No-reflow phenomenon during percutaneous coronary intervention in a patient with polycythemia vera: A case report.

RATIONALE: Acute myocardial infarction is the leading cause of mortality and morbidity in a patient with polycythemia vera (PV). However, the benefit of various percutaneous coronary intervention (PCI) technique on the patient with PV is relatively unexplored. PATIENT CONCERN: A 46-year-old woman presented to the primary hospital complained about new-onset typical chest pain. Echocardiography examination showed inferior ST-elevation myocardial infarction (STEMIs) and increased cardiac markers. Complete blood count showed elevated hemoglobin, white blood cell, and platelet. DIAGNOSIS: Coronary angiography revealed simultaneous total occlusion at proximal right coronary artery (RCA) and also at proximal left anterior descending (LAD) artery. Elevated hemoglobin and hematocrit with JAK2 mutation establish the diagnosis of PV. INTERVENTIONS: We performed multi-vessel primary PCI by using direct stenting in RCA and aspiration thrombectomy in LAD after failed with balloon dilatation and direct stenting method. This procedure resulted in thrombolysis in myocardial infarction (TIMI)-3 flow in both coronary arteries. However, the no-reflow phenomenon occurred in the LAD, followed by ventricular fibrillation. After several attempts of resuscitation, thrombus aspiration, and low-dose intracoronary thrombolysis, the patient was returned to spontaneous circulation. The patient then received dual antiplatelet and cytoreductive therapy. OUTCOMES: The patient clinical condition and laboratory finding were improved, and the patient was discharged on the 7th day after PCI. LESSONS: Cardiologist should be aware of the no-reflow phenomenon risk in the patient with PV and STEMI. Direct stenting, intracoronary thrombectomy, and thrombolysis are preferable instead of balloon dilatation for PCI technique in this patient.

Serum magnesium concentration may predict no-reflow phenomenon in primary angioplasty for ST-elevation myocardial infarction.

No-reflow phenomenon is a serious complication of percutaneous coronary intervention. Magnesium may play a role in pathogenesis of no-reflow phenomenon since it interacts with processes like platelet inhibition and endothelial-dependent vasodilatation. Relationship of serum magnesium concentration at admission and angiographic no-reflow phenomenon in ST elevation myocardial infarction patients undergoing primary percutaneous coronary intervention is investigated in the present study. A total of 2.248 consecutive patients with ST elevation myocardial infarction who underwent primary percutaneous coronary intervention were analyzed. After reopening of the infarct related artery, a TIMI flow rate ≤ 2 was defined as no-reflow. No-reflow phenomenon developed in 386 (17.1 %) patients. Serum magnesium concentration was significantly lower in no-reflow group (1.87 ± 0.25 vs. 2.07 ± 0.33 mg/dL, p<0.001). ROC curve analysis showed that Mg at a cut-point of 1.92 has 71.4% sensitivity and 75.2% specificity in detecting no-reflow phenomenon. In multivariate logistic regression analysis, age, serum magnesium concentration, and stent length were found as independent predictors of no-reflow phenomenon. Serum magnesium concentration is associated with no-reflow phenomenon in ST elevation myocardial infarction patients who underwent primary PCI.

Different inflammatory profile in young and elderly STEMI patients undergoing primary percutaneous coronary intervention (PPCI): Its influence on no-reflow and mortality.

