Coronary Blood Flow Research Articles

The role of TandemHeartTM combined with ProtekDuoTM as right ventricular support device: A simulation approach

Background and ObjectiveRight ventricular failure increases short-term mortality in the setting of acute myocardial infarction, cardiogenic shock, advanced left-sided heart failure and pulmonary arterial hypertension. Percutaneous and surgically implanted right ventricular assist devices (RVAD) have been investigated in different clinical settings. The use of the ProtekDuo™ is currently a promising approach due to its features such as groin-free approach leading to early mobilisation, easy percutaneous deployment, compatibility with different pumps and oxygenators, and adaptability to different configurations. The aim of this work was to simulate the behaviour of the TandemHeart™ pump applied “in series” and “in parallel“ mode and the combination of TandemHeart™ and ProtekDuo™ cannula as RVAD using CARDIOSIM© software simulator platform. MethodsTo achieve our aim, two new modules have been implemented in the software. The first module simulated the TandemHeart™ pump in RVAD configuration, both as a right atrial-pulmonary arterial and a right ventricular-pulmonary arterial connection, driven by four different rotational speeds. The second module reproduced the behaviour of the ProtekDuo™ cannula plus TandemHeart™. ResultsThe effects induced on the main haemodynamic and energetic variables were analysed for both the right atrial-pulmonary arterial and right ventricular-pulmonary arterial configuration with different pump rotational speed and following Milrinone administration. The TandemHeart™ increased right ventricular end systolic volume by 10 %, larger increases were evident for higher speeds (6000 and 7500 rpm) and connections with 21-Fr inflow and 17-Fr outflow cannula, respectively. Both TandemHeart™ and ProtekDuo™ support increased left ventricular preload. When different RVAD settings were used, Milrinone therapy increased the left ventricular pressure-volume area and decreased the right pressure-volume area slightly. A reduction in oxygen consumption (demand) was observed with reduced right stroke work and pressure volume area and increased oxygen supply (coronary blood flow). ConclusionsThe outcome of our simulations confirms the effective haemodynamic assistance provided by the ProtekDuo™ as observed in the acute clinical setting. A simulation approach based on pressure-volume analysis combined with modified time-varying elastance and lumped-parameter modelling remains a suitable tool for clinical applications.

Prevalence of coronary microvascular disease in myocardial infarction with non-obstructive coronary artery disease

Abstract Background Six percent of patients presenting with acute myocardial infarction (MI) have MI with non-obstructed coronary artery disease (MINOCA). Coronary microvascular disease (CMD) is common in angina with non-obstructive coronary artery disease (ANOCA), but its prevalence and severity in MINOCA is undefined. Purpose Patients with CMD may have elevated risk of myocardial infarction despite no significant stenosis. We tested the hypothesis that patients with MINOCA have more significant burden of CMD than patients with ANOCA. Methods A retrospective case-control study was performed on patients who underwent invasive testing for signs of coronary ischemia and found to have non-obstructive disease (stenoses< 50%). Cases of MI were classified as MINOCA (n=87) and compared to patients with ANOCA (n=552). Patients with spontaneous coronary artery dissection, myocarditis, Takotsubo cardiomyopathy or prior atherothrombotic MI were excluded. Coronary catheterization was performed followed by invasive provocation testing with adenosine and acetylcholine using a Doppler flow wire. CMD was subdivided into endothelium-independent, defined as coronary flow reserve (CFR) < 2.5 with intra-coronary adenosine, and endothelium dependent, defined as < 50% increase in coronary blood flow with acetylcholine. Epicardial vasoconstriction > 90% with typical anginal symptoms was classified as epicardial vasospasm. Results There was no difference in age, sex or traditional coronary risk factors between the MINOCA and ANOCA groups (Table 1). Fifty (57%) of patients with MINOCA had type 2 MI secondary to supply-demand mismatch. Both MINOCA and suspected ANOCA patients had a high prevalence of CMD (71% vs 67%) and endothelium-independent CMD is more prevalent in MINOCA (64.5% vs 50.4%). Although odds of endothelium-dependent CMD were similar, the CFR within this group and CMD overall was worse in MINOCA patients (Figure 1). There was no difference in epicardial spasm. Conclusion Coronary microvascular disease and vasomotor dysfunction are common in patients with MINOCA, with a higher prevalence of endothelium-independent CMD and more severe CMD overall compared to patients with ANOCA. Treatment of CMD in patients with MINOCA may help reduce recurrence and warrants further investigation.

Using anginal symptoms to predict underlying etiology in patients with angina and no obstructive coronary disease (ANOCA)

Abstract Background Patients with angina with no obstructive coronary disease (ANOCA) can present with exertional anginal symptoms or angina at rest. Invasive coronary functional angiography (CFA) is used to diagnose endothelial-dependent and independent coronary microvascular dysfunction (CMD), microvascular spasm, and epicardial spasm. Historically, the type of anginal symptoms has been thought to be suboptimal in predicting the etiology of ANOCA. However, the sensitivity, specificity, predictive value, and correlation of angina type related to CFA abnormalities are unknown. We hypothesize that patients with predominantly exertional angina are more likely to have endothelial-independent and dependent CMD, and patients with angina at rest are more likely to have microvascular or epicardial spasm. Objective To explore sensitivity, specificity, predictive value, and correlation of angina type with underlying etiology of ANOCA as diagnosed by CFA. Methods A prospective registry-based cohort study of consecutive CFA performed in 197 ANOCA patients between 2020 and 2023 using the Doppler-tipped guidewire method. ANOCA was defined as <50% stenosis in any major epicardial artery at time of CFA. Patients were classified based on CFA diagnosis: (1) endothelial-independent CMD (coronary flow reserve [CFR] < 2.5 in response to adenosine), (2) endothelial-dependent CMD (coronary blood flow [CBF] < 50% or no change in vessel diameter in response to 54mcg intracoronary acetylcholine), (3) microvascular (<90% constriction) and epicardial spasm (>90% constriction) to 108 mcg intracoronary acetylcholine. Patients were categorized based on anginal symptoms (exertional angina or at rest angina) documented at cardiologist visit prior to CFA. McNemar’s test and Spearman correlations were performed for both types of angina and the 3 ANOCA underlying diagnoses. Results Among 197 ANOCA patients, the average age was 56.5 ± 11.9 years and 91% were female. Angina at rest had a high specificity (91.3%) but a low sensitivity (25.2%) for the diagnosis of spasm with a PPV of 90.5 (Table 1). There was a significant correlation between angina at rest and spasm (p=0.012). Angina at rest had a similarly intermediate sensitivity and specificity for endothelial independent and dependent CMD. Exertional angina had similar sensitivity, specificity, and a high PPV for endothelial independent and dependent CMD. There was a significant correlation between exertional angina and endothelial dependent CMD (p=0.025). McNemar’s test was statistically significant (p<0.001) for all analyses. Conclusion ANOCA patients with symptoms of angina at rest had a significant correlation with coronary spasms and exertional angina correlates with endothelial-dependent CMD. We demonstrate that angina at rest can be 90% specific for the diagnosis of spasm. Our findings warrant further investigation but suggest that empiric therapy based on angina type is a reasonable first step before invasive testing.

