Accelerated Atherosclerosis and Cardiovascular Toxicity Induced by Radiotherapy in Breast Cancer.

The number of patients diagnosed with breast cancer and cardiovascular disease is continuously rising. Treatment options for breast cancer have greatly evolved, but radiotherapy (RT) still has a key role in it. Despite many advances in RT techniques, cardiotoxicity is one of the most important side effects. The new cardio-oncology guidelines recommend a baseline evaluation, risk stratification and follow-up of these patients. Cardiotoxicity induced by RT can be represented by almost all forms of cardiovascular disease, with atherosclerosis being the most frequent. An interdisciplinary team should manage these patients, in order to have maximum therapeutic effect and minimum cardiovascular toxicity. This review will summarize the current incidence, risk factors, mechanisms and follow-up of RT-induced cardiovascular toxicity.

Multimodality Imaging and Biomarker Approach to Characterize the Pathophysiology of Heart Failure in Left Ventricular Non-Compaction with Preserved Ejection Fraction.

Left ventricular non-compaction (LVNC) with preserved ejection fraction (EF) is still a controverted entity. We aimed to characterize structural and functional changes in LVNC with heart failure with preserved EF (HFpEF). METHODS: We enrolled 21 patients with LVNC and HFpEF and 21 HFpEF controls. For all patients, we performed CMR, speckle tracking echocardiography (STE), and biomarker assessment for HFpEF (NT-proBNP), for myocardial fibrosis (Galectin-3), and for endothelial dysfunction [ADAMTS13, von Willebrand factor, and their ratio]. By CMR, we assessed native T1 and extracellular volume (ECV) for each LV level (basal, mid, and apical). By STE, we assessed longitudinal strain (LS), globally and at each LV level, base-to-apex gradient, LS layer by layer, from epicardium to endocardium, and transmural deformation gradient. RESULTS: In the LVNC group, mean NC/C ratio was 2.9 ± 0.4 and the percentage of NC myocardium mass was 24.4 ± 8.7%. LVNC patients, by comparison with controls, had higher apical native T1 (1061 ± 72 vs. 1008 ± 40 ms), diffusely increased ECV (27.2 ± 2.9 vs. 24.4 ± 2.5%), with higher values at the apical level (29.6 ± 3.8 vs. 25.2 ± 2.8%) (all p < 0.01); they had a lower LS only at the apical level (-21.4 ± 4.4 vs. -24.3 ± 3.2%), with decreased base-to-apex gradient (3.8 ± 4.7 vs. 6.9 ± 3.4%) and transmural deformation gradient (3.9 ± 0.8 vs. 4.8 ± 1.0%). LVNC patients had higher NT-proBNP [237 (156-489) vs. 156 (139-257) pg/mL] and Galectin-3 [7.3 (6.0-11.5) vs. 5.6 (4.8-8.3) ng/mL], and lower ADAMTS13 (767.3 ± 335.5 vs. 962.3 ± 253.7 ng/mL) and ADAMTS13/vWF ratio (all p < 0.05). CONCLUSION: LVNC patients with HFpEF have diffuse fibrosis, which is more extensive at the apical level, explaining the decrease in apical deformation and overexpression of Galectin-3. Lower transmural and base-to-apex deformation gradients underpin the sequence of myocardial maturation failure. Endothelial dysfunction, expressed by the lower ADAMTS13 and ADAMTS13/vWF ratio, may play an important role in the mechanism of HFpEF in patients with LVNC.

Hyperglycosylated-hCG: Its Role in Trophoblast Invasion and Intrauterine Growth Restriction.

Human chorionic gonadotropin (hCG) is produced by the placenta and its roles have been studied for over a century, being the first known pregnancy-related protein. Although its main role is to stimulate the production of progesterone by corpus luteal cells, hCG does not represent just one biologically active molecule, but a group of at least five variants, produced by different cells and each with different functions. The hyperglycosylated variant of hCG (H-hCG) plays a key role in trophoblast invasion, placental development and fetal growth. During trophoblast invasion, H-hCG promotes extravillous cytotrophoblast cells to infiltrate the decidua, and also to colonize and remodel the spiral arteries in to low resistance, larger-diameter vessels. As fetal growth is heavily reliant on nutrient availability, impaired trophoblast invasion and remodeling of the uterine arteries, leads to a defective perfusion of the placenta and fetal growth restriction. Understanding the function of H-hCG in the evolution of the placenta might unveil new ways to manage and treat fetal growth restriction.

