Preemptive heme oxygenase-1 gene delivery reveals reduced mortality and preservation of left ventricular function 1 yr after acute myocardial infarction

2007 ◽  
Vol 293 (1) ◽  
pp. H48-H59 ◽  
Author(s):  
Xiaoli Liu ◽  
Jeremy A. Simpson ◽  
Keith R. Brunt ◽  
Christopher A. Ward ◽  
Sean R. R. Hall ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Gene Delivery ◽  
Heme Oxygenase ◽  
Left Ventricular ◽  
Heme Oxygenase 1 ◽  
Term Survival ◽  
Long Term Survival ◽  
Lv Remodeling

We reported previously that predelivery of heme oxygenase-1 (HO-1) gene to the heart by adeno-associated virus-2 (AAV-2) markedly reduces ischemia and reperfusion (I/R)-induced myocardial injury. However, the effect of preemptive HO-1 gene delivery on long-term survival and prevention of postinfarction heart failure has not been determined. We assessed the effect of HO-1 gene delivery on long-term survival, myocardial function, and left ventricular (LV) remodeling 1 yr after myocardial infarction (MI) using echocardiographic imaging, pressure-volume (PV) analysis, and histomorphometric approaches. Two groups of Lewis rats were injected with 2 × 1011 particles of AAV-LacZ (control) or AAV-human HO-1 (hHO-1) in the anterior-posterior apical region of the LV wall. Six weeks after gene transfer, animals were subjected to 30 min of ischemia by ligation of the left anterior descending artery followed by reperfusion. Echocardiographic measurements and PV analysis of LV function were obtained at 2 wk and 12 mo after I/R. One year after acute MI, mortality was markedly reduced in the HO-1-treated animals compared with the LacZ-treated animals. PV analysis demonstrated significantly enhanced LV developed pressure, elevated maximal dP/d t, and lower end-diastolic volume in the HO-1 animals compared with the LacZ animals. Echocardiography showed a larger apical anterior-to-posterior wall ratio in HO-1 animals compared with LacZ animals. Morphometric analysis revealed extensive myocardial scarring and fibrosis in the infarcted LV area of LacZ animals, which was reduced by 62% in HO-1 animals. These results suggest that preemptive HO-1 gene delivery may be useful as a therapeutic strategy to reduce post-MI LV remodeling and heart failure.

scholarly journals Long-term survival benefit of ramipril in patients with acute myocardial infarction complicated by heart failure

Heart ◽  
2021 ◽  
Vol 107 (5) ◽  
pp. 389-395
Author(s):  
Jianhua Wu ◽  
Alistair S Hall ◽  
Chris P Gale
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Life Expectancy ◽  
Survival Benefit ◽  
Ace Inhibition ◽  
Survival Times ◽  
Term Survival ◽  
Long Term Survival

AimsACE inhibition reduces mortality and morbidity in patients with heart failure after acute myocardial infarction (AMI). However, there are limited randomised data about the long-term survival benefits of ACE inhibition in this population.MethodsIn 1993, the Acute Infarction Ramipril Efficacy (AIRE) study randomly allocated patients with AMI and clinical heart failure to ramipril or placebo. The duration of masked trial therapy in the UK cohort (603 patients, mean age=64.7 years, 455 male patients) was 12.4 and 13.4 months for ramipril (n=302) and placebo (n=301), respectively. We estimated life expectancy and extensions of life (difference in median survival times) according to duration of follow-up (range 0–29.6 years).ResultsBy 9 April 2019, death from all causes occurred in 266 (88.4%) patients in placebo arm and 275 (91.1%) patients in ramipril arm. The extension of life between ramipril and placebo groups was 14.5 months (95% CI 13.2 to 15.8). Ramipril increased life expectancy more for patients with than without diabetes (life expectancy difference 32.1 vs 5.0 months), previous AMI (20.1 vs 4.9 months), previous heart failure (19.5 vs 4.9 months), hypertension (16.6 vs 8.3 months), angina (16.2 vs 5.0 months) and age >65 years (11.3 vs 5.7 months). Given potential treatment switching, the true absolute treatment effect could be underestimated by 28%.ConclusionFor patients with clinically defined heart failure following AMI, ramipril results in a sustained survival benefit, and is associated with an extension of life of up to 14.5 months for, on average, 13 months treatment duration.

scholarly journals Long-term outcomes in patients with critical limb ischemia and heart failure with preserved or reduced ejection fraction

