Sickle cell disease related chronic thromboembolic pulmonary hypertension: challenging clinical scenario.

Sickle cell disease (SCD), a haemoglobinopathy characterized by chronic haemolysis with acute exacerbations and vascular occlusion episodes, may be complicated by pulmonary hypertension. The latter may be caused by chronic thromboembolic disease of pulmonary artery branches and its management is not well-defined. Herein, we present a case of SCD complicated by chronic thromboembolic pulmonary hypertension of subsegmental pulmonary artery branches successfully treated with endothelin receptor antagonists, orally administered prostacyclin analogs and balloon pulmonary angioplasty. This challenging case highlights the need for clinical awareness of chronic thromboembolic pulmonary hypertension as a specific and potentially curable form of pulmonary hypertension complicating SCD course that may necessitate combined pharmacologic and interventional management.

Phenotypic Heterogeneity within Members of a Family Carrying the Same RBM20 Mutation R634W.

OBJECTIVE: We present the genotypic and phenotypic characterization of a family displaying dilated cardiomyopathy (DCM). METHODS: The proband and his relatives underwent full cardiological assessment. Genetic analysis of the proband was performed with the use of next-generation sequencing technology. RESULTS: In this study, we present 6 members of a family carrying the RBM20 mutation NM_001134363.2:c.1900C>T. The proband was initially diagnosed with DCM at the age of 18 years and received an implantable cardioverter defibrillator (ICD) due to ventricular arrhythmias. His brother, carrier of the mutation, has been diagnosed with borderline left ventricular function. The mutation was shown to be of paternal origin, but their father remains asymptomatic with a mild DCM, while his electrocardiogram at the initial evaluation showed a right bundle branch block pattern. The mutation was also detected in the index case's aunt who was resuscitated from sudden cardiac death. Her echocardiography revealed early stages of DCM and a bicuspid aortic valve. Her children are both carriers of the mutation. Her daughter is unaffected, but her son has an ICD implanted due to sustained ventricular tachycardia and presents early signs of DCM. CONCLUSION: Our findings are the first report of co-segregation of the mutation in 6 family members, supporting its pathogenic role.

The pathophysiological relationship and clinical significance of left atrial function and left ventricular diastolic dysfunction in ß-thalassemia major.

Iron deposition in combination with inflammatory and immunogenetic factors is involved in the pathophysiology of cardiac dysfunction in ß-thalassemia major. We investigated the mechanical and endocrine function of the left atrium and ventricle to identify early signs of dysfunction. We studied 90 patients (mean age: 29 ± 11 years) with ß-thalassemia and normal left ventricular function and 90 age and sex-matched healthy controls. Patients and controls underwent a thorough cardiac echocardiographic study and measurements of the b-type (NT-proBNP) and atrial natriuretic peptides (proANP). Patients underwent 24-hr Holter recordings for arrhythmia monitoring. In the patient group, atria were affected early during the course of the disease, prior to diastolic and systolic left ventricular dysfunction. The E/E'ratio (E Doppler mitral fast inflow to the corresponding tissue Doppler E) continually increased with age (P < 0.05) and reached levels indicating left ventricular diastolic dysfunction (E/E' > 15) in the third decade whereas indexes of active and passive atrial function decreased gradually throughout life. In controls, the E/E' ratio continually increased with age but with later (fifth decade) appearance of diastolic dysfunction and a compensatory increase in atrial active function. Both natriuretic peptides were significantly increased in patients compared to controls (558 ± 141 and 2,580 ± 1,830 fmol/mL for NT-proBNP and proANP versus 332 ± 106 and 1,331 ± 1,134 fmol/mL, respectively). Atrial fibrillation was found in a subgroup of 23 (26%) patients, older in age with mild diastolic function and enlarged, depressed atria. In conclusion, atrial mechanical depression seems to be a very early sign of cardiac damage. It may become echocardiographically evident even before diastolic and systolic dysfunction and is associated to supraventricular arrhythmias.

Haemolytic Anaemia-Related Pulmonary Hypertension.

