Chiara Lazzeri

Role of hemodynamic shear stress in cardiovascular disease

Atherosclerosis is the main cause of morbidity and mortality in the Western world. Inflammation and blood flow alterations are new markers emerging as possible determinants for the development of atherosclerotic lesions. In particular, blood flow exerts a shear stress on vessel walls that alters cell physiology. Shear stress arises from the friction between two virtual layers of a fluid and is induced by the difference in motion and viscosity between these layers. Regions of the arterial tree with uniform geometry are exposed to a unidirectional and constant flow, which determines a physiologic shear stress, while arches and bifurcations are exposed to an oscillatory and disturbed flow, which determines a low shear stress. Atherosclerotic lesions develop mainly in areas of low shear stress, while those exposed to a physiologic shear stress are protected. The presence of areas of the arterial tree with different wall shear stress may explain, in part, the different localization of atherosclerotic lesions in both coronary and extracoronary arteries. The measurement of this parameter may help in identifying atherosclerotic plaques at higher risk as well as in evaluating the efficacy of different pharmacological interventions. Moreover, an altered shear stress is associated with the occurrence of both aortic and intracranial aneurysms, possibly leading to their growth and rupture. Finally, the evaluation of shear stress may be useful for predicting the risk of developing restenosis after coronary and peripheral angioplasty and for devising a coronary stent with a strut design less thrombogenic and more conducive to endothelization.

The diabetic cardiomyopathy.

Diabetic cardiomyopathy has been defined as “a distinct entity characterized by the presence of abnormal myocardial performance or structure in the absence of epicardial coronary artery disease, hypertension, and significant valvular disease”. The diagnosis stems from the detection of myocardial abnormalities and the exclusion of other contributory causes of cardiomyopathy. It rests on non-invasive imaging techniques which can demonstrate myocardial dysfunction across the spectra of clinical presentation. The presence of diabetes is associated with an increased risk of developing heart failure, and the 75% of patients with unexplained idiopathic dilated cardiomyopathy were found to be diabetic. Diabetic patients with microvascular complications show the strongest association between diabetes and cardiomyopathy, an association that parallels the duration and severity of hyperglycemia. Metabolic abnormalities (that is hyperglycemia, hyperinsulinemia, and hyperlipemia) can lead to the cellular alterations characterizing diabetic cardiomyopathy (that is myocardial fibrosis and/or myocardial hypertrophy) directly or indirectly (that is by means of renin-angiotensin system activation, cardiac autonomic neuropathy, alterations in calcium homeostasis). Moreover, metabolic abnormalities represent, on a clinical ground, the main therapeutic target in the patients with diabetes since the diagnosis of diabetes is made. Since diabetic cardiomyopathy is highly prevalent in the asymptomatic type 2 diabetic patients, screening for its presence at the earliest stage of development can lead to prevent the progression to chronic heart failure. The most sensitive test is standard echocardiogram, while a less expensive pre-screening method is the detection of microalbuminuria.

Uric acid in the acute phase of ST elevation myocardial infarction submitted to primary PCI: Its prognostic role and relation with inflammatory markers: A single center experience

BACKGROUND AND METHODS Scarce data are available on the prognostic role of uric acid (UA ) in patients with ST elevation myocardial infarction (STEMI). We aimed at assessing the relation between uric acid, measured on Intensive Cardiac Care Unit (ICCU) admission, and mortality at short term follow-up in 466 consecutive STEMI patients submitted to percutaneous coronary intervention (PCI), as well as its relation with inflammatory markers (C-reactive protein, CRP-fibrinogen, erythrocyte sedimentation rate ESR). RESULTS Higher UA were detectable in the 21.5%.. In-hospital mortality was higher in patients with elevated UA (p<0.01 O.R. (95% C.I.): 3.9 (1.5-10.2)). At backward stepwise regression analysis UA resulted an independent predictor for in-hospital mortality (OR 1.82, 95%CI 1.15-2.86; p=0.01). CONCLUSION Our data strongly suggest that in the acute phase of STEMI patients submitted to PCI, uric acid holds a prognostic role for in-hospital mortality.

Prognostic role of insulin resistance as assessed by homeostatic model assessment index in the acute phase of myocardial infarction in nondiabetic patients submitted to percutaneous coronary intervention

