Hemodynamic Heterogeneity of Reduced Cardiac Reserve Unmasked by Volumetric Exercise Echocardiography
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Exercise Testing Procedures
2.3. Stress Echocardiography
2.4. Volume Analysis
2.5. Heart Rate Response
2.6. Stroke Volume Index and Cardiac Index
2.7. Data Storage
2.8. Statistical Analysis
3. Results
3.1. Hemodynamic Correlates of Normal Cardiac Index Reserve
3.2. Hemodynamic Correlates of Abnormal Cardiac Index Reserve
3.3. Cardiac Index Reserve in Different Hemodynamic Subsets
4. Discussion
4.1. Comparison with Previous Studies
4.2. Clinical Implications
4.3. Limitations
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviation
CI | cardiac index |
CO | cardiac output |
EDV | end-diastolic volume |
EF | ejection fraction |
ESE | exercise stress echocardiography |
ESV | end-systolic volume |
HR | heart rate |
HRR | heart rate reserve |
LVCR | left ventricular contractile reserve |
SV | stroke volume |
References
- Abudiab, M.M.; Redfield, M.M.; Melenovsky, V.; Olson, T.P.; Kass, D.A.; Johnson, B.D.; Borlaug, B.A. Cardiac output response to exercise in relation to metabolic demand in heart failure with preserved ejection fraction. Eur. J. Heart Fail. 2013, 15, 776–785. [Google Scholar] [CrossRef] [Green Version]
- Galderisi, M.; Cardim, N.; D’Andrea, A.; Bruder, O.; Cosyns, B.; Davin, L.; Donal, E.; Edvardsen, T.; Freitas, A.; Habib, G.; et al. The multi-modality cardiac imaging approach to the Athlete’s heart: An expert consensus of the European association of cardiovascular imaging. Eur. Heart J. Cardiovasc. Imaging 2015, 16, 353. [Google Scholar] [CrossRef]
- Bombardini, T.; Nevola, E.; Giorgetti, A.; Landi, P.; Picano, E.; Neglia, D. Prognostic value of left- ventricular and peripheral vascular performance in patients with dilated cardiomyopathy. J. Nucl. Cardiol. 2008, 15, 353–362. [Google Scholar] [CrossRef]
- Picano, E.; Ciampi, Q.; Citro, R.; D’Andrea, A.; Scali, M.C.; Cortigiani, L. Stress echo 2020: The international stress echo study in ischemic and non-ischemic heart disease. Cardiovasc. Ultrasound. 2017. [Google Scholar] [CrossRef] [Green Version]
- Ponikowski, P.; Voors, A.A.; Anker, S.D.; Bueno, H.; Cleland, J.G.F.; Coats, A.J.S.; Falk, V.; González-Juanatey, J.R.; Harjola, V.P.; Jankowska, E.A.; et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur. Heart J. 2016, 37, 2129–2200, Erratum in 2018, 39, 860. [Google Scholar] [CrossRef]
- Fletcher, G.F.; Ades, P.A.; Kligfield, P.; Arena, R.; Balady, G.J.; Bittner, V.A.; Coke, L.A.; Fleg, J.L.; Forman, D.E.; Gerber, T.C.; et al. American heart association exercise, cardiac rehabilitation, and prevention committee of the council on clinical cardiology, council on nutrition, physical activity and metabolism, council on cardiovascular and stroke nursing, and council on epidemiology and prevention. exercise standards for testing and training: A scientific statement from the American Heart Association. Circulation 2013, 128, 873–934. [Google Scholar] [CrossRef] [PubMed]
