Impaired Left Ventricular Performance Research Articles

Mesenchymal stem cells improve cardiac function in diabetic rats by reducing cardiac injury biomarkers and downregulating JAK/STAT/iNOS and iNOS/Apoptosis signaling pathways

Cardiovascular complications are prevalent manifestations of type 2 diabetes mellitus (T2DM) and are usually the main cause of death. This study aims to show the underlying mechanisms of the potential therapeutic effect of mesenchymal stem cells (MSCs) on diabetic cardiac dysfunction. Twenty-four male Wistar rats were randomly assigned to one of three groups The control group received standard laboratory chow, and the groups with T2DM received a single dose of 45 mg/kg body weight of streptozotocin (STZ) after 3 weeks of pretreatment with a high-fat diet (HFD). Eight weeks after the diagnosis of T2DM, rats were divided into two groups: the T2DM model group and the T2DM + MSCs group. BM-MSCs were administered systemically at 2 × 106 cells/rat doses.A Significant amelioration in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and dyslipidemia was noted 2 weeks post-administration of MSCs. Administration of MSCs improved dyslipidemia, the altered cardiac injury biomarkers (p ≤ 0.0001), downregulated Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)/inducible Nitric oxide synthase (iNOS) and iNOS/Apoptosis signaling pathways. This was associated with improved cardiac dysfunction (impaired left ventricular performance and decreased contractility index).Our results show that MSCs ameliorate cardiac dysfunction associated with diabetic cardiomyopathy by lowering dyslipidemia and insulin resistance, inhibiting oxidative stress, and inflammation, downregulating JAK2/STAT3/iNOS and iNOS/Apoptosis signaling pathways.

Echocardiography Assessment of Left Ventricular Function in Extremely Preterm Infants, Born at Less Than 28 Weeks’ Gestation, With Bronchopulmonary Dysplasia and Systemic Hypertension

The survival of smaller and more immature premature infants has been associated with lifelong cardiorespiratory comorbidities. Infants with bronchopulmonary dysplasia (BPD) undergo routine screening echocardiography to evaluate for development of chronic pulmonary hypertension, a late manifestation of pulmonary vascular disease. Our aim was to evaluate left ventricular (LV) performance in infants with BPD and pulmonary vascular disease who developed systemic hypertension. We hypothesized that infants with hypertension were more likely to have impaired LV performance. We present a single-center cross-sectional study of premature infants born at less than 28 0/7weeks'gestational age with a clinical diagnosis of BPD. Infants were categorized by the systolic arterial pressure (SAP) at time of echocardiography as hypertensive (SAP ≥90mm Hg) or normotensive (SAP <90mm Hg). Sixty-four patients were included. Infants with hypertension showed altered LV diastolic function with prolonged tissue Doppler imaging-derived isovolumic relaxation time (54.2±5.1 vs 42.9±8.2, P<.001), lower E:A, and higher E:e'. Indices of left heart volume/pressure loading (left atrium:aorta and LV end-diastolic volume [6.1±2 vs 4.2±1.2, P<.001]) were also higher in the hypertensive group. Finally, infants in the hypertensive group had higher pulmonary vascular resistance index (4.42±1.1 vs 3.69±0.8, P=.004). We conclude that extremely preterm infants with BPD who develop systemic hypertension are at risk of abnormal LV diastolic dysfunction. Increased pulmonary vascular resistance index in the hypertensive group may relate to pulmonary venous hypertension secondary to LV dysfunction. This is an important consideration in this cohort when selecting the physiologically most appropriate treatment.

Speckle-tracking echocardiography provides sensitive measurements of subtle early alterations associated with cardiac dysfunction in T2DM rats

