OCTOBER 2021 I 1

Leader in digital CPD for Southern African healthcare professionals

Cardiovascular diseaseEarn 2 free CEUs

© 2021 deNovo Medica

This report was made possible by an unrestricted educational grant from Bayer, Biotronik and Boehringer Ingelheim. The content of the report is independent of the sponsor.

Click here – you need to watch the video in order to complete the CPD questionnaire.

Dr Jens HitzerothCardiologistGroote SchuurCape Town

Heart failure

New guidelines, new treatments

Learning objectivesYou will learn:

• Important aspects of the management of heart failure with reduced ejection fraction (HFrEF)

• The latest clinical evidence on the use of angiotensin receptor-neprilysin inhibitors, sodium-glucose co-transporter-2 inhibitors, and newer agents not yet available in South Africa for the treatment of HFrEF

• Heart failure guideline recommendations for the management of HFrEF using drug therapies and ancillary interventions.

Introduction

The 2016 iteration of the European Society of Cardiology (ESC) guidelines for the diagnosis and treatment of acute and chronic heart failure (HF) took a very linear approach to the treatment of the condition, with the gradual introduction of various drugs to ensure that the patient received optimal therapy.1 This approach to the management of HF has changed in recent years and the ESC HF guidelines have therefore been updated, as presented at the 2021 ESC meeting.2 Dr Jens Hitzeroth discusses the evidence supporting current HF treatment approaches and the important changes in the 2021 ESC guidelines with regard to drug therapy and the management of the specific HF patient.

© iS

tock

/112

6160

344

2 I OCTOBER 2021

Heart failure – new guidelines, new treatments

Patients are usually not treated aggressively enough at the initial diagnosis of HFrEF; it is often only at the end stage, when the patient has deteriorated quite significantly, that medical therapy is intensified

HF with reduced ejection fraction (HFrEF) – important aspects

Why is it important to ascertain the primary cause of left ventricular (LV) dysfunction?

When a patient presents with HF, it is impor-tant to establish if the primary cause is LV dysfunction or if there are other non-LV dysfunction causes of HF syndromes. Other conditions that may manifest as a clinical HF

syndrome include valvular heart disease (aor-tic and mitral valve disease) and pericardial disease; these conditions are reversible in the sense that they can be treated surgically.

Is LV dysfunction reversible? When assessing the patient with HFrEF, it is necessary to rule out reversible causes of LV dysfunction (Table 1). Treatment of these causes often results in improvements in the patient’s myocardial function. Dr Hitzeroth is of the view that hypertension, a very common cause of HF in sub-Saharan Africa, is often neglected in terms of aggressive therapy; when hypertension is treated aggressively, there is usually a marked improvement in the patient’s clinical condition.

Table 1. Reversible causes of LV dysfunction

• Toxic – Ethanol – Chemotherapy

• Metabolic – Thiamine – Haemochromatosis – Tachycardia

• Peripartum • Ischaemia • Tachycardia • Hypertension.

What is the importance of early aggressive HF treatment?Patients are usually not treated aggressively enough when initially diagnosed with HFrEF; it is often only at the end stage, when the patient has deteriorated quite significantly, that medical therapy is intensified, with the patient potentially requiring palliative care

(Figure 1).3 Dr Hitzeroth emphasises that escalating intensive medical therapy earlier in the disease course can prevent the deteriora-tion of the patient for as long as possible, so that the long-term outcomes are better.

Figure 1. The natural history of HF3

Transition to advanced heart failure

• Oral therapies• A time for many major

decisions• Consider MCS and/or

transplantation, if eligible• Consider inversion of care

plan to one dominated by a palliative approach, which may involve formal hospice

Onset of CHF Sudden death Pump failureDecompensations

Time

Clinical courseTraditional care: including disease modifying therapiesPalliative care: including symptom management

Qua

lity

of li

feIn

tens

ity o

f car

e

OCTOBER 2021 I 3

Heart failure – new guidelines, new treatments

EARN FREECPD POINTS

Join our CPD community at

and start to earn today!

www.denovomedica.com

Most of the patient outcomes trial data relate to HFrEF, considered as an EF <40%. Those patients who have HF with a mildly reduced EF (HFmrEF) of 40-50% are phenotypically and in terms of response to therapy much more closely aligned to patients with HFrEF than to patients with HF with a preserved EF (HFpEF). It is for this reason that most clinicians will treat patients with HFmrEF similarly to patients with HFrEF. HFpEF is still a very difficult entity to treat; these patients are more heterogeneous and at this point there is no specific therapy that can be offered to them.

