Maria Teresa La Rovere

Baroreflex sensitivity: measurement and clinical implications.

Alterations of the baroreceptor‐heart rate reflex (baroreflex sensitivity, BRS) contribute to the reciprocal reduction of parasympathetic activity and increase of sympathetic activity that accompany the development and progression of cardiovascular diseases. Therefore, the measurement of the baroreflex is a source of valuable information in the clinical management of cardiac disease patients, particularly in risk stratification. This article briefly recalls the pathophysiological background of baroreflex control, and reviews the most relevant methods that have been developed so far for the measurement of BRS. They include three “classic” methods: (i) the use of vasoactive drugs, particularly the α‐adrenoreceptor agonist phenylephrine, (ii) the Valsalva maneuver, which produces a natural challenge for the baroreceptors by voluntarily increasing intrathoracic and abdominal pressure through straining, and (iii) the neck chamber technique, which allows a selective activation/deactivation of carotid baroreceptors by application of a negative/positive pressure to the neck region. Two more recent methods based on the analysis of spontaneous oscillations of systolic arterial pressure and RR interval are also reviewed: (i) the sequence method, which analyzes the relationship between increasing/decreasing ramps of blood pressure and related increasing/decreasing changes in RR interval through linear regression, and (ii) spectral methods, which assess the relationship (in terms of gain) between specific oscillatory components of the two signals. The limitations of the coherence criterion for the computation of spectral BRS are discussed, and recent proposals for overcoming them are presented. Most relevant clinical applications of BRS measurement are finally reviewed with particular reference to patients with myocardial infarction and heart failure.

Ambulatory electrocardiogram-based tracking of T wave alternans in postmyocardial infarction patients to assess risk of cardiac arrest or arrhythmic death.

Introduction: This is the first study to assess T wave alternans (TWA) analyzed from routine ambulatory electrocardiograms (AECGs) to identify postmyocardial infarction (post‐MI) patients at increased risk for arrhythmic events.

Comparison of baroreflex sensitivity and heart period variability after myocardial infarction

In animals, baroreflex sensitivity is inversely related to the likelihood of ventricular fibrillation during myocardial ischemia. After myocardial infarction in human patients, reduced baroreflex sensitivity is associated with increased mortality. A reduced standard deviation of normal RR intervals over a 24 h period is also associated with reduced survival after myocardial infarction. Therefore, 32 normotensive men who had survived their first myocardial infarction were studied to define the relation between baroreflex sensitivity assessed with phenylephrine injection and three Holter electrocardiographic measures of tonic vagal activity: the percent of successive normal RR intervals greater than 50 ms, the root mean square successive difference of normal RR intervals and the power in the high frequency energy of the normal RR interval power spectrum. Correlations among the Holter measures of heart period variability were greater than or equal to 0.94, indicating that these measures are so strongly correlated that any one of them can be used to represent the others. Baroreflex sensitivity showed weaker correlations with the three Holter variables (0.57 to 0.63), indicating that the Holter measures did not accurately predict baroreflex sensitivity. Baroreflex sensitivity showed a stronger correlation with the three Holter variables during the night than during the day. Baroreflex sensitivity and tonic vagal activity reflected by Holter variables were reduced more in patients with inferior myocardial infarction than in those with anterior infarction. The relative utility of baroreflex sensitivity and Holter measures of tonic vagal activity in predicting sudden cardiac death after myocardial infarction needs to be evaluated in a large prospective study.

Risk stratification for sudden cardiac death: current status and challenges for the future

Sudden cardiac death (SCD) remains a daunting problem. It is a major public health issue for several reasons: from its prevalence (20% of total mortality in the industrialized world) to the devastating psycho-social impact on society and on the families of victims often still in their prime, and it represents a challenge for medicine, and especially for cardiology. This text summarizes the discussions and opinions of a group of investigators with a long-standing interest in this field. We addressed the occurrence of SCD in individuals apparently healthy, in patients with heart disease and mild or severe cardiac dysfunction, and in those with genetically based arrhythmic diseases. Recognizing the need for more accurate registries of the global and regional distribution of SCD in these different categories, we focused on the assessment of risk for SCD in these four groups, looking at the significance of alterations in cardiac function, of signs of electrical instability identified by ECG abnormalities or by autonomic tests, and of the progressive impact of genetic screening. Special attention was given to the identification of areas of research more or less likely to provide useful information, and thereby more or less suitable for the investment of time and of research funds.

Nonlinear indices of heart rate variability in chronic heart failure patients: Redundancy and comparative clinical value

Aims: We aimed to assess the mutual interrelationships and to compare the prognostic value of a comprehensive set of nonlinear indices of heart rate variability (HRV) in a population of chronic heart failure (CHF) patients.

Neural control of heart rate is an arrhythmia risk modifier in long QT syndrome.

