Intracoronary Administration Research Articles

Abstract 4129675: Effective Transcatheter Intracoronary Delivery of mRNA-Lipid Nanoparticle Targeting on The Heart

Introduction: mRNA has great potential to provide new medical innovations in the treatment of heart failure. Lipid nanoparticles (LNPs) are an established and effective mRNA delivery system. However, effectively delivering LNPs to the heart remains a significant challenge. We evaluated the efficacy of transcatheter intracoronary (IC) administration compared to intravenous (IV) and intramyocardial (IM) administration as methods for delivering. Methods: Normal rabbits were used to examine each route of administration. Fluorescence (ATTO 700)-labeled LNP encapsulating Firefly Luciferase (FLuc) mRNA (25 ug/kg) were used to confirm the in vivo mRNA-LNP dynamics. The LNP accumulation and FLuc expression were verified using an in vivo imaging system (IVIS) 4 hours post-administration, followed by immunohistochemical analysis. The same experiments were conducted in an ischemia-reperfusion (I/R) model. Results: In the normal model, IVIS spectrum data showed that LNPs accumulated in the order of IM, IC and IV groups, with FLuc expression significantly higher in the IC group than in the IV group and comparable to the IM group (A). Histological analysis revealed that FLuc-expressing cells were mainly found in troponin T-positive cardiomyocytes at the injection site in the IM group and throughout the heart in the IC group (B). In the I/R model, LNP accumulation and FLuc expression were increased in the IV group compared to the normal model, whereas, in the IC and IM groups LNP accumulation and FLuc expression levels were similar to those in the normal model (C). Histological analysis revealed more FLuc-expressing cells in the infarcted area in all groups, but higher FLuc expression was observed in remote areas in the IC group (D). Conclusions: IC administration effectively delivered mRNA-LNPs not only to the damaged area but also to the remote area (non-damaged area) in the diseased heart, suggesting a safe and useful method for delivery to a wider range of cardiomyocytes in the heart.

VERMONT non-optimised: can baseline diagnostic catheter images be used to measure angiography based CAAS-vFFR?

Abstract Background We have previously reported strong diagnostic accuracy and validity of angiography-based vessel Fractional Flow Reserve (CAAS-vFFR) compared to conventional wire based Fractional Flow Reserve (FFR)(1). The CAAS-vFFR system requires at least two additional optimised angiographic cine images taken after intracoronary glyceryl trinitrate administration, separated by ≥ 30 degrees at a frame-rate of ≥ 15 frames/seconds with minimal overlap and foreshortening, no table movement and adequate contrast opacification. At present, there is a paucity of data regarding the validity of using baseline non-optimised diagnostic cine images in the assessment of CAAS-vFFR. Purpose To assess the concordance and validity of using baseline non-optimised diagnostic cine images in measuring angiography based CAAS-vFFR. Methods We conducted an investigator-initiated, single centre, blinded, prospective observational study performing wire based FFR and CAAS-vFFR conducted simultaneously in patients undergoing routine wire-based FFR for intermediate coronary stenoses. All eligible patients had baseline diagnostic and optimised guide-catheter based angiographic images acquired. Results 195 consecutive patients with 205 lesions were recruited over 19 months; 56 (27.3%) lesions were excluded due to inadequate baseline cine angiogram images (Picture 1). 102 (68.5%) had stable symptoms and 107 (71.8%) were male. The median age was 65.0 years (interquartile range 59.0 – 73.0) and mean body-mass-index was 29.2 kg/m2 (± 5.8). There were 117 (78.5%) lesions in the left anterior descending artery/diagonal branches, 20 (13.4%) in the right coronary artery and 12 (8.1%) in the left circumflex artery/marginal branches. There were 93 (62.4%) diffuse (≥ 20 cm), 23 (15.4%) bifurcation and 15 (10.1%) ostial lesions. The mean optimised vFFR and non-optimised vFFR were 0.80 (± 0.1) and 0.79 (± 0.1) respectively with a Pearson correlation of 0.87 (p<0.001). Overall, 52 lesions (34.9%) and 73 lesions (49.0%) had a wire-based FFR and non-optimised vFFR value of ≤ 80 respectively. The mean wire-based FFR and non-optimised vFFR were 0.82 (± 0.1) and 0.79 (± 0.1) respectively. Receiver operating characteristic (ROC) curve analysis revealed excellent diagnostic accuracy of non-optimised vFFR in predicting a wire based FFR of ≤ 80 (AUC 0.91; 95% CI; 0.87-0.96) (Picture 2). Baseline non-optimised diagnostic vFFR images produced a sensitivity of 94.2%, specificity of 75.3%, positive-predictive-value (PPV) of 67.1% and negative-predictive-value (NPV) of 96.1% compared with wire-based FFR. Conclusions CAAS-vFFR derived values from baseline non-optimised diagnostic cine images were strongly concordant with those derived from optimised images and displayed a high sensitivity and NPV compared to wire-based FFR. This reflects the potential for CAAS-vFFR to have broader clinical applications and be utilised as a retrospective screening tool for intermediate lesions.Excluded baseline angiogram lesionsROC Curve

