Immunosuppression in Myocarditis
Immunosuppression in patients with active lymphocytic myocarditis is most likely to be beneficial when there are circulating cardiac autoantibodies and no viral genome in the myocardium, according to Italian researchers in this week’s issue of Circulation (Circulation. 2003;107:857–863).
In this study led by Andrea Frustaci, MD, from the Department of Cardiology at Catholic University in Rome, Italy, 41 of 112 patients with a histological diagnosis of active lymphocytic myocarditis and lack of response to conventional therapy were treated with prednisone and azathioprine for 6 months. All underwent cardiac catheterization, angiography, and endomyocardial biopsy after 1 and 6 months of treatment. All were monitored for 1 year.
Of 41 patients, 21 had prompt improvement in left ventricular ejection fraction and showed evidence of healed myocarditis when they underwent biopsy. However, the other 20 patients did not respond. Twelve remained the same, 3 underwent heart transplantation, and 5 died.
Polymerase chain reaction of frozen endomyocardial tissue showed viral genomes present in 17 nonresponders. Among the viruses found were enterovirus, Epstein-Barr virus, adenovirus, influenza A virus, and parvovirus-B19. Viral genomes were also identified in 3 responders—all of them hepatitis C. Cardiac autoantibodies were present in 19 of the responders and in none of those who did not respond.
ACE Inhibitors in the Elderly
Treating older patients with high-blood pressure angiotensin converting enzyme (ACE) inhibitors resulted in better outcomes than treatment with diuretics, even though the blood pressures achieved were similar, according to Australian researchers in this week’s issue of the New England Journal of Medicine (N Engl J Med. 2003;348:583–592).
The researchers, led by Lindon M.H. Wing, MB, BS, of the School of Medicine at Flinders University in Adelaide, Australia, randomized 6083 hypertensive subjects aged 65 to 84 years to receive either ACE inhibitors or diuretics. The prospective study was randomized and open label with blinded assessment of end points. The subjects in the study were followed for a median of 4.1 years. The total number of cardiovascular events in the two treatment groups was assessed.
By the end of the study, each group had achieved a similar decrease in blood pressure. However, there were 695 cardiovascular events or deaths from any cause in the ACE-inhibitor group and 736 cardiovascular events or deaths from any cause in the diuretic group. Among male subjects, the hazard ratio was 0.83; among female subjects, it was 1.00. Rates of nonfatal cardiovascular events and myocardial infarctions decreased with ACE-inhibitor treatment. However, the number of strokes was similar in each group although there were more fatal strokes in the group that took ACE inhibitors.
The researchers concluded, “In elderly subjects with hypertension, particularly among male subjects, ACE–inhibitor-based therapy resulted in an outcome advantage over a diuretic-based regimen, despite similar reductions in blood pressure. This finding was observed in family practices, where most elderly persons with hypertension receive their care. The question of whether the relative benefit of beginning treatment with an ACE–inhibitor-based regimen is confined to men requires examination in large, ongoing trials.”
In an accompanying editorial (JAMA. 2002;288:2981–2997), Edward D. Frolich, MD, of the Ochsner Clinic Foundation in New Orleans, La, noted the conflict of these findings with those of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). In his opinion piece titled “Treating Hypertension: What are We to Believe?” Dr Frolich noted that in considering how to apply such results, physicians should consider the sources of information. In both the trial led by Dr Wing and ALLHAT, the studies were supervised by national health research institutions and had no commercial influence. However, he noted that the diuretics in each study were different. The Australian study used hydrochlorothiazide and ALLHAT used chlorthalidone.
“There have been no head-to-head trial comparing the efficacy of and outcomes with these two diuretics,” he said. The Australians used enalapril whereas ALLHAT used lisinopril. Again, he noted, there have been no head-to-head comparisons between those two drugs.
“We may also ask whether these were the only drugs used to control blood pressure in these trials. The answer to this question is equivocal in both trials, other antihypertensive medications were frequently required to achieve blood pressure goals, and the use of these additional agents also compounds the complexities of any comparison between the trials,” he wrote.
He concluded: “Treatment of the individual patient with hypertension is complicated, requiring time and judgment. In choosing between a diuretic and an ACE inhibitor, the physician can make a reasonable selection by reviewing the patient’s history and course. We must remember that trials describe population averages for the purposes of developing guidelines, whereas physicians must focus on the individual patient’s clinical responses.”
Genetic Cause of Inherited Long–QT-Syndrome Found
An international consortium led by researchers at Duke University Medical Center and the Howard Hughes Medical Institute has identified a novel mechanism of cardiac arrhythmia involved in inherited long–QT-syndrome (LQTS), a fatal form of inherited dysrhythmia that usually strikes young, seemingly healthy people.
In a report in the February 6, 2003, issue of the journal Nature (Nature. 2003;421:634–639), researchers led by Peter Mohler, PhD, a Howard Hughes post-doctoral fellow at Duke, found a mutation in a specific gene that coded for ankyrin-B, a protein found within heart muscle cells. When normal, this protein insures that the ion channels in heart muscles open and close in a coordinated manner, allowing chemicals such as calcium, potassium, and chloride to go into and out of heart muscle cells as the heart beats. This insures the proper regulation of electrical activity within the heart.
When the gene for ankyrin-B is mutated in the disease studied by the researchers, the channels do not open in the right place or at the right time. LQTS is a dominant genetic disorder. The researchers studied a large French family in which LQTS occurred frequently. They found a specific mutation in the gene associated with LQTS in 22 of 24 family members and with abnormal heart rhythms in 23 of 24. There was no mutation found in 400 control samples.
“We found that two normal copies of the ankyrin-B gene are necessary for normal calcium signaling, and that the E1425G mutation leads to a loss of function,” said Dr Mohler in a released statement, “So, ankyrin-B is the first identified protein implicated in a congenital LQTS that is not an ion channel.”