Evaluation of angiogenic factors in prediction of growth-related neonatal morbidity at term and comparison with competing-risks model.

OBJECTIVES: First, to describe the distribution of biomarkers of impaired placentation in small-for-gestational-age (SGA) pregnancies with neonatal morbidity; second, to examine the predictive performance for growth-related neonatal morbidity of a high soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio or low PlGF; and, third, to compare the performance of a high sFlt-1/PlGF ratio or low PlGF with that of the competing-risks model for SGA in predicting growth-related neonatal morbidity. METHODS: This was a prospective observational study of women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation in two maternity hospitals in England. The visit included recording of maternal demographic characteristics and medical history, an ultrasound scan and measurement of serum PlGF and sFlt-1. The primary outcome was delivery within 4 weeks after assessment and at < 42 weeks' gestation of a SGA neonate with birth weight < 10th or < 3rd percentile, combined with neonatal unit (NNU) admission for ≥ 48 h or a composite of major neonatal morbidity. The detection rates in screening by PlGF < 10th percentile, sFlt-1/PlGF ratio > 90th percentile, sFlt-1/PlGF ratio > 38 and the competing-risks model for SGA, using combinations of maternal risk factors and Z-scores of estimated fetal weight (EFW) with multiples of the median values of uterine artery pulsatility index, PlGF and sFlt-1, were estimated. The detection rates by the different methods of screening were compared using McNemar's test. RESULTS: In the study population of 29 035 women, prediction of growth-related neonatal morbidity at term provided by the competing-risks model was superior to that of screening by low PlGF concentration or a high sFlt-1/PlGF concentration ratio. For example, at a screen-positive rate (SPR) of 13.1%, as defined by the sFlt-1/PlGF ratio > 38, the competing-risks model using maternal risk factors and EFW predicted 77.5% (95% CI, 71.7-83.3%) of SGA < 10th percentile and 89.3% (95% CI, 83.7-94.8%) of SGA < 3rd percentile with NNU admission for ≥ 48 h delivered within 4 weeks after assessment. The respective values for SGA with major neonatal morbidity were 71.4% (95% CI, 56.5-86.4%) and 90.0% (95% CI, 76.9-100%). These were significantly higher than the respective values of 41.0% (95% CI, 34.2-47.8%) (P < 0.0001), 48.8% (95% CI, 39.9-57.7%) (P < 0.0001), 37.1% (95% CI, 21.1-53.2%) (P = 0.003) and 55.0% (95% CI, 33.2-76.8%) (P = 0.035) achieved by the application of the sFlt-1/PlGF ratio > 38. At a SPR of 10.0%, as defined by PlGF < 10th percentile, the competing-risks model using maternal factors and EFW predicted 71.5% (95% CI, 65.2-77.8%) of SGA < 10th percentile and 84.3% (95% CI, 77.8-90.8%) of SGA < 3rd percentile with NNU admission for ≥ 48 h delivered within 4 weeks after assessment. The respective values for SGA with major neonatal morbidity were 68.6% (95% CI, 53.1-83.9%) and 85.0% (95% CI, 69.4-100%). These were significantly higher than the respective values of 36.5% (95% CI, 29.8-43.2%) (P < 0.0001), 46.3% (95% CI, 37.4-55.2%) (P < 0.0001), 37.1% (95% CI, 21.1-53.2%) (P = 0.003) and 55.0% (95% CI, 33.2-76.8%) (P = 0.021) achieved by the application of PlGF < 10th percentile. CONCLUSION: At 36 weeks' gestation, the prediction of growth-related neonatal morbidity by the competing-risks model for SGA, using maternal risk factors and EFW, is superior to that of a high sFlt-1/PlGF ratio or low PlGF. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Ophthalmic artery Doppler and biomarkers of impaired placentation at 36 weeks' gestation in pregnancies with small fetuses.