BackgroundDiabetic cardiomyopathy results in cardiac structural and functional abnormalities. Previous studies have demonstrated that inhibiting the RhoA/ROCK signalling pathway increases the injury resistance of cardiomyocytes. The early detection of cardiac structural and functional alterations may facilitate an improved understanding of the pathophysiologic progress and guide therapy. This study aimed to identify the optimal diagnostic measures for the subtle early alterations of cardiac dysfunction in type 2 diabetes mellitus (T2DM) rats.MethodsTwenty-four rat models were divided into four groups and received treatments for 4 weeks: the CON group (control rats), the DM group (T2DM rats), the DMF group (T2DM rats receiving fasudil) and the CONF group (control rats receiving fasudil) group. Left ventricular (LV) structure was quantified by histological staining and transmission electron microscopy. LV function and myocardial deformation were assessed by high-frequency echocardiography.ResultsTreatment with fasudil, a ROCK inhibitor, significantly protected against diabetes-induced myocardial hypertrophy, fibrosis and mitochondrial dysfunction. Impaired LV performance was found in T2DM rats, as evidenced by significant reductions in the ejection fraction (EF), fractional shortening (FS) and the mitral valve (MV) E/A ratio (which decreased 26%, 34% and 20%, respectively). Fasudil failed to improve the conventional ultrasonic parameters in T2DM rats, but the myocardial deformation measured by speckle-tracking echocardiography (STE) were significantly improved (global circumferential strain, GCS: P = 0.003; GCS rate, GCSR: P = 0.021). When receiver operating characteristic (ROC) curves were used in combination with linear regression analysis, STE parameters were found to be characterized by both optimal prediction of cardiac damage [AUC (95% CI): fractional area change, FAC: 0.927 (0.744, 0.993); GCS: 0.819 (0.610, 0.945); GCSR: 0.899 (0.707, 0.984)] and stronger correlations with cardiac fibrosis (FAC: r = -0.825; GCS: r = 0.772; GCSR: r = 0.829) than conventional parameters.ConclusionThe results suggest that STE parameters are more sensitive and specific than conventional parameters in predicting the subtle cardiac functional changes that occur in the early stage, providing new insight into the management of diabetic cardiomyopathy.

Impaired Left Ventricular Circumferential Midwall Systolic Performance Appears Linked to Depressed Preload, but Not Intrinsic Contractile Dysfunction or Excessive Afterload, in Paradoxical Low-Flow/Low-Gradient Severe Aortic Stenosis.

Paradoxical low-flow/low-gradient aortic stenosis (P-LFLG-AS) occurs in about one-third of patients with severe AS and preserved left ventricular (LV) ejection fraction (EF). Our aim was to differentiate between altered LV loading conditions and contractility as determinants of subtle LV systolic dysfunction in P-LFLG-AS. We retrospectively analyzed medical records of patients with isolated severe degenerative AS and preserved EF (30 subjects with P-LFLG-AS and 30 patients with normal-flow/high-gradient severe AS (NFHG-AS)), without relevant coexistent diseases (e.g., diabetes, coronary artery disease and chronic kidney disease) or any abnormalities which could account for a low-flow state. Patients with P-LFLG-AS and NFHG-AS did not differ in aortic valve area index and most clinical characteristics. Compared to NFHG-AS, subjects with P-LFLG-AS exhibited smaller LV end-diastolic diameter (LVd) (44 ± 5 vs. 54 ± 5 mm, p < 0.001) (consistent with lower LV preload) with pronounced concentric remodeling, higher valvulo-arterial impedance (3.8 ± 1.1 vs. 2.2 ± 0.5 mmHg per mL/m2, p < 0.001) and diminished systemic arterial compliance (0.45 ± 0.11 vs. 0.76 ± 0.23 mL/m2 per mmHg, p < 0.001), while circumferential end-systolic LV midwall stress (cESS), an estimate of afterload at the LV level, was similar in P-LFLG-AS and NFHG-AS (175 ± 83 vs. 198 ± 69 hPa, p = 0.3). LV midwall fractional shortening (mwFS) was depressed in P-LFLG-AS vs. NFHG-AS (12.3 ± 3.5 vs. 14.7 ± 2.9%, p = 0.006) despite similar EF (61 ± 6 vs. 59 ± 8%, p = 0.4). By multiple regression, the presence of P-LFLG-AS remained a significant predictor of lower mwFS compared to NFHG-AS upon adjustment for cESS (β ± SEM: −2.35 ± 0.67, p < 0.001); however, the significance was lost after further correction for LVd (β = −1.10 ± 0.85, p = 0.21). In conclusion, the association of P-LFLG-AS with a lower cESS-adjusted mwFS, an index of afterload-corrected LV circumferential systolic function at the midwall level, appears secondary to a smaller LV end-diastolic cavity size according to the Frank–Starling law. Thus, low LV preload, not intrinsic contractile dysfunction or excessive afterload, may account for impaired LV circumferential midwall systolic performance in P-LFLG-AS.

