Primary Myocardial Involvement Research Articles

Risk of Cardiac Arrhythmias in Patients with Late-Onset Pompe Disease—Results from a Long Follow-Up in a Group of 12 Patients and Review of Literature

Background. Pompe disease is a rare, severe, autosomal recessive genetic disorder caused by GAA gene mutations, which cause α-1,4-glucosidase enzyme deficiency. There are two forms of Pompe disease based on the age of onset, the infantile and the adult form (LOPD). Cardiac involvement, previously recognized only in infantile cases, is now also reported in adults. Cardiomyopathy remains an exceptional finding while heart rhythm disorders appear to be more frequent. Methods. We retrospectively evaluated cardiac involvement in 12 patients with late-onset Pompe disease (LOPD) followed for an overall period of 143 years (mean 12.7 ± 7.7) using ECG, Holter ECG, and echocardiography. Results. The mean age of patients (M8:F4) at the first visit was 40.7 ± 16.1 (range 14–63) and 53.7 ± 16.9 (range 21–76) at last visit. Conduction delay was present in three patients; one patient developed ascending aorta ectasia but had a history of hypertension, and one patient showed right heart enlargement on echocardiography, probably due to pulmonary hypertension. No patient died during the FU, nor developed cardiomyopathy. Ectopic supraventricular beats and repeated episodes of ablation-resistant atrial fibrillation were observed in only one patient (8.3%) who required PMK implantation. Conclusions. Benefitting from the long follow-up, this study allows us to state that primary myocardial involvement is rare in patients with LOPD, while rhythm disorders are more frequent and require monitoring to avoid the risk of possible life-threatening complications.

Association of Systemic Sclerosis With Incident Clinically Evident Heart Failure.

Primary myocardial involvement is an important cause of death in systemic sclerosis (SSc). Subclinical diastolic/systolic heart dysfunction is recognized; however, whether this indicates a subsequent increased risk of clinically overt heart failure (HF) remains largely unknown. We aimed to investigate the risk of clinically overt HF in a large, unselected SSc cohort. This matched, retrospective cohort study was conducted using a nationwide insurance database in Taiwan. Incident SSc patients with no history of HF were identified, and non-SSc comparison groups were selected and matched to the SSc groups by age, sex, and cohort entry time. The cumulative HF incidence was estimated using the Kaplan-Meier method. Multivariable Cox proportional hazards regression was used to calculate adjusted hazard ratios (HRs) for HF hospitalization. A total of 1,830 SSc patients and 27,981 controls were identified. The cumulative incidence of hospitalized HF at 3, 5, and 10 years among patients with SSc were 3.5%, 5.3%, and 9.7%, respectively. Compared with non-SSc individuals, SSc patients had an increased risk of HF (adjusted HR 3.26 [95% confidence interval (95% CI) 2.49-4.28]). Subgroup analyses revealed that the impact of SSc on the occurrence of HF was greater among patients ages <50 years than those ages ≥50 years (HR 7.8 [95% CI 4.03-15.1] versus HR 2.78 [95% CI 2.06-3.76]). SSc is associated with a markedly higher risk of clinically evident HF and not asymptomatic ventricular dysfunction alone. These findings provide real-world evidence suggesting the use of appropriate screening strategies to detect these lethal complications early in SSc.

