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  • 1
    In: ESC Heart Failure, Wiley, Vol. 7, No. 1 ( 2020-02), p. 368-377
    Abstract: Ventilation vs. carbon dioxide production (VE/VCO 2 ) is among the strongest cardiopulmonary exercise testing prognostic parameters in heart failure (HF). It is usually reported as an absolute value. The current definition of normal VE/VCO 2 slope values is inadequate, since it was built from small groups of subjects with a particularly limited number of women and elderly. We aimed to define VE/VCO 2 slope prediction formulas in a sizable population and to test whether the prognostic power of VE/VCO 2 slope in HF was different if expressed as a percentage of the predicted value or as an absolute value. Methods and results We calculated the linear regressions between age and VE/VCO 2 slope in 1136 healthy subjects (68% male, age 44.9 ± 14.5, range 13–83 years). We then applied age‐adjusted and sex‐adjusted formulas to predict VE/VCO 2 slope to HF patients included in the metabolic exercise test data combined with cardiac and kidney indexes score database, which counts 6112 patients (82% male, age 61.4 ± 12.8, left ventricular ejection fraction 33.2 ± 10.5%, peakVO 2 14.8 ± 4.9, mL/min/kg, VE/VCO 2 slope 32.7 ± 7.7) from 24 HF centres. Finally, we evaluated whether the use of absolute values vs. percentages of predicted VE/VCO 2 affected HF prognosis prediction (composite of cardiovascular mortality + urgent transplant or left ventricular assist device). We did so in the entire cardiac and kidney indexes score population and separately in HF patients with severe (peakVO 2 〈 14 mL/min/kg, n = 2919, 61.1 events/1000 pts/year) or moderate (peakVO 2 ≥ 14 mL/min/kg, n = 3183, 19.9 events/1000 pts/year) HF. In the healthy population, we obtained the following equations: female, VE/VCO 2 = 0.052 × Age + 23.808 ( r = 0.192); male, VE/VCO 2 = 0.095 × Age + 20.227 ( r = 0.371) ( P = 0.007). We applied these formulas to calculate the percentages of predicted VE/VCO 2 values. The 2‐year survival prognostic power of VE/VCO 2 slope was strong, and it was similar if expressed as absolute value or as a percentage of predicted value (AUCs 0.686 and 0.690, respectively). In contrast, in severe HF patients, AUCs significantly differed between absolute values (0.637) and percentages of predicted values (0.650, P = 0.0026). Moreover, VE/VCO 2 slope expressed as a percentage of predicted value allowed to reclassify 6.6% of peakVO 2 〈 14 mL/min/kg patients (net reclassification improvement = 0.066, P = 0.0015). Conclusions The percentage of predicted VE/VCO 2 slope value strengthens the prognostic power of VE/VCO 2 in severe HF patients, and it should be preferred over the absolute value for HF prognostication. Furthermore, the widespread use of VE/VCO 2 slope expressed as percentage of predicted value can improve our ability to identify HF patients at high risk, which is a goal of utmost clinical relevance.
    Type of Medium: Online Resource
    ISSN: 2055-5822 , 2055-5822
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2814355-3
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  • 2
    In: ESC Heart Failure, Wiley, Vol. 5, No. 3 ( 2018-06), p. 267-274
    Abstract: Mineralocorticoid receptor antagonists (MRAs) have been demonstrated to improve outcomes in reduced ejection fraction heart failure (HFrEF) patients. However, MRAs added to conventional treatment may lead to worsening of renal function and hyperkalaemia. We investigated, in a population‐based analysis, the long‐term effects of MRA treatment in HFrEF patients. Methods and results We analysed data of 6046 patients included in the Metabolic Exercise Cardiac Kidney Index score dataset. Analysis was performed in patients treated ( n  = 3163) and not treated ( n  = 2883) with MRA. The study endpoint was a composite of cardiovascular death, urgent heart transplantation, or left ventricular assist device implantation. Ten years' survival was analysed through Kaplan–Meier, compared by log‐rank test and propensity score matching. At 10 years' follow‐up, the MRA‐untreated group had a significantly lower number of events than the MRA‐treated group ( P   〈  0.001). MRA‐treated patients had more severe heart failure (higher New York Heart Association class and lower left ventricular ejection fraction, kidney function, and peak VO 2 ). At a propensity‐score‐matching analysis performed on 1587 patients, MRA‐treated and MRA‐untreated patients showed similar study endpoint values. Conclusions In conclusion, MRA treatment does not affect the composite of cardiovascular death, urgent heart transplantation or left ventricular assist device implantation in a real‐life setting. A meticulous patient follow‐up, as performed in trials, is likely needed to match the positive MRA‐related benefits observed in clinical trials.
