The role of renin angiotensin system antagonists in the prevention of doxorubicin and trastuzumab induced cardiotoxicity.

BACKGROUND: Cardio-Oncology is an evolving discipline that focuses on the management of cancer patients who develop cardiovascular complications as a result of their treatment. Although the current combination of surgical resection, radiation, and chemotherapy may lead to a cure in cancer patients, the administration of anti-cancer drugs, in particular Doxorubicin (DOX) and Trastuzumab (TRZ), is associated with an increased risk of cardiotoxicity. Little is known on the potential cardioprotective role of renin angiotensin system (RAS) antagonists in the prevention of DOX+TRZ mediated cardiotoxicity. OBJECTIVE: The aim of the study was to determine whether RAS antagonists would be useful in attenuating DOX+TRZ induced cardiotoxicity. METHODS: A total of 240 C57Bl/6 mice were randomized to prophylactic treatment with placebo, Aliskiren, Perindopril, or Valsartan for a total of 13 weeks. Within each arm, mice received treatment with either DOX, TRZ, or the combination of both drugs. Serial murine echocardiography was performed weekly to characterize the degree of cardiovascular remodeling within each group. RESULTS: In wild-type (WT) mice treated with DOX+TRZ, LV end diastolic internal diameter (LVID) increased from 3.1 ± 0.2 mm at baseline to 4.6 ± 0.3 mm at week 13 (p < 0.05) and the LV fractional shortening (FS) decreased from 52 ± 2% at baseline to 26 ± 2% at week 13 (p < 0.05). Prophylactic treatment with Aliskiren, Perindopril, or Valsartan attenuated the degree of LV cavity dilatation with LVID dimensions of 3.9 ± 0.2 mm, 4.1 ± 0.2 mm, and 4.2 ± 0.1 mm at week 13, respectively (p < 0.05). Similarly, prophylactic treatment with Aliskiren, Perindopril, or Valsartan was partially cardioprotective with FS of 40 ± 1%, 32 ± 1%, and 33 ± 2% at week 13, respectively (p < 0.05). As compared to WT mice receiving DOX+TRZ, prophylactic treatment with RAS inhibition was also associated with improved survival, corroborating the echocardiographic findings. CONCLUSION: The cardiotoxic effects of DOX+TRZ were partially attenuated by the prophylactic administration of RAS antagonists in a chronic murine model of chemotherapy induced cardiac dysfunction.

Does a Heart Team Improve Clinical Outcomes?

Consultation by a Heart Team (HT) is a class I recommendation by the American College of Cardiology, American Heart Association, and the European Society of Cardiology for the management of patients with complex cardiac disease. Despite the class I recommendation, there is a paucity of data to support the role of an HT with only level C quality of evidence. This study was performed to follow patients who were referred for HT consultation and long-term outcomes in relation to whether the recommendation of the HT was followed or not. We performed a prospective analysis of our cohort of patients who underwent consultation by the HT. A total of 342 cases have been followed. Patient characteristics, referring physicians' favored treatment, and key outcomes were followed. A total of 336 patients were reviewed; 70.4% were male patients with a median age of 66.3 years and an average EuroSCORE II score of 7.2%. A total of 79.9% of the discussions resulted in a unanimous decision. The recommendations made by the HT differed from those documented by the referring physician in 54% of cases. In conclusion, recommendations made by the HT were followed in 269 cases (83.8%). There was a significant reduction in cardiac death (6.3% vs 15.3%, p = 0.042), composite cardiac outcome (23.4% vs 51.9%, p ≤0.001), and hospital admissions (10.4% vs 36.5%, p ≤0.001) when recommendations were followed. There was no statistical difference between the 2 groups when looking at noncardiac death, stroke, ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, dialysis, or an emergency room visit.

A previously undescribed pathogenic variant in FBN1 gene causing Marfan syndrome: a case report.

Background: Marfan syndrome (MFS) is an autosomal dominant multisystem connective tissue disorder with increased risk of aortopathy with a high risk of subsequent life-threatening aortic dissection. Diagnosing this condition is reliant on recognizing clinical features and genetic testing for confirming diagnosis, using the revised Ghent criteria. Case summary: We identified a 49-year-old patient who presented with dyspnoea, with Marfan syndrome (MFS) and a previously unreported variant in the fibrillin-1 gene (FBN1), designated c.7016G>C. Prior to identifying the new gene variant, this patient did not meet the revised Ghent criteria for MFS diagnosis. We present clinical and molecular evidence supporting the likely pathogenic nature of this variant, leading to earlier therapy and intervention. Discussion: The discovery of a new pathogenic gene will expand the current aortopathy and MFS database and may lead to more informed clinical management decisions for the timing and nature of interventions.

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.

Cardiovascular magnetic resonance in mild to moderate clozapine-induced myocarditis: is there a role in the absence of electrocardiographic and echocardiographic abnormalities?

