Nocturnal Hypoxemic Burden in Patients with Heart Failure: Emerging Prognostic Role of Its Non-Specific Component.

BACKGROUND: Nocturnal hypoxemic burden has been shown to be a robust, independent predictor of all-cause mortality in patients with heart failure and reduced ejection fraction (HFrEF) and to occur in a severe form even in patients with low or negligible frequency of respiratory events (apneas/hypopneas). This suggests the existence of two components of hypoxemic burden: one unrelated to respiratory events and the other related. The aim of this study was to characterize these two components and to evaluate their prognostic value. METHODS: Nocturnal hypoxemic burden was assessed in a cohort of 280 patients with HFrEF by measuring the percentage of sleep with an oxygen saturation (SpO2) <90% (T90), and the area of the SpO2 curve below 90% (Area90). Both indices were also recalculated within the sleep segments associated with respiratory events (event-related component: T90Eve, Area90Eve) and outside these segments (non-specific component: T90Nspec, Area90Nspec). The outcome of the survival analysis (Cox regression) was all-cause mortality. RESULTS: During a median follow-up of 60 months, 87 patients died. T90, Area90, and their components were significant in univariate analysis (p<0.05 all). However, when these indices were adjusted for known risk factors, T90, T90Nspec, Area90, and Area90Nspec remained statistically significant (p=0.018, hazard ratio (HR)=1.12, 95%CI=(1.02, 1.23); p=0.007, HR=1.20, 95%CI=(1.05, 1.37); p=0.020, HR=1.05, 95%CI=(1.01, 1.10); p=0.0006, HR=1.15, 95%CI=(1.06, 1.25)), whereas T90Eve and Area90Eve did not (p=0.27, p=0.28). These results were internally validated using bootstrap resampling. CONCLUSIONS: By demonstrating a significant independent association of non-specific hypoxemic burden with all-cause mortality, this study suggests that this component of total nocturnal hypoxemic burden may play an important prognostic role in patients with HFrEF.

Effect of lateral position on rostral fluid shift and relationship to severity of Cheyne-Stokes respiration in heart failure patients.

PURPOSE: Lateral sleep position has a significant beneficial effect on the severity of Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) in patients with heart failure (HF). We hypothesized that a reduction in rostral fluid shift from the legs in this position compared with the supine position may contribute to this effect. METHODS: In patients with CSR-CSA and an apnea-hypopnea index (AHI) ≥ 15/h (by standard polysomnography), uncalibrated leg fluid volume was measured in the supine, left lateral decubitus, and right lateral decubitus positions (in-laboratory assessment). The correlation between postural changes in fluid volume and corresponding changes in AHI was evaluated. Since there was no difference in both leg fluid volume and AHI between the right and left positions, measurements in these two conditions were combined into a single lateral position. RESULTS: In 18 patients with CSR-CSA, leg fluid volume increased by 2.7 ± 3.1% (p = 0.002) in the lateral position compared to the supine position, while AHI decreased by 46 ± 20% (p < 0.0001) with the same postural change. The correlation between postural changes in AHI and leg fluid volume was 0.22 (p = 0.42). Changes in leg fluid volume were a slow phenomenon, whereas changes in CSR-CSA severity were almost synchronous with changes in posture. CONCLUSION: Lateral position causes a reduction in rostral fluid shift compared to the supine position, but this change does not correlate with the corresponding change in CSR-CSA severity. The two changes occur on different time scales. These findings question the role of postural changes in rostral fluid shift as a determinant of corresponding changes in CSR-CSA severity.

CARDIAC chronotropic effects of sleep-disordered breathing in patients with heart failure.