OBJECTIVES: First, to compare ophthalmic artery peak systolic velocity (PSV) ratio and biomarkers of impaired placentation at 36 weeks' gestation in women who delivered a small-for-gestational-age (SGA) or growth-restricted (FGR) neonate, in the absence of hypertensive disorder, with those of women who developed pre-eclampsia (PE) or gestational hypertension (GH) and of women unaffected by SGA, FGR, PE or GH. Second, to examine the associations of PSV ratio, uterine artery pulsatility index (UtA-PI), placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) with birth-weight Z-score or percentile. METHODS: This was a prospective observational study of women with a singleton pregnancy attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, ultrasound examination of fetal anatomy and growth, and measurement of maternal ophthalmic artery PSV ratio, UtA-PI, PlGF and sFlt-1. Values of PSV ratio, UtA-PI, PlGF and sFlt-1 were converted to multiples of the median (MoM) or delta values. Median MoM or deltas of these biomarkers in the SGA, FGR, PE and GH groups were compared with those in the unaffected group. Regression analysis was used to examine the relationship of PSV ratio delta, UtA-PI MoM, PlGF MoM and sFlt-1 MoM with birth-weight Z-score, after exclusion of PE and GH cases. RESULTS: The study population of 9033 pregnancies included 7696 (85.2%) that were not affected by FGR, SGA, PE or GH, 182 (2.0%) complicated by FGR in the absence of PE or GH, 698 (7.7%) with SGA in the absence of FGR, PE or GH, 236 (2.6%) with PE and 221 (2.4%) with GH. Compared with unaffected pregnancies, in the FGR and SGA groups, the PSV ratio delta and sFlt-1 MoM were increased and PlGF MoM was decreased; UtA-PI MoM was increased in the FGR group but not the SGA group. The magnitude of the changes in biomarker values relative to the unaffected group was smaller in the FGR and SGA groups than that in the PE and GH groups. In non-hypertensive pregnancies, there were significant inverse associations of PSV ratio delta and UtA-PI MoM with birth-weight Z-score, such that the values were increased in small babies and decreased in large babies. There was a quadratic relationship between PlGF MoM and birth-weight Z-score, with low PlGF levels in small babies and high PlGF levels in large babies. There was no significant association between sFlt-1 MoM and birth-weight Z-score. CONCLUSIONS: Ophthalmic artery PSV ratio, reflective of peripheral vascular resistance, and UtA-PI, PlGF and sFlt-1, biomarkers of impaired placentation, are altered in pregnancies complicated by hypertensive disorder and, to a lesser extent, in non-hypertensive pregnancies delivering a SGA or FGR neonate. The associations between the biomarkers and birth-weight Z-score suggest the presence of a continuous physiological relationship between fetal size and peripheral vascular resistance and placentation, rather than a dichotomous relationship of high peripheral resistance and impaired placentation in small compared to non-small fetuses. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

The use of the acute Pd/Pa drop after intracoronary nitroglycerin infusion to rule out significant FFR: CANICA (Can intracoronary nitroglycerin predict fractional flow reserve without adenosine?) multicenter study.

OBJECTIVE: Functional assessment of coronary artery stenosis is performed by measuring the fractional flow reserve (FFR) under hyperemic conditions (Adenosine). However, the use of adenosine portends limitations. OBJECTIVE: We sought to investigate the relationship and correlation between FFR and the Pd/Pa value obtained just after the intracoronary infusion (acute drop) of nitroglycerin (Pd/Pa-NTG) and if this parameter enhances diagnostic accuracy for FFR prediction compared to the resting baseline Pd/Pa. METHODS: We conducted a multicenter study including prospectively patients presenting intermediate coronary artery stenosis (30-70%) evaluated with pressure wire. Resting baseline Pd/Pa, Pd/Pa-NTG and FFR were measured. RESULTS: 283 patients (335 lesions) were included. Resting baseline Pd/Pa value was 0.72 to 1.0 (0.93 ± 0.04), Pd/Pa-NTG was 0.60 to 1.0 (0.87 ± 0.07) and FFR 0.55 to 1.0 (0.83 ± 0.08). The ROC curves for resting baseline Pd/Pa and for Pd/Pa-NTG, using a FFR ≤ 0.80 showed an AUC of 0.88 (95% CI: 0.84-0.92, P < 0.001) and 0.94 (95% CI: 0.92-0.96, P < 0.001) respectively. The optimal cutoff values of resting baseline Pd/Pa and Pd/Pa-NTG for an FFR > 0.80, were >0.96 and >0.88, respectively. These values were present in a 29.8% (n = 100) and a 47.1% (n = 158), of the total lesions. Scatter plots showed a better correlation and agreement points with Pd/Pa-NTG than resting baseline Pd/Pa. The cutoff value of Pd/Pa-NTG > 0.88 showed an excellent NPV (96.2% for FFR > 0.8 and 100% for FFR > 0.75) and sensitivity (95% for FFR > 0.8 and 100% for FFR > 0.75) which were consistently high across all the subgroups analysis. CONCLUSION: The cutoff value of acute Pd/Pa-NTG > 0.88 has a high NPV meaning adenosine-FFR can be avoided in almost half of lesions.

