ROLE OF OSCILLATORY BREATHING DURING CARDIOPULMONARY EXERCISE TEST FOR PROGNOSTIC STRATIFICATION OF ELDERLY PATIENTS WITH CHRONIC HEART FAILURE

We sought to determine the prognostic role of EOB compared with other ventilatory parameters in risk stratification of elderly CHF patients capable to perform a maximal exercise test

Different correlates but similar prognostic implications for right ventricular dysfunction in heart failure patients with reduced or preserved ejection fraction

Aims: To evaluate whether the clinical and echocardiographic correlates and the prognostic significance of right ventricular (RV) dysfunction are different in heart failure patients with reduced (HFrEF), mid-range (HFmrEF), or preserved (HFpEF) left ventricular ejection fraction. Methods and results: The study included 1663 patients with heart failure caused by ischaemic or hypertensive heart disease or by idiopathic cardiomyopathy. Left ventricular ejection fraction was 40mmHg was by far the strongest correlate of a reduced TAPSE in HFpEF and HFmrEF patients (interaction analysis, P=0.0011). TAPSE/PASP proved to be a powerful predictor of prognosis in all patients. Conclusions: The correlates of RV dysfunction differ in HFrEF compared with HFpEF and HFmrEF patients. Regardless of the extent of LV dysfunction, the TAPSE/PASP ratio is a powerful independent predictor of prognosis in all heart failure patients

Exercise tolerance can explain the obesity paradox in patients with systolic heart failure: Data from the MECKI Score Research Group

Aims Obesity has been found to be protective in heart failure (HF), a finding leading to the concept of an obesity paradox. We hypothesized that a preserved cardiorespiratory fitness in obese HF patients may affect the relationship between survival and body mass index (BMI) and explain the obesity paradox in HF. Methods and results A total of 4623 systolic HF patients (LVEF 31.5 ± 9.5%, BMI 26.2 ± 3.6 kg/m 2 ) were recruited and prospectively followed in 24 Italian HF centres belonging to the MECKI Score Research Group. Besides full clinical examination, patients underwent maximal cardiopulmonary exercise test at study enrolment. Median follow-up was 1113 (553-1803) days. The study population was divided according to BMI (30 to ≤35 kg/m 2 ) and predicted peak oxygen consumption (peak VO 2 , 80%). Study endpoints were all-cause and cardiovascular deaths including urgent cardiac transplant. All-cause and cardiovascular deaths occurred in 951 (28.6%, 57.4 per person-years) and 802 cases (17.4%, 48.4 per 1000 person-years), respectively. In the high BMI groups, several prognostic parameters presented better values [LVEF, peak VO 2 , ventilation/carbon dioxide slope, renal function, and haemoglobin (P < 0.01)] compared with the lower BMI groups. Both BMI and peak VO 2 were significant positive predictors of longer survival: both higher BMI and peak VO 2 groups showed lower mortality (P < 0.001). At multivariable analysis and using a matching procedure (age, gender, LVEF, and peak VO 2 ), the protective role of BMI disappeared. Conclusion Exercise tolerance affects the relationship between BMI and survival. Cardiorespiratory fitness mitigates the obesity paradox observed in HF patients

Severe heart failure prognosis evaluation for transplant selection in the era of beta-blockers: role of peak oxygen consumption

Peak oxygen consumption (VO2) is used to define the severity of heart failure (HF) [1] and [2] and as a criteria for heart transplant (HT) listing [3], [4] and [5]. Progressive improvement of HF patients' survival [6], even due to beta-blockers therapy [7] and [8], requires a continuous re-evaluation of severity judgment by peakVO2. The decision to list HF patients for HT is complex and maximal CPX is a useful test for this purpose, being peakVO2 values used in the decision making for HT according to the last published HT guidelines by the International Society for Heart and Lung Transplantation (ISHLT) [4]. More recently, American and European guidelines for the management of HF indicated lower limits, making crucial the constant re-evaluation of listing criteria [1] and [3]. Moreover, the post-HT survival rate has showed some but relatively minor improvement in the past years, being, at present, 90% at 1 year, 75% at 5 years and 50% at 10 years in the general population of transplanted patients [6]. In contrast, survival for HF patients, independently of HT, has significantly improved in the current era, even due to beta-blocker therapy [3] and [6]

Long-term prognostic role of diabetes mellitus and glycemic control in heart failure patients with reduced ejection fraction

Background The prognostic role of diabetes mellitus (DM) in heart failure (HF) patients is undefined, since DM is outweighed by several DM-related variables when confounders are considered. We determined the prognostic role of DM, treatment, and glycemic control in a real-life HF population. Methods 3927 HF patients included in the Metabolic Exercise Cardiac Kidney Index (MECKI) score database were evaluated with a median follow-up of 3.66 years (IQR 1.70\u20136.67). Data analysis considered survival between DM (n = 897) vs. non-DM (n = 3030) patients, and, in diabetics, between insulin (n = 304), oral antidiabetics (n = 479), and dietary only (n = 88) treatments. The role of glycemic control was evaluated grouping DM patients according to glycated hemoglobin (HbA1c): &lt;7% (n = 266), 7.1\u20138% (n = 133), &gt;8% (n = 149). All analyses were performed also adjusting for ejection fraction, renal function, hemoglobin, sodium, exercise peak oxygen uptake, and ventilation/carbon dioxide relationship slope. Study primary endpoint was the composite of cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation. Secondary endpoints were cardiovascular and all causes death. Results For all endpoints, upon adjustment for confounders, DM status and insulin treatment or dietary regimen were not significantly associated with adverse long-term prognosis compared to non-DM and oral antidiabetic treated patients, respectively. A worse prognosis was observed in HbA1c &gt;8% patients (Log-Rank p &lt; 0.001), even after correction for confounding factors. All results were replicated by hazard ratio analysis. Conclusion In HF patients, DM, insulin treatment and dietary regimen are not adverse outcome predictors. The only condition related to long-term prognosis, considering potential confounders, is poor glycemic control

