AIMS Cardiac resynchronization therapy is currently used in selected patients with end-stage heart failure. However, 30% of patients do not respond to CRT. The aim of our study was to find echocardiographic (TDI), electrocardiographic (QRS interval and electric distance between right and left catheter), clinical (6MW test) or autonomical (HRV) parameters able to predict responsiveness to CRT. MATERIALS AND METHODS 47 patients (mean age 74+/-10 years) with end-stage heart failure, symptomatic, with left ventricular (LV) ejection fraction less than 35% and QRS 120 ms, underwent CRT. RESULTS At thirteen months follow up, all clinical and echocardiographic parameters significantly improves (EF p<0.001; LVED volume p<0.001; 6MWT p<0.001; max delay TDI p<0.001; HRV p<0.05; Right-left distance p<0.05). A positive response was documented in 31/47 (67.4%) patients who presented an increase in LVEF > or = 5 units. There was a significant difference of LVED diameter (p<0.05) and HRV (p<0.05) between responders and non responders. Receiver-operating curve analysis showed that a positive response to CRT may be predicted in patients with LVED diameter <67 mm (with a sensitivity of 77% and a specificity of 88%). CONCLUSIONS Our results confirm the clinical improvement obtained by CRT in end-stage heart failure patients as well as the limited value of QRS duration and intraventricular dyssynchrony as predictor of clinical recovery after CRT. While a most-advanced clinical stage of disease (HRV) without an advance left ventricular remodeling (LVED diameter) demonstrated to predict response to CRT, with sensitivity of 77% and specificity of 88%.

Obesity is a well-established risk factor for congestive heart failure. Evidence has been provided indicating that insulin resistance could be the mediator between obesity and congestive heart failure, but the pathogenic mechanisms leading to myocardial alterations remain unclear. The aim of this study was to investigate, by ultrasonic integrated backscatter (IBS) analysis, subclinical alterations of left ventricular (LV) structure and function in severe obesity. Sixty consecutive, severely obese people, who were otherwise healthy (15 men, 45 women; mean age +/- SD = 31.8 +/- 7 years), were enrolled. A total of 48 sex- and age-matched nonobese healthy participants were recruited as control subjects. All participants underwent conventional 2-dimensional color Doppler echocardiography, pulsed wave Doppler tissue imaging at mitral annulus level, and IBS. The homeostasis model assessment insulin resistance index was used to assess insulin resistance; the index values in the obese group were significantly higher (mean +/- SD = 4.9 +/- 1.4) than in the control group (0.92 +/- 0.5, P < .0001). Obese patients had a greater LV mass index by height (58.5 +/- 14 g/m(2.7)) than did control subjects (37 +/- 8 g/m(2.7), P < .0001) because of compensation response to volume overload caused by a greater cardiac output (P < .02). Preload reserve was increased in obese patients, as demonstrated by the significant increase in left atrial dimension (P < .0001). This volumetric increase activated the Frank-Starling mechanism, and determined a significantly higher LV ejection fraction (P < .03) in obese patients as compared with control subjects. A slightly reduced LV diastolic function was demonstrated in obese patients (transmitral early to late peak diastolic transmitral flow velocities ratio = 1.1 +/- 0.7) as compared with control subjects (1.5 +/- 0.5, P < .02). Pulsed wave Doppler tissue imaging showed an impairment of diastolic LV longitudinal function and increased LV diastolic filling pressure. The IBS values at septum level, indexed by pericardium interface, were significantly higher for septum in the obese group (57.8 +/- 8%) than in the control group (42.3 +/- 9%, P < .0001). Additional IBS alterations were observed in the obese group, with a significantly lower cyclic variation index both at septum (P < .0001) and at posterior wall (P < .001) levels. A significant association was found between insulin resistance index and both the IBS index of myocardial reflectivity at septum level (expression of increased myocardial collagen content) or LV mass. In conclusion, this study demonstrates that obese patients exhibit myocardial structural and functional alterations related to insulin resistance and to LV volume overload, which could be considered the very early stage of incipient obesity cardiomyopathy.

females, 28-63 years, mean 49±9 years).A control group was made up with 30 individuals (15 females, 36-56 years, mean 44±5 years).Etiologic diagnosis for PE was tuberculosis (2 patients), pulmonary adenocarcinoma (1 patient), hypothyroidism (1 patient), rheumatologic condition (3 patients), rheumatoid arthritis (2 patients), sclerodermy CREST syndrome (1 patient) and idiopathic (8 patients), and for CP was tuberculosis (2 patients), in all others, it was idiopathic.Patients were evaluated by standard transthoracic echocardiography and NT-proBNP levels detected by electrochemiluminescence.Results: PE NT-proBNP log mean of 2.24 pg/mL (CI 95%: 1.97-2.50log pg/ mL), CP log mean of 2.67 pg/mL (CI 95% 2.43-2.92log pg/mL), and EMF log mean of 2.91 pg/mL (CI 95% 2.70-3.12log pg/mL) were higher when compared to control group log mean of 1.45 pg/mL (CI 95% 1.32-1.60log pg/ mL) (p<0.05).No difference of NT-proBNP levels was reported between CP and EMF (p=0.149).All patients presented normal left ventricular ejection fraction.The NT-proBNP log mean was correlated to transmitral E-wave peak velocity (r=0.439;p=0.006).Conclusion: NT-proBNP levels are increased in patients with restrictive syndromes, but could not differentiate restrictive cardiomyopathy from pericardial diseases.Also, NT-proBNP levels increase in parallel with transmitral E-wave, reflecting diastolic dysfunction in restrictive syndromes.