OBJECTIVESnThe purpose of this study was to test the hypothesis that differences in autonomic responses might modify clinical severity in long QT syndrome type 1 (LQT1) patients, those with KCNQ1 mutations and reduced I(Ks), in whom the main arrhythmia trigger is sympathetic activation.nnnBACKGROUNDnSome long QT syndrome (LQTS) patients experience life-threatening cardiac arrhythmias, whereas others remain asymptomatic throughout life. This clinical heterogeneity is currently unexplained.nnnMETHODSnIn a South African LQT1 founder population segregating KCNQ1-A341V, we correlated major cardiac events to resting heart rate (HR) and to baroreflex sensitivity (BRS) on and off beta-adrenergic blockers (BB).nnnRESULTSnIn 56 mutation carriers (MCs), mean HR was lower among asymptomatic patients (p < 0.05). Among MCs with a QT interval corrected for heart rate <or=500 ms, those in the lower HR tertile were less likely to have suffered prior cardiac events (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.04 to 0.79, p < 0.02). The BRS was lower among asymptomatic than symptomatic MCs (11.8 +/- 3.5 ms/mm Hg vs. 20.1 +/- 10.9 ms/mm Hg, p < 0.05). A BRS in the lower tertile was associated with a lower probability of being symptomatic (OR 0.13, 95% CI 0.02 to 0.96, p < 0.05). A similar trend was observed during BB. The MCs in the lower tertile for both HR and BRS were less frequently symptomatic than MCs with different patterns (20% vs. 76%, p < 0.05). Subjects with either ADRA2C-Del322-325 or homozygous for ADRB1-R389, 2 polymorphisms predicting enhanced adrenergic response, were more likely to have BRS values above the upper tertile (45% vs. 8%, p < 0.05).nnnCONCLUSIONSnLower resting HR and relatively low BRS are protective factors in KCNQ1-A341V carriers. A plausible underlying mechanism is that blunted autonomic responses prevent rapid HR changes, arrhythmogenic when I(Ks) is reduced. These findings help understanding phenotypic heterogeneity in LQTS and identify a physiological risk modifier, which is probably genetically determined.

Interaction Between Exercise Training and Ejection Fraction in Predicting Prognosis After a First Myocardial Infarction

BACKGROUNDnAlthough recent meta-analysis trials have shown that exercise training may improve survival after myocardial infarction, the mechanism of this beneficial effect is still unknown. The purpose of this study was to detect possible interactions between exercise training and predictors of prognosis after a first myocardial infarction.nnnMETHODS AND RESULTSnPatients with uneventful clinical courses after a first myocardial infarction were randomly assigned to a 4-week training period (125 patients, group 1) or to a control group (131 patients, group 2). Before randomization, all patients underwent a symptom-limited exercise test (28 +/- 2 days after myocardial infarction), 24-hour Holter monitoring, and coronary arteriography (31 +/- 3 days after the acute episode). After a mean follow-up period of 34.5 months, 18 patients had cardiac deaths (5 in group 1 and 13 in group 2). Multivariate analysis by Cox regression model showed that ejection fraction was the only independent prognostic indicator (P = .03). Evidence existed of an interaction between ejection fraction and exercise training, showing an effect of physical training on survival that depended on the patients ejection fraction. Among patients with ejection fractions < 41%, the relative risk for an untrained patient was 8.63 times higher than for a trained patient (P = .04), whereas for ejection fractions > 40%, the estimated risks for trained and untrained patients were similar.nnnCONCLUSIONSnThese data show that exercise training may prolong survival in post-myocardial infarction patients with depressed left ventricular function. A randomized trial in such patients seems warranted.

Vagal reflexes following an exercise stress test: A simple clinical tool for gene-specific risk stratification in the long QT syndrome

OBJECTIVESnThe study assessed whether heart rate (HR) reduction following an exercise stress test (ExStrT), an easily quantifiable marker of vagal reflexes, might identify high- and low-risk long QT syndrome (LQTS) type 1 (LQT1) patients.nnnBACKGROUNDnIdentification of LQTS patients more likely to be symptomatic remains elusive. We have previously shown that depressed baroreflex sensitivity, an established marker of reduced vagal reflexes, predicts low probability of symptoms among LQT1.nnnMETHODSnWe studied 169 LQTS genotype-positive patients < 50 years of age who performed an ExStrT with the same protocol, on and off β-blockers including 47 South African LQT1 patients all harboring the KCNQ1-A341V mutation and 122 Italian LQTS patients with impaired (I(Ks)-, 66 LQT1) or normal (I(Ks)+, 50 LQT2 and 6 LQT3) I(Ks) current.nnnRESULTSnDespite similar maximal HR and workload, by the first minute after cessation of exercise the symptomatic patients in both I(Ks)- groups had a greater HR reduction compared with the asymptomatic (19 ± 7 beats/min vs. 13 ± 5 beats/min and 27 ± 10 beats/min vs. 20 ± 8 beats/min, both p = 0.009). By contrast, there was no difference between the I(Ks)+ symptomatic and asymptomatic patients (23 ± 9 beats/min vs. 26 ± 9 beats/min, p = 0.47). LQT1 patients in the upper tertile for HR reduction had a higher risk of being symptomatic (odds ratio: 3.28, 95% confidence interval: 1.3 to 8.3, p = 0.012).nnnCONCLUSIONSnHR reduction following exercise identifies LQT1 patients at high or low arrhythmic risk, independently of β-blocker therapy, and contributes to risk stratification. Intense exercise training, which potentiates vagal reflexes, should probably be avoided by LQT1 patients.

Autonomic Response to Cardiac Dysfunction in Chronic Heart Failure: A Risk Predictor Based on Autonomic Information Flow

Background: Chronic heart failure (CHF) is associated with a complex dysfunction of cardiac, cardiovascular, autonomic, and other mechanisms. Autonomic information flow (AIF) characteristics calculated from heart rate patterns were recently found as promising predictors of outcome in several cardiovascular diseases.

Assessment of Baroreflex Sensitivity

By governing autonomic outflow to the heart and circulation, arterial baroreceptors play a central role in controlling short-term blood pressure responses to the continuous perturbations produced by various stimuli occurring in daily life. Although in a physiological setting baroreflex mediated changes in autonomic outflow affect heart rate, myocardial contractility and peripheral resistance, the baroreflex control of heart rate in pathological conditions is of particular interest, since it has been associated with an increased propensity for cardiac mortality and sudden cardiac death.1