Hypertrophic Cardiomyopathy Group Research Articles

Evolutionary dissection of mtDNA hg H: a susceptibility factor for hypertrophic cardiomyopathy

Mitochondrial DNA (mtDNA) haplogroup (hg) H has been reported as a susceptibility factor for hypertrophic cardiomyopathy (HCM). This was established in genetic association studies, however, the SNP or SNP’s that are associated with the increased risk have not been identified. Hg H is the most frequent European mtDNA hg with greater than 80 subhaplogroups (subhgs) each defined by specific SNPs. We tested the hypothesis that the distribution of H subhgs might differ between HCM patients and controls. The subhg H distribution in 55 HCM index cases was compared to that of two Danish mtDNA hg H control groups (n = 170 and n = 908, respectively). In the HCM group, H and 12 different H subhgs were found. All these, except subhgs H73, were also found in both control groups. The HCM group was also characterized by a higher proportion of H3 compared to H2. In the HCM group the H3/H2 proportion was 1.7, whereas it was 0.45 and 0.54 in the control groups. This tendency was replicated in an independent group of Hg H HCM index cases (n = 39) from Queensland, Australia, where the H3/H2 ratio was 1.5. In conclusion, the H subhgs distribution differs between HCM cases and controls, but the difference is subtle, and the understanding of the pathogenic significance is hampered by the lack of functional studies on the subhgs of H.

Advanced myocardial characterization in hypertrophic cardiomyopathy: feasibility of CMR-based feature tracking strain analysis in a case-control study.

This study aimed to evaluate the feasibility and reproducibility of using cardiovascular magnetic resonance feature tracking (CMR-FT) for analysis of bi-ventricular strain and strain rate (SR) in hypertrophic cardiomyopathy (HCM) patients as well as to explore the correlation between right ventricular (RV) and left ventricular (LV) deformation. A total of 60 HCM patients and 48 controls were studied. Global and segmental peak values of bi-ventricular longitudinal, circumferential, radial strain, and systolic SR were analyzed. Pearson analysis was performed to investigate the correlation of RV and LV deformation. Intra-observer and inter-observer reproducibility were also assessed. LV mass in the HCM group was significantly higher than that in the control group. LV end-systolic and end-diastolic volume and RV end-systolic and end-diastolic volume in the HCM group were all significantly lower than the correlated parameters in the control group (p < 0.001, respectively), whereas no statistical difference was found in ejection fraction (p > 0.05). Global longitudinal strain (GLS), global longitudinal strain rate (GLSR), global circumferential strain (GCS), global circumferential strain rate (GCSR), global radial strain (GRS), and global radial strain rate (GRSR) of the LV and RV were all significantly lower than the control group, and segmental strain and SR were also true (p < 0.001, respectively). Bi-ventricular strain and SR measurements were highly reproducible at both intra- and inter-observer levels. Additionally, Pearson analysis showed RV GCS, GLS, and GRS positively correlated with LV GCS, GLS, and GRS (r = 0.713, p < 0.001; r = 0.728, p < 0.001; r = 0.730, p < 0.001, respectively). CMR-FT is a promising approach to analyze impairment of global and segmental myocardium deformation in HCM patients non-invasively and quantitatively. • CMR-FT allows for advanced myocardial characterization with high reproducibility. • As compared with controls, HCM patients have significant differences in CMR-FT strain analysis while ejection fraction was similar. • CMR-FT may serve as an early biomarker of HCM in subjects at risk.

Combined right and left ventricular mechanical dispersion enhance the arrhythmic risk stratification in hypertrophic cardiomyopathy

BackgroundVentricular arrhythmias are the most frequent cause of sudden cardiac death in individuals with hypertrophic cardiomyopathy (HCM). In the present study we investigated if combined left ventricular (LV) and right ventricular (RV) mechanical dispersion (MD) are correlated with ventricular arrhythmias. We aimed also to analyze if MD enhances the arrhythmic risk stratification in HCM. MethodsThe cohort included 47 subjects with HCM and 36 healthy individuals. All the studied population underwent clinical, 24-h electrocardiographic (ECG) monitoring for detection and description of non-sustained ventricular tachycardia (NSVT) in terms of number of events, maximal rate and length and comprehensive transthoracic echocardiography, including strain rate imaging. MD was calculated as standard deviation of time from the peak of R wave on ECG to maximum LV or RV shortening in 17 LV and 3 RV segments. ResultsHCM subjects with NSVT on ECG monitoring had increased LVMD (81±18ms vs 42±8ms) and RVMD (52±26 vs 25±23ms) compared with the HCM group without NSVT or compared with the healthy controls. On receiver operating characteristic curves the cut-off values associated with optimal specificity and sensitivity were 62ms for LVMD and 39ms for RVMD. LVMD (OR=1.86, 95% CI 1–1.06, p=0.01) and RVMD (OR=1.04, 95% CI 1.01–1.07, p=0.003) were the only independent variables that correlated with longer and faster NSVT and furthermore improved the risk stratification of NSVTs. ConclusionsIn a cohort of subjects with HCM, LVMD and RVMD correlates with the presence of NSVT on ECG monitoring. Combined LVMD and RVMD may improve the risk stratification of HCM with NSVT.

