Characterisation of parathyroid hormone concentration in extremely preterm or very low birthweight infants in routine clinical screening for metabolic bone disease: A service evaluation cohort study.

AIM: To characterise parathyroid hormone (PTH) concentrations in infants at high risk for metabolic bone disease, in order to assist clinical decisions around the use of PTH for screening. METHODS: Infants born under 28 weeks' postmenstrual age or with birthweight under 1.5 kg in a tertiary neonatal unit in the UK were included. Clinical guidance was to assess PTH concentration in the first 3 weeks after birth. Clinical information was extracted from prospective records. RESULTS: Sixty-four infants had mean birth gestation of 26 weeks and birthweight of 882 g. Median PTH (sent on median day 18 of life) was 9.2 pmol/L (interquartile range 5.3-17 pmol/L). Sixty-seven per cent of infants had a PTH greater than 7 pmol/L. For 22% of the infants, raised PTH was not accompanied by abnormal phosphate or alkaline phosphatase. Eighty-nine per cent of infants tested were insufficient or deficient for 25-hydroxyvitamin D. CONCLUSIONS: Universal screening highlights the high frequency of high PTH in this high-risk population, implying a need for calcium supplementation. A considerable number of infants would not be identified as showing potential signs of metabolic bone disease if the assessment excludes the use of PTH. The high level of 25-hydroxyvitamin D deficiency may be a confounder.

Unusual presence of the immune evasion gene cluster in livestock-associated MRSA of lineage CC398 causing peridural and psoas abscesses in a poultry farmer.

OBJECTIVE: To characterize a methicillin-resistant Staphylococcus aureus (MRSA) isolate responsible for an aggressive infection (peridural and psoas abscess secondary to haematogenous septic arthritis) in a poultry farmer. METHODS: Molecular characterization was performed, including spa- and multilocus sequence typing of the isolate, assessment of its resistance phenotype and detection of tetracycline resistance and of virulence and immune evasion cluster (IEC) genes were performed. RESULTS: The MRSA isolate was tetracycline- and fluorquinolone-resistant, and was ascribed to CC398, spa-t1451. The isolate harboured tet(M) (distinctive of livestock-associated (LA) MRSA-CC398 clade) and IEC-type B system (characteristic of the methicillin-susceptible human lineage, but typically absent in LA-MRSA-CC398 strains), and lacked toxin-coding genes lukF/lukS-PV, tsst-1, eta and etb. CONCLUSION: IEC re-acquisition by LA-MRSA-CC398-LA strains is an unusual finding, but could constitute an emerging public health problem. It would represent an evolutionary step towards LA-MRSA-CC398's adaptation to human hosts, and might enhance its invasiveness and ability to be transmitted to humans.

Comparison of neuropsychological and functional outcomes in Alzheimer's disease patients with good or bad response to a cognitive stimulation treatment: a retrospective analysis.

BACKGROUND: The benefit of cognitive stimulation (CS) treatments in dementia is unequal. This study has sought to identify cognitive and functional measurements before and after the treatment which are indicative of a better response to a one-year CS program. METHODS: A retrospective observational study was conducted between 2004 and 2012 in a sample of 60 users diagnosed with mild Alzheimer's disease (AD) who followed a one-year CS program and underwent a cognitive and functional assessment before and after the intervention. As a primary measure of treatment response, we used the annual change of the Mini-Mental State Examination (MMSE) scores, which distinguished good responders (R) from non-responders (NR). RESULTS: 51.7% of patients classified as R at baseline had a higher cognitive performance in attention, immediate verbal memory, language, and working memory compared to NR. No initial statistically significant differences were found between R and NR in any sociodemographic variables, medical conditions, anxiety and/or depressive symptoms, treatment with cholinesterase inhibitors (ChEIs), level of insight, global cognitive function (MMSE), or functional capacity. After 12 months of treatment, R had significantly better results than NR on MMSE, temporal orientation, category evocation, and Philadelphia Geriatric Center-Instrumental Activities of Daily Living (PGC-IADL). CONCLUSION: The response to a CS treatment of some subjects over others is linked to cognitive and functional capacity. This research contributes to characterize the neuropsychological profile that differentiates subjects who respond better than others before and after the treatment. This should contribute to customize and optimize neuropsychological interventions in patients with AD.

