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Addressing Orthostatic Hypotension in Heart Failure: Pathophysiology, Clinical Implications and Perspectives

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Abstract

Heart failure (HF)is a condition at high risk for orthostatic hypotension (OH)given the large proportion of patients at an advanced age and high burden of comorbidities contributing to OH, as well as a high prevalence of medications with neurovascular and volume modulating properties. Early identification of OH in HF seems to be crucial as OH can have an impact on patient symptoms, activity level and independence, be a marker of specific pathophysiological changes or be an indicator of need for personalized treatment. OH might contribute significantly to bad enough prognosis in HF, as, besides a risk of falls and cognitive decline, it was found to be associated with cardiovascular morbidity and mortality. In this review, we aimed to incentivize the routine use of orthostatic testing in HF, as well as stimulate future research in this field, which could lead to significant advances in the treatment and outcomes.

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Abbreviations

ACCORD BP trial:

The Action to Control Cardiovascular Risk in Diabetes-Blood Pressure trial

ACE-I:

Angiotensin-converting-enzyme inhibitors

ARIC Study:

The Atherosclerosis Risk in Communities Study

BP:

Blood pressure

DBP:

Diastolic blood pressured

HF:

Heart failure

HFpEF:

Heart failure with preserved ejection fraction

HFrEF:

Heart failure with reduced ejection fraction

HR:

Heart rate

LV:

Left ventricular

ОН:

Orthostatic hypotension

OHtn:

Orthostatic hypertension

SBP:

Systolic blood pressure

SPRINT:

The Systolic Blood Pressure Intervention Trial

References

  1. Jones, N. R., Roalfe, A. K., Adoki, I., Hobbs, F. D. R., & Taylor, C. J. (2019). Survival of patients with chronic heart failure in the community: a systematic review and meta-analysis. Eur J Heart Fail, 21(11), 1306–1325. https://doi.org/10.1002/ejhf.1594.

    Article  PubMed  Google Scholar 

  2. Conrad, N., Judge, A., Tran, J., Mohseni, H., Hedgecott, D., Crespillo, A. P., et al. (2018). Temporal trends and patterns in heart failure incidence: a population-basedstudy of 4 million individuals. Lancet, 391(10120), 572–580. https://doi.org/10.1016/S0140-6736(17)32520-5.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Mazurek, J. A., & Jessup, M. (2017). Understanding heart failure. Heart Fail Clin, 13(1), 1–19. https://doi.org/10.1016/j.hfc.2016.07.001.

    Article  PubMed  Google Scholar 

  4. Metra, M., & Teerlink, J. R. (2017). Heart failure. Lancet, 390(10106), 1981–1995. https://doi.org/10.1016/S0140-6736(17)31071-1.

    Article  PubMed  Google Scholar 

  5. Mareev, V. Y., Fomin, O. V., Ageev, F. T., Begrambekova, Y. L., Vasyuk, Y. A., Garganeeva, A. A., et al. (2018). Russian heart failure society, Russian society of cardiology. Russian scientific medical society of internal medicine guidelines for heart failure: Chronic (CHF)and acute decompensated (ADHF). Diagnosis, prevention and treatment. Kardiologiya, 58, 8–164. https://doi.org/10.18087/cardio.2475.

    Article  Google Scholar 

  6. Pieske, B., Tschöpe, C., De Boer, R. A., Fraser, A. G., Anker, S. D., Donal, E., et al. (2019). How to diagnose heart failure with preserved ejection fraction: The HFA-PEFFdiagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA)of the European Society of Cardiology (ESC). Eur Heart J, 40(40), 3297–3317. https://doi.org/10.1093/eurheartj/ehz641.

    Article  PubMed  Google Scholar 

  7. Ponikowski, P., Voors, A. A., Anker, S. D., Bueno, H., Cleland, J. G. F., Coats, A. J. S., et al. (2016). 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. Eur J Heart Fail, 18(8), 891–975. https://doi.org/10.1002/ejhf.592.

    Article  PubMed  Google Scholar 

  8. Yancy, C. W., Jessup, M., Bozkurt, B., Butler, J., Casey, D. E., Drazner, M. H., et al. (2013). 2013 ACCF/AHAguideline for the management of heart failure: A report of the American College of Cardiology Foundation/AmericanHeart Association task force on practice guidelines. J Am Coll Cardiol, 62(16), 240–327. https://doi.org/10.1016/j.jacc.2013.05.019.

    Article  Google Scholar 

  9. Hartog, L. C., Schrijnders, D., Landman, G. W. D., Groenier, K., Kleefstra, N., Bilo, H. J. G., & van Hateren, K. J. J. (2017). Is orthostatic hypotension related to falling? A meta-analysisof individual patient data of prospective observational studies. Age Ageing, 46(4), 568–575. https://doi.org/10.1093/ageing/afx024.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Mol, A., Bui Hoang, P. T. S., Sharmin, S., Reijnierse, E. M., van Wezel, R. J. A., Meskers, C. G. M., & Maier, A. B. (2019). Orthostatic hypotension and falls in older adults: a systematic review and meta-analysis. J Am Med Dir Assoc, 20(5), 589–597. https://doi.org/10.1016/j.jamda.2018.11.003.

    Article  PubMed  Google Scholar 

  11. Finucane, C., O’Connell, M. D. L., Donoghue, O., Richardson, K., Savva, G. ,. M., & Kenny, R. A. (2017). Impaired orthostatic blood pressure recovery is associated with unexplained and injurious falls. J Am Geriatr Soc, 65(3), 474–482https://doi.org/10.1111/jgs.14563.

  12. Rawlings, A. M., Juraschek, S. P., Heiss, G., Hughes, T., Meyer, M. L., Selvin, E., et al. (2018). Association of orthostatic hypotension with incident dementia, stroke, and cognitive decline. Neurology, 91(8), 759–768. https://doi.org/10.1212/WNL.0000000000006027.

    Article  Google Scholar 

  13. Peters, R., Anstey, K. J., Booth, A., Beckett, N., Warwick, J., Antikainen, R., et al. (2018). Orthostatic hypotension and symptomatic subclinical orthostatic hypotension increase risk of cognitive impairment: an integrated evidence review and analysis of a large older adult hypertensive cohort. Eur Heart J, 39(33), 3135–3143. https://doi.org/10.1093/eurheartj/ehy418.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ricci, F., Fedorowski, A., Radico, F., Romanello, M., Tatasciore, A., Di Nicola, M., et al. (2015). Cardiovascular morbidity and mortality related to orthostatic hypotension: a meta-analysisof prospective observational studies. Eur Heart J, 36(25), 1609–1617. https://doi.org/10.1093/eurheartj/ehv093.

    Article  PubMed  Google Scholar 

  15. Min, M., Shi, T., Sun, C., Liang, M., Zhang, Y., Bo, G., & Sun, Y. (2019). Orthostatic hypotension and the risk of atrial fibrillation and other cardiovascular diseases: An updated meta-analysisof prospective cohort studies. J Clini Hypertens, 21(8), 1221–1227. https://doi.org/10.1111/jch.13613.

