scholarly journals Effects of candesartan on left ventricular hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Maqsood ◽  
H.A Shakeel ◽  
H.F Shoukat ◽  
M.D Khan ◽  
S.A.Y Shah ◽  
...  

Abstract Introduction Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular (LV) hypertrophy in the absence of pressure overload. Manifestations of the disease include heart failure associated with diastolic dysfunction and atrial and ventricular tachyarrhythmias. Pathological features of HCM include myocyte hypertrophy, interstitial fibrosis, and myocyte disarray and are mediated by angiotensin II. Purpose This study aimed to evaluate the effects of candesartan on left ventricular (LV) hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy (HCM). Methods In double-blind fashion, 30 patients (6 women, 24 men; age: 55±11 years) with HCM were randomly assigned to receive placebo (n=13) or candesartan 50 mg twice a day (n=17) for 1 year. To measure LV mass and extent of fibrosis, cardiac magnetic resonance imaging was performed at baseline and 1 year as assessed by late gadolinium enhancement. Results There was a trend toward a significant difference in the percent change in LV mass (median: +5% with placebo vs. −5% with candesartan; p=0.06). There was a significant difference in the percent change in the extent of late gadolinium enhancement, with the placebo group experiencing a larger increase (+30±27% with placebo vs. −22±44% with candesartan; p=0.03). Conclusion Our study concludes reduction of the progression of myocardial hypertrophy and fibrosis with candesartan in patients with hypertrophic cardiomyopathy. Our study population was limited so we warrant larger trials to confirm a place for angiotensin receptor blockers in the management of patients with hypertrophic cardiomyopathy. Figure 1 Funding Acknowledgement Type of funding source: Other. Main funding source(s): Self funding

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Naka Sakamoto ◽  
Nobuyuki Sato ◽  
Ahmed Talib ◽  
Keisuke Otsu ◽  
Eitaro Sugiyama ◽  
...  

[Background]: Late gadolinium enhancement (LGE) on cardiac MRI (CMR) predicts the mortality in hypertrophic cardiomyopathy (HCM) patients. T-wave alternans (TWA) is a potential cardiac mortality predictor. However, whether LGE localization affects TWA is unclear. [Purpose]: To elucidate the localization relationship between the LGE and maximal TWA lead (TWAmax-lead) and maximal TWA voltage (TWAmax) using 12-lead Holter ECGs (Holter12) in HCM. [Methods]: Holter12s and CMR were performed in 46 HCM patients. TWA was assessed using a modified moving average method and the TWAmax was determined in each lead. The average transmural LGE extent was scored using a 4 point score (Score 0:no LGE, 1:1-25%, 2:26-50%, 3:51-75%, 4:76-100%) in 12 left ventricular segments and the sum (LGEtotal) was calculated. Left ventricular LGE sites were classified into anterior, septal, inferior, and lateral. Corresponding ECG lead groups were defined as V3-4 for anterior, V1-2 for septal, II, III, aVF for inferior, and I, aVL, and V5-6 for lateral. The TWAmax was analyzed depending on the Score of the 5 stages, and the coincidence between the LGE distribution and TWAmax-lead was investigated. Furthermore, the differences in the TWAmax, LGEtotal, and left ventricular ejection fraction (LVEF) in the presence or absence of ventricular tachycardia (VT) were also studied. [Results]: The TWAmax was 50±11μV for Score=0, 54±13μV for Score=1, 61±18μV for Score=2, 67±20μV for Score=3, and 47±16μV for Score=4. The TWAmax for Scores 2 and 3 was significantly greater than for Score=0 (p<0.001, p<0.001, respectively), but there was no significant difference between Scores 1 and 4, and Score=0 (p=0.14, p=0.41). The TWAmax-lead revealed scores ranging from 1 to 3 in all segments. The LGEtotal and TWAmax were significantly greater in patients with VT (n=23) than without (17±7 vs. 10±7 [p<0.01], 83±17μV vs. 64±18μV [p<0.001], respectively). The LVEF did not statistically differ between the two groups (48±16% vs. 54±10%, p=0.21). [Conclusions]: The LGE distribution correlated with the TWA, i.e., a 50-75% transmural extent of the LGE yielded the maximal local TWA. The spatial distribution of the LGE strongly affects myocardial repolarization abnormalities indicated by TWA as VT substrates in HCM.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Anna Price ◽  
Victoria Stoll ◽  
Ravi Vijapurapu ◽  
Kirsty McGee ◽  
Roman Wesolowski ◽  
...  

