Comparison of Outcomes in Patients With COVID-19 and Thrombosis Versus Those Without Thrombosis.

The occurrence of venous thromboembolisms in patients with COVID-19 has been established. We sought to evaluate the clinical impact of thrombosis in patients with COVID-19 over the span of the pandemic to date. We analyzed patients with COVID-19 with a diagnosis of thrombosis who presented to the MedStar Health system (11 hospitals in Washington, District of Columbia, and Maryland) during the pandemic (March 1, 2020, to March 31, 2021). We compared the clinical course and outcomes based on the presence or absence of thrombosis and then, specifically, the presence of cardiac thrombosis. The cohort included 11,537 patients who were admitted for COVID-19. Of these patients, 1,248 had noncardiac thrombotic events and 1,009 had cardiac thrombosis (myocardial infarction) during their hospital admission. Of the noncardiac thrombotic events, 562 (45.0%) were pulmonary embolisms, 480 (38.5%) were deep venous thromboembolisms, and 347 (27.8%) were strokes. In the thrombosis arm, the mean age of the cohort was 64.5 ± 15.3 years, 53.3% were men, and the majority were African-American (64.9%). Patients with thrombosis tended to be older with more co-morbidities. The in-hospital mortality rate was significantly higher (16.0%) in patients with COVID-19 with concomitant non-cardiac thrombosis than in those without thrombosis (7.9%, p <0.001) but lower than in patients with COVID-19 with cardiac thrombosis (24.7%, p <0.001). In conclusion, patients with COVID-19 with thrombosis, especially cardiac thrombosis, are at higher risk for in-hospital mortality. However, this prognosis is not as grim as for patients with COVID-19 and cardiac thrombosis. Efforts should be focused on early recognition, evaluation, and intensifying antithrombotic management for these patients.

Cardiovascular and Cerebrovascular Complications With COVID-19.

The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 has affected the health of people across the globe. Cardiovascular diseases (CVDs) have a significant relationship with COVID-19, both as a risk factor and prognostic indicator, and as a complication of the disease itself. In addition to predisposing to CVD complications, the ongoing pandemic has severely affected the delivery of timely and appropriate care for cardiovascular conditions resulting in increased mortality. The etiology behind the cardiac injury associated with severe acute respiratory syndrome coronavirus-2 is likely varied, including coronary artery disease, microvascular thrombosis, myocarditis, and stress cardiomyopathy. Further large-scale investigations are needed to better determine the underlying mechanism of myocardial infarction and other cardiac injury in COVID-19 patients and to determine the incidence of each type of cardiac injury in this patient population. Telemedicine and remote monitoring technologies can play an important role in optimizing outcomes in patients with established CVD. In this article, we summarize the various impacts that COVID-19 has on the cardiovascular system, including myocardial infarction, myocarditis, stress cardiomyopathy, thrombosis, and stroke.

Provisional Stenting for the Treatment of Bifurcation Lesions: In Vitro Insights.

Provisional stenting is considered the gold standard approach for most bifurcation lesions, but the benefit of routine side branch (SB) strut dilatation has not been fully elucidated. A benchtop model was used to determine the benefits of routine side branch (SB) dilatation techniques on strut apposition, acute thrombogenicity, and flow disruption. Three different provisional bifurcation techniques were compared: no SB dilatation "keep it open" method (KIO), sequential balloon dilatation (SBD), and kissing balloon inflation (KBI). Stents were deployed in a silicon bifurcation model and perfused with blood at a flow rate of 200 ml/min for 60 min. Optical coherence tomography (OCT) pullbacks were obtained before and after flow perfusion to conduct strut analysis and acute thrombus measurement respectively. Computational fluid dynamics (CFD) models were created using OCT pullbacks and simulated based on experimental conditions to analyze flow disruption. The strut analysis showed that KBI had the lowest percentage of floating (10.6 ± 2.3%) (p = 0.0004) and malapposed (41.2 ± 8.5%) struts (p = 0.59), followed by SBD and then KIO. This correlated to KBI having the lowest amount of thrombus formed at the SB, followed by SBD, with KIO being the most thrombogenic (KBI: 0.84 ± 0.22mm2, SBD: 1.17 ± 0.25mm2, KIO: 1.31 ± 0.36mm2, p = 0.18). CFD models also predicted a similar trend, with KBI having the lowest amount of area of high shear rate as well as flow recirculation. Based on this benchtop model, SB intervention strategies demonstrated a reduction in number of struts and resulting thrombogenicity at the bifurcation ostia. Graphical abstract.

