Left Ventricular Internal Diameter In Diastole Research Articles

Reduced Cardiac Index Reserve and Hypovolemia in Severe Falciparum Malaria.

BackgroundImpaired microvascular perfusion is central to the development of coma and lactic acidosis in severe falciparum malaria. Refractory hypotension is rare on admission but develops frequently in fatal cases. We assessed cardiac function and volume status in severe falciparum malaria and its prognostic significance.MethodsPatients with severe (N = 101) or acute uncomplicated falciparum malaria (N = 83) were recruited from 2 hospitals in India and Bangladesh, and healthy participants (N = 44) underwent echocardiography.ResultsPatients with severe malaria had 38% shorter left ventricular (LV) filling times and 25% shorter LV ejection times than healthy participants because of tachycardia; however, stroke volume, LV internal diameter in diastole (LVIDd), and LV internal diameter in systole (LVIDs) indices were similar. A low endocardial fraction shortening (eFS) was present in 17% (9 of 52) of severe malaria patients. Adjusting for preload and afterload, eFS was similar in health and severe malaria. Fatal cases had smaller baseline LVIDd and LVIDs indices, more collapsible inferior vena cavae (IVC), and higher heart rates than survivors. The LVIDs and IVC collapsibility were independent predictors for mortality, together with base excess and Glasgow Coma Scale.ConclusionsPatients with severe malaria have rapid ejection of a normal stroke volume. Fatal cases had features of relative hypovolemia and reduced cardiac index reserve.

Follow-up after biventricular repair of the hypoplastic left heart complex

In hypoplastic left heart complex patients, biventricular repair is preferred over staged-single ventricle palliation; however, there are too few studies to support either strategy. Therefore, we retrospectively characterized our patient cohort with hypoplastic left heart complex after biventricular repair to measure left-sided heart structures and assess our treatment strategy. Patients with hypoplastic left heart complex who had biventricular repair between 2004 and 2018 were retrospectively reviewed. Operative results were evaluated and echocardiographic mitral valve (MV) and aortic valve (AoV) dimensions, left ventricular length and left ventricular internal diastolic diameter (LVIDd) were measured preoperatively and during follow-up after 0.5, 1, 3, 5 and 10 years. In 32 patients, the median age at surgery was 10 (interquartile range 5.0) days. The median follow-up was 6.19 (interquartile range 6.04) years. During the 10-year follow-up, the mean Z-scores increased from -2.82 to -1.49 and from -2.29 to 0.62 for MV and AoV, respectively. Analysis of variance results with post hoc paired t-tests showed that growth of left-sided heart structures was accelerated in the first year after repair, but was not equal, with the MV lagging behind the AoV (P = 0.033), resulting in significantly smaller MV Z-scores compared with AoV Z-scores at 10-year follow-up (P < 0.001). There were 2 (6%) early deaths. The major adverse events occurred in 4 (13%) patients. The surgical or catheter-based reintervention was required in 14 (44%) patients. The growth rate of heart structures was most prominent during the first year after biventricular repair with lower growth rate of the MV compared with the AoV.

An Asian Perspective on Gender Differences in Clinical Outcomes and Echocardiographic Profiles of Patients With Medically Managed Severe Aortic Stenosis

Gender differences in valvular heart disease are increasingly recognised. A prior study has suggested better surgical outcomes in women with symptomatic aortic stenosis (AS). We investigate gender differences in medically managed severe AS. We studied 347 patients with severe AS (aortic valve area index <0.6 cm2/m2) in terms of baseline clinical background, echocardiographic characteristics, and clinical outcomes. Appropriate univariate and multivariate models were employed, while Kaplan-Meier curves were constructed to compare mortality outcomes. In total, 205 (59%) patients were women. Despite higher incidences of hypertension (75.6% vs 47.3%) and diabetes mellitus (46.5% vs 29.5%) in women, women had improved survival (Kaplan-Meier log-rank = 6.24, p = 0.012). After adjusting for age (hazard ratio [HR], 1.034; 95% confidence interval [CI], 1.014-1.054), hypertension (HR, 1.469; 95% CI, 0.807-2.673), diabetes (HR, 1.219; 95% CI, 0.693-2.145), and indexed aortic valve area (HR 0.145, 95% CI 0.031-0.684) on multivariate analyses, female gender remained independently associated with lower mortality (HR, 0.561; 95%, CI 0.332-0.947). Women tended to have smaller body surface area (BSA), left ventricular (LV) internal diastolic diameter, and smaller LV outflow tract diameter but were similar to men in terms of LV ejection fraction, AS severity, and patterns of LV remodelling. Women appeared to have better outcomes compared to men in medically managed severe AS. These gender differences warrant further study and may affect prognosis, follow-up, and timing of valve surgery.

