From the Guidelines
Heart failure occurs through several key mechanisms that disrupt the heart's ability to pump blood effectively, including reduced contractility, volume overload, and pressure overload, with neurohormonal activation and ventricular remodeling playing crucial roles in the progression of the disease. The primary mechanisms of heart failure can be understood by considering the various factors that contribute to the development and progression of the condition. These include:
- Reduced contractility, where the heart muscle weakens and cannot generate adequate force
- Volume overload, where excess fluid accumulates in the circulatory system
- Pressure overload, where the heart must pump against increased resistance
- Neurohormonal activation, where the sympathetic nervous system and renin-angiotensin-aldosterone system become chronically activated, initially as compensatory mechanisms but eventually causing further cardiac damage
- Ventricular remodeling, which occurs as the heart chambers enlarge and change shape in response to injury or increased workload
- Diastolic dysfunction, which develops when the heart cannot relax properly between contractions, reducing filling capacity
- Valvular dysfunction, arrhythmias, and myocardial ischemia, which can further compromise cardiac function
These mechanisms often occur simultaneously and create vicious cycles, where one problem exacerbates others, leading to progressive worsening of heart failure 1. Understanding these mechanisms has led to targeted therapies including ACE inhibitors, beta-blockers, diuretics, and aldosterone antagonists that interrupt these pathological processes and improve outcomes. The most recent and highest quality study, published in 2016, provides a comprehensive overview of the mechanisms of heart failure and highlights the importance of considering the various factors that contribute to the development and progression of the condition 1.
Key factors that contribute to the development of heart failure include:
- Coronary artery disease
- Hypertension
- Dilated cardiomyopathy
- Valvular heart disease
- Arrhythmias
- Myocardial ischemia
A detailed history and physical examination are essential in diagnosing and managing heart failure, and symptoms and signs of heart failure need to be assessed at each visit, with particular attention to evidence of congestion 1. The clinical syndrome of heart failure may result from disorders of the pericardium, myocardium, endocardium, or great vessels, but the majority of patients with heart failure have symptoms due to an impairment of left ventricular myocardial function 1.
The most effective approach to managing heart failure is to target the underlying mechanisms of the disease, using a combination of pharmacological and non-pharmacological interventions to improve symptoms, reduce morbidity and mortality, and enhance quality of life. This approach is supported by the most recent and highest quality evidence, which highlights the importance of considering the various factors that contribute to the development and progression of heart failure 1.
From the FDA Drug Label
The precise mechanism for the beneficial effects of beta-blockers in heart failure has not been elucidated The mechanism of heart failure is not directly explained in the provided drug label. However, it is mentioned that beta-blockers, such as metoprolol succinate, have beneficial effects in heart failure, although the precise mechanism is not known.
- The label does mention that metoprolol reduces the oxygen requirements of the heart by blocking catecholamine-induced increases in heart rate and blood pressure, which can be useful in managing angina pectoris and potentially beneficial in heart failure.
- The MERIT-HF study showed that metoprolol succinate extended-release tablets reduced the risk of all-cause mortality and all-cause hospitalization in patients with heart failure 2.
From the Research
Heart Failure Mechanisms
The mechanisms of heart failure are complex and involve various physiological and pathological processes. Some of the key mechanisms include:
- Activation of the sympathoadrenergic and renin-angiotensin-aldosterone-system, leading to adaptive mechanisms such as volume overload, tachycardia, and dyspnea 3
- Cellular, structural, and neurohumoral modulations that affect the phenotype of heart failure, including changes in cell function and intercellular behavior 3
- Increased levels of neurohormones, such as norepinephrine, and natriuretic peptides, such as NT-pro BNP, which are measures of cellular dysfunction 3
- Impaired cardiac relaxation or contraction, leading to reduced cardiac output and/or elevated intracardiac pressures at rest or during stress 4, 5
Pathophysiology
The pathophysiology of heart failure involves a vicious circle of events, including:
- Cardiac injury, such as myocardial infarction, increased preload or afterload, leading to cellular, structural, and neurohumoral modulations 3
- Activation of the sympathoadrenergic and renin-angiotensin-aldosterone-system, leading to volume overload, tachycardia, and dyspnea 3
- Progressive deterioration of cellular function, leading to increased levels of neurohormones and natriuretic peptides 3
Classification
Heart failure can be classified into different types, including: