scholarly journals Adenoviral intramyocardial VEGF-DΔNΔC gene transfer increases myocardial perfusion reserve in refractory angina patients: a phase I/IIa study with 1-year follow-up

2017 ◽  
Vol 38 (33) ◽  
pp. 2547-2555 ◽  
Author(s):  
Juha Hartikainen ◽  
Iiro Hassinen ◽  
Antti Hedman ◽  
Antti Kivelä ◽  
Antti Saraste ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Myocardial Perfusion ◽  
Phase I ◽  
Myocardial Perfusion Reserve ◽  
Refractory Angina ◽  
Perfusion Reserve

Abstract 11987: Adenoviral Intramyocardial VEGF-D Gene Transfer Increases Myocardial Perfusion in Refractory Angina Patients

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Iiro Hassinen ◽  
Juha Hartikainen ◽  
Antti Hedman ◽  
Antti Kivelä ◽  
Antti Saraste ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Gene Transfer ◽  
Myocardial Perfusion ◽  
Left Ventricle ◽  
Control Group ◽  
Transseptal Puncture ◽  
Refractory Angina ◽  
Intramyocardial Injection ◽  
Perfusion Reserve ◽  
Flow Reserve

Background: There is a rapidly growing number of refractory angina patients who in spite of the optimal medical therapy are severely symptomatic and who are not suitable for revascularization. Proangiogenic gene therapy is a potential new treatment for these patients. We evaluated for the first time safety, feasibility and efficacy of adenoviral (Ad) gene therapy using a new member of the VEGF family, VEGF-D, in the treatment of refractory angina. Methods and Results: KAT301 trial is a randomized, placebo-controlled, single-blinded phase I/II study. A total of 30 patients were randomized to intramyocardial AdVEGF-D gene transfer (VEGF group) or placebo (control group) with a 4:1 ratio. VEGF group underwent transseptal puncture and electroanatomical mapping of left ventricle with NOGA system (Cordis Corp), followed by intramyocardial injection of AdVEFG-D in the ischemic areas. The control group underwent transseptal puncture, left ventricle mapping and intracardiac saline infusion. Vital signs and laboratory assessments were measured at baseline and at 1, 2, 7,14 days and 3 months after the gene therapy to evaluate the safety and feasibility. Twenty patients underwent assessment of myocardial perfusion and blood flow reserve at rest and during adenosine induced exercise with positron emission tomography (15O-PET) at baseline and three months after the procedure. Mild transient elevation in body temperature and CRP and moderate hypotension was detected in VEGF group after the procedure. Troponine-T was elevated in both groups after the procedure but was normalized in two days. Perfusion reserve at 3 months in the myocardial segment with the lowest perfusion reserve at baseline increased significantly in the VEGF group (0.93±0.30 to 1.21±0.39, p=0.035) but not in the controls (1.21±0.63 to 1.53±0.67, p=0.343). No antibody responses were found against the transgene in the VEGF group after the treatment. Conclusion: Intramyocardial AdVEGF-D gene therapy is well tolerated in refractory angina patients. Changes in PET analysis at 3 months indicate that gene therapy can enhance myocardial perfusion in segments with the lowest perfusion reserve. Based on the results a randomized, controlled, blinded phase II/III trial is justified.

scholarly journals Temporal Trends in Angina, Myocardial Perfusion, and Left Ventricular Remodeling in Women With No Obstructive Coronary Artery Disease Over 1‐Year Follow‐Up: Results From WISE‐CVD

2020 ◽  
Vol 9 (13) ◽  
Author(s):  
Odayme Quesada ◽  
Melody Hermel ◽  
Nissi Suppogu ◽  
Haider Aldiwani ◽  
Chrisandra Shufelt ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Myocardial Perfusion ◽  
Obstructive Coronary Artery Disease ◽  
Myocardial Perfusion Reserve ◽  
Perfusion Reserve ◽  
Myocardial Perfusion Reserve Index ◽  
Lv Mass ◽  
Artery Disease

Background Women with ischemia and no obstructive coronary artery disease are increasingly recognized and found to be at risk for major adverse cardiovascular events. Methods and Results In 214 women with suspected ischemia and no obstructive coronary artery disease who completed baseline and 1‐year follow‐up vasodilatory stress cardiac magnetic resonance imaging, we investigated temporal trends in angina (Seattle Angina Questionnaire [SAQ]), myocardial perfusion reserve index, blood pressure, and left ventricular (LV) remodeling and function from baseline to 1‐year follow‐up and explored associations between these different parameters. We observed concordant positive trends in 4/5 SAQ domains, SAQ‐7, myocardial perfusion reserve index, blood pressure, LV mass, and LV mass‐to‐volume ratio. There was no association between SAQ‐7 improvement and myocardial perfusion reserve index improvement over 1‐year follow‐up ( P =0.1). Higher indexed LV end‐diastolic volume and time to peak filling rate at baseline were associated with increased odds of clinically relevant SAQ‐7 improvement (odds ratio [OR], 1.05; 95% CI, 1.0–1.1; and OR, 2.40; 95% CI, 1.1–5.0, respectively). Hypertension was associated with decreased odds of SAQ‐7 improvement (OR, 0.41; 95% CI, 0.19–0.91). Conclusions In women with ischemia and no obstructive coronary artery disease clinically treated with cardiac medications over 1 year, we observed concurrent temporal trends toward improvement in SAQ, myocardial perfusion reserve index, blood pressure, LV mass, and LV mass‐to volume ratio. We showed that abnormalities in LV morphology and diastolic function at baseline were predictive of clinically significant improvement in angina at follow‐up, whereas history of hypertension was associated with lower odds. Future studies are needed to assess the mechanisms and treatments responsible for the improvements we observed. Registration URL: https://www.clini​caltr​ials.gov ; Unique identifier: NCT02582021.

