Consensus statement India May 23

Expert Opinion on the Identification and Pharmacological

Management of Worsening Heart Failure: A Consensus

Statement from India

Sandeep Seth, Johann Bauersachs1, Sanjay Mittal2, Vishal Rastogi3, Rajeev Kumar Rajput4,
Dheeraj Gandotra5, Ripen Gupta6, Manoj Sahu7, S.N Pathak8, Mohit Bhagwati9, Simmi
Minocha10, Pawan Sharma11, Deepankar Vatsa12, Raghav Aggarwal13, Gyanti RB Singh14,
Gaurav Arora15, Samir Kubba16, Meera Rajeev17, Pratik Jha17, B. S. Vivek18, Mohit
Gupta19, Rameshwar Bishnoi20, Rashi Khare21, Vipul Gupta22, Naresh Kumar Goyal23,
Aseem Dhall24, Amit Madan25, B D Sharma26, Atul D Abhyankar27, Pravin Kahale28,
Talha Meeran29, Babu Ezhumalai30, B C. Kalmath31, V T Shah32, Sandip Rungta33,
P Ashok Kumar34, Sunil Christopher35, Alok A Shah36, Ramesh Dargad37, Kaushik
Sheth38, Abhay Khode39, Sunil P Mehta40, Bommareddy V A Ranga Reddy41, Puneet
Gupta42, BK Tripathi43, Ritwick Raj Bhuyan44

Department of Cardiology, AIIMS, New Delhi, 1Department of Cardiology, Hannover Medical School (MHH), Germany,2Department of Cardiology, Director, Clinical and Preventive Cardiology- Heart Institute, Medanta-The Medicity, Gurugram, 3Department of Cardiology, Director Cardiology and Head -Medical Advanced Heart Failure Program at Fortis Escorts Heart Institute, Delhi, 4Department of Cardiology, Senior Consultant Cardiologist & Intervention Cardiologist, Indraprastha Apollo Hospital, Sarita Vihar, 5Department of Cardiology, Fortis Hospital, Gurugram, 6Department of Cardiology, Senior Director & Unit Head, Cardiac Sciences, Cardiology, Cardiac Electrophysiology-Pacemaker, Interventional Cardiology, Max Smart Super Speciality Hospital, Saket, 7Department of Cardiothoracic and Vascular Surgery, AIIMS, New Delhi, 8Department of Cardiology, Consultant- Interventional Cardiologist, Indraprastha Apollo Hospital Sarita Vihar, 9Department of Cardiology and Incharge, Acute Cardiac Care and Heart Failure Clinic, Holy Family Hospital, New Delhi, 10Department of Cardiology, Director Cardiology Accord Hospital Faridabad, 11Department of Cardiology, Associate Director-Cardiac Science Max Super Speciality Hospital, Patparganj, (Delhi), 12Department of Cardiology, Consultant, Yatharth
Super Specialty Hospital, Greater Noida, 13Department of Cardiology, Consultant Cardiologist, Max Hospital, Vaishali, Ghaziabad, 14Department of Cardiology, Senior Consultant, Cardiology & CTVS, Metro Group of Hospitals, Noida, Uttar Pradesh, 15Department of Cardiology, Assistant Professor, Safdarjung Hospital, New Delhi, 16Department of Interventional Cardiology, Director -Clinical and Interventional Cardiology, Max Super Speciality Hospital, Vaishali, 17Department of Cardiothoracic and Vascular Surgery, Senior Resident, CTVS, AIIMS, New Delhi, 18Department of Cardiology, Consultant Cardiologist, Sir Gangaram Hospital, New Delhi,

Worsening heart failure (WHF) is a distinct under‑diagnosed and under‑treated condition,
independent of location of care. Heart failure (HF) progression is punctuated by repeated
WHF events, each resulting in reduced cardiac function. One‑third of the patients with HF
with reduced ejection fraction experience a decompensation event. These decompensation
events often result in the emergency department visits and HF hospitalization. Despite its
inclusion in recent guidelines, there is no precise definition of WHF or its various forms. It is
worth noting that WHF signals a need for treatment optimization as per guideline‑directed
medical therapy and the addition of novel drugs like a stimulator of soluble guanylate
cyclase that benefit this high‑risk patient population. This practical document is based on
the expert opinion of cardiologists, cardiothoracic surgeons, and physicians that discussed
the definition, assessment, pharmacological management, and monitoring of WHF patients
in a hospitalized setting. In addition, there is also a need for an expert opinion for the
management of WHF in an outpatient setting.