Patients with HFrEF are usually treated with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB), a beta-blocker and a mineralocor-ticoid receptor antagonist (MRA). More recently the angiotensin receptor-neprilysin inhibitor (ARNI) class has become available, e.g. the valsartan/sacubitril combination, and it has become increasingly clear that this type of drug should be introduced early on and that patients should be switched from an ACE/ARB-based regimen to an ARNI-based regimen.

Clinical outcomes trials – the latest evidence

ARNI – sacubitril/valsartan

The PIONEER-HF trial4 randomly assigned patients admitted with acute decompensated HF and diagnosed with HFrEF to sacubitril/valsartan or enalapril. The patients were initi-ated on enalapril and then, prior to discharge, switched to sacubitril/valsartan or continued

on enalapril. The outcomes in terms of cardiovascular death or rehospitalisation were quite reduced in the sacubitril/valsartan group at two months (Figure 2). This empha-sises that early introduction of sacubitril/vals-artan improves outcomes for patients.

HFpEF is still a very difficult entity to treat; these patients are more heterogeneous and at this point there is no specific therapy that can be offered to them

Figure 2. PIONEER-HF: Cumulative incidence of cardiovascular death or rehospitalisation for HF at eight weeks4

Days from randomisation

15.2%

9.2%

0 7 14 21 28 35 42 49 56

Effect through week 8HR 0.58 (95% CI: 0.39, 0.87)

p=0.007

Enalapril

Sacubitril/Valsartan

17.5

15.0

12.5

10.0

7.5

5.0

2.5

0.0

Cum

ulat

ive

inci

denc

e of

CV

deat

h or

reh

osp

for

HF

(%)

4 I OCTOBER 2021

Heart failure – new guidelines, new treatments

The SGLT-2 inhibitor class improves outcomes for patients with HFrEF

Sodium-glucose co-transporter-2 (SGLT-2) inhibitorsThe SGLT-2 inhibitors have been more extensively studied than the ARNIs. A trial examining the effect of sotagliflozin on total hospitalisation in patients with type 2 diabetes with worsening HF was stopped prematurely due to the COVID-19 pandemic.

Although these data are underpowered, the hospitalisation for HF in the sotagliflozin group was lower than for the placebo group.6 Similar data for empagliflozin and dapagliflo-zin indicate that the SGLT-2 inhibitor class improves outcomes for patients with HFrEF.

Omecamtiv mecarbilOmecamtiv mecarbil is a cellular-based drug that improves contractility. Compared to pla-cebo in patients with systolic HF, omecamtiv mecarbil did not show improved outcomes in

terms of cardiovascular death and there was only a mild reduction in the primary outcome of HF hospitalisations or cardiovascular death (Figure 4).7

Figure 3. TRANSITION: Primary and secondary endpoints during pre-discharge and post-discharge initiation of sacubitril valsartan5

Primary endpointOn target dose of 97/103mg

sac/val at week 10

Acheived and maintained a sac/val dose of 49/51 or 97/103mg for ≥2 weeks

leading to week 10

Achieved and maintained any dose of sac/val for ≥2 weeks leading to week 10

Permanently discontinued sac/val due to AE

RRR 0.90 (0.79, 1.02)P=0.099

45.450.7

RRR 0.91 (0.83, 0.99)P=0.034

RRR 0.96 (0.79, 1.01)P=0.089

RRR 1.49 (0.90, 2.46)P=0.117

100

90

80

70

60

50

40

30

20

10

0

Prop

orti

on o

f pat

ient

s (%

)

Pre-discharge initiation (N=493) Post-discharge initiation (N=489)

62.1

68.5

86.089.6

7.34.9

There have been concerns about the tol-erability of sacubitril/valsartan. The TRANSITION study5 of sacubitril/valsartan initiation in haemodynamically stabilised HF patients in hospital or early after discharge showed tolerability outcomes at 10-week

follow-up. Almost half of the patients were on target dose, many patients achieved a very high dose of sacubitril/valsartan and perma-nent discontinuation due to adverse events was quite low (Figure 3).

