Francesco Soriano

Increased pulse wave velocity and not reduced ejection fraction is associated with impaired baroreflex control of heart rate in congestive heart failure.

Background It is known that baroreflex sensitivity (BRS) is impaired in cardiac patients with myocardial infarction (MI). Nevertheless, it is unknown whether factors other than a reduced ejection fraction play a role in the baroreflex impairment of these patients. Methods and results Heart failure patients [congestive heart failure (CHF), n = 31, age 63 ± 1.2 years, mean ± SEM)], age-matched controls (n = 29) and coronary artery disease (CAD) patients without MI (n = 29) had RR interval and arterial blood pressure (BP) continuously monitored. Baroreflex function was assessed by the slope of the regression of RR interval, and BP responses to graded (−10, −20 and −40 mmHg) neck suction stimulation, the slope of bradycardic or tachycardic responses to spontaneous increases or reductions of SBP (sequence analysis) and the baroreflex efficiency index. Pulse wave velocity (PWV) was also measured. Compared with controls, CHF patients had RR interval and BP reflex responses to neck suction reduced by −36 and −54%, respectively (P < 0.01). By contrast, no differences were found between CHF and CAD patients. Similar reductions were observed for the sequence analysis (P < 0.01) in both CHF and CAD patients. Multiple regression analysis showed that in CHF and CAD patients, PWV and SBP and not ejection fraction were correlated with BRS. Conclusion The baroreflex function is impaired in CHF patients, the extent and the degree of baroreflex impairment being similar to that of CAD patients without MI. In CHF and CAD patients, the baroreflex impairment correlates significantly with the increased PWV and not with ejection fraction.

Iron Stores, Hepcidin, and Aortic Stiffness in Individuals with Hypertension.

Background & Aims Iron accumulation within the arterial wall has been hypothesized to promote atherosclerosis progression. Aim of this study was to evaluate whether the hormone hepcidin and iron stores are associated with arterial stiffness in subjects with essential hypertension. Methods Circulating hepcidin, ferritin, and mutations in the hemochromatosis gene were compared between subjects included in the first vs. third tertile (n=284 each) of carotid-femoral pulse wave velocity (PWV) in an unselected cohort of patients with arterial hypertension. Results At univariate logistic regression analysis, high PWV was associated with higher ferritin levels (p=0.010), but lower hepcidin (p=0.045), and hepcidin ferritin/ratio (p<0.001). Hemochromatosis mutations predisposing to iron overload were associated with high PWV (p=0.025). At multivariate logistic regression analysis, high aortic stiffness was associated with older age, male sex, lower BMI, higher systolic blood pressure and heart rate, hyperferritinemia (OR 2.05, 95% c.i. 1.11-3.17 per log ng/ml; p=0.022), and lower circulating hepcidin concentration (OR 0.29, 95% c.i. 0.16-0.51 per log ng/ml; p<0.001). In subgroup analyses, high PWV was associated with indices of target organ damage, including micro-albuminuria (n=125, p=0.038), lower ejection fraction (n=175, p=0.031), cardiac diastolic dysfunction (p=0.004), and lower S wave peak systolic velocity (p<0.001). Ferritin was associated with cardiac diastolic dysfunction, independently of confounders (p=0.006). Conclusions In conclusion, hyperferritinemia is associated with high aortic stiffness and cardiac diastolic dysfunction, while low circulating hepcidin with high aortic stiffness.

Right anterior mini-thoracotomy direct aortic self-expanding trans-catheter aortic valve implantation: A single center experience

