Effects of Nebivolol on Left Ventricular and Left Atrial Morphodynamics in Adults With Hypertension and Isolated Diastolic Dysfunction
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Improvement in Exercise Tolerance
研究概览
简要总结
To investigate whether treatment with Nebivolol in subjects with high blood pressure and abnormal filling of left ventricle (LVDD) improves exercise time by improving Left Ventricular deformation and filling.
详细描述
Background:
The left ventricle (LV) ejects blood with a wringing motion, where the LV apex rotates counterclockwise and the base rotates in clockwise directions respectively. Rapid untwisting and recoil of LV during isovolumic relaxation and early diastole releases energy stored in ejection for LV suction and rapid early diastolic restoration. The LV geometry and its rotational mechanics also give rise to intracavitary blood flow rotation resulting into LV intracavitary vortex ring formation. LV torsion and vortex ring formation confer morphodynamic advantages that gain importance as blood flow velocities, heart rate and rates of change of momentum increase with exertion for improving LV efficiency. We have recently characterized the significance of LV twist mechanics and vortex ring formation in human hearts using novel high resolution speckle and contrast particle tracking echocardiography. Although data on a favorable effect of nebivolol on exercise capacity and LV diastolic filling exists, the changes in left ventricular (LV) rotational mechanics and blood flow vortex ring formation that may explain the potential hemodynamic benefits seen with nebivolol have not been previously characterized.
Aims:
In patients with hypertension and left ventricular diastolic dysfunction (LVDD) treatment with nebivolol for 6 months improves exercise time by enhancing:
- LV deformation, torsion and untwisting mechanics
- LA-to-LV blood flow transport and characteristics of intra-cavitary vortex formation
- LA reservoir and booster pump function and LA-LV interaction during the conduit phase
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •History of mild (140-160 / 90-100) to moderate (160-200 / 100-120) hypertension
- •LV diastolic dysfunction (>/= Grade1)
- •LV ejection fraction >50%
- •Indexed left atrial volume >/= 28 mL/m^2
- •In sinus rhythm at the time of enrollment
- •Willingness to return for the 6-month follow up investigations
排除标准
- •Presence or history of any of the following at baseline:
- •History of mitral valve disease of greater than mild severity or prosthetic mitral valve, congenital heart disease or permanent pacemaker
- •Calculated creatinine clearance <50 mL/min
- •Terminal Illness with expected Survival of <1 year
- •Previous Heart Transplant
- •Individuals who are institutionalized
- •Systolic BP>180 mm Hg or diastolic BP > 120 mm Hg
- •Medical treatment for elevated BP with:
- •Calcium channel blocker (e.g. verapamil, nifedipine);
- •Alpha blocker (e.g. prazosin);
- •Alpha agonist (e.g. α-methyldopa, hydralazine, clonidine)
- •Patient unwilling or unable to provide informed consent for study participation
- •Pregnancy (current, or anticipated within the study period)
- •Secondary Hypertension
- •Previous echo contrast allergy
- •Poor echocardiography window
- •Previous stroke, known carotid stenosis
- •Contraindication for beta-blocker therapy (sinus bradycardia <50 beats/min);
- •2nd or 3rd degree AV conduction block
- •Overt congestive cardiac failure (NYHA Class III-IV)
- •Known bronchospastic disease
- •Known hepatic dysfunction (SGOT/PT > twice above normal levels)
研究组 & 干预措施
Nebivolol
Nebivolol 5 mg (titrated to a maximal dose of 10mg for optimal blood pressure) for 6 months
干预措施: Nebivolol (Drug)
结局指标
主要结局
Improvement in Exercise Tolerance
时间窗: at 6 months
measured by stress echocardiogram, number of participants who had improvement in METS and improvement in exercise time as compared to their baseline.
次要结局
- E Velocity Indexed to e' (E/e' Ratio) of the Left Ventricle(at 6 months)
- Untwist Rate of the Left Ventricle(at 6 months)
研究者
Partho Sengupta
Associate Professor
Icahn School of Medicine at Mount Sinai