High AN1 variability and interaction with basic helix-loop-helix co-factors related to anthocyanin biosynthesis in potato leaves.

AN1 is a regulatory gene that promotes anthocyanin biosynthesis in potato tubers and encodes a R2R3 MYB transcription factor. However, no clear evidence implicates AN1 in anthocyanin production in leaves, where these pigments might enhance environmental stress tolerance. In our study we found that AN1 displays intraspecific sequence variability in both coding/non-coding regions and in the promoter, and that its expression is associated with high anthocyanin content in leaves of commercial potatoes. Expression analysis provided evidence that leaf pigmentation is associated to AN1 expression and that StJAF13 acts as putative AN1 co-regulator for anthocyanin gene expression in leaves of the red leaf variety 'Magenta Love,' while a concomitant expression of StbHLH1 may contribute to anthocyanin accumulation in leaves of 'Double Fun.' Yeast two-hybrid experiments confirmed that AN1 interacts with StbHLH1 and StJAF13 and the latter interaction was verified and localized in the cell nucleus by bimolecular fluorescence complementation assays. In addition, transgenic tobacco (Nicotiana tabacum) overexpressing a combination of either AN1 with StJAF13 or AN1 with StbHLH1 showed deeper purple pigmentation with respect to AN1 alone. This further confirmed AN1/StJAF13 and AN1/StbHLH1 interactions. Our findings demonstrate that the classical loci identified for potato leaf anthocyanin accumulation correspond to AN1 and may represent an important step to expand our knowledge on the molecular mechanisms underlying anthocyanin biosynthesis in different plant tissues.

ß-Lactamases, transferable quinolone resistance determinants, and class 1 integron-mediated antimicrobial resistance in human clinical Salmonella enterica isolates of non-Typhimurium serotypes.

This work investigates the occurrence and features of class 1 integrons and the presence of transferable quinolone resistance determinants (TQRD) among 382 clinical Salmonella enterica isolates of non-Typhimurium serotypes as well as the ß-lactamases produced by amoxicillin-resistant isolates. These isolates were recovered in 2001 and from 2004 to 2009 from patients from the health region of Terres de l'Ebre (Catalonia, Spain) and comprised 41 different serotypes, mostly of serovar Enteritidis (n=272), being 16.5% multidrug-resistant (MDR). Among the 93 amoxicillin-resistant isolates, 84 produced TEM-1,4 produced an extended-spectrum ß-lactamase (CTX-M-9 in one S. Grumpensis and in one S. Virchow, CTX-M-15 in S. Kapemba, and SHV-12 in S. Enteritidis), one produced DHA-1 (S. Newport), and 4 did not present any of the investigated ß-lactamases. TQRD were found in 2 isolates (qnrA1 in CTX-M-9-producing S. Grumpensis and qnrB4 in DHA-1-producing S. Newport). Overall, 35 isolates (9.2% of all isolates and 54% of MDR isolates) belonging to 15 different serotypes carried class 1 integrons that were transferred by conjugation in 17 isolates. Eleven distinct cassette arrangements were identified, with dfrA1-aadA1, dfrA17-aadA5, and dfrA12-orfF-aadA2 being the most prevalent and widely distributed ones. Atypical sul3-associated integrons were detected in 5 isolates of serotypes Rissen and Enteritidis. Moreover, the presence of integrons in the serotypes Kapemba, Mikawasima, and [9,12:Iv:i:-], of the estX-psp (linked to sul3) and aadA13-sat cassette arrangements in S. enterica, of extended-spectrum ß-lactamases in S. Kapemba and S. Grumpensis, and of TQRD in S. Grumpensis is reported here for the first time.

[Transcatheter aortic valve implantation: results of a new therapeutic option for high surgical risk aortic stenosis]. / Implantação percutânea de próteses valvulares aórticas: resultados de uma nova opção terapêutica na estenose aórtica com alto risco cirúrgico.

INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is an alternative to surgical aortic valve replacement in patients with severe aortic stenosis (AS) and unacceptably high surgical risk. METHODS: We present our first two years' experience with TAVI. A total of 76 AS patients were evaluated for TAVI and 23 of them underwent a TAVI procedure. These patients had a mean EuroSCORE of 22.4% and a mean age of 81.5 years, and were prospectively followed for a mean of 12.9 ± 11 months. RESULTS: The percutaneous aortic valve was successfully implanted in 100% of the patients. Mortality at 30 days was 4%. The most common complications were access site-related bleeding and transfusion (22%), followed by new permanent pacemaker implantation (9%). After a mean follow-up of 12.9 months, survival was 87%. In a maximum follow-up of 30 months there were no cases of prosthesis dysfunction or cardiovascular death. CONCLUSIONS: Two years after the introduction of a TAVI program in our center, the procedure has established itself as a safe and effective alternative for patients with severe AS and unacceptably high surgical risk.

Pneumococcal meningitis secondary to otitis media in two patients with COVID-19 omicron variant.

BACKGROUND: The SARS-CoV-2 omicron variant produces more symptoms in the upper respiratory tract than in the lower respiratory tract. This form of "common cold" can cause inflammation of the oropharynx and the Eustachian tube, leading to the multiplication of bacteria such as Streptococcus pneumoniae in the oropharynx. Eustachian tube dysfunction facilitates migration of these bacteria to the middle ear, causing inflammation and infection (otitis media), which in turn could lead to further complications such as acute mastoiditis and meningitis. CASE PRESENTATION: In January 2022, during the rapid spread of the omicron variant of the SARS-CoV-2 virus, two patients presented to the emergency room at our hospital complaining of headache and a low level of consciousness. A few days prior to admission, the patients had been diagnosed with COVID-19 based on clinical manifestations of a cold virus, without respiratory failure. Cranial computed tomography revealed signs of bilateral invasion of the middle ear in both cases. Lumbar puncture was compatible with acute bacterial meningitis, and S. pneumoniae was isolated in cerebrospinal fluid in both patients. RT-PCR tests for SARS-CoV-2 were repeated, confirming the presence of the omicron variant in one of the patients. We were unable to confirm the variant in the second patient due to the low viral load in the nasopharyngeal sample obtained at admission. However, the time of diagnosis (i.e., during the peak spread of the omicron variant), strongly suggest the presence of the omicron variant. Both patients were admitted to the intensive care unit and both showed rapid clinical improvement after initiation of antibiotic treatment. CONCLUSIONS: The omicron variant of the SARS-CoV-2 virus can promote the development of otitis media and secondary acute bacterial meningitis. S. pneumoniae is one of the main bacteria involved in this process.

Mechanisms of Linezolid Resistance Among Clinical Staphylococcus spp. in Spain: Spread of Methicillin- and Linezolid-Resistant S. epidermidis ST2.

This study aimed at determining the mechanisms of linezolid resistance and the molecular characteristics of clinical Staphylococcus aureus (n = 2) and coagulase-negative staphylococci (n = 15) isolates obtained from four Spanish hospitals. The detection of linezolid resistance mechanisms (mutations and acquisition of resistance genes) was performed by PCR/sequencing. The antimicrobial resistance and virulence profile was determined, and the isolates were typed by different molecular techniques. Moreover, the genetic environment of the cfr gene was determined by whole-genome sequencing. The cfr gene was detected in one methicillin-resistant S. aureus (MRSA) that also displayed the amino acid change Val118Ala in the ribosomal protein L4. The second S. aureus isolate was methicillin susceptible and showed different alterations in the ribosomal protein L4. All remaining linezolid-resistant Staphylococcus epidermidis (n = 14) and Staphylococcus hominis isolates (n = 1) showed the mutation G2576T (n = 14) or C2534T (n = 1) in the 23S rRNA. Moreover, different amino acid changes were detected in the ribosomal proteins L3 and L4 in S. epidermidis isolates. All S. epidermidis isolates belonged to the multilocus sequence type ST2. Linezolid-resistant staphylococci (LRS) showed a multiresistance phenotype, including methicillin resistance that was detected in all isolates but one, and was mediated by the mecA gene. The cfr gene in the MRSA isolate was located together with the fexA gene on a conjugative 38,864 bp plasmid. Linezolid- and methicillin-resistant S. epidermidis ST2 showing mutations in the 23S rRNA and in the ribosomal proteins L3 and L4 are spread among Spanish hospitals, whereas LRS carrying acquired linezolid resistance genes are rarely detected.

