Robin A. Ducas

Chlamydia pneumoniae Stimulates Proliferation of Vascular Smooth Muscle Cells Through Induction of Endogenous Heat Shock Protein 60

Abstract— Chlamydia pneumoniae infection has been linked with atherosclerosis. However, the mechanism responsible for the atherogenic effects of C pneumoniae remains unclear. Heat shock proteins (HSPs) have been found in atherosclerotic lesions. HSPs of HSP70 and HSP90 families are involved in the regulation of cell cycle progression and cell proliferation. We assessed the hypothesis that HSP60 is induced in vascular cells infected with C pneumoniae and stimulates cell proliferation. Rabbit vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs) were infected with C pneumoniae. Western blot analysis demonstrated the induction of endogenous HSP60 expression in C pneumoniae-infected VSMCs. C pneumoniae infection significantly increased the number of VSMCs, and the mitogenic effect correlated with the expression level of endogenous HSP60. In contrast to VSMCs, C pneumoniae infection had no effect on the expression level of HSP60 and did not stimulate cell proliferation in HUVECs. Exogenous addition of recombinant chlamydial HSP60 had no mitogenic effect on VSMCs and HUVECs. However, overexpression of HSP60 within VSMCs by infection with adenovirus encoding human HSP60 resulted in a significant increase in cell numbers compared with uninfected VSMCs. These results suggest that overexpression of endogenous HSP60 may be a central intracellular event responsible for the mitogenic effects induced by C pneumoniae infection. In addition to C pneumoniae, other infectious agents and atherogenic risk factors may also stimulate VSMC proliferation and contribute to the lesion formation through the induction of HSP60.

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.

The impact of repeated marathon running on cardiovascular function in the aging population

BackgroundSeveral studies have correlated elevations in cardiac biomarkers of injury post marathon with transient and reversible right ventricular (RV) systolic dysfunction as assessed by both transthoracic echocardiography (TTE) and cardiovascular magnetic resonance (CMR). Whether or not permanent myocardial injury occurs due to repeated marathon running in the aging population remains controversial.ObjectivesTo assess the extent and severity of cardiac dysfunction after the completion of full marathon running in individuals greater than 50 years of age using cardiac biomarkers, TTE, cardiac computed tomography (CCT), and CMR.MethodsA total of 25 healthy volunteers (21 males, 55 ± 4 years old) from the 2010 and 2011 Manitoba Full Marathons (26.2 miles) were included in the study. Cardiac biomarkers and TTE were performed one week prior to the marathon, immediately after completing the race and at one-week follow-up. CMR was performed at baseline and within 24 hours of completion of the marathon, followed by CCT within 3 months of the marathon.ResultsAll participants demonstrated an elevated cTnT post marathon. Right atrial and ventricular volumes increased, while RV systolic function decreased significantly immediately post marathon, returning to baseline values one week later. Of the entire study population, only two individuals demonstrated late gadolinium enhancement of the subendocardium in the anterior wall of the left ventricle, with evidence of stenosis of the left anterior descending artery on CCT.ConclusionsMarathon running in individuals over the age of 50 is associated with a transient, yet reversible increase in cardiac biomarkers and RV systolic dysfunction. The presence of myocardial fibrosis in older marathon athletes is infrequent, but when present, may be due to underlying occult coronary artery disease.

To Transmit or Not to Transmit: How Good Are Emergency Medical Personnel in Detecting STEMI in Patients With Chest Pain?

