Preventing broken hearts in women with breast cancer: a concise review on chemotherapy-mediated cardiotoxicity.

Cancer and cardiovascular disease are the leading causes of death for Canadian women. One in eight Canadian women will receive the life-changing diagnosis of breast cancer (BC) in their lifetime, with 1 in 34 dying from the disease. Although doxorubicin (DOX) and trastuzumab (TRZ) have significantly improved survival in women diagnosed with human epidermal growth factor receptor 2 (HER2)-positive BC, approximately one in four women who receive this treatment are at risk of developing chemotherapy-induced cardiotoxicity. Cardiotoxicity is defined as a decline in left ventricular ejection fraction (LVEF) of >10% to an absolute value of <53%. Current guidelines recommend the serial monitoring of LVEF in this patient population using non-invasive cardiac imaging modalities including transthoracic echocardiography or multi-gated acquisition scan; however, this will only allow for the detection of established cardiotoxicity. Recent studies have demonstrated that a reduction in global longitudinal strain by speckle tracking echocardiography can identify pre-clinical systolic dysfunction prior to a decline in overall LVEF. Implementation of early detection techniques would allow for the prompt initiation of cardioprotective strategies. In addition to the early detection of chemotherapy-mediated cardiotoxicity, the prophylactic use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, ß-blockers, statins, exercise, and nutraceutical therapies have been studied in the setting of cardio-oncology.

Scleraxis as a prognostic marker of myocardial fibrosis in hypertrophic cardiomyopathy (SPARC) study.

Interstitial fibrosis is a histopathological hallmark of hypertrophic cardiomyopathy (HCM). Although extracellular matrix (ECM) biomarkers, including matrix metalloproteinases, are overexpressed in HCM patients, they do not correlate with sudden cardiac death (SCD) risk. The objective of this study was to determine whether scleraxis, a transcription factor that regulates collagen gene expression, is detectable in HCM patients and correlates with disease burden. Between 2017 and 2018, a total of 46 HCM patients were enrolled (58 ± 14 years (31 males, 15 females)) with a mean 5 year SCD risk of 2.3% ± 1.3%. Cardiac MRI confirmed HCM in all patients with a mean interventricular septal thickness of 20 ± 2 mm. Late gadolinium enhancement (LGE) was present in 32 (70%) study participants occupying 18% ± 7% of the left ventricular (LV) myocardium. Serum scleraxis levels were significantly higher in the HCM patients by approximately twofold as compared to controls (0.76 ± 0.06 versus 0.32 ± 0.02 ng/mL, p < 0.05). No correlation was demonstrated between serum scleraxis levels and markers of disease severity in HCM patients, including maximum LV wall thickness, %LGE, and SCD risk factors. Serum scleraxis is elevated in the HCM population. Future studies are warranted to evaluate the prognostic value of scleraxis in identifying high-risk HCM patients who require aggressive management for prevention of SCD.

In-Hospital Cardiac Arrest in the Cardiac Catheterization Laboratory: Effective Transition from an ICU- to CCU-Led Resuscitation Team.

OBJECTIVES: (1) To examine the incidence and outcomes of in-hospital cardiac arrests (IHCAs) in a large unselected patient population who underwent coronary angiography at a single tertiary academic center and (2) to evaluate a transitional change in which the cardiologist is positioned as the cardiopulmonary resuscitation (CPR) leader in the cardiac catheterization laboratory (CCL) at our local tertiary care institution. BACKGROUND: IHCA is a major public health concern with increased patient morbidity and mortality. A proportion of all IHCAs occurs in the CCL. Although in-hospital resuscitation teams are often led by an Intensive Care Unit- (ICU-) trained physician and house staff, little is known on the role of a cardiologist in this setting. METHODS: Between 2012 and 2016, a single-center retrospective cohort study was performed examining 63 adult patients (70 ± 10 years, 60% males) who suffered from a cardiac arrest in the CCL. The ICU-led IHCAs included 19 patients, and the Coronary Care Unit- (CCU-) led IHCAs included 44 patients. RESULTS: Acute coronary syndrome accounted for more than 50% of cardiac arrests in the CCL. Pulseless electrical activity was the most common rhythm requiring chest compression, and cardiogenic shock most frequently initiated a code blue response. No significant differences were observed between the ICU-led and CCU-led cardiac arrests in terms of hospital length of stay and 1-year survival rate. CONCLUSION: In the evolving field of Critical Care Cardiology, the transition from an ICU-led to a CCU-lead code blue team in the CCL setting may lead to similar short-term and long-term outcomes.