Haemolytic anaemia represents a risk factor for the development of pulmonary hypertension (PH), currently classified as World Health Organization group 5 PH, and data regarding appropriate therapeutic strategy are limited. A total of 28 patients, 85.7% with thalassaemia and 14.3% with sickle cell disease, with a diagnosis of PH confirmed by right heart catheterization were included in the study. The patients were divided into three groups according to the PH haemodynamic definition and overall diagnostic approach: 42.9% had precapillary PH (pulmonary arterial hypertension-PAH group), 25% had post-capillary PH, and 32.1% had chronic thromboembolic PH (CTEPH) (29% of b-thalassemia and 50% of SCD patients). The therapeutic approach in each group and its impact on the outcome and haemodynamics were recorded. PAH-specific drug therapy received 82.1% of patients, and balloon pulmonary angioplasty (BPA) was performed in six patients with CTEPH. There were statistically significant differences in baseline mPAP and PVR values between the CTEPH-haemolytic anaemia group and other groups. PAH-specific drug therapy resulted in haemodynamic improvement for the PAH group. Patients who underwent BPA had improved pulmonary haemodynamics. The median survival time was 162 months, and the survival rate was 1 year-100%; 2, 3, 4, 5, and 6 years-96%; 9 years-90%; and 13 years-78%. In patients with haemolytic anaemia, the wide spectrum of induced PH highlighted the importance of a correct predominant diagnosis. BPA in CTEPH patients and specific-PAH drug therapy for PAH patients represent potential therapeutic strategies; however, the management should be offered in expert PH centres under individualized approaches for patients.

Practical guidance and clinical applications of transoesophageal echocardiography. A position paper of the working group of echocardiography of the Hellenic Society of Cardiology.

Transoesophageal echocardiography (TOE) is a well-established imaging modality, providing more accurate and of higher quality information than transthoracic echocardiography (TTE) for a wide spectrum cardiac and extra-cardiac diseases. The present paper represents an effort by the Echocardiography Working Group (WG) of the Hellenic Cardiology Society to state the essential steps of the typical TOE exam performed in echo lab. This is an educational text, describing the minimal requirements and the preparation of a meticulous TOE examination. Most importantly, it gives practical instructions to obtain and optimize TOE views and analyses the implementation of a combined two-and multi-dimensional protocol for the imaging of the most common cardiac structures during a TOE. In the second part of the article a comprehensive review of the contemporary use of TOE in a wide spectrum of valvular and non-valvular cardiac diseases is provided, based on the current guidelines and the experience of the WG members.

Transoesophageal echocardiography beyond the echo-laboratory. An expert consensus paper of the working group of echocardiography of the hellenic society of cardiology.

Transoesophageal echocardiography (TOE) is a well-established and valid imaging modality, providing more accurate and of higher quality information than transthoracic echocardiography (TTE) for several specific diagnoses and recently a useful guide of an increasing number of catheter-based and surgical interventions. The present paper represents an effort by the Echocardiography Working Group (WG) of the Hellenic Society of Cardiology to state the essential steps of the TOE exam performed beyond the echo lab: a) in the operating rooms intraoperatively during either transcatheter interventions, or cardiothoracic surgery and b) in the intensive care unit for critically ill patients' monitoring. This paper includes information and tips and tricks about the pre-procedural evaluation, the procedural echocardiographic guidance, and post-procedural evaluation of the result and potential complications.

Acute and chronic effects of smoking on myocardial function in healthy heavy smokers: a study of Doppler flow, Doppler tissue velocity, and two-dimensional speckle tracking echocardiography.

BACKGROUND: The purpose of the study was to evaluate the acute and chronic effect of smoking on left ventricular function in healthy heavy smokers by conventional Doppler flow, tissue Doppler, and two-dimensional speckle tracking echocardiography (2D-STE). METHODS: Echocardiograms were performed in 42 healthy heavy (>20 cigarettes/day) smokers (age 34 ± 5 years), before (group SM-1), 15 minutes (SM-2) and 30 minutes (SM-3) after starting smoking 2 cigarettes. Nonsmokers (n = 41, age 33 ± 4 years) served as controls. Transmitral flow, isovolumetric relaxation time (IVRT), and myocardial performance index (MPI) were measured. Tissue velocity measurements were averaged from lateral and septal mitral annulus. Longitudinal strain (GS), systolic (SRs), early diastolic (SRe), late diastolic (SRa), and isovolumetric relaxation (SRivr) strain rate were measured. The percent change in strain from end-systole to the first one-third of diastole (SI-DI = [(GS - strain at one-third diastole)/GS] × 100) was also measured. RESULTS: IVRT and MPI were increased and early diastolic mitral annular velocity was decreased in SM-2; they returned to baseline in SM-3. There was no difference in GS and SRs. SRe and SRivr were reduced in SM-1 (P < 0.05), and remained significantly reduced in SM-2 and SM-3. SI-DI was lower in SM-1 (P = 0.011) and was further reduced in SM-2 and SM-3 (P < 0.001). CONCLUSION: Acute and chronic smoking inhalation has adverse effects on myocardial function in healthy heavy smokers. 2D-STE is able to detect both baseline differences and late acute effects of smoking.

