Estimating maximum work rate during cardiopulmonary exercise testing from the six-minute walk distance in patients with heart failure.

Background: Exercise is recommended for patients with chronic heart failure (CHF) and its intensity is usually set as a percentage of the maximal work rate (MWR) during cardiopulmonary exercise testing (CPX) or a symptom-limited incremental test (SLIT). As these tests are not always available in cardiac rehabilitation due to logistic/cost constraints, we aimed to develop a predictive model to estimate MWR at CPX (estMWR@CPX) in CHF patients using anthropometric and clinical measures and the 6-min walk test (6 MWT), the most widely used exercise field test. Methods: This is a multicentre cross-sectional retrospective study in a cardiac rehabilitation setting. Six hundred patients with HF in New York Heart Association (NYHA) functional class I-III underwent both CPX and 6 MWT and, through multivariable linear regression analysis, we defined several predictive models to define estMWR@CPX. Results: The best model included 6 MWT, sex, age, weight, NYHA class, left ventricular ejection fraction (LVEF), smoking status and chronic obstructive pulmonary disease COPD (adjusted R2 = 0.55; 95% LoA -39 to 33 W). When LVEF was excluded as a predictor, the resulting model performed only slightly worse (adjusted R2 = 0.54; 95% LoA -42 to 34 W). Only in 34% of cases was the percentage difference between estMWR@CPX and real MWR@CPX <10% in absolute value. EstMWR@CPX tended to overestimate low values and underestimate high values of true MWR@CPX. Conclusions: Our results showed a lack of accuracy in the predictive model evaluated; therefore, for an accurate prescription of cycle-ergometer exercise training, it is necessary to assess MWR by CPX or SLIT.

Psychosocial and behavioral correlates of self-efficacy in treatment adherence in older patients with comorbid hypertension and type 2 diabetes.

BACKGROUND: Adhering to clinical prescriptions is known to protect against the effects of uncontrolled hypertension and of acute and chronic cardiovascular diseases, including diabetes. Contextually, positive associations between self-care behaviors and psychological constructs, such as self-efficacy, are widely acknowledged in the literature. However, still little is known about the psychological factors underlying the patient's self-efficacy. This study aimed to investigate the psychosocial and behavioral correlates of self-efficacy related to treatment adherence in older patients with comorbid hypertension and type 2 diabetes mellitus. PARTICIPANTS AND PROCEDURE: Italian and Polish patients (≥ 65 years; N = 180) consecutively responded to self-report questionnaires measuring psychosocial (i.e., beliefs about medicines, perceived physician's communication effectiveness, medication-specific social support, self-efficacy) and behavioral factors (i.e., pharmacological adherence, medications refill adherence, intentional non-adherence) related to treatment adherence. Between-group comparisons and regression analyses were performed. RESULTS: Fisher's least significant difference (LSD) test showed significant differences between the Italian and Polish groups in all questionnaires (p < .01) with the Italian patients reporting more satisfactory scores. Younger age (ß = .08, p = .045), female gender (ß = 1.03, p = .042), higher medication refills adherence (ß = -.07, p = .024), lower intentional non-adherence (ß = -.03, p = .009), positive beliefs about medications (ß = .13, p < .001), better quality of communication with the physician (ß = .09, p < .001), and stronger perceived medication-specific social support (ß = .06, p = .001) were significantly associated with self-efficacy related to treatment adherence. CONCLUSIONS: Future research and interventions should leverage psychosocial and behavioral factors to address self-efficacy contributing to enhancing adherence to clinical prescriptions.

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.

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.

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.

Comparison of the prognostic values of invasive and noninvasive assessments of baroreflex sensitivity in heart failure.