scholarly journals Relation between minimal luminal dimensions and myocardial perfusion reserve immediately after stenting and at 6 months follow-up

1996 ◽  
Vol 27 (2) ◽  
pp. 391
Author(s):  
Michael Haude ◽  
Dietrich Baumgart ◽  
Guido Caspari ◽  
Günter Görge ◽  
Junbo Ge ◽  
...  
Keyword(s):  
Myocardial Perfusion ◽  
Myocardial Perfusion Reserve ◽  
Perfusion Reserve

scholarly journals Long-term safety and efficacy of intramyocardial adenovirus-mediated VEGF-DΔNΔC gene therapy eight-year follow-up of phase I KAT301 study

Gene Therapy ◽  
2021 ◽  
Author(s):  
Aleksi J. Leikas ◽  
Iiro Hassinen ◽  
Antti Hedman ◽  
Antti Kivelä ◽  
Seppo Ylä-Herttuala ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Phase I ◽  
Myocardial Perfusion Reserve ◽  
Control Group ◽  
Cardiovascular Adverse Event ◽  
Safety And Efficacy ◽  
Perfusion Reserve ◽  
Canadian Cardiovascular Society Class

AbstractIn phase I KAT301 trial, intramyocardial adenovirus-mediated vascular endothelial growth factor -DΔNΔC (AdVEGF-D) gene therapy (GT) resulted in a significant improvement in myocardial perfusion reserve and relieved symptoms in refractory angina patients at 1-year follow-up without major safety concerns. We investigated the long-term safety and efficacy of AdVEGF-D GT. 30 patients (24 in VEGF-D group and 6 blinded, randomized controls) were followed for 8.2 years (range 6.3–10.4 years). Patients were interviewed for the current severity of symptoms (Canadian Cardiovascular Society class, CCS) and perceived benefit from GT. Medical records were reviewed to assess the incidence of major cardiovascular adverse event (MACE) and other predefined safety endpoints. MACE occurred in 15 patients in VEGF-D group and in five patients in control group (21.5 vs. 24.9 per 100 patient-years; hazard ratio 0.97; 95% confidence interval 0.36–2.63; P = 0.95). Mortality and new-onset comorbidity were similar between the groups. Angina symptoms (CCS) were less severe compared to baseline in VEGF-D group (1.9 vs. 2.9; P = 0.006) but not in control group (2.2 vs. 2.6; P = 0.414). Our study indicates that intramyocardial AdVEGF-D GT is safe in the long-term. In addition, the relief of symptoms remained significant during the follow-up.

Epicardial coronary stenosis severity and myocardial perfusion

2020 ◽  
pp. 12-16
Keyword(s):  
Myocardial Perfusion ◽  
Myocardial Ischemia ◽  
Coronary Disease ◽  
Myocardial Perfusion Reserve ◽  
Pharmacological Intervention ◽  
Fractional Flow ◽  
Perfusion Reserve ◽  
Flow Reserve ◽  
Stenosis Severity ◽  
Microvascular Resistance

Patients suspected of having epicardial coronary disease are often investigated with noninvasive myocardial ischemia tests to establish a diagnosis and guide management. However, the relationship between myocardial ischemia and coronary stenoses is affected by multiple factors, and there is marked biological variation between patients. The ischemic cascade represents the temporal sequence of pathophysiological events that occur after interruption of myocardial oxygen delivery. The earliest part of the cascade is examined via perfusion imaging, and fractional flow reserve (FFR) is a corresponding index which is specific to the coronary artery. Whereas FFR has come to be regarded a clinical reference standard against which other newer invasive and noninvasive tests are validated, the diagnostic FFR threshold for detecting ischemia was established against a combination of noninvasive ischemia tests that assessed different stages of the ischemic cascade. Moreover, the validity of invasive pressure-derived indices of stenosis severity are contingent on the assumption that pressure is proportional to flow if microvascular resistance is constant, a condition induced by pharmacological intervention or by examining specific segments of the cardiac cycle. Furthermore, myocardial perfusion reserve depends on dynamic modulation of microvascular resistance, and dysfunction of the microvasculature can lead to ischemia even in the absence of epicardial coronary disease.

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