The paradox of pulmonary arterial hypertension in Italy in the COVID-19 era: is risk of disease progression around the corner?

OBJECTIVE: The coronavirus disease 2019 (COVID-19) outbreak has led to significant restrictions on routine medical care. We conducted a multicentre nationwide survey of patients with pulmonary arterial hypertension (PAH) to determine the consequences of governance measures on PAH management and risk of poor outcome in patients with COVID-19. MATERIALS AND METHODS: The present study, which included 25 Italian centres, considered demographic data, the number of in-person visits, 6-min walk and echocardiographic test results, brain natriuretic peptide/N-terminal pro-brain natriuretic peptide test results, World Health Organization functional class assessment, presence of elective and non-elective hospitalisation, need for treatment escalation/initiation, newly diagnosed PAH, incidence of COVID-19 and mortality rates. Data were collected, double-checked and tracked by institutional records between March 1 and May 1, 2020, to coincide with the first peak of COVID-19 and compared with the same time period in 2019. RESULTS: Among 1922 PAH patients, the incidences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 were 1.0% and 0.46%, respectively, with the latter comparable to that in the overall Italian population (0.34%) but associated with 100% mortality. Less systematic activities were converted into more effective remote interfacing between clinicians and PAH patients, resulting in lower rates of hospitalisation (1.2% versus 1.9%) and related death (0.3% versus 0.5%) compared with 2019 (p<0.001). A high level of attention is needed to avoid the potential risk of disease progression related to less aggressive escalation of treatment and the reduction in new PAH diagnoses compared with 2019. CONCLUSION: A cohesive partnership between healthcare providers and regional public health officials is needed to prioritise PAH patients for remote monitoring by dedicated tools.

A multicentric quality-control study of exercise Doppler echocardiography of the right heart and the pulmonary circulation. The RIGHT Heart International NETwork (RIGHT-NET).

PURPOSE: This study was a quality-control study of resting and exercise Doppler echocardiography (EDE) variables measured by 19 echocardiography laboratories with proven experience participating in the RIGHT Heart International NETwork. METHODS: All participating investigators reported the requested variables from ten randomly selected exercise stress tests. Intraclass correlation coefficients (ICC) were calculated to evaluate the inter-observer agreement with the core laboratory. Inter-observer variability of resting and peak exercise tricuspid regurgitation velocity (TRV), right ventricular outflow tract acceleration time (RVOT Act), tricuspid annular plane systolic excursion (TAPSE), tissue Doppler tricuspid lateral annular systolic velocity (S'), right ventricular fractional area change (RV FAC), left ventricular outflow tract velocity time integral (LVOT VTI), mitral inflow pulsed wave Doppler velocity (E), diastolic mitral annular velocity by TDI (e') and left ventricular ejection fraction (LVEF) were measured. RESULTS: The accuracy of 19 investigators for all variables ranged from 99.7 to 100%. ICC was > 0.90 for all observers. Inter-observer variability for resting and exercise variables was for TRV = 3.8 to 2.4%, E = 5.7 to 8.3%, e' = 6 to 6.5%, RVOT Act = 9.7 to 12, LVOT VTI = 7.4 to 9.6%, S' = 2.9 to 2.9% and TAPSE = 5.3 to 8%. Moderate inter-observer variability was found for resting and peak exercise RV FAC (15 to 16%). LVEF revealed lower resting and peak exercise variability of 7.6 and 9%. CONCLUSIONS: When performed in expert centers EDE is a reproducible tool for the assessment of the right heart and the pulmonary circulation.

Role of cardiac imaging in Anderson-Fabry cardiomyopathy.

The Anderson-Fabry disease (AFD, or simply Fabry Disease, FD; MIM #301500) is a rare X-linked lysosomal storage disorder (Xq22.1) characterized by progressive renal failure, leading to morbidity through cardio- and cerebro-vascular involvement. Despite the classic phenotype, only cardiac involvement (cardiac variant of AFD; MIM 301500) is frequent in about 40% of male and 28% of female AFD patients, as reported by the Fabry Registry ( https://www.registrynxt.com ). Morphologically, the cardiac characteristic of the disease, occurs as left ventricular hypertrophy, is accompanied by myocardial fibrosis. Cardiologists may come across these patients during clinical and instrumental evaluation in individuals with non-specific symptoms such as chest pain and arrhythmias, or after instrumental evidence of left ventricular hypertrophy/hypertrophic cardiomyopathy (HCM; MIM 192600). A comprehensive cardiological work-up, including a cardiological visit, a baseline electrocardiogram (ECG) and imaging by both echocardiography (ECHO) and magnetic resonance (MRI) enables identification of the cardiac involvement in patients with a proven diagnosis of AFD. The heart involvement is present in up to 75% of AFD patients irrespective of their sex. Involvement includes ECG and echocardiography features which suggest AFD and not HCM. Cardiac imaging plays an important role in detecting this sub-type of cardiomyopathy, which, since 2001, has benefited from the introduction of the enzyme replacement therapy (ERT) in symptomatic and pre-symptomatic patients.

