Indian Experience with Vericiguat A Review Based upon Case

REVIEW ARTICLE

Indian Experience with Vericiguat: A Review Based upon Case Series

Upendra Kaul^1*, Jamshed Dalal², Jagdish Hiremath³, Sandeep Seth⁴, Ashwani Mehta⁵,
Nazir Juvale⁶, Pankaj V Jariwala⁷
Received: 27 June 2024; Accepted: 05 August 2024

Abstract
Heart failure (HF) is a condition that can result in repeated hospitalizations every year and can result in worsening HF (WHF). Although current pharmacological treatment for HF is fairly effective, there is a need to lower the residual risk of cardiovascular events and hospitalizations. Vericiguat, a soluble guanylate cyclase (sGC) stimulator, a new entrant, seems to present a promising therapeutic option for HF with signs of worsening, and early initiation of this therapy may be beneficial in certain patient profiles. This article explores the potential benefits of early vericiguat initiation in four patient profiles who presented with WHF.

Journal of The Association of Physicians of India (2024): 10.59556/japi.72.0696

Introduction

In India, heart failure (HF) causes 1.8 million hospital admissions annually, and HF admissions are seen in middle-aged patients (~53 years) in India compared to an older population (~70 years) in the United States and Europe.1 Based on data from the recent Trivandrum HF registry, HF with reduced ejection fraction (HFrEF), is the most common form of HF. Patients with HFrEF have higher rates of both inhospital death and overall mortality when compared to patients with HF with preserved ejection fraction (HFpEF).2 According to data from the Cardiology Society of India-Kerala Acute Heart Failure Registry (CSI-KHFR) and Trivandrum HF Registry, only 25% of HFrEF patients in India received guideline-directed medical therapy (GDMT).³ The Manipal Heart Failure Registry (MHFR) reports that the average hospital stay for HF during the initial admission is 5.3 ± 2.9 days, with the average cost per patient being 1,560 USD.4 HF continues to be a progressive clinical syndrome with a poor prognosis, even though chronic HF management has greatly improved. HF causes millions of hospitalizations annually worldwide.⁵ 

Recurrent episodes of worsening HF (WHF), each leading to reduced cardiac function, are characteristic of the natural progression of HF.6–9 These decompensation events often result in emergency department (ED) visits and hospitalizations. Historically, WHF has typically been defined as an episode of hospitalization due to deteriorating symptoms. According to the 2023 European Society of Cardiology (ESC) consensus on WHF, WHF can refer to the aggravation of symptoms and signs in patients with preexisting HF, necessitating intensified treatment, usually involving increased diuretic therapy.
The distinction between WHF and acute HF is important. The definition of WHF does not include newly diagnosed (“de novo”) patients and necessitates a prior diagnosis of chronic HF. While WHF often results in hospitalization, many patients experience worsening symptoms outside of the hospital and face similarly poor outcomes. 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 condition that is often underdiagnosed and undertreated, regardless of location of care.¹⁰ 

The guidelines from the 2021 ESC and the 2022 American Heart Association/American College of Cardiology Foundation/Heart Failure Society of America (AHA/ACC/HFSA) clearly establish the management of HFrEF with four standard background therapies [angiotensin receptor neprilysin inhibitor (ARNI), evidence-based β-blockers, mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2i)].^11,12 The 2022 AHA/ACC/HFSA guideline recommends simultaneous or rapid sequencing for HF to achieve quadruple therapy within 4 weeks of treatment initiation (uptitration of target doses thereafter).¹²

The STRONG-HF study, a multinational, open-label, randomized, prospective clinical trial, evaluated the safety, tolerability, and efficacy of rapid uptitration of GDMT before discharge with the aid of NT-proBNP testing in patients admitted for acute HF against usual care. The findings showed intensive treatment involving rapid escalation of GDMT and frequent follow-up after hospitalization for acute HF decreased symptoms and lowered the risk of all-cause death or HF readmission within 180 days, compared to standard care. Furthermore, the intensive treatment strategy improved quality of life and was readily accepted by patients.^13,14 

