Maternal Left Ventricular Function in Uncomplicated Twin Pregnancies: A Speckle-Tracking Imaging Longitudinal Study.

OBJECTIVE: The knowledge of maternal cardiovascular hemodynamic adaptation in twin pregnancies is incomplete. We aimed to longitudinally investigate maternal left ventricular (LV) function in uncomplicated twin pregnancies. METHODS: 30 healthy and uncomplicated twin pregnant women and 30 controls with normal singleton pregnancies were prospectively enrolled to undergo transthoracic echocardiography at 10-15 week's gestation (w) (T1), 19-26 w (T2) and 30-38 w (T3). LV dimensions and volumes, as well as LV ejection fraction (LVEF), mass (LVM) and diastolic parameters (at transmitral pulsed wave Doppler and mitral annular plane tissue Doppler), were calculated. Speckle-tracking imaging was also applied to evaluate LV global longitudinal (GLS), radial and circumferential 2D strains. RESULTS: During twin pregnancy, maternal LV dimensions, volumes and LVM had an increasing trend from T1 to T3, similar to singletons, while LVEF remained stable. There was LV remodeling/hypertrophy in 50% of women at T2 and T3 in both groups. Diastolic function had a worsening trend from T1 to T3 with no differences between twins and singletons, except for higher LV filling pressure (i.e., E/E') at T2 in twins. Two-dimensional strains did not vary during gestation in either group, except for a linear trend to increase (i.e., worsen) GLS in singletons. Radial and circumferential 2D strains were impaired in about half of the women at each trimester, while GLS was altered in one-fourth/one-third of them in both groups. CONCLUSION: Maternal LV geometry, dimensions and function are significantly impaired during twin pregnancies, in particular in the second half of gestation, with no significant differences compared to singletons.

Maternal Right Ventricular and Left Atrial Function in Uncomplicated Twin Pregnancies: A Longitudinal Study.

Objective: The knowledge regarding maternal cardiovascular hemodynamic adaptation in twin pregnancies is incomplete. We performed a longitudinal investigation of maternal right ventricular (RV) and left atrial (LA) function in a cohort of uncomplicated twin pregnancies compared to singleton pregnancies. Study design: Healthy women with uncomplicated twin pregnancies were prospectively enrolled and assessed by transthoracic echocardiography at 10−15 weeks' (w) gestation (T1), 19-26 w gestation (T2), and 30−38 w gestation (T3). Subjects with uneventful singleton pregnancies were selected as controls at the same gestational ages. Cardiac findings were compared to those of women with uneventful singleton gestations. RV systolic and diastolic functions were assessed by conventional echocardiography (FAC, TAPSE, sPAP, E, A, DT) and tissue Doppler imaging (TDI) (E', A', S', IVA, IVCT, IVRT, ET, MPI), and LA dimensions were calculated. Speckle-tracking imaging was also applied to evaluate RV global longitudinal strain and LA 2D strains (at LV end-systole (LAS) and at atrial contraction (LAA)). Results: Overall, 30 uncomplicated twin and 30 uncomplicated singleton pregnancies were included. Regarding maternal RV function in twins, all the parameters (FAC, TAPSE, sPAP, E, A, E/A, DT, E/E', IVA, IVCT, MPI and 2D longitudinal strain) were almost stable throughout gestation, with the exception of the TDI findings (E' decreased from T1 to T3 (p = 0.03), while E'/A' increased from T1 to T2 and then decreased (p = 0.01); A' and basal S' increased (p = 0.04 and p = 0.03, respectively), while IVRT and ET significantly decreased (p = 0.009 and p = 0.007, respectively)). These findings were similar to those found for singleton pregnancies. LA dimensions significantly increased throughout gestation in both twins and singletons (p < 0.001), without intergroup difference. LA strains did not vary during either twin or singleton pregnancies, except for LAA in T1, which was higher among twins than among singletons. Conclusion: Maternal RV and LA function in uncomplicated twin pregnancies does not seem to undergo more significant changes than in singletons, being characterized by similar findings in RV systolic and diastolic functions, as well as LA dimensions and strains.

