Feasibility of Quantitative Flow Ratio Virtual Stenting for Guidance of Serial Coronary Lesions Intervention.

Background Coronary physiology measurement in serial coronary lesions with multiple stenoses is challenging. Therefore, we evaluated the feasibility of Murray fractal law-based quantitative flow ratio (µQFR) virtual stenting for guidance of serial coronary lesions intervention. Methods and Results Patients who underwent elective coronary angiography and had 2 serial de novo coronary lesions of 30% to 90% diameter stenosis by visual estimation were prospectively enrolled. µQFR and fractional flow reserve (FFR) were assessed after coronary angiography. In vessels with an FFR ≤0.80, the lesion with the larger pressure gradient was considered to be the primary lesion and treated firstly, followed by FFR measurement. The second lesion was stented when FFR ≤0.80. All µQFR and predicted µQFR after stenting were calculated from diagnostic coronary angiography before interventions, with the analysts masked to the FFR data. A total of 54 patients with 61 target vessels were interrogated. Percutaneous coronary intervention was performed in 44 vessels with FFR ≤0.80. After stenting the primary lesions, 14 nonprimary lesions had FFR ≤0.80 and a second drug-eluting stent was implanted. There was excellent correlation (r=0.97, P<0.001) and good agreement (mean difference: 0.00±0.03) between baseline µQFR and FFR in identifying flow-limiting lesions. Per-vessel diagnostic accuracy of µQFR on de novo lesions was 96.7% (95% CI, 88.7%-99.6%). µQFR and FFR are highly consistent (93.2%) in identifying the primary lesion requiring revascularization. After stenting the primary lesions, per-vessel diagnostic accuracy of predicted µQFR for identifying the significance of the nonprimary lesion was 90.9%. Predicted residual µQFR with virtual stenting was higher than final FFR (mean difference: 0.05±0.06). Conclusions In vessels with serial coronary lesions, virtual stenting by µQFR can identify the primary flow-limiting lesion for revascularization.

Diagnostic accuracy of CCTA-derived versus angiography-derived quantitative flow ratio (CAREER) study: a prospective study protocol.

INTRODUCTION: Coronary CT angiography (CCTA)-derived quantitative flow ratio (CT-QFR) is a novel non-invasive technology to assess the physiological significance of coronary stenoses, which enables fast and on-site computation of fractional flow reserve (FFR) from CCTA images. The objective of this investigator-initiated, prospective, single-centre clinical trial is to evaluate the diagnostic performance of CT-QFR with respect to angiography-derived QFR, using FFR as the reference standard. METHODS AND ANALYSIS: A total of 216 patients who have at least one lesion with a diameter stenosis of 30%-90% in an artery with ≥2.0 mm reference diameter will be enrolled in the study. FFR will be measured during invasive coronary angiography. CT-QFR and QFR will be assessed in two independent core laboratories in a blinded fashion. The primary endpoint is the diagnostic accuracy of CT-QFR in identifying haemodynamically significant coronary stenosis with FFR as the reference standard. The major secondary endpoint is the non-inferiority of CT-QFR compared with QFR in the patients without extensively calcified lesions. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of Huadong Hospital Affiliated to Fudan University (2020K192). Outcomes will be disseminated through publications in peer-reviewed journals and presentations at scientific conferences. TRIAL REGISTRATION NUMBER: NCT04665817.

The association between the prognostic nutritional index and 28-day mortality among atrial fibrillation patients in China over 80 years of age.

BACKGROUNDS AND AIMS: The most prevalent form of cardiac rhythm abnormality among older populations is atrial fibrillation (AF). The prognostic nutritional index (PNI) is a reliable predictor of mortality in various diseases. The association between the PNI and mortality among AF patients over 80 years remains uncleared. METHODS AND RESULTS: A retrospective assessment of AF cases admitted to a single cardiovascular disease unit in China between January 2015 and June 2020 was performed. The PNI at admission was defined as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). The association between PNI and cardiovascular disease (CVD)-related or all-cause mortality within 28 days was assessed via multivariable Cox regression. The analysis included 1141 patients. The CVD-related and all-cause mortality rates were 3.3% and 8.7%. Kaplan-Meier analyses revealed that cases with lower PNI tertiles exhibited higher all-cause mortality (T1: 7.6%; T2: 6.1%; T3: 2.4%, P < 0.001) or CVD mortality (T1: 6.3%; T2: 2.9%; T3: 0.8%, P < 0.001). After adjusting for potential confounders, continuous PNI was negatively related to the hazard of all-cause mortality (HR 0.92, 95% CI 0.89, 0.96) and CVD-related mortality (HR 0.90, 95% CI 0.84, 0.95). Compared to the T1 group, patients with a higher PNI exhibited a lower risk of all-cause mortality (P for trend 0.003) and CVD-related mortality (P for trend 0.005). Among most subgroups, CVD-related and all-cause mortality decreased with elevating PNI values. CONCLUSIONS: PNI is significantly negatively correlated with CVD-related and all-cause mortality among AF cases over 80 years.