Autoimmune myocarditis is not associated with left ventricular systolic dysfunction

BackgroundExperimental autoimmune myocarditis (EAM) is a common animal model for the investigation of the pathophysiology of myocarditis. Because of diverging findings from previous studies, we performed serial echocardiographic examinations throughout the course of the disease and investigated the dimensions of the murine heart and left ventricular (LV) systolic function.Materials and MethodsExperimental autoimmune myocarditis was induced in male Balb/c mice by subcutaneous injection of a fragment of the α‐myosin heavy chain (MyHC‐α 614‐629: Ac‐SLKLMATLFSTYASAD). Transthoracic echocardiography was performed on days 0, 7 and 21 in healthy animals and mice with EAM.ResultsExperimental autoimmune myocarditis was associated with a reduction in LV systolic function and an increase in LV internal diameter in diastole (LVIDd) and systole (LVIDs) 7 days postimmunization. After 21 days, EAM led to a significant increase in LV‐thickness (1.3‐fold increase in LV anterior wall diameter in diastole [LVAWDd]), but there was no difference in LV systolic function between immunized animals and healthy controls. LV‐thickness correlated well with the severity of myocarditis in the histopathological examination (LVAWDd: rs = 0.603, P = 0.003, LV anterior wall diameter in systole (LVAWDs): rs = 0.718, P < 0.0001).ConclusionOur results indicate that EAM leads to an initial dilatation of the LV that is followed by ventricular “hypertrophy.” On day 21, there was no significant difference in LV systolic function between immunized animals and controls. Furthermore, the ageing of the animals had a major impact on the echocardiographic parameters; therefore, the use of healthy age‐matched controls seems warranted when echocardiography is performed in rodents.

Speckle tracking echocardiography in cats with preclinical hypertrophic cardiomyopathy

BackgroundCats with hypertrophic cardiomyopathy (HCM) have decreased left ventricular (LV) longitudinal deformation detected by mitral annular plane systolic excursion (MAPSE) and speckle tracking echocardiography. People with preclinical HCM have decreased systolic LV longitudinal and radial strain (S) and strain rate (SR), with preserved circumferential S and SR.Hypothesis/ObjectivesCats with preclinical HCM have decreased systolic LV deformation compared to normal cats.AnimalsSeventy‐three client‐owned cats with (n = 37) and without (n = 36) preclinical HCM.MethodsRetrospective echocardiographic study. Left and right ventricular longitudinal S and SR, LV radial and circumferential S and SR were calculated by STE. Left ventricular mass was also calculated. Correlation between STE variables and LV hypertrophy was determined and receiver‐operating characteristic (ROC) curves were plotted for prediction of HCM.ResultsCats with HCM had smaller absolute longitudinal S (−14.8 ± 3.3% vs −19.7 ± 2.7%, P < .001), longitudinal SR (−2.36 ± 0.62 vs −2.95 ± 0.68 second−1, P < .001), radial S (46.2 ± 21.3% vs 66.7 ± 17.6%, P < .001), and radial SR (5.60 ± 2.08 vs 6.67 ± 1.8 second−1, P < .001) compared to healthy controls. No difference was observed for circumferential S and SR. Cats with HCM had greater LV mass (13.2 ± 3.7 g vs 8.6 ± 2.7 g, P < .001). The ROC with the greatest area under the curve (AUC) for the identification of HCM (0.974) was plotted from a logistic regression equation combining LV mass, MAPSE at the free wall, and LV internal diameter in diastole (LVIDd).Conclusions and clinical importanceCats with preclinical HCM have decreased long axis and radial deformation. Decreased longitudinal deformation and decreased LVIDd are factors that would support a diagnosis of HCM.

Feasibility of RA-LV pacing in patients with symptomatic left bundle branch block: a pilot study.

