Abstract 486: Increased Afterload In Sub-acute Phase Of Myocardial Infarction Exacerbates Heart Failure

Background: Hypertension (HT) increases cardiac afterload and is one of the risk factors of poor prognosis after myocardial infarction (MI). However, there is little information on how HT impacts the healing processes during sub-acute phase MI. We investigated the role of an increased afterload on left ventricular (LV) performance and remodeling shortly after MI. Methods: Anterior MIs were created in 15 Yorkshire pigs via percutaneous access. To mimic HT condition, 7 pigs (Banding, n=7) underwent surgical banding of the ascending aorta 10 days after the MI, and were compared to the remaining pigs (Control, n=8). LV remodeling and function were assessed one month after MI using 3-D echocardiography and invasive hemodynamic measurements. Results: Echocardiographic assessment at day 10 revealed no significant differences in LV ejection fraction (EF) or LV volumes. One month after MI, aortic banding increased the systemic vascular resistance index, but was not statistically significant (1658±282 dyn/s/cm5/m 2 vs 1153±658 dyn/s/cm5/m 2 , P=0.08). Banding group presented with significantly impaired LVEF (Figure, P=0.002), larger end systolic volume (Figure, P=0.045), lower cardiac index (3.1±0.9 L/min/m 2 vs 4.4±0.6 L/min/m 2 , P=0.01), and elevated LV end diastolic pressure (22.4±5.0 mmHg vs 14.4±7.5 mmHg: P=0.04, Banding vs Control, respectively). Reduced EF was associated with remote myocardial dysfunction and histological analysis revealed increased interstitial fibrosis in this area. Conclusion: Increased afterload in sub-acute phase of MI induces more severely impaired cardiac function and LV remodeling, and was associated with worse heart failure status.

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Abstract 370: Type 2 Diabetes Is Associated with the Exacerbation of Heart Failure via Increasing Myocardial NAD(P)H Oxidase-Derived Superoxide Production

Circulation ◽

10.1161/circ.118.suppl_18.s_292-c ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Shintaro Kinugawa ◽

Shouji Matsushima ◽

Takashi Yokota ◽

Yukihiro Ohta ◽

Naoki Inoue ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Diastolic Pressure ◽

Interstitial Fibrosis ◽

Left Ventricular ◽

Lung Weight ◽

Tissue Mass ◽

Tibial Length ◽

Lv Remodeling

Type 2 diabetes mellitus (DM) adversely affects the outcomes in patients with myocardial infarction (MI), which is associated with the development of left ventricular (LV) remodeling and failure. NAD(P)H oxidase-derived superoxide (O 2 − ) production is increased in DM. However, its pathophysiological significance in advanced post-MI LV failure associated with DM remains unestablished. We thus determined whether an inhibitor of NAD(P)H oxidase activation, apocynin, could attenuate the exacerbated LV remodeling and heart failure after MI in high-fat diet (HFD)-induced obese mice with DM. Male C57BL/6J mice were fed on either HFD or normal diet (ND) for 8 weeks. At 4 weeks of feeding, MI was created in all mice by ligating left coronary artery. MI mice were treated with either apocynin (10 mmol/l in drinking water; n = 10 for ND and n = 11 for HFD) or vehicle (n = 15 for ND and n = 13 for HFD). HFD significantly increased body weight (BW), adipose tissue mass, fasting plasma glucose and insulin levels compared to ND after 4 and 8 weeks. HFD + MI had significantly greater LV end-diastolic diameter (LVEDD; 5.7 ± 0.1 vs. 5.3 ± 0.2 mm) by echocardiography, end-diastolic pressure (EDP; 12 ± 2 vs. 8 ± 1 mmHg) and lung weight/tibial length (10.1 ± 0.3 vs. 8.7 ± 0.7 mg/mm) than ND + MI, which was accompanied by an increased interstitial fibrosis of non-infarcted LV. Treatment of HFD + MI with apocynin significantly decreased LVEDD (5.4 ± 0.1 mm), LVEDP (9.7 ± 0.8 mmHg), lung weight/tibial length (9.0 ± 0.3 mg/mm), and concomitantly interstitial fibrosis of non-infarcted LV to ND + MI level without affecting BW, glucose metabolism, infarct size and aortic pressure. On the other hand, treatment of ND + MI with apocynin did not affect LV remodeling and failure. NAD(P)H oxidase activity, O 2 − production measured by lucigenin chemiluminescence, and thiobarbituric acid-reactive substances were increased in non-infarcted LV tissues from HFD + MI, all of which were also attenuated by apocynin to ND + MI level. Type 2 DM was associated with the exacerbation of LV remodeling and failure after MI via increasing NAD(P)H oxidase derived O 2 − production, which may be a novel important therapeutic target in advanced heart failure with DM.