OBJECTIVE Transcatheter aortic valve implantation (TAVI) has been designed to treat elderly patients with severe aortic stenosis at high risk for surgery. These patients are also often affected by severe iliac-femoral arteriopathy, rendering the trans-femoral approach unusable. We report our experience with the direct-aortic approach to treat these patients. METHODS From May 2008 to November 2013 two hundred and thirty-two patients (131 female, 56%) with severe symptomatic aortic stenosis and no reasonable surgical option due to excessive risk were evaluated for TAVI at our department. Of these patients, 202 were deemed eligible for TAVI. Of this group, 50 underwent CoreValve implantation by the direct aortic approach through a right anterior mini-thoracotmy (28 female, 56%), mean age 81.2±6.9. A combined team of cardiologists, cardiac surgeons with expertise in hybrid procedures, and anesthetists performed all the procedures. RESULTS Twenty-eight (56%) patients were female and 11 (22%) were redo at TAVI. We used a 23-mm CoreValve Evolute in 3 patients (6%), and the most used valve size was the 29mm in 46% of patients. Mean hemodynamic trans-aortic gradient was less than 5mmHg. The paravalvular regurgitation was ≤ grade 1 in 46 patients as assessed by peri-procedural transesophageal echocardiography (TEE). Seven patients (7/43, 16%) required a permanent pacemaker implantation; 30-day mortality was 6% (3 patients). Seven patients (14.8%) died during follow-up. Actuarial survival at 2years is 84.7±5.3%. CONCLUSIONS Transcatheter aortic valve implantation with the direct aortic approach is safe and feasible, offering a new attractive option to treat selected high-risk patients with severe aortic stenosis and peripheral vasculopathy, including those requiring a re-do procedure.

Infusion of escherichia coli lipopolysaccharide toxin in rats produces an early and severe impairment of baroreflex function in absence of blood pressure changes

ABSTRACT The assessment of baroreflex function since the first appearance of endotoxemia is important because the arterial baroreflex should exert a protective role during sepsis. Nevertheless, contrasting results were previously reported. This could be due to the hemodynamic instability characterizing this condition that may per se interfere with reflex cardiovascular adjustments. The aim of our study was therefore to study the baroreflex function (a) since the very beginning of infusion of Escherichia coli lipopolysaccharide (LPS) toxin and (b) in absence of the unloading effect produced by a decrease in blood pressure. Lipopolysaccharide was infused in 10 rats for 20 min at the infusion rate of 0.05 mg · kg−1 · min−1. Blood pressure was continuously measured before, during, and after infusion, and the baroreflex function was evaluated analyzing spontaneous fluctuations of systolic blood pressure and pulse interval by the sequence and transfer-function techniques. Plasma concentrations of inflammatory (interleukin 6, tumor necrosis factor &agr;) and anti-inflammatory (interleukin 10) cytokines were measured in other eight rats, similarly instrumented, four of which receiving the same LPS infusion. We found that blood pressure levels did not change with the infusion of LPS, whereas inflammatory cytokines increased significantly. The baroreflex sensitivity was significantly reduced 10 min after the beginning of LPS infusion, reached values about half those at baseline within 15 min after the start of infusion, and remained significantly low after the end of infusion. In conclusion, we documented that septic shock inducing LPS infusion is responsible for a very rapid impairment of the baroreflex function, independent from the level of blood pressure.

Impact of blood glucose variability on carotid artery intima media thickness and distensibility in type 1 diabetes mellitus

Abstract Aims. Diabetes mellitus is characterized by structural and functional alterations of the large- and medium-size arteries. Whether blood glucose variability, i.e. the glycemic oscillations occurring during the 24-h period, represents a risk factor for vascular alterations additional to and independent on HbA1c in type 1 diabetes mellitus is still undefined. The present study was carried out with the aim at investigating the impact of different measures of blood glucose variability on arterial structure and function. We studied 17 non-complicated type 1 diabetic patients (11 males, six females) with an age of 40.8 ± 7.6 years (mean ± SD). In each patient, 24-h glucose profile was obtained by continuous glucose monitoring system and glucose variability was expressed as mean ± SD of 24-h blood glucose levels, mean amplitude of glycemic excursions and postprandial hyperglycemic spikes. Arterial structure and function was measured as carotid IMT and stiffness. Major findings. The different approaches to assessing blood glucose variability well correlated between and with HbA1c. Carotid IMT and stiffness showed significant correlations with age, blood pressure, heart rate and daily insulin intake but a non- significant correlation with blood glucose variability. Principal conclusion. Thus, in type 1 diabetes mellitus, measures of glycemic variability are useful in predicting both actual and long-lasting glycemic control. In absence of diabetes-related complications and of any intima-media thickness alterations, the major predictors of arterial distensibility are represented by traditional risk factors beside glycemic 24-h control.