New Advanced Imaging Parameters and Biomarkers-A Step Forward in the Diagnosis and Prognosis of TTR Cardiomyopathy.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an infiltrative disorder characterized by extracellular myocardial deposits of amyloid fibrils, with poor outcome, leading to heart failure and death, with significant treatment expenditure. In the era of a novel therapeutic arsenal of disease-modifying agents that target a myriad of pathophysiological mechanisms, timely and accurate diagnosis of ATTR-CM is crucial. Recent advances in therapeutic strategies shown to be most beneficial in the early stages of the disease have determined a paradigm shift in the screening, diagnostic algorithm, and risk classification of patients with ATTR-CM. The aim of this review is to explore the utility of novel specific non-invasive imaging parameters and biomarkers from screening to diagnosis, prognosis, risk stratification, and monitoring of the response to therapy. We will summarize the knowledge of the most recent advances in diagnostic, prognostic, and treatment tailoring parameters for early recognition, prediction of outcome, and better selection of therapeutic candidates in ATTR-CM. Moreover, we will provide input from different potential pathways involved in the pathophysiology of ATTR-CM, on top of the amyloid deposition, such as inflammation, endothelial dysfunction, reduced nitric oxide bioavailability, oxidative stress, and myocardial fibrosis, and their diagnostic, prognostic, and therapeutic implications.

New insights into the potential utility of the left atrial function analysis in heart failure with preserved ejection fraction diagnosis.

AIMS: None of the conventional echocardiographic parameters alone predict increased NTproBNP level and symptoms, making diagnosis of heart failure with preserved ejection fraction (HFpEF) very difficult in some cases, in resting condition. We evaluated LA functions by 2D speckle tracking echocardiography (STE) on top of conventional parameters in HFpEF and preHF patients with diastolic dysfunction (DD), in order to establish the added value of the LA deformation parameters in the diagnosis of HFpEF. METHODS: We prospectively enrolled 125 patients, 88 with HFpEF (68±9 yrs), and 37 asymptomatic with similar risk factors with DD (preHF) (61±8 yrs). We evaluated them by NTproBNP, conventional DD parameters, and STE. Global longitudinal strain (GS) was added. LA reservoir (R), conduit (C), and pump function (CT) were assessed both by volumetric and STE. 2 reservoir strain (S) derived indices were also measured, stiffness (SI) and distensibility index (DI). RESULTS: LA R and CT functions were significantly reduced in HFpEF compared to preHF group (all p<0.001), whereas conduit was similarly in both groups. SI was increased, whereas DI was reduced in HFpEF group (p<0.001). By adding LA strain analysis, from all echocardiographic parameters, SR_CT<-1.66/s and DI<0.57 (AUC = 0.76, p<0.001) demonstrated the highest accuracy to identify HFpEF diagnosis. However, by multivariate logistic regression, the model that best identifies HFpEF included only SR_CT, GS and sPAP (R2 = 0.506, p<0.001). Moreover, SR_CT, DI, and sPAP registered significant correlation with NTproBNP level. CONCLUSIONS: By adding LA functional analysis, we might improve the HFpEF diagnosis accuracy, compared to present guidelines. LA pump function is the only one able to differentiates preHF from HFpEF patients at rest. A value of SR_CT < -1.66/s outperformed conventional parameters from the scoring system, reservoir strain, and LA overload indices in HFpEF diagnosis. We suggest that LA function by STE could be incorporated in the current protocol for HFpEF diagnosis at rest as a major functional criterion, in order to improve diagnostic algorithm, and also in the follow-up of patients with risk factors and DD, as a prognostic marker. Future studies are needed to validate our findings.

COVID-19 presented as acute kidney injury with secondary myocardial damage.

The most common manifestations of the 2019 novel coronavirus disease (COVID-19) include fever, cough, dyspnea. Nevertheless, many atypical forms of presentation might be present, delaying a correct diagnosis. Acute kidney injury (AKI) is one of the important complications of COVID-19, occurring in 0.5-7% of cases and in 2.9-23% of ICU patients. The exact mechanisms by which COVID-19 induces AKI in different clinical settings is still a matter of debate. We present the case of a 53-year old woman, without any prior renal pathology, admitted to a Cardiology Department for atypical thoracic pain and oligo-anuria, without respiratory symptoms, who was diagnosed with SARS-CoV-2 infection. The patient had a significant rise in high-sensitivity cardiac troponin (from 304 ng/L to 889 ng/L in one hour) and mild systolic dysfunction (LVEF 45%), which led to the initial misdiagnosis of an acute myocardial infarction. Blood tests confirmed the diagnosis of acute kidney injury (creatinine 8.8 mg/dL in two different samples). She received hydro-electrolytic rebalancing treatment, with good clinical and biological evolution. To our knowledge this is one of the first reports, that highlights the existence of myocardial injury secondary to acute kidney injury caused by SARS-CoV-2 infection, in a patient without respiratory symptoms.

