Maximal Left Ventricular Wall Thickness Research Articles

Predictors of right ventricular function and size in patients with hypertrophic cardiomyopathy

We investigated factors associated with right ventricular (RV) function and size in hypertrophic cardiomyopathy (HCM) patients. Two hundred fifty-three consecutive HCM patients and 20 healthy volunteers underwent cardiac magnetic resonance examination. In addition to measuring RV function (ejection fraction—RVEF) and size (end-diastolic volume—RVEDV), each image was inspected for the presence of RV and left ventricular (LV) hypertrophy, and the maximal wall thickness of the left and right ventricles was recorded. HCM patients had higher RVEF and lower RVEDV than healthy volunteers and similar RV mass. The mean RV wall thickness was higher in HCM patients than in controls. LV late gadolinium enhancement (LGE) was present in 89.7% of patients, and RV LGE was present in 3.1% of patients (p < 0.0001). Univariate and multivariable analyses revealed that LVEF, peak LV outflow tract gradient, LV LGE, maximal LV wall thickness, and tricuspid regurgitation (TR) volume by magnetic resonance imaging were positive predictors of RVEF. In addition to TR volume, the only independent predictor of RVEF < 45% was LVEF (odds ratio = 0.80, 95% confidence interval 0.67–0.95). Multivariable analysis revealed that LVEDV and TR volume were positive predictors of RVEDV, whereas negative predictors were RVEF, maximal RV wall thickness, LV LGE, and age. Neither estimated systolic pulmonary artery pressure nor TR grade by echocardiography proved to be predictors of RVEF. There were no differences in either the maximal RV wall thickness or the maximal left ventricular (LV) wall thickness in patients stratified according to NYHA functional class (p = 0.93 and p = 0.15, respectively). There were no differences in mean RV wall thickness in patients categorised based on the number of clinical risk factors for sudden cardiac death (SCD), i.e., non-sustained ventricular tachycardia, family history of SCD, or unexplained syncope (p = 0.79). On the other hand, there was a weak positive association between RV hypertrophy and the estimated probability of SCD at 5 years (rho = 0.16, p = 0.01). RV systolic dysfunction measured as decreased RVEF was uncommon in HCM and was associated with poor LV systolic function. LV also had a significant impact on RV size.

447 Pathology of conduction tissue in cardiac amyloid: correlation with arrhythmic manifestations

Abstract Aims Pathology of conduction tissue (CT) and relative arrhythmic manifestations in living subjects with cardiac amyloid (CA) have never been reported. Methods and results In 17 out of 45 consecutive patients with CA, a left ventricular (LV) endomyocardial biopsy included CT sections. Extensive clinical examination, non-invasive (resting ECG, Holter monitoring, echocardiography), and invasive cardiac studies (selective coronary angiography, LV angiography, and LV endomyocardial biopsy) were performed in all patients. Cardiac magnetic resonance (CMR) was performed in 12 of the 17 patients (70%). CT was identified by Aschoff-Monckeberg histologic criteria associated to positive immunostaining for HCN4. Degree of CT infiltration was defined as mild when ≤ 30% of CT area was replaced by fibrous tissue and Congo red+ material, moderate in 30–70% CT area involvement and severe in &amp;gt; 70% CT cell area replacement. CT infiltration was correlated with ventricular arrhythmias, echocardiographic LV maximal wall thickness (MWT) and type of amyloid protein identified by myocardial immunohistochemistry. CMR confirmed the presence of cardiac hypertrophy with preserved systolic function in all but one patient. LGE was present in all patients, predominantly with diffuse (5/11) or subendocardial (4/11) pattern compared to focal (2/11). In 7/11 patients T1 mapping sequences have been acquired; nT1 and ECV were increase in all patients (nT1: 1171 ± 61 ms; ECV: 59.9 ± 7.5%). Mild CT involvement was observed in 5 cases; moderate in 3; severe compromise in 9. CT involvement was associated with a parallel infiltration of CT artery. CT infiltration correlated with severity of arrhythmias (Spearman rho = 0.8, P &amp;lt; 0.001) but not with age, MWT or type of amyloid protein. In particular, major ventricular tachyarrhythmias requiring pharmacologic treatment or ICD implantation occurred in 7 patients with severe, 1 patient with moderate and none with mild CT infiltration. Pacemaker implantation was required in 3 patients with complete CT area replacement. Conclusion CA associated arrhythmias correlate with severity of CT infiltration. CT involvement is independent from type and severity of CA suggesting a variable affinity of amyloid protein to CT.

