What are the characteristics of cardiac markers such as troponin and natriuretic peptides (e.g., B-type Natriuretic Peptide (BNP) and N-terminal pro b-type natriuretic peptide (NT-proBNP)) in patients with cardiomyopathy?

Cardiac Markers in Cardiomyopathy

In cardiomyopathy, natriuretic peptides (BNP/NT-proBNP) are elevated due to ventricular wall stress and volume/pressure overload, while troponin elevation reflects ongoing myocyte injury and necrosis, with both markers providing distinct but complementary prognostic information. 1

Natriuretic Peptides (BNP and NT-proBNP)

Pathophysiology and Release Mechanism

• In cardiomyopathy, ventricular myocytes re-express fetal genes including BNP in response to pressure or volume overload, shifting production from primarily atrial to predominantly ventricular release. 1

• BNP requires de novo synthesis for substantial release, but the BNP gene responds rapidly to cardiac stress, making it a quantitative marker related to the extent of left ventricular dysfunction. 1

• Natriuretic peptides are elevated in all conditions with increased atrial or ventricular wall tension and salt/fluid overload, serving as markers of cardiac stress rather than specific disease entities. 1

Diagnostic Characteristics

• BNP >100 pg/mL or NT-proBNP >300 pg/mL have high sensitivity for heart failure diagnosis, with NT-proBNP <300 pg/mL having 98% negative predictive value, effectively ruling out heart failure. 2, 3

• Age-adjusted thresholds improve diagnostic accuracy: NT-proBNP >450 pg/mL for patients <50 years, >900 pg/mL for 50-75 years, and >1800 pg/mL for >75 years. 2

• Both BNP and NT-proBNP provide diagnostic and prognostic information, though their absolute values and cutpoints cannot be used interchangeably. 1

Prognostic Value

• A reduction of >30% in BNP/NT-proBNP levels indicates good treatment response and favorable prognosis, while persistent elevation or rising levels suggest inadequate therapy. 2

• NT-proBNP >2000 pg/mL is associated with significantly worse outcomes, including increased risk of death or heart failure readmissions. 2

• Predischarge NT-proBNP is more strongly associated with outcomes than admission levels, making it a critical monitoring timepoint. 2

Important Confounders

• Obesity significantly reduces natriuretic peptide levels through increased clearance and suppression of pro-BNP synthesis, potentially masking underlying cardiac dysfunction despite significant disease. 1, 3

• Atrial fibrillation increases BNP and NT-proBNP concentrations even without heart failure, requiring higher diagnostic cutoff values in this population. 1

• Renal dysfunction elevates NT-proBNP independent of cardiac function, with severe renal failure producing extremely high levels (4000-20,000 pg/mL) driven more by renal dysfunction than heart failure severity. 2

• ACE inhibitors, ARBs, beta-blockers, and spironolactone reduce natriuretic peptide levels through reduction in filling pressures and reversal of pathological remodeling. 1

ARNI-Specific Consideration

• ARNI (sacubitril/valsartan) increases BNP levels because BNP is a substrate for neprilysin, but does NOT increase NT-proBNP levels—therefore, only NT-proBNP should be used for monitoring patients on ARNI therapy. 1

Cardiac Troponin (cTnI and cTnT)

Pathophysiology in Cardiomyopathy

• Troponin elevation in cardiomyopathy reflects ongoing myocyte injury or necrosis, not acute coronary syndrome, and must be interpreted in clinical context. 1

• Troponins I and T respond similarly in both acute coronary syndromes and acute decompensated heart failure, providing prognostic significance in both settings. 1

Characteristics in Specific Cardiomyopathies

Hypertrophic Cardiomyopathy (HCM)

• Serum cTnI in HCM is independently associated with maximum left ventricular wall thickness, left ventricular dysfunction, and male gender, reflecting the LV remodeling process rather than cardiac load. 4

• cTnI levels range from 0.01 to 0.83 ng/mL in HCM patients, with higher values in males, those with atrial fibrillation, and LV systolic dysfunction. 4

• Combined measurements of cTnI ≥0.04 ng/ml and BNP ≥200 pg/ml provide superior prognostic stratification in HCM, with patients having both elevated markers showing 11.7-fold increased risk of cardiovascular events. 5

• cTnI ≥0.025 ng/ml combined with maximum wall thickness ≥21 mm indicates myocardial fibrosis on cardiac MRI with 95% specificity or 88% sensitivity in hypertrophic obstructive cardiomyopathy. 6

Ischemic vs. Dilated Cardiomyopathy

• In chronic heart failure, troponin levels are significantly higher in ischemic cardiomyopathy compared to idiopathic dilated cardiomyopathy (cTnT: 0.373 vs. 0.064 ng/mL; cTnI: 2.02 vs. 0.21 ng/mL), correlating with worse prognosis. 7

• BNP levels are also higher in ischemic cardiomyopathy (776 vs. 532 pg/mL), with cardiovascular mortality of 48% vs. 23% during 10-month follow-up. 7

• These differential biomarker levels reflect differences in disease pathogenesis between ischemic and non-ischemic etiologies. 7

Relationship Between Troponin and BNP

• Troponin and BNP provide complementary but distinct information—troponin reflects myocyte injury/necrosis while BNP reflects wall stress and volume overload. 4

• In HCM, cTnI shows very weak correlation with BNP (r = 0.18), indicating these markers reflect different pathophysiologic processes. 4

• cTnI is not significantly different among NYHA functional classes in HCM, whereas BNP shows clear differences, further demonstrating their distinct clinical significance. 4

Critical Clinical Pitfall: Disproportion Between Markers

• In fulminant myocarditis, persistently elevated troponin with "seemingly normal" BNP levels indicates severe myocardial injury with inadequate neurohormonal compensation and portends poor prognosis—this disproportion is an ominous sign requiring aggressive intervention. 8

• This pattern reflects diffuse inflammatory infiltration with severe cardiomyocyte injury and necrosis, where BNP's dual role as both a marker and cardioprotective factor is overwhelmed. 8

• Lower BNP levels in end-stage heart failure similarly represent an adverse prognostic marker, indicating failure of compensatory mechanisms. 8

Multimarker Strategy

• Combining troponin with natriuretic peptides improves risk stratification beyond either marker alone, particularly in hypertrophic cardiomyopathy where combined elevation identifies highest-risk patients. 5

• Multiple emerging biomarkers (soluble ST2, galectin-3, GDF-15) may provide incremental prognostic value over natriuretic peptides, but require validation before routine clinical use. 1

• Multimarker panels including troponin and natriuretic peptides with other biomarkers representing different pathophysiologic pathways should be considered to improve specificity in clinical trials and potentially in clinical practice. 1