- Pellikka, P.A.; Arruda-Olson, A.; Chaudhry, F.A.; Chen, M.H.; Marshall, J.E.; Porter, T.R.; Sawada, S.G. Guidelines for performance, interpretation, and application of stress echocardiography in ischemic heart disease: From the American society of echocardiography. J. Am. Soc. Echocardiogr. 2020, 33, 1–41.e8. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ciampi, Q.; Picano, E.; Paterni, M.; Daros, C.B.; Simova, I.; de Castro e Silva Pretto, J.L.; On behalf of Stress Echo 2020 Study Group of the Italian Society of Cardiovascular Echography. Quality control of regional wall motion analysis in stress echo 2020. Int. J. Cardiol. 2017, 249, 479–485. [Google Scholar] [CrossRef] [PubMed]
- Cortigiani, L.; Huqi, A.; Ciampi, Q.; Bombardini, T.; Bovenzi, F.; Picano, E. integration of wall motion, coronary flow velocity, and left ventricular contractile reserve in a single test: Prognostic value of vasodilator stress echocardiography in patients with diabetes. J. Am. Soc. Echocardiogr. 2018, 31, 692–701. [Google Scholar] [CrossRef]
- Carpeggiani, C.; Ciampi, Q.; Paterni, M.; Zagatina, A.; Simova, I.; Djordievic-Dikic, A.; Citro, R.; Colonna, P.; Picano, E. Multi-step web-based training: The road to stress echo 2020. Rev. Arg. Cardiol. 2018, 86, 250–256. [Google Scholar] [CrossRef]
- Bombardini, T.; Correia, M.J.; Cicerone, C.; Agricola, E.; Ripoli, A.; Picano, E. Force-frequency relationship in the echocardiography laboratory: A noninvasive assessment of Bowditch treppe? J. Am. Soc. Echocardiogr. 2003, 16, 646–655. [Google Scholar] [CrossRef]
- Cortigiani, L.; Carpeggiani, C.; Landi, P.; Raciti, M.; Bovenzi, F.; Picano, E. Usefulness of blunted heart rate reserve as an imaging-independent prognostic predictor during dipyridamole-echocardiography test. Am. J. Cardiol. 2019, 124, 972–977. [Google Scholar] [CrossRef]
- Nedeljkovic, I.; Banovic, M.; Stepanovic, J.; Giga, V.; Djordjevic-Dikic, A.; Trifunovic, D.; Nedeljkovic, M.; Petrovic, M.; Dobric, M.; Dikic, N.; et al. The combined exercise stress echocardiography and cardiopulmonary exercise test for identification of masked heart failure with preserved ejection fraction in patients with hypertension. Eur. J. Prev. Cardiol. 2016, 23, 71–77. [Google Scholar] [CrossRef] [PubMed]
- Picano, E.; Bombardini, T.; Kovačević Preradović, T.; Cortigiani, L.; Wierzbowska-Drabik, K.; Ciampi, Q. Left ventricular contractile reserve in stress echocardiography: The bright side of the force. Kardiol. Pol. 2019, 77, 164–172. [Google Scholar] [CrossRef] [Green Version]
- Bombardini, T.; Zagatina, A.; Ciampi, Q.; Cortigiani, L.; D’Andrea, A.; Borguezan Daros, C.; Zhuravskaya, N.; Kasprzak, J.D.; Wierzbowska-Drabik, K.; De Castro e Silva Pretto, J.L.; et al. Feasibility and value of two-dimensional volumetric stress echocardiography. Minerva Cardioangiol. 2020. [Google Scholar] [CrossRef]