2017 ◽  
Vol 22 (4) ◽  
pp. 307-315 ◽  
Author(s):  
Kavita B Khaira ◽  
Ellen Brinza ◽  
Gagan D Singh ◽  
Ezra A Amsterdam ◽  
Stephen W Waldo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Critical Limb Ischemia ◽  
Limb Ischemia ◽  
Left Ventricular ◽  
Term Survival ◽  
Long Term Survival ◽  
Reduced Ejection Fraction ◽  
History Of

The impact of heart failure (HF) on long-term survival in patients with critical limb ischemia (CLI) has not been well described. Outcomes stratified by left ventricular ejection fraction (EF) are also unknown. A single center retrospective chart review was performed for patients who underwent treatment for CLI from 2006 to 2013. Baseline demographics, procedural data and outcomes were analyzed. HF diagnosis was based on appropriate signs and symptoms as well as results of non-invasive testing. Among 381 CLI patients, 120 (31%) had a history of HF and 261 (69%) had no history of heart failure (no-HF). Within the HF group, 74 (62%) had HF with preserved ejection fraction (HFpEF) and 46 (38%) had HF with reduced ejection fraction (HFrEF). The average EF for those with no-HF, HFpEF and HFrEF were 59±13% vs 56±9% vs 30±9%, respectively. The likelihood of having concomitant coronary artery disease (CAD) was lowest in the no-HF group (43%), higher in the HFpEF group (70%) and highest in the HFrEF group (83%) ( p=0.001). Five-year survival was on average twofold higher in the no-HF group (43%) compared to both the HFpEF (19%, p=0.001) and HFrEF groups (24%, p=0.001). Long-term survival rates did not differ between the two HF groups ( p=0.50). There was no difference in 5-year freedom from major amputation or freedom from major adverse limb events between the no-HF, HFpEF and HFrEF groups, respectively. Overall, the combination of CLI and HF is associated with poor 5-year survival, independent of the degree of left ventricular systolic dysfunction.

scholarly journals Impact of aspirin and statins on long-term survival in patients hospitalized with acute myocardial infarction complicated by heart failure: an analysis of 1706 patients

2013 ◽  
Vol 16 (1) ◽  
pp. 95-102 ◽  
Author(s):  
Christian Lewinter ◽  
John M. Bland ◽  
Simon Crouch ◽  
John G.F. Cleland ◽  
Patrick Doherty ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Term Survival ◽  
Long Term Survival

Abstract 17335: Cluster Analysis of Cardiac Resynchronization Response Parameters Predicts Long-Term Survival With Heart Failure

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Kenneth C Bilchick ◽  
Xu Gao ◽  
Derek Bivona ◽  
Rohit Malhotra ◽  
Michael Mangrum ◽  
...  
Keyword(s):  
Machine Learning ◽  
Heart Failure ◽  
Cluster Analysis ◽  
Patient Characteristics ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Term Survival ◽  
Long Term Survival ◽  
Systolic Volume

Introduction: Machine learning methods such as cluster analysis can identify commonality in patterns of short-term response measures after cardiac resynchronization therapy (CRT) to predict classes of patients with distinct long-term prognoses. Hypothesis: Distinct response clusters identified within 6 months of CRT implantation would provide independent prognostic value relative to known pre-CRT patient characteristics. Methods: Patients with heart failure (HF) undergoing CRT had assessments of left ventricular end-systolic volume fractional change (LVESV-FC), peak VO 2 , and B-type natriuretic peptide (BNP) based on cardiac magnetic resonance (CMR), echocardiography, exercise testing, and blood tests before and 6 months after CRT. Statistical methods included multivariate multiple linear regression, cluster analysis based on a mixture model, survival analysis, and receiver operating characteristic (ROC) analysis. Results: During a median of 5.0 years of follow-up after CRT, the cohort of 146 patients (age 66.0 ± 11.3 years, 34.9% female) had a death rate of 28.1%. A significant correlation was observed for BNP response and LVESV-FC (r=0.42, p>0.01), but not for the other response comparisons. Three clusters of patients (1: n=27; 2: n=82; 3: n=37) were identified. Kaplan-Meier analysis (Figure) demonstrated the best long-term survival in cluster 2, intermediate survival in cluster 3, and the worst survival in cluster 1 (p<0.0001). ROC curve comparisons for 4-year survival based on pre-CRT findings with or without the 6-month response cluster showed that the cluster increased the AUC from 0.818 to 0.870 (p=0.069). Conclusions: Response clusters based on 6-month parameters were strongly associated with long-term survival and improved prognostication compared with just pre-CRT predictors alone. This response clustering approach based on machine learning promises to be very useful for clinical risk stratification in heart failure after CRT.

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