refers to an abnormality in the heart's (i.e. left ventricle
's) filling during diastole
. Diastole is that phase of the cardiac cycle
when the heart (i.e. ventricle
) is not contracting but is actually relaxed and filling with blood that is being returned to it, either from the body (into right ventricle
) or from the lungs (into left ventricle
Significance of Diastolic Dysfunction
In optimal left sided performance of the heart, blood mass loads forward in an unobstructed manner from the lungs, into the pulmonary veins
, into the left atrium
, through the mitral valve
, and finally into the left ventricle
. When the left ventricle
cannot be normally filled due to deterioration of preload
and during diastole, blood regurgitates into the left atrium
and, eventually, in a backward gradient into the lungs. Physiologically this results in a higher than normal [mismatch] pressure gradient of blood within the vessels of the lung. As a result of hydrostatic forces
, this pressure mismatch leads to leaking of fluid (i.e. transudate
) from the pulmonary blood vessels into the air-spaces (alveoli
) of the lungs. The result is pulmonary edema
, a condition characterized by difficulty breathing, inadequate oxygenation
of blood, and, if severe and untreated, death. Pulmonary edema developed as a result of diastolic dysfunction is not fully imparted by failing pump function of the left ventricle. Indeed, it may result from the left ventricle's inability to readily accept blood trying to enter it from the left atrium.
Diastolic dysfunction is characterized by elevated diastolic pressure in the left ventricle despite normal or sub-normal diastolic volume. Diastolic dysfunction is further characterized by measurable deterioration of compliance
of the myocardium. Histologic evidence supporting diastolic dysfunction demonstrates hypertrophy of the cardiomyocytes
, increased interstitial collagen deposition and/or infiltration of the myocardium. These influences collectively lead to a downhill spiral in distensibility of the myocardium. The ventricle then behaves as a balloon made from abnormally thick rubber. Despite filling with high pressure, the volume cannot expand adequately. If the heart cannot fill with blood easily, either the cardiac output becomes diminished or compensation ensues to increase the ventricular diastolic pressure to higher levels. When the left ventricular diastolic pressure is elevated, venous pressure in the lungs must also become elevated to maintain forward flow. Increased pulmonary venous pressure results in alveolar edema causing the patient to be short of breath.
It is crucial to note that a normal heart that is overfilled with blood may demonstrate increased stiffness and decreased compliance characteristics. This is analogous to a balloon that is over-filled with air. Blowing more air into the balloon becomes difficult because the balloon acts stiff and non-compliant at a filling volume it wasn't designed to hold. It is wrong to classify the volume overloaded heart as having diastolic dysfunction just because it is behaving stiff and non-compliant. The term diastolic dysfunction should therefore not be applied to the dilated heart. Dilated hearts are overly distensible due to cardiomyopathy or myocardial infarction. The term diastolic dysfunction is often erroneously applied in this circumstance when increased fluid volume retention causes the heart to be over-filled.
Compliance of the failing myocardium is well described in axis theory of general physics. Inexpensive echocardiographically reproducible short axis performance of the myocardium has been best described by the work of Pierre LaPlace. Long axis performance physics of the myocardium are best described in the work of Robert Hooke.
Risk Factors and Causes
Any condition or process that leads to stiffening of the left ventricle can lead to diastolic dysfunction.