An Unusual Clinical Presentation of Danon Disease in a Female

<h3>Introduction</h3> Danon disease is a rare X-linked dominant skeletal and cardiac muscle disorder with multisystem clinical manifestations caused by mutations in the <i>LAMP2</i> gene. <i>LAMP2</i> mutations are identified in unselected cardiomyopathy cohorts in <0.3% of cases. We report a patient with Danon cardiomyopathy and no skeletal muscle involvement who underwent successful left ventricular assist device (LVAD) implantation. <h3>Case Report</h3> A 39-year-old patient with stage D heart failure (HF) and a LV ejection fraction of 20%, paroxysmal atrial fibrillation, Wolf-Parkinson-White (WPW) syndrome, and type 2 diabetes mellitus was admitted with decompensated HF. There was no family history of cardiomyopathy or sudden cardiac death. She was diagnosed with HF 4 years prior at that time she had concentric LV hypertrophy (interventricular septal thickness 1.4 mm) and LV end diastolic diameter of 5 cm. A cardiac PET did not identify any areas of ischemia and no FDG uptake to suggest active sarcoidosis. Left heart catheterization revealed angiographically normal coronary arteries. Genetic testing identified a heterozygous deletion in <i>LAMP2</i> (5'UTR_3'UTRdel), resulting in complete deletion of 1 allele. She was started on inotrope therapy due to low cardiac output but deteriorated due to incessant ventricular arrhythmias. She underwent HeartMate 3 (HM3) LVAD implantation as a bridge to heart transplant. The LV apical core biopsy revealed vacuolated and hypertrophic cardiomyocytes with endocardial fibrosis, consistent with Danon disease. In 6 months since surgery, she is doing well without LVAD-related complications. She was referred to genetic counseling and her now 10 years old daughter is being genetically tested. <h3>Summary</h3> This case reports an unusual clinical presentation of severe HF due to Danon disease in a female. She had primary myocardial involvement with WPW and mild learning disability but had no skeletal muscle or retinal involvement. Because of the X-linked nature of the disease, males are more severely affected, though progression to advanced HF has rarely been reported in females. This case highlights the importance of genetic testing for cardiomyopathies and subsequent genetic counseling of family members.

Phenotype of limited cutaneous systemic sclerosis patients with positive anti-topoisomerase I antibodies: data from the EUSTAR cohort.

To characterize patients with positive anti-topoisomerase I (ATA) in lcSSc. SSc patients enrolled in the EUSTAR cohort with a disease duration of ≤3 years at database entry were considered. We assessed the risk of major organ involvement in the following groups: ATA-lcSSc vs ACA-lcSSc and vs ANA without specificity (ANA)-lcSSc, and ATA-lcSSc vs ATA-dcSSc. Cox regression models with time-dependent covariates were performed with the following outcomes: new-onset interstitial lung disease (ILD), ILD progression [forced vital capacity (FVC) decline ≥10% and ≥5% vs values at ILD diagnosis), primary myocardial involvement (PMI), pulmonary hypertension (PH), any organ involvement and all-cause mortality. We included 1252 patients [194 ATA-lcSSc (15.5%)], with 7.7 years (s.d. 3.5) of follow-up. ILD risk was higher in ATA-lcSSc vs ACA- and ANA-lcSSc and similar to ATA-dcSSc, although with less frequent restrictive lung disease. The risk of FVC decline ≥10% (35% of ATA-lcSSc) was lower in ATA-lcSSc than in ATA-dcSSc, whereas FVC decline ≥5% occurs similarly between ATA-lcSSc (58% of patients) and other SSc subsets, including ATA-dcSSc. The risk of PMI was similar in ATA-lcSSc and ANA-lcSSc but lower than in ACA-lcSSc; no difference in PH and mortality risk was observed among lcSSc subsets. The risk of any organ involvement, PMI and PH was lower and the mortality tended to be lower in ATA-lcSSc vs ATA-dcSSc. ATA-lcSSc patients have a high risk of ILD, albeit with a lower risk of progression compared with ATA-dcSSc, supporting careful screening for ILD in this subgroup.

Higher Ventricular-Arterial Coupling Derived from Three-Dimensional Echocardiography Is Associated with a Worse Clinical Outcome in Systemic Sclerosis.