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.

High output cardiac state: evaluating the incidence, plausible etiologies and outcomes.

INTRODUCTION: The high output cardiac state (HOCS) [cardiac index (CI) >4 L/min/m2 ], primarily driven by abnormally low systemic vascular resistance (SVR), is a relatively under-recognized condition. Although, majority of these patients meet criteria for heart failure (HF), their treatment should be aimed at the primary pathology, as the majority of guideline directed HF therapies can reduce SVR further. OBJECTIVES: To characterize patients with HOCS and provide valuable insight into the condition. METHODS: Patients investigated by right heart catheterization (RHC) at the St. Boniface Hospital, Winnipeg, Canada between January 2009 and November 2021 were reviewed. Two groups of patients were included: 1) HOCS [CI >4 L/min/m2], and 2) pre-HOCS [CI between 3.8-4.0 L/min/m2]. Their medical records were reviewed to identify plausible etiologies, relevant investigations, and outcomes. RESULTS: 177/2950 (6 %) patients met criteria for inclusion: 144/177 (81 %) with HOCS [mean age 51 years (range 19 - 82); 67/144 (47 %) female] and 33/177 (19 %) with pre-HOCS [mean age 55 years (range 30 - 83); 6/33 (18 %) female]. The most common plausible etiologies for the HOCS included anemia (36 %), obesity (34 %), cirrhosis (17 %), and lung disease (32 %). Trans-thoracic echocardiography and magnetic resonance imaging findings were non-specific and predominantly described preserved left ventricular ejection fraction, and pulmonary hypertension. The population experienced high rates of hospitalization, and significantly high mortality [36/144 (25 %) of HOCS at a median follow-up of 31.5 months, and 13/33 (39 %) of pre-HOCS at a median follow-up of 17 months]. CONCLUSIONS: HOCS is not an uncommon condition and is associated with high mortality. Current HF guideline should incorporate such evaluation into the diagnostic criteria.

Alternatives to Hospitalization: Adding the Patient Voice to Advanced Heart Failure Management.

Advanced heart failure (HF) is associated with the extensive use of acute care services, especially at the end of life, often in stark contrast to the wishes of most HF patients to remain at home for as long as possible. The current Canadian model of hospital-centric care is not only inconsistent with patient goals, but also unsustainable in the setting of the current hospital-bed availability crisis across the country. Given this context, we present a narrative to discuss factors necessary for the avoidance of hospitalization in advanced HF patients. First, patients eligible for alternatives to hospitalization should be identified through comprehensive, values-based, goals-of-care discussions, including involvement of both patients and caregivers, and assessment of caregiver burnout. Second, we present pharmaceutical interventions that have shown promise in reducing HF hospitalizations. Such interventions include strategies to combat diuretic resistance, as well as nondiuretic treatments of dyspnea, and the continuation of guideline-directed medical therapies. Finally, to successfully care for advanced HF patients at home, care models, such as transitional care, telehealth, collaborative home-based palliative care programs, and home hospitals, must be robust. Care must be individualized and coordinated through an integrated care model, such as the spoke-hub-and-node model. Although barriers exist to the implementation of these models and strategies, they should not prevent clinicians from striving to provide individualized person-centred care. Doing so will not only alleviate strain on the healthcare system, but also prioritize patient goals, which is of the utmost importance.

