Evidence based guidelines for heart failure

1. 11th - 14th May, 2024
Lisbon
An educational update from
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Tablets
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Spotlights of Day 2

2. ESC #HeartFailure 2024 Spotlights
1) Evidence-based strategies for guidelines implementations:
Real-world data from registries
Real-world data from registries, including observations from Canada, indicate
stagnant progress in implementing GDMT
Despite various algorithms for quadruple therapy, uncertainty persists in
choosing optimal treatment strategies
The Evolution Heart Failure Registry highlights delayed initiation and high
discontinuation rates for newer therapies like SGLT2 inhibitors and ARNI
ARNI and SGLT2i offer promising avenues for improving HF management.
However, their adoption has been slow, with delayed initiation. The
introduction of ARNI and SGLT2i presents an opportunity to enhance
treatment outcomes, particularly in reducing mortality and optimizing
therapy uptitration
Initiating GDMT is more likely after a heart failure hospitalization,
emphasizing the importance of these events as opportunities for optimization
Barriers to GDMT initiation include older age, renal dysfunction, and low
blood pressure, reflecting real-life challenges
The CAN-AIM study underscores the need for improved GDMT utilization,
especially during hospitalization, where many eligible patients do not receive
appropriate therapy
Implementation considerations suggest slow progress despite the availability
of guideline-recommended therapies
Workforce shortages and limited exposure to heart failure clinics during
training further hinder GDMT optimization
Nudge interventions, such as real-time alerts in electronic health records,
show promise in increasing GDMT prescription rates
Rosuvastatin 40 / 20 / 10 / 5 mg
Dapagliflozin5 mg / 10 mg
Tablets
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3. #HeartFailure 2024 Spotlights
ESC
Overall, the data highlight the imperative for enhanced implementation
strategies to optimize GDMT utilization in heart failure patients
Conclusion
Real-world evidence strongly supports the effectiveness of ARNI and SGLT2
inhibitors in managing heart failure, especially with reduced ejection
fraction (HFrEF). These therapies significantly reduce hospitalizations and
mortality rates, providing comprehensive cardiorenal protection and
improving outcomes across diverse patient populations. Their inclusion in
guideline-directed therapy represents a crucial advancement in heart
failure management, promising better patient care and reduced disease
burden
2) Contemporary GDMT sequencing and titration in de novo,
worsening, and chronic HF: first data from the TITRATE-HF study
The guideline recommends rapid titration of drugs for heart failure patients,
with real-world data needed for drug classes implementation
TITRATE-HF study is the first to provide data on the adoption of the new 2021
guidelines for titrating HF medications
The study is a national prospective registry involving 48 participating sites in
the Netherlands, covering about 70% of all Dutch hospitals
The study focused on patients with systolic heart failure, with a mean age of
70, 50% GDMT-naive patients, and about 50% already using GDMT
Side-effects were the principal reasons for reducing GDMT in chronic and
worsening heart failure patients
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4. #HeartFailure 2024 Spotlights
ESC
Documentation of reasons for non-use of GDMT was lacking in many cases,
with only 20-30% having recorded reasons
Variation in GDMT prescription among participating sites was significant, with
better adherence in dedicated heart failure specialist or nurse specialist
programs
Guideline implementation is an opportunity during hospitalization events, not
only for diuretics but also for optimizing GDMT
Conclusion
GDMT prescription in 2024 showed 44% of patients on quadruple therapy or
1% on target for new drug classes; dedicated heart failure outpatient clinics
help implementation
3) The opportunity of hospitalization and post-discharge
follow-up
Implementation research among hospitalized individuals is crucial as they are
at the highest risk of disease progression, hospitalizations, and death
Hospitalization provides an opportunity to modify risk and optimize
guideline-directed medical therapy (GDMT), with class one recommendations
for pre-discharge and in-hospital optimization
The "nudge ladder" ranges from weaker interventions (provision of
information) to stronger interventions (in-person interventions)
Simple provision of information or flagging high-risk patients in EHR systems is
not sufficient to change decision-making or patient outcomes
Smart EHR nudges, like the Prompt HF intervention, can be successful by
offering tailored suggestions to clinicians based on patient data
Transitional care programs, often nurse-driven, have not shown significant
improvements in implementation or care outcomes in a randomized trial
High-intensity, in-person interventions, like the Strong HF trial, have shown