OCTOBER 2021 I 5

Heart failure – new guidelines, new treatments

EARN FREECPD POINTS

Join our CPD community at

and start to earn today!

www.denovomedica.com

VericiguatVericiguat directly stimulates the production of cyclic guanosine monophosphate (cGMP); a cGMP deficiency is associated with myocar-dial dysfunction and impaired endothelium-dependent vasomotor regulation (Figure 5).8 Clinical trial evidence in patients with HFrEF

has shown that there is a marginal benefit for the primary outcome of death from cardio-vascular causes or first hospitalisation for HF, with a very mild risk reduction in terms of cardiovascular causes of death, when a patient is treated with vericiguat (Figure 6).9

Figure 4. Omecamtiv mecarbil: Cumulative incidence of the primary composite outcome of a HF event or cardiovascular death, whichever occurred first (A), and death from cardiovascular causes (B)7

A Primary outcome

No. at RiskPlacebo 4 112 3 310 2 889 2 102 1 349 647 141Omecamtiv mecarbil 4 120 3 391 2 953 2 158 1 430 700 164

4 112 3 821 3 560 2 722 1 788 885 2014 120 3 838 3 556 2 710 1 838 903 224

B Cardiovascular death

0 6 12 18 24 30 36 0 6 12 18 24 30 36

100

90

80

70

60

50

40

30

20

10

0

100

90

80

70

60

50

40

30

20

10

0

Cum

ulat

ive

inci

denc

e (%

)

Cum

ulat

ive

inci

denc

e (%

)

Hazard ratio 0.92 (95% CI, 0.86–0.99)P=0.03

Hazard ratio 1.01 (95% CI, 0.92–1.11)

Months since randomisation Months since randomisation

0 6 12 18 24 30 36

504540353025201510

50

0 6 12 18 24 30 36

504540353025201510

50

cGMP: cyclic guanosine monophosphate; HF: heart failure; NO: nitric oxide; sGC: soluble guanylate cyclase.

Figure 5. Vericiguat - restoration of sufficient sGC-cGMP signalling as a novel target in HF8

Endothelial dysfunction

cGMP deficiency

Enhances sensitivity of sGC to NO

Myocardial dysfunction

Vascular dysfunction

Directly stimulates

sGC

Endothelial dysfunction due to oxidative stress and inflammation reduces nitric oxide bioavailability, leading to insufficient activation of sGC. The resulting cGMP deficiency is associated with myocardial dysfunction and impaired endothelium-dependent vasomotor regulation (orange). Vericiguat directly stimulates sGC in a NO-independent manner and by sensitising the enzyme to endogenous NO (green).

6 I OCTOBER 2021

Heart failure – new guidelines, new treatments

Apart from symptomatic benefit, iron supplementation reduces hospitalisation in patients who are admitted with acute decompensated HFrEF

Iron supplementation in patients with HFrEFIron deficiency in the setting of HFrEF is defined as ferritin <100µg/l, or ferritin 100-299µg/l and transferrin saturation (TSAT) <20%. It has previously been shown that symptomatic improvement was achieved with iron supplementation (Table 2). A recent study of iron deficiency and ferric carboxy-maltose (FCM) supplementation at discharge after acute HF indicated that there was a

reduction in the primary outcome of total HF hospitalisation and cardiovascular death, and total cardiovascular hospitalisation and cardiovascular death, but the cardiovascular death risk was equivalent between the FCM and placebo groups.10 Apart from sympto-matic benefit, iron supplementation reduces hospitalisation in patients who are admitted with acute decompensated HFrEF.

Table 2. Iron dosing

Ferric carboxymaltose 500-1 000mg single dose, followed by a ferritin/TSAT at 1-3 months, then 500mg to maintain ferritin/TSAT on targetCheck haemoglobin/iron studies 1-2 times per yearCan be administered over 15 minutes with a minimal risk of adverse events

Ferric hydroxide surface 200mg weekly until repletion

Ferric gluconate 125-250mg per IV dose

Ferric hydroxide dextran

20mg/kg over 4-6 hours, maximum daily dose 1000mg

Figure 6. Vericiguat – estimates of cumulative incidence of the primary outcome, a composite of death from cardiovascular causes or first hospitalisation for HF (A), and death from cardiovascular causes (B)9