- Ellestad, M.H. Chronotropic incompetence. The implications of heart rate response to exercise. Circulation 1996, 93, 1485–1487. [Google Scholar] [CrossRef]
- Lauer, M.S.; Francis, G.S.; Okin, P.M.; Pashkow, F.J.; Snader, C.E.; Marwick, T.H. Impaired chronotropic response to exercise stress testing as a predictor of mortality. JAMA 1999, 281, 524–529. [Google Scholar] [CrossRef]
- Elhendy, A.; Mahoney, D.W.; Khandheria, B.K.; Burger, K.; Pellikka, P.A. Prognostic significance of impairment of heart rate response to exercise: Impact of left ventricular function and myocardial ischemia. J. Am. Coll. Cardiol. 2003, 42, 823–830. [Google Scholar] [CrossRef] [Green Version]
- Lancellotti, P.; Pellikka, P.A.; Budts, W.; Chaudhry, F.A.; Donal, E.; Dulgheru, R.; Edvardsen, T.; Garbi, M.; Ha, J.W.; Kane, G.C.; et al. The clinical use of stress echocardiography in non-ischaemic heart disease: Recommendations from the European Association of cardiovascular imaging and the American society of echocardiography. J. Am. Soc. Echocardiogr. 2017, 30, 101–138. [Google Scholar] [CrossRef] [Green Version]
- Pandey, A.; Khera, R.; Park, B. Relative impairments in hemodynamic exercise reserve parameters in heart failure with preserved ejection fraction: A study-level pooled analysis. JACC Heart Fail. 2018, 6, 117–126. [Google Scholar] [CrossRef]
- Kasner, M.; Sinning, D.; Lober, J.; Post, H.; Fraser, A.G.; Pieske, B.; Burkhoff, D.; Tschöpe, C. Heterogeneous responses of systolic and diastolic left ventricular function to exercise in patients with heart failure and preserved ejection fraction ESC HEART FAILURE ESC. Heart Fail. 2015, 2, 121–132. [Google Scholar] [CrossRef] [Green Version]
- Shimiaie, J.; Sherez, J.; Aviram, G.; Megidish, R.; Viskin, S.; Halkin, A.; Ingbir, M.; Nesher, N.; Biner, S.; Keren, G.; et al. Determinants of effort intolerance in patients with heart failure: Combined echocardiography and cardiopulmonary stress protocol. JACC Heart Fail. 2015, 3, 803–814. [Google Scholar] [CrossRef]
- Wachter, R.; Schmidt-Schweda, S.; Westermann, D.; Post, H.; Edelmann, F.; Kasner, M.; Luers, C.; Steendijk, P.; Hasenfuß, G.; Tschope, C.; et al. Blunted frequency-dependent upregulation of cardiac output is related to impaired relaxation in diastolic heart failure. Eur. Heart J. 2009, 30, 3027–3036. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zweerink, A.; Van Der Lingen, A.C.J.; Handoko, M.L.; Van Rossum, A.C.; Allaart, C.P. Chronotropic incompetence in chronic heart failure. Circ. Heart Fail. 2018, 11, e004969. [Google Scholar] [CrossRef]
