2.2 Heart Failure Syndromes & Cardiogenic Shock

Pathophysiology & Classification: HFrEF vs. HFpEF

Heart failure is a complex clinical syndrome characterized by cardinal symptoms (dyspnea, fatigue, ankle swelling) and clinical signs (elevated jugular venous pressure, pulmonary crackles, peripheral edema) resulting from structural or functional abnormalities of the heart. These abnormalities lead to elevated intracardiac pressures and inadequate cardiac output at rest or during physiological exertion.

The following 2022 AHA/ACC/HFSA categories use echocardiographic left ventricular ejection fraction (LVEF). ESC 2026 instead defines HFrEF as LVEF <50% and HFpEF as >=50%, removing HFmrEF; use the framework named in the question:

1. Heart Failure with Reduced Ejection Fraction (HFrEF): Defined as LVEF <= 40%. Characterized primarily by systolic dysfunction—inadequate myocardial contractility and left ventricular dilatation (eccentric hypertrophy). Ischemic heart disease, dilated cardiomyopathy, and advanced hypertensive remodeling are predominant etiologies.
2. Heart Failure with Mildly Reduced Ejection Fraction (HFmrEF): Defined as LVEF 41% to 49%. Shares overlapping pathophysiological characteristics with HFrEF and demonstrates similar benefit from neurohormonal therapies.
3. Heart Failure with Preserved Ejection Fraction (HFpEF): Defined as LVEF >= 50% accompanied by objective evidence of cardiac structural changes (left atrial enlargement, left ventricular concentric hypertrophy) and diastolic dysfunction (elevated filling pressures, abnormal E/e' ratio on Doppler echocardiography). In Caribbean regional practice, chronic uncontrolled hypertension, metabolic syndrome, obesity, and diabetes mellitus are principal drivers of HFpEF.

Neurohormonal Activation

Following myocardial injury, a sustained decline in stroke volume unloads arterial baroreceptors, triggering compensatory neurohormonal pathways:

• Renin-Angiotensin-Aldosterone System (RAAS): Enhanced renin release increases circulating angiotensin II (provoking arteriolar vasoconstriction, afterload elevation, and cellular hypertrophy) and aldosterone (promoting renal tubular sodium-water retention and progressive myocardial fibrosis).
• Sympathetic Nervous System (SNS): Chronic adrenergic overdrive drives tachycardia, increases myocardial oxygen consumption, induces beta-1 receptor downregulation, and promotes fatal ventricular arrhythmias.
• Natriuretic Peptide System: Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are released from stretched atria and ventricles to facilitate natriuresis, vasodilation, and RAAS suppression. Endogenous neutral endopeptidase (neprilysin) rapidly degrades these beneficial peptides, forming the rationale for therapeutic neprilysin inhibition.

Clinical Evaluation & Staging

Diagnosis requires a synthesized evaluation of clinical signs, symptoms, electrocardiography, chest radiography, biomarkers, and transthoracic echocardiography.

Framingham Heart Failure Diagnostic Criteria

For the Framingham definition, use two major criteria or one major plus two minor criteria present concurrently, considering whether other conditions explain the findings.

• Major Criteria: Paroxysmal nocturnal dyspnea (PND) or orthopnea (one major criterion); elevated jugular venous pressure (> 4 cm above sternal angle); pulmonary rales; cardiomegaly on chest radiograph; acute pulmonary edema; S3 gallop; hepatojugular reflux; weight loss >= 4.5 kg in 5 days in response to treatment.
• Minor Criteria: Bilateral ankle edema; nocturnal cough; dyspnea on ordinary exertion; hepatomegaly; pleural effusion; tachycardia (heart rate >= 120 bpm); decrease in vital capacity by one-third from maximum.

Functional & Staging Classifications

• NYHA Functional Classification: Grades symptom severity relative to physical activity:
  • Class I: No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, or dyspnea.
  • Class II: Slight limitation of physical activity. Comfortable at rest, but ordinary activity results in fatigue, palpitation, or dyspnea.
  • Class III: Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes symptoms.
  • Class IV: Unable to carry on any physical activity without discomfort. Symptoms of heart failure present even at rest.
• ACC/AHA Staging System: Highlights progressive structural trajectory:
  • Stage A: At risk for heart failure without structural disease or symptoms (e.g., hypertension, diabetes).
  • Stage B: Pre-heart failure: structural heart disease (e.g., prior MI, LVH) without symptoms.
  • Stage C: Structural heart disease with prior or current clinical symptoms.
  • Stage D: Advanced, refractory heart failure requiring specialized interventions (inotropes, mechanical assist devices, palliative care).

Biomarkers in Heart Failure

Circulating B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) serve as sensitive biochemical markers of myocardial wall stress. In acute presentation, thresholds of BNP < 100 pg/mL or NT-proBNP < 300 pg/mL exhibit high negative predictive value (> 95%) to rule out acute heart failure. Notably, patients receiving sacubitril/valsartan demonstrate elevated BNP (as sacubitril inhibits its degradation), while NT-proBNP is not a neprilysin substrate and remains an accurate monitoring marker.

Acute Decompensated Heart Failure (ADHF) Management

Acute decompensated heart failure presents as acute pulmonary edema, worsening congestion, or low cardiac output. Patients must be rapidly evaluated for precipitating causes using the CHAMPIT mnemonic (Coronary syndrome, Hypertensive crisis, Arrhythmia, Mechanical cause, Pulmonary embolism, Infection, Tamponade).

