Characterization of Fabry Disease cardiac involvement according to longitudinal strain, cardiometabolic exercise test, and T1 mapping.

In Anderson-Fabry disease (FD), we sought to evaluate relation between left ventricular (LV) hypertrophy, longitudinal strain (LS), myocardial T1 mapping and cardiopulmonary exercise parameters, and their prognostic value in term of cardiovascular outcomes. In this prospective, observational, monocentric study called "FABRY-Image", we evaluated consecutive adult FD patients by echocardiography, cardiac magnetic resonance, and cardiopulmonary exercise testing. We investigated regional LS, the relations between LV hypertrophy, LS, T1 mapping, and VO2 peak and VE/VCO2, and the prediction of cardiovascular events during follow-up. From 2016 to 2019, we included 35 FD patients (44 ± 17 years, 40% male), that were compared with 20 controls. In FD patients, global, basal and mid-LV LS, as well as mean T1 were significantly altered compared to controls (p < 0.05) with relative apical LS sparing. LV wall thickness was particularly related to mean of basal LS (r = - 0.73), to T1 (r = - 0.48), and to VE/VCO2 (r = 0.45). Mean of basal LS was well related to myocardial T1 (r = 0.59). A good relation was observed between VO2 peak and global LS (r = 0.39) while VE/VCO2 slope was more related to maximal LV wall thickness (r = 0.45), and T1 (r = - 0.61). During a median follow-up of 2.4 years, 6/31 patients presented de novo atrial fibrillation or stroke. In Cox univariate analyses, LV wall thickness, basal LS, T1 value, and VE/VCO2 were significantly predictive of occurrence of de novo atrial fibrillation or stroke (p < 0.05). Our study shows an apical LS sparing in FD patients as observed in amyloidosis, and a close relation between LV hypertrophy, LS, T1 mapping, and VE/VCO2 which are all associated to the occurrence of de novo atrial fibrillation or TIA/stroke during follow-up. These results need to be confirmed by future multicentric studies.

Predictors of future onset of atrial fibrillation in hypertrophic cardiomyopathy.

BACKGROUND: Novel predictors of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) are desirable. AIM: To detect new multimodality imaging variables predictive of de novo AF in HCM. METHODS: Consecutive patients with HCM underwent clinical assessment and 48-hour Holter electrocardiography to detect AF episodes. Left ventricular (LV) morphology, function and fibrosis, and the left atrium (LA) were characterized by cardiac magnetic resonance. Mitral valve, systolic pulmonary artery pressure, LV filling and maximum gradients were assessed by echocardiography. Patients with no previous history of AF were followed with Holter recordings. RESULTS: Two hundred and nine patients were included (mean age 53±16 years; 140 men), 46 (22%) of whom had a history of AF and a longer duration from HCM diagnosis, more frequent use of heart failure medication, a higher systolic pulmonary artery pressure, a lower LV ejection fraction, a higher extent of LV fibrosis and prevalence of fibrosis on right ventricular (RV)-LV insertions, a higher LA volume and lower LA phasic function. Patients with no AF at inclusion were followed for 26 (17-42) months, and 15 (9%) developed de novo AF. Among clinical characteristics, New York Heart Association class was the only significant AF predictor in the multivariable analysis (hazard ratio 2.65 per class, 95% confidence interval [CI] 1.15-6.10; P=0.02). Among imaging characteristics, two independent predictors were identified: myocardial fibrosis on RV insertions (hazard ratio 2.8, 95% CI 1.3-5.9; P=0.008); and LA volume (hazard ratio 1.03 per mL/m2, 95% CI 1.01-1.06; P=0.006). CONCLUSIONS: AF in HCM is predicted by New York Heart Association class, LA volume and LV fibrosis on RV-LV insertions on cardiac magnetic resonance imaging. The mechanisms relating the ventricular phenotype to AF should be clarified in future studies.

Characterization of hypertrophic cardiomyopathy according to global, regional, and multi-layer longitudinal strain analysis, and prediction of sudden cardiac death.

