Federico Cacciapuoti

Insulin resistance is an independent risk factor for atherosclerosis in rheumatoid arthritis

The objective of this study was to investigate the relationship between insulin resistance (IR) and sub-clinical atherosclerosis in patients with rheumatoid arthritis (RA). Carotid artery intima media thickness (IMT), using ultrasound evaluation, and other clinical and laboratory variables were investigated in 45 RA outpatients and in 48 controls with soft tissue disorders. IR was assayed by homeostasis model assessment (HOMA2) and metabolic syndrome by National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III) criteria. Insulin resistance, as defined by HOMA2-IR>1, was seen in 40 (88.9%) RA patients and in three (6.2%) controls (p<0.001). No significant difference was detected in the prevalence of metabolic syndrome. The median IMT was greater in RA patients (0.76 mm; interquartile range [IQR] 0.65, 0.85) than in the controls (0.66 mm; IQR 0.60, 0.72) (p<0.001). Dividing the RA patients according to the cut-off IMT value (0.72 mm), a difference was detected in both systolic (p=0.04) and diastolic blood pressure (p=0.02), disease activity score (DAS28) (p=0.008), HOMA2-IR (p<0.001) and cumulative oral steroid dose (p=0.001). Moreover, the frequency of cases with increased IMT was higher in glucocorticoid users than in non-users (21/23 vs. 9/22, respectively) (p<0.001). Spearmans rho correlation showed a significant positive relationship between IMT and HOMA2-IR (p<0.001). Multivariate stepwise analysis selected HOMA2-IR plus diastolic BP plus glucocorticoid exposure as the best predictive model for subclinical atherosclerosis (R2c=0.577, F=21, p<0.001). In conclusion, this study showed a significantly higher prevalence of IR in RA patients and pointed out a significant association between IR and subclinical atherosclerosis. This relationship may be driven primarily by exposure to steroid therapy.

Hyper-homocysteinemia: a novel risk factor or a powerful marker for cardiovascular diseases? Pathogenetic and therapeutical uncertainties.

Increased homocysteine levels can be responsible for arterial ischemic events, such as MI, stroke or peripheral vascular disease. Homocysteine is metabolized by two pathways: re-methylation and trans-sulfuration. Both involve folic acid, and vitamins B6–12. Several studies assumed that the folates and vitamins B supplementation or dietary source to normalize plasma homocysteine. But, even if tends to normalize homocysteine levels, lowering homocysteine by B-group vitamins and/or folates does not reduce cardiovascular risk. In fact, recent reports confirmed that hyper-homocysteinemia is not directly responsible for cardiovascular disease, but is merely present in individuals suffering for acute and/or chronic cardiovascular events, as a collateral finding. Reduced methylation potential (MP) [due to decreased S-adenosyl-methionine (AdoMet)/S-adenosyl-homocysteine (AdoHcy) ratio] induced by the elevated plasma homocysteine levels seems to be the true responsible for cardiovascular diseases (CVD). The pathogenic mechanisms responsible for CVD appear to be dependent of DNA hypomethylation inducing an inhibition of cyclin A transcription and a reduction of endothelial cells growth. But, other human studies performed in a wide range are requested.

Molecular mechanisms of left ventricular hypertrophy (LVH) in systemic hypertension (SH)—possible therapeutic perspectives

Left ventricular hypertrophy (LVH) induced by systemic hypertension (SH) represents a maladaptive response to the increased overload. It is known that the LV pathological remodeling is associated with an increased risk of cardiovascular morbidity and mortality. Secretion and production of vasoactive peptides, such as angiotensin II, endothelin-1, norepinephrine, and Rho and Ras proteins, are increased during the process and play critical roles in the hypertrophic response to systemic hypertension. Oxidative stress, heat shock proteins, calcineurin, and some kinases are also involved in the hypertrophic process. Usually, antihypertensive treatments are able to reduce elevated blood pressure levels, but are not always useful to slow or prevent LVH. Experimental studies performed in animal models demonstrate that some humoral factors, by suppressing the biochemical hypertrophic responses, could prevent their cardiac complications independently of their possible anti-hypertensive effects. Cyclosporine-A, scutellarin, and spironolactone are also included among these antihypertrophic substances. Thus, new drugs deriving from these molecules and humoral factors could be employed to antagonize LVH.

Tight glycemic control may increase regenerative potential of myocardium during acute infarction.

