A Methodological Perspective on the Function and Assessment of Peripheral Chemoreceptors in Heart Failure: A Review of Data from Clinical Trials
Abstract
:1. Introduction
2. Physiology and Pathophysiology of Peripheral Chemoreceptors
3. Methods of Assessment of PChR Phase Activity
4. Comparison of Studied Populations
5. The Impact of HF Etiology and Management on PChR Function
5.1. Digoxin
5.2. Angiotensin-Converting-Enzyme Inhibitors
5.3. Beta-Blockers
5.4. Mineralocorticoid Receptor Antagonists
5.5. Diuretics
5.6. Antiplatelet Drugs
5.7. Statins
5.8. Devices
5.9. Etiology
6. Methods of Assessment of PChR Tonic Activity
7. Predictors of Increased Chemosensitivity
8. Novel Therapies and Possibilities Research Gaps
9. Limitations
10. Conclusions—Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Study | Method | Number of Participants | Age of Patients [Years] | LVEF [%] | Etiology of HF [%] | Treatment [%] | Peripheral Chemosensitivity to Hypoxia [L · min−1 · %SpO2−1] | Prevalence of Increased PChS [%] |
---|---|---|---|---|---|---|---|---|
Chua et al. (1996) [32] | Transient hypoxia; | 38 HF patients 15 healthy controls | 60.2 ± 8 | 25.7 ± 14.17 | IHD 57.9 DCM 31.6 VHD 5.2 Alcoholic-CM 2.6 HTN-CM 2.6 | Diuretics 100 ACE-I 92.1 Digoxin 26.3 | HF: 0.707 ± 0.47 Controls: 0.293 ± 0.22 | NR |
Chua et al. (1996) [33] | Transient hypoxia | 13 HF patients 8 healthy controls | 60.5 ± 7.56 | 25.5 ± 15.48 | IHD 53.8 DCM 46.2 | Diuretics 100 ACE-I 92.3 | HF: 0.572 ± 0.295 Controls: 0.232 ± 0.062 | NR |
Chua et al. (1997) [23] | Transient hypoxia | 50 HF patients 12 healthy controls | 58.7 ± 12.1 | 26.5 ± 13 | IHD 58 DCM 34 VHD 2 Alcoholic-CM 4 HTN-CM 2 | Diuretics 100 ACE-I 100 Digoxin 24 | HF: 0.673 ± 0.41 Controls: 0.272 ± 0.201 | 40 |
Ponikowski et al. (1997) [30] | Transient hypoxia | 26 HF patients | 60 ± 8 | 25.6 ± 8.6 | IHD 80.8 DCM 19.2 | Diuretics 100 ACE-I 100 Digoxin 100 Nitrates 100 | HF: 0.72 ± 0.36 | 42 |
Ponikowski et al. (1997) [67] | Transient hypoxia | 14 HF patients | 60 ± 1.1 | 26.6 ± 11.1 | IHD 78.6 DCM 21.4 | BB 0 | HF: 0.6 ± 0.28 (mean of 9 subjects with higher PChS) | 64 |
Chua et al. (1997) [68] | Transient hypoxia | 12 HF patients | 65.5 ± 5.19 | 21.3 ± 10.38 | IHD 66.7 DCM 33.3 | Diuretics 100 ACE-I 100 | HF: 0.746 ± 0.36 | NR |
Ponikowski et al. (1999) [34] | Transient hypoxia | 74 HF patients | 57 ± 10 | 25 ± 10 | IHD 77 DCM 23 | ACE-I 93 Diuretics 97 Digoxin 29 | HF with CSR: 0.80 ± 0.48 HF with PB: 0.75 ± 0.68 HF with NB 0.34 ± 0.16 | NR |
Ponikowski et al. (1999) [69] | Transient hypoxia | 39 HF patients (13 with cachexia) 11 healthy controls | 60 ± 9 | 24 ± 9 | IHD 87.2 DCM 25.6 | Diuretics 94.8 ACE-I 87.2 Digoxin 48.7 | HF: 0.62 ± 0.34 (cachectic: 0.91 ± 0.37 non-cachectic: 0.47 ± 0.2) Controls: 0.29 ± 0.21 | NR |
Ponikowski et al. (2001) [70] | Transient hypoxia | 38 HF patients 12 healthy controls | 57.8 ± 8 | 26.2 ± 11.7 | IHD 74 DCM 26 | Diuretics 100 ACE-I 95 Digoxin 39 | HF: 0.6 ± 2.46 Controls: 0.2 ± 0.35 | NR |
