Challenges in secondary prevention after acute myocardial infarction: A call for action.

Worldwide, each year more than 7 million people experience myocardial infarction, in which one-year mortality rates are now in the range of 10%, but vary with patient characteristics. The consequences are even more dramatic: among patients who survive, 20% suffer a second cardiovascular event in the first year and approximately 50% of major coronary events occur in those with a previous hospital discharge diagnosis of ischaemic heart disease. The people behind these numbers spur this call for action. Prevention after myocardial infarction is crucial to reduce risk and suffering. Evidence-based interventions include optimal medical treatment with anti-platelets and statins, achieve-ment of blood pressure, lipid and blood glucose targets, and appropriate lifestyle changes. The European Society of Cardiology and its constituent bodies are determined to embrace this challenge by developing a consensus document in which the existing gaps for secondary prevention strategies are reviewed. Effective interventions in relation to the patients, healthcare providers and healthcare systems are proposed and discussed. Finally, innovative strategies in hospital as well as in outpatient and long-term settings are endorsed.

Challenges in secondary prevention after acute myocardial infarction: A call for action.

Worldwide, each year more than 7 million people experience myocardial infarction, in which one-year mortality rates are now in the range of 10%, but vary with patient characteristics. The consequences are even more dramatic: among patients who survive, 20% suffer a second cardiovascular event in the first year and approximately 50% of major coronary events occur in those with a previous hospital discharge diagnosis of ischaemic heart disease. The people behind these numbers spur this call for action. Prevention after myocardial infarction is crucial to reduce risk and suffering. Evidence-based interventions include optimal medical treatment with anti-platelets and statins, achievement of blood pressure, lipid and blood glucose targets, and appropriate lifestyle changes. The European Society of Cardiology and its constituent bodies are determined to embrace this challenge by developing a consensus document in which the existing gaps for secondary prevention strategies are reviewed. Effective interventions in relation to the patients, healthcare providers and healthcare systems are proposed and discussed. Finally, innovative strategies in hospital as well as in outpatient and long-term settings are endorsed.

Cardiac rehabilitation after transcatheter aortic valve implantation compared to patients after valve replacement.

AIMS: To evaluate feasibility, safety, and outcome of an exercise-based residential cardiac rehabilitation program in transcatheter aortic valve implantation (TAVI) patients compared to elderly patients after surgical valve replacement (sAVR). METHODS: From January 2010 to January 2013, 65 consecutive TAVI and 70 sAVR older than 70 years were enrolled. Six-min walk test (6MWT) distance, Barthel index, Morse Fall Scale (MFS) on admission and discharge, Cumulative Illness Rated State-Comorbidity Index (CIRS-CI), and echocardiography were assessed. Patients underwent a 3-week intensive cardiac rehabilitation program. RESULTS: Compared with sAVR, TAVI had worse CIRS-CI (4.8 ±â€Š1.5 vs. 3.4 ±â€Š1.5; P = 0.00001), left ventricle ejection fraction (55.3 ±â€Š9 vs. 59.2 ±â€Š7.7; P = 0.008), Barthel index (67 ±â€Š24 vs. 79 ±â€Š21; P = 0.0018), and MFS (36 ±â€Š22 vs. 25 ±â€Š19; P = 0.002) on admission and at discharge (Barthel index 85 ±â€Š17 vs. 93 ±â€Š14; P = 0.005 and MFS 30 ±â€Š20 vs. 20 ±â€Š12; P = 0.0001), despite a significant improvement at discharge of Barthel index (85 ±â€Š17 vs. 67 ±â€Š24; P = 0.001) and MFS (36 ±â€Š22 vs. 30 ±â€Š20; P > 0.01). TAVI attended safely cardiac rehabilitation, but tolerated a significantly lower workload and had reduced 6MWT both on admission and discharge compared with sAVR (162 ±â€Š87vs. 216 ±â€Š82; P = 0.00001, and 240 ±â€Š92 vs. 33295; P = 0.00001, respectively), despite a net improvement at discharge in 6MWT (240 ±â€Š92 vs. 162 ±â€Š92; P < 0.001). CONCLUSION: Intensive cardiac rehabilitation after TAVI is safe, well tolerated, and leads to a net improvement in disability, risk of falls, and exercise capacity, similar to that observed in less disabled sAVR patients, favoring home discharge and relatively independent life at home. A persistent higher disability, comorbidity profile, and risk of falls at discharge characterize TAVI patients compared with sAVR patients of similar age.