Chemical renal denervation-induced upregulation of the ACE2/Ang (1-7)/Mas axis attenuates blood pressure elevation in spontaneously hypertensive rats.

OBJECTIVE: Evidence has shown that the ACE2/Ang (1-7)/Mas axis plays an important role in the control of hypertension. Thus, we hypothesized that chemical renal denervation (RDN) could reduce blood pressure by regulating the ACE2/Ang (1-7)/Mas axis in spontaneously hypertensive rats. METHODS: Twelve rats were randomly divided into sham group and chemical RDN group. All the rats were sacrificed 4 weeks later. Plasma samples were collected to measure the renin-angiotensin system (RAS) activities and reactive oxygen species levels by radioimmunoassay, chromatometry and ELISA. Paraventricular nucleus (PVN) tissues were collected to examine the expression of the components of the ACE2/Ang (1-7)/Mas axis by western bolt and immunofluorescence. RESULTS: The systolic blood pressure (169.33 ± 7.50 vs 182.67 ± 7.00 mmHg, p < .05) and the diastolic blood pressure (97.50 ± 4.68 vs 109.33 ± 4.41 mmHg, p < .05) in the RDN group were obviously lower than the baseline levels, whereas the opposite results were observed in the sham group. The RDN group exhibited a significant reduction in the plasma ROS (91.59 ± 13.12 vs 72.34 ± 11.76 U/ml, p < .05) and NADPH oxidase (171.86 ± 1.14 vs 175.75 ± 1.74 nmol/ml, p < .001) compared with the sham group, while the plasma eNOS (3.47 ± 0.42 vs 2.49 ± 0.51 U/ml, p < .05) and NO (55.92 ± 8.10 vs 43.53 ± 4.58 µmol/L, p < .05) were increased. The expression of the components of the ACE2/Ang (1-7)/Mas axis was upregulated while the expression of the components of the ACE/Ang II/AT1 R axis was downregulated in the plasma and PVN in the RDN group. CONCLUSION: Our findings suggested that the reduction in blood pressure was regulated by chemical RDN-induced upregulation of the components of the ACE2/Ang (1-7)/Mas axis.

The safety of renal denervation as assessed by optical coherence tomography: pre- and post-procedure comparison with multi-electrode ablation catheter in animal experiment.

OBJECTIVE: To prove the effectiveness and safety of multi-electrode ablation catheter in renal denervation (RDN) by optical coherence tomography (OCT). METHODS: Sixteen renal arteries were enrolled from 8 pigs. Angiography and OCT were performed to analyze the morphological changes before RDN and at 1-month follow-up. Blood pressure and creatinine were measured to prove the effectiveness and safety of the catheter. RESULTS: One renal artery was excluded because of the small diameter. Fifteen renal arteries successfully underwent renal denervation and OCT. Mean blood pressure was significantly reduced at 1 month after RDN (122.40 ± 3.54 mmHg vs. 106.50 ± 2.06 mmHg, n = 8, P < .001). Creatinine follow-up after 1 month showed no significant change (45.37 ± 7.44 vs. 65.87 ± 49.20 µmol/L, n = 8, P = 0.275). The minimal lumen diameter showed that the renal artery immediately narrowed after the procedure (7.17 ± 0.60 mm vs. 5.93 ± 0.97 mm, n = 15, P < .001). Vasospasm, vascular wall edemas, and thrombus formations all showed significant changes after the procedure except renal artery dissection (0% vs. 21.4%, P = 0.067) under the OCT. Adverse event as renal artery occluded showed no significant difference (0% vs. 6.7%, P > .05). OCT results showed no significant difference in vasospasm, dissections, wall edemas, and thrombus formations (P > .05) at 1 month after the procedure. CONCLUSION: This multi-electrode ablation catheter could cause minor injury to renal artery instantly after RDN, but it is found to be safe in the animal model at 1-month follow-up.

Exogenous supplemental NAD+ protect myocardium against myocardial ischemic/reperfusion injury in swine model.

