[Process to insulin for type 2 diabetes mellitus therapy]. / Processo all'insulina nella terapia del diabete mellito di tipo 2.

In type 1 diabetes mellitus and in symptomatic and critical hyperglycemic states, insulin is a lifesaving drug; however, its value in long-term type 2 diabetes therapy, which represents more than 90% of diabetes, has not been assessed. This happens despite the fact that, in randomized studies on type 2 diabetes, insulin is used in two-thirds of cases when intensive hypoglycemic treatment is needed and in half of the patients when treatment is the standard one. This is a major issue from a clinical, economic and social-health organization point of view as insulin therapy is expensive and needs a complex organization. Observational and retrospective studies from the scientific literature show that in this type of diabetes insulin treatment is associated with increased cardiovascular and all-cause mortality. It is not clear whether this is due to a greater severity of the clinical picture, to the therapeutic target of blood glucose that may induce hypoglycemia, or to the intrinsic pharmacological activity of the drug that beyond reducing hyperglycemia can cause hypoglycemia, water retention, weight gain and hyperinsulinemia with proatherogenic effects. In particular, in patients with heart failure at high cardiovascular risk or with high insulin resistance, these clues are supported by meaningful data. Although there is no definitive evidence (the so-called "smoking gun") from randomized controlled trials, the high degree of suspicion induces the preferential choice of other drugs such as sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists and metformin beyond avoiding glycemic targets that induce hypoglycemia, especially in frail, elderly patients, or patients with cardiovascular diseases. These drugs, for their proven efficacy and the easy use within an outpatient setting (that favors their prescription and improves the inertia of the doctor and the adherence of patients), could help a more effective treatment of patients, both for quality and life expectancy beyond mere glycemic control.

[The patient in clinical research: disposable guinea pig or involved actor?] / Il paziente nella ricerca clinica: cavia a disposizione o attore interessato?

BACKGROUND: The request for informed consent to join a clinical trial often creates mistrust and hesitation in the patient who should be enrolled. In our study, we evaluated the reasons for refusing to participate in a clinical trial. METHODS: In the last 10 years of cardiovascular clinical research, we asked an informed consent to 2586 patients for intervention studies. Overall, 59% agreed to join clinical trials, 40% refused. The 1% initially accepted and then withdrew the consent. Those who refused were more frequently women, relatively younger (mean age 62 ± 5 vs 74 ± 9 years) and had a higher level of education and income. We asked all these patients who refused to answer a brief questionnaire about the reasons for rejection. RESULTS: Of 1031 patients, 629 (61%), accepted to answer the interview; 176 (28%) answered they refused on relatives', friends' or other doctors' advices, or after Internet searches; 157 (25%) answered they did not agree about how the trials were carried out (double-blind control procedure, use of placebo); 126 (20%) did not trust official medicine; 63 (10%) could not guarantee their presence at the follow-up visits; 69 (11%) did not want to undergo additional medical examinations; 31 (5%) had previous bad research experiences (feeling like a guinea pig); 7 (about 1%) refused for other reasons. CONCLUSIONS: Recruitment into clinical research studies is still a major challenge. Patients, due to a prevailing humanistic culture, are not fully aware of the importance of participation in clinical research, which is sometimes considered as exclusive economic or prestige interest. In our experience, people who refused participation in the trials were younger, with a high level of education and income, more frequently women. The researcher's task is to motivate the patient by emphasizing that participating in a study means being the actors of a treatment choice and that one is a guinea pig when taking untested therapies.

Assessment of Right Ventricular Function in Obstructive Sleep Apnea Syndrome and Effects of Continuous Positive Airway Pressure Therapy: A Pilot Study.

BACKGROUND: It is known that obstructive sleep apnea syndrome (OSAS) can affect right ventricular (RV) performance even in the absence of systemic hypertension and other known cardiac or obstructive pulmonary disease. The purpose of the present study was to assess RV function in OSAS using 3-D echocardiography and speckle tracking echocardiography (STE) and evaluate changes after continuous positive airway pressure (CPAP) treatment. METHODS: Thirty-seven patients with OSAS without comorbidities and thirty control subjects were studied using 3-D echocardiography and STE. Fifteen patients underwent CPAP therapy and were studied before and after treatment. RV 3-D ejection fraction was calculated. Peak systolic strain was determined. RV dyssynchrony was defined as SD of the 6 time to peak systolic strain values. RESULTS: 3-D RV ejection fraction was lower and RV dyssynchrony was greater in patients with moderate-severe OSAS compared with control subjects in the presence and absence of pulmonary hypertension. 3-D RV ejection fraction and RV dyssynchrony were independently associated with apnea-hypopnea index. Patients treated with CPAP had significant changes in RV parameters. CONCLUSIONS: 3-D RV ejection fraction and RV dyssynchrony were abnormal in OSAS patients compared with control subjects and associated with OSAS severity. RV 3-D STE abnormalities improved after chronic application of CPAP.

