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Diastolic dysfunction (DD) and left ventricular remodeling (LVR) characterize patients at risk for heart failure (HF). To assess the prognostic impact of different diastolic function algorithms and a complex LVR classification (CRC) in asymptomatic subjects with preserved ejection fraction (EF) at risk for HF. We analyzed 1923 asymptomatic patients (male 43%; age 57, 33-76 years) with at least one cardiovascular risk factor and preserved (> 50%) EF. We used three algorithms for LV diastolic function assessment (Paulus et al. in Eur Heart J 28(20):2539-2550, 2007; Nagueh et al. in J Am Soc Echocardiogr 22(2):107-133, 2009, Eur Heart J Cardiovasc Imaging 17(12):1321-1360, 2016), and two algorithms for LVR (classic and CRC). We considered a composite end-point: cardiac death and hospitalization for HF. The highest presence of DD was diagnosed by Nagueh 2009 (211, 11%), while the prevalence according to Nagueh 2016 (63 patients, 3.2%) turned out to be the lowest (p < 0.001 vs the other algorithms). According to CRC, 780 (48.6%) patients had normal or physiologic hypertrophy, 298 (15.5%) concentric remodeling, 85 (4.4%) eccentric remodeling, 294 (15.3%) concentric hypertrophy, 39 (2%) mixed hypertrophy, 80 (4.1%) dilated hypertrophy, 73 (3.7%) eccentric hypertrophy and 294 (15.3%) were unclassifiable. After 39-month follow-up (261 events, 13.6%), Cox-regression (adjusted for age, gender, history of stable ischemic heart disease, classic remodeling classification) identified CRC (p = 0.01) and Nagueh 2016 (p < 0.001) as independent predictors of end-point. The coexistence of an adverse LVR by CRC and DD by Nagueh 2016 was associated with the worst prognosis. A concurrent structural (CRC) and functional (Nagueh Op. Cit) analysis improves prognostic stratification in asymptomatic subjects at risk for HF with preserved EF.

Left ventricular systolic function evaluation is an essential part of all transthoracic echocardiographic (TTE) studies. 3D echocardiography (3DE) is superior to 2D and is recommended as the method of choice. However, since it is time consuming and requires training, it is rarely performed. Different automatic analysis software tries to overcome these limitations but they need to be accurate and reproducible before they can be used clinically. The aim of this study was to test the accuracy and reproducibility of new 3D automatic quantitative software in everyday clinical practice. 69 patients referred to our Echo Lab for a clinically indicated echocardiographic examination were included. All patients underwent a full TTE with 3D image acquisition. Left ventricular volumes and ejection fraction (LVEF) were obtained using Heart Model software, and compared with conventional 3D volumetric data. Automated analysis was performed using three different sliders setting, with or without regional editing if necessary. 20 patients underwent a cardiac magnetic resonance (CMR) study the same day of the echo and automated measurements were also compared with a CMR reference. Intra- and inter-technique comparisons including linear regression with Pearson correlation coefficients and Bland-Altman analyses were calculated. Mean age of the patients was 59 years, with 49.3% male. The automated 3DE model demonstrated excellent correlation with the conventional 3DE measurements of LVEF, using three different sliders settings (r = 0.906; r = 0.898 and r = 0.940). Correlations with CMR values were very good as well (r = 0.888; r = 0.869; r = 0.913). Similarly, no significant differences were noted between the values of EDV and ESV, measured with the automated model or CMR, with excellent correlation (EDV: r = 0.892, r = 0.842, 0.910; ESV: r = 0.925, r = 0.860, r = 0.907). Finally, volumes calculated with the automated software were significantly greater than those obtained manually, but they showed a very good correlation (EDV: r = 0.875, r = 0.856, r = 0.891; ESV: r = 0.929, r = 0.879, r = 949). 3D automatic software for LV quantification is feasible and shows excellent correlations with both CMR and 3D echocardiography, considered the gold standard. No clinically relevant differences were noted when applying different border settings. This technique holds promise to facilitate the integration of 3D TTE into clinical practice.

Background: Asymptomatic left ventricular (LV) dysfunction is highly prevalent in type 2 diabetes patients. Unlike the other hypoglycemic drugs, SGLT2 inhibitors have shown potential benefits for reducing cardiovascular death and risk factors, aside from lowering plasma glucose levels. With this study we aim at determining whether the treatment with empagliflozin is associated with an improvement in LV functions in diabetic patients with asymptomatic LV dysfunction against Sitagliptin, which is presumably neutral on myocardial function. To determine changes in LV systolic and diastolic functions we will use speckle-tracking echocardiography, a novel sensitive, non-invasive, bedside method allowing the calculation of LV global longitudinal strain (GLS), an index of myocardial deformability, as well as 3D echocardiography, which allows a better evaluation of LV volumes and mass., Methods: The EMPA-HEART trial will be a phase III, open label, active-controlled, parallel groups, single centre, exploratory study conducted in Pisa, Italy. A cohort of 75 diabetic patients with normal LV systolic (2D-Echo EF > 50%) and renal (eGFR sec MDRD > 60 ml/min/1.73 mq) functions and no evidence of valvular and/or ischemic heart disease will be randomized to either Empagliflozin 10 mg/die or Sitagliptin 100 mg/die. The primary outcome is to detect a change in GLS from baseline to 1 and 6 months after treatment initiation. The secondary outcomes include changes from baseline to 6 months in 3-D Echocardiography EF, left atrial volume and E/E', VO 2 max as measured at cardiopulmonary test, cardiac autonomic function tests (R-R interval during Valsalva manoeuvre, deep-breathing, lying-to-standing), and the determination of a set of plasma biomarkers aimed at studying volume, inflammation, oxidative stress, matrix remodelling, myocyte strain and injury., Discussion: SGLT2 inhibitors might affect myocardial functions through mechanisms acting both directly and indirectly on the myocardium. The set of instrumental and biohumoral tests of our study might actually detect the presence and entity of empagliflozin beneficial effects on the myocardium and shed light on the mechanisms involved. Further, this study might eventually provide information to design a clinical strategy, based on echocardiography and/or biomarkers, to select the patients who might benefit more from this intervention. Trial registration EUDRACT Code 2016-0022250-10.