Heart failure and anemia: Effects on prognostic variables.

BACKGROUND: Anemia is frequent in heart failure (HF), and it is associated with higher mortality. The predictive power of established HF prognostic parameters in anemic HF patients is unknown. METHODS: Clinical, laboratory, echocardiographic and cardiopulmonary-exercise-test (CPET) data were analyzed in 3913 HF patients grouped according to hemoglobin (Hb) values. 248 (6%), 857 (22%), 2160 (55%) and 648 (17%) patients had very low (<11g/dL), low (11-12 for females, 11-13 for males), normal (12-15 for females, 13-15 for males) and high (>15) Hb, respectively. RESULTS: Median follow-up was 1363days (606-1883). CPETs were always performed safely. Hb was related to prognosis (Hazard ratio (HR)=0.864). No prognostic difference was observed between normal and high Hb groups. Peak oxygen consumption (VO2), ventilatory efficiency (VE/VCO2 slope), plasma sodium concentration, ejection fraction (LVEF), kidney function and Hb were independently related to prognosis in the entire population. Considering Hb groups separately, peakVO2 (very low Hb HR=0.549, low Hb HR=0.613, normal Hb HR=0.618, high Hb HR=0.542) and LVEF (very low Hb HR=0.49, low Hb HR=0.692, normal Hb HR=0.697, high Hb HR=0.694) maintained their prognostic roles. High VE/VCO2 slope was associated with poor prognosis only in patients with low and normal Hb. CONCLUSIONS: Anemic HF patients have a worse prognosis, but CPET can be safely performed. PeakVO2 and LVEF, but not VE/VCO2 slope, maintain their prognostic power also in HF patients with Hb<11g/dL, suggesting CPET use and a multiparametric approach in HF patients with low Hb. However, the prognostic effect of an anemia-oriented follow-up is unknown.

Challenges in secondary prevention after acute myocardial infarction: A call for action.

Worldwide, each year more than 7 million people experience myocardial infarction, in which one-year mortality rates are now in the range of 10%, but vary with patient characteristics. The consequences are even more dramatic: among patients who survive, 20% suffer a second cardiovascular event in the first year and approximately 50% of major coronary events occur in those with a previous hospital discharge diagnosis of ischaemic heart disease. The people behind these numbers spur this call for action. Prevention after myocardial infarction is crucial to reduce risk and suffering. Evidence-based interventions include optimal medical treatment with anti-platelets and statins, achievement of blood pressure, lipid and blood glucose targets, and appropriate lifestyle changes. The European Society of Cardiology and its constituent bodies are determined to embrace this challenge by developing a consensus document in which the existing gaps for secondary prevention strategies are reviewed. Effective interventions in relation to the patients, healthcare providers and healthcare systems are proposed and discussed. Finally, innovative strategies in hospital as well as in outpatient and long-term settings are endorsed.

Five-year hospitalisations and survival in patients admitted to inpatient cardiac rehabilitation after cardiac surgery.

