Non-Invasive Evaluation of Patients Undergoing Percutaneous Coronary Intervention for Chronic Total Occlusion

Background: As percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) gains wider acceptance as a therapeutic option for coronary artery disease, the importance of appropriate patient selection has increased. Although cardiovascular magnetic resonance imaging (MRI) allows segmental and quantitative analyses of myocardial ischemia and scar transmurality, it has limitations, including contraindications, cost, and accessibility. This study established a non-invasive method to evaluate patients undergoing CTO-PCI using two-dimensional speckle-tracking echocardiography (2D-STE). Methods: Overall, we studied 55 patients who underwent successful CTO-PCI. Cardiovascular MRI and 2D-STE were performed before and 8 ± 2 months after CTO-PCI. Segmental findings of strain parameters were compared with those obtained with late gadolinium enhancement and stress-perfusion MRI. Results: With a cutoff of −10.7, pre-procedural circumferential strain (CS) showed reasonable sensitivity (71%) and specificity (73%) for detecting segments with transmural scar. The discriminatory ability of longitudinal strain (LS) for segments with transmural scar significantly improved during follow-up after successful CTO-PCI in the territory of the recanalized artery (area under the curve (AUC) 0.70 vs. 0.80, p < 0.001). LS accuracy was lower than that of CS at baseline (AUC 0.70 vs. 0.79, p = 0.048), and was increased at follow-up (AUC 0.80 vs. 0.82, p = 0.81). Changes in myocardial perfusion reserve from baseline to follow-up were significantly associated with those in LS but not in CS. Conclusions: Use of 2D-STE may allow the non-invasive evaluation of patients undergoing CTO-PCI to assess the indication before the procedure and treatment effects at follow-up.

Long-term safety and efficacy of intramyocardial adenovirus-mediated VEGF-DΔNΔC gene therapy: eight-year follow-up of phase 1 KAT301 study

Backgound/Introduction In phase I KAT301 trial, adenovirus-mediated intramyocardial vascular endothelial growth factor-DΔNΔC (VEGF-D) gene therapy (GT) resulted in a significant improvement in myocardial perfusion reserve and relieved angina at 1-year follow-up without major safety concerns. Purpose Our objective was to investigate the long-term safety and efficacy of AdVEGF-D GT. A total of 30 patients (24 VEGF-D and 6 randomized and blinded controls) participated in KAT301 trial. Methods The mean follow-up time was 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 events (MACEs) and other predefined endpoints including cancer. Results 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 0.90; 95% confidence interval 0.09–9.32; P=0.95). Mortality and 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). Conclusion(s) 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. FUNDunding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Kuopio University Hospital Heart Center Figure 1. The incidence of MACE Figure 2. CCS class

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

In 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.

HbA1c Independently Predicts Declined Myocardial Perfusion Reserve Index in Patients With Coronary Microvascular Disease Using Stress Perfusion Cardiac Magnetic Resonance: an Observational Study

Background We investigated whether glycated haemoglobin A1c (HbA1c) could independently predict the decline in the myocardial perfusion reserve index (MPRI) in patients with coronary microvascular disease (CMD) by stress perfusion cardiac magnetic resonance (CMR).Methods From November 2019, 174 patients with ischemic symptoms but without obstructive coronary disease were screened. The MPRI was recorded in 88 patients who underwent stress perfusion CMR detection. Eighty patients with an MPRI of < 2.5 were included in the study. The patients were divided into two groups based on whether their MPRI was greater or less than 1.47. The effects of each index on the MPRI were analysed using bivariate correlation analysis, and the risk factors for CMD were explored using logistic regression analysis.ResultsA total of 80 patients with an MPRI of 1.69±0.79 were included (mean age 54.07 ± 11.06 years; 66.3% male). CMD patients with an MPRI of ≤1.47 were higher than those in the group with an MPRI of >1.47 in age (57.61±9.65 years vs. 51.74±11.41 years), presence of diabetes mellitus (45.5% vs. 21.3%), fasting blood glucose levels [6.33(5.16, 8.01) vs. 5.30(5.15, 6.56)], and HbA1c levels [6.30(5.70, 7.70) vs. 5.80(5.60, 6.50)], (P < 0.05). The MPRI was negatively correlated with HbA1c (r=-0.378, P=0.004). Logistic regression analysis showed that HbA1c (OR=2.336, 95% CI: 1.119-4.876, P=0.024) was an independent risk factor for decreased MPRI in all patients with CMD, especially in patients without diabetes (OR=19.953, 95% CI: 1.743-93.449, P=0.029), but not in patients with diabetes (OR=0.984, 95% CI: 0.265-3.658, P=0.981).ConclusionsHbA1c is an independent predictor of MPRI decline in CMD patients, notably in CMD patients without diabetes, but not for those with diabetes.Trial RegistrationThis clinical trial has been registered in the Chinese clinical Trial Registry with an identifier: ChiCTR1900025810.

