[Show abstract][Hide abstract] ABSTRACT: In remote ischemic conditioning (RIC), several cycles of ischemia and reperfusion render distant organ and tissues more resistant to the ischemia-reperfusion injury. The intermittent ischemia can be applied before the ischemic insult in the target site (remote ischemic preconditioning), during the ischemic insult (remote ischemic perconditioning) or at the onset of reperfusion (remote ischemic postconditioning). The mechanisms of RIC have not been completely defined yet; however, these mechanisms must be represented by the release of humoral mediators and/or the activation of a neural reflex. RIC has been discovered in the heart, and has been arising great enthusiasm in the cardiovascular field. Its efficacy has been evaluated in many clinical trials, which provided controversial results. Our incomplete comprehension of the mechanisms underlying the RIC could be impairing the design of clinical trials and the interpretation of their results. In the present review we summarize current knowledge about RIC pathophysiology and the data about its cardioprotective efficacy.
World Journal of Cardiology (WJC) 10/2015; 7(10). DOI:10.4330/wjc.v7.i10.621 · 2.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
In patients with chronic heart failure (HF) the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score, is a predictor of cardiovascular death and urgent heart transplantation. We investigated the relationship between age, exercise tolerance and the prognostic value of the MECKI score.Methods and Results:We analyzed data from 3,794 patients with chronic systolic HF. The primary endpoint was a composite of cardiovascular death and urgent heart transplantation. Older patients had higher prevalence of comorbidities and lower exercise performance compared with younger subjects (peak V̇O2, 925 vs. 1,351 L/min; P<0.0001; V̇E/V̇CO2slope, 33.2 vs. 28.3; P>0.0001). The rate of the primary endpoint was 19% in the highest age quartile and 14% in the lowest quartile. At multivariable analysis, the independent predictors of the primary endpoint were left ventricular ejection fraction (LVEF), eGFR, peak V̇O2, serum Na(+)and the use of β-blockers in patients aged ≥70 years, and LVEF, eGFR and peak V̇O2in younger subjects. The MECKI risk score increased across age subgroups, but on receiver operating characteristic curve analysis its prognostic power was similar in both patients aged ≥70 and <70 years.
Older patients with HF are a high-risk population with lower exercise performance. The MECKI score increased according to age and maintained its prognostic value also in older patients.
[Show abstract][Hide abstract] ABSTRACT: Background: Pulmonary hypertension (PH), associated with increased left ventricular diastolic pressure and pulmonary vasoconstriction, is frequently observed in heart failure (HF), where it holds prognostic significance. We hypothesized that Cheyne-Stokes respiration (CSR), via hypoxia-hypercapnia cycles and adrenergic activation by the chemoreflex, may contribute to increased pulmonary arterial pressure (PAP) in HF.
Methods: Seventy-two HF patients (57 males, aged 65.1 SD 12.3 years, left ventricular ejection fraction <50%, 33.2 SD 7.5%), on guideline recommended pharmacological/device treatment underwent thorough clinical, echocardiographic biohumoral and neurohormonal assessment, Holter monitoring, 24-hour cardiorespiratory screening for CSR and chemoreflex test for hypoxic (HVR) and hypercapnic (HCVR) ventilatory responses.
Results: Twenty patients (28%) showed significant CSR, as defined by a 24-hour apnea-hypopnea index (AHI) ≥ 15. Patients with CSR presented with enhanced HVR (median 0.78, interquartile range -IR 0.46-1.22 vs 0.42, IR 0.18-0.67 L/min/%, p<0.05), HCVR (1.17, IR 0.97-1.29 vs 0.72, IR 0.47-0.93 L/min/mmHg, p<0.01), increased plasma norepinephrine levels (690, IR 477-868 vs 366, IR 226-508 ng/L, p<0.001) and higher systolic pulmonary arterial pressure (sPAP: 42.8 SD 10.1 vs 32.3 SD 5.7, p<0.001) at echocardiography, despite similar systolic and diastolic function. .sPAP correlated with AHI (R=0.57, p<0.001), HCVR (R=0.49, p<0.001), HVR (R=0.51, p<0.001) and norepinephrine (R=0.34, p<0.01). Univariate predictors of sPAP>35 mmHg were AHI, HVR, HCVR, with only AHI maintaining its predictive value at multivariate analysis (p=0.017).
Conclusions: CSR may contribute to increased pulmonary arterial pressure in HF, independently of the severity of LV systolic and diastolic dysfunction, likely via recurrent hypoxia/hypercapnia cycles and chemoreflex mediated adrenergic discharge.