    Article  Google Scholar 

  16. Angelousi, A., Girerd, N., Benetos, A., Frimat, L., Gautier, S., Weryha, G., & Boivin, J.-M. (2014). Association between orthostatic hypotension and cardiovascular risk, cerebrovascular risk, cognitive decline and falls as well as overall mortality. J Hypertens, 32(8), 1562–1571. https://doi.org/10.1097/HJH.0000000000000235.

    Article  CAS  PubMed  Google Scholar 

  17. Ricci, F., De Caterina, R., & Fedorowski, A. (2015). Orthostatic hypotension. J Am Coll Cardiol, 66(7), 848–860. https://doi.org/10.1016/j.jacc.2015.06.1084.

    Article  PubMed  Google Scholar 

  18. Benvenuto, L. J., & Krakoff, L. R. (2011). Morbidity and mortality of orthostatic hypotension: Implications for management of cardiovascular disease. Am J Hypertens, 24(2), 135–144. https://doi.org/10.1038/ajh.2010.146.

    Article  PubMed  Google Scholar 

  19. Low, P. A., & Tomalia, V. A. (2015). Orthostatic hypotension: mechanisms, causes, management. J Clin Neurol (Korea), 11(3), 220–226. https://doi.org/10.3988/jcn.2015.11.3.220.

    Article  Google Scholar 

  20. Saedon, N. I., Pin Tan, M., & Frith, J. (2018). The prevalence of orthostatic hypotension: a systematic review and meta-analysis. J Gerontol: Series A, 75(1), 117–122. https://doi.org/10.1093/gerona/gly188.

    Article  Google Scholar 

  21. Feldstein, C., & Weder, A. B. (2012). Orthostatic hypotension: a common, serious and underrecognized problem in hospitalized patients. J Am Soc Hypertens, 6(1), 27–39. https://doi.org/10.1016/j.jash.2011.08.008.

    Article  PubMed  Google Scholar 

  22. Benjamin, E. J., Muntner, P., Alonso, A., Bittencourt, M. S., Callaway, C. W., Carson, A. P., et al. (2019). Heart Disease and Stroke Statistics-2019update: a report from the American Heart Association. Circulation, 139(10), 56–66. https://doi.org/10.1161/CIR.0000000000000659.

    Article  Google Scholar 

  23. van Riet, E. E. S., Hoes, A. W., Wagenaar, K. P., Limburg, A., Landman, M. A. J., & Rutten, F. H. (2016). Epidemiology of heart failure: the prevalence of heart failure and ventricular dysfunction in older adults over time. A systematic review. Eur J Heart Fail, 18(3), 242–252. https://doi.org/10.1002/ejhf.483.

    Article  PubMed  Google Scholar 

  24. Steinberg, B. A., Zhao, X., Heidenreich, P. A., Peterson, E. D., Bhatt, D. L., Cannon, C. P., et al. (2012). Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies, and outcomes. Circulation, 126(1), 65–75. https://doi.org/10.1161/CIRCULATIONAHA.111.080770.

    Article  PubMed  Google Scholar 

  25. Dunlay, S. M., Roger, V. L., & Redfield, M. M. (2017). Epidemiology of heart failure with preserved ejection fraction. Nat Rev Cardiol, 14(10), 591–602. https://doi.org/10.1038/nrcardio.2017.65.

    Article  PubMed  Google Scholar 

  26. Townsend, R. R., Chang, T. I., Cohen, D. L., Cushman, W. C., Evans, G. W., Glasser, S. P., et al. (2016). Orthostatic changes in systolic blood pressure among SPRINT participants at baseline. J Am Soc Hypertens : JASH, 10(11), 847–856. https://doi.org/10.1016/j.jash.2016.08.005.

    Article  PubMed  Google Scholar 

  27. Maurer, M. S., Schwartz, J. H., Gundapaneni, B., Elliott, P. M., Merlini, G., Waddington-Cruz, M., et al. (2018). Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med, 379(11), 1007–1016. https://doi.org/10.1056/NEJMoa1805689.

    Article  CAS  PubMed  Google Scholar 

  28. Palma, J.-A., Gonzalez-Duarte, A., & Kaufmann, H. (2019). Orthostatic hypotension in hereditary transthyretin amyloidosis: epidemiology, diagnosis and management. Clin Auton Res, 29(1), 33–44. https://doi.org/10.1007/s10286-019-00623-x.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Kario, K. (2013). Orthostatic hypertension -a new haemodynamic cardiovascular risk factor. Nat Rev Nephrol, 9(12), 726–738. https://doi.org/10.1038/nrneph.2013.224.

    Article  CAS  PubMed  Google Scholar 

  30. Gorelik, O., Feldman, L., & Cohen, N. (2016). Heart failure and orthostatic hypotension. Heart Fail Rev, 21(5), 529–538. https://doi.org/10.1007/s10741-016-9541-z.

    Article  PubMed  Google Scholar 

  31. Kubo, S. H., & Cody, R. J. (1983). Circulatory autoregulation in chronic congestive heart failure: responses to head-uptilt in 41 patients. Am J Cardiol, 52(5), 512–518. https://doi.org/10.1016/0002-9149(83)90017-6.

    Article  CAS  PubMed  Google Scholar 

  32. Räihä, I., Luutonen, S., Piha, J., Seppänen, A., Toikka, T., & Sourander, L. (1995). Prevalence, predisposing factors, and prognostic importance of postural hypotension. Arch Intern Med, 155(9), 930–935. https://doi.org/10.1001/archinte.1995.00430090067008.

    Article  PubMed  Google Scholar 

  33. Potocka-Plazak, K., & Plazak, W. (2001). Orthostatic hypotension in elderly women with congestive heart failure. Aging Clin Exp Res, 13(5), 378–384. https://doi.org/10.1007/bf03351506.

    Article  CAS  Google Scholar 

  34. Mehagnoul-Schipper, D. J., Colier, W. N. J. M., Hoefnagels, W. H. L., Verheugt, F. W. A., & Jansen, R. W. M. M. (2002). Effects of furosemide versus captopril on postprandial and orthostatic blood pressure and on cerebral oxygenation in patients ≥70 years of age with heart failure. Am J Cardiol, 90(6), 596–600. https://doi.org/10.1016/S0002-9149(02)02562-6.

    Article  CAS  PubMed  Google Scholar 

  35. Gorelik, O., Fishlev, G., Litvinov, V., Almoznino-Sarafian, D., Alon, I., Shteinshnaider, M., et al. (2005). First morning standing up may be risky in acutely ill older inpatients. Blood Press, 14(3), 139–143. https://doi.org/10.1080/08037050510008968.