Should We Change the Target of Therapy in Pulmonary Hypertension?

Despite the evolution of drug therapy in pulmonary arterial hypertension and the more aggressive treatment approach according to the guidelines, patients continue to have unacceptable mortality rates. Furthermore, specific drug therapy alone in chronic thromboembolic pulmonary hypertension also does not seem to have any beneficial impact on survival. As the function of the right ventricle (RV) determines the prognosis of patients with pulmonary hypertension, the treatment strategy should focus on modifying factors involved in RV dysfunction. Although some previous reports demonstrated that the survival of patients with pulmonary hypertension was associated with mPAP, nevertheless, mPAP is still not considered as a target of therapy. There are many examples of effective mPAP lowering with early and aggressive drug therapy in pulmonary arterial hypertension, or with interventions in chronic thromboembolic pulmonary hypertension. This effective mPAP reduction can lead to reverse RV remodeling, and thus, improvement in survival. In this article, the importance of mPAP lowering is stated, as well as why the change of our current strategy and considering mPAP reduction as the target of therapy could make pulmonary hypertension a chronic but not fatal disease.

Caseous calcification of the mitral annulus presenting as recurrent strokes.

Although caseous calcification of the mitral annulus is usually diagnosed incidentally, it can cause embolic complications. The current report describes the case of caseous calcification revealed by recurrent episodes of stroke in a 64-year-old female patient. After her last ischemic episode, cerebral magnetic resonance imaging confirmed the presence of a thrombus in the right middle cerebral artery. Transthoracic echocardiogram revealed calcification of the mitral annulus and an echo-dense mass with mobile borders fixed posteriorly. Transesophageal echocardiogram allowed better evaluation of the lesion. A medical approach was preferred, with no recurrence thereafter. Learning objective: Caseous calcification of the mitral annulus is a rare form of mitral annular calcification which is associated with high risk of strokes.Medical management with optimal anticoagulation can be effective over long-term follow up.

Balloon Pulmonary Angioplasty in Patients with Chronic Thromboembolic Pulmonary Hypertension in Greece: Data from the Hellenic Pulmonary Hypertension Registry.

Balloon pulmonary angioplasty (BPA) is a novel and promising treatment option for patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are ineligible for pulmonary endarterectomy (PEA) and for those with persistent or recurrent pulmonary hypertension after PEA. We present the results of BPA procedures in CTEPH patients included in the Greek Pulmonary Hypertension Registry, evaluating the real-life efficacy and safety. We analyzed data from 180 BPA procedures (2−17/patient, mean 8 ± 4/patient, 1248 dilated vessels, 0−18/session). Significant improvements were observed in mean pulmonary arterial pressure (a reduction by 44%, p < 0.001), pulmonary vascular resistance (reduction by 60%, p < 0.001), and NT-proBNP (decrease by >70%, p: 0.003), while cardiac index improved modestly (9% increase, p = 0.143). We had 37 BPA-related non-fatal complications (20.6% in all interventions), predominantly including hemoptysis. Overall survival was 91%, 75% and 62% at 3, 4 and 5 years, respectively. Therefore, BPA may be a promising therapeutic option in patients with CTEPH in Greece.

The impact of cardiovascular comorbidities associated with risk for left heart disease on idiopathic pulmonary arterial hypertension: Data from the Hellenic Pulmonary Hypertension Registry (HOPE).

