Effects of Implantable Cardioverter-Defibrillator Leads on the Tricuspid Valve and Right Ventricle: A Randomized Trial.

BACKGROUND: There are no randomized data to inform the extent to which transvenous cardiac leads cause tricuspid regurgitation (TR). OBJECTIVES: This study sought to determine the effect of a transvenous implantable cardioverter-defibrillator (TV-ICD) on TR severity, and secondarily, on right ventricular (RV) size and function. METHODS: We evaluated TR severity before and 6 months after implantable cardioverter-defibrillator insertion in a post hoc analysis of adults randomized to receive a transvenous (n = 252) or subcutaneous implantable cardioverter-defibrillator (S-ICD) (n = 251) device. TR and RV size and systolic function were assessed by echocardiographic images analyzed in a core laboratory. RESULTS: At baseline, at least mild TR was present in 30% of individuals. At 6 months, the proportion of participants with any TR in the TV-ICD group was 42% vs 19% in the S-ICD group (P < 0.001). The proportion with moderate or severe TR was 7% in the TV-ICD group vs 2% in the S-ICD group (P = 0.021). At 6 months, the OR of at least 1 grade worsening of TR in the TV-ICD group as compared with the S-ICD group was 7.2 (95% CI: 3.3-15.8; P < 0.001). There were no differences between groups with respect to RV size or systolic function. CONCLUSIONS: Six months following TV-ICD insertion, there was a 7-fold increase in the risk of at least 1 grade worsening of TR, with 7% of individuals having TR that was moderate or severe. There was no detectable difference in RV size or function; however, longer follow-up is needed.

Cardiac Interventions in Patients With Active, Advanced Solid and Hematologic Malignancies: JACC: CardioOncology State-of-the-Art Review.

Invasive cardiac interventions are recommended to treat ST-segment elevation myocardial infarction, non-ST-segment elevation acute coronary syndromes, multivessel coronary disease, severe symptomatic aortic stenosis, and cardiomyopathy. These recommendations are based on randomized controlled trials that historically included few individuals with active, advanced malignancies. Advanced malignancies represent a significant competing risk for mortality, and there is limited evidence to inform the risks and benefits of invasive cardiac interventions in affected patients. We review the benefit conferred by invasive cardiac interventions; the periprocedural considerations; the contemporary survival expectations of patients across several types of active, advanced malignancy; and the literature on cardiovascular interventions in these populations. Our objective is to develop a rational framework to guide clinical recommendations on the use of invasive cardiac interventions in patients with active, advanced cancer.

Three-Year Outcomes Following Permissive Cardiotoxicity in Patients on Trastuzumab.

INTRODUCTION: Cardiotoxicity, manifest by reduced left ventricular ejection fraction (LVEF), is the most common reason for the premature discontinuation of trastuzumab. While permissive cardiotoxicity (where mild cardiotoxicity is accepted to enable ongoing trastuzumab) has been shown feasible, the longer-term outcomes are unknown. We aimed to study the intermediate-term clinical outcomes of patients who underwent permissive cardiotoxicity. MATERIALS AND METHODS: We performed a retrospective cohort study of patients referred to the cardio-oncology service at McMaster University from 2016 to 2021 for LV dysfunction following trastuzumab administration. RESULTS: Fifty-one patients underwent permissive cardiotoxicity. The median (25th-75th percentile) follow-up time from cardiotoxicity onset was 3 years (1.3-4 years). Forty-seven (92%) patients completed trastuzumab; 3 (6%) developed severe LV dysfunction or clinical heart failure (HF) while on trastuzumab and prematurely discontinued therapy. One discontinued trastuzumab by patient choice. At final follow-up after therapy completion, 7 (14%) patients still had mild cardiotoxicity, including 2 who had clinical heart failure and stopped trastuzumab early. Among those with recovered LV function, 50% had normalized LVEF or GLS by 6 and 3 months, respectively, after initial cardiotoxicity. There was no difference in characteristics between those who did or did not recover their LV function. CONCLUSIONS: Among patients exposed to permissive trastuzumab cardiotoxicity for HER2-positive breast cancer, 6% were unable to complete planned trastuzumab due to severe LV dysfunction or clinical HF. Although most patients recover their LV function after trastuzumab discontinuation or completion, 14% still have persistent cardiotoxicity by 3-year follow-up.

Modifiable risk factors for prostate cancer in low- and lower-middle-income countries: a systematic review and meta-analysis.