Assessment of structural and functional microvascular dysfunction using microvascular resistance reserve versus invasive exercise stress testing

Abstract Background Coronary microvascular dysfunction is an heterogenous entity with structural dysfunction present in about 60% of cases. Although Coronary Flow Reserve (CFR) is commonly used for diagnosis, this index is nonspecific to the microvasculature. The effectiveness of the recently introduced Microvascular Resistance Reserve (MRR) and absolute microvascular resistance (Rµ) in identifying microvascular dysfunction endotypes remains uncertain. Objective To evaluate whether MRR and hyperemic Rµ assessment are effective in dichotomizing functional and structural microvascular dysfunction as compared with Rµ and coronary blood flow (Q) monitoring during exercise. Methods Rµ and MRR were first assessed using continuous thermodilution with saline infusion at 10 mL/min (rest) and 20 mL/min (hyperemia) in the left anterior descending artery of consecutive patients with Angina and Non-Obstructive Coronary Arteries. An MRR<2.3 was considered the cutoff for coronary microvascular dysfunction. Q and Rµ were assessed during subsequent stress testing with an incremental workload of 30 watts every two minutes, using a dedicated supine cycling ergometer. Results Coronary microvascular dysfunction was observed in 36.6% of the participants with suspected Angina with Non-Obstructive Coronary Artery disease (11 out of 30). Median hyperemic Rµ was 561 [381; 684] Wood Unit (WU) among patients with microvascular dysfunction. Participants with structural dysfunction (MRR<2.3 and hyperemic Rµ>561WU), had a resting Rµ similar to participants without CMD (1286±410 versus 1231±291 WU) but exhibited both impaired reduction of Rµ (139 [64; 288] versus 191 [74; 317] WU per 30 watts) and increase of Q during exercise (20 [1; 37.5] versus 52 [15.5; 92.0] mL/min per 30 watts). Patients with functional dysfunction (MRR<2.3 and hyperemic Rµ<561WU) had lower resting Rµ (672±219 WU) and higher resting Q (152±39 versus 84±24 mL/min) with a similar increase of Q during exercise (55 [30.5; 103.0] than participants without CMD. Mean N-terminal pro B-type natriuretic peptide level was higher in the structural group (425±563 ng/L) as compared to the functional and normal groups (86±10 ng/L and 50±80 ng/L respectively). Conclusion The use of MRR combined to hyperemic Rµ, derived from continuous intracoronary thermodilution, enables the assessment of coronary microvascular dysfunction with an accurate distinction between functional and structural endotypes.Microvascular hemodynamic adaptationNTpBNP level

Evaluation of coronary microvascular dysfunction and vasospasm in patients with angina and non-obstructive coronary artery disease

Abstract Background Angina in the absence of obstructive coronary artery disease (CAD) is a growing cause of morbidity and mortality, exceeding the economic burden of CAD. Roughly 50-70% of patients undergoing invasive angiography for anginal symptoms have non-obstructive CAD. Within this category, there are distinct sub-populations including patients with angina without evidence of ischemia on prior stress testing (ANOCA), evidence of ischemia on stress testing (INOCA), or history of obstructive CAD with prior revascularization (ANOCA-HxCAD). Coronary microvascular dysfunction (CMD) and/or epicardial vasospasm are common causes of angina in the absence of epicardial CAD despite optimal medical therapy. Differences between these groups, in terms of risk factors and diagnoses remain relatively unknown. Purpose To compare clinical characteristics, symptoms, and diagnoses between patients with ANOCA, INOCA, and ANOCA-HxCAD. Methods In a prospective registry-based cohort study of 306 patients without obstructive CAD (<50% stenosis in epicardial artery) undergoing coronary functional angiography (CFA), we assessed differences in clinical characteristics, symptoms, and CFA diagnoses: (1) endothelial-independent CMD (coronary flow reserve [CFR] <2.5) to adenosine testing, (2) endothelial-dependent CMD (coronary blood flow [CBF]<50% or no change in vessel diameter to 54 mcg intracoronary acetylcholine [ACH]), (3) epicardial vasospasm to 108 mcg intracoronary ACH in 3 groups of patients (ANOCA, INOCA, and ANOCA-HxCAD). Results Among the 306 patients undergoing CFA, 89% were female with a median age of 58 years (49, 67). Patients with ANOCA-HxCAD had a significantly higher prevalence of hypertension, diabetes, heart failure with preserved ejection fraction, and experienced worse dyspnea on exertion as measured by University of San Diego Shortness of Breath (UCSD SOB) in comparison to ANOCA or INOCA patients. However, there were no differences between the groups in terms of anginal severity, functional capacity, or quality of life. In terms of CFA diagnoses, vasospasm was more prevalent in ANOCA-HxCAD (p<0.001) and CMD was more prevalent in ANOCA and INOCA patients (p=0.034) (Table 1). Conclusions Despite differences in clinical characteristics, patients without obstructive CAD have similar anginal severity, functional capacity, and quality of life regardless of evidence of ischemia on prior stress imaging or history of revascularization. There are differences in CFA diagnoses with higher prevalence of CMD in ANOCA and INOCA patients and higher prevalence of vasospasm in ANOCA-HxCAD patients. Determining the underlying diagnoses changes clinical management; therefore, CFA should be considered in all patients without obstructive CAD.

Differences in clinical characteristics, angina, and quality of life among patients with microvascular vs vasospastic angina and no obstructive coronary artery disease (ANOCA)

Abstract Background In patients with angina and no obstructive coronary disease (ANOCA), the underlying pathophysiology includes microvascular angina (endothelial-dependent and independent coronary microvascular dysfunction (CMD)) and vasospastic angina (microvascular spasm and epicardial spasm) diagnosed with invasive coronary functional angiography (CFA). However, whether there are differences in demographics, clinical characteristics, and outcomes by underlying diagnosis is unknown. We hypothesize that microvascular angina patients will be older and have more cardiovascular risk factors and worse outcomes than the vasospastic angina group. Objective To explore the differences in demographics, risk factors, and outcomes in ANOCA patients with microvascular and vasospastic angina. Methods A prospective registry-based cohort study of consecutive CFA was performed in 156 ANOCA patients between 2020 and 2023 using the Doppler-tipped guide wire method. Patients were classified into microvascular angina, vasospastic angina, and mixed disease. Microvascular angina was defined as endothelial-independent CMD (coronary flow reserve [CFR] < 2.5 in response to adenosine) and/or endothelial-independent CMD (coronary blood flow [CBF] < 50% or no change in vessel diameter in response to 54 mcg intracoronary acetylcholine). Vasospastic angina as microvascular (<90% constriction) and epicardial spasm (>90% constriction) to 108 mcg intracoronary acetylcholine. The mixed disease group included microvascular and vasospastic angina. Validated questionnaires evaluated angina (SAQ-7), functional capacity (DASI), dyspnea severity (UCSD SOB), and perceived stress (PSS) were obtained from patients at office visits prior to undergoing CFA. Results Among 156 ANOCA patients, 114 had microvascular angina, 10 had vasospastic angina, and 32 had mixed disease. The average age was 58.5 (SD 11.2) years. Demographics and prevalence of risk factors, such as hypertension, hyperlipidemia, or diabetes, showed no significant differences among the microvascular, vasospastic, or mixed disease groups. The prevalence of heart failure with preserved ejection fraction (HFpEF) was high across the groups, and outcomes did not differ significantly among them. The SAQ-7 score average ranged from 16.9 to 40.3, consistent with moderate to severe angina, and the DASI score ranged from 32.2 to 34.9, consistent with moderate functional capacity. Dyspnea severity ranged from 30 to 41, consistent with low to moderate severity, and perceived stress ranged from 11.5 to 13, consistent with low to moderate stress among all participants. Conclusion In patients with ANOCA undergoing invasive CFA, demographics, cardiovascular risk factors, and outcomes were similar regardless of underlying diagnosis. We demonstrate a high prevalence of risk factors and HFpEF and evidence of moderate to severe symptoms and functional capacity in ANOCA patients across all diagnoses.Abbreviation explanation for table 1

Correlation between LDL/HDL-cholesterol ratio and long term prognosis after acute coronary syndrome and severity of coronary artery disease

Abstract Introduction Dyslipidaemia is an important correctable risk factor for coronary artery disease (CAD). Many studies have confirmed that the lower the low-density lipoprotein cholesterol (LDL-C) levels are, the lower is the CAD morbidity and mortality rates (1). However, many patients who achieved low levels of LDL-C still experience a major adverse cardiovascular event (MACE) because of the other residual risk factors. Therefore, there is a constant need for better stratification of patients who are at higher risk for novel MACE following their first acute coronary syndrome (ACS). Evidence increasingly suggests that the ratio of LDL-C/HDL-C might be a new and better marker of cardiovascular disease, as it simultaneously evaluates the levels of both LDL-C and HDL-C (2). Purpose The aim of this study was to investigate the prediction value of LDL-C/HDL-C ratio for long term prognosis after ACS as well as its correlation with CAD severity. Methods We included patients hospitalized at out centre with ACS from January 2017 to January 2024. Demographic data, data on LDL-C and HDL-C levels on admission and calculated Syntax score were used. Syntax score is a comprehensive angiographic scoring system which determines complexity by using coronary anatomy and lesion characteristics (3). Follow-up data were collected either by clinical follow-up visits or by telephone interviews. The MACE was defined as the composite of cardiovascular death, acute coronary syndrome and need for elective or urgent percutaneous or surgical revascularization. Results This registry-based study included 2471 patients with ACS, median age of 64 (interquartile range 56-73) years, 31% female. Total of 1099 patients (44%) had non-ST elevation ACS and 1372 (54%) had ST elevation myocardial infarction (STEMI). Median Syntax score was 13 (IQR 7-20.5), with 1494 (61%) patients having low Syntax score (≤16), 508 (21%) patients medium (16-22), and 448 (18%) high score (>22), respectively. Median follow up was 17 (3-27) months. LDL-C/HDL-C ratio correlated significantly with cardiovascular death, with weak coefficient (2.94 vs. 2.54 p<0.001; rho=0.102, p<.0001), however did not correlate with MACE (2.88 vs. 2.92, p=0.188, rho=0.06, p=0.77). This remained identical when tested for patients with STEMI and non-STE ACS. In addition, LDL-C/HDL-C ratio did not correlate with CAD severity as assessed with Syntax score (low 2.92 vs. medium 2.83 vs. high 2.86, p=0.597; rho=0.4, p=0.09). Conclusion Our data suggest that LDL-C/HDL-C ratio cannot be used as a relevant predictor of post-ACS long-term MACE or cardiovascular death, nor it can be correlated with CAD severity. Further studies are needed to establish the real value of LDL-C/HDL-C ratio as a post-ACS predictor.

Residual ischemia location after STEMI by CMR and association with non-culprit coronary artery disease

Abstract Background Many ST-segment elevation myocardial infarction (STEMI) patients present with non-culprit coronary artery disease. In cases with incomplete revascularization, stress cardiac magnetic resonance (sCMR) could help detect and locate residual ischemia. Purpose We aim to evaluate the usefulness of sCMR to detect and locate residual ischemia in STEMI patients after discharge and correlate the findings with angiographical non-culprit coronary lesions, if any. Methods Reperfused, stable STEMI patients submitted to undergo sCMR within the first year after STEMI were included in the cohort. Index coronary angiography was revised, culprit and non-culprit coronary artery disease were registered, and significant stenoses were defined as ≥50% by visual assessment. Residual ischemia on sCMR (by first-pass vasodilator stress perfusion) was analysed and categorized as either absent or present in anterior, lateral, and inferior territories. Unrevascularized non-culprit coronary lesions were correlated with territories with residual ischemia on sCMR and lesions in subsequent coronary angiography. A p-value <0.05 was considered statistically significant. Results The study group was made up of 234 patients who underwent sCMR within the first year after STEMI (mean age 58.95±11.85 years, 78.2% male, 48.7% anterior infarction). Residual ischemia by sCMR was noted in 63 (26.9%) patients. In the 95 patients (40.6%) who underwent complete revascularization during index admission, residual ischemia by sCMR was seldom detected (n=14, 14.7%) and distributed on anterior (n=8), lateral (n=3) and inferior (n=4) territories. More than half of the cohort (n=139, 59.4%) depicted unrevascularized non-culprit coronary lesions, and residual ischemia was detected in 49 (35.3%) patients. Non-culprit lesions on left anterior descendent artery (n=62) associated with ischemia in 38.7% of cases (n=24), most commonly in the anterior territory (n=17, 70.8%). Similar findings were noted for lesions on circumflex artery (n=66), which depicted residual ischemia in 34.8% (n=23) of cases and most frequently in the lateral territory (n=13, 56.5%); and lesions in right coronary artery (n=45), which depicted residual ischemia in 42.2% (n=19) of cases, most commonly in the inferior territory (n=13, 68.4%). Significant coronary stenosis was found in most patients who underwent subsequent coronary angiography after residual ischemia detection (41 out of 47, 87.2%). Conclusions One third of STEMI patients with incomplete revascularization and non-culprit coronary artery disease depict residual ischemia on sCMR, the location of which generally correlates with index coronary anatomy and significant stenosis in subsequent coronary angiography. Residual ischemia is infrequent in patients with complete revascularization, but not inexistent. sCMR should be considered in selected STEMI patients according to coronary anatomy and/or symptoms to guide therapy.Stress CMR and ischemia location