Assessment of TIMI frame count pre- and post- intracoronary acetylcholine administration in patients with angina and non-obstructive coronary arteries (ANOCA)

Abstract Background Patients with Angina and unobstructed coronary arteries (ANOCA) represent a diagnostic challenge. Current ESC guidelines on the management of patients with chronic coronary syndrome recommend intracoronary spasm testing and coronary spasm represents a frequent diagnosis in such patients. Previous studies have shown that coronary artery flow assessments during acetylcholine testing frequently show non-uniform results. Purpose The aim of the present study was to assess changes in TIMI Frame Count (a quantitative method for the assessment of coronary artery flow) pre- and post- intracoronary acetylcholine testing in patients with ANOCA. Methods From 2007 to 2018, a total of 141 consecutive patients (51.8% female, mean age 61 ± 13.2 years) were included in the study. Among them, 63 patients (45%) presented with myocardial infarction with unobstructed coronary arteries, while 78 patients (55%) presented with stable angina and unobstructed coronaries. Following diagnostic angiography, all patients underwent intracoronary acetylcholine testing using a standardized protocol. TIMI frame count (TFC) was measured both for LAD and LCX before and after ACh injection, and post nitroglycerine injection. All counted frames were adjusted to a frame rate of 30 frames per second (fps). Furthermore, TFC of the LAD was divided by 1.7 to obtain the corrected TFC (cTFC). Results Of all 141 patients, coronary spasm was found in 98 patients (70%) during ACh testing (44% epicardial and 56% microvascular spasm). In the spasm cohort, the median cTFC in the LAD pre-ACh was 21.8 fps (quartiles: 16.3 – 30.0), decreased to 12.9 fps (8.8 - 19.2) post-ACh, and increased to 15.9 fps (10.6 - 21.3) post-nitro. The difference in the LAD between pre-ACh and post-ACh was statistically significant (p < 0.001). In the LCX the median TFC was 26.5 fps (15.0 – 40.5) pre-ACh, decreased to 16.0 fps (11.5 - 28.5) post-ACh and reached 24.0 fps (15.5 - 33.3) post-nitro. Again, this reduction from pre-ACh to post-ACh was statistically significant (p < 0.001). In the negative spasm cohort median cTFC for the LAD was 22.9 fps (16.0 – 18.2) pre-Ach, 15.3 fps (9.4 – 24.7) post-ACh and 15.8 fps (10.6 - 24.7) post-nitro, TFC for LCX was 24.0 fps (18.0 - 36.0) pre-ACh, 18.0 fps (12.0 – 33.0) post-ACh and 24.0 fps (12.0 – 34.0) post-nitro. The change in cTFC/TFC pre-ACh compared to post-ACh was statistically significant for both coronary arteries (LAD, p=0.012; LCX p=0.005, Table 1). Interestingly, in the spasm cohort 22% of LAD and 32% of LCX vessels showed higher TFC post-ACh compared to pre-ACh (Figure 1). Conclusions In patients with ANOCA and coronary spasm assessment of TIMI frame count reveals a hetereogeneous response. The majority of cases shows a decrease in TFC suggesting an increase in flow despite coronary spasm. This interesting finding allows speculations about the presence of coronary shunts.Figure 1

Predictors of microvascular spasm by spasm provocation testing in patients having angina with no obstructive coronary arteries