OBJECTIVES: No studies have compared the prognostic values of invasive (phenylephrine, Phe) and noninvasive (transfer function) assessments of baroreflex sensitivity (BRS). METHODS: Three hundred and one heart failure patients [age: 53 ±â€Š8 years, New York Heart Association class II-III: 88%, left-ventricular ejection fraction (LVEF): 28 ±â€Š8%] underwent an 8 min ECG and arterial pressure recording, followed by Phe administration. RESULTS: Phe-BRS and transfer function BRS (TF-BRS) could be measured in 89 and 72% of cases, respectively. The correlation and the 5-95th percentiles of the difference between the two methods were 0.61 (P < 0.0001), and -7.6, +7.5 ms/mmHg, respectively. During a median of 36 months, 23% of the patients experienced a cardiac event. In the common dataset of 202 patients, both BRS measurements (<3 ms/mmHg) were significantly associated with the outcome (both P < 0.001), but Phe-BRS had a better discriminatory power (area under the curve (AUC): 0.74 vs. 0.66, P  = 0.03). Patients with a missing BRS (due to high grade ectopic activity) had a higher event rate (Phe-BRS: 38 vs. 24%, P  = 0.23; TF-BRS: 37 vs. 19%, P  = 0.002). Using this information, a prognostic index was derived for each BRS method, increasing measurability to 94 and 98%, respectively. Both indexes significantly predicted the outcome after adjustment for clinical covariates [hazard ratio (95% CI): 1.9 (1.1-3.3), P  = 0.03 for Phe index and 2.0 (1.1-3.7), P  = 0.02 for transfer function index]. CONCLUSION: Although the measurability of TF-BRS in heart failure patients is impaired, prognostic information can be extended to almost all patients, with a predictive power similar to that of Phe-BRS. The two measurements, however, convey a certain amount of independent prognostic information. Hence, TF-BRS can be integrated with but not replace Phe-BRS.

Prognostic implications of baroreflex sensitivity in heart failure patients in the beta-blocking era.

OBJECTIVES: This study investigated the clinical correlates and prognostic value of depressed baroreceptor-heart rate reflex sensitivity (BRS) among patients with heart failure (HF), with and without beta-blockade. BACKGROUND: Abnormalities in autonomic reflexes play an important role in the development and progression of HF. Few studies have assessed the effects of beta-blockers on BRS in HF. METHODS: The study population consisted of 103 stable HF patients, age (median [interquartile range]) 54 years (48 to 57 years), with New York Heart Association (NYHA) functional class > or =III in 22, and with a left ventricular ejection fraction (LVEF) of 30% (24% to 36%), treated with beta-blockers; and 144 untreated patients, age 55 years (48 to 60 years), with NYHA functional class > or =III in 47%, and an LVEF of 26% (21% to 30%). They underwent BRS testing (phenylephrine technique). RESULTS: In both treated and untreated patients, a lower BRS was associated with a higher (> or =III) NYHA functional class (p = 0.0002 and p < 0.0001, respectively); a more severe (> or =2) mitral regurgitation (p = 0.007 and p = 0.0002), respectively; a lower LVEF (p = 0.0004 and p = 0.001, respectively), baseline RR interval (p = 0.0004 and p = 0.0002, respectively), and SDNN (p < 0.0001, p = 0.002, respectively); and a higher blood urea nitrogen (p = 0.004, p < 0.0001, respectively). Clinical variables explained only 43% of BRS variability among treated and 36% among untreated patients. During a median follow-up of 29 months, 17 of 103 patients and 55 of 144 patients, respectively, experienced a cardiac event. A depressed BRS (<3.0 ms/mm Hg) was significantly associated with the outcome, independently of known risk predictors and beta-blocker treatment (adjusted hazard ratio: 3.0 [95% confidence interval: 1.5 to 5.9], p = 0.001). CONCLUSIONS: Baroreceptor-heart rate reflex sensitivity does not simply mirror the pathophysiological substrate of HF. A depressed BRS conveys independent prognostic information that is not affected by the modification of autonomic dysfunction brought about by beta-blockade.

Echo-Doppler and clinical evaluations to define hemodynamic profile in patients with chronic heart failure: accuracy and influence on therapeutic management.

BACKGROUND: Correct classification of chronic heart failure (CHF) patients by dual evidence of congestion and adequate perfusion is the primary clinical focus for management. OBJECTIVES: To evaluate the accuracy of echo-Doppler compared with clinical evaluation in determining the hemodynamic profile of patients with CHF; and to compare therapeutic changes based on hemodynamic or echo-Doppler findings. METHODS: Three hundred and sixty-six consecutive CHF patients (ejection fraction 25+/-7%) in sinus rhythm, undergoing evaluation for cardiac transplantation, underwent physical examination prior to right heart catheterization and echo-Doppler studies. Subsequently, patients were randomized to therapeutic optimization using either right heart catheterization or echo-Doppler data. The end-points were: identification of low cardiac output (cardiac index <2.2 l/min/m(2)); high pulmonary wedge pressure (PWP >18 mm Hg); high right atrial pressure (RAP >5 mm Hg) and analysis of therapeutic changes made in response to the right heart catheterization and echo-Doppler studies. RESULTS: Echo-Doppler showed better accuracy in estimating abnormal hemodynamic indices than clinical variables (cardiac index <2.2 l/min/m(2): echo positive predictive accuracy (PPA) 98% vs. clinical PPA 52% p<0.00001; PWP >18 mm Hg: echo PPA 85% vs. clinical PPA 76% p=0.0011; RAP >5 mm Hg: echo PPA 82% vs. clinical PPA 57% p<0.00001). When applied to individual patients, the echo-Doppler assessment was more accurate than clinical evaluation in defining the different hemodynamic profiles: wet/cold (89% vs. 13%, p<0.0001); wet/warm (73% vs. 30%, p<0.0001); dry/cold (68% vs. 12%, p<0.0001); dry/warm (88% vs. 51%, p<0.0001). Therapeutic decision-making based on echo-Doppler findings was similar to that based on hemodynamics. CONCLUSION: Echo-Doppler hemodynamic monitoring proved accurate in estimating hemodynamic profiles and influenced therapeutic management.