Background and objectives Little information is available on the relation between insulin resistance and acute myocardial infarction. Methods In 253 consecutive nondiabetic patients with ST elevation myocardial infarction (STEMI) submitted to percutaneous coronary intervention, we assessed the prevalence of insulin resistance by homeostatic model assessment (HOMA) index and its prognostic role in early and late mortality. Results Insulin resistance was detectable in 52.9% of patients. Anterior STEMI was more frequent in insulin-resistant patients (P = 0.040), who showed higher values of probrain natriuretic peptide (P = 0.010), creatinine (P < 0.001), creatinine phosphokinase and creatinine phosphokinase-MB (MB, isoenzyme present in the myocardium; P = 0.016 and P = 0.003, respectively). At backward stepwise logistic regression analysis, the following variables were independent predictors for intra-intensive cardiac care unit mortality: HOMA index [hazard ratio 1.40; 95% confidence interval (CI) 1.02–1.95; P = 0.049]; C-peptide (hazard ratio 3.14; 95% CI 1.40–24.80; P = 0.001) and lactic acid (hazard ratio 2.50; 95% CI 1.41–4.44; P = 0.002). At long-term follow-up (Cox regression analysis), neither fasting glycaemia nor HOMA index resulted in predictors for mortality. Conclusion In nondiabetic STEMI patients submitted to percutaneous coronary intervention, insulin resistance, as assessed by HOMA index, is quite common and helps in the early prognostic stratification, as it represents an independent predictor of in-hospital mortality.

NT-proBNP on admission for early risk stratification in STEMI patients submitted to PCI. Relation with extension of STEMI and inflammatory markers

The prognostic implications of NT-proBNP measured on admission in patients with the ST-elevation myocardial infarction (STEMI) are not so far well elucidated. The present investigation, performed in 198 STEMI patients submitted to percutaneous coronary intervention (PCI), was aimed at assessing the prognostic value of NT-proBNP measured on admission to Intensive Cardiac Care Unit (ICCU) and its relation with the extension of myocardial infarction (indicated by cardiac biomarkers and ejection fraction) and inflammatory markers (C-reactive protein - CRP, erythrocyte sedimentation rate - ESR, leucocytes, fibrinogen). All patients who died during ICCU stay had increased values of NT-proBNP. Each quartile of NT-proBNP resulted directly correlated with age, heart rate, peak Tn I, admission creatinine serum levels, ESR, fibrinogen, and inversely correlated with ejection fraction. At backward logistic regression analysis, NT-proBNP values showed a significative correlation with peak Tn I (OR 1.013; 95% CI 1.001-1.025; p=0.036), and CRP positive (OR 6.450; 95% CI 1.714-24.272; p=0.006); age was close to reaching statistical significance (OR 1.043; 95% CI 0.999-1.089; p=0.055). At long term-follow-up NT-proBNP lacks any prognostic role in predicting adverse events such as hospitalization for rePCI, re-infarction and heart failure. Kaplan-Meier curves showed that all patients dead at follow-up were in the highest NT-proBNP quartiles.

Ventilatory and ECMO treatment of H1N1-induced severe respiratory failure: results of an Italian referral ECMO center.

BackgroundSince the first outbreak of a respiratory illness caused by H1N1 virus in Mexico, several reports have described the need of intensive care or extracorporeal membrane oxygenation (ECMO) assistance in young and often healthy patients. Here we describe our experience in H1N1-induced ARDS using both ventilation strategy and ECMO assistance.MethodsFollowing Italian Ministry of Health instructions, an Emergency Service was established at the Careggi Teaching Hospital (Florence, Italy) for the novel pandemic influenza. From Sept 09 to Jan 10, all patients admitted to our Intensive Care Unit (ICU) of the Emergency Department with ARDS due to H1N1 infection were studied. All ECMO treatments were veno-venous. H1N1 infection was confirmed by PCR assayed on pharyngeal swab, subglottic aspiration and bronchoalveolar lavage. Lung pathology was evaluated daily by lung ultrasound (LUS) examination.ResultsA total of 12 patients were studied: 7 underwent ECMO treatment, and 5 responded to protective mechanical ventilation. Two patients had co-infection by Legionella Pneumophila. One woman was pregnant. In our series, PCR from bronchoalveolar lavage had a 100% sensitivity compared to 75% from pharyngeal swab samples. The routine use of LUS limited the number of chest X-ray examinations and decreased transportation to radiology for CT-scan, increasing patient safety and avoiding the transitory disconnection from ventilator. No major complications occurred during ECMO treatments. In three cases, bleeding from vascular access sites due to heparin infusion required blood transfusions. Overall mortality rate was 8.3%.ConclusionsIn our experience, early ECMO assistance resulted safe and feasible, considering the life threatening condition, in H1N1-induced ARDS. Lung ultrasound is an effective mean for daily assessment of ARDS patients.

Low-Dose C-Type Natriuretic Peptide Does Not Affect Cardiac and Renal Function in Humans

In experimental animals, C-type natriuretic peptide (CNP) has vasodilating, hypotensive, and natriuretic activities. The role of circulating CNP in the overall regulation of cardiac and renal function in humans is less defined, in both health and disease. We measured cardiac volumes, diastolic and systolic functions, systemic (Doppler echocardiography) and renal hemodynamics, intrarenal sodium handling (lithium clearance method), plasma and urinary cGMP, plasma renin concentration, and plasma aldosterone level in six healthy volunteers (mean age, 33+/-3 years) receiving CNP (2 and 4 pmol/kg per minute for 1 hour each) in a single-blind, placebo-controlled, random-order, crossover study. During CNP infusion, plasma CNP increased from 1.17+/-0.23 to 41.52+/-4.61 pmol/L (ie, 4- to 10-fold higher levels than those observed in disease states) without affecting plasma and urinary cGMP, cardiac volumes, dynamics of left and right heart filling, cardiac output, arterial pressure, renal hemodynamics, intrarenal sodium handling, sodium excretion, or plasma levels of renin and aldosterone. The finding that increments in plasma CNP within the pathophysiological range have no effects on systemic hemodynamics, renal function, or the renin-angiotensin system do not support the hypothesis that CNP may act as a circulating hormone in humans.