Abstract Background and Aims Uraemic cardiomyopathy is characterized by left ventricular (LV) hypertrophy, diastolic dysfunction and myocardial fibrosis. Diffuse interstitial fibrosis of the myocardium, assessed using cardiac magnetic resonance imaging (CMR) techniques of native T1-mapping and extracellular volume (ECV), has been demonstrated in end stage chronic kidney disease (CKD) and in patients with stage 3 CKD and normal left ventricular mass. In living kidney donors estimated glomerular filtration rate (eGFR) declines by a third after donation, with 60% having a resultant eGFR comparable with stage 3 CKD. Recent studies have demonstrated small increases in LV mass at 12 months after donation as well as functional sequelae of reduced global circumferential strain and apical torsion. We sought to establish whether living kidney donors had CMR evidence of diffuse interstitial cardiac fibrosis which might contribute to observed functional correlates. Method A cross sectional blinded study of living kidney donors (n=50) and healthy controls (n=45) who underwent 3 Tesla CMR and blood samples for biomarkers of fibrosis. A modified look-locker inversion recovery (MOLLI) 5(3)3 sampling scheme was used for T1 mapping followed by T2 mapping sequences at the mid LV slice. Five minutes after the administration of gadolinium (Gadovist®) contrast (0.15mmol/kg), standard T1-weighted gradient echo inversion recovery images were repeated for the assessment of late gadolinium enhancement (assessment for focal fibrosis). Post contrast MOLLI images were acquired using identical slice positions as native images using a 4(1)3(1)2 sampling scheme 15 minutes after the administration of gadolinium. Native and post contrast T1 time was used to calculate ECV. Results There were no differences in demographics between groups; age (donors 54 ± 12yrs vs. healthy controls 50 ± 13yrs, p=0.128), ethnicity (89% Caucasian) or male gender (37%). LV mass and volumes were not significantly different. Forty four donors and 34 controls consented to receive gadolinium contrast. Native T1 in the septal mid LV slice was not significantly different between groups (donors 1223 ± 35ms vs. controls 1210 ± 36ms, p=0.102). There was also no difference in T2 time of the septal mid LV slice (donors 40 ± 2ms vs. controls 40 ± 4ms vs. p=0.455). Late gadolinium enhancement was seen in five living kidney donors in a right ventricular insertion point pattern but there was no mid wall or ischaemic pattern enhancement. There was no difference in septal ECV at the mid LV slice (donors 25 ± 2% vs. controls 25 ± 2%, p=0.896). There was also no corresponding difference in fibroblast growth factor-23 (RU/ml) in donors 74 [58-105] vs. controls 59 [47-75], p=0.081 or soluble α-klotho (pg/ml) in donors 610 [503-810] vs. controls 703 [550-955], p=0.061. Conclusion Septal T1 times and ECV in living kidney donors at 5 years from donation are no different from healthy controls. Biomarkers of cardiac fibrosis are also comparable to healthy controls in this small cohort. We found no CMR evidence of the ultrastructural changes reported in uraemic cardiomyopathy in the hearts of living kidney donors at 5 years from donation.


2021 ◽  
Vol 22 (Supplement_2) ◽  
Author(s):  
P Gac ◽  
B Kedzierski ◽  
K Truszkiewicz ◽  
R Poreba