Metabolic exercise test data combined with cardiac and kidney indexes, the MECKI score: a multiparametric approach to heart failure prognosis

OBJECTIVES: We built and validated a new heart failure (HF) prognostic model which integrates cardiopulmonary exercise test (CPET) parameters with easy-to-obtain clinical, laboratory, and echocardiographic variables. BACKGROUND: HF prognostication is a challenging medical judgment, constrained by a magnitude of uncertainty. METHODS: Our risk model was derived from a cohort of 2716 systolic HF patients followed in 13 Italian centers. Median follow up was 1041days (range 4-5185). Cox proportional hazard regression analysis with stepwise selection of variables was used, followed by cross-validation procedure. The study end-point was a composite of cardiovascular death and urgent heart transplant. RESULTS: Six variables (hemoglobin, Na(+), kidney function by means of MDRD, left ventricle ejection fraction [echocardiography], peak oxygen consumption [% pred] and VE/VCO(2) slope) out of the several evaluated resulted independently related to prognosis. A score was built from Metabolic Exercise Cardiac Kidney Indexes, the MECKI score, which identified the risk of study end-point with AUC values of 0.804 (0.754-0.852) at 1year, 0.789 (0.750-0.828) at 2years, 0.762 (0.726-0.799) at 3years and 0.760 (0.724-0.796) at 4years. CONCLUSIONS: This is the first large-scale multicenter study where a prognostic score, the MECKI score, has been built for systolic HF patients considering CPET data combined with clinical, laboratory and echocardiographic measurements. In the present population, the MECKI score has been successfully validated, performing very high AUC

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 (< 11 g/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 1363 days (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 < 11 g/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

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 (V\u2d9O2) 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 peakV\u2d9O2 (P<0.0001). Other predictors were age, sex, body mass index, HF etiology, NYHA class, atrial fibrillation, resting heart rate, Btype natriuretic peptide, hemoglobin, and treatment. After adjusting for significant covariates, the hazard ratio for primary outcome associated with peakVO2 <12 ml \u30fb kg 121 \u30fb min 121 was 1.75 (95% confidence interval (CI): 1.06\u20132.91; P=0.0292) in patients with eGFR 6560, 1.77 (0.87\u20133.61; P=0.1141) in those with eGFR of 45\u201359, and 2.72 (1.01\u2013 7.37; P=0.0489) in those with eGFR <45 ml \u30fb min 121 \u30fb 1.73 m 122. The area under the receiver-operating characteristic curve for peakV\u2d9O2 <12 ml \u30fb kg 121 \u30fb min 121 was 0.63 (95% CI: 0.54\u20130.71), 0.67 (0.56\u20130.78), and 0.57 (0.47\u20130.69), respectively. Testing for interaction was not significant. Conclusions: Renal dysfunction is correlated with peakV O2. A peakV O2 cutoff of 12 ml \u30fb kg\u20131 \u30fb min\u20131 offers limited prognostic information in HF patients with more severely impaired renal function

Heart failure prognosis over time: how the prognostic role of oxygen consumption and ventilatory efficiency during exercise has changed in the last 20 years

Aims: Exercise-derived parameters, specifically peak exercise oxygen uptake (peak VO 2 ) and minute ventilation/carbon dioxide relationship slope (VE/VCO 2 slope), have a pivotal prognostic value in heart failure (HF). It is unknown how the prognostic threshold of peak VO 2 and VE/VCO 2 slope has changed over the last 20 years in parallel with HF prognosis improvement. Methods and results: Data from 6083 HF patients (81% male, age 61 \ub1 13 years), enrolled in the MECKI score database between 1993 and 2015, were retrospectively analysed. By enrolment year, four groups were generated: group 1 1993\u20132000 (n = 440), group 2 2001\u20132005 (n = 1288), group 3 2006\u20132010 (n = 2368), and group 4 2011\u20132015 (n = 1987). We compared the 10-year survival of groups and analysed how the overall risk (cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation) changed over time according to peak VO 2 and VE/VCO 2 slope and to major clinical and therapeutic variables. At 10 years, a progressively higher survival from group 1 to group 3 was observed, with no further improvement afterwards. A 20% risk for peak VO 2 15 mL/min/kg (95% confidence interval 16\u201313), 9 (11\u20138), 4 (4\u20132) and 5 (7\u20134) was observed in group 1, 2, 3, and 4, respectively, while the VE/VCO 2 slope value for a 20% risk was 32 (37\u201329), 47 (51\u201343), 59 (64\u201355), and 57 (63\u201352), respectively. Conclusions: Heart failure prognosis improved over time up to 2010 in a HF population followed by experienced centres. The peak VO 2 and VE/VCO 2 slope cut-offs identifying a definite risk progressively decreased and increased over time, respectively. The prognostic threshold of peak VO 2 and VE/VCO 2 slope must be updated whenever HF prognosis improves