Pulmonary Circulation on the Crossroads Between the Left and Right Heart in Systemic Sclerosis: A Clinical Challenge for Cardiologists and Rheumatologists.

Involvement of the right heart-pulmonary circulation system in systemic sclerosis is a typical feature, with critical prognostic implications. Pulmonary hypertension may occur in association with interstitial lung disease or as a result of an isolated pulmonary vascular disease that may affect both the precapillary arterioles and the postcapillary venules, as well as a consequence of left heart involvement. These apparently different phenotypes often underlie a significant pathophysiologic overlap, which makes the diagnosis and management of these patients highly complex and uncertain.

The Right Heart International Network (RIGHT-NET): Rationale, Objectives, Methodology, and Clinical Implications.

The Right Heart International Network is a multicenter international study aiming to prospectively collect exercise Doppler echocardiography tests of the right heart pulmonary circulation unit (RHPCU) in large cohorts of healthy subjects, elite athletes, and individuals at risk of or with overt pulmonary hypertension. It is going to provide standardization of exercise stress echocardiography of RHPCU and explore the full physiopathologic response.

Transthoracic Echocardiography and Chest Computed Tomography Arteriography in Patients with Acute Pulmonary Embolism: A Two-Year Follow-Up Study.

BACKGROUND: Pulmonary hypertension (PH) is frequently found at the time of diagnosis of pulmonary embolism (PE). An incomplete resolution of PE can lead to chronic thromboembolic pulmonary hypertension (CTPH). Transthoracic echocardiogram (TTE) is the first step to diagnose an abnormality of the pulmonary vasculature. Based on computed tomography (CT), the Qanadli vascular obstruction index has been extensively used to assess acute PE. OBJECTIVES: Our aim was to ascertain whether at the time of diagnosis of an acute PE episode TTE variables and a Qanadli CT index score may be associated with CTPH 2 years later. METHOD: Patients with PE were prospectively enrolled. TTE was performed and the Qanadli CT obstruction index was calculated on admission to the hospital, while only TTE was repeated at the 2-year follow-up. The NYHA (New York Heart Association) functional classification was evaluated. Correlation analyses were performed. RESULTS: Twenty patients (11 males, median age 69.5 years) were considered for the study. There was no significant correlation between TTE parameters and the Qanadli CT obstruction index. A significant distribution (χ2 = 5.69, p = 0.017) was found in the analysis among patients with CTPH at 24 months and the Qanadli CT index, categorized by a receiver operating characteristic curve cutoff value of 42.5%. Additionally, a significant distribution (χ2 = 4.09, p = 0.043) was found in the analysis among patients with CTPH at 24 months and right ventricular systolic pressure on admission, categorized as PH (>31 mm Hg). CONCLUSION: Our study demonstrates that in patients with acute PE there is no relationship between the Qanadli CT obstruction index and TTE parameters on admission to the hospital. However, the occurrence of CTPH at the 24-month follow-up is associated with PH and with a high Qanadli CT obstruction index score.

SCN5A mutation is associated with a higher Shanghai Score in patients with type 1 Brugada ECG pattern.