Primary myocardial involvement is common in systemic sclerosis (SSc). Ventricular-arterial coupling (VAC) reflecting the interplay between ventricular performance and arterial load, is a key determinant of cardiovascular (CV) performance. We aimed to investigate VAC, VAC-derived indices, and the potential association between altered VAC and survival free from death/hospitalization for major adverse CV events (MACE) in scleroderma. Only SSc patients without any anamnestic and echocardiographic evidence of primary myocardial involvement who underwent three-dimensional echocardiography (3DE) were included in this cross-sectional study and compared with healthy matched controls. 3DE was used for noninvasive measurements of end-systolic elastance (Ees), arterial elastance (Ea), VAC (Ea/Ees) and end-diastolic elastance (Eed); the occurrence of death/hospitalization for MACE was recorded during follow-up. Sixty-five SSc patients (54 female; aged 56 ± 14 years) were included. Ees (p = 0.04), Ea (p = 0.04) and Eed (p = 0.01) were higher in patients vs. controls. Thus, VAC was similar in both groups. Ees was lower and VAC was higher in patients with diffuse cutaneous form (dcSSc) vs. patients with limited form (lcSSc) (p = 0.001 and p = 0.02, respectively). Over a median follow-up of 4 years, four patients died for heart failure and 34 were hospitalized for CV events. In patients with VAC > 0.63 the risk of MACE was higher (HR 2.5; 95% CI 1.13–5.7; p = 0.01) and survival free from death/hospitalization was lower (p = 0.005) than in those with VAC < 0.63. Our study suggests that VAC may be impaired in SSc patients without signs and symptoms of primary myocardial involvement. Moreover, VAC appears to have a prognostic role in SSc.

POS0318 CLINICAL PHENOTYPE IN SCLERODERMA PATIENTS WITH ANTI-TOPOISOMERASE I POSITIVITY AND LIMITED CUTANEOUS FORM: DATA FROM THE EUSTAR DATABASE

POS0318 CLINICAL PHENOTYPE IN SCLERODERMA PATIENTS WITH ANTI-TOPOISOMERASE I POSITIVITY AND LIMITED CUTANEOUS FORM: DATA FROM THE EUSTAR DATABASE

Myocardial disease and ventricular arrhythmia in Marfan syndrome: a prospective study

BackgroundAortic root dilatation and—dissection and mitral valve prolapse are established cardiovascular manifestations in Marfan syndrome (MFS). Heart failure and arrhythmic sudden cardiac death have emerged as additional causes of morbidity and mortality.MethodsTo characterize myocardial dysfunction and arrhythmia in MFS we conducted a prospective longitudinal case–control study including 86 patients with MFS (55.8% women, mean age 36.3 yr—range 13–70 yr–) and 40 age—and sex-matched healthy controls. Cardiac ultrasound, resting and ambulatory ECG (AECG) and NT-proBNP measurements were performed in all subjects at baseline. Additionally, patients with MFS underwent 2 extra evaluations during 30 ± 7 months follow-up. To study primary versus secondary myocardial involvement, patients with MFS were divided in 2 groups: without previous surgery and normal/mild valvular function (MFS-1; N = 55) and with previous surgery or valvular dysfunction (MFS-2; N = 31).ResultsCompared to controls, patients in MFS-1 showed mild myocardial disease reflected in a larger left ventricular end-diastolic diameter (LVEDD), lower TAPSE and higher amount of (supra) ventricular extrasystoles [(S)VES]. Patients in MFS-2 were more severely affected. Seven patients (five in MFS-2) presented decreased LV ejection fraction. Twenty patients (twelve in MFS-2) had non-sustained ventricular tachycardia (NSVT) in at least one AECG. Larger LVEDD and higher amount of VES were independently associated with NSVT.ConclusionOur study shows mild but significant myocardial involvement in patients with MFS. Patients with previous surgery or valvular dysfunction are more severely affected. Evaluation of myocardial function with echocardiography and AECG should be considered in all patients with MFS, especially in those with valvular disease and a history of cardiac surgery.

Restrictive Cardiomyopathy Revealing Systemic Sclerodermia

Primary myocardial involvement is common in systemic sclerosis. There is growing evidence strongly suggesting that this involvement is linked to repeated focal ischemic lesions causing irreversible myocardial fibrosis. It can affect all heart structures. We report the case of a 65 years old male patient, without any personal medical history, admitted for inaugural right heart decompensation. The diagnosis of restrictive cardiomyopathy is based mainly on the following criteria: on echocardiography, hypertrohy of the right ventricle with alteration of the longitudinal systolic function, dilation of the right atrium, with good overall contractility. On right cardiac catheterization: elevation and equalization of the telesystolic pressures of the right atrium, right ventricle, and pulmonary artery with appearance of dip plateau on the right ventricle curve. Scleroderma was evoked considering following statements: the presence of Raynaud's phenomenon, unknown by the patient (presence of dermal sclerosis with pericapillary oedema and capillary dystrophy on capillaroscopy), cutaneous involvement (presence of perivascular and perineural mononuclear infiltrates, with collagen fibers increased in number and thickness), pulmonary involvement (diffuse bilateral interstitial lung disease) and renal involvement (moderately impaired function and positive proteinuria). The concept of cardiac dysfunction in scleroderma and other rheumatologic conditions has received new interest with the advent of newer non-invasive imaging techniques. Therfore, it would be necessary to search the cardiac involvement especially subclinical one in this type of system disease, as well as to confirm the systemic origin in front of certain forms of cardiopathies in particular restrictive cardiomyopathy.

