3218A>G (p.Glu1073Gly) in exon 26 of the FBN1 gene by targeted next-generation sequencing. A literature review revealed that arachnodactyly and aortic root dilatation in the fetus are predictive of eoMFS. However, the predictive potential of ultrasonography alone is limited. Genetic testing of the FBN1 gene restriction region associated with short life expectancy and characteristic fetal ultrasound findings could be important for prenatal diagnosis of eoMFS, postnatal management, and parental preparedness. Learning objective: We identified a novel missense mutation located in exons 25-26 of the Fibrillin-1 gene in a neonate with early-onset Marfan syndrome (eoMFS) who died of severe early heart failure shortly after birth. This mutation was located in a narrowly defined critical neonatal region, recently reported to cause eoMFS, and its clinical profile was consistent with early-onset severe heart failure. In addition to ultrasonography, genetic analysis of this region is important for predicting prognosis in eoMFS.

Prevalence of cardiovascular manifestations in patients with hypermobile Ehlers-Danlos syndrome at the University of Miami.

Cardiovascular system involvements have been frequently reported in hypermobile Ehlers-Danlos Syndrome (hEDS). Mitral valve prolapse (MVP) and aortic root dilatation are included in the 2017 international classification criteria for hEDS. Different studies have found conflicting results regarding the significance of cardiac involvement in hEDS patients. We conducted a retrospective review of cardiac involvement in patients diagnosed with hEDS based on the 2017 International diagnostic criteria to provide further evidence toward more defined and reliable diagnostic criteria and recommended cardiac surveillance. A total of 75 hEDS patients with at least one diagnostic cardiac evaluation were included in the study. The most common reported cardiovascular complaints were lightheadedness (80.6%), followed by palpitations (77.6%), fainting (44.8%), and chest pain (32.8%). Of the 62 echocardiogram reports, 57 (91.9%) showed trace/trivial to mild valvular insufficiency, and 13 (21%) had additional abnormalities such as grade I diastolic dysfunction, mild aortic sclerosis, and trivial or small pericardial effusion. Of the 60 electrocardiograms (ECG) reports, 39 (65%) were normal, and 21 (35%) reported minor abnormalities or normal variants. Even though many hEDS patients in our cohort experienced cardiac symptoms, the presence of a significant cardiac abnormality was very low.

Bentall procedure as a lifesaving surgery: A single center experience.

The Bentall procedure is a surgical technique used in the management of aortic root abnormalities with ascending aorta and aortic valve issues. The present study aimed to evaluate the outcomes of 18 patients treated with the Bentall procedure in a single center. The present study was a single-center retrospective case series conducted over a period of 3 years. The patients had either acute ascending dissection and/or dilated ascending aorta with aortic valve dysfunction. The Bentall procedure was performed via standard median sternotomy. St. Jude Medical composite grafts with a valve were applied in all cases. A total number of 18 patients with either acute ascending dissection and/or dilated ascending aorta with aortic valve dysfunction were included in the study. The age of the participants ranged from 27-60 years. The ratio of males to females was 16:2 (males, 88.8%). The symptoms developed 3-4 days prior to hospital admission. Chest pain was the most common presenting symptom (n=10, 55.5%). Hypertension was the most common risk factor (n=12, 66.6%). In total, 14 cases underwent emergency surgery (77.7%). The emergency surgery was performed in 9 patients within 24 h of arrival owing to the association of aortic root dissection with tamponade. For the other cases, the surgery was performed within 2 and 7 days (n=5, 27.7% and n=4, 22.2%) respectively. Early post-operative complications occurred in 5 patients (27.7%). On the whole, as demonstrated herein, the modifications of the Bentall procedure have a notable impact on decreasing the overall mortality rates. Raising the awareness of clinicians and the general population as regards aortic dissection may aid in the early referral of patients to specialized centers and may thus decrease the overall mortality rate.

Novel phenotype of aortic root dilatation and late-onset metabolic decompensation in a patient with TMEM70 deficiency.

TMEM70 deficiency causing mitochondrial complex V deficiency, nuclear type 2 (MIM: 614052) is the most common nuclear encoded defect affecting ATP synthase and has been well described in the literature as being characterized by neonatal or infantile onset of poor feeding, hypotonia, lethargy, respiratory compromise, heart failure, lactic acidosis, hyperammonemia, and 3-methylglutaconic aciduria progressing to a phenotype of developmental delay, failure to thrive, short stature, nonprogressive cardiomyopathy, microcephaly, facial dysmorphisms, hypospadias, persistent pulmonary hypertension of the newborn, and Wolff-Parkinson-White syndrome, as well as metabolic crises followed by developmental regression. The patient with TMEM70 deficiency herein reported has the unique presentation of aortic root dilatation, differing facial dysmorphisms, and no history of neonatal metabolic decompensation or developmental delay, as well as a plasma metabolomics signature, including elevated 3-methylglutaconic acid, 3-methylglutarylcarnitine, alanine, and lactate, in addition to the commonly described increased 3-methylglutaconic acid on urine organic acid analysis that helped aid in the diagnostic interpretation of variants of uncertain significance in TMEM70.

