Alice Bonomi

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.

Vitamin D plasma levels and in-hospital and 1-year outcomes in acute coronary syndromes: a prospective study.

AbstractDeficiency in 25-hydroxyvitamin D (25[OH]D), the main circulating form of vitamin D in blood, could be involved in the pathogenesis of acute coronary syndromes (ACS). To date, however, the possible prognostic relevance of 25 (OH)D deficiency in ACS patients remains poorly defined. The purpose of this prospective study was to assess the association between 25 (OH)D levels, at hospital admission, with in-hospital and 1-year morbidity and mortality in an unselected cohort of ACS patients.We measured 25 (OH)D in 814 ACS patients at hospital presentation. Vitamin D serum levels >30 ng/mL were considered as normal; levels between 29 and 21 ng/mL were classified as insufficiency, and levels < 20 ng/mL as deficiency. In-hospital and 1-year outcomes were evaluated according to 25 (OH)D level quartiles, using the lowest quartile as a reference.Ninety-three (11%) patients had normal 25 (OH)D levels, whereas 155 (19%) and 566 (70%) had vitamin D insufficiency and deficiency, respectively. The median 25 (OH)D level was similar in ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) patients (14.1 [IQR 9.0–21.9] ng/mL and 14.05 [IQR 9.1–22.05] ng/mL, respectively; P = .88). The lowest quartile of 25 (OH)D was associated with a higher risk for several in-hospital complications, including mortality. At a median follow-up of 366 (IQR 364–379) days, the lowest quartile of 25 (OH)D, after adjustment for the main confounding factors, remained significantly associated to 1-year mortality (P < .01). Similar results were obtained when STEMI and NSTEMI patients were considered separately.In ACS patients, severe vitamin D deficiency is independently associated with poor in-hospital and 1-year outcomes. Whether low vitamin D levels represent a risk marker or a risk factor in ACS remains to be elucidated.

Surfactant-Derived Proteins as Markers of Alveolar Membrane Damage in Heart Failure

Background In heart failure (HF) alveolar-capillary membrane is abnormal. Surfactant-derived proteins (SPs) and plasma receptor for advanced-glycation-end-products (RAGE) have been proposed as lung damage markers. Methods Eighty-nine chronic HF and 17 healthy subjects were evaluated by echocardiography, blood parameters, carbon monoxide lung diffusion (DLCO) and cardiopulmonary exercise test. We measured immature SP-B, mature SP-B, SP-A, SP-D and RAGE plasma levels. Results Immature SP-B (arbitrary units), mature SP-A (ng/ml) and SP-D (ng/ml), but not mature SP-B (ng/ml) and RAGE (pg/ml) levels, were higher in HF than in controls [immature SP-B: 15.6 (13.1, 75th–25th interquartile range) Vs. 11.1 (6.4), p<0.01; SP-A, 29.6 (20.1) Vs. 18.3 (13.5), p = 0.01; SP-D: 125 (90) Vs. 78 (58), p<0.01]. Immature SP-B, SP-A, SP-D and RAGE values were related to DLCO, peak oxygen consumption, ventilatory efficiency, and brain natriuretic peptide (BNP), whereas plasma mature SP-B was not. The DLCO Vs. immature SP-B correlation was the strongest one. At multivariate analysis, RAGE was associated to age and creatinine, SP-A to DLCO and BNP, SP-D to BNP, mature SP-B to DLCO and creatinine, and immature SP-B only but strongly to DLCO. Conclusions Immature SP-B is the most reliable biological marker of alveolar-capillary membrane function in HF.

Multiparametric prognostic scores in chronic heart failure with reduced ejection fraction: a long-term comparison

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.

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.

Prognostic role of β-blocker selectivity and dosage regimens in heart failure patients. Insights from the MECKI score database

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.

Multiparametric prognostic scores in chronic heart failure with reduced ejection fraction

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.

Evaluation of coronary plaque characteristics with coronary computed tomography angiography in patients with non-obstructive coronary artery disease: a long-term follow-up study