Several studies have reported the adverse effects of right ventricular apical pacing. Permanent His bundle pacing is proved to be the most physiological. But it can be technically difficult sometimes. One recent large multicenter randomized trial showed that pacing from left ventricular apex or mid-lateral wall has the greatest potential to prevent pacing-induced reduction of cardiac pump function (by maintaining left ventricular mechanical synchrony) and, therefore, can be considered as physiological site. In our study, we have wanted to see the outcome of left ventricular pacing through coronary sinus branch with active fixation bipolar lead as a routine pacing technique in patients with symptomatic left bundle branch block. In our study we have recruited 27patients for left ventricular pacing through coronary sinus branch (as done in cardiac resynchronization therapy) with active fixation bipolar lead and 33 patients for right ventricular apical pacing (control) and compared left ventricular pacing with right ventricular apical pacing in patients with history of syncope with left bundle branch block in baseline electrocardiography who presented with atrio-ventricular block or prolonged HV interval (≥ 70ms) on electrophysiology study in term of procedure and fluoroscopy time and short-term lead performance and left ventricular function. The results of our study showed that left ventricular pacing through a tributary of coronary sinus is associated with shortened QRS duration (21.10 ± 3.92ms) and better LV function (higher left ventricular ejection fraction 64.00 ± 3.03 vs. 59.73 ± 6.73 and lower left ventricular diastolic internal diameter 4.58 ± 0.32 vs. 5.23 ± 0.40cm) in comparison to right ventricular apical pacing. However, the total procedure time and fluoroscopy time was significantly higher (73.75 ± 11.02 vs. 63.32 ± 6.06min and 7.08 ± 1.48 vs. 5.02 ± 1.39min, respectively) in left ventricular pacing group. The results of this study indicate that transvenous left ventricular epicardial pacing may be an option for physiological pacing in patients with symptomatic left bundle branch block.

QT Dispersion Changes after Transcatheter Aortic Valve Implantation in Patients with Aortic Stenosis.

ObjectiveThe aim of this study was to evaluate the QT dispersion and echocardiographic parameters in patients before and after transcatheter aortic valve implantation (TAVI).MethodsOne hundred and fifty-two patients with severe aortic valve stenosis (AS) were included in our study. Ninety five patients who underwent aortic valve replacement with TAVI were included in the TAVI group and 57 patients, who refused TAVI, were included in the medical treatment group. The QT interval and echocardiographic parameters of all patients were assessed before and after the procedure (first and sixth months and first year). The QT intervals were taken from the onset of the QRS to the end of the T wave.ResultsAll patients had severe AS. The average mean aortic valve gradient was 46.1±12. Left ventricular internal diastolic diameter (LVIDD) and interventricular septum diastolic thickness (IVSDT) did not change significantly after TAVI (P>0.05). QT dispersion, corrected QT dispersion, and mean aortic valve gradient changed significantly six months after TAVI (P<0.05). Compared to the medical treatment group, QT dispersion and corrected QT dispersion were significantly decreased at the sixth month in the TAVI group. The incidence of malignant arrhythmias was smaller in the TAVI group than in the medical treatment group. The mortality rate was lower at the first-year follow-up in the TAVI group than in the medical treatment group.ConclusionIncreased QT dispersion is associated with severe symptomatic AS. After TAVI, QT dispersion reduces.

Abstract 16825: Functional Analysis of Whole Exome Sequencing Candidate Genes for Left Ventricular Hypertrophy Demonstrate Changes in Cardiac Hypertrophic Signaling

As whole exome sequencing (WES) studies identify a large number of potential disease relevant genes and variants, a major challenge will be the subsequent functional analysis and interpretation. We performed WES in 1,382 African American subjects from NHLBI’s HyperGEN cohort to identify novel genes for Left ventricular (LV) hypertrophy. Using criteria that combine significant prior linkage/association signals, expression QTL information, database annotation, and literature search, we prioritized the candidate genes to further scrutinize those with higher functional potentials. As a result, we selected four genes ( FATP6, PDE12, HAX1, TRAPPC11 ) that had not been directly linked to LVH for experimental functional follow up using human iPSC-derived cardiomyocytes (hiPSC-CM). Each gene was knocked-down (KD) using siRNAs in triplicate followed by mRNA sequencing. Differential expression and pathway analyses were performed to evaluate influences of the candidate genes. The KDs of FATP6 and PDE12 , whose variants show significant association with increased LV internal diastolic-dimension, showed regulation changes in cardiac hypertrophy and β-adrenergic signaling pathways (p-value &lt;0.05). In FATP6 KDs we observed 2,696 genes to have significant differential expression (adj. p-value ≤0.05). Furthermore, FATP6 KDs also lead to the upregulation of cholesterol biosynthesis pathways (p-value 1.97E-4) that are important for caveolae formation and signal transduction. Additionally, FATP6 KDs had a moderate increase in FATP1 expression (p-value 0.0024) that has been reported to cause lipotoxicity and increase LV internal diastolic diameter in mice. In PDE12 KDs we observed significant differential expression of 3,276 genes (adj. p-value ≤0.05) and saw significant decreases in Ca2+ channel expression (adj. p-value ≤0.05) that likely lead to decreases in Ca2+ handling. In summary, our study demonstrates the hiPSC-CM based knockdown model as an effective approach to functionally test and characterize candidate genes identified through WES. Further development of the approach using hiPSC derived cells will offer a scalable platform for high-throughput, multi-omics analyses using genome-matched, disease-relevant tissue types.