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P4639Plasma tissue factor coagulation activity in post-acute myocardial infarction patients

European Heart Journal ◽

10.1093/eurheartj/ehz745.1021 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

X C Lim ◽

S M J M Yatim ◽

S Y Chong ◽

X Wang ◽

S H Tan ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Plasma Levels ◽

Healthy Subjects ◽

Left Ventricular ◽

Mean Difference ◽

Coagulation Activity ◽

Systolic Volume ◽

Lv Remodeling ◽

End Systolic Volume

Abstract Background Coagulation is involved in fibroproliferative responses following acute myocardial infarction (AMI). Left ventricular (LV) remodeling following AMI is closely associated with progression to heart failure. Purpose We aimed to evaluate the association of plasma tissue factor (TF) coagulation activity with LV remodeling prior to heart failure in post-AMI patients. Methods This study was conducted in 228 subjects from the Post-AMI Left Ventricular Remodeling Biomarker Analysis (PAMILA) study and 57 healthy subjects. The post-AMI patients were divided into two age- and sex-matched groups: patients with adverse LV remodeling defined as an increase in LV end systolic volume by ≥15% over 6 months and patients with reverse LV remodeling defined as an decrease in LV end systolic volume by ≥15% over 6 months. TF coagulation activity was determined using human coagulation factor Xa generation based TF chromogenic activity assay and converted into concentrations of active TF (pM). Sodium-citrate anticoagulated plasma was collected at baseline (within 3 days after revascularization), 30 days and 6 months post-AMI. Results are presented as mean±S.E.M. One-way or two-way repeated measures ANOVA or a multiple multi-level longitudinal data analysis with structural equation model was used to assess differences in coagulation activity. P<0.05 was considered statistically significant. Results Plasma from healthy subjects and post-AMI patients at baseline had similar concentrations of active TF (TFa): 29.0±1.4 versus 29.1±0.7 pM. Patients treated with warfarin (15 out of 228 patients) showed lower plasma levels of TFa (mean difference −15.2 pM, [95% CI: −18.7, −11.7], p<0.001). Compared to baseline, plasma levels of TFa in the patients was significantly lower at 30 days post-AMI (mean difference −6.9 pM, [95% CI: −4.8, −8.9], p<0.001) and 6 months post-AMI (mean difference −2.8 pM, [95% CI: −0.8, −4.8], p=0.003). Intriguingly, plasma levels of TFa tended to recover from 30 days to 6 months post-AMI (mean difference 4.1 pM, [95% CI: 2.8, 5.4], p<0.001) toward the baseline level and the level in healthy subjects. Similar trends of temporal changes of plasma TFa levels were observed in patients with adverse LV remodeling and those with reverse LV remodeling although TFa levels were slightly higher in patients with reverse LV remodeling (F(2,448)=3.112, p=0.045 for interaction). After adjusting for age, gender, ethnicity, medications, lipid profile and risk factors, the temporal changes of plasma TFa levels in patients remain significant, however, the difference between patients with adverse versus reverse LV remodeling was not significant. Conclusion Plasma TF coagulation activity decreased post-AMI but did not differ in patients with adverse versus reverse LV remodeling. Acknowledgement/Funding National University Health System Singapore (NUHS O-CRG 2016 Oct-23) to JW Wang

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Abstract 1342: The NF-kappaB P50 Subunit Protects Against Remodeling and Cardiac Dysfunction Following Myocardial Infarction

Circulation ◽

10.1161/circ.116.suppl_16.ii_275 ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Leo Timmers ◽

J Karlijn van Keulen ◽

Imo I Hoefer ◽

Joost P Sluijter ◽

Marie Jose Goumans ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Molecular Mechanisms ◽