To evaluate the severity of hypertrophic cardiomyopathy (HCM) according to global, regional, and multi-layer longitudinal strain (LS) analysis using speckle-tracking echocardiography. From February 2007 to November 2014, we prospectively evaluated 375 consecutive HCM patients referred to our specialized cardiomyopathy center. Demographics, clinical, and rest and exercise echocardiographic parameters were collected according to a completely standardized protocol. Global, regional, and multilayer strain analyses were performed. Correlations between LS and other characteristics were evaluated, and we assessed their prognostic value to predict sudden cardiac death (SCD) or appropriate implantable cardioverter defibrillator (ICD) shocks during follow-up, using Cox proportional hazards analyses. We finally included 217 patients (50.1 ± 15.6 years, 67% male) but only 179 (82%) had LS analysis of sufficient quality. An inverse relation was observed between the mean basal left ventricular (LV) LS and diastolic parameters [E/Ea (r = - 0.30) and left atrium indexed volume (r = - 0.23)], as well as between the resting LV outflow-tract maximal gradient (r = - 0.26) or during peak exercise (r = - 0.20). Mean LS in the LV hypertrophic area was particularly related with maximal wall thickness (r = - 0.47) and transmural global LS with the degree of myocardial fibrosis in cardiac magnetic resonance (r = - 0.32). During a median follow-up of 2.8 ± 1.5 years, mean transmural LS in the hypertrophic area was predictor of SCD and appropriate ICD shock (10 events/179 patients, hazard ratio = 0.83 [95% CI 0.72-0.95], p = 0.01). Basal LS and hypertrophic area LS are valuable parameters to evaluate HCM severity. Mean hypertrophic area LS particularly seems predictive of SCD occurrence and appropriate ICD shocks.

Upright treadmill vs. semi-supine bicycle exercise echocardiography to provoke obstruction in symptomatic hypertrophic cardiomyopathy: a pilot study.

Aims: Recent findings regarding hypertrophic cardiomyopathy (HCM) haemodynamics emphasized the relationship between symptoms, left ventricular outflow tract obstruction (LVOTO), and the preload condition as the venous return level. As various types of exercises have different effects on peripheral vascular beds, this study sought to compare upright treadmill exercise echocardiography (EE) to semi-supine bicycle EE in maximum provoked LVOTO in HCM patients. Methods and results: Semi-supine bicycle and upright treadmill EE were prospectively performed in HCM patients with New York Heart Association functional Class II. Maximal LVOT gradient at rest in the supine and standing position, and during Valsalva manoeuvre, LVOT gradients of both semi-supine bicycle and treadmill exercise at peak and post-exercise, maximal exercise levels, and blood pressure adaptation were recorded. One patient was excluded for not sufficient image quality during treadmill. We studied 22/23 patients (mean age: 54.9 ± 12.3 yrs; 55% male). The supine position at rest displayed a mean maximal LVOT gradient of 46.1 ± 44.8 mmHg, which increased to 51.6 ± 41.2 mmHg during Valsalva (P = 0.066), and to 55.1 ± 37.8 mmHg in the standing position (P = 0.053). Mean maximal peak exercise LVOT gradient with semi-supine bicycle was significantly lower than in treadmill EE (54.6 ± 38.2 mmHg vs. 87.5 ± 42.1 mmHg, respectively, P < 0.01). Among these patients, 41% exhibited LVOT gradient ≥ 30 mmHg at rest. Moreover, 41% exhibited LVOT gradient ≥ 50 mmHg during Valsalva, 55% in resting standing position, 41% at peak semi-supine bicycle exercise, 91% at peak treadmill exercise, and 95% in standing position during treadmill recovery period. Conclusion: This pilot study may suggest treadmill's greater value compared to semi-supine bicycle EE for determining maximum LVOT gradient in HCM.

Preoperative right ventricular dysfunction is a strong predictor of 3 years survival after cardiac surgery.

BACKGROUND: Prognostic value of right ventricular (RV) systolic function is well established in valvular disease, heart failure but has not been evaluated in patients undergoing cardiac surgery. OBJECTIVES: The aim of the present study was to evaluate the prognostic value of preoperative RV dysfunction extensively evaluated on the basis of a large set of echocardiographic parameters [S', RV fractional area change (RVFAC), right myocardial performance index (RMPI), isovolumic acceleration (IVA), RV dP/dt and basal longitudinal strain (BLS)] in a large population of unselected patient awaiting cardiac surgery. METHODS: We prospectively studied 400 consecutive patients referred for cardiac surgery, in a single surgical center. Echocardiography was performed 24 h before surgery and phone interview assessed the survival status (overall and cardiovascular death) 3-years after surgery. RESULTS: Among 400 patients, 271 were male, mean age was 70.3 ± 10.2. At 3-years the overall and cardiovascular mortality was, respectively, 10.5 and 6.8%. The univariate Cox analysis identified all RV function parameters excepted BLS as predictive factors of overall mortality, with the strongest value for RVFAC < 35% (HR 4.8), S' < 10 cm/s (HR 3.8) and IVA < 1.8 m/s2 (HR 3.2) (all P < 0.001). All parameters were associated to cardiovascular mortality. In multivariate analysis, RVFAC, S', dP/dt and IVA were significantly associated to 3-years overall mortality whatever the EuroSCORE. Abnormal RVFAC, S', IVA and BLS were associated to cardiovascular mortality. CONCLUSIONS: The presence of RV dysfunction before cardiac surgery assessed by echo significantly predicts postoperative mortality, and this is true whatever the EuroSCORE level. This result demonstrates the need of adding the assessment of echographic RV function before cardiac surgery.

