Role of Early Left Atrial Functional Decline in Predicting Cardiotoxicity in HER2 Positive Breast Cancer Patients Treated With Trastuzumab.

Trastuzumab is widely used in HER2 breast cancer. However, it may cause left ventricular (LV) dysfunction. A decrease in LV global longitudinal strain (GLS) has been previously demonstrated to be a good predictor of subsequent cancer therapy related dysfunction (CTRCD). Left atrial morphological remodeling during Trastuzumab therapy has also been shown. The aim of this study is exploring the relationship between early changes in left atrial function and the development of Trastuzumab-induced cardiotoxicity. Consecutive patients with diagnosis of HER2+non-metastatic breast cancer treated with Trastuzumab were prospectively enrolled. A clinical, conventional, and advanced echocardiographic assessment was performed at baseline and every three months, until a one-year follow-up was reached. One-hundred-sixteen patients completed the 12 months follow-up, 10 (9%) cases of CTRCD were observed, all after the sixth month. GLS and LVEF significantly decreased in the CTRCD group at 6 months of follow-up, with an earlier (3 months) significant worsening in left atrial morpho-functional parameters. Systolic blood pressure, early peak atrial longitudinal strain (PALS), peak atrial contraction (PACS) and left atrial volume (LAVI) changes resulted independent predictors of CTRCD at multivariable logistic regression analysis. Moreover, early changes in PALS and PACS resulted good predictors of CTRCD development (AUC 0.85; p = 0.008, p < 0.001 and 0.77; p = 0.008, respectively). This prospective study emphasizes that the decline in PALS and PACS among trastuzumab-treated patients could possibly increase the accuracy in identifying future CTRCD in non-metastatic HER2 breast cancer cases, adding predictive value to conventional echocardiographic assessment.

Outpatient tricuspid regurgitation in the community: Clinical context and outcome.

BACKGROUND AND AIMS: Epidemiology of tricuspid regurgitation (TR) is poorly known and its burden in the community is challenging to define. We aimed to evaluate the prevalence of TR in a geographically defined area and its outcome, in particular overall survival and hospitalization, considering different clinical contexts. METHODS: We retrospectively analyzed consecutive outpatients referred between 2006 and 2013 for echocardiography and clinical evaluation. Patients with at least moderate TR were included and five different clinical settings were defined: concomitant significant left-sided valvular heart disease (LVHD-TR), heart failure (HF-TR), previous open-heart valvular surgery (postop-TR), pulmonary hypertension (PHTN-TR) and isolated TR (isolated-TR). Primary endpoint was a composite outcome of all-cause mortality or first hospitalization for HF. RESULTS: Of 6797 consecutive patients with a clinical visit and echocardiograms performed in routine practice in a geographically defined community, moderate or severe TR was found in 4.8% of patients (327) . During median follow-up of 6.1 years, TR severity was a determinant of event-free survival. Analyzed for each clinical subset, eight-year event-free survival was 87 ± 7% for postop-TR subgroup, 75 ± 7% for isolated-TR, 67 ± 6% for PHTN-TR, 58 ± 6% for LHVD -TR and 52 ± 11% for HF-TR. CONCLUSION: Moderate or more TR is a notable finding in the community and has impact on event-free survival in all clinical settings, with the worst outcomes when associated with relevant left-sided valvular heart disease and HF.

Atrial Strain Assessment for the Early Detection of Cancer Therapy-Related Cardiac Dysfunction in Breast Cancer Women (The STRANO STUDY: Atrial Strain in Cardio-Oncology).