It is still not known whether the oscillation in heart rate (HR) induced by sleep-disordered breathing (SDB) in patients with heart failure entails significant chronotropic effects. We hypothesised that since cyclical changes in ventilation and arterial blood gases during SDB affect HR through multiple and complexly interacting mechanisms characterised by large inter-subject variability, chronotropic effects may change from patient to patient. A total of 42 patients with moderate-to-severe chronic heart failure with systolic dysfunction underwent an in-hospital sleep study. Chronotropic effects of SDB were quantified by comparing the distribution of instantaneous HR during SDB with that during periods without SDB (noSDB) within the same night in each patient. Based on distribution changes from noSDB to SDB, 12, nine, 11, and 10 patients showed a significant tachycardic, bradycardic, tachycardic and bradycardic, and neither significant tachycardic nor significant bradycardic effect, respectively. Tachycardic and bradycardic effects were primarily due to an increase in the rate rather than in the magnitude of cyclical HR elevations and reductions, and were more prevalent and severe in patients with dominant obstructive and central events, respectively. The apnea-hypopnea index did not differ between groups. Conversely, the time spent with an oxygen saturation of <90% was greater in the tachycardic and tachycardic-bradycardic groups compared to the bradycardic group. These findings indicate that HR distribution changes induced by SDB can vary from patient to patient revealing four distinct and well-characterised chronotropic effects. These effects are related to the degree of hypoxic burden brought about by SDB and are affected by the type of sleep apnea (central/obstructive).

Quantitative assessment of the quality of home sleep studies: A computer-assisted approach.

Home monitoring is the most practical means of collecting sleep data in large-scale research investigations. Because the portion of recording time with poor-quality data is higher than in attended polysomnography, a quantitative assessment of the quality of each signal should be recommended. Currently, only qualitative or semi-quantitative assessments are carried out, likely because of the lack of computer-based applications to carry out this task efficiently. This paper presents an innovative computer-assisted procedure designed to perform a quantitative quality assessment of standard respiratory signals recorded by Type 2 and Type 3 portable sleep monitors. The proposed system allows to assess the quality (good versus bad) of consecutive 1-min segments of thoraco-abdominal movements, oronasal, nasal airflow and oxygen saturation through an automatic classifier. The performance of the classifier was evaluated in a sample of 30 unattended polysomnography recordings, comparing the computer output with the consensus of two expert scorers. The difference (computer versus scorers) in the percentage of good-quality segments was on average very small, ranging from -3.1% (abdominal movements) to 0.8% (nasal flow), with an average total classification accuracy from 90.2 (oronasal flow) to 94.9 (nasal flow), a Sensitivity from 0.93 (oronasal flow) to 0.98 (nasal flow), and a Specificity from 0.74 (nasal flow) to 0.86 (abdominal movements). In practical applications, the scorer can run a check-and-edit procedure, further improving the classification accuracy. Considering a sample of 270 unattended polysomnography recordings (recording time: 545 ± 44 min), the average time taken for the check-and-edit procedure of each recording was 6.9 ± 2.1 min for all respiratory signals.

Exercise Training After Pulmonary Endarterectomy for Patients with Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: After undergoing a procedure of pulmonary endarterectomy (PEA), patients with chronic thromboembolic pulmonary hypertension (CTEPH) may still experience reduced exercise capacity. Data on effects of exercise training in these patients are scant. OBJECTIVES: To evaluate the effectiveness of exercise training after PEA for CTEPH and if the presence of "residual pulmonary hypertension" may affect the outcome. METHODS: Retrospective data analysis of CTEPH patients undergoing inpatient exercise training after PEA. According to predefined criteria, patients were divided into those with (group 1) and without (group 2) a "good" post-surgery hemodynamic response. Assessments of the 6-min walking distance test (6-min walking distance test [6 MWT]: primary outcome) were performed before and after surgery (before training), after training and at 3-month follow-up. Hemodynamic and lung function data were also analyzed. RESULTS: Data of 84 and 26 patients of groups 1 and 2, respectively, were analyzed. After surgery patients showed a reduction in 6 MWT, which significantly reversed after training and further improved at 3 months (p = 0.0001), without any significant difference between groups. The percentage of patients reaching the minimal clinically important difference in 6 MWT was similar between groups. The sig-nificant (p = 0.0001) post-surgery improvement in hemodynamics was maintained at 3 months without any significant difference between groups. New York Heart Association functional class improved in parallel to the hemodynamic improvement. CONCLUSIONS: Exercise training in patients with CTEPH after PEA, an inpatient exercise training program, improves exercise capacity for up to 3 months, independently of the post-surgery hemodynamic response.