Outcomes of Left Ventricular Assist Device for Patients with Hypertrophic Cardiomyopathy

The treatment of end stage hypertrophic cardiomyopathy (HCM) is sometimes complicated because some cases of HCM are not suitable for LVAD. Scarce data exist on outcomes of continuous-flow (CF) LVAD support in these challenging patient cohorts. We evaluated the clinical outcomes of LVAD therapy for patients with HCM. Between 2005 and 2018, 191 consecutive patients underwent CF-LVAD implantation at Osaka University Hospital. Of these, we retrospectively compared the clinical outcomes between HCM (n=29) and idiopathic dilated cardiomyopathy (DCM, n=106) patients with CF-LVAD support. The primary outcome was all-cause mortality. Median follow-up time was 815 days (interquartile range [IQR]: 373-1172). There were no significant differences between the two groups about patient's baseline characteristics. HCM group had significant smaller left ventricle (LV) than DCM group. [LV end-diastolic diameter: 67 (IQR: 55-71) vs 72 (IQR: 62-82), p<0.05] In short-term outcome, there was no significant difference about in-hospital mortality. [HCM vs DCM; 2 (7%) vs 4 (4%), p=0.47] Regarding postoperative complication, HCM group required more frequent right ventricular assist device (RVAD) support than DCM group. [8 (28%) vs 4 (4%), p<0.01] In long-term outcome, the overall survival rate at 1 and 3 years was 89% and 74% in HCM group, 92% and 90% in DCM group, respectively (p=0.03). (Figure A) During the follow up period, HCM group had significantly more LVAD pump exchanges than DCM group. [hazard ratio, 4.10 95% confidence interval, 1.67 to 10.1; p=0.002] (Figure B) CONCLUSION: The long-term outcome of LVAD therapy for patients with HCM is still challenging. In particular, careful attention is required for right heart function.

Cardiac Transplantation for Cancer Involving the Heart: Results from 35 Years of Transplants from the ISHLT Registry

Cancer of the heart is rare but lethal. For those few patients with primary or metastatic cardiac malignancy, options for treatment are limited. Heart transplantation as a treatment for cardiac malignancy has been suggested by several small case series but outcomes data are scarce. We present a series of 104 heart transplants performed for any cancer involving the heart from 1982 to 2017 from the International Society of Heart and Lung Transplant (ISHLT) Thoracic Organ Transplant Registry. 104 heart recipients were identified with cancer as the indication for transplant. We performed Kaplan-Meier survival analyses matching the 104 cancer patients with 104 patients receiving heart transplants for hypertrophic cardiomyopathy (HCM) because both cohorts are young with few co-morbidities. Matching was based on age, gender and transplant year. Median survival in the cancer cohort was 3.6 years (95% Confidence Interval (CI) = 1.2,7.2) compared to 17.5 (CI 16.6, 19.0) years in the matched HCM group (Table). Mortality was not significantly different at 30 days, but at the end of 5 years, more than half of the cancer patients were dead (Figure). 27 of these deaths were due to cancer. In the Cox-proportional hazards model, transplant for cardiac malignancy correlated with mortality (HR=1.8 (CI=1.1-3.1), p=0.02). This study presents the largest retrospective series to date of heart transplantations performed for cancer. These patients had significantly increased mortality due to tumor recurrence. This raises a concern about allocating donor hearts for malignancy.

Frequency and Significance of Coronary Artery Disease and Myocardial Bridging in Patients With Hypertrophic Cardiomyopathy

The etiology of chest pain in hypertrophic cardiomyopathy (HC) is diverse and includes coronary artery disease (CAD) as well as HC-specific causes. Myocardial bridging (MB) has been associated with HC, chest pain, and accelerated atherosclerosis. We compared HC patients with age-, gender- and CAD pre-test probability-matched outpatients presenting with chest pain to investigate differences in the presence of MB and CAD using coronary computed tomography angiography (CCTA). We studied 84 HC patients who underwent CCTA and compared these with 168 matched controls (age 54 ± 11 years, 70% men, pre-test probability 12% [5% to 32%]). MB, calcium score, plaque morphology and presence and extent of CAD were assessed for each patient. Linear mixed models were used to assess differences between cases and controls. MB was more often seen in HC patients (50% vs 25%, p <0.001). Calcium score and the presence of obstructive CAD were similar in both groups (9 [0 to 225] vs 4 [0 to 82] and 18% vs 19%; p = 0.22 and p = 0.82). In the HC group, MB was associated with pathogenic DNA variants (p = 0.04), but not with the presence of chest pain (74% vs 76%, p = 0.8), nor with worse outcome (log-rank p = 0.30). In conclusion, the prevalence and extent of CAD was equal among patients with and without HC, demonstrating that pre-test risk prediction using the CAD Consortium clinical risk score performs well in HC patients. MB was twice as prevalent in the HC group compared with matched controls, but was not associated with chest pain or decreased event-free survival in these patients.

Sex Differences in Regulating the Cardiac Transcriptome within a Murine Model for Hypertrophic Cardiomyopathy

Heart disease remains the number one killer of women in the United States. Nonetheless, studies in women and female animal models continue to be underrepresented in cardiac research. Susceptibility to hereditary hypertrophic cardiomyopathy, the most commonly inherited cardiac disorder, has been tied to sarcomeric protein variants. Among the susceptible genes, TNNC1—encoding cardiac troponin C (cTnC)—has contributed to a substantial hypertrophic cardiomyopathy (HCM) phenotype in mice. In this study we sought to characterize the sexual dimorphism observed within cardiac hemodynamics, morphology, and gene expression of a TNNC1 HCM mouse model. Adult age-matched male and female mice bearing the knock-in HCM-associated point mutation of alanine to valine in position 8 of cTnC (-A8V) were studied. The hemodynamics and cardiac morphology of the HCM mice were significantly altered. Isovolumetric contraction time was significantly higher in the female HCM mice, and female measurements for the majority of parameters trended toward the more severe disease presentation. RNA sequencing revealed several altered canonical pathways among the HCM vs WT groups including an increase in the EIF2 signaling, ILK signaling, actin nucleation by ARP-WASP complex, regulation of actin-based motility by Rho, VDR/RXR activation, and glutathione redox reactions pathways within the HCM mice. In contrast, the valine degradation, TCA Cycle II, Methionine Degradation, and Inositol Phosphate Compound pathways were notably down regulated in the HCM mice. Interestingly, seven of the genes that were differentially expressed in both the WT and HCM male vs female comparisons changed directions in fold change between the sexes. These data suggest a sexually-dimorphic HCM phenotype and identify several key pathways and genes that could be critical to sex differences seen in disease manifestation. NIH R01HL103840 and F31HL137408.