Ponikowski et al. (2001) [25] | Transient hypoxia | 80 HF patients | 58 ± 9 | 24 ± 12 | IHD 69 DCM 31 | ACE-I 93 Diuretics 98 Digoxin 31 | HF: 0.69 ± 0.50 | 34 |
Giannoni et al. (2008) [24] | Hypoxic isocapnic rebreathing technique; | 60 HF patients 12 healthy controls | 66 ± 7.75 | 31 ± 6.98 | IHD 38 Idiopathic 50 Secondary 12 | Diuretics 90 BB 92 ACE-I 62 ARB 22 MRA 62 | HF: 0.74 ± 0.47 Controls: 0.35 ± 0.2 | 40 |
Giannoni et al. (2009) [35] | Hypoxic isocapnic rebreathing technique | 110 HF patients | 62 ± 15 | 31.1 ± 7.1 | IHD 47 Idiopathic 40 Secondary 13 | Diuretics 80 BB 86 ACE-I/ARB 78 MRA 42 CRT 27 ICD 17 | HF: 0.67 ± 0.45 | 40 |
Niewinski et al. (2013) [31] | Transient hypoxia | 34 HF patients 16 healthy controls | 62 ± 11 | 27 [20,21,22,23,24,25,26,27,28,29,30] | IHD 71 | BB 100 ACE-I 91 MRA 88 Diuretics 74 ICD 50 CRT 29 | HF: 0.58 [0.32–0.95] Controls: 0.17 [0.06–0.29] | 44 |
Mirizzi et al. (2016) [71] | Hypoxic isocapnic rebreathing technique | 191 HF patients | 62 ± 14 | 30 ± 8 | IHD 48 | BB 84 ACE-I/ARB 77 MRA 56 Diuretics 79 | HF: 0.5 [0.2–1.2] | 34 |
Collins et al. (2020) [73] | Transient hypoxia | 12 HF patients 12 healthy controls | 53.6 ± 12.8 | 43.0 ± 8.7 | NR | BB 83 ACE-I/ARB 100 MRA 83 Diuretics 50 | HF: 0.81 ± 0.59 Controls: 0.39 ± 0.17 | NR |
Tubek et al. (2021) [72] | Transient hypoxia | 30 HF patients 30 healthy controls | 62 ± 10 | 27.4 ± 7 | NR | BB 100 ACE-I/ARB 100 MRA 90 Diuretics 70 | HF: 0.6 ± 0.4 Controls: 0.3 ± 0.2 | 40 |
Giannoni et al. (2022) [36] | Hypoxic isocapnic rebreathing technique | 369 HF patients | 65 ± 12 | 31 [25,26,27,28,29,30,31,32,33,34,35,36,37,38] | IHD 43 | BB 95 ACE-I/ARB 89 ARNI 4 MRA 77 Diuretics 71 ICD 21 CRT 19 | HF: 0.5 [0.3–0.9] (267 subjects) | 29 |
Study | Time of O2 Inhalation | Rest/Exercise | Number of Participants | Age of Patients | LVEF [%] | Etiology of HF [%] | Treatment [%] | Effects of Hyperoxia |
---|---|---|---|---|---|---|---|---|
Chua et al. (1996) [33] | 3 breaths | rest; exercise | 13 HF patients 8 healthy controls | 60.5 ± 7.6 | 25.5 ± 15.5 | IHD 53.8 DCM 46.2 | Diuretics 100 ACE-I 92.3 | ↓ Ventilation (HF and Controls, p = NS) |
Chua et al. (1996) [33] | NR | exercise | 12 HF patients | 65.5 ± 5.2 | 21.3 ± 10.4 | IHD 66.7 DCM 33.3 | Diuretics 100 ACE-I 100 | ↑ exercise time ↓ ventilatory response to exercise |
Ponikowski et al. (1997) [30] | 20 min | rest | 12 HF patients | NR | NR | NR | NR | ↑ LFr and HFr power of HRV ↑ α index |
Hennersdorf et al. (2001) [74] | 5 min | rest | 23 HF patients 26 healthy controls | 62.9 ± 7.9 | 29.9 ± 9.6 | IHD 91 DCM 9 | ACE-I 100 Digoxin 100 Diuretics 100 | ↓ HR (HF < Controls) |
Franchitto et al. (2010) [75] | 15 min | rest | 18 HF + anemia patients 18 HF controls | 63.4 ± 11 | 29.9 ± 8.9 | IHD 77 | BB 89 ACE-I/ARB 66 Diuretics 72 | ↓ MSNA (HF + anemia) |
Despas et al. (2012) [29] | 15 min | rest | 18 HF patients with augmented chemosensitivity 20 HF controls | 63.7 ± 16.1 | 29.5 ± 10.6 | IHD 67 DCM 28 VHD 6 | BB 78 ACE-I 72 Diuretics 83 | ↑ arterial baroreflex gain (HF with augmented PChS) ↓ MSNA (HF with augmented PChS) |