    Article  PubMed  Google Scholar 

  36. Weiss, A., Beloosesky, Y., Kornowski, R., Yalov, A., Grinblat, J., & Grossman, E. (2006). Influence of orthostatic hypotension on mortality among patients discharged from an acute geriatric ward. J Gen Intern Med, 21(6), 602–606. https://doi.org/10.1111/j.1525-1497.2006.00450.x.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Bouhanick, B., Meliani, S., Doucet, J., Bauduceau, B., Verny, C., Chamontin, B., & Le Floch, J. P. (2014). Orthostatic hypotension is associated with more severe hypertension in elderly autonomous diabetic patients from the French Gerodiab study at inclusion. Annales de Cardiologie et d’Angeiologie, 63(3), 176–182. https://doi.org/10.1016/j.ancard.2014.05.013.

    Article  CAS  PubMed  Google Scholar 

  38. Veronese, N., De Rui, M., Bolzetta, F., Zambon, S., Corti, M. C., Baggio, G., et al. (2015). Orthostatic changes in blood pressure and mortality in the elderly: the Pro.V.A study. Am J Hypertens, 28(10), 1248–1256. https://doi.org/10.1093/ajh/hpv022.

    Article  CAS  PubMed  Google Scholar 

  39. Chou, R.-H., Liu, C.-J., Chao, T.-F., Chen, S.-J., Tuan, T.-C., Chen, T.-J., & Chen, S.-A. (2015). Association between orthostatic hypotension, mortality, and cardiovascular disease in Asians. Int J Cardiol, 195, 40–44. https://doi.org/10.1016/j.ijcard.2015.05.060.

    Article  PubMed  Google Scholar 

  40. Fleg, J. L., Evans, G. W., Margolis, K. L., Barzilay, J., Basile, J. N., Bigger, J. T., et al. (2016). Orthostatic hypotension in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) blood pressure trial: prevalence, incidence, and prognostic significance. Hypertension, 68(4), 888–895. https://doi.org/10.1161/HYPERTENSIONAHA.116.07474.

    Article  CAS  PubMed  Google Scholar 

  41. Juraschek, S. P., Daya, N., Appel, L. J., Miller, E. R., Windham, B. G., Pompeii, L., et al. (2017). Orthostatic hypotension in middle-ageand risk of falls. Am J Hypertens, 30(2), 188–195. https://doi.org/10.1093/ajh/hpw108.

    Article  PubMed  Google Scholar 

  42. Ali, A., Holm, H., Molvin, J., Bachus, E., Tasevska-Dinevska, G., Fedorowski, A., et al. (2018). Autonomic dysfunction is associated with cardiac remodelling in heart failure patients. ESC Heart Failure, 5(1), 46–52. https://doi.org/10.1002/ehf2.12223.

    Article  PubMed  Google Scholar 

  43. Testa, G., Ceccofiglio, A., Mussi, C., Bellelli, G., Nicosia, F., Bo, M., et al. (2018). Hypotensive drugs and syncope due to orthostatic hypotension in older adults with dementia (syncope and dementia study). J Am Geriatr Soc, 66(8), 1532–1537. https://doi.org/10.1111/jgs.15421.

    Article  PubMed  Google Scholar 

  44. Clark CE, Thomas D, Warren FC, Llewellyn DJ, Ferrucci L, & Campbell JL (2018). Detecting Risk of Postural hypotension (DROP): derivation and validation of a prediction score for primary care. BMJ Open, 8(4). https://doi.org/10.1136/bmjopen-2017-020740.

  45. Zhu, Q. O., Tan, C. S. G., Tan, H. L., Wong, R. G., Joshi, C. S., Cuttilan, R. A., et al. (2016). Orthostatic hypotension: Prevalence and associated risk factors among the ambulatory elderly in an Asian population. Singap Med J, 57(8), 444–451. https://doi.org/10.11622/smedj.2016135.

    Article  Google Scholar 

  46. Januszko-Giergielewicz, B., Gromadziński, L., Dudziak, M., & Dębska-Ślizień, A. (2019). Orthostatic hypotension in asymptomatic patients with chronic kidney disease. Medicina (Lithuania), 55(4), 113. https://doi.org/10.3390/medicina55040113.

    Article  Google Scholar 

  47. Juraschek, S. P., Daya, N., Appel, L. J., Miller, E. R., McEvoy, J. W., Matsushita, K., et al. (2018). Orthostatic hypotension and risk of clinical and subclinical cardiovascular disease in middle-agedadults. J Am Heart Assoc, 7(10), e008884. https://doi.org/10.1161/JAHA.118.008884.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Freeman, R., Wieling, W., Axelrod, F. B., Benditt, D. G., Benarroch, E., Biaggioni, I., et al. (2011). Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res, 21(2), 69–72. https://doi.org/10.1007/s10286-011-0119-5.

    Article  PubMed  Google Scholar 

  49. Shen, W. K., Sheldon, R. S., Benditt, D. G., Cohen, M. I., Forman, D. E., Goldberger, Z. D., et al. (2017). 2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope: a report of the American college of cardiology/AmericanHeart Association task force on clinical practice guidelines and the Heart Rhythm Society. Circulation, 136(5), 60–122. https://doi.org/10.1161/CIR.0000000000000499.

    Article  Google Scholar 

  50. Brignole, M., Moya, A., De Lange, F. J., Deharo, J. C., Elliott, P. M., Fanciulli, A., et al. (2018). 2018 ESC guidelines for the diagnosis and management of syncope. Eur Heart J, 39(21), 1883–1948. https://doi.org/10.1093/eurheartj/ehy037.

    Article  PubMed  Google Scholar 

  51. Fanciulli, A., Jordan, J., Biaggioni, I., Calandra-Buonaura, G., Cheshire, W. P., Cortelli, P., et al. (2018). Consensus statement on the definition of neurogenic supine hypertension in cardiovascular autonomic failure by the American Autonomic Society (AAS)and the European Federation of Autonomic Societies (EFAS): endorsed by the European Academy of Neurology. Clin Auton Res: official journal of the Clinical Autonomic Research Society, 28(4), 355–362. https://doi.org/10.1007/s10286-018-0529-8.

    Article  Google Scholar 

  52. Fessel, J., & Robertson, D. (2006). Orthostatic hypertension: when pressor reflexes overcompensate. Nat Clin Pract Nephrol. https://doi.org/10.1038/ncpneph0228.

  53. Freeman, R., Abuzinadah, A. R., Gibbons, C., Jones, P., Miglis, M. G., & Sinn, D. I. (2018). Orthostatic hypotension: JACC state-of-the-artreview. J Am Coll Cardiol, 72(11), 1294–1309. https://doi.org/10.1016/j.jacc.2018.05.079.

    Article  PubMed  Google Scholar 

  54. Abelmann, W. H., & Fareeduddin, K. (1967). Circulatory response to upright tilt in patients with heart disease. Cardiovasc Res, 21(5), 362–368.