Interstitial Fibrosis ◽

Systolic Dysfunction ◽

Protective Role ◽

Left Ventricular ◽

Lv Remodeling ◽

Nf Kappab

Introduction Left ventricular (LV) remodeling leads to congestive heart failure and is a main determinant of morbidity and mortality following myocardial infarction (MI). To further improve the treatment of post infarct LV remodeling, a better understanding of the molecular mechanisms involved in this complicated process is required. The nuclear factor (NF)- κB family (p50, p52, p65) usually forms dimers that regulate DNA transcription in response to a variety of stimuli including pro-inflammatory cytokines, oxidative stress and also ischemia. Inhibition of NF- κB has been shown to reduce heart failure following MI in rats. The specific role of the different NF- κB subunits during LV remodeling, however, has not been clarified thus far. In this study, we elucidate the role of the NF- κB p50 subunit in post infarct LV remodeling. Methods and Results MI was induced in wild type C57Bl6 mice and NF- κB p50 KO mice. Without affecting infarct size (45.4 ± 4.3 vs. 42.5 ± 4.6%; p=0.461), the absence of NF- κB p50 increased the extent of LV remodeling (EDV: 175 ± 13 vs. 107 ± 11 μl; p=0.005) and aggravated systolic dysfunction (LVEF: 16.1 ± 1.5 % vs. 24.7 ± 3.7%; p=0.045) 28 days following MI as assessed by magnetic resonance imaging (9.4 T). In the non-infarcted myocardium, interstitial fibrosis (1.53 ± 0.28 vs. 1.05 ± 0.15 grayvalue/μm 2 ; p=0.042) and hypertrophy (426 ± 51 vs. 251 ± 12 μm 2 /cardiomyocyte; p=0.018) were increased in NF-κB p50 KO mice. In the infarct area, however, collagen density was decreased (15.11 ± 1.16 vs. 27.28 ± 4.93 grayvalue/μm 2 ; p=0.028), which was accompanied by increased TNF-alpha mRNA expression (0.086 ± 0.04 vs. 0.026 ± 0.015; p=0.046) and increased MMP9 activity (0.31 ± 0.03 vs. 0.19 ± 0.03; p=0.049) Conclusion These data provide evidence for a protective role of NF- κB p50 in post infarct maladaptive LV remodeling, most likely by reducing inflammatory cytokine production and matrix degradation.

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Left ventricular diastolic function of remodeled myocardium in dogs with pacing-induced heart failure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1998.274.3.h945 ◽

1998 ◽

Vol 274 (3) ◽

pp. H945-H954 ◽

Cited By ~ 6

Author(s):

Steven B. Solomon ◽

Srdjan D. Nikolic ◽

Stanton A. Glantz ◽

Edward L. Yellin

Keyword(s):

Heart Failure ◽

Elastic Properties ◽

Diastolic Pressure ◽

Left Ventricular Diastolic Function ◽

Left Ventricular ◽

Diastolic Filling ◽

Elastic Recoil ◽

Systolic Volume ◽

Left Ventricular Chamber ◽

Volume Relation

In patients with heart failure, decreased contractility resulting in high end-diastolic pressures and a restrictive pattern of left ventricular filling produces a decrease in early diastolic filling, suggesting a stiff ventricle. This study investigated the elastic properties of the myocardium and left ventricular chamber and the ability of the heart to utilize elastic recoil to facilitate filling during pacing-induced heart failure in the anesthetized dog. Elastic properties of the myocardium were determined by analyzing the myocardial stress-strain relation. Left ventricular chamber properties were determined by analyzing the pressure-volume relation using a logarithmic approach. Elastic recoil was characterized using a computer-controlled mitral valve occluder to prevent transmitral flow during diastole. We conclude that, during heart failure, the high end-diastolic pressures suggestive of a stiff ventricle are due not to stiffer myocardium but to a ventricle whose chamber compliance characteristics are changed due to geometric remodeling of the myocardium. The restrictive filling pattern is a result of the ventricle being forced to operate on the stiff portion of the diastolic pressure-volume relation to maintain cardiac output. Slowed relaxation and decreased contractility result in an inability of the heart to contract to an end-systolic volume below its diastolic equilibrium volume. Thus the left ventricle cannot utilize elastic recoil to facilitate filling during heart failure.