Left ventricular global longitudinal strain (GLS) has an important role in the diagnosis of cancer therapy-related cardiac dysfunction (CTRCD). Little is known about the role of atrial function in diagnosing CTRCD. The aim of our study was to assess the impact of anti-cancer drugs on atrial function measured by speckle-tracking echocardiography in breast cancer women. A prospective multicenter study was conducted enrolling 169 breast cancer women treated with anthracyclines. A cardiological evaluation including an electrocardiogram and echocardiogram with an analysis of GLS, left atrial (LA) strain, and LA stiffness (LASi) was performed at baseline (T0), 3 (T1), and 6 months (T2) after starting chemotherapy. The patients were divided into two groups: patients with asymptomatic mild cardiotoxicity at T1 (with a relative reduction in GLS > 15%; Group 1) and those without (Group 2). We did not find a significant change in left ventricular ejection fraction (LVEF) at T1 and T2; we found a significant change in GLS (p-value < 0.0001) in the peak atrial longitudinal strain (PALS) and in LASi (p-value < 0.0001). Impairment of atrial function was greater in Group 1 compared to Group 2. A PALS variation > 20.8% identified patients who were most likely to develop asymptomatic mild cardiotoxicity [AUC 0.62; CI (0.51-0.73) p = 0.06, sensitivity 45%, specificity 69.5%]. Conclusions: PALS and LASi significantly change during chemotherapy in association with GLS. Atrial strain is an additional parameter that could be measured together with GLS to detect cardiotoxicity early.

Right Atrial Function Role in Tricuspid Regurgitation-Related Systemic Venous Congestion.

Tricuspid regurgitation (TR) is a frequent valvular pathology and when significant, may cause systemic venous congestion (SC). The right atrium (RA) is an intermediate structure between the tricuspid valve and the venous system and its role in SC is not yet defined. A total of 116 patients with a measurable TR effective regurgitant orifice area (EROA) and regurgitant volume (RVol) were selected from 2020 to 2022. SC was estimated by echocardiography using inferior vena cava diameter and estimated right atrial pressure (eRAP) and by clinical congestive features. TR grade was mild in 23 patients (20%), moderate in 53 patients (46%), and severe in 40 patients (34%). There was a significant decrease in RA function measured by strain with increasing TR severity (p <0.001). There was a marked difference in RA strain between the groups with eRAP >10 and ≤10 mm Hg (25 ± 11% vs 11 ± 7%, p <0.0001). Variables independently associated with inferior vena cava diameter were RA strain (ß -0.532, p <0.001), RA volume indexed (ß 0.249, p = 0.002), RVol (ß 0.229, p = 0.005) and EROA (ß 0.185, p = 0.016), and independently associated with eRAP >10 mm Hg were EROA (odds ratio [OR] 1.024, 95% confidence interval [CI] 1.002 to 1.046), RVol (OR 1.039, 95% CI 1.007 to 1.072) and RA strain (OR 0.863, 95% CI 0.794 to 0.940). The addition of RA strain to models containing EROA or RVol significantly improved the power of the model. RA strain was independently associated with the presence of 3 or more congestive features. In conclusion, echocardiographic and clinical signs of SC are frequent in higher degrees of TR, and RA function seems to play a key role in modulating the downstream effect of TR.

Proof of concept study on coronary microvascular function in low flow low gradient aortic stenosis.

OBJECTIVES: We hypothesised that low flow low gradient aortic stenosis (LFLGAS) is associated with more severe coronary microvascular dysfunction (CMD) compared with normal-flow high-gradient aortic stenosis (NFHGAS) and that CMD is related to reduced cardiac performance. METHODS: Invasive CMD assessment was performed in 41 consecutive patients with isolated severe aortic stenosis with unobstructed coronary arteries undergoing transcatheter aortic valve implantation (TAVI). The index of microcirculatory resistance (IMR), resistive reserve ratio (RRR) and coronary flow reserve (CFR) were measured in the left anterior descending artery before and after TAVI. Speckle tracking echocardiography was performed to assess cardiac function at baseline and repeated at 6 months. RESULTS: IMR was significantly higher in patients with LFLGAS compared with patients with NFHGAS (24.1 (14.6 to 39.1) vs 12.8 (8.6 to 19.2), p=0.002), while RRR was significantly lower (1.4 (1.1 to 2.1) vs 2.6 (1.5 to 3.3), p=0.020). No significant differences were observed in CFR between the two groups. High IMR was associated with low stroke volume index, low cardiac output and reduced peak atrial longitudinal strain (PALS). TAVI determined no significant variation in microvascular function (IMR: 16.0 (10.4 to 26.1) vs 16.6 (10.2 to 25.6), p=0.403) and in PALS (15.9 (9.9 to 26.5) vs 20.1 (12.3 to 26.7), p=0.222). Conversely, left ventricular (LV) global longitudinal strain increased after TAVI (-13.2 (8.4 to 16.6) vs -15.1 (9.4 to 17.8), p=0.047). In LFLGAS, LV systolic function recovered after TAVI in patients with preserved microvascular function but not in patients with CMD. CONCLUSIONS: CMD is more severe in patients with LFLGAS compared with NFHGAS and is associated with low-flow state, left atrial dysfunction and reduced cardiac performance.

