Prevalence of papillary muscle hypertrophy in fabry disease.

BACKGROUND AND AIMS: Fabry disease (FD) is an X-linked genetic lysosomal disease, in which a deficit in the alpha-galactosidase A enzyme results in lysosomal build-up of globotriaosylceramide in several organs, causing cardiac, renal and cerebrovascular complications. The aim of this study was to assess the prevalence of papillary muscle hypertrophy (PMH) in patients with FD. METHODS: A group of 63 patients with FD and a positive genetic diagnosis were studied and were divided into two groups: one included 24 patients with FD and LVH and another group included 39 patients with FD and without LVH. Papillary muscles were measured from the left parasternal short axis view, defining PMH as a diastolic thickness greater than 11 mm in any diameter. RESULTS: Patients with FD and LVH had a high prevalence of anterolateral PMH (66.6%), and such prevalence was lower for the posteromedial PMH (33.3%). However, patients who had not yet developed LVH had a high prevalence of anterolateral PMH (33.3%). CONCLUSIONS: Patients with FD in the pre-clinical stage (without LVH) have a high prevalence of PMH, especially involving the anterolateral papillary muscle. This finding could be an early marker for the development of LVH, allowing to suspect the disease during its early stages, and begin enzyme replacement therapy in the appropriate patients.

Genetic Deletion of Galectin-3 Exacerbates Age-Related Myocardial Hypertrophy and Fibrosis in Mice.

BACKGROUND/AIMS: Aging is accompanied by progressive and adverse cardiac remodeling characterized by myocardial hypertrophy, fibrosis, and dysfunction. We previously reported that galectin-3 (Gal-3) is a critical regulator of inflammation and fibrosis associated with hypertensive heart disease and myocardial infarction. Nevertheless, the role and mechanism of Gal-3 in age-related cardiac remodeling have not been previously investigated. We hypothesized that Gal-3 plays a critical role in cardiac aging and that its deficiency exacerbates the underlying mechanisms of myocardial hypertrophy and fibrosis. METHODS: Male C57BL/6 (control) (n=24) and Gal-3 knockout (KO) (n=29) mice were studied at 24 months of age to evaluate the role of Gal-3 in cardiac aging. We assessed 1) survival rate; 2) systolic blood pressure (SBP) by plethysmography; 3) myocardial hypertrophy, apoptosis, and fibrosis by quantification of histological and immunohistochemical analysis; 4) cardiac expression of angiotensin (Ang) II, Ang (1-7) by Radioimmunoassay; 5) transforming growth factor-ß (TGF-ß), sirtuin (SIRT) 1, SIRT 7 and metalloproteinase 9 (MMP-9) by RT-qPCR and 6) ventricular remodeling and function by echocardiography. RESULTS: We found that aged Gal-3 KO mice had a lower survival rate and exhibited exacerbated myocardial hypertrophy and fibrosis without changes in SBP. Similarly, myocardial apoptosis and MMP-9 mRNA expression was significantly increased in the hearts of Gal-3 KO mice compared to controls. Additionally, cardiac Ang II and TGF-ß expression were higher in aged Gal-3 KO mice while SIRT1 and SIRT7 expression were reduced. CONCLUSION: Our findings strongly suggest that Gal-3 is involved in age-related cardiac remodeling by regulating critical mechanisms associated with the development of pathological hypertrophy. The gene deletion of Gal-3 reduced the lifespan and markedly increased age-dependent mechanisms of myocardial hypertrophy, apoptosis, and fibrosis, including Ang-II, TGF-ß, and MMP-9. At the same time, there was diminished cardiac-specific expression of SIRT1 and SIRT7, which are extensively implicated in delaying age-dependent cardiomyopathies.

Value of Electrocardiography to Distinguish Fabry Disease from Sarcomeric Hypertrophic Cardiomyopathy.

