Heart Failure Pathophysiology, Diagnosis, and Management

Vocabulary flashcards covering core concepts, pathophysiology, diagnostic criteria, clinical trial evidence, and guideline-directed medical therapy in Heart Failure based on ACC/AHA/HFSA 2022 and ESC 2023 guidelines.

Heart Failure (ACC/AHA/HFSA 2022 Definition)

A complex clinical syndrome with symptoms and/or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion.

Heart Failure (ESC 2023 Definition)

A clinical syndrome consisting of cardinal symptoms (breathlessness, ankle swelling, fatigue) accompanied by signs (elevated JVP, pulmonary crackles, peripheral oedema) caused by structural and/or functional cardiac abnormality, resulting in reduced cardiac output and/or elevated intracardiac pressures at rest or during stress.

Preload

The degree of myocardial stretch at end-diastole, determined by ventricular end-diastolic volume. Operates via the Frank-Starling mechanism, where excessive volume loading beyond optimal points elevates filling pressures and generates congestion.

Afterload

The wall stress against which the left ventricle contracts during systole, functionally equivalent to systemic vascular resistance (SVR); elevated in hypertension, aortic stenosis, and neurohormonal activation in heart failure.

Contractility

The intrinsic ability of myocardial fibres to generate force independent of preload and afterload, which is fundamentally impaired in heart failure with reduced ejection fraction due to lost, disordered, or energetically compromised cardiomyocytes.

Ventricular-Arterial Coupling

The mechanical matching of ventricular elastance ($E_{es}$) and effective arterial elastance ($E_a$), ideally at a ratio of $1:1$, which becomes uncoupled in heart failure to impair cardiac performance and efficiency.

Renin-Angiotensin-Aldosterone System (RAAS) Activation

A compensatory neurohormonal cascade triggered by reduced renal perfusion in heart failure that releases renin to produce angiotensin II and aldosterone, driving vasoconstriction, sodium/water retention, myocardial fibrosis, and pathological hypertrophy.

Sympathetic Nervous System (SNS) Activation

Baroreceptor-mediated compensation for reduced cardiac output in heart failure that increases circulating noradrenaline $3\text{ to }4 \times$, causing direct cardiomyocyte toxicity, beta-1 receptor downregulation, and arrhythmogenesis.

Eccentric Hypertrophy

Left ventricular structural remodelling characteristic of heart failure with reduced ejection fraction, where the ventricle progressively dilates, becomes spherical, and thins, increasing wall stress according to Laplace's Law.

Concentric Hypertrophy

Left ventricular structural remodelling often driven by chronic hypertension, where wall thickness increases, leading to ventricular stiffness, impaired relaxation, and elevated filling pressures characteristic of heart failure with preserved ejection fraction.

Heart Failure with Reduced Ejection Fraction (HFrEF)

A heart failure classification defined by left ventricular ejection fraction $\text{LVEF} < 40\text{\%}$; characterised by dilated LV and systolic dysfunction, requiring full guideline-directed medical therapy.

Heart Failure with Mildly Reduced Ejection Fraction (HFmrEF)

A heart failure classification defined by left ventricular ejection fraction $\text{LVEF}$ of $41\text{\%} \text{ to } 49\text{\%}$; represents an intermediate phenotype treated similarly to HFrEF with strong SGLT2 inhibitor evidence.

Heart Failure with Preserved Ejection Fraction (HFpEF)

A heart failure classification defined by left ventricular ejection fraction $\text{LVEF} \rightleftharpoons 50\text{\%}$ (specifically $\text{LVEF} \rho 50\text{\%}$ or \text{LVEF} \begin{cases} \text{LVEF} \to \text{preserved} \rightleftharpoons \text{LVEF} \rho 50\text{\%} \text{ where } \text{LVEF} \rightleftharpoons 50\text{\%} \text{ or } \text{LVEF} \text{ exceeds } 50\text{\%}\text{; formally } \text{LVEF} \rightleftharpoons 50\text{\%} or $\text{LVEF} \rightleftharpoons 50\text{\%}$); characterized by diastolic dysfunction, LV hypertrophy, and elevated filling pressures, responsive to SGLT2 inhibitors and diuretics.

Paroxysmal Nocturnal Dyspnoea (PND)

Episodes of severe breathlessness awakening a patient from sleep, caused by gradual reabsorption and redistribution of peripheral fluid into the pulmonary circulation during recumbency; highly specific for heart failure.

Orthopnoea

Dyspnoea occurring when lying flat due to redistribution of peripheral oedema fluid into the pulmonary circulation; possesses a specificity of $89\text{\%}$ for elevated left ventricular filling pressures.

Third Heart Sound ($S_3$)

The cardinal auscultatory sign of heart failure, produced by rapid blood inflow into a dilated, non-compliant ventricle during early diastole, carrying a positive likelihood ratio of $3.4$ for elevated LV filling pressures and poor systolic function.

Jugular Venous Pressure (JVP) Elevated

The most reliable clinical marker of elevated right atrial pressure and systemic venous congestion, measured at $>4\text{\,cm}$ above the sternal angle at a $45^\text{o}$ angle.

Left Bundle Branch Block (LBBB)

An electrocardiographic abnormality suggesting significant LV dysfunction in heart failure; a QRS duration $\rightleftharpoons 150\text{\,ms}$ with LBBB represents the strongest indication for cardiac resynchronisation therapy (CRT).

Kerley B Lines

Short horizontal lines seen at the lung bases on a chest X-ray, representing fluid accumulation in interlobular septa due to interstitial pulmonary oedema.

Bat-Wing Shadowing

Bilateral perihilar alveolar opacification on a chest X-ray indicative of frank alveolar pulmonary oedema, representing a medical emergency.