- Palau, P.; Seller, J.; Domínguez, E.; Gómez, I.; Ramón, J.M.; Sastre, C.; De La Espriella, R.; Santas, E.; Miñana, G.; Chorro, F.J.; et al. Beta-blockers withdrawal in patients with heart failure with preserved ejection fraction and chronotropic incompetence: Effect on functional capacity rationale and study design of a prospective, randomized, controlled trial (The Preserve-HR trial). Clin. Cardiol. 2020, 43, 423–429. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rivas-Lasarte, M.; Álvarez-García, J.; Fernández-Martínez, J.; Maestro, A.; López-López, L.; Solé-González, E.; Pirla, M.J.; Mesado, N.; Mirabet, S.; Fluvià, P.; et al. Lung ultrasound-guided treatment in ambulatory patients with heart failure: A randomized controlled clinical trial (LUS-HF study). Eur. J. Heart Fail. 2019, 21, 1605–1613. [Google Scholar] [CrossRef]
- Tschöpe, C.; Butler, J.; Farmakis, D.; Morley, D.; Rao, I.; Filippatos, G. Clinical effects of cardiac contractility modulation in heart failure with mildly reduced systolic function. ESC Heart Fail. 2020. [Google Scholar] [CrossRef]
- Tsang, W.; Salgo, I.S.; Medvedofsky, D.; Takeuchi, M.; Prater, D.; Weinert, L.; Yamat, M.; Mor-Avi, V.; Patel, A.R.; Lang, R.M. Transthoracic 3D echocardiographic left heart chamber quantification using an automated adaptive analytics algorithm. JACC Cardiovasc. Imaging 2016, 9, 769–782. [Google Scholar] [CrossRef]
- Bombardini, T.; Sicari, R.; Bianchini, E.; Picano, E. Abnormal shortened diastolic time length at increasing heart rates in patients with abnormal exercise-induced increase in pulmonary artery pressure. Cardiovasc. Ultrasound. 2011, 9, 36. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Silverman, D.N.; Shah, S.J. Treatment of heart failure with preserved ejection fraction (HFpEF): The phenotype-guided approach. Curr. Treat. Options. Cardiovasc. Med. 2019, 21, 20. [Google Scholar] [CrossRef]
Overall (n = 1344) | Low CI Reserve First Tertile (n = 448) | Medium CI Reserve Second Tertile (n = 448) | High CI Reserve High Tertile (n = 448) | p Value | |
---|---|---|---|---|---|
Male gender, n (%) | 794 (59.1%) | 244 (54.5%) | 254 (56.7%) | 296 (66.1%) | 0.001 |
Age (years) | 59.8 ± 11.4 | 62.6 ± 11.1 | 60.4 ± 10.4 | 56.4 ± 11.8 | <0.001 |
Hypertension, n (%) | 909 (67.6%) | 333 (74.3%) | 321 (71.7%) | 255 (56.9%) | <0.001 |
Diabetes mellitus, n (%) | 249 (18.5%) | 107 (23.9%) | 84 (18.8%) | 58 (12.9%) | <0.001 |
History of dyspnea, n (%) | 129 (9.6%) | 54 (12.1%) | 48 (10.7%) | 27 (6%) | 0.006 |
History of myocardial infarction, n (%) | 344 (25.6%) | 137 (30.6%) | 106 (23.7%) | 101 (22.5%) | 0.012 |
History of PCI/CABG, n (%) | 327 (24.3%) | 145 (32.4%) | 102 (22.8%) | 80 (17.9%) | <0.001 |
Beta blockers, n (%) | 601 (44.7%) | 248 (55.4%) | 207 (46.2%) | 146 (32.6%) | <0.001 |
Nitrates, n (%) | 47 (3.5%) | 27 (6%) | 14 (3.1%) | 6 (1.3%) | 0.001 |
Calcium channel blockers, n (%) | 211 (15.7%) | 86 (19.2%) | 73 (16.3%) | 52 (11.6%) | 0.007 |
Statins, n (%) | 648 (48.2%) | 229 (51.1%) | 233 (52%) | 186 (41.5%) | 0.002 |
ACEi/ARB, n (%) | 727 (54.1%) | 260 (58%) | 259 (57.8%) | 208 (46.4%) | <0.001 |
Diuretics, n (%) | 43 (3.2%) | 7(1.6%) | 18 (4%) | 18 (4%) | 0.055 |
