Symptom-related screening programme for early detection of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: the SYSPPE study.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is the most severe long-term complication of acute pulmonary embolism (PE). We aimed to evaluate the impact of a symptom screening programme to detect CTEPH in PE survivors. METHODS: This was a multicentre cohort study of patients diagnosed with acute symptomatic PE between January 2017 and December 2018 in 16 centres in Spain. Patients were contacted by phone 2 years after the index PE diagnosis. Those with dyspnoea corresponding to a New York Heart Association (NYHA)/WHO scale≥II, visited the outpatient clinic for echocardiography and further diagnostic tests including right heart catheterisation (RHC). The primary outcome was the new diagnosis of CTEPH confirmed by RHC. RESULTS: Out of 1077 patients with acute PE, 646 were included in the symptom screening. At 2 years, 21.8% (n=141) reported dyspnoea NYHA/WHO scale≥II. Before symptom screening protocol, five patients were diagnosed with CTEPH following routine care. In patients with NYHA/WHO scale≥II, after symptom screening protocol, the echocardiographic probability of pulmonary hypertension (PH) was low, intermediate and high in 76.6% (n=95), 21.8% (n=27) and 1.6% (n=2), respectively. After performing additional diagnostic test in the latter 2 groups, 12 additional CTEPH cases were confirmed. CONCLUSIONS: The implementation of this simple strategy based on symptom evaluation by phone diagnosed more than doubled the number of CTEPH cases. Dedicated follow-up algorithms for PE survivors help diagnosing CTEPH earlier. TRIAL REGISTRATION NUMBER: NCT03953560.

Targeted sequencing of selected functional genes in patients with wild-type transthyretin amyloidosis.

OBJECTIVE: Wild-type transthyretin (ATTRwt) amyloidosis is caused by the misfolding and deposition of the transthyretin protein (TTR) in the absence of mutations in the TTR gene. Studies regarding the variant form of ATTR amyloidosis (ATTRv) suggest that the presence of single-nucleotide polymorphisms (SNP) in genes other than the TTR, may influence the development of the disease. However, other genetic factors involved in the aetiopathogenesis of ATTRwt are currently unknown. This work investigates the presence of sequence variants in genes selected for their possible impact on ATTRwt amyloidosis. To do so, targeted sequencing of 84 protein-coding genes was performed in a cohort of 27 patients diagnosed with ATTRwt. RESULTS: After applying quality and frequency filtering criteria, 72 rare or novel genetic variants were found. Subsequent classification according to the ACMG-AMP criteria resulted in 17 variants classified as of uncertain significance in 14 different genes. To our knowledge, this is the first report associating novel gene variants with ATTRwt amyloidosis. In conclusion, this study provides potential insights into the aetiopathogenesis of ATTRwt amyloidosis by linking novel coding-gene variants with the occurrence of the disease.

Echocardiographic markers of cardiac amyloidosis in patients with heart failure and left ventricular hypertrophy.

BACKGROUND: Cardiac amyloidosis (CA), following a non-invasive diagnosis, constitutes an increasingly prevalent heart failure (HF) etiology. This study aims to determine which echocardiography findings help to diagnose CA in patients with left ventricular hypertrophy (LVH) admitted for decompensated HF. METHODS: The present study is a retrospective observational study on a cohort of 85 LVH patients admitted for HF decompensation, in which 99mTc-DPD scanning was performed to rule out transthyretin CA. The echocardiographic findings obtained were compared between CA and non-CA groups. RESULTS: From a total number of 85 patients, 49 (57.6%) met the CA criteria and 36 (42.3%) were ruled out for the disease. Interventricular septum thickness (16 ± 3 mm vs. 14 ± 3 mm), left ventricular posterior wall thickness (14 ± 3 mm vs. 11 ± 2 mm), left ventricular mass (259 ± 76 g vs. 224 ± 53 g), left ventricular end-diastolic diameter (48 ± 7 mm vs. 53 ± 6 mm), left ventricular end-diastolic indexed volume (51 ± 18 cm3/m2 vs. 59 ± 16 cm3/m2), tricuspid annular plane systolic excursion (16 ± 5 mm vs. 20 ± 4 mm), right atrial area (27.4 ± 8.4 cm2 vs. 22.2 ± 5.7 cm2) and strain relative apical sparing (2.2 ± 0.9 vs. 1.03 ± 0.4; p = 0.04) were significantly associated with the diagnosis of CA. CONCLUSIONS: In patients with LVH admitted for HF decompensation, there are several echocardiographic features (LVH, reduced left ventricular cavity size, strain relative apical sparing, right atrial dilation, and altered right ventricular function) that are associated with the diagnosis of cardiac amyloidosis.