Venous-arterial extracorporeal membrane oxygenation for refractory cardiac arrest: a clinical challenge:

Guidelines stated that extracorporeal membrane oxygenation (ECMO) may improve outcomes after refractory cardiac arrest (CA) in cases of cardiogenic shock and witnessed arrest, where there is an underlying circulatory disease amenable to immediate corrective intervention. Due to the lack of randomized trials, available data are supported by small series and observational studies, being therefore characterized by heterogeneity and controversial results. In clinical practice, using ECMO involves quite a challenging medical decision in a setting where the patient is extremely vulnerable and completely dependent on the medical team’s judgment. The present review focuses on examining existing evidence concerning inclusion and exclusion criteria, and outcomes (in-hospital and long-term mortality rates and neurological recovery) in studies performed in patients with refractory CA treated with ECMO. Discrepancies can be related to heterogeneity in study population, to differences in local health system organization in respect of the management of patients with CA, as well as to the fact that most investigations are retrospective. In the real world, patient selection occurs individually within each center based on their previous experience and expertise with a specific patient population and disease spectrum. Available evidence strongly suggests that in CA patients, ECMO is a highly costly intervention and optimal utilization requires a dedicated local health-care organization and expertise in the field (both for the technical implementation of the device and for the intensive care management of these patients). A careful selection of patients guarantees optimal utilization of resources and a better outcome.

Residual platelet reactivity is an independent predictor of myocardial injury in acute myocardial infarction patients on antiaggregant therapy.

In this study we sought to evaluate if platelet function measured after percutaneous coronary intervention (PCI) affects the severity of myocardial infarction (MI), measured by markers of cardiac necrosis. We measured platelet function by both a point-of-care assay (PFA-100) and platelet-rich plasma aggregation by two agonists (arachidonic acid -AA- and 2 and 10 microM ADP) in 367 patients with MI after PCI (200 patients on dual antiplatelet agents - group A- and 167 on dual antiplatelet agents plus GpIIb/IIIa inhibitors - group B). One hundred twenty-one (32.9%) patients were found to have a residual platelet reactivity (RPR) by PFA (CT/EPI <203 sec): 74/200 (37%) in group A and 47/167 (28.1%) in group B (p = 0.07). In 129 (35.1%) patients we found a RPR by AA-PA: 80/200 (40%) in group A and 49/167 (29.3%) in group B (p < 0.05). Seventeen out of 367 (4.6%) were found to have a RPR by ADP2-PA [15/200 (7.5%) in group A and 2/167 (1.2%) in group B; p < 0.005] and 88/367 (23.9%) by ADP10-PA [64/200 (32%) in group A and 24/167 (14.4%) in group B, p < 0.0001]. CK-MB and cTnI mean peak values were significantly higher in the first tertile of CT/ADP and CT/EPI distribution with respect to the other tertiles and they were significantly higher in patients with RPR by CT/EPI in both group A and group B patients. CK-MB and cTnI peak values were significantly higher in the third tertile of AA-PA, ADP 2 microM-PA and ADP 10 microM-PA distribution with respect to the other tertiles and were significantly higher in patients with RPR by AA-PA and by ADP 10-PA in both group A and group B patients. Multivariate analysis revealed platelet function as an independent predictor of CK-MB and cTnI peak values in both groups of patients independently of clinical, laboratory ad procedural parameters. In conclusion, we found that the severity of MI in patients with MI undergoing primary PCI is influenced by a persistent platelet activation on multiple antiplatelet therapy.

Effects of exercise on natriuretic peptides and cardiac function in man

We evaluated cardiac function and the plasma levels of atrial (ANP) and brain (BNP) natriuretic peptides during bicycle (B) and hand-grip (HG) exercises in eight healthy males. Each test was preceded by a control protocol in resting conditions. Left ventricular (LV) function (echocardiography) was evaluated during both exercises. Atrial function was assessed only during HG. Plasma ANP significantly increased during B (+236%) and HG (+77%), while there was a significant trend towards higher plasma BNP levels during B (+41%) and HG (+30%) than during the corresponding control tests. Plasma ANP correlated with heart rate in both tests, with left atrial volume, pulmonary vein flow systolic fraction and mitral flow E/A ratio in HG; BNP in both test correlated with LV dimensions and function. These data suggest that during exercise the cardiac release of ANP and BNP is differently regulated and related to changes in left atrial and LV function, respectively.