Contemporary use of excimer laser in percutaneous coronary intervention with indications, procedural characteristics, complications and outcomes in a university teaching hospital.

BACKGROUND: Excimer laser coronary atherectomy (ELCA) can be used as an adjunctive percutaneous coronary intervention treatment for challenging, heavily calcified lesions. Although previous studies have documented high rates of complication and restenosis, these predate the introduction of the smaller 0.9 mm laser catheter. As the coronary complexity has increased, there has been a renewed interest in the ELCA. This study investigates the indications, procedural characteristics, complications and outcomes of ELCA in a contemporary coronary interventional practice. METHODS: This single-centre study retrospectively analysed 50 patients treated with ELCA between January 2013 and January 2019. RESULTS: Patients had a mean age of 67.9±11.4 years with a male predominance (65.3%). 25 (50%) cases were performed in patients with stable angina. Failure to deliver the smallest available balloon/microcatheter was the most frequent indication in 32 (64%) cases for ELCA use. 30 (60%) of the procedures were performed via radial access. The 0.9 mm X-80 catheter was used in 41 (82%) of cases, delivering on average 9000±3929 pulses. ELCA-related complications included 2 coronary dissections and 1 perforation, all of which were covered with stents. No major complications could be directly attributed to the use of ELCA. There was one death and one case of stent thrombosis within 30 days of the procedure. CONCLUSION: ELCA can be performed safely via the radial approach with a 0.9 mm catheter with a high success rate by suitably trained operators. The low procedure-related complications with contemporary techniques make this a very useful tool for complex coronary interventions, especially for difficult to dilate lesions and chronic total occlusion vessels.

Human monocyte-derived macrophages: Pathogenetic role in plaque rupture associated to systemic inflammation.

BACKGROUND: Macrophages play a key role in coronary plaque destabilization. In-vitro human monocyte-derived macrophages (MDMs) are used to study macrophages infiltrating tissue. Optical coherence tomography (OCT) provides an in-vivo insight of the coronary arteries. We compared the MDMs morpho-phenotype and culprit plaque features at OCT in acute coronary syndrome (ACS) patients according to the underlying plaque pathobiology. METHODS: Sixty-six patients undergoing coronary angiography and pre-angioplasty OCT of the culprit vessel were allocated to three groups according to mechanism of ACS at OCT and C-reactive protein levels (cut-off: 2 mg/Ll): 1) plaque rupture with systemic inflammation; 2) plaque rupture without systemic inflammation, 3) plaque with intact fibrous cap. A blood sample was collected to obtain MDMs, categorized as having "round" or "spindle" morphology. RESULTS: Thirty-two patients (48.5%) were assigned to Group 1, 10 (15.2%) to Group 2 and 24 (36.4%) to Group 3. The "round" MDMs were significantly more frequent in Group 1 (39.25 ± 4.98%) than in Group 2 (23.89 ± 3.10%) and Group 3 (23.02 ± 7.89%), p = 0.008. MDMs in Group 1 as compared to Groups 2 and 3 showed lower efferocytosis (8.74 ± 1.38 vs 9.74 ± 2.15 vs 11.41 ± 2.41; p = 0.012), higher tissue factor levels (369.84 ± 101.13 vs 301.89 ± 59.78 vs 231.74 ± 111.47; p = 0.001) and higher heme oxygenase-1 expression (678.78 ± 145.43 vs 419.12 ± 74.44 vs 409.78 ± 64.33; p = 0.008). CONCLUSIONS: MDMs of ACS patients show morpho-phenotypic heterogeneity with prevalence of pro-thrombotic and pro-oxidative properties in case of plaque rupture and systemic inflammation. Such MDMs subpopulation may take part to the cellular pathways leading to fibrous cap rupture with the subsequent thrombus formation.

Macrophage infiltrates in coronary plaque erosion and cardiovascular outcome in patients with acute coronary syndrome.