Coexistence of Positive 99mTc-DPD Scintigraphy and Monoclonal Gammopathy: A Frequent Challenge.

Background: Cardiac involvement is common in amyloidosis, and the vast majority of cases of amyloid cardiomyopathy are attributed to primary amyloidosis or transthyretin amyloidosis (ATTR). Although the coexistence of scintigraphy suggestive of ATTR with monoclonal gammopathy of undetermined significance is well documented, the correct diagnosis is still challenging in non-referral centers. Methods: We performed a retrospective study reviewing all amyloid cardiomyopathy cases diagnosed at our center over the last 5 years, and described our experience and diagnostic approach. Results: During the last 5 years, 74 patients with positive scintigraphy were identified. Of these patients, 41 were included in this study as they had all necessary tests for a complete diagnosis. Two of these 41 patients had variant ATTR and 29 had wild-type ATTR. Ten patients had monoclonal gammopathy (24.4%), and it was consequently impossible to obtain a specific diagnosis. During follow-up, 14 patients (34.1%), five of them from the monoclonal gammopathy group, died, reflecting the severity of disease. Conclusions: In patients with ATTR-suggestive scintigraphy, monoclonal gammopathy frequently occurs concomitantly, thus not allowing to establish a specific diagnosis. A biopsy could only be replaced by genetic testing in selected cases.

Characterization of hereditary transthyretin cardiac amyloidosis in Spain.

INTRODUCTION AND OBJECTIVES: Hereditary transthyretin amyloidosis (hATTR) is a disease caused by mutations in the transthyretin gene that frequently shows cardiac involvement due to amyloid deposition in the myocardium. Our objective was to identify cardiac involvement in a Spanish cohort. METHODS: Retrospective multicenter study of patients diagnosed with hATTR with cardiac involvement from Spanish centers. We collected demographic, clinical, and genetic data. RESULTS: A total of 181 patients from 26 centers were included (65.2% men, with a median age at diagnosis of 62 years). The most frequent mutations were Val50Met (67.7%) and Val142Ile (12.4%). The main reason for consultation was extracardiac symptoms (69%), mainly neurological. The mean N-terminal pro-B-type natriuretic peptide level was 2145±3586 pg/mL. The most characteristic electrocardiogram findings were a pseudoinfarct pattern (25.9%) and atrioventricular block (25.3%). Mean ventricular thickness was 15.4±4.1mm. Longitudinal strain was reduced in basal segments by 29.4%. Late diffuse subendocardial enhancement was observed in 58.8%. Perugini grade 2 or 3 uptake was observed in 75% of scintigraphy scans. During follow-up, 24.9% of the patients were admitted for heart failure, 34.3% required a pacemaker, and 31.6% required a liver transplant. One third (32.5%) died during follow-up, mainly due to heart failure (28.8%). The presence of non-Val50Met mutations was associated with a worse prognosis. CONCLUSIONS: HATTR cardiac amyloidosis in Spain shows heterogeneous genetic and clinical involvement. The prognosis is poor, mainly due to cardiac complications. Consequently early diagnosis and treatment are vital.

Cardiac Transthyretin Amyloidosis: A Nuclear Medicine Leading Role. Situation in a Spanish Center and "State of the Art" in Nuclear Medicine.

PURPOSE: Amyloidosis is a heterogeneous group of diseases caused by abnormal extracellular deposition of insoluble proteins and can involve myocardium. One of the causes of myocardial involvement is TTR amyloidosis. Our objective has been to evaluate the situation of cardiac amyloidosis (CA) in our center and the role of nuclear medicine, and to review the state of the art of nuclear medicine in this entity. PATIENTS AND METHODS: We have evaluated retrospectively 186 patients with clinical suspicion of CA and analyzed the clinical characteristics, free light chains and immunofixation in serum and/or urine, and the most relevant biomarkers associated with transthyretin CA (C-ATTR) of these patients and compared them with the results of the 99mTc-DPD scintigraphy. RESULTS: We have verified the growing bibliographic evidence concerning C-ATTR. A total of 51 scintigraphies (27.4%) were positive, 2 (1.1%) indeterminate and 133 (71.5%) negative according to the Perugini score. ATTR was diagnosed in 22 (11.8%; 77.3% males; mean age, 79.4 years). Of these, 12 (75% men; 82.3 years) were ATTRwt (wild-type or age-associated) patients, 2 (50% men; 52 years) experienced ATTRv (variant or hereditary), and 8 (87.5% men; 82.3 years) were not classified because of the absence genetic test. The origin of amyloidosis could not be determined in 31 (16.7%; 80.7% males; 84.5 years). In 29 of them (93.6%), it was because there was no study of free light chains or immunofixation. CONCLUSIONS: Nuclear medicine is playing an increasing role in the diagnosis and classification of CA. However, the monitoring of these is still patchy.

