Effects of sacubitril/valsartan on exercise capacity: a prognostic improvement that starts during uptitration.

PURPOSE: Sacubitril/valsartan is a mainstay of the treatment of heart failure with reduced ejection fraction (HFrEF); however, its effects on exercise performance yielded conflicting results. Aim of our study was to evaluate the impact of sacubitril/valsartan on exercise parameters and echocardiographic and biomarker changes at different drug doses. METHODS: We prospectively enrolled consecutive HFrEF outpatients eligible to start sacubitril/valsartan. Patients underwent clinical assessment, cardiopulmonary exercise test (CPET), blood sampling, echocardiography, and completed the Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Sacubitril/valsartan was introduced at 24/26 mg b.i.d. dose and progressively uptitrated in a standard monthly-based fashion to 97/103 mg b.i.d. or maximum tolerated dose. Study procedures were repeated at each titration visit and 6 months after reaching the maximum tolerated dose. RESULTS: Ninety-six patients completed the study, 73 (75%) reached maximum sacubitril/valsartan dose. We observed a significant improvement in functional capacity across all study steps: oxygen intake increased, at peak exercise (from 15.6 ± 4.5 to 16.5 ± 4.9 mL/min/kg; p trend = 0.001), while minute ventilation/carbon dioxide production relationship reduced in patients with an abnormal value at baseline. Sacubitril/valsartan induced positive left ventricle reverse remodeling (EF from 31 ± 5 to 37 ± 8%; p trend < 0.001), while NT-proBNP reduced from 1179 [610-2757] to 780 [372-1344] pg/ml (p trend < 0.0001). NYHA functional class and the subjective perception of limitation in daily life at KCCQ-12 significantly improved. The Metabolic Exercise Cardiac Kidney Index (MECKI) score progressively improved from 4.35 [2.42-7.71] to 2.35% [1.24-4.96], p = 0.003. CONCLUSIONS: A holistic and progressive HF improvement was observed with sacubitril/valsartan in parallel with quality of life. Likewise, a prognostic enhancement was observed.

The importance of re-evaluating the risk score in heart failure patients: An analysis from the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score database.

BACKGROUND: The role of risk scores in heart failure (HF) management has been highlighted by international guidelines. In contrast with HF, which is intrinsically a dynamic and unstable syndrome, all its prognostic studies have been based on a single evaluation. We investigated whether time-related changes of a well-recognized risk score, the MECKI score, added prognostic value. MECKI score is based on peak VO2, VE/VCO2 slope, Na+, LVEF, MDRD and Hb. METHODS: A multi-centre retrospective study was conducted involving 660 patients who performed MECKI re-evaluation at least 6 months apart. Based on the difference between II and I evaluation of MECKI values (MECKI II - MECKI I = ∆ MECKI) the study population was divided in 2 groups: those presenting a score reduction (∆ MECKI <0, i.e. clinical improvement), vs. patients presenting an increase (∆ MECKI >0, clinical deterioration). RESULTS: The prognostic value of MECKI score is confirmed also when re-assessed during follow-up. The group with improved MECKI (366 patients) showed a better prognosis compared to patients with worsened MECKI (294 patients) (p < 0.0001). At 1st evaluation, the two groups differentiated by LVEF, VE/VCO2 slope and blood Na+ concentration, while at 2nd evaluation they differentiated in all 6 parameters considered in the score. The patients who improved MECKI score, improved in all components of the score but hemoglobin, while patients who worsened the score, worsened all parameters. CONCLUSIONS: This study shows that re-assessment of MECKI score identifies HF subjects at higher risk and that score improvement or deterioration regards several MECKI score generating parameters confirming the holistic background of HF.

Why Levosimendan Improves the Clinical Condition of Patients With Advanced Heart Failure: A Holistic Approach.

BACKGROUND: In advanced heart failure (HF), levosimendan increases peak oxygen uptake (VO2). We investigated whether peak VO2 increase is linked to cardiovascular, respiratory, or muscular performance changes. METHODS AND RESULTS: Twenty patients hospitalized for advanced HF underwent, before and shortly after levosimendan infusion, 2 different cardiopulmonary exercise tests: (a) a personalized ramp protocol with repeated arterial blood gas analysis and standard spirometry including alveolar-capillary gas diffusion measurements at rest and at peak exercise, and (b) a step incremental workload cardiopulmonary exercise testing with continuous near-infrared spectroscopy analysis and cardiac output assessment by bioelectrical impedance analysis.Levosimendan significantly decreased natriuretic peptides, improved peak VO2 (11.3 [interquartile range 10.1-12.8] to 12.6 [10.2-14.4] mL/kg/min, P < .01) and decreased minute ventilation to carbon dioxide production relationship slope (47.7 ± 10.7 to 43.4 ± 8.1, P < .01). In parallel, spirometry showed only a minor increase in forced expiratory volume, whereas the peak exercise dead space ventilation was unchanged. However, during exercise, a smaller edema formation was observed after levosimendan infusion, as inferable from the changes in diffusion components, that is, the membrane diffusion and capillary volume. The end-tidal pressure of CO2 during the isocapnic buffering period increased after levosimendan (from 28 ± 3 mm Hg to 31 ± 2 mm Hg, P < .01). During exercise, cardiac output increased in parallel with VO2. After levosimendan, the total and oxygenated tissue hemoglobin, but not deoxygenated hemoglobin, increased in all exercise phases. CONCLUSIONS: In advanced HF, levosimendan increases peak VO2, decreases the formation of exercise-induced lung edema, increases ventilation efficiency owing to a decrease of reflex hyperventilation, and increases cardiac output and muscular oxygen delivery and extraction.

X-Ray Exposure in Cardiac Electrophysiology: A Retrospective Analysis in 8150 Patients Over 7 Years of Activity in a Modern, Large-Volume Laboratory.

BACKGROUND: Only a few studies have systematically evaluated fluoroscopy data of electrophysiological and device implantation procedures. Aims of this study were to quantify ionizing radiation exposure for electrophysiological/device implantation procedures in a large series of patients and to analyze the x-ray exposure trend over years and radiation exposure in patients undergoing atrial fibrillation ablation considering different technical aspects. METHODS AND RESULTS: We performed a retrospective analysis of all electrophysiological/device implantation procedures performed during the past 7 years in a modern, large-volume laboratory. We reported complete fluoroscopy data on 8150 electrophysiological/device implantation procedures (6095 electrophysiological and 2055 device implantation procedures); for each type of procedure, effective dose and lifetime attributable risk of cancer incidence and mortality were calculated. Over the 7-year period, we observed a significant trend reduction in fluoroscopy time, dose area product, and effective dose for all electrophysiological procedures (P<0.001) and a not statistically significant trend reduction for device implantation procedures. Analyzing 2416 atrial fibrillation ablations, we observed a significant variability of fluoroscopy time, dose area product and effective dose among 7 different experienced operators (P<0.0001) and a significant reduction of fluoroscopy use over time (P<0.0001) for all of them. Considering atrial fibrillation ablation techniques, fluoroscopy time was not different (P = 0.74) for radiofrequency catheter ablation in comparison with cryoablation, though cryoablation was still associated with higher dose area product and effective dose values (P<0.001). CONCLUSIONS: Electrophysiological procedures involve a nonnegligible x-ray use, leading to an increased risk of malignancy. Awareness of radiation-related risk, together with technological advances, can successfully optimize fluoroscopy use.