Concetta Torromeo

Cardiac dysfunction in cirrhosis is not associated with the severity of liver disease

BACKGROUND Cirrhotic cardiomiopathy is described as the presence of cardiac dysfunction in cirrhotic patients. The aim of the study was to investigate factors associated with cardiac dysfunction in cirrhotic patients. PATIENTS AND METHODS Seventy-four cirrhotic patients and twenty-six controls performed a conventional echocardiography and Tissue Doppler Imaging (TDI) for systolic and diastolic function. Results were analyzed by using the Guidelines of American Society of Echocardiography. RESULTS In patients with cirrhosis, left ventricular end-diastolic diameter was increased (p<0.001) , peak systolic velocities were decreased (11.3±2.7 vs 13.9±1.4cm/s; p<0.001) and left atrial volumes were increased (32.7±8.3 vs 24±8.5ml, p<0.001) as well as cardiac mass (90.6±23 vs 70.5±22g/m(2), p<0.001). Forty-seven cirrhotic patients (64%) showed diastolic dysfunction at rest: grade I in 37 and grade II in 10 patients. Systolic and/or diastolic dysfunction were not influenced by a more severe liver impairment. Diastolic dysfunction was more prevalent in patients with ascites vs those without (77% vs 56%; p=0.04). CONCLUSION A mild diastolic dysfunction at rest is frequent in cirrhotic patients but cardiac load conditions are confounding factors in this diagnosis. We did not identify an association between severity of liver disease and cardiac dysfunction.

Torsion of the human left ventricle: Experimental analysis and computational modeling

We set a twofold investigation: we assess left ventricular (LV) rotation and twist in the human heart through 3D-echocardiographic speckle tracking, and use representative experimental data as benchmark with respect to numerical results obtained by solving our mechanical model of the LV. We aim at new insight into the relationships between myocardial contraction patterns and the overall behavior at the scale of the whole organ. It is concluded that torsional rotation is sensitive to transmural gradients of contractility which is assumed linearly related to action potential duration (APD). Pressure-volume loops and other basic strain measures are not affected by these gradients. Therefore, realistic torsional behavior of human LV may indeed correspond to the electrophysiological and functional differences between endocardial and epicardial cells recently observed in non-failing hearts. Future investigations need now to integrate the mechanical model proposed here with minimal models of human ventricular APD to drive excitation-contraction coupling transmurally.

Thalidomide does not modify the prognosis of plasma cell leukemia patients: Experience of a single center

Plasma cell leukemia (PCL) represents the most advanced stage of multiple myeloma (MM) with the neoplastic cells circulating in the peripheral blood. Its diagnosis requires an absolute peripheral blood plasma cell count of 426 10/l or 420% of the differential white blood cell count [1]. PCL is classified into two clinical types: the primary type occurs in individuals without being preceded by MM, whereas the secondary one is a rare complication of the late-stage MM. Based on observations that in PCL the response to standard therapy is extremely poor and the use of Thalidomide (Thal) in advanced myeloma has resulted in marked responses even in patients with advanced diseases, including those who relapsed after high-dose chemotherapy [2], we decided to use this promising drug also in patients with PCL. According to the schedule reported by Singhal et al. [2], between March 2000 and July 2002, after written informed consent, five PCL (two primary and three secondary) patients were considered eligible for Thal treatment at our Institution. Thal was administered as single agent, according to a compassionate-use protocol. The starting dose of Thal was 100 mg daily for 2 weeks; subsequently, this dosage was increased by 100 mg every other week, to a maximum of 600 mg per day or according to the maximum tolerated dose. According to the International Stage criteria, two patients were in stage III (b2 microglobulin 45.5 mg/dl) and three in stage II (one for a b2 microglobulin of 4.2 mg/dl and two for serum albumin levels of 2.4 and 2.9 g/dl, respectively). No cytogenetics, labeling index or FISH data are available for these patients. Three were males and two females; median age was 68 years (range 51 – 72). Two cases were IgG, 1 IgA and two expressed light chains; one patient had serum creatinine 42 mg/dl. With regard to disease status, three patients (two primary and one secondary PCL) were refractory (defined as progression while on therapy) to prior chemotherapies and two were in relapse. All had been treated with at least two lines of treatment, including high-dose induction therapy for one of them, and were included in this study after 14 months (range 8 – 41) of median follow-up. All patients received Thal for at least 1 month and were, therefore, evaluable for response. No patient responded, although a reduction of circulating PC was observed in two. Survival was very short, all patients died after 40, 45, 60, 75 and 120 days of Thal treatment, respectively. During the same time period we treated with the same protocol 75 MM patients (33 refractory to prior chemotherapies and 42 in relapse). The median age was 63.5 years (range 33 – 84); 47 patients were IgG, 20 IgA and eight had light chain MM. Highdose induction therapy was utilized for 29 of them and the MM patients were included in this study after 36 months of median follow-up from diagnosis. The median daily dose of Thal administered to all patients was 400 mg (range 100 – 600 mg). Among the 75 MM patients, 67 received Thal for at least 1 month and were evaluable for response; the remaining eight patients were not evaluable because four