BACKGROUND AND AIMS: Plaque erosion (PE) is responsible for at least one-third of acute coronary syndrome (ACS), and inflammation plays a key role in plaque instability. We assessed the presence of optical coherence tomography (OCT)-defined macrophage infiltrates (MØI) at the culprit site in ACS patients with PE, evaluating their clinical and OCT correlates, along with their prognostic value. METHODS: ACS patients undergoing OCT imaging and presenting PE as culprit lesion were retrospectively selected. Presence of MØI at culprit site was assessed. The incidence of major adverse cardiac events (MACEs), defined as the composite of cardiac death, recurrent myocardial infarction and target-vessel revascularization (TVR), was assessed [follow-up median (interquartile range, IQR) time 2.5 (2.03-2.58) years]. RESULTS: We included 153 patients [median age (IQR) 64 (53-75) years, 99 (64.7%) males]. Fifty-one (33.3%) patients presented PE with MØI and 102 (66.7%) PE without MØI. Patients having PE with MØI compared with PE patients without MØI had more vulnerable plaque features both at culprit site and at non-culprit segments. MACEs were significantly more frequent in PE with MØI patients compared with PE without MØI [11 (21.6%) vs. 6 (5.9%), p = 0.008], mainly driven by a higher risk of cardiac death and TVR. At multivariable Cox regression, PE with MØI was an independent predictor of MACEs [HR = 2.95, 95% CI (1.09-8.02), p = 0.034]. CONCLUSIONS: Our study demonstrates that among ACS patients with PE the presence of MØI at culprit lesion is associated with more vulnerable plaque features, along with a worse prognosis at a long-term follow-up.

Reversal of Bioprosthetic Aortic Valve Thrombosis Using Rivaroxaban-A Case Report.

Background: Bioprosthetic valve thrombosis (BPVT) is a rare but recognized complication causing valve dysfunction. In subacute valve thrombosis, systemic oral anticoagulation is recommended. However, there is little data comparing the efficacy of warfarin and novel oral anticoagulant (NOAC) therapy in this setting. Case Summary: A patient developed subacute BPVT 11 years post-implantation. The patient was initially treated with warfarin for a period of 6 months, with limited effect. Following replacement of warfarin with rivaroxaban, there was significant reversal of the BPVT, as represented by a reduction in transaortic maximal velocity (Vmax) from 4.1 to 3 m/s over 7 months. Discussion: Systemic oral anticoagulation can be an effective treatment for subacute valve thrombosis. Guidelines currently recommend warfarin as first line but NOACs can be considered in such patients and may be more effective than warfarin. Randomized controlled trials are required to further establish the optimal anticoagulation for patients with subacute BPVT.

Recurrence of angina after ST-segment elevation myocardial infarction: the role of coronary microvascular obstruction.

BACKGROUND: The recurrence of angina after percutaneous coronary intervention affects 20-35% of patients with stable coronary artery disease; however, few data are available in the setting of ST-segment elevation myocardial infarction. We evaluated the relation between coronary microvascular obstruction and the recurrence of angina at follow-up. METHODS: We prospectively enrolled patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Microvascular obstruction was defined as thrombolysis in myocardial infarction flow less than 3 or 3 with myocardial blush grade less than 2. The primary endpoint was the recurrence of angina at follow-up. Moreover, angina status was evaluated by the Seattle angina questionnaire summary score (SAQSS). Therapy at follow-up and the occurrence of major adverse cardiovascular events were also collected. RESULTS: We enrolled 200 patients. Microvascular obstruction occurred in 52 (26%) of them. Follow-up (mean time 25.17±9.28 months) was performed in all patients. Recurrent angina occurred in 31 (15.5%) patients, with a higher prevalence in patients with microvascular obstruction compared with patients without microvascular obstruction (13 (25.0%) vs. 18 (12.2%), P=0.008). Accordingly, SAQSS was lower and the need for two or more anti-anginal drugs was higher in patients with microvascular obstruction compared with patients without microvascular obstruction. At multiple linear regression analysis a history of previous acute coronary syndrome and the occurrence of microvascular obstruction were the only independent predictors of a worse SAQSS. Finally, the occurrence of major adverse cardiovascular events was higher in patients with microvascular obstruction compared with patients without microvascular obstruction. CONCLUSIONS: The recurrence of angina in ST-segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention is an important clinical issue. The occurrence of microvascular obstruction portends a worse angina status and is associated with the use of more anti-anginal drugs.

Optical coherence tomography and C-reactive protein in risk stratification of acute coronary syndromes.