CT-perfusion quantitation of cardiac infarct size - a novel technique

Abstract Introduction Cardiac infarct size is associated with cardiac prognosis after AMI. Cardiac CT is able to delineate both coronary anatomy and myocardial pefusion. Thus far, CT identification of infarction has been qualitative. We describe a novel technique for quantitation of myocardial infarct size in CT-perfusion imaging. Methods Patient Population comprised 51 patients that were previously clinically diagnosed with myocardial infarction on the basis of clinical presentation, ECG findings and elevated cardiac enzymes. CTP Imaging All patients had undergone dynamic rest, vasodilator-stress, rest, delayed enhancement CT perfusion imaging performed on a dual-source, third generation scanner (FORCE, Siemens Healthcare). Image Analysis 2 trained investigators independently quantified the infarct volume in 51 patient studies using Siemens SmartSimulator software. Mean ± SD HU were taken from a 1cm² circular ROI of normal myocardium used in a thresholding method. The epicardium and endocardium of infarcted areas were manually contoured from apex to base. Volumetric measurements were obtained of the infarct and total myocardium. Interpolation of contours for segmentation objects was performed. Subtraction of left ventricle cavity from total left ventricle allowed volumetric measurements of total left ventricular myocardium. ROIs of the infarct were estimated using SDs above mean HU of normal myocardium (0.5, 1, 1.5 and 2 SDs) in delayed imaging. Selection of optimal threshold HU was based on visual assessment that best mapped the hyperenhanced infarct area. This allowed volumetric asessment of infarct and total myocardium. Inter-investigator variability was evaluated with Bland-Altman and Intra-Class Correlation Coefficient (ICC). Results Patient characteristics are follow: Age 60.20±11.35 years, 41(89%)male, BMI 25.41±4.17kg/m², Hypertension 23(50%), diabetes 10(22%), hyperlipidemia 40(87%), smoking 7(15%), family history of premature CAD 4(8.7%), previous PCI 45(97.8%). In 51 patients, 23(41%), 24 (46%) & 5(10%) of the infarctions were quantitated as being medium-sized (10%-20%), large (20% -30%) and very large (>30%). Thirty-seven (70%), 6 (11%) & 10(19%) involved the LAD, LCx and RCA territories respectively. 49 (94%) of infarctions were transmural. Identical thresholding was selected by both investigators for each SD above mean (mean 1.42; SD 0.46). 93% of the total cases were within a set threshold of 1 to 2 SDs above the mean HU for both. Interclass correlation coefficient was 0.95, CI range 0.90 – 0.97. Bland-Altman analysis did not demonstrate systemic variations or proportional bias from the plot. Conclusion The study suggests that a method of quantifying cardiac infarct size using a threshold technique and delayed hyperenhancement images with dynamic perfusion imaging is clinically feasible and consistent.Rest-Stress-Delayed Enhancement infarct

Association between completeness of revascularization and cardiovascular outcomes in patients with diabetes and non-ST elevation myocardial infarction: a population-based registry analysis

Abstract Introduction Approximately one-third of the patients presenting with non-ST elevation myocardial infarction (NSTEMI) have diabetes. From these, two-thirds have multivessel coronary disease. The impact of completeness of revascularization in this population remains unclear. Purpose To evaluate the contemporary patterns of coronary revascularization among patients with diabetes and NSTEMI, and the clinical outcomes stratified by anatomic completeness of revascularization. Methods All patients with diabetes and multivessel disease admitted for NSTEMI between April 2009 and March 2020 in Ontario, Canada were included. Patients with previous coronary artery bypass graft surgery (CABG) at any time, percutaneous coronary intervention (PCI) in the previous 90 days, or shock were excluded. Patients were classified in four groups, from the most to the least complete revascularization strategy: CABG, complete revascularization with PCI, incomplete revascularization with PCI, or no revascularization. Outcomes included all-cause death and the composite of all-cause death, myocardial infarction, and stroke. Multivariable Cox regression was used to account for confounding (demographics, comorbidities, left ventricular function, coronary anatomy, laboratory tests, and diabetes treatment). Results We included 14,511 patients (mean age: 68.7±11.5y; 69.6% males). A total of 4,525 (31.2%) patients were treated with CABG, 3,008 (20.7%) with complete PCI, 3,624 (25.0%) with incomplete PCI and 3,354 (23.1%) were not revascularized. Patients with more complex coronary disease were more frequently treated with CABG, while PCI was more common in those with less complex disease (p<0.001; Fig 1). The mean number of grafts in the CABG group was 3.4±1.0. The mean number of stents in the complete and incomplete PCI groups was 2.4±1.3 and 1.7±0.9, respectively. Adjusted 5-y risks of all-cause death following CABG, complete PCI, incomplete PCI and no revascularization were, respectively, 25.9%, 29.8%, 32.2%, and 39.4%. Over a median follow-up of 5.8ys, CABG was associated with reduced all-cause death compared with complete PCI (HR 0.82; 95%CI 0.75 - 0.90), incomplete PCI (HR 0.73; 95%CI 0.67 - 0.80), or no revascularization (HR 0.54; 95%CI 0.50 - 0.58); p<0.001 for all (Fig 2). Adjusted 5-y risks of the composite endpoint following CABG, complete PCI, incomplete PCI and no revascularization were, respectively, 34.0%, 41.5%, 44.6%, and 52.9%. CABG was associated with reduced rates of the composite endpoint compared with complete PCI (HR 0.75; 95%CI 0.69 - 0.81), incomplete PCI (HR 0.67; 95%CI 0.62 - 0.72), or no revascularization (HR 0.50; 95%CI 0.47 - 0.54); p<0.001 for all. Conclusion In this contemporary real-world cohort study, almost a quarter of the patients with diabetes and NSTEMI did not receive any revascularization procedure. Cardiovascular outcomes were incrementally improved with CABG or complete revascularization with PCI, compared to no revascularization.Figure 1Figure 2

Comparative characteristics and invasive management in patients with non-ST elevation acute coronary syndromes in two high-volume hospitals from Romania and Germany