4D-Analysis of Left Ventricular Heart Cycle Using Procrustes Motion Analysis

The aim of this study is to investigate human left ventricular heart morphological changes in time among 17 healthy subjects. Preliminarily, 2 patients with volumetric overload due to aortic insufficiency were added to our analyses. We propose a special strategy to compare the shape, orientation and size of cardiac cycle’s morphological trajectories in time. We used 3D data obtained by Speckle Tracking Echocardiography in order to detect semi-automated and homologous landmarks clouds as proxies of left ventricular heart morphology. An extended Geometric Morphometrics toolkit in order to distinguish between intra- and inter-individual shape variations was used. Shape of trajectories with inter-individual variation were compared under the assumption that trajectories attributes, estimated at electrophysiologically homologous times are expressions of left ventricular heart function. We found that shape analysis as commonly applied in Geometric Morphometrics studies fails in identifying a proper morpho-space to compare the shape of morphological trajectories in time. To overcome this problem, we performed a special type of Riemannian Parallel Transport, called “linear shift”. Whereas the two patients with aortic insufficiency were not differentiated in the static shape analysis from the healthy subjects, they set apart significantly in the analyses of motion trajectory’s shape and orientation. We found that in healthy subjects, the variations due to inter-individual morphological differences were not related to shape and orientation of morphological trajectories. Principal Component Analysis showed that volumetric contraction, torsion and twist are differently distributed on different axes. Moreover, global shape change appeared to be more correlated with endocardial shape change than with the epicardial one. Finally, the total shape variation occurring among different subjects was significantly larger than that observable across properly defined morphological trajectories.

Gender and Cardiovascular Mortality in Northern and Southern European Populations

BACKGROUND There are no ready explanations for differences in ischemic heart disease incidence between women and men under an epidemiological perspective. However, when myocardial infarction occurs, there are more likely individuals who happen to die. METHODS This review from a more recent literature was performed for a two-fold purpose, to describe gender wise: a) the role of classical and novel factors defined to evaluate coronary artery disease (CAD) risk and mortality, aimed at assessing applicability and relevance for primary and secondary prevention; b) the differences in northern versus southern European Countries in risk factors and CAD mortality. RESULTS Age-related risk patterns differ in men and women. It is uncertain whether standard factors may index CAD risk, including mortality, in different ways and/or whether specific factors might be targeted gender-wise. A list might be compiled: HDL-cholesterol levels, higher in pre-menopausal women than in men, are more strictly related to CAD; high triglycerides and Lp(a) have a similar relationship; HDL-cholesterol levels have an inverse relation with CAD incidence and mortality. The role of statins is not completely defined in primary prevention for women. However, in secondary prevention statins are equally effective in both genders. Weight and glycemic control are effective to reduce cardiovascular disease (CVD) mortality in women from middle to older age. Similarly, CVD mortality in women, from middle to older age, might be reduced by controlling blood pressure, particularly among diabetic or over weighted women. Renal dysfunction, either defined by UAE or eGFR or both may usefully predict primary CVD incidence and risk in both genders. In secondary prediction, kidney dysfunction predicts sudden death in women when left ventricular ejection fraction is also evaluated. Serum uric acid that normally increases with age, differentiates gender-related CVD incidences with a peculiar importance in women as compared to men. There has been much interest to investigate loss of ovarian function in explaining age-related differences between genders. More recently, some emphasis has been laid on the loss of ovarian function-related iron stores. There are subgroups of women as those with mitral valve prolapse and increased circulating levels of catecholamines in whom QT interval, physiologically longer in women than men, may be an arrhythmogenic risk index. However, no large population-based studies were ever conducted to assess this. Therefore, in the future, it will be important to implement risk score instruments (charts and softwares) in women using novel parameters, and among these inflammatory markers and reproductive hormones and serum uric acid. The important results of the WHO MONICA Project confirmed the northern versus southern European gradient in both men and women, for death rates and the proportion of all deaths from cardiovascular causes (including CAD, stroke and other CVD causes). The coronary event rate was initially as high as 1, 000 per 100, 000 inhabitants in Finland and less than 1 fifth of that in Spain with the corresponding figures in women of 200 and 30, respectively. CONCLUSION No doubt might still exist that all efforts need be undertaken for both men and women, for health and prolongation of life to effectively treat common risk factors such as cigarette consumption, high blood pressure, cholesterol levels and physical inactivity by also paying attention to optimal diet.