L'insuffisance cardiaque avancée est associée à une utilisation considérable des services de soins de courte durée, surtout en fin de vie et souvent en contradiction totale avec les désirs de la plupart des patients, qui sont de rester à la maison le plus longtemps possible. Le modèle canadien actuel, centré sur les soins hospitaliers, n'est pas seulement incompatible avec les objectifs des patients, mais il est n'est pas viable vu le manque criant de lits constaté dans des hôpitaux de partout au pays. En tenant compte de ce contexte, nous présentons une perspective permettant de discuter des facteurs nécessaires pour éviter l'hospitalisation des patients atteints d'insuffisance cardiaque avancée. Il faut d'abord identifier les patients admissibles à des soins non hospitaliers en menant des discussions exhaustives sur les objectifs de soins qui se fondent sur les valeurs et qui portent notamment sur la participation du patient et de ses aidants et sur l'évaluation de l'épuisement des aidants. Nous présentons ici les interventions pharmaceutiques qui se sont révélées prometteuses dans la réduction des hospitalisations pour cause d'insuffisance cardiaque. Il s'agit de stratégies visant à lutter contre la résistance aux diurétiques et de traitements non diurétiques de la dyspnée, ainsi que de la poursuite des traitements médicaux indiqués par les lignes directrices. Enfin, pour bien soigner les patients atteints d'insuffisance cardiaque avancée à domicile, les modèles de soins, comme les soins de transition, la télémédecine, les programmes collaboratifs de soins palliatifs à domicile et les programmes d'hospitalisation à domicile, doivent être robustes. Les soins doivent être personnalisés et coordonnés par un modèle de soins intégré, comme le modèle en étoile (spoke-hub-and-node). Bien qu'il existe des obstacles à l'instauration de ces modèles et stratégies, ceux-ci ne devraient pas empêcher les médecins de s'employer à offrir des soins adaptés axés sur la personne. Cette pratique libérera le système de santé d'un poids et permettra de mettre de l'avant les objectifs des patients, qui sont de la plus grande importance.

COVID-19 Vaccination-Induced Myopericarditis: An Imager's Perspective.

COVID-19 vaccine-induced myocarditis is a rare adverse event in the current pandemic. The following is a case series of 10 individuals with COVID-19 vaccine-related myocarditis confirmed by cardiac magnetic resonance imaging. In this cohort of predominantly male patients, with a mean age of 23 years, chest discomfort and positive cardiac biomarkers occurred at a median of 3 days after the second COVID-19 vaccine dose. Although systolic function was relatively preserved on noninvasive cardiac imaging, evidence was seen of delayed enhancement on cardiac magnetic resonance imaging, confirming myocarditis. As COVID-19 vaccine-induced myocarditis has a relatively benign clinical course, the benefits of vaccination still, by far, outweigh this small risk.

La myocardite induite par le vaccin contre la COVID-19 est un événement indésirable rare de la pandémie actuelle. Voici une série de cas de 10 individus atteints d'une myocardite liée au vaccin de la COVID-19 confirmée par l'imagerie par résonance magnétique cardiaque (RMC). Dans cette cohorte principalement composée d'hommes, dont l'âge moyen était de 23 ans, qui ont manifesté un inconfort à la poitrine et montré des biomarqueurs cardiaques positifs à une médiane de trois jours après la deuxième dose du vaccin contre la COVID-19. Bien que l'imagerie cardiaque non invasive a montré une fonction systolique relativement préservée, la RMC mettait en évidence un rehaussement tardif qui confirmait la myocardite. Puisque la myocardite induite par le vaccin contre la COVID-19 a une évolution clinique relativement bénigne, les avantages de la vaccination restent de loin supérieurs à ce risque minime.

The Long Road to the Left Main: A Multidisciplinary Approach to the Revascularization of Complex Left Main Coronary Artery Disease.

Severe aortic stenosis (AS) is considered a contraindication to the use of mechanical circulatory support (MCS) devices, including the Impella heart pump (Abiomed, Aachen, Germany). We describe a case in which a 72-year-old female with severe AS and peripheral vascular disease (PVD) presented with retractable ischemia in the setting of a non-ST elevation myocardial infarction (NSTEMI). Using a coordinated multidisciplinary approach, our case is the first to combine iliac angioplasty, balloon aortic valvuloplasty (BAV), and the insertion of an Impella CP device in the setting of severe AS to facilitate successful coronary artery revascularization in a non-surgical patient.

Prophylactic benefits of systemically delivered simvastatin treatment in a house dust mite challenged murine model of allergic asthma.