Morphological and functional abnormalities pattern in hypertrophy-free HCM mutation carriers detected with echocardiography.

To evaluate if morphological or functional abnormalities could be detected with echocardiography in hypertrophic myocardiopathy (HCM) mutation carriers without left ventricle (LV) hypertrophy has developed. HCM is caused by extensive genes mutations found in two-third of patients. Because screening for carriership of a large population is unreasonable, identification of asymptomatic subjects is confined to the use of imaging such as echocardiography, by which subtle abnormalities can be detected. Comprehensive echocardiographic studies including morphological and functional assessment were performed. Asymptomatic HCM mutation carriers without hypertrophy (Phe-/Gen+, n = 14), and HCM patients (Phe+/Gen+, n = 17) were compared with healthy control subjects (n = 32) in a prospective design. Compared to controls, septum thickness was significantly higher with an elongated mitral valve in both groups. Thickened LV muscular band (LVMB) are more likely found in Phe-/Gen+ and Phe+/Gen+. The thickness of LVMB was higher in the Phe-/Gen+ versus controls. A LVMB thickness ≥3.6 mm was associated with HCM mutation carriership (sensitivity: 76.9 %, specificity: 94.1 %). The regional strain was significantly impaired in the basal segments of the septum in the Phe-/Gen+. The GLS was significantly impaired in the Phe+/Gen+ (-16.4 % ± 2.9 vs. -21.4 % ± 2.3 in control subjects, p = 0.01). Mitral A wave velocity, septal E/e', averaged E/e' were increased in both groups. E/A ratio was significantly lower in Phe+/Gen+. Morphological and functional abnormalities in hypertrophy-free HCM mutation carriers could be detected with echocardiography. Anomalous thickened LVMB could be representing a morphological marker for the HCM disease without overt hypertrophy has developed or in patients with an ambiguous diagnosis.

Global longitudinal strain is associated with heart failure outcomes in hypertrophic cardiomyopathy.

OBJECTIVE: We hypothesised that abnormal global longitudinal strain (GLS) would predict outcome in hypertrophic cardiomyopathy (HCM) better than current echocardiographic measures. METHODS: Retrospective analysis of risk markers in relation to outcomes in 472 patients with HCM at a single tertiary institution (2006-2012). Exclusion criteria were left ventricular (LV) hypertrophy of other origin, patients in atrial fibrillation, lost to follow-up and insufficient image quality to perform strain analysis. Standardised echocardiogram recordings were reviewed and standard variables and LV GLS were measured. The primary end-point included all cardiac deaths, appropriate defibrillator shocks and heart failure (HF) admissions. The secondary end-point was death by HF and admissions related to HF. RESULTS: Mean age was 50.0±15.0 years; 322 (68%) were men. At a median of 4.3 years (IQR 0.1-7.8) follow-up, 21 (4.4%) patients experienced cardiovascular death: 6 (1.3%) died from HF, 13 (2.7%) had sudden cardiac death and 2 (0.4%) died secondary to stroke. Four (0.8%) patients experienced appropriate defibrillator shock, and 13 (2.7%) were admitted for HF. On multivariate Fine-Gray proportional hazard analyses, GLS was significantly associated with the primary end-point (HR=0.90, 95% CI 0.83 to 0.98, p=0.018) independently of age, maximal provoked LV outflow-tract gradient and LV end-systolic volume. Moreover, GLS was particularly associated with the secondary end-point (HR=0.82, 95% CI 0.75 to 0.90, p<0.0001) independently of age, previous atrial fibrillation, New York Heart Association (NYHA) class III-IV, LV end-systolic volume, E/E', and outflow-tract gradient. Survival curves confirmed that GLS was associated with HF events (GLS <15.6%, p=0.0035). CONCLUSIONS: In patients with HCM, reduced GLS is an independent factor associated with poor cardiac outcomes, and particularly HF outcomes.

