Katsuhisa Ishii

Adding thiazide to a renin-angiotensin blocker improves left ventricular relaxation and improves heart failure in patients with hypertension.

Hypertension is associated with an increased risk of diastolic dysfunction. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) have failed to show improvement in clinical outcomes for patients with diastolic dysfunction. In this study, we investigated the effect of changing an ACEi or ARB to a combination of losartan and hydrochlorothiazide (HCTZ) on left ventricular (LV) preload and relaxation in patients with hypertension and diastolic dysfunction. We enrolled 371 hypertensive patients with diastolic dysfunction who had not achieved their treatment goals with an ACEi or ARB. We switched the ACEi or ARB to losartan/HCTZ and followed the patients for 24 weeks. The primary end points were changes in septal mitral annular velocity during diastole (e′) and in the ratio of mitral inflow velocity to e′ velocity (E/e′ ratio) from baseline to the end of follow-up. Mean systolic and diastolic blood pressures (BP) decreased by 22 and 11u2009mmu2009Hg, respectively, after changing from an ACEi or ARB to losartan/HCTZ. The e′ velocity increased, and the E/e′ ratio and brain natriuretic peptide level decreased significantly. High-sensitivity C-reactive protein also decreased significantly (0.50 vs. 0.29u2009mgu2009dl−1, P<0.0001). There were only slight or no changes in glucose levels, homeostasis model assessment insulin resistance (HOMA-R), uric acid and electrolytes after the drug change. Changing from an ACEi or ARB to losartan/HCTZ is associated with a reduction in BP, improvement in LV relaxation, improvement in heart failure state and attenuation of systemic inflammation with few adverse effects in patients with hypertension and diastolic dysfunction.

Effect of Diuretic or Calcium-Channel Blocker Plus Angiotensin-Receptor Blocker on Diastolic Function in Hypertensive Patients

BACKGROUNDnHypertension increases the risk of left ventricular (LV) diastolic dysfunction, and anti-hypertensive therapy may improve LV relaxation. The aim of this study was to investigate whether combining an angiotensin-receptor blocker (ARB) with either hydrochlorothiazide (HCTZ) or a calcium-channel blocker (CCB) improves LV relaxation in patients with hypertension and diastolic dysfunction.nnnMETHODSANDRESULTSnHypertensive patients who had not achieved their target blood pressure with at least 4 weeks of ARB therapy were randomly assigned to receive either a fixed-dose combination of losartan and HCTZ (losartan/HCTZ; n=110) or a combination of amlodipine and a typical ARB dosage (CCB/ARB; n=121) and followed for 24 weeks. The primary endpoint was change in early diastolic mitral annular velocity (e, cm/s). Systolic blood pressure decreased in both groups after switch to the combination therapies. E velocity increased both in the losartan/HCTZ (0.52 cm/s) and in the CCB/ARB (0.59 cm/s) groups. The mean (95% CI) treatment difference was -0.02 (-0.37 to 0.34) cm/s, indicating that improvement in LV relaxation was similar between the groups. The ratio of early mitral inflow velocity to e velocity and left atrial volume index were significantly decreased in the losartan/HCTZ group.nnnCONCLUSIONSnThe combination of losartan and HCTZ is as effective as amlodipine plus ARB in improving LV relaxation in hypertensive patients.

Adding thiazide to a rennin-angiotensin blocker regimen to improve left ventricular relaxation in diabetes and nondiabetes patients with hypertension

The urinary albumin to creatinine ratio (UACR) is an independent predictor of outcomes in patients with diastolic dysfunction. Thus, we investigated the relationship between diastolic dysfunction, UACR, and diabetes mellitus (DM) in the EDEN study. We investigated the effect of switching from an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) to a combination of losartan and hydrochlorothiazide on left ventricular (LV) relaxation in patients with hypertension and diastolic dysfunction. We enrolled 106 patients with and 265 patients without DM. All patients had diastolic dysfunction and had not achieved their treatment goals with an ACEi or ARB. The measurements of e′ velocity and E/e′ ratio was performed with echocardiography as markers of LV diastolic function. We switched the ACEi or ARB to losartan/hydrochlorothiazide and followed these patients for 24 weeks. UACR was decreased in patients with DM (123.4 ± 288.4 to 66.5 ± 169.2 mg/g creatinine; P = 0.0024), but not in patients without DM (51.2 ± 181.8 to 39.2 ± 247.9 mg/g creatinine; P = 0.1051). Among DM patients, there was a significant relationship between changes in UACR and changes in e′ velocity (r = −0.144; P = 0.0257) and between changes in estimated glomerular filtration rate and changes in the E/e′ ratio (r = −0.130; P = 0.0436). Among patients without DM, there was a significant relationship between changes in high-sensitivity C-reactive protein (hs-CRP) and changes in E/e′ (r = 0.205; P = 0.0010). Multivariate analysis demonstrated changes in hemoglobin A1c levels as one of the determinants of change of e′ and E/e′ in patients with DM, whereas hs-CRP was the determinant of change of e′ among patients without DM. These data suggest that improvement in LV diastolic function is associated with an improvement of DM and a concomitant reduction in UACR among DM patients, and with a reduction of hs-CRP in patients without DM when thiazide is added to a renin–angiotensin blocker treatment regimen.

