Pharmacological effects of medications used in the management of symptomatic aortic stenosis not eligible for surgery



Pharmacological effects of medications used in the management of symptomatic aortic stenosis not eligible for surgery

QUESTION
1. A review/overview of the pathophysiology of the aortic stenosis
2. review of the pharmacological agents used for treatment and important information related to the advanced practice nurse:
2.1 Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-2 receptor blockers (ARB)
2.2 Calcium Channel Blocker
2.3 Diuretics
2.4 Beta blockers
2.5. Digoxin
2.6 Nitrate derivatives
2.7 Statins
Pharmacological effects of medications used in the management of symptomatic aortic stenosis not eligible for surgery

ANSWER
Pharmacological Effects of Medications used in the Management of Symptomatic Aortic Stenosis Not Eligible for Surgery

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Introduction
Aortic stenosis is a common valve disorder affecting the heart defined by narrowing the aortic valve opening, restricting blood flow from the left ventricle to the aorta. The constriction is caused due to fibrosis or calcium build-up, which limits the valve opening restricting the blood flow in the heart and making the heart’s workload much more difficult. The disorder is common in individuals over 65, with 29% of older adults affected within the United States, and prevalence among individuals below 65 is below 2% of the patient population. Causal etiologies for Aortic Stenosis include congenitally abnormal valve with overlying calcification. The calcific aortic valve is the most prevalent cause of aortic constriction in persons under 70. The acquired, i.e., Rheumatic Valve Disorder where the leaflet commissures fuse to form a small central orifice, among other causes such as homozygous type II lipoproteinemia and Fabry Disease (Pujari & Agashi, 2022). This paper will discuss the pathophysiology of valve disorder and pharmacological agents used to manage symptomatic aortic stenosis not eligible for surgery.
Pathophysiology of Aortic Stenosis
Aortic Stenosis increases the pressure burden on the heart, which causes compensatory thickening of the left ventricle without cavity expansion. However, the systolic pressure causes the left ventricular volume to increase. The volume increase eventually leads to increased left ventricular ejection time and terminal pressure and an associated decrease in ejection percentage with time. The gradient throughout proximal angioplasty is also relatively low and is referred to as a low gradient severe Aortic Stenosis. Even if Aortic Stenosis is not severe, cardiac patients with elevated afterload and decreased Ejection Fraction, for example, myocardial infarction and intrinsic cardiomyopathy, may create an insufficient flow to open a sclerotic valve entirely and have a perceptible small valve area, i.e., pseudosevere Aortic Stenosis which can result in increasing Ventricular volume overload, which can eventually lead to Valvular disease and failure (Armstrong, 2021). Patients with low-gradient severe Aortic Stenosis are the only ones who can benefit from a valve replacement. Due to the increase in the ventricle mass, systolic pressure and ejection time, myocardial oxygen consumption also rises with a reduced supply, affecting the myocardial function further.
Pharmacological Agents for Treatment
The prognosis for medically managed therapy of severe aortic stenosis is bleak, with an estimated total mean lifespan of 3 years from the beginning of symptoms. Surgical valve replacement effectively heals patients, bringing them to a nearly average life expectancy. However, some individuals are restricted from performing surgeries due to t the high health risks associated; therefore, pharmacological intervention is prescribed. Elderly individuals are at higher risk, with surgical death rates ranging from 5% to 10% for aortic valve replacement and 15% to 25% for coronary artery bypass graft surgery (Sawhney et al., 2012). When the Valve replacement surgery is performed as an emergency operation, the death rate is uniformly more excellent.