Technique of Coronary Button Transfer Has no Impact on Neoaortic Root Size in Simple Transposition.

We studied the effect of various coronary transfer techniques (CTT) on neo-aortic root size after an arterial switch operation (ASO) in simple transposition by excluding the impact of recognized predisposing factors. One hundred and seventy-eight patients with simple transposition were reviewed retrospectively (January 2004-December 2018) and grouped as Punch Hole (n = 83/178), Nonpunch Hole (n = 65/178; Trapdoor or Standard) and Mixed (n = 30/178). Factors predicting the neo-aortic root z-scores- annulus, mid-sinus, and sinotubular junction (STJ) were analyzed by uni/multivariable linear regression. Follow-up was 6 years, Interquartile range (IQR) 3.4,10.6. Preoperative aortic (7.4 mm, IQR 6.9,8) and pulmonary annulus (7.5 mm, IQR 6.8,8.1) sizes were identical (P = 0.831). The changes in preoperative, postoperative, and latest median z-scores for neo-aortic annulus (-0.2, IQR -1.2,0.9; 0.0, IQR -0.9,0.9; 0.9, IQR -0.4,2.6; P < 0.001), mid-sinus (1.1, IQR-0.1,2; 2.6, IQR 1.6,3.7; 2.9, IQR 1.8,4.3; P < 0.001) and STJ (-0.1, IQR -0.8,1.1; 2.1, IQR 0.7,3; 2.4, IQR 1,3.5; P < 0.001) were significant. On multivariate analysis, preoperative pulmonary annulus z-score predicted the latest neo-aortic annulus z-score [Beta estimate (BE) = 0.32, 95% confidence interval (CI) = 0.03,0.62; P = 0.03] and STJ z-score (BE= 0.45, 95% CI= 0.20,0.70; P < 0.0001). CTT did not predict any of the latest neo-aortic z-scores (all P > 0.05). Mild plus neo-aortic regurgitation (neoAR) was not significantly different across CTT groups [punch hole 20% (n = 15/74), mixed 37% (n = 11/30), nonpunch hole 21% (n = 13/62); Fisher-exact P = 0.186], one patient required valve replacement for severe neoAR. The neo-aortic root enlarges significantly over time at all 3 levels following an ASO in simple transposition, however, this is not significantly influenced by the CTT utilized.

New-onset aortic dilatation in the population: a quarter-century follow-up.

BACKGROUND: Aortic size tends to increase with aging but the extent of this dynamic process has not been evaluated in long-term longitudinal population-based studies. We investigated the incidence of new-onset aortic root (AR) dilatation and its principal correlates among middle-aged adults over a 25-year time period. METHODS: A total of 471 participants with measurable echocardiographic parameters at baseline and after a 25-year follow-up were included in the analysis. Sex-specific upper limits of normality for absolute AR diameter, AR diameter indexed to body surface area (BSA) and to height were derived from healthy normotensive PAMELA participants. RESULTS: New AR dilatation occurred in 7.4% (AR/BSA), 9.1% (AR/height) and 14.6% (absolute AR), respectively. According to the AR/height index, the risk of new dilation was similar in men and women. As for echocardiographic parameters, baseline AR diameter emerged as a key predictor of AR dilation, regardless of the diagnostic criteria and the 10-year change in LVMI was positively associated to new AR/height dilatation. No significant relationship was observed between baseline office and ambulatory systolic/diastolic blood pressure or their changes over time with incident AR dilatation. Baseline and the 25-year change in 24-h pulse pressure were negatively related to new AR dilatation. CONCLUSIONS: The incidence of AR dilatation from mid to late adulthood occurs in a small but clinically relevant fraction of participants and is unaffected by both office and out-office BP. It is significant related to baseline AR diameter and to the 25-year change in LVMI. Our data suggest that echocardiography performed in middle-aged individuals of both sexes may identify those at increased risk of future AR dilatation; moreover, preventing LVH may reduce the risk of progressive AR enlargement.

A Case of Trisomy 13 Mosaicism With Aortic Root Dilatation.

We present a 6-year-old female child, with prenatal diagnosis of trisomy 13 mosaicism and nondisjunction, a bicuspid aortic valve, and severe aortic root dilatation. This patient is only the third reported case of aortic dilatation in the setting of trisomy 13 mosaicism. (Level of Difficulty: Intermediate.).

