Abstract 14295: Increasing QRS Duration Over Time Is Associated With Mortality and Morbidity in an Outpatient Heart Failure Population

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Hassan Alfraidi ◽  
William F McIntyre ◽  
Lindsay Torbiak ◽  
Shelley Zieroth ◽  
Colette M Seifer
Keyword(s):  
Heart Failure ◽  
Systolic Function ◽  
Nyha Class ◽  
Tertiary Care ◽  
Left Ventricular ◽  
Conduction Delay ◽  
Mortality And Morbidity ◽  
Qrs Duration ◽  
Lv Systolic Function ◽  
Over Time

Introduction: Heart failure is a leading cause of morbidity and mortality. Prolonged QRS duration (QRSd), a marker of intra-ventricular conduction delay, has been shown to be associated with worse left ventricular (LV) systolic function, LV dilation and mitral regurgitation as well as with mortality. There are minimal data in the literature on the progression of QRSd over time, and the association with clinical outcomes. Hypothesis: We hypothesized that the progression of QRSd over time would be associated with mortality and hospitalizations in an outpatient heart failure population. Methods: Retrospective study of consecutive new adult referrals to a tertiary heart failure clinic over a 1 year period (2012). All patients with a narrow QRSd (defined as <130 ms) were included. Data were collected on demographics, ejection fraction (EF), clinical course and major clinical events. Primary endpoint was mortality and secondary endpoint was heart failure hospitalization. Results: A total of 147 patients were included, 90 were males (61%). Mean age was 66 years (+/-15), mean EF was 33% (+/- 15) and mean NYHA class 2.2 (+/- 0.9) at baseline. An ischemic aetiology accounted for 50% of the patients. Mean QRSd was 100 ms (+/- 13) at baseline and 119 ms (+/- 25) at last follow-up, which was a mean of 2.5 years from baseline. Death occurred in 27 patients (18%) and there were 114 hospitalizations in 54 patients. Results of univariate regression analysis are presented in the table. Conclusion: An increase in QRSd over time is associated with increased heart failure hospitalizations and all cause mortality in a tertiary care outpatient heart failure population.

scholarly journals Comparison between Spironolactone and Eplerenone on LV Systolic Function in Patients with Chronic Heart Failure

2020 ◽  
Vol 16 (2) ◽  
pp. 65-70
Author(s):  
Md Noornabi Khondokar ◽  
Khurshed Ahmed ◽  
Mohammad Ashraf Hossain ◽  
Rakibulh Rashed ◽  
Mohamed Mausool Siraj ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Side Effects ◽  
Chronic Heart Failure ◽  
Ejection Fraction ◽  
Systolic Function ◽  
Nyha Class ◽  
Left Ventricular ◽  
Group I ◽  
Lv Systolic Function