Extended-Spectrum ß-Lactamase- and Carbapenemase-Producing Enterobacterales Intestinal Carriage Among Outpatients: Microbiological and Epidemiological Differences Between Private Dwelling Residents and Nursing Home Residents.

The aim of this work was to assess the prevalence of carbapenemase-producing and extended-spectrum ß-lactamase-producing Enterobacterales (ESBLPE) intestinal carriage among private dwelling residents (PDR) and nursing home residents (NHR) from the catchment area of Hospital Verge de la Cinta (Tortosa. North-Eastern Spain), and to depict clinicoepidemiological features of colonized individuals. Prevalence of ESBLPE carriage amid 762 PDR (0-94 years) who had feces collected for routine culture was 7.3% and 31% among 71 NHR (68-98 years) screened upon hospital admission. The mean age of colonized and noncolonized subjects was 30 and 32.8 years in PDR (p = 0.58) and 85 and 87 years in NHR (p = 0.32). The predominant ESBLPE was CTX-M-15-producing Escherichia coli (42.8% in PDR and 68.2% in NHR [25% and 86.7% belonging to O25b-ST131 clone; p < 0.0001]), followed by CTX-M-9-group- and SHV-producing E. coli and by CTX-M-15-producing Klebsiella pneumoniae. Overall, 72.7% of ESBLPE were multidrug resistant and 46.2% carried transferable quinolone determinants. Institutionalization in a nursing home was a risk factor for ESBLPE and extended-spectrum ß-lactamase (ESBL)-producing O25b-ST131 E. coli carriage in individuals over 67 years (odds ratio 7.7 and 14.1). Previous antibiotic use and skin ulcers were significantly associated with ESBLPE carriage in NHR. Age <25 years in PDR and amoxicillin/clavulanate exposure in NHR protected against ESBL-producing O25b-ST131 E. coli colonization. Only two PDR, with known risk factors, bore OXA-48-producing isolates. These results highlight the role of nonhospitalized intestinal carriers, particularly NHR, as ESBLPE reservoirs and the preponderance of CTX-M-15, mainly linked to O25b-ST131 clone, as well as the emergence of carbapenemase-producing Enterobacterales carriers.

Mechanisms of Linezolid Resistance Among Enterococci of Clinical Origin in Spain-Detection of optrA- and cfr(D)-Carrying E. faecalis.

The mechanisms of linezolid resistance among 13 E. faecalis and 6 E. faecium isolates, recovered from six Spanish hospitals during 2017-2018, were investigated. The presence of acquired linezolid resistance genes and mutations in 23S rDNA and in genes encoding for ribosomal proteins was analyzed by PCR and amplicon sequencing. Moreover, the susceptibility to 18 antimicrobial agents was investigated, and the respective molecular background was elucidated by PCR-amplicon sequencing and whole genome sequencing. The transferability of the linezolid resistance genes was evaluated by filter-mating experiments. The optrA gene was detected in all 13 E. faecalis isolates; and one optrA-positive isolate also carried the recently described cfr(D) gene. Moreover, one E. faecalis isolate displayed the nucleotide mutation G2576T in the 23S rDNA. This mutation was also present in all six E. faecium isolates. All linezolid-resistant enterococci showed a multiresistance phenotype and harbored several antimicrobial resistance genes, as well as many virulence determinants. The fexA gene was located upstream of the optrA gene in 12 of the E. faecalis isolates. Moreover, an erm(A)-like gene was located downstream of optrA in two isolates recovered from the same hospital. The optrA gene was transferable in all but one E. faecalis isolates, in all cases along with the fexA gene. The cfr(D) gene was not transferable. The presence of optrA and mutations in the 23S rDNA are the main mechanisms of linezolid resistance among E. faecalis and E. faecium, respectively. We report the first description of the cfr(D) gene in E. faecalis. The presence of the optrA and cfr(D) genes in Spanish hospitals is a public health concern.

