Search

Il rachitismo ipofosforemico comprende un gruppo di rare patologie ereditarie caratterizzate da un deficit di riassorbimento renale del fosfato, ipofosfatemia e deformazioni ossee. Le forme più comuni sono il rachitismo ipofosforemico a trasmissione X-linked dominante e il rachitismo ipofosforemico autosomico dominante (AD). Il caso che vi proponiamo è quello di una donna con una diagnosi clinica e biochimica di rachitismo ipofosforemico. La nostra discussione verterà sull'uso della terapia con vitamina D e fosfati che, nel bambino è codificata da oltre 20 anni e ha lo scopo di correggere e prevenire le deformità scheletriche, mentre nel paziente adulto non è uno standard condiviso ed è controverso se sia opportuno proseguirla. L'obiettivo terapeutico nell'adulto è quello di contrastare l'astenia, i dolori ossei, la perdita di massa ossea e l'osteomalacia. Tuttavia è difficile definire criteri sicuri di riferimento e la dose di 1,25 (OH)2D e fosfati capace di raggiungere tali obiettivi. La terapia con fosfato, inoltre, stimola la produzione di PTH ed espone al rischio di iperplasia paratiroidea. È questo il caso della paziente da noi seguita, che dopo un lungo periodo di iperparatiroidismo secondario ha sviluppato un adenoma paratiroideo. Questo caso clinico conferma che l'iperparatiroidismo è una complicanza del trattamento del rachitismo ipofosforemico e indica nel calciomimetico un utile presidio per la sua gestione in questi pazienti.

Background: Whether left ventricular non-compaction (LVNC) bears a different prognosis than dilated cardiomyopathy (DCM) is still a matter of debate., Methods: From a multicenter French prospective registry, we compared the outcomes of 98 patients with LVNC and 65 with DCM. The primary endpoint combined cardiovascular death, heart transplantation, and hospitalization for cardiovascular events. The two groups presented similar outcomes but different left ventricular ejection fractions (LVEF) (43.3% in LVNC vs. 35.95% in DCM, p = 0.001). For this reason, a subgroup analysis was performed comparing only patients with LVEF ≤ 45%, including 56 with LVNC and 49 with DCM., Results: Among patients with LVEF ≤ 45%, at 5-year follow-up, the primary endpoint occurred in 33 (58.9%) among 56 patients with LVNC and 18 (36.7%) among 49 patients with DCM ( p = 0.02). Hospitalization for heart failure (18 [32.14%] vs. 5 [10.20%], p = 0.035) and heart transplantation were more frequent in the LVNC than in the DCM group. The incidences of rhythmic complications (24 [42.85%] vs. 12 [24.48%], p = 0.17), embolic events, and cardiovascular death were similar between LVNC and DCM cases. Among the 42 patients with LVNC and LVEF > 45%, the primary endpoints occurred in only 4 (9.52%) patients, including 2 hospitalizations for heart failure and 3 rhythmic complications, but no embolic events., Conclusion: In this prospective cohort, patients with LVNC who have left ventricular dysfunction present a poorer prognosis than DCM patients. Heart failure events were especially more frequent, but embolic events were not. Patients with LVNC and preserved ejection fraction present very few events in 5 years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gerard, Iline, Martel, Nguyen, Richard, Donal, Eicher, Huttin, Selton-Suty, Raud-Raynier, Jondeau, Mansencal, Sawka, Ader, Pruny, Casalta, Michel, Donghi, Faivre, Giorgi, Charron and Habib.)