Vericiguat is a novel therapy that addresses endothelial dysfunction, a frequently unacknowledged aspect of HF syndrome. The NO–soluble guanylate cyclase (sGC)–cGMP pathway is one of the primary signal transduction pathways that regulate the cardiovascular system. Vericiguat functions as an sGC stimulator (sGCS), targeting the NO–sGC–cGMP pathway through a distinct mechanism that complements existing HF treatments. Based on the VICTORIA trial, the 2022 AHA/ACC/HFSA and 2021 ESC guidelines recommend vericiguat to be considered in patients with WHF.15 Vericiguat is the first oral sGCS approved by the US Food and Drug Administration (FDA) in January 2021 and approved in India in February 2022. Vericiguat is indicated to reduce the risk of cardiovascular death and HF hospitalization in adults with symptomatic chronic HF and an ejection fraction below 45% who have recently been hospitalized for HF or required outpatient intravenous diuretics. Vericiguat is recommended to be taken at 2.5 mg orally once daily (OD) with food. This dose should be doubled approximately every 2 weeks until the patient reaches the tolerated maintenance dose of 10 mg OD.16–18 According to the VICTORIA trial, vericiguat therapy decreased the occurrence of cardiovascular death or hospitalization for HF. In terms of safety, the vericiguat group exhibited lower rates of adverse events (AEs) 

¹Batra Hospital and Medical Research Centre, Delhi; ²Department of Cardiology, Kokilaben
Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai; ³Senior Interventional
Cardiologist and Director Cath Lab, Department of Cardiology, Ruby Hall Clinic, Pune,
Maharashtra; ⁴Professor, Department of Cardiology, All India Institute of Medical Sciences;
⁵Department of Cardiology, Sir Ganga Ram Hospital, Delhi; ⁶Consultant Interventional
Cardiologist, Department of Cardiology, Saifee Hospital, Mumbai, Maharashtra; 
⁷Department of Cardiology, Yashoda Hospital, Hyderabad, Telangana, India; 
*Corresponding Author How to cite this article: Kaul U, Dalal J, Hiremath J, et al. Indian
Experience with Vericiguat: A Review Based upon Case Series.
J Assoc Physicians India 2024;72(10):63–68.

and serious adverse events (SAEs) compared to the placebo group. Additionally, there
were no statistically significant differences between the groups in terms of symptomatic
hypotension (9.1 vs 7.9%, p = 0.12) and syncope (4 vs 3.5%, p = 0.30). After approximately 12 months, 90.3% of the patients received the optimal dose of 10 mg of vericiguat. Medication adherence of >80% to vericiguat was observed in 93.8% of the patients (Fig. 1).¹⁵
 

The 2023 ESC consensus on WHF recommends initiating vericiguat, alongside
the four foundational therapies for HFrEF, for patients with a left ventricular ejection fraction (LVEF) below 45% following a WHF event.¹⁰ The recent 2023 Indian consensus on WHF gave the following expert recommendations in Table 1.¹⁹ This is important because the VICTORIA study did not have any patients from India.¹⁵

 

Need to Identify Patient Profiles for Vericiguat

The WHF population represents a diverse pool presenting with varying characteristics such as worsening symptoms, decreased exercise capacity, volume status, elevated biomarkers, frequent HF hospitalizations and ED visits, and escalation of oral/intravenous (IV) therapy. The rate of HF hospitalization or cardiovascular death continues to be significantly high, as seen in the landmark trials of ARNI (PARADIGM-HF study), dapagliflozin (DAPAHF), and empagliflozin (EMPEROR-Reduced).¹⁸ WHF events or cardiovascular death occurred in 16.3% of patients who received all four medications, including dapagliflozin (DAPAHF). ²⁰ Therefore, there remains a need for therapy optimization and further reduction of residual risk of cardiovascular events and hospitalization.²¹