Subclinical Myocardial Fibrosis in Systemic Lupus Erythematosus as Assessed by Pulse-Cancellation Echocardiography: A Pilot Study.

The aim of this study was to examine whether scar imaging echocardiography with ultrasound multi-pulse scheme (eSCAR) can detect subclinical myocardial involvement in systemic lupus erythematosus (SLE). We consecutively recruited SLE patients and controls matched for age, sex, and cardiovascular risk factors. Participants with cardiac symptoms or a prior history of heart disease were excluded. All participants underwent eSCAR and speckle tracking echocardiography (STE) with global longitudinal strain (GLS) assessment. SLE patients were assessed for disease activity and were followed up for 12 months. Myocardial scars by eSCAR were observed in 19% of SLE patients, almost exclusively localized at the inferoseptal myocardial segments, and in none of the controls. GLS was significantly lower in most myocardial segments of SLE patients compared with the controls, especially in the inferoseptal segments. eSCAR-positive SLE patients received a higher cumulative and current dose of prednisone, and had significantly higher levels of anti-dsDNA antibodies (p = 0.037). eSCAR-positive patients were at higher risk of having SLE flares over follow-up (hazard ratio: 4.91; 95% CI 1.43-16.83; p = 0.0001). We identified inferoseptal myocardial scars by eSCAR in about one-fifth of SLE patients. Subclinical myocardial involvement was associated with glucocorticoid use and anti-dsDNA antibodies.

Determinants of exercise intolerance symptoms considered non-specific for heart failure in patients with stage A and B: role of the left atrium in the transition phase to overt heart failure.

To assess to what extent left atrial (LA) structure and function are associated with non-specific heart failure symptoms, so that patients were classified as HF stage A and B. Mechanisms underlying the transition to overt HF in patients with stage A and B HF are unclear. Consecutive outpatients undergoing echocardiography and clinical evaluation and classified as HF stage A and B with preserved left ventricular ejection fraction (LVEF) were included. The association between LA measures [volume (LAVi), peak longitudinal-(PALS), contraction-(PACS) and conduit-strain] and non-specific HF symptoms was assessed using adjusted logistic regression analyses. The incremental value of atrial myopathy in symptoms prediction on top of clinical or echocardiographic confounders was assessed through ROC curves analyses. The cohort comprehended 185 patients (63 ± 16 years, 47% women) of whom 133 (72%) were asymptomatic, and 52 (28%) reported non-specific HF symptoms. After adjustment for clinical and echocardiographic confounders for HF symptoms, LAVi, PALS and PACS were associated with symptoms (p < 0.05). Among echocardiographic variables, only LA parameters were significantly associated with symptoms on top of clinical confounders (for LAVi OR [95% CI] 1.56 [1.21-2.00], p < 0.0001; for PALS 1.45 (1.10-1.91), p = 0.0009; for PACS 2.10 [1.33-3.30], p = 0.002). After adjustment for age, hypertension and COPD or E/E', LV mass-i and mitral ERO, atrial myopathy added predictive value for symptoms presence compared to the clinical variables or echocardiographic parameters described (AUC increase 0.80 to 0.88, p = 0.004, and 0.79 to 0.84, p = 0.06, respectively). In patients with HF stages A-B and preserved LVEF, measures of LA structure and function were associated with non-specific HF symptoms. A comprehensive LA remodeling evaluation may help clinicians in the appropriate identification of overt HF.

Echocardiographic parameters according to insulin dose in young patients affected by type 1 diabetes.