Long-Term Performance of Right Ventricular Implantable Cardioverter-Defibrillator Leads in Arrhythmogenic Right Ventricular Cardiomyopathy and Hypertrophic Cardiomyopathy.

Patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and hypertrophic cardiomyopathy (HCM) implanted with implantable cardioverter-defibrillators (ICDs) may show a large decrease in R-wave amplitude during long-term follow-up. However, it is unclear whether this decrease is higher in these patients than in those without structural heart disease. This study investigated ICD-lead intracardiac parameters over a long duration in patients with ARVC and HCM and compared these parameters with those of a control group. We included 50 patients (mean age, 55.2 ± 17.2 years; 26% female) with ICD leads in the right ventricular apex, and compared 7 ARVC and 14 HCM patients with 29 control patients without structural heart disease. ICD-lead parameters, including R-wave amplitude, pacing threshold, and impedance during follow-up, were compared. The difference in these parameters between the time of implantation and year 5 were also compared. There were no significant differences in R-wave amplitude at implantation among the 3 groups. The change in R-wave amplitude between the time of implantation and year 5 was significantly greater in the ARVC group (-3.3 ± 5.4 mV, P = 0.012) in comparison to the control group (1.3 ± 2.8 mV); the HCM group showed no significant difference (-0.4 ± 2.3 mV, P = 0.06). Thus, in the ARVC group, R-wave amplitude at year 5 was significantly lower than that in the control group (5.7 ± 4.8 mV versus 12.5 ± 4.5 mV, P = 0.001). In ARVC patients with ICDs, ventricular sensing is likely to deteriorate during long-term follow-up; however, in HCM patients, sensing may not deteriorate.

The relationship between β1 -adrenergic and M2 -muscarinic receptor autoantibodies and hypertrophic cardiomyopathy.

What is the central question of this study? The concentrations of β1 -adrenergic receptor and M2 -muscarinic receptor autoantibodies in hypertrophic cardiomyopathy (HCM) patients and the relationship between the cardiac autoantibodies and clinical manifestations of HCM have rarely been reported. What is the main finding and its importance? We found that the concentrations of the two autoantibodies in HCM patients were significantly higher than those in control subjects. Furthermore, we found that the concentrations of the two autoantibodies could reflect myocardial injury and diastolic dysfunction in HCM patients to some extent and might be involved in the occurrence of arrhythmia. These findings might be valuable in exploration of the mechanisms of occurrence and progression of HCM. Increasing attention is being given to the role of immunological mechanisms in the development of heart failure. The purpose of this study was to investigate the concentration of serum β1 -adrenergic receptor autoantibody (β1 -AAb) and M2 -muscarinic receptor autoantibody (M2 -AAb) in patients with hypertrophic cardiomyopathy (HCM), and the relationship between β1 -AAb, M2 -AAb and clinical indices. One hundred and thirty-four patients with HCM were recruited consecutively into the HCM group. Forty healthy subjects were assigned as the normal controls (NCs). Serum samples were collected to measure the concentrations of β1 -AAb and M2 -AAb by enzyme-linked immunosorbent assay. The clinical data of HCM patients were collected. The serum concentrations of β1 -AAb and M2 -AAb of HCM patients were significantly higher than those of NCs. In HCM patients, those with a left atrial diameter ≥50mm or moderate-to-severe mitral regurgitation had significantly higher concentrations of the two autoantibodies. Patients with a history of syncope had higher concentrations of β1 -AAb. Female patients and patients with a family history of sudden cardiac death or atrial fibrillation had higher concentrations of M2 -AAb. Maximal wall thickness, interventricular septum thickness and resting left ventricular outflow tract gradient were positively correlated with logβ1 -AAb or logM2 -AAb in HCM patients. In conclusion, the serum concentrations of β1 -AAb and M2 -AAb of HCM patients were significantly higher than those of NCs. Being female, syncope, a family history of sudden death, atrial fibrillation, left atrial diameter ≥50mm, moderate-to-severe mitral regurgitation, maximal wall thickness, interventricular septum thickness and resting left ventricular outflow tract gradient may affect the concentrations of the two autoantibodies.

