The treatment of chronic heart failure has undergone a major shift since the 1990s, from aiming to improve short-term hemodynamic status to long-term restorative strategies , with the goal of preventing or reversing cardiac remodeling, that is, switching from “cardiotonic, diuretic, and vasodilator” to the use of neuroendocrine inhibitors. In the 2022ACC/AHA/HFSA guidelines, GDMT includes four classes of drugs: ACEI/ARB/ARNI, β-receptor inhibitors, SGLT-2 inhibitors and MRA. So do vasodilators still have a place in the treatment of heart failure? At the 2022 China Congress of Clinical Cardiovascular Diseases (4C 2022), Professor Song Yu from TEDA International Cardiovascular Hospital explained the mechanism and characteristics of various vasodilators The rational use of vasodilators for different types of heart failure is explained in combination with the latest guidelines, and the individualized application of such drugs is also emphasized.
Staging and Types of Heart Failure< /span>
Professor Song Yu pointed out that the staging standards of heart failure in the latest guidelines have not changed much, but the classification of heart failure has been improved and increased. Heart failure with improved ejection fraction (HFimpEF), as follows: 1. Heart failure staging span>➤ Stage A: Patients at risk for heart failure, without symptoms of heart failure, without structural heart disease, and without cardiac biomarkers suggesting myocardial stretch or injury; ➤ Stage B: The patient has no past or current symptoms or signs of heart failure, but one of the following: ●structural heart disease, < span>●Increased filling pressure,
●with stage A risk factors and elevated BNP or cardiac troponin (need to exclude other diseases in which this biomarker is elevated).
➤ Stage C: Patients with past or current symptoms or signs of heart failure; ➤ Stage D : Despite attempts to optimize GDMT, patients had significant HF symptoms that interfered with daily life and resulted in repeated hospitalizations.
Figure 1 Heart failure stagestrong> .Heart failure classification
➤Heart failure with reduced ejection fraction (HFrEF): LVEF≤40%;
➤ Heart failure with improved ejection fraction (HFimpEF): previous LVEF≤40%, follow-up LVEF>40%;
➤ Heart failure with mildly reduced ejection fraction (HFmrEF): LVEF 41%-49% with evidence of increased left ventricular filling pressure;
➤ HF with preserved ejection fraction (HFpEF): LVEF ≥ 50% with evidence of increased left ventricular filling pressure.
Figure 2 LVEF-based HF classification and trajectory< >
Classification of Vasodilators
➤Depending on the type of dilated vessels
● Dilate arterioles: dilate systemic arterioles, reduce peripheral resistance, and significantly reduce left ventricular afterload. It is suitable for patients with increased peripheral resistance caused by various reasons, and is contraindicated in patients with severe low cardiac output. Commonly used preparations are phentolamine, nifedipine. ●Dilate venules: Redistribute blood in the venous system, reduce the blood return to the heart rapidly, reduce cardiac preload and reduce pulmonary congestion. Common preparations nitroglycerin, meprotamol. ●Dilation of arterioles and veins: suitable for patients with increased cardiac preload and postload. Common preparations are sodium nitroprusside and prazosin.
➤Depending on the drug target
< span>●It acts on vascular smooth muscle, such as nitrates such as sodium nitroprusside, which can dilate coronary arteries.
●Sympathetic blocking drugs, such as phentolamine.
●Calcium channel blockers are mainly used to dilate arteries, among which levamlodipine has a certain dilating effect on coronary arteries.
●renin-angiotensin- Aldosterone antagonists such as enalapril, captopril and perindopril.
Vasodilator Details
➤Recombinant human brain natriuretic peptide (rhBNP) for injection
●Pharmacological effects: It works by correcting hemodynamics, diuresis and natriuresis, antagonizing the RAAS system, and resisting cardiac remodeling. A drug with multiple actions, unique in the treatment of heart failure.
●In 2013, 2016, 2017 ACC/AHA Heart Failure Management Guidelines, 2016 ESC Acute and Chronic Heart Failure Diagnosis and Treatment Guidelines, 2018 Chinese Heart Failure Diagnosis and Treatment Guidelines , 2018 AHA Scientific Statement on the Assessment and Management of Right Heart Failure, and 2016 Heart Failure Rational Medication Guidelines, rhBNP is included in the heart failure treatment recommendations.