How to Distinguish Marfan Syndrome from Marfanoid Habitus in a Physical Examination-Comparison of External Features in Patients with Marfan Syndrome and Marfanoid Habitus.

Marfan Syndrome (MFS) is a systemic disorder caused by mutations in fibrillin-1. The most common cause of mortality in MFS is dissection and rupture of the aorta. Due to a highly variable and age-dependent clinical spectrum, the diagnosis of MFS still remains sophisticated. The aim of the study was to determine if there exist phenotypic features that can play the role of "red flags" in cases of MFS suspicion. The study population included 306 patients (199 children and 107 adults) who were referred to the Department of Pediatric Cardiology due to suspicion of MFS. All patients underwent complete clinical evaluation in order to confirm the diagnosis of MFS according to the modified Ghent criteria. MFS was diagnosed in 109 patients and marfanoid habitus in 168 patients. The study excluded 29 patients with other hereditary thoracic aneurysm syndromes. Comparative analysis between patients with Marfan syndrome and marfanoid habitus was performed. Symptoms with high prevalence and high positive likelihood ratio were identified (pectus carinatum, reduced elbow extension, hindfoot deformity, gothic palate, downslanting palpebral fissures, lens subluxation, myopia ≥ 3 dioptres remarkably high stature). The differentiation between patients with MFS and marfanoid body habitus is not possible by only assessing external body features; however, "red flags" could be helpful in the screening phase.

Impact of aortic arch curvature in flow haemodynamics in patients with transposition of the great arteries after arterial switch operation.

AIMS: In this study, we will describe a comprehensive haemodynamic analysis and its relationship to the dilation of the aorta in transposition of the great artery (TGA) patients post-arterial switch operation (ASO) and controls using 4D-flow magnetic resonance imaging (MRI) data. METHODS AND RESULTS: Using 4D-flow MRI data of 14 TGA young patients and 8 age-matched normal controls obtained with 1.5 T GE-MR scanner, we evaluate 3D maps of 15 different haemodynamics parameters in six regions; three of them in the aortic root and three of them in the ascending aorta (anterior-left, -right, and posterior for both cases) to find its relationship with the aortic arch curvature and root dilation. Differences between controls and patients were evaluated using Mann-Whitney U test, and the relationship with the curvature was accessed by unpaired t-test. For statistical significance, we consider a P-value of 0.05. The aortic arch curvature was significantly different between patients 46.238 ± 5.581 m-1 and controls 41.066 ± 5.323 m-1. Haemodynamic parameters as wall shear stress circumferential (WSS-C), and eccentricity (ECC), were significantly different between TGA patients and controls in both the root and ascending aorta regions. The distribution of forces along the ascending aorta is highly inhomogeneous in TGA patients. We found that the backward velocity (B-VEL), WSS-C, velocity angle (VEL-A), regurgitation fraction (RF), and ECC are highly correlated with the aortic arch curvature and root dilatation. CONCLUSION: We have identified six potential biomarkers (B-VEL, WSS-C, VEL-A, RF, and ECC), which may be helpful for follow-up evaluation and early prediction of aortic root dilatation in this patient population.

Personalized external aortic root support - how to implant it.

Personalized External Aortic Root Support (PEARS) is an evolving method of treatment for patients with a dilated aortic root or ascending aorta. This treatment is being adopted in an increasing number of centres. For the sake of the safety of the procedure a standardized surgical technique is necessary. The authors describe a surgical technique of implantation that is derived from their extensive experience.

Aortic Root Dilatation Is Attenuated with Diabetes but Is Not Associated with Renal Progression in Chronic Kidney Disease.

Patients with chronic kidney disease (CKD) often have cardiac functional and structural abnormalities which can lead to adverse cardiovascular outcomes. In this study, we investigated associations between diabetes mellitus (DM) and cardiac functional and structural parameters in patients with CKD focusing on aortic root diameter (ARD). We also investigated associations of renal outcomes with DM and cardiac functional and structural characteristics. We enrolled 419 patients with CKD stage 3-5 were enrolled. ARD was normalized to body surface area (BSA) (ARD/BSA), and the rate of decline in renal function was assessed by the estimated glomerular filtration rate (eGFR) slope (mL/min/1.73 m2/year). ARD/BSA ≥2.1 cm/m2 in men or ≥2.2 cm/m2 in women was defined as indicating aortic root dilatation. The patients with DM had lower ARD/BSA, higher left atrial dimension (LAD), lower left ventricular ejection fraction, lower ratio of peak early transmitral filling wave velocity to peak late transmitral filling wave velocity, and higher left ventricular relative wall thickness, than those without DM. After multivariable analysis, DM (vs. non-DM; coefficient ß, -0.060; p = 0.018) was significantly associated with low ARD/BSA. Significantly fewer patients with DM had aortic root dilatation compared to those without DM (14.3% vs. 23.1%, p = 0.022). In the patients with DM, there were significant associations between a high left ventricular mass index (LVMI) (per 1 g/m2, ß, -0.016; p = 0.040) and high LAD (per 1 cm; ß, -1.965; p < 0.001) with a low eGFR slope. However, other parameters, including ARD/BSA, were not associated with eGFR slope. Furthermore, there were no associations between eGFR slope and any of the echocardiographic parameters in the patients without DM. Aortic root dilatation was attenuated in the patients with DM, but it was not associated with a decline in renal function. However, high LAD and LVMI were associated with rapid renal function decline in the CKD patients with DM.