Phenotypic expression and clinical outcomes in a South Asian PRKAG2 cardiomyopathy cohort

The PRKAG2 syndrome is a rare autosomal dominant phenocopy of sarcomeric hypertrophic cardiomyopathy (HCM), characterized by ventricular pre-excitation, progressive conduction system disease and left ventricular hypertrophy. This study describes the phenotype, genotype and clinical outcomes of a South-Asian PRKAG2 cardiomyopathy cohort over a 7-year period. Clinical, electrocardiographic, echocardiographic, and cardiac MRI data from 22 individuals with PRKAG2 variants (68% men; mean age 39.5 ± 18.1 years), identified at our HCM centre were studied prospectively. At initial evaluation, all of the patients were in NYHA functional class I or II. The maximum left ventricular wall thickness was 22.9 ± 8.7 mm and left ventricular ejection fraction was 53.4 ± 6.6%. Left ventricular hypertrophy was present in 19 individuals (86%) at baseline. 17 patients had an WPW pattern (77%). After a mean follow-up period of 7 years, 2 patients had undergone accessory pathway ablation, 8 patients (36%) underwent permanent pacemaker implantation (atrio-ventricular blocks—5; sinus node disease—2), 3 patients developed atrial fibrillation, 11 patients (50%) developed progressive worsening in NYHA functional class, and 6 patients (27%) experienced sudden cardiac death or equivalent. PRKAG2 cardiomyopathy must be considered in patients with HCM and progressive conduction system disease.

Progression of Myocardial Fibrosis in Hypertrophic Cardiomyopathy: A Cardiac Magnetic Resonance Study

ObjectivesThis study examined fibrosis progression in hypertrophic cardiomyopathy (HCM) patients, as well as its relationship to patient characteristics, clinical outcomes, and its effect on clinical decision making. BackgroundMyocardial fibrosis, as quantified by late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR), provides valuable prognostic information in patients with HCM. MethodsA total of 157 patients with HCM were enrolled in this study, with 2 sequential CMR scans separated by an interval of 4.7 ± 1.9 years. ResultsAt the first CMR session (CMR-1), 70% of patients had LGE compared with 85% at CMR-2 (p = 0.001). The extent of LGE extent increased between the 2 CMR procedures, from 4.0 ± 5.6% to 6.3 ± 7.4% (p < 0.0001), with an average LGE progression rate of 0.5 ± 1.0%/year. LGE mass progression was correlated with higher LGE mass and extent on CMR-1 (p = 0.0017 and p = 0.007, respectively), greater indexed left ventricular (LV) mass (p < 0.0001), greater LV maximal wall thickness (p < 0.0001), apical aneurysm at CMR-1 (p < 0.0001), and lower LV ejection fraction (EF) (p = 0.029). Patients who were more likely to have a higher rate of LGE progression presented with more severe disease at baseline, characterized by LGE extent >8% of LV mass, indexed LV mass >100 g/m2, maximal wall thickness ≥20 mm, LVEF ≤60%, and apical aneurysm. There was a significant correlation between the magnitude of LGE progression and future implantation of insertable cardioverter-defibrillators (p = 0.004), EF deterioration to ≤50% (p < 0.0001), and admission for heart failure (p = 0.0006). ConclusionsMyocardial fibrosis in patients with HCM is a slowly progressive process. Progression of LGE is significantly correlated with a number of clinical outcomes such as progression to EF ≤50% and heart failure admission. Judicious use of serial CMR with LGE can provide valuable information to help patient management.

Abstract 15889: The Role of Physical Deconditioning in Distinguishing Hypertrophic Cardiomyopathy From Athlete's Heart

Background: Vigorous systematic physical training can result in increased left ventricular wall thickness (LVWT) (i.e., “athlete’s heart”) which can be challenging to differentiate diagnostically from mild non-obstructive hypertrophic cardiomyopathy (HCM). The efficacy of a deconditioning strategy to observe changes in LVWT using cardiovascular magnetic resonance (CMR) that would support a diagnosis of athlete’s heart vs. HCM is not well established. Methods: We identified 9 highly trained patients involved in various organized sports who were referred to the Tufts Medical Center HCM center with a maximal LVWT in a diagnostic “gray area” of 13-15 mm. Maximal LVWT and other clinical and imaging variables were compared at baseline and following &gt; 3 months of deconditioning from athletic training. A clinically relevant change in maximal LVWT at the end of athletic deconditioning was defined as a decrease of ≥2 mm, consistent with “athlete’s heart”. Imaging studies were interpreted blinded to study time period. Results: Among the 9 patients (23.1 ± 12.3 years old; 100% male), 4 demonstrated a ≥ 2 mm decrease in maximal LVWT (range: 2 mm to 3 mm) to ≤ 12 mm in 3 patients and 13 mm in one patient, with an average decrease of 2.3 mm. Among these 4 patients, LV and LA size also decreased (217.3 ± 31.5 ml to 208.9 ± 16.8 ml; and 55.4 ± 10.0 mm to 51.7 ± 9.1 mm, respectively), and there was no late gadolinium enhancement, pathogenic sarcomere mutation, or family history of HCM. Parameters of diastolic function were normal prior to deconditioning. After deconditioning evaluation and significant change in LVWT, these 4 patients were judged to not have a clinical diagnosis of HCM. The remaining 5 patients had a non-significant change in maximal LVWT after deconditioning of 0.2 mm, with maximal LVWT remaining ≥ 13 mm, and no change in LV or LA cavity size (p&gt;0.2 for each). After deconditioning, these 5 patients were judged to have a clinical diagnosis of HCM. In the 9 patients that underwent a period of deconditioning, there was an average heart rate increase of 6.33. Conclusion: In athletes with maximal LVWT within the “gray zone” (13-15 mm) of overlap with HCM, athletic deconditioning using CMR to detect changes in maximal LVWT can aid in the differential diagnosis and inform management decisions.