Maternal hemodynamics, arterial stiffness and elastic aortic properties in twin pregnancy.

OBJECTIVE: There is scant information about maternal cardiovascular hemodynamic change during twin pregnancies. Aim of the study is to investigate longitudinal changes in maternal arterial stiffness, elastic aortic properties and ventricular-arterial coupling (VAC) in uncomplicated twin pregnancies compared to singleton ones. APPROACH: In this prospective longitudinal study, we performed applanation tonometry and transthoracic echocardiography in the first (T1; 10-15 weeks' gestation (w)), second (T2; 19-26 w) and third trimesters (T3; 30-38 w) in women with uncomplicated twin pregnancies, both monochorionic and dichorionic. Heart-rate-corrected augmentation index (AIx@75) was studied as indicator of arterial stiffness. Aortic diameters and elastic properties were calculated. VAC was defined as the ratio between aortic elastance (Ea) and left ventricular end-systolic elastance (Ees). Finally, stroke volume (SV), cardiac output (CO) and total vascular resistance (TVR) were evaluated. The findings were compared to those of women with uncomplicated singleton pregnancies. MAIN RESULTS: Thirty women with twin gestations (11 monochorionic) and 30 singleton controls were obtained for analysis. Blood pressure and TVR significantly decreased from T1 to T2 and then rose in T3, with higher values in twins than in singletons. AIx@75 showed the same trend in both groups with lower values at T2 in twins. SV and CO linearly increased throughout gestation with no significant intergroup difference. Aortic diameters and elastic properties remained stable throughout gestation, with no significant intergroup differences. Both Ea and Ees were greater (i.e. worse) in twins than in singletons at T1 and T3, showing a significant linear trend towards reduction in the two groups, meaning lower vascular and ventricular loads. Using longitudinal analysis blood pressure, TVR, Ea and Ees depended from both multiple gestation and gestational age. SIGNIFICANCE: In twins, maternal hemodynamics does not seem to undergo more significant changes than in singletons being characterized by higher blood pressures and TVR with no differences in CO, SV, aortic dimensions and elastic properties. Despite VAC is maintained within its normal range, total vascular load (i.e., Ea) resulted higher in twin than singleton pregnancies throughout gestation. It is conceivable that these findings may represent one of the underlying cause for the increased risk of adverse obstetric outcomes described in multiple gestations.

The role of heart rate and ivabradine in acute heart failure.

Resting heart rate (HR) is considered a powerful predictor of mortality both in healthy subjects and in cardiovascular (CV) patients, including those affected by heart failure (HF). Its reduction below 70 bpm is the treatment target in chronic HF with reduced ejection fraction (HFrEF) when sinus rhythm is present. In acute HF (AHF) HR is usually elevated but its role as risk marker is still unknown. Notably, in unstable patients, beta-blockers can be reduced or stopped, thus enhancing this phenomenon. Moreover, some data in literature suggest that HR reduction during hospitalization or HR at discharge or in the vulnerable phase after it are more predictive of early-term events and may be therapeutic targets. On the other hand, ivabradine is a pure HR-lowering drug with no effects on inotropism. Its role in the AHF setting has been recently investigated and is the object of this review.

Wellens' syndrome: a case report with atypical features.

Wellens' syndrome is a pattern of electrocardiographic T-wave changes seen in the precordial leads in patients with unstable angina. Two different patterns have been described. Type A presents with biphasic T-waves in V2-V3 and type B presents with symmetrical deep T-wave inversions in V2-V3. The etiology is related to a critical stenosis in the proximal left anterior descending artery (LAD). We describe a patient who presented at our emergency department with intermittent chest pain and showing Wellens' pattern T-wave inversions in the precordial leads of the electrocardiogram. She was found to have 95% stenosis in mid LAD.

Elastic aortic properties in cystic fibrosis adults without cardiovascular risk factors: A case-control study.