BACKGROUND: Patients with acute coronary syndrome (ACS) associated to high C-reactive protein (CRP) levels exhibit a higher risk of future acute ischemic events. Yet, the positive predictive value of CRP is too low to guide a specific treatment. Our study aims to identify a high-risk patient subset who might mostly benefit from anti-inflammatory treatment on the basis of the combination of optical coherence tomography (OCT) assessment of the culprit vessel and CRP serum levels. METHODS: Patients admitted for ACS and undergoing pre-interventional OCT assessment of the culprit vessel were selected from "Agostino Gemelli" Hospital OCT Registry. The primary end-point was recurrent ACS (re-ACS). CRP levels ≥2 mg/L were considered abnormal. RESULTS: The overall study population consisted of 178 patients. Among these, 156 patients were included in the primary end-point analysis. The re-ACS rate was 23% at 3-year follow-up. High CRP (2.587, 95% CI:1.345-10.325, p = 0.031), plaque rupture (3.985, 95% CI:1.698-8.754, p = 0.009), macrophage infiltration (3.145, 95% CI:1.458-9.587, p = 0.012) and multifocal atherosclerosis (2.734, 95% CI:1.748-11.875, p = 0.042) were independent predictors of re-ACS. All patients (14/14) with high CRP and with all OCT high-risk features had re-ACS. At the other extreme, only 4 of the 82 patients with low CRP levels and lack of high-risk features at OCT examination exhibited re-ACS at follow-up. CONCLUSIONS: The combination of systemic evidence of inflammation and OCT findings in the culprit plaque identifies very high-risk ACS. Future studies are warranted to confirm these findings and to test an anti-inflammatory treatment in this patient subset.

The 9p21 Rs 1333040 polymorphism is associated with coronary microvascular obstruction in ST-segment elevation myocardial infarction treated by primary angioplasty.

BACKGROUND: Microvascular obstruction (MVO) after primary percutaneous coronary intervention (pPCI) leads to higher incidence of both early and late complications. A number of single nucleotide polymorphisms in 9p21 chromosome have been shown to affect angiogenesis in response to ischaemia. In particular, Rs1333040 with its three genotypic vriants C/C, T/C and T/T might influence the occurrence of MVO after pPCI. METHODS: We enrolled ST-elevation myocardial infarction (STEMI) patients undergoing pPCI. The Rs1333040 polymorphism was evaluated by polymerase chain reaction-restriction fragment length polymorphism using restriction endonucleases (Bsml). Two expert operators unaware of the patients' identity performed the angiographic analysis; collaterals were assessed applying Rentrop's classification. Angiographic MVO was defined as a post-pPCI Thrombolysis In Myocardial Infarction (TIMI)<3 or TIMI 3 with myocardial blush grade 0 or 1, whereas electrocardiographic MVO was defined as ST segment resolution <70% one hour after pPCI. RESULTS: Among our 133 STEMI patients (mean age 63 ± 11 years, men 72%), 35 (26%) and 53 (40%) respectively experienced angiographic or electrocardiographic MVO. Angiographic and electrocardiographic MVO were different among the three variants (p= 0.03 and p=0.02 respectively). In particular, T/T genotype was associated with a higher incidence of both angiographic and electrocardiographic MVO compared with C/C genotype (p=0.04 and p=0.03 respectively). Moreover, Rentrop score <2 detection rate differed among the three genotypes (p=0.03). In particular T/T genotype was associated with a higher incidence of a Rentrop score <2 as compared with C/C genotype (p= 0.02). CONCLUSION: Rs1333040 polymorphism genetic variants portend different MVO incidence. In particular, T/T genotype is related to angiographic and electrocardiographic MVO and to worse collaterals towards the culprit artery.

Recurrence of angina after ST-segment elevation myocardial infarction: the role of coronary microvascular obstruction.