INFUSION OF E. COLI LIPOPOLYSACCHARIDES TOXIN IN RATS PRODUCES A SEVERE IMPAIRMENT OF BAROREFLEX FUNCTION IN ABSENCE OF BLOOD PRESSURE CHANGES: PP.32.261

Septic shock is characterized by a severe impairment of baroreflex function and by high mortality rate. In these patients baroreflex dysfunction is a negative prognostic factor. Nevertheless the causes of baroreflex dysfunction during septic shock have not been completely clarified. In particular it is not clear whether this is consequence of acute changes in blood pressure or it is a direct effect of the toxin. Our aim was to verify whether E. coli lipopolysaccharides (LPS) infusion could alter the baroreflex function even in absence of blood pressure (BP) changes. Methods: E.Coli LPS was infused in 7 rats for 20 minutes at an infusion rate (0.05 mg/kg/min) that we previously observed not to have any significant effect on BP. Systolic BP (SBP), diastolic BP (DBP) and pulse interval (PI) were continuously recorded for 30 minutes before, during and for 1 hour after the E. Coli LPS infusion. Baroreflex sensitivity was evaluated by applying the sequence method (BRS seq) and by calculating the alpha index in the high-frequency band (HF-BRS). Results: Neither SBP, nor DBP or PI showed significant differences after the infusion of E.Coli LPS with respect to the basal condition (SBP mean ± SD: from 93 ± 22 to 99 ± 25 mmHg; DBP: from 57 ± 23 to 50 ± 20 mmHg; PI from 166 ± 49 to 158 ± 43 ms). By contrast, the baroreflex sensitivity was significantly reduced after LPS infusion (BRS seq: from 1.29 ± 0.79 to 0.46 ± 0.27 ms/mmHg, p < 0.02; HF-BRS from 1.28 ± 0.97 to 0.31 ± 0.12 ms/mmHg). Conclusion: In rats, E coli LPS infusion can produce a severe impairment of baroreflex function even in absence of significant changes in blood pressure.

Portico Sheathless Transcatheter Aortic Valve Implantation via Distal Axillary Artery

Transcatheter aortic valve implantation has been designed to treat older patients affected by severe aortic stenosis who are considered high-risk surgical candidates because of multiple comorbidities. The least invasive approach for transcatheter aortic valves implantation should be considered the transfemoral retrograde route, because it is minimally invasive and is feasible with local anesthesia and mild sedation. Despite significant technical improvements in recent years, the transfemoral approach is contraindicated in cases of severe peripheral artery disease. We describe the first case of a Portico transcatheter aortic valve implantation system (St. Jude Medical, Minneapolis, MN) made through the distal axillary artery in a 90-year-old patient affected by severe aortic stenosis.

Direct Flow Implantation in a Patient With Mechanical Mitral Prostheses

We describe a case of Direct Flow (Direct Flow Medical Inc, Santa Rosa, CA) transcatheter aortic valve implantation in a patient with a mechanical valve in a mitral position.

Evolut R Implantation to Treat Severe Pure Aortic Regurgitation in a Patient With Mitral Bioprosthesis

Transcatheter aortic valves have been designed to treat high-risk surgical candidates affected by severe aortic stenosis, but little is known about the use of transcatheter valves in patients with severe pure aortic regurgitation. We describe the implantation of Medtronic CoreValve Evolut R (Medtronic, Minneapolis, MN) to treat an 82-year-old patient affected by severe pure aortic regurgitation who underwent prior mitral valve replacement with a biological valve protruding into the left ventricular outflow tract.

Allogeneic peripheral blood stem cell transplantation and accelerated atherosclerosis: An intriguing association needing targeted surveillance. Lessons from a rare case of acute anterior myocardial infarction

We report the case of a 23-year-old man who developed an acute ST-elevation myocardial infarction secondary to acute thrombotic occlusion of the proximal left anterior descending coronary artery five years after undergoing chemotherapy, radiotherapy, haematopoietic stem cell transplantation for acute lymphoblastic leukaemia and bulky mediastinal mass involving the pleura and pericardium. His medical history also included Graft versus Host Disease developed 13 months after transplantation and acute myocarditis three months before the actual hospital admission. To the best of our knowledge, coronary artery disease as a complication of haematopoietic stem cell transplantation and low-dose mediastinal radiation therapy in young patients has been rarely reported in the medical literature. Clinicians should have a high degree of suspicion of coronary artery disease in patients treated with allogeneic haematopoietic stem cell transplantation, especially in patients previously treated with target mediastinal radiotherapy, as a group at risk of premature and significantly accelerated atherosclerosis, in order to make a timely and correct diagnosis.