➤Sodium Nitroprusside
< span>●Pharmacological effects: vascular endothelial cells release NO to activate GC, increase intracellular cGMP level, and dilate blood vessels.
1) Can work on both arteries and veins;
2) Can reduce left ventricular filling pressure and increase CO , but can cause coronary ischemia;
3) can increase myocardial and pulmonary arteriovenous shunt, increase total blood flow but not necessarily the part that improves perfusion Blood flow increases;
4) The increase in stroke volume can counteract the decrease in peripheral vascular resistance, so arterial blood pressure will not drop significantly;
< p>5) Heart rate generally does not increase, and may even decrease due to improved hemodynamics.
●Indications: acute left-sided heart failure, pulmonary edema, acute myocardial infarction with left Heart failure, refractory heart failure, acute mitral regurgitation. Aortic regurgitation and its perforation of the interventricular septum. ●Adverse reactions:1) Toxicity is cyanide poisoning, and the symptoms of poisoning are For ataxia, blurred vision, delirium, dizziness, headache, etc., attention should be paid to clinical medication; high;3) The blood pressure drops too fast, and reflex tachycardia or arrhythmia occurs. ➤Nitrates
● span>Pharmacological action: It binds to the sulfhydryl group of specific nitrate receptors on vascular smooth muscle, converts it into nitrothiol and nitrous oxide, and then dilates blood vessels.
●Affinity to veins (regular dose) is stronger than arterial (high dose), and to large arteries than small arteries powerful.
●It mainly dilates large coronary arteries, but also dilates small coronary arteries, improves myocardial ischemia, and does not cause “steal blood” ” ➤Urapidil
Pharmacological action: selective α1 receptor body blocker, and has dual peripheral and central antihypertensive effects.
●The effect of peripheral vasodilation is mainly by blocking postsynaptic a1 receptors, resulting in a significant decrease in peripheral resistance. Dilate blood vessels;
●The central effect is to activate serotonin-1A receptors and reduce the extension of cardiovascular and cerebrovascular Regulates the sympathetic feedback of the central nervous system and exerts an antihypertensive effect; and can reduce renal vascular resistance;
● has no antihypertensive effect on normal blood pressure, and has no effect on heart rate. No significant effect;
●Adverse reactions: headache, dizziness, nausea, vomiting, arrhythmia, pressure in the upper abdomen or difficulty breathing.
Vasodilators in the treatment of heart failure
Professor Song Yu pointed out that in the “humid and warm” and “humid and cold” types, it is often necessary to use blood vessels expander. Because the contraindication of vasodilators is SBP<90mmHg, such drugs should be used with caution in the "cold and wet" type with hypotension. However, the use of such drugs in different disease stages cannot be generalized, and specific analysis is required. Fig. ]; peripheral perfusion [warm and cold])
Summary span>
➤ Indications: Patients with systolic blood pressure >110 mmHg can usually use it safely; systolic blood pressure between 90 and 110 mmHg should be used with caution; systolic blood pressure <90 mmHg, Contraindicated use. ➤Main mechanism of action: It can reduce left and right ventricular filling pressure and systemic vascular resistance, reduce cardiac load and improve symptoms.
➤Drug types and usage:
● strong>Nitrates (lla, B): do not reduce stroke volume, do not increase myocardial oxygen consumption, can reduce pulmonary congestion, especially for patients with acute coronary syndrome and heart failure.
●Sodium nitroprusside (llb, B): for patients with severe heart failure, pulmonary congestion or pulmonary edema .
●Recombinant human natriuretic peptide BNP (lla, B): mainly dilates veins and arteries (including coronary arteries) to reduce preload and afterload. The drug is a multi-action drug, which has a certain promotion of sodium excretion and diuresis; it can also inhibit RAAS and the sympathetic nervous system.
●Urapidil (lla, B): is a receptor blocker, which can effectively reduce vascular resistance and increase Cardiac output for patients with hypertension complicated by acute heart failure and aortic dissection complicated by acute heart failure. ➤ Vasodilators are contraindicated: ● span>Systolic blood pressure <90mmHg, or persistent hypotension with symptoms, especially in patients with renal insufficiency, in order to avoid decreased perfusion of vital organs. ●Severe obstructive heart valve disease, such as aortic stenosis or hypertrophic obstructive cardiomyopathy, should not be used in patients with mitral stenosis , may cause a significant decrease in cardiac output.