Kazuaki Wakami

Correlation between Left Ventricular End-diastolic Pressure and Peak Left Atrial Wall Strain during Left Ventricular Systole

OBJECTIVE Left atrial (LA) reservoir function is determined by integration of LA relaxation and left ventricular (LV) systolic function, and LV diastolic dysfunction increases LA volume at end systole. This study investigates the effect of LV end-diastolic pressure on LA wall tension during LV systole. METHODS A total of 101 stable patients with sinus rhythm undergoing cardiac catheterization were studied. LA wall extension during LV systole was evaluated as LA wall strain in the longitudinal direction obtained using two-dimensional ultrasound speckle tracking imaging. LV end-diastolic pressure and LV end-systolic and end-diastolic volumes were obtained in cardiac catheterization, and LV ejection fraction was determined. RESULTS Peak LA wall strain during LV systole had a significant inverse correlation with LV end-diastolic pressure (r = - 0.76, P < .0001). This correlation was also significant in patients with preserved LV systolic function (LV ejection fraction > or =50%) (r = - 0.64, P < .0001). In patients with peak LA wall strain during LV systole of less than 30%, 89% had elevated LV end-diastolic pressure (> or =16 mm Hg). CONCLUSION Elevated LV end-diastolic pressure is associated with a decrease of peak LA wall strain in the longitudinal direction during LV systole. In patients with peak LA wall strain during LV systole of less than 30%, the majority had elevated LV end-diastolic pressure, while most patients with peak LA wall strain during LV systole 45% or higher had normal LV end-diastolic pressures. In patients whose LV ejection fraction is 50% or more, when peak LA wall strain during LV systole is between 30% and 44%, it is not possible to predict LV end-diastolic pressure from peak LA wall strain measures.

Effects of drug and exercise intervention on functional capacity and quality of life in heart failure with preserved ejection fraction: A meta-analysis of randomized controlled trials:

Background Patients with heart failure with preserved ejection fraction (HFpEF) are often elderly and their primary chronic symptom is severe exercise intolerance that results in a reduced quality of life (QOL).Thus, improvement of exercise capacity and QOL presents an important clinical outcome in HFpEF patients. Although the effects of interventions such as cardiovascular drugs and exercise training on exercise capacity and QOL in HFpEF patients have been examined in a number of clinical trials, the results are inconsistent due in part to limited power with small sample sizes. We aimed to conduct a meta-analysis of the randomized controlled trial (RCT)s on the effect of drug or exercise intervention on exercise capacity and QOL in HFpEF patients. Method and results The search of electronic databases identified five RCTs on exercise (245 patients) and eight RCTs on cardiovascular drugs (1080 patients). The pooled analysis showed that exercise training improved peak exercise oxygen uptake (VO2) (weighted mean difference (WMD) 2.283, 95% confidence interval (CI)) (1.318–3.248) ml/min/kg), six-minute walk distance (6MWD) (30.275 m (4.315–56.234)), and Minnesota Living with Heart Failure Questionnaire (MLHFQ) total score (8.974 points (3.321–14.627)) compared with usual care. In contrast, drug intervention did not improve peak VO2 (WMD (95% CI), –0.393 (−1.005–0.220) ml/min/kg), 6MWD (−9.463 (−21.455–2.530) m), or MLHFQ total score (1.042 (−0.982–3.066) point) compared with placebo or no treatment. Conclusion Our meta-analysis indicates that exercise training may be a therapeutic option to improve functional capacity and QOL in HFpEF patients.

The effect of statins on mortality in heart failure with preserved ejection fraction: a meta-analysis of propensity score analyses

BACKGROUND Nearly half of patients with heart failure (HF) have preserved ejection fraction (EF) and the mortality and morbidity of patients with HF with preserved EF (HFpEF) are high. However, no pharmacological therapy has been shown to improve survival in HFpEF patients. Previous retrospective and prospective observational studies have examined the prognostic impact of hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) in patients with HFpEF. However, the results are inconsistent due to limited power with small sample sizes and/or lack of adjustment for known prognostic factors and differences in baseline characteristics between patients treated with and without statins. METHODS We aimed to conduct a meta-analysis of prospective observational studies examining the effect of statin therapy on mortality in HFpEF patients with the use of propensity score analysis. RESULTS A total of 4 studies with 5,536 patients (2,768 patients [50%] on statins; mean age, 65-77 years; male, 43-66%; coronary artery disease, 42-64%; hypertension, 61-82%; diabetes, 20-29%; follow-up duration, 12-36 months) were included in this meta-analysis. The pooled analysis showed that statin therapy was associated with reduced mortality (odds ratio [95% CI] = 0.690 [0.493-0.965], P=0.030). CONCLUSION Our meta-analysis suggests the potential mortality benefit of statins in HFpEF. Further prospective observational studies and randomized controlled trials should be planned to confirm our observed potential survival benefit of statins in HFpEF.