A cardiovascular magnetic resonance imaging-based pilot study to assess coronary microvascular disease in COVID-19 patients

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and is primarily characterised by a respiratory disease. However, SARS-CoV-2 can directly infect vascular endothelium and subsequently cause vascular inflammation, atherosclerotic plaque instability and thereby result in both endothelial dysfunction and myocardial inflammation/infarction. Interestingly, up to 50% of patients suffer from persistent exercise dyspnoea and a post-viral fatigue syndrome (PVFS) after having overcome an acute COVID-19 infection. In the present study, we assessed the presence of coronary microvascular disease (CMD) by cardiovascular magnetic resonance (CMR) in post-COVID-19 patients still suffering from exercise dyspnoea and PVFS. N = 22 patients who recently recovered from COVID-19, N = 16 patients with classic hypertrophic cardiomyopathy (HCM) and N = 17 healthy control patients without relevant cardiac disease underwent dedicated vasodilator-stress CMR studies on a 1.5-T MR scanner. The CMR protocol comprised cine and late-gadolinium-enhancement (LGE) imaging as well as velocity-encoded (VENC) phase-contrast imaging of the coronary sinus flow (CSF) at rest and during pharmacological stress (maximal vasodilation induced by 400 µg IV regadenoson). Using CSF measurements at rest and during stress, global myocardial perfusion reserve (MPR) was calculated. There was no difference in left ventricular ejection-fraction (LV-EF) between COVID-19 patients and controls (60% [57–63%] vs. 63% [60–66%], p = NS). There were only N = 4 COVID-19 patients (18%) showing a non-ischemic pattern of LGE. VENC-based flow measurements showed that CSF at rest was higher in COVID-19 patients compared to controls (1.78 ml/min [1.19–2.23 ml/min] vs. 1.14 ml/min [0.91–1.32 ml/min], p = 0.048). In contrast, CSF during stress was lower in COVID-19 patients compared to controls (3.33 ml/min [2.76–4.20 ml/min] vs. 5.32 ml/min [3.66–5.52 ml/min], p = 0.05). A significantly reduced MPR was calculated in COVID-19 patients compared to healthy controls (2.73 [2.10–4.15–11] vs. 4.82 [3.70–6.68], p = 0.005). No significant differences regarding MPR were detected between COVID-19 patients and HCM patients. In post-COVID-19 patients with persistent exertional dyspnoea and PVFS, a significantly reduced MPR suggestive of CMD—similar to HCM patients—was observed in the present study. A reduction in MPR can be caused by preceding SARS-CoV-2-associated direct as well as secondary triggered mechanisms leading to diffuse CMD, and may explain ongoing symptoms of exercise dyspnoea and PVFS in some patients after COVID-19 infection.