AIMS We analyzed the effects of tight glycemic control on regenerative potential of myocardium during acute myocardial infarction. PATIENTS AND METHODS Seventy-five patients with their first acute myocardial infarction undergoing coronary bypass surgery were studied: 25 patients with glycemia below 140 mg/dl served as the control group; hyperglycemic patients (glucose>140 mg/dl) were randomized to intensive glycemic control (IGC; n=20; glucose goal, 80-140 mg/dl), conventional glycemic control (CGC; n=20; glucose goal, 180-200 mg/dl), or glucose-insulin-potassium (GIK; n=10; glucose goal, 180-200 mg/dl) for almost 3 d before surgery, using insulin infusion followed by sc insulin treatment. During surgery, myocyte precursor cells (MPC) (c-kit/MEFC2/GATA4-positive cells), oxidation of MPC DNA (c-kit/8-hydroxydeoxyguanosine-positive cells), senescent MPC (c-kit/p16INK4a-positive cells), and cycling cardiomyocytes (Ki-67-positive cells) were analyzed in biopsy specimens taken from the peri-infarcted area. RESULTS AND DISCUSSION Before surgery, plasma glucose reduction was greater in the IGC group than in the CGC and GIK groups (P<0.001 for both). IGC patients had higher MPC (P<0.01) and cycling myocytes (P<0.01), as well as less oxidized (P<0.01) and senescent MPC (P<0.01) in peri-infarcted specimens compared with both CGC and GIK patients. Tight glycemic control, by reducing senescent MPC, may increase regenerative potential of the ischemic myocardium.

Left Atrial Volume Index as Indicator of Left Ventricular Diastolic Dysfunction: Comparation between Left Atrial Volume Index and Tissue Myocardial Performance Index

Background To point out a possible correlation between left atrial volume index (LAVI) and left ventricular (LV) diastolic time interval to better define LV diastolic dysfunction, this study was performed. Methods In 62 hypertensive-hypertrophic patients without LV systolic dysfunction, LV volumes, myocardial mass index, ejection fraction% (EF%) and LAVI were measured by two-dimensional echocardiography. Instead, tissue Doppler echocardiography (TDE) was used to measure myocardial performance index (MPI) and its systo-diastolic time intervals, such as: iso-volumetric contraction time (IVCT); iso-volumetric relaxation time (IVRT); ejection time. LAVI, TDE-MPI and time intervals where also measured in 15 healthy controls, to obtain the reference values. Results Results shown a significant increase of LV volumes in hypertensives in comparison to the control group (p < 0.05). LV mass index also augmented (p < 0.001). Instead, EF% not significantly changed in hypertrophic patients in comparison with healthy controls. LAVI raised in hypertensives wih left ventricular hypertrophy, whereas IVCT resulted within the normal limits. On the contrary, IVRT significantly raised. Accordingly, MPI resulted higher in controls. Conclusion LAVI, MPI and its time intervals appear as reliable tools to non-invasively individualize LV diastolic dysfunction in systemic hypertension, in absence of mitral valve disease.

Echocardiographic evaluation of right heart function and pulmonary vascular bed

The aim of this review was to describe the different ultrasonic modalities to non-invasively evaluate right cardiac chambers and pulmonary vascular bed function. M-Mode, 2-D, conventional pulsed doppler, tissue doppler imaging (TDI), strain rate imaging (SRI) and 3D echocardiography are illustrated in order to obtain both regional and global right heart and pulmonary function. The results have a good correlation with other invasive and non-invasive diagnostic techniques, as magnetic resonance imaging (MRI). All these echocardiograpic techniques can be employed to evaluate the morphologic and functional pictures of right heart and pulmonary circulation in presence of pulmonary hypertension (PH). The hemodynamic profile obtained consent to anatomically and functionally characterize PH. But, other experiences performed on more wide range of healthy and PH patients are necessary to confirm the described results.

Ranolazine and Ivabradine: Two different modalities to act against ischemic heart disease

Among the innovative drugs recently introduced for the management of chronic stable angina, Ranolazine and ivabradine represent two most true innovations. In fact, even if both drugs act by reducing myocardial work and thus oxygen consumption, this happens by a peculiar mechanism unlike that of conventional antischemic drugs. Ranolazine mediates its antianginal effects by the inhibition of cardiac late sodium current. This improves myocardial relaxation favoring myocardial perfusion. Ivabradine is a selective If channel blocker and acts by reducing firing rate of pacemaker cells in the sinoatrial node, without affecting the duration of action potential. The reduction of heart rate causes a reduction of left ventricular end diastolic pressure and increases the time useful to coronary flow by a prolongation of the diastole. A body of evidence found that two drugs are useful in ischemic patients whether at rest or during exercise. In addition, they can be used in monotherapy or in association with other conventional anti-ischemic drugs. The two medications could be used with advantage also in microvascular angina when standard therapy is ineffective. Thus, the two drugs represent an adjunctive and powerful therapeutic modality for the treatment of chronic stable angina, especially when conventional antianginal drugs were insufficient or inadequate.