Restrictive Cardiomyopathy Revealing Systemic Sclerodermia

Primary myocardial involvement is common in systemic sclerosis. There is growing evidence strongly suggesting that this involvement is linked to repeated focal ischemic lesions causing irreversible myocardial fibrosis. It can affect all heart structures. We report the case of a 65 years old male patient, without any personal medical history, admitted for inaugural right heart decompensation. The diagnosis of restrictive cardiomyopathy is based mainly on the following criteria: on echocardiography, hypertrohy of the right ventricle with alteration of the longitudinal systolic function, dilation of the right atrium, with good overall contractility. On right cardiac catheterization: elevation and equalization of the telesystolic pressures of the right atrium, right ventricle, and pulmonary artery with appearance of dip plateau on the right ventricle curve. Scleroderma was evoked considering following statements: the presence of Raynaud's phenomenon, unknown by the patient (presence of dermal sclerosis with pericapillary oedema and capillary dystrophy on capillaroscopy), cutaneous involvement (presence of perivascular and perineural mononuclear infiltrates, with collagen fibers increased in number and thickness), pulmonary involvement (diffuse bilateral interstitial lung disease) and renal involvement (moderately impaired function and positive proteinuria). The concept of cardiac dysfunction in scleroderma and other rheumatologic conditions has received new interest with the advent of newer non-invasive imaging techniques. Therfore, it would be necessary to search the cardiac involvement especially subclinical one in this type of system disease, as well as to confirm the systemic origin in front of certain forms of cardiopathies in particular restrictive cardiomyopathy.

Five-year follow-up of left ventricular diastolic function in systemic sclerosis patients: Determinants of mortality and disease progression

ObjectivesIn systemic sclerosis (SSc), left ventricular diastolic dysfunction reflects primary myocardial involvement of the disease. We aimed to assess the abnormalities of the diastolic function, analyze the characteristics of the disease progression, and investigate the prognostic value of diastolic dysfunction in SSc patients. Patients and methodsA total of 34 SSc patients (57 ± 12 years, 31 female) were involved in the study. The following traditional or tissue Doppler parameters of left ventricular diastolic function were obtained: E/A, lateral E׳, E/E׳, left ventricular mass index (LVM index), and maximal left atrial (LA) volume index. Measurements were repeated after 5.5 years. ResultsAt baseline, diastolic dysfunction was found in 62% of the SSc patients. Follow-up time was 5.4 ± 1.2 years. A total of 6 patients died of heart failure. In univariate Cox regression analysis, age (HR = 1.08, p < 0.05), LVM index (HR = 1.07, p < 0.01), lateral E׳ (HR = 1.57, p = 0.05), and LA volume index (HR = 1.11, p < 0.01) were predictors of survival. During the follow-up, significant increase in LA volume index (27.5 ± 9.7 vs. 35.4 ± 10.6cm3/m2, p < 0.001) and E/E׳ was found (7.6 ± 2.5 vs. 8.7 ± 3.8, p < 0.05) while E׳ did not change (9.6 ± 2.6 vs. 9.2 ± 1.9cm/s, NS). The increase in LA volume index showed positive correlation (r = 0.46, p < 0.05) while the decrease in E׳ values showed negative correlation (r = −0.54, p < 0.01) with the duration of the SSc. ConclusionIn SSc patients, left ventricular diastolic dysfunction is highly prevalent and is associated with increased risk of mortality. Our data suggest that in the advanced phase of the disease, the myocardial fibrotic processes burns out while the increase of the filling pressure progresses continuously.