Anemia in chronic heart failure patients: comparison between invasive and non-invasive prognostic markers.

BACKGROUND: The prognosis of chronic heart failure (CHF) remains poor despite advances in medical management. Several different variables determine prognosis. Recently anemia has emerged as an independent prognostic variable in the evaluation of CHF. It is therefore important to analyze the role of anemia in patients with mild to severe CHF already well characterized by hemodynamic, echo-Doppler, and cardiopulmonary exercise testing. OBJECTIVE: We performed this study to evaluate, in a large general cohort of CHF patients, the frequency of anemia and its correlation with their clinical profile. We assessed the prognostic value of anemia in relation to other known prognostic variables. METHODS: Two-dimensional echocardiography, right heart catheterization, cardiopulmonary tests and laboratory examinations were performed in a population of 980 consecutive patients with CHF (53 +/- 9.4 years, 85% male, LVEF 25 +/- 8%; 45% with NYHA class III-IV). A hemoglobin (Hb) concentration less than 12 g/dl was used to define anemic patients. The primary end point was cardiac death or urgent heart transplantation. RESULTS: Nineteen percent of patients were anemic. These patients had a lower body mass index (24 +/- 3 vs. 25 +/- 4 Kg/m2 p < 0.0004), a worse functional class (64% were in NYHA class III-IV vs 41% in the non-anemic group, p < 0.0001), poorer exercise capacity (12.4 vs. 14.8 ml/kg/min peak VO2, p < 0.0001) and increased right (7 +/- 5 vs. 5 +/- 4 mmHg, p < .0004) and left (21 +/- 9 vs. 19 +/- 10 p < 0.007) ventricular filling pressures. During a 3-year follow-up cardiac deaths occurred in 236 (24%) and 52 (5%) of patients received an urgent heart transplant. On univariate regression analysis anemia was significantly correlated with these "hard" cardiac events (39% of anemic patients vs 27% of non-anemic patients). By multivariate logistic regression analysis different prognostic models were identified using non-invasive, with or without peak VO2, or invasive parameters. The prognostic model including anemia (AUC(ROC): 0.720) showed similar accuracy in predicting cardiac events to other prognostic models with peak VO2 (AUC(ROC): 0.719) or invasive variables (AUC(ROC): 0.719). CONCLUSIONS: The present study demonstrates that anemia in CHF patients is associated with prognosis, worse NYHA functional class, exercise capacity and hemodynamic profiles. The relationship between anemia and mortality is independent of other simple non-invasive prognostic factors. Prognostic models with more complex or invasive independent predictors did not increase the accuracy to predict cardiac mortality or the need for urgent transplantation.

Cost/utility ratio in chronic heart failure: comparison between heart failure management program delivered by day-hospital and usual care.