Paced Breathing Increases the Redundancy of Cardiorespiratory Control in Healthy Individuals and Chronic Heart Failure Patients.

Synergy and redundancy are concepts that suggest, respectively, adaptability and fault tolerance of systems with complex behavior. This study computes redundancy/synergy in bivariate systems formed by a target X and a driver Y according to the predictive information decomposition approach and partial information decomposition framework based on the minimal mutual information principle. The two approaches assess the redundancy/synergy of past of X and Y in reducing the uncertainty of the current state of X. The methods were applied to evaluate the interactions between heart and respiration in healthy young subjects (n = 19) during controlled breathing at 10, 15 and 20 breaths/minute and in two groups of chronic heart failure patients during paced respiration at 6 (n = 9) and 15 (n = 20) breaths/minutes from spontaneous beat-to-beat fluctuations of heart period and respiratory signal. Both methods suggested that slowing respiratory rate below the spontaneous frequency increases redundancy of cardiorespiratory control in both healthy and pathological groups, thus possibly improving fault tolerance of the cardiorespiratory control. The two methods provide markers complementary to respiratory sinus arrhythmia and the strength of the linear coupling between heart period variability and respiration in describing the physiology of the cardiorespiratory reflex suitable to be exploited in various pathophysiological settings.

Spontaneous baroreceptor reflex sensitivity for risk stratification of heart failure patients: optimal cut-off and age effects.

Baroreceptor reflex sensitivity (BRS) is an important prognostic factor because a reduced BRS has been associated with an adverse cardiovascular outcome. The threshold for a 'reduced' BRS was established by the ATRAMI study at BRS <3 ms/mmHg in patients with a previous myocardial infarction, and has been shown to improve risk assessment in many other cardiac dysfunctions. The successful application of this cut-off to other populations suggests that it may reflect an inherent property of baroreflex functioning, so our goal is to investigate whether it represents a 'natural' partition of BRS values. As reduced baroreflex responsiveness is also associated with ageing, we investigated whether a BRS estimate <3 ms/mmHg could be the result of a process of physiological senescence as well as a sign of BRS dysfunction. This study involved 228 chronic heart failure patients and 60 age-matched controls. Our novel method combined transfer function BRS estimation and automatic clustering of BRS probability distributions, to define indicative levels of different BRS activities. The analysis produced a fit clustering (cophenetic correlation coefficient 0.9 out of 1) and identified one group of homogeneous patients (well separated from the others by 3 ms/mmHg) with an increased BRS-based mortality risk [hazard ratio (HR): 3.19 (1.73, 5.89), P<0.001]. The age-dependent BRS cut-off, estimated by 5% quantile regression of log (BRS) with age (considering the age-matched controls), provides a similar mortality value [HR: 2.44 (1.37, 4.43), P=0.003]. In conclusion, the 3 ms/mmHg cut-off identifies two large clusters of homogeneous heart failure (HF) patients, thus supporting the hypothesis of a natural cut-off in the HF population. Furthermore, age was found to have no statistical impact on risk assessment, suggesting that there is no need to establish age-based cut-offs because 3 ms/mmHg optimally identifies patients at high mortality risk.

Pre-Discharge Evaluation in Heart Failure ­ Additive Predictive Value of the 6-Minute Walking Test to Clinical Scores.

BACKGROUND: We aimed to investigate whether the assessment of functional capacity by the 6-minute walking test (6MWT) might improve the predictive ability of 2 validated clinical scores for risk stratification in heart failure (HF). METHODS AND RESULTS: The Cardiac and Comorbid Conditions HF (3C-HF) and the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) scores were evaluated in 466 consecutive HF patients who completed a pre-discharge 6MWT. The 12-month event rate was 7.7%. Both the 2 scores and the 6MWT predicted all-cause mortality (all P<0.0001), with a hazard ratio of 2.650 [95%CI 1.879-3.737], 2.754 [95%CI 1.870-4.056] for each one SD increase in the 3C-HF and MAGGIC, respectively, and of 2.080 [95% CI 1.619-2.671] for each one SD decrease in the meters walked. The addition of a 6MWT to both the 3C-HF and MAGGIC scores significantly improved predictive discrimination (c-index 0.793 [95% CI 0.722-0.864] and 0.802 [95% CI 0.733-0.871], respectively) and risk classification (integrated discrimination improvement, IDI 0.052 [95% CI 0.024-0.101] and 0.046 [95% CI 0.020-0.102], respectively). In the intermediate and high risk strata identified on the basis of both the 3C-HF and MAGGIC scores, mortality rates significantly differed according to a distance walked < or ≥376 m. CONCLUSIONS: In HF patients, a pre-discharge evaluation combining the 6MWT to clinical scores improves prediction of 12-month mortality.