Rupture of a thoracic aorta pseudoaneurysm: rare presentation and role of real-time 3D transoesophageal echocardiography.

A 59-year-old man presented with cardiogenic shock caused by acute right ventricular failure due to extrinsic compression of the right coronary artery by a thoracic aorta pseudoaneurysm. Angiography and real-time 3D transoesophageal echocardiography (TEE) were performed and enough diagnostic accuracy was achieved to operate on the patient without further image techniques and consequent delay. Three-dimensional TEE is a new technology that combines high-quality anatomic and colour Doppler information with bedside performance, essential in emergent clinical scenarios.

Percutaneous PFO closure using the Premere device occluder: initial experience.

INTRODUCTION: Most data on percutaneous closure of patent foramen ovale (PFO) relate to devices not specifically designed for this pathology. OBJECTIVE: Our aim in this article is to share our initial experience with the Premere PFO closure system. METHODS: In our hospital 14 consecutive patients presenting cryptogenic stroke underwent percutaneous closure using this device. The device was successfully implanted in 11 of the 14 patients (78.5%). Implantation was impossible in three patients because of a significant atrial septal aneurysm (ASA) or a multiperforated septum. RESULTS: Mean clinical and echocardiographical follow-up was 7 +/- 7 months. A residual shunt was seen in only one patient (9%) three months after device implantation. During follow-up, no device-related complications were observed, such as device thrombosis or fistula. None of the patients presented other significant clinical events such as strokes or arrhythmia. CONCLUSION: According to our experience the Premere is a secure and reliable device for PFO closure, but patients must be selected carefully for implantation to exclude those presenting significant ASA.

Detection of spleen, kidney and liver infarcts by abdominal computed tomography does not affect the outcome in patients with left-side infective endocarditis.

Extra-cardiac abdominal complications are common in left-side infective endocarditis (LS-IE). The aim of this work was to study whether patients with LS-IE presenting splenic, renal, or liver (SRL) involvement seen in abdominal computed tomography (CT) had different clinical features, therapeutic plans, and outcome than those without these findings on CT.From January 2008 to April 2010, multidisciplinary teams have prospectively collected all consecutive cases of IE, diagnosed according to the Duke criteria, in which abdominal CT was performed.A total of 147 patients with LS-IE had abdominal CT. Fifty (34%) had SRL lesions: 46 splenic, 15 renal, 1 liver infarct, and 2 liver abscesses. Patients with SRL lesions were mainly men (P = .01), had liver disease (P = .001) with natural valve (P = .050) and mitro-aortic valve involvement (P = .042), splenomegaly (P = .001), nonabdominal emboli (P = .001), and a greater number and larger vegetation (>15 mm, P = .049) in the mitro-aortic valves (P = .051) than patients with normal abdominal CT. The site of acquisition, clinical characteristics, microbiology, surgical treatment, days of hospitalization, hospital death, and 1-year mortality were similar in patients with and without SRL emboli on CT. In the stepwise logistic regression analysis, male gender (odds ratio [OR] = 3.6, 95% confidence interval [CI] = 1.4-9.1), liver disease (OR = 8.3, 95% CI = 2.1-31.8), and nonabdominal emboli (OR = 5.2, 95% CI = 2.3-11.7) were independently associated with SRL lesions.Male patients with native LS-IE who had liver disease and nonabdominal emboli had more frequent abdominal lesions seen on CT. The presence of SRL infarcts on abdominal CT scan performed on patients with LS-IE seems to have poor practical implications, and as a consequence, its realization should only be considered when there are symptoms or signs that suggest them.

Role of Amyloid Precursor Protein (APP) and Its Derivatives in the Biology and Cell Fate Specification of Neural Stem Cells.