Changes in left ventricular relaxation after azelnidipine treatment in hypertensive patients with diabetes: subanalysis of a prospective single-arm multicentre study

Objectives We previously demonstrated that a calcium channel blocker, azelnidipine, improves left ventricular relaxation in patients with hypertension and diastolic dysfunction in a multicentre, Clinical impact of Azelnidipine on Left VentricuLar diastolic function and OutComes in patients with hypertension (CALVLOC) trial. The objectives of the present subanalysis were to investigate the differences in diastolic function in hypertensive patients with and without diabetes, and the efficacy of azelnidipine on diastolic function among them. Design Subanalysis of a prospective single-arm multicentre study. Participants 228 hypertensive patients with normal ejection fraction and impaired left ventricular relaxation (septal e′ velocity <8u2005cm/s on echocardiography) enrolled for CALVLOC trial. They were divided into two groups based on presence or absence of diabetes. Interventions Administration of 16u2005mg of azelnidipine for 8u2005months (range 6–10u2005months). Main outcome measures Septal e′ velocity before and at the end of the study. Results Whereas patients with diabetes (n=53, 23.2%) had lower systolic blood pressure (BP) than patients without diabetes (155±17 vs 161±16u2005mmu2005Hg, p=0.03), they had lower e′ velocity (5.7±1.5 vs 6.1±1.4u2005cm/s, p=0.04) at baseline. Azelnidipine decreased BP and heart rate, and increased e′ velocity similarly in patients with diabetes (5.7±1.5 to 6.3±1.5u2005cm/s, p=0.0003) and without diabetes (6.1±1.4 to 6.9±1.4u2005cm/s, p<0.0001). Increase in e′ velocity was not influenced by presence of diabetes, and patients with diabetes still had lower e′ velocity after treatment (p=0.006). There was a significant correlation between increase in e′ velocity and decrease in systolic BP (R=0.25, p=0.0001), which was not influenced by diabetes. Conclusions Comorbid diabetes could impair left ventricular relaxation independently in patients with hypertension, which might not be improved solely by BP lowering.

A novel global strain diastolic index correlates with plasma NT-proBNP levels in asymptomatic hypertensive patients with preserved left ventricular ejection fraction

BackgroundThe strain imaging diastolic index (SI-DI) was reported to be a sensitive marker of regional left ventricular (LV) delayed relaxation induced by ischemia. However, the clinical usefulness of the global SI-DI has not been evaluated. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a sensitive biomarker for the detection of asymptomatic diastolic LV dysfunction. This study investigated the ability of a novel parameter, the global SI-DI, obtained using 2D speckle tracking imaging (2DSI) to correlate with the plasma NT-proBNP levels in asymptomatic hypertensive patients with preserved LV ejection fraction.MethodsWe performed 2D echocardiography and 2DSI in 83 asymptomatic hypertensive patients with preserved ejection fraction (>45xa0%) and in 37 control subjects. In 2DSI, the LV longitudinal peak strain and the SI-DI of 18 LV segments were measured. NT-proBNP was measured in all subjects. The data were compared between hypertensive patients and normal controls.ResultsThe average peak strain and global SI-DI of 18 LV segments were significantly reduced in hypertensive patients compared with control subjects (Pxa0<xa00.05); however, only the global SI-DI was significantly correlated with log10 NT-proBNP (rxa0=xa0−0.469, Pxa0=xa00.001). In Pearson’s correlation analyses, log10 NT-proBNP was significantly correlated with E/e′, E/A ratio, early diastolic mitral annular velocity (e′), global peak strain, deceleration time of the E-wave, and LV ejection fraction. In the multiple stepwise regression analysis, the global SI-DI was the strongest independent determinant of log10 NT-proBNP (βxa0=xa0−0.386, Pxa0=xa00.008).ConclusionsThe global SI-DI derived from 2DSI correlates well with plasma NT-proBNP levels and may have prognostic value in asymptomatic hypertensive patients with preserved ejection fraction.