Donato Mele

Speckle-Tracking Echocardiography A New Technique for Assessing Myocardial Function

Speckle‐tracking echocardiography has recently emerged as a quantitative ultrasound technique for accurately evaluating myocardial function by analyzing the motion of speckles identified on routine 2‐dimensional sonograms. It provides non‐Doppler, angle‐independent, and objective quantification of myocardial deformation and left ventricular systolic and diastolic dynamics. By tracking the displacement of the speckles during the cardiac cycle, strain and the strain rate can be rapidly measured offline after adequate image acquisition. Data regarding the feasibility, accuracy, and clinical applications of speckle‐tracking echocardiography are rapidly accumulating. This review describes the fundamental concepts of speckle‐tracking echocardiography, illustrates how to obtain strain measurements using this technique, and discusses their recognized and developing clinical applications.

Oxidative stress during myocardial ischaemia and heart failure.

Oxidative stress is a condition in which oxidant metabolites exert their toxic effect because of an increased production or an altered cellular mechanism of protection. The heart needs oxygen avidly and, although it has powerful defence mechanisms, it is susceptible to oxidative stress, which occurs, for instance, during post-ischaemic reperfusion. Ischaemia causes alterations in the defence mechanisms against oxygen free radicals, mainly a reduction in the activity of mitochondrial superoxide dismutase and a depauperation of tissue content of reduced glutathione. At the same time, production of oxygen free radicals increases in the mitochondria and leukocytes and toxic oxygen metabolite production is exacerbated by re-admission of oxygen during reperfusion. Oxidative stress, in turn, causes oxidation of thiol groups and lipid peroxidation leading first to reversible damage, and eventually to necrosis. In man, there is evidence of oxidative stress (determined by release of oxidised glutathione in the coronary sinus) during surgical reperfusion of the whole heart, or after thrombolysis, and it is related to transient left ventricular dysfunction or stunning. Data on oxidative stress in the failing heart are scant. It is not clear whether the defence mechanisms of the myocyte are altered or whether the production of oxygen free radicals is increased, or both. Recent data have shown a close link between oxidative stress and apoptosis. Relevant to heart failure is the finding that tumour necrosis factor, which is found increased in failing patients, induces a rapid rise in intracellular reactive oxygen intermediates and apoptosis. This series of events is not confined to the myocytes, but occurs also at the level of endothelium, where tumour necrosis factor causes expression of inducible nitric oxide synthase, production of the reactive radical nitric oxide, oxidative stress and apoptosis. It is therefore, possible that the immunological response to heart failure results in endothelial and myocyte dysfunction through oxidative stress mediated apoptosis. Clarification of these mechanisms may lead to novel therapeutic strategies.

A new integrated system for three-dimensional echocardiographic reconstruction: Development and validation for ventricular volume with application in human subjects☆

OBJECTIVES The purpose of this study was to improve three-dimensional echocardiographic reconstruction by developing an automated mechanism for integrating spark gap locating data with corresponding images in real time and to validate use of this mechanism for the measurement of left ventricular volume. BACKGROUND Initial approaches to three-dimensional echocardiographic reconstruction were often limited by inefficient reconstructive processes requiring manual coordination of two-dimensional images and corresponding spatial locating data. METHODS In this system, a single computer overlays the binary-encoded positional data on the two-dimensional echocardiographic image, which is then recorded on videotape. The same system allows images to be digitized, traced, analyzed and displayed in three dimensions. This system was validated by using it to reconstruct 11 ventricular phantoms (19 to 271 ml) and 11 gel-filled excised ventricles (21 to 236 ml) imaged in intersecting long- and short-axis views and by apical rotation. To measure cavity volume, a surface was generated by an algorithm that takes advantage of the full three-dimensional data set. RESULTS Reconstructed cavity volumes agreed well with actual values: y = 0.96x + 2.2 for the ventricular phantoms in long- and short-axis views (r = 0.99, SEE = 2.7 ml); y = 0.95x + 2.9 for the phantoms, reconstructed by apical rotation (r = 0.99, SEE = 2.7 ml); and y = 0.99x + 0.11 ml for the excised ventricles (reconstructed in long- and short-axis views; r = 0.99, SEE = 5.9 ml). The mean difference between three-dimensional and actual volumes was 3% of the mean (3.0 ml) for the phantoms and 6% (4.6 ml) for the excised ventricles. Observer variability was 2.3% for the phantoms and 5.6% for the excised ventricles. Application to 14 normal subjects demonstrated feasibility of left ventricular reconstruction, which provided values for stroke volume that agreed well with an independent Doppler measure (y = 0.97x + 0.94; r = 0.95, SEE = 3.2 ml), with an observer variability of 4.9% (2.4 ml). CONCLUSIONS A system has therefore been developed that automatically integrates locating and imaging data in no more time than the component two-dimensional echocardiographic scans. This system can accurately reconstruct ventricular volumes in vitro over a wide range and is feasible in vivo, thus laying the foundation for further applications. It has increased the efficiency of three-dimensional reconstruction and enhanced our ability to address clinical and research questions with this technique.