    Type of Medium: Online Resource
    ISSN: 2055-5822 , 2055-5822
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2814355-3
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  • 3
    In: European Journal of Heart Failure, Wiley, Vol. 20, No. 4 ( 2018-04), p. 700-710
    Abstract: Risk stratification in heart failure (HF) is crucial for clinical and therapeutic management. A multiparametric approach is the best method to stratify prognosis. In 2012, the Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score was proposed to assess the risk of cardiovascular mortality and urgent heart transplantation. The aim of the present study was to compare the prognostic accuracy of MECKI score to that of HF Survival Score (HFSS) and Seattle HF Model (SHFM) in a large, multicentre cohort of HF patients with reduced ejection fraction. Methods and results We collected data on 6112 HF patients and compared the prognostic accuracy of MECKI score, HFSS, and SHFM at 2‐ and 4‐year follow‐up for the combined endpoint of cardiovascular death, urgent cardiac transplantation, or ventricular assist device implantation. Patients were followed up for a median of 3.67 years, and 931 cardiovascular deaths, 160 urgent heart transplantations, and 12 ventricular assist device implantations were recorded. At 2‐year follow‐up, the prognostic accuracy of MECKI score was significantly superior [area under the curve (AUC) 0.781] to that of SHFM (AUC 0.739) and HFSS (AUC 0.723), and this relationship was also confirmed at 4 years (AUC 0.764, 0.725, and 0.720, respectively). Conclusion In this cohort, the prognostic accuracy of the MECKI score was superior to that of HFSS and SHFM at 2‐ and 4‐year follow‐up in HF patients in stable clinical condition. The MECKI score may be useful to improve resource allocation and patient outcome, but prospective evaluation is needed.
    Type of Medium: Online Resource
    ISSN: 1388-9842 , 1879-0844
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 1500332-2
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  • 4
    In: European Journal of Heart Failure, Wiley, Vol. 21, No. 2 ( 2019-02), p. 208-217
    Abstract: 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 ± 13 years), enrolled in the MECKI score database between 1993 and 2015, were retrospectively analysed. By enrolment year, four groups were generated: group 1 1993–2000 ( n  = 440), group 2 2001–2005 ( n  = 1288), group 3 2006–2010 ( n  = 2368), and group 4 2011–2015 ( 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 16–13), 9 (11–8), 4 (4–2) and 5 (7–4) was observed in group 1, 2, 3, and 4, respectively, while the VE/VCO 2 slope value for a 20% risk was 32 (37–29), 47 (51–43), 59 (64–55), and 57 (63–52), 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.