substantial risk reductions in 180-day readmission and all-cause death but
may not be feasible for all health systems
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5. #HeartFailure 2024 Spotlights
ESC
High-intensity interventions involve rapid up-titration of GDMT and close
follow-up, resulting in large magnitude risk reductions and improved
outcomes
A middle ground could be centralized, virtual teams reviewing charts and
offering daily recommendations to clinicians, which has shown success in
increasing in-hospital initiation and optimization of GDMT
Post-discharge clinics with less-trained staff optimizing GDMT have also
shown positive results, demonstrating the potential for democratizing care
and involving non-clinicians in the process
Conclusion
Implementation science in the hospitalized high-risk window can improve
heart failure population health through various interventions, including
high-intensity and virtual team approaches
Probability
of
event-free
survival
(%)
Primary endpoint
180-Day Readmission for HF or All-Cause Death
100
95
High intensity care
90
85
80
Usual care
75
180-day risk difference 8.1%
(95% CI 2.9 to 13.2; p=0.0021)
70
0 15 30 45 60 75 90 105 120 135 150 165 180
Time since randomization (days)
Oral HF therapies prescribed in high intensity and usual care
Half to Full optimal dose
High Intensity Care
100
90
80
70
60
50
40
30
20
10
0
Patients
,
(%)
Pre-R a n d D90 D180 D180
ACE/ARBS/ARNI
Pre-R a n d D90
BB
Pre-R a n d D90 D180
MRA
ACEi, angiotensin converting enzyme inhibitors, ARB angiotensin receptors blocker, ARNi angiotensin receptors inhibitors, BB beta blockers, Pre- Rand, pre-randomization
Usual Care
1/2 - Full optimal dose
1/2 - Full optimal dose
Full optimal dose
Full optimal dose
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6. GDMT clinic patients showed significant improvement in congestion,
reduction in NT-proBNP, and a decrease in overall diuretic use
Safety and tolerability were good, with only two serious adverse events
ESC #HeartFailure 2024 Spotlights
4) TEAM HF- Implementation study of accelerated HF GDMT in a
general cardiology clinic
Despite proven heart failure therapies and guidelines, treatment gaps exist,
with only fewer than 20% of hospitalized heart failure patients receiving
comprehensive GDMT
The Strong HF trial demonstrated the safety and efficacy of rapid
deployment of heart failure therapies among hospitalized patients, but it is
unknown whether this is feasible in a general cardiology clinic setting
The GDMT clinic was established at Massachusetts General Hospital to deliver
optimal treatment for patients in general cardiology, with a team-based
approach involving nurse practitioners, physician assistants, and pharmacists
trained in GDMT titration
The study evaluated the efficacy and safety of the GDMT clinic team-based
approach relative to matched controls treated via usual care
Primary endpoint: The proportion of GDMT clinic patients without
contraindications receiving four-drug GDMT was compared to usual care
Secondary endpoints: The proportion of patients achieving at least 50%
target doses, change in New York Heart Association (NYHA) class, and
NT-proBNP from baseline to the final visit
From baseline to the final visit, the percentage of patients receiving
comprehensive four-drug GDMT increased from 21% to 88% in the GDMT
clinic, compared to no increase in usual care
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7. #HeartFailure 2024 Spotlights
ESC
Conclusion
The GDMT clinic team-based approach was highly effective and
well-tolerated compared to matched usual care, with the majority of
patients achieving comprehensive four-drug therapy and at least 50%
target doses. Rapid titration resulted in improved heart failure signs and
symptoms despite diuretic dose reduction. The TEAM HF study supports the
feasibility of a Strong HF-like approach to outpatient GDMT administration
for heart failure with impaired ejection fraction, but more data is needed
regarding the benefits of this approach
5) After worsening HF, when to proceed to remote cardiac
monitoring
Congestion remains an issue after hospital discharge, with 48% of patients
having some congestion and 65% experiencing congestion within 60 days
Monitoring pressure dynamics can help detect worsening HF earlier, with
hemodynamic changes occurring almost one month before symptoms and
hospitalization
Hemodynamic monitoring has been shown to reduce hospitalization for heart
failure and the combined endpoint of cardiovascular death and
hospitalization for heart failure
Sacubitril/valsartan and SGLT2 inhibitors have been shown to reduce filling
pressures, highlighting the importance of monitoring pressures even in chronic
patients
EmpagliflozinEffectsonPulmonaryArtery
PressureinPatientsWithHeartFailure
Results From the EMBRACE-HF Trial
65 pts with HFrEF and CardioMems
Early Reduction in Ambulatory Pulmonary
Artery Pressures After Initiation of
Sacubitril/Valsartan
PA
Dastolic
Pressure
(mmHg)
Difference
in
PA
Diastolic
Pressure
(mmHg)
(Empagliflozin
vs.