Correlation between three-dimensional speckle tracking echocardiography combined with cardiac magnetic resonance imaging-late gadolinium enchancemet on left ventricular global systolic function and myocardial fibrosis in adult hypertrophic cardiomyopathy

Objective To evaluate the left ventricular global systolic function and myocardial fibrosis in adult hypertrophic cardiomyopathy (HCM) patients by three-dimensional speckle tracking echocardiography(3D-STE) combined with cardiac magnetic resonance imaging-late gadolinium enchancemet (CMRI-LGE) sequence, and to explore the association between left ventricular global systolic function and myocardial fibrosis. Methods Thirty patients with HCM(HCM group) and 33 healthy controls(control group) were enrolled in the study. All patients underwent conventional two-dimensional echocardiography (2DE), tissue Doppler imaging (TDI), and 3D-STE. The following parameters were acquired and compared between the groups: interventricular septal end-diastolic thickness (IVSD), left ventricular posterior wall end-diastolic thickness (LVPWD), left ventricular mass(LVM), left ventricular mass index (LVMI), left atrial volume (LAV), and left ventricular end-systolic volume(LVESV), left ventricular end-diastolic volume (LVEDV), left ventricular outflow tract pressure gradient (LVOT-PG), left ventricular outflow tract velocity time integral (LVOT-VTI), isovolumic relaxation time (IVRT), global strain (GS), global longitudinal strain (GLS), global radial strain (GRS), global circumferential strain (GCS). And 28 patients who met the CMRI indications underwent CMRI-LGE to obtain the LVM, and the correlation and consistency of LVM results obtained from CMRI and 3D-STE were performed.According to LGE results, HCM patients were divided into LGE(+ ) group and LGE (-) group, the differences of GLS, GRS and GCS between the two groups were analyzed. Results ①Compared with the control group, IVSD, LVPWD, LVMI, LAV, LVOT-PG, LVOT-VTI and IVRT were significantly increased in the HCM group (all P 0.05), while GLS and GRS decreased and GCS increased significantly in HCM group (P<0.05); ③The correlation between 3D-STE and CMRI in measuring measured LVM in HCM patients was good, and the results showed good concordance(r=0.807, P<0.01). ④GLS in LGE(+ ) group was lower than in LGE(-) group(P=0.004), but there was no significant difference in GCS and GRS between the two groups(P=0.597, 0.534). Conclusions ①3D-STE can detect the early damage of left ventricular global systolic function in patients with HCM; ②3D-STE combined with CMRI-LGE technology can provide an important imaging reference for the evaluation of the relationship between left ventricular global systolic function and myocardial fibrosis in patients with HCM. Key words: Echocardiography; Three-dimensional speckle tracking imaging; Cardiomyopathy, hypertrophic; Cardiac magnetic resonance imaging; Ventricular function, left; Myocardial fibrosis

Role of deformation imaging in left ventricular non-compaction and hypertrophic cardiomyopathy: an Indian perspective

BackgroundSpeckle tracking echocardiography (STE) has emerged as a novel feasible tool for the assessment of left ventricular rotational parameters. Since hypertrophic cardiomyopathy(HCM) shares morphologic features with left ventricular non-compaction (LVNC), we used this imaging modality to compare rotational mechanics between these two entities.ResultsWe compared global and regional LV function and rotational mechanics between LVNC, HCM, and healthy subjects using STE. Longitudinal strain and torsion were obtained from echocardiographic images from parasternal short axis as well as standard LV apical views. Twelve patients with LVNC [mean age 46.12 ± 14.66 years; median 47.5 IQR (39.25–58.5) years] were compared with 18 HCM patients [mean age 49.48± 17.22 years; median 56 IQR (33–65) years] and 18 healthy subjects [mean age: 51.50± 12.51 years; median 51(45.75-58) years]. LVNC group showed a significantly reduced longitudinal strain at the apical region compared to HCM group (− 12.18 ± 6.25 vs − 18.37 ± 3.67; P < 0.05). Rigid body rotation(RBR) was found in 50% of patients whereas the other half had a normal rotation at the apex and the base. Among the patients with RBR, all patients had a uniform counterclockwise rotation.ConclusionLongitudinal strain was impaired in both the forms of cardiomyopathy; however, LVNC showed a more significant reduction in the apical region compared to patients with HCM suggesting a development abnormality in these regions. A reduction in left ventricular torsion was specifically noted among patients with LVNC with a uniform anticlockwise rotation of LV base and apex.

How to distinguish athlete's heart from hypertrophic cardiomyopathy in cardiac MRI?

The distinction between the athlete's heart and hypertrophic cardiomyopathy (HCM) is important because the HCM constitutes an absolute counter-indication to the practice of sport. Cardiac remodeling related to intense physical activity can sometimes make the distinction between athlete's heart and the HCM difficult. An inappropriate diagnosis of HCM can therefore lead to unnecessary exclusion from the practice of sport. The objective of this work is to study in cardiac MRI the difference between the physiological hypertrophy of the myocardium of the athlete's heart and the hypertrophy of the pathological myocardium by comparing athletes (athlete group) to a group of subjects. non-athlete followed for HCM (HCM group). We conducted a prospective comparative study including 61 subjects. The group of athletes comprised 31 subjects. TheHCM group consisted of 30 subjects. All subjects were paired to age and body surface and had cardiac MRI with the late enhancement study. The thickness of the LV wall (measured at the 17 segments of AHA) in healthy athletes was lower than that in the HCM with a significant difference ( P < 0.0001 for mean thickness and P < 0.0001 for the maximum thickness and P = 0.02 for the minimum thickness). Calculation of left ventricular mass indexed was similar between the athlete group and the HCM group ( P = 0.9) The size of the left atrium was larger in the HCM group with a significant difference between the area of the left atrium indexed between the two groups ( P = 0.0001). Cardiac MRI is of great benefit to the delicate differential diagnosis between myocardial hypertrophy of the athlete's heart and HCM.