BACKGROUND: Coronary no-reflow phenomenon in ST-segment elevation myocardial infarction (STEMI) is associated with a poor clinical prognosis. Although its pathophysiology is not fully elucidated, a deregulated systemic inflammatory response plays an important role. Specifically, the relationship between age-associated differences in inflammatory markers and either no-reflow or mortality in STEMI patients undergoing primary percutaneous coronary intervention (pPCI) has never been investigated. METHODS AND RESULTS: We retrospectively enrolled 625 consecutive STEMI patients undergoing pPCI for whom a complete laboratory inflammatory pattern was available. Routinely blood measured laboratory parameters were collected at the moment of admission. No reflow was defined as Thrombolysis in Myocardial Infarction (TIMI) flow-grade lower than 3. The population was divided into two groups using a cut-off centered at 65 years. Compared to younger patients, elderly patients had higher mean values of fibrinogen, brain natriuretic peptide (BNP), leukocytes, neutrophil-to-lymphocyte ratio (NLR), C reactive protein/albumin ratio (CAR). Conversely, lymphocyte count and albumin levels were higher in young patients. In elderly patients, the values of NLR, CAR as well as leukocytes, fibrinogen and neutrophils were associated with no-reflow, while in young patients only BNP value was associated. At multivariate Cox regression analysis, only BNP and NLR resulted as independent predictors of all-cause mortality in the whole population and in elderly patients. CONCLUSIONS: Elderly STEMI patients on admission had a higher acute pro-inflammatory profile than young patients, associated to coronary no-reflow and mortality outcome. These results suggest that a different therapeutic approach between elderly and young STEMI patients should be agreed.

Intracoronary Nicorandil and the Prevention of the No-Reflow Phenomenon During Primary Percutaneous Coronary Intervention in Patients with Acute ST-Segment Elevation Myocardial Infarction.

BACKGROUND This study aimed to investigate intracoronary nicorandil treatment on the no-reflow phenomenon (NRP) during primary percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI) and to compare nicorandil with sodium nitroprusside. MATERIAL AND METHODS Patients with sustained acute STEMI who underwent primary PCI (N=120) were randomly assigned to three groups: the nicorandil-treated group (N=40) had 2 mg of nicorandil injected into the coronary artery at 2 mm beyond the occlusion with balloon pre-dilation; the sodium nitroprusside-treated group (N=40) underwent the same procedure, but with 200 µg of sodium nitroprusside; the control group (N=40) received PCI and balloon pre-dilation only. Coronary angiography, incidence of NRP, hypotensive episodes, ST-segment resolution (STR) rate, levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), wall motion score index (WMSI), and left ventricular ejection fraction (LVEF) were measured before and after primary PCI. Major adverse cardiovascular events (MACEs) post-PCI and at three-month follow-up were recorded. RESULTS Patients in the sodium nitroprusside and nicorandil groups had significantly improved thrombolysis in myocardial infarction (TIMI) scores, TIMI myocardial perfusion grade (TMPG), and ST-segment elevation resolution (STR) (P<0.05), and a significantly lower incidence of NRP (P=0.013). The incidence of intraoperative hypotension in the sodium nitroprusside group was significantly greater than the nicorandil and control groups (P=0.035). CONCLUSIONS Patients with sustained acute STEMI undergoing primary PCI, treated with intracoronary nicorandil had a reduced incidence of the NRP, improved myocardial perfusion and cardiac function.

The role of SCUBE1 in the pathogenesis of no-reflow phenomenon presenting with ST segment elevation myocardial infarction.

OBJECTIVE: SCUBE1 [signal peptide-CUB (complement C1r/C1 s)-EGF (epidermal growth factor)-like domain-containing protein 1] might function as a novel platelet-endothelial adhesion molecule and play pathological roles in cardiovascular biology. Acute myocardial infarction is one of the most common causes of death in modern society. The concept of "no reflow" (NR) refers to a state of myocardial tissue hypoperfusion in the presence of a patent epicardial coronary artery. The main mechanisms of this phenomenon are thought to be high platelet activity and much thrombus burden. So, we researched the role of SCUBE1 in the pathogenesis of NR. METHODS: A total of 142 patients with ST elevation myocardial infarction (STEMI) (n=42 with NR and n=100 without NR) and 50 healthy individuals were prospectively case-control recruited between March 2015 and October 2016 from our outpatient clinics of cardiology department. Patients with STEMI were diagnosed according to American Heart Association (AHA) guideline for the management of STEMI. RESULTS: The mean SCUBE1 levels of the control subjects were 34±8.4 ng/mL, the mean SCUBE1 levels of patients with STEMI who were treated successfully with primary percutaneous coronary intervention (PCI) were 51±6.2, and the mean SCUBE1 levels of patients with STEMI who had NR phenomenon after primary PCI procedure were 97.2±8.9 ng/mL. CONCLUSION: In our opinion, SCUBE1 might contribute to NR phenomenon via thrombus activation and aggregation. The pathophysiology of NR phenomenon is unclear. The present study is the first clinical study that demonstrated that serum SCUBE1 level was significantly higher in patients with NR and that serum SCUBE1 was an independent predictor for the presence of NR in our study population.