Placebo)
24
23
22
21
20
19
18
17
16
15
0 1 2 3 4 5 6 7 8 9 10 11 12 13
Weeks
p-value = 0.02
2
1
0
-1
-2
-3
-4
-5
0 1 2 3 4 5 6 7 8 9 10 11 12 13
Weeks
p-value = 0.02
A Effects of Empagliflozin vs. Placebo on Pulmonary B Difference in Pulmonary Artery Diastolic Pressure
Artery Diastolic Pressure between Empagliflozin and Placebo over Time
25 3
Placebo Empagliflozin
Change
in
PAP
from
Baseline
to
30
days
(mm
Hg)
-3.5
-5
-3
-2
-1.5
-2
-2.5
-0.5
0
33 32
-0.2
-2.7
-2.9
-2.1
47 45
-0.4
24 21
-0.0001
Baseline Pressure (mm Hg)
PA mean PA systolic PA diastolic
Sacubitril/Valsartan HFrEF Control
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8. ESC #HeartFailure 2024 Spotlights
European guidelines suggest that monitoring of pulmonary artery pressures
may be considered for symptomatic patients with heart failure, while US
guidelines recommend pressure monitoring for patients with recent or
recurrent heart failure hospitalization
Limitations of hemodynamic monitoring include invasiveness, need for
anticoagulation, postimplantation complications, resource utilization, time
consumption, and cost
Monitoring congestion through device algorithms or patches has not shown
significant benefits in terms of heart failure hospitalization or mortality
Telemonitoring and telephone support have demonstrated benefits in
reducing mortality and heart failure hospitalization, with telemonitoring being
more suitable for advanced heart failure patients and telephone support for
stable patients
Limitations of telemedicine include digital literacy, human needs, time
consumption, and logistical and bureaucratic issues
Conclusion
Remote cardiac monitoring, particularly hemodynamic and telemedicine
approaches, can positively impact the reduction of heart failure
hospitalization. However, there are doubts regarding their effect on
mortality. Hemodynamic monitoring is more suitable for "frequent fliers"
or advanced heart failure patients, while telemedicine is better for stable
patients. Proactive intervention with effective medical therapy is crucial
for preventing heart failure deterioration
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9. ESC #HeartFailure 2024 Spotlights
6) Unlocking cardiac health: natriuretic peptides for enhancing
risk prediction, enabling early diagnosis, and guiding
interventions in HF
Natriuretic peptides are established biomarkers for heart failure and are
increasingly recognized as indicators of risk for cardiovascular disease,
particularly heart failure
Natriuretic peptides independently define risk for heart failure and other
cardiovascular diseases, as they reflect the presence of inflammation, fibrosis,
pressure, or volume overload caused by risk factors
The STOP-HF and PONTIAC studies demonstrated that natriuretic
peptide-guided prevention strategies significantly reduced the prevalence of
heart failure stage B, new-onset incident heart failure, and other
cardiovascular events
Guidelines worldwide now recommend natriuretic peptides as a guiding tool
for preventive strategies in heart failure and cardiovascular disease in general
The American Diabetes Association suggests that diabetic patients should
have a natriuretic peptide assessment as part of their routine care, and if
elevated, they should undergo echocardiography
Serial measurements of natriuretic peptides may help identify individuals at
higher risk for incident heart failure and cardiac death
Natriuretic peptides can potentially aid in the earlier diagnosis of heart failure
when used as a screening tool, even if prevention efforts fail
A proposed algorithm incorporates natriuretic peptides into risk assessment,
biomarker triage, and evaluation for early diagnosis of heart failure or other
cardiovascular conditions
Conclusion
Natriuretic peptides play a crucial role in enhancing risk prediction,
enabling early diagnosis, and guiding interventions in heart failure and
cardiovascular disease. By incorporating natriuretic peptides into clinical
algorithms, clinicians can provide more precise, personalized risk
predictions and interventions for patients, ultimately reducing
cardiovascular events and improving patient outcome
Natriuretic Peptide-Guided HF (CV) Risk Modulation
Age, Hypertension,
Diabetes, Vascular
disease, Cardiotoxins,
etc
Normal Level
? Biomarker Review Interval
Enhanced Protection ? Biomarker Review Interval
• SGLT2i
• Finerenone
• Other -ARNI?