Abstract Introduction Cardiovascular disease (CVD) carries the highest mortality burden across Europe, acute coronary syndromes (ACS) being responsible for most CVD-related deaths. However, significant regional differences in ACS management have been reported. Purpose To describe the characteristics and management of patients with higher-risk non-ST elevation ACS (NSTE-ACS) in 2 high-volume hospitals from 2 European countries with different prevalence of CVD and different income (Germany – GER and Romania – RO). Methods All consecutive invasively managed high and very-high risk NSTE-ACS patients admitted in 2022 in two high-volume hospitals from GER and RO were identified. Patient clinical profiles, coronary anatomy, revascularization strategies, and in-hospital outcomes were compared. Results were adjusted for age and gender. Results 707 patients (345 GER, 66.7% male; 362 RO, 71.5% male; p>0.05) were included. RO patients were younger (65.5 vs. 70.1 years), with higher rates of hypertension (88.7% vs. 82.0%), dyslipidemia (95.6% vs. 81.7%), diabetes (46.1% vs. 34.5%), and active smoking (37.3% vs. 23.5%) (all p<0.05); whereas GER patients had higher rates of atrial fibrillation (36.2% vs. 23.2%), chronic respiratory disease (24.6% vs. 10.5%), sleep apnoea (9.0% vs. 1.4%), thyroid disorders (24.1% vs. 6.4%), and prior revascularization by percutaneous coronary interventions (PCI) (36.5% vs. 20.2%) or coronary artery bypass grafting (CABG) (15.7% vs. 3.0%) (all p<0.05). Mean left ventricular ejection fraction (LVEF) was lower in the RO cohort (43.4% vs. 48%, p<0.001). Rates of myocardial infarction diagnosed by high-sensitivity troponin I assays (88.7% GER, 87.6% RO), and median diagnosis-to-cathlab intervals (12.8 hours GER, 15.5 hours RO) were similar (all p>0.05). In the obstructive coronary artery disease (CAD) group (80.3% GER, 84.3% RO), no differences were found in multivessel disease rates (67.1% GER, 69.8% RO) or mean SYNTAX score (18.6 GER, 16.9 RO) (all p>0.05). For type 1 NSTE-ACS (67% GER vs. 79% RO, p<0.001), PCI represented the main revascularization method (88.3% GER vs. 78.3% RO, p<0.05). Excluding patients with prior CABG undergoing PCI, complete revascularization (residual SYNTAX score ≤8), was reported in 77.1% GER and 84.4% RO of the PCI cases (p>0.05). Intravascular imaging was used in 28.4% of PCIs in GER, and in none in RO. In-hospital mortality (7.0% GER, 6.8% RO), and rates of major adverse cardiovascular events, defined as a composite of death, myocardial infarction, and stroke (8.1% GER, 9.1% RO), were similar (all p>0.05). Conclusions Higher-risk NSTE-ACS patient profiles mirror overall country CVD risk patterns. Compared to Germany, patients in Romania are younger, with a higher CVD risk factor burden, lower LVEF, underdiagnosis of major non-CVD comorbidities, and delayed CAD diagnosis. Despite similar guideline-directed management and in-hospital outcomes in both centres, these aspects may influence the long-term prognosis.

Changes of angiography-derived coronary microcirculatory resistance before and after drug-coated balloon treatment

Abstract Background Drug coated balloon (DCB) is a treatment option for a lesion in a small coronary artery. The effect of DCB is proven in mechanistic and clinical outcomes, however, its influence on the microvascular function has not been elucidated. In addition, because there are differences in the types of drugs and coatings among different DCBs, their effects on microvascular function may vary. Angiography-derived microcirculatory resistance (AMR) is a novel angiographic parameter calculated from angiography-derived quantitative flow ratio and flow velocity estimation. AMR is reported to have a good correlation with the wire-based index of microvascular resistance. Purpose To investigate the AMR in coronary vessels treated with sirolimus or paclitaxel coated balloon. Methods This is a subanalysis of the TRANSFORM I (The TReAtmeNt of Small Coronary Vessels: MagicTouch Sirolimus Coated Balloon) trial. TRANSFORM I is a prospective, randomized, multi-center, open-label noninferiority trial conducted in Europe that enrolled 121 patients (126 vessels) with stabilized acute coronary syndrome or chronic coronary syndrome who had at least one de novo coronary artery lesion in a small coronary vessel. Patients were randomized 1:1 to treatment with the sirolimus coated balloon (SCB) or paclitaxel coated balloon (PCB). The SCB is coated with phospholipid encapsulated sirolimus nanocarrier, whereas the PCB is coated with crystalline paclitaxel. In this subanalysis, angiography at baseline and post-procedure were analyzed to calculate the AMR by an imaging core lab. Coronary microvascular dysfunction (CMD) was defined as AMR≧2.5 mmHg*s/cm. Results In the total of 126 vessels, 63 were included in each of the SCB and PCB group. Angiography both at baseline and post-procedure were analyzable for AMR in 59 vessels in SCB and in 59 vessels in PCB group. In SCB group, the median AMR increased significantly after procedure (baseline; 2.03 [1.58-2.42], post-procedure;2.21 [1.78-2.53], p=0.03). However, the proportion of vessels with CMD did not significantly change (baseline; 22.0% [13/59], post-procedure; 32.2% [18/59], p=0.19) (Figure). In the PCB group, the median AMR increased significantly after procedure (baseline; 2.22 [1.66-2.53], post-procedure;2.45 [1.93-2.96], p=0.003). Furthermore, the proportion of vessels with CMD significantly increased (baseline; 27.1% [16/59], post-procedure; 47.5% [28/59], p=0.046) (Figure). The AMR measurement was not significantly different between SCB and PCB at baseline (p=0.53), but it was significantly higher in PCB than in SCB at post-procedure (p=0.04). Conclusion After DCB treatment, AMR significantly increased in both arms. The proportion of the vessel with CMD after procedure did not significantly change in the SCB group but increased in the PCB group. The potential mechanism of increase in AMR after DCB treatment (e.g. embolization of small crystals) may warrant further investigation.Proportion of AMR≥2.5

Impact of chronic kidney disease on patients with Myocardial Infarction with Non Obstructive Coronary Arteries (MINOCA)