Estimating the prevalence of allelic variants in the transthyretin gene by analysing large-scale sequencing data.

Transthyretin amyloidosis (ATTR amyloidosis) is a rare disease characterised by extracellular deposition of amyloid fibrils composed by transthyretin. ATTR amyloidosis can be sub-classified as wild-type ATTR (ATTR-wt) or as hereditary amyloidosis (ATTR-m); the prevalence of both types are likely underestimated. There are tools that can help us to study ATTR-m, as gnomAD database. Our primary aim was to estimate prevalence of variants, especially amyloidogenic variants, in the TTR gene using gnomAD database. We analysed TTR missense variants found in gnomAD. The variables studied were classified according to their clinical significance and according to the different populations. We found 71 missense variants in the TTR gene. Eleven variants were described as affects function variants (prevalence 1:230). The most frequently detected variant were c.424G>A (p.(Val142Ile)) (prevalence 1:332, MAF 0.00151) and c.148G>A (p.(Val50Met)) (prevalence 1:4924, MAF 0.000102), which represented 88% and 5%, respectively, of all affects function variants detected. Seventeen variants were classified as probably affects function, 29 as unknown variants, 4 as probably does not affect function and 10 as does not affect function variants. In terms of different populations, c.424G>A (p.(Val142Ile)) was especially prevalent in African population (MAF 0.01602; prevalence of 1:31) and c.148G>A (p.(Val50Met)) in European population (MAF 0.000179; prevalence of 1:2792). Prevalence of amyloidogenic variants in the general population was higher than prevalence heretofore described. This difference could be explained by incomplete penetrance of the disease, but other factors contributing to this fact, fundamentally the underdiagnosis of the disease.

Amiloidosis cardiaca secundaria a la mutación familiar Glu54Gln del gen de la transtiretina / Cardiac involvement secondary to a familial form of transthyretin amyloidosis resulting from the Glu54Gln mutation

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Empiemas pleurales por Gemella spp: una etiología no tan infrecuente / Pleural empyema due to Gemella spp: Report of 12 cases

Background: Gemella genus bacteria can produce localized or generalized severe infections, but very rarely they have been described as causingpulmonary infections or pleural empyemas. Aim: To characterize patients with empyema caused by Gemella genus bacteria. Material and Methods: The database of a Microbiology laboratory of a Spanish hospital was reviewed, searchingfor Gemella positive cultures ofpleural effusions in a period offive years. Results: We identified 12 patients (11 males) with Gemella spp pleural empyema. Eight were infected with G. haemolysans and four with G. morbillorum. All patients had predisposingfactors such as poor oral hygiene, smoking, chronic cardiovascular or respiratory disease, alcoholism or malignancies. In ten cases, a thoracic drainage tube was placed with fibrinolysis in seven. One patient needed surgery because of a relapse of the empyema. Two patients died because of an advanced neoplasm, and the empyema was resolved in the rest. Conclusions: Gemella pleural empyema can occur and its isolation must not be seen as a contamination.

[Pleural empyema due to Gemella spp: report of 12 cases]. / Empiemas pleurales por Gemella spp: una etiología no tan infrecuente.

BACKGROUND: Gemella genus bacteria can produce localized or generalized severe infections, but very rarely they have been described as causing pulmonary infections or pleural empyemas. AIM: To characterize patients with empyema caused by Gemella genus bacteria. MATERIAL AND METHODS: The database of a Microbiology laboratory of a Spanish hospital was reviewed, searching for Gemella positive cultures of pleural effusions in a period of five years. RESULTS: We identified 12 patients (11 males) with Gemella spp pleural empyema. Eight were infected with G. haemolysans and four with G. morbillorum. All patients had predisposing factors such as poor oral hygiene, smoking, chronic cardiovascular or respiratory disease, alcoholism or malignancies. In ten cases, a thoracic drainage tube was placed with fibrinolysis in seven. One patient needed surgery because of a relapse of the empyema. Two patients died because of an advanced neoplasm, and the empyema was resolved in the rest. CONCLUSIONS: Gemella pleural empyema can occur and its isolation must not be seen as a contamination.

