MicroRNA-mediated vascular intercellular communication is altered in chronic kidney disease.

AIMS: Chronic kidney disease (CKD) is an independent risk factor for the development of coronary artery disease (CAD). For both, CKD and CAD, the intercellular transfer of microRNAs (miRs) through extracellular vesicles (EVs) is an important factor of disease development. Whether the combination of CAD and CKD affects endothelial function through cellular crosstalk of EV-incorporated miRs is still unknown. METHODS AND RESULTS: Out of 172 screened CAD patients, 31 patients with CAD + CKD were identified and matched with 31 CAD patients without CKD. Additionally, 13 controls without CAD and CKD were included. Large EVs from CAD + CKD patients contained significantly lower levels of the vasculo-protective miR-130a-3p and miR-126-3p compared to CAD patients and controls. Flow cytometric analysis of plasma-derived EVs revealed significantly higher numbers of endothelial cell-derived EVs in CAD and CAD + CKD patients compared to controls. EVs from CAD + CKD patients impaired target human coronary artery endothelial cell (HCAEC) proliferation upon incubation in vitro. Consistent with the clinical data, treatment with the uraemia toxin indoxyl sulfate (IS)-reduced miR-130a-3p levels in HCAEC-derived EVs. EVs from IS-treated donor HCAECs-reduced proliferation and re-endothelialization in EV-recipient cells and induced an anti-angiogenic gene expression profile. In a mouse-experiment, intravenous treatment with EVs from IS-treated endothelial cells significantly impaired endothelial regeneration. On the molecular level, we found that IS leads to an up-regulation of the heterogenous nuclear ribonucleoprotein U (hnRNPU), which retains miR-130a-3p in the cell leading to reduced vesicular miR-130a-3p export and impaired EV-recipient cell proliferation. CONCLUSION: Our findings suggest that EV-miR-mediated vascular intercellular communication is altered in patients with CAD and CKD, promoting CKD-induced endothelial dysfunction.

Contemporary use of guideline-based higher potency P2Y12 receptor inhibitor therapy in patients with moderate-to-high risk non-ST-segment elevation myocardial infarction: Results from the Canadian ACS reflective II cross-sectional study.

BACKGROUND: After myocardial infarction, guidelines recommend higher-potency P2Y12 receptor inhibitors, namely ticagrelor and prasugrel, over clopidogrel. HYPOTHESIS: We aimed to determine the contemporary use of higher-potency antiplatelet therapy in Canadian patients with non-ST-elevation myocardial infarction (NSTEMI). METHODS: A total of 684 moderate-to-high risk NSTEMI patients were enrolled in the prospective Canadian ACS Reflective II registry at 12 Canadian hospitals and three clinics in five provinces between July 2016 and May 2018. Multivariable logistic regression modeling was performed to assess factors independently associated with higher-potency P2Y12 receptor inhibitor use at discharge. RESULTS: At hospital discharge, 78.3% of patients were treated with a P2Y12 receptor inhibitor. Among patients discharged on a P2Y12 receptor inhibitor, use of higher-potency P2Y12 receptor inhibitor was 61.4%. After adjustment, treatment in-hospital with PCI (OR 4.48, 95%CI 3.34-6.03, p < .0001) was most strongly associated with higher use of higher-potency P2Y12 receptor inhibitor, while oral anticoagulant use at discharge (OR 0.03, 95%CI 0.01-0.12, p < .0001), and atrial fibrillation (OR 0.40, 95%CI 0.17-0.98, p = .046) were most strongly associated with lower use of higher-potency P2Y12 receptor inhibitor. Use of higher-potency P2Y12 receptor inhibitor varied across provinces (range, 21.6%-78.9%). DISCUSSION: In contemporary Canadian practice, approximately 60% of moderate-to-high risk NSTEMI patients discharged on a P2Y12 receptor inhibitor are treated with a higher-potency P2Y12 receptor inhibitor. In addition to factors that increase risk of bleeding, interprovincial differences in practice patterns were associated with use of higher-potency P2Y12 receptor inhibitor at discharge. Opportunities remain for further optimization of evidence-based, guideline-recommended antiplatelet therapy use.