Sleep-wake fluctuations and respiratory events during Cheyne-Stokes respiration in patients with heart failure.

Fluctuations in sleep-wake state are thought to contribute to the respiratory instability of Cheyne-Stokes respiration in patients with heart failure by promoting the rhythmic occurrence of central apnea and ventilatory overshoot. There are no data, however, on the relationship between vigilance state and respiratory events. In this study we used a novel method to detect the occurrence of state transitions (time resolution: 0.25 s, minimum duration of state changes: 2 s) and to assess their time relationship with apnoeic events. We also evaluated whether end-apnoeic arousals are associated with a ventilatory overshoot. A polysomnographic, daytime laboratory recording (25 min) was performed during Cheyne-Stokes respiration in 16 patients with heart failure. Automatic state classification included wakefulness and non-rapid eye movement sleep stages 1-2. As a rule, wakefulness occurred during hyperpnoeic phases, and non-rapid eye movement sleep occurred during apnoeic events. Ninety-two percent of the observed central apneas (N = 272) were associated with a concurrent wakefulness → non-rapid eye movement sleep → wakefulness transition. The delay between wakefulness → non-rapid eye movement sleep transitions and apnea onset was -0.3 [-3.1, 3.0] s [median (lower quartile, upper quartile); P = 0.99 testing the null hypothesis: median delay = 0], and the delay between non-rapid eye movement sleep â†’ wakefulness transitions and apnea termination was 0.2 [-0.5, 1.2] s (P = 0.7). A positive/negative delay indicates that the state transition occurred before/after the onset or termination of apnea. Non-rapid eye movement sleep â†’ wakefulness transitions synchronous with apnea termination were associated with a threefold increase in tidal volume and a twofold increase in ventilation (all P < 0.001), indicating ventilatory overshoot. These findings highlight that wakefulness â†’ non-rapid eye movement sleep → wakefulness transitions parallel apnoeic events during Cheyne-Stokes respiration in patients with heart failure. The relationships between state changes and respiratory events are consistent with the notion that state fluctuations promote ventilatory instability.

Beneficial effects of physical activity on baroreflex control in the elderly.

The baroreflex mechanisms, by controlling autonomic outflow to the heart and circulation, contribute importantly to neural circulatory control. The main function of the baroreflex is to prevent wide fluctuations in arterial blood pressure and to maintain the physiological homeostasis under basal resting conditions and in response to acute stress. Baroreflex-mediated changes in autonomic outflow affect heart rate, myocardial contractility, and peripheral vascular resistance. The baroreflex control of heart rate is of particular interest in pathological conditions, since it has been associated with increased propensity for cardiac mortality and sudden death. Aging is associated with significant cardiovascular modifications. The changes in baroreflex function that occur with age have been systematically studied by several methodological approaches. The available evidence indicates a reduced arterial baroreflex control of heart rate favoring an increase in sympathetic and a decrease in parasympathetic drive to the heart as well as an impairment in the baroreceptor control of blood pressure. Both kinds of changes have resultant clinical implications. Exercise training can modulate the age-related decline in baroreflex function and the attending abnormalities in autonomic control, thus accounting for some of the beneficial effects of physical activity in reducing the risk of cardiovascular morbidity and mortality.

Can cardiorespiratory polygraphy replace portable polysomnography in the assessment of sleep-disordered breathing in heart failure patients?

