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Influence of Vitamin C on Baroreflex Sensitivity in Chronic Heart Failure

Abstract— Chronic heart failure (CHF) reduces baroreflex sensitivity. Low baroreflex sensitivity, a risk factor for sudden death, could arise partly from CHF‐dependent endothelial dysfunction. Vitamin C at high doses has a protective role against CHF‐related endothelial damage. This study was conducted to investigate the effect of vitamin C on baroreflex sensitivity in CHF. A study group of 33 subjects with CHF secondary to postischemic dilated cardiomyopathy with an ejection fraction <=35% and a control group (11 subjects) underwent assessment of baroreflex sensitivity by the phenylephrine method and an autonomic nervous system study by power spectral analysis. Variables were assessed after infusion of placebo and high doses of vitamin C (2.5 mg). In subjects with CHF, baroreflex sensitivity was significantly higher after vitamin C than after placebo infusion (placebo: 4.1±0.4 versus vitamin C: 5.3±0.5 ms/mm Hg, P <0.001). Low‐frequency of R‐R (LFRR), expressed in normalized units (NU) (P <0.05); LF/high‐frequency (HF) ratio (P <0.05), and LF of SBP (LFSBP) decreased significantly; HF power (P <0.05), and [alpha]‐HF (P <0.001) increased. Conversely, in the control group, baroreflex sensitivity and other spectral variables measured at baseline, after placebo, and after vitamin C infusion remained statistically unchanged (placebo: 10.2±0.1 versus vitamin C: 10.0±0.2 ms/mm Hg, NS). Acute administration of vitamin C at high doses improves baroreflex sensitivity and vagal sinus modulation in patients with CHF. This finding could have notable clinical and therapeutic implications. Key issues to understand are whether the beneficial effect persists during chronic administration and whether it helps to improve survival.

Effects of Long-Term Beta-Blocker (Metoprolol or Carvedilol) Therapy on QT Variability in Subjects With Chronic Heart Failure Secondary to Ischemic Cardiomyopathy

Chronic heart failure (CHF) is a risk factor for sudden death. Temporal and spatial changes in repolarization are among the most studied mechanisms for inducing fatal ventricular arrhythmias. Beta blockers effectively reduce the risk of sudden death in CHF. Our aim in this study was to investigate changes induced by metoprolol and carvedilol on the QT variability index (QTVI), a new measure reflecting the temporal heterogeneity of cardiac repolarization. A total of 82 subjects, who were in New York Heart Association functional class II or III, underwent short-term spectral analysis of RR and QT variability before and after a 1-year course of high-dose metoprolol (40 subjects) or carvedilol (42 subjects) at baseline (rest) and after sympathetic stress (head-up tilt). At rest, both drug-treated groups had lower QTVI (p <0.001) than after placebo, but during tilt patients treated with carvedilol had a lower QTVI than those treated with metoprolol (p <0.05). Although both beta-blocker treatments helped to normalize the QTVI measured in normal subjects at rest, they each differentially altered the index after tilt. Carvedilol seemed to improve the QTVI more than metoprolol.

Autonomic Modulation and QT Interval Dispersion in Hypertensive Subjects With Anxiety

Anxiety is associated with an increased risk of sudden death. QT dispersion is a marker of cardiac repolarization instability and is seen in conditions of high risk of sudden death. The purpose of this study was to evaluate autonomic nervous system control and QT dispersion in hypertensive subjects with anxiety symptoms. In a recent preliminary study, we observed that hypertensive individuals reporting high scores on a self-assessment anxiety scale had more marked left ventricular hypertrophy. In 105 hypertensive subjects divided into 3 groups according to severity of anxiety, we evaluated autonomic control by short-term power spectral analysis of RR and arterial pressure variability at rest (baseline) and during sympathetic stress (tilt test), left ventricular mass index, and heart rate-corrected QT (QTc) dispersion. At baseline, hypertensive subjects with higher anxiety symptom scores had significantly lower high-frequency RR values expressed in absolute terms (P<0.05) and in normalized units (P<0.05) than their counterparts without anxiety symptoms. Hypertensive subjects with anxiety also had a higher mean left ventricular mass index (P<0.001) and greater QTc dispersion (P<0.001). Both indexes and high frequency (P<0.05) correlated with severity of anxiety. These findings suggest that anxiety is associated with autonomic imbalance. This condition could favor an increase in left ventricular mass. Myocardial hypertrophy alone or combined with neuroautonomic imbalance may lead to QT dispersion.