Acute myocardial infarction is one of the leading causes of deaths worldwide. Although ameliorative therapies against ischemic injury have remarkably reduced death rates among patients, they are inevitably complicated by reperfusion injury. Therefore, it is essential to explore other approaches to reduce ischemia/reperfusion injury (IRI). Modulating the levels of nicotinamide adenine dinucleotide (NAD+) is a promising therapeutic strategy against some aging-related diseases. The aim of this study was to determine the role of NAD+ in a swine model of myocardial IRI. Fourteen Bama miniature pigs were subjected to 90 min transluminal balloon occlusion, and then randomly administrated with 20 mg/kg NAD+ or saline before reperfusion. Emission computerized tomography (ECT) was performed immediately and 4 weeks after reperfusion, and the cardiac tissues were analyzed histologically. In addition, the levels of cardiac function markers and the pro-inflammatory cytokines IL-1ß and TNF-α were also measured. NAD+ administration markedly reduced myocardial necrosis, enhanced glucose metabolism, and promoted cardiac function recovery. The extent of inflammation was also reduced in the NAD+ treated animals, and corresponded to less cardiac fibrosis and better ventricular compliance. Thus, NAD+ supplementation protected the myocardium from IRI, making it a promising therapeutic agent against acute myocardial ischemic disease.

Chemical renal artery denervation with appropriate phenol in spontaneously hypertensive rats.

OBJECTIVE: To explore the effectiveness of renal denervation (RDN) on blood pressure with the appropriate dosage of phenol/ethanol solution in spontaneously hypertensive rats (SHRs). METHODS: RDN was performed on the bilateral renal artery. Forty SHRs were divided into four groups according on the dosage of phenol (10% phenol in absolute ethanol): sham group, 0.5 mL phenol group, 1 mL phenol group and 1.5 mL phenol group (n = 10 in each group). Blood pressure was measured by tail-cuff plethysmography. Plasma creatinine was determined four weeks after the treatment. The kidneys and renal arteries were collected and processed for histological examination. RESULTS: A sustained decrease in systolic blood pressure (SBP) was only observed after the application of 1 mL phenol for four weeks, while SBP was lowered during the first week after RDN and increased in the following three weeks in the 0.5 mL and 1.5 mL phenol groups compared with the sham group. Renal norepinephrine (NE) was significantly decreased four weeks after RDN in the 1 mL and 1.5 mL phenol group compared with the sham group, but not in the 0.5 ml group. RDN with 1 mL phenol obviously reduced glomerular fibrosis. Histopathological analysis showed that tyrosine hydroxylase immunoreactivity was lower in the 1 mL and 1.5 mL phenol groups compared with the sham group. Moderate renal artery damage occurred in the 1.5 mL phenol group. CONCLUSION: Chemical denervation with 1 ml phenol (10% phenol in absolute ethanol) effectively and safely damaged peripheral renal sympathetic nerves and contributed to the sustained reduction of blood pressure in SHRs.

Long-term renal sympathetic denervation ameliorates renal fibrosis and delays the onset of hypertension in spontaneously hypertensive rats.

This study was designed to explore the effects of long-term renal denervation (RDN) on blood pressure and renal function in spontaneously hypertensive rats (SHR). RDN was performed in bilateral renal arteries with 10% phenol in absolute ethanol in SHR and Wistar-Kyoto rats (WKY) at 13 weeks. Age-matched SHR and WKY served as controls. Blood pressure was measured. Plasma, urine and kidneys were collected 8 months after the RDN operation. Plasma renin activity (PRA), aldosterone levels, reactive oxidative stress, renal function and structural remodeling were assessed. RDN-treated SHR demonstrated a lower spontaneous rise in systolic blood pressure than rats in the SHR-Sham group (P < 0.01, at 20, 27, 34 and 41 weeks), except at 48 weeks (198.2 ± 12.9 vs 209.4 ± 11.9 mmHg, P = 0.145). WKY were not affected by RDN. Renal tissue norepinephrine was decreased by RDN in both SHR and WKY. Plasma PRA activity, aldosterone levels, and NAD(P)H oxidase activity were reduced by the RDN in SHR. Plasma eNOS and NO were increased by RDN only in SHR. The renal nerve was destroyed by RDN with no regeneration after 8 months. The progression of renal dysfunction associated with urinary protein excretion, glomerular sclerosis, and tubulointerstitial fibrosis was attenuated by RDN only in SHR through downregulation of the ACE/Ang II/AT1R axis and upregulation of the ACE2/Ang-(1-7)/MasR axis in the kidney. Thus, RDN delays the onset of hypertension and ameliorates glomerular sclerosis and tubulointerstitial fibrosis in SHR.