1. Management of malignant hypertension Bert-Jan van den Born, MD, PhD University of Amsterdam Medical Centres, location AMC Amsterdam, the Netherlands

2. . doi:10.1093/ehjcvp/pvy032

3.  Simplified stratification system: ‘hypertensive emergency’, while abandoning ‘hypertensive crisis’ and ‘hypertensive urgencies’  Up-to-date overview on the current epidemiology, pathophysiology and management of hypertensive emergencies  Hierarchical diagnostic work-up to quickly assess patients at the emergency department based on emergency symptoms.  Treatment recommendations based on current clinical practice and available intravenous blood pressure lowering agents. Main subjects covered

4. Key messages Patients with a hypertensive emergency should be admitted for close monitoring and, in most cases, treated with intravenous BP-lowering agents to reach the recommended BP target in the designated time-frame. Patients that have no hypertensive emergency can usually be treated with oral BP-lowering agents and discharged after a brief period of observation.

5.  Hypertensive emergencies are situations where very high BP values are associated with acute hypertension-mediated organ damage.  Key target organs are the aorta, heart, brain, retina & kidneys.  The type of target organ damage is the principal determinant of the choice of treatment, target BP and timeframe by which BP should be lowered. Hypertensive Emergencies

6. Acute HT mediated organ damage Aorta – dissection, aneurysm Heart – MACE, acute pulmonary oedema Brain – stroke, HT encephalopathy Retina & Kidneys – malignant hypertension

8.  Hypertensive emergency characterized by severe BP elevation (usually >200/120 mmHg) and advanced retinopathy, defined as the bilateral presence of flame- shaped haemorrhages, cotton wool spots or papilloedema. Malignant Hypertension Acute hypertensive microangiopathy?

9.  Characterized by acute microvascular damage with obliteration of small vessels of the retina (by definition), brain and kidney. Pathogenesis severe hypertension pressure natriuresis RAAS activation vascular hypertrophy & damage ischaemia

10.  Prevalence approximately 1/3 in unselected patients with malignant hypertension  Coombs-negative haemolysis (elevated lactic dehydrogenase levels, unmeasurable haptoglobin or schistocytes) and thrombocytopenia Thrombotic Microangiopathy

11. TMA also observed in: - severe sepsis - HELLP syndrome - cytotoxic therapy (cyclosporine, tacrolimus) - HUS-TTP - antiphospholipid syndrome

12.  Hypertensive emergency characterized by severe hypertension and (one or more of the following): seizures, lethargy, cortical blindness and coma, in the absence of an alternative explanation.  1 in 10 patients with MHT. Retinal abnormalities may be lacking in up to 1/3 ! Hypertensive Encephalopathy

13. Diagnostic work-up

14. Acute management  Aimed at preventing further microcirculatory damage (retinopathy, nephropathy)  Maintaining perfusion of vital organs ~ brain

15.  Close HD monitoring at ICU, MC or CCU  Table 4. IV drugs with onset and duration of action  Precipitous falls in BP treated with IV saline (half-life labetalol 4-6 hrs!) Acute management

16.  Halt offending drugs and/or agents (NSAID’s, cytotoxic or anti-angiogenic treatment)  Institute oral BP lowering medication after BP has stabilized and lower BP to high normal BP values within 5-7 days.  Not discussed: specific situations (e.g. hypertensive emergencies related to amphetamine and/or cocaine use, adrenergic crisis) Further considerations

17.  Survival improved, but mortality 5x higher than hypertensive patients without emergency  Need for KRT 20% in first 5 years  BP control strong predictor of progressive renal failure  Initial follow-up frequent (monthly)  Consider work-up secondary causes (e.g. renal parenchymal disease, renal artery stenosis) Prognosis and follow-up

18.  Malignant hypertension is a disease characterized by acute microcirculatory damage that leads to obliteration of small blood vessels and TMA  Affected organs: retina (by definition), kidneys and brain  Acute treatment aimed at preventing further damage while maintaining perfusion ~ reduction in MAP by 20-25% in a controlled way  Administration of labetalol or nicardipine under close HD monitoring  Prognosis strongly dependent on level of future BP control Summary