Fabry disease (FD) is a rare genetic disorder that leads to left ventricular hypertrophy (LVH), frequently misdiagnosed as hypertrophic cardiomyopathy (HCM). We sought to assess the value of electrocardiography for distinguishing FD from HCM. We retrospectively reviewed and compared standard electrocardiograms and echocardiograms from 26 patients with FD and LVH and 33 sarcomeric patients with HCM, matched for gender, age, and degree of LVH. The mean age of patients with FD was 46 years (interquartile range) (28 to 53) and of HCM 50 (30 to 61) years (p = 0.27). Of them, 16 (61%) and 25 (76%) were male, respectively (p = 0.26). Indexed left ventricular mass was 166 g/m2 in FD versus 181 g/m2 in HCM (p = 0.88). All patients with FD and 30 (91%) with HCM were in sinus rhythm (p = 0.25). A higher prevalence of right bundle branch block (RBBB) was observed in FD (27%) versus HCM (6%) (p = 0.03). The PR interval was shorter in FD, 140 ms (120-160) versus 160 ms (140 to 180) (p = 0.004). P-wave duration was longer in patients with FD, 100 ms (80 to 120) versus 80 ms (80 to 100) (p = 0.01). The PQ interval (PR interval minus P-wave duration) was shorter in patients with FD, 40 ms (20 to 45) versus 80 ms (40 to 80) (p = 0.001). There were no differences regarding P-wave amplitude, QRS complex duration, corrected QT length, conduction or repolarization abnormalities, Sokolow-Lyon index, and Cornell index. After multivariate adjustments for RBBB, PR interval, P-wave duration, and PQ interval, a PQ interval ≤40 ms and RBBB were significantly associated with FD. In conclusion, there are electrocardiogram characteristics, such as the presence of RBBB or a PQ interval ≤40 ms, that may be helpful for screening and reducing the delay in FD diagnosis.

Speckle Tracking Imaging in Patients with Pulmonary Hypertension.

BACKGROUND: Right ventricular (RV) systolic dysfunction is a strong predictor of mortality in pulmonary hypertension (PH). The goal of this study was to investigate whether right atrium (RA) and RV myocardial strain related to PH using speckle tracking echocardiography provide a superior estimation of RV systolic function than 2-dimensional (2D)-echo. METHODS: This cross-sectional study analyzed 22 patients with a diagnosis of PH stratified by right heart catheterization, and they were compared to a control group of 22 age- and sex-matched healthy subjects. RESULTS: Global longitudinal peak systolic strain measured in the RV free wall from the apical 4 chamber view was -15% vs. -14.5% when measured from the subcostal view (p = 0.99). Mean longitudinal strain during reservoir phase, and longitudinal strain rate during atrial reservoir and passive conduit function was significantly impaired measured in the right atrial free wall in patients with PH. CONCLUSIONS: This study showed impaired LV contractility in patients with PH assessed by speckle tracking strain. RV free wall longitudinal strain does not correlate with any of the measurements of RV systolic function obtained by 2D echocardiography. A major strength of RV longitudinal strain is its ability to assess the RV function without the limitations of 2D parameters. The subcostal RV strain is a feasible and accurate alternative to conventional RV strain from the apical view in patients with poor acoustic apical 4-chamber windows. The RA strain and strain rates values may be a valuable additive to assess right-sided heart function.

Speckle tracking echocardiography in the indeterminate form of Chagas disease.

BACKGROUND: Chagas disease is one of the most common diseases in Latin-America, and cardiac involvement is a significant cause of death. Assessment of myocardial strain may detect early myocardial damage. OBJECTIVES: To determine differences in longitudinal strain using speckle tracking to assess regional and global left ventricular function in patients with the indeterminate form of Chagas disease, in comparison with a control group. METHODS: This is a retrospective matched case-control study, conducted in a single center. We evaluated 45 adult patients with Chagas disease, diagnosed with 2 serological methods, without evidence of cardiac involvement, who were compared with 45 healthy control subjects, who were sex- and age-matched. All patients underwent Doppler echocardiography and longitudinal strain with speckle tracking. RESULTS: Median age was 59 years, and 60% were female. Echocardiographic parameters were similar in patients with Chagas and control subjects. In patients with Chagas, global strain differed significantly from that of control subjects (-17 vs -20.3, P < .001). Segmental strain showed 7 abnormal segments in patients with Chagas (P < .05). CONCLUSIONS: In patients with the indeterminate form of Chagas disease, global and segmental longitudinal peak systolic strain is reduced compared with healthy subjects, thus suggesting that it could be a sensitive technique to detect early myocardial damage. These findings could provide useful information regarding the pathophysiology of cardiac involvement and understand whether they might have prognostic usefulness or help develop strategies to modify the course and prognosis of patients with Chagas disease. A longitudinal prospective study would be necessary to validate our findings.