Keywords: Guideline directed medical therapy, heart failure hospitalization, heart failure with
reduced ejection fraction, vericiguat, worsening heart failure

Introduction
Heart failure (HF) remains a highly prevalent disorder
worldwide with a high morbidity and mortality rate. It has
an estimated prevalence of 64 million people worldwide and
contributes to increased health‑care costs.[1] HF with reduced
ejection fraction (HFrEF) is the most prevalent type of HF in

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How to cite this article: Seth S, Bauersachs J, Mittal S, Rastogi V,
Rajput RK, Gandotra D, et al. Expert opinion on the identification and
pharmacological management of worsening heart failure: A consensus
statement from India. J Pract Cardiovasc Sci 2023;9:1-10.

Seth,

et al.:

Expert opinion on management of worsening heart failure

¹⁹Department of Cardiology, Professor, GB Pant Hospital, New Delhi, ²⁰Department of Cardiology, Senior Consultant Cardiac Sciences, Max Superspeciality Hospital, Shalimaar Bagh Delhi, ²¹Department of Cardiology, Senior Consultant-Cardiology, Fortis Shalimar Bagh, ²²Department of Cardiology, Consultant Cardiologist and Physician, Gupta Ultrasound and Heart Care Centre, West Delhi, ²³Department of Cardiology, Director & HOD Cardiology & Heart Failure Programme, Fortis Hospital Shalimar Bagh, ²⁴Department of Cardiology, Director & Head, ISIC -Saroj Cardiac Sciences, Vasant Kunj New Delhi, ²⁵Department of Interventional Cardiology, Consultant Interventional Cardiologist, Fortis Hospital, Noida, ²⁶Department of Internal Medicine, Senior Consultant Internal Medicine, Max Super Speciality Hospital, Patparganj, ²⁷Department of Interventional Cardiology, Director of Interventional Cardiology - Mahavir Heart Institute, Surat, ²⁸Department of Interventional Cardiology, Senior Interventional Cardiologist & HF Specialist, Kokilaben Dhirubhai Ambani Hospital & Research Centre, Andheri Mumbai, ²⁹Department of Advanced Cardiac
Sciences & Heart Transplant, Consultant- Advanced Cardiac Sciences & Heart Transplant, Sir H.N. Reliance Foundation Hospital & Research Centre, Mumbai, ³⁰Department of Interventional Cardiology, Senior Consultant Interventional Cardiologist & Heart Failure Specialist, Apollo Hospitals, Chennai, ³¹Department of Cardiology, Professor of Cardiology & Senior Interventional Cardiologist, Bombay Hospital/Horizon Hospital, Mumbai, ³²Department of Interventional Cardiology, Senior Interventional Cardiologist, Dr. V T Shah's Diagnostic Centre & Clinic, Mumbai, ³³Department of Cardiology, Senior Cardiologist, AMRI Hospital, Kolkata, ³⁴Department of Interventional Cardiology, Senior Interventional Cardiologist, Sparsh Hospital, Bangalore, ³⁵Department of Interventional Cardiology, Senior Interventional Cardiologist, SS Sparsh Hospital, Bangalore, 36Physician & Intensivist, Aarav Clinic, Surat, ³⁷Department of Cardiology, Consultant Physician Cardiology, Lilavati Hospital, Mumbai, ³⁸Department of Interventional Cardiology, Interventional Cardiologist, Ruby Hospital, Pune, ³⁹Department of Interventional Cardiology, Interventional Cardiologist, Cardio Vision, Pune, ⁴⁰Department of Cardiology, Senior Consulting & Cardiac Physician, HCG Hospital, Ahmedabad, ⁴¹Department of
Interventional Cardiology, Interventional Cardiologist, Apollo Hospital, Hyderabad, ⁴²Department of Cardiology, Associate Professor, Safdarjung Hospital, New Delhi, ⁴³Department of Medicine, CGHS, Safdarjung Hospital, New Delhi, ⁴⁴Department of Cardiothoracic and Vascular Surgery, Director-CTVS, Fortis Escorts, Delhi, India

