We now move on to valvular disease. This is not to talk about patients in acute shock, many of these patients would need a mechanical support device in order to get out of shock. Medical management could be considered if blood pressure allows. There is not a lot of discussion about the medical management of valvular disorders because medical management as the primary treatment is not typical in severe valvular disease. This had led to practitioners not knowing what the best medical treatments are for these patients if it is required. Patients will present to the hospital or ICU with severe valvular disease and often must be stabilized or optimized before someone will consider them candidates for intervention or they are not candidates for advanced therapies and are medical management only. It is important to know how to manage these patients medically to optimize or give time for the workup to be completed. This blog is not going to go in-depth on the different ways that people can get valvular disease either, it is going to look at the physiology of the valvular disease independent of the cause in order to show how medications can be beneficial.
Categorizing the valves:
There are four valves of the heart, two on the right and two on the left. The right side has the tricuspid and the pulmonic and the left has the mitral and aortic. These valves can be categorized based on the side of the heart or by which phase of the cardiac cycle they are involved.
Valvular dysfunction and valvular disease etiology
Valvular Dysfunction:
Each valve can have two types of dysfunctions: stenosis and regurgitation.
Stenosis: The valve does not open completely and the opening area decreases leading to decreased blood across the valve or high pressures needed to have the same amount of blood cross the valve.
Regurgitation: The valve is unable to coapt correctly leading to a reversal of flow.
Categorizing Valvular Dysfunction: Valvular dysfunction can be divided by the type of dysfunction, listed above, or by whether it is during systole or diastole.
Categorizing Valvular Disease Etiology:
Valvular disease can be further broken down by its etiology. This will further separate it into 2 more categories: organic and functional. Organic valvular disease implies that there is a problem with the valve itself, whereas functional valvular disease is where there is a valvular problem due to ventricular dysfunction. Functional causes are only seen with regurgitation. Figure 1 is an example of organic vs functional disease of the mitral valve.
Figure 1: Categorizing Mitral Valvular Disease
Categorizing Valvular Disease Etiology:
Management of Valvular Disorders:
The answer to management for valvular dysfunction is often valve repair or replacement. Replacing or repairing a diseased valve is curative in many situations, but I will be focusing on medical management. Hospitalized patients are often not candidates for immediate valve repair/replacement. This could be from the disease process not being advanced enough for surgery, or stabilization is needed while the workup for candidacy can be completed. Being able to understand how to medically treat someone with valvular disease can improve patient morbidity and mortality.
The medical management for valvular disease can be simplified to two options depending on the cause:
Afterload Reduction or Rate Reduction
Regurgitation Treatment:
All of the regurgitation disorders can be lumped together into one category because the medical management is the same: afterload reduction. Blood will always travel in the path of least resistance. If you decrease the resistance, you will get better forward flow. This is true for both regurgitation during diastole and regurgitation during systole.
Systolic Regurgitation:
Regurgitation during systole will cause the reversal of blood back into the atrium. This will cause atrial dilation, venous dilation, and organ congestion. The decreased forward flow will mean less cardiac output and oxygen delivery.
Figure 2: Mitral/Tricuspid Regurgitation Hemodynamics
Figure 3: Mitral/Tricuspid Regurgitation Hemodynamics with Afterload Reduction
Treatment Medications:
Mitral Regurgitation: Nitroprusside, ACE inhibitors/ARBs, and Hydralazine are very common. Nitroglycerin will arteriovasodilate at high doses.
Tricuspid regurgitation: Systemic vasodilators (listed above) can be tried, but they may need pulmonary artery vasodilators, the most common in the hospital are Epoprostenol, nitric oxide, and sildenafil.
My recommendations:
I will sometimes allow a lower MAP goal of >60 mmHg, as long as there are signs of good perfusion, to increase afterload reduction and more forward flow.
Diastolic Regurgitation:
Regurgitation during diastole will cause the reversal of blood back into the ventricle. This will cause overdistention of the ventricle, atrial dilation, venous dilation, and organ congestion. Just like systolic regurgitation, the decreased forward flow will cause reduced cardiac output and oxygen delivery.
Figure 4: Aortic/Pulmonic Regurgitation with Hemodynamics
Figure 5: Aortic/Pulmonic Regurgitation Hemodynamics with Afterload Reduction
Treatment Medications:
Aortic Regurgitation: Nitroprusside, ACE inhibitors/ARBs, and Hydralazine are very common. Nitroglycerin will arterial vasodilate at high doses.