Anti-platelet agents, n (%) | 719 (53.5%) | 265 (59.2%) | 257 (57.4%) | 197 (44%) | <0.001 |
Overall (n = 1344) | Low CI Reserve First Tertile (n = 448) | Medium CI Reserve Second Tertile (n = 448) | High CI Reserve High Tertile (n = 448) | p Value | |
---|---|---|---|---|---|
Heart rate, beats/min | |||||
Rest | 71.2 ± 12.1 | 72.3 ± 13.5 | 71.6 ± 11.5 | 69.8 ± 11.1 | 0.007 ^ |
Peak | 132.8 ± 19.2 | 122.9 ± 20.0 | 133.3 ± 15.9 | 142.1 ± 16.3 | <0.001 * |
Peak/rest | 1.90 ± 0.35 | 1.73 ± 0.30 | 1.90 ± 0.31 | 2.07 ± 0.35 | <0.001 * |
Mean pressure, mmHg | |||||
Rest | 94.0 ± 11.5 | 93.3 ± 12.3 | 94.8 ± 10.6 | 94.1 ± 11.5 | 0.143 |
Peak | 121.1 ± 16.3 | 118.4 ± 17.8 | 121.7 ± 15.8 | 123.4 ± 14.8 | <0.001° |
Reserve | 27.1 ± 15.7 | 25.1 ± 17.5 | 26.9 ± 14.7 | 29.3 ± 14.4 | <0.001 ^ |
End-diastolic volume index, mL × m−2 | |||||
Rest | 52.0 ± 21.7 | 44.6 ± 16.0 | 46.9 ± 15.5 | 64.4 ± 26.2 | <0.001 ^ |
Peak | 48.8 ± 20.2 | 37.1 ± 12.4 | 44.7 ± 12.2 | 64.6 ± 22.8 | <0.001 * |
Reserve | −3.1 ± 11.2 | −7.4 ± 10.5 | −2.2 ± 8.9 | 0.2 ± 12.4 | <0.001 * |
End-systolic volume index, mL × m−2 | |||||
Rest | 20.0 ± 10.9 | 16.8 ± 7.8 | 17.4 ± 7.6 | 25.7 ± 13.8 | <0.001 ^ |
Peak | 14.4 ± 9.0 | 12.6 ± 7.4 | 12.9 ± 7.0 | 17.8 ± 11.1 | <0.001 ^ |
Reserve | −5.3 ± 6.3 | −4.2 ± 5.2 | −4.4 ± 4.7 | −7.9 ± 7.7 | <0.001 ^ |
Stroke volume index, mL × m−2 | |||||
Rest | 32.0 ± 12.9 | 27.8 ± 10.1 | 29.6 ± 9.6 | 38.7 ± 15.3 | <0.001 ^ |
Peak | 34.4 ± 14.5 | 24.6 ± 7.4 | 31.8 ± 7.3 | 46.8 ± 16.2 | <0.001 * |
Reserve | 2.4 ± 8.6 | −3.2 ± 6.9 | 2.2 ± 5.7 | 8.1 ± 8.8 | <0.001 * |
Ejection fraction (%) | |||||
Rest | 62.5 ± 8.0 | 62.9 ± 8.0 | 63.4 ± 7.3 | 61.2 ± 8.3 | <0.001° |
Peak | 71.2 ± 10.2 | 67.8 ± 10.8 | 72.2 ± 8.7 | 73.7 ± 10.1 | <0.001° |
Reserve | 8.7 ± 7.6 | 4.9 ± 7.8 | 8.8 ± 6.0 | 12.5 ± 6.9 | <0.001 * |
Left ventricular contractile reserve (LVCR, Peak/Rest Force) | |||||
Rest Force (mmHg/mL) | 4.17 ± 1.99 | 4.83 ± 2.28 | 4.45 ± 1.71 | 3.23 ± 1.53 | <0.001 * |
Peak Force (mmHg/mL) | 9.38 ± 6.33 | 10.70 ± 7.65 | 9.52 ± 5.19 | 7.94 ± 5.63 | <0.001 * |
LVCR | 2.32 ± 1.33 | 2.29 ± 1.61 | 2.17 ± 0.93 | 2.51 ± 1.35 | 0.001 ^ |
WMSI (ratio) | |||||
Rest | 1.110 ± 0.265 | 1.110 ± 0.232 | 1.066 ± 0.190 | 1.152 ± 0.343 | <0.001 § |
Peak | 1.064 ± 0.179 | 1.086 ± 0.200 | 1.046 ± 0.153 | 1.061 ± 0.179 | 0.003 ^ |
Viability, n (%) | 157 (11.7%) | 47 (10.5%) | 42 (9.4%) | 68 (15.2%) | 0.016 |
Cardiac index, mL/min × m−2 | |||||
Rest | 2276 ± 991 | 2013 ± 834 | 2119 ± 818 | 2695 ± 2271 | <0.001 ^ |
Peak | 4590 ± 2125 | 2980 ± 904 | 4194 ± 897 | 6596 ± 2271 | <0.001 * |
Reserve | 2314 ± 1507 | 967 ± 515 | 2075 ± 288 | 3901 ± 1441 | <0.001 * |
Stress impaired hemodynamic phenotypes, n (%) | |||||
Reduced heart rate response | 630 (46.9%) | 303 (67.6%) | 214 (47.8%) | 113 (25.2%) | <0.001 * |
Reduced preload response | 808 (60.1%) | 341 (76.1%) | 252 (56.3%) | 215 (48.0%) | <0.001 * |