Optimal use of lipid-lowering therapy after acute coronary syndromes: A Position Paper endorsed by the International Lipid Expert Panel (ILEP).

Atherosclerotic cardiovascular disease (ASCVD) and consequent acute coronary syndromes (ACS) are substantial contributors to morbidity and mortality across Europe. Much of these diseases burden is modifiable, in particular by lipid-lowering therapy (LLT). Current guidelines are based on the sound premise that with respect to low density lipoprotein cholesterol (LDL-C), "lower is better for longer", and the recent data have strongly emphasized the need of also "the earlier the better". In addition to statins, which have been available for several decades, the availability of ezetimibe and inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) are additional very effective approach to LLT, especially for those at very high and extremely high cardiovascular risk. LLT is initiated as a response to an individual's calculated risk of future ASCVD and is intensified over time in order to meet treatment goals. However, in real-life clinical practice goals are not met in a substantial proportion of patients. This Position Paper complements existing guidelines on the management of lipids in patients following ACS. Bearing in mind the very high risk of further events in ACS, we propose practical solutions focusing on immediate combination therapy in strict clinical scenarios, to improve access and adherence to LLT in these patients. We also define an 'Extremely High Risk' group of individuals following ACS, completing the attempt made in the recent European guidelines, and suggest mechanisms to urgently address lipid-medicated cardiovascular risk in these patients.

Impaired Cardiac Function in Patients with Multiple Sclerosis by Comparison with Normal Subjects.

Multiple sclerosis (MS), neurologic disease affecting young population, may cause cardiovascular dysfunction, due to autonomous nervous dysfunction, physical invalidity, increased oxidative stress, and systemic inflammatory status. However, cardiovascular function is rarely evaluated in these patients. We assessed left and right ventricular (LV and RV) function by 2D, 3D, tissue Doppler, and speckle tracking echocardiography, and vascular function by remodeling, stiffness, and endothelial dysfunction parameters in patients with MS, compared to control subjects. 103 subjects (35 ± 10 years,70 women) were studied: 67 patients with MS and 36 control subjects. Patients with MS had decreased LV systolic function, confirmed by lower 2D and 3D ejection fraction, mitral annular plane systolic excursion, longitudinal myocardial systolic velocities, and 2D and 3D global longitudinal strain. The RV function was also decreased, as demonstrated by lower fractional area change, tricuspid annular plane systolic excursion, longitudinal systolic velocities, and longitudinal strain. Additionally, LV diastolic and left atrial (LA)  function were decreased compared to controls. The parameters of arterial and endothelial function were similar between groups. Patients with MS have impaired biventricular function by comparison with normal subjects, with reduced LA function, but normal arterial and endothelial function. The noninvasive echocardiographic techniques might help to determine patients with MS at risk of developing cardiovascular dysfunction.

The Relationship of Carotid Arterial Stiffness and Left Ventricular Concentric Hypertrophy in Hypertension.