Impact of a pulmonary embolism response team (PERT) in the prognosis of patients with acute symptomatic pulmonary embolism.

BACKGROUND: The effect of a pulmonary embolism response team (PERT) in the short-term prognosis of patients with acute symptomatic pulmonary embolism (PE) lacks clarity. We therefore aimed at evaluating the effect of a PERT team on short-term mortality among patients with acute PE. METHODS: We retrospectively reviewed consecutive patients with acute symptomatic PE enrolled in a single-center registry between 2007 and 2022. We used propensity score matching to compare treatment effects for patients with similar predicted probabilities of receiving management by the PERT team. The primary outcome was all-cause mortality within 30 days following the diagnosis of PE. The secondary outcome was 30-day PE-related mortality. RESULTS: Of the 2,902 eligible patients who had acute symptomatic PE, 223 (7.7%; 95% confidence interval [CI], 6.7%-8.7%) were managed by the PERT team. Two hundred and seven patients who were treated by the PERT were matched with 207 patients who were not. Matched pairs did not show a statistically significant lower all-cause (odds ratio [OR], 1.09; 95% CI, 0.63-1.89) or PE-related death (OR, 1.30; 95% CI, 0.47-3.62) for PERT management compared with no PERT management through 30 days after diagnosis of PE. CONCLUSIONS: Our results suggest that multidisciplinary care of patients with acute symptomatic PE by a PERT team is not associated with a significant reduction in short-term all-cause or PE-related mortality.

Discrete subaortic stenosis in adults: increased prevalence and slow rate of progression of the obstruction and aortic regurgitation.

OBJECTIVES: We sought to determine the prevalence and rate of progression of left ventricular outflow tract obstruction (LVOTO) and aortic regurgitation (AR) in adults with discrete subaortic stenosis (DSS). BACKGROUND: Discrete subaortic stenosis is an uncommon form of LVOTO, with rapid hemodynamic progression in children, but the prevalence and rate of progression in adults have not been studied so far. METHODS: The prevalence of DSS was determined in 2,057 consecutive adults diagnosed with congenital heart disease (CHD). The relationship between LVOTO on Doppler echocardiography and patient age was analyzed. Sequential changes in LVOTO and AR were determined for patients with two or more Doppler echocardiograms obtained with at least a two-year interval. RESULTS: A total of 134 adults (mean age 31 +/- 17 years) were diagnosed with DSS. The prevalence was 6.5% for all adults with CHD. Sixty patients (44%) had other associated CHD. The mean age of 29 patients who had undergone an operation for DSS during their adult life (56 +/- 15 years) was significantly higher than that of 64 patients (27 +/- 13 years) who had not required a surgical intervention (p < 0.0001). A significant relationship between LVOTO and patient age (r = 0.61, p < 0.0001) was found: 21 +/- 16 mm Hg in patients <25 years old, 51 +/- 47 mm Hg for those between 25 and 50 years old, and 78 +/- 36 mm Hg for those >50 years old. The LVOTO increased from 39.2 +/- 28 to 46.8 +/- 34 mm Hg (p = 0.01) during a mean follow-up of 4.8 +/- 1.8 years in 25 patients. The slope of the change in LVOTO was 2.25 +/- 4.7 mm Hg per year of follow-up. Aortic regurgitation was detected by color Doppler imaging in 109 patients (81%), but it was hemodynamically significant in <20%. An increase in the mean degree of AR over time was not significant (baseline: 1.3 +/- 0.8; follow-up: 1.5 +/- 0.9; p = 0.096). CONCLUSIONS: The prevalence of DSS is increasing in adults due to the greater number of repaired CHDs that develop into evolutive DSS. In contrast to infants and children, adults with DSS show a slow rate of LVOTO progression. Aortic regurgitation is a common but usually mild and nonprogressive consequence. The current indications for surgical intervention should be revised.