Anatomic and Flow Characteristics of Left Anterior Descending Coronary Artery Angiographic Stenoses Predisposing to Myocardial Infarction.

The impact of the anatomic characteristics of coronary stenoses on the development of future coronary thrombosis has been controversial. This study aimed at identifying the anatomic and flow characteristics of left anterior descending (LAD) coronary artery stenoses that predispose to myocardial infarction, by examining angiograms obtained before the index event. We identified 90 patients with anterior ST-elevation myocardial infarction (STEMI) for whom coronary angiograms and their reconstruction in the three-dimensional space were available at 6 to 12 months before the STEMI, and at the revascularization procedure. The majority of culprit lesions responsible for STEMI occurred between 20 and 40 mm from the LAD ostium, whereas the majority of stable lesions not associated with STEMI were found in distances >60 mm (p < 0.001). Culprit lesions were significantly more stenosed (diameter stenosis 68.6 ± 14.2% vs 44.0 ± 10.4%, p < 0.001), and significantly longer than stable ones (15.3 ± 5.4 mm vs 9.2 ± 2.5 mm, p < 0.001). Bifurcations at culprit lesions were significantly more frequent (88.8%) compared with stable lesions (34.4%, p < 0.001). Computational fluid dynamics simulations demonstrated that hemodynamic conditions in the vicinity of culprit lesions promote coronary thrombosis due to flow recirculation. A multiple logistic regression model with diameter stenosis, lesion length, distance from the LAD ostium, distance from bifurcation, and lesion symmetry, showed excellent accuracy in predicting the development of a culprit lesion (AUC: 0.993 [95% CI: 0.969 to 1.000], p < 0.0001). In conclusion, specific anatomic and hemodynamic characteristics of LAD stenoses identified on coronary angiograms may assist risk stratification of patients by predicting sites of future myocardial infarction.

Fisiopatología de la enfermedad cardiovascular en pacientes con COVID-19. Isquemia, trombosis y disfunción cardiaca / Physiopathology of cardiovascular disease in patients with COVID-19. Ischemia, thrombosis and heart failure

Las complicaciones cardiovasculares tienen una alta prevalencia en los pacientes con COVID-19 y son motivo frecuente de hospitalización, mortalidad y secuelas. En está revisión se describen los principales mecanismos fisiopatológicos implicados en la aparición de estas complicaciones. Tras la viremia inicial, se produce una infiltración y reproducción en los pulmónes, con activación del sistema inmunitario, liberación de citocinas y generación de un estado proinflamatorio con sepsis y fallo multiorgánico. El daño miocárdico puede deberse a una afección viral directa con respuesta inflamatoria local, o indirectamente a una inflamación sistémica inapropiada con marcada liberación de citocinas. Además, se genera un estado protrombótico que, junto con la afección viral vascular, pueden desencadenar eventos trombóticos e isquémicos secundarios a daño microvascular o inestabilización de placas de ateroma previas. Son necesarios nuevos estudios para esclarecer la fisiopatología tras estos eventos cardiovasculares y contribuir al desarrollo de nuevos tratamientos efectivos

Cardiovascular complications are highly prevalent in patients with COVID-19 and frequently lead to hospitalization, death and long-term morbidity. This article describes the principle pathophysiological mechanisms involved in the development of these complications. After the initial viremia, viralinvasión and replication occurs in the lungs, accompanied by immune system activation, cytokine release and the induction of a proinflammatory state, with sepsis and multiorgan failure. Myocardial injury could be due to the direct effect of viralinvasión and a local inflammatory response or to the indirect effect of inappropriate systemic inflammation involving a cytokine storm. Furthermore, the development of a prothrombotic state, together with vascular disease due to the virus, could trigger ischemic and thrombotic events secondary to microvascular damage or to the destabilization of pre-existing atheromatous plaque. New research is needed to reveal the pathophysiological mechanisms underlying these cardiovascular events and to support the development of effective new treatments

Role of Occlusion Position in Coronary Artery Fistulas with Terminal Aneurysms: A Hemodynamic Perspective.