Aims: Currently, there are few available data regarding a possible role for subclinical atherosclerosis as a risk factor for mortality in Coronavirus Disease 19 (COVID-19) patients. We used coronary artery calcium (CAC) score derived from chest computed tomography (CT) scan to assess the in-hospital prognostic role of CAC in patients affected by COVID-19 pneumonia., Methods: Electronic medical records of patients with confirmed diagnosis of COVID-19 were retrospectively reviewed. Patients with known coronary artery disease (CAD) were excluded. A CAC score was calculated for each patient and was used to categorize them into one of four groups: 0, 1-299, 300-999 and at least 1000. The primary endpoint was in-hospital mortality for any cause., Results: The final population consisted of 282 patients. Fifty-seven patients (20%) died over a follow-up time of 40 days. The presence of CAC was detected in 144 patients (51%). Higher CAC score values were observed in nonsurvivors [median: 87, interquartile range (IQR): 0.0-836] compared with survivors (median: 0, IQR: 0.0-136). The mortality rate in patients with a CAC score of at least 1000 was significantly higher than in patients without coronary calcifications (50 vs. 11%) and CAC score 1-299 (50 vs. 23%), P < 0.05. After adjusting for clinical variables, the presence of any CAC categories was not an independent predictor of mortality; however, a trend for increased risk of mortality was observed in patients with CAC of at least 1000., Conclusion: The correlation between CAC score and COVID-19 is fascinating and under-explored. However, in multivariable analysis, the CAC score did not show an additional value over more robust clinical variables in predicting in-hospital mortality. Only patients with the highest atherosclerotic burden (CAC ≥1000) could represent a high-risk population, similarly to patients with known CAD., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: Few data exist concerning genotype-phenotype relationships in left ventricular noncompaction (LVNC)., Methods and Results: From a multicenter French Registry, we report the genetic and clinical spectrum of 95 patients with LVNC, and their genotype-phenotype relationship. Among the 95 LVNC, 45 had at least 1 mutation, including 14 cases of mutation in ion channel genes. In a complementary analysis including 16 additional patients with ion channel gene mutations, for a total of 30 patients with ion channel gene mutation, we found that those patients had higher median LV ejection fraction (60% vs 40%; P < .001) and more biventricular noncompaction (53.1% vs 18.5%; P < .001) than the 81 other patients with LVNC. Among them, both the 19 patients with an HCN4 mutation and the 11 patients with an RYR2 mutation presented with a higher LV ejection fraction and more frequent biventricular noncompaction than the 81 patients with LVNC but with no mutation in the ion channel gene, but only patients with HCN4 mutation presented with a lower heart rate., Conclusions: Ion channel gene mutations should be searched systematically in patients with LVNC associated with either bradycardia or biventricular noncompaction, particularly when LV systolic function is preserved. Identifying causative mutations is of utmost importance for genetic counselling of at-risk relatives of patients affected by LVNC., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The incremental prognostic value of left atrial (LA) dysfunction, emerging in various clinical contexts, remains poorly explored in hypertrophic cardiomyopathy (HCM)., Objective: To assess LA strain correlation with outcome in HCM., Methods: A cohort of all 307 consecutive patients presenting with HCM between 2007 and 2017 (54±17 years; 34% women), with comprehensive echocardiography at diagnosis and LA peak longitudinal strain (PALS) and LA peak contraction strain (PACS) measurement, was enrolled and occurrence of HCM related cardiac events analysed., Results: Clinically, atrial fibrillation (AF) was present in 13%, New York Heart Association functional class II-III in 54%, and B-type natriuretic peptide (BNP) concentration was 199±278pg/mL. By echocardiography, left ventricular (LV) ejection fraction (EF) was 67±10%, LV thickness 21±5mm and European Society of Cardiology HCM risk score 3±3%, with 109 patients (36%) presenting obstructive HCM (LV outflow gradient 21±32mmHg). LA diameter was 41±8mm [with 109 (36%) presenting