India, as seen in the recent Trivandrum HF registry (THFR). The in‑hospital mortality and all‑cause
mortality rate are higher in patients with HFrEF compared to those with HF with preserved ejection
fraction.^[2] HF leads to 1.8 million hospitalizations each year in India. According to the Manipal HF
Registry, the average length of a hospital stay for HF during the initial admission is 5.3 ± 2.9 days
and the average overall cost per patient is 1.3 lakh INR.^[3] Although chronic HF management has
improved significantly, HF remains a progressive clinical syndrome with a poor prognosis, leading
to millions of hospitalizations worldwide.^[4]

Progression of heart failure to worsening heart failure

HF progression is punctuated by repeated worsening HF (WHF) events, each resulting in reduced
cardiac function. ^[6‑9] These decompensation events often result in the emergency department
(ED) visits and hospitalizations.^[6] WHF has traditionally been synonymous with an episode of
in‑hospital care for worsening symptoms. However, WHF should be differentiated from the term
acute HF in that it excludes “de novo” patients and requires a chronic HF diagnosis. Although
WHF often leads to hospitalization, many patients experience it outside of the hospital setting
and have a similar poor prognosis. However, outpatient WHF is not commonly recognized as a
clinical concern and is mostly not included in WHF clinical trials. These findings support WHF as
a distinct under‑diagnosed and under‑treated condition, independent of location of care. The
current definition of WHF necessitates hospitalization, treatment in the ED, or receipt of IV diuretic
therapy in the outpatient setting.^[7] In a large United State registry (n = 11,064), 56% of patients
were re‑hospitalized within 30 days of a WHF event.^[9] Not only HF hospitalization but also
escalation of oral diuretic therapy means increased risk in patients with HF.^[10] Each episode of
worsening event has long‑term effects on patients, with more than one‑fifth of patients dying
within 2 years of their first event in the Practice Innovation and Clinical Excellence registry.^[9]
Risk of cardiovascular (CV) death or HFH was 46% higher in patients with recent hospitalization
than in those patients with no prior hospitalization prospective comparison of arni with acei to
determine impact on global mortality and morbidity in heart failure
(PARADIGM-HF).^[11] In the THFR, 33% of patients with HF

were readmitted at least once over 1 year, indicating progression of disease.^[1] In addition,
the Cardiology Society of India‑Kerala Acute HF Registry (CSI‑KHFR) found that 37% of
patients with HFrEF experienced a decompensated event (CSI‑KHFR). Despite advances in HF
management, the residual risk in HFrEF remains high despite the use of HF medications as seen
in landmark clinical trials of angiotensin receptor‑neprilysin inhibitor (ARNI) (PARADIGM‑HF),
dapagliflozin and prevention of adverse outcomes in heart failure (DAPAHF),
and Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection
Fraction (EMPERORReduced). Even patients on quadruple therapy remain at risk of WHF and CV
death. In the DAPA‑HF trial, about one in seven patients experienced a primary outcome event
(composite of an episode of WHF or CV death, whichever occurred first) despite confirmed the
use of quadruple therapy (ARNi, beta blocker, mineralocorticoids receptor antagonist [MRA], and
sodium‑glucose cotransporter‑2 inhibitors [SGLT2i]).^[12] The progression of HF to WHF can be
clinically measured by (a) Increased hospitalization for HF, (b) increased length of hospital
stay, (c) more hospital readmission, and (d) higher mortality^[6,13].