AIMS: Brugada syndrome (BrS) is an inherited arrhythmic disease characterized by a coved ST-segment elevation in the right precordial electrocardiogram leads (type 1 ECG pattern) and is associated with a risk of malignant ventricular arrhythmias and sudden cardiac death. In order to assess the predictive value of the Shanghai Score System for the presence of a SCN5A mutation in clinical practice, we studied a cohort of 125 patients with spontaneous or fever/drug-induced BrS type 1 ECG pattern, variably associated with symptoms and a positive family history. METHODS: The Shanghai Score System items were collected for each patient and PR and QRS complex intervals were measured. Patients were genotyped through a next-generation sequencing (NGS) custom panel for the presence of SCN5A mutations and the common SCN5A polymorphism (H558R). RESULTS: The total Shanghai Score was higher in SCN5A+ patients than in SCN5A- patients. The 81% of SCN5A+ patients and the 100% of patients with a SCN5A truncating variant exhibit a spontaneous type 1 ECG pattern. A significant increase in PR (P = 0.006) and QRS (P = 0.02) was detected in the SCN5A+ group. The presence of the common H558R polymorphism did not significantly correlate with any of the items of the Shanghai Score, nor with the total score of the system. CONCLUSION: Data from our study suggest the usefulness of Shanghai Score collection in clinical practice in order to maximize genetic test appropriateness. Our data further highlight SCN5A mutations as a cause of conduction impairment in BrS patients.

Exercise Stress Echocardiography of the Right Ventricle and Pulmonary Circulation.

BACKGROUND: Exercise echocardiography is used for assessment of pulmonary circulation and right ventricular function, but limits of normal and disease-specific changes remain insufficiently established. OBJECTIVES: The objective of this study was to explore the physiological vs pathologic response of the right ventricle and pulmonary circulation to exercise. METHODS: A total of 2,228 subjects were enrolled: 375 healthy controls, 40 athletes, 516 patients with cardiovascular risk factors, 17 with pulmonary arterial hypertension, 872 with connective tissue diseases without overt pulmonary hypertension, 113 with left-sided heart disease, 30 with lung disease, and 265 with chronic exposure to high altitude. All subjects underwent resting and exercise echocardiography on a semirecumbent cycle ergometer. All-cause mortality was recorded at follow-up. RESULTS: The 5th and 95th percentile of the mean pulmonary artery pressure-cardiac output relationships were 0.2 to 3.5 mm Hg.min/L in healthy subjects without cardiovascular risk factors, and were increased in all patient categories and in high altitude residents. The 5th and 95th percentile of the tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio at rest were 0.7 to 2.0 mm/mm Hg at rest and 0.5 to 1.5 mm/mm Hg at peak exercise, and were decreased at rest and exercise in all disease categories and in high-altitude residents. An increased all-cause mortality was predicted by a resting tricuspid annular plane systolic excursion to systolic pulmonary artery pressure <0.7 mm/mm Hg and mean pulmonary artery pressure-cardiac output >5 mm Hg.min/L. CONCLUSIONS: Exercise echocardiography of the pulmonary circulation and the right ventricle discloses prognostically relevant differences between healthy subjects, athletes, high-altitude residents, and patients with various cardio-respiratory conditions. (Right Heart International NETwork During Exercise in Different Clinical Conditions; NCT03041337).

sPAP/PAAT Ratio as a New Index of Pulmonary Vascular Load: A Study in Normal Subjects and Ssc Patients with and without PH.

In pulmonary hypertension (PH), the development of right ventricular (RV) dilatation and RV failure are signs of accelerated progression of the disease, resulting in an increased risk of cardiac death. Even the noninvasive assessment of systolic blood pressure in the pulmonary artery undertaken by echocardiography does not provide a measure of ventricle-pulmonary interaction. Some studies have shown the potential for echocardiography to indirectly evaluate pulmonary vascular resistance (PVR) and the acceleration time of pulmonary outflow (PAAT). We used systolic pulmonary artery pressure (sPAP) and pulmonary vascular resistance to develop an sPAP/PAAT ratio (strength/surface unit)/(time) for this study. From January 2017 to December 2018, 60 healthy subjects and 63 patients with systemic scleroderma (Ssc) (60 females, 3 males), 27 with PH and 36 without PH at two-dimensional echocardiographic/Doppler, were screened. In normal subjects, the mean sPAP/PAAT ratio was 0.26 ± 0.063, which indicated optimal pulmonary arterial ventricle coupling and biventricular function. The data derived from the analysis of the Ssc patients showed that those presenting pre-capillary PH at cardiac catheterization had an sPAP/PAAT ratio of 0.40 ± 0.05. There was a significant correlation between sPAP/PAAT with Walk Distance (WD) and PVR, but not with TAPSE. Interobserver variability was less than 5%. The sPAP/PAAT ratio is a new parameter that may indicate pulmonary vascular afterload and interaction, both in normal subjects and in patients with Ssc and PH.