Aim: We aimed to evaluate the usefulness of left atrial (LA) mechanics and stiffness over global left ventricular (LV) longitudinal strain (GLS) for risk stratification in severe aortic stenosis (AS)., Methods: From a cohort of 89 prospective asymptomatic patients with severe AS and normal LV ejection fraction, 82 (32 men, mean age 73±10 years) truly asymptomatic patients, scheduled after a negative exercise echocardiogram, were enrolled. Forty age- and gender-matched prospective, asymptomatic subjects served as controls. Predefined end points were the occurrence of symptoms (dyspnea, angina, syncope), and death during follow-up., Results: At study entry, patients had: impaired LV GLS (p=0.001), reduced LA reservoir (p<0.001), high LA stiffness (p<0.001), and increased valvulo-arterial impedance (p<0.001) compared to controls. During follow-up [16±14.9 months (ranging from 1 month to 4.2 years)], 53 patients (64.6%) reached one of the endpoints. Patients with events showed lower LV GLS (p>0.001), lower LA reservoir (p<0.001), and greater LA stiffness (p<0.001) than those asymptomatic. On univariate Cox regression analysis, LV GLS (p<0.001), LA reservoir (p<0.001), and LA stiffness (p=0.004) were strong predictors of adverse events. Kaplan-Meier curves showed that event-free survival was significantly higher in patients with a LV GLS ≥16.8% [p<0.001; area under the curve (AUC)=0.922; sensitivity=86%, specificity=80%], a LA reservoir ≥19.8% (p=0.001; AUC=0.860, sensitivity=71%, specificity=84%), and a LA stiffness <0.78 (p<0.001; AUC 0.819, sensitivity 70%, specificity 89%). On multivariate analysis, only LV GLS remained significantly associated with patients' prognosis (hazard ratio=1.49, 95% CI=1.11-2.01, p=0.008)., Conclusions: In asymptomatic patients with severe AS, an efficient cardiovascular system is based on an effective atrial-ventricular interplay. LA function assessment is useful for early identification of risk in these patients. LV GLS however was confirmed to be the best predictor of patients' outcome., (Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Wave intensity (WI) is a hemodynamic index used to evaluate the interaction between the heart and the arterial system, measured with an echo-Doppler system at the level of the common carotid artery. WI has two peaks: W1 during early systole that represents left ventricular (LV) contractility, and W2 in late systole that is related to the inertia force during isovolumetric relaxation. The aim of this study was to determine whether WI parameters improve the prediction of poor outcome in patients with heart failure and reduced ejection fraction (HFrEF). Sixty-two patients (mean age 69.4 ± 11.5 years) in NYHA class II-III were followed up for 43.5 months. They underwent routine clinical work-up, transthoracic echocardiography and WI measurement. A stratified survival analysis was conducted using the Kaplan-Meier method. During follow-up, 23 patients died from cardiovascular causes. Survivors and non-survivors were similar in age, blood pressure, heart rate and echocardiographic parameters, except for LV end-diastolic volume indexed to body surface area, E/A ratio (higher in non-survivors) and deceleration time (lower in non-survivors). W2 (1950 ± 1006 vs 1117 ± 708 mmHg m/s(3), p = 0.001) was significantly lower in non-survivors, whereas W1 (6951 ± 4119 vs 5748 ± 3891 mmHg m/s(3), p = NS) was similar. At the end of follow-up, cardiovascular mortality was higher in patients with W1 ≤ 3900 mmHg m/s(3) (p = 0.02) and W2 ≤ 1000 mmHg m/s(3) (p = 0.0002). Only E/A (cut-off 1.5) was predictive of mortality (p = 0.05). In patients with HFrEF, WI parameters derived from the carotid artery better identified patients with poor prognosis and were significant predictors of cardiovascular mortality.

