A Comparative Study on The Effects of Arni and Beta Blocker on Renal Function in Patients with Heart Failure

A chronic condition known as heart failure (HF) develops when the heart is unable to pump blood efficiently enough to fulfill the body’s oxygen uptake needs. Heart failure may develop from any condition that effects the heart’s ability to beat (diastolic dysfunction) or relax (systolic dysfunction). The abbreviation HFrEF stands for heart failure associated with reduced ejection fraction, often known as diminished left ventricular ejection fraction (LVEF). Maintaining left ventricular systolic function (normal LVEF) with suspecting diastolic deterioration is what called as heart failure with preserved ejection fraction (HFpEF).^[1]

Table No.1- Classification Of Heart Failure

Etiology

There are many causes of HF, and coronary artery disease (CAD) causing ischemic heart disease is the most common cause. Ischemic heart disease is by far the most common cause of HF worldwide. Ischemia leads to a lack of blood flow to heart muscles, reducing the EF^[2].Valvular heart disease is another common intrinsic heart condition that can cause HF. Rheumatic heart disease is the most common cause of valvular heart disease in children and young adults worldwide. It is caused by an immune response to group A Streptococcus and primarily causes mitral and aortic stenosis^[3]. Hypertension causes HF even in the absence of CAD or ischemic heart disease. High blood pressure causes mechanical stress by increased afterload and neuro hormonal changes that increase ventricular mass. HTN is also strongly associated with other comorbidities for HF development, and aggressively treating hypertension is shown to lower the incidence of HF. Cardiomyopathy is a heterogeneous group of diseases characterized by enlarged ventricles with impaired function not related to secondary causes such as ischemic heart disease, valvular heart disease, hypertension, or congenital heart disease. The most common types of cardiomyopathies are hypertrophic, dilated, restrictive, arrhythmogenic right ventricular, and left ventricular non compaction. In addition to HF, cardiomyopathy can present as arrhythmia or sudden cardiac death, further compelling the identification of underlying disorders^[4].Obesity is a leading cause of HF in patients younger than 40 years, Patients with obesity are more likely to have HFpEF, possibly secondary to adipose-produced cytokines such as IL-1b, IL-8, and TNFα. Adipose tissue also degrades natriuretic peptides^[5].

Signs And Symptoms

Pulmonary symptoms: The major symptoms, which include dyspnea (especially with exercise) and fatigue, make physical activity intolerable, orthopnea, tachypnea, cough, nocturnal paroxysmal dyspnea, Peripheral edema, pulmonary embolism, fluid retention. Nonspecific symptoms: Fatigue, nocturia, hemoptysis, stomach discomfort, anorexia, nausea, bloating, changes in mental state, weight gain^[6].

Pathophysiological Differences Between HFpEF and HFrEF

Evidence-based treatment improves symptoms and prognosis only in HFrEF but not in HFpEF. These variations underline how important it is to comprehend how the pathophysiology of HFrEF and HFpEF differs, as this may also affect the therapy goals. The high death rate and rising incidence are shared by both. Variations in the pathological development of HFrEF and HFpEF have been documented in relation to fibrosis, changes in the giant spring titin, cardiomyocyte hypertrophy and death, inflammation, and endothelial function^[7]. Cardiomyocyte hypertrophy, intercellular fibrosis, altered cardiomyocyte relaxation, and inflammation are some of the anatomical and cellular changes that characterize HFpEF and impair the left ventricle's ability to relax. Chronic comorbid conditions such arterial hypertension, type 2 diabetes mellitus (T2DM), obesity, renal insufficiency, lung illness, liver disease, sleep apnea, gout, and cancer are frequently linked to HFpEF. These concomitant conditions, such as diabetes, which also activate inflammation, are frequently associated with the inflammatory process in HFpEF. About 60% of non-cardiomyocytes are endothelial cells, and HFpEF is more likely than HFrEF to have endothelial dysfunction, which is frequently observed early in cardiovascular disease. Numerous adaptive processes, such as neurohumoral activation, vasoconstriction, increased oxidative stress, nitric oxide imbalance, or energy bioavailability, might lead to endothelial dysfunction after decreased cardiac output^[7]. However, in HFpEF, endothelial dysfunction (caused by comorbidities) may also be a prelude to cardiac dysfunction. There is a wide range of variability in HFpEF. In addition to being older, patients with HFpEF are twice as likely to be female^[8]. There may be a link between a higher incidence of myocardial infarction and the prevalence of men in HFrEF. The hallmark of HFrEF is a significant loss of cardiomyocytes, either acutely or chronically, which leads to systolic dysfunction. Examples of such conditions include myocardial infarction-related myocyte loss, genetic mutations, myocarditis with cell loss, or valvular disease with overload-induced cell death (apoptosis antigen 1 activation)^[9,10], which is followed by an inability of the left ventricle to contract normally. The most common feature in HFpEF is concentric cardiomyocyte hypertrophy, which might result in eccentric remodeling with an excess of fibrotic tissue. Moreover, cardiomyocytes in HFrEF have reduced myofibrillar density, are more elongated, and are thinner^[11]. Both HFrEF and HFpEF have distinct effects on cardiac titin and calcium levels. Although HFmrEF can develop into either HFrEF or HFpEF, like HFrEF, its phenotype is primarily characterized by coronary artery disease.