End-systolic volume increase | 222 (16.5%) | 95 (21.2%) | 66 (14.7%) | 61 (13.6%) | 0.004 ^ |
Reduced contractile response | 707 (52.6%) | 252 (56.3%) | 247 (55.1%) | 208 (46.4%) | 0.006 ^ |
Univariable Analysis | Multivariable Model | |||
---|---|---|---|---|
OVERALL (n = 1344) | ||||
Variables | OR (95%CI) | p | OR (95%CI) | p |
Female Sex | 1.329 (1.056–1.672) | 0.015 | 1.819 (1.372–2.413) | <0.001 |
Age | 1.035 (1.024–1.046) | <0.001 | 1.027 (1.013–1.040) | <0.001 |
Hypertension (yes) | 1.609 (1.250–2.070) | <0.001 | ||
Diabetes (yes) | 1.666 (1.257–2.208) | <0.001 | ||
Rest WMSI | 0.984 (0.642–1.509) | 0.942 | ||
Rest Ejection Fraction % | 1.009 (0.995–1.024) | 0.205 | ||
Peak Ejection Fraction % | 0.951 (0.940–0.962) | <0.001 | 0.932 (0.916–0.948) | <0.001 |
Inability to perform 85% age-predicted HR | 2.752 (2.177–3.749) | <0.001 | 2.363 (1.177–3.140) | <0.001 |
Blunted LVCR (peak FORCE/rest FORCE ≤ 2) | 1.246 (0.992–1.565) | 0.059 | 1.579 (1.105–2.259) | 0.012 |
Chronotropic incompetence (stress/rest HR < 1.85) | 3.636 (2.860–4.623) | <0.001 | 3.923 (2.915–5.279) | <0.001 |
Reduced preload reserve (peak EDV < rest EDV) | 2.928 (2.272–3.773) | <0.001 | 5.610 (4.025–7.821) | <0.001 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Bombardini, T.; Zagatina, A.; Ciampi, Q.; Arbucci, R.; Merlo, P.M.; Haber, D.M.L.; Morrone, D.; D'Andrea, A.; Djordjevic-Dikic, A.; Beleslin, B.; et al. Hemodynamic Heterogeneity of Reduced Cardiac Reserve Unmasked by Volumetric Exercise Echocardiography. J. Clin. Med. 2021, 10, 2906. https://doi.org/10.3390/jcm10132906
Bombardini T, Zagatina A, Ciampi Q, Arbucci R, Merlo PM, Haber DML, Morrone D, D'Andrea A, Djordjevic-Dikic A, Beleslin B, et al. Hemodynamic Heterogeneity of Reduced Cardiac Reserve Unmasked by Volumetric Exercise Echocardiography. Journal of Clinical Medicine. 2021; 10(13):2906. https://doi.org/10.3390/jcm10132906
Chicago/Turabian StyleBombardini, Tonino, Angela Zagatina, Quirino Ciampi, Rosina Arbucci, Pablo Martin Merlo, Diego M. Lowenstein Haber, Doralisa Morrone, Antonello D'Andrea, Ana Djordjevic-Dikic, Branko Beleslin, and et al. 2021. "Hemodynamic Heterogeneity of Reduced Cardiac Reserve Unmasked by Volumetric Exercise Echocardiography" Journal of Clinical Medicine 10, no. 13: 2906. https://doi.org/10.3390/jcm10132906
APA StyleBombardini, T., Zagatina, A., Ciampi, Q., Arbucci, R., Merlo, P. M., Haber, D. M. L., Morrone, D., D'Andrea, A., Djordjevic-Dikic, A., Beleslin, B., Tesic, M., Boskovic, N., Giga, V., de Castro e Silva Pretto, J. L., Daros, C. B., Amor, M., Mosto, H., Salamè, M., Monte, I., ... on behalf of the Stress Echo 2020 Study Group of the Italian Society of Cardiovascular Imaging. (2021). Hemodynamic Heterogeneity of Reduced Cardiac Reserve Unmasked by Volumetric Exercise Echocardiography. Journal of Clinical Medicine, 10(13), 2906. https://doi.org/10.3390/jcm10132906