Definition of worsening heart failure

The most recent definition of WHF is “deterioration of HF signs and symptoms in a patient with
chronic HF, despite previous stable background therapy or requires urgent escalation of
therapy, including hospitalization, ED visit, or outpatient IV diuretic therapy, ± outpatient oral
therapy.”[7] The definition of WHF has evolved from just considering worsening of symptoms
requiring hospitalization to escalation of oral diuretics. Despite its inclusion in recent guidelines,
there is no precise definition of WHF or its various forms. It is worth noting that WHF signals a
need for treatment optimization as per guideline‑directed medical therapy (GDMT) and the
addition of novel drugs that benefit this high‑risk patient population. 

Guideline recommendations for heart failure with reduced ejection fraction

Both the 2021 European‑Society of Cardiology (ESC) and 2022 American College of Cardiology
Foundation/American Heart Association (AHA)/HFSociety of America (HFSA)
 

Seth, et al.: Expert opinion on management of worsening heart failure

Table 1: Guideline‑directed medical therapy as per European‑Society of Cardiology 2021 guidelines^[14]

ACEi: Angiotensin‑converting enzyme inhibitor, HF: Heart failure, HFrEF: HF with reduced ejection
fraction, MRA: Mineralocorticoids receptor antagonist

guidelines firmly establish the management of HFrEF using quadruple therapy (ARNI,
evidence‑based β blockers, MRA, and SGLT2i).^[5,14] The major goals of treatment for
patients with HFrEF are reduction in mortality, prevention of recurrent hospitalizations
due to WHF, and improvement in clinical status, functional capacity, and quality of life
(QoL).^[14] [Table 1] The 2022 American College of Cardiology (ACC)/AHA/HFSA
classified WHF as a potential stage C trajectory, along with new onset/De novo HF;
resolution of symptoms; persistent HF or WHF.^[5] In India, only 25% of the HFrEF
patients received GDMT as seen in the THFR and CSI‑KHFR.^[2,15] This is
predominantly attributed to the lack of awareness regarding GDMT among health‑care
professionals (HCPs) and poor tolerability among patients, resulting in an inability to
reach the target dose.

Management of worsening heart failure
Currently, there are no specific guideline recommendations exclusively for the
management of WHF, although all international guidelines recognize WHF patients as
a distinct population.^[7] However, the goals of therapy for WHF would include reduction
in HF hospitalization and preventing the progression to an advanced stage of which
would require advanced therapies such as mechanical circulatory support, cardiac
transplantation, or palliative care.[16] WHF should be recognized as a clinical condition
to first optimize existing GDMT (ARNI, beta‑blocker, SGLT2i, and MRA) if possible
and second add novel drug that improve patient outcomes.

Renin‑angiotensin‑aldosterone system inhibitors – Angiotensin‑converting enzyme
inhibitors/angiotensin receptor blocker/angiotensin receptor neprilysin inhibitor
Angiotensin‑converting enzyme inhibitors (ACEi) (e.g. enalapril, ramipril, captopril, and
lisinopril) are recommended as a first‑line drug in all guidelines. From the 1980s onward,
numerous clinical trials have consistently demonstrated that ACEi can lower mortality
and morbidity, enhance functional capacity, and provide benefits in terms of clinical
symptoms, hemodynamic features, and ventricular remodeling in patients with HFrEF.
High‑dose ACEi should be used with caution in patients with risk of hypotension.^[17]
Sacubitril/valsartan is the first dual neprilysin and ARNI. In the PARADIGM‑HF trial,
sacubitril/valsartan, an ARNI, was shown to be superior to enalapril in reducing
hospitalizations for WHF, CV mortality, and all‑cause mortality in patients with ambulatory
HFrEF.^[11] ARNI improves diastolic function, left ventricular (LV) function, QoL, and burden
of ventricular arrhythmias prospective study of biomarkers, symptom improvement, and
ventricular remodeling during sacubitril/valsartan therapy for heart failure (PROVE-HF).^[18]
Sacubitril/valsartan demonstrates benefits in patients with HFrEF, in terms of mortality
reduction, disease progression, cardiac remodeling, and QoL.^[19] Angiotensin receptor
blockers (ARBs) are recommended for patients who cannot tolerate ACEi or ARNI because
of serious side effects, however, no ARB has successfully shown to reduce all‑cause
mortality in any clinical trial.^[14]