Prevalence and Outcomes of Primary Left Ventricular Dysfunction in Marfan Syndrome

Even in the absence of significant valvular disease, patients with Marfan syndrome (MFS) have evidence of impaired left ventricular (LV) performance, suggestive of a primary cardiomyopathy. However, the true prevalence and long-term outcomes of this disease process remain largely unknown. We performed a retrospective analysis of all adult patients with confirmed MFS followed at Stanford Health Care. Those with significant valvular regurgitation, coronary artery disease, or previous cardiac surgery were excluded. LV systolic dysfunction was defined as a LV ejection fraction (LVEF) <55% on transthoracic echocardiography. A total of 753 patients with confirmed MFS were followed up over a median duration of 8 years (interquartile range 4 to 13). Of those, 241 patients (53% women, 71% White) met inclusion criteria and comprised the study cohort. LV systolic dysfunction was present in 30 patients (12%), with a median age of onset of 25 years (interquartile range 19 to 37), median EF of 52% (interquartile range 48 to 54), and evidence of clinical heart failure (New York Heart Association functional class ≥II) in 10% of patients. LV systolic dysfunction was more common in patients with larger aortic root diameters (≥4.0 cm: Odds ratio=4.5, 95% confidence interval=1.2 to 17.1) but was not associated with other cardiovascular manifestations of MFS or traditional atherosclerotic risk factors. In conclusion, apart from significant valvular pathology, LV systolic dysfunction was prevalent in MFS from a young age, suggestive of a primary cardiomyopathy. LV dysfunction was typically mild and subclinical and occurred more commonly in patients with more pronounced aortopathies.

Associations between the Severity of the Post-Acute COVID-19 Syndrome and Echocardiographic Abnormalities in Previously Healthy Outpatients Following Infection with SARS-CoV-2.

Simple SummaryWith the COVID-19 pandemic lasting over a year and affecting all continents, a new problem has arisen—that of convalescents, who continue to have various symptoms at more than 4 and up to 12 weeks after the acute disease, the so called post-acute COVID-19 syndrome. In this article, we tried to determine if previously healthy adults with post-acute COVID-19 syndrome also have cardiac complications related to the number of persisting symptoms, the quality of life scores and the initial pulmonary injury. Using transthoracic echocardiography, we found cardiac abnormalities (pulmonary hypertension, systolic and diastolic dysfunction, pericarditis) in about a quarter of the 150 participants in our study. Their gravity was significantly correlated with the severity of COVID-19, the number of weeks passed since the acute illness, the number of persisting symptoms, and the quality of life. Post-acute COVID-19 is a recently proposed term which aims to characterize the various symptoms persisting after an acute SARS-CoV-2 infection, their severity being explained partially by residual multi-system alterations, with an important impact on the functional status and quality of life of the affected individuals.The COVID-19 pandemic affected over 130 million individuals during more than one year. Due to the overload of health-care services, a great number of people were treated as outpatients, many of them subsequently developing post-acute COVID-19 syndrome. Our study was conducted on 150 subjects without a history of cardiovascular diseases, treated as outpatients for a mild/moderate form of COVID-19 4 to 12 weeks prior to study inclusion, and who were diagnosed with post-acute COVID-19 and attended a cardiology evaluation with transthoracic echocardiography (TTE) for persisting symptoms. We detected various cardiac abnormalities in 38 subjects (25.33%), including pulmonary hypertension (9.33%), impaired left ventricular performance (8.66%), diastolic dysfunction (14%) and/or evidence of pericarditis (10%). We highlighted statistically significant correlations between the intensity of symptoms and quality of life scores with the severity of initial pulmonary injury, the number of weeks since COVID-19 and with TTE parameters characterizing the systolic and diastolic performance and pulmonary hypertension (p < 0.001). (Post-acute COVID-19 is a complex syndrome characterized by various symptoms, the intensity of which seem to be related to the severity and the time elapsed since the acute infection, and with persisting cardiac abnormalities.

Abstract 14712: Cardiometabolic Differences Between Male and Female Obese-insulin Resistant Rats Following Sex Hormone Deprivation