Endovascular stenting for treatment of a left internal mammary artery pseudoaneurysm following redo-sternotomy: a case report.

An 85-year-old gentlemen with a history of previous triple vessel coronary bypass grafting presented with severe aortic stenosis and occlusion of the previous saphenous vein grafts but with patent left internal mammary artery (LIMA)-left anterior descending. The patient underwent uncomplicated repeat sternotomy and aortic valve replacement with repeated coronary bypass. On post-operative day 21 the patient was successfully resuscitated from a pulseless electrical activity (PEA) arrest, and was found to have a 1-cm pseudoaneurysm of the left internal mammary artery at the level of sternomanubrial junction with associated hemothorax. The LIMA remained patent and a pinhole source of extravasation was discovered by angiography at the aneurysmal site. The defect was successfully repaired by endovascular implant of a 3.5 mm × 12 mm Graft Master covered stent (Abbott Vascular). The patient recovered well from the procedure without further complications and was discharged after a total of 48 days of hospital stay. Our experience confirms the feasibility of repairing post-operative pseudoaneurysm in the internal mammary artery by endovascular stent grafting, thereby avoiding the risks and complications of a repeat open chest procedure.

The impact of telemetry on survival of in-hospital cardiac arrests in non-critical care patients.

OBJECTIVE: Since the introduction of telemetry over a half century ago, it has expanded to various units and wards within health care institutions outside of the traditional critical care setting. Little is known on whether routine telemetry use is beneficial in this patient population. The aim of this study was to determine the impact of telemetry monitoring on survival of in-hospital cardiac arrests in patients admitted to non-critical care units. METHODS: A retrospective study of cardiac arrests in patients admitted to non-critical care units within the Winnipeg Regional Health Authority from 2002 to 2006 inclusive was performed. Baseline demographic, cardiac arrest, and outcome data were collected. RESULTS: Of the total 668 patients, the mean age was 70±14 years with 404 (61%) males. Patients presenting with asystole or pulseless electrical activity (PEA) demonstrated an increased mortality as compared to those presenting with ventricular tachycardia (VT) or ventricular fibrillation (VF). Overall, 268 of 668 patients (40%) survived their initial arrest, 66 (10%) survived to hospital discharge and 49 (7%) survived transfer to another facility. Patients on telemetry vs. no telemetry had higher survival rates immediately following cardiac arrest (66% vs. 34%, OR=3.67, p=0.02), as well as higher survival to hospital discharge (30% vs. 6%, OR=7.17, p=0.01). Finally, patients with cardiac arrest during the night and early morning benefited proportionally the greatest from telemetry use. CONCLUSION: Regardless of whether cardiac arrest was witnessed or unwitnessed, telemetry use was an independent and strong predictor of survival to hospital discharge.

The presence of ST-elevation in lead aVR predicts significant left main coronary artery stenosis in cardiogenic shock resulting from myocardial infarction: the Manitoba cardiogenic shock registry.

INTRODUCTION: Electrocardiographic (ECG) predictors of significant angiographic left main coronary artery stenosis (LMCS>50%) have been described in acute myocardial infarction using ST-segment elevation in lead aVR (aVR-STE). However, there is a paucity of data on its association with LMCS>50% in the setting of cardiogemic shock (CGS). METHODS: We investigated 210 consecutive, unselected, patients from Sept. 2002-2006 with CGS due to acute myocardial infarction undergoing cardiac catheterization. Of those, 191 patients with interpretable ECG tracings for aVR-STE analysis formed our study sample. aVR-STE was defined as ST-segment elevation≥1mm in aVR while LMCS>50% on coronary angiogram was defined as any left main lesion that demonstrated >50% lumen narrowing or equivalent by direct visualization or quantitative coronary angiography analysis. RESULTS: There was 59% survival to discharge of this predominantly male cohort (median age 68±12years; 31% females). Fifty three (28%) cases had aVR-STE while 27 (14%) had LMCS>50%. Of those, 16 patients who had aVR-STE also had LMCS>50% (sensitivity 59%, specificity 77%, positive predictive value 30%, negative predictive value 92% for predicting LMCS>50%). Multivariate analysis revealed that aVR-STE was the only significant predictor of LMCS>50% was (p=0.014; Odds Ratio=3.06; 95% Confidence Interval 1.26-7.47). CONCLUSION: In CGS due to acute myocardial infarction, aVR-STE>1mm proves to be an important predictor of LMCS>50%. Such data could be helpful in further risk stratification for optimal management during CGS.

