Pathophysiology of Heart Failure and Acute Decompensated Heart Failure
Core Pathophysiologic Mechanism
The fundamental pathophysiology of both chronic and acute heart failure centers on the myocardium's critical inability to maintain cardiac output sufficient to meet peripheral circulatory demands, triggering a vicious cycle of neurohormonal activation, hemodynamic deterioration, and progressive organ dysfunction. 1
The Vicious Cycle in Heart Failure
Myocardial dysfunction initiates a cascade where reduced cardiac output leads to decreased tissue oxygen delivery, triggering compensatory vasoconstriction that paradoxically increases systemic vascular resistance and further burdens the failing heart. 1, 2
This creates a self-perpetuating cycle: elevated systemic resistance increases left ventricular afterload, which worsens cardiac output, leading to more neurohormonal activation and progressive decompensation. 2
Left ventricular dysfunction specifically causes decreased blood pressure with impaired tissue oxygen delivery and neurohormonal activation, resulting in systemic venous congestion that affects kidneys, liver, lungs, and gut. 1
Structural and Cellular Mechanisms
Myocardial Injury Pathways
Myocyte stress from any cause (ischemia, pressure overload, volume overload) triggers inflammatory and immune responses that acutely and chronically impair contractile function. 1
Ischemic heart disease—now the dominant cause of adult heart failure (60-70% of cases)—initiates inadequate coronary blood flow that prevents the myocardium from meeting metabolic demands, causing direct loss of contractile function. 3, 4
Chronic remodeling involves altered cardiac gene expression, cardiomyocyte loss, impaired vascular development, and interstitial fibrosis, all worsening prognosis. 4
Reversible Myocardial Dysfunction
"Stunned" myocardium represents transient severe dysfunction following prolonged ischemia that persists even after blood flow restoration; intensity and duration depend on the severity and duration of the ischemic insult. 1
"Hibernating" myocardium is impaired function due to severely reduced coronary blood flow while myocardial cells remain intact; restoring blood flow and oxygenation can restore normal function. 1
Rapid restoration of oxygenation and blood flow is mandatory to reverse these pathophysiological alterations, as both mechanisms depend on the duration of myocardial damage. 1
Acute Decompensated Heart Failure: Distinct Pathophysiology
Congestion as the Central Feature
Acute decompensation is fundamentally a congestive syndrome where systemic venous congestion decreases venous return to right cavities (causing systemic interstitial fluid accumulation) and increases left filling pressures (causing pulmonary fluid accumulation), impairing organ perfusion. 1
Right ventricular dysfunction worsens decreased venous return and aggravates systemic congestion, creating a bidirectional hemodynamic crisis. 1
Elevated diastolic pressures play a pivotal role in both systolic heart failure (EF <50%) and diastolic heart failure (EF ≥50%), with acute decompensation associated with significant increases in estimated pulmonary artery diastolic pressure (from 17±7 to 22±7 mm Hg in diastolic HF; from 21±9 to 24±8 mm Hg in systolic HF). 5
Hemodynamic Profiles
Acute heart failure hemodynamics include decreased cardiac output and mixed venous oxygen saturation, together with increased left ventricular filling pressure and systemic vascular resistance. 2
When hypotension accompanies failure, there is markedly decreased cardiac output or inappropriate increase in systemic resistance; if acidosis is also present, cardiac output is severely decreased with elevated lactic acid. 2
Mismatched right- and left-sided filling pressures occur in approximately 25% of patients, impeding effective decongestion strategies. 3
Differences Between Heart Failure Phenotypes
HFrEF vs HFpEF Pathophysiology
Heart failure with reduced ejection fraction (HFrEF, EF <40%) typically shows end-diastolic dimension of 68±11 mm, estimated pulmonary artery diastolic pressure of 18±7 mm Hg, and diastolic distensibility index of 0.06±0.04 mm Hg/mL. 5
Heart failure with preserved ejection fraction (HFpEF, EF ≥50%) demonstrates EF of 58±8%, end-diastolic dimension of 50±10 mm, estimated pulmonary artery diastolic pressure of 16±9 mm Hg, and diastolic distensibility index of 0.11±0.06 mm Hg/mL. 5
Despite lower natriuretic peptide levels in HFpEF, both phenotypes show similar elevation of biomarkers reflecting renin-angiotensin-aldosterone system activation, oxidative stress, and collagen synthesis during acute decompensation. 6
HFpEF patients have more impaired vascular and renal function (higher cystatin C) but similar acute decompensated heart failure severity compared to HFrEF. 6
Acute Decompensation Triggers and Mechanisms
Ischemic Mechanisms
In patients with preexisting heart failure or left ventricular systolic dysfunction, relatively small ischemic events can precipitate acute decompensation due to baseline vulnerability. 1
In patients without prior cardiac dysfunction, large ischemic events lead to severe myocardial dysfunction that may be transient (stunned myocardium) or permanent with long-term ejection fraction changes and new wall motion abnormalities. 1
Patients often have underlying subclinical cardiac abnormalities related to comorbidities—especially atrial fibrillation, type 2 diabetes mellitus, or renal disease—making them vulnerable to ischemia-induced cardiac stress. 1
Gradual vs Acute Onset
Most hospitalizations for acute decompensated heart failure are not truly "acute" but follow a gradual rise in cardiac filling pressures over days to weeks superimposed on chronic structural heart disease. 3, 7
Patients presenting with elevated systolic blood pressure usually have pulmonary congestion, relatively preserved left ventricular ejection fraction, and symptoms that develop abruptly (typically elderly women). 7
Patients with normal systolic blood pressure presenting with systemic congestion and reduced ejection fraction are usually younger with chronic heart failure history and symptoms developing gradually over days or weeks. 7
Neurohormonal and Systemic Responses
Pathophysiologic processes behind remodeling reflect systemic neurohormonal activation (renin-angiotensin-aldosterone system, sympathetic nervous system), peripheral vascular effects, and localized changes affecting the cardiac substrate. 8
Although systemic neurohormonal blockade slows disease progression, localized ventricular remodeling still adversely affects contractile function, explaining persistent morbidity and mortality despite guideline-directed medical therapy. 8
Myocardial injury during acute decompensation—related to decreased coronary perfusion and/or further neurohormonal activation—contributes to short-term and post-discharge cardiac events, along with renal dysfunction (cardiorenal syndrome). 7
Critical Clinical Pitfalls
Do not attribute decompensation solely to volume overload; an acute precipitant (ischemia, arrhythmia, infection) is present in the majority of cases and must be identified. 3
Do not overlook silent myocardial ischemia in diabetic patients, who have reduced pain perception and higher incidence of acute coronary events. 3
Clinical evaluation of left-sided filling pressure may be misleading in acute conditions due to rapidly evolving hemodynamics; chest X-ray confirmation is essential. 1
High central venous pressure in acute heart failure may reflect decreased venous and right ventricular compliance even with low right ventricular filling, not just volume overload. 1