Heart rate and blood pressure variability in subjects with vasovagal syncope

Autonomic nervous system control in subjects with vasovagal syncope is controversial. In the present study, we used short-term spectral analysis to evaluate autonomic control in subjects with recurrent vasovagal syncope. We assessed the ability of spectral indices of HR (heart rate) variability to predict tilt-test responses. A series of 47 outpatients with recurrent vasovagal syncope and with positive responses to head-up tilt testing underwent a further study of RR variability during controlled breathing at rest and during tilt testing. During controlled breathing, RR interval variability of total power (TP(RR); P<0.001), low-frequency power (LF(RR); P<0.05), high-frequency power (HF(RR); P<0.001) and HF expressed in normalized units (HFnu(RR); P<0.001) were all higher, and LF expressed in normalized units (LFnu(RR)) and LF/HF ratio were lower in subjects with vasovagal syncope than in controls (P<0.001). To assess the ability of spectral components of RR variability to predict tilt-test responses, we prospectively studied 109 subjects with recurrent vasovagal syncope. The two normalized measures, HFnu(RR) and LFnu(RR), determined during controlled breathing alone predicted a positive tilt-test response (sensitivity, 76%; specificity, 99%; positive predictive value, 96%; and negative predictive value, 90%). During tilting, subjects with vasovagal syncope had lower SBP (systolic blood pressure; P<0.05), LF component of peak SBP variability (LF(SBP)) and LFnu(RR) than controls, and higher TP(RR), HF(RR), HFnu(RR) and alpha HF (P<0.001). These spectral data indicate that vagal sinus modulation is increased at rest in subjects with vasovagal syncope. Spectral analysis of RR variability during controlled breathing, a procedure that predicts tilt-test responses, could be a useful guide in choosing the method of tilt testing.

QT interval dispersion and autonomic modulation in subjects with anxiety

This study was designed to assess Q-T interval dispersion as a marker of electrical instability in subjects with anxiety. Recent observations have shown that the presence of anxiety symptoms increases the risk of sudden death. The Kawachi anxiety questionnaire identified 29 subjects (male/female ratio 13:16) who scored 0, 22 subjects (male/female ratio 14:8) who scored 1, and 37 subjects (male/female ratio 13:24) who scored 2 or more. In all subjects we measured electrocardiographic interlead QT dispersion and autonomic function through spectral analysis of R-R interval and blood pressure variabilities and left ventricular mass. Compared with subjects who scored 0, those reporting 2 or more symptoms showed increased heart rate-corrected QT dispersion (54.9+/-1.7 ms vs. 34.9+/-3.2 ms, P<.001), sympathetic modulation (normal logarithm low-frequency power/high-frequency power 0.59+/-0.1 vs. 0.12+/-0.04, P<.05), and left ventricular mass (120.7+/-3.5 g/m2 vs. 97.9+/-2.8 g/m2, P<.001). Probably because it augments sympathetic activity, anxiety causes left ventricular mass to increase and, like hypertension, increases heart rate-corrected Q-T interval dispersion. The consequent electrical instability could be the substrate responsible for inducing fatal ventricular arrhythmias.

Factors influencing heart rate variability power spectral analysis during controlled breathing in patients with chronic heart failure or hypertension and in healthy normotensive subjects

A decreased LFP (low-frequency power) spectral component of HRV [HR (heart rate) variability] is a risk factor for sudden death in patients with CHF (chronic heart failure). In the present study, we evaluated factors (age, arterial pressures and HR) influencing LFP and HFP (high-frequency power) components in short-term recordings during controlled breathing in patients with CHF or hypertension, and healthy normotensive subjects. In patients with CHF, we also compared LFP values with known markers of sudden death [NYHA (New York Heart Association) class, HR and ejection fraction]. All HRV measures were significantly lower in patients with CHF than in hypertensive and normotensive subjects (P<0.001), and in hypertensive than in normotensive subjects (P<0.05). Stepwise multiple regression analysis showed that, in patients with CHF, LFP was inversely associated with NYHA class (beta=-0.5, P<0.0001) and HR (beta=-0.2, P=0.001) and was positively associated with ejection fraction (beta=0.28, P<0.0001). In patients with CHF, LFP remained unchanged with age. In normotensive and hypertensive subjects, HFP decreased with age, but in patients with CHF it did not. In the >/=60<70 and >/=70 years of age subgroups, we found no difference between HFP in the three groups studied. Hence, in normotensives and hypertensives, LFP tended to diminish with age (beta=-0.4, P<0.0001 in normotensives; beta=-0.4, P<0.001 in hypertensives) and was inversely associated with HR (beta=-0.2, P=0.002 in normotensives; beta=-0.3, P=0.002 in hypertensives). Conversely, in patients with CHF, LFP is predominantly influenced by NYHA class, HR and ejection fraction, but not by age. LFP might therefore increase the sensitivity of factors already used in stratifying the risk of sudden death in patients with CHF.