Whereas younger female patients were diagnosed with idiopathic pulmonary arterial hypertension (IPAH) in 1980s, it is now frequently encountered in elderly patients with cardiovascular comorbidities (CVCs) associated with increased risk for left heart disease. We present data until November 2019 regarding specific features and clinical outcomes of IPAH population from the Hellenic Pulmonary Hypertension Registry (HOPE). Patients were divided into two groups based on the presence of ≥ or <3 CVCs, arterial hypertension, diabetes mellitus, obesity, presence of coronary artery disease, or atrial fibrillation. Overall, 77 patients with IPAH (55.1 [interquartile range, IQR: 24.1] years, 62.8% women) have been recorded. Fifteen patients (19.2%) had ≥3 CVCs, while 25 (32%) were over 65 years old. Patients with ≥3 CVCs were older, presented an almost equal female to male ratio, walked less in 6-min walk test, and had lower mean arterial pulmonary pressure and pulmonary vascular resistance at baseline than patients with less CVCs. Fewer patients with ≥3 CVCs received PAH-specific treatment compared to patients with less comorbidities (n = 11 [73.3%] versus n = 58 [95.5%], p = 0.02). During a median follow-up period of 3.8 (IQR: 2.7) years, 18 patients died (all-cause mortality 24.3%). Male sex and older age were independent predictors of mortality and/or lung transplantation, while CVCs did not have a significant impact on clinical outcomes. In this nationwide, register-based study, the epidemiology of IPAH involves older patients with CVCs, who seem to have less hemodynamic compromise, but worse functional impairment and are treated less aggressively with PAH pharmacotherapy.

Updated knowledge and practical implementations of stress echocardiography in ischemic and non-ischemic cardiac diseases: An expert consensus of the Working Group of Echocardiography of the Hellenic Society of Cardiology.

Stress echocardiography (SE) is a well established and valid technique, widely used for the diagnostic evaluation of patients with ischemic and nonischemic cardiac diseases. This statement of the Echocardiography Working Group of the Hellenic Society of Cardiology summarizes the consensus of the writing group regarding the applications of SE, based on the expertise of their members and on a critical review of present medical literature. The main objectives of the consensus document include a comprehensive review of SE methodology and training-which focus on the preparation, the protocols used, the analysis of the SE images, and updated, evidence-based knowledge about SE applications on ischemic and nonischemic heart diseases, such as in cardiomyopathies, heart failure, and valvular heart disease.

Long term effects of cardiac resynchronization therapy in non-ambulatory NYHA IV heart failure patients.

BACKGROUND: We aimed at evaluating the long-term effects of cardiac resynchronization therapy (CRT) in nonambulatory New York Heart Association (NYHA) IV heart failure patients (NAIVHFP). METHODS: Eighteen patients, 15 men and three women, eight with ischemic and 10 with nonischemic cardiomyopathy, who underwent biventricular pacemaker implantation while they were in nonambulatory NYHA IV class, were studied. Patients' age was 58 ± 9 years and left ventricular ejection fraction (LVEF) 18 ± 3%. Follow-up data were obtained through review of follow-up visits notes, stored echocardiographic studies, device interrogation data, and death certificates. RESULTS: After a mean duration of 1223 ± 846 days, 11 patients were alive, including five patients who underwent heart transplantation (OCT) and seven dead. Three of 11 patients who received a CRT-defibrillator, experienced at least one appropriate discharge, but eventually they either died or received an OCT during follow-up. Sustained improvements in NYHA class (Z = 2.4, P = 0.015) and 6-minute walk distance (0 vs 212 ± 95 m, P 0.001) were documented after a median duration of 855 days postimplantation. Cumulative proportion of death or OCT at 18 months-when full follow-up data were available-was 18%, which compared favorably with historical controls. Full echocardiographic and clinical follow-up data at 12-months postimplantation were available for 10 patients, documenting a significant reduction in end-systolic volume (248 ± 82 vs 269 ± 97 mL, P = 0.039). CONCLUSIONS: CRT can be safely applied in this subset of extreme severity heart failure patients, achieving encouraging survival rates and reverse remodeling effects. These observations can form an evidence-based rationale for including NAIVHFP in randomized CRT trials.

The wide spectrum of ß-thalassaemia intermedia-induced pulmonary hypertension: two case reports on the possible role of specific pulmonary arterial hypertension therapy.