Severe hypertrophic cardiomyopathy in a patient with a homozygous MYH7 gene variant.

Background: Hypertrophic cardiomyopathy is an autosomal dominant disease. The main feature of this disorder is its occurrence in patients who present a left ventricular hypertrophy, unexplained by the loading conditions, usually asymmetric with greatest involvement most commonly of the interventricular septum.Case presentation During a sports medicine control, a ultrasound scan in a 17 years old patient has shown a concentric left ventricular parietal hypertrophy associated with a 23 mm mid- basal interventricular septum thickness. After genetic counselling, a positive family history for hypertrophic cardiac disease and parents' consanguineity was found. The genetic basis of the hypertrophic cardiomyopathy was investigated through a dedicated gene panel. The genetic test has revealed the presence of the variant c.3424G>A (p.Glu1142Lys) in the MYH7 gene in a homozygous state. Genotyping of the parents and of the two brothers revealed the presence of the MYH7 variant in heterozygosity in both parents and in the younger brother. In all of them, variable signs of hypertrophic cardiomyopathy were found. Conclusions: Our findings report the presence of a homozygous variant in a sarcomeric gene (MYH7) which gave rise to early HCM, whereas the variant in a heterozygous state was associated to much milder cardiac phenotypes in the affected relatives. The onset and the progression of the hypertrophic cardiomyopathy in the reported family is to be referred to the presence of the variant in hetero- or homo-zygosity in a gene dosage manner.

Chronic thromboembolic pulmonary hypertension risk score evaluation and validation (CTEPH SOLUTION): proposal of a study protocol aimed to realize a validated risk score for early diagnosis.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is the most serious long-term complication of acute pulmonary embolism (PE) though it is the only potentially reversible form of pulmonary hypertension (PH). Its incidence is mainly limited to the first 2 years following the embolic event, however it is often underdiagnosed or misdiagnosed. METHODS: This is a multicenter observational cross-sectional and prospective study. Patients with a prior diagnosis of PE will be enrolled and undergo baseline evaluation for prevalent PH detection through a clinical examination and an echocardiogram as first screening exam. All cases of intermediate-high echocardiographic probability of PH will be confirmed by right heart catheterization and then identified as CTEPH through appropriate imaging and functional examinations in order to exclude other causes of PH. A CTEPH Risk Score will be created using retrospective data from this prevalent cohort of patients and will be then validated on an incident cohort of patients with acute PE. RESULTS: One thousand retrospective and 218 prospective patients are expected to be enrolled and the study is expected to be completed by the end of 2021. Up to now 841 patients (620 retrospective and 221 prospective) have been enrolled. CONCLUSIONS: This study is the first large prospective study for the prediction of CTEPH development in patients with PE. It aims to create a comprehensive scoring tool that includes echocardiographic data which may allow early detection of CTEPH and the application of targeted follow-up screening programs in patients with PE.

Chronic thromboembolic pulmonary hypertension: take care to a "favourable" apparently evolution. A case report.

Chronic thromboembolic pulmonary hypertension (CTEPH) caused by intraluminal thrombus organization and fibrous stenosis or complete obliteration of pulmonary arteries, is a not rare but life-threatening complication of acute pulmonary embolism. The prognosis of medically treated patients with CTEPH is poor and worsens as pulmonary hypertension exacerbates. We describe the case of a 43-years old with a history of progressive shortness of breath, hemoptysis, chest discomfort and syncope. Echocardiographic and imaging studies showed changes consistent with chronic thromboembolic pulmonary hypertension. Further work-up showed only moderate increase of homocysteine level with negative features for lupus and others primary thrombophilic disease. The patient was managed adequately with thrombolytic and inotropic therapy; oral anticoagulation was started with improvement of his clinical status and was screened for pulmonary thrombo endarterectomy, but he refused. The case presented despite its evolution 'temporarily' positive perhaps related to the reduction of hemodynamic overload through bronchial arteries, reiterates the importance of early surgical intervention, before it establishes the hypertensive vasculopathy. Abnormal pulmonary function at rest and after exercise stress test associated to non invasive echocardiographic measurements are an excellent tool to identify the bad prognosis patients in CTEPH. We discuss the pathophysiology and conclude that in selected cases, pulmonary thromboendarterectomy is the best therapy, but only if executed early.

Improved efficiency and cost reduction in the emergency department by replacing contemporary sensitive with high-sensitivity cardiac troponin immunoassay.