BACKGROUND: Most of the epidemiological data on prostate cancer risk factors come from high-income countries (HIC). Reducing exposure to prostate cancer modifiable risk factors may significantly lower PCa morbidity and mortality in LIC and MIC. The objective of this study was to summarize the evidence on modifiable risk factors (RFs) for PCa in LIC and lower-middle-income countries (LMIC). METHODS: We conducted a systematic search on MEDLINE, EMBASE, and Global Health databases. We selected case-control and cohort studies from 2010 onwards that studied modifiable RFs for PCa in LIC and LMIC with a population of 30 million or more, as defined by the World Bank in January 2021. Risk of bias was assessed by the Ottawa-Newcastle tool. Individual study estimates were pooled when estimates were available for at least two studies. RESULTS: 5740 studies were initially identified; 16 studies met inclusion criteria. All were case-control studies except one retrospective cohort study. Higher fat intake was associated with a higher risk of PCa incidence with an odds ratio (OR) of 3.13 (95% CI 1.33-7.33). Higher vegetable intake (OR 0.48, 95% CI 0.24-0.97) and tea consumption (OR 0.51, 95% CI 0.32-0.83) were associated with a lower risk for PCa. There was no association between fruits, fish, and chicken consumption and risk of PCa. Alcohol consumption, smoking, red meat intake, and a BMI ≥ 25-30 kg/m2 showed a trend towards an increased risk, although these were not statistically significant. CONCLUSIONS: In LIC and LMIC, high fat intake was associated with higher risk of PCa while a diet rich in vegetables and tea intake was associated with a lower risk. Future prospective studies will be important to elucidate whether other modifiable risk factors for PCa specific to LIC and LMIC can be identified to inform impactful and cost-effective preventive strategies in these countries.

The Cardiologist's Role in the Management of Patients with a Genitourinary Cancer.

BACKGROUND: Increased life expectancy due to improved cancer prognosis, shared determinants (e.g., tobacco use), and cardiovascular toxicities related to cancer therapies, including the adverse cardiometabolic effects of androgen deprivation therapy for prostate cancer, make cardiovascular disease an frequent and important co-morbidity in patients with a genitourinary malignancy. Complex cardiovascular disease can pose significant challenges in the management of these patients given the uncertainties related to the best approach to reconcile ischemic and bleeding risks, and the role of invasive cardiovascular interventions in individuals with advanced cancer. In this review, we discuss the current evidence that informs decision-making in this clinical context.

The cardiovascular effects of gonadotropin-releasing hormone antagonists in men with prostate cancer.

AIMS: The aim of this study was to determine whether gonadotropin-releasing hormone (GnRH) antagonists (an emerging class of drugs to suppress testosterone synthesis in the treatment of prostate cancer) cause less adverse cardiovascular events than the more commonly use GnRH agonists. METHODS AND RESULTS: We conducted a systematic review to identify all randomized, controlled trials in which a GnRH antagonist was compared with a GnRH agonist in men with prostate cancer. We identified 10 eligible studies including two different GnRH antagonists, degarelix (n = 1681) and relugolix (n = 734), which were compared with the GnRH agonists, leuprolide (n = 714) and goserelin (n = 600). The pooled risk ratios (95% confidence intervals) among GnRH antagonist recipients for adverse cardiovascular events, cardiovascular death, and all-cause mortality were 0.57 (0.39-0.81); 0.49 (0.25-0.96); and 0.48 (0.28-0.83), respectively. Important limitations of the included trials were their short duration of follow-up, unblinded study design and (in most of the studies) the identification of adverse cardiovascular events through safety reporting mechanisms rather than as a pre-specified outcome. There was no evidence of heterogeneity of findings among the studies. CONCLUSIONS: There is consistent but methodologically limited data to suggest that GnRH antagonists-a relatively new class of androgen deprivation therapy for prostate cancer-cause significantly less cardiovascular adverse effects than the more frequently used GnRH agonists.

ALK inhibitor-induced bradycardia: A systematic-review and meta-analysis.

INTRODUCTION: Anaplastic Lymphoma Kinase (ALK) inhibitors have revolutionized the treatment of advanced ALK-positive non-small cell lung cancer (NSCLC), improving progression-free survival. Bradycardia is a potential adverse effect of these agents. We aimed to determine the risk of bradycardia associated with ALK inhibitors in patients with advanced NSCLC. MATERIALS AND METHODS: We conducted a systematic search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, National clinical trial registry, and Web of Science Core Collection. We included all randomized controlled trials in which an ALK-inhibitor was compared with another ALK-inhibitor or standard chemotherapy. Meta-analyses were conducted to evaluate the pooled incidence rates of bradycardia and dizziness using fixed effect models. RESULTS: The pooled incidence of bradycardia among 1737 individuals prescribed ALK inhibitors was 8% during a mean follow-up of 1.26 years. Crizotinib led to more bradycardia than standard chemotherapy (relative risk, RR 24.68, 95% CI 7.11-85.), while no difference was seen between crizotinib and alectinib (RR 1.12, 95% CI 0.79-1.59). The next-generation ALK inhibitors alectinib, brigatinib and lorlatinib combined resulted in a similar rate of bradycardia when compared to crizotinib (RR 0.77, 95% CI 0.57-1.04). All ALK inhibitors (as an aggregate) caused more dizziness (as a potential symptom of bradycardia) than standard chemotherapy (RR 1.88, 95% CI 1.44-2.44). CONCLUSION: Crizotinib for the treatment of NSCLC is associated with a higher risk for bradycardia compared to standard chemotherapy. There is no evidence of a difference in bradycardia risk between crizotinib and newer ALK inhibitors.