A Rare Right Ventricular Involvement of Eosinophilic Granulomatosis Demonstrated by Cardiac MRI.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic vasculitis with a prevalence rate of seven per million. Cardiac involvement was reported in 20-50%, yet with improved diagnostic methods, the frequency of cardiac involvement is expected to be even higher. It can result in significant morbidity and mortality, accounting for about 50% of death. Cardiac magnetic resonance (CMR) imaging is used to evaluate the myocardium, valves, coronary arteries, pericardium, also to assess cardiac structure and function. Perfusion study allows tissue characterisation with a suggestive pattern of late gadolinium enhancement. CASE REPORT: We report a rare case of EGPA in a 54-year-old male patient who presented with fever, sore throat and dizziness. Echocardiography showed a filling defect at the apex of the right ventricle (RV). CMR findings suggested the diagnosis of EGPA by demonstrating an impressive lesion at RV apex with the typical 3-layer appearance and thrombus formation. Post-gadolinium subendocardial hyperenhancement suggested focal involvement at the inferolateral wall of the left ventricle. Computed Tomography (CT) was done to rule out calcific or soft plaques of the coronary arteries, small vessel vasculitis and small aneurysm. CT scan showed a low-attenuation lesion at the inner wall of the right ventricle. In the lungs, bilateral interstitial changes and bilateral cystic bronchiectases were found. Under appropriate treatment, the patient improved clinically. CONCLUSIONS: It is of crucial importance to perform full cardiac imaging that includes CMR even in asymptomatic patients with suspected EGPA, since early identification of cardiac involvement may allow to apply appropriate therapy and full recovery of the patient.

Epicardial myocardial strain abnormalities may identify the earliest stages of arrhythmogenic cardiomyopathy.

The aim of this cohort study was to evaluate the value of echocardiographic multilayer strain analysis in the identification of arrhythmogenic cardiomyopathy (AC) in its earliest stages in which sudden cardiac death can occurs. Twenty seven asymptomatic relatives of AC probands (mean age 39.6 ± 19.5 years, 37 % male) with a desmosomal pathogenic mutation but no additional criteria for AC (group II) were compared to age and sex-matched healthy controls (group I). In addition, 70 patients harboring a pathogenic desmosomal mutation with "definitive" diagnosis of AC (group IV), and 19 subjects with "borderline" diagnosis (group III) were also studied. A standard echocardiographic evaluation plus left (LV) and right ventricular global and regional transmural, endocardial, and epicardial longitudinal strain (LS) analysis, was performed. In group II, while LV ejection fraction, fractional shortening, and S' were not significantly reduced compared to controls, transmural global LS was significantly reduced to 19.3 ± 1.8 % in group II versus 20.9 ± 1.1 % in controls (p = 0.0003). Compared to controls, group II presented significant (p < 0.05) regional LS decrease in the basal infero-lateral, antero-lateral, latero-apical, infero-septal, and septo-apical segments. Moreover, LS of the latero-apical and the basal antero-lateral segments was significantly altered in the epicardium (p < 0.05) but not significantly in the endocardium. Global and regional LV LS analysis allows detection of AC in an early or non-diagnostic stage of the disease. Moreover, epicardial LS analysis allows the detection of abnormalities earlier than endocardial LS.

Abnormal left ventricular contraction sequence in hypertrophic cardiomyopathy patients: first description of hypersynchrony and invert synchrony.

The aim of this study was to compare left ventricular contraction sequence in patients with hypertrophic cardiomyopathy (HCM) and healthy controls. Normal left ventricular contraction sequence in healthy controls exhibits an apex-to-base delay (ABD) contributing to efficient cardiac mechanics (physiologic asynchrony). Echocardiographic data from 20 controls and 40 HCM patients were prospectively analyzed. Endocardial longitudinal and circumferential strains and ABD were measured using custom-built software. HCM patients had increased circumferential (-36.4 ± 6.0 vs. -32.9 ± 5.0, p < 0.01) and decreased longitudinal (-19.3 ± 6.4 vs. -23.4 ± 5.7, p < 0.01) strains. In controls, physiologic ABD was observed (35.7 ± 18.1 ms). This delay was reduced in HCM patients (5.5 ± 22.7 ms, p < 0.01 vs. controls). There was no interaction between ABD and common clinical or echocardiographic parameters in the HCM population. Left ventricular contraction sequence can be modified in HCM patients, with the loss of the physiologic ABD. This phenomenon is independent from commonly measured parameters.

Clinical and imaging description of the Maron subtypes of hypertrophic cardiomyopathy.