The relation between monocyte to HDL ratio and no-reflow phenomenon in the patients with acute ST-segment elevation myocardial infarction.

BACKGROUND: No-reflow phenomenon is a prognostic value in ST-segment elevation myocardial infarction (STEMI). Monocyte to high density lipoprotein ratio (MHR) has recently emerged as a marker of inflammation and oxidative stress in the cardiovascular disease. PURPOSE: In this study, we aimed to investigate the relation between MHR and no-reflow phenomenon in patients with STEMI undergoing primary percutaneous coronary intervention (pPCI). MATERIAL AND METHODS: A total of 600 patients with STEMI (470 men; mean age, 62 ± 12 years) admitted within 12 hours from symptom onset were included into this study. Patients were classified into 2 groups based on postintervention Thrombolysis in Myocardial Infarction (TIMI) flow grade: no-reflow-TIMI flow grade 0, 1, or 2 (group 1); angiographic success-TIMI flow grade 3 (group 2). RESULTS: According to admission whole-blood cell count results, the patients in the no-reflow group had significantly higher monocyte count and MHR values when compared with those of the reflow patients. After multivariate backward logistic regression, MHR remained independent predictors of no reflow after pPCI. Adjusted odds ratios were calculated as 1.09 for MHR (P< .001; confidence interval [CI], 1.07-1.12). Receiver operating characteristic curve analysis suggested that the optimum MHR level cutoff point for patients with no-reflow was 22.5, with a sensitivity and specificity of 70.2% and 73.3%, respectively (area under curve, 0.768; 95% CI, 0.725-0.811). CONCLUSION: In conclusion, MHR levels are one of the independent predictors of no reflow in patients with STEMI after pPCI.

Clinical significance of no-reflow in different stages of primary angioplasty among patients with acute myocardial infarctions.