P1825 Myocardial bridging and coronary artery disease in hypertrophic cardiomyopathy: a matched case control study

Abstract Funding Acknowledgements None. Introduction The etiology of chest pain in hypertrophic cardiomyopathy (HCM) is diverse and includes coronary artery disease (CAD) as well as HCM-specific causes. Myocardial bridging (MB) has been associated with HCM, chest pain, and accelerated atherosclerosis. To investigate differences in the presence of MB and CAD, we compared HCM patients with age-, gender- and CAD pre-test probability (PTP)-matched outpatients presenting with chest pain. Methods We studied 84 HCM patients who underwent cardiac computed tomography and compared these with 168 matched controls (age 54 ± 11 years, 70% men, PTP 12% [5%–32%]). MB, calcium score, plaque morphology and presence and extent of CAD were assessed for each patient. Linear mixed models were used to assess differences between cases and controls. Results Differences between HCM patients and controls are described in the table. In summary, MB was more often seen in HCM patients (50% vs. 25%, p &amp;lt; 0.001), who were also more likely to have &amp;gt;1 segment affected (14% vs. 2%, p &amp;lt; 0.05). In the HCM group, MB was associated with pathogenic mutation status. Calcium score and the presence of obstructive CAD were similar in both groups (9 [0-225] vs. 4 [0-82] and 18% vs. 19%; p &amp;gt; 0.05 for both). Conclusion MB was twice as prevalent in the HCM group. However, in a matched analysis, the prevalence and extent of CAD was equal among patients with and without HCM. These finding illustrate that despite a higher prevalence of MB, the prevalence of CAD is similar between groups, also demonstrating satisfactory performance of pre-test risk prediction in HCM patients. Assessment of CAD by CT HCM group(n = 84) Control group (n = 168) p-value Agatston score 9 [0-225] 4 [0-82] 0.22 No. of pts with score* 0.07 0-399 31 (89%) 149 (91%) &amp;gt;400 8 (11%) 15 (9%) Obstructive CAD 15 (18%) 32 (19%) 0.82 No. of pts with MB 42 (50%) 42 (25%) &amp;lt;0.001 No. of vessels with MB &amp;lt;0.001 1 34 (40%) 39 (23%) 2 8 (10%) 3 (2%) No. of pts with &amp;gt;1 segment with MB 12 (14%) 4 (2%) &amp;lt;0.001 Abbreviations CAD = Coronary artery disease, MB = Myocardial bridging, pts = patients *Only measured in 73/84 HCM patients and in 164/168 control patients

417 Can myocardial stiffness measurements distinguish the underlying pathology in hearts with thick walls? A shear wave imaging study using ultra-high frame rate echocardiography

Abstract Background Different pathophysiologic pathways in the development of left ventricular (LV) hypertrophy may alter passive myocardial stiffness differently. Recently, cardiac shear wave (SW) elastography has been proposed as new non-invasive technique for assessing myocardial stiffness. Purpose To explore the relationship between myocardial stiffness and the underlying pathological substrates for cardiac hypertrophy. Methods We included 17 patients with cardiac amyloidosis (AML) (69 ± 10 years, 41% male), 17 patients with hypertrophic cardiomyopathy (HCM) (59 ± 16 years, 65% male) matched for interventricular septum (IVS) thickness and 17 hypertensive patients (HT) with prominent myocardial remodelling (56 ± 15 years, 71% male). LV parasternal long axis views were acquired with an experimental ultrasound scanner at 1255 ± 354 frames per seconds. Myocardial acceleration maps were created from the HFR-datasets and an anatomical M-mode line was drawn along the midline of the IVS (Figure A). The propagation velocity of natural SWs occurring at mitral valve closure (MVC) was measured on these M-modes in order to assess operating myocardial stiffness. To compare myocardial stiffness among hearts with differing loading conditions and chamber geometry, SW velocities were normalized to operating end-diastolic wall stress. The end-diastolic wall stress was estimated at the IVS from regional wall thickness, longitudinal and circumferential regional radii of curvature, and noninvasively estimated left ventricular end-diastolic pressure (EDP). Results IVS thickness was significant different among groups (AML: 1.63 ± 0.33 cm, HCM: 1.69 ± 0.21 cm, HT: 1.48 ± 0.14 cm; p = 0.037). HT patients had significant higher septal radius of curvature compared to other two groups (p &amp;lt; 0.05), while the AML patients had the highest estimated EDP (p &amp;lt; 0.05). All groups had comparable, elevated SW velocities at MVC (AML: 6.49 ± 1.00 m/s, HCM: 6.46 ± 1.45 m/s, HT: 6.22 ± 0.96 m/s; p = 0.752). Considering end-diastolic wall stress, HT patients had the same SW velocity at higher wall stress compared to AML and HCM (Figure B), indicating lower myocardial stiffness in the HT group. SW velocities normalized for wall stress indicated significantly different myocardial stiffness among groups (p = 0.003) (Figure C). The HT group had the lowest normalized myocardial stiffness, whereas values of the AML group overlapped with the HCM group (p = 1.00). Conclusions Our study demonstrated that shear wave elastography can detect differences in myocardial stiffness in hearts with thick walls. Considering the effect of wall stress, our results suggest that factors other than chamber geometry and loading condition mediate myocardial stiffness in hearts with thick walls. We hypothesize that differential changes in cardiomyocytes and/or the extracellular matrix contribute to the differential myocardial stiffening in different pathologic entities of LV hypertrophy. Abstract 417 Figure.

