Duration of Dual Antiplatelet Treatment After Percutaneous Coronary Intervention in Patients With Diabetes: A Systematic Review and Meta-analysis.

ABSTRACT: Aim of our systematic review and meta-analysis is to compare shortened (≤3 months) dual antiplatelet therapy (DAPT) with longer DAPT in diabetic patients undergoing percutaneous coronary interventions.We systematically screened 3 major databases (MEDLINE, Cochrane Central Register of Controlled Trials, and Scopus) searching for randomized-controlled trials or subanalyses of them, which compared shortened DAPT (S-DAPT) with longer DAPT regimens of DAPT. Primary end point of systematic review and meta-analysis is the net adverse clinical events (NACE), and secondary are major adverse cardiac events (MACE), mortality, bleedings, myocardial infarction, and stent thrombosis. Subgroup analyses included studies using only ticagrelor-based regimens and 3-month duration of DAPT.A total of 8 studies and 12,665 patients were included in our analysis. Our meta-analysis met its primary end point because S-DAPT was associated significantly with a reduced risk ratio (RR) by 17% [RR: 0.83, 95% confidence intervals (CI), 0.72-0.96]. Nonsignificant difference among the rest end points was detected between the 2 groups. Subgroup analyses showed that ticagrelor-based regimens were associated with a significant reduction of mortality (RR: 0.67, 95% CI, 0.48-0.93) and 3-month DAPT reduced furtherly NACE by 27% (RR: 0.73, 95% CI, 0.60-0.89).In conclusion, our systematic review and meta-analysis showed that (i) S-DAPT was significantly associated with a lower incidence of NACE, (ii) ticagrelor-based S-DAPT was associated with decreased mortality rates, and (iii) the benefit of 3-month duration of DAPT achieved an even greater NACE reduction. Thus, S-DAPT could be considered as a safe and feasible option in diabetic patients.

Intracoronary Imaging: Current Practice and Future Perspectives.

Intracoronary imaging has brought new insight in the field of interventional cardiology. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) are the most commonly used imaging modalities. Regarding their technical characteristics IVUS and OCT have similarities as well as differences, a fact that could have significant clinical implications. Both techniques play an important role in percutaneous coronary intervention (PCI) guidance and demonstrated superiority compared to intravascular coronary angiography (ICA) guidance alone. Furthermore, their use can notably assist coronary plaque evaluation; both provide additional information of plaque characteristics, which can lead to a better understanding of the cause of an acute coronary syndrome (ACS) and better clinical outcomes. However, there is not enough clinical evidence for the superiority of one method compared to the other, something that is, also, reflected in the guidelines. In this review, we aim to compare role of IVUS and OCT in the different aspects of coronary artery disease (CAD), according to the latest scientific data. In addition, we present the future perspectives regarding the IVUS and OCT, with co-registration of the two methods or hybrid OCT-IVUS catheters.

Imaging of Left Main Coronary Artery; Untangling the Gordian Knot.

Left Main Coronary Artery (LMCA) disease is considered a standout manifestation of coronary artery disease (CAD), because it is accompanied by the highest mortality. Increased mortality is expected, because LMCA is responsible for supplying up to 80% of total blood flow to the left ventricle in a right-dominant coronary system. Due to the significant progress of biomedical technology, the modern drug-eluting stents have remarkably improved the prognosis of patients with LMCA disease treated invasively. In fact, numerous randomized trials provided similar results in one- and five-year survival of patients treated with percutaneous coronary interventions (PCI) -guided with optimal imaging and coronary artery bypass surgery (CABG). However, interventional treatment requires optimal imaging of the LMCA disease, such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT). The aim of this manuscript is to review the main pathophysiological characteristics, to present the imaging techniques of LMCA, and, last, to discuss the future directions in the depiction of LMCA disease.

OCT Guidance in Bifurcation Percutaneous Coronary Intervention.

Coronary bifurcation is defined by the European Bifurcation Consensus as a coronary artery stenosis adjacent to the origin of a significant side branch. Its anatomy is composed of 3 different segments: proximal main vessel, distal main vessel and side branch. Coronary artery bifurcation lesions are encountered in approximately 15-20% of all percutaneous coronary interventions and constitute a complex subgroup of lesions characterized by lower procedural success rates and higher rates of adverse outcomes. In recent years, a growing focus in the European and Japanese bifurcation club meetings has been the emerging role of intravascular imaging, in guiding successful bifurcation percutaneous coronary interventions (PCI). In this review we will present the main ways optical coherence tomography (OCT) can be used to improve outcomes during bifurcation PCI.

Protein tyrosine phosphatase receptor-ζ1 deletion triggers defective heart morphogenesis in mice and zebrafish.