Abnormal
Treat
?HF patient
?PAF
General at-risk cohort
NP, Tp, other
Biomarker Triage
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10. ESC #HeartFailure 2024 Spotlights
7) Combination therapy: Thiazides, acetazolamide, HSS & SGLT2i
Combination therapy with thiazides, acetazolamide, hypertonic saline (HSS),
and SGLT2 inhibitors is recommended for patients with residual congestion
despite routine use of high-dose loop diuretics
The European Society of Cardiology guidelines suggest a sequential
approach to achieve decongestion, but the optimal strategy is unclear
The combination of i.v. furosemide and i.v. acetazolamide was more effective
in reducing weight and congestion at 72 hours than i.v. furosemide alone, but
there was no difference in renal function or clinical outcomes
The ADVOR trial demonstrated that the addition of i.v. acetazolamide to i.v.
furosemide resulted in more successful decongestion at 72 hours and
discharge, with greater urine output and natriuresis
Hypertonic saline solution may improve renal function and diuresis in patients
with diuretic resistance, but its mechanism of action is not well understood
SGLT2 inhibitors, such as empagliflozin and dapagliflozin, have been shown to
enhance diuresis and improve clinical outcomes in patients with heart failure,
both in the short and long-term
Conclusion
Intravenous loop diuretics are the mainstay of therapy for patients with
acute decompensated heart failure, but combination therapy with
thiazides, acetazolamide, HSS, and SGLT2 inhibitors may be more effective
in achieving decongestion and improving clinical outcomes
Adjusted OR: 0.65 (95% CI 0.41-1.02);
P = 0.06
Cumulative
Loop
Diuretic
Dose
(mg)
Cumulative
W
eight
Change
(kg)
Cumulative
Weight
Loss
(kg)/40
mg
IV
Furosemide
Dapagliflozin Usual Care Dapagliflozin Usual Care
P=1.0
0.0
0
-5
-10
-15
-0.5
-1.0
-1.5
Primary Outcome
A
C
B
Cumulative W eight Change
Cumulative Loop Diuretic Dose
4,000
3,000
2,000
1,000
0
Dapagliflozin
Rosuvastatin 40 / 20 / 10 / 5 mg
Dapagliflozin5 mg / 10 mg
Tablets
9
Usual Care
Median 560 m g Median 800 mg
(IQR: 260-1,150) (IQR: 380-1,715)
P = 0.006
N o ↑
adverse
events:
Cardiac, diabetic,
renal and infectious.

11. The decline in heart failure hospitalizations reported at the beginning of the
century has leveled off, with an increase in younger people and a more
recognized prevalence of heart failure with preserved ejection fraction
Treatment for heart failure hospitalizations shows significant variation
worldwide, with inconsistent use of evidence-based therapies and wide
disparities in length of stay
ESC #HeartFailure 2024 Spotlights
8) State-of-the-art: The conundrum of HF hospitalizations in the
current era
Heart failure hospitalizations represent a complex issue with many questions
surrounding definitions, statistics, and variations in treatment
Defining heart failure hospitalizations can be challenging due to factors such
as primary vs. secondary diagnosis, first-time vs. repeated admissions, and
varying clinical presentations
Heart failure hospitalizations are extremely common, accounting for nearly
as many hospitalizations as myocardial infarction and stroke combined
The statistics on heart failure hospitalizations vary greatly by country and
region, with differences in healthcare provision, data collection, and
definitions contributing to the variability
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12. #HeartFailure 2024 Spotlights
ESC
Outcomes after discharge remain a concern, with variable use of
evidence-based therapies and high between-hospital variability
Readmission and mortality rates are high, with repeated hospitalizations
having a cumulative negative prognostic impact
Addressing the conundrum of heart failure hospitalizations requires focusing
on prevention, facilitating early discharge, improving inpatient care,
monitoring patients for deterioration, and intervening early
Conclusion
Heart failure hospitalizations present a complex and challenging issue in the
current era, with variations in definitions, statistics, and treatment
contributing to the conundrum. To tackle this problem, a comprehensive
approach is needed, focusing on prevention, early discharge, improving
inpatient care, and monitoring patients to detect deterioration and
intervene early. Addressing the variability in evidence-based therapy use
and ensuring adequate decongestion before discharge are crucial aspects
of improving patient outcomes
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13. * HF- Heart Failure
** to reduce the risk of cardiovascular death and hospitalisation for heart failure in adult patients with chronic heart failure.
References
*Imported from the innovator (Novartis); #Significant future risk reduction related to CV/mortality/hospitalisation for HF
1) McMurray et al. N Engl J Med 2014;371(11):993-1004 2 Desai et al. Eur Heart J 2015,36(30) 1990-7 3. Packer et al Circulation 2015,131(1):54-61)
2) Source Haddad H et al. The PARASAIL study-Patient reported outcomes from the Canadian real-world experience use of Vymada in patients with heart failure and reduced ejection fraction, European
Journal of Heart Failure(2017) 19 (Suppl. S1), 34. Source Canu A et al. Results of a single center experience on 200 consecutive patients treated with Entresto (Vymada), European Journal of Heart
Failure(2017) 19 (Suppl S1), 413
THE ONLY* ONE:
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