Background: Asymptomatic left ventricular dysfunction (ALVD) is relatively common in both community and high-risk populations. Early pharmacological intervention can improve clinical outcomes in subjects with this condition., Objectives: This multicentre study consists on electrocardiographic and echocardiographic examination of stage A and B heart failure (HF) asymptomatic subjects with one or more cardiovascular risk factors, to assess the prognostic value of cardiovascular risk factors per se, clinical history, and electrocardiographic and echocardiographic parameters in prediction of progression of HF and/or in development of cardiovascular primary or secondary events., Material and Methods: A total of 2142 asymptomatic subjects (mean age 63 years, 1162 males) performed an electrocardiographic and echocardiographic examination. Electrocardiogram (ECG) pathological signs according to Minnesota code and left ventricular dysfunction both systolic and diastolic by echocardiography were evaluated. There were 2002 subjects who were followed up for 26 ± 11 months, observing their primary and secondary end points., Results: At follow up, the study population presented 111 primary end points (5.2%) and 441 secondary end points (20.6%). ECG criteria of LV hypertrophy and signs of ischaemia or previous myocardial infarction (p < 0.0001) were highly significantly related to primary end points. Both ECG and echocardiography (systolic function) are able at Kaplan-Meier cumulative survival curves to predict primary end points (p < 0.0001)., Conclusions: Presence or absence of left ventricular systolic and /or diastolic dysfunction has an incremental value in comparison to cardiovascular risk factors, clinical history, and ECG findings to predict both the evolution towards a more severe HF stage (stage C) and also the occurrence of cardiovascular events., (© The European Society of Cardiology 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Background: In recent years, right ventricular (RV) function has acquired greater relevance as a clinical and prognostic marker in many physiopathological conditions. The study aims to point out the value of real time three-dimensional echocardiography (RT3DE) and tissue Doppler imaging (TDI) in the evaluation of patients affected by pulmonary hypertension (PH), compared with conventional two-dimensional (2D) echocardiography., Methods: We enrolled 44 subjects affected by PH who underwent 2D and Doppler echocardiography, RT 3D Echocardiography and TDI evaluation of the RV, and a healthy control group. PH itself can induce severe functional and structural abnormalities of the RV, such as RV hypertrophy, RV dilation, and RV systolic and diastolic dysfunction., Results: In this study, RV FAC, and TAPSE showed marked alterations in patients with PH compared to the control group (C): (RVFAC: [PH] 0.29 ± 0.07 vs. [C] 0.49 ± 0.05%, P < 0.0001; TAPSE: [PH] 15.3 ± 3.2 vs. [C] 21.1 ± 2.6 mm, P > 0.0001). The 3D RV end-diastolic volume was significantly higher in PH than in C (PH) (138.7 ± 25.3 vs. [C] 82.8 ± 12.5 mL, P < 0.0001] as well as 3D RV end-systolic volume (PH) (97.6 ± 21.5 vs. [C] 39.3 ± 9.5 mL, P < 0.0001). The 3D RV ejection fraction (EF) was significantly lower in the pulmonary hypertension group than in healthy subjects (31.8 ± 6.8 vs. [C] 52.5 ± 4.7%, P < 0.0001)., Conclusions: In patients with PH, evaluation of the RV diastolic and systolic volume and EF by RT3DE has shown a higher discriminating power in comparison, respectively, with 2DRV diastolic area and the relative fractional area changes., (© 2013, Wiley Periodicals, Inc.)

Measurement of force-frequency relationship (FFR) is useful in the evaluation of heart rate-dependent contractile dysfunction. The purpose of this study was to evaluate a new Doppler-derived method for assessing FFR. Doppler velocity spectra at the left ventricular (LV) outflow tract was used to estimate mean blood flow velocity (mBFV), ejection time (ET) and velocity-time integral. LV ejection force (LVF) was then calculated according to the law of conservation of momentum: 1060 kg/m³ × (mBFV[m/sec]/ET [s]) × Stroke volume (mL). A symptom-limited, graded, bicycle semi-supine exercise test was performed in 56 patients with LV dysfunction (LV ejection fraction = 27 ± 6%). Measurements were obtained at baseline and serially during the test. The change in FFR was defined as up-sloping when the peak LVF was higher than the baseline value. The change was biphasic when the trend was initially up-sloping, then down-sloping; it was flat or negative when peak LVF was less than the baseline value. LVF was 30 ± 12 mN in patients with up-sloping FFR (n = 39) and 15 ± 6 mN in those with biphasic or flat FFR (n = 17; p < 0.0001). The ultrasound assessment of the FFR was highly concordant with a previously validated method based on pressure-end-systolic volume index ratio (κ = 0.75; 95% confidence interval, 0.55-94.0). The evaluation of the LVF using Doppler is an alternative method for the assessment of FFR during stress echocardiography in patients with LV dysfunction., (Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

There is still some debate regarding the prognostic significance of left ventricular longitudinal systolic dysfunction as assessed by tissue Doppler (TD) imaging in patients with chronic heart failure (HF), since previous studies have included patients with postischemic wall motion abnormalities. Thus, this study was designed to ascertain whether TD-derived longitudinal systolic dysfunction may influence the outcome of patients with nonischemic chronic HF. In 200 consecutive patients with chronic HF secondary to dilated cardiomyopathy and no history of ischemic heart disease, peak systolic mitral annular velocity (S(m) ) was measured by pulsed TD at the septal and lateral annular sites. The end points were cardiac death or hospitalization for worsening HF. Mean follow-up duration was 30 months. In a time independent analysis, averaged S(m) calculated as the average of septal and lateral S(m) , resulted to be a significant predictor of outcome in the study population (area under receiver-operator characteristic curve: cardiovascular death, 0.69, P < 0.0001; cardiovascular events, 0.64, P = 0.0005). In a time-dependent analysis, average S(m) was associated with both cardiovascular death (hazard ratio 0.832, P = 0.0019) and cardiovascular events (hazard ratio 0.904, P = 0.039), independently of other clinical risk factors and echocardiographic parameters of systolic function. Septal S(m) but not lateral S(m) was independently associated with the outcome measures. In conclusion, the assessment of systolic mitral annular velocity by pulsed TD is a useful indicator for prognostic stratification of patients with nonischemic dilated cardiomyopathy and chronic HF., (© 2011, Wiley Periodicals, Inc.)