Micro- and Macrovascular Treatment Targets in Scleroderma Heart Disease

Cardiac involvement in systemic sclerosis (SSc) is a frequent visceral complication that considerably affects the prognosis of the disease. The pathophysiologic hallmark is myocardial fibrosis which can progress leading to arrhythmia, right and/or left heart dysfunction and failure. Symptoms range from unusual to prominent and from mild to dramatic, but clinically overt disease is a poor prognostic factor. Primary myocardial involvement is related to focal ischemia due to transient coronary spasm, and the available data support that microvascular functional and structural abnormalities rather than macrovascular coronary involvement represent the main underlying mechanism of the disease. However, the existence and prevalence of atherosclerotic coronary artery disease in SSc remain to be determined, as several studies have generated conflicting reports. Despite the lack of effective targeted therapy for SSc itself, sensitive and quantitative techniques have demonstrated the ability of vasodilators to improve myocardial function and perfusion and to prevent the evolution of subclinical heart involvement to decompensated heart failure. Further research will provide a better understanding of the disease by detecting the potent contribution of coronary artery involvement, explaining differences in accelerated atherosclerosis between SSc and other autoimmune disorders, and opening directions for the development of novel treatment strategies for this life-threatening complication of SSc.

Miocardiopatías. Clasificación

Cardiomyopathies are a heterogeneous group of diseases associated with primary myocardial involvement. Unlike other heart conditions (pericardial diseases, hypertension, congenital heart disease, valvular or ischemic heart disease), cardiomyopathies are not the result of other diseases. The major morphological patterns are: dilated, hypertrophic, restrictive and arrhythmogenic right ventricular noncompaction. There are various classifications of cardiomyopathies. The most widely accepted are the World Health Organization (WHO) classification (1995), the American Heart Association (AHA) classifications (2006) and the European Society of Cardiology (ESC) classification (2007). AHA classification distinguishes between primary and secondary cardiomyopathies. ESC classification identifies the major morphological pattern types and thereafter distinguishes between familiar and unfamiliar cardiomyopathies.

Five-year follow-up of left ventricular diastolic dysfunction in systemic sclerosis patients: determinants of mortality and disease progression

Diastolic dysfunction in systemic sclerosis (SSc) reflects the primary myocardial involvement of the disease. No data are available about the progression rate of the diastolic dysfunction or about the prognostic value of the parameters characterizing the diastolic function. Patients and methods: 34 SSc patients (57±12 years, 31 female) were involved in the study. E/A ratio, lateral mitral annular E', E/E', left ventricular mass index (LVM index) and maximal left atrial volume index (Vmax index) were measured. Measurements were repeated after 5 years. Results: Follow-up time was 1976±420 days. Six patients died of heart failure. With univariate Cox regression analysis LVM index, E' and Vmax index were risk factors of mortality. Multivariate regression analysis showed that E' was the only independent predictor of mortality (p=0.048, HR=1.943). Based on ROC curves, Vmax index 8.55 cm/s (AUC 0.768, sensitivity: 100%, specificity: 64.3%); and LVM index<112.8 g (AUC: 0.899, sensitivity: 100%, specificity: 75.0%) were independent predictors of survival. In the survivors Vmax index (27.5±9.7 vs. 35.4±10.6 cm3/m2; p=0.000) and E/E' (7.6±2.5 vs. 8.7±3.8; p=0.043) worsened significantly while E' (9.6±2.6 vs. 9.2±1.9 cm/s, p= 0.163) did not change. During the follow-up, the increase in the V max index showed a positive correlation (r=-0.455; p=0.015) while the decrease in the E' values (r=-0.544; p=0.003) showed a negative correlation with the duration of the disease. ![Figure][1] Kaplan-Meier survival curves Conclusion: Parameters of the diastolic function predict mortality in SSc. The deterioration of myocardial relaxation slows down during the disease course while the progression rate of the parameters characterizing left ventricular filling pressure remains unchanged. [1]: pending:yes