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Prognostic implications of left ventricular torsion by feature-tracking cardiac magnetic resonance in patients with ST-elevation myocardial infarction

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeab090.095 ◽

2021 ◽

Vol 22 (Supplement_2) ◽

Author(s):

LAI Wei ◽

HENG Ge ◽

JUN Pu

Keyword(s):

Myocardial Infarction ◽

Acute Phase ◽

Risk Model ◽

Left Ventricular ◽

Independent Predictive Factor ◽

Normal People ◽

Lv Remodeling ◽

St Elevation ◽

Prognostic Implications ◽

Lv Aneurysm

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): the National Key Research and Development Program of China OnBehalf Renji Hospital Affiliated to Medical College of Shanghai Jiaotong University Background The prognostic implications of left ventricular (LV) torsion on the long-term prognosis of patients with acute ST-elevation myocardial infarction (STEMI) is not clear. Methods We analyzed Cardiac Magnetic Resonance (CMR) images and followed up 420 first STEMI patients from the EARLY Assessment of MYOcardial Tissue Characteristics by CMR in STEMI (EARLY-MYO-CMR) registry (NCT03768453). These patients received timely primary percutaneous coronary intervention (PCI) within 12h and CMR examination within 1 week (median,5 days; range, 2-7 days) after infarction. Besides, CMR images of 40 normal people were enrolled as the control group. LV torsion, torsion rate and other conventional CMR indexes were measured. Ultrasound cardiogram examinations were performed in the acute phase and 1 year post-STEMI to assess LV remodeling (≥ 20% increase in LV end-diastolic volume). Primary end point was composite major adverse cardiac and cerebrovascular events (MACCEs) including cardiovascular death, re-infarction, re-hospitalization for heart failure and stroke. Secondary end points were the formation of LV aneurysm/thrombus in hospital as well as LV remodeling at 1 year post-STEMI. Results During follow-up (median: 52 months, inter-quartile range: 29–78 months), 80 patients developed MACCEs. Compared with normal people, patients with STEMI had more decreased LV torsion (P < 0.001) and torsion rate (P = 0.033). Patients who experienced MACCEs had more impaired LV torsion (P < 0.001) and torsion rate (P < 0.001) than those who didn’t. LV torsion ≤ 0.876 deg/cm in the acute phase of STEMI was an independent predictive factor of MACCE (P = 0.001) and LV remodeling (P = 0.001). Patients with impaired LV torsion were more likely to experience MACCEs (P < 0.001). The impairment of LV torsion was also associated with the higher incidence of LV aneurysm (P < 0.001) and thrombus (P = 0.006). The addition of LV torsion to a risk model comprising LV ejection fraction (LVEF), infarct size (IS), and microvascular obstruction (MVO) led to a net reclassification improvement (continuous NRI 0.499 [95% CI, 0.261–0.737]; P < 0.001). Hypertension (P = 0.047), tobacco use (P = 0.005), worse TIMI flow post-PCI (P < 0.001), more extensive IS (P < 0.001) / MVO size (P = 0.002) were associated with the impairment of LV torsion. Conclusions Compared with normal people, patients with STEMI had more decreased LV torsion and torsion rate. LV torsion ≤ 0.876 deg/cm in the acute phase was an independent predictive factor of MACCE and LV remodeling. The addition of LV torsion to a risk model comprising LVEF, LV-IS and LV-MVO significantly improved risk stratification of patients with STEMI .

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Vascular β-adrenergic receptor system is dysfunctional after myocardial infarction

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2001.280.3.h1129 ◽

2001 ◽

Vol 280 (3) ◽

pp. H1129-H1135 ◽

Cited By ~ 8

Author(s):