Patients experiencing WHF can receive care in various settings, including inpatient, outpatient, or the ED. Outpatient management is a feasible option for a significant portion of patients with WHF. Many of these patients have a gradual onset and progression of symptoms, allowing for effective outpatient interventions that can enhance their clinical condition without necessitating hospitalization or a visit to the ED.22 As per the consensus statement and definition and classification of HF,23 there is a clear distinction between worsening and advanced HF (Stage D HF). Vericiguat may be considered for patients with chronic HFrEF who experience a WHF event.15 Although long-term follow-up data is currently lacking, discussing early vericiguat initiation in different WHF patient profiles will help clinicians better manage WHF patients in their clinical settings. In this report, we have identified various patient profiles as case studies who could benefit from vericiguat therapy.

Case Studies

Patient on All Four Drugs in Maximally Tolerated Dose but Still Symptomatic
or NT-proBNP is Still Very High

Case Description

A 74-year-old female weighing 54 kg with a body mass index of 19 kg/m2
presented with breathlessness and fatigue that gradually worsened over
the last 3 years and rapidly

Table 1: Recommendations from the Indian consensus on WHF 2023

Fig. 1: Appropriate patient profiles for vericiguat based on the VICTORIA study¹⁵

patients with WHF. Many of these patients have a gradual onset and progression of symptoms, allowing for effective outpatient interventions that can enhance their clinical condition without necessitating hospitalization or a visit to the ED.²² As per the consensus statement and definition and classification of HF,²³ there is a clear distinction between worsening and advanced HF (Stage D HF). Vericiguat may be considered for patients with chronic HFrEF who experience a WHF event.15 Although long-term follow-up data is currently lacking, discussing early vericiguat initiation in different WHF patient profiles will help clinicians better manage WHF patients in their clinical settings. In this report, we have identified various patient profiles as case studies who could benefit from vericiguat therapy.

Case Studies

Patient on All Four Drugs in Maximally Tolerated Dose but Still

Symptomatic or NT-proBNP is Still Very High

Case Description
A 74-year-old female weighing 54 kg with a body mass index of 19 kg/m² presented with
breathlessness and fatigue that gradually worsened over the last 3 years and rapidly

Table 1: Recommendations from the Indian consensus on WHF 2023

worsened in the past month. Her symptoms included reduced appetite and pedal edema. She was admitted to the hospital for furthermanagement and treated as an inpatient. On examination, her LVEF was 22%, herblood pressure was 96/58 mm Hg, and her pulse rate was 106/minute. She had a narrow QRS sinus rhythm, and her eGFR was
32 mL/minute/1.73 m². NT-proBNP was 6150 pg/mL, her potassium level was 5.3 mmol/L, and her LDL-C was 62 mg/dL. Additionally, her jugular venous pressure (JVP)
was raised, pedal edema was present, and her oxygen saturation was 92% at rest.
Her medical history included wellcontrolled T2DM on oral hypoglycemic agents
(OHAs), hypothyroidism, and multivessel coronary artery disease (CAD) with three
percutaneous transluminal coronary angioplasties (PTCAs). Her first PTCA was in
2000, her second in 2016, and her third in 2020, along with a cardiac resynchronization
therapy defibrillator (CRT-D) implant. She visited the ED four times in the last year and
was managed in the ED with intravenous diuretics. Prior to hospital admission, she
was on eplerenone 25 mg OD, sacubitril/valsartan 100 mg BD, carvedilol 3.125 mg BD,
torsemide 20 mg BD, empagliflozin 10 mg OD, and ivabradine 5 mg BD. Additionally, she
had paroxysmal atrial fibrillation. During her inhospital treatment, the following drugs were administered: amiodarone 100 mg OD, trimetazidine OD, and IV iron supplementation. The previous GDMT regimen was continued. Before discharge, vericiguat 2.5 mg OD was initiated. The vericiguat dose will be doubled every 2 weeks until reaching a target dose of 10 mg OD by the end of 1 month. At the end of 3 months, her HF symptoms improved, LVEF increased to 24%, blood pressure stabilized at 108/76 mm Hg, NT-proBNP reduced to 845 pg/mL, and potassium level reduced to 4.8 mmol/L. Her ECG showed normal sinus rhythm, and her eGFR remained the same (32 mL/minute/1.73 m²).
The patient had no further hospitalizations. Discussion Patients in the early post discharge phase following HF admission are at high risk and remain vulnerable. Within 30 days of discharge after hospitalization for HF, approximately 1 in 4 patients are readmitted, and about 1 in 10 patients die.²⁴ GDMT ideally should be started and optimized before discharge from an HF hospitalization or immediately postdischarge. According to the ESC-HFA consensus, vericiguat is recommended, alongside the four main HFrEF therapies, for symptomatic patients following a WHF event.¹⁰