Structural myocardial involvement in adult patients with type 1 myotonic dystrophy

Myotonic dystrophy type 1 (DM1) is the commonest muscular dystrophy in adults, affecting multiple organs in addition to skeletal muscles. Cardiac conduction system abnormalities are well recognized as an important component of DM1 phenotype; however, primary structural myocardial abnormalities, which may predispose these patients to congestive heart failure, are not as well characterized. We reviewed the retrospective analysis of the clinical and echocardiographic findings in adult patients with DM1. Among 27 patients (16 male; age 19–61 years) with DM1, the echocardiogram (ECHAO) was abnormal in 10 (37%) including one of 6 patients (16%) with congenital myotonic dystrophy. Reduced left ventricular ejection fraction (LVEF ≤50%) was noted in 5, diastolic dysfunction in 4, left atrial dilatation in 3, left ventricular hypertrophy in 2, apical hypokinesia in 1 and mitral valve prolapse in 3 patients. One patient had paradoxical septal movement in the setting of left bundle branch block. Echocardiographic abnormalities significantly correlated with older age; however, patients with systolic dysfunction on echocardiogram ranged in age from 27 to 52 years including 2 patients aged 27 and 34 years. We can conclude that echocardiographic abnormalities are frequent in adult patients with DM1. The incidence is similar in the classical and congenital type of DM1. Overall, echocardiographic abnormalities in DM1 correlate with increasing age; however, reduced LVEF is observed even at young age. Cardiac assessment and monitoring in adult patients with DM1 should include evaluation for primary myocardial involvement.

Prognostic impact of coronary microcirculation abnormalities in systemic sclerosis: a prospective study to evaluate the role of non-invasive tests

IntroductionMicrocirculation dysfunction is a typical feature of systemic sclerosis (SSc) and represents the earliest abnormality of primary myocardial involvement. We assessed coronary microcirculation status by combining two functional tests in SSc patients and estimating its impact on disease outcome.MethodsForty-one SSc patients, asymptomatic for coronary artery disease, were tested for coronary flow velocity reserve (CFR) by transthoracic-echo-Doppler with adenosine infusion (A-TTE) and for left ventricular wall motion abnormalities (WMA) by dobutamine stress echocardiography (DSE). Myocardial multi-detector computed tomography (MDCT) enabled the presence of epicardial stenosis, which could interfere with the accuracy of the tests, to be excluded. Patient survival rate was assessed over a 6.7- ± 3.5-year follow-up.ResultsNineteen out of 41 (46%) SSc patients had a reduced CFR (≤2.5) and in 16/41 (39%) a WMA was observed during DSE. Furthermore, 13/41 (32%) patients showed pathological CFR and WMA. An inverse correlation between wall motion score index (WMSI) during DSE and CFR value (r = -0.57, P <0.0001) was observed; in addition, CFR was significantly reduced (2.21 ± 0.38) in patients with WMA as compared to those without (2.94 ± 0.60) (P <0.0001). In 12 patients with abnormal DSE, MDCT was used to exclude macrovasculopathy. During a 6.7- ± 3.5-year follow-up seven patients with abnormal coronary functional tests died of disease-related causes, compared to only one patient with normal tests.ConclusionsA-TTE and DSE tests are useful tools to detect non-invasively pre-clinical microcirculation abnormalities in SSc patients; moreover, abnormal CFR and WMA might be related to a worse disease outcome suggesting a prognostic value of these tests, similar to other myocardial diseases.

Pleuro-pericarditis, vasculitis, subendocardial and nodular biventricular fibrosis. The multiple faces of systemic sclerosis detected by cardiac magnetic resonance in the same patient

