Risk Stratification in Hypertrophic Cardiomyopathy. Insights from Genetic Analysis and Cardiopulmonary Exercise Testing
Abstract
:1. Introduction
2. Methods
2.1. Study Sample
2.2. Patients Clinical and Functional Assessment
2.3. Genetic Testing
2.4. Clinical Outcomes
2.5. Statistical Analysis
3. Results
3.1. Genetic Results
3.2. Clinical and Functional Characteristics
3.3. End-Point Analysis
4. Discussion
5. Limitations
6. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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General Data | |
---|---|
Age, years | 49 ± 16 |
Male, n (%) | 238 (64) |
Age at diagnosis, years | 40 ± 19 |
NYHA III–IV, n (%) | 24 (6) |
ICD, n (%) | 43 (12) |
Previous myectomy, n (%) | 20 (5) |
SCD risk factors | |
NSVT, n (%) | 121 (32) |
FH-SCD, n (%) | 48 (13) |
MWT > 30 mm, n (%) | 26 (7) |
Unexplained syncope, n (%) | 56 (15) |
ABPRE, n (%) | 45 (16) |
Echocardiographic data | |
LVEDd, mm | 45 ± 5 |
LAd, mm | 43 ± 7 |
MWT, mm | 20 ± 5 |
LVOT obstruction, n (%) | 125 (33) |
LVOTGmax, mmHg | 11 (6–39) |
LVEF, % | 62 ± 7 |
CPET data | |
Peak HR, % of predicted | 79 ± 13 |
Peak VO2, mL/kg/min | 23 ± 7 |
Peak VO2, % of predicted | 77 ± 18 |
Peak SBP, mmHg | 164 ± 27 |
CP%, % of predicted * mmHg | 12,937 ± 4300 |
VE/VCO2 slope | 28.4 ± 5.5 |
Medical treatment | |
β-blocker, n (%) | 228 (61) |
Nondihydropyridine CCB, n (%) | 31 (8) |
ACE-I/ARB, n (%) | 107 (29) |
Diuretics, n (%) | 78 (21) |
Amiodaron, n (%) | 33 (9) |
General Data | No Variants and VUS (n = 168) | LP/P Variants (n = 203) | p-Values |
---|---|---|---|
Age, years | 53 ± 18 | 45 ± 16 | <0.001 |
Male, n (%) | 112 (67) | 124(61) | NS |
Age at diagnosis, years | 47 ± 20 | 35 ± 17 | <0.001 |
NYHA III-IV, n (%) | 10 (6) | 14 (7) | NS |
ICD, n (%) | 11 (6) | 32 (16) | 0.019 |
Previous myectomy, n (%) | 9 (5) | 11 (5) | NS |
SCD risk factors | |||
NSVT, n (%) | 48 (28) | 73 (36) | NS |
FH-SCD, n (%) | 16 (9) | 32 (16) | 0.049 |
MWT > 30 mm, n (%) | 10 (6) | 16 (8) | NS |
Unexplained syncope, n (%) | 29 (17) | 26 (13) | NS |
ABPRE, n (%) | 11 (7) | 34 (17) | 0.003 |
Echocardiographic data | |||
LVEDd, mm | 46 ± 4 | 45 ± 6 | NS |
LAd, mm | 43 ± 7 | 43 ± 7 | NS |
MWT, mm | 20 ± 5 | 20 ± 5 | NS |
LVOT obstruction, n (%) | 79 (47) | 45 (22) | <0.001 |
LVOTGmax, mmHg | 16 (9–39) | 10 (5–33) | 0.023 |
LVEF, % | 63 ± 4 | 61 ± 6 | <0.001 |
CPET data | |||
Peak HR, % of predicted | 78 ± 12 | 79 ± 13 | NS |
Peak VO2, mL/kg/min | 23 ± 7 | 23 ± 7 | NS |
Peak VO2, % of predicted | 79 ± 18 | 75 ± 18 | 0.032 |
Peak SBP, mmHg | 175 ± 26 | 157 ± 26 | <0.001 |
CP%, % of predicted * mmHg | 14,070 ± 4269 | 12,015 ± 4020 | <0.001 |
VE/VCO2 slope | 27.5 ± 4.9 | 29.1 ± 6.0 | 0.019 |
Medical treatment | |||
β-blocker, n (%) | 105 (62) | 122 (60) | NS |
Non dihydropyridine CCB, n (%) | 11 (7) | 20 (10) | NS |
ACE-I/ARB, n (%) | 58 (34) | 48 (24) | 0.014 |
Diuretics, n (%) | 37 (22) | 41 (21) | NS |
Amiodaron, n (%) | 16 (9) | 17 (8) | NS |
HF Endpoint (n = 52) | SCD Endpoint (n = 14) | |||||
---|---|---|---|---|---|---|
H.R. (95% C.I.) | p-Values | C-Index | H.R. (95% C.I.) | p-Values | C-Index | |
