Objectives We investigated the reliability of fractional flow reserve (FFR) of nonculprit coronary stenoses during percutaneous coronary intervention (PCI) in acute myocardial infarction. Background ...Assessing the hemodynamic severity of the nonculprit coronary artery stenoses at the acute phase of a myocardial infarction could improve risk stratification and shorten the diagnostic work-up. Methods One hundred one patients undergoing PCI for an acute myocardial infarction (n = 75 with ST-segment elevation myocardial infarction STEMI, and n = 26 with non–ST-segment elevation myocardial infarction) were prospectively recruited. The FFR measurements in 112 nonculprit stenoses were obtained immediately after PCI of the culprit stenosis and were repeated 35 ± 4 days later. In addition, left ventricular ejection fraction, quantitative coronary angiographic measurements of the nonculprit stenoses, Thrombolysis In Myocardial Infarction (TIMI) flow, corrected TIMI frame count (cTFC), and the index of microcirculatory resistance (n = 14) of the nonculprit vessels were assessed in the acute phase and at control angiogram. Results The FFR value of the nonculprit stenoses did not change between the acute and follow-up (0.77 ± 0.13 vs. 0.77 ± 0.13, respectively, p = NS). In only 2 patients, the FFR value was higher than 0.8 at the acute phase and lower than 0.75 at follow-up. The TIMI flow, cTFC, percentage diameter stenosis, minimum lumen diameter, and index of microcirculatory resistance did not change. Left ventricular ejection fraction increased significantly in patients with STEMI (from 54 ± 13% to 57 ± 13%, p = 0.03). Conclusions During the acute phase of acute coronary syndromes, the severity of nonculprit coronary artery stenoses can reliably be assessed by FFR. This allows a decision about the need for additional revascularization and might contribute to a better risk stratification.
Abstract
Background
High glycated-hemoglobin (HbA1c) levels correlated with an elevated risk of adverse cardiovascular outcomes despite renin-angiotensin system (RAS) inhibition in type-2 diabetic ...(T2DM) patients with reduced ejection fraction. Using the routine biopsies of non-T2DM heart transplanted (HTX) in T2DM recipients, we evaluated whether the diabetic milieu modulates glycosylated ACE2 (GlycACE2) levels in cardiomyocytes, known to be affected by non-enzymatic glycosylation, and the relationship with glycemic control.
Objectives
We investigated the possible effects of GlycACE2 on the anti-remodeling pathways of the RAS inhibitors by evaluating the levels of Angiotensin (Ang) 1–9, Ang 1–7, and Mas receptor (MasR), Nuclear-factor of activated T-cells (NFAT), and fibrosis in human hearts.
Methods
We evaluated 197 first HTX recipients (107 non-T2DM, 90 T2DM). All patients were treated with angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) at hospital discharge. Patients underwent clinical evaluation (metabolic status, echocardiography, coronary CT-angiography, and endomyocardial biopsies). Biopsies were used to evaluate ACE2, GlycACE2, Ang 1–9, Ang 1–7, MasR, NAFT, and fibrosis.
Results
GlycACE2 was higher in T2DM compared tonon-T2DM cardiomyocytes. Moreover, reduced expressions of Ang 1–9, Ang 1–7, and MasR were observed, suggesting impaired effects of RAS-inhibition in diabetic hearts. Accordingly, biopsies from T2DM recipients showed higher fibrosis than those from non-T2DM recipients. Notably, the expression of GlycACE2 in heart biopsies was strongly dependent on glycemic control, as reflected by the correlation between mean plasma HbA1c, evaluated quarterly during the 12-month follow-up, and GlycACE2 expression.
Conclusion
Poor glycemic control, favoring GlycACE2, may attenuate the cardioprotective effects of RAS-inhibition. However, the achievement of tight glycemic control normalizes the anti-remodeling effects of RAS-inhibition.
Trial registration
:
https://clinicaltrials.gov/
NCT03546062.
Increased intima-media thickness (IMT) of common carotid artery (CA) is considered the hallmark of vascular hypertension-mediated target organ damage, even if vessel remodeling due to mechanical ...stress may also induce changes in diameter. We developed a method computing both diameter and IMT of CA, to assess correlates and prognostic impact of carotid cross-sectional area (CCSA) in a large registry of treated hypertensive patients. We selected 6300 hypertensive patients of the Campania Salute Network registry free of overt cardiovascular (CV) disease and with available CA ultrasound (54 ± 11 years; 57% male). CCSA was computed as:Formula: see textCCSA was considered high if >90th percentile of the sex-specific distribution (>48 mm
in men and >41 mm
in women). Patients with high CCSA were male, with older age, higher pulse pressure (PP), more prevalent obese and diabetic, with higher total and LDL cholesterol (p < 0.01 for all). During a median follow-up of 60 months (IQR 19-87), 206 incident composite major and minor CV events occurred. In Cox regression analysis high CCSA was associated with more than 100% increased risk of incident CV events ((HR 2.11, 95%CI 1.46-3.1, p < 0.0001), independently of the effect of older age, male sex, PP > 60 mmHg, presence of left ventricular hypertrophy (LVH), carotid plaque (CP), and less anti-RAS therapy (p < 0.05 for all). In treated hypertensive patients, increased CCSA is associated with worse metabolic and lipid profile and predict incident CV events, independently of high PP, presence of LVH and CP.
