Sacubitril/valsartan: preliminary experience in post-acute stabilized patients with reduced ejection fraction heart failure.

INTRODUCTION: We investigated the effectiveness of sacubitril/valsartan by performing laboratory tests and a 6-minute walking test (6-MWT) at 1 and 6 months after treatment initiation. METHODS: We evaluated patients admitted to our Cardiology Department, stabilized after an episode of acute decompensated heart failure (HF), who were considered eligible for sacubitril/valsartan therapy. Therapy was initiated after interrupting angiotensin-converting enzyme (ACE) inhibitors for at least 36 h or after the last dose of an angiotensin receptor blocker (ARB). In naïve patients, we initiated a low dose of sacubitril/valsartan combination following patient stabilization. Before discharge, a 6-MWT was performed to evaluate patient's functional capacity, measuring total walked distance (in meters), oxygen saturation and heart rate at the beginning and at the end of the test; Borg Scale was applied to evaluate the intensity of dyspnoea. After discharge, follow-up visits at 1 and 6 months, 2D-echocardiography, blood tests and 6-MWT were performed to re-evaluate the efficacy of the treatment. RESULTS: A total of 14 patients (85.7% males) were included. Mean age was 66.0 ± 10.3 years. Body mass index (BMI) was 29.9 ± 4.7 kg/m2. There were no differences in creatinine at admission compared with values at 1 and 6 months. Mean left ventricular ejection fraction (LVEF) was 28.7 ± 4.7% at baseline and increased to 33.5 ± 6.6% and 38.0 ± 2.9% at 1 and 6 months, respectively (p = .028). Total distance covered at 6-MWT increased over the study period (baseline: 227.4 ± 62.8 m; 6 months: 257.3 ± 65.2 m, p = .317) although the increase was not statistically significant. CONCLUSIONS: The present experience showed that angiotensin receptor-neprilysin inhibitor (ARNi) might represent a new valuable therapeutic strategy, even at the earlier stages of stabilized acute HF. Therefore, we suggest a clinical practice algorithm, to consider before discharge, which should be validated by further analyses.

Different ST2 Serum Concentrations in Asymptomatic and Symptomatic Carotid Artery Stenosis.

BACKGROUND: ST2 represents an interesting biomarker associated with the progression of atherosclerotic disease. METHODS: This study aims to detect different ST2 serum concentrations, and intraplaque ST2 expression, in patients with symptomatic and asymptomatic carotid artery stenosis. RESULTS: The analysis of ST2 expression in the atheromatous plaque did not show any significant difference between symptomatic and asymptomatic patients (39.61 ± 35.97 vs. 38.49 ± 35.26; P = ns). ST2 serum concentrations of asymptomatic and symptomatic patients were statistically different with a concentration of 11.04 ± 8.95 ng/mL and 13.91 ± 8.01 ng/mL, respectively (P = 0.037). We observed statistical difference in serum ST2 levels between asymptomatic and symptomatic patients for cerebrovascular acute disease. No differences have been obtained in intraplaque ST2 expression. CONCLUSIONS: Soluble serum ST2 levels can be a useful biomarker to identify patients at risk for cerebrovascular events.

Outcomes of early invasive treatment strategy in elderly patients with non-ST elevation acute coronary syndromes.

BACKGROUND: As benefits of revascularization in non-ST elevation acute coronary syndromes (NSTEACSs) in the elderly are still unproven, we sought to assess the association between invasive or conservative management of NSTEACS and short-, mid- and long-term mortality or composite outcome of all-cause mortality and myocardial infarction in a cohort of consecutive elderly patients. METHODS AND RESULTS: Consecutive NSTEACS patients older than 75 years discharged between 2006 and 2010 from a single intensive cardiac care unit, and managed with invasive or conservative strategy according to available guidelines were retrospectively surveyed. By multivariate regression and sensitivity analysis, crude and adjusted mortality and composite outcome were estimated at prespecified time points of short-term (in-hospital or 30 days mortality), mid-term (T1: 31 days to 6 months), and long-term (T2: 31 days to 12 months). A total of 453 patients (median age 80 years, 47% men) were evaluated; 301 (66.5%) underwent invasive treatment. Invasive was associated with significantly lower risk of short- [odds ratio (OR) 0.28, 95% confidence interval (CI) 0.12-0.67, P = 0.004], mid- (OR 0.33, 95% CI 0.16-0.67, P = 0.003) and long-term mortality (OR 0.34, 95% CI 0.20-0.58, P < .0001). Invasive strategy was also associated with nonsignificant lower short- (OR 0.55, 95% CI 0.28-1.07, P = 0.077), and highly significant lower mid- (OR 0.52, 95% CI 0.34-0.81, P = 0.003) and long-term adjusted cumulative composite outcome rate (OR 0.68, 95% CI 0.46-0.98, P = 0.004). CONCLUSION: In NSTEACS elderly patients, invasive strategy is independently associated with lower short-, mid- and long-term mortality and composite outcome.

T2238C ANP gene variant and risk of recurrent acute coronary syndromes in an Italian cohort of ischemic heart disease patients.

