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 Table of Contents  
Year : 2023  |  Volume : 9  |  Issue : 1  |  Page : 1-10

Expert opinion on the identification and pharmacological management of worsening heart failure: A consensus statement from India

1 Department of Cardiology, AIIMS, New Delhi, India
2 Department of Cardiology, Hannover Medical School (MHH), Germany
3 Department of Cardiology, Director, Clinical and Preventive Cardiology- Heart Institute, Medanta-The Medicity, Gurugram, India
4 Department of Cardiology, Director Cardiology and Head -Medical Advanced Heart Failure Program at Fortis Escorts Heart Institute, Delhi, India
5 Department of Cardiology, Senior Consultant Cardiologist & Intervention Cardiologist, Indraprastha Apollo Hospital, Sarita Vihar, Gurugram, India
6 Department of Cardiology, Fortis Hospital, Gurugram, India
7 Department of Cardiology, Senior Director & Unit Head, Cardiac Sciences, Cardiology, Cardiac Electrophysiology-Pacemaker, Interventional Cardiology, Max Smart Super Speciality Hospital, Saket, India
8 Department of Cardiothoracic and Vascular Surgery, AIIMS, New Delhi, India
9 Department of Cardiology, Consultant- Interventional Cardiologist, Indraprastha Apollo Hospital Sarita Vihar, New Delhi, India
10 Department of Cardiology and Incharge, Acute Cardiac Care and Heart Failure Clinic, Holy Family Hospital, New Delhi, India
11 Department of Cardiology, Director Cardiology Accord Hospital, Faridabad, India
12 Department of Cardiology, Associate Director-Cardiac Science Max Super Speciality Hospital, Patparganj, (Delhi), India
13 Department of Cardiology, Consultant, Yatharth Super Specialty Hospital, Greater Noida, India
14 Department of Cardiology, Consultant Cardiologist, Max Hospital, Vaishali, Ghaziabad, India
15 Department of Cardiology, Senior Consultant, Cardiology & CTVS, Metro Group of Hospitals, Noida, Uttar Pradesh, India
16 Department of Cardiology, Assistant Professor, Safdarjung Hospital, New Delhi, India
17 Department of Interventional Cardiology, Director -Clinical and Interventional Cardiology, Max Super Speciality Hospital, Vaishali, India
18 Department of Cardiothoracic and Vascular Surgery, Senior Resident, CTVS, AIIMS, New Delhi, India
19 Department of Cardiology, Consultant Cardiologist, Sir Gangaram Hospital, New Delhi, India
20 Department of Cardiology, Professor, GB Pant Hospital, New Delhi, India
21 Department of Cardiology, Senior Consultant Cardiac Sciences, Max Superspeciality Hospital, Shalimaar Bagh Delhi, India
22 Department of Cardiology, Senior Consultant-Cardiology, Fortis Shalimar Bagh, India
23 Department of Cardiology, Consultant Cardiologist and Physician, Gupta Ultrasound and Heart Care Centre, West Delhi, India
24 Department of Cardiology, Director & HOD Cardiology & Heart Failure Programme, Fortis Hospital Shalimar Bagh, India
25 Department of Cardiology, Director & Head, ISIC -Saroj Cardiac Sciences, Vasant Kunj New Delhi, India
26 Department of Interventional Cardiology, Consultant Interventional Cardiologist, Fortis Hospital, Noida, India
27 Department of Internal Medicine, Senior Consultant Internal Medicine, Max Super Speciality Hospital, Patparganj, India
28 Department of Interventional Cardiology, Director of Interventional Cardiology - Mahavir Heart Institute, Surat, India
29 Department of Interventional Cardiology, Senior Interventional Cardiologist & HF Specialist, Kokilaben Dhirubhai Ambani Hospital & Research Centre, Andheri Mumbai, India
30 Department of Advanced Cardiac Sciences & Heart Transplant, Consultant- Advanced Cardiac Sciences & Heart Transplant, Sir H.N. Reliance Foundation Hospital & Research Centre, Mumbai, India
31 Department of Interventional Cardiology, Senior Consultant Interventional Cardiologist & Heart Failure Specialist, Apollo Hospitals, Chennai, India
32 Department of Cardiology, Professor of Cardiology & Senior Interventional Cardiologist, Bombay Hospital/Horizon Hospital, Mumbai, India
33 Department of Interventional Cardiology, Senior Interventional Cardiologist, Dr. V T Shah's Diagnostic Centre & Clinic, Mumbai, India
34 Department of Cardiology, Senior Cardiologist, AMRI Hospital, Kolkata, India
35 Department of Interventional Cardiology, Senior Interventional Cardiologist, Sparsh Hospital, Bangalore, India
36 Department of Interventional Cardiology, Senior Interventional Cardiologist, SS Sparsh Hospital, Bangalore, India
37 Physician & Intensivist, Aarav Clinic, Surat, India
38 Department of Cardiology, Consultant Physician Cardiology, Lilavati Hospital, Mumbai, India
39 Department of Interventional Cardiology, Interventional Cardiologist, Ruby Hospital, Pune, India
40 Department of Interventional Cardiology, Interventional Cardiologist, Cardio Vision, Pune, India
41 Department of Cardiology, Senior Consulting & Cardiac Physician, HCG Hospital, Ahmedabad, India
42 Department of Interventional Cardiology, Interventional Cardiologist, Apollo Hospital, Hyderabad, India
43 Department of Cardiology, Associate Professor, Safdarjung Hospital, New Delhi, India
44 Department of Medicine, CGHS, Safdarjung Hospital, New Delhi, India
45 Department of Cardiothoracic and Vascular Surgery, Director-CTVS, Fortis Escorts, Delhi, India

Date of Submission06-Apr-2023
Date of Acceptance07-Apr-2023
Date of Web Publication04-May-2023

Correspondence Address:
Sandeep Seth
Department of Cardiology, AIIMS, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpcs.jpcs_32_23

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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

How to cite this article:
Seth S, Bauersachs J, Mittal S, Rastogi V, Rajput RK, Gandotra D, Gupta R, Sahu M, Pathak S N, Bhagwati M, Minocha S, Sharma P, Vatsa D, Aggarwal R, B Singh GR, Arora G, Kubba S, Rajeev M, Jha P, Vivek B S, Gupta M, Bishnoi R, Khare R, Gupta V, Goyal NK, Dhall A, Madan A, Sharma B D, Abhyankar AD, Kahale P, Meeran T, Ezhumalai B, Kalmath B C, Shah V T, Rungta S, Kumar P A, Christopher S, Shah AA, Dargad R, Sheth K, Khode A, Mehta SP, A Ranga Reddy BV, Gupta P, Tripathi B K, Bhuyan RR. 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

How to cite this URL:
Seth S, Bauersachs J, Mittal S, Rastogi V, Rajput RK, Gandotra D, Gupta R, Sahu M, Pathak S N, Bhagwati M, Minocha S, Sharma P, Vatsa D, Aggarwal R, B Singh GR, Arora G, Kubba S, Rajeev M, Jha P, Vivek B S, Gupta M, Bishnoi R, Khare R, Gupta V, Goyal NK, Dhall A, Madan A, Sharma B D, Abhyankar AD, Kahale P, Meeran T, Ezhumalai B, Kalmath B C, Shah V T, Rungta S, Kumar P A, Christopher S, Shah AA, Dargad R, Sheth K, Khode A, Mehta SP, A Ranga Reddy BV, Gupta P, Tripathi B K, Bhuyan RR. Expert opinion on the identification and pharmacological management of worsening heart failure: A consensus statement from India. J Pract Cardiovasc Sci [serial online] 2023 [cited 2023 May 29];9:1-10. Available from: https://www.j-pcs.org/text.asp?2023/9/1/1/375808

  Introduction Top

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 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],[7],[8],[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 (DAPA-HF), and Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction (EMPEROR-Reduced). 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)/HF Society of America (HFSA) 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]
Table 1: Guideline-directed medical therapy as per European-Society of Cardiology 2021 guidelines[14]

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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]


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, they are 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 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]


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 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],[25],[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.
Table 2: Comparison of baseline characteristics, efficacy and safety of angiotensin receptor-neprilysin inhibitor, sodium-glucose cotransporter-2 inhibitors and vericiguat for worsening heart failure

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Table 3: Percentage agreement on consensus statements

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  Need For Consensus Top

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 Top

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:

  1. Definition of WHF
  2. Clinical entities to be included in WHF
  3. Drugs to be initiated for a newly diagnosed chronic HFrEF patient, as part of GDMT
  4. 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
  5. Proportion of patients receive target dose of ARNI
  6. estimated glomerular-filtration rate (eGFR) cut-off for using ARNI, SGLT2-inhibitor, MRA
  7. Use of Vericiguat in clinical practice
  8. Clinical scenarios for initiating vericiguat
  9. 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 Top

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.
Table 4: Final consensus statements for management of WHF

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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 patients reach target dose of ARNI (200 mg BD as seen in PARADIGM trial). Possible reasons include hypotension and less usage in chronic kidney disease patients. Most experts selected 30–50 ml/min/m3 as the cut-off eGFR for using ARNI, SGLT2-inhibitor and MRA.

Vericiguat was used by many cardiologists and cardio-physicians in their clinical practice, while all surgeons have yet not started using it in routine practice, which indicates a lack of awareness and adoption among such HCPs.

Most experts agreed that Vericiguat could be used for:

  1. In-patient on IV diuretics and now stabilized on oral diuretic and ready for discharge
  2. Patient with history of recent hospitalization presenting in the clinic for follow-up and optimization of treatment
  3. Outpatient WHF patient (requires escalation of diuretic therapy)
  4. WHF patient (previous history of HF hospitalization with tolerability issues) on existing GDMT (hypotension/hyperkalemia/low eGFR).