Abstract 13424: Demographic and Echocardiographic Predictors of Later-onset Cardiac Variant of Fabry Disease Among Chinese Patients With Left Ventricular Hypertrophy

Introduction: The genetic mutation IVS4+919G&gt;A commonly found among Chinese is associated with later-onset cardiac variant of Fabry disease (FD). Patients with left ventricular hypertrophy (LVH) may be screened for FD by measuring plasma α-galactosidase activity. Objective: The aim of our study is to determine the prevalence of FD among Chinese LVH patients and to define demographic and echocardiographic predictors of FD. Methods: We measured plasma α-galactosidase activity using dried blood spot test in 500 Hong Kong Chinese patients with LVH (defined as maximal left ventricular septal or posterior wall thickness ≥13 mm on transthoracic echocardiography). LVH and deficiency in α-galactosidase activity prompted genetic analysis of galactosidase alpha gene. Demographic and echocardiographic predictors of FD were analysed. Results: There are 9 (1.8%) of 500 LVH patients (all men, age 53–74 years) had low α-galactosidase activity (0.64±0.32 μmol/L wb/hr) and all were confirmed to have the FD genotype IVS4+919G&gt;A. Among these 9 FD patients, 6 (66.7%) could be traced to the ancestral home Chaozhou (southern part of China), 4 had hypertension, but none exhibited extracardiac manifestations of FD. The left ventricular mass of FD patients ranged from 64.91–811.81 g. Ancestral home Chaozhou (odds ratio, 10.28; 95% confidence Interval, 2.52–41.94; p=0.001) and LVM ≥290 g (odds ratio, 7.39; 95% confidence Interval, 1.94–28.20; p=0.003) were predictors of FD. On receiver operating characteristic curve analysis, sensitivity and specificity of LVM ≥290 g to diagnose FD vs non-FD LVH are 67% and 86.4% respectively (area under curve, 0.8; p=0.002). Conclusion: There is a high prevalence of later-onset cardiac variant FD among Hong Kong Chinese LVH patients that is associated with IVS4+919G&gt;A genotype. Male patients with ancestral home Chaozhou and LVM ≥290 g are at an increased risk of FD among Chinese LVH patients and should be screened with dried blood spot test.

Abstract 16685: Shared Genetic Pathways Contribute to Risk of Hypertrophic and Dilated Cardiomyopathies With Opposite Directions of Effect

Introduction: Hypertrophic (HCM) and dilated (DCM) cardiomyopathies are leading causes of sudden death and heart failure requiring transplantation in young individuals. While some cases have a monogenic underlying cause, the majority remain unexplained. Objective: To better understand the contribution of common genetic variants in susceptibility and severity of cardiomyopathy. Methods: We conducted three genome-wide association studies (GWAS) and multi-trait analyses in European-ancestry individuals, including a HCM (1,733 cases) and DCM meta-analyses (5,521 cases), and a GWAS of 9 left ventricular (LV) traits in 19,260 healthy participants from the UK Biobank that underwent cardiac magnetic resonance imaging. We investigated genetic correlations between LV traits, HCM and DCM using LD score regression. We used two-sample mendelian randomization (MR) to assess the causal relationship of increased LV contractility with HCM risk. Lastly, we derived a polygenic risk score and assessed whether it modulates maximal LV wall thickness (maxLVWT) and clinical events in 368 sarcomeric mutation carriers, using linear and Cox mixed effects models, respectively. Results: We identified 16 genetic loci (15 novel) associated with HCM, 13 loci (7 novel) associated with DCM, and 23 loci associated with LV traits. We showed strong genetic correlations between LV volumes and contractility traits in the general population and cardiomyopathies, with opposing effects in HCM and DCM. Using MR, we demonstrated a causal association linking increased LV contractility with HCM risk and estimated that each unit (1%) increase in LV ejection fraction increases the risk of HCM by 37% (95% CI 10%-69%, P=0.004). Lastly, a polygenic risk score (PRS HCM ) derived from the HCM GWAS was associated with maxLVWT (P=0.0001) and clinical events (P=0.009) in carriers of HCM-causing rare variants. Conclusion: Our findings highlight the contribution of common genetic variants in susceptibility for HCM and DCM, and in severity in sarcomeric mutation carriers. Our data also point to increased LV contractility as an important mechanism of HCM independently of sarcomere activating rare variants, and highlight the potential clinical relevance of PRS for risk stratification in HCM.