INTRODUCTION: The presence of CFTR in smooth muscle and endothelial cells, systemic inflammation, and oxidative stress could explain vascular alterations in cystic fibrosis. Aortic elastic properties are determinants of left ventricular function by means of ventriculo-arterial coupling and indicators of cardiovascular risk. OBJECTIVES: The purpose of the present study was to compare clinically stable patients affected by cystic fibrosis without overt pulmonary hypertension with controls to evaluate aortic tissue Doppler elastic properties, such as distensibility, stiffness, and strain. METHODS: A total of 22 adults affected by cystic fibrosis, and 24 healthy volunteers matched for age and sex were enrolled. None had known cardiovascular risk factors, secondary diabetes, neither aortic stenosis nor regurgitation. All people underwent blood pressure measurement and transthoracic echocardiography. RESULTS: Aortic diameter measured at Valsalva sinuses was significantly higher in patients with cystic fibrosis than healthy people, median 32.0 (interquartile range 29.8-35.0) vs 24.3 (22.2-30.0) mm; P < 0.001. Aortic distensibility was significantly lower among patients than controls, being 2.4 (1.3-3.3) vs 5.6 (3.4-8.3) per mm Hg (P < 0.001), while stiffness higher, 7.7 (6.0-14.8) vs 3.7 (2.9-6.7); P < 0.001. Finally, M-mode strain of ascending aorta was lower in patients, 4.1 (3.4-7.3)% than in controls, 13.4 (7.7-19.4)%; P < 0.001. CONCLUSION: For the first time in humans, we demonstrated subclinical alterations in aortic elastic properties in young adults affected by cystic fibrosis without pulmonary hypertension or secondary diabetes. This phenomenon could influence left ventricular function earlier by means of ventriculo-arterial coupling and may be a tool to identify patients who benefit from a closer follow-up.

Macro- and microvascular functions in cystic fibrosis adults without cardiovascular risk factors: A case-control study.

Increasing survival from cystic fibrosis show untypical systems involvement, such as cardiocirculatory. In particular, the presence of CFTR in smooth muscle and endothelial cells, systemic inflammation and oxidative stress could explain vascular alterations in these patients. We aimed at noninvasely evaluating macro- and microvascular dysfunction in cystic fibrosis adults without cardiovascular risk factors. Twenty-twoadults affected by cystic fibrosis and 24 healthy volunteers matched for age and sex were enrolled. None had known cardiovascular risk factors. All people underwent blood pressure measurement, microvascular function assessment by EndoPAT-2000 device (calculating RH-PAT index) and macrovascular evaluation by pulse wave velocity (PWV). RH-PAT index was significantly lower in patients than in controls (1.74±0.59 vs 2.33±0.34; p<0.001). Thirteen patients of 22 had a value inferior to the threshold of 1.67 (59.1%), while no controls had (p<0.001). Carotid-femoral PWV did not differ between the two groups (5.2±1.5 m/s vs 5.4±1.1; p=0.9), while brachial-ankle one did (11.0±2.2 m/s vs 10.1±0.8 m/s; p=0.04).Adults patients affected by cystic fibrosis show peripheral endothelial dysfunction, which is the first alteration in atherosclerotic phenomenon. Moreover, arterial stiffness measured by PWV unclearly seems to differ respect of healthy people, perhaps because PWV alterations are typical of above 50 years old people. It is unclear what prognostic role of future developing of atherosclerotic disease these findings could be, but it seems evident that cystic fibrosis directly affects cardiovascular system itself.

Focus on echocardiographic right ventricular strain analysis in cystic fibrosis adults without cardiovascular risk factors: a case-control study.