PURPOSE: Portable polysomnography (PSG) and cardiorespiratory polygraphy are increasingly being used in the assessment of sleep-disordered breathing (SDB) in heart failure patients. Scoring of SDB from cardiorespiratory polygraphy recordings is based only on respiratory signals, while electroencephalographic, electrooculographic and electromyographic channels are taken into account when using PSG recordings. The aim of this study was to assess the agreement between these two scoring methods. METHODS: An overnight sleep study was performed in 67 heart failure patients using a standard portable polysomnograph. Each recording was scored twice, once using all acquired signals (PSG mode) and, after a median of 64 days, using only respiratory signals (cardiorespiratory mode). Agreement was assessed by Bland-Altman analysis and Cohen's kappa. RESULTS: We found that (1) more respiratory events were detected using cardiorespiratory analysis [median (25th percentile, 75th percentile), 75 (39, 200) events] compared to analysis of portable PSG [69 (29, 173) events, p < 0.0001], the extra events being, for the vast majority, central in origin; (2) the apnea/hypopnea index (AHI) estimated by cardiorespiratory polygraphy [11.9 (5.7, 30.8)/h] showed a negligible negative bias relative to portable PSG [15.1 (5.7, 33.6)/h; bias, -0.8 (-2.9, 0.4)/h, p = 0.0002]; (3) limits of agreement between the two systems (-6.2/h, 1.7/h) were much smaller than those previously observed between two nights using the same scoring modality; and (4) the kappa coefficient using categorised AHI was 0.89 (95% confidence interval (CI) 0.82, 0.96). CONCLUSIONS: We found a high degree of agreement between the AHIs obtained from the two scoring methods, thus suggesting that cardiorespiratory polygraphy may be used as an alternative to portable PSG in the assessment of SDB in heart failure patients.

Postural changes in lung volumes in patients with heart failure and Cheyne-Stokes respiration: Relationship with sleep apnea severity.

BACKGROUND AND AIM: It has been proposed that the increased severity of sleep apnea frequently observed in heart failure (HF) patients with Cheyne-Stokes respiration (CSR) when sleeping in the supine compared to the lateral position, may be caused by the concomitant reduction in functional residual capacity (FRC). We assessed positional changes in FRC in patients with CSR and investigated the relationship between these changes in the laboratory and corresponding changes in CSR severity during sleep. METHODS: After a diagnostic polysomnography, 18 HF patients with dominant CSR and an apnea-hypopnea index (AHI)≥15 events/h underwent a standard pulmonary function test in the sitting position. Measurements were repeated in the supine, left lateral and right lateral. The latter two measurements were averaged to obtain a single lateral measurement. RESULTS: The FRC in the seated position was 3.0 ± 0.5 L (85 ± 13% of predicted), decreased to 2.3 ± 0.3 L (-21 ± 8%, p < 0.0001) in the supine position, and increased to 2.8 ± 0.4 L (+21 ± 12%, p < 0.0001) from the supine to the lateral position (-5±8% vs seated, p = 0.013). During sleep, the AHI and the apnea index (AI) decreased from 47 ± 15 events/h to 26 ± 12 events/h (-46 ± 20%, p < 0.0001) and from 29 ± 21 events/h to 12 ± 10 events/h (-61 ± 40%, p < 0.001) from the supine to the lateral position. Changes in the AI were significantly correlated with corresponding changes in FRC (ρ = -0.55, p = 0.032). CONCLUSION: In patients with HF and CSR, lying in the supine position causes a significant reduction in FRC in the context of a chronically reduced FRC. The negative correlation between postural changes in FRC and AI supports the hypothesis that the reduction in lung gas stores in the supine position may promote/exacerbate respiratory control instability.

Automated versus interactive spectral analysis of heart rate variability from 24-hour Holter recordings in heart failure patients.

Accurate spectral analysis of 24-hour heart rate variability (HRV) requires time consuming interactive control of the overall processing, limiting its feasibility in large scale clinical trials. Fully automatic procedures allow a dramatic reduction of analysis time but the level of accuracy loss is unknown. In this study we compared automatic and interactive measurements of HRV indexes in a sample of 246 Holter recordings from chronic heart failure patients. We measured the total power of HRV and the power in the very low (0.01-0.04 Hz), low (0.04-0.15 Hz) and high (0.15-0.4 Hz) frequency bands. The comparison between the two methods was performed by computing the normalized difference between automatic and interactive measurements and estimating the bias and 95% limits of agreement. Automatic measurements showed a small bias (< ±8%) compared to interactive measurements, while the limits of agreement were ≤±23% in all spectral indexes. Our results indicate that the systematic and random difference between automatic and interactive measurements of spectral indexes of HRV are acceptable for clinical studies.