Insulin dose has been found to associate to several cardiometabolic risk factors in type 1 diabetes. Changes over time in body weight and composition may partly explain this association. However, no data are available on the relationship between insulin dose and echocardiographic parameters of both systolic and diastolic function in type 1 diabetes. Therefore, the aim of the present study was to examine systolic and diastolic echocardiographic parameters in relation to insulin dose in young patients with type 1 diabetes. The study was carried out on 93 consecutive outpatients with type 1 diabetes with a mean age of 32.8 ± 9.8 years. All patients were examined with a transthoracic echocardiography. Clinical and laboratory data were collected. The median value of daily insulin dose was used to categorized patients in two groups: high and low insulin dose group. Patients belonging to the high insulin dose group showed higher levels of cardiometabolic risk factors such as BMI, triglycerides and TG/HDL cholesterol ratio. Indexes of both systolic and diastolic function were similar in both groups except isovolumetric relaxation time (IVRT), that was significantly prolonged in patients of the high insulin group (94.4 ± 15.0 vs 86.7 ± 13.1 ms, p = 0.008). In the multivariate regression analysis, insulin dose was positively and significantly associated with IVRT. In this study we report an association between insulin dose and impaired active diastolic myocardial relaxation. Future studies are needed to further explore this observation.

Mitral regurgitation and dyspnoea: the expanding role of mitral effective regurgitant orifice among un-selected patients.

AIMS: Mitral regurgitation is frequent in the general population and among suspected heart failure patients; however, to what extent it contributes to dyspnoea is unclear. We hypothesized mitral regurgitation to have a role in determining dyspnoea in unselected ambulatory patients. METHODS: Consecutive outpatients referred for echocardiography were retrospectively screened and included. We excluded patients with mitral stenosis or prosthesis, congenital heart disease, cardiac surgery (previous 6 months) and atrial fibrillation. Patients were classified into four dyspnoea grades based on how they perceived their disability. We assessed mitral regurgitation severity through the effective regurgitant orifice area (ERO). RESULTS: One hundred and fifty-four patients (58% men; age 67 ±â€Š14 years; mean ejection fraction 54 ±â€Š12%) formed the study population; 76 (49%) classified asymptomatic (grade I), 63 (41%) dyspnoea grade II and 15 (10%) grade III; none was in grade IV. Mitral regurgitation was present in 102 patients (66%): primary in 14 (14%) and secondary in 88 (86%); among grades I, II and III patients, mitral regurgitation was present in 35 (46%; ERO 0.05 ±â€Š0.10 cm), 52 (82%; ERO 0.10 ±â€Š0.13 cm) and 15 (100%; ERO 0.20 ±â€Š0.11 cm) patients, respectively (P < 0.0001). After adjusting for clinical (age, hypertension, ischemic heart disease, chronic kidney injury, chronic pulmonary disease) and echocardiographic confounders (ejection fraction, E/e'), ERO remained associated with symptoms presence (grade I versus II - III; P = 0.01 and P = 0.03, respectively). CONCLUSION: Among unselected heterogeneous ambulatory patients, mitral ERO was associated with the presence of dyspnoea and could therefore help in identifying symptomatic patients and in clinical characterization of patients with perceived dyspnoea.

Mitral regurgitation, left atrial structural and functional remodelling and the effect on pulmonary haemodynamics.

AIMS: To assess the association between mitral regurgitation (MR) and left atrial (LA) structural and functional remodelling and their effect on pulmonary haemodynamics. METHODS AND RESULTS: Consecutive unselected patients undergoing comprehensive echocardiography were enrolled. Parameters of cardiac structure and function were obtained as well as mitral effective regurgitant orifice area (ERO) and estimation of pulmonary artery systolic pressure (PASP). Measures of LA structure [LA volume (LAV)] and function [peak atrial longitudinal strain (PALS), peak atrial contraction strain (PACS) and conduit strain (CS)] were also calculated. The study population included 102 patients (mean age 70 ± 14 years, 42% women), with a mean ejection fraction of 52 ± 13%. MR was classified as organic due to mitral valve prolapse in 14 patients (14%) and functional in 88 patients (86%). Mean ERO was 0.12 ± 0.12 cm2 and 86 patients (84%) had an ERO ≤0.2 cm2 . ERO was significantly associated with worse measures of LA structure and function. Despite the low burden of MR, the association remained significant after adjusting for clinical and echocardiographic confounders (ß: 3.7, P = 0.022 for LAV; ß: -3.0, P = 0.003 for PALS; ß: -1.8, P = 0.027 for PACS) and was significantly related with functional MR (P for interaction <0.001). ERO was also significantly associated with PASP, and measures of LA function (PALS and PACS) significantly modified this relationship (P for interaction <0.001). CONCLUSIONS: Even a mild degree of MR contributes to LA remodelling and this relationship plays an active role in pulmonary circulation, suggesting a potential mechanism by which these parameters contribute to the development of heart failure.