Strain echocardiography is able to detect subclinical ventricular systolic and diastolic dysfunction. Prolonged survival to cystic fibrosis favors heart and vessel involvement. The purpose of the present study was to compare clinically stable adult patients affected by cystic fibrosis without overt pulmonary hypertension with controls to evaluate right ventricular (RV) systolic and diastolic function by means of strain and tissue Doppler imaging (TDI), respectively. 22 adults affected by cystic fibrosis and 24 healthy volunteers matched for age and sex were enrolled. None had known cardiovascular risk factors or overt pulmonary hypertension. All people underwent blood pressure measurement and transthoracic echocardiography. Cystic fibrosis patients showed higher sPAP [median 25 (IQR 21-30) vs 22 (22-22) mmHg; p = 0.02] and more frequent RV diastolic dysfunction (p < 0.001). Among cases, some RV systolic parameters were significantly altered than controls, such as TAPSE [20 (18-24) vs. 23 (21-28) mm; p = 0.001], FAC [34 (26-44) vs. 49 (48-50)%; p < 0.001], midwall tissue strain [- 25.0 (- 31.3 to - 22.8) vs. - 30.5 (- 31.8 to - 29.3)%; p = 0.03], apical tissue strain [- 22 (- 29.3 to - 19.0) vs. - 30.5 (- 32.8 to - 28.3)%; p = 0.001] and 2D strain [- 22.0 (- 25.1 to - 19.0) vs. - 29.5 (- 31.8 to - 27.3)%; p < 0.001]. Finally, 2D strain correlated with spirometric FEV1 (ρ = - 0.463, p = 0.03) and nearly with FEF25-75% (ρ = - 0.393, p = 0.07). Our study confirmed a RV subclinical systo-diastolic dysfunction in clinically stable patients affected by cystic fibrosis without overt pulmonary hypertension nor cardiovascular risk factors. This may be due to systemic inflammation and temporary recurrent pulmonary hypertension. We retain that RV 2D strain and TDI echocardiography could become an important tool in the follow-up of these patients.

On-Pump Coronary Artery Bypass Graft: The State of the Art.

BACKGROUND: Coronary artery bypass grafting (CABG) remains the standard of care for patients with coronary artery disease (CAD). Debate exists concerning several factors, which include percutaneous coronary intervention (PCI) vs. CABG, single vs. bilateral mammary artery grafts, radial artery vs. saphenous vein grafts, right internal mammary artery vs. radial artery grafts, endoscopic vs. open vein-graft harvesting, and on-pump vs. off- pump surgery. Moreover, challenging is the management of diabetic patients with CAD undergoing CABG. This review reports current indications, practice patterns, and outcomes of CABG. METHODS: Randomized controlled trials comparing CABG to other therapeutical strategies for CAD were searched through MEDLINE, EMBASE, Cochrane databases, and proceedings of international meetings. RESULTS: Large multicenter randomized and observational studies (SYNTAX, BEST, PRECOMBAT, ASCERT) have reported excellent outcomes in CABG patients, with always fewer rates of operative mortality and major morbidity, than PCI. The 10-year follow-up of ARTS II trial showed no difference between single and bilateral mammary artery. BARI 2D, MASS II, CARDia, FREEDOM trials showed that CABG is the best choice for diabetic patients. CONCLUSION: CABG still represents one of the most widespread major surgeries, with well-known benefits on symptoms and prognosis in patients with CAD. However, further studies and follow-up data are needed to validate these evidences.

The Effect of Chorionicity on Maternal Cardiac Adaptation to Uncomplicated Twin Pregnancy: A Prospective Longitudinal Study.

OBJECTIVE: The objective of this study was to longitudinally evaluate maternal echocardiographic findings in uncomplicated twin gestations according to chorionicity. METHODS: Healthy women with twin pregnancy were assessed with transthoracic echocardiography across the first, second, and third trimesters. Cardiac findings were compared within each group and between monochorionic (MC) and dicho-rionic (DC) pregnancies. RESULTS: Overall, 19 MC and 48 DC uncomplicated twin pregnancies were included. In the MC group, no significant maternal haemodynamic changes were documented across gestation, with the exception of a decrease in ejection fraction. Compared to DC pregnancies, in the MC set lower cardiac output (second and third trimester, p = 0.001 and p = 0.006, respectively) and higher total vascular resistance (first trimester, p = 0.032) were observed. Regarding the diastolic function in MC twins, significantly higher values were observed for mitral E/A ratio (third trimester, p = 0.014), septal mitral E1/A1 ratio (third trimester, p = 0.030), lateral mitral E1 (second and third trimester, p = 0.014 and p = 0.029, respectively), and E1/A1 ratio (third trimester, p = 0.006). CONCLUSIONS: Maternal cardiac adaptation in twin pregnancy seems to differ significantly according to chorionicity. In particular, in MC pregnancies the impairment of diastolic function is less pronounced, presumably due to the lower circulating volume.