Computer-Assisted Assessment of the Interaction Between Arousals, Breath-by-Breath Ventilation, and Chemical Drive During Cheyne-Stokes Respiration in Heart Failure Patients.

Transient increases in ventilation induced by arousal from sleep during Cheyne-Stokes respiration in heart failure patients are thought to contribute to sustaining and exacerbating the ventilatory oscillation. The only possibility to investigate the validity of this notion is to use observational data. This entails some significant challenges: (i) accurate identification of both arousal onset and offset; (ii) detection of short arousals (<3 s); (iii) breath-by-breath analysis of the interaction between arousals and ventilation; (iv) careful control for important confounding factors. In this paper we report how we have tackled these challenges by developing innovative computer-assisted methodologies. The identification of arousal onset and offset is performed by a hybrid approach that integrates visual scoring with computer-based automated analysis. We use a statistical detector to automatically discriminate between dominant theta-delta and dominant alpha activity at each instant of time. Moreover, a statistical detector is used to validate visual scoring of K complexes, delta waves or artifacts associated with an EEG frequency shift, as well as frequency shifts to beta activity. A high-resolution (250 ms) state-transition diagram providing continuous information on the sleep-wake state of the subject is finally obtained. Based on this information, arousals are automatically identified as any state change from sleep to wakefulness lasting ≥2 s. The assessment of the interaction between arousals and ventilation is performed using a breath-by-breath, case-control approach. The arousal-associated change in ventilation is measured as the normalized difference between minute ventilation in the case breath (i.e., with arousal) and that in the control breath (i.e., without arousal), controlling for sleep stage and chemical drive. The latter is estimated by using information from pulse oximetry at the finger. In the last part of the paper, we discuss main potential sources of error inherent in the described methodologies.

Effect of Algorithmic Music Listening on Cardiac Autonomic Nervous System Activity: An Exploratory, Randomized Crossover Study.

It is proven that music listening can have a therapeutic impact in many clinical fields. However, to assume a curative value, musical stimuli should have a therapeutic logic. This study aimed at assessing short-term effects of algorithmic music on cardiac autonomic nervous system activity. Twenty-two healthy subjects underwent a crossover study including random listening to relaxing and activating algorithmic music. Electrocardiogram (ECG) and non-invasive arterial blood pressure were continuously recorded and were later analyzed to measure Heart Rate (HR) mean, HR variability and baroreflex sensitivity (BRS). Statistical analysis was performed using a general linear model, testing for carryover, period and treatment effects. Relaxing tracks decreased HR and increased root mean square of successive squared differences of normal-to-normal (NN) intervals, proportion of interval differences of successive NN intervals greater than 50 ms, low-frequency (LF) and high-frequency (HF) power and BRS. Activating tracks caused almost no change or an opposite effect in the same variables. The difference between the effects of the two stimuli was statistically significant in all these variables. No difference was found in the standard deviation of normal-to-normal RR intervals, LFpower in normalized units and LFpower/HFpower variables. The study suggests that algorithmic relaxing music increases cardiac vagal modulation and tone. These results open interesting perspectives in various clinical areas.

Baroreceptor Sensitivity in Individuals with CKD and Heart Failure.