Role of Speckle Tracking Echocardiography in the Evaluation of Breast Cancer Patients Undergoing Chemotherapy: Review and Meta-analysis of the Literature.

Diagnosis and management of Cancer therapeutics-related cardiac dysfunction is of crucial importance in breast cancer (BC) patients. The role of advanced echocardiographic techniques, such as deformation imaging, in the diagnosis and characterization of patients receiving cancer therapy has so far involved relatively small studies in the research setting. Therefore, we conducted a meta-analysis and systematic review of observational studies evaluating myocardial changes during chemotherapy detected through conventional echocardiographic parameters, such as 2D left ventricular ejection fraction (2D LVEF), and 2D Speckle tracking echocardiography (STE). The literature search retrieved 487 research works, articles, of which 17 were found to be pertinent with this topic. After full article review, 16 studies were considered suitable for the present analysis. Two separate analyses, one for the anthracyclines-based therapeutic regimen and one for the trastuzumab based therapeutic regimen, were performed. A significant reduction in 2D LVEF and 2D STE parameters during cancer therapy was found in both the investigations. Peak systolic global longitudinal strain demonstrated to be the most consistent 2D STE parameter in detecting early myocardial changes among all the studies. Thus, we confirmed the role of 2D STE for the early detection of myocardial damage, suggesting its crucial role in monitoring BC patients and eventually driving the introduction of cardioprotective treatment.

The E/e' ratio difference between subjects with type 2 diabetes and controls. A meta-analysis of clinical studies.

Type 2 diabetes is associated with an increased risk of heart failure. Left ventricular diastolic dysfunction and type 2 diabetes are frequently associated. Using echocardiography, we know that tissue Doppler imaging E/e' ratio is a reliable predictor of left ventricular filling pressure. We performed a systematic review and meta-analysis to investigate the averaged E/e' ratio value in patients with type 2 diabetes compared to non-diabetic controls. In the analysis we included cross-sectional studies providing the averaged E/e' ratio. Subgroup/sensitivity analyses were conducted according to variables known to influence E/e' ratio measurements. The analysis included 15 cross sectional studies with 877 type 2 diabetes patients and 1193 controls. The weighted mean difference showed higher values in diabetes (WMD 2.02; 95% CI 1.35, 2.70; p<0.001). The result was consistent in the subgroup/sensitivity analyses. Visual inspection of the funnel plot did not identify substantial asymmetry and the Egger test for funnel plot asymmetry showed a p value of 0.36. In conclusion, our assessment suggests that averaged E/e' ratio is consistently increased in patients with type 2 diabetes compared to non-diabetic controls in the absence of cardiovascular diseases and complicated hypertension. This alteration may be a precocious diastolic alteration in the diabetic cardiomyopathy.

Usefulness of Left Atrial Remodeling in Predicting CardiacToxicity During Trastuzumab Therapy for Breast Cancer.