Elastic properties of ascending aorta and ventricular-arterial coupling in women with previous pregnancy complicated by HELLP syndrome.

OBJECTIVE: To compare the elastic properties of the ascending aorta and ventricular-arterial coupling (VAC) in women with a previous pregnancy complicated by hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, women who experienced preeclampsia, and healthy controls. METHODS: Women with a history of preeclampsia (n = 60) or HELLP syndrome (n = 49) and matched healthy controls (n = 60) underwent transthoracic echocardiography at 6 months to 4 years after delivery. Aortic M-mode and tissue Doppler imaging (TDI) parameters were measured. Aortic diameters were assessed at end-diastole at four levels: Valsalva sinuses, sinotubular junction, tubular tract, and aortic arch. Aortic compliance, distensibility, stiffness index, Peterson's elastic modulus, pulse-wave velocity, and M-mode strain were calculated using standard formulae. Aortic expansion velocity, early and late diastolic retraction velocities, and peak systolic tissue strain (TDI-ε) were determined. VAC was defined as the ratio between aortic elastance (Ea) and left ventricular end-systolic elastance (Ees). All women were free from cardiovascular risk factors. RESULTS: Women with a history of HELLP syndrome showed larger aortas than those with previous preeclampsia or controls, probably related to a higher blood pressure. Aortic elastic properties, including Ea, were similar between HELLP and preeclampsia groups, even comparing cases with early-onset preeclampsia and HELLP. In contrast, Ees was more impaired in the HELLP group than in the other two. Consequently, about one-quarter of women who experienced HELLP syndrome had a pathological VAC, whereas only 5% of previously preeclamptic patients did. Multivariate analysis confirmed the association between HELLP syndrome and VAC, whereas other parameters including aortic compliance, distensibility, stiffness index, and elastic modulus are linked only to gestational age at preeclampsia onset, ad also Ea and Ees did. CONCLUSIONS: We found a significant overlap between the aortic elastic properties in women with a history of preeclampsia and those with a previous HELLP syndrome, suggesting a common pathophysiologic pathway. However, women who experienced HELLP syndrome showed a higher blood pressure than other cases and controls, probably determining larger aortas. In addition, VAC was more altered in the HELLP group than in the others because of a higher Ea and a lower Ees.

Systemic Lupus Erythematosus and Endothelial Dysfunction: A Close Relationship.

BACKGROUND: Accelerated atherosclerosis, responsible for premature cardiovascular disease, has been estimated to develop or progress in 10% of systemic lupus erythematosus (SLE) patients each year and to be 6-fold more frequent in SLE compared with the general population. The mechanisms underlying accelerated atherosclerosis in SLE are complex and involve classical and "non-classical" cardiovascular risk factors. Subclinical and disseminated atherosclerosis is associated with endothelial dysfunction and arterial stiffness. OBJECTIVE: The aim of this review is to analyze the association between SLE and endothelial dysfunction. RESULTS AND CONCLUSION: Different mechanisms have been proposed to explain the prevalence of endothelial dysfunction in SLE, which are briefly reported in this review: impaired clearance of apoptotic cells, oxidative stress markers, B cell activation with different circulating autoantibodies, different subtypes of T lymphocytes, cytokine cascade. Several studies and meta-analyses show a significant trend towards a prevalence of subclinical accelerated atherosclerosis in patients with SLE compared with healthy controls, since childhood. Based on general considerations, we suggest a multidisciplinary management to assess endothelial dysfunction at the diagnosis of the disease and to periodically search for and treat the traditional cardiovascular risk factors. Prospective studies are needed to confirm the benefits of this management.