Left ventricular septal convexity in differentiating hypertrophic cardiomyopathy from hypertensive heart disease – cardiac MRI study

Abstract Background Subjects with hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD) have left ventricular hypertrophy (LVH). It is a common clinical problem to distinguish HCM from HHD. Septal convexity (SC) into the left ventricle is increased in subjects with hypertrophic cardiomyopathy (HCM)-causing mutations with and without LVH. Purpose Our objective was to study if SC by cardiac magnetic resonance (CMR) differentiates between HCM and HHD. Methods We measured SC in 29 subjects with hypertension and LVH (left ventricular maximal wall thickness (LVMWT) ≥13 mm), in 49 subjects with HCM (LVMWT ≥13 mm) caused by the D175N mutation in the alpha-tropomyosin (TPM1) or the Q1061X mutation in the myosin binding protein C (MYBPC3) genes, and in 20 healthy controls with no LVH. SC into the LV was measured in end-diastolic 4-chamber images as the maximal distance between LV septal endocardial border and a line connecting septal mid-wall points at the level of tricuspid valve insertion and at the level of apical right ventricular insertion on the LV. Results Subjects with HCM had significantly increased septal convexity compared to subjects with HHD both in non-indexed and in BSA-indexed measurements (10.7±4.0 mm vs 4.9±2.7 mm, P&amp;lt;0.001 and 5.5±2.1 mm/m2 vs 2.4±1.3 mm/m2, P&amp;lt;0.001). To differentiate between HCM and HHD, septal convexity cutoff value of 7.85 mm performed best with sensitivity of 77% and specificity of 90%. BSA-indexed SC cutoff value of 3.68 mm differentiated between HCM and HHD with sensitivity of 81% and specificity of 86%. Conclusions CMR derived septal convexity is easily measured and is useful in discriminating between HCM caused by sarcomere mutations versus HHD. Measurement of septal convexity Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Finnish Foundation of Cardiovascular Research, the special governmental subsidy for health sciences research of the University Hospital of Kuopio

Prognostic impact of suspected cardiac amyloidosis in aortic stenosis patients referred for transcatheter aortic valve implantation

Abstract Background The prevalence of cardiac amyloidosis (CA) and aortic stenosis (AS) both increase with age. Transcatheter aortic valve implantation (TAVI) expands the number of patients (P) eligible for treatment of AS, emphasizing the need to understand the prevalence of CA in AS and its prognostic associations. Echocardiography with speckle tracking has emerged as a useful method to enhance the clinical suspicion and to provide prognostic information. Purpose To estimate the prevalence of CA in P with severe AS referred for TAVI and to evaluate the impact of concomitant CA in prognosis. Methods 94 consecutive AS P who underwent TAVI with maximum left ventricular wall thickness (LVWT)&amp;gt;12 mm were retrospectively identified. Clinical data, pre TAVI echocardiographic parameters and follow up (FU) data regarding all-cause mortality and MACE (including all-cause mortality, admission for heart failure, pacemaker implantation and stroke) were analysed. We registered apical sparing pattern in bull's eye plots (ASPB), calculated relative apical longitudinal strain formula (RALS) [average apical LS/(average basal LS + mid-LS)] and ejection fraction/global longitudinal strain (EF/GLS) ratio. Results Mean age was 82.2±5.8 years (Y), with 43 men (45.7%). 27.7% were in NYHA functional class II, 64.9% in functional class III and 7.4% in functional class IV. Median EF was 57±15% and 26.6% presented EF&amp;lt;50%. Suspected CA evaluated by ASPB was found in 39 P (41.5%) and RALS &amp;gt;1 was identified in 22 P (23.4%). An EF/GLS ratio &amp;gt;4.1 was obtained in 53 P (56.4%). Over a median follow-up of 13.4±25.8 months, 28 deaths (29.8%) and 31 MACEs (33.0%) occurred. The presence of ASPB was associated with increased all-cause mortality (33.3% vs. 5.6%, p=0.002) and MACE (48.7% vs 22.2%, p=0.01). RALS&amp;gt;1 correlated also with all-cause mortality (31.8% vs. 12.5%, p=0.04) and with new bundle branch block and indication for pacemaker implantation (46.2% vs 37.0%, p=0.05). P with GLS&amp;gt;−14.8% and ASPB had significantly worse prognosis regarding all-cause mortality (p=0.003) and MACE (p=0.007). Kaplan–Meier survival analysis showed that survival was significantly worse for P with ASPB (log-rank 0.002). With multivariate Cox regression analysis, ASPB was independently associated with all-cause mortality (HR=4.49, p=0.039). Conclusions Suspected CA appears prevalent among patients with AS and associates with all-cause mortality. The importance of screening for CA in older AS patients and optimal treatment strategies in those with CA warrant further investigation, especially in the era of transcatheter aortic valve implantation. Funding Acknowledgement Type of funding source: None