The optimal treatment of patients undergoing percutaneous coronary interventions (PCI) for lesions located at coronary bifurcations is still debated.
Data on 5036 consecutive patients who underwent ...PCI on coronary bifurcation at 17 major coronary intervention centers between January 2012 and December 2014 were collected.
Follow-up at a median 18 months (IQR 11-28) was available for 4506 patients (89%). Major Adverse Cardiac Events (MACE) occurred in 395 patients (8.8%): cardiac death in 152 (3.4%), myocardial infarction, excluding periprocedural, in 156 (3.5%) and stent thrombosis in 110 cases (2.4%).
At multivariable Cox regression, left ventricular ejection fraction ≤30% (P < 0.001), bail-out stenting (beyond a planned strategy of either single or double stenting) (P < 0.001), admission for an acute coronary syndrome (P < 0.001), age >66 years (P < 0.001), multivessel disease (P < 0.001) and diabetes (P < 0.001) were independently associated with MACE. Sensitivity analysis identified premature discontinuation of dual antiplatelet therapy (DAPT) (P < 0.001) and side branch (SB) lesion length ≥9 mm (P < 0.05) as additional independent predictors of MACE.
Beyond traditional risk factors, multivessel disease, the length of the SB lesion, “bail-out” stenting and premature DAPT discontinuation are independent predictors of mid-term MACE after PCI of coronary bifurcations. This highlights the importance of a carefully planned PCI strategy and adequate therapy adherence to improve the clinical outcomes in these patients.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT01967615.
•In PCI on coronary bifurcations age, diabetes, ACS and reduced LVEF are clinical variables independently associated with MACE.•Among angiographic variables, multivessel CAD and the SB lesion length, not Medina, are independent predictors of MACE.•In the treatment strategy, a “bail-out” placement of stent beyond planning is independently associated with adverse events.•Discontinuation from DAPT <6 months in patients with SCAD and <12 months with after an ACS is an independent predictor of MACE.
The impact of chronic kidney disease (CKD) on residual platelet reactivity (PR) in patients undergoing percutaneous coronary intervention (PCI) is still debatable. We sought to investigate the ...interaction between PR and renal function and the related clinical outcomes in patients with coronary artery disease treated with PCI. Immediately before PCI, we measured PR (as P2Y12 reaction units PRUs) in 800 patients on clopidogrel with the VerifyNow P2Y12 assay. High PR was defined as a PRU value of ≥240 and low PR as a PRU value of ≤178. Based on a glomerular filtration rate of < or ≥60 ml/min/1.73 m2 , patients were respectively grouped into those with or without moderate-to-severe CKD. Primary end point was the incidence of 30-day net adverse clinical events (NACEs). Patients with moderate-to-severe CKD (n = 173, 21.6%) and those without showed similar PRU values (208 ± 67 vs 207 ± 75, p = 0.819). Yet, NACEs were significantly higher in patients with moderate-to-severe CKD (19.7% vs 9.1%, p <0.001), in terms of both ischemic (12.1% vs 7.2%, p = 0.036) and bleeding events (8.7% vs 2.1%, p <0.001). NACEs were significantly higher when moderate-to-severe CKD was associated with either high PR or low PR (25.4%, p for trend <0.001); this association was the strongest predictor of NACE at multivariate analysis (odds ratio 3.4, 95% confidence interval 2.0 to 5.6, p <0.001). In conclusion, we did not find an association between moderate-to-severe CKD and residual PR on clopidogrel. However, the association of moderate-to-severe CKD with either high or low PR was a strong determinant of adverse events after PCI.
The aim of this study is to validate a novel monorail infusion catheter for thermodilution-based quantitative coronary flow measurements.
Based on the principles of thermodilution, volumetric ...coronary flow can be determined from the flow rate of a continuous saline infusion, the temperature of saline when it enters the coronary artery, and the temperature of the blood mixed with the saline in the distal part of the coronary artery. In an in vitro set-up of the systemic and coronary circulation at body temperature, coronary flow values were varied from 50-300 ml/min in steps of 50 ml/min. At each coronary flow value, thermodilution-based measurements were performed at infusion rates of 15, 20, and 30 ml/min. Temperatures and pressures were simultaneously measured with a pressure/temperature sensor-tipped guidewire. Agreement of the calculated flow and the measured flow as well as repeatability were assessed. A total of five catheters were tested, with a total of 180 measurements. A strong correlation (ρ=0.976, p<0.0001) and a difference of -6.5±15.5 ml/min were found between measured and calculated flow. The difference between two repeated measures was 0.2%±8.0%.