A "no-option" left main PCI registry: outcomes and predictors of in hospital mortality-utility of the logistic EuroSCORE.

BACKGROUND: Although high-risk left main PCI populations have been previously described, there is little data describing outcomes and the role of the logistic EuroSCORE in surgical turndown cohorts or patients in extremis due to acute infarction or cardiogenic shock from left main ischemia. METHODS: Consecutive patients with unprotected LM PCI who were surgical turndowns or in extremis were included in this retrospective cohort from 2004 to 2009 at two tertiary centers. Predictors of in-hospital mortality were identified utilizing routine and stepwise logistic regression. RESULTS: There were a total of 56 patients with mean age of 69 (±13). There were 23 (41%) patients with cardiogenic shock. The mean logistic EuroSCORE was 23.5% ± 21%. In-hospital death occurred in 12 (21%) patients, largely restricted to the shock subgroup (11/12). Univariate predictors of mortality included peak CK levels (P = 0.01), transfusion (P = 0.01), cardiogenic shock (P < 0.002), male gender (P = 0.027), and logistic EuroSCORE (P = 0.01). Stepwise logistic regression yielded logistic EuroSCORE (P = 0.04, OR: 1.25 (95% CI: 1.01-1.56) for every 5% increase) and peak CK level (P = 0.001, OR: 1.23 (95% CI: 1.09-1.40) for every 500 unit increase) as independent predictors of in-hospital mortality. The AUC ROC for logistic EuroSCORE was 0.73; and for logistic EuroSCORE plus peak CK level was 0.89. CONCLUSION: PCI appears to be a reasonable option in the high risk "no option" LM population, with the logistic EuroSCORE and peak CK levels being independent predictors of in-hospital mortality. Specifically, the logistic EuroSCORE and peak CK level combined discriminate in-hospital mortality with a high degree of certainty.

The acutely occluded left main coronary artery culprit in cardiogenic shock and initial percutaneous coronary intervention: a substudy of the Manitoba "no option" left main PCI registry.

We aim to describe the in-hospital outcomes of the first reported Canadian cohort of patients with cardiogenic shock and acute myocardial infarction (MI) due to acute and total occlusion of the left main coronary artery, treated with initial percutaneous coronary intervention (PCI). Acute left main thromboses with cardiogenic shock were identified (N = 8) from a retrospective consecutive cohort of high risk left main PCI (N = 56) performed at our institution from 2004-2009. The mean age was 62.3 ± 13.2 years, with 6 (75%) male patients. Successful PCI was performed in all patients, with thrombectomy utilized in 4 patients (50%), stenting in 7 patients (88%), and intra-aortic balloon pump augmentation in 7 patients (88%). Two patients (25%) required extracorporeal membrane oxygenation (ECMO) and 2 other patients required ventricular assist devices. Post-PCI coronary artery bypass grafting (CABG) was performed for 2 patients (25%). The mean SYNTAX score was 26.6 ± 10.5. The mean logistic EuroSCORE was 30.4 ± 12.6%. In-hospital mortality occurred in 3 patients (38%). Acute left main occlusion is a rare but devastating presentation of myocardial infarction, invariably with cardiogenic shock. Emergent PCI may be an effective method to acutely revascularize this subset of patients; however, aggressive post-PCI care including ECMO, CABG, and ventricular support may be required to improve patient survival.