Clinical characteristics and natural history of PRKAG2 syndrome

Abstract Purpose Mutations in the PRKAG2 gene cause a syndrome characterized by hypertrophic cardiomyopathy, conduction disease and ventricular preexcitation. Only a small number of cases have been reported, and the natural history of the disease is poorly understood. The aim of this study is to describe phenotype and natural history of PRKAG2 mutation in a large multicenter international cohort. Methods We retrospectively studied clinical, electrocardiographic and echocardiographic data from 90 individuals with PRKAG2 mutations (53% males, 33±21 years) from 27 centers. Results At baseline evaluation, 93% of patients were in NYHA functional class I-II. Maximum left ventricular (LV) wall thickness was 18±8 mm and LV hypertrophy (LVH) was present in 60 (67%) subjects at baseline. LV ejection fraction was 61±12%. Seventeen pactients (19%) had a pacemaker (mean age at implantation 37±15and 16 (18%) had atrial fibrillation (AF) (mean age 41±23 years) and 33% had ventricular preexcitation or had undergone an accessory pathway ablation. After a median follow-up of 6 years (IQR:2.3–13.9), 71% of individuals had LVH, 29% had AF, 21% a de novo pacemaker (mean age at implantation 38±18 years), 14% required admission for heart failure (HF), 8% experienced sudden cardiac death or equivalent, 4% required a heart transplant and 13% died. Conclusions PRKAG2 syndrome is a severe, progressive cardiomyopathy characterized by high rates of AF, conduction disease, advanced HF and life-threatening arrhythmias. Outcome is not clearly related to the classical features of preexcitation and severe LVH, which are not always present. Natural history of PRKAG2 syndrome Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Instituto de Salud Carlos III (ISCIII)

Biomarker changes with systolic anterior motion of the mitral valve in cats with hypertrophic cardiomyopathy.

BackgroundN‐terminal pro B‐type natriuretic peptide (NT‐proBNP) and cardiac troponin‐I (cTnI) are biomarkers commonly evaluated in cats with suspected heart disease. Many cats with hypertrophic cardiomyopathy (HCM) have systolic anterior motion of the mitral valve (SAM), but its influence on circulating NT‐proBNP or cTnI concentrations is currently unknown.Hypothesis/ObjectivesCats with HCM and SAM (HCMSAM+) have higher NT‐proBNP and cTnI concentrations than do cats with HCM but without SAM (HCMSAM−).AnimalsOne hundred forty cats with HCM: 70 with SAM and 70 without SAM.MethodsRetrospective case‐to‐case study. Cats were recruited if diagnosed with HCM by echocardiography and results were available for NT‐proBNP or cTnI concentrations or both. Cats with SAM were matched to those without SAM for clinical presentation, left atrial (LA) size and left ventricular (LV) fractional shortening.ResultsA total of 119 NT‐proBNP and 123 cTnI results were available. The HCMSAM+ cats had higher median concentrations than did HCMSAM− cats for NT‐proBNP (729 pmoL/L; interquartile range [IQR], 275‐1467 versus 65 pmoL/L; IQR, 25‐271; P < .001) and cTnI (0.27 ng/mL; IQR, 0.10‐0.81 versus 0.07 ng/mL; IQR, 0.01‐0.43; P = .002). In general linear models for both NT‐proBNP and cTnI, the independent explanatory variables were SAM, congestive heart failure, maximal LV wall thickness, and LA size.Conclusions and Clinical ImportanceFor cats with HCM and equivalent LA size and LV systolic function, those with SAM had higher NT‐proBNP and cTnI concentrations than did those without SAM. Presence of SAM should be considered when interpreting biomarker concentrations in cats with HCM.

Left Ventricular Outflow Tract Obstruction in Hypertrophic Cardiomyopathy: The Utility of Myocardial Strain Based on Cardiac MR Tissue Tracking