A 60-year old woman with early diffuse systemic sclerosis(SSc) (disease duration 2 years, positive anti-topoisomerase I an-tibodies, megaesophagus, arrythmias and lungfibrosis with PA=30 mm Hg), under treatment with steroids, cyclophosphamide,amiodarone, domperidone, ACE inhibitors and protease pump in-hibitors, presented with recent onset of dyspnoea.The patient was referred to cardiac magnetic resonance (CMR)for evaluation of systolic function of right (RV), left ventricle (LV),myocardial perfusion and presence of myocardial scar. Cine CMR,using steady state free precession sequence (SSFP), applied for functionassessment, detected pleuro-pericarditis, RV dilatation with RVEDV=229.32 ml, RVESV=152.54 ml, RVEF=33.48% and LVEDV=138.17 ml,LVESV=66.81 ml, LVEF=52.37% ( Fig. 1A). For evaluation of myocardialperfusion, the first-pass perfusion imaging (FPP), using gadolinium ‐DTPA (Gd-DTPA), documented a subendocardial hypoenhancementcharacterized by a darker appearance compared to normal myocardium,whichisthetypicalmorphologicalfinding of autoimmune vasculitis(Fig. 1B) [1]. The evaluation of scar tissue was performed from the lategadolinium enhanced (LGE) images, taken 15 min after the Gd-DTPAinjection and using an inversion recovery (IR) sequence. LGE imagesrevealed the coexistence of bo th subendocardial and nodular fibrosis inLV and also free wall RV fibrosis (Fig. 2A, B).SScisamulti-system,connectivetissuediseaseofunknownetiology,characterized by vascular dysfunction, autoimmunity, and enhanced fi-broblast activity resulting in fibrosis of internal organs that conducts toincreased mortality. Primary myocardial involvement is common inSSc and has been recognized as a poor prognostic factor, when clinicallyevident. Recent data strongly suggest that the myocardial involvementisrelatedtocontinuouslyrepeatedepisodesoffocalischemia,duetomi-crocirculation impairment with abnormal vasoreactivity that finallyleadstodevelopmentofirreversiblemyocardial fibrosisandLV–RVdys-function [2,3]. Recentquantitative methods,such as perfusion magneticresonance imaging, have underlined these results [2,3]. Myocardial fi-brosis has been detected by CMR, as a mainly linear and, more rarely,nodular lesion. It is usually mid-wall and, more rarely, subendocardialor subepicardial. Usually, it predominates in mid-anterior, mid-anteroseptal and mid-inferoseptal segment and has no correlation

Biventricular Performance in Patients with Marfan Syndrome without Significant Valvular Disease: Comparison to Normal Subjects and Longitudinal Follow-Up

The presence and progressive nature of primary myocardial involvement in Marfan syndrome are debated. The aim of this study was to evaluate the clinical relevance of left ventricular (LV) and right ventricular (RV) strain in adult patients with Marfan syndrome without significant valvular disease. Adult patients with Marfan syndrome (n= 50; mean age, 35.2 ± 12.9 years) were followed prospectively. Echocardiography was performed annually and consisted of comprehensive assessment of ventricular and valvular function. Using speckle-tracking imaging, the baseline strain values of the Marfan population were calculated and compared with the values of normal controls. The follow-up evaluations were used to assess changes in ventricular strain. The association between the incidence of adverse events (heart failure, [supra]ventricular arrhythmias, and proximal aorta surgery) and baseline strain values was investigated. Compared with controls, patients with Marfan syndrome had significantly lower peak longitudinal LV strain (-18.9 ± 2.3% vs -20.1 ± 1.9%, P < .01) and RV strain (±26.9 ± 5.2% vs ±29.3 ± 4.25%, P < .01). The absolute changes in LV longitudinal, radial, and circumferential strain and RV longitudinal strain during a median 4 years of follow-up were 0.1 ± 2.8%, 1.12 ± 7.6%, 0.3 ± 3.7%, and 0.9 ± 5.5%, respectively, which was not statistically significant. Cox regression demonstrated that reduced LV or RV strain was not associated with adverse outcome (supraventricular arrhythmias, n= 3; proximal aorta surgery, n= 4). This study suggests that patients with Marfan syndrome show lower ventricular strain and strain rate values compared with healthy controls. However, no relevant changes in LV and RV function occurred during midterm follow-up in patients with Marfan syndrome without valvular disease at baseline. Although ventricular strain and strain rate were mildly reduced in patients with Marfan syndrome, this did not affect outcomes negatively in the present study.