Abstract Background Chronic kidney disease (CKD) in patients with myocardial infarction (MI) is associated with more advanced disease, a higher risk of complications and poorer prognosis, as well as increased mortality. The aim of this study is to assess the impact of CKD in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) and its influence on the prognosis of these patients. Methods it was an observational, prospective and analytic study. We analyzed all consecutive patients with MI who underwent coronary angiography admitted to our Hospital between 2016 and 2023; MINOCA patients were classified following the 2023 ESC Guidelines definition. The patients were divided into two groups depending on whether they had CKD or not. Median follow-up was 43 months [20-71]. Results we included 136 patients with MINOCA, of whom 11 (8.1%) had CKD. Patients with impaired kidney function were older and mostly male. They also exhibited a higher prevalence of classic cardiovascular risk factors such as hypertension, diabetes, or dyslipidemia. However, there were fewer smokers in this group. We did not find significant differences in coronary artery anatomy (smooth or small plaques) between both groups. Additionally, the majority of patients in both groups had preserved left ventricular function. Despite that, patients with CKD typically had ST segment elevation in the ECG and higher myocardial injury biomarkers’ levels as well as NT-proBNP. During hospitalization, patients without renal dysfunction had more complications (11.2% vs 0%, p=0.062) such as inotropic requirements, stroke or cardiogenic shock, but overall there were very few. In terms of treatment, it was fairly similar in both groups, although patients with kidney disease received diuretics significantly more often. Throughout the follow up, there were no significant differences in MACE (major adverse cardiovascular events) between death (27.3% vs 7.4%, p=0.06), readmission (10% vs 10.8%, p=1) or MI (0% vs 3.4%, p=1), but patients with CKD suffered more frequently from stroke (40% vs 4.2%, p<0.01). Conclusions 1) Patients with MINOCA and CKD are typically older and predominantly male with a high prevalence of cardiovascular comorbidities (hypertension, diabetes, dyslipidaemia). 2) The severity of MI appears to be slightly higher in this group, as evidenced by more ST-segment elevation upon admission and higher hs Troponine T levels. However, they experience fewer cardiovascular complications and maintain normal left ventricular function. 3) Although we found no significant differences in major adverse cardiovascular events (MACE), patients with CKD were more likely to suffer from stroke.Table 1Table 1

Inhibition of microRNA-181c-5p rescues diabetes-impaired angiogenesis through activation of key mediators of angiogenesis, cell survival and novel genes, elmo3 and trib1

Abstract Introduction Patients with diabetes have impaired angiogenesis and poor coronary collateral vessel formation post-myocardial infarction (MI), which associates with higher mortality. There is a significant unmet clinical need for new agents that stimulate angiogenesis in response to ischaemia in diabetes. We have identified that miR-181c-5p has anti-angiogenic properties, but it’s role in diabetes remains unknown. Aim To elucidate the role of miR-181c-5p in diabetes-impaired angiogenesis. Methods Human coronary artery endothelial cells were transfected with a miR-181c-5p inhibitor (antimiR-181c-5p) or negative control (antimiR-Neg), exposed to glucose (5–25mM, 48h) then underwent Matrigel tubulogenesis assay or Boyden Chamber migration assay. Levels of proteins important for angiogenesis (e.g., VEGFA, p-ERK2, p-eNOS) were determined by Western Blot. Whole transcriptome sequencing was performed in vitro to identify novel gene targets of miR-181c-5p. In vivo, diabetic mice underwent hindlimb ischaemia or wound healing surgery and were injected with antimiR-181c-5p or antimiR-Neg. Tissues were extracted early (day 3) and late (days 10-14) post-surgery. Hindlimb blood-flow reperfusion was measured by Laser Doppler imaging. Hindlimb apoptosis was assessed by TUNEL and necrotic area was assessed by H&E. Wound area was calculated daily. Neovascularisation was assessed by CD31 (capillaries) and α-actin (arterioles) immunostaining. Results Inhibition of miR-181c-5p increased endothelial tubule number (+28%, P<0.01), tubule length (+12%, P<0.01) and cell migration (+67%, P<0.05). This associated with increased VEGFA (+21%, P<0.05) and p-ERK2 (+32%, P<0.05). Whole transcriptome and pathway analysis revealed changes to angiogenesis pathways and identified a first-time involvement of genes Elmo3 and Trib1 in the pro-angiogenic action of antimiR-181c-5p in diabetes. In vivo, inhibition of miR-181c-5p increased blood flow reperfusion to ischaemic hindlimbs (+30%, P<0.001) and arteriolar density (+45%, P<0.05) in diabetic mice. Mechanistically, this was associated with early changes to mediators of angiogenesis, Erk2 mRNA (+35%, P<0.05), p-ERK2 (+35%, P<0.05) and Trib1 mRNA (+80%, P<0.05); cell survival, Bcl-2 mRNA (+44%, P<0.05); and late apoptotic clearance, Elmo3 mRNA (+57%, P<0.001). Furthermore, this was also associated with an increase in late stage hindlimb apoptosis (+94%, P<0.05) and reduced necrotic area (-90%, P<0.05) in diabetic mice. Inhibition of miR-181c-5p increased diabetic wound closure (+22%, P<0.01), wound capillaries (+61%, P<0.05), Bcl-2 mRNA (+52%, P<0.05) and Elmo3 mRNA (+50%, P<0.05) in diabetic wounds. Conclusions Inhibition of miR-181c-5p rescues diabetes-impaired angiogenesis by activation of angiogenesis and cell survival mediators, and through novel genes, Trib1 and Elmo3. Our findings have implications for a novel miRNA-based strategy that improves myocardial neovascularisation and the prognosis of diabetic patients post-MI.

Long-term clinical-pathologic results of enzyme replacement therapy in pre-hypertrophic fabry disease cardiomyopathy

Abstract Background Limited ability of ERT in removing Gb-3 from cardiomyocytes is recognized for advanced FDCM. Pre-hypertrophic FDCM is believed to be cured or stabilized by ERT. However, no pathologic confirmation is available. We report here in the long-term clinical-pathologic impact of ERT on pre-hypertrophic FDCM. Purpose Long-term clinical-pathologic impact of ERT on pre-hypertrophic FDCM. Methods Fifteen Fabry patients with LVMWT ≤ 10.5 mm at CMR required EMB because of angina and/or ventricular arrhythmias. EMB showed coronary small vessel disease in angina cohort and vacuoles in smooth muscle cells and cardiomyocytes around 20% of cell surface containing myelin bodies at electron microscopy. Patients received α-agalsidase in 8 and β-agalsidase in 7 cases. Both groups referred symptoms improvement except 2 patients treated with α- and β-agalsidase respectively. After ERT administration ranging from 4 and 20 years all patients had control CMR and LVEMB because of persistence of symptoms or patients enquiry on disease resolution. Results In 13 asymptomatic FDCM patients, LVMWT and LV-mass, cardiomyocyte diameter, vacuole surface/cell surface ratio and vessels remained unchanged or minimally increased (LV-mass augmented by < 2%) even after 20 years observation and storage material was still present at electron microscopy. In 2 symptomatic patients, FDCM progressed with larger and more engulfed by Gb-3 myocytes being associated to myocardial virus-negative lymphocytic inflammation. Conclusions ERT stabilizes storage deposits and myocyte dimensions in 87% of patients with pre-hypertrophic FDCM. Gb-3 is never completely removed even after long-term treatment. Immune-mediated myocardial inflammation can overlap limiting ERT activity. Figure Legend Patient 11 (24-year-old man) with genetic and biopsy-proven diagnosis of FDCM before and after 20 years ERT. CineMR (A,B) and LGE (C,D) images, performed at baseline (A,C) and 20 years after ERT (B,D) show normal LV wall thickness (8mm and 10 mm) and absence of fibrotic areas. Panel E and F represent semithin section of Epon-embedded EMB samples, stained with basic fuchsin, showing mildly hypertrophied cardiomyocytes containing storage material that result unmodified after long-term ERT administration. Panel G and H are ultrastructural evidence of storage material to consist of myelin bodies (panel G) that remain unchanged after ERT (Panel H).