PURPOSE: Thrombosis within an occluded coronary arterial fistula (CAF) may cause angina and myocardial infarction. This study aims to estimate how the occlusion position of CAFs with terminal aneurysm affects the risk stratification of thrombosis in the fistula in terms of hemodynamics. METHODS: Twelve CAF models were reconstructed based on patient-specific computed tomography angiogram (CTA) images. They were classified into three groups: preserved group (untreated fistula), aneurysm-reserved group (occluded at the fistula terminal: distal occlusion) and aneurysm-removed group (occluded before the aneurysm: proximal occlusion). Hemodynamics results were analyzed and compared with the clinical follow-up results. RESULTS: The results showed that: (1) Hemodynamic patterns within the fistula before and after treatment were significantly different among patients. (2) Aneurysm-removed occlusions showed better improvements with respect to the CAF blood-stealing phenomena. (3) Irrespective of whether aneurysms were removed or not, a disturbed flow pattern was observed. Areas having high OSI and low TAWSS were present in the post-occluded CAFs. The removal of the aneurysm, however, would alleviate the flow disturbance, and decrease the proportion of the area of OSI > 0.3. (4) The thrombosis region spotted in the follow-up patient CTAs was consistent with the computed high OSI area. CONCLUSIONS: A proximal occlusion, namely, removing the aneurysm of the CAF, may help in reducing the risk of thrombosis after surgery. However, follow-up studies with a larger cohort should be carried out to test and verify this speculation in the future.

A simple score to select patients for manual thrombectomy in emergent percutaneous coronary interventions: the DDTA score.

BACKGROUND: The objective of manual thrombectomy is the removal of occlusive thrombus to improve the results of primary angioplasty. The better understanding of the factors associated with successful manual thrombectomy may provide relevant information regarding thrombus formation and resolution. METHODS: Observational study of all consecutive patients remitted for emergent percutaneous coronary intervention (PCI) in a single centre. Successful manual thrombectomy was considered when TIMI 3 was achieved after using the device and a score to predict successful manual thrombectomy was designed. RESULTS: We included 618 patients, 65.1% treated with manual thrombectomy. No relevant differences in clinical features or time delays were observed between patients treated with vs. without manual thrombectomy, but manual thrombectomy treated patients received more often dual antiplatelet treatment (DAPT) before PCI. Final TIMI flow 3 was achieved in most patients and more frequently in manual thrombectomy treated patients (94.8 vs. 86.6%; P < 0.01). The successful manual thrombectomy rate was 81.3% and it was higher in patients pretreated with DAPT (89.0 vs. 73.3%; P < 0.01). The time delay to first medical contact was not related to the final TIMI 3, but it was significantly and negatively related to successful manual thrombectomy. According to the multivariate analysis, we designed the DDTA score: DAPT pretreatment (2), delay less than 2 h (3) or 2-4 h (2), TIMI flow improvement after wiring the lesion (2) and age less than 55 years (3). Patients with DDTA score at least 4 had lower no-reflow, mortality and major cardiovascular complications incidence. CONCLUSION: The DDTA score (DAPT pretreatment, time delays, TIMI flow improvement after wiring the lesion and age) identifies patients who benefit mostly from manual thrombectomy.

Effect of thrombus aspiration on microcirculatory resistance and ventricular function in patients with high thrombus burden.

BACKGROUND: Studies have not demonstrated consistent outcomes following thrombus aspiration in Primary Percutaneous Coronary Intervention (PPCI). We investigated the relationship between thrombus aspiration and microvascular obstruction as measured using Index of Microcirculatory Resistance (IMR) immediately following PPCI and Left Ventricle Function Improvement measured using Global Longitudinal Strain (GLS) six months following PPCI. Our aim is to determine microvascular obstruction and left ventricle function improvement six months following thrombus aspiration during PPCI. METHODS: This was a single-center, observational, prospective non-randomized study involving 45 patients with thrombus score 4-5 (defined as high thrombus burden) and Thrombolysis in Myocardial Infarction (TIMI) flow of 0-2 who subsequently underwent PPCI. Thrombus aspiration was conducted based on physician discretion. The IMR was measured immediately following the procedure. All patients underwent echocardiography to measure GLS at 24 h, 3 months and 6 months following PPCI. RESULTS: Thirty-three (73%) patients underwent thrombus aspiration during PPCI and twelve (27%) patients underwent the conventional PPCI. No significant difference in IMR was found between the group that underwent thrombus aspiration and the group that underwent conventional PCI (51.9 ± 41.5 vs 47.1 ± 35.6 p = 0.723). TIMI flow after PPCI was worse in thrombus aspiration group (OR 5.2 [1.2-23.2], p = 0.041). There was no difference in GLS between two groups at 6-month follow-up (- 13.0 ± 3.4 vs - 12.8 ± 4.6, p = 0.912). CONCLUSION: This study indicates no benefit of thrombus aspiration during PPCI in reducing either microvascular obstruction or left ventricular function at 6-month follow-up for patients with high thrombus burden. Nevertheless, further studies are required before definite conclusions can be made.