Amyloid precursor protein (APP) is a member of the APP family of proteins, and different enzymatic processing leads to the production of several derivatives that are shown to have distinct biological functions. APP is involved in the pathology of Alzheimer's disease (AD), the most common neurodegenerative disorder causing dementia. Furthermore, it is believed that individuals with Down syndrome (DS) have increased APP expression, due to an extra copy of chromosome 21 (Hsa21), that contains the gene for APP. Nevertheless, the physiological function of APP remains unclear. It is known that APP plays an important role in neural growth and maturation during brain development, possibly by influencing proliferation, cell fate specification and neurogenesis of neural stem cells (NSCs). Proteolytic cleavage of APP occurs mainly via two mutually exclusive pathways, the non-amyloidogenic pathway or the amyloidogenic pathway. Other alternative pathways (η-secretase, δ-secretase and meprin pathways) have also been described for the physiological processing of APP. The different metabolites generated from these pathways, including soluble APPα (sAPPα), soluble APPß (sAPPß), ß-amyloid (Aß) peptides and the APP intracellular domain (AICD), have different functions determined by their structural differences, equilibrium and concentration with respect to other fragments derived from APP. This review discusses recent observations regarding possible functions of APP and its proteolytic derivatives in the biology and phenotypic specification of NSCs. This can be important for a better understanding of the pathogenesis and the development of future therapeutic applications for AD and/or DS, diseases in which alterations in neurogenesis have been described.

Radial versus longitudinal myocardial deformation from gray-scale echocardiography.

The objectives of this work are to evaluate a novel non-Doppler-based echocardiographic method that makes it possible to simultaneously obtain the radial and longitudinal components of myocardial velocity (V) and strain (S), and to assess whether left ventricular fiber architecture affects the net function of the myocardium. Previous reports state that differences in the estimation of regional function between septum and lateral walls can be related to the anatomic disposition of myocardial fibers. In this work we measure and compare in 21 healthy volunteers longitudinal and radial peak systolic velocity V (V(long), V(rad): cm/s), peak systolic strain S (S(long), S(rad): %) and time-to-peak S and V (T-Smax, T-V(max): ms) at the midsegments of the septal and lateral walls. Results show that V was higher, both in the radial and longitudinal components, in the lateral wall than in the septum (V(rad): 4.77 +/- 0.26 cm/s vs. 3.77 +/- 0.20 cm/s, p = 0.007; V(long): 5.60 +/- 0.48 cm/s vs. 4.13 +/- 0.11 cm/s, p = 0.01). Radial strain was higher in the septum (S(rad): 28.63 +/- 2.25% vs. 22.54 +/- 1.5%, p = 0.015), and longitudinal strain, in the lateral wall (S(long): -25.89 +/- 1.43% vs. -22.20 +/- 0.87%, p = 0.02). There was a significant delay in longitudinal T-Smax between the lateral and septal medial segments (mean: 14.5 ms; CI 95%: 0.3-28.6 ms; p = 0.04), with no difference in radial T-Smax (277.1 +/- 8.6 ms vs. 277.2 +/- 12.4 ms, p = 0.93). The assessment of regional myocardial function by this new method enables the simultaneous analysis of its radial and longitudinal components. These measurements correlate well with previous anatomical knowledge of the architecture of myocardial fibers, emphasizing its functional significance in regional myocardial function analysis.

Group B streptococcal bacteriuria during pregnancy as a risk factor for maternal intrapartum colonization: a prospective cohort study.

PURPOSE: Current evidence is inconclusive regarding the intrapartum administration of chemoprophylaxis, merely based on the presence of group B streptococcal (GBS) bacteriuria of any colony count, in the prevention of early-onset neonatal GBS infection. The aim of this study was to assess whether GBS bacteriuria is a risk factor for intrapartum colonization (IPC) regardless of urinary concentration or the results of late third-trimester rectovaginal screening cultures (RVSCs). METHODOLOGY: Six hundred and eight pregnant women, with urine specimens cultured between May 2011 and May 2013, were enrolled in this prospective cohort study. RVSCs were available for 582 women and intrapartum rectovaginal cultures for 246. RESULTS: The prevalence of GBS bacteriuria and positive RVSCs was 10.8 and 16.5 %, respectively. The frequency of IPC was 15.9 % (39/246). Sensitivity, specificity, positive and negative predictive values of urine culture and of RVSC in predicting GBS IPC were 41, 94.7, 59.3 and 89.5 %, and 76.9, 95.4, 76.9 and 95.4 %, respectively. GBS bacteriuria was significantly associated with IPC, overall [relative risk (RR) 5.6] and in women with negative RVSC (RR 8.5), with bacteriuria <104 c.f.u. ml-1 (RR 5.9) or when both circumstances coexisted (RR 8.9). The urinary colony count was <104 c.f.u. ml-1 in 13 of the 16 women with GBS bacteriuria and IPC. CONCLUSION: GBS bacteriuria is a risk factor for IPC, irrespective of urinary GBS concentration or of colonization status at late gestation. Therefore, microbiology laboratories should search, and report, GBS of any colony count in urine from pregnant women, and not only in the presence of ≥104 c.f.u. ml-1 as the 2010 CDC guidelines recommend.