LA diameter ≥40mm], LA volume index 50±26mL/m 2 , PALS 24±13%, PACS 11±7% and LA peak systolic strain rate (LASRs) 1.7±0.6 s -1 . In addition to AF, age, BNP, LVEF and LV thickness were all independent determinants of lower PALS, with odd ratios almost unchanged after adjustment (all P ≤0.0004). At a mean follow-up of 21 (range 18-23) months, patients with adverse cardiac events (n=65) presented with more impaired LA function (all P ≤0.0005), with a significant association between impaired PALS and worse outcome, hazard ratio 0.94 [95% confidence interval (CI) 0.92-0.97, P<0.0001]. After comprehensive adjustment, PALS remained strongly associated with worse outcome, adjusted hazard ratio 0.86 (95% CI 0.79-0.94; P=0.0008)., Conclusions: The present study, by gathering a unique HCM cohort, suggests a strong link between LA dysfunction and poor outcome, to be further investigated., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Aims: Whether pulmonary artery (PA) dimension and coronary artery calcium (CAC) score, as assessed by chest computed tomography (CT), are associated with myocardial injury in patients with coronavirus disease 2019 (COVID-19) is not known. The aim of this study was to explore the risk factors for myocardial injury and death and to investigate whether myocardial injury has an independent association with all-cause mortality in patients with COVID-19., Methods and Results: This is a single-centre cohort study including consecutive patients with laboratory-confirmed COVID-19 undergoing chest CT on admission. Myocardial injury was defined as high-sensitivity troponin I >20 ng/L on admission. A total of 332 patients with a median follow-up of 12 days were included. There were 68 (20.5%) deaths; 123 (37%) patients had myocardial injury. PA diameter was higher in patients with myocardial injury compared with patients without myocardial injury [29.0 (25th-75th percentile, 27-32) mm vs. 27.7 (25-30) mm, P < 0.001). PA diameter was independently associated with an increased risk of myocardial injury [adjusted odds ratio 1.10, 95% confidence interval (CI) 1.02-1.19, P = 0.01] and death [adjusted hazard ratio (HR) 1.09, 95% CI 1.02-1.17, P = 0.01]. Compared with patients without myocardial injury, patients with myocardial injury had a lower prevalence of a CAC score of zero (25% vs. 55%, P < 0.001); however, the CAC score did not emerge as a predictor of myocardial injury by multivariable logistic regression. Myocardial injury was independently associated with an increased risk of death by multivariable Cox regression (adjusted HR 2.25, 95% CI 1.27-3.96, P = 0.005). Older age, lower estimated glomerular filtration rate, and lower PaO2/FiO2 ratio on admission were other independent predictors for both myocardial injury and death., Conclusions: An increased PA diameter, as assessed by chest CT, is an independent risk factor for myocardial injury and mortality in patients with COVID-19. Myocardial injury is independently associated with an approximately two-fold increased risk of death., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: Myocardial injury is frequent among patients hospitalized with coronavirus disease-2019 (COVID-19) and is associated with a poor prognosis. However, the mechanisms of myocardial injury remain unclear and prior studies have not reported cardiovascular imaging data., Objectives: This study sought to characterize the echocardiographic abnormalities associated with myocardial injury and their prognostic impact in patients with COVID-19., Methods: We conducted an international, multicenter cohort study including 7 hospitals in New York City and Milan of hospitalized patients with laboratory-confirmed COVID-19 who had undergone transthoracic echocardiographic (TTE) and electrocardiographic evaluation during their index hospitalization. Myocardial injury was defined as any elevation in cardiac troponin at the time of clinical presentation or during the hospitalization., Results: A total of 305 patients were included. Mean age was 63 years and 205 patients (67.2%) were male. Overall, myocardial injury was observed in 190 patients (62.3%). Compared with patients without myocardial injury, those with myocardial injury had more electrocardiographic abnormalities, higher inflammatory biomarkers and an increased prevalence of major echocardiographic abnormalities that included left ventricular wall motion abnormalities, global left