Upgrade to his bundle pacing in pacing-dependent patients referred for pulse generator change: Feasibility and intermediate term follow up

BackgroundRight ventricular pacing (RVP) is associated with an increased incidence of heart failure and may impair cardiac function. Permanent His bundle pacing (HBP) has the potential to physiologically preserve and prevent cardiac dysfunction. This study was to evaluate the feasibility and intermediate follow-up results of upgrade to HBP implantation in patients referred for pulse generator change with long term RVP. MethodsTwelve of 14 pacing dependent patients who were referred for pulse generator exchange underwent upgrade into HBP successfully in our center. QRS duration, New York Heart Association (NYHA) functional class, echocardiography, use of diuretics and lead parameters were measured at baseline and during the follow-up. ResultsAmong the 12 patients attempted (mean age, 70.8 ± 8.9 years, 75% males) successfully, the average ejection fraction (EF) was 52.2 ± 11.2%. Nine of 12 patients underwent upgrade to HBP, and three patients with EF < 40% underwent HBP and biventricular pacing (BVP) as well. A significant reduction in mean QRS duration was observed compared with pre-implantation, from 157.8 ± 13.3 ms to 109.3 ± 16.9 ms (p < 0.001). After 6 months follow-up period, median NYHA functional class was improved from 2.7 ± 0.6 to 1.8 ± 0.6 (p = 0.007) and left ventricular internal diastolic diameter (LVIDd) was reduced from 5.5 ± 0.4 cm to 5.3 ± 0.3 cm (p = 0.03). ConclusionsHBP improves heart failure symptoms with preserved EF by long term RVP. Permanent HBP is feasible and safe for upgrade in patients with long term RVP irrespective of LVEF.

Epigallocatechingallate attenuates myocardial injury in a mouse model of heart failure through TGF‑β1/Smad3 signaling pathway.

The present study aimed to assess the protective effect of epigallocatechingallate (EGCG) against myocardial injury in a mouse model of heart failure and to determine the mechanism underlying regulation of the transforming growth factor-β1/mothers against decapentaplegic homolog 3 (TGF-β1/Smad3) signaling pathway. Mouse models of heart failure were established. Alterations in ejection fraction, left ventricular internal diastolic diameter (LVIDd) and left ventricular internal systolic diameter (LVIDs) were measured by echocardiography. Pathological alterations of myocardial tissue were determined by hematoxylin and eosin, and Masson staining. The levels of serum brain natriuretic peptide (BNP), N-terminal-proBNP, interleukin (IL)-1β, IL-6, tumor necrosis factor-α, malondialdehyde, superoxide dismutase and glutathione peroxidase were detected with ELISA. Expression of collagen I, collagen III were detected by western blotting and reverse transcription quantitative polymerase chain reaction. Transforming growth factor-β1 (TGF-β1), Smad3, phosphorylated (p)-Smad3, apoptosis regulator BAX (Bax), caspase-3 and apoptosis regulator Bcl2 in mouse cardiac tissue were measured by western blotting. P-smad3 and TGF-β1 were measured by immunofluorescence staining. EGCG reversed the alterations in LVIDd and LVIDs induced by establishment of the model of heart failure, increased ejection fraction, inhibited myocardial fibrosis, attenuated the oxidative stress, inflammatory and cardiomyocyte apoptosis and lowered the expression levels of collagen I and collagen III. Following treatment with TGF-β1 inhibitor, the protective effect of EGCG against heart failure was attenuated. The results of the present study demonstrated that EGCG can inhibit the progression and development of heart failure in mice through inhibition of myocardial fibrosis and reduction of ventricular collagen remodeling. This protective effect of EGCG is likely mediated through inhibition of TGF-β1/smad3 signaling pathway.

Ginsenoside Rb1 inhibits autophagy through regulation of Rho/ROCK and PI3K/mTOR pathways in a pressure-overload heart failure rat model.