Introduction: Male gender and menopause increase the risk for cardiovascular incidence. However, less is known about gender differences in cardiometabolic disorders, particularly under obese-insulin resistant and sex hormone-deprived conditions. Hypothesis: Male have worse cardiometabolic disorders than female under obese-insulin resistant and sex hormone-deprived conditions. Methods: Adult Wistar rats of both sexes (n=20) were randomly assigned into four groups (n = 5/group): male normal diet sham (M-NDS), male high fat-diet with orchiectomy (M-HFO), female normal diet sham (F-NDS) and female high fat-diet with ovariectomy (F-HFO). Rats were fed either a normal diet (19.77% of energy fat) or a high-fat diet (57.60% of energy fat) for 12 weeks following the induction of sex hormone deprivation by either bilateral orchiectomy or ovariectomy. Temporal determinations of metabolic parameters, heart rate variability (HRV), left ventricular (LV) function, and cardiac mitochondrial function at 4, 8, and 12 weeks were done after starting each feeding program. Results: Insulin resistance was initially observed after 8 weeks of high-fat diet consumption in both M-HFO and F-HFO groups. In addition, M-HFO had depressed HRV, impaired LV performance indicated by decreased ejection fraction (%EF) and cardiac mitochondrial dysfunction indicated by increased mitochondrial ROS level, depolarization and swelling, as early as week 4, whereas F-HFO exhibited them at week 8 or 12. Moreover, at week 12, M-HFO have worse cardiometabolic disorders than F-HFO, particularly %EF and HRV. Conclusions: Under sex hormone-deprived condition, male are generally more susceptible to cardiometabolic disorders and cardiac mitochondrial dysfunction, especially in the presence of obese-insulin resistant condition.

From the Editor's Desk…

From the Editor's Desk…

Abstract P2003: Loss of Trpa1 in Mice Leads to Age-Related Dilated Cardiomyopathy

Activation of the transient receptor potential ankyrin 1 (TRPA1) channel, a mechanical and oxidative stress sensor, has been shown to slow down aging process and promote longevity in invertebrate animal models like Caenorhabditis elegans . Although physiologic sensory functions of TRPA1 are conservative across species, the role of TRPA1 in regulation of organ development and function in mammals in the aging process is unknown. The present study tests the hypothesis that TRPA1 ablation leads to cardiac dilation and cardiomyopathy in aging mice. Echocardiography was performed in male 12-week-old (young) and 52-week-old (older) Trpa1 gene knockout ( Trpa1 -/- ) mice and wild-type (WT) littermates on a mixed C57BL/6 x 129 genetic background. Echocardiogram data showed that, compared to young WT littermates, young Trpa1 -/- mice had similar cardiac dimensions and left ventricular function, as demonstrated by left ventricular end-diastolic internal dimension (LVIDd, WT 4.29±0.62 vs. Trpa1 -/- 4.50±0.41 mm, P&gt;0.05), left ventricular ejection fraction (LVEF, a parameter of systolic function, WT 66.73±9.50 vs. Trpa1 -/- 63.39±12.76 %, P&gt;0.05), and E/A ratio (a parameter of diastolic function, WT 1.23±0.03 vs. Trpa1 -/- 1.39±0.14, P&gt;0.05). In contrast, older Trpa1 -/- mice developed dilated cardiomyopathy with dilated left ventricle (LVIDd: WT 4.60±0.16 vs. Trpa1 -/- 5.00±0.37 mm, P&lt;0.05) and impaired left ventricular systolic function (LVEF: WT 58.04±9.27 vs. Trpa1 -/- 41.79±7.19 %, P&lt;0.05) when compared to older WT mice. In addition, older Trpa1 -/- mice had impaired left ventricular myocardial performance index (LV MPI, a parameter of ventricular systolic and diastolic function, WT 0.62±0.15 vs. Trpa1 -/- 0.89±0.18, P&lt;0.05) albeit left ventricular diastolic function was not different between old Trpa1 -/- and WT mice (E/A ratio: WT 1.53±0.22 vs. Trpa1 -/- 1.99±0.92, P&gt;0.05). These results show that genetic knockout of TRPA1 leads to age-related left ventricular dilation and systolic dysfunction. These findings suggest that TRPA1 activation protects against age-related dilated cardiomyopathy.

Contribution of Levosimendan in Weaning from Mechanical Ventilation in Patients with Left Ventricular Dysfunction: A Pilot Study.