OBJECTIVE: This study compared the effectiveness and cost/utility ratio between a heart failure (HF) management program delivered by day-hospital (DH) and usual care in chronic heart failure (CHF) outpatients. BACKGROUND: Previous studies showed that about 50% of readmissions for CHF can be prevented by a multidisciplinary approach. However, the performance, effectiveness, and cost/utility ratio of a process of HF outpatient management related to evidence-based medicine have not been considered. METHODS: A total of 234 prospective patients discharged by a HF Unit were randomized to two management strategies: 122 patients to usual community care and 112 patients to a HF management program delivered by the DH. Management (rate of readmissions, therapeutic interventions), functional parameters (New York Heart Association [NYHA] functional class, left ventricular diameters, and ejection fraction, deceleration time of early diastolic mitral flow, peak oxygen uptake, and mitral regurgitation) and hard outcomes (cardiac death and urgent cardiac transplantation) were evaluated. The cost/utility ratios of the two strategies were compared. RESULTS: After 12 +/- 3 months of follow-up, the individual rate access in DH was 5.5 +/- 3.8 days. The DH subjects were readmitted to the hospital less frequently than were the usual-care group patients (13 vs. 78, p < 0.00001). Patients allocated to usual-care management showed heterogeneous changes in NYHA functional class (13% improved and 16% worsened p = NS); In contrast, the DH group showed significant changes in NYHA functional class (23% improved and 11% worsened, p < 0.009). Hard cardiac events in the one-year follow-up occurred in 25/234 (10.6%) patients; cardiac death occurred in 21/122 (17.2%) of the community group and in 3/112 (2.7%) in the DH group (p < 0.0007). One DH patient underwent urgent transplantation. Comparison of the two managerial models by Cox regression analysis showed that DH management significantly protected against the appearance of hard events (relative risk [RR] 0.17; confidence interval [CI] 0.06 to 0.66). The cost/utility ratio of the two management strategies was similar (usual care $2,409 vs. DH $2,244). The incremental analysis revealed a cost savings of $1,068 for each quality-adjusted life year gained. The cost/utility ratio for the integration of DH management of CHF was $19,462 (CI $13,904 to $34,048). CONCLUSIONS: A heart failure outpatient management program delivered by a DH can reduce mortality and morbidity of CHF patients. This management strategy is cost-effective and has an equitable value from a societal point of view.

[Home exercise therapy in chronic congestive heart failure: observational study of factors affecting adherence to the program]. / Training fisico domiciliare nello scompenso cardiaco cronico: studio osservazionale sui fattori condizionanti l'aderenza al programma.

BACKGROUND: Physical training has proven to be a valid and effective therapeutic tool capable of counteracting muscle changes that occur in chronic heart failure (CHF) patients. Nevertheless, few studies have analyzed the frequency of use of this therapy and the reasons for any reduced compliance and adherence to the prescription. The aim of this study was to quantify the frequency of the participation of CHF patients in a program of domiciliary physical training and to analyze the factors that can influence adherence to the program. METHODS: Three hundred and twenty-two consecutive CHF patients (ejection fraction 28 +/- 7%) in a stable condition with optimized medical therapy performed a cardiopulmonary test, including determination of peak oxygen consumption, at baseline and after 9 +/- 3 months. All the patients had participated in sessions of health education on the relationship between illness/physical activity. The prescription of physiotherapy was decided by the physician on the basis of each patient's clinical need assessed in the diagnostic-therapeutic management. The patient referred for physiotherapy entered a therapeutic strategy that included sessions of training on anaerobic threshold, self-management of the session, and formulation of a domiciliary physical training program. During the follow-up evaluation the patients were asked to complete a questionnaire, which investigated the relationship between several factors and the patient's adherence to the physical training program, which was objectively evaluated by the change in peak oxygen consumption recorded at the end of the training, taking into account the spontaneous variations found in the control group. RESULTS: Two hundred and eighty-two of the patients (88%) satisfied the criteria for inclusion in the study. Only 61 (22%) of them were judged to have adhered to the recommended physical training. Type of employment (chi 2 = 7.08, p < 0.02), the state of retirement (chi 2 = 8.9, p < 0.01), ischemic etiology (chi 2 = 5.91, p < 0.01), compatibility with employment (chi 2 = 15.8, p < 0.0004), availability of suitable domestic conditions (chi 2 = 14.5, p < 0.0008), the structure of the training program (chi 2 = 22.33, p < 0.0001) and a learning phase in a gym (chi 2 = 71.33, p < 0.0001) were significantly correlated at univariate analysis with the performance of the physical training. Multivariate analysis identified the structure of the training program (odds ratio 9.6, 95% confidence interval 2.8-33) and a learning phase in a gym (odds ratio 49.6, 95% confidence interval 11-210.8) as independent factors (r2 = 0.48) determining adherence to the physical training program. CONCLUSIONS: Adherence to unmonitored, recommended domiciliary physical training appears to be modest even in patients who have been in-patients in a cardiac rehabilitation center. Various factors seem to influence the adherence of the patient to this therapy, but structural factors, such as the organization and learning of the program, more strongly influenced the patient's subsequent compliance.