Doppler-derived ejection intraventricular pressure gradients provide a reliable assessment of left ventricular systolic chamber function.

BACKGROUND: Ejection intraventricular pressure gradients are caused by the systolic force developed by the left ventricle (LV). By postprocessing color Doppler M-mode (CDMM) images, we can measure noninvasively the ejection intraventricular pressure difference (EIVPD) between the LV apex and the outflow tract. This study was designed to assess the value of Doppler-derived EIVPDs as noninvasive indices of systolic chamber function. METHODS AND RESULTS: CDMM images and pressure-volume (conductance) signals were simultaneously acquired in 9 minipigs undergoing pharmacological interventions and acute ischemia. Inertial, convective, and total EIVPD curves were calculated from CDMM recordings. Peak EIVPD closely correlated with indices of systolic function based on the pressure-volume relationship: peak elastance (within-animal R=0.98; between-animals R=0.99), preload recruitable stroke work (within-animal R=0.81; between-animals R=0.86), and peak of the first derivative of pressure corrected for end-diastolic volume (within-animal R=0.88; between-animals R=0.91). The correlation of peak inertial EIVPD with these indices was also high (all R>0.75). Load dependence of EIVPDs was studied in another 5 animals in which consecutive beats obtained during load manipulation were analyzed. During caval occlusion (40% EDV reduction), dP/dtmax, ejection fraction, and stroke volume significantly changed, whereas peak EIVPD remained constant. Aortic occlusion (40% peak LV pressure increase) significantly modified dP/dtmax, ejection fraction, and stroke volume; a nearly significant trend toward decreasing peak EIVPD was observed (P=0.06), whereas inertial EIVPD was unchanged (P=0.6). EIVPD beat-to-beat and interobserver variabilities were 2+/-12% and 5+/-11%, respectively. CONCLUSIONS: Doppler-derived EIVPDs provide quantitative, reproducible, and relatively load-independent indices of global systolic chamber function that correlate closely with currently available reference methods.

A noninvasive method for assessing impaired diastolic suction in patients with dilated cardiomyopathy.

BACKGROUND: Diastolic suction is a major determinant of early left ventricular filling in animal experiments. However, suction remains incompletely characterized in the clinical setting. METHODS AND RESULTS: First, we validated a method for measuring the spatio-temporal distributions of diastolic intraventricular pressure gradients and differences (DIVPDs) by digital processing color Doppler M-mode recordings. In 4 pigs, the error of peak DIVPD was 0.0+/-0.2 mm Hg (intraclass correlation coefficient, 0.95) compared with micromanometry. Forty patients with dilated cardiomyopathy (DCM) and 20 healthy volunteers were studied at baseline and during dobutamine infusion. A positive DIVPD (toward the apex) originated during isovolumic relaxation, reaching its peak shortly after mitral valve opening. Peak DIVPD was less than half in patients with DCM than in control subjects (1.2+/-0.6 versus 2.5+/-0.8 mm Hg, P<0.001). Dobutamine increased DIVPD in control subjects by 44% (P<0.001) but only by 23% in patients with DCM (P=NS). DIVPDs were the consequence of 2 opposite forces: a driving force caused by local acceleration, and a reversed (opposed to filling) convective force that lowered the total DIVPD by more than one third. In turn, local acceleration correlated with E-wave velocity and ejection fraction, whereas convective deceleration correlated with E-wave velocity and ventriculo:annular disproportion. Convective deceleration was highest among patients showing a restrictive filling pattern. CONCLUSIONS: Patients with DCM show an abnormally low diastolic suction and a blunted capacity to recruit suction with stress. By raising the ventriculo:annular disproportion, chamber remodeling proportionally increases convective deceleration and adversely affects left ventricular filling. These previously unreported mechanisms of diastolic dysfunction can be studied by using Doppler echocardiography.