Background: Early diagnosis of left ventricular (LV) dysfunction represents a major challenge in asymptomatic subjects with cardiovascular (CV) risk factors. Tissue Doppler imaging (TDI) has emerged as an important tool with clinical relevance in several cardiac diseases., Hypothesis: To evaluate the prognostic ability of TDI in detecting early longitudinal ventricular dysfunction in a large group of asymptomatic subjects with CV risk factors (RsF), normal LV systolic function, and normal diastolic function., Methods: A total of 554 subjects (mean age 55 ± 13 years, 39% men) formed our study population: controls, 144 healthy subjects; group 1, 163 subjects with 1 CV RsF; group 2, 147 subjects with 2 CV RsF; group 3, 100 subjects with ≥3 CV RsF. All subjects underwent a comprehensive standard echo-Doppler evaluation, including posterior wall TDI study. Follow-up data were available in all the studied samples (mean 28 ± 16 mo)., Results: Upon follow-up, 18 individuals (3.2%) developed a first overt CV event. The presence of a peak systolic velocity <7.5 cm/second showed a significant additional predictive value compared with the presence of CV RsF (P<0.001)., Conclusions: Tissue Doppler imaging is able to identify early longitudinal LV systolic abnormalities in the presence of apparently normal systolic and diastolic function. It demonstrated a significant additional prognostic value compared with the simple presence of coexisting CV RsF. These findings could be clinically relevant in identifying asymptomatic subjects with CV RsF who need early, tailored preventive treatment., (© 2011 Wiley Periodicals, Inc.)

Background: Nowadays early diagnosis of left ventricular (LV) dysfunction represents a major challenge in asymptomatic subjects with cardiovascular (CV) risk factors. Tissue Doppler imaging (TDI) recently emerged as an important tool with clinical relevance in several cardiac diseases., Aim: To evaluate the ability of TDI in detecting early longitudinal ventricular dysfunction in asymptomatic subjects, with LV ejection fraction >55%, normal diastolic function, and its relationship with CV risk factors., Methods: A total of 1,371 subjects (median age 60 years, 595 males) formed our study population: Controls, 265 healthy subjects; Group I, 434 subjects with one CV risk factor; Group II, 401 subjects with two CV risk factors; Group III, 271 subjects with ≥ 3 CV risk factors. All subjects underwent a comprehensive standard echo Doppler evaluation, including PW-TDI study., Results: Diastolic parameters such as (E\A, A-wave, Em\Am; E\Em) were able to discriminate the number of CV risk factors. The only systolic parameter that progressively reduced by increasing the number of CV risk factors was LV global longitudinal systolic function (Sm), (P < 0.0001). At multivariate analysis, the only functional parameter able to predict the increasing number of CV risk factors was Sm (P < 0.001)., Conclusions: TDI is able to identify early longitudinal LV systolic abnormalities in presence of apparently normal systolic and diastolic function and progressively impairs with increasing CV risk factors. These findings could be clinically relevant in identifying asymptomatic subjects who need a early tailored preventive treatment., (© 2011, Wiley Periodicals, Inc.)