A Primary outcome

No. at RiskPlacebo 2 524 2 053 1 555 1 097 772 559 324 110 0Omecamtiv mecarbil 2 526 2 099 1 621 1 154 826 577 348 125 1

2 524 2 370 1 951 1 439 1 045 768 471 157 0 2 526 2 376 1 968 1 468 1 070 779 487 185 1

B Death from cardiovascular causes

0 4 8 12 16 20 24 28 32 0 4 8 12 16 20 24 28 32

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

Cum

ulat

ive

inci

denc

e (%

)

Cum

ulat

ive

inci

denc

e (%

)

Hazard ratio 0.90 (95% CI, 0.82–0.98)P=0.02

Hazard ratio 0.93 (95% CI, 0.81–1.06)

Months since randomisation Months since randomisation

0 4 8 12 16 20 24 28 32 0 4 8 12 16 20 24 28 32

0.550.500.450.400.350.300.250.200.150.100.050.00

0.550.500.450.400.350.300.250.200.150.100.050.00

Placebo

PlaceboVericiguat

Vericiguat

OCTOBER 2021 I 7

Heart failure – new guidelines, new treatments

EARN FREECPD POINTS

Join our CPD community at

and start to earn today!

www.denovomedica.com

The EMPEROR-Preserved trial found that empagliflozin reduced the combined risk of cardiovascular death or hospitalisation for HF in patients with HFpEF, regardless of the presence or absence of diabetes

HFpEF

The EMPA-REG OUTCOME trial11 of empagliflozin in patients with type 2 diabetes at high cardiovascular risk showed a marked risk reduction for hospitalisation for HF and cardiovascular death; this outcome was confirmed in the DAPA-HF trial12 of diabetic and non-diabetic patients with HFrEF, who were treated with dapagliflozin in addition to traditional HF management, as well as in the EMPEROR-Reduced trial,13 which showed that in the presence or absence of diabetes, patients receiving empagliflozin for the treatment of HF had a lower risk of

cardiovascular death or hospitalisation for HF (Figure 7).

The EMPEROR-Preserved trial14 found that empagliflozin reduced the combined risk of cardiovascular death or hospitalisation for HF in patients with HFpEF, regardless of the presence or absence of diabetes, mostly driven by a reduction in HF hospitalisation (Figure 8). In this cohort, the group of patients that gained most benefit from empagliflozin were those with LVEF <50%.

Figure 7. EMPEROR-Reduced: Primary outcome of cardiovascular death or hospitalisation for HF in diabetic and non-diabetic patients with HFrEF13

No. at RiskPlacebo 1 867 1 715 1 612 1 345 1 108 854 611 410 224 109Empagliflozin 1 863 1763 1 677 1 424 1 172 909 645 423 231 101

0 90 180 270 360 450 540 630 720 810

100

90

80

70

60

50

40

30

20

10

0

Esti

mat

ed c

umul

ativ

e in

cide

nce

(%)

Days since randomisation

0 90 180 270 360 450 540 630 720 810

353025201510

50

Hazard ratio 0.75 (95% CI, 0.65–0.86)P<0.001

Placebo

Empagliflozin

Figure 8. EMPEROR-Preserved: Primary outcome of cardiovascular death or hospitalisation for HF in diabetic and non-diabetic patients with HFpEF14

No. at RiskPlacebo 2 991 2 888 2 786 2 706 2 627 2 424 2 066 1 821 1 534 1 278 961 681 400Empagliflozin 2 997 2 928 2 843 2 780 2 708 2 491 2 134 1 858 1 578 1 332 1 005 709 402

0 3 6 9 12 15 18 21 24 27 30 33 36

100

90

80

70

60

50

40

30

20

10

0

Cum

ulat

ive

inci

denc

e (%

)

Months since randomisation

0 3 6 9 12 15 18 21 24 27 30 33 36

25

20

15

10

5

0

Hazard ratio 0.79 (95% CI, 0.69–0.90)P<0.001

Placebo

Empagliflozin

8 I OCTOBER 2021

Heart failure – new guidelines, new treatments

What do the guidelines say?The updated Canadian Cardiovascular Society HF guidelines16 have moved away from a linear approach to drug therapy for HFrEF (Figure 10), with the four pil-lars of HF therapy being ARNIs, beta-blockers, MRAs and SGLT-2 inhibitors. The

advantage of the SGLT-2 inhibitors is that no uptitration of the dose is required, as com-pared to MRAs (uptitrated once), ARNIs (uptitrated twice) and beta-blockers (many dose escalations).