Protein tyrosine phosphatase receptor-ζ1 (PTPRZ1) is a transmembrane tyrosine phosphatase receptor highly expressed in embryonic stem cells. In the present work, gene expression analyses of Ptprz1-/- and Ptprz1+/+ mice endothelial cells and hearts pointed to an unidentified role of PTPRZ1 in heart development through the regulation of heart-specific transcription factor genes. Echocardiography analysis in mice identified that both systolic and diastolic functions are affected in Ptprz1-/- compared with Ptprz1+/+ hearts, based on a dilated left ventricular (LV) cavity, decreased ejection fraction and fraction shortening, and increased angiogenesis in Ptprz1-/- hearts, with no signs of cardiac hypertrophy. A zebrafish ptprz1-/- knockout was also generated and exhibited misregulated expression of developmental cardiac markers, bradycardia, and defective heart morphogenesis characterized by enlarged ventricles and defected contractility. A selective PTPRZ1 tyrosine phosphatase inhibitor affected zebrafish heart development and function in a way like what is observed in the ptprz1-/- zebrafish. The same inhibitor had no effect in the function of the adult zebrafish heart, suggesting that PTPRZ1 is not important for the adult heart function, in line with data from the human cell atlas showing very low to negligible PTPRZ1 expression in the adult human heart. However, in line with the animal models, Ptprz1 was expressed in many different cell types in the human fetal heart, such as valvar, fibroblast-like, cardiomyocytes, and endothelial cells. Collectively, these data suggest that PTPRZ1 regulates cardiac morphogenesis in a way that subsequently affects heart function and warrant further studies for the involvement of PTPRZ1 in idiopathic congenital cardiac pathologies.NEW & NOTEWORTHY Protein tyrosine phosphatase receptor ζ1 (PTPRZ1) is expressed in fetal but not adult heart and seems to affect heart development. In both mouse and zebrafish animal models, loss of PTPRZ1 results in dilated left ventricle cavity, decreased ejection fraction, and fraction shortening, with no signs of cardiac hypertrophy. PTPRZ1 also seems to be involved in atrioventricular canal specification, outflow tract morphogenesis, and heart angiogenesis. These results suggest that PTPRZ1 plays a role in heart development and support the hypothesis that it may be involved in congenital cardiac pathologies.

Heart failure and atrial fibrillation: new concepts in pathophysiology, management, and future directions.

A bidirectional pathophysiological link connects heart failure and atrial fibrillation, creating a frequent and challenging comorbidity, which includes neurohormonal hyperactivation, fibrosis development, and electrophysiologic remodeling, while they share mutual risk factors. Management for these devastating comorbidities includes most of the established treatment measures for heart failure as well as rhythm or rate control and anticoagulation mostly for atrial fibrillation, which can be achieved with either pharmaceutical or non-pharmaceutical approaches. The current manuscript aims to review the existing literature regarding the underlying pathophysiology, to present the novel trends of treatment, and to predict the future perspective of these two linked diseases with the numerous unanswered questions.

Radial versus femoral access in patients with coronary artery bypass surgery: Frequentist and Bayesian meta-analysis.

BACKGROUND: The optimal access site for cardiac catheterization in patients with prior coronary artery bypass surgery (CABG) continues to be debated. METHODS: We performed a random effects frequentist and Bayesian meta-analysis of 4 randomized trials and 18 observational studies, including 60,192 patients with prior CABG (27,236 in the radial group; 32,956 in the femoral group) that underwent cardiac catheterization. Outcomes included (1) access-site complications, (2) crossover to a different vascular access, (3) procedure time, and (4) contrast volume. Mean differences (MD) and 95% confidence interval (CI) were calculated for continuous outcomes and odds ratios (OR) and 95% CI for binary outcomes. RESULTS: Among randomized trials, crossover (OR: 7.63; 95% CI: 2.04, 28.51; p = 0.003) was higher in the radial group, while access site complications (OR: 0.96; 95% CI: 0.34, 2.87; p = 0.94) and contrast volume (MD: 15.08; 95% CI: -10.19, 40.35; p = 0.24) were similar. Among observational studies, crossover rates were higher (OR: 5.09; 95% CI: 2.43, 10.65; p < 0.001), while access site complication rates (OR: 0.52; 95% CI: 0.30, 0.89; p = 0.02) and contrast volume (MD: -7.52; 95% CI: -13.14, -1.90 ml; p = 0.009) were lower in the radial group. Bayesian analysis suggested that the odds of a difference existing between radial and femoral are small for all endpoints except crossover to another access site. CONCLUSION: In a frequentist and Bayesian meta-analysis of patients with prior CABG undergoing coronary catheterization, radial access was associated with lower incidence of vascular access complications and lower contrast volume but also higher crossover rate.

Pharmacologic Rate versus Rhythm Control for Atrial Fibrillation in Heart Failure Patients.