Purpose Mechanically ventilated patients with left ventricular (LV) dysfunction are at risk of weaning failure. We hypothesized that optimization of cardiovascular function might facilitate the weaning process. Therefore, we investigated the efficacy of levosimendan in difficult-to-wean patients with impaired LV performance. Materials and Methods Nineteen mechanically ventilated patients, with LV ejection fraction (LVEF) 34 ± 8%, difficult-to-wean from the ventilator, were assessed by transthoracic echocardiography before the start and at the end of a spontaneous breathing trial (SBT) (first SBT). Eight patients successfully weaned. The remaining 11 failed-to-wean patients received a 24-hour infusion of levosimendan, and they were reassessed during a second SBT. Results After levosimendan administration, LVEF increased from 30 ± 10 to 36 ± 3% (p=0.01). End-SBT peak e′ velocity increased from 7 to 9 cm/s (p=0.02). E/e′ increased from 10.5 to 12.9 during the first SBT, whereas it remained constant at 10 throughout the second SBT (p=0.01). During the second SBT, partial pressure of arterial oxygen and central venous oxygen saturation improved, compared to the first one (93 ± 34 vs. 67 ± 28 mmHg, p=0.03, and 66 ± 11% vs. 57 ± 9%, p=0.02, respectively). Nine of the 11 patients were successfully weaned from the ventilator. Conclusions In difficult-to-wean from mechanical ventilation patients with LV dysfunction, levosimendan might contribute to successful weaning by improving both systolic and diastolic LV function.

Depressed systemic arterial compliance and impaired left ventricular midwall performance in aortic stenosis with concomitant type 2 diabetes: a retrospective cross-sectional study

BackgroundDegenerative aortic stenosis (AS), a disease of the elderly, frequently coexists with concomitant diseases, including type 2 diabetes (T2DM) which amplifies the cardiovascular (CV) risk. T2DM affects left ventricular (LV) structure and function via hemodynamic and metabolic factors. In concentric LV geometry, typical for AS, indices of LV midwall mechanics are better estimates of LV function than ejection fraction (EF). Effects of T2DM coexisting with AS on circumferential LV midwall systolic function and large artery properties have not been reported so far. Our aim was to compare characteristics of AS patients with and without T2DM, with a focus on LV midwall systolic function and arterial compliance.MethodsMedical records of 130 electively hospitalized patients with moderate or severe isolated degenerative AS were retrospectively analyzed. Exclusion criteria included clinical instability, atrial fibrillation, coronary artery disease and relevant non-cardiac diseases. From in-hospital echocardiography and blood pressure, we calculated LV midwall fractional shortening (mwFS), circumferential end-systolic LV wall stress (cESS) and valvulo-arterial impedance (Zva), estimates of LV afterload, as well as systemic arterial compliance.ResultsPatients with (n = 50) and without T2DM (n = 80) did not differ in age, AS severity, LV mass and LV diastolic diameter. T2DM patients exhibited elevated cESS (247 ± 105 vs. 209 ± 84 hPa, p = 0.025) and Zva (5.8 ± 2.2 vs. 5.1 ± 1.8 mmHg per mL/m2, p = 0.04), and lower stroke volume index (33 ± 10 vs. 38 ± 12 mL/m2, p = 0.01) and systemic arterial compliance (0.53 ± 0.16 vs. 0.62 ± 0.22 mL/m2 per mmHg, p = 0.01). mwFS (11.9 ± 3.9 vs. 14.1 ± 3.7%, p = 0.001), but not EF (51 ± 14 vs. 54 ± 13%, p = n.s.), was reduced in T2DM. mwFS and cESS were inversely interrelated in patients both with (r = − 0.59, p < 0.001) and without T2DM (r = − 0.53, p < 0.001) By multiple regression, higher cESS (p < 0.001) and T2DM (p = 0.02) were independent predictors of depressed mwFS.ConclusionsIn AS, coexistent T2DM appears associated with reduced systemic arterial compliance and LV dysfunction at the midwall level, corresponding to slightly depressed myocardial contractility.

Impact of procedure‐related conduction disturbances after transcatheter aortic valve implantation on myocardial performance and survival evaluated by conventional and speckle tracking echocardiography

Although procedure-related new cardiac conduction disturbances (CCDs) remain an important issue in transcatheter aortic valve implantation (TAVI), their effect on myocardial function and overall patient outcome remains unclear. The goal of this study was to analyze the influence of procedure-related CCDs on systolic and diastolic LV performance and on patient survival after TAVI. Ninety-five patients who underwent TAVI for severe symptomatic aortic stenosis (AS) and had a complete follow-up were evaluated with respect to procedure-related CCDs. Left ventricular (LV) performance was measured using standard echocardiographic parameters and speckle tracking analysis. Survival was assessed during longer-term follow-up (mean: 29.1±16.9months). After TAVI, the improvement of global LV function expressed as ejection fraction (LVEF; from 45.5±10.0 to 47.8±13.9%, P=.13) was not significant. New CCDs were found in 35.7% of TAVI recipients. A comparison between patients with and without new CCDs showed that LV systolic function improved in those without CCDs, while it tended to deteriorate in patients with CCDs (change in LVEF: 5.5±12.3% vs -4.9%±11.5%, P=.001; change in global longitudinal strain (GLS): -1.1±4.6% vs 1.2±4.5%, P=.01). Changes in diastolic function did not differ significantly between the groups (changes in transmitral E/A-ratio: -0.3±0.6 vs -0.5±0.5, P=.1). Kaplan-Meier survival analysis revealed no significant differences between the two cohorts (P=.795). Procedure-related conduction abnormalities after TAVI lead to an LBBB-related dyssynchrony with impairment of LV performance but not of overall survival.