Some causes of left ventricular stiffening include:
- high blood pressure (i.e. hypertension, where, as a result of left ventricular muscle hypertrophy to deal with the high pressure, the left ventricle has become stiff)
- aortic stenosis of any cause (here as with hypertension, the ventricular muscle has hypertrophied and thence become stiff, as a result of the increased pressure load placed on it by the stenosis)
- scarred heart muscle (e.g. occurring after a heart attack) (scars are relatively stiff)
- diabetes (stiffening occurs presumably as a result of glycosylation of heart muscle)
- severe systolic dysfunction that has led to ventricular dilation (i.e when the ventricle has been stretched to a certain point, any further attempt to stretch it more, as by blood trying to enter it from the left atrium, meets with increased resistance - it has become stiff
- reversible stiffening as can occur during periods of cardiac ischemia
Diagnosis of diastolic dysfunction or diastolic heart failure remains imprecise. This has made it difficult to conduct clinical trials of treatments for diastolic heart failure. In some studies, diastolic dysfunction has been defined as heart failure with normal systolic function. That is, a patient is defined as having diastolic dysfunction if they have signs and symptoms of heart failure but the left ventricular ejection fraction is normal. A second approach is to use an elevated BNP level in the presence of normal EF to diagnose diastolic heart failure. These are both probably too broad a definition for diastolic heart failure and this group of patients is more precisely described as heart failure with normal systolic function. Echocardiography can be used to diagnose diastolic dysfunction. However, no one single echocardiographic parameter can make the diagnosis of diastolic heart failure. Multiple echo parameters have been proposed including mitral inflow velocity patterns, pulmonary vein flow patterns, tissue Doppler measurements, and M-mode echo measurements (ie. left atrial size). Algorithms have been developed which combine multiple echocardiographic parameters to diagnose diastolic heart failure.
There are four basic Echocardiographic patterns of diastolic heart failure, graded I to IV. The mildest form is called an abnormal relaxation pattern or grade I diastolic dysfunction. On the mitral inflow Doppler echocardiogram, there is reversal of the normal E/A ratio. This pattern may develop normally with age in some patients and many grade I patients will not have any clinical signs or symptoms of heart failure. Grade II diastolic dysfunction is called pseudonormal filling dynamics. This is considered moderate diastolic dysfunction and is associated with elevated left atrial filling pressures. These patients more commonly have symptoms of heart failure and many have left atrial enlargement due to the elevated pressures in the left heart. Grade III and IV diastolic dysfunction are called restrictive filling dynamics. These are both severe forms of diastolic dysfunction and patients tend to have advanced heart failure symptoms. Class III diastolic dysfunction patients will demonstrate reversal of their diastolic abnormalities on echocardiogram when they perform the Valsalva maneuver and are called reversible restrictive diastolic dysfunction. Class IV diastolic dysfunction patients will not demonstrate reversibility of their echocardiogram abnormalities and are therefore called fixed restrictive diastolic dysfunction. The presence of either class III and IV diastolic dysfunction is associated with a significantly worse prognosis. These patients will have left atrial enlargement and many will have a reduced left ventricular ejection fraction indicating a combination of systolic and diastolic dysfunction.
By and large, diastolic dysfunction is chronic process (except during acute ischemia
- see above). When this chronic condition is well tolerated by an individual, no specific treatment may be indicated. Rather, therapy should be directed at the root cause of the stiff left ventricle with things like high blood pressure and diabetes treated appropriately. Conversely, and as noted above, diastolic dysfunction tends to be better tolerated if the atrium is able to pump blood into the ventricles in a coordinated fashion. This does not occur in atrial fibrillation
where there is no coordinated atrial activity. Hence, atrial fibrillation should be treated aggressively in people with diastolic dysfunction. In the same light, and also as noted above, if the atrial fibrillation persists and is leading to a rapid heart rate, treatment must be given to slow down that rate.
At this date, the role of specific treatments for diastolic dysfunction per se is unclear. There is some evidence that calcium channel blocker drugs may be of benefit in reducing ventricular stiffness in some cases. Likewise, treatment with angiotensin converting enzyme inhibitors such as enalapril, ramipril, and many others, may be of benefit due to their effect on ventricular remodeling.
A major treatment consideration in people with diastolic dysfunction is when pulmonary edema develops. Unlike treatment of pulmonary edema occurring the setting of systolic dysfunction (where the primary problem is poor ventricular pumping as opposed to poor filling), the treatment of pulmonary edema complicating diastolic dysfunction emphasizes heart rate control (i.e. lowering it). Diuretics are often given as well. The role of afterload reduction in this setting is unknown.
Until recently, it was generally assumed that the prognosis for individuals with diastolic dysfunction and associated, intermittent pulmonary edema was better than those with systolic dysfunction. In fact, in two studies appearing in the New England Journal of Medicine
in 2006, evidence was presented to suggest that the prognosis in diastolic dysfunction is the same as that in systolic dysfunction