Role of endothelial dysfunction in determining angina after percutaneous coronary intervention: Learning from pathophysiology to optimize treatment.

Endothelial dysfunction (EnD) is a hallmark feature of coronary artery disease (CAD), representing the key early step of atherosclerotic plaque development and progression. Percutaneous coronary intervention (PCI) is performed daily worldwide to treat symptomatic CAD, however a consistent proportion of patients remain symptomatic for angina despite otherwise successful revascularization. EnD plays a central role in the mechanisms of post-PCI angina, as it is strictly associated with both structural and functional abnormalities in the coronary arteries that may persist, or even accentuate, following PCI. The assessment of endothelial function in patients undergoing PCI might help to identify those patients at higher risk of future cardiovascular events and recurrent/persistent angina who might therefore benefit more from an intensive treatment. In this review, we address the role of EnD in determining angina after PCI, discussing its pathophysiological mechanisms, diagnostic approaches and therapeutic perspectives.

Novel use of a stent graft for uncontrollable intraprocedural stent thrombosis in a patient with acute myocardial infarction.

We report the case of a patient who developed uncontrollable intraprocedural stent thrombosis (IPST) during an emergent percutaneous coronary intervention for acute myocardial infarction that was mitigated only by covering the culprit lesion with a stent graft. Although several factors can induce stent thrombosis, IPST was likely a result of intrastent plaque protrusion in this patient. This is the first case report on the use of stent graft implantation as an effective bailout procedure for uncontrolled IPST. The findings described in this case study warrant the adoption of stent grafts for the complete sealing of plaque protrusion in lesions.

Technical consideration in acute myocardial infarction with cardiogenic shock: A review of antithrombotic and PCI therapies.

In this review, we report a contemporary appraisal of the available evidence focusing on adjunctive antithrombotic therapy and technical aspects of percutaneous coronary interventions (PCI) in patients with acute myocardial infarction and cardiogenic shock (AMICS). Only few randomized trials have been conducted to evaluate the optimal arterial access choice, antithrombotic therapy, stent type, or the role of aspiration thrombectomy in this population. Observational data suggest that a transradial approach should be preferred for experienced operators, although knowledge and experience of transfemoral access is required to place any mechanical support device. In the absence of high-quality evidence to guide choice of the adjunctive antithrombotic drugs to support PCI in patients with AMICS, knowledge of the altered pharmacokinetics and pharmacodynamics in shock is required to inform decisions. Drug-eluting stents should be favored over bare-metal stents, and routine thrombectomy is not encouraged. Owing to the challenges inherent to the conduct of randomized trials in this acutely ill patient population, concerted multicenter, and international efforts are paramount to orchestrate the development of high-quality evidence to guide clinical practice.

Challenges associated with treatment of left internal mammary artery graft thrombosis.

Acute occlusion of the left internal mammary artery (LIMA) graft late after coronary artery bypass grafting surgery is a rare and potentially life-threatening complication. We describe a case of acute myocardial infarction 19 years after coronary artery bypass graft surgery due to acute occlusion of the distal anastomosis of a LIMA graft to the left anterior descending artery. Aspiration thrombectomy failed to remove the thrombus. Laser thrombectomy caused perforation. After drug-eluting and covered stent implantation, antegrade TIMI 3 flow was restored with an uneventful postprocedural course.

Impact of preprocedural TIMI flow on clinical outcome in low-risk patients with ST-elevation myocardial infarction: Results from the ATLANTIC study.