    Google Scholar 

  55. Fudim, M., Hernandez, A. F., & Felker, G. M. (2017). Role of volume redistribution in the congestion of heart failure. J Am Heart Assoc, 6(8), e006817. https://doi.org/10.1161/JAHA.117.006817.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Gheorghiade, M., Follath, F., Ponikowski, P., Barsuk, J. H., Blair, J. E. A., Cleland, J. G., et al. (2010). Assessing and grading congestion in acute heart failure: a scientific statement from the acute heart failure committee of the heart failure association of the European Society of Cardiology and endorsed by the European Society of Intensive Care Medicine. Eur J Heart Fail, 12(5), 423–433. https://doi.org/10.1093/eurjhf/hfq045.

    Article  PubMed  Google Scholar 

  57. Mclachlan, C. Y. L., Yi, M., Ling, A., & Jardine, D. L. (2014). Adverse drug events are a major cause of acute medical admission. Intern Med J, 44(7), 633–638. https://doi.org/10.1111/imj.12455.

    Article  CAS  PubMed  Google Scholar 

  58. Posch, A. M., Luippold, A. J., Mitchell, K. M., Bradbury, K. E., Kenefick, R. W., Cheuvront, S. N., & Charkoudian, N. (2017). Sympathetic neural and hemodynamic responses to head-uptilt during isoosmotic and hyperosmotic hypovolemia. J Neurophysiol, 118(4), 2232–2237. https://doi.org/10.1152/jn.00403.2017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Obokata, M., Reddy, Y. N. V., & Borlaug, B. A. (2019). Diastolic dysfunction and heart failure with preserved ejection fraction. JACC Cardiovasc Imaging, 1, 245–257. https://doi.org/10.1016/j.jcmg.2018.12.034.

    Article  Google Scholar 

  60. Morris, R. I., Sobotka, P. A., Balmforth, P. K., Stöhr, E. J., McDonnell, B. J., Spencer, D., et al. (2020). Iliocaval venous obstruction, cardiac preload reserve and exercise limitation. J Cardiovasc Transl Res. https://doi.org/10.1007/s12265-020-09963-w.

  61. Sengstock, D., Vaitkevicius, P. V., & Supiano, M. A. (2005). Does increased arterial stiffness increase the risk for postural hypotension? Am J Geriatr Cardiol, 14(5), 224–229. https://doi.org/10.1111/j.1076-7460.2005.04503.x.

    Article  PubMed  Google Scholar 

  62. Kobayashi, Y., Fujikawa, T., Kobayashi, H., Sumida, K., Suzuki, S., Kagimoto, M., et al. (2017). Relationship between arterial stiffness and blood pressure drop during the sit-to-standtest in patients with diabetes mellitus. J Atheroscler Thromb, 24(2), 147–156. https://doi.org/10.5551/jat.34645.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Takahashi, M., Miyai, N., Nagano, S., Utsumi, M., Oka, M., Yamamoto, M., et al. (2015). Orthostatic blood pressure changes and subclinical markers of atherosclerosis. Am J Hypertens, 28(9), 1134–1140. https://doi.org/10.1093/ajh/hpu301.

    Article  CAS  PubMed  Google Scholar 

  64. Kirkham, F. A., Rankin, P., Parekh, N., Holt, S. G., & Rajkumar, C. (2019). Aortic stiffness and central systolic pressure are associated with ambulatory orthostatic BP fall in chronic kidney disease. J Nephrol. https://doi.org/10.1007/s40620-019-00655-6.

  65. Fudim, M., Rogers, J. G., Frazier-Mills, C., & Patel, C. B. (2018). Orthostatic hypotension in patients with left ventricular assist devices: acquired autonomic dysfunction. ASAIO J (American Society for Artificial Internal Organs : 1992), 64(3), e40–e42. https://doi.org/10.1097/MAT.0000000000000640.

    Article  Google Scholar 

  66. Chatterjee, N. A., & Singh, J. P. (2015). Novel interventional therapies to modulate the autonomic tone in heart failure. JACC: Heart Failure, 3(10), 786–802. https://doi.org/10.1016/j.jchf.2015.05.008.

    Article  PubMed  Google Scholar 

  67. Fraser, K. S., Heckman, G. A., McKelvie, R. S., Harkness, K., Middleton, L. E., & Hughson, R. L. (2015). Cerebral hypoperfusion is exaggerated with an upright posture in heart failure: impact of depressed cardiac output. JACC: Heart Failure, 3(2), 168–175. https://doi.org/10.1016/j.jchf.2014.07.017.

    Article  PubMed  Google Scholar 

  68. Juraschek, S. P., Miller, E. R., & Appel, L. J. (2018). Orthostatic hypotension and symptoms in the AASK trial. Am J Hypertens, 31(6), 665–671. https://doi.org/10.1093/ajh/hpy010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Williams, B., Mancia, G., Spiering, W., Rosei, E. A., Azizi, M., Burnier, M., et al. (2018). 2018 ESC/ESHguidelines for themanagement of arterial hypertension. Eur Heart J, 39(33), 3021–3104. https://doi.org/10.1093/eurheartj/ehy339.

    Article  PubMed  Google Scholar 

  70. Whelton, P. K., Carey, R. M., Aronow, W. S., Casey, D. E., Collins, K. J., Himmelfarb, C. D., et al. (2018). 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults a report of the American College of Cardiology/AmericanHeart Association Task Force on clinical practice guidelines. Hypertension, 71(6), 13–115. https://doi.org/10.1161/HYP.0000000000000065.

    Article  CAS  Google Scholar 

  71. Slavachevsky, I., Rachmani, R., Levi, Z., Brosh, D., Lidar, M., & Ravid, M. (2000). Effect of enalapril and nifedipine on orthostatic hypotension in older hypertensive patients. J Am Geriatr Soc, 48(7), 807–810. https://doi.org/10.1111/j.1532-5415.2000.tb04757.x.

    Article  CAS  PubMed  Google Scholar 

  72. Weir, M. R., Weber, M. A., Neutel, J. M., Vendetti, J., Michelson, E. L., & Wang, R. Y. (2001). Efficacy of candesartan cilexetil as add-ontherapy in hypertensive patients uncontrolled on background therapy: a clinical experience trial. Am J Hypertens, 14(6 I), 567–572. https://doi.org/10.1016/S0895-7061(00)01304-2.

    Article  CAS  PubMed  Google Scholar 

  73. Pool, J. L., Glazer, R., Chiang, Y. T., & Gatlin, M. (1999). Dose-responseefficacy of valsartan, a new angiotensin II receptor blocker. J Hum Hypertens, 13(4), 275–281. https://doi.org/10.1038/sj.jhh.1000788.

  74. Romero, R., Castellote, E., OcóN, J., & Wagner, B. (1995). Controlled multicenter study with quinapril, hydrochlorothiazide, and combination in patients with moderate to severe hypertension. J Cardiovasc Pharmacol, 26(1), 114–118. https://doi.org/10.1097/00005344-199507000-00018.