BACKGROUND: The effect of an early comprehensive rehabilitation programme on the evolution of disability after cardiac surgery and the long-term effect of the residual functional status has not yet been investigated. AIM: To analyse the recovery from disability after cardiac surgery and to assess the impact of residual disability on long-term outcomes. METHODS: Data prospectively recorded from 5261 patients, consecutively admitted to an inpatient rehabilitation programme after cardiac surgery, were retrospectively analysed. Disability was assessed twice, on admission (to evaluate the post-surgery disability) and at discharge (to evaluate the recovery after rehabilitation). Study cohort survival at 5-year follow-up was also compared with that of a reference population matched for age and sex. RESULTS: On admission, severe, moderate, mild or no disability was documented in 18.2%, 29.4%, 39.8% and 12.5% of patients, respectively. After rehabilitation, 75.1% of patients with severe disability improved their functional status, with an associated 50% reduction in mortality at 5-year follow-up. The Barthel index was the major predictor of survival and hospitalisations at follow-up. Comparison of the observed versus expected survival showed a worse outcome in patients with persistent moderate to severe residual disability. CONCLUSIONS: The reduction in all-cause mortality at follow-up documented in those patients with severe disability post-surgery who improved after rehabilitation underscores the effectiveness of a comprehensive inpatient cardiac rehabilitation programme and should encourage a more widespread use of rehabilitation early after an acute cardiac event.

Prognostic value of angiopoietin-2 in patients with chronic heart failure.

PURPOSE: The analysis of biomarkers with a prognostic value in chronic heart failure (CHF) is in constant progress. This study aimed to evaluate the short-term prognostic value of angiopoietin-2 (Ang2), galectin-3 (Gal-3), myeloperoxidase (MPO), endostatin (End), and pro-brain natriuretic peptide (pro-BNP) as a conventionally accepted prognosis biomarker in CHF patients. METHODS AND RESULTS: 146 consecutive patients with CHF due to left ventricular systolic dysfunction (LVEF<40% at echocardiography) were enrolled, and underwent serum/blood sample analysis after 12-h fasting. Within 1year, 25 (17%) patients died (D) or underwent heart transplantation (HT). D+HT patients showed higher values of Ang2 (Log Ang2: 8.97±0.52 vs. 8.45±0.69, p=0.0004), myeloperoxidase (MPO) (Log MPO: 5±1.1 vs. 4.2±1.3, p=0.005) and pro-BNP (Log pro-BNP: 8.70±0.9 vs. 7.45±1.3, p<0.00001). At univariate Cox regression, pro-BNP and Ang2 were the best predictors of 1-year mortality, with area under the curve (AUC)=0.78 for pro-BNP (68% sensitivity and 82% specificity to predict outcome for a cut-off value of 5109pg/mL, 95% confidence interval [CI] 0.70-0.85, p<0.0001) and AUC=0.73 for Ang2 (84% sensitivity and 61% specificity to predict outcome for a cut-off value of 5175pg/mL, 95% CI 0.65-0.80, p<0.0001). At multivariate analysis, pro-BNP was the only predictor of one-year D/HT. CONCLUSION: In our series of CHF patients, Ang2 and pro-BNP showed the best predictive value for 1-year outcome, while only pro-BNP could independently predict D/HT.

Sex Profile and Risk Assessment With Cardiopulmonary Exercise Testing in Heart Failure: Propensity Score Matching for Sex Selection Bias.

BACKGROUND: In heart failure (HF), women show better survival despite a comparatively low peak oxygen consumption (V˙o2): this raises doubt about the accuracy of risk assessment by cardiopulmonary exercise testing (CPET) in women. Accordingly, we aimed to check (1) whether the predictive role of well-known CPET risk indexes, ie, peak V˙o2 and ventilatory response (V˙e/V˙co2 slope), is sex independent and (2) if sex-related characteristics that impact outcome in HF should be considered as associations that may confound the effect of sex on survival. METHODS: The study population consisted of 2985 patients with HF, 498 (17%) of whom were women, from the multicentre Metabolic Exercise Test Data Combined with Cardiac and Kidney Indexes (MECKI): the end point was cardiovascular death within a 3-year period. RESULTS: During the follow-up, 305 (12%) men and 39 (8%) women (P = 0.005) died, and female sex was linked to better survival on univariate analysis (P = 0.008) and independent of peak V˙o2 and V˙e/V˙co2 slope on multivariate analysis. According to propensity score matching for female sex to exclude a sex selection bias and sample discrepancy, 498 men were selected: the standardized percentage bias ranged from 20.8 (P < 0.0001) to 3.3 (P = 0.667). After clinical profile harmonizing, female sex was predictive of HF at univariate analysis. CONCLUSIONS: The low peak V˙o2 and female association with better outcome in HF might be counterfeit: the female prognostic advantage is lost when sex-specific differences are correctly taken into account with propensity score matching, suggesting that for an effective and efficient HF model, adjustment must be made for sex-related characteristics.