This study was designed to explore the relationship between ginsenoside Rb1 (Grb1) and high-load heart failure (HF) in rats. The parameters of cardiac systolic function (left ventricular posterior wall thickness (LVPWT), left ventricular internal diastolic diameter (LVID), fraction shortening (FS) and mitral valves (MVs)) of rat hearts in each group were inspected by echocardiogram. The expressions of rat myocardial contractile proteins, autophagy-related proteins and the activation of Rho/ROCK and PI3K/mTOR pathways were detected by Western blot. LVPWT, FS, MVs and the expression of myocardial contractile proteins α-MHC, apoptosis-related proteins Bcl-2 and signalling pathway involved proteins pAkt and mTOR were significantly reduced in the HF, HF+5mg/kg Grb1 (HF+Grb1-5) and HF+Grb1+arachidonic acid (AA) groups with LVID, β-MHC, cell apoptosis, cell autophagy and Rho/ROCK significantly increased compared with the control group, of which the tendency was contrary to the HF+20mg/kg Grb1 (HF+Grb1-20) group compared with the HF group (P<0.05). In the HF+Grb1+AA group, there was no significant change in the above indexes compared with the HF group. The results indicated that Grb1 can exert anti-HF function by inhibiting cardiomyocyte autophagy of rats through regulation of Rho/ROCK and PI3K/mTOR pathways.

Na+/H+ exchanger isoform 1-induced osteopontin expression facilitates cardiac hypertrophy through p90 ribosomal S6 kinase.

Cardiovascular diseases are the leading cause of death worldwide. One in three cases of heart failure is due to dilated cardiomyopathy. The Na+/H+ exchanger isoform 1 (NHE1), a multifunctional protein and the key pH regulator in the heart, has been demonstrated to be increased in this condition. We have previously demonstrated that elevated NHE1 activity induced cardiac hypertrophy in vivo. Furthermore, the overexpression of active NHE1 elicited modulation of gene expression in cardiomyocytes including an upregulation of myocardial osteopontin (OPN) expression. To determine the role of OPN in inducing NHE1-mediated cardiomyocyte hypertrophy, double transgenic mice expressing active NHE1 and OPN knockout were generated and assessed by echocardiography and the cardiac phenotype. Our studies showed that hearts expressing active NHE1 exhibited cardiac remodeling indicated by increased systolic and diastolic left ventricular internal diameter and increased ventricular volume. Moreover, these hearts demonstrated impaired function with decreased fractional shortening and ejection fraction. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) mRNA was upregulated, and there was an increase in heart cell cross-sectional area confirming the cardiac hypertrophic effect. Moreover, NHE1 transgenic mice also showed increased collagen deposition, upregulation of CD44 and phosphorylation of p90 ribosomal s6 kinase (RSK), effects that were regressed in OPN knockout mice. In conclusion, we developed an interesting comparative model of active NHE1 transgenic mouse lines which express a dilated hypertrophic phenotype expressing CD44 and phosphorylated RSK, effects which were regressed in absence of OPN.

Post infarction left ventricular aneurysm—our experience

Left ventricular aneurysms (LVAs) stand as one of the serious complications of myocardial infarction and are associated with increased mortality. Considerable differences exist regarding the optimal surgical management of LVAs. In this study, we report our single center/single surgeon experience with post infarction LVAs. This is a retrospective analysis of 25 patients, who underwent endoventricular circular patch plasty (Dor procedure) for LVAs of ischemic origin from 2009 to 2013. The demographic data was collected in addition to patients mode of presentation, New York Heart Association (NYHA) class, past medical history particularly ischemic heart disease, preoperative electrocardiography, chest X-ray, echocardiography, and coronary angiography. The postoperative functional class and the echocardiography data were also collected and analysed. All patients underwent follow-up cardiac computerized tomogram (CT) scan to calculate the sphericity index (SI). The mean age of presentation was 60.76 ± 9.57 years. Seventeen were males and eight were females. The associated comorbidities were, diabetes and hypertension. The most common presentations were, the angina and the left ventricular failure. Among the study group, two (8%) patients presented within 72 h of myocardial infarction (MI) owing to the hemodynamic instability due to ventricular septal rupture (VSR) and severe mitral regurgitation (MR), and required moderate doses of inotropes and intra-aortic balloon pump. The time of presentation in the remaining 23 (92%) patients ranged from 14 to 38 days following the MI (mean −21.36 ± 0.38 days). The preoperative mean NYHA functional class was 2.44 ± 0.71. Posterior aneurysms were predominated in our study. The mean left ventricular internal diameter in diastole (LVIDd), the left ventricular internal diameter in systole (LVIDs) and the ejection fraction (EF) were; 6.52 ± 0.40 cm, 5.24 ± 0.37 cm, and 37.44 ± 3.92% respectively. The mean end-diastolic volume (EDV) was 167 ± 28.38 ml and the mean end-systolic volume (ESV) was 87.84 ± 12.90 ml. The mean pulmonary artery systolic pressure (PASP) was 51.48 ± 5.72 mmHg. The mean tricuspid annular plane systolic excursion (TAPSE) was 11.52 ± 0.71 mm. Six cases showed mural thrombus, four had MR, and one had an associated ventricular septal defect (VSD). The coronary angiogram showed multivessel coronary artery disease in majority of patients. The hospital mortality was 8% (two cases). The mean follow-up period was 2.4 ± 0.91 years. The postoperative mean NYHA class was 1.76 ± 0.43. There was a significant improvement in the left ventricular function. There was a significant improvement in MR following concomitant Dor procedure and mitral valve interventions. Patients with mitral interventions had trivial to mild MR and were asymptomatic. The mean SI was 0.5 ± 0.11. Dor procedure is reproducible and simple to perform, restores the natural left ventricular geometry and is associated with significant improvement in the left ventricular performance and hemodynamics, which translates into improved functional class of the patient.