Beta‑blockers
The activation of the sympathetic nervous system (SNS) is one of the significant
pathophysiological abnormalities in HFrEF patients. Beta‑blockers (BB) are one among
the “fantastic four” disease‑modifying drugs for HFrEF that have the greatest impact on
the long‑term prognosis of patients with HFrEF. β‑blockers (e.g. Carvedilol, Bisoprolol,
Metoprolol, and Nebivolol) are mainly used for such patients due to their ability to reverse
the neurohumoral effects of the SNS with consequent prognostic and symptomatic
benefits. The optimal use of β‑blockers has been shown to improve symptoms,
reduce hospitalizations, induce LV reverse remodelling, and increase survival in HFrEF
patients. Recent evidence shows that, in patients with HFrEF and multiple comorbidities,
β‑blockers are still able to achieve favorable prognostic effects. Despite the proven benefit
of β‑blockers in chronic HF, theyare often underutilized in current clinical practice.^[20]

Mineralocorticoids receptor antagonist
MRAs such as spironolactone and eplerenone reduce mortality and readmissions for patients
with HFrEF.^[21] Based on compelling evidence from these trials, MRAs received Class I
recommendations in both American and European guidelines in patients with HFrEF. Eplerenone
is more specific for aldosterone blockade and therefore, causes less gynecomastia.^[14] In
addition, Eplerenone does induce less blood pressure drop than spironolactone and may be
therefore advantageous in hypotensive HF patients. Sodium‑glucose cotransporter‑2 inhibitors
SGLT2 inhibitors (mainly dapagliflozin and empagliflozin) have already revolutionized the
management of HFrEF patients through a significant reduction in CV mortality

Seth, et al.: Expert opinion on management of worsening heart failure

EF: Ejection fraction, ARR: Absolute risk reduction, HF: Heart failure, HFH: Hospitalization for HF,
HR: Hazard ratio, NNT: Number needed to treat, NYHA: New York Heart Association, RRR:
Relative risk reduction, S/V: Sacubitril/Valsartan, CV: Cardiovascular, WHF: Worsening HF, LVEF:
Left ventricular EF, NT‑proBNP: N‑terminal pro‑B natriuretic peptide, DAPA‑HF: Dapagliflozin and
prevention of adverse outcomes in HF, PARADIGM: Prospective comparison of ARNI with ACEI to
determine impact on global mortality and morbidity in heart failure and HF hospitalizations.
Based on clinical trials, the 2021 ESC guidelines recommend dapagliflozin (DAPA‑HF) or
empagliflozin (EMPEROR‑Reduced trial), in addition to GDMT with an ACEi/ARNI, a beta‑blocker
and an MRA, for patients with HFrEF regardless of diabetes status.^[14]

Diuretics
Loop diuretics (e.g. torsemide and furosemide) are recommended to reduce the signs and/or
symptoms of congestion in patients with HFrEF.[14] Diuretic resistance, defined as an
inadequate quantity of natriuresis despite an Journal of the Practice of Cardiovascular
Sciences ¦ Volume 9 ¦ Issue 1 ¦ January-April 2023 5 adequate diuretic regimen, is a major
clinical challenge that generally portends a poor prognosis. Furthermore, robust clinical trial
evidence to guide the use of diuretics is sparse.^[22]

