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Gene targeting in ischemic heart disease and failure: translational and clinical studies.

ABSTRACT: Alternative and innovative targeted strategies hold relevance in improving the current treatments for ischemic heart disease (IHD). One potential treatment modality, gene targeting, may provide a unique alternative to current IHD therapies. The principal function of gene targeting in IHD is to augment the expression of an endogenous gene through amplification of an exogenous gene, delivered by a plasmid or a viral vector to enhance myocardial perfusion, and limit the long-term sequelae. The initial clinical studies of gene targeting in IHD were focused upon induction of angiogenic factors and the outcomes were equivocal. Nevertheless, significant advancements have been made in viral vectors, mode of delivery, and potentially relevant targets for IHD. Several of these advancements, particularly with a focus on translational large animal studies, are the focus of this review. The development of novel vectors with prolonged transduction efficiency and minimal inflammation, coupled with hybrid perfusion-mapping delivery devices, and improving the safety of vector use and efficacy of gene systems are but a few of the exciting progresses that are likely to proceed to clinical studies in the near future.

SUBMITTER: Eckhouse SR

PROVIDER: S-EPMC3575101 | biostudies-other | 2013 Jan

REPOSITORIES: biostudies-other

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Gene targeting in ischemic heart disease and failure: translational and clinical studies.

Eckhouse Shaina R SR Jones Jeffrey A JA Spinale Francis G FG

Biochemical pharmacology 20120828 1

Alternative and innovative targeted strategies hold relevance in improving the current treatments for ischemic heart disease (IHD). One potential treatment modality, gene targeting, may provide a unique alternative to current IHD therapies. The principal function of gene targeting in IHD is to augment the expression of an endogenous gene through amplification of an exogenous gene, delivered by a plasmid or a viral vector to enhance myocardial perfusion, and limit the long-term sequelae. The init ...[more]

PMID: 22935384

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Project description:Importance:The Department of Veterans Affairs (VA) operates a nationwide system of hospitals and hospital-affiliated clinics, providing health care to more than 2 million veterans with cardiovascular disease. While data permitting hospital comparisons of the outcomes of acute cardiovascular care (eg, myocardial infarction) are publicly available, little is known about variation across VA medical centers (VAMCs) in outcomes of care for populations of patients with chronic, high-risk cardiovascular conditions. Objective:To determine whether there are substantial differences in cardiovascular outcomes across VAMCs. Design, Setting, and Participants:Retrospective cohort study comprising 138 VA hospitals and each hospital's affiliated outpatient clinics. Patients were identified who received VA inpatient or outpatient care between 2010 and 2014. Separate cohorts were constructed for patients diagnosed as having either ischemic heart disease (IHD) or chronic heart failure (CHF). The data were analyzed between June 24, 2015, and November 21, 2017. Exposures:Hierarchical linear models with VAMC-level random effects were estimated to compare risk-standardized mortality rates for IHD and for CHF across 138 VAMCs. Mortality estimates were risk standardized using a wide array of patient-level covariates derived from both VA and Medicare health care encounters. Main Outcomes and Measures:All-cause mortality. Results:The cohorts comprised 930 079 veterans with IHD and 348 015 veterans with CHF; both cohorts had a mean age of 77 years and were predominantly white (IHD, n = 822 665 [89%] and CHF, n = 287 871 [83%]) and male (IHD, n = 916 684 [99%] and CHF n = 341 352 [98%]). The VA-wide crude annual mortality rate was 7.4% for IHD and 14.5% for CHF. For IHD, VAMCs' risk-standardized mortality varied from 5.5% (95% CI, 5.2%-5.7%) to 9.4% (95% CI, 9.0%-9.9%) (P < .001 for the difference). For CHF, VAMCs' risk-standardized mortality varied from 11.1% (95% CI, 10.3%-12.1%) to 18.9% (95% CI, 18.3%-19.5%) (P < .001 for the difference). Twenty-nine VAMCs had IHD mortality rates that significantly exceeded the national mean, while 35 VAMCs had CHF mortality rates that significantly exceeded the national mean. Veterans Affairs medical centers' mortality rates among their IHD and CHF populations were not associated with 30-day mortality rates for myocardial infarction (R2 = 0.01; P = .35) and weakly associated with hospitalized heart failure 30-day mortality (R2 = 0.16; P < .001) and the VA's star rating system (R2 = 0.06; P = .005). Conclusions and Relevance:Risk-standardized mortality rates for IHD and CHF varied widely across the VA health system, and this variation was not well explained by differences in demographics or comorbidities. This variation may signal substantial differences in the quality of cardiovascular care between VAMCs.

Dataset Information

Gene targeting in ischemic heart disease and failure: translational and clinical studies.

Publications

Gene targeting in ischemic heart disease and failure: translational and clinical studies.

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