We tested the hypothesis of beneficial effects of the calcium-blocker verapamil in a model of ischemia-reperfusion, and investigated its effects against coronary microcirculation and cardiomyocyte apoptosis. Isolated working rat hearts were subjected to 15 min global ischemia and 22-180 min reperfusion in the presence or absence of verapamil (0.25 &mgr;M). We evaluated creatinephosphokinase (CK) in coronary effluent, heart weight changes, microvascular permeability (extravasation of fluoresceine-labeled albumin), ultrastructural alterations, and cardiomyocyte apoptosis (by 1.5% agarose gel electrophoresis and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling technique). In this model, 0.25 &mgr;M verapamil significantly reduced myocardial damage, CK release and vascular hyperpermeability, concomitant with a reduction in endothelial and cardiomyocyte lesions; on the contrary, 0.25 &mgr;M verapamil was unable to reduce cardiomyocyte apoptosis. In conclusion, in the absence of perfusing granulocytes, the acute administration of a pharmacologically relevant verapamil concentration reduces ischemia-reperfusion injury and prevents coronary endothelial cell and cardiomyocyte necrotic cell death but it is unable to reduce apoptotic cell death in isolated working rat hearts.

In order to identify subjects at higher risk for carotid stenosis and to provide insights into mechanisms of disease development at different age-intervals, a color duplex ultrasound of extracranial arteries was performed in 624 consecutive patients (mean age 62.9+/-10.7, 483 males) undergoing coronary angiography. Significant carotid atherosclerosis (> or =50% stenosis) was documented in 87 patients (14%): the disease was moderate (50/69% stenosis) in 51 patients (8%), severe (> or =70% stenosis) in 36 patients (6%). Age (P<0.0001), smoking (P<0.0001), diabetes (P=0.0002), renal dysfunction (P=0.0119) and hypertension (P=0.0202) were independent predictors of significant carotid atherosclerosis; age (P=0.0001), smoking (P=0.0009) and diabetes (P=0.0201) were independent predictors of severe disease. Among 262 candidates for cardiac surgery, significant carotid artery disease was identified in 57 cases (2.63 Relative Risk, 95% Confidence Intervals: 1.32/5.24). Correlation and regression tree analysis demonstrated that diabetes was associated with greater severity of carotid stenosis in younger patients and hypertension in older ones. In conclusion age is the primary determinant of carotid artery disease; diabetes and smoking accelerate progression of atherosclerosis in younger patients, hypertension and smoking in older ones. Among patients undergoing coronary angiography, carotid ultrasonography should be recommended in high risk subgroups of patients.