1027 Mechanical dispersion of the left and right ventricle and the correlation with ventricular arrhythmias in hypertrophic cardiomyopathy

Abstract Funding Acknowledgements CREDO Project - ID: 49182, financed through the SOP IEC -A2-0.2.2.1-2013-1 cofinanced by the ERDF Introduction One important cause of sudden cardiac death in hypertrophic cardiomyopathy (HCM) are ventricular arrhythmias. In patients with HCM, non-sustained ventricular arrhythmias were analysed in relation with 2D speckle tracking mechanical dispersion of left ventricle (LVMD), but not in relation with mechanical dispersion of the right ventricle. Purpose To investigate the possible associations between mechanical dispersion and other echocardiographic parameters and the development of non-sustained ventricular tachycardias (NSVT) in HCM patients. Methods Clinical, 24 hours ECG-Holter, 2D and 3D echocardiography data were registered in HCM patients and in a healthy control group (with normal echocardiography). The 24 hours ECG-Holter was used for detecting NSVT. LVMD was calculated as the standard deviation of time to peak negative strain in the sixteenth segments of the left ventricle. The right ventricle mechanical dispersion (RVMD) was calculated on a three free wall segments model (FWMD), but also in six segments (three RV free wall segments plus three septal segments). Right and left ventricle function was evaluated by conventional echography and 2D speckle tracking imaging. Results Fifty-two patients with HCM and thirty-six age and sex matched subjects were included in the study. In HCM group, 6 patients (11,5%) associated biventricular hypertrophy, while 15 (28.8%) had NSVT on ECG monitoring (group HCM1). HCM1 patients had a much higher LVMD (77.38 ± 11.19 ms) compared with HCM patients without NSVT (group HCM2) (55.8 ± 23.85 ms, p = 0.001, CI:-33.9,-9.3) or compared with controls (43.07 ± 14.19 ms, p &amp;lt;0.001, CI: -44.68, -25.99). The 6 segments RVMD (60.23 ± 10.2 ms) was significantly higher in the CMH1 group compared with CMH2 (45.22 ± 9.8 ms, p = 0.01, CI: -32.1, -28.1) or with the control group (22 ±14 ms, p &amp;lt; 0.001,CI: -36.28, -30.12) independently of the existence of RV hypertrophy. Also, FWMD (55.2 ± 4.8 ms) was significantly higher in CMH1 group in comparation with CMH2 (42.3 ± 5.6 ms, p = 0.02, CI: -27.1, -8.2) or controls (32.1 ± 2.2 ms, p = 0.006, CI: -28.1, -12.1). The presence of NSVT correlated with global longitudinal strain (GS) 2C (-0.442, p = 0.009), GS LAX (r=-0.373, p = 0.03), GS mean value (r=-0.345, p = 0.046), LVMD (r = 0.462, p = 0.006), FWMD (r = 0.51, p = 0.004), 6 segments RVMD (r = 0.46, p = 0.05), 2D and 3D left atrial volume (r = 0.446, p = 0.008 and respectively, r = 0.512, p = 0.002). In a logistic regression, the only parameters associated with NSVT were LVMD (OR = 1.046, p = 0.05), FWMD (OR = 1.03, p = 0.05) and 6 segments MD (OR = 1.1, p = 0.04). Conclusions Increased mechanical dispersion of the left, but also right ventricle is associated with the risk of non-sustained ventricular tachycardias in HCM patients.

P363 Cardiac magnetic resonance characteristics of patients in the grey zone of hypertrophy

Abstract Funding Acknowledgements National Research, Development and Innovation Office (NKFIH) of Hungary (K 120277); Project no. NVKP_16-1-2016-0017. Supported by the ÚNKP-18-3-IV Background Differentiation between athlete’s heart and hypertrophic cardiomyopathy (HCM) may cause difficulties especially in patients in the grey zone of hypertrophy. Purpose We aimed to analyse cardiac magnetic resonance (CMR) characteristics of healthy athletes, sedentary HCM and athletic HCM patients in the grey zone of hypertrophy. Methods Male HCM patients with slightly elevated maximal end-diastolic wall thickness (EDWT 13-18 mm) and highly trained healthy athletes (n = 34, 20.4 ± 2.3 training hrs/week) were consecutively enrolled. HCM patient group was divided to sedentary (n = 35, &amp;lt;7 training hrs/week) and athletic HCM group (n = 13; &amp;gt;7 h/week, 13.2 ± 5.0 h training hrs/week).We determined conventional CMR parameters (left ventricular (LV) ejection fraction (EF),BSA-corrected end-diastolic (EDVi) and end-systolic volume (ESVi), mass (Mi)), derived parameters such as EDWT/LVEDVi, LVM/LVEDV and CMR based strain parameters such as global longitudinal (GLS), radial (GRS) and circumferential strain (GCS), standard deviation of peak LS, RS and CS (SD LS peak, SD RS peak, SD CS peak), standard deviation of time to peak LS, RS and CS (TTP LS, TTP RS, TTP CS) using feature tracking. Presence of late gadolinium enhancement (LGE) was determined on delayed contrast enhanced images. Inter-observer analysis for strain values was performed in a subgroup of 20 patients conducted by two blinded observer. Results Healthy athletes showed lower LVEF, GCS and GRS than sedentary and athletic HCM patients, respectively (57.9 ± 5.2 vs 65.3 ± 7.4, 62.7 ± 5.1; -19.7 ± 7.0 vs -24.4 ± 4.6, -22.8 ± 4.8; 61.7 ± 11.2 vs 75.4 ± 21.4, 69.3 ± 19.8). Both healthy athletes and athletes with HCM showed higher LVEDVi, LVESVi, LVSVi and LVMi than sedentary HCM patients. Although sedentary athletes showed higher SD peak strain values and more pronounced intraventricular dyssynchrony than healthy athletes (TTP LS 15.4 ± 4.9 vs 11.7 ± 4.3), none of the global strain values, SD of peak strain values or TTP strain values showed any difference between athletic HCM and healthy athletes. EDWT/LVEDVi ratio was significantly lower in healthy athletes than in sedentary and athletic HCM, respectively (0.11 ± 0.02 vs 0.19±.0.04; 0.18 ± 0.04). Inter-observer analysis showed good agreement in GLS (κ=0.77), GRS (κ=0.69) and TTP LS (κ=0.74), moderate agreement in GCS (κ=0.54), and only fair or poor agreement in SD peak strain, TTP CS and TTP RS values. None of the healthy athletes showed LGE, 62% of athletic HCM and 71% of sedentary HCM patients showed LGE in the hypertrophic segments or in the insertion points. Conclusions Based on our results CMR characteristics of sedentary and athletic HCM differs significantly, therefore establishing diagnostic parameters and cut-off values based on comparison between athletic HCM and healthy athletes would be essential. Presence of late gadolinium enhancement and derived parameters may have an important role in the differential diagnosis.