Usefulness of Plasma Brain Natriuretic Peptide Measurement and Tissue Doppler Imaging in Identifying Isolated Left Ventricular Diastolic Dysfunction Without Heart Failure

Left ventricular (LV) diastolic dysfunction carries a substantial risk for the subsequent development of heart failure and reduced survival, even when it is asymptomatic. Plasma brain natriuretic peptide (BNP) level and tissue Doppler imaging indexes provide powerful incremental assessment of LV diastolic function. Accordingly, the aim of this study was to clarify whether these methodologies could identify LV diastolic dysfunction without heart failure in 280 patients with preserved LV ejection fractions (> or =50%) who underwent echocardiography and cardiac catheterization for the evaluation of coronary artery disease. Patients were classified into 2 groups, those with diastolic dysfunction (tau > or =48 ms; n = 91) and those with normal diastolic function (tau <48 ms; n = 189). Plasma BNP > or =22.4 pg/ml, an unexpectedly low value, had sensitivity of 74.7% and specificity of 60.8% for identifying isolated LV diastolic dysfunction; the combined use of BNP > or =22.4 pg/mL and mitral annular velocity during early diastole <7.4 cm/s had relatively low sensitivity of 44.0% but high specificity of 86.8%. In conclusion, using plasma BNP level and with the combination of BNP level and mitral annular velocity during early diastole, invasively proved isolated LV diastolic dysfunction without heart failure could be identified in patients with coronary artery disease.

Left ventricular global strain for estimating relaxation and filling pressure: A multicenter study

BACKGROUND Speckle-tracking echocardiography (STE)-derived parameters may have better correlation with left ventricular (LV) relaxation and filling pressure than tissue Doppler-derived parameters. However, it has not been elucidated which parameter - strain or strain rate - and which direction of myocardial deformation - longitudinal or circumferential - is the most useful marker of LV relaxation and filling pressure. METHODSANDRESULTS We conducted a prospective multicenter study and compared the correlation of tissue Doppler- and STE-derived parameters with the time constant of LV pressure decay (τ) and LV mean diastolic pressure (MDP) in 77 patients. The correlation of early-diastolic mitral annular velocity (e´) with τ was weak (r=-0.32, P<0.01), and that of peak longitudinal strain (LS) was the strongest (r=-0.45, P<0.001) among the STE-derived parameters. There was a modest correlation between LVMDP and the ratio of early-diastolic inflow velocity (E) to e´ (E/e´) (r=0.50, P<0.001). In contrast, the ratio of E to LS (E/LS) correlated strongly with LVMDP (r=0.70, P<0.001). The correlation of E/LS with LVMDP was significantly better than that for E/e´ (P<0.01). Receiver-operating characteristic analysis showed that E/LS had the largest area under the curve for distinguishing elevated LVMDP (E/LS 0.86, E/e´ 0.74, E/A 0.67). CONCLUSIONS STE-derived longitudinal parameters correlated well with LV relaxation and filling pressure. In particular, E/LS could be more accurate than E/e´ for estimating LV filling pressure. (Circ J 2016; 80: 1163-1170).

Reduced renal function is associated with combined increases in ventricular-systolic stiffness and arterial load in patients undergoing cardiac catheterization for coronary artery disease

Although mildly reduced renal function is associated with increased risk for heart failure in patients with coronary artery disease (CAD), mechanisms underlying the association remain unclear. We tested the hypothesis that abnormal ventricular-arterial interaction may occur in mildly reduced renal function. We examined the relationships of the estimated glomerular filtration rate (eGFR) with various indices reflecting ventricular–arterial coupling [effective arterial elastance (the ratio of left ventricular (LV) end-systolic pressure to stroke volume, Ea], LV end-systolic elastance (the ratio of LV end-systolic pressure to end-systolic volume, Ees), and the total arterial compliance (the ratio of stroke volume to aortic pulse pressure)] and those of LV systolic and diastolic function [peak systolic and diastolic mitral annular velocities (S′ and E′) and the ratio of peak early diastolic mitral inflow to annular velocity (E/E′)] in 320 consecutive patients who underwent cardiac catheterization for CAD and had normal (≥0.50) ejection fractions (EF). As eGFR decreased, Ea and Ees increased and total arterial compliance and E′ decreased. eGFR did not correlate with Ea/Ees, S′, or E/E′. After adjusting for potential confounders, the findings were generally similar, but the correlation of eGFR with E′ did not remain significant. In conclusion, reduced renal function may be associated with combined increases in ventricular-systolic stiffness and arterial load in known or suspected CAD patients with normal EF.

Relation of Plasma Levels of Adiponectin to Left Ventricular Diastolic Dysfunction in Patients Undergoing Cardiac Catheterization for Coronary Artery Disease

In the present study, we hypothesized that hypoadiponectinemia and hyperleptinemia might be associated with left ventricular (LV) diastolic dysfunction. To test the hypothesis, we examined the relation of the plasma levels of adiponectin and leptin with the indexes of LV diastolic and systolic function (relaxation time constant, end-diastolic pressure, and ejection fraction) in 193 consecutive patients undergoing cardiac catheterization for coronary artery disease (age 69 ± 9 years, 74% men; ejection fraction 68.4 ± 9.9%). Regardless of gender, the adiponectin levels correlated negatively with the relaxation time constant and end-diastolic pressure, and the correlations remained significant after adjustment for potential confounders, including age, body mass index, heart rate, blood pressure, and coronary artery disease severity. Adiponectin levels did not significantly correlate with the ejection fraction in either men or women. The leptin levels did not significantly correlate with the indexes of LV diastolic or systolic function in either men or women. In conclusion, we found that decreased adiponectin levels were associated with LV diastolic dysfunction in patients with known or suspected coronary artery disease.