BACKGROUND: The coronary no-reflow (NR) phenomenon, which is associated with poor clinical outcomes, is usually referred to as a post-percutaneous coronary intervention (PCI) state. NR can occur in different stages of the PCI procedure, not only including the post-stenting stage, but from balloon pre-dilation to pre-stenting. The clinical significance of NR in the different stages of the PCI procedure is unclear. The purpose of the current study was to analyze the clinical and angiographic characteristics, the prognosis for NR patients in the aforementioned two stages and to determine the predictors of NR in the early stage. METHODS: Between January 2009 and December 2013, a total of 420 consecutive patients with ST-segment elevation myocardial infarction (STEMI) underwent primary PCI. Sixty-three patients (15%) with NR constituted the study population. The patients were divided into an early NR group and a subsequent NR group. The clinical and angiographic findings were compared between the two groups. Multivariate logistic regression was used to determine the predictors for early NR. The long-term clinical outcomes after PCI were analyzed. RESULTS: Regarding the baseline characteristics, we identified that the early NR group had statistically significant effects on the higher percentage of diabetes mellitus (42.9% vs. 20%), lower admission systolic blood pressure (SBP) (102.2 ± 8.3 mmHg vs. 110.5 ± 7.6 mmHg), higher percentage of Killip classification III (71.4% vs. 45.7%,) and longer reperfusion time (7.1 ± 2.3 h vs. 5.88 ± 2.2 h) compared to the subsequent NR group.There were significant differences between the two groups with respect to the percentage of initial thrombolysis in myocardial infarction (TIMI) flow 0/1 (64.3% vs. 37.1%), target lesion length (31.4 ± 13.6 mm vs. 20.5 ± 17.3 mm) and thrombus score ⩾ 4 (67.9% vs. 42.9%; p < 0.05 for all). Multiple stepwise logistic regression analysis indicated that an admission SBP < 100 mmHg (OR = 4.580; 95% CI = 1.385-15.150; p = 0.0130), reperfusion time ⩾ 6 h (OR = 4.978; 95% CI = 1.468-16.882; p = 0.010) and a thrombus score ⩾ 4 (OR = 2.708; 95% CI = 0.833-8.799; p = 0.008) were the independent determinants of the early NR. During a 1-year follow-up, the all-cause mortality and overall major adverse cardiac events (MACEs) in the early NR group occurred significantly more often than in the subsequent NR group (28.6% vs. 5.7% and 35.7% vs. 14.3%, respectively, p ITALIC! <0.05). The early NR group had a lower left ventricular ejection fraction (LVEF) (42.5 ± 4.7 vs. 47.8 ± 3.5, p ITALIC! < 0.001) and a larger left ventricular end diastolic diameter (LVEDD) (56.0 ± 4.0 vs. 51.5 ± 4.7, p = 0.001) at the end of the follow-up. CONCLUSION: Early NR patients during primary PCI have more severe baseline clinical and angiographic characteristics, as well as a poorer long-term prognosis.

The no-reflow phenomenon: State of the art.

Primary percutaneous coronary intervention (PCI) is the best available reperfusion strategy for acute ST-segment elevation myocardial infarction (STEMI), with nearly 95% of occluded coronary vessels being reopened in this setting. Despite re-establishing epicardial coronary vessel patency, primary PCI may fail to restore optimal myocardial reperfusion within the myocardial tissue, a failure at the microvascular level known as no-reflow (NR). NR has been reported to occur in up to 60% of STEMI patients with optimal coronary vessel reperfusion. When it does occur, it significantly attenuates the beneficial effect of reperfusion therapy, leading to poor outcomes. The pathophysiology of NR is complex and incompletely understood. Many phenomena are known to contribute to NR, including leukocyte infiltration, vasoconstriction, activation of inflammatory pathways and cellular oedema. Vascular damage and haemorrhage may also play important roles in the establishment of NR. In this review, we describe the pathophysiological mechanisms of NR and the tools available for diagnosing it. We also describe the microvasculature and the endothelial mechanisms involved in NR, which may provide relevant therapeutic targets for reducing NR and improving the prognosis for patients.

The Utility of the Platelet-Lymphocyte Ratio for Predicting No Reflow in Patients With ST-Segment Elevation Myocardial Infarction.

The aim of the study was to evaluate the utility of the preprocedural platelet-lymphocyte ratio (PLR) for predicting no reflow in patients undergoing primary percutaneous intervention (PCI) for the treatment of ST-segment elevation myocardial infarction. The thrombolysis in myocardial infarction (TIMI) flow grades of 287 patients treated with primary PCI were assessed retrospectively. Patients were divided into 3 tertiles based upon preprocedural PLR. Pre- and postprocedural TIMI flow grades were evaluated. No reflow developed in 6, 14, and 43 patients in the lower, middle, and higher tertiles, respectively (P < .001). After multivariate analysis, PLR remained a significant predictor of no reflow together with neutrophil-lymphocyte ratio (NLR). A cutoff value of 160 for PLR and 5.9 for NLR predicted no reflow with sensitivities and specificities of 75% and 71% and 74% and 70%, respectively. In conclusion, high preprocedural PLR and NLR levels are significant and independent predictors of no reflow in patients undergoing primary PCI.

Successful prevention of no-reflow phenomenon in a high-risk patient using excimer laser coronary atherectomy.