Background: Surgical aortic valve replacement (SAVR) is the definitive proven therapy for patients with severe aortic stenosis who have symptoms or decreased left ventricular (LV) function. The development of transcatheter aortic valve implantation (TAVI) offers a viable and "less invasive" option for the treatment of patients with critical aortic stenosis at high risk with conventional approaches. The main objective of this study was the comparison of LV hemodynamic and structural modifications (reverse remodeling) between percutaneous and surgical approaches in the treatment of severe aortic stenosis., Methods: Fifty-eight patients who underwent TAVI with the CoreValve bioprosthetic valve were compared with 58 patients with similar characteristics who underwent SAVR. Doppler echocardiographic data were obtained before the intervention, at discharge, and after 6-month to 12-month follow-up., Results: Mean transprosthetic gradient at discharge was lower (P<.003) in the TAVI group (10±5 mm Hg) compared with the SAVR group (14±5 mm Hg) and was confirmed at follow-up (10±4 vs 13±4 mm Hg, respectively, P<.001). Paravalvular leaks were more frequent in the TAVI group (trivial to mild, 69%; moderate, 14%) than in the SAVR group (trivial to mild, 30%; moderate, 0%) (P<.0001). The incidence of severe prosthesis-patient mismatch (PPM) was significantly lower (P<.004) in the TAVI group (12%) compared with the SAVR group (36%). At follow-up, LV mass and LV mass indexed to height and to body surface area improved in both groups, with no significant difference. In patients with severe PPM, only the TAVI subgroup showed significant reductions in LV mass. LV ejection fraction improved at follow-up significantly only in TAVI patients compared with baseline values (from 50.2±9.6% to 54.8±7.3%, P<.0001)., Conclusions: Hemodynamic performance after TAVI was shown to be superior to that after SAVR in terms of transprosthetic gradient, LV ejection fraction, and the prevention of severe PPM, but with a higher incidence of aortic regurgitation. Furthermore, LV reverse remodeling was observed in all patients in the absence of PPM, while the same remodeling occurred only in the TAVI subgroup when severe PPM was present., (Copyright © 2011 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Objective: This multicenter study consisted of echocardiographic examination of subjects with stage A heart failure (HF) with cardiovascular risk factors and normal electrocardiogram and clinical examination results to (a) define whether stage A subjects with risk factors are really free of functional or structural cardiac abnormalities and (b) assess the impact of the presence of risk factors and incremental value of echocardiographic parameters in the prediction of progression of HF or in the development of cardiovascular events., Methods: A total of 1097 asymptomatic subjects underwent echocardiographic examination as a screening evaluation in the presence of cardiovascular risk factors. Left ventricular (LV) dysfunction, both systolic (ejection fraction) and diastolic (transmitral flow velocity pattern), was evaluated according to standard criteria. The subjects were divided according to different criteria: the presence of one or more risk factors, presence or absence of LV systolic dysfunction, and presence or absence of LV diastolic dysfunction. A follow-up period of 26 ± 11 months was performed, observing primary (cardiac death, myocardial infarction, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, acute pulmonary edema, stroke, and transient ischemic attack) and secondary (cardiologist-made diagnosis of HF and HF hospitalization) end points., Results: The multivariate analysis for independent predictors of primary end points showed that age (P = .001), gender (P = .02), dyslipidemia (P = .01), obesity (P = .001), and systolic dysfunction (P = .048) represented the significant predictors. The multivariate logistic regression analysis for independent predictors of secondary end points showed that gender (P = .02), LV systolic dysfunction (P = .01), and LV diastolic dysfunction (P < .01) represented the significant predictors. The multivariate analysis for independent predictors of combined end points showed that only age (P < .003), gender (male: P < .001), obesity (P < .04), and systolic dysfunction (P < .001) represented the significant predictors. Echocardiography showed a high incremental value in the detection of systolic LV dysfunction and the prediction of cardiovascular events during follow-up in subjects with at least two risk factors., Conclusion: This study demonstrated that preclinical functional or structural myocardial abnormalities could be detected by echocardiography in asymptomatic subjects with two or more cardiovascular risk factors and without electrocardiogram abnormalities (stage A of HF classification). The presence or absence of LV systolic dysfunction or LV diastolic dysfunction, as demonstrated by echocardiography, has an incremental value to cardiovascular risk factors in predicting both the evolution toward more severe HF stage C and the occurrence of cardiovascular events., (Copyright © 2010 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

Aims: Cardiac resynchronization therapy (CRT) was shown to reverse left ventricular (LV) remodelling in heart failure (HF) patients. We aimed to investigate whether intraoperative electrical parameters (IEP) were predictive factors of LV reverse remodelling and were correlated with mechanical dyssynchrony indexes., Methods: Eighty-six patients with HF underwent CRT. At implant, several electrical and echocardiographic parameters were evaluated and, at 6 months, responders were defined by a relative increase in LV ejection fraction ≥25% compared with baseline., Results: Several IEPs were shown to predict LV reverse remodelling. Receiver operating curve analysis revealed the ratio between QRS duration during biventricular pacing (BVp) and right ventricular pacing (RVp) [QRS(BVp)/QRS(RVp)] as the best predictor of LV functional recovery after CRT (AUC = 0.72; 95% confidence limit 0.57-0.82; P < 0.001). Responders showed a lower value of QRS(BVp)/QRS(RVp) when compared with non-responders (0.74 ± 0.05 vs. 0.8 ± 0.1; P < 0.005) and 0.78 was the value associated with the best predictive accuracy. The interval between the onset of RV lead and LV lead electrograms (RVegm-LVegm) during baseline rhythm correlated directly with the interventricular mechanical delay (IVMD) (r = 0.68; P < 0.0001) and with its reduction (delta IVMD) at follow-up (r = 0.66; P < 0.0005)., Conclusion: Intraoperative electrical parameters can predict LV functional recovery after CRT and they are correlated with interventricular mechanical resynchronization at follow-up.

Background: Prehypertension predicts established hypertension. In this study, the aim was to analyze left ventricular (LV) mechanics in borderline prehypertensive (pre-HT) and hypertensive (HT) subjects through two-dimensional (2D)-strain echocardiography and then evaluate possible relations between cardiac parameters and insulin metabolism (homeostasis model assessment of insulin resistance (HOMA(IR))., Methods: Seventy-four consecutive newly diagnosed, untreated HT were divided, on the basis of their office blood pressure (BP) measurements, confirmed by ambulatory BP monitoring (ABPM), in 41 borderline pre-HT (ABPM: 122.5 +/- 6.7/76.2 +/- 5.2 mm Hg) and 33 never-treated mild HT (ABPM: 138.3 +/- 7.3/87.6 +/- 7.1 mm Hg). Thirty-three healthy normotensive (NT) controls (ABPM: 114.8 +/- 6.3/73.1 +/- 6.1 mm Hg) (P < 0.0001) were also studied (NT). All subjects performed 2D color Doppler and pulsed-wave tissue Doppler imaging (PW-TDI)., Results: Left ventricular mass (LVM) was significantly higher in pre-HT (39.2 +/- 8.7 g/m(2.7)) and in HT (43.6 +/- 8.5 g/m(2.7)) compared with NT (30.9 +/- 7.4 g/m(2.7)) (P < 0.0001). A mild LV diastolic dysfunction was found both with Doppler mitral flow velocity and PW-TDI at mitral annulus level analysis. Longitudinal 2D strain in pre-HT (-18.9% +/- 3.4) and in HT (-18.0% +/- 3.3) was significantly lower than in NT (-23.9% +/- 3.0) (P < 0.002). These LV abnormalities were associated with systolic ABPM, LVM, and HOMA(IR)., Conclusions: Early abnormalities of LV longitudinal systolic deformation were found both in pre-HT and HT, together with a mild LV diastolic dysfunction. In both groups this early cardiac systolic and diastolic dysfunction is associated to insulin resistance, systolic pressure load, and cardiac remodeling.