Kinetics study of human retrovirus antigens expression in T lymphocytic cell lines by indirect immunofluorescence assay.

Indirect immunofluorescence assay (IFA) is a well-accepted assay for the confirmation of human retrovirus infection. Fluctuations in HIV-1 antigen expression in infected E-B2 cells depending on several factors have been reported. Cells kept in log phase expressed the highest levels of viral antigen. Thus, we studied the time kinetics of IFA positivity in MT-2 (HTLV-I), MO-T (HTLV-II), CEM, and H9 (HIV-1) cell lines. Uninfected T cell line, HT, was used as nonspecific control. Reference HTLV-I/II and HIV-1 serum panels from the Centers for Disease Control and Prevention (CDC) were tested by conventional IFA procedure on slides of each cell line made on different days. On the second day after subculture, HTLV-I strongly positive sera reacted on MT-2 and MO-T cells with a bright pericytoplasmic fluorescence pattern. Weakly positive sera showed a faint staining from the fifth day on, when all the sera showed the highest degree of fluorescence. With HIV-1 cell lines, sera predominantly reacted with a diffuse cytoplasmic pattern, although some sera showed a granular and pericytoplasmic capping staining. The highest degree of fluorescence was found at 3-5 days after subculture. We demonstrated that the sensitivity of the IFA for the detection of antibodies against human retroviruses depended on the day when the slides were assayed and on the serum antibody titer. The fifth day was the most appropriate for HTLV-I/II and HIV-1/H9 systems, whereas for HIV-1/CEM, the fourth day was better. Furthermore, the intensity of the immunofluorescence pattern differed with the antibody titers and the level of antigens expressed on the four cell lines studied. The IFA, improved in our laboratory, proved to be very sensitive, specific, and rapid and could be used as a supplementary/confirmatory assay for retrovirus infection.

Successful treatment of prosthetic aortic valve mucormycosis.

Mucor endocarditis after cardiovascular surgery is rare and usually fatal. We report the first known case of prosthetic aortic valve mucormycosis in a patient without predisposing risk factors who was successfully treated using a combination of early antifungal drug therapy and surgical removal of infected material.

Prevalence of antibody to human T cell lymphotropic virus types 1/2 among aboriginal groups inhabiting northern Argentina and the Amazon region of Peru.

We carried out a seroepidemiologic survey to define the prevalence of human T cell lymphotropic virus types 1/2 (HTLV-1/2) infections among aboriginal populations from isolated regions of northern Argentina and the Amazon region of Peru. Antibodies against HTLV were measured with agglutination tests and confirmed with by an immunofluorescence assay (IFA) and Western blotting. Five (6.94%) of 72 samples from the Tobas Indians in Argentina were positive by the IFA; two samples were typed as HTLV-1 (2.78%), two as HTLV-2 (2.78%), and one (1.39%) could not be typed because it had similar antibody titers against both viruses. No positive samples were found among 84 Andinos Puneños and 47 Matacos Wichis Indians. Seroprevalences of 2.50% (1 of 40) and 1.43% (1 of 70) for HTLV-1 were observed among Wayku and San Francisco communities in the Amazon region of Peru, and seroprevalences of 4.54% (1 of 22) and 2.38% (1 of 42) for HTLV-2 were observed among Boca Colorada and Galilea communities. No serologic evidence of human immunodeficiency virus (HIV) infection was found among the Indians tested. These results indicated the presence of HTLV-1 and HTLV-2 in the indigenous populations of Argentina and Peru. Moreover, the lack of HIV infection indicates that the virus has probably not yet been introduced into these populations.

Left atrial dissection: pathogenesis, clinical course, and transesophageal echocardiographic recognition.

Left atrial dissection is an uncommon entity. It is generally associated with mitral valve replacement, but other predisposing factors should be considered in pathogenesis. We discuss a series of 11 patients with pathologically confirmed left atrial dissection who had been diagnosed previously by transesophageal echocardiography. Predisposing factors and surgical or pathologic findings were reviewed to identify the pathogenic mechanism and to explain the clinical course, hemodynamic disorder, and echocardiographic features. Dissection of the coronary sinus secondary to retrograde cardioplegia, endocarditis, cardiac rupture after myocardial infarction, and blunt chest trauma also could be related to its development. Transesophageal echocardiography identified a mobile intimal flap of the atrial wall that was creating a false chamber and allowed accurate diagnosis of prosthetic mitral valve function, endocarditis complications, and a left ventricular pseudoaneurysm after acute myocardial infarction. Color flow Doppler was particularly useful in identifying complications: communication between the false chamber and true left atria, permitting mitral regurgitation through the periannular route; development of atrial shunts; and severe tricuspid regurgitation caused by disruption of the anterior papillary muscle.