Pulmonic regurgitation: Systemic vasodilators (listed above) can be tried, but they may need pulmonary artery vasodilators, the most common in the hospital are Epoprostenol, nitric oxide, and sildenafil.
My recommendations:
I target a systolic goal with aortic regurgitation since the diastolic pressure is unreliable. My goal depends on the patient's initial systolic but usually my goal is <110 or 120 mmHg.
Stenosis Treatment:
Stenosis treatment is more complicated. It must be separated out by filling valves and ejection valves.
Filling valves:
The tricuspid and mitral valve must open during diastole in order to fill the ventricle and create preload. When a patient has stenosis of one of these valves they have difficulty with ventricular filling which leads to hypotension and decreased cardiac output. Upstream from the stenosis gets overloaded and congested. The medical management for stenosis of a filling valve is rate control. Lowering the rate increases time spent in diastole. With increased time in diastole, the ventricle has more time to fill and is able to get higher on the Starling curve.
Figure 6: Tricuspid/Mitral Stenosis Hemodynamics with Rate Reduction
My recommendations:
I would try to get the heart rate < 60-70 bpm as long as there is good perfusion.
Ejection valves:
The aortic and pulmonic valve must open for the ventricle to eject. The medical management for ejection valve stenosis is more complicated. Pulmonic stenosis is rare and usually congenital. There are so many excuses for why someone does not want to start a medication for significant aortic stenosis.
Concerns about giving medications in severe aortic stenosis:
1. Afterload reduction would cause significant systemic hypotension on the aortic side of the valve.
2. Afterload reduction increases the gradient across the valve and can make things worse.
3. Rate reduction worsens cardiac output because there is a fixed obstruction and so it would lower cardiac output.
4. Inotropes lead to arrhythmias and tachycardia in severe AS which can be detrimental.
This is why aortic stenosis medical management is so difficult, you can talk yourself in circles until you are too scared to do any management. What does the data say?
As stated above, there is not a lot of time dedicated to the medical management of valvular disorders. It is even stated in some guidelines that for severe aortic stenosis that there is no appropriate medical management. While this does show the importance of surgical aortic valve replacement (AVR) and transcutaneous aortic valve replacement (TAVR), it does not consider patients that are not candidates for these procedures or patients that are decompensated and are awaiting the workup for these procedures. There needs to be some guidance on medical treatment for severe aortic stenosis that can optimize a non-surgical patient or increase the time needed to allow the workup.
Aortic stenosis:
Let’s focus on aortic stenosis from a hemodynamic standpoint. The left ventricle is broken down in Figure 7.
Figure 7: Left Ventricular Hemodynamics
With aortic stenosis, LV afterload is the biggest issue and has to be looked at using the actual definition of LV afterload using Laplace’s law and not systemic vascular resistance.
Figure 8: LV Afterload using Laplace's Law
The pressure in the left ventricle, P, is a large proportion of the wall tension which is the afterload. Because of the stenosis, the LV pressure is not just due to the systemic vascular resistance, it is also due to the aortic stenosis. The aortic stenosis has to be able to be included in the assessment of the total LV afterload. The best way to measure how the valve and the arterial system affect the afterload is to look at the impedance.
The valvulo-arterial impedance looks at the global LV afterload.
Valvulo-Arterial Impedance
Z = (SBP + Pmg)/SVI
Z = impedance
SBP = systolic blood pressure
Pmg = valvular mean pressure gradient
SVI = stroke volume index
The higher the impedance, the worse the afterload. Impedance has been used to diagnose severe AS, where severe AS >4.5-5 mmHg/mL·m2. It has also been used to identify patients with low flow, low gradient severe AS due to high arterial pressure, and it has been used as a prognostic indicator. Patients with asymptomatic severe AS and an impedance >3.5 mmHg/mL·m2 had significantly worse outcomes.
Medical Management:
Afterload reduction:
The reluctance to start afterload reduction was the worry that there was a fixed cardiac output, and that peripheral vasodilation would lead to severe hypotension. But, using the knowledge of impedance and knowing that the decreased flow activates the renin-angiotensin-aldosterone-system (RAAS), if hypertension or systemic vascular resistance is a component of the afterload the LV is experiencing, then reducing that afterload should lead to better outcomes.