Newer agents – Soluble guanylate cyclase stimulators
Newer treatment options are warranted in patients for whom rehospitalization or urgent
outpatient treatment for HF is warranted despite the use of GDMT. On the basis of the
VICTORIA trial, vericiguat is the only treatment that is specifically recognized for WHF
in recent guidelines for HFrEF. Vericiguat, a novel oral soluble guanylate cyclase
stimulator (sGCS), emerged as a promising and disease‑modifying therapy for WHF.
Vericiguat enhances the cyclic guanosine monophosphate (GMP) pathway by directly
stimulating soluble guanylate cyclase (sGC) through a binding site independent of nitric
oxide, and it sensitizes sGC to endogenous nitric oxide by stabilizing nitric oxide
binding to the binding site.^[23] The nitric oxide‑sGC‑cyclic GMP pathway is important in
the development and progression of HF. Vericiguat is the first oral sGCS approved by
the FDA in January 2021. Vericiguat is indicated for reducing the risk of CV death and
hospitalization for HF in adults with symptomatic chronic HF and an ejection fraction of
< 45% who have been recently hospitalized for HF or required outpatient intravenous
(IV) diuretics. The recommended starting dose of vericiguat is 2.5 mg orally once daily
with food which is to be doubled approximately every 2 weeks to reach the target
maintenance dose of 10 mg once daily, as tolerated by the patient. No other disease‑
modifying HF drugs act on this pathway.^[24‑26] The VICTORIA study evaluated the
efficacy and safety of vericiguat in patients with HFrEF and recent WHF event.
Compared to patients on background therapy, vericiguat was found to reduce the
incidence of death from CV causes or hospitalization for HF by 10% (P = 0.02)
with a superior annualized absolute risk reduction of 4.2% for CV death or HF
hospitalization compared to placebo. The difference in benefit was observed after
approximately 3 months of treatment and persisted throughout the trial. The target
dose of 10 mg was achieved in 89% of patients treated with vericiguat and the overall
frequency of adverse events was similar in the two groups.^[25] Current treatments for
HFrEF were established based on large randomized, controlled trials, focused on
patients with more stable chronic HFrEF, whereas VICTORIA study included patients
with WHF. Compared to DAPA‑HF and EMPEROR‑Reduced trial, the VICTORIA study
included patients with more severe disease (New York Heart Association [NYHA]
Class III or IV), higher event rate and shorter follow‑up.^[26] [Table 2] Patients in
VICTORIA had a very high observed event rate (37.8 subjects with an event per 100
patient‑years at risk for the composite endpoint of CV death or first HF hospitalization
in the placebo group).These annualized event rates for the composite of CV death or
HF hospitalization in the placebo group of VICTORIA are approximately 3 times higher
than those observed in the PARADIGM‑HF, DAPA‑HF studies and 1.5 times higher than
EMPEROR Reduced trial conducted in more stable chronic HFrEF populations,
consistent with the higher‑risk population enrolled in VICTORIA. It is noteworthy that
despite higher baseline N‑terminal pro‑B‑type natriuretic peptide in VICTORIA,
Vericiguat showed an absolute benefit comparable with other HF therapies.

Need For Consensus
The current management of WHF is limited by the lack of a clear definition leading to misdiagnosis or delay in
diagnosis. The current definition of WHF has gaps and limitations including inability to detect asymptomatic
cases, nonconsideration of HF pathophysiology, ambiguity in “background therapy,” and “escalated oral therapy.”
The ESC and ACC/AHA/ HFSA guidelines do not discuss the impact of varying HF phenotypes and disease
trajectories on management decisions. Furthermore, WHF remains inadequately defined, especially in the
outpatient setting. Since WHF has been recently introduced (last 5 years) in European and American guidelines,
robust‑evidence‑based recommendations are lacking. Despite residual risk and poor outcomes following WHF
events, there are no dedicated guideline recommendations for the management of such patients.^[7] A consensus
is needed for the definition, assessment, pharmacological management, and monitoring of patients in a
hospitalized setting. In addition, the expert opinion for the management of WHF as an outpatient is also warranted.
Methodology
A group of cardiologists, CV Thoracic Surgeons (CVTS), and Physicians in India held an expert group meeting to
discuss the identification and pharmacological management of WHF. The meeting was moderated by a leading
cardiologist in the country and included a panel of experts from across India. The development of the consensus
statements involved discussing the role and clinical evidence of drugs available for the management of WHF.
The other objective was to understand the current clinical practice of managing WHF in hospital and outpatient
setting in India. The consensus was formed when majority of experts agreed on the statement.
The points discussed by the panel are listed below:
i. Definition of WHF
ii. Clinical entities to be included in WHF
iii. Drugs to be initiated for a newly diagnosed chronic HFrEF
patient, as part of GDMT
iv. Starting dose and target dose of the drugs (BB, ACEi/ARB/
ARNI, SGLT2i, MRA, diuretics) commonly initiated in
clinical practice, as part of quadruple therapy
v. Proportion of patients receive target dose of ARNI
vi. estimated glomerular‑filtration rate (eGFR) cut‑off for
using ARNI, SGLT2‑inhibitor, MRA
vii. Use of Vericiguat in clinical practice