The metabolic exercise test data combined with Cardiac And Kidney Indexes (MECKI) score and prognosis in heart failure. A validation study.

BACKGROUND: The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score is a prognostic model to identify heart failure (HF) patients at risk for cardiovascular mortality (CVM) and urgent heart transplantation (uHT) based on 6 routine clinical parameters: hemoglobin, sodium, kidney function by the Modification of Diet in Renal Disease (MDRD) equation, left ventricle ejection fraction (LVEF), percentage of predicted peak oxygen consumption (VO2) and VE/VCO2 slope. OBJECTIVES: MECKI score must be generalizable to be considered useful: therefore, its performance was validated in a new sequence of HF patients. METHODS: Both the development (MECKI-D) and the validation (MECKI-V) cohorts were composed of consecutive HF patients with LVEF <40% able to perform a symptom-limited cardiopulmonary exercise testing. The CVM or uHT rates were analyzed at one, two and three years in both cohorts: all patients with a censoring time shorter than the scheduled follow-up were excluded, while those with events occurring after 1, 2 and 3 years were considered as censored. RESULTS: MECKI-D and MECKI-V consisted of 2009 and 992 patients, respectively. MECKI-V patients had a higher LVEF, higher peak VO2 and lower VE/VCO2 slope, higher prescription of beta-blockers and device therapy: after the 3-year follow-up, CVM or uHT occurred in 206 (18%) MECKI-D and 44 (13%) MECKI-V patients (p<0.000), respectively. MECKI-V AUC values at one, two and three years were 0.81 ± 0.04, 0.76 ± 0.04, and 0.80 ± 0.03, respectively, not significantly different from MECKI-D. CONCLUSIONS: MECKI score preserves its predictive ability in a HF population at a lower risk.

Disability after cardiac surgery is the major predictor of infections occurring in the rehabilitation phase.

BACKGROUND: Few data have assessed the incidence, site and predictors of infections following cardiac surgery after discharge, particularly during an early rehabilitation phase. AIM: To assess the epidemiology and predictors of infections occurring after cardiac surgery. METHODS: Data prospectively recorded from 5464 patients, consecutively included in a residential cardiac rehabilitation programme after cardiac surgery, were retrospectively analysed. Major infections were arbitrarily defined as (1) demonstration of bacterial growth in a sample collected to rule out a clinical suspected infection and (2) requiring an intravenous antibiotic treatment. Infections were grouped as (1) surgery-site infections (SSIs), and (2) healthcare associated infections (HCAIs). Barthel index was used as a measure of disability. RESULTS: Major infections occurred in 10.9% of patients, with SSI documented in 4.1% and HCAI in 6.8% of patients. In 50% of the cases, infections were diagnosed within four days from admission, 18 ± 16 days from intervention. A Barthel index <60 was the strongest independent predictor of SSI or HCAI. An older age, the presence of chronic renal failure or chronic obstructive pulmonary disease were all significantly associated with HCAI but not with SSI. CONCLUSIONS: In a large cohort of patients, residual disability after cardiac surgery was the strongest independent predictor of infections. Disability is readily accessible, and can be used to recognize patients at higher risk of infections. The 10.9% rate of major infections observed after discharge from the surgical department confirms the importance of prolonging infection surveillance after discharge from the cardiac surgery department.