Cycling coupled to intra-coronary thermodilution to evaluate angina with non-obstructive coronary artery disease

Abstract BACKGOUND Patients with Angina and Non-Obstructive Coronary Artery disease (ANOCA) face misdiagnosis and inadequate treatment. A new continuous thermodilution method enables assessment of absolute coronary blood flow (Q) and microvascular resistance (Rµ). The effectiveness of saline-induced hyperemia in capturing exercise-induced coronary flow regulation remains unknown. OBJECTIVE To describe Q and Rµ adaptation during exercise and to explore the correlation between Coronary Flow Reserve (CFR) derived from saline and exercise-induced hyperemia, as well as Microvascular Resistance Reserve (MRR). Methods Q, Rµ, CFR and MRR were first assessed using continuous thermodilution with saline infusion at 10 mL/min (rest) and 20 mL/min (hyperemia) in the left anterior descending artery, followed by subsequent stress testing using a dedicated supine cycling ergometer. The microvascular parameters were assessed during incremental workload of 30 watts every two minutes. CFRsaline<2.5 was considered the cutoff for coronary microvascular dysfunction. A minimal sample size of 29 participants was required to detect a hypothesized Spearman coefficient correlation r=0.5 between CFRsaline and CFRexercise using a 80% power and 5% significance level test. Results Coronary microvascular dysfunction was observed in 53.3% of the participants with suspected ANOCA (16 out of 30). During cycling, participants with coronary microvascular dysfunction had a lower reduction in Rµ (-109 [32; 286] versus -202 [102; 379] WU per 30 watts, p<0.01) and a lower ability to increase coronary flow (7 [30.5; 103.0] versus 21 [5.8; 45.0] mL/min per 30 watts, p=0.01) compared with those without coronary microvascular dysfunction. In the overall population, average CFRsaline and CFRexercise were 2.70±0.90 and 2.85±1.54, respectively (p=0.46) with an agreement classification of 83.3%. A good correlation between the two techniques was observed for both CFR (Spearman coefficient r=0.73, p<0.0001) and MRR (r=0.76, p<0.0001). Monitoring of CFR and Rµ during exercise unmasked functional coronary microvascular dysfunction priorly labeled as normal by saline induced hyperemia in 13.3% of the study population. These individuals had a moderate and late decrease of Rµ during the early stages of exercise, with a plateau up to 75% of their theoretical workload. Conclusion Participants with coronary microvascular dysfunction demonstrated compromised CFR due to impaired reduction of Rµ during physical workload. Saline-induced hyperemia provided a valid surrogate for exercise physiology independently of the absolute level of CFR and MRR, although exercise provided more granularity to evaluate hemodynamic adaptation among participants with functional dysfunction.

Assessment of cardiopulmonary exercise capacity in suspected heart failure with preserved ejection fraction: impact of coronary flow velocity reserve and body fat

Abstract Background and objectives Heart failure with preserved ejection fraction (HFpEF) has various pathophysiology including coronary microvascular dysfunction (CMD), obesity, and frailty. In the present study, we aimed to assess the cardiopulmonary exercise capacity according to coronary microvascular function and body composition in patients with suspected HFpEF. Methods Patients with chest symptoms with non-obstructive coronary artery disease (<50% stenosis) and preserved left ventricle (LV) ejection fraction (≥50%) were enrolled. LV end-diastolic pressure was measured during coronary angiography. All patients underwent body composition analysis, adenosine stress echocardiography with the evaluation of coronary blood flow, and cardiopulmonary exercise test assessing maximal oxygen consumption (VO2max). Coronary flow velocity reserve (CFvR) was defined as the ratio of peak to baseline mean diastolic velocity of coronary blood flow. Association between VO2max and CFvR as well as body composition was assessed. Results Of the 106 patients (mean age 63.5), 54 (50.9%) were women, 52.4% had hypertension, and 28.6% had diabetes. Baseline LV end-diastolic pressure was 15.3 ± 5.5 mmHg. Median Heart Failure Association-PEFF score was 3, while medial e’ velocity was 6.7 ± 2.0 cm/s and E/e’ was 9.6 (7.6 – 12.0). Mean diastolic velocity of coronary blood flow was 0.17 [interquartile range (IQR) 0.13 – 0.23] m/sec at baseline, while it increased to 0.46 [IQR 0.38 – 0.57] m/sec at peak, resulting in CFvR of 2.75 [IQR 2.10 – 3.67]. Eighteen (17.1%) patients had CMD (CFvR <2.0). VO2max was 23.1 ± 5.4 mL/kg/min with lower value in women (21.7 ± 4.8 vs. 24.5 ± 5.6 mL/kg/min, p = 0.007). CFvR was directly related to VO2max (r = 0.350, p <0.001). In body composition, skeletal muscle mass index, percent body fat, and visceral fat area were associated with VO2max. In multivariable analysis, age, visceral fat area or percent body fat, and CFvR were linearly correlated with VO2max, and estimated VO2max was well correlated with measured VO2max. Conclusions Cardiopulmonary exercise capacity represented by VO2max was correlated with CFvR and body composition including skeletal muscle mass index, percent body fat, and visceral fat area in patients with suspected HFpEF. VO2max could be estimated by CFvR and fat component in the body.