Abstract Background Microvascular dysfunction in patients having angina with no obstructive coronary arteries (ANOCA) has been recognized to be associated with poor prognosis, while microvascular spasm (MVS) has not been fully studied due to its diagnostic challenge. Purpose We aimed to explore clinical and coronary physiological characteristics of MVS. Methods We retrospectively studied patients with ANOCA who underwent spasm provocation test (SPT) with intracoronary acetylcholine administration followed by coronary physiological assessment. Epicardial spasm and MVS were diagnosed in accordance with the latest guideline. Physiological indices such as coronary flow reserve (CFR), index of microcirculatory resistance (IMR) and microvascular resistance reserve (MRR) were assessed by bolus thermodilution method using pressure temperature wire in LAD and RCA. Results In a total of 141 patients, 40 (28.4%) patients were diagnosed as epicardial spasm and 22 (15.6%) were diagnosed as MVS according to the diagnostic criteria of the latest guideline. Women was more frequent (63.9% vs 27.3%, P=0.002) and IMR of LAD was significantly higher (34.80 vs 22.95, P=0.005) in patients with versus without MVS. In addition, hypertension tended to be frequent (81.8% vs 60.5%, P=0.089) in patients with MVS. In a multivariable logistic regression analysis, women (odds ratio 5.64 [OR], 95% CI 1.90 – 16.7, P=0.0018) and IMR of LAD (OR 1.02, 95% CI 1.00 – 1.05, P=0.029) were independently associated with the diagnosis of MVS. On the other hand, no clinical characteristics and physiological parameter were significantly associated with epicardial spasm. In a comparison between microvascular and epicardial spasm, women (OR 8.30, 95%CI 2.23 – 30.9, P=0.0016) and IMR of LAD (OR 1.04, 95%CI 1.00 – 1.08, P=0.0462) were still significantly more frequent in MVS patients in multivariable analysis. Conclusion Women and higher IMR of LAD were significantly frequent in patients with versus without MVS, and hypertension tended to be frequent in MVS patients.

Association of vasospastic angina with myocardial bridging and pericoronary adipose tissue attenuation on computed tomography angiography

Abstract Background Recent studies have suggested that vasospastic angina (VSA) is associated with myocardial bridging (MB). The relationship between VSA and pericoronary adipose tissue (PCAT) inflammation has also been reported but still remains to be determined. Purpose We investigated clinical and coronary computed tomography angiographic (CCTA) features in patients with VSA diagnosed by spasm provocation test (SPT). Methods We retrospectively studied patients with clinically suspected VSA who underwent both SPT with intracoronary acetylcholine administration and CCTA within three months before SPT at Tsuchiura Kyodo General Hospital. PCAT inflammation was evaluated on CCTA images by fat attenuation index (FAI) which has been recently used as a novel biomarker of coronary inflammation. In FAI analysis, we measured FAI of the proximal segments not only for 4mm (FAI4mm) but also for the inner and thinner 2mm pericoronary adipose tissue layer from the vessel wall (FAI2mm), since FAI2mm has been reported to provide better discriminating efficacy for VSA diagnosis than FAI4mm. We also evaluated the presence or absence of MB and its features including length, depth and location on CCTA images. Results A total of 172 patients were studied and VSA was diagnosed in 39.0% (67/172) of patients by SPT according to the latest guideline. Male (74.6% vs 49.5%, P=0.001), smoking history (74.6% vs 48.6%, P=0.001) were more frequent, and prevalence of CCTA-defined MB (47.8% vs 34.3%, P=0.082) and RCA-FAI2mm (-68.73 HU vs -73.35 HU, P<0.001) were higher in patients with versus without VSA. In multivariable analysis, presence of CCTA-defined MB (odds ratio [OR] 2.56, 95% confidence interval [CI] 1.26-5.19, P=0.0095), RCA-FAI2mm (OR 1.05, 95% CI 1.01-1.09, P=0.025), and smoking (OR 3.40, 95% CI 1.57-7.36, P=0.0019) were independently associated with VSA. A combination of high RCA-FAI2mm (≥-68.93HU, the best cut-off obtained by ROC analysis with AUC of 0.64, 95% CI 0.551 - 0.728), smoking history and existence of MB could predict VSA with 73.7% of probability, while an absence of all 3 covariates could exclude VSA with 85.3% of probability. Conclusion CCTA-defined MB, high RCA-FAI2mm and smoking were independently predictive of VSA.

The efficacy of an intracoronary cocktail administration in preventing no-reflow during excimer laser coronary angioplasty in patients with in-stent restenosis: A pilot study. (ELCA- cocktail study)