Effect of paroxetine on left ventricular remodeling in an in vivo rat model of myocardial infarction.

Left ventricular (LV) remodeling following a myocardial infarction (MI) involves formation of reactive oxygen species (ROS). Paroxetine, a selective serotonin reuptake inhibitor, has an antioxidant effect in the vascular wall. We investigated whether paroxetine reduces myocardial ROS formation and LV remodeling following a MI. In a total of 32 Wistar rats, MI was induced by a 30-min ligation of the left anterior descending artery followed by 7- or 28-day reperfusion. During the 28days of reperfusion, LV remodeling was evaluated by magnetic resonance imaging (MRI) and echocardiography (n=20). After 28days of reperfusion, the susceptibility to ventricular tachycardia was evaluated prior to sacrifice and histological assessment of myocyte cross-sectional area, fibrosis, and presence of myofibroblasts. Myocardial ROS formation was measured with dihydroethidium after 7days of reperfusion in separate groups (n=12). Diastolic LV volume, evaluated by MRI (417±60 vs. 511±64µL, p<0.05), and echocardiography (515±80 vs. 596±83µL, p<0.05) as well as diastolic LV internal diameter evaluated with echocardiography (7.2±0.6 vs. 8.1±0.7mm, p<0.05) were lower in the paroxetine group than in controls. Furthermore, myocyte cross-sectional area was reduced in the paroxetine group compared with controls (277±26 vs. 354±23mm3, p<0.05) and ROS formation was reduced in the remote myocardium (0.415±0.19 normalized to controls, p<0.05). However, no differences in the presence of fibrosis or myofibroblasts were observed. Finally, paroxetine reduced the susceptibility to ventricular tachycardia (induced in 2/11 vs. 6/8 rats, p<0.05). Paroxetine treatment following MI decreases LV remodeling and susceptibility to arrhythmias, probably by reducing ROS formation.

EFFECT OF PAROXETINE TREATMENT ON LEFT VENTRICULAR REMODELING IN AN IN VIVO RAT MODEL OF MYOCARDIAL INFARCTION

Left ventricular (LV) remodeling following a myocardial infarction (MI) involves formation of reactive oxygen species (ROS). Paroxetine, a selective serotonin reuptake inhibitor, has an antioxidant effect in the vascular wall. We investigated whether paroxetine reduces myocardial ROS formation and LV remodeling following a MI. In a total of 32 Wistar rats, MI was induced by a 30-min ligation of the left anterior descending artery followed by 7- or 28-day reperfusion. During the 28 days of reperfusion, LV remodeling was evaluated by magnetic resonance imaging (MRI) and echocardiography (n = 20). After 28 days of reperfusion, the susceptibility to ventricular tachycardia was evaluated prior to sacrifice and histological assessment of myocyte cross-sectional area, fibrosis, and presence of myofibroblasts. Myocardial ROS formation was measured with dihydroethidium after 7 days of reperfusion in separate groups (n = 12). Diastolic LV volume, evaluated by MRI (417 ± 60 vs. 511 ± 64 µL, p < 0.05), and echocardiography (515 ± 80 vs. 596 ± 83 µL, p < 0.05) as well as diastolic LV internal diameter evaluated with echocardiography (7.2 ± 0.6 vs. 8.1 ± 0.7 mm, p < 0.05) were lower in the paroxetine group than in controls. Furthermore, myocyte cross-sectional area was reduced in the paroxetine group compared with controls (277 ± 26 vs. 354 ± 23 mm3, p < 0.05) and ROS formation was reduced in the remote myocardium (0.415 ± 0.19 normalized to controls, p < 0.05). However, no differences in the presence of fibrosis or myofibroblasts were observed. Finally, paroxetine reduced the susceptibility to ventricular tachycardia (induced in 2/11 vs. 6/8 rats, p < 0.05). Paroxetine treatment following MI decreases LV remodeling and susceptibility to arrhythmias, probably by reducing ROS formation.