International Journal of Cardiology 09/2015; 202. DOI:10.1016/j.ijcard.2015.09.007 · 4.04 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The study aims are to evaluate the analytical performance and the clinical results of the chemiluminescent Access AccuTnI + 3 immunoassay for the determination of cardiac troponin I (cTnI) with DxI 800 and Access2 platforms and to compare the clinical results obtained with this method with those of three cTnI immunoassays, recently introduced in the European market. The limits of blank (LoB), detection (LoD), and quantitation (LoQ) at 20% CV and 10% CV were 4.5 ng/L and 10.9 ng/L, 17,1 and 30,4 ng/L, respectively. The results of STAT Architect high Sensitive TnI (Abbott Diagnostics), ADVIA Centaur Troponin I Ultra (Siemens Healthcare Diagnostics), ST AIA-Pack cTnI third generation (Tosoh Bioscience), and ACCESS AccuTnI + 3 (Beckman Coulter Diagnostics) showed very close correlations (R ranging from 0901 to 0994) in 122 samples of patients admitted to the emergency department. However, on average there was a difference up to 2.4 folds between the method measuring the highest (ADVIA method) and lowest cTnI values (AccuTnI + 3 method). The consensus mean values between methods ranged from 6.2% to 29.6% in 18 quality control samples distributed in an external quality control study (cTnI concentrations ranging from 29.3 ng/L to 1557.5 ng/L). In conclusion, the results of our analytical evaluation concerning the AcccuTnI + 3 method, using the DxI platform, are well in agreement with those suggested by the manufacturer as well as those reported by some recent studies using the Access2 platform. Our results confirm that the AccTnI + 3 method for Access2 and DxI 800 platforms is a clinically usable method for cTnI measurement.
Clinica chimica acta; international journal of clinical chemistry 09/2015; 451(Pt B). DOI:10.1016/j.cca.2015.09.016 · 2.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In nonischaemic dilated cardiomyopathy (NICM), replacement myocardial fibrosis as detected by late gadolinium enhancement (LGE) at cardiovascular magnetic resonance (CMR) is associated with poor prognosis. We investigated the as-yet unexplored prognostic significance of interstitial fibrosis in NICM, using T1-mapping CMR.
Eighty-nine NICM patients (63 men, age 59 ± 14 years) with left ventricular systolic dysfunction (ejection fraction 41 ± 13%) underwent comprehensive clinical and CMR evaluation, with extracellular volume fraction (ECV) estimation from pre and postcontrast T1 mapping. Fifteen healthy individuals (11 men, mean age 52 ± 11 years) were used as controls. The end-point was a composite of cardiovascular death, hospitalization for heart failure and appropriate defibrillator intervention.
Myocardial ECV was higher in NICM patients (0.31 ± 0.05) than controls (0.25 ± 0.04, P < 0.01). In NICM patients, myocardial ECV correlated with left ventricular ejection fraction (R = 0.13), LGE extent (R = 0.17), Doppler E/E' (R = 0.17) and ventricular tachycardias (R = 0.21) at 24-h ECG monitoring (P < 0.05 for all). During a median follow-up of 24 months (interquartile range 12-42 months), 12 events occurred and higher myocardium ECV was independently associated with the occurrence of the composite end-point (P < 0.01).
In NICM patients, myocardial ECV was increased compared with normal individuals, likely reflecting extracellular matrix remodelling and collagen deposition, and resulted an independent prognostic predictor beyond all other conventional clinical, electrocardiographic and echocardiographic parameters.
Journal of Cardiovascular Medicine 06/2015; 16(10). DOI:10.2459/JCM.0000000000000275 · 1.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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 (V̇O2) 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 peakV̇O2(P<0.0001). Other predictors were age, sex, body mass index, HF etiology, NYHA class, atrial fibrillation, resting heart rate, B-type natriuretic peptide, hemoglobin, and treatment. After adjusting for significant covariates, the hazard ratio for primary outcome associated with peakV̇O2<12 ml·kg(-1)·min(-1)was 1.75 (95% confidence interval (CI): 1.06-2.91; P=0.0292) in patients with eGFR ≥60, 1.77 (0.87-3.61; P=0.1141) in those with eGFR of 45-59, and 2.72 (1.01-7.37; P=0.0489) in those with eGFR <45 ml·min(-1)·1.73 m(-2). The area under the receiver-operating characteristic curve for peakV̇O2<12 ml·kg(-1)·min(-1)was 0.63 (95% CI: 0.54-0.71), 0.67 (0.56-0.78), and 0.57 (0.47-0.69), respectively. Testing for interaction was not significant.
Renal dysfunction is correlated with peakV̇O2. A peakV̇O2cutoff of 12 ml·kg(-1)·min(-1)offers limited prognostic information in HF patients with more severely impaired renal function. (Circ J 2015; 79: 583-591).
[Show abstract][Hide abstract] ABSTRACT: The aim of this review article is to give an update on the state of the art of the immunoassay methods for the measurement of B-type natriuretic peptide (BNP) and its related peptides. Using chromatographic procedures, several studies reported an increasing number of circulating peptides related to BNP in human plasma of patients with heart failure. These peptides may have reduced or even no biological activity. Furthermore, other studies have suggested that, using immunoassays that are considered specific for BNP, the precursor of the peptide hormone, proBNP, constitutes a major portion of the peptide measured in plasma of patients with heart failure. Because BNP immunoassay methods show large (up to 50%) systematic differences in values, the use of identical decision values for all immunoassay methods, as suggested by the most recent international guidelines, seems unreasonable. Since proBNP significantly cross-reacts with all commercial immunoassay methods considered specific for BNP, manufacturers should test and clearly declare the degree of cross-reactivity of glycosylated and non-glycosylated proBNP in their BNP immunoassay methods. Clinicians should take into account that there are large systematic differences between methods when they compare results from different laboratories that use different BNP immunoassays. On the other hand, clinical laboratories should take part in external quality assessment (EQA) programs to evaluate the bias of their method in comparison to other BNP methods. Finally, the authors believe that the development of more specific methods for the active peptide, BNP1–32, should reduce the systematic differences between methods and result in better harmonization of results.