BACKGROUND: Left ventricular hypertrophy (LVH) and geometry patterns vary in different hemodynamic profiles The concentric hypertrophy (CH) pattern has been proved to have the worst prognosis. OBJECTIVES: The aim of the study was to test the hypothesis that carotid artery stiffness, as a marker of vascular damage, is associated with CH, independently of other potential determinants such as demographic factors (age, sex, BMI), clinical parameters (smoking, diabetes, creatinine level) and hemodynamic variables (blood pressure, pulse pressure [PP]). MATERIAL AND METHODS: The study involved 262 subjects (89 men): 202 patients with hypertension (153 untreated, 49 on medication), aged 55.7 ± 10 years, and 60 age-matched normal controls. The subjects were examined by echocardiography and carotid ultrasound with a high-resolution echo-tracking system. Based on the left ventricular mass index (LVMI) and relative wall thickness (RWT), the patients with hypertension were divided into four patterns of LVH and geometry: normal geometry (N, n = 57), concentric remodeling (CR, n = 48), concentric hypertrophy CH (n = 62) and eccentric hypertrophy (EH, n = 35). Intima-media thickness (IMT) and the parameters of arterial stiffness were also assessed using the ß stiffness index (ß), Young elastic modulus (Ep), arterial compliance (AC), one-point pulse wave velocity (PWVß) and the wave reflection augmentation index (AI). RESULTS: Univariate analysis showed that the following variables are significant in determining CH: ß > 8.4, Ep > 136 kPa, PWVß > 7.1 m/s, AI > 21.9%, systolic BP > 151 mm Hg, PP > 54, IMT > 0.56 and the presence of diabetes. However, by multivariate analysis only AI (OR 3.65, p = 0.003), PWVß > 7.1 m/s (OR 2.86, p = 0.014), systolic BP (OR 3.12, p = 0037) and the presence of diabetes (OR 3.75, p = 0.007) were associated independently with the occurrence of CH. CONCLUSIONS: Concentric hypertrophy in hypertension is strongly associated with carotid arterial stiffness and wave reflection parameters, independently of the influence of systolic blood pressure and diabetes.

Comparison of pulse wave velocity assessed by three different techniques: Arteriograph, Complior, and Echo-tracking.

Arterial stiffness estimated by pulse wave velocity (PWV) is an independent predictor of cardiovascular morbidity and mortality. Although recommended by the current guidelines, clinical applicability of this parameter is difficult, due to differences between the various techniques used to measure it and to biological variability. Our aim was to compare PWV assessed by 3 different commercially available systems. 100 subjects (51 ± 16 years, 45 men) were evaluated using the 3 methods: an oscillometric technique (Arteriograph, PWV-A); a piezo-electric method (Complior, PWV-C); and an high-resolution ultrasound technique implemented with an Echo-tracking system (Aloka, PWV-E). Conventional biological markers were measured. Correlations of PWV measured by the 3 methods were poor (r = 0.39, r = 0.39, and r = 0.31 for PWV-A vs. PWV-C, PWV-A vs. PWV-E, and PWV-C vs. PWV-E, respectively, all p < 0.05). By Bland-Altman analysis, mean difference (±SD) of PWV-A vs. PWV-C was -1.9 ± 2.0 m/s, of PWV-A vs. PWV-E -3.6 ± 1.9 m/s, and of PWV-C vs. PWV-E -2.7 ± 1.9 m/s, with a wide coefficient of variation (22.3, 25.7, and 25.7 %, respectively). As expected, PWV-A, PWV-C, and PWV-E correlated with other arterial stiffness parameters, such as intima-media thickness (r = 0.22, r = 0.22, and r = 0.36, respectively), E p (r = 0.37, r = 0.26, and r = 0.94, respectively), and augmentation index measured by Arteriograph method (r = 0.66, r = 0.35, and r = 0.26, respectively); all p < 0.05. Assessment of PWV is markedly dependent on the technique used to measure it, related to various methods for measuring traveled distance of the arterial wave. Our results suggest the urgent need to establish reference values of PWV for each of these techniques, separately, to be used in routine clinical practice.

The Assessment of Subclinical Cardiovascular Dysfunction in Treated Rheumatoid Arthritis.

BACKGROUND AND PURPOSE: Rheumatoid arthritis (RA) causes frequently cardiovascular complications, probably determined by early atherosclerosis in connection to chronic systemic inflammation. Purpose of our study was to assess subclinical cardiac and vascular dysfunction, and to evaluate the mechanisms of ventriculo-arterial interaction, in patients with correctly treated RA vs. normal subjects. METHODS: We evaluated 46 subjects (55±10 years, 2 men): 29 patients with seropositive treated RA (mean duration of 11±9 years), without documented cardiovascular or pulmonary disease, and 17 control subjects, matched for age, sex, and distribution of conventional major risk factors. All RA patients were under long-term treatment (more than 6 months) with Methotrexat + Sulfasalasine (22 patients) or Methotrexat + Sulfasalasine + Infliximab (7 patients). We determined biomarkers of inflammation (P-selectin, interleukines 1, 6, 10, 18, seric amiloid A, á-TNF, ã-interferon, C-reactive protein, anti-oxidated LDL antibodies), myocardial fibrosis (â-crosslaps) and ventricular overload (BNP). We assessed the parameters of cardiac function by standard and tissue Doppler echocardiography, intima-media thickness and arterial stiffness by "e-tracking" and "wave intensity analysis" (at the level of the right carotid artery), endothelial function by flow mediated dilation (FMD), and carotid-femoral pulse wave velocity by the Complior method. RESULTS: Biological parameters of inflammation, markers of myocardial fibrosis and of ventricular overload were not different between the 2 study groups. Also, parameters of subclinical cardiac and vascular function were similar between the two groups. RA patients had subclinical RV dysfunction, correlated to the duration of the disease. They also tended to have higher values of systolic pulmonary artery pressure than normals. CONCLUSION: Correctly treated patients with RA, with controlled systemic inflammation, have normal LV, endothelial and arterial function. However, in the absence of documented pulmonary disease, they do have subclinical RV dysfunction, correlated with the duration of disease. This suggests an intrinsic RV myocardial involvement but, since pulmonary artery pressure was also higher, a secondary mechanism might be also involved.

