What are the implications of Grade 3 diastolic dysfunction (diastolic heart failure)?

From the Guidelines

Grade 3 diastolic dysfunction is a severe form of diastolic heart failure that requires aggressive management of symptoms and underlying causes, including the use of diuretics, ACE inhibitors, and beta-blockers, as well as lifestyle modifications to reduce morbidity and mortality. This condition is characterized by impaired relaxation of the left ventricle during diastole, diagnosed by Doppler echocardiography showing a high E/A ratio, shortened deceleration time, and increased E/e' ratio, indicating elevated left atrial pressures 1.

Diagnosis and Treatment

The diagnosis of Grade 3 diastolic dysfunction is based on the presence of typical symptoms and signs of heart failure, a normal left ventricular ejection fraction, and no valvular abnormalities on echocardiography 1. Treatment focuses on managing the underlying cause and symptoms, including:

• Diuretics like furosemide (20-80 mg daily) to reduce fluid overload
• ACE inhibitors such as lisinopril (5-40 mg daily) or ARBs like valsartan (80-320 mg daily) to reduce afterload
• Beta-blockers such as metoprolol (12.5-200 mg daily) to improve ventricular filling time Lifestyle modifications are crucial, including:
• Sodium restriction (<2g daily)
• Fluid restriction (1.5-2L daily)
• Regular monitoring of weight
• Moderate physical activity as tolerated

Prognosis and Management

This condition carries a poor prognosis compared to milder forms of diastolic dysfunction, with higher rates of hospitalization and mortality, as the stiff ventricle struggles to accommodate blood volume without causing significant increases in filling pressures 1. The management of patients with Grade 3 diastolic dysfunction is frequently determined by a set of therapeutic principles, including control of blood pressure, control of tachycardia, reduction in central blood volume, and alleviation of myocardial ischemia 1.

Key Considerations

It is essential to note that the morbidity and mortality associated with Grade 3 diastolic dysfunction may be nearly as profound as that with low LVEF, and frequent and repeated hospitalizations characterize the patient with this condition 1. Therefore, aggressive management of symptoms and underlying causes is crucial to reduce morbidity and mortality.

From the Research

Definition and Prevalence of Diastolic Dysfunction

• Diastolic dysfunction refers to impaired relaxation or filling of the ventricles during the diastolic phase of the cardiac cycle 2.
• Left ventricular diastolic dysfunction (LVDD) is common in hypertensive individuals and is associated with increased morbidity and mortality 2.

Pathophysiology of Diastolic Dysfunction

• The pathophysiology of LVDD in hypertension is complex, involving alterations in cardiac structure and function, neurohormonal activation, and vascular stiffness 2.
• Diastolic dysfunction is present in half of patients with hypertension and has been shown to be associated with increased cardiovascular morbidity and mortality, as well as the development of heart failure 3.

Diagnosis of Diastolic Dysfunction

• The diagnosis of LVDD relies primarily on echocardiography 2.
• Grade 3 diastolic dysfunction is a severe form of diastolic dysfunction, but the specific diagnostic criteria are not provided in the available evidence.

Treatment of Diastolic Dysfunction

• Angiotensin converting enzyme inhibitors and angiotensin receptor blockers have been shown to be effective in improvement of measures of diastolic function and are recommended as first-line agents in the control of hypertension in patients with diastolic heart failure 3.
• Beta-blockers, calcium channel blockers, and diuretics have also shown some efficacy in improved indices of diastolic filling 3.
• Higher doses of ACE inhibitors and ARBs reduce the risk of HF worsening compared to lower doses, and higher doses of ARBs also reduce the risk of HF hospitalization 4.
• However, the independent impact of these pharmacologic interventions on prognosis and outcome in diastolic dysfunction has yet to be clarified 3.

Clinical Trials and Future Research

• The Irbesartan in Heart Failure with Preserved Ejection Fraction (I-PRESERVE) study, Candesartan in Heart Failure: Assessment in Reduction of Mortality and Morbidity (CHARM-Preserved) trial and the Losartan Intervention For End-point Reduction in Hypertension (LIFE) Study all failed to show improved morbidity and mortality with these drugs 3.
• The Trial Of Preserved Cardiac function heart failure with an Aldosterone anTagonist (TOPCAT) is an on-going large, international study evaluating the effect of spironolactone on cardiovascular mortality, aborted cardiac arrest, or hospitalization for diastolic heart failure 3.
• Ongoing clinical trials and future research may provide further insight into the pathophysiology and management of patients with diastolic dysfunction 5.