Cardiac Outcomes Through Digital Evaluation (CODE) STEMI project: prehospital digitally-assisted reperfusion strategies.

BACKGROUND: Guidelines for reperfusion in ST-elevation myocardial infarction (STEMI) were recently adopted by the Canadian Cardiovascular Society. We have developed a blended model of prehospital thrombolytic (PHL) therapy or primary percutaneous coronary intervention (PPCI) activation, in order to achieve guideline times. METHODS: In our urban centre of 658,700 people, emergency medical services (EMS) were trained to perform and screen electrocardiograms (ECGs) for suspected STEMI. Suspected ECGs were transmitted to a physician's hand-held device. If the physician confirmed the diagnosis they coordinated initiation of either PHL or PPCI. In cases where physicians found the prehospital ECG negative for STEMI (PHENST), patients were transported to the closest emergency room. RESULTS: From July 21, 2008 to July 21, 2010, the Cardiac Outcomes Through Digital Evaluation (CODE) STEMI project received 380 transmitted calls. There were 226 confirmed STEMI by the on-call physician, 158 (70%) received PPCI, 48 (21%) received PHL, and 20 (9%) had angiography but no revascularization. The PPCI, median time from first medical contact to reperfusion was 76 minutes (interquartile range [IQR], 64-93). For PHL, median time from first medical contact to needle was 32 minutes (IQR, 29-39). The overall mortality rate for the STEMI patients was 8% (PHL = 4 [8.3%], PPCI = 8 [5%], medical therapy = 7 [35%]). There were 154 PHENST patients, 44% later diagnosed with acute coronary syndrome. The mortality rate for PHENST was 14%. CONCLUSIONS: Through a model of EMS prehospital ECG interpretation, digital transmission, direct communication with a physician, and rapid coordinated service, we demonstrate that benchmark reperfusion times in STEMI can be achieved.

The ability to achieve complete revascularization is associated with improved in-hospital survival in cardiogenic shock due to myocardial infarction: Manitoba cardiogenic SHOCK Registry investigators.

OBJECTIVES: To identify predictors of survival in a retrospective multicentre cohort of patients with cardiogenic shock undergoing coronary angiography and to address whether complete revascularization is associated with improved survival in this cohort. BACKGROUND: Early revascularization is the standard of care for cardiogenic shock. Coronary bypass grafting and percutaneous intervention have complimentary roles in achieving this revascularization. METHODS: A total of 210 consecutive patients (mean age 66 ± 12 years) at two tertiary centres from 2002 to 2006 inclusive with a diagnosis of cardiogenic shock were evaluated. Univariate and multivariate predictors of in-hospital survival were identified utilizing logistic regression. RESULTS: ST elevation infarction occurred in 67% of patients. Thrombolysis was administered in 34%, PCI was attempted in 62% (88% stented, 76% TIMI 3 flow), CABG was performed in 22% (2.7 grafts, 14 valve procedures), and medical therapy alone was administered to the remainder. The overall survival to discharge was 59% (CABG 68%, PCI 57%, medical 48%). Independent predictors of mortality included complete revascularization (P = 0.013, OR = 0.26 (95% CI: 0.09-0.76), hyperlactatemia (P = 0.046, OR = 1.14 (95% CI: 1.002-1.3) per mmol increase), baseline renal insufficiency (P = 0.043, OR = 3.45, (95% CI: 1.04-11.4), and the presence of anoxic brain injury (P = 0.008, OR = 8.22 (95% CI: 1.73-39.1). Within the STEMI with concomitant multivessel coronary disease subgroup of this population (N = 101), independent predictors of survival to discharge included complete revascularization (P = 0.03, OR = 2.5 (95% CI: 1.1-6.2)) and peak lactate (P = 0.02). CONCLUSIONS: The ability to achieve complete revascularization may be strongly associated with improved in-hospital survival in patients with cardiogenic shock.

Interprovincial spoke-to-hub transport using the Impella Recover LP 5.0 left ventricular assist device as a bridge to long-term circulatory support.