Left ventricular function in relation to chronic residential air pollution in a general population.

BackgroundIn view of the increasing heart failure epidemic and awareness of the adverse impact of environmental pollution on human health, we investigated the association of left ventricular structure and function with air pollutants in a general population.MethodsIn 671 randomly recruited Flemish (51.7% women; mean age, 50.4 years) we echocardiographically assessed left ventricular systolic strain and strain rate and the early and late peak velocities of transmitral blood flow and mitral annular movement (2005−2009). Using subject-level data, left ventricular function was cross-sectionally correlated with residential long-term exposure to air pollutants, including black carbon, PM2.5, PM10 (particulate matter) and nitrogen dioxide (NO2), while accounting for clustering by residential address and confounders.ResultsAnnual exposures to black carbon, PM2.5, PM10 and NO2 averaged 1.19, 13.0, 17.7, and 16.8 µg/m3. Systolic left ventricular function was worse (p ≤ 0.027) with higher black carbon, PM2.5, PM10 and NO2 with association sizes per interquartile interval increment ranging from −0.339 to −0.458% for longitudinal strain and from −0.033 to −0.049 s−1 for longitudinal strain rate. Mitral E and a′ peak velocities were lower (p ≤ 0.021) with higher black carbon, PM2.5 and PM10 with association sizes ranging from −1.727 to −1.947 cm/s and from −0.175 to −0.235 cm/s, respectively. In the geographic analysis, the systolic longitudinal strain sided with gradients in air pollution. The path analysis identified systemic inflammation as a possible mediator of associations with black carbon.ConclusionsLong-term low-level air pollution is associated with subclinical impairment of left ventricular performance and might be a risk factor for heart failure.

Vorticity is a marker of diastolic ventricular interdependency in pulmonary hypertension.

Our objective was to determine whether left ventricular (LV) vorticity (ω), the local spinning motion of a fluid element, correlated with markers of ventricular interdependency in pulmonary hypertension (PH). Maladaptive ventricular interdependency is associated with interventricular septal shift, impaired LV performance, and poor outcomes in PH patients, yet the pathophysiologic mechanisms underlying fluid-structure interactions in ventricular interdependency are incompletely understood. Because conformational changes in chamber geometry affect blood flow formations and dynamics, LV ω may be a marker of LV-RV (right ventricular) interactions in PH. Echocardiography was performed for 13 PH patients and 10 controls for assessment of interdependency markers, including eccentricity index (EI), and biventricular diastolic dysfunction, including mitral valve (MV) and tricuspid valve (TV) early and late velocities (E and A, respectively) as well as MV septal and lateral early tissue Doppler velocities (e'). Same-day 4-dimensional cardiac magnetic resonance was performed for LV E (early)-wave ω measurement. LV E-wave ω was significantly decreased in PH patients (P = 0.008) and correlated with diastolic EI (Rho = -0.53, P = 0.009) as well as with markers of LV diastolic dysfunction, including MV E(Rho = 0.53, P = 0.011), E/A (Rho = 0.56, P = 0.007), septal e' (Rho = 0.63, P = 0.001), and lateral e' (Rho = 0.57, P = 0.007). Furthermore, LV E-wave ω was associated with indices of RV diastolic dysfunction, including TV e' (Rho = 0.52, P = 0.012) and TV E/A (Rho = 0.53, P = 0.009). LV E-wave ω is decreased in PH and correlated with multiple echocardiographic markers of ventricular interdependency. LV ω may be a novel marker for fluid-tissue biomechanical interactions in LV-RV interdependency.

Obese-insulin resistance accelerates and aggravates cardiometabolic disorders and cardiac mitochondrial dysfunction in estrogen-deprived female rats.