[Nephritic colic management in an emergency room of a referral hospital]. / Manejo del cólico renal en urgencias de un hospital de tercer nivel.

BACKGROUND: To evaluate the diagnostic and therapeutic management of patients with nephritic colic in a referral hospital, their monitoring and the incidence of alternative diagnoses. METHODS: This is a retrospective review of 182 randomly selected patients who presented a clinical diagnosis compatible with nephritic colic in a referral hospital. In these cases initial treatment, monitoring and alternative diagnoses have been evaluated. RESULTS: Fifty-five point four percent of the patients were male, the mean age was 47.7 years and 40% of the cases were in spring. Urinalysis was carried out in every patient (62.7% dipstick and 72% urinary sediment); they were pathological in over 70%. In 26.4% of cases renal function deteriorated, always transiently. Abdominal radiography (81.9%) was the most frequently diagnostic test performed, followed by ultrasound (25.8%). Treatment included a serum therapy in 31.3%; metamizol (61%) was the most commonly used analgesic followed by ketorolac (44.5%). More than one non-steroidal anti-inflammatory was used by 46.2%. Hospital admission was required by 24 patients, and 5 of them needed emergency surgery. Twenty-four point one percent of patients had relapses during the next six months. Forty-one point six percent were referred to urology discharge on from the emergency room. Eighteen point one percent of patients had alternative diagnoses; acute pyelonephritis was the most frequent of these (55%). CONCLUSIONS: In our work we found a significant variation in the diagnostic and therapeutic management of these patients. The use of clinical guidelines could help us to unify the management of patients with nephritic colic, both in the emergency room and on discharge. Due to the high prevalence of alternative diagnoses, we have to systematically exclude more serious diseases.

Hemólisis como complicación en una válvula cardíaca protésica / Hemolysis as a complication of prosthetic mitral valve

La anemia hemolítica es una complicación poco frecuente asociada a prótesis valvular, tanto mecánica como biológica y se produce por varios fenómenos. Se presenta el caso clínico de un paciente portador de anuloplastia mitral que acude a urgencias por astenia, cambios en el color de la orina e ictericia y a través de la presencia de hemólisis se diagnostica de disfunción protésica valvular mediante una ecocardiograma. Se realiza una revisión bibliográfica de la fisiopatoogía de las hemólisis mecánica producida por prótesis valvulares y su repercusión clínico-analítica, así como de las indicaciones de reintervención quirúrgica (AU)

Haemolytic anaemia is an uncommon complication associated with mechanical or biological prosthetic valve. It is developed by different mechanisms. A case of patient with mitral valve repair is presented, who arrive at the emergency room with asthenia, changes in urine colour and jaundice. Haemolysis is proved, and an echocardiogram is necessary to diagnose of prosthtic valve dysfunction. A review of literature about mechanical haemolysis physiopathology, its clinical and analyticial consequences and indication for reoperation is made (AU)

Hemóllsis como complicación en una válvula cardíaca protésica / Hemolysis as a complication of prosthetic mitral valve

La anemia hemolítica es una complicación poco frecuente asociada a prótesis valvular, tanto mecánica como biológica, y se produce por varios fenómenos. Se presenta el caso clínico de un paciente portador de anuloplastia mitral que acude a urgencias por astenia, cambios en el color de la orina e ictericia, y a través de la presencia de hemólisis se diagnostica de disfunción protésica valvular mediante un ecocardiograma. Se realiza una revisión bibliográfica de la fisiopatología de la hemólisis mecánica producida por prótesis valvulares y su repercusión clínico-analítica, así como de las indicaciones de reintervención quirúrgica (AU)

Haemolytic anaemia is an uncommon complication associated with mechanical or biological prosthetic valve. It is developed by different mechanisms. A case of patient with mitral valve repair is presented, who arrive at the emergency room with asthenia, changes in urine colour and jaundice. Haemolysis is proved, and an echocardiogram is necessary to diagnose of prosthetic valve dysfunction. A review of literature about mechanical haemolysis physiopathology, its clinical and analytical consequences and indications for reoperation is made (AU)