One-year mortality with combinations of medical therapy

The one-year mortality rates associated with various drug combinations are depicted in Figure 9.15 As treatment is intensified,

mortality declines progressively. This high-lights the importance of getting HFrEF patients on optimal foundational therapy.

Triple therapy includes β-blocker, MRA, and either ACEI/ ARB, or ARNI, as indicated

Figure 9. One-year outpatient mortality rates with combinations of medical therapy for a typical patient with ischaemic cardiomyopathy15

Figure 10. Canadian Cardiovascular Society HF guidelines 202116

HR >70bpm and sinus rhythm

Consider ivabradine

Recent HF hospitalisation

Consider vericiguat

Black patients on optimal GDMT, or patients unable to

tolerate ARNI/ACEi/ARB

Consider combination hydralazine-nitrates

Suboptimal rate control for AF, or persistent symptoms despite optimised GDMT

Consider digoxin

HFrEF: LVEF ≤40% and symptoms

Untreated ACEI/ARB and BB

ACEI/ARB triple therapy

ARNI triple therapy

Foundational therapy

Foundational therapy + SNI

18

16

14

12

10

8

6

4

2

0

Untreated Three agents Five agentsTwo agents Four agents

17.0

9.4

7.0

5.64.7 4.2

Initiate standard therapies

Assess clinical factors for additional interventions

Initiate standard therapies as soon as possible and titrate every 2–4 weeks to target or maximally tolerated dose over 3–6 months

ARNI or ACEi/ARB then substitute ARNI

Beta-blocker MRA SGLT-2 inhibitor

OCTOBER 2021 I 9

Heart failure – new guidelines, new treatments

EARN FREECPD POINTS

Join our CPD community at

and start to earn today!

www.denovomedica.com

A proposed new sequencing of drug therapy for HFrEF is more foundational than the pre-vious linear approach; it entails initiating the patient on a beta-blocker plus SGLT-2 inhibi-tor and thereafter introducing an ARNI and a MRA to establish the patient on all four agents very quickly (Figure 11).17 The use of these agents and ancillary interventions for the treatment of HFrEF are summarised in Figure 12.18

Figure 11. Proposed sequencing of drug therapy for HFrEF17

ACE-I: angiotensin-converting enzyme inhibitor; Afib: atrial fibrillation; ARB: angiotensin receptor blocker; ARNI: angiotensin receptor/neprilysin inhibitor; CRT: cardiac resynchronisation therapy; HTX: heart transplantation; LBBB: left bundle branch block; LVAD: left ventricular assist device; MR: mitral regurgitation; MRA: mineralocorticoid receptor antagonist; PVI: pulmonary vein isolation; SGLT-2: sodium–glucose co-transporter 2; SR: sinus rhythm; TSAT: transferrin saturation

Figure 12. Drug, interventional, and device treatment for HFrEF18

Step 1

Step 2

Step 3

+

All 3 steps achieved within 4 weeksUptitration to target doses thereafter

β-blocker

ARNI

MRA

SGLT-2i

Ferric carboxymaltose

If costs concerns

Self identified

blacks

If disproportio

nate

functional M

R

Hydralazine/Nitrate

Mitral edge-to-edge repair

ACE-I/ARB

Anticoagulant

Digitalis (if high ventricular rate)

Refer for PVI

Ivabradine

CRT

Loop diuretic

Thiazide

Refer for LVAD/HTX

Vericiguat

Omecamtiv

Digitalis

If in AFib

If LBBB & wide QRS

If recent decompensation/

advanced heart failure

If congestion

If SR >70bpm

Drugs/interventions

for HFrEF

ARNI

MRA

Beta-blocker

SGLT-2 inhibitor

If fermtin <100

or TSAT <20%

ESC guidelinesThe 2021 ESC guidelines2 are outlined in Figure 13. Dr Hitzeroth draws attention to the foundational approach to drug therapy, the fact that implantable cardioverter defibril-lation is reserved mainly for patients with an

ischaemic aetiology of HFrEF, anticoagula-tion for atrial fibrillation and then ultimately, heart transplantation for patients who remain symptomatic.