Edgell et al. (2015) [27] | 2 min | rest | 11 HF patients 10 healthy controls | 60.3 ± 10 | 38.7 ± 15.3 | NR | BB 100 ACE-I 90.9 Diuretics 81.8 | ↓ HR (HF and Controls) ↓Ventilation (HF) |
Tubek et al. (2021) [72] | 1 min | rest | 30 HF patients 30 healthy controls | 62 ± 10 | 27.4 ± 7 | no data | BB 100 ACE-I/ARB 100 MRA 90 Diuretics 70 | ↑ SVR, MAP (Controls) ↔ HR, MAP (HF) ↓ CO (HF and Controls) ↓ HR (Controls) ↓ Ventilation (HF) |
Study | Dose of Dopamine [µg·kg−1·min−1] | Rest/Exercise | Number of Participants | Age of Patients | LVEF [%] | Etiology of HF [%] | Treatment [%] | Effects of Dopamine |
---|---|---|---|---|---|---|---|---|
Van der Borne et al. (1998) [28] | 5 | rest | 8 HF patients 8 healthy controls | 57 ± 12 | NR | IHD 62.5 Idiopathic 37.5 | NR | ↔ MAP, HR ↓ MV, HVR |
Collins et al. (2020) [73] | 2 | exercise | 12 HF patients 12 healthy controls | 53.6 ± 12.8 | 43.0 ± 8.7 | NR | BB 83 ACE-I/ARB 100 MRA 83 Diuretics 50 | ↑ PETCO2, CO, SV, CO/MAP ↔ exercise time, MAP, HR |
Edgell et al. (2015) [27] | 2 | rest | 11 HF patients 10 healthy controls | 60.3 ± 10 | 38.7 ± 15.3 | NR | BB 100 ACE-I 90.9 Diuretics 81.8 | ↑ CO, SV ↔ HR, MAP ↓ MV |
Group of Predictors | Characteristics of Patients with High Chemosensitivity |
---|---|
Biochemical | ↓Hb [75] ↑GGT [71] ↑NA [24,36,71] ↑NT-proBNP [24,31,36,71] ↑BNP [24] |
Clinical | Cardiac cachexia [69] ↑NYHA class [23,24,35,70,74] ↑Age [71] ↑MSNA [29] ↓Arterial baroreflex sensitivity [29] ↓Renal function [36] |
Haemodynamic | ↓LVEF [23,25,31,70,71,74] ↑nsVT [23,35,74] ↑AF [35] ↓HRV [31] ↑RV dimensions [71] ↑SBP [31] ↑Systolic pulmonary pressure [36] |
Respiratory | ↓Peak VO2 [31,35,70] ↑VE/VCO2 slope [23,35,36,70,71] |
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Jura, M.; Garus, M.; Krakowska, K.; Urban, S.; Błaziak, M.; Iwanek, G.; Zymliński, R.; Biegus, J.; Paleczny, B. A Methodological Perspective on the Function and Assessment of Peripheral Chemoreceptors in Heart Failure: A Review of Data from Clinical Trials. Biomolecules 2022, 12, 1758. https://doi.org/10.3390/biom12121758
Jura M, Garus M, Krakowska K, Urban S, Błaziak M, Iwanek G, Zymliński R, Biegus J, Paleczny B. A Methodological Perspective on the Function and Assessment of Peripheral Chemoreceptors in Heart Failure: A Review of Data from Clinical Trials. Biomolecules. 2022; 12(12):1758. https://doi.org/10.3390/biom12121758
Chicago/Turabian StyleJura, Maksym, Mateusz Garus, Kornelia Krakowska, Szymon Urban, Mikołaj Błaziak, Gracjan Iwanek, Robert Zymliński, Jan Biegus, and Bartłomiej Paleczny. 2022. "A Methodological Perspective on the Function and Assessment of Peripheral Chemoreceptors in Heart Failure: A Review of Data from Clinical Trials" Biomolecules 12, no. 12: 1758. https://doi.org/10.3390/biom12121758
APA StyleJura, M., Garus, M., Krakowska, K., Urban, S., Błaziak, M., Iwanek, G., Zymliński, R., Biegus, J., & Paleczny, B. (2022). A Methodological Perspective on the Function and Assessment of Peripheral Chemoreceptors in Heart Failure: A Review of Data from Clinical Trials. Biomolecules, 12(12), 1758. https://doi.org/10.3390/biom12121758