Growth hormone deficiency in adults impacts left ventricular mechanics: a two-dimensional speckle-tracking study.

BACKGROUND: Growth hormone deficiency (GHD) in adults is associated with increased cardiovascular events, but detailed assessment of cardiac and vascular function is lacking. Thus we assessed cardiac, arterial, and endothelial functions, using conventional and speckle-tracking echocardiography, in adults with GHD compared with controls with similar cardiovascular risk. METHODS: Fifty-two patients with GHD (47 ± 16 years; 34 men) and no cardiovascular disease or diabetes were enrolled prospectively and compared with 50 age- and sex-matched controls. Comprehensive echocardiography was performed in all participants. Regional left ventricular (LV) function was assessed from global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS), whereas LV torsion (LVtor) was calculated from basal (RotB) and apical (RotA) rotations. Arterial function was assessed from intima-media thickening, local wave speed, and beta index of stiffness, whereas endothelial function was assessed from flow-mediated dilation. Levels of pro-brain natriuretic peptide (proBNP) were measured. RESULTS: GLS and GCS were decreased more in patients with GHD than in controls (-17.2% ± 2.7% vs. -19.3% ± 3.3% and -15.9% ± 5.4% vs. -18.8% ± 3.5%; both P < 0.01), whereas GRS was similar. RotB and LVtor were also decreased in patients with GHD (-4.8° ± 2.6° vs. -6.2° ± 2.1°/cm and 1.8° ± 0.6° vs. 2.3° ± 1.1°/cm; both P < 0.05). ProBNP was increased in patients with GHD (61.0 ± 74 pg/dL vs. 24.7 ± 21 pg/dL; P = 0.002). Arterial and endothelial functions were similar between groups. CONCLUSIONS: In conclusion, adults with GHD had LV longitudinal dysfunction and increased proBNP levels compared with controls, suggesting intrinsic myocardial disease. Further studies are needed to assess if this cardiac impairment in adults with GHD is reversible after GH replacement.

Atherosclerosis in Systemic Sclerosis: a Modern Controversy.

Systemic sclerosis (SSc) is a chronic disease of unknown etiology. The main feature of SSc is microvascular disease, but contemporary studies in the field have confirmed the presence of macrovascular affectation. Due to its inflammatory background, and higher cardio- and cerebrovascular death rates, it is presumed that SSc is more frequently associated to accelerated atherosclerosis, similarly to other autoimmune diseases, such as systemic lupus erythematosus or rheumatoid arthritis. The assessment of subclinical atherosclerosis in patients with SSc through different methods (such as intima media thickness, echo-tracking, wave intensity, pulse wave velocity, flow mediated dilation, nitroglycerin mediated dilation, ankle brachial pressure index or coronary angiotomography) has failed to show concordant results, regardless of the used tool. In this review, we try to synthetise the most recent evidence about atherosclerotic involvement in SSc, reviewing the association between SSc and risk factors and also performing a summary of studies that compared atherosclerosis in SSc to controls. Our research leads to the conclusion that in order to elucidate the extent of atherosclerosis and its consequences in SSc, further investigations are needed, combining atherosclerosis assessment tools and larger number of patients.

The efficiency of continuous positive airway pressure therapy in reducing cardiovascular dysfunction in a patient with arterial hypertension and obstructive sleep apnea.