Healthy lifestyle interventions to combat noncommunicable disease-a novel nonhierarchical connectivity model for key stakeholders: a policy statement from the American Heart Association, European Society of Cardiology, European Association for Cardiovascular Prevention and Rehabilitation, and American College of Preventive Medicine.

Noncommunicable diseases (NCDs) have become the primary health concern for most countries around the world. Currently, more than 36 million people worldwide die from NCDs each year, accounting for 63% of annual global deaths; most are preventable. The global financial burden of NCDs is staggering, with an estimated 2010 global cost of $6.3 trillion (US dollars) that is projected to increase to $13 trillion by 2030. A number of NCDs share one or more common predisposing risk factors, all related to lifestyle to some degree: (1) cigarette smoking, (2) hypertension, (3) hyperglycemia, (4) dyslipidemia, (5) obesity, (6) physical inactivity, and (7) poor nutrition. In large part, prevention, control, or even reversal of the aforementioned modifiable risk factors are realized through leading a healthy lifestyle (HL). The challenge is how to initiate the global change, not toward increasing documentation of the scope of the problem but toward true action-creating, implementing, and sustaining HL initiatives that will result in positive, measurable changes in the previously defined poor health metrics. To achieve this task, a paradigm shift in how we approach NCD prevention and treatment is required. The goal of this American Heart Association/European Society of Cardiology/European Association for Cardiovascular Prevention and Rehabilitation/American College of Preventive Medicine policy statement is to define key stakeholders and highlight their connectivity with respect to HL initiatives. This policy encourages integrated action by all stakeholders to create the needed paradigm shift and achieve broad adoption of HL behaviors on a global scale.

Healthy Lifestyle Interventions to Combat Noncommunicable Disease­A Novel Nonhierarchical Connectivity Model for Key Stakeholders: A Policy Statement From the American Heart Association, European Society of Cardiology, European Association for Cardiovascular Prevention and Rehabilitation, and American College of Preventive Medicine.

Noncommunicable diseases (NCDs) have become the primary health concern for most countries around the world. Currently, more than 36 million people worldwide die from NCDs each year, accounting for 63% of annual global deaths; most are preventable. The global financial burden of NCDs is staggering, with an estimated 2010 global cost of $6.3 trillion (US dollars) that is projected to increase to $13 trillion by 2030. A number of NCDs share one or more common predisposing risk factors, all related to lifestyle to some degree: (1) cigarette smoking, (2) hypertension, (3) hyperglycemia, (4) dyslipidemia, (5) obesity, (6) physical inactivity, and (7) poor nutrition. In large part, prevention, control, or even reversal of the aforementioned modifiable risk factors are realized through leading a healthy lifestyle (HL). The challenge is how to initiate the global change, not toward increasing documentation of the scope of the problem but toward true action-creating, implementing, and sustaining HL initiatives that will result in positive, measurable changes in the previously defined poor health metrics. To achieve this task, a paradigm shift in how we approach NCD prevention and treatment is required. The goal of this American Heart Association/European Society of Cardiology/European Association for Cardiovascular Prevention and Rehabilitation/American College of Preventive Medicine policy statement is to define key stakeholders and highlight their connectivity with respect to HL initiatives. This policy encourages integrated action by all stakeholders to create the needed paradigm shift and achieve broad adoption of HL behaviors on a global scale.

Hemodynamic, not ventilatory, inefficiency is associated with high VE/VCO2 slope in repaired, noncyanotic congenital heart disease.