BACKGROUND: The recurrence of angina after percutaneous coronary intervention affects 20-35% of patients with stable coronary artery disease; however, few data are available in the setting of ST-segment elevation myocardial infarction. We evaluated the relation between coronary microvascular obstruction and the recurrence of angina at follow-up. METHODS: We prospectively enrolled patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Microvascular obstruction was defined as thrombolysis in myocardial infarction flow less than 3 or 3 with myocardial blush grade less than 2. The primary endpoint was the recurrence of angina at follow-up. Moreover, angina status was evaluated by the Seattle angina questionnaire summary score (SAQSS). Therapy at follow-up and the occurrence of major adverse cardiovascular events were also collected. RESULTS: We enrolled 200 patients. Microvascular obstruction occurred in 52 (26%) of them. Follow-up (mean time 25.17±9.28 months) was performed in all patients. Recurrent angina occurred in 31 (15.5%) patients, with a higher prevalence in patients with microvascular obstruction compared with patients without microvascular obstruction (13 (25.0%) vs. 18 (12.2%), P=0.008). Accordingly, SAQSS was lower and the need for two or more anti-anginal drugs was higher in patients with microvascular obstruction compared with patients without microvascular obstruction. At multiple linear regression analysis a history of previous acute coronary syndrome and the occurrence of microvascular obstruction were the only independent predictors of a worse SAQSS. Finally, the occurrence of major adverse cardiovascular events was higher in patients with microvascular obstruction compared with patients without microvascular obstruction. CONCLUSIONS: The recurrence of angina in ST-segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention is an important clinical issue. The occurrence of microvascular obstruction portends a worse angina status and is associated with the use of more anti-anginal drugs.

Successful treatment of a spontaneous right coronary artery dissection with a 4-mm diameter cutting balloon: a case report.

BACKGROUND: Guidelines recommend conservative management for a spontaneous coronary artery dissection (SCAD) in the absence of ongoing ischaemia, haemodynamic instability, or left main dissection. Conventional percutaneous coronary intervention methods for SCAD are associated with an unfavourable prognosis due to difficulties wiring the lesion, dissection propagation, and potential 'milking' of the intramural haematoma along the vessel or into other vessels. These factors promote implantation of multiple stents which are often undersized, increasing the risk of in-stent restenosis significantly. There have been several case reports demonstrating the novel use of small diameter cutting balloons in the left anterior descending artery system. Here, we describe the successful use of a larger 4 mm cutting balloon to treat a spontaneous right coronary artery (RCA) dissection. CASE SUMMARY: A 53-year-old woman with troponin negative chest pain and was diagnosed with unstable angina due to ischaemic electrocardiographic features. Coronary angiography revealed a tight discrete lesion in the RCA. Intravascular imaging confirmed SCAD and a 4 mm cutting balloon was used to dissect the tunica intima to allow complete resorption of the intramural haematoma and resolution of symptoms. DISCUSSION: This case demonstrates the safe use of a larger 4 mm cutting balloon to treat an RCA SCAD, resulting in complete resolution of the haematoma.

What is the cause of hypotension? A rare complication of percutaneous coronary intervention of a chronic total occlusion: a case report.

BACKGROUND: In the last few years, complex techniques and advanced equipment became available to treat chronically occluded coronary arteries. Such procedures portend a series of possible complications that operators should be ready to quickly recognize and deal with. CASE SUMMARY: A 75-year-old lady with uncontrolled stable angina underwent percutaneous treatment of a chronically occluded right coronary artery. After balloon angioplasty and stenting, she developed a severe hypotension, refractory to fluid resuscitation and vasopressors. Computerized tomography scan demonstrated an intramural haematoma (IMH) of the right atrioventricular groove resulting in life-threatening pseudotamponade (or dry tamponade), as further confirmed by cardiac magnetic resonance imaging (MRI). The decision was for conservative management and haemodynamic support by intra-aortic balloon pump. Clinically, the patient improved and was discharged a few days later. Follow-up MRI confirmed resolution of the IMH. DISCUSSION: Severe hypotension during percutaneous treatment of chronically occluded coronary arteries may be related to various causes. Differential diagnosis is thus important in this setting and should include IMH, a rare but potentially fatal complication as it may cause compression of cardiac chambers and lead to pseudotamponade. A high index of suspicion is required to diagnose IMH but there are no clear guidelines for management of such cases.

Effect of hemorheological parameters on myocardial injury after primary or elective percutaneous coronary intervention.