ACE Inhibitors: They have been found to decrease the progression of LV hypertrophy, decreased calcium accumulation, decreased the reduction of AV area, and improved functional class and 6-minute walk test. ACE inhibitors are the most study peripheral vasodilator and therefore is the medication of choice for afterload reduction.
Angiotensin-receptor blocker: There is not much data on ARBs vs ACEi, but theoretically should have a similar benefit.
Rate reduction:
As with decompensated heart failure, there is always concern that with severe aortic stenosis that reducing heart rate in someone with low stroke volume with lead to worsening cardiac output. However, when the rate is reduced, there is prolonged ejection time. With a fixed obstruction, a prolonged systolic ejection time will lead to an increase in stroke volume. An increase in stroke volume can increase cardiac output if the SV increase is more that the rate decrease. Additionally, looking at the impedance equation, an increased stroke volume means an increased stroke volume index which lowers impedance.
Beta Blockers: Patients with severe AS were followed and the patients on beta blockers at four years had lower all-cause mortality, lower cardiovascular mortality, and lower sudden death. In another retrospective study, patients who were not able to undergo surgery for severe AS had a >60% reduction in mortality.
In a study by Hannsen et al., patients with moderate to severe aortic stenosis were randomized to metoprolol or placebo for almost 6 months. The patients on metoprolol had a statistically significant decrease in heart rate (-8 bpm) which lead to a statistically significant increase in systolic ejection time (26 msec). Additionally, the peak and mean gradient across the aortic valve decreased (- 7 mmHg and -4 mmHg respectively).
My recommendations:
I would start with ACE inhibitors if no contraindication with a goal systolic < 120 -130 mmHg and then add a beta blocker for a goal heart rate < 80bpm. This varies from patient to patient much more than any other valvular disorder.
Summary:
Valvular repair or replacement will always be the mainstay for severe valvular disease, whether it is surgical or transcutaneous, but there will always be patients who need medical management. Being able to medically manage these complicated patients can be the difference between the patient being able to qualify for a procedure later or being deemed too sick. It is important to know the physiology and hemodynamics behind these disease processes to make timely interventions.
Valvular Dysfunction Medical Management Summary
The next blog will discuss the management of LVOT obstruction and SAM.
Left Ventricular Heart Failure Series:
Part 1a: Introducing Preload
Part 1b: Measuring Preload
Part 2a: Physiological Contractility
Part 2b: Clinical Contractility
Part 3a: Simplifying Afterload
Part 3b: The Physiology of Afterload
Part 4: Managing LV dysfunction
Other Left Sided Heart Failure:
Part 1: Valvular disease
Part 2: LVOT obstruction/SAM
Cardiogenic Shock:
Part 1: Why a Protocol is Needed
Part 2: Cardiogenic Shock Protocols
References:
1. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines [published correction appears in Circulation. 2014 Jun 10;129(23):e650]. Circulation. 2014;129(23):2440-2492. doi:10.1161/CIR.0000000000000029
2. Marquis-Gravel G, Redfors B, Leon MB, Généreux P. Medical Treatment of Aortic Stenosis. Circulation. 2016;134(22):1766-1784. doi:10.1161/CIRCULATIONAHA.116.023997
3. Joseph J, Naqvi SY, Giri J, Goldberg S. Aortic Stenosis: Pathophysiology, Diagnosis, and Therapy. Am J Med. 2017;130(3):253-263. doi:10.1016/j.amjmed.2016.10.005
4. Mantha Y, Futami S, Moriyama S, Hieda M. Valvulo-Arterial Impedance and Dimensionless Index for Risk Stratifying Patients With Severe Aortic Stenosis. Front Cardiovasc Med. 2021;8:742297. Published 2021 Dec 2. doi:10.3389/fcvm.2021.742297
5. Kang TS, Park S. Antihypertensive Treatment in Severe Aortic Stenosis. J Cardiovasc Imaging. 2018;26(2):45-53. doi:10.4250/jcvi.2018.26.e9
6. Basile C, Fucile I, Lembo M, et al. Arterial Hypertension in Aortic Valve Stenosis: A Critical Update. J Clin Med. 2021;10(23):5553. Published 2021 Nov 26. doi:10.3390/jcm10235553
7. Hansson NH, Sörensen J, Harms HJ, et al. Metoprolol Reduces Hemodynamic and Metabolic Overload in Asymptomatic Aortic Valve Stenosis Patients: A Randomized Trial. Circ Cardiovasc Imaging. 2017;10(10):e006557. doi:10.1161/CIRCIMAGING.117.006557