Abstract Funding Acknowledgements Type of funding sources: None. Background The LGE (late gadolinium enhancement) sequence is a recognized classic tool for imaging focal myocardial injury. The T1-mapping sequence to assess native T1 myocardial time, post-contrast T1 time, and myocardial extracellular volume (ECV) is a widely studied tool for imaging focal and diffused myocardial injury. Purpose The aim of the study was to evaluate the native T1 time, the post-contrast T1 time and the myocardial extracellular volume in the T1-mapping sequence in patients with hypertrophic cardiomyopathy without focal LGE myocardial injury. Methods The study group consisted of 28 consecutive patients who met the criteria for diagnosis of hypertrophic cardiomyopathy without focal LGE myocardial injury (HCM group; mean age 52.17 ± 6.35 years). 28 patients without cardiomyopathy (CON group; mean age 51.76 ± 6.49 years) with similar anthropometric parameters were selected by the case-to-case method as a control group. All patients underwent 1.5 T cardiac magnetic resonance, including cinematographic sequences (CINE), LGE sequence and T1-mapping sequences before (native) and 20-minutes after intravenous administration of a paramagnetic agent (post-contrast). In the T1-mapping sequences, the mean T1 time of the whole myocardium (T1 whole myocardium) was assessed, as well as the T1 time in the basal layers (T1 basal), middle layers (T1 middle) and apical layers (T1 apical) of the myocardium. Moreover, the mean T1 time was assessed in the 16-segment myocardial AHA model (T1 segment 1-16). The extracellular volume of the myocardium was estimated in an analogous way. Results In CINE sequences, in the HCM group compared to the CON group, the end-diastolic thickness of the anterior part of interventricular septum, the end-diastolic thickness of the left ventricular posterior wall and the left ventricular mass index were significantly higher. The studied groups did not differ in left ventricular ejection fraction. In both groups, no foci of myocardial injury in the LGE sequence were found. There were no statistically significant differences in T1 times between the study groups. In the HCM group as compared to the CON group, the ECV whole myocardium, ECV basal, ECV apical and ECV segments 1-3, 8, 13-16 were statistically significantly higher. Conclusion Patients with hypertrophic cardiomyopathy without myocardium focal injury in the LGE sequence are characterized by higher myocardial ECV values, assessed in the T1-mapping sequence.


EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
V Pooranachandran ◽  
A Mistry ◽  
Z Vali ◽  
X Li ◽  
B Sidhu ◽  
...  

Abstract Funding Acknowledgements None Introduction Myocardial fibrosis detected using late gadolinium enhancement(LGE) on cardiac magnetic resonance(CMR) imaging holds prognostic value in dilated cardiomyopathy(DCM). Recent reports have demonstrated the localisation of LGE to be promising predictors of ventricular arrhythmic (VA).Aim: To determine the localisation of LGE associated with high risk of VA in DCM patients. Methods: Retrospective review of consecutive DCM patients(n = 85) implanted with an implantable cardioverter defibrillator(ICD) at a single tertiary centre between 2011-2018. All patients with insufficient follow-up data, cardiac channelopathies, primary valvular pathology and congenital heart disease were excluded from analysis(n = 11). Details of VA occurrence were obtained from medical and pacing notes. VA was defined as VA causing haemodynamic compromise or appropriate device therapy (anti-tachycardia pacing/shock). Localisation of LGE was defined as midwall, patchy, subepicardial or transmural. Left ventricular ejection fraction(LVEF) &lt;35% was defined as severely impaired function. Results:74 DCM patients implanted with an ICD were identified for analysis; LGE was observed in 18(60%) VA and 29(66%) non-VA patients(p = 0.6). There was no observed difference in mean age for patients with and without LGE (68 ± 10 vs. 65 ± 10 years,p = 0.07). A significant difference was seen between localisation and VA (p = 0.04), with patchy LGE demonstrating a higher arrhythmic risk(p = 0.005). There was no association between LVEF and LGE(p = 0.2) however, a significant difference was seen in LVEF and arrhythmic risk, with a more severely impaired LV function seen in patients without VA(p = 0.01). Conclusion:This study has demonstrated a patchy LGE localisation to be strongly associated with ventricular arrhythmia in DCM. Whilst this is a valuable tool in risk stratification, a prospective study with a larger population is required to confirm the validity of this finding. Moreover, an additional method will need to be considered to identify high risk patients without LGE. Ventricular Arrhythmia (n = 30) No Ventricular Arrhythmia (n = 44) P Value Male(%) 20(67%) 24(55%) p = 0.29 Age(Mean ± SD) 65 ± 12 65 ± 10 p = 0.36 LGE Midwall 10(56%) 24(83%) p = 0.04 Subepicardial 1(5.5%) 2(7%) p = 0.85 Transmural 1(5.5%) 2(7%) p = 0.85 Patchy 6(33%) 1(3%) p = 0.005 LVEF &lt;35% 23(77%) 42(95%) p = 0.01


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