BACKGROUND: Abnormal blood viscosity favors atherosclerosis owing to endothelial dysfunction and changes in shear stress. Its effect on coronary microvasculature during percutaneous coronary intervention (PCI) is still unknown. We aimed to investigate the role of hemorheological parameters in the incidence of microvascular obstruction (MVO) and the periprocedural necrosis after primary or elective PCI, and secondarily, we evaluated their prognostic significance. MATERIALS AND METHODS: We enrolled 25 patients with ST-elevation myocardial infarction (STEMI), 30 patients with non-ST-elevation myocardial infarction (NSTEMI), and 30 patients with stable angina (SA) undergoing PCI. MVO in patients with STEMI and periprocedural necrosis in patients with NSTEMI and those with SA were assessed using angiographic/electrocardiographic and laboratory methods, respectively. Hemorheological profile included blood viscosity (η) at shear rates 200 s and 1 s, the erythrocyte aggregation index (η1/η200), and plasma viscosity. Major adverse cardiovascular events occurrence was evaluated at follow-up. RESULTS: Patients with STEMI experiencing angiographic MVO (28%) had higher η200 (5.42±1.28 vs. 3.98±1.22 mPa[BULLET OPERATOR]s; P=0.015). Similarly, patients with STEMI experiencing electrocardiographic MVO (56%) had higher η200 (4.58±0.36 vs. 3.94±0.19 mPa[BULLET OPERATOR]s; P<0.001). Among patients with SA and patients with NSTEMI, those experiencing periprocedural necrosis (23.3%) had higher η200 (5.30±0.86 vs. 4.37±0.88 mPa[BULLET OPERATOR]s; P=0.001), η1 (19.52±9.62 vs. 13.29±7.65 mPa[BULLET OPERATOR]s; P=0.015) and η1/η200 values (3.64±1.50 vs. 2.72±0.92; P=0.007). These significant differences were maintained after adjustment for age, sex, and cardiovascular risk factors. At follow-up (30±6 months), 25 (29.4%) patients presented major adverse cardiovascular events, and they had higher η200 (5.18±1.00 vs. 4.25±1.01 mPa[BULLET OPERATOR]s; P<0.001). CONCLUSION: In patients undergoing either urgent or elective PCI, hemorheological parameters might contribute to myocardial injury and, if furtherly confirmed, to an unfavorable outcome.

Endothelial dysfunction as predictor of angina recurrence after successful percutaneous coronary intervention using second generation drug eluting stents.

Background The role of endothelial dysfunction in predicting angina recurrence after percutaneous coronary intervention is unknown. Design We assessed the role of peripheral endothelial dysfunction measured by reactive-hyperaemia peripheral-artery tonometry (RH-PAT) in predicting recurrence of angina after percutaneous coronary intervention. Methods We enrolled consecutive patients undergoing percutaneous coronary intervention with second-generation drug-eluting stents. RH-PAT was measured at discharge. The endpoint was repeated coronary angiography for angina recurrence and/or evidence of myocardial ischaemia at follow-up. Patients with in-stent restenosis and/or significant de novo stenosis were defined as having angina with obstructed coronary arteries (AOCA); all other patients as having angina with non-obstructed coronary arteries (ANOCA). Results Among 100 patients (mean age 66.7 ± 10.4 years, 80 (80.0%) male, median follow-up 16 (3-20) months), AOCA occurred in 14 patients (14%), ANOCA in nine patients (9%). Repeated coronary angiography occurred more frequently among patients in the lower RH-PAT index tertile compared with middle and upper tertiles (14 (41.2%) vs. 6 (18.2%) vs. 3 (9.1%), p = 0.006, respectively). ANOCA was more frequent in the lower RH-PAT index tertile compared with middle and upper tertiles. In the multivariate regression analysis, the RH-PAT index only predicted angina recurrence. The receiver operating characteristic curve of the RH-PAT index to predict the angina recurrence demonstrated an area under the curve of 0.79 (95% confidence interval: 0.69-0.89; p < 0.001), with a cut-off value of 1.705, having sensitivity 74% and specificity 70%. Conclusions Non-invasive assessment of peripheral endothelial dysfunction using RH-PAT might help in the prediction of recurrent angina after percutaneous coronary intervention, thus identifying patients who may need more intense pharmacological treatment and risk factor control.