Diagnosis

• Patients exhibiting HF side symptoms should be carefully considered for HF diagnosis. In addition to pertinent research center work, patients with HF should have a thorough history and physical evaluation.
• Conditions that might cause or destroy HF are typically evaluated with a full blood count, serum electrolytes (including calcium and magnesium), urinalysis, lipid profile, thyroid capability tests, glycated hemoglobin (A1C), and B-type natriuretic peptide (BNP) generally at 100 pg/mL.
• Although systolic or diastolic dysfunction cannot be definitively determined by calculating theleft ventricular discharge fraction (LVEF), echocardiography may differentiate abnormalities of the pericardium, myocardium, and cardiovascular valves.
• The main goal of the doctor's subjective assessment based on the NYHA Functional Classification System for Patients with Symptomatic HF is this. Physical activity levels are completely up to the discretion of the patients in Functional Class (FC)-I. The limits experienced by FC-II patients are mild, those of FC-III are substantial, and those of FC-IV are severe.
• Electrocardiograms and chest x-rays may also reveal ventricular enlargement (ECG).Pulmonary edema and pleural effusions are other possible findings on a chest x-ray. In order to assess systolic and diastolic dysfunction, echocardiography may measure the left ventricular ejection fraction and rule out problems with the myocardium, pericardium, or cardiovascular valves (LVEF)^[12].
• Blood examinations: Blood tests to measure certain chemicals, like brain natriuretic peptide external link (BNP), may be prescribed by physician. When heart failure occurs, these levels rise.
• Ejection Fraction Measurement

To determine ejection fraction, physician may prescribe an echocardiogram (echo) or other imaging procedures. The percentage of blood in the left ventricle, the lower left chamber of the heart, that is pumped out of the heart with each heartbeat is known as your ejection fraction. The Ejection Fraction is a measure of cardiac pumping efficiency ^[13].

Treatment

Beta Blockers: Decrease in hospitalizations, mortality, and disease progression are all observed in patients with systolic heart failure (HF) who take particular β-blockers, as supported by substantial evidence from clinical trials. In the absence of contraindications or a documented history of β-blocker intolerance, the ACC/AHA guidelines advise treating all stable individuals with HF and a decreased LVEF with β-blockers. Even if patients' symptoms are well-controlled with ACE inhibitor and diuretic medication, they should nevertheless receive a β-blocker. Optimizing ACE inhibitor dosages prior to initiating a β-blocker is not necessary, as the addition of a β- blocker is probably more advantageous than an increase in ACE inhibitor dose. For asymptomatic patients with a decreased LVEF (stage B), β-blockers are also advised in order to lower the chance of developing HF. In stable individuals with little to no indication of fluid excess, start β-blockers. Owing to their adverse inotropic effects, begin β-blockers at very low dosages and titrate up gradually to prevent symptom exacerbation or rapid decompensation. When it's feasible, titrate to target doses to maximize survival benefits. Large HF trials have demonstrated that the only β-blockers that reduce mortality are bisoprolol, carvedilol, and metoprolol succinate (CR/XL). The options are usually restricted to either carvedilol or metoprolol succinate since bisoprolol is not readily accessible in the required 1.25 mg starting dose. In placebo-controlled clinical trials, the initial and target doses are those that are linked to decreased mortality. Until the target dose or the maximally tolerated dose is attained, doses should be doubled no more frequently than every two weeks, as tolerated. Patients should be aware that reaching the target dose is crucial to maximizing benefits from dose up-titration, which is a lengthy and slow process. Additionally, there's a chance that the therapy won't work right away and that the HF symptoms will get worse right after starting.