Tumor Necrosis Factor-α Receptor 1 Is a Major Predictor of Mortality and New-Onset Heart Failure in Patients With Acute Myocardial Infarction The Cytokine-Activation and Long-Term Prognosis in Myocardial Infarction (C-ALPHA) Study

Background—Tumor necrosis factor alpha-&agr; (TNF-&agr;) activation is an independent prognostic indicator of mortality in patients with heart failure (HF). Despite the recognition that several TNF family cytokines are elevated during myocardial infarction, their role in predicting subsequent prognosis in these setting remains poorly understood. Methods and Results—We performed a systematic evaluation of TNF-&agr; and its type 1 and 2 soluble receptors, together with interleukin (IL)-6, IL-1 receptor antagonist, and IL-10, in 184 patients (132 men; mean age, 64±12) consecutively admitted for myocardial infarction. We correlated their values to short- and long-term incidence of death and HF (primary outcome). In 10 patients, we also studied the presence of transcardiac gradients for TNF-&agr; and its soluble receptors. The control group comprised 45 healthy subjects who were sex and age matched (33 men; mean age, 65±6 years) to the patients. All tested cytokines were increased in patients, and no transcardiac or systemic AV difference was found. After a median follow-up of 406 days (range, 346 to 696 days), 24 patients died and 32 developed HF. Univariate analysis showed that all cytokines were related to outcome, whereas after adjustment for baseline and clinical characteristics, sTNFR-1 remained the only independent predictor of death and HF (hazard ratio, 2.9; 95% CI, 1.9 to 3.8, tertile 1 versus 3), together with left ventricular ejection fraction, Killip class, and creatine kinase-MB at peak. Conclusions—sTNFR-1 is a major short- and long-term predictor of mortality and HF in patients with acute myocardial infarction.

Therapeutic Effects of l-Carnitine and Propionyl-l-carnitine on Cardiovascular Diseases: A Review