    Article  CAS  PubMed  Google Scholar 

  75. Juraschek, S. P., Simpson, L. M., Davis, B. R., Beach, J. L., Ishak, A., & Mukamal, K. J. (2019). Effects of antihypertensive class on falls, syncope, and orthostatic hypotension in older adults: the ALLHAT trial. Hypertension, 74(4), 1033–1040. https://doi.org/10.1161/HYPERTENSIONAHA.119.13445.

    Article  CAS  PubMed  Google Scholar 

  76. Krum, H., Conway, E. L., Broadbear, J. H., Howes, L. G., & Louis, W. J. (1994). Postural hypotension in elderly patients given carvedilol. BMJ, 309(6957), 775. https://doi.org/10.1136/bmj.309.6957.775.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Cleophas, T. J., Grabowsky, I., Niemeyer, M. G., Mäkel, W. M., & Van der Wall, E. E. (2002). Paradoxical pressor effects of β-blockersin standing elderly patients with mild hypertension: a beneficial side effect. Circulation, 105(14), 1669–1671. https://doi.org/10.1161/01.CIR.0000012745.50229.AC.

    Article  CAS  PubMed  Google Scholar 

  78. Juraschek, S. P., Appel, L. J., Miller, E. R., Mukamal, K. J., & Lipsitz, L. A. (2018). Hypertension treatment effects on orthostatic hypotension and its relationship with cardiovascular disease results from the AASK trial. Hypertension, 72(4), 986–993. https://doi.org/10.1161/HYPERTENSIONAHA.118.11337.

    Article  CAS  PubMed  Google Scholar 

  79. Romero, S. A., Moralez, G., Rickards, C. A., Ryan, K. L., Convertino, V. A., Fogt, D. L., & Cooke, W. H. (2011). Control of cerebral blood velocity with furosemide-inducedhypovolemia and upright tilt. J Appl Physiol, 110(2), 492–498. https://doi.org/10.1152/japplphysiol.01060.2010.

    Article  PubMed  Google Scholar 

  80. Imhof, P. R., Sieber, A., Hodler, J., Muller, P., Ott, B., Fankhauser, P., et al. (1982). Plasma concentrations and haemodynamic effects of nitroglycerin during and after intravenous infusion in healthy volunteers. Eur J Clin Pharmacol, 23(2), 99–106. https://doi.org/10.1007/BF00545962.

    Article  CAS  PubMed  Google Scholar 

  81. Juraschek, S. P., Taylor, A. A., Wright, J. T., Evans, G. W., Miller, E. R., Plante, T. B., et al. (2020). Orthostatic hypotension, cardiovascular outcomes, and adverse events: results from SPRINT. Hypertension (Dallas, Tex : 1979), 75(3), 660–667. https://doi.org/10.1161/HYPERTENSIONAHA.119.14309.

    Article  CAS  Google Scholar 

  82. Kamaruzzaman, S., Watt, H., Carson, C., & Ebrahim, S. (2010). The association between orthostatic hypotension and medication use in the British Women’s Heart and Health Study. Age Ageing, 39(1), 51–56. https://doi.org/10.1093/ageing/afp192.

    Article  PubMed  Google Scholar 

  83. Valbusa, F., Labat, C., Salvi, P., Vivian, M. E., Hanon, O., & Benetos, A. (2012). Orthostatic hypotension in very old individuals living in nursing homes: the PARTAGE study. J Hypertens, 30(1), 53–60. https://doi.org/10.1097/HJH.0b013e32834d3d73.

    Article  CAS  PubMed  Google Scholar 

  84. Fisher, A. A., McLean, A. J., Davis, M. W., & Le Couteur, D. G. (2003). A multicenter, case-controlstudy of the effects of antihypertensive therapy on orthostatic hypotension, postprandial hypotension, and falls in octo-and nonagenarians in residential care facilities. Curr Ther Res Clin Exp, 64(3), 206–214. https://doi.org/10.1016/S0011-393X(03)00023-7.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Wong, A. K. W., Lord, S. R., Sturnieks, D. L., Delbaere, K., Trollor, J. N., & Close, J. C. T. (2013). Angiotensin system-blockingmedications are associated with fewer falls over 12 months in community-dwellingolder people. J Am Geriatr Soc, 61(5), 776–781. https://doi.org/10.1111/jgs.12205.

    Article  PubMed  Google Scholar 

  86. Canney, M., O’Connell, M. D. L., Murphy, C. M., O’Leary, N., Little, M. A., O’Seaghdha, C. M., & Kenny, R. A. (2016). Single agent antihypertensive therapy and orthostatic blood pressure behaviour in older adults using beat-to-beatmeasurements: the Irish longitudinal study on ageing. PLoS One, 11(1), e0146156. https://doi.org/10.1371/journal.pone.0146156.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Weir, M. R., Yeh, F., Silverman, A., Devereux, R. B., Galloway, J. M., Henderson, J. A., et al. (2009). Safety and feasibility of achieving lower systolic blood pressure goals in persons with type 2 diabetes: the SANDS trial. J Clin Hypertens, 11(10), 540–548. https://doi.org/10.1111/j.1751-7176.2009.00121.x.

    Article  CAS  Google Scholar 

  88. Pflugfelder, P. W., Baird, G., Tonkon, M. J., Di Bianco, R., Pitt, B., & The Quinapril Heart Failure Trial Investigators. (1993). Clinical consequences of angiotensin-convertingenzyme inhibitor withdrawl in chronic heart failure: a double-blind, placebo-controlledstudy of quinapril. J Am Coll Cardiol, 22(6), 1557–1563. https://doi.org/10.1016/0735-1097(93)90578-O.

    Article  CAS  PubMed  Google Scholar 

  89. Halliday, B. P., Wassall, R., Lota, A. S., Khalique, Z., Gregson, J., Newsome, S., et al. (2019). Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial. Lancet, 393(10166), 61–73. https://doi.org/10.1016/S0140-6736(18)32484-X.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Gilstrap, L. G., Fonarow, G. C., Desai, A. S., Liang, L., Matsouaka, R., DeVore, A. D., et al. (2017). Initiation, continuation, or withdrawal of angiotensin-convertingenzyme inhibitors/angiotensinreceptor blockers and outcomes in patients hospitalized with heart failure with reduced ejection fraction. J Am Heart Assoc, 6(2), e004675. https://doi.org/10.1161/JAHA.116.004675.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Fonarow, G. C., Abraham, W. T., Albert, N. M., Stough, W. G., Gheorghiade, M., Greenberg, B. H., et al. (2008). Influence of Beta-blockercontinuation or withdrawal on outcomes in patients hospitalized with heart failure. Findings from the OPTIMIZE-HFprogram. J Am Coll Cardiol, 52(3), 190–199. https://doi.org/10.1016/j.jacc.2008.03.048.