ventricular dysfunction, left ventricular diastolic dysfunction grade II or III, right ventricular dysfunction and pericardial effusions. Rates of in-hospital mortality were 5.2%, 18.6%, and 31.7% in patients without myocardial injury, with myocardial injury without TTE abnormalities, and with myocardial injury and TTE abnormalities. Following multivariable adjustment, myocardial injury with TTE abnormalities was associated with higher risk of death but not myocardial injury without TTE abnormalities., Conclusions: Among patients with COVID-19 who underwent TTE, cardiac structural abnormalities were present in nearly two-thirds of patients with myocardial injury. Myocardial injury was associated with increased in-hospital mortality particularly if echocardiographic abnormalities were present., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Diagnosis of left ventricular non-compaction (LVNC) is challenging, and different imaging techniques propose different criteria., Aim: To compare the value of two-dimensional transthoracic echocardiography (2D-TTE) and cardiac magnetic resonance (CMR) criteria in diagnosing LVNC, and to test a new trabecular quantification method obtained by 2D-TTE, exploring its relationship with CMR non-compacted mass quantification., Methods: From a multicentre French study, we selected 48 patients with LVNC and 20 with dilated cardiomyopathy (DCM) who underwent 2D-TTE and CMR. Current 2D-TTE (Jenni et al.) and CMR criteria (Petersen et al., Jacquier et al.), were tested. A new 2D-TTE method of trabecular quantification (percentage of trabecular area) was also proposed, and compared with current criteria., Results: The best cut-off values for the diagnosis of LVNC were a non-compacted/compacted ratio≥2.3 (Petersen et al.), a trabeculated left ventricular mass≥20% (Jacquier et al.) and a non-compacted/compacted ratio≥1.8 (Jenni et al.). Lowering the threshold for the criterion of Jenni et al. from>2 to ≥1.8 improved its sensitivity from 69% to 98%. The 2D-TTE percentage of trabecular area was 25.9±8% in the LVNC group vs. 9.9±4.4% in the DCM group (P<0.05), and was well correlated with CMR non-compacted mass (r=0.65; P<0.05). A 15.8% threshold value for 2D-TTE percentage of trabecular area predicted LVNC diagnosis with a specificity of 95% and a sensitivity of 92%; its sensitivity was better than that for the criteria of Jenni et al. (P<0.01) and Petersen et al. (P=0.03)., Conclusions: Revision of the current threshold for the criterion of Jenni et al. from>2 to ≥1.8 is necessary to improve LVNC diagnosis in patients with left ventricular dysfunction. A new 2D-TTE trabecular quantification method improves TTE diagnosis of LVNC., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Context: Hypophosphatemic rickets (HR) is a rare disease that includes a group of hereditary and sporadic conditions characterized by renal phosphate loss associated with normal to low vitamin D serum concentration. The most common form is the X-linked hypophosphatemic rickets, with an incidence of 1:20,000. Several mutations have recently been identified in the PHEX, FGF23, DMP1 and ENPP1 genes in patients with HR. Moreover, in vitro and in vivo studies suggested an involvement of MEPE for defective mineralization in HR., Objective: The present case series describes the clinical features and the analysis of genes implicated in HR in a cohort of 26 Italian HR patients., Setting and Design: All patients were analyzed for the PHEX and FGF23 genes by direct sequencing. When no mutations were detected, Multiplex Ligation-dependent Probe Amplification (MLPA) analysis was performed. The negative patients were screened for the DMP1, MEPE and ENPP1 genes by direct sequencing., Results: Twenty-two patients (84%) harbored mutations in the PHEX gene. In particular, we detected 19 different mutations, 15 of which were novel. One patient presented a novel splice variation in the ENPP1 gene while no alterations were identified in the FGF23, DMP1 and MEPE genes. The genetic study of the families showed that 11 patients (55%) had de novo mutations. Clinical presentation and disease severity did not show an evident correlation between the mutation types., Conclusions: This report represents the first large familial study performed on Italian patients. It confirms that mutations in PHEX are the most frequent cause of HR. Furthermore, the variety of clinical manifestations identified in