BACKGROUND: A high slope of the ventilation vs. carbon dioxide relationship (VE/VCO2 slope) during incremental exercise has been reported in several congenital heart disease (CHD) types, but it is not clear whether the main cause of high VE/VCO2 slope is excessive ventilation or reduced perfusion. METHODS: We studied 169 adolescent and adult patients with repaired, noncyanotic CHD, divided into 2 groups according to VE/VCO2 slope %predicted values (≤120 and >120), and 15 age- and sex-matched normals. VCO2/VE max and VO2/VE max were considered proxies of the perfusion/ventilation relationship, with VCO2 and VO2 as indirect descriptors of cardiac output. RESULTS: VCO2/VE max was significantly and inversely related to VE/VCO2 slope (r=-0.73, p<0.0001), and higher in normals and ≤120 than in >120 (39.6 ± 7.7, 36.1 ± 5.3 and 28.5 ± 4.1, respectively, p<0.0001). Similarly, VCO2 at VCO2/VE max was higher in normals and ≤120 than in >120 (1701 ± 474, 1480 ± 492 and 1169 ± 388 ml/min, respectively, p<0.0001), whereas ventilation at VCO2/VE max showed no changes (43 ± 8, 41 ± 12, 41 ± 11 and 41 ± 9l/min, respectively, p=0.82) between groups. Thus, differences in VCO2/VE max and VE/VCO2 slope between groups were due mostly to changes in VCO2, i.e. in cardiac output, rather than ventilation. The same behavior was observed for VO2/VE max. CONCLUSIONS: A high VE/VCO2 slope observed in patients with repaired, noncyanotic CHD seems not to depend on excessive ventilation but on hypoperfusion due to impaired cardiac output response to incremental exercise. This finding should focus researchers' attention mainly on the heart when addressing exercise pathophysiology of this patient population.

Renal function and peak exercise oxygen consumption in chronic heart failure with reduced left ventricular ejection fraction.

BACKGROUND: Chronic kidney disease is associated with sympathetic activation and muscle abnormalities, which may contribute to decreased exercise capacity. We investigated the correlation of renal function with peak exercise oxygen consumption (V̇O2) in heart failure (HF) patients. METHODS AND RESULTS: We recruited 2,938 systolic HF patients who underwent clinical, laboratory, echocardiographic and cardiopulmonary exercise testing. The patients were stratified according to estimated glomerular filtration rate (eGFR). Mean follow-up was 3.7 years. The primary outcome was a composite of cardiovascular death and urgent heart transplantation at 3 years. On multivariable regression, eGFR was predictor of peakV̇O2(P<0.0001). Other predictors were age, sex, body mass index, HF etiology, NYHA class, atrial fibrillation, resting heart rate, B-type natriuretic peptide, hemoglobin, and treatment. After adjusting for significant covariates, the hazard ratio for primary outcome associated with peakV̇O2<12 ml·kg(-1)·min(-1)was 1.75 (95% confidence interval (CI): 1.06-2.91; P=0.0292) in patients with eGFR ≥60, 1.77 (0.87-3.61; P=0.1141) in those with eGFR of 45-59, and 2.72 (1.01-7.37; P=0.0489) in those with eGFR <45 ml·min(-1)·1.73 m(-2). The area under the receiver-operating characteristic curve for peakV̇O2<12 ml·kg(-1)·min(-1)was 0.63 (95% CI: 0.54-0.71), 0.67 (0.56-0.78), and 0.57 (0.47-0.69), respectively. Testing for interaction was not significant. CONCLUSIONS: Renal dysfunction is correlated with peakV̇O2. A peakV̇O2cutoff of 12 ml·kg(-1)·min(-1)offers limited prognostic information in HF patients with more severely impaired renal function.

The Italian MacNew heart disease health-related quality of life questionnaire: a validation study.