To evaluate coronary microvascular obstruction by myocardial contrast echocardiography and its influence on prognosis in patients with ST-segment elevation myocardial infarction

Abstract Background The goal of primary PCI (pPCI) is not only to restore epicardial coronary blood flow quickly but also to provide continuous myocardial tissue level reperfusion through coronary microcirculation. However, the incidence of coronary microvascular obstruction (MVO) after pPCI is as high as 50%-60%, which is closely related to the occurrence of heart failure and increased mortality of patients. Myocardial contrast echocardiography (MCE) is a new noninvasive technique for real-time observation of myocardial microcirculation perfusion in a specific imaging mode. At present, there are few studies on the application of MCE in the evaluation of coronary MVO in STEMI patients in China. Purpose To evaluate coronary MVO by MCE and its influencing factors and prognosis value after pPCI in patients with STEMI. Methods Patients with STEMI who received pPCI from October 2020 to June 2023 in the CCU were enrolled. MCE examination was performed on the 5th to 7th day after pPCI. The patients were divided into the MVO group and Non-MVO group. Major adverse cardiovascular events (MACE) were observed by 6-month follow-up after STEMI onset. Multiple Logistic regression analysis was used to analyze the risk factors for MVO, Multiple Cox regression analysis of the risk factors for MACE and Kaplan-Meier survival curve to compare the cumulative event-free survival of the two groups. Results A total of 98 patients were included in the analysis. The age was 59.88±11.71 years old, and 76(77.55%) were male. MCE examination showed 52 cases in the MVO group and 46 cases in the Non-MVO group. The incidence of MVO was 53.1% (52/98). There were 15 patients with MACE during follow-up. The results of stepwise Multivariate Logistic regression analysis showed that the peak value of cardiac troponin T (cTnT) (OR=1.354,95%CI 1.103-1.661, P=0.004) and without thrombus aspiration (TA) were independent risk factors for MVO (OR=5.588,95%CI 1.915-16.308, P=0.002). Multivariate Cox regression analysis indicated that female (HR=2.891, 95%CI 1.027-8.135, P=0.044), left ventricular ejection fraction (LVEF) <40% (HR=9.960, 95%CI 3.370-29.435, P<0.001) and MVO (HR=5.759,95%CI 1.279-25.935, P=0.023) were independent risk factors for MACE. Kaplan-Meier survival curve showed that the cumulative event-free survival rate in the Non-MVO group was higher than that in the MVO group, and the difference was statistically significant (P=0.0047). Conclusion The incidence of coronary MVO was higher in STEMI patients after pPCI, the peak value of cTnT and without TA were independent risk factors of MVO. The independent risk factors for MACE were female, LVEF < 40%, and MVO.

Myocardial Bridging: a bridge to spasm?

Abstract Introduction Myocardial bridges (MBs) represent a congenital anomaly where a segment of a coronary artery passes through the myocardium, resulting in systolic compression. The role of MBs in causing chest pain has been debated, as coronary blood flow occurs primarily in diastole. MBs are generally considered benign, there is growing evidence implicating them in the pathogenesis of coronary artery spasm (CAS). However, the prevalence of CAS in patients in Europe with MBs, particularly assessed through acetylcholine (ACh) testing, remains poorly defined. Methods We conducted a retrospective analysis of consecutive patients with angina with no obstructive CAD (ANOCA), ischemia with no obstructive CAD (INOCA), or myocardial infarction with no obstructive coronary arteries (MINOCA) undergoing ACh testing between 2021 and 2024 at our centre. Patients with documented MBs on coronary angiography were included. The presence of epicardial CAS, defined as >90% reduction in coronary diameter with symptoms and/or ischemic electrocardiographic changes, was assessed during ACh provocation testing. Clinical characteristics, Fractional flow reserve (FFR), resting full-cycle ratio (RFR), coronary flow reserve (CFR) and the index of microvascular resistance (IMR) were also analyzed. Results From a total of 299 patients who underwent ACh Testing, 21 patients were identified with MBs, (17 Male, 4 Female). The prevalence of focal CAS in the MB among these patients was 90%. None of these patients had abnormal hyperemic (FFR) or non-hyperemic (RFR) measurements. 9 of the 21 patients with MB had increased IMR, and only 1 had a CFR < 2. 1 Patient had both microvascular CAS in addition to focal epicardial CAS. Conclusion This analysis provides valuable insights into the prevalence of CAS in patients with MBs undergoing ACh testing. The findings underscore the importance of considering CAS in the evaluation and management of patients with MBs, particularly during provocative testing. Further prospective studies are warranted to validate these findings and elucidate the clinical implications for risk stratification and treatment strategies in this patient population.

Safety and feasibility of drug eluting and perfusion therapy for left main disease: JDEPTH-LM pilot study

Abstract Background Reducing cardiovascular events arising from ostial lesions of the left circumflex artery (LCx) remains an issue following percutaneous coronary intervention (PCI) for left main disease (LMD). Despite expert consensus recommendation for the drug coated balloon (DCB) use to address it, there are concerns in using DCB following the standard practice of crossover-stenting from the left main trunk (LMT) to left anterior descending artery (LAD). Specifically, utilizing a DCB in isolation for the ostial LCx after stenting may result in additional carina shift. The combination of a conventional balloon for LMT-LAD and a DCB for LMT-LCx in KBT could potentially cause hemodynamical instability due to prolonged occlusion time for the entire left coronary artery system. Accordingly, we hypothesized the combined usage of DCB and perfusion balloon (PB) could provide a safe and effective approach for drug-eluting therapy in ostial LCx lesion. This approach aims to facilitate prolonged inflation while maintaining coronary blood flow during KBT for LMD. Purpose The aim of this study was to assess the safety and feasibility of prolonged KBT with DCB and PB for LMD. Methods In this single-center prospective observational study, we enrolled patients of de-novo LMD with ostial LCx lesion, requiring crossover stenting for the LMT-LAD followed by conventional KBT (C-KBT). IVUS-guided procedure was mandated as per the study protocol. Following confirming the achievement of optimal left main PCI by IVUS, a double-effect KBT (W-KBT) was employed. This technique involved the use of a PB for the LMT-LAD and a DCB for the LMT-LCx, sized in a 1:1 ratio to the balloons used in C-KBT. Patients in cardiogenic shock, those requiring a two-stent technique for LMD, and individuals without achievement of TIMI3 flow in the LCx after C-KBT were excluded. The primary endpoint was procedural success, defined as device delivery and balloon inflation time ≥30 sec. Secondary endpoints included the total balloon inflation time (W-KBT time), the incidence of ST-change cases, time to ST-change (ST-change time), changes in blood pressure and heart rate (delta BP and delta HR, respectively), and the frequency of inotrope usage following W-KBT. Results Between January 2023 and December 2023, 12 patients were included among 73 patients with LMD who underwent PCI during this study period. Mean age was 73.8±7.2 years (91.7% men) and median SYNTAX score was 29 (IQR: 26.3 to 34.5). The incidence of ACS was 8.3%. Procedural success was achieved in 100% of cases. The results of secondary endpoints were as follows: median W-KBT time: 60 sec (IQR: 60 to 60); the incidence of ST-change: 50% (no cases with ST-elevation); mean ST-change time: 41.2±7.1 sec; mean delta BP: -13.7±11.4 mmHg; mean delta HR: -3.4±5.9 bpm; and the use of inotrope: 0%. Conclusion Within the limited sample size of this pilot study, the safety and feasibility of the "first-in-man" technique of W-KBT were confirmed.Procedure of W-KBTStrength of W-KBT