Biomass fuel smoke exposure was associated with adverse cardiac remodeling and left ventricular dysfunction in Peru.

While household air pollution from biomass fuel combustion has been linked to cardiovascular disease, the effects on cardiac structure and function have not been well described. We sought to determine the association between biomass fuel smoke exposure and cardiac structure and function by transthoracic echocardiography. We identified a random sample of urban and rural residents living in the high-altitude region of Puno, Peru. Daily biomass fuel use was self-reported. Participants underwent transthoracic echocardiography. Multivariable linear regression was used to examine the relationship of biomass fuel use with echocardiographic measures of cardiac structure and function, adjusting for age, sex, height, body mass index, diabetes, physical activity, and tobacco use. One hundred and eighty-seven participants (80 biomass fuel users and 107 non-users) were included in this analysis (mean age 59years, 58% women). After adjustment, daily exposure to biomass fuel smoke was associated with increased left ventricular internal diastolic diameter (P=.004), left atrial diameter (P=.03), left atrial area (four-chamber) (P=.004) and (two-chamber) (P=.03), septal E' (P=.006), and lateral E' (P=.04). Exposure to biomass fuel smoke was also associated with worse global longitudinal strain in the two-chamber view (P=.01). Daily biomass fuel use was associated with increased left ventricular size and decreased left ventricular systolic function by global longitudinal strain.

Left ventricular assist device outcomes based on flow configuration and pre-operative left ventricular dimension: An Interagency Registry for Mechanically Assisted Circulatory Support Analysis

Axial configuration (AC) and centrifugal configuration (CC) left ventricular assist devices (LVAD) have different flow characteristics, and whether the interaction between device flow configuration and the pre-operative left ventricular internal diastolic diameter (LVIDD) mediates adverse events after LVAD implantation is unknown. We queried 9,424 continuous-flow LVAD recipients who received LVADs from April 2008 to June of 2015 in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). The pre-operative LVIDD * flow configuration interaction term was tested in multivariable models to determine its relationship to adverse events. The pre-operative LVIDD * flow configuration interaction was a significant predictor of device thrombosis. As the LVIDD increased, the risk of AC device thrombosis increased compared with CC devices (p = 0.0099). At 7.0 cm, the hazard ratio (HR) for AC device thrombosis compared with the CC device was 1.61 (95% confidence interval [CI], 1.17-2.22; p = 0.004) and continued to rise as the LVIDD increased. The LVIDD * flow configuration interaction did not predict stroke, gastrointestinal bleeding, or patient survival. In multivariable models, the hazard of stroke was higher with the CC device regardless of the LVIDD (HR, 1.96; 95% CI, 1.64-2.36; p < 0.0001). Adjusted analyses showed LVAD implantation into a larger left ventricle was associated with a lower risk of death (HR, 0.90; 95% CI, 0.85-0.95; p = 0.0004) per centimeter of LVIDD. Our study suggests that the pre-operative LVIDD, flow configuration, and interaction terms should be considered individually when choosing the appropriate LVAD to mitigate the rates of device thrombosis, stroke, and death.

Heart involvement in systemic lupus erythematosus: a systemic review and meta-analysis.

Cardiovascular diseases are one of the most important causes of the disability and mortality in patients with systemic lupus erythematosus (SLE). The present study examined the cardiac abnormalities in patients with SLE by echocardiography. Case-control studies were obtained by searching PubMed MEDLINE, Embase, and MD Consult. Systemic review and meta-analysis were performed to assess the cardiac abnormalities based on the changes in the echocardiography in patients with SLE. Twenty-two studies including 1117 SLE patients and 901 healthy controls were enrolled into this study. We found that patients with SLE developed the pericardial effusion (odds ratio (OR) (95% confidence interval (CI)) 30.52 (9.70-96.02); p<0.00001) and the combined valvular alterations (OR (95%CI) 11.08 (6.98-17.59); p<0.00001). In addition, SLE patients also exhibited an increase in the left atrial diameter (LAD) (WMD-weighted mean difference (95%CI) 0.18 (0.06-0.29); p=0.002), the left ventricular internal diameter in diastole (LVDd) (WMD (95%CI) 0.07 (0.02-0.12); p=0.01), and the left ventricular mass index (LVMI) (WMD (95%CI) 5.69 (2.69-8.69); p=0.0002). In contrast, the left ventricular systolic function (WMD (95%CI) -1.22 (-1.69 to -0.75); p<0.00001) and diastolic function including E/A ratio and E/E' ratio (WMD (95% CI) -0.13 (-0.24 to -0.01); p=0.04; WMD (95% CI) 1.71 (0.43 to 2.99); p=0.009) were decreased in SLE patients. Patients with SLE are associated with significant alterations in cardiac structure and function as demonstrated by echocardiography. Data from this study suggest that echocardiographic assessment should be considered as a part of routine examinations for SLE patients clinically.

