What does reduced global longitudinal strain consistent with subclinical cardiomyopathy mean and how is it managed?

Understanding Reduced Global Longitudinal Strain and Subclinical Cardiomyopathy

What This Finding Means

Reduced global longitudinal strain (GLS) consistent with subclinical cardiomyopathy indicates early myocardial dysfunction that precedes overt heart failure and is detectable before ejection fraction declines—this represents a critical window for intervention to prevent progression to symptomatic disease. 1

Physiologic Interpretation

• GLS measures the maximal shortening of left ventricular myocardium during systole, expressed as a negative percentage—values closer to zero (less negative) represent worse function 2
• Normal GLS ranges from -18% to -22%, with values between -16% to -18% considered borderline, and anything above -16% (less negative) classified as abnormal 2
• GLS is more sensitive than ejection fraction for detecting early myocardial dysfunction, often identifying abnormalities months before EF declines 2
• The measurement reflects function of subendocardial longitudinal myocardial fibers, which are particularly vulnerable to early cardiac injury 2

Clinical Significance

• Strain measurements are abnormal in many clinical settings with preserved LV EF, making this a marker of subclinical dysfunction 1
• Each 1% worsening in GLS is associated with a 5% increased risk for mortality in heart failure patients 3
• Patients with severely reduced GLS (≤8.0%) have 49% five-year mortality compared to 34% in those with mildly reduced GLS (>12.6%) 3

Workup Algorithm

Step 1: Confirm and Characterize the Measurement

• Repeat echocardiography with the same equipment vendor within 2-3 weeks, as significant vendor variability exists between different ultrasound machines and software versions 2
• Measure left ventricular ejection fraction using 3D echocardiography when available for superior reproducibility 4
• Document the absolute GLS value and compare to normal range (normal: -18% to -22%) 2

Step 2: Comprehensive Echocardiographic Assessment

• Assess diastolic function using four key variables: septal e′ velocity (<7 cm/sec abnormal), lateral e′ velocity (<10 cm/sec abnormal), average E/e′ ratio (>14 abnormal), and LA maximum volume index 1
• Evaluate right ventricular function to exclude biventricular involvement, as this has prognostic implications 4
• Measure mitral annular plane systolic excursion and tissue Doppler-derived mitral annulus systolic velocity as additional markers of longitudinal function 1
• In post-cardiac surgery patients, focus on lateral wall assessment as septal strain may be artifactually reduced due to paradoxical septal motion 2

Step 3: Identify Underlying Etiology

Specific etiologies to systematically exclude:

• Stress-induced (Takotsubo) cardiomyopathy: Look for recent acute illness or emotional stressor with transient reversible global systolic dysfunction 4
• Toxic cardiomyopathy: Obtain detailed history of chemotherapy exposure, alcohol use, or catecholamine excess 4
• Infiltrative diseases: Consider amyloidosis, sarcoidosis, or storage diseases if restrictive physiology is present 4
• Myocarditis: Assess for recent viral illness, regional dysfunction, or increased wall thickness from edema 4
• Ischemic disease: Perform stress testing if regional wall motion abnormalities suggest coronary artery disease 1

Step 4: Advanced Imaging When Indicated

• Cardiac MRI is indicated when diagnostic uncertainty exists regarding etiology of reduced GLS, particularly for suspected infiltrative disease where MRI provides superior tissue characterization 4
• MRI with late gadolinium enhancement can differentiate ischemic from non-ischemic cardiomyopathy and identify specific patterns of infiltration 4

Step 5: Laboratory and Clinical Assessment

• Measure NT-proBNP, which correlates strongly with GLS and provides complementary prognostic information 5
• Screen for reversible causes: thyroid function, iron studies, nutritional deficiencies (thiamine, selenium)
• Assess for systemic diseases that may cause cardiomyopathy: autoimmune markers if clinically indicated

Step 6: Risk Stratification and Monitoring

• Implement serial GLS monitoring every 3-6 months to detect progression, as worsening GLS over time indicates pathological deterioration requiring intervention 2
• A relative percentage reduction of GLS >15% from baseline is considered abnormal and warrants escalation of therapy 2
• In chemotherapy patients, a 10-15% reduction in peak systolic GLS is a useful parameter to predict cardiotoxicity 4

Management Approach

Immediate Actions

• Initiate or optimize guideline-directed medical therapy if heart failure risk factors are present: ACE inhibitors/ARBs and beta-blockers should be started even with preserved ejection fraction when GLS is reduced 2
• Address modifiable risk factors: hypertension control, diabetes management, smoking cessation, alcohol abstinence
• Discontinue cardiotoxic medications if identified as the cause 4

Prognostic Implications

• In patients with chronic ischemic cardiomyopathy, GLS ≤-11.5% predicts superior outcome compared to GLS >-11.5% 6
• GLS has greater prognostic value than LVEF in acute heart failure, with each 1% increase in GLS associated with 5% decreased mortality risk 3
• Baseline LV GLS ≤10% is independently associated with higher risk of worsening heart failure and all-cause mortality in HFrEF patients 7

Critical Pitfalls to Avoid

• Do not dismiss borderline GLS values (between -16% to -18%) as normal—these represent early dysfunction requiring close monitoring 2
• GLS values are not applicable to patients currently receiving inotropic agents or mechanical circulatory support, as these interventions alter the measurement 2
• A single borderline GLS value in asymptomatic patients with no cardiac risk factors and normal ejection fraction may represent normal variation, particularly in athletes 2
• Diastolic abnormalities often precede systolic dysfunction and cause symptoms despite normal EF—always perform comprehensive diastolic assessment 4
• Reduction in GLS over time is more concerning than a single abnormal value and mandates therapeutic intervention 4