Current hospital administrative practices categorize health care centres in a network of  'spokes' (primary care centres) and 'hubs' (tertiary care centres). For the treatment of cardiogenic shock, long-term left ventricular assist devices (LVADs) and transplant therapies are only used at a few hub centres nationwide and are, thus, only available to patients living in close proximity to these centres. The relatively lower technical requirements of the Impella Recover LP 5.0 LVAD (ABIOMED Inc, USA) translate into greater use by spoke centres for the short-term treatment of cardiogenic shock, and facilitate appropriate stabilization and subsequent transportation to a suitable hub centre. Based on a review of the literature, the present report describes the first case demonstrating successful use of the Impella Recover LP 5.0 LVAD, implanted under local anesthetic, for the purposes of interprovincial spoke-to-hub transport in a bridge-to-bridge-to-transplant procedure. By providing an economical and technically straightforward alternative to traditional extracorporeal membrane oxygenation, the present case demonstrates that less invasive LVADs are valuable to the spoke-and-hub model for delivery of specialized cardiac care.

HITT and stent thrombosis: a "clinical" diagnosis not to be missed.

Heparin induced thrombocytopenia and thrombosis (HITT) syndrome is a rare but potentially life threatening disorder, which is increasingly recognized with the widespread use of heparin. We report a rare case of early stent thrombosis secondary to HITT in a patient initially presenting with cardiogenic shock, which occurred 9 days after primary bare metal stent implantation due to subcutaneous heparin exposure. The most important factor in detection of HITT remains a high index of clinical suspicion and close monitoring of the temporal trend of thrombocytopenia, particularly when trying to distinguish HITT from other sources of thrombocytopenia seen in critically ill patients.

Old technique, new use: novel use of a buddy wire to deploy a detached stent.

Stent dislodgement or loss in a coronary artery carries significant risks of infarction, thrombosis and requirement for emergency bypass surgery. Even with the advent of premounted stents, stent loss can occasionally occur, especially when performing intervention in calcified and tortuous anatomy. Multiple stent retrieval/stent exclusion techniques have been described to overcome this dreaded complication. We describe the first case of deploying a dislodged stent using a buddy wire technique with both wires through the center of the dislodged stent, and subsequent use of the small balloon technique to successfully deploy a dislodged stent in a heavily calcified and tortuous circumflex artery.

Secondary pulmonary arterial hypertension: treated with endothelin receptor blockade.

Secondary pulmonary arterial hypertension (SPAH) is an adverse outcome of a variety of systemic disorders. These include collagen vascular diseases, chronic thromboembolism, human immunodeficiency virus, portopulmonary hypertension, and other diseases. Progression of SPAH may persist despite stabilization of the causative disease, thereby contributing to the poor quality of life and unfavorable survival in these patients. Treatment of the underlying cause and oxygen supplementation may alleviate symptoms, but no specific therapy to treat SPAH currently exists. Endothelin receptor blockade with bosentan has been shown to be beneficial in the treatment of primary pulmonary hypertension, but efficacy of this therapy in SPAH has not been established. We describe a case series of 6 patients with disparate causes of SPAH, who benefited from endothelin receptor blockade therapy. The causes of SPAH included collagen vascular disease (scleroderma) (1); systemic lupus erythematosus (2); chronic thromboembolic disease (2); and granulomatous vasculitis from sarcoidosis (1). Therapy with bosentan led to improvements in symptoms, New York Heart Association functional class, and walking distance in all patients. Distance walked in 6 minutes increased from a mean of 151.67 +/- 69.30 m at baseline to 314.83 +/- 89.09 m after an average of 14 months of bosentan treatment. Pulmonary arterial pressure decreased in most but not all 6 patients on follow-up echocardiography. This case series suggests a role for endothelin receptor blockade therapy in SPAH and should generate further interest in pharmacologic management of SPAH. A prospective controlled clinical trial of bosentan in SPAH is urgently needed.