Background: Heart failure is the most common cardiovascular complication of chronic kidney disease (CKD) and foreshadows a high morbidity and mortality rate. Baroreflex impairment likely contributes to cardiovascular mortality. We aimed to study the associations between CKD, heart failure, and baroreflex sensitivity (BRS) and their association with cardiovascular outcomes. Methods: We retrospectively analyzed data from a cohort of 247 individuals with moderate to severe HF. All subjects underwent BRS measurements after intravenous phenylephrine along with electrocardiography, echocardiography, and laboratory measurements. We used logistic regression models to assess the association of CKD (estimated glomerular filtration rate <60 ml/min per 1.73 m2) with BRS using iterative models. Cox proportional hazards models were used to assess associations of binary BRS and subgroups according to categorizations of CKD and BRS with cardiovascular mortality. Results: Median eGFR among individuals with CKD was 52 (IQR 44-56) ml/min per 1.73 m2. eGFR was lower in those with depressed BRS (65 [IQR 54-76] ml/min per 1.73 m2) compared with those with preserved BRS (73 [IQR 64-87] ml/min per 1.73 m2; P≤0.001). The majority of individuals with CKD had depressed BRS compared with those without CKD (60% versus 29%; P=0.05). In regression models, CKD and BRS were independently associated. Cardiovascular mortality was significantly increased in individuals with or without CKD and depressed BRS compared with those with preserved BRS and CKD. Conclusions: Cardiac BRS is depressed in patients with mild to moderate CKD and HF and associated with cardiovascular mortality. Additional study to confirm its contribution to cardiovascular mortality, particularly in advanced CKD, is warranted.

Clinical and haemodynamic correlates of heart rate turbulence as a non-invasive index of baroreflex sensitivity in chronic heart failure.

HRT (heart rate turbulence), describing the heart rate changes following a premature ventricular contraction, has been regarded as an indirect index of baroreflex function. However, limited data are available on its relationship with invasive assessment by phenylephrine injection (Phe-slope). In the present study, we therefore compared these methodologies in a series of patients with HF (heart failure) in which both measures together with clinical and haemodynamic data were available. HRT parameters [TO (turbulence onset) and TS (turbulence slope)] were measured from 24-h Holter recordings obtained within 1 week of baroreflex sensitivity assessment and right heart haemodynamic evaluation (Swan-Ganz catheter). HRT was computable in 135 out of 157 (86%) patients who had both a phenylephrine test and haemodynamic evaluation. TO and TS significantly correlated with Phe-slope (r=-0.39, P<0.0001 and r=0.66, P<0.0001 respectively). Age, baseline heart rate, LVEF (left ventricular ejection fraction), PCP (pulmonary capillary pressure), CI (cardiac index) and sodium were significant and independent predictors of Phe-slope, accounting for 51% of its variability. Similarly, age, baseline heart rate and PCP, and NYHA (New York Heart Association) classes III-IV were independent predictors for TS and explained 48% of its variability, whereas only CI and LVEF were found to be significantly related to TO and explained a very limited proportion (20%) of the variability. In conclusion, these results suggest that HRT may be regarded as a surrogate measure of baroreflex sensitivity in clinical and prognostic evaluation in patients with HF.

Additive prognostic value of subjective assessment with respect to clinical cardiological data in patients with chronic heart failure.

BACKGROUND: Health-related quality of life tools that better reflect the unique subjective perception of heart failure (HF) are needed for patients with this disorder. The aim of this study was to explore whether subjective satisfaction of HF patients about daily life may provide additional prognostic information with respect to clinical cardiological data. METHODS: One hundred and seventy-eight patients (age 51 ± 9 years) with moderate to severe HF [New York Heart Association (NYHA) class 2.0 ± 0.7; left ventricular ejection fraction (LVEF) 29 ± 8%] in stable clinical condition underwent a standard clinical evaluation and compiled the Satisfaction Profile (SAT-P) questionnaire focusing on subjective satisfaction with daily life. Cox regression analysis was used to assess whether SAT-P factors (psychological functioning, physical functioning, work, sleep/eating/leisure, social functioning) had any prognostic value. RESULTS: Forty-six cardiac deaths occurred during a median of 30 months. Patients who died had higher NYHA class, more depressed left ventricular function, reduced systolic blood pressure (SBP), increased heart rate (HR), and worse biochemistry (all p < 0.05). Among the SAT-P factors, only physical functioning (PF) was significantly reduced in the patients who died (p = 0.003). Using the best subset selection procedure, resistance to physical fatigue (RPF) was selected from among the items of the PF factor. RPF showed independent predictive value when entered into a prognostic model including NYHA class, LVEF, SBP, and HR with an adjusted hazard ratio of 0.86 per 10 units increase (95% CI 0.75-0.98, p = 0.02). CONCLUSIONS: Patients' dissatisfaction with physical functioning is associated with reduced long-term survival, after adjustment for known risk factors in HF. Given its user-friendly structure, simplicity, and significant prognostic value, the RPF score may represent a useful instrument in clinical practice.

