Isolated diastolic heart failure is a common form of heart failure, especially in the elderly, and is now a recognized cause of increased morbidity and mortality. In a focused session on echocardiography and diastolic function, existing predictors of outcome in diastolic dysfunction were evaluated in large patient data sets and newer parameters were investigated in select patient cohorts.
Prognostic role of known mortality predictors
Left ventricular (LV) hypertrophy
In 47,701 patients without severe valvular heart disease and preserved LV systolic function, relative wall thickness and LV mass index were independent predictors of mortality over a mean 1.7 years of follow-up in all age groups (<50, 50-70, and >70 years). *Three categories of LV geometry were evaluated: normal, eccentric hypertrophy (evaluated by LV mass index), and concentric hypertrophy (evaluated by relative wall thickness).1 Both LV mass index and relative wall thickness were independently associated with increased mortality in all groups.
Relative wall thickness was by far the strongest independent predictor of all-cause mortality, especially in younger patients. The mean hazard ratio for increased relative wall thickness was 34 for those younger than age 50; 10 for those between 50 and 70 years; and 5.5 for those older than age 70. Baseline demographics of the study population were not discussed, including prevalence of hypertension, diabetes, and coronary artery disease (CAD), use of medications, or the independent influence of these risk factors on mortality.
Left atrial (LA) volume index
In the same cohort of patients (47,865), LA volume index was an independent predictor of mortality in all 4 geometric groups: normal, concentric remodeling, eccentric hypertrophy, and concentric hypertrophy. Mean ± 1 standard deviation of LA volume index was 32. There was a 15% versus 6% mortality in those with increased LA volume index compared with those who had a normal index.2 A more recent study has shown that an increased LA volume index has the same prognostic significance as a low ejection fraction in patients with CAD.3 The presented study shows the prognostic power of LA volume index over the pattern of LV hypertrophy in subjects with normal LV systolic function.
LA volume index and LA function
Other investigators examined the predictive value of a combined evaluation of LA function and geometry in patients presenting with dyspnea (mean age, 63 years). In 163 patients, LA volume index/A’ (annular A’ velocity averaged over medial and lateral annulus) had a similar predictive value as B-type natriuretic peptide (BNP) and E/E’ (ratio of mitral peak velocity of early filling [E] to early diastolic mitral annular velocity [E’]) in determining diastolic dysfunction grade (area under the curve = 0.91, 0.90, and 0.93, respectively; P was not significant).4 The best cut off value of LA volume index/A’ was 4. In the 68 patients with LA volume index/A’ of 4 or more, BNP was much higher (1207 vs 176 pg/mL) and pulmonary atrial reversal duration was greater than mitral inflow A duration (25 vs -3). At 13-month follow-up, this parameter was an independent predictor of a combined outcome of death and rehospitalization for heart failure (odds ratio [OR] = 3.9) in those 65 years or older (OR = 3.8) with an ejection fraction less than 50% (OR = 4.8).
LA diameter and LA function
One group used left atrial diameter along with LA systolic force (derived from mitral valve orifice area and peak A velocity with a cutoff point of 14.33 Kdynes) as a surrogate of LA function in 2808 subjects with a mean age of 59 years in the Strong Heart study. Of these subjects, 43% had hypertension, 47% had diabetes, and 54% were obese. There was a 2.7% incidence of heart failure over an 8-year follow-up. When adjusting for age, sex, hypertension, diabetes, obesity, LV mass, ejection fraction, and E/A ratio (ratio of early [E] to late atrial [A] mitral Doppler peak flow velocity), the presence of LA enlargement or increased LA force was not associated with a higher risk of heart failure, but when combined there was a higher risk of heart failure (OR = 1.9).5
E/E’ and LA volume index in heart failure
E/E’ (septal) has been shown to correlate with pulmonary capillary wedge pressure. One group evaluated the predictive power of E/E’ and LA volume index for first heart failure.6 Of 917 patients with a mean age of 73 years and no history of heart failure, atrial arrhythmia, or valvular disease, and who were followed for a mean of 3.5 years, E/E’ above 14 predicted first heart failure with a sensitivity and specificity of 54% and 83%, respectively. The prediction of first heart failure was more accurate when both LA volume index and E/E’ were included (C-statistic for the multivariate model including both factors was 0.76 versus 0.70 for LA volume index alone).
