NEW ORLEANS — A study that was unable to prove its primary hypothesis was still able to showcase a new way to assess diastolic dysfunction of the heart, a technique poised to help researchers explore new approaches to heart therapy.
“To our knowledge, this was the first study to demonstrate directly that blood pressure lowering can improve diastolic function, even in mildly hypertensive patients,” said Dr. Scott D. Solomon, director of noninvasive cardiology at the Brigham and Women's Hospital in Boston.
The findings also suggest that “diastolic dysfunction is an early measure of end-organ damage and suggest a potential mechanistic link between hypertension and heart failure with preserved ejection fraction.”
The technique used in the study is known as Doppler tissue imaging (DTI), which uses standard Doppler echocardiography hardware and software to directly measure myocardial relaxation velocity at the mitral anulus, a way to noninvasively assess diastolic dysfunction, Dr. Solomon said at the annual meeting of the American College of Cardiology. DTI already has a role for assessing patients with hypertension to determine whether high blood pressure has begun to impair heart relaxation, which can lead to diastolic dysfunction and heart failure.
“If a patient has a DTI abnormality and even mild hypertension, it makes me more aggressive [about reducing] blood-pressure,” he said in an interview.
Most Doppler echocardiography units made in recent years can assess DTI. The most robust measure of DTI to gauge heart relaxation is Eé (E prime), the measure of the heart's early relaxation velocity. The study that Dr. Solomon reported at the meeting was designed to test whether blood pressure reduction using the angiotensin receptor blocker valsartan was especially effective for improving Eé, compared with other antihypertensive drugs in patients with hypertension and an impaired relaxation velocity.
The underlying hypothesis was that a drug that reduces activation of the renin-angiotensin-aldosterone system (RAAS) would be more effective than other antihypertensive medications for reducing left ventricular hypertrophy and fibrosis and thereby improving diastolic function. The Valsartan in Diastolic Dysfunction study was sponsored by Novartis, which markets valsartan (Diovan). Dr. Solomon is a consultant to and has received honoraria from Novartis.
The study involved 384 patients aged 45 years or older with stage 1 or 2 hypertension, who also showed diastolic dysfunction based on their lateral Eé measure. The average Eé reading for all patients in the study was 7.5 cm/sec, substantially below the normal level for age (see box). The middle-aged patients had an average Eé level comparable with that of a 76-year-old person with no history of hypertension, Dr. Solomon said. Their average blood pressure at entry was about 144/86 mm Hg, and their average left ventricular ejection fraction was about 57%. About 4% of the participants had left ventricular hypertrophy.
The patients were randomized to two different antihypertensive regimens. One group received as its primary drug 320 mg/day of valsartan, followed by other, non-RAAS-affecting drugs as needed to reach a goal blood pressure of less than 135/80 mm Hg. The second group had the same goal blood pressure but did not receive any drugs that affect the RAAS. Alternative agents were used in this order: a diuretic, β-blocker, calcium channel blocker, and α-blocker. The control patients received significantly more antihypertensive medications, especially diuretics and calcium channel blockers.
After 9 months of treatment, the average blood pressure was 129/78 mm Hg in the patients treated with valsartan, and an average of 134/82 in the patients who did not get an RAAS-active drug. Follow-up DTI data were available for 341 patients. The study's primary end point was an improvement in the Eé measure, which rose by an average of 0.60 cm/sec in patients treated with valsartan and by an average of 0.44 cm/sec in the control patients. The difference between average improvements in the two groups was not statistically significant. But Eé was significantly improved over baseline levels in both groups, indicating that lowering blood pressure improves diastolic function.
The two groups did show a significant difference in two secondary efficacy measures made using DTI. Both the isovolumic relaxation time and the systolic contraction velocity showed improvements that were significantly greater in the valsartan group, compared with the control patients.
A DTI echocardiogram shows an early-relaxation velocity (Eé) of 17 cm/sec, an indication of normal diastolic function. Courtesy Dr. Scott D. Solomon