Niklas Vartiainen

A characteristic feature of obstructive coronary artery disease (CAD) is impaired myocardial blood flow (MBF). Previous studies have shown that atrial fibrillation (AF) is also associated with reduced hyperemic MBF. However, it is unknown whether an independent association exists between AF and MBF in symptomatic patients with suspected obstructive CAD. We studied 874 patients at Kuopio University Hospital (Finland) who underwent coronary computed tomography angiography (CCTA) and [ ¹⁵ O]H ₂ O myocardial perfusion positron emission tomography due to suspected obstructive CAD in 2017–2023. The final cohort comprised 31 AF patients and 120 propensity score-matched sinus rhythm (SR) patients. The matching criteria were age, sex, body mass index, number of traditional risk factors for CAD (0–5), calcium score, and total CCTA status (i.e., the overall severity of CCTA findings). Global hyperemic MBF was lower in AF patients than in SR patients (median 1.9 mL/g/min [IQR 1.4–2.6 mL/g/min] vs. 3.0 mL/g/min [IQR 2.4–3.6 mL/g/min], p < 0.001). Impaired hyperemic MBF (< 2.3 mL/g/min in ≥ 1 segment) was more frequent in AF patients (n = 25/31, 81%) than in SR patients (n = 50/120, 42%, p < 0.001). Furthermore, the presence of AF was independently associated with reduced hyperemic MBF in three multivariate general linear models (p < 0.001 in each model). To summarize, AF was independently associated with impaired hyperemic MBF in patients with suspected obstructive CAD. This association should be considered in clinical practice when interpreting the results of myocardial perfusion imaging in patients with AF.

Background: In patients with suspected coronary artery disease (CAD), diffusely impaired hyperaemic myocardial blood flow (MBF) may indicate a multivessel epicardial CAD but also impaired coronary microcirculation. We assessed whether relative hyperaemic MBF—that is, the ratio of the lowest to the highest regional hyperaemic MBF—predicts obstructive CAD in patients with diffusely impaired hyperaemic MBF. Methods: We studied 874 patients who underwent coronary computed tomography angiography and [ ¹⁵ O]H ₂ O myocardial perfusion imaging with positron emission tomography at Kuopio University Hospital, Finland, in 2017–2023. The final analyses included 64 patients who had diffusely impaired hyperaemic MBF and were subsequently referred to invasive coronary angiography (ICA). Results: In ICA, 34/64 (53%) patients had obstructive CAD. Compared to patients with non‐obstructive CAD, those with obstructive CAD had lower relative hyperaemic MBF: 66% (95% CI 62–69%) versus 52% (95% CI 47–57%), respectively ( p < 0.001). When relative hyperaemic MBF was used to predict the presence of obstructive CAD in ICA, the receiver operating characteristic analysis showed an area under the curve of 0.778 (95% CI 0.666–0.891). In binary logistic regression analysis, relative hyperaemic MBF independently predicted obstructive CAD (OR = 0.92 [95% CI 0.86–0.97], p = 0.004). Conclusion: Obstructive CAD is more likely in patients with lower relative hyperaemic MBF. Consequently, relative hyperaemic MBF may have clinical utility in patients with suspected CAD and diffusely impaired hyperaemic MBF.

Background: Despite tremendous therapeutic advancements, a significant proportion of coronary artery disease patients suffer from refractory angina pectoris, that is, quality-of-life-compromising angina that is non-manageable with established pharmacological and interventional treatment options. Adenoviral vascular endothelial growth factor-D^ΔNΔC (AdVEGF-D)-encoding gene therapy (GT) holds promise for the treatment of refractory angina. Methods: ReGenHeart is an investigator-initiated, multicentre, randomised, placebo-controlled and double-blinded phase 2 clinical trial that aims to study the safety and efficacy of intramyocardially administered angiogenic AdVEGF-D GT for refractory angina. Patients will be randomised in a 2:1 ratio and blocks of six to receive either AdVEGF-D or placebo. Primary endpoints are improvements in functional capacity assessed with the 6 min walking test and angina symptoms with Canadian Cardiovascular Society class after 6 month follow-up. Secondary endpoints are improvements in myocardial perfusion assessed with either positron emission tomography or single-photon emission CT after 6 month follow-up and functional capacity and angina symptoms after 12 months. In addition, changes in the quality of life, the use of angina medication and the incidence of major adverse cardiac and cerebrovascular events will be evaluated. Conclusions: The phase 2 ReGenHeart trial will provide knowledge of the safety and efficacy of AdVEGF-D GT to ameliorate symptoms in refractory angina patients, extending and further testing positive results from the preceding phase 1/2a trial.

Endothelial dysfunction is a systemic disorder and risk factor for atherosclerosis. Our aim was to assess whether there is a relation between peripheral endothelial function and myocardial perfusion in patients with coronary artery disease (CAD). We prospectively studied 54 patients, who had a positive result for obstructive CAD in coronary CT angiography. Myocardial perfusion (¹⁵O)H₂O positron emission tomography was imaged at rest and during adenosine-induced maximal vasodilation. Peripheral endothelial function was assessed by measuring flow-mediated dilation (FMD) with ultrasound from the left brachial artery. There was a statistically significant correlation between FMD and global hyperaemic myocardial blood flow (MBF; r = 0.308, P = 0.023). The correlation remained statistically significant when controlling for gender, height, and diastolic blood pressure at rest (r = 0.367, P = 0.008). Receiver operating character analysis, however, yielded an area under curve of only 0.559 (P = 0.492) when FMD was used to predict reduced MBF (below 2.3 mL/g/min). Patients with significantly decreased MBF (n = 14) underwent invasive coronary angiography. FMD showed an inverse correlation with the severity of the most significant stenosis (r = −0.687, P = 0.007). Peripheral endothelial function is related with hyperaemic MBF and with the severity of CAD in invasive coronary angiography. Due to insufficient sensitivity and specificity in the identification of reduced MBF, FMD is not suitable for clinical practice at the individual level. However, it works at the population level as a research tool when assessing endothelial dysfunction in patients with CAD.