In this WHF case, the patient, despite being on maximally tolerated GDMT (sacubitril/
valsartan, beta-blocker, SGLT2i, and MRA), CRT-D, and ivabradine, had persisting
symptoms for the past 3 years and high NT-proBNP. Given her frequent hospitalization
history, she can be considered a “frequent flyer” to the hospital. Since each hospitalization increases the mortality risk, such WHF patients must be initiated on additional HF medication postdischarge to decrease the chances of rehospitalization and death. This is a classic case of WHF despite being on all four drugs. In such cases, aggressive treatment and intensification of GDMT are crucial, along with the initiation of novel disease-modifying drugs like vericiguat.
In this patient, initiation of vericiguat improved cardiac function, post-discharge outcomes, and prevented further hospitalization.

Patient on All Four Drugs in Maximally Tolerated Dose but Develops Worsening Heart Failure

Case Description

A 62-year-old male weighing 78 kg, diagnosed with HF for 1 year, was brought to the ED with complaints of orthopnea, pulmonary edema, and HF with an LVEF of 35% and New York Heart Association (NYHA) class III. His medical history includes hypertension for 25 years and a PTCA 3 years ago. Prior to the ED visit, his medication history included eplerenone 25 mg OD, sacubitril/valsartan 200 mg BD, carvedilol 25 mg BD, torsemide 20 mg BD, empagliflozin 10 mg OD, aspirin, and atorvastatin. In the ED, his vitals were as follows: SpO₂ 90%, BP 140/90 mm Hg, and HR 70 bpm.

Initial management included IV furosemide 20 mg twice within 1 hour; brisk output was
observed, and SpO₂ increased to 98%. Laboratory investigation revealed an eGFR of 25
mL/minute/1.73 m² and NT-proBNP of 1800 pg/mL. He was discharged the next day from the ED. Discharge medication included eplerenone 25 mg OD, sacubitril/ valsartan 200 mg BD, carvedilol 25 mg BD, torsemide 20 mg BD, empagliflozin 10 mg OD, and vericiguat 2.5 mg OD. The dosage of vericiguat will be increased every 2 weeks, doubling each time, to achieve a target dose of 10 mg OD by the end of 1 month. At the end of 2 months, LVEF improved to 45%, eGFR increased to 40 mL/minute/1.73 m², and NT-proBNP reduced to 400 pg/mL. His vitals were stable (BP 120/80 mm Hg, HR 65 bpm), and his weight slightly reduced to 76 kg.

Discussion

The secondary analysis of the DAPA-HF trial showed that patients who required urgent
intravenous diuretics had a three times higher risk of mortality compared to those who did not experience a WHF event.⁷ In the VICTORIA trial, 15.9% of patients received IV diuretics in the outpatient (OP) setting.¹⁵ This is a classic case of hypertensive HF in which the patient, initially treated as an outpatient, required an urgent emergency visit and IV diuretic treatment due to WHF. Efforts to reduce HF hospitalization included using novel therapies like vericiguat for the management of outpatient WHF. In this case, early initiation of vericiguat after volume correction led to improvement in LVEF, NT-proBNP, and eGFR. No further hospitalization episodes were noted after 2 months of initiation of vericiguat.