Patient-centered treatment outcomes such as health-related quality of life are recommended in clinical care and research studies. Health-related quality of life questionnaires need to be validated in the language of the target population. The reliability and validity of the Italian version of the MacNew Questionnaire was determined in patients with angina, myocardial infarction, or ischemic heart failure. Sociodemographic and clinical data were collected on 298 patients [angina, n = 88; MI, n = 106; heart failure, n = 104; mean age, 64.8 (±10.6) years] at three centers in Italy. MacNew mean scores were higher (p < 0.001) in patients with myocardial infarction than in patients with either angina or heart failure with no floor and minimal ceiling effects. The three-factor structure of the original MacNew form was largely confirmed explaining 54.6% of the total variance. The Italian MacNew version demonstrates high internal consistency reliability (Cronbach's α ≥ 0.86), confirms the convergent validity hypotheses with strong correlations on six of eight comparisons (r ≥ 0.86), partially confirms discriminative validity with the SF-36 health transition item, and fully confirms discriminative validity with the Hospital Anxiety and Depression Scale. The Italian version of the MacNew Questionnaire demonstrates satisfactory psychometric properties, and is reliable and valid in Italian-speaking patients with angina, MI, or heart failure. Responsiveness could not be tested due to the cross-sectional design of the parent study, and needs to be investigated in an intervention study.

The 10-year anniversary of the European Association for Cardiovascular Prevention and Rehabilitation: achievements and challenges.

On the occasion of the 2014 European Society of Cardiology annual congress in Barcelona the European Association for Cardiovascular Prevention and Rehabilitation (EACPR) will celebrate its 10-year anniversary, having been initiated in Munich in 2004. In this article each EACPR president gives their personal recollections and views on the main achievements under their leadership and discusses the challenges for preventive cardiology that still lay ahead.

EaRly-start ExerciSe training afTer acute hemodynAmic decompensation in patients with chRonic hearT failure (RE-START). A multicenter, randomized, controlled trial on short-term feasibility and impact on functional capacity, symptoms and neurohumoral activation .

RE-START is a multicenter, randomized, prospective, open, controlled trial aiming to evaluate the feasibility and the short- and medium-term effects of an early-start AET program on functional capacity, symptoms and neurohormonal activation in chronic heart failure (CHF) patients with recent acute hemodynamic decompensation. Study endpoints will be: 1) safety of and compliance to AET; 2) effects of AET on i) functional capacity, ii) patient-reported symptoms and iii) AET-induced changes in beta-adrenergic receptor signaling and circulating angiogenetic and inflammatory markers. Two-hundred patients, randomized 1:1 to training (TR) or control (C), will be enrolled. Inclusion criteria: 1) history of systolic CHF for at least 6 months, with ongoing acute decompensation with need of intravenous diuretic and/or vasodilator therapy; 2) proBNP > 1000 pg/mI at admission. Exclusion criteria: 1) ongoing cardiogenic shock; 2) need of intravenous inotropic therapy; 3) creatinine > 2.5 mg/dl at admission. After a 72-hour run-in period, TR will undergo the following 12-day early-start AET protocol: days 1-2: active/passive mobilization (2 sessions/day, each 30 minutes duration); days 3-4: as days 1-2 + unloaded bedside cycle ergometer (3 sessions/day, each 5-10 minutes duration); days 5-8: as days 1-2 + unloaded bedside cycle ergometer (3 sessions/day, each 15-20 minutes duration); days 9-12: as days 1-2 + bedside cycle ergometer at 10-20 W (3 sessions/day, each 15-20 minutes duration). During the same period, C will undergo the same activity protocol as in days 1-2 for TR. All patients will undergo a 6-min WT at day 1, 6, 12 and 30 and echocardiogram, patient-reported symptoms on 7-point Likert scale and measurement of lymphocyte G protein coupled receptor kinase, VEGF, angiopoietin, TNF alfa, IL-1, IL-6 and eNOS levels at day 1, 12 and 30.

Fibrosis markers and CRIM1 increase in chronic heart failure of increasing severity.

BACKGROUND: Fibrosis suppressors/activators in chronic heart failure (CHF) is a topic of investigation. AIM: To quantify serum levels of fibrosis regulators in CHF. METHODS: ELISA tests were used to quantify fibrosis regulators, procollagen type-(PIP)I, (PIP)III, collagen-I, III, BMP1,2,3,7, SDF1α, CXCR4, fibulin 1,2,3, BMPER, CRIM1 and BAMBI in 66 CHF (NYHA class I, n = 9; II, n = 34; III n = 23), and in 14 controls. RESULTS: In CHF, TGFßR2, PIPIII, SDF1α and CRIM1 were increased. PIPIII correlated with CRIM1. CONCLUSIONS: The BMPs inhibitor CRIM1 is increased and correlates with higher levels of serum PIPIII showing an imbalance in favor of pro-fibrotic mechanisms in CHF.

