Coronary Artery RIsk MAnagement Programme (CARIMAP) delivered by a rehabilitation day-hospital: impact on patients with coronary artery disease.

PURPOSE: Previous studies have shown that correct management of different coronary risk factors can reduce coronary event rates. However, significant undertreatment of hyperlipidemia, diabetes, and hypertension is still found during clinical practice. The purpose of this study was to evaluate the effectiveness of an individualized management program to modify coronary disease risk profile. METHODS: One hundred sixty-eight patients discharged from a cardiac rehabilitation department after acute coronary events were prospectively randomized into 2 management strategies: 84 started usual community care and 84 entered a Coronary Artery RIsk MAnagement Programme (CARIMAP) delivered by the rehabilitation day-hospital. Coronary risk profile, optimized therapy, and management were evaluated after the acute event and again after a followup of 9 ± 4 months in both groups. RESULTS: Patients accessed the day-hospital an average of 4 ± 1 months (range, 1-13 months) after the acute event. The duration of the CARIMAP was 5 ± 2 months and the individual number of accesses to the day-hospital was 4 ± 3.8. After the CARIMAP, patients received better-optimized therapy (ß-blockers 57% vs 85%, P < .0001; angiotensin-converting enzyme inhibitors 54% vs 84%, P < .00001; statins 38% vs 78%, P < .0001; and amlodipine 22% vs 51%, P < .0001) and had a better risk profile (low-density lipoprotein-cholesterol < 100 mg/dL 30% vs 42%, P < .0001; blood pressure < 140/90 mmHg 63% vs 88%, P < .00001). CONCLUSION: The CARIMAP of secondary prevention delivered by a rehabilitation day-hospital to patients who had undergone an acute coronary event, enabled individually titrated therapy and better control of coronary artery risk factors.

Pentraxin-3 predicts functional recovery and 1-year major adverse cardiovascular events after rehabilitation of cardiac surgery patients.

BACKGROUND: Inflammatory and vascular markers have proved to be predictors of outcome in myocardial infarction and heart failure. We evaluated several circulating markers of cardiac stress, inflammation, and endothelial function to investigate their ability to predict short-term functional recovery and long-term clinical outcome in heart surgery patients undergoing inpatient rehabilitation. METHODS: This prospective, multicenter study enrolled 223 patients after heart surgery, included in a 3-week program of standardized and supervised physical training. The association between biomarkers (pentraxin-3 [PTX3], brain natriuretic peptide, high-sensitivity cardiac troponin-T [hs-cTnT] and C-reactive protein [hsCRP], creatine kinase, myoglobin, and urinary albumin excretion [UACR]) and exercise capacity (6-minute walk test, 6MWT) or 1-year incidence of major adverse cardiovascular events (MACE) was tested in models that included biohumoral markers, and clinical and instrumental variables. RESULTS: The patients (69.5% men, mean age of 67 ± 11 years) were enrolled after valvular surgery (52.7%) and 58.6% after coronary artery bypass grafting (CABG). Exercise capacity improved during rehabilitation (6MWT distance from 279 ± 95 to 386 ± 91 m; P < .0001); concentrations of most biomarkers decreased (hsCRP: 79% [P < .0001]; hs-cTnT: 57% [P < .0001]; UACR: 36% [P = .05]). Among the tested markers, PTX3 showed the closest association with 6MWT distance (P = .01) and was the only predictor of MACE, also in the subgroup of CABG patients (OR [95% CI] = 1.14 [1.03-1.27]; P = .015). CONCLUSION: PTX3, a marker of vascular inflammation and cardiovascular damage, is a predictor of short-term functional recovery and 1-year MACE in patients undergoing rehabilitation after cardiac surgery, regardless of clinical and instrumental parameters.

Home telemonitoring in heart failure patients: the HHH study (Home or Hospital in Heart Failure).