10 I OCTOBER 2021

Heart failure – new guidelines, new treatments

South African guidelines

The 2020 South African guidelines19 for the diagnosis and treatment of chronic HF are very much in line with the 2021 ESC guidelines, emphasising therapy that reduces mortality, hospitalisation and symptoms,

although emerging evidence indicates that the recommendations for IV iron and pulmonary vein isolation should probably move into the hospitalisation category (Figure 14).

Figure 13. Summary of 2021 ESC guidelines for the management of HFrEF2

To reduce mortality – for all patients

To reduce HF hospitalisation/mortality – for selected patients

To reduce HF hospitalisation and improve QOL – for all patients

For selected advanced HF patients

He

ACE-I/ARNI

Diuretics

Exercise rehabilitation

Multi-professional disease management

CRT-P/D

ICD

Anticoagulation

SAVR/TAVI

Heart transplantation

CRT-P/D

ICD

Ferric carboxymaltose

Hydralazine/ISDN ARB

CABG

Ivabradine

Long-term MCS as DT

TEE MV repair

MCS as BTT/BTC

BB MRA SGLT-2i

Volume overload

SR with LBBB ≥150ms

Ischaemic aetiology

Atrial fibrillation

Aortic stenosis

Atrial fibrillation

Mitral regurgitation

SR with LBBB 130–149ms or non LBBB ≥150ms

Non-ischaemic aetiology

Iron deficiency

Black race ACE-I/ARNI intolerance

Coronary artery disease

Heart rate SR >70bpm

Digoxin PVI

OCTOBER 2021 I 11

Heart failure – new guidelines, new treatments

EARN FREECPD POINTS

Join our CPD community at

and start to earn today!

www.denovomedica.com

The 2020 South African guidelines for the diagnosis and treatment of chronic HF are very much in line with the 2021 ESC guidelines

ConclusionsDr Hitzeroth’s closing remarks include an appeal: “Evidence-based practice consists not only of basing one’s therapy on the latest research evidence or recommendations from the guidelines, it has to be integrated with

one’s own clinical experience of what may be the best course of action for the individual patient. The guidelines summarise our latest evidence, but they are guidelines and not commandments.”

Key learnings

• It is important to establish the primary cause of HF and treat any cause of reversible LV dysfunction

• Early intensive medical therapy in HF optimises long-term outcomes

• It is becoming increasingly clear that patients should be switched early from an ACE/ARB-based regimen to an ARNI-based regimen

• The SGLT-2 inhibitor class improves outcomes for patients with HFrEF

• Iron supplementation in the patient with acute decompensated HFrEF provides symptomatic benefit and reduces hospitalisation

• Empagliflozin shows benefit for the HFpEF patient in the presence or absence of diabetes

• The 2021 ESC guidelines for the management of HFrEF incorporate a foundational approach to drug therapy.

NOW EARN FREE CPD POINTS

Click here to access and submit deNovo Medica’s CPD modules

Figure 14. 2020 South African guidelines for the management of HFrEF19

Management of HFrEF

MortalityARNI

ACE-I/ARBB Blocker

AldosteroneAntagonist (MRA)

Hydralazine + NitrateSGLT-2 Inhibitor

Cardiac resynchronisation therapy (CRT-P/D)

ICD

HospitalisationIvabradine

Digoxin

SymptomsDiureticIV Iron

AF ManagementCardioversion

AFlutter RF ablationPulmonary vein

isolation

SurgicalCABG

Valvular interventionLV assist deviceHeart transplant

Therapy that reduces:

DisclaimerThe views and opinions expressed in the article are those of the presenters and do not necessarily reflect those of the publisher or its sponsor. In all clinical instances, medical practitioners are referred to the product insert documentation as approved by relevant control authorities.

12 I OCTOBER 2021

Heart failure – new guidelines, new treatments

EARN FREECPD POINTS

Are you a member of Southern Africa’s leading

digital Continuing Professional Development

website earning FREE CPD points with access to

best practice content?