The Authors planned this study to evaluate the impact of replacing a contemporary-sensitive with HS cTnI immunoassay on hospital and laboratory workload. The authors say that, 'Despite some evidence, the clinicians are still hesitant to replace the former so-called contemporary-sensitive methods with HS-cTn techniques, justifying this reluctance with concerns of overutilization, possible over diagnosis of cardiac injuries, overcrowding of emer-gency departments (EDs), and excess of cardiac invasive testing. Several factors have lead clinicians to use terms such as "troponin leak", "false-positive" troponin elevation, or "troponinemia". The results of this study show substantial organizational and economic benefits by replacing con-temporary-sensitive with HS cTnI immunoassays. This is very important question because there are some areas such as acute non-ST elevation coro-nary syndromes (NSTEMI) and in elderly patients, the specificity is very low for the simultaneous presence of factors that can alter the dosage of HS-cTnI values.

Echocardiography may help detect pulmonary vasculopathy in the early stages of pulmonary artery hypertension associated with systemic sclerosis.

BACKGROUND: Pulmonary arterial hypertension (PAH) in patients with systemic sclerosis is associated with a poor prognosis, but this can be improved by early disease detection. Abnormal pulmonary and cardiac function can be detected early by means of echocardiography, whereas right heart catheterization is usually performed later. OBJECTIVES: The purpose of this prospective study was to detect early the presence of pulmonary artery vasculopathy in patients with verified systemic sclerosis without significant pulmonary fibrosis, normal lung volumes and a mildly reduced lung diffusion capacity of carbon monoxide (DLCO). METHODS: Nineteen consecutive female NYHA class I-II patients with scleroderma and a PAPs of < 35 mm/Hg measured by echocardiography, were enrolled between September 2007 and September 2009. They had a mean age of 51 +/- 13 years, body mass index of 25 +/- 5 kg/m2). They all underwent complete Doppler echocardiography, CPET, a pulmonary ventilation test (carbon monoxide lung diffusion, DLCO), HRCT. To investigate PAH by means of complete resting Doppler echocardiography estimates of systolic pulmonary artery pressure (PAPs) derived from tr icuspid regurgitation, mean PAP derived from pulmonary regurgitation, pulmonary vessel resistance (PVR) derived from the acceleration time of the pulmonary outflow tract (ACTpo), and right ventricular function derived from tricuspid annular plane systolic excursion (TAPSE). Right heart catheterisation was conducted only, if pulmonary hypertension was suggested by echocardiography and an abnormal ventilator test.The data are given as mean values +/- SD, unless otherwise stated. The correlations between the variables were analysed using Pearson's r coefficient, and the predictive value of the variables was calculated using linear regression analysis. A p value of > 0.05 was considered significant. RESULTS: Right heart catheterization detected PAH in 15/19 patients; mean PAP was 30.5 mm/Hg and RVP 3.6 UW. Coronary angiography of the patients aged more than 55 years showed some evidence of significant coronary artery disease. Echocardiography showed high systolic PAP values (46 +/- 8 mmHg), whereas right ventricular function was normal (TAPSE 23 +/- 3 mm), and in line with the NYHA class. ACTpo was reduced in the patients with a systolic PAP of < 46 mm/Hg (p > 0.001) and positively correlated with DLCO (p > 0.001) and the hemodynamic data.There was a good correlation between ACTpo and PVR (hemodynamic data) (r = -0615; p > 0.01). CONCLUSIONS: Although they need to be confirmed by studies of larger series of patients, our findings suggest that, in comparison with hemodynamic data, non-invasive echocardiographic measurements are an excellent means of identifying early-stage PAH.

Second-opinion stress tele-echocardiography for the Adonhers (Aged donor heart rescue by stress echo) project.