Trastuzumab is a key therapy for patients with human epidermal growth factor receptor 2 positive breast cancer (BC). However, it may cause left ventricular dysfunction, resulting in withdrawal of therapy. Left atrium (LA) enlargement has proven to cue subclinical ventricular dysfunction in various clinical setting. Aim of the study was to investigate the association between LA volume index (LAVI) change over time and the development of Cancer Therapeutics Related Cardiac Dysfunction (CTRCD). Consecutive human epidermal growth factor receptor 2 positive BC patients were retrospectively included. Transthoracic echocardiography was performed before starting Trastuzumab and at every 3 up to 12 months. LA volume was measured using the modified Simpson's rule and indexed for body surface area. Ninety patients formed the study population. All patients had a complete 12 months follow-up. Mean baseline LAVI was 27 ± 8 ml/m2 and it was dilated (≥34 ml/m2) in 10 patients (11%). During follow-up, CTRCD occurred in 19 (21%) patients and there was modest LAVI enlargement, with a mean increase of 3 ± 2 ml/m2 (p = 0.0002 vs. baseline). LAVI dilation was significantly higher in patients with CTRCD (average increase at the time of CTRCD vs. baseline: 7 ± 6 ml/m2, p = 0.008), versus patients without CTRCD (average increase at 12 months of follow-up 2±1, p = 0.02), p for comparison = 0.004. LAVI dilatation over time predicted CTRCD independently from baseline LAVI values and the presence of systemic arterial hypertension (OR for 5 ml/m2 dilation was 1.56 [95%CI 1.09 to 2.37], p = 0.01). Trastuzumab related CTRCD is associated with significant LAVI morphological remodeling in BC patients.

Left ventricular chamber dilation and filling pressure may help to categorise patients with type 2 diabetes.

BACKGROUND: Type 2 diabetes may alter cardiac structure and function. Many patients with type 2 diabetes have diastolic dysfunction with preserved ejection fraction (EF). Recently, this latter measure was criticised. Thus, this research looked at the impact of left ventricular end-diastolic volume and E/e' ratio variations in patients with type 2 diabetes and preserved EF with the aim to recognise different clinical phenotypes. METHODS: In this cross-sectional study, we evaluated 176 men affected by type 2 diabetes with transthoracic echocardiography. All subjects have preserved EF (>50%). Patients were stratified into four groups based on the median value of both left ventricular end-diastolic volume and E/e' ratio, and the clinical variables were registered. The independent predictors associated with the groups were analysed by a multinomial logistic regression model. RESULTS: Diabetes duration, age, estimated glomerular filtration rate and antihypertensive treatments were significantly different among the groups as were EF, left atrial volume index (LAVI), E/A, septum thickness and s' mean wave. Multinomial regression analysis showed that the groups significantly differed for age, diabetes duration, EF, LAVI, septum thickness and s' mean wave. The main result of this study was that patients with higher left ventricular volume and higher E/e' ratio (group 2) showed the worse clinical profile. CONCLUSIONS: Our study might suggest that variations of left ventricular end-diastolic volume along with E/e' ratio variations, even in the normal range, may allow to recognise phenotypes of patients with type 2 diabetes with worse clinical characteristics. This finding should be tested in prospective studies to assess the predictive roles of these phenotypes.

Left atrial volume in patients with HER2-positive breast cancer: One step further to predict trastuzumab-related cardiotoxicity.

BACKGROUND: Trastuzumab (TZ) therapy requires careful monitoring of left ventricular (LV) ejection fraction (LVEF) because it can be potentially cardiotoxic. However, LVEF is an imperfect parameter and there is a need to find other variables to predict cardiac dysfunction early. Left atrium (LA) enlargement has proven to be a powerful predictor of adverse outcomes in several disease entities. HYPOTHESIS: Baseline LA volume enlargement might predict TZ-related LV dysfunction. METHODS: HER2-positive breast cancer patients receiving TZ and undergoing transthoracic echocardiography at baseline and at follow-up every 3 months were retrospectively recruited. One-hundred sixty-two patients formed the study population. RESULTS: Baseline LAVI was dilated in 14 patients (8.6%). Mean follow-up was 14 ± 4 months. Cardiotoxicity occurred in 24 patients (14.8%). LAVI was an independent predictor of TZ-induced LV dysfunction in a clinical model, after adjustment for age and hypertension (odds ratio per 5-mL/m2 LAVI increase: 1.34, 95% confidence interval: 1.03-1.82, P = 0.03); and in a hemodynamic model, including ventricular sizes and systolic blood pressure level (odds ratio per 5-mL/m2 LAVI increase: 1.34, 95% confidence interval: 1.01-1.81, P = 0.04). The predicted probability of developing cardiotoxicity increased progressively, in parallel with LAVI values. CONCLUSIONS: Baseline LA dilatation emerges as a condition associated with the development of cardiotoxicity in HER2-positive breast cancer patients treated with TZ.