Background:Chronic heart failure (CHF) is the most common and prognostically unfavorable outcome of many diseases of the cardiovascular system. Clinical trials have demonstrated mortality and morbidity benefits of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure. These studies have used either eplerenone or spironolactone as the MRA. Eplerenone is a selective aldosterone antagonist expected to have a lower incidence of hormonal side effects than spironolactone. The present study is designed to compare these two drugs in chronic heart failure patients as no head to head trial between these two drugs is found regarding improvement of systolic function, tolerability and safety. The aim of this study is to compare the effects of eplerenone and spironolactone on LV systolic function in patients with chronic heart failure in a single center. Methods:It was a randomized clinical trial single blind study. A total of 224 cases of chronic heart failure with reduced ejection fraction and NYHA class III or IV were selected by random sampling, from July 2017 to June 2018. Each patient was randomly allocated into either of the two arms, and was continued receiving treatment with either spironolactone (Arm-I) or eplerenone(Arm-II). Each patient was evaluated clinically, biochemically and echocardiographically at the beginning of treatment (baseline) at 1 month and at the end of 6th month. Echocardiography was performed to find out change in left ventricular systolic function. Result: After 6 months of treatment, ejection fraction was found higher in the eplerenonearm (40.3 ± 6.5 versus 38.3 ± 4.6%; P < 0.05). Ejection fraction (EF) changes were 6.2% in eplerenone group and 4.1% in spironolactonearm. A significant reduction in left ventricular end-systolic volume (21.9±2.5 in group I versus 14.9±5.7 in group II; P < 0.05) and left ventricular systolic diameter (48.7±4.0 in arm I versus 45.2±4.9 in arm II; P<0.05) occurred after 6 months of treatment. But no significant differences were observed in left ventricular end-diastolic volume (187.8±37.4 versus 184.5±33.9; P=0.101) and left ventricular diastolic diameter (60.1±4.5 versus 61.0±4.9; P=0.0818) between arms. Assessment of blood pressure six months after treatment shows, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were improved in both arms but difference between two arms were statistically non-significant (p>0.05). Conclusion: In this study, the improvement in systolic function was more in eplerenone arm, which also had fewer adverse side effects when compared to spironolactone arm. So, it can be concluded that eplerenone can be advised in patient with chronic heart failure in addition to other drugs that are used to treat heart failure. University Heart Journal Vol. 16, No. 2, Jul 2020; 65-70

2371Electrocardiographic features and their echocardiographic correlates in peripartum cardiomyopathy based on the EURObservational registry on PPCM

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A C Mbakwem ◽  
J Bauersachs ◽  
C Viljoen ◽  
P Van Der Meer ◽  
M Petrie ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ethnic Differences ◽  
Regional Differences ◽  
Sinus Tachycardia ◽  
Systolic Function ◽  
Nyha Class ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Peripartum Cardiomyopathy ◽  
Qtc Interval

Abstract Background Cardiac disease remains an important cause of maternal morbidity and mortality globally. Peripartum cardiomyopathy (PPCM), defined as heart failure secondary to left ventricular (LV) systolic dysfunction in previously healthy women towards the end of pregnancy or up to five months following delivery, can result in cardiogenic shock due to severe LV dysfunction or arrhythmias leading to sudden cardiac death. Cardiac electrical activity and its relationship to cardiac dysfunction have not yet been interrogated in large multi-centre studies. Purpose This study aimed to identify the ECG abnormalities associated with PPCM; their relationship with echocardiographic structural and functional abnormalities and explore regional and ethnic differences in ECG features. Methods We included the first 411 patients enrolled into the EURObservational PPCM registry (EORP). Baseline demographic, clinical and echocardiographic data were collected. ECGs were analysed for rate; rhythm; QRS width, axis and morphology; and QTc interval. Results Mean age of the women (from >40 countries) was 30.7±6.4 years. More than two thirds of patients presented with NYHA class III or IV (with no regional differences). The median QRS rate was 102bpm (IQR 87–117). More than half presented with sinus tachycardia (QRS rate >100bpm), whereas atrial fibrillation was rare (2.27%). The mean QRS width was 90.1ms ±21.5, with regional differences (ESC 93.8ms ±21.7 vs. non-ESC 86.8ms ±20.8, P<0.001). Left bundle branch block (LBBB) was reported in 9.30% with no regional or ethnic differences. Left ventricular hypertrophy (LVH) was present in a quarter of the cohort, and more prevalent amongst African (59.62%) and Asian (23.17%) than Caucasians (7.63%, P<0.001). The median QTc by Bazett was 456.7ms (IQR 409–490.7) and almost half (47.11%) had prolonged QTc (>460ms). The median LVEDD was 60mm (IQR 55–65) on echocardiography. Compared with their Asian and Caucasian counterparts, African patients were more likely to have LV dilatation (LVEDD>53mm: 70.11%, 79.31% and 89.42% respectively; P=0.004). The median LV ejection fraction (LVEF) was 32.50% (IQR 25–39) with no significant regional or ethnic differences. Sinus tachycardia predicted poor systolic function (OR 1.85 [95% CI 1.20–2.85], p=0.006). LVEF <35% was associated with a significantly higher QRS rate (median rate 107 vs. 98bpm, p=0.002). Women with LVEDD ≥53mm had a longer mean QRS duration (92.0±22.4 vs. 82.4±15.4ms, p<0.001) and frequency of LBBB (11.15% vs 1.54%, p=0.016). LBBB was a predictor of LVEDD >53mm (sensitivity 11.15%; specificity 98.46%; PPV 97.14%; NPV 19.10%; OR 8.02 [95% CI 1.08–59.66], p=0.042). Conclusion Patients with PPCM commonly present with sinus tachycardia, LVH, and/or prolonged QTc interval on their ECG. Wide QRS and/or LBBB, were associated with LVEDD>53mm. Sinus tachycardia, however, was associated with LVEF<35%. Risk of arrhythmia in those with prolonged QTc remains to be ascertained. Acknowledgement/Funding Heart Failure Association of the ESC