Inappropriate left ventricular mass after preeclampsia: another piece of the puzzle Inappropriate LVM and PE.

Excessive left ventricular (LV) mass (LVM) increase results in inefficient LV work with high energy waste and a negative prognostic effect. We aimed to investigate the presence of inappropriate LVM and to calculate the myocardial mechanoenergetic efficiency index (MEEi) in asymptomatic women with a history of early-onset (EO) or late-onset (LO) pre-eclampsia (PE). Among all women diagnosed with PE in the years 2009-2013, after applying inclusion/exclusion criteria and cost-effectiveness analysis, we randomly selected thirty women who experienced EO-PE, thirty with a previous LO-PE and thirty healthy controls to undergo echocardiography from 6 months to 4 years after delivery. Data regarding gestational age (GA) and mean uterine artery (UtA) pulsatility index (PI) at PE onset were collected from medical records. All women were free from cardiovascular risk factors. LVM excess was calculated as the ratio between observed LVM and predicted LVM (by sex, stroke work and height), while MEEi was calculated as the ratio between stroke work and "double product" (to approximate energy consumption), indexed to LVM. Concentric remodeling was present in 60% of EO-PE and 53% of LO-PE. LVM excess was significantly more often present in the EO-PE group than in the control group. LVM was inappropriate in 52% of EO-PE and 17% of LO-PE. MEEi showed a tendency towards lower values in the EO-PE group. Multivariate regression analysis showed that both LVM excess and MEEi were independently associated with lower GA and higher mean UtA PI at PE onset. Inappropriate LVM with a tendency towards reduced MEEi in the first 4 years after delivery may partially explain the elevated cardiovascular risk in former pre-eclamptic women compared to the general population.

Echocardiographic evaluation of diastolic dysfunction in young and healthy patients with psoriasis: A case-control study.

Psoriasis is a systemic inflammatory disease with a great prevalence in general population. The inappropriate activation of the cellular immune system has been hypothesized to be an independent cardiovascular risk factor, given the higher incidence of cardiovascular disorders in psoriatic patients. Echocardiographic abnormalities have been demonstrated too: the aim of our study was to evaluate the presence of preclinical cardiac dysfunction in a cohort of psoriatic patients without cardiovascular risk factors. We enrolled 52 patients with the diagnosis of chronic plaque psoriasis, compared with a control group not affected by any relevant systemic diseases and inflammatory disorders. In all patients and control group, echocardiographic conventional and tissue Doppler (TDI) studies were conducted. The analysis of echocardiographic parameters revealed normal dimension, mass and systolic function of the left ventricle. Left ventricular diastolic dysfunction was found in 36.5% patients in the psoriasis group versus 0% in control group, and significant reduction of the E/A ratio was found also for the right ventricle. A significant increase of mitral regurgitation has been found in psoriatic patients (p=0.005). The early recognition of cardiovascular pre-clinic disease in psoriatic patients may guide a strict follow up and an early treatment, potentially improving cardiovascular prognosis.

Prognostic evaluation of the elastic properties of the ascending aorta in dilated cardiomyopathy.