BACKGROUND: The role of C2238/atrial natriuretic peptide (ANP) minor allele, at the T2238C ANP gene variant, as a predisposing risk factor for acute cardiovascular events, has been previously reported. We aimed at evaluating, by a retrospective approach, the long-term impact of C2238/ANP-minor allele carrier status toward the risk of recurrent acute coronary syndromes (re-ACS) in an Italian cohort of ischemic heart disease patients. METHODS: A total of 379 patients (males = 80.5%; mean age = 62.5 ±â€Š9.2 years) presenting with ACS were retrospectively analyzed. Mean follow-up was 5.1 ±â€Š3.5 years (range 1-26 years). Occurrence of new episodes of unstable angina, non-ST-segment elevation myocardial infarction and STE myocardial infarction over the years was recorded and compared between subjects not carrying and carrying C2238/ANP-minor allele. RESULTS: At univariate analysis, C2238/ANP-minor allele carrier status and treatment with beta-blocker, aspirin and statin were associated with risk of re-ACS. Multivariate analysis confirmed that hypercholesterolemia (P < 0.0001) and C2238/ANP-minor allele carrier status (P < 0.05) were both significantly and independently associated with increased risk of re-ACS. Both treatments with beta-blocker and with statin were significantly associated with reduced risk of re-ACS (P = 0.01 and P < 0.01, respectively). Age above 55 years was associated with recurrence of ACS in C2238/ANP-minor allele carriers (hazard ratio 1.427, 95% confidence interval 1.066-1.911, P = 0.017). Kaplan-Meier curves confirmed highest risk of new events occurrence in C2238/ANP-minor allele carriers (P = 0.035). CONCLUSIONS: The present results demonstrate that C2238/ANP-minor allele carrier status is an independent risk factor for ACS recurrence in an Italian cohort of ischemic heart disease patients over the long term, and they support the role of C2238/ANP-minor allele as a negative prognostic factor in coronary artery disease patients.

A survey on blood pressure levels and hypertension control in a sample of the Italian general population.

BACKGROUND: Hypertension represents a major cardiovascular risk factor with relevant consequences on morbidity and mortality in the general population. An optimal control of blood pressure (BP) is far from being achieved. AIM: The objective of this study was to explore awareness of BP levels, prevalence of risk factors and status of hypertension control in a sample of the Italian general population. METHODS: Subjects aged 18 years or older were enrolled on a voluntary basis during the 7th and 8th World Hypertension Days at our hospital centre, S. Andrea Hospital in Rome, and at other hospitals throughout the Italian Lazio region. Along with BP measurement, a short questionnaire was completed at the time of the interview. RESULTS: Of 1165 individuals enrolled into the analysis, 71.7% were aware of their BP levels (82.5% among hypertensive patients). Within the whole cohort, 31.9% of subjects were under antihypertensive treatment, while the overall rate of subjects found to be hypertensive patients at our visit was 52.9% (n = 616). Among hypertensive patients taking antihypertensive drugs, 47.1% had controlled BP values with the remaining 52.9% showing uncontrolled hypertension. Mean systolic blood pressure (SBP) was 138.2 ± 20.7 mmHg and mean diastolic blood pressure (DBP) was 80.4 ± 11.3 mmHg in subjects receiving antihypertensive treatment. Among older hypertensive patients (71-94 years of age), only 76.9% were under treatment. Hypertensive males were more frequently treated than females in all age groups (p = 0.001). Smoking habit negatively affected efficacy of antihypertensive therapy in the age groups of 48-53 and 54-62 years (p = 0.008 and p = 0.01, respectively). Diabetic patients had higher mean SBP values than non-diabetic subjects (137.3 ± 22.1 vs 129.3 ± 18.2 mmHg, p = 0.02). CONCLUSION: The results of our survey strongly support the need for a continuing educational effort aimed at providing correct advertisement of healthy lifestyles and awareness of adequate BP control. Based on our observations, particular attention has to be paid to women, younger subjects, elderly subjects and diabetic patients in order to reach appropriate BP control and reduction of cardiovascular risk in these subject categories.

IGF-1 and atherothrombosis: relevance to pathophysiology and therapy.

IGF-1 (insulin-like growth factor-1) plays a unique role in the cell protection of multiple systems, where its fine-tuned signal transduction helps to preserve tissues from hypoxia, ischaemia and oxidative stress, thus mediating functional homoeostatic adjustments. In contrast, its deprivation results in apoptosis and dysfunction. Many prospective epidemiological surveys have associated low IGF-1 levels with late mortality, MI (myocardial infarction), HF (heart failure) and diabetes. Interventional studies suggest that IGF-1 has anti-atherogenic actions, owing to its multifaceted impact on cardiovascular risk factors and diseases. The metabolic ability of IGF-1 in coupling vasodilation with improved function plays a key role in these actions. The endothelial-protective, anti-platelet and anti-thrombotic activities of IGF-1 exert critical effects in preventing both vascular damage and mechanisms that lead to unstable coronary plaques and syndromes. The pro-survival and anti-inflammatory short-term properties of IGF-1 appear to reduce infarct size and improve LV (left ventricular) remodelling after MI. An immune-modulatory ability, which is able to suppress 'friendly fire' and autoreactivity, is a proposed important additional mechanism explaining the anti-thrombotic and anti-remodelling activities of IGF-1. The concern of cancer risk raised by long-term therapy with IGF-1, however, deserves further study. In the present review, we discuss the large body of published evidence and review data on rhIGF-1 (recombinant human IGF-1) administration in cardiovascular disease and diabetes, with a focus on dosage and safety issues. Perhaps the time has come for the regenerative properties of IGF-1 to be assessed as a new pharmacological tool in cardiovascular medicine.