$E/e'$ Ratio

An echocardiographic tissue Doppler measure of left ventricular diastolic function, where an $E/e' > 14$ strongly suggests elevated left ventricular filling pressures.

Brain Natriuretic Peptide (BNP)

A cardiac biomarker released in response to myocardial wall stretch; levels $<35\text{\,pg/mL}$ rule out chronic heart failure with high sensitivity, whereas levels $>100\text{\,pg/mL}$ suggest acute heart failure.

Four Pillars of HFrEF GDMT

The foundational combination of four evidence-based drug classes (ARNI/ACEi/ARB, Beta-blocker, MRA, and SGLT2 inhibitor) initiated simultaneously or in rapid sequence to target distinct pathophysiological pathways and lower mortality.

Angiotensin Receptor-Neprilysin Inhibitor (ARNI)

A dual-acting agent (Sacubitril/Valsartan) that blocks $AT_1$ receptors and inhibits neprilysin to reduce cardiovascular mortality and heart failure hospitalisation by $20\text{\%}$ compared to enalapril.

36-Hour Washout Period

The mandatory time delay required between stopping an ACE inhibitor and initiating an ARNI (Sacubitril/Valsartan) to prevent bradykinin accumulation and severe angioedema risk.

Mineralocorticoid Receptor Antagonist (MRA)

A drug class (e.g., Spironolactone, Eplerenone) that competitively blocks aldosterone receptors, reducing cardiac fibrosis, sodium retention, and sudden cardiac death; contraindicated if $\text{eGFR} < 30\text{\,mL/min}$ or $K^+ \rightleftharpoons 5.0\text{\,mmol/L}$.

SGLT2 Inhibitor

A medication class (e.g., Dapagliflozin, Empagliflozin) that blocks renal glucose reabsorption in the proximal tubule, providing cardiovascular and renal benefits across the entire heart failure ejection fraction spectrum ($\text{HFrEF}$, $\text{HFmrEF}$, $\text{HFpEF}$).

Loop Diuretic

A drug class (e.g., Furosemide) that inhibits the $\text{Na-K-2Cl}$ cotransporter ($\text{NKCC2}$) in the thick ascending limb of Henle to relieve congestive symptoms, though it does not lower long-term mortality.

Sequential Nephron Blockade

The combination strategy of adding a thiazide or thiazide-like diuretic (e.g., Metolazone) to a loop diuretic to overcome diuretic resistance by blocking sodium reabsorption at multiple nephron sites.

Hydralazine + Isosorbide Dinitrate (H-ISDN)

A vasodilator combination providing combined arterial and venous dilation; serves as a mortality-reducing alternative in HFrEF when RAAS blockers are contraindicated due to severe renal impairment, angioedema, or hyperkalaemia.

Ivabradine

A therapeutic agent that selectively blocks the $I_f$ channel in the sinoatrial node, reducing heart rate without affecting contractility or blood pressure; indicated in HFrEF with sinus rhythm and resting $\text{HR} \rightleftharpoons 70\text{\,bpm}$ on maximal beta-blockers.

Digoxin

A cardiac glycoside that inhibits $\text{Na}^+/\text{K}^+\text{-ATPase}$, increasing intracellular calcium and slowing AV nodal conduction; used for rate control in atrial fibrillation with HFrEF or symptom relief in refractory HFrEF, carrying a risk of toxicity potentiated by hypokalaemia.

Cardiorenal Syndrome

The complex, bidirectional pathophysiological interaction where acute or chronic dysfunction in the heart or kidneys induces acute or chronic dysfunction in the other organ, affecting $40\text{ to }50\text{\%}$ of heart failure patients.

Thiazolidinediones (TZDs)

Antidiabetic agents (e.g., Pioglitazone, Rosiglitazone) that activate $\text{PPAR-}\text{gamma}$ receptors in the distal nephron to cause renal sodium and water retention; absolutely contraindicated in heart failure due to a $30\text{ to }50\text{\%}$ increase in HF hospitalisations.

Non-dihydropyridine Calcium Channel Blockers

Negative inotropic drugs (e.g., Diltiazem, Verapamil) that impair left ventricular systolic function and are strictly contraindicated in heart failure with reduced ejection fraction ($\text{HFrEF}$).

"FAILURE" Mnemonic

A clinical tool for identifying acute heart failure precipitants: Forgot medications, Arrhythmia, Ischaemia/Infarction, Lifestyle indiscretion, Uncontrolled hypertension, Renal dysfunction, and Extra-cardiac causes (e.g., infection, anaemia).

PARADIGM-HF Trial

A landmark 2014 trial of $8442$ HFrEF patients demonstrating that Sacubitril/Valsartan reduced the primary composite outcome of cardiovascular death or heart failure hospitalisation by $20\text{\%}$ compared to enalapril.

DAPA-HF Trial

A landmark 2019 trial demonstrating that Dapagliflozin reduced worsening heart failure or cardiovascular death by $26\text{\%}$ in HFrEF patients, regardless of the presence of type 2 diabetes mellitus.

EMPEROR-Preserved Trial

A landmark 2021 trial of $5988$ patients with $\text{LVEF} > 40\text{\%}$ demonstrating that Empagliflozin reduced cardiovascular death or heart failure hospitalisations by $21\text{\%}$, establishing the first proven drug therapy for HFpEF.

DELIVER Trial

A landmark 2022 trial enrolling $6263$ heart failure patients with $\text{LVEF} > 40\text{\%}$ that confirmed Dapagliflozin reduces worsening heart failure or cardiovascular death by $18\text{\%}$, cementing SGLT2 inhibitors as a class effect across the entire ejection fraction spectrum.