Women have a lower incidence of cardiovascular diseases (CVD) than men at a similar age but have an increased incidence of CVD and metabolic syndrome after menopause, indicating the possible protective effects of estrogen on cardiometabolic function. Although obesity is known to increase CVD risks, its impact on the heart on estrogen deprivation is still inconclusive. We investigated the effects of obese-insulin resistance on cardiometabolic function in estrogen-deprived ovariectomized rats. Adult female ovariectomized (O) or sham (S)-operated rats randomly received either normal diet (ND, 19.77 % fat) or high-fat diet (HF, 57.60 % fat) (n = 6/group) for 12 weeks. The heart rate variability (HRV), left ventricular (LV) performance, cardiac autonomic balance, cardiac mitochondrial function, metabolic parameters, oxidative stress, and apoptotic markers were determined at 4, 8, and 12 weeks. Insulin resistance developed at week 8 in NDO, HFS, and HFO rats as indicated by increased plasma insulin and HOMA index. However, only HFO rats had elevated plasma cholesterol level at week 8, whereas HFS rats had showed elevation at week 12. In addition, only HFO rats had depressed HRV, impaired LV performance indicated by decreased fractional shortening (%FS) and cardiac mitochondrial dysfunction indicated by increased mitochondrial ROS level, mitochondrial depolarization and swelling, as early as week 8, whereas other groups exhibited them at week 12. Either estrogen deprivation or obesity alone may impair metabolic parameters, cardiac autonomic balance, and LV and mitochondrial function. However, an obese insulin-resistant condition further accelerated and aggravated the development of these cardiometabolic impairments in estrogen-deprived rats.

Subacute giant left ventricular pseudoaneurysm mimicking pneumonia.

Case report A 79-year-old housewife experienced sudden-onset chest tightness and was diagnosed with an inferoposterior wall myocardial infarction (MI). Coronary angiography showed two-vessel coronary artery disease with lesions of 70–80 % stenosis of the proximal left anterior artery (LAD) and total occlusion of the proximal left circumflex artery (LCX). An emergent percutaneous coronary intervention (PCI) was performed for the culprit lesion of the proximal LCX. It took about 6 h from chest tightness to revascularization. Transthoracic echocardiogram (TTE) showed impaired left ventricular performance (LVP), with mild mitral regurgitation. Two weeks later, a chest radiography showed progressive left lower lung consolidation. Uncontrolled pneumonia was resent initially; however, symptoms of advanced heart failure progressed. Therefore, PCI was performed for the lesion of the proximal LAD. Unfortunately, symptoms of heart failure did not improve after total coronary revascularization and optimal medical treatment. The anteroposterior view showed delayed regression of the left lower lung consolidation (Fig. 1a), and the lateral view showed a giant bulging mass in the posterior wall of the heart (Fig. 1b). Follow-up TTE showed poor LVP (LV ejection fraction: 36 %), posterior and lateral wall near akinesia, and moderate mitral regurgitation. A huge pseudoaneurysm (diameter 5.5 cm) of the inferoposterior aspect of the lateral wall of the LV (Fig. 2a, b; supplemental Fig. S1) presented with a narrow base and was contained by the pericardium. Chest computed tomography showed a single 7.4 9 8.0-cm lobulated pseudoaneurysm abutting the posterior wall of the LV (Fig. 2c). The surgical intervention performed was concomitant LV repair and mitral valve repair. Then, the patient died due to uncontrolled heart failure one month after surgery.

Can arterial stiffness and aortic pulse pressure be reduced better if antihypertensive treatment is performed according to Laragh and Alderman Idea?

femoral pulse wave velocity (PWV) and carotid intimamedia thickness (IMT) evaluation. Dietary habits were evaluated through a special diet score (MedDiet score, range 0-55), which assesses adherence to the Mediterranean dietary pattern. Higher values indicate greater adherence to this pattern. Results: Based on the Med-Diet Score, three groups were formed (high 30, intermediate: 21-29 and low 20) with no significant differences in main risk factors between them. Patients with low score had significantly higher LVM, LVMI and E/E’ compared to others. Regarding vascular parameters, aortic stiffness and IMT were inversely correlated to the Med-Diet score. Associations between cardiac and vascular parameters remained significant after adjustment for age and cardiovascular risk factors. Conclusion: Low adherence to the Mediterranean type of diet is significantly associated to impaired left ventricular and vascular structure and performance. Physicians should advise for healthier dietary habits and identify those who may need more intensive follow up.

Ventriculoarterial decoupling in human septic shock.