scholarly journals Sequential left ventricular electro-mechanical changes in presence of left bundle branch block

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
J Duchenne ◽  
S Calle ◽  
A Puvrez ◽  
F Rega ◽  
F Timmermans ◽  
...  
Keyword(s):  
Animal Model ◽  
Wall Thickness ◽  
Lateral Wall ◽  
Mechanical Dyssynchrony ◽  
Left Ventricular ◽  
Conduction Delay ◽  
Bundle Branch Block ◽  
Septal Wall ◽  
Qrs Duration ◽  
Over Time

Abstract Introduction Recent cross-sectional studies suggest a relationship between persisting left bundle branch block (LBBB) and the extent of left ventricular (LV) electro-mechanical alterations over time. When patients are referred for cardiac resynchronization therapy (CRT), temporal data during the sub-clinical phase of disease is often missing. A longitudinal study using an animal model would provide a better understanding of the relationship between the onset of LBBB and the electro-mechanical changes. Purpose To investigate the sequential alterations in LV structure and function that develop over time in an animal model of LBBB. Methods Thirteen sheep were subjected to rapid DDD pacing (180 bpm; leads on right atrium and right ventricular free wall) in order to induce a LBBB-like conduction delay. All animals underwent an 8-week pacing protocol, whereas 4 of them were subjected to 16 weeks of pacing in total. Echocardiographic speckle tracking was used to assess circumferential strain of the septal and lateral wall. Septal and lateral wall thickness were measured at end-diastole. Cardiac magnetic resonance imaging was used to determine LV volumes and ejection fraction (LVEF). Examinations took place at baseline (before and after start of pacing), and after 8 and 16 weeks of pacing. All examinations were performed at a physiologic heart rate of 110 bpm. Results At baseline, DDD pacing induced an increase in QRS duration (+85%, p&lt;0.0001) and LBBB-like mechanical dyssynchrony, with mild early-systolic notching and preserved systolic shortening of the septal wall. The lateral wall demonstrated early pre-stretch followed by increasing systolic shortening. No acute changes in LV end-diastolic volume, LVEF or septal or lateral wall thickness were observed (all p&gt;0.05). After 8 weeks of DDD pacing, mechanical dyssynchrony worsened: septal notching increased, followed by reduced systolic shortening. After 16 weeks, the initial septal shortening was followed by profound stretching throughout systole. Lateral wall systolic shortening was reduced compared to baseline. QRS duration increased further by +12% (week 8) and +20% (week 16) (all p&lt;0.001). End-diastolic volumes had increased by +39% (week 8) and +72% (week 16), whereas LVEF had decreased by −48% (week 8) and −56% (week 16) (all p&lt;0.001). Septal wall thickness had reduced by −24% (week 8) and −33% (week 16), while lateral wall thickness had increased by +21% (week 8) and +30% (week 16) (all p&lt;0.05). Conclusion A persisting LBBB-like conduction delay induces sequential changes in LV deformation patterns, and triggers morphological and electrical remodelling. These changes are similar to those observed in patients with LBBB and different degrees of LV dysfunction. Our data suggest a continuum due to the progression of LBBB-induced LV disease. In the clinic, patients with mild dysfunction should be closely monitored in order to treat dyssynchrony as soon as guideline indications are reached. FUNDunding Acknowledgement Type of funding sources: Other. Main funding source(s): This work was supported by a KU Leuven research grant