NYHA: New York Heart Association, HF: Heart failure, EF: Ejection fraction, CV: Cardiovascular,
GDMT: Guideline directed medical therapy, MRA: Mineralocorticoids receptor antagonist,
SGLT2i: Sodium‑glucose cotransporter‑2 inhibitors, ARNI: Angiotensin receptor‑neprilysin inhibitor,
ACEi: Angiotensin‑converting enzyme inhibitor, HFrEF: HF with reduced EF, OPD:
Outpatient department, eGFR: Estimated glomerular filtration rate, BB: Beta
blockers, ARB: Angiotensin II receptor blocker, IV: Intravenous, ER: Emergency room

HF: Heart failure, WHF: Worsening HF, SGLT2i: Sodium‑glucose cotransporter‑2 inhibitors, ACEi:
Angiotensin‑converting enzyme inhibitor, ARNI: Angiotensin receptor‑neprilysin inhibitor,
BP: Blood pressure, HFrEF: HF with reduced ejection fraction, eGFR: Estimated glomerular
filtration rate, ARB: Angiotensin II receptor blocker, ED: Emergency department, IV: Intravenous,
GDMT: Guideline directed medical therapy

viii. Clinical scenarios for initiating vericiguat
ix. Expected outcomes and benefits with vericiguat therapy. The drugs included in this consensus
are ACEi (Captopril, Enalapril, Lisinopril, Ramipril, Trandopril); ARB Losartan, Valsartan, Candesartan,
Telmisartan); ARNI (Sacubitril/valsartan); BB (Bisoprolol, Carvedilol, Metoprolol succinate, Nebivolol);
MRA Spironolactone, Eplerenone); diuretics (Furosemide, Torsemide, Metolazone, and
Chlorthiazide); SGLT2i (Dapagliflozin and Empagliflozin).
Consensus Results
Most experts agreed [Table 4] upon the proposed definition of WHF and not only included the need
for IV diuretics, but also considered an escalation of oral diuretics and the need for hospitalization
as part of the WHF definition. Increasing severity of previous HF should be a clinical entity to be
included in WHF. As part of GDMT, ARNI, BB, SGLT2i, and MRA should be initiated for a newly
diagnosed HFrEF patient. Ramipril was the most commonly prescribed ACEi amongst cardiologists,
whereas CVTS and cardio‑physicians preferred Enalapril. A similar trend was observed with ARBs
wherein Losartan was preferred by CVTS and cardio‑physicians, whereas cardiologists preferred
Valsartan. All three groups of experts prescribe BB, SGLT2i, and MRA as per GDMT. Most cardiologists
use the guideline‑recommended starting dose and target dose of ACEi and ARB, while CVTS and physicians
do not reach the target dose of both ACEi and ARBs. This may be due to less use of ACEi/ARB than
ARNI. Most cardiologists prefer Valsartan as the ARB for HF management, whereas Losartan is
commonly prescribed by surgeons and cardio‑physicians. Carvedilol was preferred over Bisoprolol
among cardiologists and surgeons whereas cardio‑physicians preferred Bisoprolol. Regarding the use
of SGLT2i for HF management, cardiologists preferred Empagliflozin while other two groups of
experts prescribe dapagliflozin more frequently. All the experts use ARNI in their clinical practice.
All the experts agreed that not all

Seth, et al.: Expert opinion on management of worsening heart failure