Three-dimensional echocardiography and 2D-3D speckle-tracking imaging in chronic pulmonary hypertension: diagnostic accuracy in detecting hemodynamic signs of right ventricular (RV) failure.

BACKGROUND: Our aim was to compare three-dimensional (3D) and 2D and 3D speckle-tracking (2D-STE, 3D-STE) echocardiographic parameters with conventional right ventricular (RV) indexes in patients with chronic pulmonary hypertension (PH), and investigate whether these techniques could result in better correlation with hemodynamic variables indicative of heart failure. METHODS AND RESULTS: Seventy-three adult patients (mean age, 53±13 years; 44% male) with chronic PH of different etiologies were studied by echocardiography and cardiac catheterization (25 precapillary PH from pulmonary arterial hypertension, 23 obstructive pulmonary heart disease, and 23 postcapillary PH from mitral regurgitation). Thirty healthy subjects (mean age, 54±15 years; 43% male) served as controls. Standard 2D measurements (RV-fractional area change-tricuspid annular plane systolic excursion) and mitral and tricuspid tissue Doppler annular velocities were obtained. RV 3D volumes and global and regional ejection fraction (3D-RVEF) were determined. RV strains were calculated by 2D-STE and 3D-STE. RV 3D global-free-wall longitudinal strain (3DGFW-RVLS), 2D global-free-wall longitudinal strain (GFW-RVLS), apical-free-wall longitudinal strain, basal-free-wall longitudinal strain, and 3D-RVEF were lower in patients with precapillary PH (P<0.0001) and postcapillary PH (P<0.01) compared to controls. 3DGFW-RVLS (hazard ratio 4.6, 95% CI 2.79 to 8.38, P=0.004) and 3D-RVEF (hazard ratio 5.3, 95% CI 2.85 to 9.89, P=0.002) were independent predictors of mortality. Receiver operating characteristic curves showed that the thresholds offering an adequate compromise between sensitivity and specificity for detecting hemodynamic signs of RV failure were 39% for 3D-RVEF (AUC 0.89), -17% for 3DGFW-RVLS (AUC 0.88), -18% for GFW-RVLS (AUC 0.88), -16% for apical-free-wall longitudinal strain (AUC 0.85), 16 mm for tricuspid annular plane systolic excursion (AUC 0.67), and 38% for RV-FAC (AUC 0.62). CONCLUSIONS: In chronic PH, 3D, 2D-STE and 3D-STE parameters indicate global and regional RV dysfunction that is associated with RV failure hemodynamics better than conventional echo indices.

Left ventricular torsion abnormalities in patients with obstructive sleep apnea syndrome: an early sign of subclinical dysfunction.

BACKGROUND: Previous echocardiographic studies using tissue Doppler imaging (TDI) and speckle tracking imaging (STI) have demonstrated that obstructive sleep apnea syndrome (OSAS) patients may develop subclinical left ventricular (LV) systolic and diastolic dysfunction. Our purpose was to evaluate the impact of OSAS on LV torsion dynamics and aortic stiffness by using TDI and STI echocardiography. METHODS: Forty-two patients with OSAS and no comorbidities were studied. They were classified into mild and severe OSAS according to the apnea-hypopnea index (AHI). Thirty-five healthy subjects were selected as controls. Fifteen patients with severe OSAS underwent chronic nocturnal nasal continuous positive airway pressure (CPAP) therapy. Standard echocardiographic parameters were assessed. Global LV longitudinal strain (LS), radial and circumferential strain were determined by STI. Averaged LV rotation and rotational velocities from the base and apex were obtained and used for calculation of LV torsion (LVtor). Mitral annular velocities and aortic wall velocities and strain (AoS) were also obtained by TDI. RESULTS: Severe OSAS had decreased LS compared with control subjects. LVtor increased significantly in severe OSAS compared to normals (p<.001) as a result of a predominant increase in apical rotation and was independently related to AHI and AoS in a multiple stepwise linear regression model. The group treated with CPAP had a significant decrease in LVtor and aortic stiffness index and significant increase in LS and AoS. CONCLUSIONS: LVtor, LS and AoS were identified as parameters demonstrating an association between LV dysfunction, aortic stiffness and severity of OSAS independently of other possible factors or comorbidities.

Assessment of right ventricular function by three-dimensional echocardiography and myocardial strain imaging in adult atrial septal defect before and after percutaneous closure.