Background: the cardiac Renin-Angiotensin system (RAS) plays an important role in the regulation of coronary flow and cardiac function and structure in normal and pathological conditions such as ischemia-reperfusion (I/R) injury. The aim of this study was to investigate the effects of the Angiotensin II type 1 (AT-1) receptor antagonist MK-954 (losartan potassium) on postischemic endothelial dysfunction and NOS mRNA expression (inducible nitric oxide synthase, iNOS; endothelial nitric oxide synthase, eNOS) in isolated working rat hearts. Methods: isolated working rat hearts were subjected to 15 min global ischemia and 180 min reperfusion. MK-954 was added to perfusion buffer (a modified Krebs-Henseleit solution) at 1 muM concentration. We assessed functional parameters, creatin kinase (CK) release, heart weight changes, microvascular postischemic hyperpermeability (FITC-albumin extravasation) and morphological ultrastructural alterations. eNOS and iNOS mRNA levels were also detected by the means of multiplex RT-PCR technique using glyceraldehyde-3-phosphate dehydrogenase (G3PDH) gene as internal control; results were expressed as densitometric ratio. Results: in Losartan-treated hearts we observed a significant reduction of postischemic contractile dysfunction, CK release and myocardial ultrastructural damage; postischemic FITC-albumin extravasation was significantly reduced respect to controls. Moreover, 1 muM Losartan produced a significant reduction of eNOS/G3PDH respect to untreated hearts submitted to I/R. Regarding iNOS/G3PDH ratio, no significant changes were detected in Losartan-treated hearts compared with controls. Conclusions: our study revealed that Losartan treatment before ischemia, and during reperfusion, is able to reduce the reperfusion injury of the rat heart by reducing mechanical and microcirculatory dysfunction and necrotic cell death, ameliorating cardiac ultrastructure and endothelial protection, probably inducing eNOS over-expression and reducing post-ischemic hyperpermeability of coronary microcirculation. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Objective: We tested the hypothesis of beneficial effects of the 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA)-reductase inhibitor simvastatin in a model of ischemia-reperfusion, and investigated potential mechanisms. Methods: Isolated working rat hearts were subjected to 15 min global ischemia and 22-180 min reperfusion in the presence or absence of simvastatin (10-100 muM). We evaluated creatinephosphokinase and nitrite levels in coronary effluent, heart weight changes, microvascular permeability (extravasation of fluoresceine-labeled albumin), ultrastructural alterations, and the expression of endothelial (e) and inducible (i) nitric oxide synthase (NOS) (by reverse-transcribed polymerase chain reaction and Western blotting) in the presence or absence of the transcriptional inhibitor actinomycin-D. Results: Simvastatin (25 muM) significantly reduced myocardial damage and vascular hyperpermeability, concomitant with a reduction in endothelial and cardiomyocyte lesions. Protection became less evident at 50 muM and reverted to increased damage at 100 muM. At 25 muM, simvastatin significantly increased eNOS mRNA and protein compared with untreated hearts, probably due to a post-transcriptional regulation since unaltered by animal pretreatment with actinomycin D. Simvastatin also significantly decreased iNOS mRNA and protein, as well as nitrite production after ischemia-reperfusion. The addition of the NOS inhibitor N-w-nitro-L-arginine methylester (L-NAME, 30 muM) to 25 muM simvastatin-treated hearts significantly reduced cardioprotection against ischemia-reperfusion. Conclusions: In this model, in the absence of perfusing granulocytes, the acute administration of a pharmacologically relevant simvastatin concentration reduces ischemia-reperfusion injury and prevents coronary endothelial cell and cardiomyocyte damage by cholesterol-independent, NO-dependent mechanisms. (C) 2001 Elsevier Science BY. All rights reserved.

Relevant hemodynamic information can be obtained by a comprehensive Doppler echocardiographic examination in patients with various cardiac diseases. The assessment of left heart hemodynamics by Doppler echocardiography has been addressed by several investigators. The feasibility and the accuracy of methods for the estimation of left ventricular filling pressure and cardiac output have been validated by comparative right heart catheterization. Studies have shown that Doppler echocardiography can allow the measurement of pulmonary artery pressures from the pressure gradients across the tricuspid and pulmonary valves. The possibility of completely characterizing cardiac hemodynamics noninvasively has recently been documented: in patients with acute myocardial infarction, automated cardiac output measurement along with the assessment of left ventricular filling by Doppler echocardiography may be used for the identification of hemodynamic subsets. Although Doppler echocardiography can provide noninvasive measures of hemodynamic indices, its value has been disputed since the technique is patient-dependent, time-consuming and requires meticulous acquisition and interpretation by skilled operators. The use of contrast agents may improve the accessibility of both right-sided and left-sided Doppler signals, potentially increasing the number of patients to whom the noninvasive hemodynamic assessment could be applied.

Myocardial infarction is the major cause of death in the world. Over the last two decades, coronary reperfusion therapy has become established for the management of acute myocardial infarction (AMI). However, restoration of blood flow to previously ischemic myocardium results in the so-called ischemia/reperfusion (IR)-injury. The different clinical manifestations of this injury include myocardial necrosis, arrhythmia, myocardial stunning and endothelial- and microvascular dysfunction including the no-reflow phenomenon. The pathogenesis of ischemia/reperfusion injury consists of many mechanisms. Recently, there's increasing evidence for an important role in IR-injury on hypercontracture induced by high levels of cytosolic calcium or by low concentrations of ATP.In the last years, many studies on experimental models were investigated, but the clinical trials confirming these effects remain spare. Recently, the beneficial effect of Na+/H+-exchange inhibitor cariporide and of the oxygen-derived free radical (ODFR) scavenger vitamin E on coronary bypass surgery-induced IR-injury were demonstrated. Also recently, the beneficial effect of allopurinol on the recovery of left ventricular function after rescue balloon-dilatation was demonstrated. The beneficial effect of magnesium and trimetazidine on IR-injury remains controversial. The beneficial effect of adenosine remains to be further confirmed. There's also increasing interest in agentia combining the property of upregulating NO-synthase (e.g. l-arginine) and restoring the balance between NO and free radicals (e.g. tetrahydrobiopterin). One of such agents could be folic acid.In this review article the authors give an overview of the recent insights concerning pathogenesis and therapeutic possibilities to prevent IR-induced injury.