Effects of surgical septal myectomy on survival in patients with hypertrophic obstructive cardiomyopathy.

Objective:The purpose of this study was to determine the effects of surgical resection of muscle layer on the long-term survival of patients with hypertrophic obstructive cardiomyopathy (HOCM).Methods:The original study cohort consisted of 552 patients with hypertrophic cardiomyopathy (HCM), including 380 patients with HOCM and 172 patients with nonobstructive HCM. All these patients had a definite diagnosis in our center from October 1, 2009, to December 31, 2012. They were divided into three groups, viz., HOCM with myectomy group (n=194), nonoperated HOCM group (n=186), and nonobstructive HCM group (n=172). Median follow-up duration was 57.57±13.71 months, and the primary end point was a combination of mortality from all causes.Results:In this survival study, we compared the prognoses of patients with HOCM after myectomy, patients with nonoperated HOCM, and patients with nonobstructive HCM. Among the three groups, the myectomy group showed a lower rate of reaching the all-cause mortality with statistically indistinguishable overall survival compared with patients with nonobstructive HCM (p=0.514). Among patients with left ventricular outflow tract (LVOT) obstruction, the overall survival in the myectomy group was noticeably better than that in the nonoperated HOCM group (log-rank p<0.001). Parameters that showed a significant univariate correlation with survival included age, previous atrial fibrillation (AF), NT-proBNP, Cr, myectomy, and LV ejection fraction. When these variables were entered in the multivariate model, the only independent predictors of survival were myotomy [hazard ratio (HR): 0.109; 95% CI: 0.013–0.877, p<0.037], age (HR: 1.047; 95% CI: 1.007–1.088, p=0.021), and previous AF (HR: 2.659; 95% CI: 1.022–6.919, p=0.021).Conclusion:Patients with HOCM undergoing myectomy appeared to suffer from a lower risk of reaching the all-cause mortality and demonstrated statistically indistinguishable overall survival compared with patients with nonobstructive HCM. Multivariate analysis clearly demonstrated myectomy as a powerful, independent factor of survival, confirming that the differences in long-term survival recorded in this study may be due to surgical improvement in the LVOT gradient.

Clinical characteristics of left atrial appendage thrombus in patients with hypertrophic cardiomyopathy and non-valvular atrial fibrillation

Objective: To investigate the incidence and clinical characteristics of left atrial appendage (LAA) thrombus in patients with hypertrophic cardiomyopathy (HCM) and non-valvular atrial fibrillation (AF) . Methods: Data from 10 440 patients with AF who had undergone transesophageal echocardiography (TEE) before cardioversion or catheter ablation at Beijing Anzhen Hospital from April 2006 to December 2018 were retrospectively screened. Two hundred and five HCM patients were included, 820 AF patients with the same CHA(2)DS(2)-VASc score over the same period were selected as the control group. HCM patients were divided into two subgroups based on presence or absence of LAA thrombus/sludge. The baseline of clinical information, transthoracic echocardiographic and TEE measures were compared among all the groups. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of left atrial diameter (LAD) for LAA thrombus/sludge. Multivariate logistic regression analysis was applied to analyze the correlative factors of LAA thrombus/sludge in HCM patients. Results: The incidences of LAA thrombus or sludge were higher in HCM group than in control group (10.7% (22/205) vs. 0.7% (6/820); 8.8% (18/205) vs.7.0% (57/820), P<0.001) . In HCM patients, LAD was significantly larger in LAA thrombus/sludge subjects than in those without thrombus/sludge ((48.9±5.1)mm vs. (45.2±6.1) mm, P<0.001). CHA(2)DS(2)-VASc score was similar between the two subgroups ((2.0±1.4) vs. (1.8±1.4), P>0.05). There was no difference in the rate of patients with a CHA(2)DS(2)-VASc scores ≥2 between the subgroups(62.5% (25/40) vs. 57.0% (94/165), P=0.525). The incidences of LAA thrombus in HCM and AF patients with CHA(2)DS(2)-VASc scores of 0, 1 and 2 were 8.8% (3/34) , 9.6% (5/52) , 11.8% (11/119) , respectively; and the rate of LAA sludge were 8.8% (3/52) , 7.7% (4/52) , 9.2% (11/119) , respectively. The cut off value of LAD for the diagnosis of LAA thrombus/sludge was 44.5 mm. Multivariate logistic regression analysis showed that LAD≥44.5 mm (OR=5.134, 95%CI 1.862-14.156, P=0.002) , non-paroxysmal AF (OR=2.782, 95%CI 1.238-6.252, P=0.013) , previous thromboembolism or stroke (OR=1.820, 95%CI 0.774-4.227, P=0.017) were independent determinants of LAA thrombus/sludge. Conclusions: The incidence of LAA thrombus/sludge is higher in patients with HCM and AF than in AF patients without HCM. The CHA(2)DS(2)-VASc score is similar between HCM and AF patients with LAA thrombus/sludge and those without thrombus/sludge. Patients with CHA(2)DS(2)-VASc score 0-1 are also likely to suffer LAA thrombus/sludge. Left atrial enlargement is associated with LAA thrombus/sludge.