Cardiovascular mortality and chronotropic incompetence in systolic heart failure: the importance of a reappraisal of current cut-off criteria.

AIMS: An independent role for the exercise-induced heart rate (HR) response-and specifically the chronotropic incompetence (CI)-in the prognosis of heart failure (HF) is still debated. The multicentre study reported here sought to investigate the prognostic values of HR and CI variables on cardiovascular mortality in a large cohort of systolic HF patients. METHODS AND RESULTS: A total of 1045 HF patients were recruited and prospectively followed in three Italian HF centres. The study endpoint was cardiovascular mortality. Besides a full clinical examination, each patient underwent a maximal cardiopulmonary exercise test at study enrolment. The age-predicted peak HR (%pHR) and the peak HR reserve (%pHRR) according to different cut-off values (60-80% of the maximum predicted) were adopted to identify the presence of CI. The median follow-up was 876 days (interquartile range 386-1590 days). Cardiovascular death occurred in 145 cases (13.8%). Besides LVEF, peak oxygen uptake, ventilation vs. carbon dioxide production slope, and beta-blocker therapy, the multivariate analysis showed that both %pHR and %pHRR were able to predict prognosis when considered as continuous variables. Conversely, the presence of CI was associated with the study endpoint only when the 70% (%pHR <70%, hazard ratio 1.80, confidence interval 1.24-2.61, P = 0.002; %pHRR <70%, hazard ratio 1.77, confidence interval 1.09-2.86, P = 0.020) or the 65% cut-off values (%pHR <65%, hazard ratio 2.04, confidence interval 1.34-3.10, P = 0.001; %pHRR <65%, hazard ratio 1.54, confidence interval 1.03-2.32, P = 0.038) were adopted. CONCLUSIONS: Our findings demonstrated an additive role of CI in stratifying cardiovascular mortality. Both the 65% and the 70% cut-off values, regardless of the method (%pHR and %pHRR), allow identification of HF patients with the worst prognosis, thus supporting such definitions of CI in HF.

Secondary prevention in the clinical management of patients with cardiovascular diseases. Core components, standards and outcome measures for referral and delivery: a policy statement from the cardiac rehabilitation section of the European Association for Cardiovascular Prevention & Rehabilitation. Endorsed by the Committee for Practice Guidelines of the European Society of Cardiology.

Despite major improvements in diagnostics and interventional therapies, cardiovascular diseases remain a major health care and socio-economic burden both in western and developing countries, in which this burden is increasing in close correlation to economic growth. Health authorities and the general population have started to recognize that the fight against these diseases can only be won if their burden is faced by increasing our investment on interventions in lifestyle changes and prevention. There is an overwhelming evidence of the efficacy of secondary prevention initiatives including cardiac rehabilitation in terms of reduction in morbidity and mortality. However, secondary prevention is still too poorly implemented in clinical practice, often only on selected populations and over a limited period of time. The development of systematic and full comprehensive preventive programmes is warranted, integrated in the organization of national health systems. Furthermore, systematic monitoring of the process of delivery and outcomes is a necessity. Cardiology and secondary prevention, including cardiac rehabilitation, have evolved almost independently of each other and although each makes a unique contribution it is now time to join forces under the banner of preventive cardiology and create a comprehensive model that optimizes long term outcomes for patients and reduces the future burden on health care services. These are the aims that the Cardiac Rehabilitation Section of the European Association for Cardiovascular Prevention & Rehabilitation has foreseen to promote secondary preventive cardiology in clinical practice.