Immediate Resuscitation Sequence

1. Patient Positioning: Place the patient in a high Fowler's (sitting upright) position with legs dangling over the edge of the bed to promote peripheral venous pooling and reduce right and left ventricular preload.
2. Non-Invasive Positive Pressure Ventilation (NIPPV): Continuous Positive Airway Pressure (CPAP 5-10 cmH2O) or Bilevel Positive Airway Pressure (BiPAP) should be initiated early in patients with respiratory distress (tachypnea > 25 breaths/min, SpO2 < 90%). NIPPV improves functional residual capacity, drives fluid back from alveoli into interstitial capillaries, decreases work of breathing, and reduces left ventricular afterload by lowering transmural wall tension, substantially reducing the need for invasive endotracheal intubation.
3. Intravenous Loop Diuretics: The cornerstone of acute decongestion. Administer IV furosemide immediately. For diuretic-naive patients, an initial dose of 20 to 40 mg IV is given. For patients on chronic oral therapy, the initial IV bolus should equal 1.0 to 2.5 times their total daily oral dose given as an intravenous bolus (e.g., if taking 40 mg PO daily, administer 40 to 100 mg IV). Furosemide induces rapid venodilation within 5 to 15 minutes before its natriuretic peak occurs at 30 to 60 minutes. Adequacy of diuresis is evaluated by spot urine sodium (> 50-70 mEq/L at 2 hours) and hourly urine output (> 100-150 mL/h).
4. Intravenous Vasodilators: In patients with acute hypertensive pulmonary edema (systolic blood pressure > 110 mmHg), intravenous nitroglycerin (starting at 10-20 mcg/min and uptitrated rapidly by 10-20 mcg/min every 3-5 minutes) provides potent venodilation and arteriolar dilation, reducing intracardiac filling pressures rapidly.
5. Critical Beta-Blocker Rule: Do not initiate or increase beta-blockers during ongoing acute congestion, hypoperfusion or shock. Continue established treatment when clinically stable, but reassess or withhold it for shock, marked bradycardia, second- or third-degree AV block, or significant intolerance. Initiate or optimize an evidence-based beta-blocker after stabilization, often before hospital discharge.

Guideline-Directed Medical Therapy (GDMT): The Four Pillars

For chronic HFrEF (LVEF <= 40%), contemporary international guidelines mandate the rapid initiation and titration of four foundational pharmacotherapeutic classes proven to reduce all-cause mortality, cardiovascular death, and heart failure hospitalization:

Cardiogenic Shock & Forrester Hemodynamic Profiling

Cardiogenic shock is a state of critical end-organ tissue hypoperfusion caused by primary cardiac pump failure. Typical findings considered alongside the clinical assessment include:

• Sustained systolic blood pressure < 90 mmHg (or mean arterial pressure < 65 mmHg) for > 30 minutes, or requirement of inotropes/vasopressors to maintain blood pressure.
• Reduced Cardiac Index (typically CI <2.2 L/min/m2), interpreted with the clinical state and any hemodynamic support.
• Elevated Pulmonary Capillary Wedge Pressure (PCWP >15 mmHg) is common in LV failure; PCWP may be normal with euvolemic or predominantly RV cardiogenic shock.
• Clinical signs of hypoperfusion: Cool extremities, mottled skin, oliguria (< 0.5 mL/kg/h), altered mental status, and elevated serum lactate (> 2.0 mmol/L).

The Forrester Hemodynamic Classification

The Forrester classification stratifies heart failure and shock patients into four quadrants based on physical examination and invasive hemodynamics (perfusion [warm vs cold] and congestion [dry vs wet]):

• Subset I: Warm & Dry (Cardiac Index > 2.2 L/min/m2, PCWP <= 18 mmHg). Normal hemodynamics or compensated heart failure. Maintain GDMT.
• Subset II: Warm & Wet (Cardiac Index > 2.2, PCWP > 18 mmHg). Congested with preserved perfusion. Treated with intravenous loop diuretics and vasodilators (nitroglycerin).
• Subset III: Cold & Dry (Cardiac Index <= 2.2, PCWP <= 18 mmHg). Hypoperfused without elevated pulmonary filling pressure. Assess preload and RV function; give a cautious fluid challenge (for example, 250 mL) only if underfilling is likely, and consider inotropic support for persistent pump failure.
• Subset IV: Cold & Wet (Cardiac Index <= 2.2, PCWP > 18 mmHg). Classic congested low-output profile. Use vasopressor support for hypotension and an inotrope when needed, reassessing perfusion and considering mechanical support; address congestion as circulation stabilizes.

Inotropes and Vasopressors in Cardiogenic Shock

• First-Line Vasopressor: Noradrenaline (Norepinephrine). Potent alpha-1 agonist with modest beta-1 activity. Increases MAP and coronary perfusion pressure without excessive tachycardia, demonstrating lower arrhythmic risk and lower mortality compared to dopamine.
• First-Line Inotrope: Dobutamine. Beta-1 and beta-2 adrenergic agonist. Increases myocardial contractility and stroke volume while producing mild peripheral vasodilation (afterload reduction). In patients with severe hypotension (MAP < 65 mmHg), dobutamine must be paired with noradrenaline to avoid worsening vasodilatory hypotension.
• Alternative Inotrope: Milrinone. Phosphodiesterase-3 (PDE-3) inhibitor. Enhances cyclic AMP, increasing inotropy and lusitropy (diastolic relaxation) while reducing systemic and pulmonary vascular resistance. Ideal in pulmonary hypertension or chronic beta-blocker therapy, but renally cleared and can cause prolonged hypotension; vasopressor support depends on blood pressure and perfusion.