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<8 cm/s on echocardiography) enrolled for CALVLOC trial. They were divided into two groups based on presence or absence of diabetes. INTERVENTIONS: Administration of 16 mg of azelnidipine for 8 months (range 6-10 months). 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±16 mm Hg, p=0.03), they had lower e' velocity (5.7±1.5 vs 6.1±1.4 cm/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±1.5 cm/s, p=0.0003) and without diabetes (6.1±1.4 to 6.9±1.4 cm/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.

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 11 mm Hg, 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. 0.29 mg dl(-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.

Local coronary flow is associated with an unsuccessful complete block line at the mitral isthmus in patients with atrial fibrillation.

BACKGROUND: The addition of a mitral isthmus (MI) block line after pulmonary vein isolation could lead to a favorable outcome of catheter ablation in patients with atrial fibrillation (AF). However, it is sometimes tough to create a complete MI block line, and the cooling effect because of the local coronary flow may prevent the creation of a successful MI block line. METHODS AND RESULTS: This study enrolled 81 AF patients in whom the creation of an MI block line was attempted in those with persistent or pacing-inducible AF after pulmonary vein isolation. A local coronary artery (LCA) across the MI block line was observed in 43 (53%) of 81 patients, and a bidirectional MI block was successfully accomplished in 53 (65%) of 81 patients, at the estimated MI line. The ratio of a successful MI block line was significantly lower in the patients with an LCA than in those without an LCA (42% versus 92%; P<0.001). The mean diameter of the coronary sinus (0.59 ± 0.18 versus 0.82 ± 0.22 cm; P<0.001) and length of the estimated MI line (33.4 ± 9.9 versus 29.4 ± 7.1 mm; P=0.032) were significantly shorter in the patients with a successful MI block line than in those without a successful MI block line. In the multivariable analysis, an LCA at the MI and a larger coronary sinus diameter were independent risk factors for an unsuccessful MI block line. CONCLUSIONS: Local coronary flow at the MI is associated with an increased incidence of an unsuccessful MI block line.

A pre-existent elevated C-reactive protein is associated with the recurrence of atrial tachyarrhythmias after catheter ablation in patients with atrial fibrillation.

AIMS: It has been reported that an inflammatory process is involved in the development of atrial fibrillation (AF). In this study, we examined the hypothesis that a pre-existent inflammatory response may enhance the recurrence of AF after catheter ablation (CA). METHODS AND RESULTS: A total of 257 consecutive AF patients undergoing CA were enrolled in this study. The C-reactive protein was assessed by a high-sensitive radio-immunoassay 1 day before the procedure. Of the clinical characteristics, an advanced age, structural heart disease, and the left atrial (LA) diameter were significantly increased when the C-reactive protein level was elevated. Atrial fibrillation occurrences were significantly increased when the C-reactive protein level was elevated. A multivariate analysis demonstrated that an elevated C-reactive protein level [hazard ratio (95% CI); 2.23 (1.04-4.35)], the LA diameter [1.26 (1.10-1.66)], and persistent AF duration [2.13 (1.13-3.79)] were independent factors related to the recurrence of AF after CA. In the procedural findings, burst-inducible AF after pulmonary vein (PV) isolation was significantly increased, and the incidence of AF from the PVs was significantly lower when the C-reactive protein level was elevated. CONCLUSION: An elevated C-reactive protein level was associated with atrial structural and electrical remodelling maintaining AF, and the increased re-entrant atrial substrate might increase the recurrence of AF after the CA procedure.

Multiple arrhythmogenic foci associated with the development of perpetuation of atrial fibrillation.

BACKGROUND: The presence of multiple arrhythmogenic sources may be associated with the perpetuation of atrial fibrillation (AF). In this study, we investigated the hypothesis that multiple foci might be involved in the development of AF persistency. METHODS AND RESULTS: Two hundred fourteen consecutive patients with AF undergoing catheter ablation were enrolled in this study. The location of the arrhythmogenic foci was determined using simultaneous recordings from multipolar catheters before and after pulmonary vein isolation during an isoproterenol administration. We detected 500 arrhythmogenic foci (263 foci as AF initiators, and 237 foci as non-AF initiators). High-dose isoproterenol infusions (ranging from 2 to 20 microg/min) revealed potential arrhythmogenic foci, especially non-pulmonary vein foci (55%). Persistent AF was more highly associated with an incidence of multiple (>2) foci than paroxysmal AF (88% versus 65%, P=0.002), and a multivariate analysis demonstrated that multiple foci (>2) were an independent contributing factor for persistent AF (odds ratio; 95% confidence interval, 4.69; 1.82 to 12.09, P<0.001). In paroxysmal AF, the number of foci was higher in patients with long-term AF (>24 hours) than in those with short-lasting AF (2.64+/-0.14 versus 1.77+/-0.16, P=0.001). In the persistent AF group, the patients with short-lasting AF (<12 months) had a greater number of foci than did those with long-term AF (>12 months) (3.62+/-0.15 versus 1.92+/-0.16, P=0.04). CONCLUSIONS: Multiple foci were likely to be involved in the development of persistent AF. However, if AF persisted for >12 months, they may not have had a significant effect on the AF perpetuation.