Clozapine is an atypical, neuroleptic medication that can cause myocarditis. While the "gold standard" for diagnosis of myocarditis is perceived to be via myocardial biopsy, cardiovascular magnetic resonance (CMR) has also proven its utility in this respect, primarily through its ability to detect myocardial scar by late-gadolinium enhancement (LGE). Until recently, however, clozapine-induced myocarditis specifically has not been known to be associated with LGE on CMR. In that particular case, LGE was demonstrated in a patient with clozapine-induced myocarditis. However, quite important, that patient also had specific abnormalities on the electrocardiogram (ECG) and echocardiogram that corresponded to the area of LGE demonstrated by CMR. We highlight a case series of three patients with clozapine-induced myocarditis and provide a literature review to discuss and critically appraise the true incremental diagnostic value of CMR in such patients with normal ECG and echocardiography.

Impact of Routine 24 Hour Coronary Care Unit Stay in Stable Patients After Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction.

With the routine use of primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI), the rate of short-term complications is low and the optimal length-of-stay in the coronary care unit (CCU) following reperfusion is unknown. We hypothesized that the rate of complications would not differ between two groups of stable patients admitted to the CCU following primary-PCI for STEMI: (1) those for whom a minimum 24-hour stay was enforced (≥24 hour Standard Stay) and (2) those with no minimum length-of-stay (Physician-guided Stay). Data were collected retrospectively. We performed a regression analysis to determine predictors of the primary endpoint (a composite of in-hospital death, re-infarction and/or re-intervention, heart failure requiring intravenous diuretics, cardiac arrest, central nervous system and/or peripheral embolization, bleeding requiring transfusion, arrhythmia resulting in initiation of a class I or III antiarrhythmic drug, initiation of assisted ventilation, requirement for vasopressors or inotropes, or transfer to intensive care). A total of 242 patients were included in the analysis. The rate of the primary endpoint was 8% in the physician-guided stay group and 16% in the standard ≥24 hour stay group (p = 0.06). The most common complication in both groups was heart failure requiring diuretics (42%), which was predicted by the left ventricular end diastolic pressure on catheterization (area under the Receiver-Operator Curve of 0.75). In conclusion, Patients who are stable following primary PCI for STEMI have a low rate of complications. Stable STEMI patients do not appear to benefit from a mandatory ≥24 hours stay in the CCU.

Spinal Epidural Hematoma Secondary to Tenecteplase for ST-Elevation Myocardial Infarction in the Setting of Trauma and Cervical Endplate Fracture.

A 78-year-old woman presented with an inferior ST-segment elevation myocardial infarction in the setting of a fall resulting in facial trauma causing an unrecognized C6 cervical endplate fracture. After administration of tenecteplase, she developed a spinal epidural hematoma requiring intubation for airway protection and cessation of antiplatelet therapies. The need to delay coronary intervention in this setting led to a recurrent inferolateral ST-segment elevation myocardial infarction that eventually required coronary bypass grafting. In the first report of a spinal epidural hematoma after tenecteplase for ST-segment elevation myocardial infarction, we emphasize the need for imaging after significant trauma before initiating thrombolysis.

Une femme de 78 ans a été vue en consultation pour un infarctus du myocarde inférieur avec élévation du segment ST, dans un contexte de trauma facial entraîné par une chute, causant une fracture du plateau vertébral de C6 non diagnostiquée. Après avoir reçu du ténectéplase, la patiente a présenté un hématome épidural rachidien ayant nécessité l'intubation pour protéger les voies respiratoires et l'arrêt des traitements antiplaquettaires. La nécessité de retarder l'intervention coronarienne dans ce contexte a entraîné un nouvel infarctus du myocarde inférolatéral avec élévation du segment ST, ayant par la suite nécessité un pontage aortocoronarien. Relativement au premier rapport d'hématome épidural rachidien survenu après l'administration de ténectéplase pour le traitement de l'infarctus du myocarde avec élévation du segment ST, nous insistons sur l'importance de procéder, avant d'instaurer la thrombolyse, à des examens d'imagerie chez les patients ayant subi un trauma important.

Apical hypertrophic cardiomyopathy treated as ST-elevation myocardial infarction.

Electrocardiographic changes resulting from apical hypertrophic cardiomyopathy may mimic an acute coronary syndrome. A 67-year-old Sudanese male without cardiac risk factors presented to hospital with chest pain and electrocardiographic findings of septal ST-segment elevation, ST-segment depression in V4-V6, and diffuse T-wave inversion. He was treated as an acute ST-elevation myocardial infarction with thrombolytics. There was no cardiac biomarker rise and coronary angiography did not reveal evidence of significant coronary arterial disease. Ventriculography, transthoracic echocardiography, and cardiac magnetic resonance imaging were consistent with apical hypertrophic cardiomyopathy. The patient was discharged three days later with outpatient cardiology follow-up. We highlight the clinical and electrocardiographic findings of apical hypertrophic cardiomyopathy, with an emphasis on distinguishing this from acute myocardial infarction.

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.