BACKGROUND: Nowadays there is an increased interest in the role of aortic stiffness in the pathophysiology of heart failure (HF), as it is a major determinant of left ventricular (LV) performance. We aimed at assessing the predictive value of the aortic stiffness parameters, measured by echocardiography, in patients affected by nonischaemic dilated cardiomyopathy (DCM) regarding three end-points: death, HF rehospitalization, combined death or HF rehospitalization in a long-term follow-up. MATERIALS AND METHODS: A total of 202 patients affected by nonischaemic DCM underwent an outpatient examination by echocardiography and blood pressure check at the brachial artery, in order to calculate aortic elastic properties (ie, compliance, distensibility, stiffness index, Peterson's elastic modulus, M-mode strain). ROC curves, Kaplan-Meier curves and multivariable Cox regressions (correcting for age, LV ejection fraction (LVEF), atrial fibrillation, cardiac resynchronization therapy (CRT)) were run to assess the predictive ability of aortic elastic properties against the 3 end-points. RESULTS: Mean follow-up was 9.83 ± 2.80 years. 24.8% of patients died, while 34.7% were rehospitalized for HF cause and 44.6% experienced the combined end-point. LVEF did not correlate with aortic elastic properties. ROC curves and Kaplan-Meier curves were elaborated. Aortic stiffness did not predict death in our cohort. Otherwise, all aortic elastic properties predicted HF rehospitalization and combined death or HF rehospitalization, after correcting for age, LVEF, atrial fibrillation, CRT. CONCLUSIONS: Elastic properties of the ascending aorta measured by echocardiography in patients with nonischaemic DCM predict long-term HF rehospitalization and combined death or HF rehospitalization, also after correcting for the confounding factors.

Kounis syndrome, a disease to know: Case report and review of the literature.

The case deals with an anaphylactoid reaction to intravenous ampicillin/sulbactam resulting in cardiogenic syncope and myocardial damage. Symptoms and ECG modifications promptly disappeared after corticosteroids administration. The Kounis syndrome is an acute coronary syndrome, including coronary spasm, acute myocardial infarction and stent thrombosis, resulting from an anaphylactic or anaphylactoid or allergic or hypersensitivity insult. First described in 1991, it can be caused by a lot of substances, particularly antibiotics. The management should be directed to both the allergic reaction and the myocardial damage. The Kounis syndrome is a not rare disease that every physician should know because of the wideness of triggers and the possible fatal evolution if not promptly recognized.

Mechanism of cardiovascular toxicity by proteasome inhibitors: New paradigm derived from clinical and pre-clinical evidence.

Proteasome Inhibitors (PI) have now become the cornerstone of treatment of multiple myeloma (MM). Carfilzomib has been demonstrated to cause more frequent cardiovascular side effects such as dyspnea, hypertension, and heart failure. Recent pre-clinical studies have investigated the effects of proteasome on myocardial and vascular cells, but the pathogenic mechanism underlying the effects of proteasome inhibition on these cells is poorly understood. We reviewed the evidence from clinical trials, post-hoc analysis and small observational studies currently available and summarized the data from experimental, focusing on the pathogenic mechanisms potentially implicated in the cardiovascular toxicity of proteasome inhibitor, particularly of carfilzomib that is most responsible for cardiovascular side effects. Finally, we tried to suggest future perspectives for diagnostic and therapeutic approach to this type of cardiovascular damage.

Effects of ivabradine on endothelial function, aortic properties and ventricular-arterial coupling in chronic systolic heart failure patients.

AIM: Heart rate (HR) is an important prognostic factor in patients affected by chronic heart failure (CHF); ivabradine has been demonstrated to significantly reduce nonfatal myocardial infarction and hospitalization rate for acute heart failure and to improve left ventricular (LV) reverse remodeling, quality of life, exercise capacity, and arterial elastance (Ea) in these patients. We aimed at evaluating the short-term effects of ivabradine on ventricular-arterial coupling (VAC), aortic stiffness, and endothelial function in stable patients with CHF. METHODS: We evaluated 30 consecutive CHF patients (LVEF≤ 35%, NYHA class II) with sinus rhythm and HR ≥ 70 bpm on optimized pharmacological therapy. All of them underwent both transthoracic echocardiogram to assess aortic elastic properties (aortic distensibility, AD; aortic stiffness index, ASI; systolic aortic strain, SAS) and VAC, and peripheral arterial tonometry to measure endothelial function. Therapy with ivabradine 5 mg bid was added and each patient was evaluated with the same examinations after 4 months. RESULTS: At the baseline, 73% of patients had impaired VAC and 63% endothelial dysfunction. After 4 months, there was a significant improvement in the VAC value (ΔVAC -0.10 ± 0.18, P = .021), mainly linked to Ea (ΔEa -0.40 ± 0.23 mm Hg/mL; P = .003). All the parameters of aortic elasticity underwent significant improvement (ΔAD 1.82 ± 1.43 cm² × dyn- ¹, P = .004; ΔASI -4.73 ± 6.07, P = .033; ΔSAS -7.98 ± 4.37%, P = .003). Lastly, we also noted a significant improvement of endothelial function (Δ RHI 0.35 ± 0.35; P < .001). At follow-up 40% of patients had impaired VAC (P = .018) and 33% endothelial dysfunction (P = .038). CONCLUSION: In patients with CHF adding ivabradine on top to the standard optimized medical therapy, when indicated, seems to improve endothelial function, aortic properties, and VAC.