Complete dexrazoxane cardioprotection for cardiac function but incomplete female cardioprotection for cardiac structure in doxorubicin-treated osteosarcoma survivors: Hearts too small for the body.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10519-10519
Author(s):  
Lisa M. Kopp ◽  
Mark L. Bernstein ◽  
Cindy L. Schwartz ◽  
David Ebb ◽  
Vivian L Franco ◽  
...  
Keyword(s):  
Heart Failure ◽  
Wall Thickness ◽  
Systolic Function ◽  
Posterior Wall ◽  
Left Ventricular ◽  
The Body ◽  
Lv Function ◽  
Lv Systolic Function ◽  
Trastuzumab Cardiotoxicity

10519 Background: Dexrazoxane is protective for lower-dose doxorubicin ( < 300 mg/m2) cardiotoxicity in childhood cancer, but the effect of dexrazoxane (DXRZ) administered with higher-dose (HD) doxorubicin (DOXO) is unknown. Methods: We evaluated patients from Children’s Oncology Group trials for localized (P9754) and metastatic (AOST0121) osteosarcoma (OS) who received HD DOXO (375-600 mg/m2) preceded by DXRZ (10:1 ratio), methotrexate, and cisplatin; some also received ifosfamide alone or ifosfamide/etoposide ± trastuzumab. Cardiotoxicity was identified by echocardiography and by serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations. Results: 81 DXRZ -treated OS patients ( age at enrollment = 13.7 years; range 3.8 - 23.7 years) had normal left ventricular (LV) systolic function as measured by LV fractional shortening and no heart failure. Female sex and longer follow-up since DOXO were associated with a significantly smaller LV dimension z-score normalized to BSA (μ = -1.20, 95%CI [-1.70, -0.70]). Similarly, in the one-third of patients treated > 81 days after minimal expected treatment (groups equally partitioned by time), significantly thinner LV posterior wall thickness for BSA (μ = -0.57, [-1.05, -0.09]) was found. Interventricular septal wall thickness (μ = -0.84, [-1.2, -0.48]) and LV mass (μ = -0.73, [-1.06, -0.40]) were significantly smaller for BSA than normal for both sexes. For females, these became significantly more abnormal with increasing length of follow-up. Females also showed progressive increases in NT-proBNP. Conclusions: DXRZ is cardioprotective for HD DOXO in terms of LV function and heart failure. Females had progressive abnormalities of LV structure, leading to smaller hearts for body size. This was associated with increasing cardiac stress, as measured by NT-proBNP. DXRZ protection was incomplete for HD DOXO effects on LV structure, resulting in higher LV stress and risk for late LV dysfunction. DXRZ should continue to be used in this population, including for females who exhibit more cardiotoxicity than males at specific cumulative DOXO doses.

Abstract 16989: Impaired Systolic Function Assessed by Strain Imaging Predicts Cardiovascular Morbidity and Mortality in Heart Failure with Preserved Ejection Fraction

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Amil M Shah ◽  
Brian Claggett ◽  
Nancy K Sweitzer ◽  
Sanjiv J Shah ◽  
Inder S Anand ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Systolic Function ◽  
Strain Imaging ◽  
Left Ventricular ◽  
Morbidity And Mortality ◽  
Preserved Ejection Fraction ◽  
Composite Outcome ◽  
History Of ◽  
Lv Systolic Function