Effect of Valve Height on the Opening and Closing Performance of the Aortic Valve Under Aortic Root Dilatation.

Patients with aortic valve disease can suffer from valve insufficiency after valve repair surgery due to aortic root dilatation. The paper investigates the effect of valve height (Hv) on the aortic valve opening and closing in order to select the appropriate range of Hv for smoother blood flow through the aortic valve and valve closure completely in the case of continuous aortic root dilatation. A total of 20 parameterized three-dimensional models of the aortic root were constructed following clinical surgical guidance. Aortic annulus diameter (DAA) was separately set to 26, 27, 28, 29, and 30 mm to simulate aortic root dilatation. HV value was separately set to 13.5, 14, 14.5, and 15 mm to simulate aortic valve alterations in surgery. Time-varying pressure loads were applied to the valve, vessel wall of the ascending aorta, and left ventricle. Then, finite element analysis software was employed to simulate the movement and mechanics of the aortic root. The feasible design range of the valve size was evaluated using maximum stress, geometric orifice area (GOA), and leaflet contact force. The results show that the valve was incompletely closed when HV was 13.5 mm and DAA was 29 or 30 mm. The GOA of the valve was small when HV was 15 mm and DAA was 26 or 27 mm. The corresponding values of the other models were within the normal range. Compared with the model with an HV of 14 mm, the model with an HV of 14.5 mm could effectively reduce maximum stress and had relatively larger GOA and less change in contact force. As a result, valve height affects the performance of aortic valve opening and closing. Smaller HV is adapted to smaller DAA and vice versa. When HV is 14.5 mm, the valve is well adapted to the dilatation of the aortic root to enhance repair durability. Therefore, more attention should be paid to HV in surgical planning.

Valve-sparing aortic root replacement in adult patients with congenital heart disease.

OBJECTIVES: Aortic root dilatation is frequently observed in patients with congenital heart defects (CHD), but has received little attention in terms of developing a best practice approach for treatment. In this study, we analysed our experience with aortic valve-sparing root replacement in patients following previous operations to repair CHD. METHODS: In this study, we included 7 patients with a history of previous surgery for CHD who underwent aortic valve-sparing operations. The underlying initial defects were tetralogy of Fallot (n = 3), transposition of great arteries (n = 2), coarctation of the aorta (n = 1), and pulmonary atresia with ventricle septum defect (n = 1). The patients' age ranged from 20 to 40 years (mean age 31 ± 6 years). RESULTS: David reimplantation was performed in 6 patients and a Yacoub remodelling procedure was performed in 1 patient. Four patients underwent simultaneous pulmonary valve replacement. The mean interval between the corrective procedure for CHD and the aortic valve-sparing surgery was 26 ± 3 years. There was no operative or late mortality. The patient with transposition of great arteries following an arterial switch operation was re-operated 25 months after the valve-sparing procedure due to severe aortic regurgitation. In all other patients, the aortic valve regurgitation was mild or negligible at the latest follow-up (mean 8.7 years, range 2.1-15.1 years). CONCLUSIONS: Valve-sparing aortic root replacement resulted in good aortic valve function during the first decade of observation in 6 of 7 patients. This approach can offer a viable alternative to root replacement with mechanical or biological prostheses in selected patients following CHD repair.

Surgical management of an aortic root dilatation in a patient suffering from Hunter syndrome.

Hunter syndrome is a rare disease leading to glycosaminoglycan accumulation in tissues. Multiple organs are involved, but prognosis is mainly conditioned by cardiac and respiratory failures. Cardiac valvular impairment is quite common but aortic root dilatation is rarely described. This article covers a case of surgical root replacement due to aortic valve insufficiency and aortic root dilatation documented with magnetic resonance and computed tomography angiographies. Anatomic pathology reported both aortic valve and aorta with mucoid overload and elastic fibre depletion. These patients do have a risk of aortic root dilatation, which justifies periodic monitoring. Diagnosis must be made using indexed measures.