Mohamed A. Gaballa ◽

Andrea Eckhart ◽

Walter J. Koch ◽

Steven Goldman

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Carotid Artery ◽

Membrane Protein ◽

Adrenergic Receptor ◽

Vascular Reactivity ◽

Diastolic Pressure ◽

Systolic Pressure ◽

Left Ventricular ◽

Receptor System

We identified abnormalities in the vascular β-adrenergic receptor (β-AR) signaling pathway in heart failure after myocardial infarction (MI). To examine these abnormalities, we measured β-AR-mediated hemodynamics, vascular reactivity, and the vascular β-AR molecular signaling components in rats with heart failure after MI. Six weeks after MI, these rats had an increased left ventricular (LV) end-diastolic pressure, decreased LV systolic pressure, and decreased rate of LV pressure change (dP/d t). LV dP/d t responses to isoproterenol were shifted downward, although the responses for systemic vascular resistance were shifted upward in heart failure rats ( P < 0.05). Isoproterenol- and IBMX-induced vasorelaxations were blunted in heart failure rats ( P< 0.05) with no change in the forskolin-mediated vasorelaxation. These changes were associated with the following alterations in β-AR signaling ( P < 0.05): decreases in β-AR density (aorta: 58.7 ± 6.0 vs. 35.7 ± 1.9 fmol/mg membrane protein; carotid: 29.6 ± 5.6 vs. 18.0 ± 3.9 fmol/mg membrane protein, n = 5), increases in G protein-coupled receptor kinase activity levels (relative phosphorimage counts of 191 ± 39 vs. 259 ± 26 in the aorta and 115 ± 30 vs. 202 ± 7 in the carotid artery, n = 5), and decreases in cGMP and cAMP in the carotid artery (0.85 ± 0.10 vs. 0.31 ± 0.06 pmol/mg protein and 2.3 ± 0.3 vs. 1.2 ± 0.1 pmol/mg protein, n = 5) with no change in Gαs or Gαi in the aorta. Thus in heart failure there are abnormalities in the vascular β-AR system that are similar to those seen in the myocardium. This suggests a common neurohormonal mechanism and raises the possibility that treatment in heart failure focused on the myocardium may also affect the vasculature.

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Left Ventricular End-Diastolic Pressure and Risk of Subsequent Heart Failure in Patients Following an Acute Myocardial Infarction

Congestive Heart Failure ◽

10.1111/j.1527-5299.2007.06624.x ◽

2007 ◽

Vol 13 (4) ◽

pp. 209-214 ◽

Cited By ~ 34

Author(s):

Lisa M. Mielniczuk ◽

Gervasio A. Lamas ◽

Greg C. Flaker ◽

Gary Mitchell ◽

Sidney C. Smith ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Acute Myocardial Infarction ◽

Diastolic Pressure ◽

Left Ventricular

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Elevated Swelling-Activated Chloride Current Densities in Hypertrophied Ventricular Myocytes in a Rabbit Heart Failure Model

The Heart Surgery Forum ◽

10.1532/hsf.2255 ◽

2019 ◽

Vol 22 (2) ◽

pp. E107-E111

Author(s):

Hongwei Shi ◽

Zhenming Jiang ◽

Teng Wang ◽

Yongting Chen ◽

Feng Cao

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Protein Expression ◽

Diastolic Pressure ◽

Rabbit Model ◽

Systolic Pressure ◽

Left Ventricular ◽

Control Group ◽

Sham Operation ◽

Failure Group

Background: The status of the swelling-activated chloride channel (ICl, swell) during heart failure remains unclear. This study aimed to investigate whether the ICl, swell activity is altered during heart failure and to determine how the ICl, swell influences atrial arrhythmias of the failing heart. Methods: We established a heart failure rabbit model and analyzed the hemodynamic indicators 8 weeks after myocardial infarction, which include left ventricular systolic pressure (LVSP) and left ventricular end-diastolic pressure (LVDEP). Five untreated rabbits and 5 receiving a sham operation served as the control group. Left auricular appendage tissues were obtained and CLCN3 mRNA/CLCN3 protein expression levels were examined by using reverse transcription–polymerase chain reaction and Western blot, respectively. Results: Compared to the control group, the heart failure group showed a significantly decreased LVSP (14.2 ± 0.27 versus 16.9 ± 0.86 kPa, P <.05)and elevated LVDEP (2.49 ± 0.30 versus 0.15 ± 0.03 kPa, P <.05), indicating that myocardial infarction leads to progressive heart failure of rabbits in the heart failure group. CLCN3 mRNA and CLCN3 protein expression were both significantly elevated in the heart failure group compared to the control group (P <.05). Conclusion: In sum, we propose that the dynamic nature of ICl, swell upregulation may contribute to the elevated expression of CLCN3 mRNA and CLCN3 protein, resulting in myocardial cell remodeling induced by heart failure. However, further study is needed to investigate the potential functions of ICl, swell, especially the relation between ICl, swell augmentation and arrhythmia after heart failure.