Worsening Heart Failure Patient Requiring Escalation of Oral Diuretics: Outpatient
Management

Case Description

A 40-year-old female was recently diagnosed with HF and iron deficiency anemia (IDA) and presented with cough and hemoptysis. Her chief complaints included cough for >1 month, chest pain associated with the cough, and dyspnea on exertion (DOE). She had no history of hospitalization but had frequent OPD visits and did not want hospitalization. Her medication history included sacubitril/valsartan 100 mg BD, bisoprolol 5 mg OD, torsemide 10 mg OD, spironolactone 50 mg OD, intravenous iron 1 gm, intravenous furosemide 40 mg, and ferrous ascorbate OD. During examination, her LVEF was found to be 20%, her BP was 145/85 mm Hg, her NT-proBNP level was 3243 pg/mL, and her HF was categorized as NYHA class III. Laboratory results included Hb 8.5 gm/dL, serum iron 36 μg/dL, and TSAT 14%, indicating severe IDA.

Treatment included intensification of oral diuretics (torsemide from 10 to 40 mg), sacubitril/ valsartan (from 100 to 200 mg BD), initiation of dapagliflozin 10 mg OD, and initiation of vericiguat 2.5 mg due to her WHF symptoms like cough and dyspnea. The dosage of
vericiguat was increased twofold every 2 weeks, reaching a daily dose of 10 mg by the end of 1 month. She was also continued on bisoprolol 5 mg OD and spironolactone 50 mg OD. At the end of 6 months, the NYHA class improved from class III to I. Her walking distance improved, symptoms of cough and dyspnea reduced, LVEF increased to 35%, NT-proBNP reduced to 675 pg/mL, and eGFR was 79 mL/minute/1.73 m². She has not been hospitalized since then.

Discussion

This patient was managed in the outpatient setting since she refused hospitalization.
According to guidelines, patients with WHF can be addressed in inpatient, outpatient,
or ED settings. Outpatient management of WHF is an option for a significant portion of
the WHF population who have less severe symptoms or are not hospitalized due to
patient refusal or resource constraints. This patient was successfully managed with
outpatient intervention, which improved her condition without requiring admission to the
hospital or a visit to the ED.
Patient Cannot Tolerate All Four Drugs or Maximally Tolerated Dose, due to Tolerability
Issues (Hypotension/High Creatinine/Hyperkalemia)

Case Description

A 72-year-old female patient with a history of HF for 6 years, type 2 diabetes mellitus
(T2DM), hypertension (HTN), chronic kidney disease (CKD), and CAD with coronary artery bypass grafting (CABG) 12 years ago presented to the cardiology OPD with complaints of breathlessness on minimal exertion, frequent UTI, and pedal edema. She had four previous hospitalization episodes. On examination, her blood pressure was 88/58 mm Hg, and HF was classified as NYHA class III. Her LVEF was 20%, NT-proBNP was 4900 pg/mL, and eGFR was 35 mL/minute/1.73 m². Other laboratory details were as follows: Hb 11.8 gm/dL, sodium 134 mEq/L, potassium 5.5 mEq/L, and HbA1c 6.8%. Prior to the WHF event, her medication history included furosemide 40 mg BD, bisoprolol 1.25 mg OD, aspirin 75 mg OD, and rosuvastatin 20 mg OD. The patient was admitted and treated in the inpatient setting. Her GDMT was optimized to furosemide 40 mg BD, bisoprolol 1.25 mg OD, aspirin 75 mg OD, rosuvastatin 20 mg OD, and vericiguat 2.5 mg OD was initiated. Empagliflozin was also initiated but had to be stopped because of recurrent urinary tract infections. The dosage of vericiguat was increased twofold every 2 weeks, reaching a daily dose of 10 mg by the end of 1 month. An attempt was made to initiate low-dose sacubitril/valsartan, which was not tolerated. At the 1-month follow-up, her LVEF improved to 25%, and NT-proBNP reduced to 2840 pg/mL. Her eGFR remained the same, at 35 mL/minute/1.73 m2. The patient has not been hospitalized since the initiation of vericiguat treatment, and her HF improved from NYHA class III to class I.