    Article  CAS  PubMed  Google Scholar 

  92. Khalil, C. A., Sulaiman, K., Mahfoud, Z., Singh, R., Asaad, N., Alhabib, K. F., et al. (2017). Non-withdrawalof beta blockers in acute decompensated chronic and de novo heart failure with reduced ejection fraction in a prospective multicentre study of patients with acute heart failure in the Middle East. BMJ Open, 7(7), e014915. https://doi.org/10.1136/bmjopen-2016-014915.

  93. Prins, K. W., Neill, J. M., Tyler, J. O., Eckman, P. M., & Duval, S. (2015). Effects of Beta-blockerwithdrawal in acute decompensated heart failure. A systematic review and meta-analysis. JACC: Heart Failure, 3(8), 647–653. https://doi.org/10.1016/j.jchf.2015.03.008.

    Article  PubMed  Google Scholar 

  94. Kapelios, C. J., Malliaras, K., Kaldara, E., Vakrou, S., & Nanas, J. N. (2018). Loop diuretics for chronic heart failure: a foe in disguise of a friend? Eur Heart J -Cardiovasc Pharmacother, 4(1), 54–63. https://doi.org/10.1093/ehjcvp/pvx020.

    Article  PubMed  Google Scholar 

  95. Martens, P., Verbrugge, F. H., Boonen, L., Nijst, P., Dupont, M., & Mullens, W. (2018). Value of routine investigations to predict loop diuretic down-titrationsuccess in stable heart failure. Int J Cardiol, 250, 171–175. https://doi.org/10.1016/j.ijcard.2017.10.018.

    Article  PubMed  Google Scholar 

  96. Rohde, L. E., Rover, M. M., Figueiredo Neto, J. A., Danzmann, L. C., Bertoldi, E. G., Simões, M. V., et al. (2019). Short-termdiuretic withdrawal in stable outpatients with mild heart failure and no fluid retention receiving optimal therapy: a double-blind, multicentre, randomized trial. Eur Heart J, 40(44), 3605–3612. https://doi.org/10.1093/eurheartj/ehz554.

  97. Fudim, M., Blumer, V. L., Lopes, R. D., Rossignol, P., Feldschuh, M., Miller, W. L., & Sobotka, P. A. (2019). Correlation of quantitated intravascular volume with blood pressure in patients with systemic hypertension. J Cardiovasc Transl Res. https://doi.org/10.1007/s12265-019-09910-4.

  98. Gibbons, C. H., Schmidt, P., Biaggioni, I., Frazier-Mills, C., Freeman, R., Isaacson, S., et al. (2017). The recommendations of a consensus panel for the screening, diagnosis, and treatment of neurogenic orthostatic hypotension and associated supine hypertension. J Neurol, 264(8), 1567–1582. https://doi.org/10.1007/s00415-016-8375-x.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Pandey, A., Khera, R., Park, B., Haykowsky, M., Borlaug, B. A., Lewis, G. D., et al. (2018). Relative impairments in hemodynamic exercise reserve parameters in heart failure with preserved ejection fraction: a study-levelpooled analysis. JACC: Heart Failure, 6(2), 117–126. https://doi.org/10.1016/j.jchf.2017.10.014.

    Article  PubMed  Google Scholar 

  100. Pal, N., Sivaswamy, N., Mahmod, M., Yavari, A., Rudd, A., Singh, S., et al. (2015). Effect of selective heart rate slowing in heart failure with preserved ejection fraction. Circulation, 132(18), 1719–1725. https://doi.org/10.1161/CIRCULATIONAHA.115.017119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Fudim, M., Sobotka, A. A., Yin, Y.-H., Wang, J. W., Levin, H., Esler, M., et al. (2018). Selective vs. global renal denervation: a case for less is more. Curr Hypertens Rep, 20(5), 37. https://doi.org/10.1007/s11906-018-0838-2.

    Article  PubMed  Google Scholar 

  102. Bapna, A., Adin, C., Engelman, Z. J., & Fudim, M. (2019). Increasing blood pressure by greater splanchnic nerve stimulation: a feasibility study. J Cardiovasc Transl Res. https://doi.org/10.1007/s12265-019-09929-7.

  103. Fudim, M., Yalamuri, S., Herbert, J. T., Liu, P. R., Patel, M. R., & Sandler, A. (2017). Raising the pressure: hemodynamic effects of splanchnic nerve stimulation. J Appl Physiol (Bethesda, Md : 1985), 123(1), 126–127. https://doi.org/10.1152/japplphysiol.00069.2017.

    Article  Google Scholar 

  104. Zannad, F. (2019). Autonomic nervous system modulation in heart failure: do we need another trial? Circulation. Heart failure, 12(11), e006491. https://doi.org/10.1161/CIRCHEARTFAILURE.119.006491.

    Article  PubMed  Google Scholar 

  105. Cooper, V. L., & Hainsworth, R. (2002). Effects of dietary salt on orthostatic tolerance, blood pressure and baroreceptor sensitivity in patients with syncope. Clin Auton Res, 12(4), 236–241. https://doi.org/10.1007/s10286-002-0018-x.

    Article  PubMed  Google Scholar 

  106. El-Sayed, H., & Hainsworth, R. (1996). Salt supplement increases plasma volume and orthostatic tolerance in patients with unexplained syncope. Heart, 75(2), 134–140. https://doi.org/10.1136/hrt.75.2.134.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Ponikowski, P., Voors, A. A., Anker, S. D., Bueno, H., Cleland, J. G. F., Coats, A. J. S., et al. (2016). 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Revista espanola de cardiologia (English ed), 69(12), 1167. https://doi.org/10.1016/j.rec.2016.11.005.

    Article  Google Scholar 

  108. Jordan, J., Shannon, J. R., Grogan, E., Biaggioni, I., & Robertson, D. (1999). A potent presser response elicited by drinking water. Lancet, 353(9154), 723. https://doi.org/10.1016/S0140-6736(99)99015-3.

    Article  CAS  PubMed  Google Scholar 

  109. Mathias, C. J., Holly, E., Armstrong, E., Shareef, M., & Bannister, R. (1991). The influence of food on postural hypotension in three groups with chronic autonomic failure--clinical and therapeutic implications. J Neurol Neurosurg Psychiatry, 54(8), 726–730. https://doi.org/10.1136/jnnp.54.8.726.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Podoleanu, C., Maggi, R., Brignole, M., Croci, F., Incze, A., Solano, A., et al. (2006). Lower limb and abdominal compression bandages prevent progressive orthostatic hypotension in elderly persons. A randomized single-blind controlled study. J Am Coll Cardiol, 48(7), 1425–1432. https://doi.org/10.1016/j.jacc.2006.06.052.