Real-time three-dimensional (3D) echocardiography allows us to measure right ventricular (RV) end-diastolic volume irrespective of its shape. Tissue Doppler imaging (TDI) and speckle tracking imaging (STI) are new tools to assess myocardial function. We sought to evaluate RV function by 3D echocardiography and myocardial strain imaging in adult patients with atrial septal defect (ASD) before and 6 months after transcatheter closure in order to assess the utility of these new indexes in comparison with standard two-dimensional (2D) and Doppler parameters. Thirty-nine ASD patients and 39 healthy age- and sex-matched controls were studied using a commercially available cardiovascular ultrasound system. 2D-Doppler parameters of RV function (fractional area change, tricuspid annular plane systolic excursion, myocardial performance index) were calculated. 3D RV volumes were also obtained. RV peak-systolic velocities, peak-systolic strain, and peak systolic and diastolic strain-rate were measured in the basal, mid and apical segments of lateral and septal walls in apical 4-chamber view by TDI and STI. In open ASD, RV ejection fraction (3D-RVEF) and global and regional RV longitudinal strain were significantly higher than control group and decreased significantly after closure. By multivariate analysis 3D-RVEF, apical strain and strain rate were independent predictors of functional class. ROC analysis showed 3D-RVEF and apical strain to be more sensitive predictors of unfavorable outcome after defect closure compared to 2D-Doppler indexes. 3D echocardiography and myocardial strain imaging give useful insights in the quantitative assessment of RV function in ASD patients before and after closure.

Assessment of ascending aorta distensibility after successful coarctation repair by strain Doppler echocardiography.

BACKGROUND: Increased arterial stiffness may participate in the genesis of hypertension and increase of left ventricular (LV) mass after surgical correction of coarctation of the aorta. The purpose of the current study was to assess the aortic elastic properties using Doppler tissue imaging and strain rate imaging in patients after coarctoplasty. METHODS: Echocardiography with Doppler tissue/strain rate imaging capabilities was performed in 26 adult normotensive patients who had successful repair of coarctation of the aorta in infancy and in 24 control subjects. Transesophageal aortic transverse sections were imaged at the level of the proximal and distal segments to the repair site. Doppler tissue imaging wall velocities during systole (S(w)), early relaxation (E(w)), and atrial systole (A(w)) and peak systolic strain (ps epsilon) were measured in both groups. Transthoracic ascending aorta (AAo) measurements were also obtained. RESULTS: In the patients with coarctoplasty, S(w) velocities and ps epsilon were significantly decreased in the proximal segments compared with control subjects. Both peak systolic blood pressure after exercise (P < .001) and pulse pressure after exercise (P < .001) were directly related to AAo wall strain. LV annular early diastolic velocity was significantly reduced compared with control subjects in patients with decreased AAo wall strain and exercise-induced hypertension (P < .001) and related to AAo wall velocity (P < .005) and strain (P < .001). In multiple linear regression analysis, only weight, study group, and AAo wall strain were correlated to LV mass index. CONCLUSIONS: Patients with coarctation of the aorta have reduced proximal aortic wall velocities and strain and increased stiffness even after successful repair. This amplifies stress-induced hypertension and increases LV burden.

Assessment of severity in aortic stenosis-incremental value of endocardial function parameters compared with standard indexes.

Several studies have reported that patients (pts) with severe aortic stenosis and similar pressure gradients or even similar aortic valve areas may have quite different symptomatic status and clinical outcomes suggesting that other factors might have a significant impact on the pathophysiology of this disease. Our purpose was to assess the severity of subendocardial wall dysfunction in symptomatic and asymptomatic pts with aortic stenosis using tissue Doppler imaging (TDI), strain rate imaging (SRI) and cyclic variation of integrated backscatter (IB). We studied 68 pts with aortic valvar stenosis and 46 subjects with no signs of heart disease. SRI/IB indexes were calculated in the apical four chambers views at endocardial level. Early diastolic endocardial strain rate showed the best correlation with transvalvar pressure gradients and valve areas. Compared with controls, symptomatic pts showed a more marked decrease in endocardial strain, strain rate and cyclic variation of IB. Receiver operating characteristic (ROC) curves suggested that the thresholds offering an adequate compromise between sensitivity and specificity for the prediction of symptoms were >/=60 mm Hg for the pressure gradient, less than 0.60 cm(2)/m(2) for aortic valve area, less than 20% for strain, less than 2.0 s(-1) for strain rate and less than 3.0 dB for cyclic variation. The combination of pressure gradient, aortic valve area and SRI/IB parameters resulted in an improvement of the overall performance for predicting the symptomatic state. Thus, SRI/IB parameters have an incremental value in differentiating symptomatic and asymptomatic pts with aortic stenosis compared with conventional hemodynamic parameters.