Introduction: Left ventricular (LV) systolic function by strain imaging is impaired in heart failure with preserved ejection fraction (HFpEF) but its prognostic relevance is not known. Hypothesis: We hypothesized that worse longitudinal strain (LS) is independently associated with adverse outcomes. Methods: LS was assessed by 2D speckle-tracking echocardiography in a blinded core laboratory at baseline in 447 patients with HFpEF (left ventricular ejection fraction [LVEF] ≥45%) enrolled in the Treatment Of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial and was related to the primary composite outcome of cardiovascular (CV) death, HF hospitalization, or aborted cardiac arrest, and its components. Results: At a median follow-up of 2.6 (IQR 1.5-3.9) years, 115 patients experienced the primary outcome. Impaired LS, defined as an absolute LS < 15.8%, was present in 53% of patients and was associated with the composite outcome (adjusted HR 2.14, 95% CI 1.26-3.66; p=0.005), CV death alone (adjusted HR 3.20, 95% CI 1.44-7.12; p=0.004), and HF hospitalization alone (adjusted HR 2.23, 95% CI 1.16-4.28; p=0.016) after adjusting for age, gender, race, randomization strata (prior HF hospitalization vs elevated B-type natriuretic peptide level), region of enrollment (Americas vs Russia or Georgia), randomized treatment assignment, history of atrial fibrillation, heart rate, New York Heart Association class, history of stroke, creatinine, hematocrit, LVEF, mass, end-systolic volume index, and E/E’ ratio. These findings were similar in the subgroup of 354 patients with LVEF ≥55%. Conclusions: Among HFpEF patients enrolled in TOPCAT, impaired LV systolic function, measured by LS, is predictive of adverse CV outcomes independent of clinical and conventional echocardiographic predictors. Impaired LS represents a novel imaging biomarker to identify HFpEF patients at particularly high risk for CV morbidity and mortality.

scholarly journals Correlation of N-terminal pro-B-type natriuretic peptide with clinical parameters in patients with hypertension

2013 ◽  
Vol 70 (8) ◽  
pp. 728-734
Author(s):  
Janko Pejovic ◽  
Svetlana Ignjatovic ◽  
Marijana Dajak ◽  
Nada Majkic-Singh ◽  
Zarko Vucinic ◽  
...  
Keyword(s):  
Heart Failure ◽  
Systolic Function ◽  
Nyha Class ◽  
Left Ventricular Systolic Function ◽  
Left Ventricular ◽  
Control Group ◽  
Ventricular Systolic Function ◽  
Function Group ◽  
Group 2 ◽  
Group 1

Background/Aim. Identification of patients with arterial hypertension and a possible onset of heart failure by determining the concentration of N-terminal pro-B-type natriuretic peptide (NT-proBNP) enables timely intensification of treatment and allows clinicians to prescribe and implement optimal and appropriate care. The aim of this study was to evaluate NT-proBNP in patients with longstanding hypertension and in patients with signs of hypertensive cardiomyopathy. Methods. The study involved 3 groups, with 50 subjects each: ?healthy? persons (control group), patients with hypertension and normal left ventricular systolic function (group 1) and patients with longstanding hypertension and signs of hypertensive cardiomyopathy with impaired left ventricular systolic function (group 2). We measured levels of NT-proBNP, Creactive protein and creatinine according to the manufacturer?s instructions. All the patients were clinically examined including physical examination of the heart with blood pressure, pulse rate, electrocardiogram (ECG) and echocardiogram. Results. Our results showed that the determined parameters generally differed significantly (Student?s t-test) among the groups. The mean (? SD) values of NT-proBNP in the control group, group 1 and group 2 were: 2.794 (? 1.515) pmol/L, 9.575 (? 5.449) pmol/L and 204.60 (84,93) pmol/L, respectively. NTproBNP correlated significantly with the determined parameters both in the group 1 and the group 2. In the group 1, the highest correlation was obtained with Creactive protein (r = 0.8424). In the group 2, the highest correlation was obtained with ejection fraction (r = - 0.9111). NT-proBNP showed progressive increase in proportion to the New York Heart Association (NYHA) classification. The patients in thegroup 2 who belonged to the II and III NYHA class had significantly higher levels of NTproBNP than those in the NYHA class I (ANOVA test, p = 0.001). Conclusion. The obtained results suggest that NTproBNP is a useful biomarker in the treatment of patients with longstanding hypertension who are at risk for heart failure.