OBJECTIVES: This study sought to analyze the impact of the preprocedural thrombolysis in myocardial infarction (TIMI) flow on clinical outcome in patients with ST-elevation myocardial infarction (STEMI). BACKGROUND: Previous studies have shown that the TIMI flow 0/1 prior to primary percutaneous coronary intervention (PCI) is associated with a poor clinical outcome. However, it is unclear whether the same is true in patients with ongoing STEMI of less than 6 hr duration, rapid reperfusion, and modern guideline-adherent therapy. METHODS: The ATLANTIC study compared prehospital versus inhospital treatment with ticagrelor in patients with acute STEMI. For this analysis, patients were divided into three groups according to the preprocedural TIMI flow grade of the infarct vessel: TIMI 0/1, TIMI 2, and TIMI 3. RESULTS: From a total of 1,680 patients, 1,113 had TIMI 0/1, 279 TIMI 2, and 288 TIMI 3 flow before primary PCI. At 30 days, the composite ischemic endpoint (5.5, 2.9, and 2.1%, p < .05) and all-cause death (3.0, 1.4, and 2.1%, p = .30) were highest in patients with TIMI flow 0/1. After adjustment, preprocedural TIMI flow <3 (versus 3) was not an independent predictor of major adverse ischemic events within 30 days (odds ratio 1.89, 95% confidence interval 0.74-4.85). However, definite stent thrombosis occurred only in patients with initial TIMI flow 0/1 (1.0%). Among these patients, those with prehospital administration of ticagrelor were less often affected (0.3% vs. 1.3%, p < .05). CONCLUSION: In this post-hoc analysis, preprocedural TIMI flow was not independently associated with a higher rate of adverse ischemic events.

Computational fluid dynamic-derived wall shear stress of non-significant left main bifurcation disease may predict acute vessel thrombosis at 3-year follow-up.

Wall shear stress (WSS) plays a pivotal role on plaque progression in coronary artery disease. We assess the prognostic role of baseline mean WSS in developing a bifurcation-located myocardial infarction (B-MI) over the following 3 years in angiographically non-significant LM bifurcation disease. For this purpose, we retrospectively reviewed the procedural and medical records of consecutive patients evaluated in our center from 1st January 2014 to 1st January 2019 who had a non-significant LM bifurcation disease as evaluated at coronary computed tomography angiography (CCTA) and confirmed by coronary angiography. Each bifurcation model was reconstructed on the patient-specific geometries derived from the CCTA. The population was divided into two groups: patients with (n = 12) and without B-MI (n = 20) over the following 3 years. Both the mean WSSprox of each branch and the WSSentire_lesion of each vessel, adjusted for the respective mean lesions lengths and 3-dimensional percentage of stenosis (DS%), resulted in independent predictors of 3-year B-MI. Multivariate Cox-regression analysis confirmed that a baseline mean WSSentire_model ≥ 5.05 Pa (HR 1.98, 95% CI 1.83-2.10, p = 0.001) was a predictor of 3-year B-MI independently from the entire mean lesions lengths (HR 1.56. 95% CI 1.43.1.68, p = 0.002) and DS% (HR 1.26, 95% CI 1.18-1.37, p = 0.03). In conclusion, in patients with angiographically non-significant LM bifurcation disease, both the mean WSSprox of each branch and WSSentire_lesion of each stenotic vessel predicted the occurrence of B-MI over the following 3 years. Moreover, the WSSentire_bifurcation ≥ 5.05 Pa seems to be a predictor of 3-year B-MI independently from the DS% and lesions lengths.

Anatomical features and clinical outcome of a honeycomb-like structure in the coronary artery: reports from 16 consecutive patients.

BACKGROUND: Recanalization of thrombus in coronary artery tree is defined as a honeycomb-like structure. However, the anatomic features and appropriate treatment of honeycomb-like structure still remain largely unclear. METHODS AND RESULTS: Between 2014 July and 2017 December, 17 honeycomb-like structure in 16 patients based on optical coherence tomography and intravascular ultrasound were included. Fractional flow reserve was measured for patients who had thrombolysis in myocardial infarction flow grade 3. Angiographic and optical coherence tomography/intravascular ultrasound-derived variables were studied. Clinical events (until to 2018 December) were collected. Honeycomb-like structures mostly involved left anterior descending artery (68.8%) and localized at proximal-mid (88.2%) segment of vessels. Eight patients had a side branch ≥ 2 mm in diameter taking from honeycomb-like structure. Only one patient had a normal fractional flow reserve. Fifteen patients underwent implantation of a stent. Stent implantation was associated with side branch compromise or closure (4 in each). Of 4 patients with side branch closure, all had a creatine kinase myocardial band > 5 times increase in hospital, with 3 deaths and 1 target lesion revascularization during follow-up. CONCLUSIONS: Despite the presence of recanalization, most honeycomb-like structure lesion have a positive fractional flow reserve. Further study is required to address how to protect a large side branch taking from honeycomb-like structure.