Myocardial strain for assessment of hypertrophic cardiomyopathy (HCM) is of importance and may play a role in identifying obstruction in HCM patients. To evaluate the utility of myocardial strain for detecting left ventricular (LV) outflow tract (LVOT) obstruction in HCM patients based on magnetic resonance tissue tracking. Retrospective. In all, 44 adult HCM patients with LVOT obstruction and 108 adult HCM patients without LVOT obstruction. 1.5 T; Steady-state free-precession cine sequence; phase-sensitive inversion-prepared segmented gradient echo sequence for late gadolinium enhancement (LGE) imaging. Strain parameters including the local and global levels of LV myocardium and the subtraction (Sub) of myocardial strain variables between interventricular septal segments (IVSS) and noninterventricular septal segments (NIVSS) were measured for differentiating HCM with obstruction from nonobstruction. Average and maximum LV wall thickness (Average and Maximum LVWT) were also analyzed. Univariate and multivariate logistic regression analysis, area under the receiver operating characteristic (ROC) curve (AUC), intraclass correlation coefficient. In multivariate analysis, Average LVWT, Maximum LVWT, and the subtraction of radial peak strain (Sub Radial PS) between NIVSS and IVSS were independently associated with LVOT obstruction. The AUCs were 0.731, 0.840, and 0.890 for Average LVWT, Maximum LVWT, and Sub Radial PS, respectively. Sub Radial PS (cutoff value: 8.1%) demonstrated the highest sensitivity of 75.0% and a high specificity of 87.9% for identifying LVOT; Maximum LVWT (cutoff value: 22.9 mm) showed good sensitivity (72.7%) and specificity (83.3%). Combining Maximum LVWT >22.9 mm and Sub Radial PS > 8.1% achieved a better diagnostic performance (specificity 95.4%, sensitivity 70.5%). Combining Maximum LVWT >22.9 mm and Sub Radial PS >8.1% holds promise for objectively evaluating LVOT obstruction in HCM patients with very high specificity and acceptable sensitivity. 3 TECHNICAL EFFICACY STAGE: 2.

Myocardial Work in Nonobstructive Hypertrophic Cardiomyopathy: Implications for Outcome

Noninvasive left ventricular (LV) pressure-strain loop analysis is emerging as a new echocardiographic method to evaluate LV function, integrating longitudinal strain by speckle-tracking analysis and sphygmomanometrically measured blood pressure to estimate myocardial work. The aims of this study were (1) to describe global and segmental myocardial work in patients with hypertrophic cardiomyopathy (HCM), (2) to assess the correlation between myocardial work and other echocardiographic parameters, and (3) to evaluate the association of myocardial work with adverse outcomes. One hundred ten patients with nonobstructive HCM (mean age, 55±15years; 66% men), with different phenotypes (apical, concentric, and septal hypertrophy), and 35 age- and sex-matched healthy control subjects were included. The following myocardial work indices were included: myocardial work index, constructive work (CW), wasted work, and cardiac efficiency. The combined end point included all-cause mortality, heart transplantation, heart failure hospitalization, aborted sudden cardiac death, and appropriate implantable cardioverter-defibrillator therapy. Mean global CW (1,722±602 vs 2,274±574mm Hg%, P<.001), global cardiac efficiency (93% [89%-95%] vs 96% [96%-97%], P<.001), and global MWI (1,534±551 vs 1,929±473mm Hg%) were significantly reduced, while global wasted work (104mm Hg% [66-137mm Hg%] vs 71mm Hg% [49-92mm Hg%], P<.001) was increased in patients with HCM compared with control subjects. Segmental impairment in CW colocalized with maximal wall thickness (HCM phenotype), and global CW correlated with LV wall thickness (r=-0.41, P<.001), diastolic function (r=-0.27, P=.001), and QRS duration (r=-0.28, P=.001). Patients with global CW>1,730mm Hg% (the median value) experienced better event-free survival than those with global CW<1,730mm Hg% (P<.001). Myocardial work, assessed noninvasively using echocardiography and blood pressure measurement, is reduced in patients with nonobstructive HCM; it correlates with maximum LV wall thickness and is significantly associated with a worse long-term outcome.

Clinical Features and Natural History of PRKAG2 Variant Cardiac Glycogenosis

BackgroundPRKAG2 gene variants cause a syndrome characterized by cardiomyopathy, conduction disease, and ventricular pre-excitation. Only a small number of cases have been reported to date, and the natural history of the disease is poorly understood. ObjectivesThe aim of this study was to describe phenotype and natural history of PRKAG2 variants in a large multicenter European cohort. MethodsClinical, electrocardiographic, and echocardiographic data from 90 subjects with PRKAG2 variants (53% men; median age 33 years; interquartile range [IQR]: 15 to 50 years) recruited from 27 centers were retrospectively studied. ResultsAt first evaluation, 93% of patients were in New York Heart Association functional class I or II. Maximum left ventricular wall thickness was 18 ± 8 mm, and left ventricular ejection fraction was 61 ± 12%. Left ventricular hypertrophy (LVH) was present in 60 subjects (67%) at baseline. Thirty patients (33%) had ventricular pre-excitation or had undergone accessory pathway ablation; 17 (19%) had pacemakers (median age at implantation 36 years; IQR: 27 to 46 years), and 16 (18%) had atrial fibrillation (median age 43 years; IQR: 31 to 54 years). After a median follow-up period of 6 years (IQR: 2.3 to 13.9 years), 71% of subjects had LVH, 29% had AF, 21% required de novo pacemakers (median age at implantation 37 years; IQR: 29 to 48 years), 14% required admission for heart failure, 8% experienced sudden cardiac death or equivalent, 4% required heart transplantation, and 13% died. ConclusionsPRKAG2 syndrome is a progressive cardiomyopathy characterized by high rates of atrial fibrillation, conduction disease, advanced heart failure, and life-threatening arrhythmias. Classical features of pre-excitation and severe LVH are not uniformly present, and diagnosis should be considered in patients with LVH who develop atrial fibrillation or require permanent pacemakers at a young age.