Objectives: Aortic valve implantation through peripheral vascular access is an option for high-risk patients with severe aortic valve stenosis. The authors aimed to compare the acute effect of endovascular and surgical aortic valve procedures on left ventricular diastolic function., Design: A case-matched, nonrandomized study., Setting: A university hospital., Participants: Patients with aortic stenosis., Interventions: B-natriuretic peptide was measured in 30 patients with a logistic EuroSCORE > or =20% undergoing endovascular aortic valve implantation. Patients were case matched (age, mitral flow propagation velocity, mitral annulus early diastolic velocity, and B-natriuretic peptide measurement) with 30 control patients undergoing surgical aortic valve replacement through sternotomy. Left ventricular diastole was evaluated initially and after valve procedures with echocardiography by mitral flow propagation velocity and mitral annulus early diastolic velocity., Measurements and Main Results: B-natriuretic peptide was similar preoperatively in the 2 groups (346 [188-438] v 367 [211-458] pg/mL) and higher (p = 0.006) in the surgical group postoperatively (389.5 [237-479] v 710.5 [389-822] pg/mL), with a postprocedural statistically significant increase only in the surgical group. Diastolic function was similar in the 2 groups preoperatively, improved postoperatively in the endovascular group, and worsened in the surgical group., Conclusions: B-natriuretic peptide increased after surgical but not after endovascular aortic valve replacement. Furthermore, endovascular aortic valve implantation acutely improved left ventricular diastolic function as documented by increases in mitral flow propagation velocity and mitral annulus early diastolic velocity., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: The prognostic role of echocardiography is well established in patients with previous or current symptoms of heart failure (HF). Less is understood about patients with stage B HF, who have structural heart disease but no symptoms at any stage. This study investigated the role of plasma N-terminal protype-B natriuretic peptide (NT-proBNP) and Doppler-echo parameters of diastolic and systolic function for risk stratification in stage B HF patients., Hypothesis: We investigated whether plasma NT-proBNP and Doppler-echo parameters of diastolic and systolic function have a role in risk stratification of stage B HF patients., Methods: Doppler echocardiography was performed in 155 outpatients with asymptomatic left ventricular (LV) dysfunction (ejection fraction [EF] < 50%) and comprised conventional diastolic variables, including pulsed-Doppler mitral E-wave deceleration time (EDT). Plasma NT-proBNP was assessed at the time of the echocardiogram. The prespecified end point was cardiac death or HF hospitalization or any new HF episode requiring a change in medication., Results: Mean EF was 35% +/- 7%. Median NT-proBNP was 745 pg/mL (interquartile range [IQR], 442-1672). Patients with events at follow-up (n = 46) had higher prevalence of risk factors for developing HF. Plasma NT-proBNP, EDT, and EF were independently associated with cardiac events at multivariable analysis and receiver operating characteristic curves were used to determine the optimal prognostic cut points for each: NT-proBNP > or = 831 pg/mL, EDT < 145 msec, and EF < 37%. When used in combination, event-free survival was incrementally worse with each additional abnormality., Conclusion: Plasma NT-proBNP, EDT, and EF are independently useful for prognostic stratification of stage B HF patients and suggest an incremental prognostic deficit is associated with the combination of each. This study supports the complementary role of comprehensive echocardiography and natriuretic peptide assay in asymptomatic LV dysfunction.

Background: Conduction disturbances and arrhythmias characterize the cardiac feature of myotonic dystrophy type 1 (MD1), and a myocardial involvement has been suggested as part of the cardiac disease. The aim of the study was to investigate the role of novel ultrasonic techniques, such as integrated backscatter (IBS) and color Doppler myocardial imaging (CDMI), in the assessment of the subclinical functional and structural myocardial involvement in patients with MD1., Methods: Thirty-one patients with MD1 (MD1 group) without known heart failure were evaluated and compared with 31 healthy, age-matched controls. In all patients, 19 conventional and 28 new echocardiographic parameters (14 tissue Doppler, 10 CDMI, and 4 IBS indexes) were analyzed., Results: In regard to ultrastructural left ventricular (LV) properties, a significantly higher IBS echointensity was found at the septum level in the MD1 group, with a statistically significant correlation with MPI (myocardial performance index) (r = 0.34; P = .05) and PR interval duration (r = 0.40; P = .05). In regard to LV systolic function, the MD1 group showed an early alteration of systolic function compared with controls, evidenced by a significant higher MPI and lower peak strain, strain rate, and cyclic variation index (CVI). In regard to LV diastolic function, the MD1 group showed an early alteration of diastolic function compared with controls, evidenced by lower tissue Doppler imaging, E/A, and E/A strain rate, with a statistically significant inverse correlation to the muscular disability rating scale. On receiver operating characteristic curve analysis, MPI and CVI showed the highest discriminating ability to differentiate the hearts of patients with MD1 from healthy subjects., Conclusion: Highly sensitive ultrasonic techniques can detect early functional and structural alterations of the LV myocardium in patients with MD1.