Abstract 17367: Infusion of the Ketone Body β-Hydroxybutyrate Improves Left Ventricular Systolic Function in an Animal Model of Heart Failure With Reduced Ejection Fraction

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Carlos G SantosGallego ◽  
Juan Antonio Requena-Ibanez ◽  
Rodolfo San Antonio ◽  
Kiyotake Ishikawa ◽  
Belén Picatoste ◽  
...  
Keyword(s):  
Heart Failure ◽  
Feature Tracking ◽  
Ketone Bodies ◽  
Systolic Function ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Lv Function ◽  
Contractile Reserve ◽  
Hemodynamic Assessment ◽  
Lv Systolic Function

Introduction: In vitro, ketone bodies (KB) are the most energetically efficient fuel for myocardium. Ex vivo, KB infusion in the perfusion medium of working rat hearts increases the heat of combustion (produced energy) by 31%. However, there is no report about the in vivo effects of KB on LV function. We hypothesized that KB infusion in HFREF would improve energy production and thus LV systolic function. Methods: HFREF was induced in 15 pigs by 2-hour balloon occlusion of LAD: proximal LAD (n=8, severe HREF) and mid LAD (n=7, moderate HFREF). At 2 months, LV systolic function was evaluated during saline infusion and during infusion of the KB β-hydroxybutyrate. Severe HFREF animals underwent cardiac MRI for baseline LVEF, feature tracking strains, and contractile reserve (ΔLVEF under dobutamine 5μg/kg/min). Moderate HFREF pigs underwent invasive hemodynamic assessment (dP/dt) and 3D-echocadiography (3D-LVEF and 3D-strains). Simultaneous sampling from coronary artery and coronary sinus was performed to measure myocardial fuel consumption. Results: Proximal and mid LAD occlusion resulted in severe and moderate LV systolic dysfunction, respectively. In the severe HFREF, ketone infusion improved baseline LVEF, feature-tracking strains (both longitudinal and circumferencial strain), and contractile reserve. In the moderate HFREF, ketone infusion improved 3D-LVEF, 3D-strains and dP/dt (Table). Ketone infusion switched myocardial metabolism from glucose to ketone consumption. Conclusions: Continuous infusion of the KB hydroxybutyrate improves LV systolic function independent of LV systolic dysfunction severity via a shift in myocardial fuel metabolism away from glucose oxidation (energy inefficient) toward a more energy-efficient fuel like KB. This effect can explain the mechanism of action of the benefits of SGLT2 inhibitors in heart failure, as empagliflozin-induced mild kyperketonemia may increase LV systolic function and thus improve patient outcomes.

scholarly journals Endogenous Ouabain: An Old Cardiotonic Steroid as a New Biomarker of Heart Failure and a Predictor of Mortality after Cardiac Surgery

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Marco Simonini ◽  
Simona Pozzoli ◽  
Elena Bignami ◽  
Nunzia Casamassima ◽  
Elisabetta Messaggio ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Surgery ◽  
Nyha Class ◽  
Left Ventricular ◽  
Perioperative Mortality ◽  
Mortality And Morbidity ◽  
Elective Cardiac Surgery ◽  
Endogenous Ouabain ◽  
Postoperative Time ◽  
Independent Cohort