BACKGROUND: To resolve the current shortage of donor hearts, we established the Adonhers protocol. An upward shift of the donor age cut-off limit (from the present 55 to 65 years) is acceptable if a stress echo screening on the candidate donor heart is normal. This study aimed to verify feasibility of a "second opinion" of digitally transferred images of stress echo results to minimize technical variability in selection of aged donor hearts for heart transplant. METHODS: The informatics infrastructure was created for a core lab reading with a second opinion from the Pisa stress echo lab. To test the system, simulation standard stress echo cineloops were sent digitally from 5 peripheral labs to the central core lab.Starting January 2009, real marginal donor stress echos were sent via internet to the central core echo lab, Pisa, for a second opinion before heart transplant. RESULTS: In the simulation protocol, 30 dipyridamole stress echocardiograms were sent from the five peripheral echo labs to the central core lab in Pisa. Both the echo images and reports were correctly uploaded in the web system and sent to the core echo lab; the second opinion evaluation was obtained in all cases (100% feasibility). In the transplant protocol, eight donor cases were sent to the Pisa core lab for the second opinion protocol, and six of them were transplanted in marginal recipients. CONCLUSIONS: Second-Opinion Stress Tele-Echocardiography can effectively be performed in a network aimed to safely expand the heart donor pool for heart transplant.

Severe acute respiratory failure due to a multifactorial diffuse alveolar haemorrhage.

Diffuse alveolar haemorrhage (DAH) is a life-threatening syndrome caused by infection, coagulation disorders or autoimmune diseases. We here report the case of an 81-year-old male subject affected by a multifactorial DAH, in which the bleeding was related to the administration of clopidogrel and warfarin, both implicated in the context of a polycythaemia. He developed a severe acute respiratory failure treated with a ventilatory support by means of a continuous positive airway pressure (C-PAP) therapy. An improvement of patient's clinical conditions was observed only after clopidogrel and warfarin discontinuation.

Left ventricular free-wall rupture, a potentially lethal mechanical complication of coronaric angioplasty : an unusual case report.

The incidence of complications of coronary perforation varied significantly among studies probably due to population heterogeneity and interventional techniques applied in each centre. Free wall rupture, cardiac tamponade and miocardial infarction are the most  feared. The treatment of perforation remains a challenge of every cath- lab team. The management strategies range from observation to urgent operation depending on patient's hemodynamic status, severity and location of the perforation, coronary anatomy, interventional practice and equipment in each centre and operators' skills on-site. In this case an extracorporeal circulation and cardioplegic arrest with anterograde hot blood cardioplegia was done. A composite Dacron with autologous pericardium patch was used for left ventricular free wall rupture repair and the geometry of the left ventricle was restored. Subsequently aorta was declamped; the patient was weaned from CEC and a good spontaneous hemodynamic was recovered.

Cardiac imaging in congenital heart disease during the coronavirus disease-2019 pandemic: recommendations from the Working Group on Congenital Heart Disease of the Italian Society of Cardiology.

: The recent outbreak of 2019 severe acute respiratory syndrome coronavirus-2 is having major repercussions on healthcare services provision in Italy and worldwide. Data suggest the virus has a strong impact on the cardiovascular system, and cardiac imaging will play an important role in patients affected by coronavirus disease-2019. Although paediatric patients are mildly affected, they represent a clear accelerator in spreading the virus, and healthcare workers are at higher risk of infection. The aim of this position paper is to provide clinical recommendation regarding the execution of imaging investigations for the cardiac diagnostic work-up of paediatric patients with suspected or confirmed infection.

Role of Transesophageal 3D Echocardiography in Adult Cor Triatriatum Diagnosis.

Cor triatriatum is a very rare congenital abnormality, symptomatic during childhood;the non restrictive form is usually diagnosed as an incidental finding. We report the case of a 88 years old man referred to our hospital for elective endovascular repair of an aortic aneurysm; transthoracic cardiac bidimensional echocardiography showed an abnormal mass into the left atrium and a the diagnosis of cor triatriatum was fully made by a three dimensional transesophageal echocardiography. 3D echocardiography is an excellent noninvasive method that provides a rapid bedside diagnosis , without having to use ionizing radiation.

Pulmonary embolism and patent foramen ovale thrombosis: the key role of TEE.

This is a case report of a 35 young man with Klinefelter Syndrome presented breathlessness, palpitations and chest pain. It shows a rare case of a thrombus located through the PFO, in patient with pulmonary and paradoxical embolism, which takes back to exciting hypothesis on thrombus growth. A thrombus, which has grown 'in situ' or trapped through the patent foramen ovale, may be a cause of relapsing pulmonary or systemic embolism during anticoagulation therapy. To prevent recurrent paradoxical embolism, percutaneous closure of PFO is recommended, but in this case, thrombus was trapped through the PFO and the patient was referred to the surgeon. We believe that under these circumstances the clinician should be informed of the presence of PFO in critical pulmonary embolism; this case points out the key role of TEE to face a diagnostic and therapeutic scenarios.