    Article  PubMed  Google Scholar 

  111. Gorelik, O., Fishlev, G., Almoznino-Sarafian, D., Alon, I., Weissgarten, J., Shteinshnaider, M., et al. (2004). Lower limb compression bandaging is effective in preventing signs and symptoms of seating-induced postural hypotension. Cardiology, 102(4), 177–183. https://doi.org/10.1159/000081007.

    Article  PubMed  Google Scholar 

  112. Figueroa, J. J., Basford, J. R., & Low, P. A. (2010). Preventing and treating orthostatic hypotension: As easy as A, B, C. Cleve Clin J Med, 77(5), 298–306. https://doi.org/10.3949/ccjm.77a.09118.

    Article  PubMed  PubMed Central  Google Scholar 

  113. Fanciulli, A., Goebel, G., Metzler, B., Sprenger, F., Poewe, W., Wenning, G. K., & Seppi, K. (2016). Elastic abdominal binders attenuate orthostatic hypotension in Parkinson’s disease. Mov Disord Clin Pract, 3(2), 156–160. https://doi.org/10.1002/mdc3.12270.

    Article  PubMed  Google Scholar 

  114. Figueroa, J. J., Singer, W., Sandroni, P., Sletten, D. M., Gehrking, T. L., Gehrking, J. A., et al. (2015). Effects of patient-controlled abdominal compression on standing systolic blood pressure in adults with orthostatic hypotension. Arch Phys Med Rehabil, 96(3), 505–510. https://doi.org/10.1016/j.apmr.2014.10.012.

    Article  PubMed  Google Scholar 

  115. Zion, A. S., De Meersman, R., Diamond, B. E., & Bloomfield, D. M. (2003). A home-based resistance-training program using elastic bands for elderly patients with orthostatic hypotension. Clin Auton Res, 13(4), 286–292. https://doi.org/10.1007/s10286-003-0117-3.

    Article  PubMed  Google Scholar 

  116. Smith, G. D. P., & Mathias, C. J. (1995). Postural hypotension enhanced by exercise in patients with chronic autonomic failure. QJM, 88(4), 251–256. https://doi.org/10.1093/oxfordjournals.qjmed.a069056.

    Article  CAS  PubMed  Google Scholar 

  117. Tutaj, M., Marthol, H., Berlin, D., Brown, C. M., Axelrod, F. B., & Hilz, M. J. (2006). Effect of physical countermaneuvers on orthostatic hypotension in familial dysautonomia. J Neurol, 253(1), 65–72. https://doi.org/10.1007/s00415-005-0928-3.

    Article  PubMed  Google Scholar 

  118. Krediet, C. T. P., Van Dijk, N., Linzer, M., Van Lieshout, J. J., & Wieling, W. (2002). Management of vasovagal syncope: controlling or aborting faints by leg crossing and muscle tensing. Circulation, 106(13), 1684–1689. https://doi.org/10.1161/01.CIR.0000030939.12646.8F.

    Article  PubMed  Google Scholar 

  119. Krediet, C. T. P., de Bruin, I. G. J. M., Ganzeboom, K. S., Linzer, M., van Lieshout, J. J., & Wieling, W. (2005). Leg crossing, muscle tensing, squatting, and the crash position are effective against vasovagal reactions solely through increases in cardiac output. J Appl Physiol, 99(5), 1697–1703. https://doi.org/10.1152/japplphysiol.01250.2004.

    Article  PubMed  Google Scholar 

  120. Fan, C. W., Walsh, C., & Cunningham, C. J. (2011). The effect of sleeping with the head of the bed elevated six inches on elderly patients with orthostatic hypotension: an open randomised controlled trial. Age Ageing, 40(2), 187–192. https://doi.org/10.1093/ageing/afq176.

    Article  PubMed  Google Scholar 

  121. Ten Harkel, A. D., Van Lieshout, J. J., & Wieling, W. (1992). Treatment of orthostatic hypotension with sleeping in the head-up tilt position, alone and in combination with fludrocortisone. J Intern Med, 232(2), 139–145. https://doi.org/10.1111/j.1365-2796.1992.tb00563.x.

    Article  PubMed  Google Scholar 

  122. Wright, R. A., Kaufmann, H. C., Perera, R., Opfer-Gehrking, T. L., McElligott, M. A., Sheng, K. N., & Low, P. A. (1998). A double-blind, dose-response study of midodrine in neurogenic orthostatic hypotension. Neurology, 51(1), 120–124. https://doi.org/10.1212/WNL.51.1.120.

    Article  CAS  PubMed  Google Scholar 

  123. Jankovic, J., Gilden, J. L., Hiner, B. C., Kaufmann, H., Brown, D. C., Coghlan, C. H., et al. (1993). Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine. Am J Med, 95(1), 38–48. https://doi.org/10.1016/0002-9343(93)90230-m.

    Article  CAS  PubMed  Google Scholar 

  124. Low, P. A. (1997). Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. JAMA, 277(13), 1046. https://doi.org/10.1001/jama.1997.03540370036033.

    Article  CAS  PubMed  Google Scholar 

  125. Midodrine - FDA prescribing information, side effects and uses. (n.d.). https://www.drugs.com/pro/midodrine.html#s-34070-3. Accessed 10 December 2019.

  126. Zakir, R. M., Folefack, A., Saric, M., & Berkowitz, R. L. (2009). The use of midodrine in patients with advanced heart failure. Congestive Heart Fail, 15(3), 108–111. https://doi.org/10.1111/j.1751-7133.2008.00042.x.

    Article  CAS  Google Scholar 

  127. Freeman, R., Landsberg, L., & Young, J. (1999). The treatment of neurogenic orthostatic hypotension with 3,4-DL-threo- dihydroxyphenylserine: a randomized, placebo-controlled, crossover trial. Neurology, 53(9), 2151–2157. https://doi.org/10.1212/wnl.53.9.2151.

    Article  CAS  PubMed  Google Scholar 

  128. Kaufmann, H., Saadia, D., Voustianiouk, A., Goldstein, D. S., Holmes, C., Yahr, M. D., et al. (2003). Norepinephrine precursor therapy in neurogenic orthostatic hypotension. Circulation, 108(6), 724–728. https://doi.org/10.1161/01.CIR.0000083721.49847.D7.

    Article  CAS  PubMed  Google Scholar 

  129. Kaufmann, H., Freeman, R., Biaggioni, I., Low, P., Pedder, S., Hewitt, L. A., et al. (2014). Droxidopa for neurogenic orthostatic hypotension: a randomized, placebo-controlled, phase 3 trial. Neurology, 83(4), 328–335. https://doi.org/10.1212/WNL.0000000000000615.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Biaggioni, I., Freeman, R., Mathias, C. J., Low, P., Arthur Hewitt, L., & Kaufmann, H. (2015). Randomized withdrawal study of patients with symptomatic neurogenic orthostatic hypotension responsive to droxidopa. Hypertension, 65(1), 101–107. https://doi.org/10.1161/HYPERTENSIONAHA.114.04035.