AIMS: The Home or Hospital in Heart failure (HHH) study was a European Community-funded, multinational, randomized controlled clinical trial, conducted in the UK, Poland, and Italy, to assess the feasibility of a new system of home telemonitoring (HT). The HT system was used to monitor clinical and physiological parameters, and its effectiveness (compared with usual care) in reducing cardiac events in heart failure (HF) patients was evaluated. Measurements were patient-managed. METHODS AND RESULTS: From 2002 to 2004, 461 HF patients (age 60 +/- 11 years, New York Heart Association class 2.4 +/- 0.6, left ventricular ejection fraction 29 +/- 7%) were enrolled at 11 centres and randomized (1:2) to either usual outpatient care or HT administered as three randomized strategies: (i) monthly telephone contact; (ii) strategy 1 plus weekly transmission of vital signs; and (iii) strategy 2 plus monthly 24 h recording of cardiorespiratory activity. Patients completed 81% of vital signs transmissions, as well as 92% of cardiorespiratory recordings. Over a 12-month follow-up, there was no significant effect of HT in reducing bed-days occupancy for HF or cardiac death plus HF hospitalization. Post hoc analysis revealed a heterogeneous effect of HT in the three countries with a trend towards a reduction of events in Italy. CONCLUSION: Home or Hospital in Heart failure indicates that self-managed HT of clinical and physiological parameters is feasible in HF patients, with surprisingly high compliance. Whether HT contributes to a reduction of cardiac events requires further investigation.

Home telemonitoring of vital signs and cardiorespiratory signals in heart failure patients: system architecture and feasibility of the HHH model.

BACKGROUND: The Home or Hospital in Heart Failure Study (HHH) is a European Community funded trial (QLGA-CT-2001-02424) which compares usual care of heart failure (HF) with three home-based interventions in a multicenter, multicountry (Italy, Poland and UK), randomized controlled clinical trial. Home telemonitoring (HT) of clinical parameters represents a potential alternative (or addition) to traditional home care models. Nocturnal respiratory disorders (periodic breathing, sleep apnea) are very common in HF, and are associated with increased morbidity and mortality. We developed an integrated HT system for monitoring of both vital signs and respiration. All measurements were patient-managed. This paper describes the architecture of this system, and assesses its feasibility. METHODS AND RESULTS: 461 clinically stable patients were randomized first to usual vs home-monitored care; the latter were further randomized to 3 strategies. Over a 12-month follow-up 2 of these 3 groups (195 patients, age: 60+/-11 years, NYHA class II-III: 97%, LVEF 28+/-7%) underwent self-administered home monitoring of vital signs (weekly--12 parameters using an interactive voice response system) and respiration (monthly--24-hour recording). Data were transmitted over conventional telephone lines; 81% of actually practicable vital signs measurements were completed by the patients (range: 75% (PL)-93% (UK)), as well as 92% of practicable respiratory recordings (range: 85% (PL)-99% (UK)). 87% of nighttime recordings were eligible for the study (good quality signals for > or = 2.5 h). CONCLUSIONS: This study, the largest so far, demonstrates that self-managed home telemonitoring of both vital signs and respiration is feasible in HF patients, with surprisingly high compliance. We found an excellent rate of acceptable nocturnal respiratory recordings, which are those with the greatest clinical relevance.

Applicability and clinical relevance of the transfer function method in the assessment of baroreflex sensitivity in heart failure patients.

OBJECTIVES: We sought to assess applicability, clinical correlates, and prognostic value of the transfer function method for measuring baroreflex sensitivity (TF-BRS). BACKGROUND: Abnormalities in autonomic reflexes play an important role in the development and progression of chronic heart failure (CHF). Simple and non-invasive techniques for clinical measurement of such reflexes are desirable. METHODS: In 317 stable CHF patients in sinus rhythm (median age [interquartile range]: 54 years [48 to 59 years], New York Heart Association [NYHA] functional class II to III: 88%, left ventricular ejection fraction [LVEF]: 27% [22% to 33%]) we recorded electrocardiograms and non-invasive arterial pressure during paced breathing to measure TF-BRS. RESULTS: Owing to a high number of ectopic beats, TF-BRS could be computed in 72% of the patients; TF-BRS was lower in NYHA functional class III to IV and mitral regurgitation 2 to 3 (p < 0.0005 for both). Correlation with LVEF and standard deviation of all normal-to-normal intervals was 0.18 and 0.31 (p < 0.001 for both). During a mean follow-up of 26 months, 23% of the patients experienced a cardiac event. A depressed TF-BRS (< or =3.1 ms/mm Hg) was significantly associated with the outcome (hazard ratio 3.2, 95% confidence interval [CI] 1.7 to 6.0, p = 0.0003). Patients with a missing TF-BRS had a high event rate (36%). Combining this information with available TF-BRS measurements, a new prognostic index could be computed in 97% of the patients that significantly predicted the outcome after adjustment for clinical and functional variables (hazard ratio 2.5, 95% CI 1.3 to 4.6 p = 0.004). CONCLUSIONS: In CHF patients in sinus rhythm, TF-BRS conveys relevant clinical and prognostic information, but its measurability is markedly affected by ectopic activity. Nevertheless, a TF-BRS-based risk index carrying significant and independent prognostic information can be computed in almost all patients.

