Effects of short-acting and long-acting loop

diuretics on heart rate variability in

patients with chronic compensated
congestive heart failure.
Tomiyama H, Nakayama T, Watanabe G, Shiojima K, Sakuma Y, Yamamoto A, Imai Y,
Yoshida H, Doba N. - Am. Heart J. - ; 137 (3); 543-8

Abstract
We investigated the effects of a short-acting loop diuretic (furosemide) and a long-acting loop
diuretic (azosemide) on heart rate variability, fluid balance, and neurohormonal responses in
patients with mild to moderate chronic congestive heart failure.
Nineteen patients with mild to moderate chronic congestive heart failure received furosemide
(40 to 60 mg/day) or azosemide (60 to 90 mg/day) for 5 days in a crossover manner. We
performed time-domain and frequency-domain analyses of 24-hour Holter
electrocardiographic recordings to assess heart rate variability.
The 24-hour urinary sodium excretion was similar during the furosemide and azosemide
treatment periods but was significantly greater in the first 2 hours after drug administration
during furosemide treatment. Plasma renin activity and the hematocrit level increased and
high-frequency power significantly decreased 2 hours after the administration of furosemide
only. The standard deviation of all normal R-R intervals and the root mean square of
successive differences in the R-R interval were lower with furosemide than with azosemide
(P <.05).
Furosemide, a short-acting loop diuretic, has a greater influence on heart rate variability and
fluid balance than azosemide, a long-acting loop diuretic, in patients with mild to moderate
chronic congestive heart failure.

Citation
Effects of short-acting and long-acting loop diuretics on heart rate variability in patients
with chronic compensated congestive heart failure. Tomiyama H, Nakayama T, Watanabe G,
Shiojima K, Sakuma Y, Yamamoto A, Imai Y, Yoshida H, Doba N - Am. Heart J. - ; 137 (3);
543-8
MEDLINE is the source for the citation and abstract for this record

Superiority of long-acting to short-acting

loop diuretics in the treatment of congestive
heart failure.
Masuyama T, Tsujino T, Origasa H, Yamamoto K, Akasaka T, Hirano Y, Ohte N, Daimon T,
Nakatani S, Ito H. - Circ. J. - ; 76 (4); 833-42

Abstract
Diuretics are the most prescribed drug in heart failure (HF) patients. However, clinical
evidence about their long-term effects is lacking. The purpose of this study was to compare
the therapeutic effects of furosemide and azosemide, a short- and long-acting loop diuretic,
respectively, in patients with chronic heart failure (CHF).
In this multicenter, prospective, randomized, open, blinded endpoint trial, we compared the
effects of azosemide and furosemide in patients with CHF and New York Heart Association
class II or III symptoms. 320 patients (160 patients in each group, mean age 71 years) were
followed up for a minimum of 2 years. The primary endpoint was a composite of
cardiovascular death or unplanned admission to hospital for congestive HF. During a median
follow-up of 35.2 months, the primary endpoint occurred in 23 patients in the azosemide
group and in 34 patients in the furosemide group (hazard ratio [HR], 0.55, 95% confidence
interval [CI] 0.32-0.95: P=0.03). Among the secondary endpoints, unplanned admission to
hospital for congestive HF or a need for modification of the treatment for HF were also
reduced in the azosemide group compared with the furosemide group (HR, 0.60, 95%CI
0.36-0.99: P=0.048).
Azosemide, compared with furosemide, reduced the risk of cardiovascular death or
unplanned admission to hospital for congestive HF.

Citation
Superiority of long-acting to short-acting loop diuretics in the treatment of congestive heart
failure. Masuyama T, Tsujino T, Origasa H, Yamamoto K, Akasaka T, Hirano Y, Ohte N,
Daimon T, Nakatani S, Ito H - Circ. J. - ; 76 (4); 833-42
MEDLINE is the source for the citation and abstract for this record

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Abstract
MEDLINE

Novel measures of heart rate variability

predict cardiovascular mortality in older
adults independent of traditional
cardiovascular risk factors: the
Cardiovascular Health Study (CHS).
Stein PK, Barzilay JI, Chaves PH, Mistretta SQ, Domitrovich PP, Gottdiener JS, Rich
MW, Kleiger RE. - J. Cardiovasc. Electrophysiol. - ; 19 (11); 1169-74

Abstract
Novel HRV Predicts CV Mortality in the Elderly.
It is unknown whether abnormal heart rate turbulence (HRT) and abnormal fractal properties
of heart rate variability identify older adults at increased risk of cardiovascular death
(CVdth).
Data from 1,172 community-dwelling adults, ages 72 +/- 5 (65-93) years, who participated in
the Cardiovascular Health Study (CHS), a study of risk factors for CV disease in people
>or=65 years. HRT and the short-term fractal scaling exponent (DFA1) derived from 24-hour
Holter recordings. HRT categorized as: normal (turbulence slope [TS] and turbulence onset
[TO] normal) or abnormal (TS and/or TO abnormal). DFA1 categorized as low (<or=1) or
high (>1). Cox regression analyses stratified by Framingham Risk Score (FRS) strata (low =
<10, mid = 10-20, and high >20) and adjusted for prevalent clinical cardiovascular disease
(CVD), diabetes, and quartiles of ventricular premature beat counts (VPCs).
CVdths (N = 172) occurred over a median follow-up of 12.3 years. Within each FRS stratum,
low DFA1 + abnormal HRT predicted risk of CVdth (RR = 7.7 for low FRS; 3.6, mid FRS;
2.8, high FRS). Among high FRS stratum participants, low DFA1 alone also predicted CVdth
(RR = 2.0). VPCs in the highest quartile predicted CVdth, but only in the high FRS group.
Clinical CV disease predicted CVdth at each FRS stratum (RR = 2.9, low; 2.6, mid; and 1.9,
high). Diabetes predicted CVdth in the highest FRS group only (RR = 2.2).
The combination of low DFA1 + abnormal HRT is a strong risk factor for CVdth among
older adults even after adjustment for conventional CVD risk measures and the presence of
CVD.

CECIL :

Goldman's Cecil Medicine. Goldman, Lee, MD and Schafer, Andrew I., MD

Heart Rate and Rhythm

Heart rate affects cardiac performance by two mechanisms. First, increasing the heart rate
enhances the inotropic state by upregulating cytosolic calcium concentrations. Second, heart
rate is an important determinant of cardiac output and is the primary mechanism by which
cardiac output is matched to demand in situations such as exercise. Because stroke volume is
relatively fixed in the failing heart, heart rate becomes a major determinant of cardiac output.
Chronic tachycardia impairs ventricular performance, however, and cardiac function can
decline rapidly with sustained tachyarrhythmias (as seen in atrial fibrillation, atrial flutter,
chronic atrial tachycardia, and even inappropriate sinus tachycardia).
Optimal cardiac performance depends on a well-coordinated sequence of
contraction. Normal atrioventricular conduction times (0.16 to 0.20 second)
enhance the contribution of atrial contraction to LV filling, which is particularly
important in the noncompliant ventricle. Patients with heart failure frequently
have intraventricular conduction abnormalities, which result in dyssynchronous
contractions, such that the septum and parts of the anterior wall begin
contracting only after systole has ended in other regions. Cardiac
resynchronization therapy can prevent the onset of heart failure in patients with
significant ventricular dyssynchrony, usually manifest electrically as a left bundle
branch block.