Perilipin 2 levels are increased in patients with in-stent neoatherosclerosis: A clue to mechanisms of accelerated plaque formation after drug-eluting stent implantation.

BACKGROUND: Perilipin 2 (PLIN2) is a protein that potentially facilitates atherogenesis in native coronary arteries or arteries with an implanted drug-eluting stent (DES). The aim of the study was to determine PLIN2 protein levels in peripheral monocytes of enrolled subjects and compare them between patients with native coronary artery disease (CAD) and those with an in-stent restenosis (ISR) due to neoatherosclerosis occurring >1 year after DES implantation. METHODS: Forty-two patients were prospectively enrolled in the study in 3:1 fashion and underwent coronary catheterization. Both groups were angiographically matched for CAD burden with respect to the number of diseased vessels. Neoatherosclerosis was determined by intracoronary optical coherence tomography (OCT) among patients with ISR. RESULTS: Patients with ISR due to neoatherosclerosis had significantly higher PLIN2 protein levels in peripheral blood monocytes compared to patients with native CAD (342.47 ±â€¯75.63[SE] versus 119.51 ±â€¯20.95, p < 0.001). PLIN2 protein levels did not significantly differ between unstable and stable disease phenotype (125.59 ±â€¯131.02 vs. 146.14 ±â€¯111.87, p = 0.109). CONCLUSIONS: In this explorative study, PLIN2 protein levels are significantly increased in patients with neoatherosclerosis, irrespective of clinical presentation, implicating that it might play a pathogenetic role in accelerated atherosclerosis after DES implantation. Further larger clinical studies are warranted to confirm these initial findings.

Ivabradine in acute coronary syndromes: Protection beyond heart rate lowering.

Ivabradine is a heart rate reducing agent that exhibits anti-ischemic effects through the inhibition of funny electrical current in the sinus node resulting in heart rate reduction, thus enabling longer diastolic perfusion time, and reduced myocardial oxygen consumption without detrimental changes in arterial blood pressure, coronary vasomotion, and ventricular contractility. The current guideline-based clinical use of Ivabradine is reserved for patients with stable angina pectoris who cannot tolerate or whose symptoms are inadequately controlled with beta blockers. In patients with chronic heart failure and reduced ejection fraction, Ivabradine has demonstrated beneficial effects in improving clinical outcomes when added to conventional therapy. However, the role of Ivabradine in acute coronary syndromes has not been established. Based on the results from some relevant preclinical studies and a limited amount of clinical data that were reported recently, the role of Ivabradine in acute ischemic events warrants further investigation. The aim of this review is to provide an overview of the available literature on the potential role of Ivabradine in the clinical context of acute coronary syndromes.

Clinical outcome and correlates of coronary microvascular obstruction in latecomers after acute myocardial infarction.

AIMS: Microvascular obstruction (MVO) is associated with a worse prognosis in patients with ST-elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI). However, data about incidence, clinical outcome and correlates of MVO in latecomers after STEMI are still lacking. METHODS: We prospectively enrolled consecutive patients that were latecomers after STEMI (symptoms onset >12h) undergoing PCI. We performed an angiographic analysis to assess the occurrence of MVO [defined as TIMI flow grade ≤2 or 3 with a myocardial blush grade <2]. Moreover, we performed a clinical and echocardiographic follow-up to assess the occurrence of major adverse cardiovascular events (MACE), defined as the composite of cardiac death, myocardial infarction and rehospitalization for heart failure, and to evaluate left ventricle remodelling. RESULTS: Seventy-eight patients were enrolled [mean age 67.58±11.72years, 57 (73%) male; mean time of symptom onset 23.14±16.06h] with a mean follow-up time of 29.7±14.1months. MVO occurred in 39 (50%) patients. Patients with MVO had a higher rate of MACE [18 (46%) vs. 3 (8%), p<0.001] and LV remodelling [25 (64%) vs. 6 (15%), p<0.001] compared with patients without MVO. By multivariable Cox regression MVO and left anterior descending artery were independent predictors of MACE. CONCLUSIONS: Latecomers after STEMI have a high risk to develop MVO that is related to an adverse prognosis. Appropriate management and follow-up strategies should be implemented in such high-risk patients group.