This novel infusion catheter used in combination with a pressure/temperature sensor-tipped guidewire allows accurate and repeatable absolute coronary flow measurements. This opens a window to a better understanding of the coronary microcirculation.
The early re-canalization of culprit coronary artery by primary percutaneous coronary intervention (pPCI) reduces the myocardial ischaemic injury but induces the micro-embolization phenomenon and the ...reperfusion injury. Because the controversial efficacy of therapeutic strategies in the treatment of coronary micro-embolization and given no proven treatment able to fight inflammation determined by reperfusion, the role of drugs aimed to improve myocardial cell survival and regulate the extracellular matrix (ECM) homoeostasis became pivotal to prevent post-STEMI LVR. ARBs, angiotensin receptor blockers; ARNI, angiotensin receptor neprilysin inhibitor; AT-1Rs and AT-2Rs, angiotensin receptors type 1 and 2; LVR, left ventricular remodelling; MRAs, mineralocorticoid receptor antagonists. Because the controversial efficacy of mechanical interventions (thrombus aspiration) and of pharmacological therapies (Gp IIb IIIa inhibitors and adenosine) in the treatment of coronary micro-embolization, and given no proven treatment able to fight the inflammation determined by reperfusion, the role of drugs aimed to improve the myocardial cell survival and regulate the extracellular matrix (ECM) homoeostasis became pivotal to prevent post-STEMI LVR. 8 In this context, SAC/VAL might represent an interesting choice. ...plasmatic AT-2Rs stimulation by Ang II leads to the AT-2Rs translocation from plasmatic to mitochondrial membrane, where they suppress the formation of reactive-oxygen species. 12 Thus, concomitant inhibition of plasmatic AT1-Rs by valsartan blocks pro-apoptotic mechanisms mediated by these receptors and empowers pro-survival pathways induced by increased Ang II through AT-2Rs. To this aim, SAC/VAL use is supported by large pathophysiological and little, so far, clinical evidence. ...we can speculate that the early initiation of SAC/VAL may reduce cardiovascular events compared with ACE-inhibitors/ARBs, in STEMI with acute moderate LVEF reduction, not only through a better regulation of circulating volume but also through the reduction of the necrotic area and fibrosis inside the ischaemic myocardium leading to prevention of post-infarction LVR.
Sodium-glucose co-transporter 2 inhibitors (SGLT2-i) have shown significant cardiovascular benefits in patients with and without type 2 diabetes mellitus (T2DM). They have also gained interest for ...their potential anti-arrhythmic role and their ability to reduce the occurrence of atrial fibrillation (AF) and ventricular arrhythmias (VAs) in T2DM and heart failure patients.
To investigate in-hospital new-onset cardiac arrhythmias in a cohort of T2DM patients presenting with acute myocardial infarction (AMI) treated with SGLT2-i vs. other oral anti-diabetic agents (non-SGLT2-i users).
Patients from the SGLT2-I AMI PROTECT registry (NCT05261867) were stratified according to the use of SGLT2-i before admission for AMI, divided into SGLT2-i users vs. non-SGLT2-i users. In-hospital outcomes included the occurrence of in-hospital new-onset cardiac arrhythmias (NOCAs), defined as a composite of new-onset AF and sustained new-onset ventricular tachycardia (VT) and/or ventricular fibrillation (VF) during hospitalization.
The study population comprised 646 AMI patients categorized into SGLT2-i users (111 patients) and non-SGLT2-i users (535 patients). SGLT2-i users had a lower rate of NOCAs compared with non-SGLT2-i users (6.3 vs. 15.7%,
= 0.010). Moreover, SGLT2-i was associated with a lower rate of AF and VT/VF considered individually (
= 0.032). In the multivariate logistic regression model, after adjusting for all confounding factors, the use of SGLT2-i was identified as an independent predictor of the lower occurrence of NOCAs (OR = 0.35; 95%CI 0.14-0.86;
= 0.022). At multinomial logistic regression, after adjusting for potential confounders, SGLT2-i therapy remained an independent predictor of VT/VF occurrence (OR = 0.20; 95%CI 0.04-0.97;
= 0.046) but not of AF occurrence.
In T2DM patients, the use of SGLT2-i was associated with a lower risk of new-onset arrhythmic events during hospitalization for AMI. In particular, the primary effect was expressed in the reduction of VAs. These findings emphasize the cardioprotective effects of SGLT2-i in the setting of AMI beyond glycemic control.
Data are part of the observational international registry: SGLT2-I AMI PROTECT. ClinicalTrials.gov, identifier: NCT05261867.
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