Obstructive sleep apnea (OSA) has been included by European and American hypertension therapy guidelines as a common cause of high blood pressure. Recent studies have demonstrated a strong link between OSA and HBP and the treatment thereof should consist of combination therapy, especially in patients with refractory AHT and a non-dipping profile. We present the case of a patient with high grade hypertension, with secondary organ damage and severe OSA. The ultimate method for controlling blood pressure and reversing subclinical cardiac and cerebrovascular dysfunction of this patient was the specific therapy with continuous positive airway pressure (cPAP).

The effect of indapamide versus hydrochlorothiazide on ventricular and arterial function in patients with hypertension and diabetes: results of a randomized trial.

OBJECTIVE: The objective of this study is to compare the effects of 2 types of diuretics, indapamide and hydrochlorothiazide, added to an angiotensin-converting enzyme inhibitor, on ventricular and arterial functions in patients with hypertension and diabetes. METHODS: This is a prospective, randomized, active-controlled, PROBE design study in 56 patients (57 ± 9 years, 52% men) with mild-to-moderate hypertension and type 2 diabetes, with normal ejection fraction, randomized to either indapamide (1.5 mg Slow Release (SR)/day) or hydrochlorothiazide (25 mg/d), added to quinapril (10-40 mg/d). All patients had conventional, tissue Doppler and speckle tracking echocardiography and assessment of endothelial and arterial functions and biomarkers, at baseline and after 6 months. RESULTS: Baseline characteristics were similar between groups; systolic and diastolic blood pressures decreased similarly, by 15% and 9% on indapamide and by 17% and 10% on hydrochlorothiazide (P < .05). Mean longitudinal systolic velocity and longitudinal strain increased by 7% and 14% on indapamide (from 5.6 ± 1.8 to 6.0 ± 1.1 cm/s and from 16.2% ± 1.8% to 18.5% ± 1.1%, both P < .05), but did not change on hydrochlorothiazide (P < .05 for intergroup differences), whereas ejection fraction and radial systolic function did not change. Similarly, mean longitudinal early diastolic velocity increased by 31% on indapamide (P < .05), but did not change on hydrochlorothiazide (P < .05 for intergroup differences). These changes were associated with improved endothelial and arterial functions on indapamide, but not on hydrochlorothiazide. CONCLUSION: Indapamide was found to improve measures of endothelial and arterial functions and to increase longitudinal left ventricular function compared with hydrochlorothiazide in patients with hypertension and diabetes, after 6 months of treatment. This study suggests that indapamide, a thiazide-like diuretic, has important vascular effects that can improve ventriculoarterial coupling.

New Echocardiographic Tehniques in Pulmonary Arterial Hypertension vs. Right Heart Catheterization - A Pilot Study.

BACKGROUND: Pulmonary arterial hypertension (PAH) represents an emerging pathology in modern medicine. Transthoracic echocardiography is an inexpensive and reproducible method and it is the most commonly used non-invasive diagnostic tool to asses pulmonary artery pressure (PAP) and the function of the right ventricle. Although, the right heart catheterization is still considered as the standard for the diagnosis, according to the last guidelines, the new echocardiographic methods may offer an improved value in the PAH evaluation. AIM: To evaluate if cardiac ultrasonography data correlate with catheterization results in patients with PAH (Group I Dana Point 2008), and to compare the ultrasonography evaluation of PAH patients with that of normal. METHODS: 15 consecutive patients (pts) (52±15 yrs, 5 men, time from onset of symptoms 1.6±1.7 years) with PAH of different aetiologies (12 pts with idiopathic PAH, 2 pts with PAH associated with scleroderma and one with persistent PAH after atrial septal defect (ASD) closure) were evaluated through: 1. clinical examination (NYHA class); 2. exercise capacity (6 minute walking test - 6MWT); 3. conventional echocardiography (diameter of right ventricle - RVD and right atrium, fractional area shortening - FAS, TAPSE, pulmonary ascension time - PA, systolic and mean PAP -sPAP, mPAP, tricuspid E/A ratio, cardiac index-CI) and 4. Tissue Doppler Imaging - TDI (systolic and diastolic myocardial velocities at the tricuspid annulus - S, D, A); 5. right heart catheterization (sPAP, mPAP, CI, pulmonary vascular resistance - PVR)We compared classical and TDI echo parameters with those obtained from 15 normal subjects, matched in age and sex. RESULTS: PAH patients had high sPAP and mPAP with right heart dilation (RV - 44.8±7.3 mm), depressed TAPSE (16.2±5.9 mm) and cardiac index and low TDI systolic velocities at tricuspid level (7.3±2.9 cm/s). All parameters differed statistically significant from normal. There were no significant correlations between ultrasonography and catheterization (cath) parameters (sPAP 92±28.2 echo vs. 106.4±25.8 mmHg cath; mPAP 47.9±8.4 echo vs. 65.8±17.3 mmHg cath), excepting for CI 2.3±1.2 l/min/m(2) vs. 2.08±0.3 ml/min/m(2)) and PVR (16.5 ± 15.3 Wood U echo, vs. 19.6 ± 7.9 cath). CONCLUSION: Classic and TDI cardiac ultrasonography represents a good screening and monitoring tool for PAH patients, but tends to underestimate the severity of the disease, leaving right heart catheterization as the essential diagnostic method for this rare disease.