Prognostic significance of tissue-Doppler imaging in chronic heart failure patients on transplant waiting list: a comparative study with right heart catheterization.

AIMS: Several echo-Doppler parameters, particularly the E/e' ratio, have been explored in the attempt to improve prognostic stratification in chronic heart failure (CHF) patients. In most studies, however, left ventricular filling pressure was not measured and patients with severe impairment of left ventricular function were not considered. The aim of this study was to assess the prognostic value of E/e' when compared with both traditional echo-Doppler parameters and pulmonary wedge pressure (PWP) in patients with advanced CHF. METHODS AND RESULTS: Right heart catheterization and a two-dimensional echo-Doppler examination were performed at baseline in 49 patients (male: 88%, age: 53 ± 9 years, New York Heart Association class: 2.7 ± 0.7, left ventricular ejection fraction: 29 ± 7%). Traditional pulsed-wave and tissue Doppler velocity parameters (DT, E, SFPVF, E', and E/e') were measured. Endpoint of survival analysis was cardiac death or urgent transplantation. During a median follow-up of 47 months (range: 1-58), 18 patients had experienced a major event (cardiac death or urgent transplantation). Both DT and E/e' were significantly and independently associated with the outcome (the Cox analysis), but the strength of the association was stronger for the latter (P= 0.008 vs. P= 0.03). Moreover, DT became non-significant when adjusted for PWP, whereas E/e' preserved its prognostic value (P= 0.04). The prognostic value of E' and PWP was borderline non-significant or clearly non-significant in both univariate and multivariable analyses. CONCLUSION: Among the echo-Doppler parameters, E/e' shows the highest predictive value in patients with advanced CHF and provides prognostic information independent of PWP. These results support the use of the feasible and easy obtainable E/e' ratio as a prognostic indicator in these patients.

Night-to-night repeatability of measurements of nocturnal breathing disorders in clinically stable chronic heart failure patients.

BACKGROUND: Portable sleep apnea monitors are often used to screen for sleep-disordered breathing in chronic heart failure patients (CHF), but night-to-night repeatability of obtained measurements of nocturnal breathing disorders has not been fully assessed. METHODS: Fifty-six stable, moderate-to-severe CHF patients [male, 87%; age, 57 ± 9 years; NYHA class, 2.6 ± 0.6; left ventricular ejection fraction (LVEF), 32% ± 9%] underwent an unattended in-hospital cardiorespiratory recording using a portable sleep apnea monitor during two consecutive nights. The apnea/hypopnea index (AHI), apnea index (AI), oxygen desaturation index (ODI), and periodic breathing (PB) duration were computed. Intra-subject night-to-night variability was assessed by the 95% limits of random variation (LoV). We also estimated the contribution of intra-rater variability to the overall intra-subject variability. Dichotomizing the AHI and PB duration according to conventional cutoffs of, respectively, ≥5 events per hour, ≥15 events per hour, and ≥120 min, the percentage of patients concordantly classified by the two measurements was finally computed. RESULTS: The 95% LoV were ±10.6, ±7.7, ±11.3 events per hour for AHI, AI and ODI, and ±63.2 min for PB duration, respectively. The contribution of intra-rater variability to total intra-subject variability was 1.7%, 1.4%, 2.5%, and 1.3% for AHI, AI, ODI, and PB duration, respectively. Most patients (85%, 82%, and 95% for AHI ≥ 5, AHI ≥ 15, and PB duration, respectively) were classified concordantly by the two measurements. CONCLUSIONS: In patients with heart failure, measurements of severity of sleep-disordered breathing derived from portable sleep apnea monitors show significant night-to-night intra-subject variation with a negligible contribution from intra-rater variability; however, using the same measurements for classification purposes, as commonly performed in clinical practice to screen patients for sleep-disordered breathing, very stable results are obtained.