A New 4D Trajectory-Based Approach Unveils Abnormal LV Revolution Dynamics in Hypertrophic Cardiomyopathy

The assessment of left ventricular shape changes during cardiac revolution may be a new step in clinical cardiology to ease early diagnosis and treatment. To quantify these changes, only point registration was adopted and neither Generalized Procrustes Analysis nor Principal Component Analysis were applied as we did previously to study a group of healthy subjects. Here, we extend to patients affected by hypertrophic cardiomyopathy the original approach and preliminarily include genotype positive/phenotype negative individuals to explore the potential that incumbent pathology might also be detected. Using 3D Speckle Tracking Echocardiography, we recorded left ventricular shape of 48 healthy subjects, 24 patients affected by hypertrophic cardiomyopathy and 3 genotype positive/phenotype negative individuals. We then applied Generalized Procrustes Analysis and Principal Component Analysis and inter-individual differences were cleaned by Parallel Transport performed on the tangent space, along the horizontal geodesic, between the per-subject consensuses and the grand mean. Endocardial and epicardial layers were evaluated separately, different from many ecocardiographic applications. Under a common Principal Component Analysis, we then evaluated left ventricle morphological changes (at both layers) explained by first Principal Component scores. Trajectories’ shape and orientation were investigated and contrasted. Logistic regression and Receiver Operating Characteristic curves were used to compare these morphometric indicators with traditional 3D Speckle Tracking Echocardiography global parameters. Geometric morphometrics indicators performed better than 3D Speckle Tracking Echocardiography global parameters in recognizing pathology both in systole and diastole. Genotype positive/phenotype negative individuals clustered with patients affected by hypertrophic cardiomyopathy during diastole, suggesting that incumbent pathology may indeed be foreseen by these methods. Left ventricle deformation in patients affected by hypertrophic cardiomyopathy compared to healthy subjects may be assessed by modern shape analysis better than by traditional 3D Speckle Tracking Echocardiography global parameters. Hypertrophic cardiomyopathy pathophysiology was unveiled in a new manner whereby also diastolic phase abnormalities are evident which is more difficult to investigate by traditional ecocardiographic techniques.

Decline in platelet count and long-term post-PCI ischemic events: Implication of the intra-aortic balloon pump

AIMS Thrombocytopenia (TC) following a percutaneous coronary intervention (PCI) has been associated not only with hemorrhagic, but also with ischemic outcomes. The purpose of this study was to re-examine the relationship of TC with ischemic events at a 1-year follow-up, and investigate the possible associations. METHODS AND RESULTS We studied a real-world, unselected population of ischemic patients undergoing PCI, totaling 861 patients-year, and divided into two groups: with TC (delta platelet count ≥25% from baseline to post-PCI during the hospital admission) and without TC. Compared with patients without TC, patients with TC had a higher and earlier incidence of both hemorrhagic and ischemic events. In them, the use of intra-aortic balloon pump (IABP) was ten-fold higher. In Kaplan-Meier curves assessing the contribution of both TC and IABP to outcome, IABP was a univariate detrimental factor additive to the role of TC. In a forced Cox model, the relative decline (delta) in platelet count (p=0.05) and the use of IABP (p=0.0001) were both associated with ischemic outcomes. After excluding all patients with IABP, the delta platelet count was no longer significantly associated with ischemic outcomes (p=0.66). After excluding all patients with shock and all those who undergone thrombolysis, there was still a relationship (p=0.0042) between the delta platelet count and ischemic events. CONCLUSIONS In this patient population the use of IABP, but not thrombocytopenia per se, is a possible primary cause of worse ischemic outcomes.