Discussion

As per the VICTORIA trial, the rates of adverse effects were similar to those of placebo, and there was no notable difference between the two groups in the development of syncope or hypotension. Furthermore, approximately 90% of patients received the optimal dose of vericiguat (10 mg OD), indicating good compliance and tolerability. In this WHF case, the patient was unable to tolerate sacubitril/valsartan due to hypotension, MRAs were not added due to hyperkalemia, and she had frequent UTIs on SGLT2i. Thus, this patient was not on two out of four drugs, indicating tolerability issues, and vericiguat was added with the objective of improving clinical outcomes related to mortality and hospitalization. Initiation of vericiguat becomes important in such a patient who cannot tolerate all four drugs or the maximally tolerated dosage of GDMT due to tolerability issues such as hypotension, hyperkalemia, and UTI. Furthermore, this patient had CKD. Vericiguat does not affect eGFR and serum creatinine. It does not require electrolyte monitoring since it does not have a clinically relevant impact on sodium and potassium. Thus, vericiguat can be safely used in patients with CKD without constant monitoring of electrolytes.

Worsening Heart Failure Management: Locations of Care, Monitoring, and Follow-up Plan

The early postdischarge phase from HF hospitalization is expected to be high-risk
with poor outcomes and is often referred to as the vulnerable phase. Despite the availability of various drugs for HF management, patients remain at substantial risk of poor
postdischarge outcomes, including ED visits and hospitalizations. Clinicians must optimize GDMT within 30 days postdischarge to reduce postdischarge morbidity and mortality. The goals for treating WHF include reducing HF hospitalizations and preventing
progression to an advanced stage, which would require advanced treatments like
mechanical circulatory support, heart transplantation, and palliative care.²³ While
the management of WHF has historically been hospital-centric, the rising prevalence of
HF and its healthcare costs have necessitated the exploration and development of alternative care options to prolonged hospital stays.

Transition from Hospital to Home

The transition from hospital to home care for patients with HF is a critical phase due to the progressive nature of the disease, complex medication regimens, and the presence of multiple comorbidities. This period represents the highest risk for deterioration, potentially leading to hospital readmission within days or weeks after discharge. Effective transitions of care can reduce avoidable readmissions and enhance patient satisfaction. Implementing multidisciplinary care systems that enhance communication among healthcare providers, ensure consistent use and monitoring of GDMT,conduct thorough medication reconciliation, and maintain accurate documentation are essential standards of patient safety for all HF patients transitioning from hospital care. According to the 2022 AHA/ACC/HFSA guidelines, scheduling an early follow-up visit, typically within 7 days of hospital discharge for WHF, is advisable to enhance care optimization and lower the likelihood of readmission.25 The 2021 ESC guidelines recommend scheduling a
follow-up visit within 1–2 weeks after hospital discharge. This visit should involve monitoring HF signs and symptoms, assessing volume status, blood pressure, heart rate, and laboratory parameters such as renal function, electrolytes, and potentially NPs. Additionally, iron status and liver function should be evaluated if not previously done before discharge. Based on clinical assessment and laboratory results, adjustments or initiation of disease-modifying treatments for HFrEF should be considered.