Pulmonary hypertension (PH) development remains a significant cardiovascular complication of haemoglobinopathies, severely affecting the morbidity and mortality of such patients. According to the 5th World Symposium on PH, PH related with chronic haemolytic anaemias is classified in group 5, mainly due to the multifactorial pathophysiology of PH in this patient population. There are no clear guidelines regarding the management of PH in patients with haemoglobinopathies; the use of specific pulmonary arterial hypertension (PAH) therapy in patients with ß-thalassaemia and PH is based on data derived from other forms of PH, expert opinion and small series or case reports. The existing knowledge on the use of specific-PAH therapy in ß-thalassaemia patients with PH is limited, and in most cases the diagnosis of PH is based on echocardiographic findings only. We herein report two patients with ß-thalassaemia intermedia (TI) and PH, who got same initial approach but different outcome, to highlight the wide spectrum of TI-induced PH, the importance of optimal disease-directed therapy and the possible role of specific-PAH therapy. We also emphasize the central role of right heart catheterization in the diagnosis and follow-up of PH, since this information does facilitate the suitable use or withdrawal of specific PAH drugs in these patients.

Echocardiography in Pulmonary Arterial Hypertension: Is It Time to Reconsider Its Prognostic Utility?

Pulmonary arterial hypertension (PAH) is characterized by an insult in the pulmonary vasculature, with subsequent right ventricular (RV) adaptation to the increased afterload that ultimately leads to RV failure. The awareness of the importance of RV function in PAH has increased considerably because right heart failure is the predominant cause of death in PAH patients. Given its wide availability and reduced cost, echocardiography is of paramount importance in the evaluation of the right heart in PAH. Several echocardiographic parameters have been shown to have prognostic implications in PAH; however, the role of echocardiography in the risk assessment of the PAH patient is limited under the current guidelines. This review discusses the echocardiographic evaluation of the RV in PAH and during therapy, and its prognostic implications, as well as the potential significant role of repeated echocardiographic assessment in the follow-up of patients with PAH.

Epidemiology and Management of Chronic Thromboembolic Pulmonary Hypertension in Greece. Real-World Data from the Hellenic Pulmonary Hypertension Registry (HOPE).

Chronic Thromboembolic Pulmonary Hypertension (CTEPH) is a rare disease with poor prognosis if left untreated, characterized by pulmonary vascular bed obstruction due to unresolving thromboembolic material. The Hellenic pulmonary hypertension registry (HOPE) was launched in Greece in early 2015 and enrolls patients from all pulmonary hypertension subgroups in Greece. In total, 98 patients with CTEPH were enrolled from January 2015 until November 2019. Of these patients, 55.1% represented incident population, 50% were classified in the World Health Organization functional class II and 49% had a history of acute pulmonary embolism. The median values of pulmonary vascular resistance (PVR) and cardiac index were 7.4 (4.8) WU and 2.4 (1.0) L/min/m2, respectively, the mean diffusing capacity for carbon monoxide was 74.8 ± 20.6%, the median 6-minute walk distance was 347 (220) meters and the median value of N Terminal-pro brain natriuretic peptide was 506.0 (1450.0) pg/mL. In total, 60.2% of the patients were under pulmonary arterial hypertension-targeted therapy at the time of enrolment; specifically, riociguat was received by 35.7% of the patients and combination therapy was the preferred strategy for 16% of the patients. In total, 74 patients were evaluated for pulmonary endarterectomy (PEA), 34 (45.9%) were assessed as operable but only 23 of those (31.1%) finally underwent PEA. The remaining 40 patients were ineligible for PEA according to the operability assessment and 13 (17.6%) of them underwent balloon pulmonary angioplasty. The age of the non-operable patients was significantly higher than the operable patients (p < 0.001), while there was no significant difference with regard to the history of coagulopathies between the operable and non-operable patients (p = 0.33).

Predictive value of B-type natriuretic peptides in detecting latent left ventricular diastolic dysfunction in beta-thalassemia major.