ARB-Neprilysin Inhibitor (ARNI):

Angiotensin receptor/neprilysin inhibitor valsartan/sacubitril is authorized for the treatment of HFrEF. The medication is a crystalline compound made up of both medications. Among the enzymes that degrade endogenous natriuretic peptides is neprilysin. Because the peptides induce diuresis, natriuresis, enhanced glomerular filtration, and vasodilation, they are advantageous. Sacubitril is a prodrug that inhibits neprilysin and promotes vasodilation through a different mechanism than ARBs. Sacubitril cleaves into its active form. Neprilysin alone would cause increased levels of AT2, however combination with valsartan removes this effect[14],[15],[16],[17].

Aim And Objective:

Aim: Assessing the efficacy of ARNI and Beta blockers on renal function in heart failure patients is the main goal of this study.

Objectives:

• In order to learn how ARNI affects renal function in heart failure patients whose ejection fraction is low.

• Determine how ARNI affects renal function in heart failure patients whose ejection fractions are maintained.

• To compare the efficacy of ARNI with Beta blockers.

• An essential result is the evaluation of the patient's quality of life.

MATERIALS AND METHODS:

Study Design: A prospective observational study was conducted over a period of six months in the Departments of Cardiology and Nephrology at Durgabai Deshmukh Hospital and Research Centre, Hyderabad.

Study Population: A total of 100 patients diagnosed with heart failure were enrolled. Patients were categorized into two groups based on ejection fraction.

Inclusion Criteria

• Age ≥18 years

• Diagnosed HF (HFrEF or HFpEF)

• Receiving ARNI or beta-blocker therapy

Exclusion Criteria

• Acute kidney injury or ESRD

• Dialysis or kidney transplant

• Pregnant/lactating women

Data Collection:

Patient case records and lab reports were used to collect demographic data, echocardiographic findings, renal function parameters (serum creatinine, GFR, BUN), serum electrolytes, and BNP levels.

Ethical Considerations:

The study was approved by the Institutional Ethics Committee. Written informed consent was obtained from all participants.

Statistical Analysis:

Data were analyzed using Student’s t-test and Chi-square test. A p-value <0.05 was considered statistically significant.

RESULTS AND DISCUSSION:

In this study, a total of 100 case reports were reviewed and categorized into HFrEF and HFpEF groups. Parameters such as serum electrolytes, creatinine, GFR, BUN, and BNP levels were evaluated using ARNI (drug 1) and Beta blocker (drug 2) and their efficacies were compared.

Table no. 1.1 – serum electrolyte values in subjects administered with drug 1 along with mean and standard deviation.

Table No 1.2 – Serum Electrolyte Values in Subjects Administered with Drug 2 Along with Mean and Standard Deviation.

No significant differences were observed in serum sodium, potassium, chloride, or calcium between the two groups (p > 0.05).

Table no 2.1- Serum Creatinine Values in Drug 1

Table No 2.2 – Serum Creatinine Values in Drug 2

ARNI therapy significantly reduced serum creatinine levels in HFrEF patients. Beta-blockers showed minimal change.

Table no 3.1- GFR Values When Drug 1 Was Given

Table no3.2 – GFR Values When Drug 2 Is Given

Both groups showed improvements, but the ARNI group had slightly better outcomes, especially in HFrEF patients.

Table no 4.1 – Bun values when Drug 1 is Given

Table no 4.2- BUN values when drug 2 is given

ARNI therapy resulted in a statistically significant decrease in BUN levels (p < 0.001). Beta-blocker group showed higher BUN, particularly in HFrEF.

Table no 5.1 – BNP Levels When Drug 1 Was Given

Table NO 5.2- BNP Levels When Drug 2 Was Given