Association between subclinical left ventricular systolic dysfunction and glycemic control in asymptomatic type 2 diabetic patients with preserved left ventricular function.

BACKGROUND: Type 2 diabetes is strongly associated with the occurrence of cardiovascular diseases, especially heart failure. Some studies have suggested that subclinical systolic dysfunction as assessed by tissue Doppler imaging (TDI) is already present in uncomplicated diabetic patients with normal left ventricular ejection fraction (LVEF). Considering the importance of this aspect, the aim of this cross-sectional study was to examine the relationship between glycated hemoglobin and mean s' wave velocity (a reliable measure of early LV systolic dysfunction) in a cohort of type 2 diabetic outpatients with preserved LVEF and without ischemic heart disease. METHODS: Forty-four male patients with newly diagnosed and 172 male patients with established type 2 diabetes were recruited for this cross-sectional study. All patients were evaluated with a transthoracic echocardiographic Doppler. The statistical analysis was conducted by a linear multivariate regression analysis, including several potential confounders. RESULTS: The mean values of mean s' wave velocity were lower in patients with a worse glycemic control and progressively decreased across the quartiles of glycated hemoglobin. The multivariate linear regression analysis showed that mean s' wave velocity was inversely and independently associated with glycated hemoglobin (standardized beta coefficient -0.178; p = 0.043) after adjustment for age, duration of diabetes, body mass index, pulse pressure, estimated glomerular filtration rate, microvascular complication status, and indexed cardiac mass. CONCLUSIONS: These results suggest that s' wave velocity, as evaluated by TDI echocardiography, was an early marker of systolic dysfunction in type 2 diabetic patients with preserved LVEF and without prior ischemic heart disease. Moreover, early systolic dysfunction was independently associated with poor glycemic control in these patients. Future studies are needed to elucidate the pathogenic role of chronic hyperglycemia in the development of early LV systolic dysfunction.

Left ventricular end-diastolic volume as early indicator of trastuzumab-related cardiotoxicity in HER2+ breast cancer patients: results from a single-center retrospective study.

BACKGROUND: Adjuvant trastuzumab therapy increases survival rates in patients with early HER2-positive breast cancer, although it can be potentially cardiotoxic. The aim of this study was to evaluate the prevalence of left ventricular (LV) systolic dysfunction; and the relationship between the presence of cardiovascular risk factors, cardiac therapy and/or echocardiographic parameters of systolic function at baseline and the development of cardiotoxicity in such patients. METHODS: A total of 227 patients were retrospectively reviewed. Cardiotoxicity was defined as a decrease in LV ejection fraction (EF) below 50% or an absolute decrease of >10 points below the baseline value or any indication of heart failure. Each patient underwent echocardiography at baseline and at follow-up every three months. RESULTS: The prevalence of cardiotoxicity was 17.6% (15.4% asymptomatic, 2.2% symptomatic). Patients developing LV dysfunction presented hypertension (P=0.041) and diabetes (P=0.01) and used cardiac therapy at baseline more frequently. Smoke habit, age >50 and use of angiotensin-converting enzyme (ACE)-inhibitors, were independent predictors of cardiac damage. Furthermore, patients with LV dysfunction showed baseline LV end-diastolic volume (EDV) higher than those who did not and baseline EDV (OR=1.02; 95% CI: 1.00-1.04; P=0.027) independently predicted cardiotoxicity with 58 mL/m2 as best cut-off point (AUC=0.65, 95% CI: 0.55-0.75]). CONCLUSIONS: The prevalence of trastuzumab-related cardiotoxicity in patients with HER2-positive early breast cancer is relatively frequent, although asymptomatic in most cases. Baseline EDV resulted as independent predictor of cardiotoxicity suggesting that EDV may be more reliable than LVEF to identify patients at higher risk of developing cardiac damage.