BACKGROUND: Beta-thalassemia major is a unique disease characterized by early diastolic dysfunction, related exclusively to iron myocardial deposition. N-terminal-proBNP(amino-terminal) (NT-proBNP) and B-type natriuretic peptide (BNP) are sensitive biomarkers for the detection of asymptomatic left ventricular (LV) dysfunction, and they have important diagnostic and prognostic implications. Using beta-thalassemia as a model disease with isolated diastolic dysfunction, we sought to investigate the predictive value of NT-proBNP and BNP levels in comparison with the conventional and new Doppler echocardiography indexes in detecting this disorder. METHODS: Seventy beta-thalassemia major patients (mean age 27.2 +/- 12.5 years) with normal LV systolic function (mean LV ejection fraction = 59% +/- 6.8%), and 50 healthy age-matched adults (control group: mean age 25.5 +/- 10.1 years, mean LV ejection fraction = 60% +/- 4.5%) were included. All subjects were studied thoroughly by tissue Doppler echocardiography and blood samples were taken for plasma NT-proBNP and BNP measurements at the same time. To examine LV diastolic function, patients were divided in 3 groups according to the E mitral/E mitral annulus ratio (E/E'): group A, patients without diastolic dysfunction: E/E' ratio <8; group B, patients with suspected diastolic dysfunction: E/E' ratio 8 to 15; group C, patients with documented diastolic dysfunction: E/E' ratio, >15. RESULTS: NT-proBNP and BNP levels were higher in thalassemic patients compared with the control group (NT-proBNP levels: 80 +/- 19 vs 21 +/- 4 pg/mL, P < .001; BNP levels: 34 +/- 6 vs 9 +/- 3 pg/mL, P < .001). NT-proBNP levels showed a statistically significant increase in group C in comparison to groups A and B, which was also detected between groups A and B (A vs B: P < .05). BNP levels were also significantly increased in group C in comparison to the other 2 groups, but there was no statistically significant difference between groups A and B. Using receiver operating characteristic analysis, NT-proBNP at a cut point of 49.2 pg/mL was highly accurate (area under curve: 0.97, P < .001) in ruling out diastolic dysfunction (E/E' <8) with a sensitivity of 93.7% and a specificity of 89.6%. CONCLUSIONS: BNP and NT-proBNP levels are significantly increased in documented left ventricular diastolic dysfunction, while NT-proBNP seems to have better predictive value in detecting latent left ventricular diastolic dysfunction in beta-thalassemia major.

Effect of combined chelation therapy with deferiprone and deferoxamine on left ventricular diastolic function in adult beta-thalassemia major patients.

Beta-thalassemia major (beta-TM), patients, asymptomatic and with preserved left ventricular ejection fraction (LVEF) were studied echocardiographically. Group A (26 patients), on deferiprone (L1) and deferoxamine (DFO) combination therapy (L1: 80 +/- 27 mg/kg/day, DFO: 160 +/- 87 mg/kg/week) and group B (35 patients) on DFO monotherapy (240 +/- 40 mg/kg/week) for the last 2 years were compared. Another group, C (14 patients), switched to L1 (74 +/- 15 mg/kg/day) plus DFO (158 +/- 48 mg/kg/week) for 20-30 months, was prospectively studied for 2 years. In group A, MRI T2* values were increased and improved in group C during follow-up. The LVEF was better in group A than in group B, while such an improvement was also detected in the group C follow-up study. The Tissue Doppler study E' velocity and E/E' ratio was not different. Similarly, in the group C follow-up no significant change in E/E' ratio was detected. It seems that although LVEF significantly improves with combined therapy, diastolic function indexes do not show a similar change.

Pulmonary arterial hypertension associated with interferon-beta treatment for multiple sclerosis. Case report and literature review.

Drug-Induced Pulmonary Arterial Hypertension (PAH) represents a well-known entity, predominantly related to anorexigens. Interferon-ß (IFN) is considered to be a drug with a possible risk of inducing PAH. We report a patient with Multiple Sclerosis treated with IFN-ß who diagnosed with PAH and her course of disease under specific PAH drug therapy. A review of the literature in IFN-ß-induced PAH is provided.

A new phenotype of severe dilated cardiomyopathy associated with a mutation in the LAMP2 gene previously known to cause hypertrophic cardiomyopathy in the context of Danon disease.

Danon disease is a rare X-linked cardiac and skeletal muscle disorder with multisystem clinical manifestations. Genetic defects at the lysosome-associated membrane 2 protein (LAMP2) are the cause of the disorder. Due to the rarity of the disease, there is limited progress in understanding the correlation between genotype and phenotype, and explaining the large variability of the clinical features of the disease. In this study, we report two patients, twin sisters, referred to our hospital for end stage heart failure due to dilated cardiomyopathy, requiring heart transplant evaluation. Genetic analysis, using targeted next generation sequencing, showed that the proband carried a LAMP2 missense variant, c.928G > A. The mutation was also detected in her twin sister by sanger sequencing. This variant has already been reported by other investigators and was correlated with the clinical triad of Danon disease i.e. hypertrophic cardiomyopathy, mental retardation and peripheral myopathy. The new phenotype of dilated cardiomyopathy associated with this mutation, confirms the phenotypic heterogeneity of the particular mutation, as well as of Danon disease.