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Pathophysiology of heart failure
M Chiariello1, P Perrone-Filardi
1Division of Cardiology, University Federico II, Naples, Italy.
Insights
Heart failure, a major cause of death, involves impaired heart muscle contractility. Compensatory mechanisms initially help but ultimately worsen cardiac function and lead to disease progression.
Area of Science:
- Cardiology
- Pathophysiology
- Molecular Biology
Background:
- Heart failure is a significant cause of mortality and morbidity, primarily due to ischemic and hypertensive heart disease.
- Clinically, heart failure signifies impaired cardiac performance unable to meet peripheral energy demands.
- Pathophysiologically, symptoms appear late, after compensatory mechanisms fail to sustain cardiac output.
Purpose of the Study:
- To elucidate the pathophysiological mechanisms underlying heart failure.
- To understand the role of myocyte contractility impairment in heart failure.
- To explore compensatory mechanisms and their detrimental effects in heart failure progression.
Main Methods:
- Review of existing literature on heart failure etiology and pathophysiology.
- Analysis of compensatory mechanisms including preload reserve, neurohormonal stimulation, and cardiac hypertrophy.
- Examination of molecular and cellular changes affecting myocyte contractility.
- Investigation of endothelial function and cytokine involvement in heart failure pathogenesis.
Main Results:
- Reduced myocyte contractility is a hallmark of heart failure, irrespective of etiology.
- Compensatory mechanisms like increased preload, neurohormonal activation, and hypertrophy initially support cardiac function but ultimately contribute to deterioration.
- Increased end-diastolic volume, sympathetic/angiotensin stimulation, and hypertrophic changes impair systolic performance, compliance, and relaxation.
- Diastolic dysfunction often accompanies systolic dysfunction, and can be the primary issue in preserved ejection fraction heart failure.
- Biological causes include altered myosin composition, sarcoplasmic ATPase activity, and impaired endothelial function; circulating cytokines are also implicated.
Conclusions:
- Heart failure involves complex interactions between reduced myocyte contractility and maladaptive compensatory responses.
- Understanding these mechanisms is crucial for developing effective therapeutic strategies for heart failure.
- Further research into molecular and cellular underpinnings, including endothelial dysfunction and cytokine roles, is warranted.
Abstract:
Heart failure is a leading cause of mortality and morbidity in Western countries. Common etiology is mostly represented by ischemic and hypertensive heart disease. Clinically, heart failure can be defined as an impaired cardiac performance, unable to meet the energy requirements of the periphery. Pathophysiologically, the clinical onset of heart failure symptoms already represents an advanced stage of disease when compensatory mechanisms triggered by the underlying decrease in contractility are no longer capable of maintaining adequate cardiac performance during exercise and, subsequently, under resting conditions. Independent of its underlying etiology, cardiac failure is always characterized by an impairment in the intrinsic contractility of myocytes. As a consequence of reduced contractility, a number of central and peripheral compensatory mechanisms take place that are capable of effectively counteracting reduced intravascular intrinsic performance for a long period of time. Among them, recruitment of preload reserve, enhanced neurohormonal stimulation and cardiac hypertrophy are the most important. All of them, however, also carry unfavorable effects that contribute to further deterioration of cardiac function. In fact, increased end-diastolic volume determines increased wall stress that further reduces systolic performance; sympathetic and angiotensin stimulation increases peripheral resistance and contributes to increase volume expansion; hypertrophic myocytes demonstrate impaired intrinsic contractility and relaxation, and hypertrophy causes a clinically relevant deterioration of ventricular relaxation and compliance that substantially participates in increased end-diastolic pressure, and, therefore, to limited exercise performance. Diastolic dysfunction usually accompanies systolic dysfunction, although in some cases it may represent the prevalent mechanism of congestive heart failure in patients in whom systolic performance is preserved. Biological causes of reduced contractility in heart failure are not completely elucidated. Changes in myosin composition and in sarcoplasmic ATPase activity, causing reduced Ca2+ availability during contraction, have been reported, although their exact contribution is not clear. Recently, impaired endothelial function has also been described in heart failure, and new appealing hypotheses have been made regarding the causative role of circulating cytokines like tumor necrosis factor in the pathogenesis of heart failure.