OUTPATIENT CARE FOR  WORSENING HEART FAILURE PATIENT 

Traditionally, the management of WHF has been hospital-based, but not all patients who
visit the ED for WHF need to be admitted. Patients deemed low-risk after ED evaluation
may be discharged or managed in an ED-based observation unit for 24–48 hours. Many
patients show improvement in dyspnea or complete symptom resolution within 24 hours
of receiving intravenous therapy, such as diuretics or vasodilators, during their ED stay.
This approach necessitates transitioning to outpatient care with close follow-up.¹⁰
The advantages of outpatient HF units include timely up-titration of GDMT, more home
time, and prevention of hospitalization. Intravenous diuretic (3–6 hours intravenous
diuretic infusion, dose depending on the diuretic) or intensification of oral diuretic
therapy is done in the outpatient setting. The treatment response is assessed by urine
output, sodium excretion, clinical relief of congestion, electrolyte levels, biomarkers, and/ or ultrasound.²² The next frontier in monitoring WHF patients is virtual consultation.

Virtual Heart Failure Clinic

The virtual HF clinic includes virtual communications between patients and clinicians
through an online portal.²⁶ Recently, the Heart Failure Society of America released
an expert consensus statement on the utilization of telehealth in HF.²⁷ The HF virtual
clinic is a novel concept introduced for managing patients who do not require
hospitalization due to less severe symptoms or resource constraints (e.g.,
nonavailability of hospital beds). At present, this concept has been implemented in the
Department of Cardiology, AIIMS, New Delhi. Based on symptoms and clinical status, patients are managed accordingly, and the appropriate treatment regimen is initiated (Fig. 2).

Fig. 2: Transition from hospital to virtual HF clinic²⁸

Fig. 3: Proposed follow-up algorithm

This concept can provide effective homebased care to patients with HF who show worsening of symptoms without a need for hospitalization.²⁷ Telehealth has become a crucial means of providing outpatient care for chronic HF. A virtual clinic may be more efficient in resource-limited settings like India. Implementing a virtual HF clinic may maximize GDMT without conventional face to-face interaction.²⁶ For WHF patients, switching between physical consultation and teleconsultation as part of planned follow-up would benefit patients and clinicians, ultimately reducing the healthcare burden. Supportive laboratory tests like ECHO and NT-proBNP levels can be done on the day of the inperson visit. Further adjustments should be made during the early postdischarge period based on the patient’s clinical condition. Therefore, scheduling a follow-up visit (preferably within the first 2 weeks after discharge) is crucial to assess symptoms, clinical status, volume status, and basic laboratory markers such as renal function, NT-proBNP, and echocardiogram results (Fig. 3). Visit 1 should be 1–2 weeks after discharge.
The following visits should be every 15 days for 1.5 months, then after 1 month, and then once a month up to months 3 and 4. An algorithm for follow-up is proposed in Figure 3. This practice may be considered for WHF patients, as these patients require a more aggressive follow-up plan compared to chronic HFrEF patients without worsening, owing to the high risk of morbidity and mortality.

Conclusion

The objective of this paper is to help treating clinicians manage different patient profiles of WHF, such as those with frequent hospitalizations or ED visits requiring IV diuretics or escalation of oral diuretics. Management of WHF patients should be proactive, which includes early initiation of vericiguat during outpatient visits for patients who present with worsening symptoms or tolerability issues to GDMT, at predischarge, or at the first follow-up for hospitalized patients, along with dose optimization of background HF drugs. Quintuple therapy with vericiguat should be the cornerstone for the management of patients with WHF or tolerability issues to GDMT, irrespective of the location of care. The need of the day is to be aggressive in the management of HF, especially in those presenting as WHF. HF mortality is high, similar to many cancers, and treatment, therefore, has to be multi-pronged and started early. The four pillars of HF treatment need to be upgraded to quintuplet therapy once the earliest signs of WHF have been detected.

Author Contributions

UK: Conceptualization, Writing–review and editing; JD: Conceptualization, Writing–review and editing; JH: Conceptualization, Writing–review and editing; SS: Writing–review and editing, Visualization; AM: Writing–review and editing; NJ: Writing–review and editing, Visualization; PJ: Writing–review and editing.

Acknowledgments

The grant for medical writing was provided by Bayer. IntelliMed Healthcare Solutions Pvt.Ltd., India, supported manuscript writing and submission.