BackgroundThe no-reflow phenomenon is a significant complication during excimer laser coronary angioplasty (ELCA) procedures, which can lead to adverse outcomes. This study explores the efficacy of intracoronary administration of a cocktail solution comprising nitroglycerin, heparin, and verapamil on preventing no-reflow during ELCA in patients with in-stent restenosis (ISR). MethodsThis study included patients undergoing ELCA with contrast infusion for ISR. Based on whether receiving the intracoronary cocktail solution during ELCA, participants were divided into two groups: the cocktail (+) group and the cocktail (−) group. The primary endpoint was the incidence of no-reflow, which was defined as the cessation of blood flow into the distal coronary artery in the absence of a clear angiographic explanation for impairment of flow. ResultsA total of 54 lesions in 51 patients were included. The mean age of the study population was 61.8 ± 9.7 years, with 84.3 % male. Baseline clinical characteristics were well-balanced. The incidence of no-reflow was significantly lower in the cocktail (+) group compared to the cocktail (−) group (0 % vs. 17.9 %, P = 0.024). No cases of hypotension, major bleeding or coronary perforation in either group. Major adverse cardiac events (MACE) within 6-month were no significant difference between the groups (4.0 % vs. 3.8 %, P = 0.977). ConclusionsThe pilot study suggests that intracoronary administration of a cocktail comprising heparin, nitroglycerin, and verapamil may reduce the incidence of no-reflow during ELCA in patients with ISR. However, given the limited sample size and the non-randomized design, these findings should be considered hypothesis-generating. Future validation needs to be confirmed through multicenter studies with larger sample sizes.

Effects of intracoronary administration of small doses of nicorandil and verapamil on blood pressure and heart rate

BackgroundNicorandil and verapamil can improve coronary blood flow and coronary microcirculation during percutaneous coronary intervention. However, the effects of intracoronary (IC) administration of nicorandil and verapamil on hemodynamics remain unclear. AimsTo clarify the safety and effects of IC administration of nicorandil and verapamil on blood pressure (BP) and heart rate (HR) to provide evidence-based basis for clinical intervention. MethodsThe study cohort included 70 patients with coronary artery stenosis recruited from Zhejiang Provincial Hospital of Traditional Chinese Medicine. The patients were randomly assigned to the intervention group (IC administration of 2 mg/2 ml of nicorandil and 200 μg/2 ml of verapamil) or the control group (IC administration of 2 ml of saline). BP and HR were compared before medication, after medication, and when stabilized. ResultsIC administration of verapamil at 200 μg significantly reduced systolic BP as compared to the control group (113.72 ± 3.40 vs. 123.63 ± 3.33 mmHg, respectively, p < 0.05) for a short period of time, and returned to baseline within 2 min, but had no effect on diastolic BP and HR. IC administration injection of nicorandil at 2 mg had no effect on BP or HR. There were no instances of major cardiovascular events. ConclusionIC administration of nicorandil at 2 mg is safe as an adjunctive medication during interventional angiography. Verapamil can also be used as an IC adjuvant, although BP and HR must be monitored for patients with low basal BP, especially systolic BP.

Acute coronary syndrome due to coronary vasospasm: a case report.

Coronary vasospasm can lead to decreased cardiac perfusion and result in acute coronary syndrome. Here is a case of a 49-year-old man presented to the emergency department with epigastric pain and nausea with normal initial electrocardiogram. However, 6h later, the patient experienced severe chest pain prompting a repeat electrocardiogram demonstrating inferior ST-segment elevation with troponin I levels peaked at 1.2ng/ml (normal range: 0.00-0.02ng/ml). Coronary angiography revealed angiographic stenosis in the left circumflex territory of a left dominant system which resolved with intracoronary nitroglycerin administration indicating ischemia with nonobstructive coronary arteries secondary to coronary vasospasm. He was discharged on isosorbide mononitrate and amlodipine therapy and had no recurrence of symptoms during follow-up.

Coronary and Systemic Vasodilator Responsiveness of Patients Receiving Conventional Intermittent or Nocturnal Hemodialysis.

Nocturnal hemodialysis (nHD) restores the attenuated brachial artery vasodilator responsiveness of patients receiving conventional intermittent hemodialysis (iHD). Its impact on coronary vasodilatation is unknown. We evaluated 25 patients on hemodialysis who fulfilled transplant criteria: 15 on iHD (4-hour sessions, 3 d/wk) and 10 on nHD (≈40 h/wk over 8-10-hour sessions) plus 6 control participants. Following diagnostic angiography, left anterior descending (LAD) coronary flow reserve and mean luminal diameter were quantified at baseline and during sequential intracoronary administration of adenosine (infusion and bolus), nitroglycerin (bolus), acetylcholine (infusion), acetylcholine coinfused with vitamin C, and, finally, sublingual nitroglycerin. Coronary flow reserve in those receiving nHD was augmented relative to iHD (3.28±0.26 versus 2.17±0.12 [mean±SEM]; P<0.03) but attenuated, relative to controls (4.80±0.63; P=0.011). Luminal dilatations induced by intracoronary adenosine and nitroglycerin were similar in nHD and controls but blunted in the iHD cohort (P<0.05 versus both). ACh elicited vasodilatation in controls but constriction in both dialysis groups (both P<0.05, versus control); vitamin C coinfusion had no effect. Sublingual nitroglycerin increased mid-left anterior descending diameter and reduced mean arterial pressure in controls (+15.2±2.68%; -16.00±1.60%) and in nHD recipients (+14.78±5.46%; -15.82±1.32%); iHD responses were markedly attenuated (+1.9±0.86%; -5.89±1.41%; P<0.05, all comparisons). Coronary and systemic vasodilator responsiveness to both adenosine and nitroglycerin is augmented in patients receiving nHD relative to those receiving iHD, whereas vasoconstrictor responsiveness to acetylcholine does not differ. By improving coronary conduit and microvascular function, nHD may reduce the cardiovascular risk of patients on dialysis.

