Gaia Cattadori

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/VCO2 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.

Exercise-Induced Pulmonary Edema in Heart Failure

Background—In heart failure (HF) patients, exercise may increase pulmonary capillary hydrostatic pressure and thereby generate pulmonary edema. If pulmonary edema developed, alveolar-capillary membrane conductance (Dm), measured immediately after exercise, would decrease. To test this hypothesis, we measured Dm before and at 2 and 60 minutes after exercise. Methods and Results—We studied 10 HF patients with exercise-induced periodic breathing, 10 with peak &OV0312;o2 ≤15 mL · min−1 · kg−1 (severe HF), 10 with &OV0312;o2=15 to 20 mL · min−1 · kg−1 (moderate HF), and 10 normal subjects (control). Using the Roughton-Forster technique, we measured carbon monoxide diffusion capacity (DLco) and its components, capillary blood volume (Vc) and Dm, at rest and 2 and 60 minutes after exercise. At rest, DLco and Dm were lowest in periodic breathing and highest in control subjects. Dm decreased in periodic breathing, severe HF, and moderate HF (−7.83±3.98, −5.57±2.03, and −3.85±3.53 mL · min−1 · mm Hg−1, respectively; P <0.01) at 2 minutes after exercise but not in control subjects. Vc increased in all groups at 2 minutes and remained elevated at 60 minutes only in periodic breathing. Dm/Vc was decreased in periodic breathing, severe HF, and moderate HF at 2 minutes but not in control subjects. Dm and Dm/Vc remained low at 60 minutes only in periodic breathing. Conclusions—Dm decreases after exercise in HF patients but not in control subjects, which suggests a decrease in conductance across the alveolar-capillary barrier, as with pulmonary edema. The reductions were most marked in HF patients with periodic breathing and less reduced in less severe HF.

Work-rate affects cardiopulmonary exercise test results in heart failure

Cardiopulmonary exercise test (CPET) is used to evaluate patients with chronic heart failure (HF) usually by means of a personalized ramp exercise protocol. Our aim was to evaluate if exercise duration or ramp rate influences the results.

Lung function with carvedilol and bisoprolol in chronic heart failure: Is β selectivity relevant?

Carvedilol is a β‐blocker with similar affinity for β1‐ and β2 receptors, while bisoprolol has higher β1 affinity. The respiratory system is characterized by β2‐receptor prevalence. Airway β receptors regulate bronchial tone and alveolar β receptors regulate alveolar fluid re‐absorption which influences gas diffusion.

Effects of simulated altitude-induced hypoxia on exercise capacity in patients with chronic heart failure

PURPOSE Patients with stable heart failure often wish to spend time at altitudes above those of their residence. However, it is not known whether they can safely tolerate ascent to high altitudes or what its effects on work capacity may be. SUBJECTS AND METHODS We studied 14 normal subjects and 38 patients with clinically stable heart failure, 12 of whom had normal workload [peak exercise oxygen consumption (VO(2)) greater than 20 mL/min/kg], 14 of whom had slightly diminished workload (peak VO(2) 20 to 15 mL/min/kg), and 12 of whom had markedly diminished workload (peak VO(2) less than 15 mL/min/kg) at baseline. All performed cardiopulmonary exercise tests with inspired oxygen fractions equal to those at 92, 1,000, 1,500, 2,000, and 3,000 m, and maximum achieved work rates (mean +/- SD) were measured. RESULTS All subjects completed the trial; no test was interrupted because of arrhythmia, angina, or ischemia. Maximum work rate decreased in parallel with increasing simulated altitude. The percentage decrease was greater for patients with heart failure and was most marked among those with the lowest workload at baseline. Maximum achieved work rate declined by 3% +/- 4% per 1,000 m in normal subjects, by 5% +/- 3% (P <0.01) in patients with heart failure with normal workload, by 5% +/- 4% (P <0.01) in patients with slightly diminished workload, and by 11% +/- 5% (P <0.01 vs normal subjects and vs the other patients with heart failure) in patients with markedly reduced workload. CONCLUSION Patients with stable heart failure who ascend to higher altitudes should expect to have a reduction in maximum physical activity in proportion to their exercise capacity at sea level.