Angiotensin-Converting Enzyme (ACE) Inhibitors and Angiotensin-2 Receptor Blockers (ARB)
ACE inhibitors and ARBs are blood pressure medications that help dilate the veins and arteries. ACE inhibitors hinder the body’s enzyme from making angiotensin II, a chemical constricting blood vessels. High blood pressure can result from this constriction, which causes the heart to work harder. The RIAS (Ramipril in Aortic Stenosis) study randomised 100 patients with asymptomatic moderate or severe aortic stenosis and left ventricular ejection fraction of more than 50% to either Ramipril 10 mg/day or placebo for one year. After three days of therapy, the Trandolapril group had a substantial drop in systolic blood pressure and increased systemic arterial compliance compared to the control group. None of the treated individuals reported hypotension (Gheorghe et al., 2020). In symptomatic individuals with severe Aortic Stenosis, ACEI is well tolerated. Individuals with heart failure, Left Ventricle dysfunction, and low normal blood pressure are more likely to have hypotension after ACEI medication. Enalapril improves exertion tolerance and decreases dyspnoea considerably in individuals with symptomatic Aortic Stenosis. The medications prove helpful in managing the disorder; however, they are accompanied by health risks, including systolic heart failure and hypertension. ARBs prove to be very beneficial in lowering the left ventricular volume and halting the course of aortic valve calcification, identifiable with the considerable improvement in echocardiographic parameters.

Calcium Channel Blocker
Calcium channel blockers are antihypertensive medicines. They function by blocking calcium from reaching the heart and artery cells. Calcium channel blockers enable circulatory arteries to relax and open by inhibiting calcium. Calcium channel blockers have been proven to have significant health risks as patients are 25% more likely to contract hypercholesterolemia and coronary artery disease. Therefore, the therapy should be issued with care due to the danger of hypotension and worsening heart failure; They also hurt aerobic exercises and shortened survival in individuals with aortic stenosis. Hypertension is expected in the patients, and optimal blood pressure management is recommended to lessen arterial strain.
Diuretics
Although diuretics may alleviate the symptoms of pulmonary congestion, it is vital to note that individuals with symptomatic aortic stenosis rely on sufficient arterial pressure (Cantey et al., 2020). Excessive diuretic therapy can be dangerous, and prehospital and emergency room care is centred on exacerbations of symptoms. Loop diuretics should be used to treat uncontrolled heart failure patients.
Beta-Blockers
The application of Beta-Blockers in the management of Aortic Stenosis is also a viable therapy for patients not eligible for surgery. The disease is associated with a significant increase in the β‐adrenergic state and decreased myocyte protein synthesis and extracellular matrix breakdown, akin to heart failure. Blockers could reduce oxygen intake and blood pressure to increase life in Asymptomatic aortic stenosis patients, but they may also risk impaired inotropy. The health risks, i.e., impaired long-term effect on the presence of left ventricular outflow tract obstruction, make it challenging to manage therapy for the symptomatic patients; therefore, it is not recommended as a standard therapeutic intervention (Eisen, 2017). However, it is noted that beta-blocker treatment has a favourable hemodynamic profile in moderate-to-severe aortitis stenosis as it lowers reduces valvular-arterial permeability, myocardial oxygen uptake, aortic peak, and mean gradient, heart rate, and systolic ejection time.
Digoxin
Digoxin is also used as an inotropic drug to regulate the ventricular rate in individuals with atrial fibrillation treating aortic stenosis. Digoxin inhibits Na+/K+ ATPase, the endothelial enzyme responsible for sodium extrusion and potassium transport into the myocyte (Ren, 2021). This causes an increase in calcium homeostasis in cardiac cells’ sarcoplasmic reticulum, which increases contractility. Digoxin, however, is widely used in individuals with Atrial Fibrillation and is associated with sudden cardiac death presenting several risk factors for individuals diagnosed with Aortic stenosis.
Nitrate Derivatives
In patients with symptomatic aortic stenosis, nitrate derivatives can reduce blood pressure without compromising cardiac output or end-organ perfusion. Diastolic pressure and preload reductions with nitrate derivatives reduce Ventricular oxygen consumption and enhance endocardial perfusion and diastolic performance. Intravenous nitroprusside increases the cardiac index and right ventricular stroke volume while decreasing mean arterial pressure, systemic vascular resistance, and pulmonary resistance in patients with heart failure and low cardiac index and reduced LV function (Gheorghe et al., 2020). The therapy is not recommended for patients diagnosed with symptomatic aortic stenosis as a long-term option. However, it is beneficial in the onset stages of organ failure.
Statins
The application for statins in patients not eligible for surgery is a controversial treatment option as it is unclear whether they are associated with improved health outcomes. C-reactive protein is a clinical marker of inflammation generated in the liver in response to anti-inflammatory stimuli and is characteristically evident in patients with symptomatic aortic valve stenosis. Statin medication can dramatically lower serum C-reactive expression levels in both preventive and intervention groups in a mainly Low-density lipoprotein approach. Patients taking statins have better health outcomes than those that don’t, irrespective of LDL cholesterol levels. Statins, through lowering cholesterol levels and exerting anti-inflammatory actions, have the potential to alter both health risks and inflammatory cytokines. Pleiotropic effects relate to favourable cholesterol-independent statin advantages; for example, statin-treated bacteremic patients had reduced mortality than non-statin-treated patients. Statins are, therefore, ineffective in preventing the development of aortic stenosis (Akim & Nienaber, 2017). However, Statin treatment is likely to minimise cardiovascular risk and death in patients who have undergone a transcatheter Aortic Valve implant with high risks of cardiovascular events and also as a preventative therapy for the development of symptomatic aortic stenosis