Risk Factors for Inadequate Defibrillation Safety Margins Vary With the Underlying Cardiac Disease: Implications for Selective Testing Strategies.

In view of the shift from routine toward no or selective defibrillation testing, optimization of the current risk stratification for inadequate defibrillation safety margins (DSMs) could improve individualized testing decisions. Given the pathophysiological differences in myocardial substrate between ischemic and nonischemic heart disease (IHD/non-IHD) and the accompanying differences in clinical characteristics, we studied inadequate DSMs and their predictors in relation to the underlying etiology. Cohort of routine defibrillation tests (n = 785) after first implantable cardioverter defibrillator (ICD)-implantations at the Radboud UMC (2005-2014). A defibrillation threshold >25 J was regarded as an inadequate DSM. In total, 4.3% of patients had an inadequate DSM; in IHD 2.5% versus 7.3% in non-IHD (P = 0.002). We identified a group of non-IHD patients at high risk (13-42% inadequate DSM); the remainder of the cohort (>70%) had a risk of only 2% (C-statistic entire cohort 0.74; C-statistic non-IHD 0.82). This was based upon two identified interaction terms: (1) non-IHD and age (aOR 0.94 [95% CI 0.91-0.97]); (2) non-IHD and the indexed left ventricular (LV) internal diastolic diameter (aOR 3.50 [95% CI 2.10-5.82]). The present study on risk stratification for an inadequate DSM not only confirms the importance of making a distinction between IHD and non-IHD, but also shows that risk factors in an entire cohort (LV dilatation, age) may only apply to a subgroup (non-IHD). Appreciation of this concept could favorably affect current risk stratification. If confirmed, our approach may be used to optimize individualized testing decisions in an upcoming era of non-routine testing.

Abstract MP35: Relation of Left Ventricular Structure to Incident Heart Failure in African Americans: The Jackson Cohort of the Atherosclerosis Risk in Communities Study

Introduction: Studies in non-Hispanic whites suggest that early adaptive changes in cardiac structure due to hypertension may influence the development of heart failure (HF). The predictive value of left ventricular (LV) structure to incident acute decompensated HF (ADHF) has not been well-studied in African Americans (AA) despite the higher incidence of HF in this group. Hypothesis: We hypothesized that incidence of ADHF in AA varies according to cardiac structures and LV geometry type. Methods: The study sample included 1,737 participants who attended the third examination cycle of the Jackson cohort of ARIC between 1993 and1995 and underwent echocardiography, anthropometry and phlebotomy for glucose and lipids. Left atrial size, aortic root diameter (AOD), LV wall thicknesses and chamber dimensions, LV mass, LV mass index, LV hypertrophy (LVH) and LV geometric patterns [normal geometry, concentric hypertrophy, eccentric hypertrophy (EH), concentric remodeling] were determined by echocardiography. Cutoff for LVH was defined as above the 80th percentile of LV mass index. HF data was available up to December 31, 2011. In the primary analyses we adjusted for age, sex, smoking, diabetes, body mass index, systolic blood pressure, and use of hypertension medications in the multivariable model. Results: Over a follow-up period of approximately 18 years, 188 participants developed ADHF. Incident ADHF was significantly related to AOD [HR 1.42 (1.03, 1.97)], LV internal diameter in diastole (cm) [HR 1.60 (1.24, 2.05)], LV mass [HR 1.003 (1.002, 1.005)], LVM index [HR 1.01 (1.004, 1.02) and LVH [HR 1.62 (1.16, 2.27)]. In terms of LV geometry, EH was significantly related to incident ADHF in the multivariable model [HR 2.94 (1.70-5.10)]. Conclusion: In our large community-based sample of AAs, we observed that AOD, LV internal diameter in diastole, LV mass, LV mass index, LVH and EH geometry were significantly related to long-term incidence of ADHF independent of standard risk factors. These findings suggest echocardiography may be helpful in risk stratifying members of this high risk population for ADHF.