IntroductionSeptic shock is the most severe manifestation of sepsis. It is characterized as a hypotensive cardiovascular state associated with multiorgan dysfunction and metabolic disturbances. Management of septic shock is targeted at preserving adequate organ perfusion pressure without precipitating pulmonary edema or massive volume overload. Cardiac dysfunction often occurs in septic shock patients and can significantly affect outcomes. One physiologic approach to detect the interaction between the heart and the circulation when both are affected is to examine ventriculoarterial coupling, which is defined by the ratio of arterial elastance (Ea) to left ventricular end-systolic elastance (Ees). In this study, we analyzed ventriculoarterial coupling in a cohort of patients admitted to ICUs who presented with vs without septic shock.MethodsIn this retrospective cross-sectional opportunity study, we measured routine hemodynamics using indwelling arterial and pulmonary arterial catheters and transthoracic echocardiograms in 25 septic patients (group S) and 25 non–septic shock patients (group C) upon ICU admission. Ees was measured by echocardiography using a single-beat (EesSB) method. Ea was calculated as 0.9 systolic arterial pressure/stroke volume, and then the Ea/EesSB ratio was calculated (normal value <1.36).ResultsIn group S, 21 patients had an Ea/EesSB ratio >1.36 (uncoupled). The four patients with Ea/EesSB ratios ≤1.36 had higher EesSB values than patients with Ea/EesSB ratios >1.36 (P = 0.007), although Ea measurements were similar in both groups (P = 0.4). In group C, five patients had uncoupled Ea/EesSB ratios. No correlation was found between EesSB and left ventricular ejection fraction and between Ea/EesSB ratio and mixed venous oxygen saturation in septic shock patients.ConclusionsUpon admission to the ICU, patients in septic shock often display significant ventriculoarterial decoupling that is associated with impaired left ventricular performance. Because Ea/Ees decoupling alters cardiovascular efficiency and cardiac energetic requirements independently of Ea or Ees, we speculate that septic patients with ventriculoarterial uncoupling may benefit from therapy aimed at normalizing the Ea/Ees ratio.

Trastuzumab Alters the Expression of Genes Essential for Cardiac Function and Induces Ultrastructural Changes of Cardiomyocytes in Mice

Treatment with trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of Human Epidermal Growth Factor Receptor 2 (HER2), very successfully improves outcomes for women with HER2-positive breast cancer. However, trastuzumab treatment was recently linked to potentially irreversible serious cardiotoxicity, the mechanisms of which are largely elusive. This study reports that trastuzumab significantly alters the expression of myocardial genes essential for DNA repair, cardiac and mitochondrial functions, which is associated with impaired left ventricular performance in mice coupled with significant ultrastructural alterations in cardiomyocytes revealed by electron microscopy. Furthermore, trastuzumab treatment also promotes oxidative stress and apoptosis in myocardium of mice, and elevates serum levels of cardiac troponin-I (cTnI) and cardiac myosin light chain-1 (cMLC1). The elevated serum levels of cMLC1 in mice treated with trastuzumab highlights the potential that cMLC1 could be a useful biomarker for trastuzumab-induced cardiotoxicity.

Coronary microcirculatory dysfunction is associated with left ventricular dysfunction during follow-up after STEMI

BackgroundCoronary microvascular resistance is increased after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI), which may be related in part to changed left ventricular (LV) dynamics. Therefore we studied the coronary microcirculation in relation to systolic and diastolic LV function after STEMI.MethodsThe study cohort consisted of 12 consecutive patients, all treated with primary PCI for a first anterior wall STEMI. At 4 months, we assessed pressure-volume loops. Subsequently, we measured intracoronary pressure and flow velocity and calculated coronary microvascular resistance. Infarct size and LV mass were assessed using magnetic resonance imaging.ResultsPatients with an impaired systolic LV function due to a larger myocardial infarction showed a higher baseline average peak flow velocity (APV) than the other patients (26 ± 7 versus 17 ± 5 cm/s, p = 0.003, respectively), and showed an impaired variable microvascular resistance index (2.1 ± 1.0 versus 4.1 ± 1.3 mmHg cm−1∙s−1, p = 0.003, respectively). Impaired diastolic relaxation time was inversely correlated with hyperaemic APV (r = −0.56, p = 0.003) and positively correlated with hyperaemic microvascular resistance (r = 0.48, p = 0.01). LV dilatation was associated with a reduced variable microvascular resistance index (r = 0.78, p = 0.006).ConclusionA larger anterior myocardial infarction results in impaired LV performance associated with reduced coronary microvascular resistance variability, in particular due to higher coronary blood flow at baseline in these compromised left ventricles.