The impact of blood pressure variability on subclinical ventricular, renal and vascular dysfunction, in patients with hypertension and diabetes.

BACKGROUND: Blood pressure variability (BPV) was proved as a cardiovascular risk factor. One of its mechanisms is related to arterial stiffness and ventriculo-arterial coupling; however its impact on subclinical cardiovascular dysfunction has not been evaluated yet. OBJECTIVES: To assess the relationship between BPV on 24 hours, and subclinical left ventricle (LV), renal, and vascular dysfunction in diabetic and hypertensive patients. MATERIAL AND METHODS: We studied 56 patients (57±9 years, 29 men) with mild-to-moderate hypertension and type 2 diabetes, no cardiovascular disease, normal ejection fraction and normal renal function. 24 hours ambulatory blood pressure monitoring (ABPM) was used to assess BPV, daytime (d) and night time (n), by: 1. mean (M); 2. standard deviation of mean (SD); 3. variance (Vr); 4. coefficient of variation (CV); 5. day/night variation: reverse dippers, non-dippers, dippers and extreme dippers; conventional and 2D speckle tracking echo to assess LV function; myocardial deformation was measured as global longitudinal strain (GLS). Endothelial (flow mediated dilation, FMD) and arterial function (intima media-thickness, IMT; pulse wave velocity, PWV), microalbuminuria were tested. OUTCOMES: Daytime BPV correlates inversely with subclinical myocardial function evaluated through GLS. Daytime systolic BPV correlates positively with IMT (all rho > 0.30, all p < 0.05). Also, there is a significantly inverse correlation between mean BP and GLS. We found a direct correlation between mean BP, but not BPV, and microalbuminuria (all rho > - 0.30 and all p < 0.05). We found no correlation between BPV and FMD, PWV. There were no differences for GLS, microalbuminuria and FMD between dipper groups. CONCLUSIONS: In diabetic patients with mild-to-moderate hypertension, increased daytime blood pressure variability correlates with subclinical left ventricular dysfunction and arterial function (IMT), while microalbuminuria correlates with elevated blood pressure, but not with blood pressure variability.

Comparative reproducibility of the noninvasive ultrasound methods for the assessment of vascular function.

The aim of this work was to assess the reproducibility of ultrasound parameters of vascular function, since these measurements are currently recommended by the guidelines for the evaluation of the cardiovascular risk. Twenty subjects (51 ± 17 years, 11 men) had vascular ultrasound (Aloka Prosound α10) performed by two observers, at the level of the right common carotid artery for assessment of intima-media thickness (IMT), "wall tracking", and "wave-intensity analysis", and at the level of the right brachial artery for the assessment of flow-mediated dilation (FMD). Wave intensity is a hemodynamic index, evaluating ventriculo-arterial interaction and can be measured in real time by a double-beam ultrasound technique through simultaneous recording of carotid arterial blood flow velocity and diameter. Carotido-femoral pulse wave velocity (PWV) was determined using the Complior method. Intra- and inter-observer reproducibility was assessed during a first session, when three consecutive acquisitions were made (first observer → second observer → first observer); repeatability was evaluated 1 week later (second observer). The most reproducible and repeatable parameters were PWV (intraobserver ±3.3%, interobserver ±2.6%, repeatability ±5.6%) and IMT (±3.7, ±4.3, ±4.9%, respectively). Intraobserver reproducibility for arterial stiffness and ventriculo-arterial coupling parameters was the highest for the beta index (±3.8%), and the lowest for the second systolic peak (±22.4%). Interobserver reproducibility and repeatability varied between very good for the wave speed (±5.5 and ±4.3%), and unsatisfactory for the negative area (±31.8 and ±38.6%). FMD had good reproducibility (intraobserver ±11.6%, interobserver ±8%, repeatability ±7%), whereas augmentation index had only satisfactory results (±17.8, ±8.4, ±23.8%, respectively). Only some parameters of vascular function have good reproducibility and repeatability, better or similar to other ultrasound methods and, therefore, these are ready to be used in routine clinical practice.