Atrial fibrillation (AF) and Heart failure (HF) constitute two frequently coexisting cardiovascular diseases, with a great volume of the scientific research referring to strategies and guidelines associated with the best management of patients suffering from either of the two or both of these entities. The common pathophysiological paths, the adverse outcomes, the hospitalization rates, and the mortality rates that occur from various reports and trials indicate that a targeted therapy to the common background of these cardiovascular conditions may reverse the progression of their interrelating development. Among other optimal treatments concerning the prevalence of both AF and HF, the introduction of rhythm and rate control strategies in the guidelines has underlined the importance of sinus rhythm and heart rate control in the prevention of deleterious complications. The use of these strategies in the clinical practice has led to a debate about the superiority of rhythm versus rate control. The current guidelines as well as the published randomized trials and studies have not proved that rhythm control is more beneficial than the rate control treatments in the terms of survival, all-cause mortality, hospitalization rates, and quality of life. Therefore, the current therapeutic strategy is based on the therapy guidelines and the clinical judgment and experience. The aim of this review was to elucidate the endpoints of pharmacologic randomized clinical trials and the clinical data of each antiarrhythmic or rate-limiting medication, so as to promote their effective, individualized, evidence-based clinical use.

Irreversible diffuse hypoxic-ischemic encephalopathy, secondary to type I Kounis syndrome.

We herein describe the unusual case of irreversible diffuse hypoxic-ischemic encephalopathy secondary to type I Kounis syndrome. The patient survived and remained in a vegetative state after being mechanically ventilated in the intensive care unit for long. A brief review of the literature on mechanisms for KS-associated brain injury is also presented.

Factors Affecting Platelet Reactivity 2 Hours After P2Y12 Receptor Antagonist Loading in Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction - Impact of Pain-to-Loading Time.

BACKGROUND: Delay in the onset of antiplatelet action occurs in patients with ST-elevation myocardial infarction (STEMI) and is likely due to disturbed absorption. We hypothesized that patients presenting relatively late after the onset of symptoms would have faster antiplatelet action. METHODS AND RESULTS: We analyzed patient-level data from 5 studies of 207 P2Y12 receptor antagonist-naïve patients with STEMI undergoing primary percutaneous coronary intervention (PCI). All patients had available platelet reactivity (PR) assessment with the VerifyNow assay (in P2Y12 reaction units; PRU) prior to and 2 h after loading. High PR (HPR) was defined as ≥ 208 PRU. Pain-to-antiplatelet loading time independently predicted PR at 2 h after loading: every 1-h increase in pain-to-antiplatelet loading time produced a 7% decrease in PR (P=0.001). Pretreatment PR, body mass index, morphine and novel P2Y12 receptor antagonist also affected PR 2 h after loading. Novel P2Y12 receptor antagonist use and per hour increase in pain-to-antiplatelet loading time were independently associated with lower probability for HPR with an OR (95% CI) of 0.145 (0.095-0.220) and 0.776 (0.689-0.873), P<0.001 for both (C-statistic, 0.752; 95% CI: 0.685-0.819). CONCLUSIONS: In STEMI patients undergoing primary PCI, pain-to-antiplatelet loading interval is a newly described factor affecting PR shortly after P2Y12 receptor antagonist loading, according to patient-level data pooled analysis.

Ticagrelor vs clopidogrel followed by ticagrelor re-loading in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: A randomized, pharmacodynamic comparison.

Among patients allocated to ticagrelor in the primary percutaneous coronary intervention (PCI) cohort of Platelet Inhibition and Patient Outcomes (PLATO) trial, 40.7% had received pre-randomization 600 mg of clopidogrel. This scenario is frequently employed in real-world practice. In a prospective, three-center, single-blind, parallel design study, 74 P2Y12 inhibitor-naive patients undergoing primary PCI were randomized (Hour 0) to ticagrelor 180 mg loading dose (LD) vs clopidogrel 600 mg LD followed after 2 h by ticagrelor 180 mg re-LD. Platelet reactivity (VerifyNow, in PRU) was assessed at Hour 0, 2, 4, 6, and 24. The primary comparison was non-inferiority of ticagrelor to clopidogrel followed by ticagrelor re-LD regarding platelet reactivity at 24 h using a prespecified margin of <35 PRU for the upper bound of the one-sided 97.5% confidence interval (CI). Ticagrelor was proven non-inferior to clopidogrel followed by ticagrelor re-LD with a difference between arms of 13.5 PRU (28.8 upper 97.5% CI), p = 0.001. At Hour 2, platelet reactivity was lower in ticagrelor only vs clopidogrel followed by ticagrelor re-LD groups with least square estimate mean difference (95% CI) -105.7 (-140.6 to -70.8), p < 0.001, without significant difference thereafter. In conclusion, in patients undergoing primary PCI, a strategy of ticagrelor LD only was proven non-inferior to clopidogrel LD followed by ticagrelor re-LD, in terms of antiplatelet efficacy at 24 h post-randomization and provided an earlier onset of platelet inhibition.