Prognostic Value of Left Ventricular Diastolic Dysfunction in Patients Undergoing Cardiac Catheterization for Coronary Artery Disease

We hypothesized that left ventricular (LV) diastolic dysfunction assessed by cardiac catheterization may be associated with increased risk for cardiovascular events. To test the hypothesis, we assessed diastolic function by cardiac catheterization (relaxation time constant (Tau) and end-diastolic pressure (EDP)) as well as Doppler echocardiography (early diastolic mitral annular velocity (e′) and a ratio of early diastolic mitral inflow to annular velocities (E/e′)) in 222 consecutive patients undergoing cardiac catheterization for coronary artery disease (CAD). During a followup of 1364 ± 628 days, 5 cardiac deaths and 20 unscheduled cardiovascular hospitalizations were observed. Among LV diastolic function indices, Tau > 48 ms and e′ < 5.8 cm/s were each significantly associated with lower rate of survival free of cardiovascular hospitalization. Even after adjustment for potential confounders (traditional cardiovascular risk factors, the severity of CAD, and cardiovascular medications), the predictive value of Tau > 48 ms and e′ < 5.8 cm/s remained significant. No predictive value was observed in EDP, E/e′, or LV ejection fraction. In conclusion, LV diastolic dysfunction, particularly impaired LV relaxation assessed by both cardiac catheterization and Doppler echocardiography, is independently associated with increased risk for cardiac death or cardiovascular hospitalization in patients with known or suspected CAD.

The effect of beta-blockers on mortality in heart failure with preserved ejection fraction: A meta-analysis of observational cohort and randomized controlled studies.

BACKGROUND Nearly half of patients with heart failure (HF) have preserved ejection fraction (EF) and the mortality of patients with HF with preserved EF (HFpEF) is high. However, there is no therapy to improve survival in HFpEF. Although observational cohort studies (OCSs) have examined the survival benefit of beta-blockers in HFpEF, the results are inconsistent due to limited power with small sample sizes and/or lack of adjustment for known confounders. Furthermore, recent randomized controlled trial (RCT)s failed to show the mortality benefit of beta-blockers in HFpEF. However, these RCTs were not adequately powered and thus the definite conclusion cannot be drawn. METHODS AND RESULTS We aimed to conduct a meta-analysis of the effect of beta-blockers on mortality in HFpEF. The search of electronic databases identified 5 OCSs with propensity score (PS) analysis (12,315 patients), 6 OCSs without PS analysis (15,275 patients), and 3 RCTs (1046 patients). Beta-blocker use was associated with improved survival in the pooled analysis of OCSs with PS analysis (RR [95% CI]=0.79 [0.66-0.95]) and in that of OCSs without PS analysis (0.70 [0.52-0.94]). In the pooled analysis of RCTs, beta-blocker use was associated with non-significant reduced risk for mortality (RR [95% CI]=0.80 [0.61-1.05]). Overall, use of beta-blockers reduced the risk of mortality by 21% (RR [95% CI]=0.79 [0.71-0.88]). CONCLUSION Our meta-analysis suggests the potential mortality benefit of beta-blockers in HFpEF. Well-designed and powered RCTs should be planned to confirm our observed potential survival benefit of beta-blockers in HFpEF.

Peak mitral annular velocity during early diastole and propagation velocity of early diastolic filling flow are not interchangeable as the parameters of left ventricular early diastolic function.

The difference between peak mitral annular velocity during early diastole (Ea) and the propagation velocity of left ventricular (LV) early diastolic filling flow (Vp) obtained using Doppler imaging as LV relaxation parameters was not fully elucidated. Thus, this issue was investigated in 117 patients with suspected coronary artery disease. During cardiac catheterization, LV volumes, the LV relaxation time constant Tp, and inertia force of late systolic aortic flow were obtained. Ea significantly and closely correlated with Tp (r = -0.70, p <0.0001) and significantly but weakly correlated with LV ejection fraction (r = 0.37, p <0.0001) and inertia force (r = 0.34, p = 0.0002). Conversely, Vp significantly and closely correlated with both LV ejection fraction (r = 0.66, p <0.0001) and inertia force (r = 0.72, p <0.0001) and significantly but weakly correlated with Tp (r = - 0.35, p = 0.0001). In conclusion, Ea and Vp reflect different aspects of LV behavior from end-systole to early diastole. Ea can be used to index LV relaxation, whereas Vp might not be a proper parameter of LV intrinsic relaxation because it is significantly dependent on LV systolic function and LV chamber size at end-systole. Both parameters are not interchangeable as those of LV early diastolic function. Vp may be a noninvasive parameter of LV elastic recoil.