Non-invasive assessment of functional strain lines in the real human left ventricle via speckle tracking echocardiography

A mechanics-based analysis of data from three-dimensional speckle tracking echocardiography is proposed, aimed at investigating deformations in myocardium and at assessing shape and function of distinct strain lines corresponding to the principal strain lines of the cardiac tissue. The analysis is based on the application of a protocol of measurement of the endocardial and epicardial principal strain lines, which was already tested on simulated left ventricles. In contrast with similar studies, it is established that endocardial principal strain lines cannot be identified with any structural fibers, not even along the systolic phase and is suggested that it is due to the capacity of the endocardial surface to contrast the dilation of the left ventricle.

Clopidogrel plus indobufen in acute coronary syndrome patients with hypersensitivity to aspirin undergoing percutaneous coronary intervention.

The prescription of aspirin (acetylsalicylic acid (ASA)) to patients with a history of hypersensitivity to this drug could prove harmful. The aim of the study was to assess the antiplatelet activity and safety of a combined antiplatelet treatment with indobufen and clopidogrel in acute coronary syndrome (ACS) patients with hypersensitivity to aspirin, undergoing coronary stenting. Forty-two consecutive ACS patients treated with stent implantation were randomly assigned to receive clopidogrel 75 mg daily (loading dose 300 mg) plus indobufen 100 mg twice a day (group A), or clopidogrel 75 mg daily, after 300 mg of loading dose (group B). Platelet activity and safety were monitored in both groups at 1, 3, 6, 12, and 18 months with laboratory and clinical evaluation. A lower value of max % platelet aggregation to arachidonic acid and collagen was found in group A compared to group B (31.79 ± 27.33 vs. 73.67 ± 19.92; p < 0.0001 and 28.53 ± 21.32 vs. 73.58 ± 17.71; p < 0.0001, respectively). There was no difference in max % of platelet inhibition to adenosine diphosphate between the two groups (14.23 ± 18.92 vs. 10.30 ± 18.97; p = 0.23). In the population that was under indobufen treatment, the serum thromboxane B2 (TXB2) production at 1 week and 1 month was very low (2.6 ± 1.6 ng/ml and 3.0 ± 2.7 ng/ml, respectively; p = 0.82). The combined treatment was well tolerated in group A patients. This study suggests that the combined antiplatelet treatment with clopidogrel and indobufen could be a good option in ACS patients with hypersensitivity to aspirin undergoing coronary stenting.

Homeostatic Left Heart integration and disintegration links atrio-ventricular covariation’s dyshomeostasis in Hypertrophic Cardiomyopathy

Left ventricle and left atrium are and have been practically always analyzed separately in common clinically and non-clinically oriented cardiovascular investigations. Both classic and speckle tracking echocardiographic data contributed to the knowledge about deformational impairments occurring in systo-diastolic differences. Recently new trajectory based approaches allowed a greater awareness about the entire left ventricle or left atrium revolution and on their deficiencies that take place in presence of hypertrophic cardiomyopathy. However, surprisingly, the concomitant function of the two left heart chambers has not been analyzed for their geometrical/mechanical relationship. For the first time we study here, by acquiring left ventricle and left atrial geometries on the same heartbeat, the trajectory attributes of the entire left heart treated as a whole shape and the shape covariation of its two subunits. We contrasted healthy subjects with patients affected by hypertrophic cardiomyopathy. We found impaired left heart trajectory mainly in terms of orientation and size. More importantly, we found profound differences in the direction of morphological covariation of left ventricle and left atrium. These findings open to new perspectives in pathophysiological evaluation of different diseases by allowing the appreciation of concomitant functioning of both left heart whole geometry and of its two chambers.