    Type of Medium: Online Resource
    ISSN: 1388-9842 , 1879-0844
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2019
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  • 5
    In: Neuropathology and Applied Neurobiology, Wiley, Vol. 47, No. 5 ( 2021-08), p. 664-678
    Abstract: Autophagic vacuolar myopathies (AVMs) are an emerging group of heterogeneous myopathies sharing histopathological features on muscle pathology, in which autophagic vacuoles are the pathognomonic morphologic hallmarks. Glycogen storage disease type II (GSDII) caused by lysosomal acid α‐glucosidase (GAA) deficiency is the best‐characterised AVM. Aims This study aimed to investigate the mutational profiling of seven neuromuscular outpatients sharing clinical, myopathological and biochemical findings with AVMs. Methods We applied a diagnostic protocol, recently published by our research group for suspected late‐onset GSDII (LO‐GSDII), including counting PAS‐positive lymphocytes on blood smears, dried blood spot (DBS)‐GAA, muscle biopsy histological and immunofluorescence studies, GAA activity assay and expression studies on muscle homogenate, GAA sequencing, GAA multiplex ligation‐dependent probe amplification (MLPA) and whole exome sequencing (WES). Results The patients had a limb girdle‐like muscular pattern with persistent hyperCKaemia; vacuolated PAS‐positive lymphocytes, glycogen accumulation and impaired autophagy at muscle biopsy. Decreased GAA activity was also measured. While GAA sequencing identified no pathogenic mutations, WES approach allowed us to identify for each patient an unexpected mutational pattern in genes cooperating in lysosomal‐autophagic machinery, some of which have never been linked to human diseases. Conclusions Our data suggest that reduced GAA activity may occur in any condition of impaired autophagy and that WES approach is advisable in all genetically undefined cases of autophagic myopathy. Therefore, deficiency of GAA activity and PAS‐positive lymphocytes should be considered as AVM markers together with LC3/p62‐positive autophagic vacuoles.
    Type of Medium: Online Resource
    ISSN: 0305-1846 , 1365-2990
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2008293-9
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  • 6
    In: European Journal of Heart Failure, Wiley, Vol. 19, No. 7 ( 2017-07), p. 904-914
    Abstract: The use of β‐blockers represents a milestone in the treatment of heart failure with reduced ejection fraction ( HFrEF ). Few studies have compared β‐blockers in HFrEF , and there is little data on the effects of different doses. The present study aimed to investigate in a large database of HFrEF patients ( MECKI score database) the association of β‐blocker treatment with a composite outcome of cardiovascular death, urgent heart transplantation or left ventricular assist device implantation, addressing the role of β‐selectivity and dosage regimens. Methods and results In 5242 HFrEF patients, we investigated the role of: (i) β‐blocker treatment vs. non‐β‐blocker treatment, (ii) β1‐/β2‐receptor‐blockers vs. β1‐selective blockers, and (iii) daily β‐blocker dose. Patients were followed for 3.58 years, and 1101 events (18.3%) were observed; 4435 patients (86.8%) were on β‐blockers, while 807 (13.2%) were not. At 5 years, β‐blocker‐patients showed a better outcome than non‐β‐blocker‐subjects [hazard ratio ( HR ) 0.48, P   〈  0.0001], while also considering potential confounders. A comparable prognosis was observed at 5 years in the β1‐/β2‐receptor‐blocker ( n  = 2219) vs. β1‐selective group ( n  = 2216) ( HR 0.95, P  = ns). A better prognosis was observed in high‐dose ( 〉 2 5 mg carvedilol equivalent daily dose, n  = 1005) patients than in both medium dose (12.5–25 mg, n  = 1431) and low dose ( 〈 12.5 mg, n  = 1960) ( HR 1.97, P   〈  0.001; HR 1.95, P  = 0.001, respectively), with no differences between the last two groups ( HR 0.84, P  = ns). Conclusion In a large population of chronic HFrEF patients, β‐blockers were associated with a more favourable prognosis without any difference between β1‐ and β2‐receptor‐blockers vs. β1‐selective blockers. A better outcome was observed in subjects receiving a high daily dose.