The Application of Precision Medicine in Structural Heart Diseases: A Step towards the Future.

The personalized applications of 3D printing in interventional cardiology and cardiac surgery represent a transformative paradigm in the management of structural heart diseases. This review underscores the pivotal role of 3D printing in enhancing procedural precision, from preoperative planning to procedural simulation, particularly in valvular heart diseases, such as aortic stenosis and mitral regurgitation. The ability to create patient-specific models contributes significantly to predicting and preventing complications like paravalvular leakage, ensuring optimal device selection, and improving outcomes. Additionally, 3D printing extends its impact beyond valvular diseases to tricuspid regurgitation and non-valvular structural heart conditions. The comprehensive synthesis of the existing literature presented here emphasizes the promising trajectory of individualized approaches facilitated by 3D printing, promising a future where tailored interventions based on precise anatomical considerations become standard practice in cardiovascular care.

Spontaneous Coronary Artery Dissection as a Cause of Acute Myocardial Infarction in COVID-19 Patients: A Case Report and Review of the Literature.

Patients with COVID-19 often experience significant cardiovascular complications, including heart failure, myocarditis, and acute coronary syndrome. We present the case of a male patient with severe COVID-19 pneumonia, complicated with inferior ST-segment elevation myocardial infarction (STEMI), which was attributed to spontaneous coronary artery dissection (SCAD). We also make a review of the literature on case reports of patients with COVID-19 and acute myocardial infarction due to SCAD. Through these clinical cases, a potential correlation between SCAD and COVID-19 infection is implied. Endothelial dysfunction, thrombotic complications, and disturbance of the vascular tone are established COVID-19 sequelae, triggered either by direct viral injury or mediated by the cytokines' storm. These abnormalities in the coronary vasculature and the vasa vasorum could result in SCAD. Moreover, disturbances of the vascular tone can cause coronary vasospasm, a reported precipitant of SCAD. Thus, SCAD should be considered in COVID-19 patients with acute coronary syndrome (ACS), and in the case of STEMI, an early angiographic evaluation, if feasible, should be performed rather than thrombolysis to avoid potential adverse events of the latter in the setting of SCAD.

Rapid and Precise Computation of Fractional Flow Reserve from Routine Two-Dimensional Coronary Angiograms Based on Fluid Mechanics: The Pilot FFR2D Study.

Objective: To present a novel pipeline for rapid and precise computation of fractional flow reserve from an analysis of routine two-dimensional coronary angiograms based on fluid mechanics equations (FFR2D). Material and methods: This was a pilot analytical study that was designed to assess the diagnostic performance of FFR2D versus the gold standard of FFR (threshold ≤ 0.80) measured with a pressure wire for the physiological assessment of intermediate coronary artery stenoses. In a single academic center, consecutive patients referred for diagnostic coronary angiography and potential revascularization between 1 September 2020 and 1 September 2022 were screened for eligibility. Routine two-dimensional angiograms at optimal viewing angles with minimal overlap and/or foreshortening were segmented semi-automatically to derive the vascular geometry of intermediate coronary lesions, and nonlinear pressure-flow mathematical relationships were applied to compute FFR2D. Results: Some 88 consecutive patients with a single intermediate coronary artery lesion were analyzed (LAD n = 74, RCA n = 9 and LCX n = 5; percent diameter stenosis of 45.7 ± 11.0%). The computed FFR2D was on average 0.821 ± 0.048 and correlated well with invasive FFR (r = 0.68, p < 0.001). There was very good agreement between FFR2D and invasive-wire FFR with minimal measurement bias (mean difference: 0.000 ± 0.048). The overall accuracy of FFR2D for diagnosing a critical epicardial artery stenosis was 90.9% (80 cases classified correctly out of 88 in total). FFR2D identified 24 true positives, 56 true negatives, 4 false positives, and 4 false negatives and predicted FFR ≤ 0.80 with a sensitivity of 85.7%, specificity of 93.3%, positive likelihood ratio of 13.0, and negative likelihood ratio of 0.15. FFR2D had a significantly better discriminatory capacity (area under the ROC curve: 0.95 [95% CI: 0.91-0.99]) compared to 50%DS on 2D-QCA (area under the ROC curve: 0.70 [95% CI: 0.59-0.82]; p = 0.0001) in predicting wire FFR ≤ 0.80. The median time of image analysis was 2 min and the median time of computation of the FFR2D results was 0.1 s. Conclusion: FFR2D may rapidly derive a precise image-based metric of fractional flow reserve with high diagnostic accuracy based on a single two-dimensional coronary angiogram.