Carvedilol reduces exercise-induced hyperventilation: A benefit in normoxia and a problem with hypoxia

To evaluate whether carvedilol influences exercise hyperventilation and the ventilatory response to hypoxia in heart failure (HF).

Circulating Plasma Surfactant Protein Type B as Biological Marker of Alveolar-Capillary Barrier Damage in Chronic Heart Failure

Background—Surfactant protein type B (SPB) is needed for alveolar gas exchange. SPB is increased in the plasma of patients with heart failure (HF), with a concentration that is higher when HF severity is highest. The aim of this study was to evaluate the relationship between plasma SPB and both alveolar-capillary diffusion at rest and ventilation versus carbon dioxide production during exercise. Methods and Results—Eighty patients with chronic HF and 20 healthy controls were evaluated consecutively, but the required quality for procedures was only reached by 71 patients with HF and 19 healthy controls. Each subject underwent pulmonary function measurements, including lung diffusion for carbon monoxide and membrane diffusion capacity, and maximal cardiopulmonary exercise test. Plasma SPB was measured by immunoblotting. In patients with HF, SPB values were higher (4.5 [11.1] versus 1.6 [2.9], P=0.0006, median and 25th to 75th interquartile), whereas lung diffusion for carbon monoxide (19.7±4.5 versus 24.6±6.8 mL/mm Hg per min, P<0.0001, mean±SD) and membrane diffusion capacity (28.9±7.4 versus 38.7±14.8, P<0.0001) were lower. Peak oxygen consumption and ventilation/carbon dioxide production slope were 16.2±4.3 versus 26.8±6.2 mL/kg per min (P<0.0001) and 29.7±5.9 and 24.5±3.2 (P<0.0001) in HF and controls, respectively. In the HF population, univariate analysis showed a significant relationship between plasma SPB and lung diffusion for carbon monoxide, membrane diffusion capacity, peak oxygen consumption, and ventilation/carbon dioxide production slope (P<0.0001 for all). On multivariable logistic regression analysis, membrane diffusion capacity (&bgr;, −0.54; SE, 0.018; P<0.0001), peak oxygen consumption (&bgr;, −0.53; SE, 0.036; P=0.004), and ventilation/carbon dioxide production slope (&bgr;, 0.25; SE, 0.026; P=0.034) were independently associated with SPB. Conclusion—Circulating plasma SPB levels are related to alveolar gas diffusion, overall exercise performance, and efficiency of ventilation showing a link between alveolar-capillary barrier damage, gas exchange abnormalities, and exercise performance in HF.

Long-term effectiveness of cardiac resynchronization therapy in heart failure patients with unfavorable cardiac veins anatomy comparison of surgical versus hemodynamic procedure.