Polymorphic variant rs1739843 of heat shock protein beta-7 (HSPB7) gene and its relationship with on clinical profile and outcomes in patients with hypertrophic cardiomyopathy (results of a 10-year follow-up)

Aim. To determine the impact of polymorphic variant rs1739843 of the HSPB7 gene on clinical profile and outcomes in patients with hypertrophic cardiomyopathy (HCM).Material and methods. The study population consisted of 108 patients with HCM ≥45 years old. The control group included 192 healthy donors. The design of the study included an assessment of the clinical course, determining the outcome of HCM using a new methodological approach proposed by Rowin EJ, et al. (2017). Polymorphic variant rs1739843 of the HSPB7 gene was genotyped by allele-specific real-time polymerase chain reaction (PCR) assay.Results. It was found a significant increase in frequency of TT genotype of rs1739843 of the HSPB7 gene in patients with HCM — 20,4%, compared with control group — 4,2% (ТТ: ТС+СС, odds ratio (OR) =5,88, 95% confidence interval (CI) =2,52-13,75, p&lt;0,001). High prevalence of CC genotype of rs1739843 of the HSPB7 gene was observed in control group — 80,2% vs 31,5% in HCM group (CC: ТС+TT, OR=0,11, 95% CI=0,07-0,19, p&lt;0,001). The allele frequency (С:Т) also differs between HCM and control groups — 55,6:44,4% in HCM vs 88,02:11,98% in control group (OR=5,88, 95% CI=3,91-8,85, p&lt;0,001). It was also found a significant increase in frequency of TT genotype and T allele of rs1739843 of the HSPB7 gene in HCM patients with oligosymptomatic HCM course — 16,7%, compared with control group — 4,2% (ТТ: ТС+СС, OR=4,60, 95% CI=1,63-12,99, p&lt;0,001). HCM patients ≥45 years old showed a significant increase in T allele frequency in cases of presence of 2 (FC III-IV CHF (chronic heart failure)+AF (atrial fibrillation), 18,8% vs 6,6%) and 3 adverse pathways (FC III-IV CHF+AF+SCD (sudden cardiac death), 4,2% vs 1,6%).Conclusion. HCM progression along 2 and more adverse pathways in patients ≥45 years old has been characterized with adverse outcome. The T allele and TT genotype of rs1739843 of the HSPB7 gene were more frequent in patients with HCM ≥45 years old, compared with control group. It was also found a significant increase in frequency of TT genotype and T allele of rs1739843 of the HSPB7 gene in HCM patients with oligosymptomatic HCM course, compared with control group.Allele T of rs1739843 of the HSPB7 gene is associated with 2 and more adverse pathways of HCM progression.

Quantification of left ventricular performance in different phenotypes of hypertrophic cardiomyopathy

Objective To evaluate the characteristics of left ventricular structure, function, myocardial mechanics, hemodynamics and synchrony in different phenotypes of hypertrophic cardiomyopathy (HCM) using state-of-the-art echocardiography. Methods A consecutive series of 85 adult HCM patients who were admitted to the Xi Jing HCM center from January 2016 to November 2017 were collected. According to the peak left ventricular outflow tract pressure gradient in exercise stress echocardiography, the patients were divided into three groups: patients with non-obstructive HCM (n=28), those with labile-obstructive HCM (n=27), and those with obstructive HCM (n=30). In addition, 16 normal family members of HCM patients were included as control group. Two-dimensional speckle tracking imaging, tissue Doppler imaging and exercise stress echocardiography were used to evaluate the left ventricular function in resting and exercise states. Results ①As compared with the control group, left ventricular end-diastolic diameter decreased and left ventricular ejection fraction increased in all three HCM groups(all P 0.05). The obstructive HCM had the lowest mitral annular plane systolic excursion (MAPSE) and s′, and the longest systolic peaking time standard deviation(Ts-SD) and early diastolic peaking time standard deviation(Te-SD) (all P<0.05). The left ventricular diastolic function of obstructive HCM (e′, the E/e′ ratio and the left atrial volume index) was the worst, labile-obstruction and non-obstructive HCM were better, and the control group was the best (all P<0.001). ③During exercise, the GLS, GCS, GRS, twist of the left ventricle and the MAPSE were the lowest in the obstructive HCM, which increased in the labile-obstructive and non-obstructive HCM, and were best in the control group. The Ts-SD and Te-SD were the shortest in the control group, were prolonged in non-obstructive and labile-obstruction HCM, and were longest in obstructive HCM (all P<0.05). Additionally, the exercise time of the control group was the longest, followed by non-obstructive and labile-obstruction HCM, and the shortest in the obstructive HCM (all P<0.05). The METs of obstructive HCM were significantly lower than the other three groups (all P<0.05). Conclusions In obstructive HCM, the left ventricular systolic strain and synchronization, as well as the MAPSE, are significantly impaired in patients both at rest and during exercise. The patients with labile-obstructive and non-obstructive HCM have reduced left ventricular GLS, twist, and e′, but normal left ventricular GCS, GRS, synchrony, and MAPSE at rest, which are all impaired during exercise. Key words: Two-dimensional speckle tracking imaging; Tissue Doppler imaging; Hypertrophic cardiomyopathy; Exercise stress echocardiography; Myocardial mechanics; Synchrony