A pilot study of perfusion balloon predilatation in conjunction with intracoronary nicorandil administration for acute coronary syndrome.

Slow-flow or no-reflow phenomenon is a common procedural complication during percutaneous coronary intervention (PCI). Given the presence of fragile plaque or thrombotic materials, we hypothesized that long-time predilatation using a perfusion balloon in conjunction with intracoronary nicorandil administration reduces the risk of slow-flow or no-reflow in patients presenting with acute coronary syndrome (ACS). Subjects were patients presenting with ACS who underwent PCI between April 2020 and April 2022. We retrospectively investigated the incidence of slow-flow or no-reflow during the procedure as well as in-hospital outcomes in comparison between the cases undergoing 3-min predilatation using a perfusion balloon in conjunction with intracoronary nicorandil administration followed by DES implantation (PB group) and those with direct stenting (DS group). Among 439 ACS patients, 36 patients in the PB group and 51 patients in the DS group were examined. Mean age was 70years and 78.2% was male. Distal protection devices were more frequently used in the DS group than in the PB group (31.3% vs. 11.1%, p = 0.02). The incidence rate of slow-flow or no-reflow was significantly lower in the PB group than in the DS group (2.8% vs. 23.5%; p < 0.01). Six cases (11.7%) in the DS group required intra-aortic balloon pumping (IABP), while none in the PB group required (p < 0.01). In-hospital clinical outcomes did not differ between the two groups. Prolonged perfusion balloon predilatation in conjunction with intracoronary nicorandil administration was safe and feasible. This novel strategy could be an attractive alternative to conventional direct stenting for ACS patients.

Efficiency and Safety of Intracoronary Epinephrine Administration in Patients With ST-Elevation Myocardial Infarction With Refractory Coronary No-Reflow

Studies assessing the treatment of refractory no-reflow in ST-elevation myocardial infarction (STEMI) patients are limited to clinical cases and pilot studies. This study aimed to evaluate the efficacy and safety of intracoronary epinephrine administration in such patients. Ninety consecutive patients with refractory coronary no-reflow during percutaneous coronary intervention (PCI) were prospectively included after initial failure of conventional treatment. They were randomized into 2 groups: 45 patients in group 1 received epinephrine, and 45 patients in group 2 (control) received conventional treatments alone. Following intracoronary drug administration, the epinephrine group demonstrated significantly higher rates of coronary flow restoration in the infarct-related artery to the level of thrombolysis in myocardial infarction (TIMI) grade 3 (56% versus 29% (p=0.01)) and resolution of ST-segment elevation >50% post PCI (78% versus 36% (p<0.001)). Additionally, the epinephrine group showed a lower indexed microvascular obstruction (MVO) volume compared to the control group (0.9 (0.3; 3.1)% versus 1.9 (0.6; 7.9)% (p=0.048)). A significant improvement in ejection fraction (EF) was observed in the epinephrine group (p=0.025). Intracoronary epinephrine administration during PCI in STEMI patients with refractory no-reflow is more effective compared to conventional treatments. This approach improves coronary flow in the infarct-related artery, facilitates a faster resolution of ST segment elevation, enhances EF, and reduces MVO volume. Intracoronary epinephrine administration demonstrates a comparable safety profile to conventional treatment strategies in terms of life-threatening arrhythmias occurrence. The study suggests that intracoronary epinephrine administration during PCI could be an effective treatment strategy for STEMI patients with refractory no-reflow.