Contrast-Enhanced Echocardiographic Measurement of Left Ventricular Wall Thickness in Hypertrophic Cardiomyopathy: Comparison with Standard Echocardiography and Cardiac Magnetic Resonance

Left ventricular wall thickness (LVWT) measurement is key in the diagnostic and prognostic assessment of hypertrophic cardiomyopathy (HCM). Recent investigations have highlighted discrepancies in LVWT by cardiac magnetic resonance (CMR) and standard echocardiography (S-Echo) in this condition. The aim of this study was to elucidate the role of contrast-enhanced echocardiography (C-Echo) to optimize LVWT measurement in patients with HCM. Fifty patients with HCM were prospectively enrolled, undergoing S-Echo, C-Echo, and CMR. Blinded LVWT measurements were performed according to a 16-segment left ventricular model using all three imaging techniques. Agreement between both echocardiographic modalities and CMR (as the reference technique) at the segmental level was tested using Bland-Altman analyses. Reproducibility on segmental measurements by S-Echo and C-Echo was also investigated. Patients' mean age was 47±21years, and 35 (70%) were men. Maximal mean LVWT by S-Echo (20.1±3.8mm) was greater than the values derived using C-Echo (17.6±4.0mm, P<.01) and CMR (17.7±4.5mm, P<.01), with no statistically significant difference between the latter two. Segmental Bland-Altman models demonstrated globally smaller bias and narrower 95% limits of agreement for C-Echo compared with S-Echo. Across all left ventricular segments, LVWT by C-Echo was 2.4mm lower (range, 1.0-2.5mm) than that derived by S-Echo, which accounted for a 25% intertechnique difference. Regarding maximal LVWT, the mean absolute difference between C-Echo and S-Echo was 3.0±1.9mm (range, 0.0-7.9mm), which represented a 15% intertechnique change. Data analyses demonstrated globally less intra- and interobserver variability in segmental LVWT derived from C-Echo compared with S-Echo. C-Echo rendered LVWT measurements closer to those derived by the reference technique (CMR) and improved reproducibility compared with S-Echo. C-Echo represents a suitable tool for LVWT measurement in patients with HCM as an alternative to CMR whenever this is not available or possible.

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 ± 17years, 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 2.4years, 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.

The role of three-dimensional speckle tracking imaging in the diagnosis of immunoglobulin light-chain cardiac amyloidosis with normal left ventricular ejection fraction

Objective To explore the value of three-dimensional speckle tracking imaging (3D-STI) in the diagnosis of immunoglobulin light-chain cardiac amyloidosis(AL-CA) patients with normal left ventricular ejection fraction (LVEF). Methods A total of 92 consecutive patients diagnosed with systemic immunoglobulin light chain amyloidosis(sAL) and with normal LVEF from October 2014 to January 2018 in Xijing Hospital were enrolled.Based on the diagnostic criteria of cardiac involvement, the patients were divided into AL-CA group (52 cases) and immunoglobulin light chain amyloidosis (AL) group (40 cases). The clinical data and serological markers of the patients were collected, the conventional echocardiography and full-volume three dimensional dynamic images were acquired, left ventricular global longitudinal strain (GLS), global radial strain (GRS), global circumferential strain (GCS), and global area strain (GAS) were analyzed using off-line TomTec software. The differences between the two groups were compared. Results Compared with the AL group, the NT-proBNP of AL-CA group was significantly higher (P 0.05). Compared with the AL group, the maximal left ventricular wall thickness, left ventricular mass index, left atrial volume index, and E/e′ in the AL-CA group were significantly increased (all P 0.05). Compared with the AL group, GLS, GAS, and GRS were significantly lower in AL-CA group (all P 0.05). The ROC curve analysis showed that the cut-off values discriminating cardiac involvement were 16.09% for GLS, 36.54% for GAS and 31.90% for GRS. Conclusions 3D-STI measurements of left ventricular myocardial mechanics could detect cardiac involvement in patients with sAL amyloidosis, and provides a new method for diagnosis of AL-CA. Key words: Echocardiography; Three-dimensional speckle tracking imaging; Immunoglobulin light-chain cardiac amyloidosis; Strain

Scleraxis as a prognostic marker of myocardial fibrosis in hypertrophic cardiomyopathy (SPARC) study.