BACKGROUND There is growing use of prehospital electrocardiograms (ECGs) in establishing early diagnosis of ST segment myocardial infarction (STEMI) to facilitate early reperfusion. This study aimed to determine the predictive value of prehospital ECGs interpreted by nonphysician emergency medical services (EMS) in chest pain presentations. METHODS In our city of 658,700 people, EMS/paramedics received 21 hours of instruction on STEMI management, ECG acquisition, and interpretation. Suspected STEMI ECGs were wirelessly transmitted to and discussed with a physician for possible therapy. ECGs deemed negative for STEMI by EMS were not transmitted; patients were transported to the closest hospital without prehospital physician involvement. RESULTS From July 21, 2008 to July 21, 2010, there were 5426 chest pain calls to EMS, 380 were suspected STEMI cases. The remaining ECGs were deemed negative for STEMI by EMS. To audit the nontransmitted ECGs we analyzed 323 consecutive patients over 2 selected months (January and June 2010) for comparison. Of nontransmitted cases there was 1 missed and 2 STEMIs that developed subsequently. Based on 380 transmitted and 323 nontransmitted cases, the sensitivity and specificity of EMS detecting STEMI were 99.6% and 67.6%, respectively. The positive and negative predictive values for STEMI were 59.5% and 99.7%, respectively. CONCLUSIONS Our findings demonstrate nonphysician EMS interpretation of STEMI on prehospital ECG has excellent sensitivity and high negative predictive value. This finding supports the use of prehospital ECGs interpreted by EMS to help identify and facilitate treatment of STEMI. These results may have broad implications on staffing models for first responder/EMS units.

Echocardiography and Vascular Ultrasound: New Developments and Future Directions

There have been major technological advances in echocardiography over the past decade. New and robust measures of myocardial function, both systolic and diastolic, have been identified and extensively evaluated. Some of the new measures such as annular velocities by tissue Doppler imaging have become an integral part of the echocardiographic examination, and other measures such as strain and strain rate have yet to be widely adopted. Three-dimensional (3D) echocardiography has evolved greatly since its introduction in the 1980s. Currently, its main clinical application is the perioperative assessment of the mitral valve. Though 3D echocardiography provides superior quantification of cardiac chamber size, its adoption has been limited by the lack of robust automated data analysis software with smooth integration of analysis packages into clinical workstations and suboptimal temporal and spatial resolution. With advancement in electronics and miniaturization, these limitations can be overcome. The history of contrast echocardiography is long and arduous. Use of a microbubble contrast for left ventricular opacification has become commonplace in most echocardiographic laboratories, but the routine use of microbubble contrast for myocardial perfusion will require standardization of the procedure and/or development of new contrast agents. The applications of 3D and microbubble contrast are also under active evaluation in vascular ultrasound. This review summarizes the current and future applications of these exciting developments in echocardiography and vascular ultrasound.

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 physicians 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 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.

Monomorphic ventricular tachycardia caused by arsenic trioxide therapy for acute promyelocytic leukaemia.

Arsenic trioxide has become the treatment of choice for patients with acute promyelocytic leukaemia. Cardiovascular toxicity is known to occur with this therapy, in particular heart rhythm disorders due to QT interval prolongation. We present a case of ventricular arrhythmia with no QT prolongation in a patient receiving arsenic trioxide therapy.

Functional Mitral Regurgitation: Current Understanding and Approach to Management

Functional mitral regurgitation (FMR) is a challenging clinical entity that frequently complicates ischemic and nonischemic cardiomyopathy. The underlying pathophysiology of FMR is caused primarily by ventricular and subvalvular apparatus dysfunction which causes failure of proper leaflet coaptation. Echocardiography is the primary modality used in diagnosis and characterization of FMR. Echocardiography allows for assessment of valvular and ventricular structures and their interaction. FMR portends a poor prognosis, because it is frequently associated with increased morbidity and mortality. The optimal management of FMR involves an individualized approach that incorporates medical therapy and consideration of surgical, percutaneous, and resynchronization therapies according to the severity of regurgitation, presence of symptoms, option for revascularization, and the degree of ventricular remodelling.

Left ventricular outflow tract obstruction by a bioprosthetic mitral valve: diagnosis by cardiac computed tomography.

Echocardiography has long been the mainstay of noninvasive cardiac diagnostic imaging; however, newer imaging modalities have proven useful in cases where echocardiography has been nondiagnostic. We present a case of a 42-year-old woman with hypertrophic obstructive cardiomyopathy, who despite septal myectomy and bioprosthetic mitral valve replacement, continued to have persistent symptoms of left ventricular outflow tract obstruction. Transthoracic echocardiographic evaluation did not demonstrate the etiology of the patients symptoms. The cause of our patients symptoms was clarified using cardiac computed tomography, which revealed a strut from the bioprosthetic mitral valve protruding into the left ventricular outflow tract. Although this clinical phenomenon has previously been described, we will discuss the role of cardiac imaging with computed tomography in this setting.