Intracoronary Versus Intravenous Low-Dose Tirofiban in Patients With ST-Elevation Myocardial Infarction: A Meta-Analysis of Randomised Controlled Trials

This meta-analysis aimed to evaluate the effects of intracoronary (IC) low-dose tirofiban versus intravenous (IV) administration on clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). All published randomised controlled trials (RCTs) comparing the effects of IC low-dose tirofiban (a bolus of ≤10 ug/kg) versus IV administration in patients with STEMI were identified by searching PubMed, EMBASE, Cochrane Library, and ISI Web of Science from inception to June 2023, with no language restriction. The risk ratio (RR) with 95% confidence intervals (CI) and the weighted mean difference (WMD) with 95% CI were calculated. Eleven RCTs involving 1,802 patients were included. Compared with the IV group, IC low-dose tirofiban was associated with improved major adverse cardiac events rate (RR 0.595, 95% CI 0.442-0.802; p=0.001), left ventricular ejection fraction (WMD 1.982, 95% CI 0.565-3.398; p=0.006), thrombolysis in myocardial infarction (TIMI) flow grade (RR 1.065, 95% CI 1.004-1.131; p=0.037), and TIMI myocardial perfusion grade (RR 1.194, 95% CI 1.001-1.425; p=0.049). The two groups had no significant difference in bleeding events (RR 0.952, 95% CI 0.709-1.279; p=0.745). Intracoronary low-dose tirofiban administration may be a safe and effective alternative to IV administration in STEMI patients.

Is ischemic stimulus involved for J wave augmentation during coronary angiography and intracoronary administration of normal saline?

J waves may be augmented by coronary angiography (CAG) or intracoronary drug administration but the underlying mechanism is unknown. The effect of intracoronary normal saline (NS) on J waves were investigated. After the standard CAG using iopamidol (IopamiroR Inj), NS was injected into the right coronary artery in 10 patients with and eight patients without J waves at the baseline. The 12-lead ECG was monitored, stored on a computer and retrieved later for measurement of the J wave amplitude before or during the coronary interventions. J waves in leads II, III and aVF at baseline increased significantly in each lead during the right CAG and NS injection into the right coronary artery. The J wave changes were similar between the two interventions and distinct similar alterations were observed in the QRS complex. We postulated that the ischemic myocardium that was induced during CAG or intracoronary NS administration slowed the conduction velocity of depolarization in the perfusion territory and delayed the timing of J waves to appear. Then, the delayed appearance of J waves would be less opposed by electromotive force from other areas resulting in augmentation. J wave augmentation was observed during CAG and intracoronary NS administration. As a mechanism of augmentation, we postulated that contrast media and NS induce myocardial ischemia and delay the timing of J waves to a point of less opposition by electromotive force from other areas. J wave augmentation has been reported during intracoronary injection of contrast media or drugs. The present study confirmed that normal saline alone was able to augment J waves. Mechanistically, coronary interventions using anoxic solutions can cause regional myocardial ischemia and reduce the conduction velocity of depolarization. Then, delayed J waves are less opposed by the electromotive force from remote areas which leads to augmentation. When a drug is diluted in normal saline and given intracoronarily, changes in J waves can be due to normal saline. The pathophysiological and clinical significance of J waves augmented during coronary interventions need to be established.

REGENERATE-COBRA: A phase II randomized sham-controlled trial assessing the safety and efficacy of intracoronary administration of autologous bone marrow-derived cells in patients with refractory angina

AimsThe REGENERATE-COBRA trial (NCT05711849) will assess the safety and efficacy of an intracoronary infusion of autologous bone marrow-derived mononuclear cells in refractory angina patients with no revascularization options who are symptomatic despite optimal medical and device therapy. MethodsREGENERATE-COBRA is a single site, blinded, randomized, sham-controlled, Phase II clinical trial enrolling 110 refractory angina patients with no revascularization options who are symptomatic despite optimal medical and device therapy. Patients will be randomized to either autologous bone marrow derived-mononuclear cells or a sham procedure. Patients in the cell-treated arm will undergo a bone marrow aspiration and an intracoronary infusion of autologous bone marrow derived-mononuclear cells. Patients in the control arm will undergo a sham bone marrow aspiration and a sham intracoronary infusion. The trial's primary endpoint is an improvement in Canadian Cardiovascular Society (CCS) angina class by 2 classes between baseline and 6 months. Secondary endpoints include change in: CCS class at 12 months, myocardial ischemic burden (as measured by perfusion imaging) at 6 months, quality of life at 6 and 12 months (as measured by EQ-5D-5L, EQ-5D-VAS and Seattle Angina Questionnaire), angina frequency at 6 and 12 months, total exercise time (as measured by a modified Bruce protocol) and major adverse cardiovascular events at 6 and 12 months. ConclusionsThis is the first trial to assess the safety and efficacy of an intracoronary infusion of autologous bone marrow-derived unfractionated mononuclear cells in symptomatic refractory angina patients who have exhausted conventional therapeutic options.