Interstitial fibrosis is a histopathological hallmark of hypertrophic cardiomyopathy (HCM). Although extracellular matrix (ECM) biomarkers, including matrix metalloproteinases, are overexpressed in HCM patients, they do not correlate with sudden cardiac death (SCD) risk. The objective of this study was to determine whether scleraxis, a transcription factor that regulates collagen gene expression, is detectable in HCM patients and correlates with disease burden. Between 2017 and 2018, a total of 46 HCM patients were enrolled (58 ± 14 years (31 males, 15 females)) with a mean 5 year SCD risk of 2.3% ± 1.3%. Cardiac MRI confirmed HCM in all patients with a mean interventricular septal thickness of 20 ± 2 mm. Late gadolinium enhancement (LGE) was present in 32 (70%) study participants occupying 18% ± 7% of the left ventricular (LV) myocardium. Serum scleraxis levels were significantly higher in the HCM patients by approximately twofold as compared to controls (0.76 ± 0.06 versus 0.32 ± 0.02 ng/mL, p < 0.05). No correlation was demonstrated between serum scleraxis levels and markers of disease severity in HCM patients, including maximum LV wall thickness, %LGE, and SCD risk factors. Serum scleraxis is elevated in the HCM population. Future studies are warranted to evaluate the prognostic value of scleraxis in identifying high-risk HCM patients who require aggressive management for prevention of SCD.

350 Impact of Using Maximal Left Ventricular wall Thickness Measured by Cardiac Magnetic Resonance Imaging on Risk of Sudden Cardiac Death at 5 Years Using ESC HCM-SCD Risk Calculator in Patients With Hypertrophic Cardiomyopathy

350 Impact of Using Maximal Left Ventricular wall Thickness Measured by Cardiac Magnetic Resonance Imaging on Risk of Sudden Cardiac Death at 5 Years Using ESC HCM-SCD Risk Calculator in Patients With Hypertrophic Cardiomyopathy

P827 Left atrial contractile function is the main correlate of atrial fibrillation in patients with hypertrophic cardiomyopathy

Abstract Background Given the negative impact of atrial fibrillation (AF) in patients (pts) with hypertrophic cardiomyopathy (HCM), finding new and better predictors of AF is clinically important, especially for patients considered at low or intermediate risk based on current recommendations (i.e. left atrial diameter, LAD &amp;lt;45 mm). Purpose To assess the relationship between left atrial (LA) remodelling (size and function) and the presence of paroxysmal AF in HCM patients with and without increased LAD. Methods A comprehensive echocardiogram was performed in 110 consecutive pts (52 ± 17 years, 50 men) with HCM, in sinus rhythm. Indexed LA volume (LAVi), maximum left ventricular wall thickness (LVWT), LV ejection fraction, E/e’ ratio were determined. Global longitudinal LV strain (GLS) and LA strain parameters (LAɛ, SSr, ASr) were assessed by speckle tracking echocardiography. Patients were divided into two groups according to the presence (30 pts) or absence (80 pts) of documented paroxysmal AF (24/48 h ambulatory ECG recordings) Results Patients with AF were older than pts without AF (p &amp;lt; 0.001). LAD, LAVi, E/e’ were significantly higher, while LAɛ, ESr, ASr were significantly lower in pts with AF compared to pts without AF (p &amp;lt; 0.05 for all). There were no significant differences between pts with and without AF regarding: gender, LVWT, GLS, the presence and severity of LV outflow tract obstruction (p &amp;gt; 0.05 for all). The correlates of AF in the whole HCM study population were: age (OR = 1.05, p = 0.001), ASr (OR = 10.1, p &amp;lt; 0.001), LAVi (OR = 1.03, p = 0.004), LAD (OR = 1.2, p = 0.001), E/e’(OR = 1.05, p = 0.02) and mitral regurgitation degree (OR = 1.6, p = 0.04). ASr had the best area under the curve (AUC: 0.74) with a cutoff of -0.88 s-1 for identifying HCM patients with AF (sensitivity: 80%, specificity: 65%). At multivariable logistic regression analysis, age, LAVi and ASr emerged as the only independent correlates of AF. 14 of the 71 patients with a LAD &amp;lt; 45 mm had paroxysmal AF. In this selected population, pts with AF were older (p = 0.001), had higher values for E/e’ (p = 0.04) and lower values for ASr (p = 0.02) than pts without AF. Moreover, in this subgroup of pts, at multivariable logistic regression analysis, ASr correlated with AF independently of age, LA dimensions, LV hypertrophy or E/e’ (OR = 10.008, 95% CI 1.297-77.219, p = 0.02). Conclusions In pts with HCM, age, LAVi and ASr, were independently related to the presence of AF, while LAD was not. Moreover, in the subgroup of HCM pts with LAD &amp;lt; 45 mm, ASr (reflecting LA contractile function) was the only LA remodelling parameter correlated with the presence of AF. The assessment of LA volume and function can provide further insights into the risk stratification of pts with HCM, especially in pts considered at lower risk for AF based on the assessment of classical risk parameters, such as LAD.