The role of type 2 diabetes mellitus on hypertensive-related aortic stiffness.

BACKGROUND: Hypertension is strongly related to arterial stiffness in a cause-effect fashion. Diabetes mellitus is also thought to determine vascular damage, mostly by means of advanced glycosylation end-products (AGEs). Aim of our study was to study the role of type 2 diabetes mellitus (T2DM) as regard ascending aortic elastic properties in hypertensive patients. METHODS: We prospectively enrolled outpatients with hypertension (n = 99) and type 2 diabetes mellitus plus hypertension (n = 42) without cardiovascular events. They underwent a transthoracic echocardiography to measure aortic diameters, aortic elastic properties (ie, compliance, distensibility, stiffness index, Peterson's elastic modulus, pulse wave velocity, M-mode strain), tissue Doppler imaging (TDI) to calculate diastolic (E' and A') and systolic (S') velocities, and tissue strain. Multivariable analysis was run to assess the association between T2DM and these variables after correcting for possible confounders (age, sex, body mass index [BMI], dyslipidemia). RESULTS: The two groups did not differ as regards age, sex, BMI, and blood pressure. However, T2DM patients were more likely to be dyslipidemic (43% vs 71%, P = .003). Aortic diameters were similar in the two groups, but the aortic elastic properties significantly more impaired in T2DM group. At multivariable analysis, stiffness index, Peterson's elastic modulus, the TDI waves, and the tissue strain remained associated with the co-presence of T2DM and hypertension. CONCLUSION: Our data suggest that people suffering from both T2DM and hypertension have more impaired aortic elastic properties than those hypertensive alone. Considering the prognostic role of aortic stiffness, these patients may benefit from a closer follow-up.

Endothelial dysfunction assessment by noninvasive peripheral arterial tonometry in patients with chronic obstructive pulmonary disease compared with healthy subjects.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of cardiovascular disease. The endothelial dysfunction likely plays a central role in increasing cardiovascular risk. OBJECTIVES: This cross-sectional, study investigated the prevalence and extent of endothelial dysfunction in patients with stable COPD. METHODS: Peripheral arterial tonometry (PAT) was measured by post-ischemic reactive hyperemia index (RHI) in 16 COPD patients, 16 healthy controls and 16 subjects with treated systemic arterial hypertension (AH) and analysed with covariates condition (dyslipidemia, and medications). RESULTS: The prevalence of endothelial dysfunction was significantly higher in COPD group than in the other groups. Mean RHI was significantly lower in COPD patients compared with the other groups. At linear regression FEV1 and RHI were directly correlated (Spearman index = 0.553; P = .026). COPD patients in groups C and D according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages showed lower RHI compared with patients classified as A and B (P < .01). At multiple regression analysis the presence of dyslipidemia, COPD and AH were associated with the presence of endothelial dysfunction. CONCLUSIONS: Endothelial dysfunction in stable COPD patients is probably implicated in the high cardiovascular comorbidity. This study suggests the potential utility of endothelial dysfunction evaluation in patients with COPD to a timely assessment and treatment for cardiac complications.