[Agreement between centers on the interpretation of exercise echocardiography]. / Concordancia intercentros en la interpretación de la ecocardiografía de ejercicio.

INTRODUCTION AND OBJECTIVES: A low-to-moderate level of agreement on the interpretation of dobutamine echocardiography has been reported, but there are no similar findings on exercise echocardiography. The objectives of this study were to assess the level of agreement between centers on the use of exercise echocardiography and to evaluate the accuracy of the technique when used in a blinded manner. PATIENTS AND METHOD: Six institutions with experience in exercise echocardiography each sent 25 study results to the other centers. Of these, 15 were positive or negative studies on consecutive patients undergoing coronary angiography, and 10 were on non-diabetic patients who had non-coronary chest pain or were asymptomatic and whose pretest probability of coronary artery disease was < 10%. Each institution evaluated 150 studies: 125 blinded and 25 of their own with knowledge of clinical data. RESULTS: For 116 patients (78%), four or more of the five centers blindly evaluating each study agreed with the positive or negative result. The average kappa coefficient was 0.48 (intercenter range 0.45-0.52). The percentage agreement was higher with three-vessel disease (93%, range 85%-95%), with left anterior descending coronary artery disease (83%, range 80%-86%), and when the referring institution reported baseline dyssynergy (86%, range 82%-90%), dyssynergy in left anterior descending coronary artery territory (81%, range 76%-84%), or a peak wall motion score index > 1.50 (88%, range 85%-90%). When the technique was used blinded to detect > or = 50% coronary narrowing in > or = 1 vessel, its sensitivity, specificity and accuracy were 68%, 66% and 67%, respectively, with wide variability between centers. CONCLUSIONS: There was moderate agreement between centers on the interpretation of exercise echocardiography. When used blinded, the technique's accuracy was lower than that reported when clinical data is known.

Estimation of the end of ejection in aortic stenosis: an unreported source of error in the invasive assessment of severity.

BACKGROUND: All indices of aortic stenosis (AS) rely on measurements of mean transvalvular pressure gradient (DeltaP) and flow rate. Because the gradient is reversed during late ejection, the late systolic left ventricular (LV)-aortic pressure crossover may be an erroneous landmark of end-ejection. The aortic incisura should be a better reference to calculate indices of AS invasively. METHODS AND RESULTS: The accuracy of the pressure crossover and the incisura to define end-ejection was assessed in a chronic AS experimental model (9 dogs) with the use of an implantable flowmeter and Doppler echocardiography as reference. In 288 hemodynamic recordings analyzed (aortic valve area [AVA]: 0.74+/-0.46 cm2), ejection ended 37+/-29 ms after the pressure crossover but almost simultaneously with the incisura (2+/-17 ms). Pressure crossover error accounted for significant errors in the measurement of DeltaP (95% limits of agreement, +0 to +7 mm Hg) and AVA (-0.1 to +0.2 cm2). These errors were reduced to less than half with the use of the incisura to define end-ejection. Additionally, the agreement with Doppler-derived AS indices was best with use of the incisura. Pressure crossover error was maximal in situations of higher output, moderate orifice narrowing, higher arterial compliance, and lower vascular resistance. In 32 consecutive patients undergoing cardiac catheterization for AS, the pressure crossover induced a clinically important overestimation of the DeltaP from +22 to +50%. Errors in AVA estimation were considerably smaller (-2% to +6%) because of simultaneous and offsetting errors in the measurements of DeltaP and flow. CONCLUSIONS: The aortic incisura and not the second pressure crossover should be used to obtain invasive indices of AS.