Longitudinal strain analysis enables early detection of left ventricular (LV) contraction abnormalities in patients with preserved ejection fraction. Hypertrophic cardiomyopathy (HCM) is associated with low values of regional and global longitudinal myocardial deformations. In addition to contraction abnormalities, LV regional strain abnormalities are partially related to the degree of hypertrophy. This study sought to describe global longitudinal strain (GLS) in HCM patients as categorized using the Maron's classification. Complete echocardiography examinations, including GLS analysis, were performed in consecutive HCM patients followed up in two French HCM-clinics. A total of 271 patients (mean age 49 ± 16yrs; 71 % male) were evaluated. In this population, the most frequently classified hypertrophy pattern was Type II (47 %), following the Maron's classification. Type III was characterized by a higher degree of LV hypertrophy in terms of mass and maximal wall thickness, and was more frequently obstructive at rest, with lower GLS values (-15.3 ± 3.9 %, p = 0.016), higher E/E' ratio (13.4 ± 6.7, p < 0.001), and a more frequently inadequate blood pressure response to exercise (30 %, p = 0.04) compared to other patterns. The variable that correlated best with GLS was LV mass index (r = 0.49, p < 0.01), while GLS did not significantly correlate with left ventricular outflow tract obstruction. This study demonstrated that the Type III HCM pattern presented with lower GLS, which was partially related to higher LV mass index, more elevated LV filling pressures, and a more frequently inadequate blood pressure response to exercise, in comparison with other patterns categorized using the Maron's classification.

Echocardiographic assessment of right ventricular systolic function in a population of unselected patients before cardiac surgery: a multiparametric approach is necessary.

BACKGROUND: According to recent USA guidelines, right ventricular (RV) dysfunction can be diagnosed on the basis of a single parameter, such as tricuspid lateral annular systolic velocity (S')<10 cm/s or RV fractional area change (RVFAC)<35%. AIMS: To assess these recommendations in a large unselected cohort of patients awaiting cardiac surgery and evaluate less validated RV function criteria. METHODS: Among the consecutive patients, 413 were prospectively enrolled and underwent comprehensive echocardiography, including S', RVFAC and other RV parameters (right myocardial performance index; acceleration time, isovolumic velocity and isovolumic acceleration [IVA]; RV dP/dt; isovolumic relaxation time; two-dimensional [2D] strain). We defined subgroups of highly probable RV dysfunction (S'<10 cm/s and RVFAC<35%) and highly probable normal RV function (S'≥10 cm/s and RVFAC≥35%) as reference groups. Indices of preload and afterload were also recorded. RESULTS: Of 413 patients, 320 (77.5%) had normal RV function. In 93 patients, S' and/or RVFAC were abnormal; both were abnormal in 39 (42%) patients. Using our reference groups, IVA≤1.8 m/s2 and basal 2D strain≥-17% were of most value in diagnosing RV dysfunction. IVA was least load dependent while basal 2D strain appeared to be afterload and preload dependent. CONCLUSION: In this large population, S' and RVFAC were sometimes discrepant, supporting the need for a multiparametric approach when evaluating RV function. Among seven less validated criteria, IVA and 2D strain had the best diagnostic value. Unlike 2D strain, IVA was not influenced by loading conditions.

Paradoxical response to exercise in asymptomatic hypertrophic cardiomyopathy: a new description of outflow tract obstruction dynamics.

OBJECTIVES: The purpose of this study was to analyze left ventricular obstruction in patients with hypertrophic cardiomyopathy (HCM) during exercise echocardiography. BACKGROUND: Despite the association of symptoms with left ventricular outflow tract obstruction in HCM, there exist paradoxical situations in which significant intraventricular gradients (>50 mm Hg) at rest occur in conjunction with excellent exercise tolerance. METHODS: To examine this phenomenon, we performed exercise echocardiography and analyzed the clinical status of 107 HCM patients with and without resting obstruction. RESULTS: At rest, 69 patients had no obstruction and 38 exhibited an intraventricular gradient, 9 of whom exhibited a decrease in gradient of at least 30 mm Hg (99.4 ± 35.5 mm Hg to 30.2 ± 14.3 mm Hg, p < 0.001) during exercise (paradoxical response to exercise [PRE]). The PRE patients presented with a significantly lower New York Heart Association clinical class and higher left ventricular volumes and arterial pressure both at rest and during exercise than HCM patients in whom the gradient increased or did not change during stress echocardiography. Finally, PRE patients exhibited a trend toward a reduced rate of cardiac events. CONCLUSIONS: Our study reports a subgroup of HCM patients, designated PRE based on a decreased intraventricular gradient during exercise. The reduced exertional obstruction may account for the better functional class and trend toward fewer clinical events in PRE patients.