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.

Short-term heart rate variability strongly predicts sudden cardiac death in chronic heart failure patients.

BACKGROUND: The predictive value of heart rate variability (HRV) in chronic heart failure (CHF) has never been tested in a comprehensive multivariate model using short-term laboratory recordings designed to avoid the confounding effects of respiration and behavioral factors. METHODS AND RESULTS: A multivariate survival model for the identification of sudden (presumably arrhythmic) death was developed with data from 202 consecutive patients referred between 1991 and 1995 with moderate to severe CHF (age 52+/-9 years, left ventricular ejection fraction 24+/-7%, New York Heart Association class 2.3+/-0.7; the derivation sample). Time- and frequency-domain HRV parameters obtained from an 8' recording of ECG at baseline and during controlled breathing (12 to 15 breaths/min) were challenged against clinical and functional parameters. This model was then validated in 242 consecutive patients referred between 1996 and 2001 (validation sample). In the derivation sample, sudden death was independently predicted by a model that included low-frequency power (LFP) of HRV during controlled breathing < or =13 ms2 and left ventricular end-diastolic diameter > or =77 mm (relative risk [RR] 3.7, 95% CI 1.5 to 9.3, and RR 2.6, 95% CI 1.0 to 6.3, respectively). The derivation model was also a significant predictor in the validation sample (P=0.04). In the validation sample, LFP < or =11 ms2 during controlled breathing and > or =83 ventricular premature contractions per hour on Holter monitoring were both independent predictors of sudden death (RR 3.0, 95% CI 1.2 to 7.6, and RR 3.7, 95% CI 1.5 to 9.0, respectively). CONCLUSIONS: Reduced short-term LFP during controlled breathing is a powerful predictor of sudden death in patients with CHF that is independent of many other variables. These results refine the identification of patients who may benefit from prophylactic implantation of a cardiac defibrillator.

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.

"Peak Summation" Left Ventricular Filling Pattern in Patients with Chronic Heart Failure: Frequency and Complementary Value of Pulmonary Venous Flow in Its Hemodynamic Interpretation.

In patients with chronic heart failure (CHF) and a "peak summation" left ventricular pattern, no hemodynamic and prognostic information can be drawn from Doppler examination of mitral flow. In 263 consecutive patients with CHF who were undergoing simultaneous right heart catheterization and echo-Doppler examination, we prospectively determined (1) the frequency of the peak summation left ventricular filling pattern and (2) the incremental information contributed by pulmonary venous flow velocity patterns in providing noninvasive hemodynamic profile estimation. Isovolumic relaxation time of mitral flow, peak systolic (X), diastolic forward (Y), reverse (Z) flow velocity, and systolic fraction (X/X + Y) of pulmonary venous flow were measured. Forty-six of 263 (17%) patients had a peak summation left ventricular filling pattern. This subgroup showed more clinical deterioration (New York Heart Association functional class III-IV, 57% vs 49%; P < 0.01) and left atrial dysfunction (left atrial ejection fraction, 31% vs 39%; P < 0.001). However, 40% of these patients had a pulmonary wedge pressure of <18 mmHg and a cardiac index of >2.2 L/min/m(2). The systolic fraction of peak velocities of pulmonary venous flow showed a good correlation with pulmonary wedge pressure (r = -0.70, P < 0.05). The correlation was stronger in patients without mitral regurgitation (r = -0.81, P < 0.05). A systolic fraction of <40% was accurate (sensitivity, 100%; specificity, 95%) in identifying patients with a pulmonary wedge pressure of >18 mmHg. In patients without mitral regurgitation, this variable was also correlated with cardiac index (r = -0.65, P < 0.05) and predicted a cardiac index of >2.2 L/min/m(2) (sensitivity, 91%; specificity, 71%). In conclusion, a peak summation left ventricular filling pattern is common in patients with CHF. Pulmonary venous flow provides useful information about the hemodynamic profile of these patients.