    Article  CAS  PubMed  Google Scholar 

  131. Droxidopa (professional patient advice) - Drugs.com. (n.d.). https://www.drugs.com/ppa/droxidopa.html. Accessed 10 December 2019.

  132. Isaacson, S., Vernino, S., Ziemann, A., Rowse, G. J., Kalu, U., & White, W. B. (2016). Long-term safety of droxidopa in patients with symptomatic neurogenic orthostatic hypotension. J Am Soc Hypertens, 10(10), 755–762. https://doi.org/10.1016/j.jash.2016.07.010.

    Article  CAS  PubMed  Google Scholar 

  133. Singer, W., Sandroni, P., Opfer-Gehrking, T. L., Suarez, G. A., Klein, C. M., Hines, S., et al. (2006). Pyridostigmine treatment trial in neurogenic orthostatic hypotension. Arch Neurol, 63(4), 513–518. https://doi.org/10.1001/archneur.63.4.noc50340.

    Article  PubMed  Google Scholar 

  134. Shibao, C., Okamoto, L. E., Gamboa, A., Yu, C., Diedrich, A., Raj, S. R., et al. (2010). Comparative efficacy of yohimbine against pyridostigmine for the treatment of orthostatic hypotension in autonomic failure. Hypertension (Dallas, Tex : 1979), 56(5), 847–851. https://doi.org/10.1161/HYPERTENSIONAHA.110.154898.

    Article  CAS  Google Scholar 

  135. Pyridostigmine - FDA prescribing information, side effects and uses. (n.d.). https://www.drugs.com/pro/pyridostigmine.html. Accessed 10 December 2019.

  136. Villacorta, A. S., Villacorta, H., Caldas, J. A., Precht, B. C., Porto, P. B., Rodrigues, L. U., et al. (2019). Effects of heart rate reduction with either pyridostigmine or ivabradine in patients with heart failure: a randomized, double-blind study. J Cardiovasc Pharmacol Ther, 24(2), 139–145. https://doi.org/10.1177/1074248418799364.

    Article  CAS  PubMed  Google Scholar 

  137. Schoffer, K. L., Henderson, R. D., O’Maley, K., & O’Sullivan, J. D. (2007). Nonpharmacological treatment, fludrocortisone, and domperidone for orthostatic hypotension in Parkinson’s disease. Mov Disord, 22(11), 1543–1549. https://doi.org/10.1002/mds.21428.

    Article  PubMed  Google Scholar 

  138. Fludrocortisone - FDA prescribing information, side effects and uses. (n.d.). https://www.drugs.com/pro/fludrocortisone.html. Accessed 10 December 2019.

  139. Grijalva, C. G., Biaggioni, I., Griffin, M. R., & Shibao, C. A. (2017). Fludrocortisone is associated with a higher risk of all-cause hospitalizations compared with midodrine in patients with orthostatic hypotension. J Am Heart Assoc, 6(10), e006848. https://doi.org/10.1161/JAHA.117.006848.

    Article  PubMed  PubMed Central  Google Scholar 

  140. Mahtani, K. R., Heneghan, C., Onakpoya, I., Tierney, S., Aronson, J. K., Roberts, N., et al. (2018). Reduced salt intake for heart failure: a systematic review. JAMA Intern Med, 178(12), 1693–1700. https://doi.org/10.1001/jamainternmed.2018.4673.

    Article  PubMed  Google Scholar 

  141. Heldeweg, M. L. A., Jorge, P. J. F., Ligtenberg, J. J. M., Ter Maaten, J. C., & Harms, M. P. M. (2018). Orthostatic blood pressure measurements are often overlooked during the initial evaluation of syncope in the emergency department. Blood Press Monit, 23(6), 294–296. https://doi.org/10.1097/MBP.0000000000000348.

    Article  PubMed  Google Scholar 

  142. Angelousi, A., Girerd, N., Benetos, A., Frimat, L., Gautier, S., Weryha, G., & Boivin, J.-M. (2014). Association between orthostatic hypotension and cardiovascular risk, cerebrovascular risk, cognitive decline and falls as well as overall mortality: a systematic review and meta-analysis. J Hypertens, 32(8), 1562–1571; discussion 1571. https://doi.org/10.1097/HJH.0000000000000235.

    Article  CAS  PubMed  Google Scholar 

  143. Prokopova, L. V., & Sitnikova, M. Y. (2018). Calculator “available prognosis”: method of evaluation for predicting survival of patients with chronic heart failure and reduced left ventricular ejection fraction. Kardiologiya, 58, 30–36. https://doi.org/10.18087/cardio.2438.

    Article  Google Scholar 

  144. Shlyakhto, E. V., Villevalde, S. V., Soloveva, A. E., Zvartau, N. E., Sitnikova, M. Y., Fedorova, D. N., et al. (2020). Rationale and design of multicenter prospective observational study of types, GRAde, VariabilITY, associations and prognosis of orthostatic responses in Heart Failure (GRAVITY-HF). Russ J Cardiol, 25(1), 78–82. https://doi.org/10.15829/1560-4071-2020-1-3662.

    Article  Google Scholar 

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Authors and Affiliations

  1. Almazov National Medical Research Centre, Saint Petersburg, Russian Federation

    Anzhela Soloveva, Darya Fedorova, Svetlana Villevalde, Nadezhda Zvartau, Mariya Sitnikova & Evgeny Shlyakhto

  2. National Medical Research Centre for Therapy and Preventive Medicine, Moscow, Russian Federation

    Yury Mareev

  3. Division of Cardiology, Duke University Medical Center, Durham, NC, USA

    Marat Fudim

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  8. Marat Fudim
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Corresponding author

Correspondence to Anzhela Soloveva.

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Conflict of Interest

Dr. Fudim consults for AxonTherapies, Daxor and Galvani. The other authors have no conflicts of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Editor-in-Chief Enrique Lara-Pezzioversaw the review of this article

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Main points

• Orthostatic hypotension (OH)and heart failure (HF)have an intertwined pathophysiology premised on volume status, comorbid conditions and autonomic dysfunction.

• Practitioners should recognize and address the orthostatic response in HF patients, as OH may be asymptomatic or masked by HF-associatedclinical symptoms. Personalized treatment strategies are needed.

• Adequate management of OH in HF patients is challenging due to the limited benefits of OH therapy and the risk of adverse effects or interaction with HF treatment.

• Given the projected grow in the incidence of both OH and HF, future research is needed to improve our understanding of disease overlap and interaction.

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Soloveva, A., Fedorova, D., Villevalde, S. et al. Addressing Orthostatic Hypotension in Heart Failure: Pathophysiology, Clinical Implications and Perspectives. J. of Cardiovasc. Trans. Res. 13, 549–569 (2020). https://doi.org/10.1007/s12265-020-10044-1

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  • DOI: https://doi.org/10.1007/s12265-020-10044-1

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