Aims Recent studies suggested that even non-obstructive coronary artery disease (CAD) increases major cardiovascular adverse events (MACE) rate. Aim of this study was to evaluate whether coronary computed tomography angiography (CCTA) may detect specific plaque characteristics that may affect prognosis in patients with non-obstructive CAD. Methods We enrolled 245 patients who underwent CCTA between April 2004 and April 2007 for suspected CAD and were found to have non-obstructive CAD. Positive remodelling index (PRI), low-attenuation plaque (LAP), plaque burden (PB), spotty calcification (SC), and napkin-ring sign (NRS) have been evaluated for each coronary plaque detected. Acute coronary syndrome, all-cause/cardiac death, and very late elective revascularization (vl-ER) were the endpoints of the study. Results A total of 28 events were recorded (2 STEMI, 4 NSTEMI, 6 UA, 2 cardiac deaths, 4 non-cardiac death, and 10 vl-ERs) at long-term follow-up (98 ± 20 months). When adjusted for significant clinical variables PRI > 1.4 (HR 3.31 CI 95% 1.11-9.91, P = 0.0392), LAP (HR 8.45 CI 95% 2.22-32.21, P = 0.0019), PB > 0.7 (HR 5.25 CI 95% 1.45-19.03, P = 0.0120), and NRS (HR 12.52 CI 95% 1.51-103.90, P = 0.0198) were still significantly associated with higher rate of hard cardiac events at follow-up. The Kaplan-Meyer curves confirmed lower cumulative hard cardiac events-free survival in patients presenting at least one coronary plaque with two or more high-risk characteristics when compared with patients with no lesion with more than one high-risk plaque characteristics (log-rank P < 0.0001). Conclusions High-risk plaque characteristics at CCTA (PRI > 1.4, PB > 0.7, LAP, and NRS) seem to be promising for risk stratification of patients with non-obstructive CAD.

Carotid plaque-thickness and common carotid IMT show additive value in cardiovascular risk prediction and reclassification

Background and aims Carotid plaque size and the mean common carotid intima-media thickness measured in plaque-free areas (PF CC-IMTmean) have been identified as predictors of vascular events (VEs), but their complementarity in risk prediction and stratification is still unresolved. The aim of this study was to evaluate the independence of carotid plaque thickness and PF CC-IMTmean in cardiovascular risk prediction and risk stratification. Methods The IMPROVE-study is a European cohort (n = 3703), where the thickness of the largest plaque detected in the whole carotid tree was indexed as cIMTmax. PF CC-IMTmean was also assessed. Hazard Ratios (HR) comparing the top quartiles of cIMTmax and PF CC-IMTmeanversus their respective 1–3 quartiles were calculated using Cox regression. Results After a 36.2-month follow-up, there were 215 VEs (125 coronary, 73 cerebral and 17 peripheral). Both cIMTmax and PF CC-IMTmean were mutually independent predictors of combined-VEs, after adjustment for center, age, sex, risk factors and pharmacological treatment [HR (95% CI) = 1.98 (1.47, 2.67) and 1.68 (1.23, 2.29), respectively]. Both variables were independent predictors of cerebrovascular events (ischemic stroke, transient ischemic attack), while only cIMTmax was an independent predictor of coronary events (myocardial infarction, sudden cardiac death, angina pectoris, angioplasty, coronary bypass grafting). In reclassification analyses, PF CC-IMTmean significantly adds to a model including both Framingham Risk Factors and cIMTmax (Integrated Discrimination Improvement; IDI = 0.009; p = 0.0001) and vice-versa (IDI = 0.02; p < 0.0001). Conclusions cIMTmax and PF CC-IMTmean are independent predictors of VEs, and as such, they should be used as additive rather than alternative variables in models for cardiovascular risk prediction and reclassification.

Acute Kidney Injury Definition and In-Hospital Mortality in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction.

Background Acute kidney injury (AKI) has been associated with increased mortality in ST‐segment elevation myocardial infarction. We compared the mortality predictive accuracy of the 3 AKI definitions used most widely for patients with ST‐segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Methods and Results We included 3771 patients with ST‐segment elevation myocardial infarction treated with primary percutaneous coronary intervention at 2 Italian hospitals. AKI incidence was evaluated according to creatinine increases of ≥25% (AKI‐25), ≥0.3 mg/dL (AKI‐0.3), and ≥0.5 mg/dL (AKI‐0.5). The primary end point was in‐hospital mortality. Overall, 557 (15%), 522 (14%), and 270 (7%) patients developed AKI‐25, AKI‐0.3, and AKI‐0.5, respectively (P<0.01). All AKI definitions independently predicted in‐hospital mortality (adjusted odds ratio 4.9 [95% CI 3.1–7.8], 5.4 [95% CI 3.3–8.6], and 8.3 [95% CI 5.1–13.3], respectively; P<0.01 for all). At receiver operating characteristic analysis, the addition of each AKI definition to combined clinical predictors of mortality (age, sex, left ventricular ejection fraction, admission creatinine, creatine kinase‐MB peak) found at stepwise analysis significantly improved mortality prognostication (area under the curve increased from 0.89 for clinical predictor combination alone to 0.92 for AKI‐25, 0.92 for AKI‐0.3, and 0.93 for AKI‐0.5; P<0.01 for all). At reclassification analysis, AKI‐0.5 added to clinical predictors, provided the highest score in mortality (net reclassification improvement +10% versus AKI‐0.3 [P=0.01] and +8% versus AKI‐25 [P=0.05]). Conclusions Each AKI definition significantly improved the mortality prediction beyond major clinical variables. AKI‐0.5 showed a mortality discrimination advantage, suggesting it should be the preferred definition in studies addressing ST‐segment elevation myocardial infarction and focusing on short‐term mortality.