Use of coronary physiology to guide revascularization in clinical practice: results of the F(FR)2 registry

BackgroundDespite the recommendation of coronary physiology to guide revascularization in angiographically intermediate stenoses without established correlation to ischemia, its uptake in clinical practice is slow.AimsThis study aimed to analyze the use of coronary physiology in clinical practice.MethodsBased on a multicenter registry (Fractional Flow Reserve Fax Registry, F(FR)2, ClinicalTrials.gov identifier NCT03055910), clinical use, consequences, and complications of coronary physiology were systematically analyzed.ResultsF(FR)2 enrolled 2,000 patients with 3,378 intracoronary pressure measurements. Most measurements (96.8%) were performed in angiographically intermediate stenoses. Out of 3,238 lesions in which coronary physiology was used to guide revascularization, revascularization was deferred in 2,643 (78.2%) cases.Fractional flow reserve (FFR) was the most common pressure index used (87.6%), with hyperemia induced by an intracoronary bolus of adenosine in 2,556 lesions (86.4%) and intravenous adenosine used for 384 measurements (13.0%). The route of adenosine administration did not influence FFR results (change-in-estimate -3.1% for regression model predicting FFR from diameter stenosis). Agreement with the subsequent revascularization decision was 93.4% for intravenous and 95.0% for intracoronary adenosine (p = 0.261).Coronary artery occlusion caused by the pressure wire was reported in two cases (0.1%) and dissection in three cases (0.2%), which was fatal once (0.1%).ConclusionsIn clinical practice, intracoronary pressure measurements are mostly used to guide revascularization decisions in angiographically intermediate stenoses. Intracoronary and intravenous administration of adenosine seem equally suited. While the rate of serious complications of wire-based intracoronary pressure measurements in clinical practice seems to be low, it is not negligible.Graphical abstract

#1322 VEGF therapy improves cardio-renal pathophysiology in a novel model of CKD-HFpEF

Abstract Background and Aims Patients with chronic kidney disease (CKD) have a higher risk of developing heart failure with preserved ejection fraction (HFpEF). We developed a model of CKD-HFpEF and showed that renal-cardio pathophysiology is associated with decreased expression and availability of vascular endothelial growth factor in both organs. We showed that renal VEGF therapy improved renal function in our model. We hypothesize that cardiac VEGF therapy will improve cardiac function and will investigate whether cardiac protection in CKD also carries recovery of renal function. Method CKD and normal pigs (n = 4 each, 2 males/2 females) were studied for 14 weeks. In addition, CKD-HFpEF (n = 4, 2 males/2 females) were treated after 6 weeks of disease with a single intracoronary (IC) administration of VEGF attached to a drug-delivery vector (ELP-VEGF) that increases cardiac targeting, and effects quantified 8 weeks later. Renal (multi-detector CT) and cardiac (echocardiography, PV loops) morphology and function were quantified in vivo, microvascular (MV) density (3D micro-CT) ex vivo, and cardiac expression of VEGF was quantified by qPCR. Results Cardiac function, VEGF expression, and MV density were improved after IC ELP-VEGF therapy compared to placebo. Notably, renal hemodynamics (expressed as % change) were significantly improved compared to pre-treatment values and to time-matched untreated CKD-HFpEF pigs (Figure). Conclusion Our study suggests strong crosstalk between the heart and the kidney in a pre-clinical model of CKD-HFpEF. Renal and cardiac hemodynamics were significantly improved after cardiac VEGF therapy, conceptually supporting a cardio-renal axis in CKD and showing the extent of beneficial effects of a novel targeted intervention in a translational fashion.

A-60 | Intralesional vs intracoronary administration of glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention in patients with acute coronary syndrome: a meta-analysis of randomized controlled trials

A-60 | Intralesional vs intracoronary administration of glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention in patients with acute coronary syndrome: a meta-analysis of randomized controlled trials

Mixture of Doxycycline, ML-7 and L-NAME Restores the Pro- and Antioxidant Balance during Myocardial Infarction-In Vivo Pig Model Study.

The restoration of blood flow to the ischemic myocardium inflicts ischemia/reperfusion (I/R) heart injury (IRI). The main contributors to IRI are increased oxidative stress and subsequent excessive production of ROS, increased expression of NOS and peroxinitate, activation of MMPs, and enhanced posttranslational modifications of contractile proteins, which make them more susceptible to proteolytic degradation. Since the pathophysiology of IRI is a complex issue, and thus, various therapeutic strategies are required to prevent or reduce IRI and microvascular dysfunction, in the current study we proposed an innovative multi-drug therapy using low concentrations of drugs applied intracoronary to reach microvessels in order to stabilize the pro- and antioxidant balance during a MI in an in vivo pig model. The ability of a mixture of doxycycline (1 μM), ML-7 (0.5 μM), and L-NAME (2 μM) to modulate the pro- and antioxidative balance was tested in the left ventricle tissue and blood samples. Data showed that infusion of a MIX reduced the total oxidative status (TOS), oxidative stress index (OSI), and malondialdehyde (MDA). It also increased the total antioxidant capacity, confirming its antioxidative properties. MIX administration also reduced the activity of MMP-2 and MMP-9, and then decreased the release of MLC1 and BNP-26 into plasma. This study demonstrated that intracoronary administration of low concentrations of doxycycline in combination with ML-7 and L-NAME is incredibly efficient in regulating pro- and antioxidant balance during MI.