BACKGROUND AND PURPOSE: Systemically delivered statins can blunt airway inflammation in ovalbumin-challenged mice. However, in asthma clinical trials the beneficial effects of introducing oral statins are not compelling. We have invetigated this discrepancy using a clinically relevant murine model of allergic asthma, and by including a prophylactic study arm. EXPERIMENTAL APPROACH: Adult mice were: 1) challenged with house dust mite (HDM) alone or with subcutaneous (s.c.) simvastatin for two weeks; or 2) also treated with simvastatin for one week prior to HDM challenge. We assayed lung function, inflammatory cell influx and cytokine profile, goblet cell abundance, and simvastatin concentration in serum, lung lavage and tissue. KEY RESULTS: Ultrahigh performance liquid chromatography-tandem mass spectrometry revealed that pharmacologically active simvastatin reached peak serum concentration after 8 h, but declined rapidly. Prophylactic treatment doubled peak serum simvastatin and repeated s.c. delivery established stable serum levels, but simvastatin was undetectable in the lungs. Both simvastatin treatment arms suppressed indices of HDM-induced airway inflammation and goblet cell hyperplasia, but this was significantly greater with prophylactic therapy, in particular, inhibition of neutrophil and eosinophil influx, and cytokine accumulation. Conversely, neither acute nor prophylactic delivery of simvastatin prevented HDM challenge-induced airway hyperreactivity. CONCLUSION AND IMPLICATIONS: Systemically administered simvastatin accumulates in the blood, but not in lung tissues, and reduces leukocyte influx and associated lung inflammation. Prophylactic therapy has the greatest anti-inflammatory effects, but as observed in human clinical trials, systemic simvastatin therapy does not prevent allergic airway hyperreactivity.

Iatrogenic Great Cardiac Vein Anastomosis during Coronary Artery Bypass Surgery.

Inadvertent anastomosis of the left internal mammary artery (LIMA) or a saphenous vein graft (SVG) to the great cardiac vein (GCV) is a rare complication of coronary artery bypass grafting (CABG). We present two cases with a LIMA to GCV and a SVG to GCV anastomosis, respectively, resulting in angina and dyspnea in the postoperative state. As an alternative to repeat CABG, both patients underwent percutaneous coronary intervention with percutaneous coil embolization or implantation of an Amplatzer vascular plug within the bypass graft to GCV conduit. This report highlights that percutaneous options exist for the relief of ischemic symptoms in this rare clinical setting.

Arteria Lusoria: An Anomalous Finding during Right Transradial Coronary Intervention.

Arteria Lusoria or aberrant right subclavian artery (ARSA) is present in 0.6-1.4% of individuals. It typically remains clinically silent and is often discovered during angiographic procedures. The presence of ARSA can make a right transradial approach for coronary angiography and angioplasty technically more difficult. With the use of catheter support, we describe two cases in which a right transradial approach for catheterization was successful in the setting of ARSA. As such, the presence of ARSA does not warrant abandoning a transradial approach for coronary angiography and angioplasty.

Renal Insufficiency and Early Bystander CPR Predict In-Hospital Outcomes in Cardiac Arrest Patients Undergoing Mild Therapeutic Hypothermia and Cardiac Catheterization: Return of Spontaneous Circulation, Cooling, and Catheterization Registry (ROSCCC Registry).

Objective. Out of hospital cardiac arrest (OHCA) patients are a critically ill patient population with high mortality. Combining mild therapeutic hypothermia (MTH) with early coronary intervention may improve outcomes in this population. The aim of this study was to evaluate predictors of mortality in OHCA patients undergoing MTH with and without cardiac catheterization. Design. A retrospective cohort of OHCA patients who underwent MTH with catheterization (MTH + C) and without catheterization (MTH + NC) between 2006 and 2011 was analyzed at a single tertiary care centre. Predictors of in-hospital mortality and neurologic outcome were determined. Results. The study population included 176 patients who underwent MTH for OHCA. A total of 66 patients underwent cardiac catheterization (MTH + C) and 110 patients did not undergo cardiac catheterization (MTH + NC). Immediate bystander CPR occurred in approximately half of the total population. In the MTH + C and MTH + NC groups, the in-hospital mortality was 48% and 78%, respectively. The only independent predictor of in-hospital mortality for patients with MTH + C, after multivariate analysis, was baseline renal insufficiency (OR = 8.2, 95% CI 1.8-47.1, and p = 0.009). Conclusion. Despite early cardiac catheterization, renal insufficiency and the absence of immediate CPR are potent predictors of death and poor neurologic outcome in patients with OHCA.

The Cardioprotective Role of N-Acetyl Cysteine Amide in the Prevention of Doxorubicin and Trastuzumab-Mediated Cardiac Dysfunction.