Use of tissue doppler imaging for the early detection of myocardial dysfunction in patients with the indeterminate form of Chagas disease.

INTRODUCTION: Chagas disease is one of the most common diseases in Latin America and heart involvement is the main cause of death. This study aimed to determine differences in tissue Doppler imaging (TDI) parameters in the assessment left and right ventricular function in patients with the indeterminate form of Chagas disease compared to those in healthy controls. METHODS: We compared 194 patients with the indeterminate form of Chagas disease to 72 age-matched healthy individuals. We considered p-values <0.05 to be statistically significant. RESULTS: TDI analysis of the right ventricular (RV) showed lengthened isovolumic relaxation time (IRT) and higher RV index of myocardial performance (RIMP) and left ventricle (LV) index of myocardial performance (LIMP) in the Chagas group than in the control group, indicating RV and LV systolic and diastolic myocardial damage. TDI analysis of the myocardial velocities of the interventricular septum and the lateral wall of the LV also showed a systolic and diastolic myocardial damage. CONCLUSIONS: The study results demonstrated early LV systolic and diastolic myocardial damage in the RV and LV in patients with the indeterminate form of Chagas disease by TDI. These early findings of RV and LV dysfunction may help identify patients who will progress to heart failure during the disease course. TDI should be included in initial patient evaluations because it allows adequate follow-up and treatment.

Use of tissue doppler imaging for the early detection of myocardial dysfunction in patients with the indeterminate form of Chagas disease

Abstract INTRODUCTION: Chagas disease is one of the most common diseases in Latin America and heart involvement is the main cause of death. This study aimed to determine differences in tissue Doppler imaging (TDI) parameters in the assessment left and right ventricular function in patients with the indeterminate form of Chagas disease compared to those in healthy controls. METHODS: We compared 194 patients with the indeterminate form of Chagas disease to 72 age-matched healthy individuals. We considered p-values <0.05 to be statistically significant. RESULTS: TDI analysis of the right ventricular (RV) showed lengthened isovolumic relaxation time (IRT) and higher RV index of myocardial performance (RIMP) and left ventricle (LV) index of myocardial performance (LIMP) in the Chagas group than in the control group, indicating RV and LV systolic and diastolic myocardial damage. TDI analysis of the myocardial velocities of the interventricular septum and the lateral wall of the LV also showed a systolic and diastolic myocardial damage. CONCLUSIONS: The study results demonstrated early LV systolic and diastolic myocardial damage in the RV and LV in patients with the indeterminate form of Chagas disease by TDI. These early findings of RV and LV dysfunction may help identify patients who will progress to heart failure during the disease course. TDI should be included in initial patient evaluations because it allows adequate follow-up and treatment.

Twenty Years of Clinical Experience with Cardiac Myxomas: Diagnosis, Treatment, and Follow Up.

BACKGROUND: Cardiac myxomas are the most frequent cardiac tumors. Although histologically benign, in some cases myxomas may be lethal, due to impairment of cardiac dynamics and their thromboembolic potential. The study aimed to assess the clinical presentation of cardiac myxomas and their correlation with echocardiographic features and to describe the perioperative results and long-term outcome of surgically treated patients. METHODS: A prospective study of 53 patients with cardiac myxomas who were operated the Hospital Argerich, followed clinically and with echocardiography from 1993 until 2013. All patients underwent echocardiographic studies. RESULTS: The patient's mean age was 53 ± 16 years (62.3% were women). The most common findings were dyspnea followed by embolic events. Most tumors were localized in the left atrium (77.4%), mainly in the fossa ovalis (63%). Mean size of the tumors was 4.76 x 3.50 cm. Tumors were generally mobile (88%) and went beyond the valve plane, causing mild mitral or tricuspid valve obstruction (58%) and dilation of the respective atrial chamber. Patients whose tumors were obstructive had higher pulmonary artery systolic pressures (50 vs 33 mmHg p < 0.01). According to the echocardiographic appearance 67% of tumors had a smooth surface and the remaining 32% had a villous surface. All patients with embolic manifestations had tumors with a villous surface. CONCLUSIONS: Clinical presentation relates to the ultrasound characteristics of myxomas. Smooth tumors are larger, occur with obstructive symptoms, and benefit from an elective surgery, whereas villous myxomas entailed a high embolic risk and require prompt surgical treatment.