Myocardial Perfusion Defects in Hypertrophic Cardiomyopathy Mutation Carriers

Background Impaired myocardial blood flow (MBF) in the absence of epicardial coronary disease is a feature of hypertrophic cardiomyopathy (HCM). Although most evident in hypertrophied or scarred segments, reduced MBF can occur in apparently normal segments. We hypothesized that impaired MBF and myocardial perfusion reserve, quantified using perfusion mapping cardiac magnetic resonance, might occur in the absence of overt left ventricular hypertrophy (LVH) and late gadolinium enhancement, in mutation carriers without LVH criteria for HCM (genotype‐positive, left ventricular hypertrophy‐negative). Methods and Results A single center, case‐control study investigated MBF and myocardial perfusion reserve (the ratio of MBF at stress:rest), along with other pre‐phenotypic features of HCM. Individuals with genotype‐positive, left ventricular hypertrophy‐negative (n=50) with likely pathogenic/pathogenic variants and no evidence of LVH, and matched controls (n=28) underwent cardiac magnetic resonance. Cardiac magnetic resonance identified LVH‐fulfilling criteria for HCM in 5 patients who were excluded. Individuals with genotype‐positive, left ventricular hypertrophy‐negative had longer indexed anterior mitral valve leaflet length (12.52±2.1 versus 11.55±1.6 mm/m 2 , P =0.03), lower left ventricular end‐systolic volume (21.0±6.9 versus 26.7±6.2 mm/m 2 , P ≤0.005) and higher left ventricular ejection fraction (71.9±5.5 versus 65.8±4.4%, P≤ 0.005). Maximum wall thickness was not significantly different (9.03±1.95 versus 8.37±1.2 mm, P =0.075), and no subject had significant late gadolinium enhancement (minor right ventricle‒insertion point late gadolinium enhancement only). Perfusion mapping demonstrated visual perfusion defects in 9 (20%) carriers versus 0 controls ( P =0.011). These were almost all septal or near right ventricle insertion points. Globally, myocardial perfusion reserve was lower in carriers (2.77±0.83 versus 3.24±0.63, P =0.009), with a subendocardial:subepicardial myocardial perfusion reserve gradient (2.55±0.75 versus 3.2±0.65, P =<0.005; 3.01±0.96 versus 3.47±0.75, P =0.026) but equivalent MBF (2.75±0.82 versus 2.65±0.69 mL/g per min, P =0.826). Conclusions Regional and global impaired myocardial perfusion can occur in HCM mutation carriers, in the absence of significant hypertrophy or scarring.

Impairment in Quantitative Microvascular Function in Non-Ischemic Cardiomyopathy as Demonstrated Using Cardiovascular Magnetic Resonance

Purpose Microvascular dysfunction (MVD)—defined as impaired augmentation of the microcirculation in response to stress—is present in various cardiovascular diseases and portends worse outcomes. We aimed to evaluate the relationship between MVD and non-ischemic cardiomyopathy (NICM) utilizing stress cardiovascular magnetic resonance (CMR) as compared to a cohort of control patients. Methods We retrospectively studied 41 consecutive patients with NICM (mean age 51 ± 14, 59% male) and 58 controls with preserved systolic function (mean age 51 ± 13, 31% male) who underwent adenosine stress CMR exams between 2011–2016. Microvascular function was assessed visually and with myocardial perfusion reserve index (MPRI), quantified using first pass perfusion imaging by comparing perfusion slopes of myocardium and blood pool at rest/stress. MVD was defined visually as presence of subendocardial stress perfusion defect and quantitatively by MPRI < 1.51. MPRI was compared between NICM and controls using univariate analysis and multivariable linear regression. Results Impaired MPRI was noted in 37 patients (23 in NICM and 14 in control cohorts). In patients with NICM, 23 (56%) had MVD by quantitative assessment, while 11 (27%) by visual evaluation. No differences in comorbidities were noted between cohorts. Compared with controls, NICM patients had lower rest perfusion slope (3.9 vs 4.9, p = 0.05), stress perfusion slope (8.8 vs 11.7, p < 0.001), and MPRI (1.41 vs 1.74, p = 0.02). MPRI remained associated with NICM after controlling for age, gender, hypertension, diabetes, and late gadolinium enhancement (log MPR, β coefficient = -0.17, p = 0.009). Conclusions MVD assessed with stress CMR is highly prevalent in NICM as compared to control patients with preserved systolic function. Quantitative MPRI assessment identities more NICM patients with MVD as compared to visual evaluation. NICM remains independently associated with an impaired MPRI after controlling for covariates. Further studies are needed to determine whether targeted therapies to treat MVD are beneficial in NICM.