During the treatment of coronary artery disease, the no-reflow phenomenon can lead to severe impairment of viable cardiac muscle and all necessary measures should be taken to prevent it. Excimer laser coronary atherectomy (ELCA) may be indicated for lesions with a large thrombus burden due to potential to ablate thrombi and necrotic plaques. However, there are few reports on the use of ELCA for the prevention of distal embolism. Here, we report a case involving severe left ventricular dysfunction with a previous extensive anterior infarction, where ELCA was used in the right coronary artery to prevent the no-reflow phenomenon.

Long-term follow-up of attenuated plaques in patients with acute myocardial infarction: an intravascular ultrasound substudy of the HORIZONS-AMI trial.

BACKGROUND: Intravascular ultrasound (IVUS)-attenuated plaque is characterized by absence of ultrasound signal behind hypoehcoic plaque and is seen almost exclusively in acute coronary syndromes. METHODS AND RESULTS: We analyzed poststenting and 13-month follow-up IVUS in 186 patients (195 lesions) with acute myocardial infarction who underwent primary percutaneous coronary intervention. The primary prespecified IVUS end point was the in-stent percent net volume obstruction at follow-up. Overall, 70.3% of lesions contained attenuated plaques at baseline. During follow-up, attenuation scores decreased significantly, behind paclitaxel-eluting stents (PES) (14.1 [11.9, 16.3] to 7.7 [5.4, 9.9], P<0.0001), behind bare metal stents (BMS) (18.5 [13.2, 23.8] to 12.0 [6.7, 17.3], P<0.0001), and within distal references (3.1 [1.1, 5.1] to 2.2 [0.2, 4.1], P=0.02). There was a greater calcium increase in attenuated than nonattenuated plaques in both PES (Δcalcium score of 4.4 [3.3, 5.5] versus 1.6 [0.9, 2.3], P<0.0001) and BMS (Δcalcium score of 4.1[2.3, 5.9] versus 1.0 [0.3, 1.7], P=0.001). PES implantation into attenuated plaques was particularly associated with late acquired stent malapposition (36.8% versus 15.4% compared with nonattenuated plaques treated with PES, P=0.03). Changes in attenuation scores correlated with changes in calcium scores both in PES (Pearson correlation coefficient=-0.456, P<0.0001] and BMS sites (Pearson correlation coefficient=-0.450, P=0.0006). In 3 years of follow-up, target lesion revascularization was significantly less in patients with attenuated plaque at baseline (6.0% versus 17.4% in patient without attenuated plaques, P=0.019). CONCLUSIONS: Attenuated plaques evolved into calcified plaques after stent implantation. Attenuated plaque is associated with late acquired stent malapposition and related less target lesion revascularization (consistent with less neointimal hyperplasia), especially after PES implantation in patients with acute myocardial infarction. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00433966.

Prevention and treatment of no-reflow.

No-reflow phenomenon occurs frequently during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction and it has a strong negative impact on outcome. Prevention of no-reflow has to be defined as any attempt to prevent its occurrence prior to or during the recanalization procedure. Strategy of prevention may be pharmacological or device based. Among drugs, abciximab is indicated by European Society of Cardiology (ESC) guidelines for prevention of no-reflow (class of recommendation IIa and level of evidence B). Among devices used for preventing no-reflow, manual thrombus aspiration only has been associated with a reduction of no-reflow and lower mortality at follow-up and is currently indicated in the ESC guidelines (class IIa of recommendation and level B of evidence). Treatment of no-reflow has to be defined as any attempt to treat its occurrence after coronary recanalization. Strategy of treatment may be pharmacological or device based. Adenosine and verapamil are indicated by ESC guidelines for treatment of no-reflow (class of recommendation IIb and level of evidence B and C, respectively). Serial assessment of myocardial perfusion showed that in up to 50% of patients no-reflow is spontaneously reversible. This finding may open new scenarios, as mechanisms of reversibility may become future therapeutic targets.