Comparison of left atrial size and function in hypertrophic cardiomyopathy and in Fabry disease with left ventricular hypertrophy.

BACKGROUND: Fabry disease (FD) and hypertrophic cardiomyopathy (HCM) are two diseases with a different pathophysiology, both cause left ventricular hypertrophy (LVH) and myocardial fibrosis. Although remodeling and systolic dysfunction of the left atrium (LA) are associated with atrial fibrillation and stroke in HCM, changes in the size and function of the LA have not been well studied in FD with LVH. METHODS: The following groups were studied prospectively, and their respective findings compared: 19 patients with non-obstructive HCM (Group I), 20 patients with a diagnosis of Fabry cardiomyopathy (Group II), and 20 normal subjects matched for sex and age (Group III). Left ventricular mass index was measured using Devereux' formula, left atrial volume with Simpson's biplane method and left atrial mechanical function, including strain and strain rate, was measured using the speckle tracking technique. Strain and strain rate of the reservoir were measured during the three phases: reservoir (SR S), passive conduit (SR E) and atrial contraction (SR A). RESULTS: Patients with HCM had a larger left atrial volume than patients with FD (48.16 ± 14.3 mL/m2 vs 38.9 ± 14.9 mL/m2 respectively, P < .001), but in both disorders there was a severe decrease in left atrial function: reservoir strain in the apical four-chamber view: 17.47% in HCM vs 22.5% in FD, P = .24), strain rate in the apical chamber view: SR A: -0.80/seconds in HCM vs -1.04/seconds in FD (P = .88), SR S: 0.69/seconds in HCM vs 0.93 in FD (P = .12), SR E: -0.80 seconds in HCM vs -0.97/seconds in FD (P = .18). CONCLUSIONS: In this echocardiographic study we used speckle tracking to assess left atrial mechanical function and showed that FD is associated to an atrial cardiomyopathy, affecting the three phasic functions of the LA. Although in patients with HCM left atrial volume is larger than in patients with FD, both disorders exhibit severe decrease in left atrial function. These findings should be considered, given the potentially serious complications that can occur with the two diseases.

Papillary Fibroelastoma of the Left Ventricle in a Radiation-treated Cancer Patient.

We present the case of a 69-year-old female patient with a history of endometrial carcinoma in 1996, who underwent a total hysterectomy and bilateral adnexectomy. The patient also received chemotherapy and mediastinal radiotherapy followed by cancer remission. Ten years later she presented with heart failure and her Doppler-echocardiogram showed severe mitral regurgitation with pulmonary hypertension and a papillary fibroelastoma in the left ventricle. In 2011, she underwent a mitral valve replacement with a biological prosthesis and the pathology exam revealed valve damage consistent with radiotherapy- induced changes and confirmed the presence of a papillary fibroelastoma. This unusual mechanism of papillary fibroelastoma should be disseminated among cardiology physicians and in patients who have survived for long periods after radiotherapy. It is important to remember that cardiac complications may indeed occur, and the treating physician is responsible for detecting them.

Detection of angiographically significant coronary obstruction using resting transthoracic coronary Doppler echocardiography.

BACKGROUND: Transesophageal Doppler echocardiography has shown that significant stenosis can be detected based on the presence of aliasing with color Doppler in the stenotic area. The study aimed to assess the detection of angiographically significant coronary stenosis (ASCS) by analyzing the characteristics and velocities of resting coronary artery flow (RCF) using transthoracic coronary Doppler echocardiography (TCDE). METHODS: TCDE was performed before diagnostic coronary angiography (CA). The following velocities were measured: peak systolic velocity (PSV), peak diastolic velocity (PDV), mean diastolic velocity (MDV), end-diastolic velocity (EDV), and distal to proximal velocity ratios. RESULTS: Twenty-five patients were included, and CA revealed ASCS in 14 patients. With TCDE, the proximal and distal portions of the left anterior descending artery (LAD) could be measured in 84% of cases. Among 12 patients with ASCS in the distal left main coronary artery (LMCA) or proximal or mid LAD, proximal and distal flow could be measured in ten patients. Proximal diastolic velocities were higher in patients with ASCS in the LAD, and a distal MDV/proximal MDV ratio < 0.5 had a 60% sensitivity and a 92% specificity for the detection of ASCS (AUC 0.77, 95% CI 0.56-0.92). For the detection of ASCS limited to the LMCA and/or proximal LAD, the distal MDV/proximal MDV ratio had a sensitivity of 100% and a specificity of 89% (AUC 0.98, 95% CI 0.81-0.99). CONCLUSIONS: Resting TCDE can detect ASCS in the LAD, particularly at the proximal level, analyzing the ratio between distal and proximal flow velocities. These results could not be demonstrated in the RCA and CX arteries.