VARIOUS ASPECTS OF PERCUTANEOUS CORONARY INTERVENTIONS AS PREDICTORS OF DEATH IN MYOCARDIAL INFARCTION AND CORONARY MICROVASCULAR OBSTRUCTION (NO-REFLOW)

HighlightsThe review analyzed the role of various preoperative indicators as predictors of long-term mortality in patients with myocardial infarction and coronary microvascular obstruction (no-reflow) that developed during percutaneous coronary intervention. As a result of a multifactorial analysis, taking into account the confounders available for evaluation, we have found that predilation serves as an independent predictor of death within two years. AbstractAim. To evaluate the role of various aspects of percutaneous coronary interventions (PCI) as predictors of long-term death in myocardial infarction (MI) and coronary microvascular obstruction (CMVO, no-reflow).Methods. The unmatched case-control study included 232 patients with type 1 MI and CMVO developed during PCI. CMVO criteria were as follows: TIMI flow grade &lt;3, Myocardial blush grade &lt;2, ST segment resolution after PCI &lt;70%. The “cases” group consisted of 54 (23.3%) patients who died within the next two years, the “controls” group consisted of 178 (76.7%) patients who survived. The analysis included the following indicators: predilation, high-pressure balloon post-dilation, vacuum assisted manual thromboaspiration, intra-aortic balloon pump, intracoronary administration of isosorbide dinitrate and verapamil hydrochloride, glycoprotein IIb/IIIa inhibitors and “potent” p2y12 inhibitors usage, bare-metal stents, stent implantation with exceeded rated burst pressure, 3 or more stents usage, PCI on more than one artery, the ratio of contrast agent volume to glomerular filtration rate (GFR) &gt;3.0. A univariate comparative analysis of the groups regarding PCI aspects and potential confounders was performed (Mann-Whitney, Fisher). To control the confounders, a multivariate analysis was carried out (logistic regression).Results. Differences were obtained for the following indicators: “predilation” – in 51 (94%) patients in the “cases” group and in 139 (78%) in the “control” group, p-value = 0.005; “intra-aortic balloon pump” – in 9 (17%) and 7 (4%) patients respectively, p-value = 0.003; “the ratio of contrast agent volume to GFR &gt;3.0” – in 26 (48%) and 48 (27%) patients, p-value = 0.005. Multivariate analysis revealed that only predilation was an independent predictor of death within two years – odds ratio 7.38 (95% confidence interval 1.70–49.04, p-value = 0.005).Conclusion. Predilation of the infarct-related coronary artery is an independent predictor of death within two years in MI patients who develop CMVO during PCI.

Cardioprotection with levocarnitine intracoronary administration during percutaneous coronary interventions

Currently, the number of percutaneous coronary interventions (PCI) performed in acute and chronic forms of coronary heart disease continues to grow: every year their number reaches at least 5,000,000 worldwide, and more than 200,000 of them in Russia. The main causes of postoperative mortality are perioperative myocardial infarction and acute heart failure due to inadequate protection of the myocardium from ischemia/reperfusion under conditions of balloon expansion and stenting of the affected coronary arteries. The review presents experimental and clinical literature data on the successful use of levocarnitine for cardioprotection in patients with various forms of coronary heart disease and patients with chronic heart failure, both with intravenous administration and as part of a cardioplegic solution during heart surgery. The intracoronary route of administration of levocarnitine solution during PCI in high-risk patients (elderly and senile patients, with multivessel lesions of the coronary bed, difficulties in conducting the intervention) is substantiated. The description of two clinical cases of the use of the technique in elderly patients with acute forms of coronary heart disease with multivessel lesion is given. The postoperative period proceeded without complications with smooth dynamics of biomarkers (troponin I, total creatinephosphokinase, MB-fraction of creatinephosphokinase, lactate dehydrogenase), ischemic ECG shifts were little pronounced. The expected results of the application of the technique are a reduction in intraoperative and postoperative complications of ischemia/ reperfusion and an increase in the effectiveness of the clinical results of PCI in high-risk patients.