Age at CPET | – | NS | – | 0.964 (0.934–0.996) | 0.038 | 0.613 |
Male sex | – | NS | – | – | NS | – |
Age at diagnosis | – | NS | – | 0.944 (0.906–0.983) | 0.006 | 0.729 |
FH-SCD | 1.869 (1.010–3.460) | 0.046 | 0.522 | 2.830 (0.892–8.979) | 0.077 | 0.607 |
Unexplained Syncope | – | NS | – | – | NS | – |
NSVT | 1.917 (1.102–3.333) | 0.021 | 0.548 | – | NS | – |
ABPRE | 3.418 (1.769–6.605) | <0.001 | 0.641 | – | NS | – |
MWT > 30 mm | – | NS | – | 3.956 (1.210–12.940) | 0.023 | 0.569 |
MWT | – | NS | – | 1.100 (1.012–1.195) | 0.025 | 0.593 |
LVOTO | 2.110 (1.215–3.664) | <0.01 | 0.641 | – | NS | – |
LAd | 1.077 (1.039–1.116) | <0.001 | 0.704 | 1.054 (0.984–1.129) | 0.112 | 0.660 |
LVOTGmax | 1.016 (1.008–1.024) | <0.001 | 0.672 | 0.971 (0.937–1.007) | 0.123 | 0.577 |
LVEF | 0.929 (0.899–0.959) | <0.001 | 0.587 | – | NS | – |
pVO2, mL/kg/min | 0.851 (0.799–0.905) | <0.001 | 0.739 | – | NS | – |
pVO2, % of predicted | 0.851 (0.799–0.905) | <0.001 | 0.749 | – | NS | – |
VE/VCO2 slope | 1.017 (1.069–1.146) | <0.001 | 0.724 | – | NS | – |
CP% | 0.998 (0.997–0.999) | <0.001 | 0.778 | 0.998 (0.997–1.000) | 0.052 | 0.705 |
LP or P variants | 2.395 (1.171–4.856) | 0.013 | 0.609 | – | NS | – |
Multivariate Cox Proportional Survival Analysis | ||||||
---|---|---|---|---|---|---|
HF Endpoint | SCD Endpoint | |||||
H.R. (95% C.I.) | p-Values | C-Index | H.R. (95% C.I.) | p-Values | C-Index | |
LAd | 1.083 (1.039–1.130) | <0.001 | 0.839 | 1.078 (1.005–1.163) | 0.0485 | 0.738 |
CP% | 0.998 (0.997–0.999) | <0.001 | 0.998 (0.9996–1.000) | 0.0488 | ||
VE/VCO2 slope | 1.044 (0.999–1.090) | 0.05 |
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Magrì, D.; Mastromarino, V.; Gallo, G.; Zachara, E.; Re, F.; Agostoni, P.; Giordano, D.; Rubattu, S.; Forte, M.; Cotugno, M.; et al. Risk Stratification in Hypertrophic Cardiomyopathy. Insights from Genetic Analysis and Cardiopulmonary Exercise Testing. J. Clin. Med. 2020, 9, 1636. https://doi.org/10.3390/jcm9061636
Magrì D, Mastromarino V, Gallo G, Zachara E, Re F, Agostoni P, Giordano D, Rubattu S, Forte M, Cotugno M, et al. Risk Stratification in Hypertrophic Cardiomyopathy. Insights from Genetic Analysis and Cardiopulmonary Exercise Testing. Journal of Clinical Medicine. 2020; 9(6):1636. https://doi.org/10.3390/jcm9061636
Chicago/Turabian StyleMagrì, Damiano, Vittoria Mastromarino, Giovanna Gallo, Elisabetta Zachara, Federica Re, Piergiuseppe Agostoni, Dario Giordano, Speranza Rubattu, Maurizio Forte, Maria Cotugno, and et al. 2020. "Risk Stratification in Hypertrophic Cardiomyopathy. Insights from Genetic Analysis and Cardiopulmonary Exercise Testing" Journal of Clinical Medicine 9, no. 6: 1636. https://doi.org/10.3390/jcm9061636
APA StyleMagrì, D., Mastromarino, V., Gallo, G., Zachara, E., Re, F., Agostoni, P., Giordano, D., Rubattu, S., Forte, M., Cotugno, M., Torrisi, M. R., Petrucci, S., Germani, A., Savio, C., Maruotti, A., Volpe, M., Autore, C., Piane, M., & Musumeci, B. (2020). Risk Stratification in Hypertrophic Cardiomyopathy. Insights from Genetic Analysis and Cardiopulmonary Exercise Testing. Journal of Clinical Medicine, 9(6), 1636. https://doi.org/10.3390/jcm9061636