Infarct related artery coronary flow reserve and LV diastolic function after a first acute myocardial infarction (MI)
Studies have shown the prognostic value of diastolic dysfunction in patients who have experienced a first acute MI.7 A study from Japan evaluated a combination of coronary flow velocity and LV diastolic function in 201 patients who had a first left anterior descending infarct and underwent successful primary percutaneous coronary intervention (PCI).8 After stenting, coronary flow velocity was measured distal to the lesion by an intracoronary Doppler wire. Three days following the acute MI, conventional echo Doppler was performed. Three categories of patients were evaluated: those with nonrestrictive mitral inflow (deceleration time ≥130 ms), those with normal coronary velocity (D wave deceleration time >600 ms and no systolic flow reversal), and those with restrictive inflow, microvascular dysfunction, or both. Diastolic function was measured by mitral inflow E wave deceleration time. At 6 months, repeat LV grams were performed and LV remodeling was defined as an LV end-diastolic volume index of 20% or more. The incidence of LV remodeling at 6 months was 6% in those with nonrestrictive mitral inflow; 37% in those with normal coronary velocity, but restrictive mitral inflow; and 83% in those with restrictive inflow, microvascular dysfunction, or both (P <.001). Those with LV remodeling also had a higher prevalence of thrombolysis in MI grade II flow and abnormal blush grade after PCI.
Isovolumic relaxation velocity by 2D speckle tracking in nonischemic cardiomyopathy
In 52 patients with nonischemic cardiomyopathy and a mean age of 57 years, 2D speckle tracking was used in the 18 apical segments to determine relaxation velocity in the global isovolumic relation period by strain rate.9 During a follow-up of 22 months, 15 patients developed cardiac events (sudden cardiac death, hospitalization for congestive heart failure (CHF) or refractory CHF (class III or IV). On multivariate analysis, including age, ejection fraction, end-systolic volume index, diastolic strain rate-isovolumetric relaxation (SR-IVR), and systolic dyssynchrony index, SR-IVR was the only independent echocardiographic predictor of cardiac events. In 8 of 15 patients with cardiac events, the SR-IVR value was negative.
Triphasic mitral inflow pattern
The prognostic significance of an L’ wave in patients with triphasic mitral inflow, marked by the presence of an L wave, was evaluated in 185 patients over a mean follow-up of 36 months.10 Those with an L’ wave on mitral annular Doppler (57% of those with mitral inflow L wave) had higher BNP levels, LV mass index, LA volume index, E/E’, and mitral inflow L wave velocity. These patients also had a higher incidence of all-cause death and rehospitalization for heart failure than those without (12.4% vs 10.8%). In the multivariate model including age, Killip class, renal insufficiency, and moderate-to-severe mitral regurgitation, the presence of an L’ wave was the most independent predictor of adverse outcome in these patients. The cutoff velocity when L or L’ is abnormal on mitral inflow or mitral annular Doppler was not discussed.
LV diastolic functional reserve
A study from Korea evaluated a new parameter, namely, LV diastolic function reserve index, which was calculated as E’ base x ΔE’ (ΔE’ was the change of E’ from baseline to exercise).11 This study included 227 diabetic patients with a mean ejection fraction of 0.68. Over 34 months of follow-up, the primary end point, which was a composite of all-cause death and rehospitalization for heart failure, occurred in 14 patients (6.1%). When examining age, CAD history, renal insufficiency, LV mass index, LA volume index, and ejection fraction, LV diastolic function reserve was the most independent predictor of adverse outcomes. After patients were classified by the median value of LV diastolic function reserve index at 50 W of exercise, patients with an index below 13.5 showed poorer clinical outcomes compared with those with an index of 13.5 or above (P = .001).
Studies have extended the role of LV hypertrophy pattern, LA volume index, and E/E’ as prognostic variables in asymptomatic CAD and acute MI patients. New parameters, including coronary microvascular functional reserve and LV diastolic flow reserve, were evaluated in patients presenting with a first acute MI treated with acute PCI and in diabetic patients with normal systolic function. The findings of prognostic significance of microvascular dysfunction after acute MI could add significantly to the clinical care of patients with acute MI if Doppler flow reserve could be measured by transthoracic echocardiography. Other parameters evaluated included triphasic mitral inflow pattern and LV diastolic functional reserve on stress testing. The cutoff velocity when L or L’ is abnormal on mitral inflow or mitral annular Doppler was not discussed.
*Increased relative wall thickness with normal ventricular mass (‘concentric remodeling’), increased mass with normal relative wall thickness (eccentric hypertrophy), and concentric hypertrophy (increase in both variables). Normal LV mass is considered <125 g/m2. Concentric remodeling is defined by the thickness of the septum or posterior wall divided by the LV radius at end-diastole ≥0.45.