OBJECTIVES This study sought to compare clinical, echocardiographic, and cardiopulmonary exercise testing response to cardiac resynchronization therapy (CRT) in patients with unfavorable anatomy of coronary sinus (CS) veins, randomized to transvenous versus surgical left ventricular (LV) lead implantation. BACKGROUND CRT efficacy depends on proper positioning of the LV lead over the posterolateral wall. A detailed pre-operative knowledge of CS anatomy might be of pivotal importance to accomplish a proper LV lead placement over this area. METHODS Study population included 40 patients (age 66 ± 4 years) with heart failure and indication to CRT, with unsuitable CS branches anatomy documented by pre-operative multislice computed cardiac tomography; 20 patients (Group 1) underwent surgical minithoracotomic LV lead implantation whereas 20 (Group 2) were implanted transvenously. New York Heart Association functional class, echocardiographic, and cardiopulmonary exercise testing data were assessed before and 1 year after CRT-system implant. RESULTS In all Group 1 patients, the LV leads were placed over the middle-basal segments of the posterolateral wall of the LV. This was not possible in Group 2 patients. One year after CRT, in Group 1, a significant improvement of New York Heart Association functional class, LV ejection fraction (from 28.8 ± 9.2% to 33.9 ± 7.2%, p < 0.01), LV end-systolic volume (from 165 ± 53 ml to 134 ± 48 ml, p < 0.001), and peak Vo(2)/kg (from 10.4 ± 4.5 ml/kg/min to 13.1 ± 3.1 ml/kg/min, p < 0.02) was observed. However, no improvement was observed in Group 2: LV ejection fraction varied from 27.4 ± 4.8% to 27.4 ± 5.7% (p = 0.9), LV end-systolic volume from 175 ± 46 ml to 166 ± 44 ml (p = 0.15), and peak Vo(2)/kg from 11.2 ± 3.2 ml/kg/min to 11.3 ± 3.4 ml/kg/min (p = 0.9). Changes after CRT between groups were highly significant. CONCLUSIONS In the setting of unfavorable CS branches of anatomy, CRT by a surgical minithoracotomic approach is preferable to transvenous lead implantation.

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 (<25, 25-30, >30 to ≤35 kg/m(2) ) and predicted peak oxygen consumption (peak VO2 , <50%, 50-80%, >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 VO2 , ventilation/carbon dioxide slope, renal function, and haemoglobin (P < 0.01)] compared with the lower BMI groups. Both BMI and peak VO2 were significant positive predictors of longer survival: both higher BMI and peak VO2 groups showed lower mortality (P < 0.001). At multivariable analysis and using a matching procedure (age, gender, LVEF, and peak VO2 ), 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.

Prognostic Value of Indeterminable Anaerobic Threshold in Heart Failure

Background—In patients with heart failure (HF), during maximal cardiopulmonary exercise test, anaerobic threshold (AT) is not always identified. We evaluated whether this finding has a prognostic meaning. Methods and Results—We recruited and prospectively followed up, in 14 dedicated HF units, 3058 patients with systolic (left ventricular ejection fraction <40%) HF in stable clinical conditions, New York Heart Association class I to III, who underwent clinical, laboratory, echocardiographic, and cardiopulmonary exercise test investigations at study enrollment. We excluded 921 patients who did not perform a maximal exercise, based on lack of achievement of anaerobic metabolism (peak respiratory quotient ⩽1.05). Primary study end point was a composite of cardiovascular death and urgent cardiac transplant, and secondary end point was all-cause death. Median follow-up was 3.01 (1.39–4.98) years. AT was identified in 1935 out of 2137 patients (90.54%). At multivariable logistic analysis, failure in detecting AT resulted significantly in reduced peak oxygen uptake and higher metabolic exercise and cardiac and kidney index score value, a powerful prognostic composite HF index (P<0.001). At multivariable analysis, the following variables were significantly associated with primary study end point: peak oxygen uptake (% pred; P<0.001; hazard ratio [HR]=0.977; confidence interval [CI]=0.97–0.98), ventilatory efficiency slope (P=0.01; HR=1.02; CI=1.01–1.03), hemoglobin (P<0.05; HR=0.931; CI=0.87–1.00), left ventricular ejection fraction (P<0.001; HR=0.948; CI=0.94–0.96), renal function (modification of diet in renal disease; P<0.001; HR=0.990; CI=0.98–0.99), sodium (P<0.05; HR=0.967; CI=0.94–0.99), and AT nonidentification (P<0.05; HR=1.41; CI=1.06–1.89). Nonidentification of AT remained associated to prognosis also when compared with metabolic exercise and cardiac and kidney index score (P<0.01; HR=1.459; CI=1.09–1.10). Similar results were obtained for the secondary study end point. Conclusions—The inability to identify AT most often occurs in patients with severe HF, and it has an independent prognostic role in HF.