Left atrial longitudinal speckle tracking echocardiography in healthy aging heart

Background: Left atrial volume (LAV) and function are connected to the left ventricular (LV) haemodynamic patterns. To define the changes of LAV and functions to counterbalance age-related LV diastolic impairment, this study was undertaken. Methods: 2D-Left Atrial Speckle Tracking Echocardiography (2D-LASTE) was used to define both LAV and functions in an aged healthy population (group II) respect to adult healthy controls (group I). Results: Results showed an increasing of left atrial volume indices (LAVI) (maximum, minimum, pre-a) in old subjects in comparison with those obtained in adult healthy controls. On the contrary, LAVI passive emptying unchanged and LAVI passive fraction reduced with advanced age. Finally, LAVI active emptying increased with advancing age to compensate the age-dependent left ventricular diastolic dysfunction. The values of global systolic strain (S); systolic strain rate (SrS); early diastolic strain rate (SrE), and late diastolic strain rate (SrA) were also calculated. With reference to the function, our study confirmed that LA conduit function deteriorates with age while booster pump increases respect to adult controls and reservoir phase is maintained. Conclusions: The echocardiographic findings obtained with conventional and tissue Doppler confirmed the connection between LA functions and volumes and age-related LV dysfunction. Conclusively, 2D-LASTE appears to be a reliable tool to evaluate the role of LA to compensate the derangement of left ventricle happening with ageing.

Three-dimensional trans-thoracic echocardiography of esophageal achalasia: Description of a case

Esophageal achalasia is a motility disorder characterized by impaired relaxation of the lower esophageal sphincter and dilatation of the distal two-thirds of the esophagus. This condition may be a non-frequent reason of extrinsic compression of left atrium. In turn, this can be a cause of some hemodynamic changes such as chest discomfort, dyspnea or reduced exercise tolerance, systemic hypotension and tachycardia. We describe a case of a patient with esophagus achalasia compressing the left atrium and inducing hemodynamic compromise. The diagnostic methods, as chest X-ray, computed tomography (CT), manometry, and 2D-Trans-Thoracic Echocardiography (TTE) demonstrated the esophagus dilation, the impaired relaxation of the lower esophageal sphincter, and its compression on the left atrium. Three-D Trans-Thoracic Echocardiography (3D-TTE) was firstly performed also. This last examination pointed out better than 2D-TTE the extrinsic compression of the left atrium due to the esophagus dilatation. Therefore, 3D-TTE is a true improvement for the echocardiographic diagnosis of the left atrial compression induced by esophageal achalasia.

Mitral Annulus Posterior Systolic Excursion Instead of Left Ventricular Ejection Fraction to Evaluate Left Ventricular Systolic Function Both During Urgent Hypertensive Crisis and After Blood Pressure Normalization

To the Editor: Hypertensive crisis (HC) consists of a sudden increase in systolic-diastolic blood pressure. It may be divided into two categories: emergency and urgency HCs, depending on the impairment of target organs’ dysfunction or not. Both during emergency or urgency HC, the left ventricle is unable to perform its normal function. Left ventricular (LV) systolic function is usually assessed by percentage of LV ejection fraction (LVEF%), but the Mitral Annulus Posterior Systolic Excursion (MAPSE) may also be used. Specifically, MAPSE seems to reflect the contribution of the longitudinally oriented myocardial fibers in generating LV stroke volume. LVEF% decreased during urgent HC, for LV dysfunction because of sudden growth of afterload, depending on peripheral vasoconstriction, activation of the nervous system, and activation of the renin-angiotensin-aldosterone system. Alterations of salt ⁄ water balance are also responsible for this. But when afterload is reduced (for blood pressure lowering), LV systolic function increases again, with consequent increase in LVEF%. Several reports confirm that LV systolic function may be well evaluated by MAPSE. More recently, it was also demonstrated that at rest and after exercise, MAPSE was well correlated with LV function in patients with heart failure and preserved LVEF%. There is also evidence of a satisfactory correlation between MAPSE and LVEF% by magnetic resonance imaging. Bergenzaun and colleagues demonstrated that in critically ill patients, ‘‘eyeball’’ ejection fraction can be used instead of single-plane Simpson when assessing LVEF%. But, Emilsson and coworkers showed a higher correlation between LVEF% and longitudinal fractional shortening (l-FS) than between LVEF% and MAPSE, suggesting that l-FS (which includes a correction for ventricular length) may be a more suitable index of LV systolic function than MAPSE per se. Nevertheless, LVEF% may be replaced with MAPSE, because it more rapidly defines LV dysfunction during urgent HC in the emergency department. That was evidenced by the results obtained in our 35 hypertensive patients admitted to a first aid station for HC. Some epidemiologic, clinical, and echocardiographic characteristics of these patients, with LVEF% and MAPSE values recorded during urgent HC and at blood pressure lowering, are reported in the Table.