Conclusion
Aortic valve replacement is the only therapy proven to enhance survival in patients with Aortic Stenosis. Aortic stenosis is characterised by a quiet latency strongly affected by lethargic progression at the molecular, physiological, and anatomical levels before symptoms appear. Patients with severe asymptomatic aortic stenosis must be examined regularly to identify the recurrent markers for the disease. A subsequent surgical intervention is required to improve the patient’s lifespan as soon as the symptoms occur. However, some individuals with symptomatic aortic stenosis, especially older adults, have a greater health risk in surgical treatment for valve disorder. They are deemed ineligible and issued pharmacological options depending on their health needs. The pharmaceuticals enhance the quality of life for the patients but are less ineffective than surgery.

References
Akin, I., & Nienaber, C. A. (2017). Is there evidence for statins in the treatment of aortic valve stenosis? World journal of cardiology, 9(8), 667–672. https://doi.org/10.4330/wjc.v9.i8.667
Armstrong, G. (2021) Aortic Stenosis. MSD Manual. Accessed from: https://www.msdmanuals.com/professional/cardiovascular-disorders/valvular-disorders/aortic-stenosis
Cantey, E., Chang, K., Blair, J., Brummel, K., Sweis, R., & Pham, D. et al. (2020). Impact of Loop Diuretic Use on Outcomes Following Transcatheter Aortic Valve Implantation. The American Journal of Cardiology, 131, 67-73. doi: 10.1016/j.amjcard.2020.06.033
Eisen, A., Ruff, C.T., Braunwald, E., Hamershock, R.A., Lewis, B.S., Hassanger, C., Chao, T., Heuzey, J.Y., Mercuri, M., Rutman, H. Antman, E.M., and Giugliano, R.P. (2017). Digoxin Use and Subsequent Clinical Outcomes in Patients With Atrial Fibrillation With or Without Heart Failure in the ENGAGE AF-TIMI 48 Trial. American Heart Association Retrieved from: https://www.ahajournals.org/doi/pdf/10.1161/JAHA.117.006035?download=true
Gheorghe, G. S., Hodorogea, A. S., Gheorghe, A., Nanea, I. T., & Ciobanu, A. (2020). Medical management of symptomatic severe aortic stenosis in patients non-eligible for transcatheter aortic valve implantation. Journal of geriatric cardiology: JGC, 17(11), 704–709. Retrieved from: https://doi.org/10.11909/j.issn.1671-5411.2020.11.002
Pujari, S.H. and Agasthi, P. (2022) Aortic Stenosis. In: StatPearls. Treasure Island (FL): StatPearls. Accessed from: from: https://www.ncbi.nlm.nih.gov/books/NBK557628/
Ren, X. (2021). Aortic Stenosis Medication. The Heart.Org Medscape. Accessed from: https://emedicine.medscape.com/article/150638-medication#showall
Sawhney, N., Hassankhani, A., and Greenberg, B.H. (2012). Calcific Aortic Stenosis in the Elderly: A Brief Overview. The American Journal of Geriatric Cardiology. MedScape. Accessed from: https://www.medscape.com/viewarticle/456334_4

Pharmacological effects of medications used in the management of symptomatic aortic stenosis not eligible for surgery


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