Reversal of subclinical left ventricular dysfunction by antihypertensive treatment: a prospective trial of nebivolol against metoprolol.

OBJECTIVES: To assess the effects of antihypertensive treatment on subclinical left ventricular dysfunction and to compare the effects of nebivolol with metoprolol. METHODS: This is a prospective, randomized, parallel, active-controlled, PROBE design study (ClinicalTrials.org: NCT00942487) in 60 patients (53±9 years, 67% men) with arterial hypertension, left ventricular hypertrophy, normal ejection fraction, and no coronary heart disease, randomized to either a nebivolol-based or a metoprolol-based treatment, who had conventional and tissue Doppler echocardiography, at rest and during dobutamine stress, at baseline and after 6 months. RESULTS: SBP and DBP, and resting heart rate decreased by 13, 13, and 12%, respectively, on nebivolol, and by 11, 13, and 7%, respectively, on metoprolol (all, P<0.01). Mean longitudinal early diastolic velocity increased by 16% (P<0.05) on nebivolol compared with 9% (P=not significant) on metoprolol (P=not significant for intergroup differences), whereas flow propagation velocity increased by 34% on nebivolol (P<0.05) and did not change on metoprolol (P<0.01 for intergroup differences). Mean longitudinal displacement increased by 10% on nebivolol (P<0.05) and did not change on metoprolol (P<0.05 for intergroup differences), whereas ejection time increased by 5% on nebivolol (P<0.05) and did not change on metoprolol. All the other parameters of left ventricular function were not different between the two treatment arms. CONCLUSION: Patients with mild-to-moderate hypertension have a beneficial effect from 6-month antihypertensive treatment on diastolic longitudinal left ventricular function; effects are significant with nebivolol, but not with metoprolol.

"Supranormal" cardiac function in athletes related to better arterial and endothelial function.

OBJECTIVE: Athlete's heart is associated with left ventricular (LV) hypertrophy (LVH), and "supranormal" cardiac function, suggesting that this is a physiological process. Hypertrophy alone cannot explain increase in cardiac function, therefore, other mechanisms, such as better ventriculo-arterial coupling might be involved. METHODS: We studied 60 male (21 +/- 3 years) subjects: 27 endurance athletes, and a control group of 33 age-matched sedentary subjects. We assessed global systolic and diastolic LV function, short- and long-axis myocardial velocities, arterial structure and function and ventriculo-arterial coupling, endothelial function by flow-mediated dilatation, and amino-terminal pro-brain natriuretic peptide (NT-proBNP) and biological markers of myocardial fibrosis and of oxidative stress. RESULTS: Athletes had "supranormal" LV longitudinal function (12.4 +/- 1.0 vs 10.1 +/- 1.4 cm/s for longitudinal systolic velocity, and 17.4 +/- 2.6 vs 15.1 +/- 2.4 cm/s for longitudinal early diastolic velocity, both P < 0.01), whereas ejection fraction and short-axis function were similar to controls. Meanwhile, they had better endothelial function (16.7 +/- 7.0 vs 13.3 +/- 5.3%, P < 0.05) and lower arterial stiffness (pulse wave velocity 7.1 +/- 0.6 vs 8.8 +/- 1.1 m/s, P = 0.0001), related to lower oxidative stress (0.259 +/- 0.71 vs 0.428 +/- 0.88 nmol/mL, P = 0.0001), with improved ventriculo-arterial coupling (37.1 +/- 21.5 vs 15.5 +/- 13.4 mmHg.m/s(3)x 10(3), P = 0.0001). NT-proBNP and markers of myocardial fibrosis were not different from controls. LV longitudinal function was directly related to ventriculo-arterial coupling, and inversely related to arterial stiffness and to oxidative stress. CONCLUSIONS: "Supranormal" cardiac function in athletes is due to better endothelial and arterial function, related to lower oxidative stress, with optimized ventriculo-arterial coupling; athlete's heart is purely a physiological phenomenon, associated with "supranormal" cardiac function, and there are no markers of myocardial fibrosis.