BACKGROUND: In the breast cancer setting, anticancer therapies including doxorubicin (DOX) and trastuzumab (TRZ) are associated with a significantly increased risk of cardiotoxicity. Despite the increasing support for the role of oxidative stress (OS) in its pathophysiology, we still do not have an optimal antioxidant for the prevention of DOX + TRZ-mediated cardiac dysfunction. The objective of this study was to investigate whether the novel antioxidant N-acetylcysteine amide (NACA) can attenuate DOX + TRZ-induced heart failure in a murine model. METHODS: A total of 100 C57Bl/6 female mice received 1 of the following drug regimens: (1) saline, (2) NACA, (3) DOX, (4) TRZ, (5) DOX + TRZ, (6) NACA + DOX, (7) NACA + TRZ, and (8) NACA + DOX + TRZ. Serial echocardiography was performed over a 10-day study period, after which the mice were killed for histologic and biochemical analyses. RESULTS: In mice receiving DOX, the left ventricular ejection fraction (LVEF) decreased from 73% ± 4% to 43% ± 2% on day 10. In mice receiving DOX + TRZ, the LVEF decreased from 72% ± 3% to 32% ± 2% on day 10. Prophylactic administration of NACA to mice receiving DOX or DOX + TRZ was cardioprotective, with an LVEF of 62% ± 3% and 55% ± 3% on day 10, respectively. Histologic and biochemical analyses demonstrated a loss of cellular integrity, increased OS, and increased cardiac apoptosis in mice treated with DOX + TRZ, which was attenuated by the prophylactic administration of NACA. CONCLUSIONS: NACA attenuated the cardiotoxic side effects of DOX + TRZ in a murine model of chemotherapy-induced cardiac dysfunction by decreasing OS and apoptosis.

Multimodality cardiac imaging of a left ventricular thrombus: a case report.

BACKGROUND: Left ventricular thrombus (LVT) formation occasionally complicates patient recovery post myocardial infarction, conveying a significant risk of systemic embolism. Accordingly, thrombus detection and subsequent anticoagulation is imperative in order to minimize patient morbidity and mortality. Transthoracic echocardiography (TTE) is the imaging modality most widely used to screen for thrombus formation despite its suboptimal sensitivity and specificity. CASE PRESENTATION: This report describes the discordant imaging findings of a LVT in a 56 year old Caucasian male with an anterior ST elevation myocardial infarction. Left ventriculography revealed a filling defect, suggestive of a potential left ventricular (LV) thrombus, which could not be confirmed by TTE. Cardiac magnetic resonance imaging (MRI) demonstrated evidence of a full thickness scar involving the mid to distal anterior wall and apical regions, with confirmation of a small LV apical thrombus. CONCLUSIONS: This case illustrates the limitations of TTE when used as a tool to screen for thrombus formation. It highlights the importance of multimodality cardiac imaging for the detection of post myocardial infarction (MI) complications, in the context of a high clinical suspicion.

Simultaneous quantification of simvastatin and simvastatin hydroxy acid in blood serum at physiological pH by ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC/MS/MS).

Simvastatin attenuates airway inflammation and hyperreactivity, hallmarks of asthma, in allergen-challenged mice. As such, it is under consideration as a novel therapeutic, thus it is important to quantify the levels of simvastatin and its pharmacologically active and interconvertible metabolite, simvastatin hydroxy acid, that can be attained in the body. Methods exist to measure the concentrations of these compounds in biological media; however they do not maintain a physiological pH, and as a result do not accurately measure the ratio of these two compounds that exists in vivo. We developed a new method to measure simvastatin and simvastatin hydroxy acid more accurately in serum from mice by ultra high performance liquid chromatography-tandem mass spectrometry. We minimized the time that the compounds were in aqueous solution, and buffered samples to a physiological pH value of 7.4. Limits of quantification (LOQ) were 0.16 ng mL(-1) extract (1.3 ng mL(-1) serum) for simvastatin, and 8.3 ng mL(-1) extract (66 ng mL(-1) serum) for simvastatin hydroxy acid, respectively. No interconversion was observed, based on spike-and-recovery experiments of solutions containing both compounds. The method was applied using biological samples from mice challenged with house dust mite extract and simultaneously treated with subcutaneous simvastatin injection. Simvastatin hydroxy acid concentrations became significantly increased after a 2 week pre-treatment regime, whereas simvastatin concentrations were below the LOQ for all serum samples.