The new echocardiographic techniques for the study of physiopathological intramyocardial phenomena include video densitometry (VD), integrated backscatter (IBS), and color Doppler myocardial imaging (CDMI). Being more independent from cardiac load and from rotational and translational heart motion, these new sensible, noninvasive techniques such as CDMI and IBS show a real incremental value in comparison with conventional echocardiography and allow to detect subtle functional and textural abnormalities of intramural myocardium, partially undetectable by conventional two-dimensional Doppler echocardiography. Subclinical thyroid dysfunction (STD), both in its hypo- and hyperthyroidism form, has a relatively high prevalence in general population (9-15% with a lower percentage of adult males), hence it could be very useful to study more deeply heart involvement in these physiopathological conditions and understand the complex relationship between thyroid and heart. The use of these new ultrasonic techniques in subclinical hypothyroidism helps to detect the early simultaneous involvement of both cardiac cycle phases, which causes a decrease of intramyocardial contractility and an impairment of both active and passive phases of diastole. In subclinical hyperthyroidism, these new ultrasonic techniques permitted to discover more complex and different early cardiac abnormalities of both systolic and diastolic phases.

Functional mitral regurgitation (FMR) is a common finding in patients with ischemic or nonischemic dilated cardiomyopathy as a complication of left ventricular (LV) dysfunction and remodeling associated with a fibrotic remodeling response of mitral leaflets to abnormal valvular loading. Although mitral valve tenting is the main determinant of FMR, clinical and experimental observations suggest that intraventricular delay could be a potential co-determinant of FMR. LV dyssynchrony can potentially contribute to FMR by several mechanisms, such as creating an uncoordinated regional LV mechanical activation in segments supporting the papillary muscles, determining diastolic mitral regurgitation, reducing the sphincteric function of the mitral annulus, and decreasing the efficiency of LV contraction and closing forces. Cardiac resynchronization therapy has been demonstrated to reduce FMR with correction of some of the underlying pathophysiological mechanisms. The present review article focuses on the role of mechanical dyssynchrony as a pathophysiological determinant of FMR, and on the potential role of cardiac resynchronization therapy as a therapeutic option for treatment of FMR in patients with severe heart failure and advanced LV dysfunction.

Background: Hypercholesterolemia contributes to coronary heart disease but little is known about its direct effect on myocardial function. We evaluated left ventricular function using echocardiography and the effect of treatment with rosuvastatin in a group of patients with primary hypercholesterolemia., Methods and Results: Thirty-three patients with primary hypercholesterolemia (HC) and without evidence of coronary heart disease and 25 aged matched healthy volunteers (C) were submitted to conventional echocardiography, pulsed wave tissue Doppler imaging (PWTDI), color Doppler myocardial imaging (CDMI) and integrated backscatter (IBS). Echocardiographic evaluation was repeated after 6 months of treatment with rosuvastatin (10mg/day) in 17 patients. Compared with C, patients with HC showed lower E/A ratio (p<0.0001) and higher Tei index mit (p<0.0001), as well as lower PW TDI E/A both at septum (p<0.0001) and at lateral level (p<0.0001) and higher modified Tei index both at septal annulus (p<0.0001) and lateral annulus (p<0.0001). Integrated backscatter parameters were significantly reduced in patients with HC (CVIsept p<0.0001 and CVI post wall p<0.05). CDMI derived indices in the two groups were not different. After 6 months of Rosuvastatin treatment a significant reduction of LDL cholesterol levels (51%, p<0.0001) was registered in HC patients together with a significant improvement of longitudinal global systolic and diastolic function (Tei index) and myocardial intrinsic contractility (CVI)., Conclusions: These data suggest that in patients with hypercholesterolemia exists an early cardiomyopathy characterized by systolic and diastolic dysfunction. That could produce a substratum for an "impaired preconditioning". Rosuvastatin seems able to revert systolic abnormalities.

The aim of this study was to determine whether early myocardial structural and functional systolic and diastolic alterations in asymptomatic and uncomplicated patients with type 1 diabetes mellitus (DM) could be detected using the new highly sensitive echocardiographic techniques of integrated backscatter and color Doppler myocardial imaging. Forty asymptomatic and uncomplicated patients with type 1 DM and 40 gender- and age-matched normal controls were studied. All patients were analyzed by conventional and new echocardiographic techniques (integrated backscatter and color Doppler myocardial imaging). Patients with DM showed reduced systolic function compared with controls, evidenced by significantly lower peak strain, strain rates, and cyclic variation indexes at the septum (p <0.0001, <0.01, and <0.001, respectively) and at the posterior wall level (p <0.0001, <0.0001, and <0.001, respectively). On receiver-operating characteristic curve analysis, systolic strain and the cyclic variation index showed the highest discriminating power for separating patients with DM and control subjects. Neither structural or ultrastructural nor diastolic functional abnormalities were detected. On univariate regression analysis, a significant inverse correlation was found for DM duration with conventional (E/A ratio) and unconventional (tissue Doppler imaging E/A ratio) indexes of diastolic function, in the absence of any correlation for systolic function. In conclusion, highly sensitive ultrasonic techniques demonstrate evidence of left ventricular systolic dysfunction in the early stage of type 1 DM, in the absence of ultrastructural and left ventricular diastolic functional abnormalities.

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.