Strain rate dobutamine echocardiography for prediction of recovery after revascularization in patients with ischemic left ventricular dysfunction.

BACKGROUND: The purpose of the present study was to assess the accuracy of quantitative segmental analysis by strain rate imaging (SRI) technique during dobutamine test for detecting myocardial recovery after revascularization in patients with chronic ischemic regional left ventricular (LV) dysfunction and compare results with those of 2-dimensional echocardiography (2D) and tissue Doppler imaging (TDI) as well as rest-4 hours-24 hours redistribution thallium SPECT (Tl SPECT). METHODS AND RESULTS: Forty-one patients with chronic ischemic regional LV dysfunction (EF 29 +/- 8%) underwent dobutamine 2D/TDI/SRI and Tl SPECT before and after myocardial revascularization. The sensitivity, specificity, and accuracy for the recovery of regional LV function were 73%, 81%, and 77% for dobutamine 2D; 77%, 82%, and 80% for dobutamine TDI; 86%, 88%, and 85% for dobutamine SRI; and 94%, 76%, and 84% for Tl tomography. The area under the ROC curve (AUC), which reflects the overall performance for the prediction of recovery, was 0.79 for systolic-SR, 0.81 for Tl SPECT, 0.83 for postsystolic strain, and 0.87 for isovolumic-SR. If both systolic and postsystolic SRI indexes were combined with Tl SPECT, the AUC was improved to 0.94. CONCLUSIONS: Dobutamine SRI is more accurate than TDI in identifying hibernating myocardium. Systo-diastolic values obtained using dobutamine SRI echocardiography and values derived from nuclear perfusion techniques may be complementary in assessing myocardial viability.

Aortic wall mechanics in the Marfan syndrome assessed by transesophageal tissue Doppler echocardiography.

The aim of this study was to investigate the value of tissue Doppler imaging (TDI) using transesophageal echocardiography (TEE) in assessing the elastic properties of the thoracic aorta in patients with Marfan's syndrome. Aortic distensibility, stiffness index, and pulse-wave velocity were calculated using M-mode data in a TEE short-axis view in 31 patients with Marfan's syndrome and 22 normal controls. Acceleration time, maximum wall expansion velocity (Vmax), and wall strain were determined from TDI tracings. Indexes derived from TDI differed at a greater level of significance than M-mode-derived indexes in patients with dilated and normal aortas. Significant predictors of aortic dilation were systolic blood pressure, aortic stiffness index, Vmax, and strain. Decreased aortic strain and Vmax and increased stiffness index were predictive of aortic dissection (odds ratios 4.5, 3.3, and 2.2). In conclusion, the TDI assessment of aortic wall mechanics is complementary to standard M-mode measurements in discriminating normal subjects from patients with Marfan's syndrome and is accurate in predicting aortic dilation and dissection.

Quantitative assessment of systolic and diastolic ventricular function with tissue Doppler imaging after Fontan type of operation.

BACKGROUND: There is evidence that "inappropriate hypertrophy" of the single left ventricle, which occurs as a result of acute preload reduction, leads to adverse consequences on ventricular function. However, a systematic study of the capability of tissue Doppler imaging (TDI) to assess systolic and diastolic ventricular functions after the Fontan procedure is still missing. METHODS: Twenty-four postoperative patients aged 12-33 years were prospectively evaluated with two-dimensional echocardiography equipped with TDI capabilities. Nineteen age-matched normal subjects were selected as controls. Good-quality echoes for the measurement of ejection fractions were available in 21 patients. Ten patients (group 1) had systolic dysfunction (ejection fraction < 50%), and 11 patients (group 2) had normal systolic function. Peak systolic and diastolic wall velocities were acquired from the two-chamber view in the myocardia and mitral annulus. RESULTS: Compared with controls, the Fontan patients had a significantly reduced peak systolic velocity at wall and annulus sites. A linear correlation existed between ejection fraction and systolic myocardial velocity from the annular sites. Group 1 patients had lower wall velocities and lower annulus velocities both in systole and diastole. Group 2 patients had preserved systolic velocities but decreased regional and annular early diastolic velocities, suggesting impaired filling. Multiple correlation analysis showed a relation between peak early diastolic mitral velocity and ventricular ejection fraction, mean mitral annular motion at systole, mass/volume ratio, and the number of years post Fontan revision. CONCLUSIONS: Myocardial velocities recorded after the Fontan operation give insight into systolic and diastolic ventricular functions. The peak systolic mitral annular velocity correlated well with the ventricular ejection fraction. The peak early diastolic velocity and the ratio between the early and late diastolic mitral annular velocity are reduced and reflect diastolic dysfunction even in the presence of normal systolic ejection fraction.