Impact of systemic sclerosis on electromechanical characteristics of the heart

Primary myocardial involvement is common in systemic sclerosis (SSc). We evaluated the atrial and ventricular electromechanical characteristics by using tissue Doppler echocardiography in SSc patients with subclinical cardiac involvement. Twenty-seven consecutive patients (24 women; mean age +/- SD 49.9 +/- 11.3 years) presenting with SSc without pulmonary arterial hypertension or symptomatic heart failure were prospectively studied. Electrocardiographic P-wave dispersion (Pd), corrected QT dispersion (QTcd), interatrial, intra-atrial, interventricular, and intraventricular electromechanical delays were analyzed by tissue Doppler echocardiography, and brain natriuretic peptide levels were measured. Results were compared with 17 healthy controls. There was no difference in conventional and tissue Doppler parameters between the two groups. However, patients with SSc had higher mean Pd (mean [+/-SD] 46.8 +/- 15 and 36 +/- 8 ms, respectively, P = 0.004) and mean interatrial electromechanical delay time (DT) (mean [+/-SD] 32.2 +/- 9.2 and 24.7 +/- 9.7 ms, respectively, P = 0.01), mean electromechanical delay time for all segments (Mean Ts) (mean [+/-SD] 148.8 +/- 18.8 and 129.3 +/- 13.4 ms, respectively, P < 0.001), and intraventricular DT (mean [+/-SD] 27.6 +/- 12.5 and 16.2 +/- 7.2 ms, respectively, P < 0.001). Intraventricular DT was the only parameter that correlated significantly with the Mean Ts. Brain natriuretic peptide levels were within normal limits in both groups; however, they were higher in patients with SSc than in controls (mean [+/-SD] 37.5 +/- 28.5 and 23.1 +/- 16.0 pg/ml, respectively, P = 0.03). The evaluation of atrial and ventricular electromechanical parameters by using tissue Doppler echocardiography seems to be useful for detection of subclinical cardiac involvement in SSc patients with normal conventional echocardiographic findings.

Systemic sclerosis and cardiac dysfunction: evolving concepts and diagnostic methodologies

Primary myocardial involvement is common in systemic sclerosis. There is strong evidence that this involvement is related to repeat focal ischemic injury causing irreversible myocardial fibrosis. Clinically evident cardiac involvement is recognized to be a poor prognostic factor; thus preclinical identification is highly encouraged. The severity of heart involvement has been confirmed and patients having systemic sclerosis with antitopoisomerase I antibodies seem to be at higher risk. Echocardiography, coupled, if possible, to pulsed tissue Doppler, is the cornerstone of heart assessment. Myocardial perfusion may be assessed by single photon emission computed tomography. When available, cardiac magnetic resonance imaging should be considered as it allows simultaneous measurement of volumes and ventricular function, myocardial perfusion, and assessment of possible inflammation and/or fibrosis. As a result of recent innovations, clinicians have a large panel of methods - some of these possibly reserved for research--whereas the others seem to be widely available and suitable for routine clinical practice. Indeed, conventional echocardiography, pulsed tissue Doppler, and natriuretic peptides may be used for routine assessment.

Outcome measures for heart involvement in systemic sclerosis

Primary myocardial involvement is common in SSc. Increasing evidence strongly suggests that this involvement is related to repeat focal ischaemic injury causing irreversible myocardial fibrosis. Clinically evident cardiac involvement is recognized to be a poor prognostic factor, thus pre-clinical identification is highly encouraged. Echocardiography, if possible coupled to pulsed tissue Doppler, is the cornerstone of heart assessment even if radionuclide ventriculography remains the gold standard for evaluation of ventricular function. Myocardial perfusion may be assessed by single photon emission CT, but cardiac MRI will probably supplant this technique; it, furthermore, offers the possibility to concomitantly determine, ventricular function, myocardial perfusion and tissular parameters (i.e. myocarditis or burden of fibrosis). Conduction system abnormalities are common but not serious, while arrhythmias may be life-threatening, necessitating 24-h ambulatory Holter ECG. Natriuretic peptides have been used mainly when the heart has been involved secondary to pulmonary arterial hypertension, but may also be useful for the identification of early heart dysfunction. Their predictive value should also be investigated when there is primary heart involvement.