The aim of the present study was to evaluate cardiac function and texture in patients with subclinical hypothyroidism (sHT) both by conventional and new ultrasonic intramyocardial tissue techniques. sHT was characterized by normal serum free tetraiodotironine and free triiodotironine levels and slightly increased serum TSH level. Twenty-four patients affected by sHT and 24 sex- and age-matched healthy volunteers were studied. All subjects were submitted to conventional two-dimensional (2D)-color Doppler echocardiography, pulsed wave tissue Doppler imaging (PWTDI) for the analysis of the diastolic function, color Doppler myocardial imaging (CDMI) for the analysis of regional strain and strain-rate and integrated backscatter (IBS) for the evaluation of intrinsic contractility and tissue characterization. The results of the present study were: (a) the detection in sHT subjects of a lower cyclic variation index (CVI) indicating an altered myocardial intrinsic contractility; (b) a higher ultrasonic myocardial reflectivity indicating an altered myocardial texture; (c) the detection of lower systolic strain and strain-rate indicating an alteration of myocardial regional deformability; (d) an initial impairment of left ventricular diastolic function indicated by a decrease of peak E mitral flow velocity and an increase of peak A mitral flow velocity. All parameters studied with conventional 2D-echo in sHT patients were comparable with controls, except for a mild alteration in diastolic function. A significant correlation among systo-diastolic modifications detected by CDMI and IBS and serum TSH levels were found. The CVI at septum, the PWDTI S-peak wave and the systolic strain at septum were inversely related to the serum TSH levels. In conclusion, the new intramyocardial ultrasonic techniques confirm and extend the previous knowledge on the effect of the sHT on the heart, allowing the detection of early ultrastructural and regional functional systolic and diastolic abnormalities.

Background: The aim of this study was to evaluate the relationship between insulin resistance and preclinical abnormalities of the left ventricular structure and function detected in severe obesity by Color Doppler Myocardial Imaging (CDMI). Forty-eight consecutive severely obese patients (Group O) (11 males, 37 females, mean age 32.8+/-7 years) were enrolled. Forty-eight sex- and age-matched non-obese healthy subjects were also recruited as controls (Group C). All subjects underwent conventional 2D-Color Doppler echocardiography and CDMI. The homeostasis model assessment insulin resistance index (HOMA-IR) was used to assess insulin resistance results. Obese subjects had a greater left ventricular mass index (by height) (58.8+/-14 g/m(2.7)) than controls (37+/-8 g/m(2.7)) (P<0.0001), owing to compensation response to volume overload caused by a greater cardiac output (P<0.02). Preload reserve was increased in obese subjects, as demonstrated by a significant increase in left atrial dimension (P<0.0001). Obese patients had a slightly reduced LV diastolic function (transmitral E/A ratio: Group O, 1.1+/-0.8 vs Group C, 1.5 +/-0.5; P<0.002). Cardiac deformation assessed by regional myocardial systolic strain and strain rate (SR) values was significantly lower (abnormal) in obese patients than in controls, both at the septum and lateral wall level. These strain and SR abnormalities were significantly related to body mass index. In addition, the early phase of diastolic function, evaluated using SR, was compromised in obese patients (P<0.001). The HOMA-IR values in obese patients were significantly higher (3.09+/-1.6) than those determined in the control group (0.92+/-0.5) (P<0.0001). The HOMA-IR values, in the obese group, were significantly related to systolic strain and SR values sampled at the septum level (P<0.0001)., Conclusion: In conclusion, this study has demonstrated that obese patients pointed out systolic structural and functional abnormalities at a preclinical stage, in particular through strain and SR analysis; on the other hand, those altered CDMI parameters well distinguish obese subjects as compared with the control group. Furthermore, another main finding of the study was that myocardial deformation (systolic strain) could have a correlation with insulin resistance level.

It is not known if diastolic abnormalities are independent of systolic dysfunction in arterial hypertension. We studied three groups of 10 male subjects of comparable mean age (31.6 +/- 3.5 years), weight, and height: Athletes (A) (cyclists), essential hypertensive patients (H), and controls (C). Ultrasonic myocardial integrated backscatter signals (IBS) of the septum and the posterior wall were analyzed, while the systo-diastolic variation of the backscatter was considered as a cyclic variation index (CVI(ibs)). Myocardial velocities across the left ventricular major axis were sampled at septum and lateral wall levels by pulsed-wave Doppler tissue imaging (DTI). CVI(ibs) at the septum and the posterior wall were significantly lower in the hypertensive group in comparison with athletes and controls, who were comparable. Early diastolic myocardial velocity (E(m)) of the lateral wall and of the septum were significantly lower in hypertensives, while the late diastolic myocardial velocity (A(m)) was significantly higher in hypertensives in comparison with athletes. The E(m)/A(m) at the septum level was significantly lower in hypertensives in comparison with athletes and controls. Significant correlations were found between CVI and DTI parameters: CVI(ibs) and E(m)/A(m) septum (r = 0.50, P < 0.002). Furthermore, significant correlations were found between mean arterial pressure (MAP) and E(m)/A(m) septum (r = - 0.65, P < 0.001). Ultrasonic tissue characterization with the intrinsic contractility study and the evaluation of the regional diastolic function should, therefore, represent a new integrated diagnostic modality for the evaluation of left ventricular hypertrophied intramyocardial function. This study demonstrated that diastolic abnormalities of left ventricular function, in arterial hypertension, are related and progress with systolic intrinsic dysfunction.