The difference in opinion in these specialities is predominantly attributed to the expert's individualized practice patterns and clinical setting. Cardiologists manage hospitalized WHF patients, whereas those in the outpatient setting are managed by most specialities including physicians, cardiologists, and cardiothoracic surgeons. The expected outcomes with Vericiguat therapy are a reduction in HF hospitalization, CV mortality, and improvement in signs and symptoms (NYHA class). The benefits seen with Vericiguat therapy include a reduction in HF hospitalization and improvement in signs and symptoms (NYHA class), according to all experts [Table 3].

  Clinical Checklist for the Management of Worsening Heart Failure Top

The clinical checklist for the management of WHF is represented in [Figure 1].
Figure 1: In-hospital quality improvement measures for heart failure. SGLT2i: Sodium-glucose cotransporter-2 inhibitors, ARNI: Angiotensin receptor-neprilysin inhibitor, ACEi: Angiotensin-converting enzyme inhibitor, eGFR: Estimated glomerular filtration rate, BB: Beta blockers, ARB: Angiotensin II receptor blocker, IV: Intravenous, BP: Blood pressure, AF: Atrial fibrillation, CAD: Coronary artery disease, DM: Diabetes mellitus, HbA1C: Glycated haemoglobin, ICD: implantable cardioverter-defibrillator, CRTD: Cardiac resynchronization therapy, LMWH: low-molecular weight heparin

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  Conclusion Top

Patients with WHF should be identified as a distinct population. GDMT (ARNI, beta-blocker, SGLT2i, MRA and diuretics) should be optimized. This expert opinion is dedicated to ensuring early diagnosis and appropriate management of patients with WHF. Vericiguat's novel mechanism of action provides a new and different approach to managing HF following a worsening event. There is a need to improve awareness, adoption and implementation of GDMT and addition of novel drugs to manage patients with WHF.[29]


The coordination and logistics of the expert group meeting was supported by Bayer. Medical writing assistance was provided by Intellimed Healthcare Solutions, Mumbai.

Financial support and sponsorship


Conflicts of interest

JB received honoraria for lectures/consulting from Novartis, Vifor, Bayer, Pfizer, Boehringer Ingelheim, AstraZeneca, Cardior, CVRx, BMS, Amgen, Corvia, Norgine, Edwards, Roche not related to this article; and research support for the department from Zoll, CVRx, Abiomed, Norgine, Roche, not related to this article.

  References Top

Bragazzi NL, Zhong W, Shu J, Abu Much A, Lotan D, Grupper A, et al. Burden of heart failure and underlying causes in 195 countries and territories from 1990 to 2017. Eur J Prev Cardiol 2021;28:1682-90.  Back to cited text no. 1
Harikrishnan S, Jeemon P, Ganapathi S, Agarwal A, Viswanathan S, Sreedharan M, et al. Five-year mortality and readmission rates in patients with heart failure in India: Results from the Trivandrum heart failure registry. Int J Cardiol 2021;326:139-43.  Back to cited text no. 2
Financial Burden of Heart Failure in a Developing Country: Cost Analysis from Manipal Heart Failure Registry, India | SpringerLink. Available from: https://link.springer.com/article/10.1007/s10389-019-01141-w. [Last accessed on 2022 Nov 24].  Back to cited text no. 3
Shukkoor AA, George NE, Radhakrishnan S, Velusamy S, Gopalan R, Kaliappan T, et al. Clinical characteristics and outcomes of patients admitted with acute heart failure: Insights from a single-center heart failure registry in South India. Egypt Heart J 2021;73:38.  Back to cited text no. 4
Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, et al. 2022 ACC/AHA/HFSA guideline for the management of heart failure. J Card Fail 2022;28:e1-167. Available from: https://www.onlinejcf.com/article/S1071-9164 (22) 00076-8/fulltext. [Last accessed on 2023 Mar 13].  Back to cited text no. 5
Cowie MR, Anker SD, Cleland JG, Felker GM, Filippatos G, Jaarsma T, et al. Improving care for patients with acute heart failure: Before, during and after hospitalization. ESC Heart Fail 2014;1:110-45.  Back to cited text no. 6
Greene SJ, Bauersachs J, Brugts JJ, Ezekowitz JA, Lam CS, Lund LH, et al. Worsening heart failure: Nomenclature, epidemiology, and future directions: JACC review topic of the week. J Am Coll Cardiol 2023;81:413-24.  Back to cited text no. 7
Gheorghiade M, Greene SJ, Butler J, Filippatos G, Lam CS, Maggioni AP, et al. Effect of vericiguat, a soluble guanylate cyclase stimulator, on natriuretic peptide levels in patients with worsening chronic heart failure and reduced ejection fraction: The SOCRATES-REDUCED Randomized Trial. JAMA 2015;314:2251-62.  Back to cited text no. 8
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  [Figure 1]

  [Table 1], [Table 2], [Table 3], [Table 4]


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