Only a few clicks and you can register to start

earning today

Visit

For all Southern African healthcare professionals

www.denovomedica.com

DeNovo Medica

@deNovoMedica

deNovo Medica

Find us at

Published by

70 Arlington Street, Everglen, Cape Town, 7550Tel: (021) 976 0485 I info@denovomedica.com

© 2021 deNovo MedicaReg: 2012/216456/07

This CPD-accredited programme waswritten for deNovo Medica byGlenda HardyBSc(Hons) Medical Cell Biologybased on the webinar presented byDr Jens Hitzeroth on 6 October 2021

ReferencesClick on reference to access the scientific article

1. Ponikowski P, Voors AA, Anker SD, 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(27):

2129-2200.

2. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines

for the diagnosis and treatment of acute and chronic heart

failure. Eur Heart J 2021; 42(36): 3599-3726.

3. Lanken PN, Terry PB, Delisser HM, et al. An official American

Thoracic Society clinical policy statement: palliative care for

patients with respiratory diseases and critical illnesses. Am J

Respir Crit Care Med 2008; 177(8): 912-927.

4. Morrow DA, Valzquez EJ, DeVore AD, et al. Clinical outcomes

in patients with acute decompensated heart failure randomly

assigned sacubitril/valsartan or enalapril in the PIONEER-HF trial.

Circulation 2019; 139(19): 2285-2288.

5. Wachter R, Senni M, Belohlavek J, et al. Initiation of sacubitril/

valsartan in haemodynamically stabilised heart failure patients

in hospital or early after discharge: primary results of the

randomised TRANSITION study. Eur J Heart Fail 2019; 21(8):

998-1007.

6. Szarek M, Bhatt DL, Steg PF, et al. Effect of sotagliflozin on

total hospitalizations in patients with type 2 diabetes and

worsening heart failure: A randomized trial. Ann Intern Med

2021; 174(8): 1065-1072.

7. Teerlink JR, Diaz R, Felker GM, et al. Cardiac myosin activation

with omecamtiv mecarbil in systolic heart failure. N Engl J Med

2021; 384(2): 105-116.

8. Armstrong PW, Roessig L, Patel MJ, et al. A multicenter,

randomized, double-blind, placebo-controlled trial of the

efficacy and safety of the oral soluble guanylate cyclase

stimulator: The VICTORIA trial. JACC Heart Fail 2018; 6(2):

96-104.

9. Armstrong PW, Pieske B, Anstrom KJ, et al. Vericiguat in

patients with heart failure and reduced ejection fraction. N Engl

J Med 2020; 382(20): 1883-1893.

10. Ponikowski P, Kirwan BA, Anker SD, et al. Ferric carboxymaltose

for iron deficiency at discharge after acute heart failure: a

multicentre, double-blind, randomised, controlled trial. Lancet

2020; 396(10266): 1895-1904.

11. Fitchett D, Zinman B, Wanner C, et al. Heart failure outcomes

with empagliflozin in patients with type 2 diabetes at high

cardiovascular risk: results of the EMPA-REG OUTCOME trial.

Eur Heart J 2016; 37(19): 1526-1534.

12. McMurray JJ, Solomon SD, Inzucchi SE, et al. Dapagliflozin in

patients with heart failure and reduced ejection fraction. N Engl

J Med 2019; 381(21): 1995-2008.

13. Packer M, Anker SD, Butler J, et al. Cardiovascular and renal

outcomes with empagliflozin in heart failure. N Engl J Med

2020; 383(15): 1413-1424.

14. Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart

failure with a preserved ejection fraction. N Engl J Med 2021;

Aug 27 [online ahead of print].

15. Miller RJ, Howlett JG, Fine NM. A novel approach to medical

management of heart failure with reduced ejection fraction.

Can J Cardiol 2021; 37(4): 632-643.

16. McDonald M, Virani S, Chan M, et al. CCS/CHFS heart failure

guidelines update: Defining a new pharmacologic standard

of care for heart failure with reduced ejection fraction. Can J

Cardiol 2021; 37(4): 531-546.

17. McMurray JJ, Packer M. How should we sequence the

treatments for heart failure and a reduced ejection fraction?

A redefinition of evidence-based medicine. Circulation 2021;

143(9): 875-877.

18. Bauersachs J. Heart failure drug treatment: the fantastic four.

Eur Heart J 2021; 42(6): 681-683.

19. Hitzeroth J, Mpe M, Klug E, et al. 2020 Heart Failure Society

of South Africa perspective on the 2016 European Society of

Cardiology Chronic heart failure guidelines. S Afr Med J 2020;

110(8b): 13057.