our HR patients underlines the extreme clinical and genetic heterogeneity of this disease., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Several cardiovascular diseases are characterized by an impaired O2 kinetic during exercise. The lack of a linear increase of Δoxygen consumption (VO2)/ΔWork Rate (WR) relationship, as assessed by expired gas analysis, is considered an indicator of abnormal cardiovascular efficiency. We aimed at describing the frequency of ΔVO2/ΔWR flattening in a symptomatic population of cardiac patients, characterizing its functional profile, and testing the hypothesis that dynamic pulmonary hypertension and right ventricular contractile reserve play a major role as cardiac determinants., Methods and Results: We studied 136 patients, with different cardiovascular diseases, referred for exertional dyspnoea. Cardiopulmonary exercise test combined with simultaneous exercise echocardiography was performed using a symptom-limited protocol. ΔVO2/ΔWR flattening was observed in 36 patients (group A, 26.5% of population) and was associated with a globally worse functional profile (reduced peak VO2, anaerobic threshold, O2 pulse, impaired VE/VCO2). At univariate analysis, exercise ejection fraction, exercise mitral regurgitation, rest and exercise tricuspid annular plane systolic excursion, exercise systolic pulmonary artery pressure, and exercise cardiac output were all significantly (P<0.05) impaired in group A. The multivariate analysis identified exercise systolic pulmonary artery pressure (odds ratio, 1.06; confidence interval, 1.01-1.11; P=0.01) and exercise tricuspid annular plane systolic excursion (odds ratio, 0.88; confidence interval, 0.80-0.97; P=0.01) as main cardiac determinants of ΔVO2/ΔWR flattening; female sex was strongly associated (odds ratio, 6.10; confidence interval, 2.11-17.7; P<0.01)., Conclusions: In patients symptomatic for dyspnea, the occurrence of ΔVO2/ΔWR flattening reflects a significantly impaired functional phenotype whose main cardiac determinants are the excessive systolic pulmonary artery pressure increase and the reduced peak right ventricular longitudinal systolic function., (© 2014 American Heart Association, Inc.)

Background: There are limited data comparing ultrafiltration with standard medical therapy as first-line treatment in patients with severe congestive heart failure (HF). We compared ultrafiltration and conventional therapy in patients hospitalized for HF and overt fluid overload.Methods and Results: Fifty-six patients with congestive HF were randomized to receive standard medical therapy (control group; n = 29) or ultrafiltration (ultrafiltration group; = 27). The primary endpoint of the study was rehospitalizations for congestive HF during a 1-year follow-up. Despite similar body weight reduction at hospital discharge in the 2 groups (7.5 ± 4.5 and 7.9 ± 5.0 kg, respectively;P = .75), a lower incidence of rehospitalizations for HF was observed in the ultrafiltration-treated patients during the following year (hazard ratio 0.14, 95% confidence interval 0.04-0.48; P = .002).Ultrafiltration-induced benefit was associated with a more stable renal function, unchanged furosemide dose, and lower B-type natriuretic peptide levels. At 1 year, 7 deaths (30%) occurred in the ultrafiltration group and 11 (44%) in the control group (P = .33).Conclusions: In HF patients with severe fluid overload, first-line treatment with ultrafiltration is associated with a prolonged clinical stabilization and a greater freedom from rehospitalization for congestive HF.

There are two types of vitamin D dependent rickets (VDDR) that cause rickets in children. Vitamin D dependent rickets type 1 (VDDR-I) is caused by an inborn error of vitamin D metabolism, which interferes with renal conversion of calcidiol (25OHD) to calcitriol (1,25(OH)2D) by the enzyme 1alpha-hydroxylase. Vitamin D dependent rickets type 2 (VDDR-II) is caused by a defect in the vitamin D receptor (VDR). We report cases of two African children affected by VDDR-I and VDDR-II, respectively. Establishing an early diagnosis of these genetic forms of rickets is challenging, especially in developing countries where nutritional rickets (NR) is the most common variety of the disease. A prompt diagnosis is necessary to initiate adequate treatment, resolve biochemical features and prevent complications, such as severe deformities that may require surgical intervention.