    Type of Medium: Online Resource
    ISSN: 1388-9842 , 1879-0844
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 1500332-2
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  • 7
    In: European Journal of Heart Failure, Wiley, Vol. 21, No. 12 ( 2019-12), p. 1586-1595
    Abstract: Exercise oscillatory ventilation (EOV) is a pivotal cardiopulmonary exercise test parameter for the prognostic evaluation of patients with chronic heart failure (HF). It has been described in patients with HF with reduced ejection fraction ( 〈 40%, HFrEF) and with HF with preserved ejection fraction ( 〉 50%, HFpEF), but no data are available for patients with HF with mid‐range ejection fraction (40–49%, HFmrEF). The aim of the study was to evaluate the prognostic role of EOV in HFmrEF patients. Methods and results We analysed 1239 patients with HFmrEF and 4482 patients with HFrEF, enrolled in the MECKI score database, with a 2‐year follow‐up. The study endpoint was the composite of cardiovascular death, urgent heart transplant, and ventricular assist device implantation. We identified EOV in 968 cases (16% and 17% of cases in HFmrEF and HFrEF, respectively). HFrEF EOV+ patients were significantly older, and their parameters suggested a more severe HF than HFrEF EOV− patients. A similar behaviour was found in HFmrEF EOV+ vs. EOV− patients. Kaplan–Meier analysis, irrespective of ejection fraction, showed that EOV is associated with a worse survival, and that patients with HFrEF and HFmrEF EOV+ had a significantly worse outcome than the EOV− of the same ejection fraction groups. EOV‐associated survival differences in HFmrEF patients started after 18 months of follow‐up. Conclusion Exercise oscillatory ventilation has a similar prevalence and ominous prognostic value in both HFmrEF and HFrEF patients, indicating a group of patients in need of a more intensive follow‐up and a more aggressive therapy. In HFmrEF, the survival curves between EOV+ and EOV− patients diverged only after 18 months.
    Type of Medium: Online Resource
    ISSN: 1388-9842 , 1879-0844
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 1500332-2
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  • 8
    In: European Journal of Heart Failure, Wiley
    Abstract: Improvement of left ventricular ejection fraction is a major goal of heart failure (HF) treatment. However, data on clinical characteristics, exercise performance and prognosis in HF patients who improved ejection fraction (HFimpEF) are scarce. The study aimed to determine whether HFimpEF patients have a distinct clinical phenotype, biology and prognosis than HF patients with persistently reduced ejection fraction (pHFrEF). Methods and results A total of 7948 patients enrolled in the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score database were evaluated (median follow‐up of 1490 days). We analysed clinical, laboratory, electrocardiographic, echocardiographic, exercise, and survival data from HFimpEF ( n  = 1504) and pHFrEF ( n  = 6017) patients. The primary endpoint of the study was the composite of cardiovascular death, left ventricular assist device implantation, and urgent heart transplantation. HFimpEF patients had lower HF severity: left ventricular ejection fraction 44.0 [41.0–47.0] versus 29.7 [24.1–34.5] %, B‐type natriuretic peptide 122 [65–296] versus 373 [152–888] pg/ml, haemoglobin 13.5 [12.2–14.6] versus 13.7 [12.5–14.7] g/dl, renal function by the Modification of Diet in Renal Disease equation 72.0 [56.7–89.3] versus 70.4 [54.5–85.3] ml/min, peak oxygen uptake 62.2 [50.7–74.1] versus 52.6 [41.8–64.3]% predicted, minute ventilation‐to‐carbon dioxide output slope 30.0 [26.9–34.4] versus 32.1 [28.0–38.0] in HFimpEF and pHFrEF, respectively ( p   〈  0.001 for all). Cardiovascular mortality rates were 26.6 and 46.9 per 1000 person‐years for HFimpEF and pHFrEF, respectively ( p   〈  0.001). Kaplan–Meier analysis showed that HFimpEF had better a long‐term prognosis compared with pHFrEF patients. After adjustment for variables differentiating HFimpEF from pHFrEF, except echocardiographic parameters, the Kaplan–Meier curves showed the same prognosis. Conclusions Heart failure with improved ejection fraction represents a peculiar group of HF patients whose clinical, laboratory, electrocardiographic, echocardiographic, and exercise characteristics parallel the recovery of systolic function. Nonetheless, these patients remain at risk for adverse outcome.
    Type of Medium: Online Resource
    ISSN: 1388-9842 , 1879-0844
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 1500332-2
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  • 9
    In: European Journal of Heart Failure, Wiley, Vol. 18, No. 5 ( 2016-05), p. 545-553
    Abstract: 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 VO 2 , 〈 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 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.
    Type of Medium: Online Resource
    ISSN: 1388-9842 , 1879-0844
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2016
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