Cardiomyopathy in childhood and adult life, with emphasis on hypertrophic cardiomyopathy.

Over 60 entries in the genetic catalog have cardiomyopathy features--32 autosomal dominant, 35 autosomal recessive and X-linked. Over 40 present in, or can have survival into, adult life. Major clinicopathologic categories of these cardiomyopathic disorders included: sudden death (13 entities); cardiac conduction disturbance important feature; associated myopathy or motor dysfunction; storage diseases with cardiac involvement; cardiac amyloidoses; and, other categories. Genes, abnormality of which can cause hypertrophic cardiomyopathy (HCM), have been identified on chromosomes 1, 14 and 15, the locus on chromosome 14 involving the B-myosin heavy chain gene, but at least one unidentified locus is known to exist and there is a suggestive locus on chromosome 16, so that HCM is not a single disease but a group of disorders with clinicopatholopic similarities. To investigate these aspects of HCM in some detail, sixty-six patients with "sharply demarcated" differential myocardial fiber bundle hypertrophy (DMBH), considered to be of significant degree, from a pediatric autopsy data base of approximately 8,000 cases, were reviewed. Twenty-three of the patients died suddenly, without antecedent significant cardiac dysfunction, seven had clinical congestive heart failure of varying duration, three were stillborn, six showed evidence of aspiration of amniotic sac content (three had history of fetal distress), five had ischemic bowel disease, three (two with clinical cerebral palsy and one with Ondine's curse syndrome) had cerebral atrophy and sclerosis and one had extensive more acute encephalomalacia, and a variety of other major "causes of death" were present. Whether all infants and children with DMBH meeting the criteria used, who do not have congenital heart disease, have dominant hypertrophic cardiomyopathy (HCM) cannot be established by studies of this type, but the "concentration" of a gene or genes for HCM in pediatric autopsy series because the strong effect of HCM on life expectancy is relevant to this possibility. The data raise the question that stillbirth, fetal distress with aspiration of amniotic sac content, ischemic bowel disease and cerebral atrophy and sclerosis may be hitherto underappreciated features of HCM in childhood, and that patients with HCM may be peculiarly liable to die with certain types of septic shock, such as acute meningococcemia. In the material of this study, sudden death was statistically more frequent in females than in males in childhood (p < .029).

Retrospective evaluation of gynecologic cytodiagnosis. I. Reproducibility using an experimental diagnostic scale.

A system for the exchange of specimens between two independent laboratories ("A" and "B") was designed to enable them to review a consecutive series of one another's gynecologic smears. Another cytopathologist "refereed" diagnoses differing beyond agreed limits and examined all smears called carcinoma in situ or a more severe lesion by either laboratory. A ten-numeral gradient nomenclature scale was developed to code all cytodiagnoses for data processing. This analysis of the reproducibility of the experimental diagnostic system is based on all participants' examination of 100 selected specimens, half contributed by reviewing laboratory A and half by reviewing laboratory B, with the target value of each specimen established by the contributor. Intralaboratory reproducibility, expressed by a correlation coefficient (r), ranged from 0.78 to 0.93. After adjusting for straightforward squamous-cell lesions, r ranged from 0.88 to 0.91. Intralaboratory agreement +/- 1 scalar category, defined as a "working consensus," ranged from 77% to 84%. Interlaboratory correlation ranged from r = 0.74 to 0.94. Adjustment for squamous-cell lesions exerted less effect than it had on intralaboratory reproducibility. Interlaboratory agreement within one category ranged from 58% (laboratory B reviewing specimens contributed by laboratory A) to 92% (referee examining specimens contributed by laboratory B). Initially, laboratory A tended to classify a given specimen higher on the scale than did laboratory B and the referee, but as the study progressed, both laboratories tended to converge toward a more congruent diagnostic position, with referee greater than A greater than B. The level of discrimination attained by all participants validates use of this system to compare a larger series of diagnoses.