Speckle tracking echocardiography to assess regional ventricular function in patients with apical hypertrophic cardiomyopathy.

AIM: To explore regional systolic strain of midwall and endocardial segments using speckle tracking echocardiography in patients with apical hypertrophic cardiomyopathy (HCM). METHODS: We prospectively assessed 20 patients (mean age 53 ± 16 years, range: 18-81 years, 10 were male), with apical HCM. We measured global longitudinal peak systolic strain (GLPSS) in the midwall and endocardium of the left ventricle. RESULTS: The diastolic thickness of the 4 apical segments was 16.25 ± 2.75 mm. All patients had a normal global systolic function with a fractional shortening of 50% ± 8%. In spite of supernormal left ventricular (LV) systolic function, midwall GLPSS was decreased in all patients, more in the apical (-7.3% ± -8.8%) than in basal segments (-15.5% ± -6.93%), while endocardial GLPPS was significantly greater and reached normal values (apical: -22.8% ± -7.8%, basal: -17.9% ± -7.5%). CONCLUSION: This study shows that two-dimensional strain was decreased mainly confined to the mesocardium, while endocardium myocardial deformation was preserved in HCM and allowed to identify subclinical LV dysfunction. This transmural heterogeneity in systolic strain had not been previously described in HCM and could be explained by the distribution of myofibrillar disarray in deep myocardial areas. The clinical application of this novel finding may help further understanding of the pathophysiology of HCM.

Papillary fibroelastoma: clinical and echocardiographic features and initial approach in 54 cases.

INTRODUCTION: Papillary fibroelastoma (PFE) is a benign cardiac tumor that is currently detected more often due to the technological improvements in echocardiography. OBJECTIVES: To describe the echocardiographic features of PFE and correlate them with the clinical presentation and initial treatment. MATERIALS AND METHODS: A prospective analysis of patients with a diagnosis of PFE was conducted between 2000 and 2015. We assessed the clinical history, symptoms at the time of diagnosis, echocardiographic features, and initial treatment. RESULTS: Fifty-four patients with a diagnosis of PFE by echocardiography were included. The incidence was 0.038%. Mean age was 62±16 years; 50% were male. Forty-six percent of patients had symptoms at the time of diagnosis, the most frequent of which was transient ischemic accident (TIA). Embolic episodes occurred in 31% of patients, mainly to the brain. PFEs were valvular in 70.4% of cases and multiple in 13%. Mean maximum length was 1.18±0.58 cm, and 44% were mobile. PFEs >1.5 cm were most often found in the heart valves (56.8% vs 10.8%; P=.045). There was no significant relation between size, mobility, location and number of tumors, and the presence of embolism or symptoms. Most frequent treatment was oral anticoagulation in 48.6%, followed by simple tumor resection in 42.8% of cases. CONCLUSIONS: PFE is a small tumor, predominantly valvular and benign, but entails a high incidence of cerebral embolism. The initial approach should be individualized according to clinical manifestations, comorbidities, and the experience of the surgical center.

Limitations of multimodality imaging in the diagnosis of pannus formation in prosthetic aortic valve and review of the literature.

Pannus formation is a rare complication and occurs almost exclusively in mechanical prosthetic valves. It consists of fibrous tissue that covers the surface of the prosthesis either concentrically or eccentrically, resulting in valve dysfunction. The pathophysiology seems to be associated to a chronic inflammatory process that explains the late and insidious clinical presentation. This diagnosis should be considered in patients with high transvalvular gradients on transthoracic echo, and workup should be completed with fluoroscopy and transesophageal echocardiography. Treatment is always surgical and recurrence is rare. We present a case of pannus formation in a prosthetic aortic valve and a review of the literature regarding this disorder.