ASE Guidelines on LV Diastolic Dysfunction and HFpEF
The 2016 ASE/EACVI guidelines provide a structured echocardiographic algorithm for diagnosing LV diastolic dysfunction using four key parameters: average E/e' ratio >14, septal e' velocity <7 cm/sec, peak TR velocity >2.8 m/sec, and LA volume index >34 mL/m², with diastolic dysfunction confirmed when ≥50% of these criteria are met. 1
Echocardiographic Assessment of Diastolic Function
Core Diagnostic Parameters
The ASE recommends a multiparametric approach using the following measurements 1:
- Average E/e' ratio >14 - Indicates elevated LV filling pressures
- Septal e' velocity <7 cm/sec - Reflects impaired myocardial relaxation
- Peak TR velocity >2.8 m/sec - Suggests elevated pulmonary artery pressures
- LA volume index >34 mL/m² - Demonstrates chronic elevation of filling pressures
When ≥50% (at least 2 of 4) of these parameters are abnormal, diastolic dysfunction is present. 1
Advanced Echocardiographic Techniques
LV global longitudinal diastolic strain rate during isovolumic relaxation and early diastole correlates significantly with the time constant of LV relaxation (tau) and can be used with mitral E velocity to estimate filling pressures 1
Timing of peak LV untwisting rate is valuable for diagnosing diastolic dysfunction in patients with normal LV volumes and ejection fraction, as delayed peak untwisting is frequently present 1
LA systolic strain demonstrates an inverse correlation with mean wedge pressure, though technical expertise is essential for accurate measurement 1
Management of HFpEF (LVEF ≥50%)
First-Line Pharmacotherapy
SGLT2 inhibitors are the cornerstone of HFpEF treatment, with a Class 2a recommendation from ACC/AHA guidelines, demonstrating a 21% reduction in the composite endpoint of HF hospitalization or cardiovascular death. 1, 2
- Empagliflozin reduced HF hospitalizations by 29% in EMPEROR-Preserved, with benefits regardless of diabetes status 1
- Dapagliflozin showed similar efficacy in DELIVER trial 1
- Both agents provide additional benefits including reduced eGFR decline and modest QOL improvement 1
Diuretic Therapy
- Loop diuretics should be used judiciously as needed to reduce congestion and improve symptoms, not as routine therapy 1, 2
- Titrate based on clinical signs of volume overload including elevated JVP, positive hepatojugular reflux, and peripheral edema 3
Second-Line Agents (Class 2b Recommendations)
These agents show greater benefit in patients with LVEF closer to 50% (lower end of preserved spectrum):
Mineralocorticoid receptor antagonists (spironolactone) may decrease hospitalizations, particularly with LVEF 50-57% 1
ARNi (sacubitril-valsartan) may decrease hospitalizations in selected patients 1
ARBs (candesartan) may decrease hospitalizations, particularly with LVEF closer to 50% 1
- CHARM-Preserved showed borderline reduction in HF hospitalizations but no mortality benefit 1
Essential Comorbidity Management
Blood pressure control is a Class 1 recommendation - titrate antihypertensive medications to achieve targets per hypertension guidelines 1, 2
Atrial fibrillation management (Class 2a) is useful to improve symptoms 1
- Rate or rhythm control strategies should be individualized
- Anticoagulation required for CHA₂DS₂-VASc score ≥2 (men) or ≥3 (women) 1
- AF ablation is reasonable to improve symptoms and QOL 1
Beta-Blocker Use
Beta-blockers should only be used for specific indications in HFpEF: prior MI (up to 3 years), angina, or AF with rapid ventricular response 1, 2
- Monitor exercise tolerance due to potential for chronotropic incompetence 1
Therapies to Avoid (Class 3: No Benefit)
Routine use of nitrates or phosphodiesterase-5 inhibitors is ineffective for increasing activity or QOL 1, 2
- NEAT-HFpEF and RELAX trials showed no benefit on exercise tolerance or symptoms 1
Prognostic Assessment in HFpEF
Echocardiographic Predictors
The ASE guidelines identify key prognostic markers 1:
- RV dysfunction provides independent prognostic information beyond pulmonary artery systolic pressure
- LV mass and LA size remain independently associated with increased morbidity and mortality
- Septal E/e' ratio and TR peak velocity predict outcomes beyond clinical characteristics
- LV hypertrophy is an independent predictor of adverse outcomes
Clinical and Laboratory Predictors
- NT-proBNP levels are the most powerful prognostic parameter 1
- Age, diabetes, prior HF hospitalization, and eGFR provide additional prognostic information 1
Special Diagnostic Considerations
Diastolic Dysfunction in Atrial Fibrillation
The 2016 ASE algorithm cannot be directly applied in AF due to cycle length variability, absent atrial contraction, and frequent LA enlargement regardless of filling pressures 5
- A two-step algorithm combining echocardiographic parameters plus BMI has been proposed to differentiate normal from elevated filling pressures in AF 5
- Complement echocardiography with natriuretic peptides and consider cardiac catheterization in selected cases 5
Screening for Specific Etiologies
Cardiac amyloidosis screening (Class 1) is recommended when clinically suspected 1:
- Screen with serum/urine immunofixation electrophoresis and serum free light chains
- If negative for monoclonal proteins, perform bone scintigraphy to confirm ATTR amyloidosis
- Genetic testing with TTR gene sequencing differentiates hereditary from wild-type ATTR 1
Practical Treatment Algorithm
- Initiate SGLT2 inhibitor (empagliflozin or dapagliflozin) regardless of diabetes status 1, 2
- Add loop diuretics as needed for congestion management 1, 2
- Optimize blood pressure control to guideline targets 1, 2
- Manage AF aggressively if present 1, 2
- Consider adding MRA, ARNi, or ARB for patients with LVEF 50-57% who remain symptomatic 1, 2
- Screen for and treat cardiac amyloidosis if suspected based on clinical features 1