[Coxiella burnetii endocarditis: long-term clinical course in 20 patients]. / Endocarditis por Coxiella burnetii: evolución a largo plazo de 20 pacientes.

INTRODUCTION AND OBJECTIVES: Coxiella burnetii is a causative agent of increasingly frequent subacute infective endocarditis, and is associated with elevated morbimortality. Our aim in the present study was to assess the clinical, serological and therapeutic long-term evolution of 20 patients with Coxiella burnetii endocarditis. METHODS: Twenty patients (13 male and 7 female, age 42 +/- 10 years) admitted between 1982 and 1996 were retrospectively studied. All of them fulfilled the Duke criteria modified by Raoult for Q fever endocarditis. RESULTS: Endocarditis involved prosthetic and native valves in 14 and 6 patients, respectively. All patients except one received antibiotic treatment. Patients treated with doxycycline in monotherapy showed worse evolution than those treated with doxycycline in combination with other antibiotics. Valve replacement was performed in 15 patients, due to prosthetic dysfunction in most of them. The overall mortality was 40% (8 patients). At follow-up of 74 months (range 19-156) (mean 74 +/- 47) all patients showed persistent high levels of phase I antibodies. At follow-up of 15 to 65 months (32 +/- 30) antibiotic treatment was suspended in five patients because they were asymptomatic and without microbiologic findings of valvular endocarditis. CONCLUSIONS: Q fever endocarditis was associated with severe complications, which often required valve replacement. All patients showed persistent high serological titers of Coxiella burnetii endocarditis without other signs of active infection. This finding raises the issue of suspending antibiotic treatment in patients with negative microbiologic findings and questions the persistence of abnormal serology as a monitor of treatment efficacy.

[Demonstration of accelerated growth of heart sarcoma using imaging techniques]. / Demostración del crecimiento acelerado de un sarcoma cardíaco mediante técnicas de imagen.

We report the case of a patient presenting a sarcoma of interatrial septum with an accelerated growth and a fulminate clinical course documented by non-invasive image diagnostic techniques, habitual in the cardiologic practice. The natural history of some cardiac malignant tumours, as aggressive as in this case, explains the diagnostic delay, the difficulty to establish a curative treatment such as surgery and/or chemotherapy/radiotherapy and the awful short-term prognosis.

[HTLV-I/II seroprevalence and risk factors associated with infection in a blood donor population in Córdoba, Argentina]. / Seroprevalencia de HTLV-I/II y factores de riesgo asociados a la infección en la población de donantes de sangre de Córdoba, Argentina.

In this study we have determined the seroprevalence of infections by HTLV-I/II in the blood donor population from the city of Córdoba. A total of 5476 blood donor sera were screened for HTLV-I/II antibodies by particle agglutination assay (PA) (SERODIA HTLV-I, Fujirebio INC, Tokyo, Japan). The reactive sera samples were confirmed by an "in house" indirect immunofluorescence assay (IFA). 14 out of 5476 blood donors studied were PA reactive and were confirmed positive by IFA, showing a prevalence of 0.26% (95% confidence interval: 0.126%-0.394%). All the positive samples, except one, met the criteria for HTLV-I. Although one HTLV-I infected donor was an intravenous drug abuser and two donors were born in highly endemic areas for HTLV-I, no specific risk factors were identified among the others. The demonstration that HTLV-I circulates in blood donor population of Córdoba, points out that the systematic screening of blood for HTLV-I/II antibodies must be implemented in the blood banks, in an attempt to prevent the spread of infections with this oncogenic virus in Argentina.

Acute rheumatic fever in a grown up with repaired tetralogy of Fallot: the role of acquired diseases in patients with congenital heart diseases.

We report a 20 year old patient with repaired Tetralogy of Fallot who presented with acute right side heart failure. The echocardiogram showed severe mitral regurgitation which was not present one year before. Because of mitral insufficiency, pulmonary pressure increased and it was nearby 70% systemic pressure. Pulmonary regurgitation got worse, and the patient came to the hospital in a state of anasarca. After valve replacement, histopathological study of the mitral valve and the aortic valve revealed Aschoff nodules and rheumatic fever was confirmed.