Abstract: Several experimental studies have shown that levocarnitine reduces myocardial injury after ischemia and reperfusion by counteracting the toxic effect of high levels of free fatty acids, which occur in ischemia, and by improving carbohydrate metabolism. In addition to increasing the rate of fatty acid transport into mitochondria, levocarnitine reduces the intramitochondrial ratio of acetyl‐CoA to free CoA, thus stimulating the activity of pyruvate dehydrogenase and increasing the oxidation of pyruvate. Supplementation of the myocardium with levocarnitine results in an increased tissue carnitine content, a prevention of the loss of high‐energy phosphate stores, ischemic injury, and improved heart recovery on reperfusion. Clinically, levocarnitine has been shown to have anti‐ischemic properties. In small short‐term studies, levocarnitine acts as an antianginal agent that reduces ST segment depression and left ventricular end‐diastolic pressure. These short‐term studies also show that levocarnitine releases the lactate of coronary artery disease patients subjected to either exercise testing or atrial pacing. These cardioprotective effects have been confirmed during aortocoronary bypass grafting and acute myocardial infarction. In a randomized multicenter trial performed on 472 patients, levocarnitine treatment (9 g/day by intravenous infusion for 5 initial days and 6 g/day orally for the next 12 months), when initiated early after acute myocardial infarction, attenuated left ventricular dilatation and prevented ventricular remodeling. In treated patients, there was a trend towards a reduction in the combined incidence of death and CHF after discharge. Levocarnitine could improve ischemia and reperfusion by (1) preventing the accumulation of long‐chain acyl‐CoA, which facilitates the production of free radicals by damaged mitochondria; (2) improving repair mechanisms for oxidative‐induced damage to membrane phospholipids; (3) inhibiting malignancy arrhythmias because of accumulation within the myocardium of long‐chain acyl‐CoA; and (4) reducing the ischemia‐induced apoptosis and the consequent remodeling of the left ventricle. Propionyl‐l‐carnitine is a carnitine derivative that has a high affinity for muscular carnitine transferase, and it increases cellular carnitine content, thereby allowing free fatty acid transport into the mitochondria. Moreover, propionyl‐l‐carnitine stimulates a better efficiency of the Krebs cycle during hypoxia by providing it with a very easily usable substrate, propionate, which is rapidly transformed into succinate without energy consumption (anaplerotic pathway). Alone, propionate cannot be administered to patients in view of its toxicity. The results of phase‐2 studies in chronic heart failure patients showed that long‐term oral treatment with propionyl‐l‐carnitine improves maximum exercise duration and maximum oxygen consumption over placebo and indicated a specific propionyl‐l‐carnitine effect on peripheral muscle metabolism. A multicenter trial on 537 patients showed that propionyl‐l‐carnitine improves exercise capacity in patients with heart failure, but preserved cardiac function.

Proximal Jet Size by Doppler Color Flow Mapping Predicts Severityof Mitral Regurgitation: Clinical Studies

Background Recent studies have shown that many instrument and physiological factors limit the ability of color Doppler total jet area within the receiving chamber to predict the severity of valvular regurgitation. In contrast, the proximal or initial dimensions of the jet as it emerges from the orifice have been shown to increase directly with orifice size and to correlate well with the severity of aortic insufficiency. Only limited data, however, are available regarding the value of proximal jet size in mitral regurgitation, and it has not been examined in short-axis or transthoracic views. The purpose of the present study, therefore, was to evaluate the relation between proximal jet size and other measures of the severity of mitral regurgitation. Methods and Results In 49 patients, the anteroposterior height of the proximal jet as it emerges from the mitral valve was measured in the parasternal long-axis view; proximal jet width and area were measured in the short-axis view at the same level. Results we...

Exercise intolerance in chronic heart failure: mechanisms and therapies. Part II

Muscular fatigue and dyspnoea on exertion are among the most common symptoms in chronic heart failure; however their origin is still poorly understood. Several studies have shown that cardiac dysfunction alone cannot fully explain their origin, but the contribution of the multiorgan failure present in this syndrome must be highlighted. We aimed to summarize the existing evidence and the most controversial aspects of the complex interplay of different factors involved in the symptom generation. In the first part of the review, six key factors were revised (the heart, the lung, the skeletal muscle, the hormonal changes, the O2 delivery to the periphery, the endothelium). In this second part, the role of the excitatory reflexes and the cardiac cachexia are presented. Finally, potential therapeutic implications are discussed here. We believe that a better knowledge of the pathophysiology of this syndrome may contribute to the management of the patients and to the improvement in their stress tolerance and quality of life.

Which physical factors determine tricuspid regurgitation jet area in the clinical setting