Cardiovascular diseases remain the main cause of mortality and morbidity worldwide; primary prevention is a priority for physicians. Biomarkers are useful tools able to identify high-risk individuals, guide treatments, and determine prognosis. Our aim is to investigate Endogenous Ouabain (EO), an adrenal stress hormone with hemodynamic effects, as a valuable biomarker of heart failure. In a population of 845 patients undergoing elective cardiac surgery, we have investigated the relationships between EO and echocardiography parameters/plasmatic biomarker of cardiac function. EO was found to be correlated negatively with left ventricular EF (p=0.001), positively with Cardiac End-Diastolic Diameter (p=0.047), and positively with plasmatic NT-proBNP level (p=0.02). Moreover, a different plasmatic EO level (both preoperative and postoperative) was found according to NYHA class (p=0.013). All these results have been replicated on an independent cohort of patients (147 subjects from US). Finally, a higher EO level in the immediate postoperative time was indicative of a more severe cardiological condition and it was associated with increased perioperative mortality risk (p=0.023for 30-day morality). Our data suggest that preoperative and postoperative plasmatic EO level identifies patients with a more severe cardiovascular presentation at baseline. These patients have a higher risk of morbidity and mortality after cardiac surgery.

scholarly journals Inhibition of late Na+ current, a novel target to improve diastolic function and electrical abnormalities in Dahl salt-sensitive rats

2016 ◽  
Vol 310 (10) ◽  
pp. H1313-H1320 ◽  
Author(s):  
Liguo Chi ◽  
Luiz Belardinelli ◽  
Aliya Zeng ◽  
Ryoko Hirakawa ◽  
Sridharan Rajamani ◽  
...  
Keyword(s):  
Heart Failure ◽  
Diastolic Dysfunction ◽  
Chronic Treatment ◽  
Systolic Function ◽  
Diastolic Heart Failure ◽  
Mitral Annulus ◽  
Left Ventricular ◽  
Mitral Annulus Velocity ◽  
Lv Mass ◽  
Lv Systolic Function

Late Na+ current ( INaL) is enhanced in myocytes of animals with chronic heart failure and patients with hypertrophic cardiomyopathy. To define the role of INaL in diastolic heart failure, the effects of GS-458967 (GS-967), a potent INaL inhibitor on mechanical and electrical abnormalities, were determined in an animal model of diastolic dysfunction. Dahl salt-sensitive (DSS) rats fed a high-salt (HS) diet for 8 wk, compared with a normal salt (NS) diet, had increased left ventricular (LV) mass (1,257 ± 96 vs. 891 ± 34 mg) and diastolic dysfunction [isovolumic relaxation time (IVRT): 26.8 ± 0.5 vs. 18.9 ± 0.2 ms; early transmitral flow velocity/early mitral annulus velocity (E/E') ratio: 25.5 ± 1.9 vs. 14.9 ± 0.9]. INaL in LV myocytes from HS rats was significantly increased to 0.41 ± 0.02 from 0.14 ± 0.02 pA/pF in NS rats. The action potential duration (APD) was prolonged to 136 ± 12 from 68 ± 9 ms in NS rats. QTc intervals were longer in HS vs. NS rats (267 ± 8 vs. 212 ± 2 ms). Acute and chronic treatment with GS-967 decreased the enhanced INaL to 0.24 ± 0.01 and 0.17 ± 0.02 pA/pF, respectively, vs. 0.41 ± 0.02 pA/pF in the HS group. Chronic treatment with GS-967 dose-dependently reduced LV mass, the increases in E/E' ratio, and the prolongation of IVRT by 27, 27, and 20%, respectively, at the 1.0 mg·kg−1·day−1 dose without affecting blood pressure or LV systolic function. The prolonged APDs in myocytes and QTc of HS rats were significantly reduced with GS-967 treatment. These results indicate that INaL is a significant contributor to the LV diastolic dysfunction, hypertrophy, and repolarization abnormalities and thus, inhibition of this current is a promising therapeutic target for diastolic heart failure.

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