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Progressive myocardial dysfunction associated with increased vascular resistance

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1980.239.4.h477 ◽

1980 ◽

Vol 239 (4) ◽

pp. H477-H477 ◽

Cited By ~ 2

Author(s):

Joseph A. Franciosa ◽

Richard Heckel ◽

Catherine Limas ◽

Jay N. Cohn

Keyword(s):

Heart Failure ◽

Systemic Vascular Resistance ◽

Vascular Resistance ◽

Diastolic Pressure ◽

Myocardial Dysfunction ◽

Peripheral Circulation ◽

Left Ventricular ◽

Stroke Work ◽

Low Cardiac Output

To study heart failure from a myocardial lesion, we injected glass beads into the circumflex coronary artery of 11 conscious dogs and followed hemodynamics for 10 mo. Heart rate remained unchanged. Control mean arterial pressure of 112.3 ± 3.0 (SE) mmHg was unchanged at 1 and 3 mo, but rose to 127.2 ± 8.5 to 84.0 ± 7.6 ml . kg-1 . min-1 at 10 mo (P < 0.02), but was unchanged at 1 and 3 mo. Left ventricular end-diastolic pressure (LVEDP) averaged 4.6 ± 0.8 mmHg at control and rose to 11.8 ± 1.4 mmHg at 1 mo and 14.9 ± 2.5 mmHg at 10 mo (both P < 0.01). Systemic vascular resistance rose significantly by 10 mo. The ratio of stroke work to LVEDP fell from 13.1 ± 0.1 at control to 3.8 ± 0.5 by 10 mo (P < 0.01). In this dog model, left ventricular dysfunction is manifest early by increased LVEDP and later by high systemic vascular resistance with low cardiac output, thus suggesting a role of the peripheral circulation in the progression of heart failure.

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Abstract 902: A Beta-2 Adrenergic Receptor Polymorphism Is Associated With Increased Left Ventricular Remodeling Following First ST-Elevation Myocardial Infarction

Circulation ◽

10.1161/circ.116.suppl_16.ii_177 ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Rhondalyn C McLean ◽

Glenn A Hirsch ◽

Gary Gerstenblith ◽

Steven P Schulman

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Receptor Antagonist ◽

Adrenergic Receptor ◽

Left Ventricular ◽

Regression Analyses ◽

Lv Remodeling ◽

St Elevation ◽

Lv Volumes ◽

Receptor Polymorphism

Background: Prior studies demonstrate an association between specific β-adrenergic receptor polymorphisms and clinical outcomes in patients with chronic heart failure and following an acute coronary syndrome. The mechanism may relate to an effect on left ventricular (LV) remodeling. We hypothesized that β-adrenergic receptor polymorphisms predict LV remodeling after acute ST elevation myocardial infarction (STEMI). Methods: We assessed the presence of β-1 and β-2 adrenergic receptor polymorphisms in 122 patients after their first STEMI enrolled in a single-center randomized, double-blind placebo controlled trial of L-arginine vs. placebo, 91% of whom received successful early reperfusion therapy. All patients were treated with a beta-1 receptor antagonist and underwent baseline (mean 5.9 days following STEMI) and 6-month LV volume evaluation using gated blood pool imaging. Univariate and multivariate linear and logistic regressions were used to assess the relationships between the polymorphisms, β1 Arg389Gly, β1 Ser49Gly, β2 Gly16Arg and β2 Gly27Glu and the six-month changes in LV volumes. The top quintiles of LV end-systolic (ESV) and end-diastolic (EDV) 6-month volume increases and LV ejection fraction decrease were compared to the lower quintiles in the logistic regression analyses. Results: The polymorphisms β1 Arg389Gly, β1 Ser49Gly, β2 Gly16Arg were not associated LV remodeling. However, the 25% of patients homozygous for the β2 Glu27 variant were 5.2 times more likely to have an increase in 6-month ESV than those who had the Gln27 variant (OR 5.2, 95%CI 1.4 –19.0). Multiple linear regression analyses demonstrated that absolute ESV at six months was 19 ml greater (p = 0.02) and EDV was 21 ml greater (p = 0.01) in post STEMI patients with the β2 Glu27 polymorphism compared to the wild type or heterozygous patients. Conclusions: Increased LV volumes post-STEMI are associated with an increased risk of heart failure and death. The common β2 receptor polymorphism, Glu27Glu, is associated with increased odds of adverse LV remodeling in patients treated with a beta-one receptor antagonist. Whether treatment with a non-specific β-adrenergic receptor blocker guided by this genetic polymorphism ameliorates the effect requires further study.

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