The visual assessment of jet area has become the most common method used in daily clinic practice to evaluate valvular regurgitation. Despite the high prevalence of tricuspid regurgitation, however, few studies have systematically compared TR jet areas with a quantitative standard. To evaluate this, 40 patients in sinus rhythm with tricuspid regurgitation were analyzed: 16 with centrally directed free jets and 24 with impinging wall jets. The size of the maximal planimetered color jet area (cm2) was compared with parameters derived using the pulsed Doppler 2-dimensional echocardiographic method: regurgitant fraction and the flow convergence method (peak flow rate, effective regurgitant orifice area and momentum). Mean tricuspid regurgitant fraction averaged 33 +/- 15%, peak flow rate 76 +/- 54 cm3/s, effective regurgitant orifice area 27 +/- 21 mm2 and momentum 21,717 +/- 15,014 cm4/s2. An average of 4-chamber, and long- and short-axis areas in free jets correlated well with regurgitant fraction (r = 0.81, p < 0.001), better with peak flow rate (r = 0.94, p < 0.001), effective regurgitant orifice (r = 0.92, p < 0.001) and momentum (r = 0.94, p < 0.001). The correlation was worse, but still significant, in wall jets. For the same peak flow rate, wall jets were 75% of the size of a corresponding free jet. Jet area measurement is a good semiquantitative tool to measure tricuspid regurgitation in free jets, which correlates well with regurgitant fraction and better with new parameters available from analysis of the proximal acceleration field. In patients with eccentrically directed wall jets the correlation with planimetered jet area was worse, but still significant.

Quantification of tricuspid regurgitation by means of the proximal flow convergence method: A clinical study

Quantitation of valvular regurgitation remains an important goal in clinical cardiology. It has been described previously that with the use of color Doppler flow mapping, simple measurements of apparent jet size do not correlate closely with quantitative regurgitant indices. Recently the proximal flow convergence method has been proposed to quantify valvular regurgitation by analysis of the converging flow field proximal to a regurgitant lesion. Assuming hemispherical convergence, flow rate Q can be calculated as Q = 2 pi r2va, where va is the aliasing velocity at a distance r from the orifice. For maximal accuracy, previously validated correction factors must be used to account for the flattening effect of the isovelocity contours close to the orifice and for the actual sector angle subtended by the valve leaflets (alpha), to yield a flow rate formula Q = 2 pi r2va.(vp/vp - va).(alpha/180), where vp is the orifice velocity obtained by continuous wave Doppler. In 45 patients (35 in sinus rhythm, 10 with atrial fibrillation) with tricuspid regurgitation, regurgitant stroke volume, regurgitant flow rate, and regurgitant fraction were calculated using the proximal flow convergence method and were compared with values obtained by the Doppler two-dimensional echocardiographic method. Regurgitant stroke volumes (SV) calculated by the proximal flow convergence method correlated very closely with values obtained by the Doppler two-dimensional method with r = 0.95 (y = 0.94x + 0.99) and delta SV = -0.3 +/- 5.2 cm3. Regurgitant flow rates (Q) calculated by both methods showed a similar correlation: r = 0.96 (y = 0.97x + 45) and delta Q = 1.6 +/- 429 cm3/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Echocardiographic myocardial scar burden predicts response to cardiac resynchronization therapy in ischemic heart failure.

BACKGROUND Because echocardiography is routinely applied for left ventricle (LV) evaluation before cardiac resynchronization therapy (CRT), it is important to know whether echocardiographic assessment of myocardial scar burden may also help to predict CRT response in patients with drug-refractory systolic heart failure of ischemic origin. METHODS Seventy-one patients with ischemic heart failure who underwent CRT were retrospectively analyzed. The number of LV scar segments was evaluated in each patient, defining transmural scar as an end-diastolic wall thickness < or = 5 mm associated with increased acoustic reflectance. CRT response was defined by LV end-systolic volume decrease by at least 10% after 6 months of treatment. The role of pacing site with respect to scar location was also assessed. RESULTS Thirty-nine patients (55%) were responders and 32 patients (45%) were nonresponders to CRT. At baseline, responders had a lower number of scar segments (1.7 +/- 1.6 vs 3.5 +/- 2.5, P = .001). The number of scar segments was significantly associated with CRT response and correlated significantly with end-systolic volume variation (r = 0.57, P = .0001). The presence of 3 or more scar segments allowed the identification of nonresponders with a sensitivity of 62% and specificity of 71%. In responders, the pacing stimulus was more frequently delivered remote from scar segments, whereas in nonresponders it was more often delivered over the scar segments. CONCLUSION Echocardiographic evaluation of transmural scar burden predicts CRT response after 6 months of treatment and should be performed in all candidates for CRT with ischemic heart failure before biventricular pacemaker implantation.