Reduction of dietary sodium to less than 100 mmol in heart failure (SODIUM-HF): an international, open-label, randomised, controlled trial.

BACKGROUND: Dietary restriction of sodium has been suggested to prevent fluid overload and adverse outcomes for patients with heart failure. We designed the Study of Dietary Intervention under 100 mmol in Heart Failure (SODIUM-HF) to test whether or not a reduction in dietary sodium reduces the incidence of future clinical events. METHODS: SODIUM-HF is an international, open-label, randomised, controlled trial that enrolled patients at 26 sites in six countries (Australia, Canada, Chile, Colombia, Mexico, and New Zealand). Eligible patients were aged 18 years or older, with chronic heart failure (New York Heart Association [NYHA] functional class 2-3), and receiving optimally tolerated guideline-directed medical treatment. Patients were randomly assigned (1:1), using a standard number generator and varying block sizes of two, four, or six, stratified by site, to either usual care according to local guidelines or a low sodium diet of less than 100 mmol (ie, <1500 mg/day). The primary outcome was the composite of cardiovascular-related admission to hospital, cardiovascular-related emergency department visit, or all-cause death within 12 months in the intention-to-treat (ITT) population (ie, all randomly assigned patients). Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT02012179, and is closed to accrual. FINDINGS: Between March 24, 2014, and Dec 9, 2020, 806 patients were randomly assigned to a low sodium diet (n=397) or usual care (n=409). Median age was 67 years (IQR 58-74) and 268 (33%) were women and 538 (66%) were men. Between baseline and 12 months, the median sodium intake decreased from 2286 mg/day (IQR 1653-3005) to 1658 mg/day (1301-2189) in the low sodium group and from 2119 mg/day (1673-2804) to 2073 mg/day (1541-2900) in the usual care group. By 12 months, events comprising the primary outcome had occurred in 60 (15%) of 397 patients in the low sodium diet group and 70 (17%) of 409 in the usual care group (hazard ratio [HR] 0·89 [95% CI 0·63-1·26]; p=0·53). All-cause death occurred in 22 (6%) patients in the low sodium diet group and 17 (4%) in the usual care group (HR 1·38 [0·73-2·60]; p=0·32), cardiovascular-related hospitalisation occurred in 40 (10%) patients in the low sodium diet group and 51 (12%) patients in the usual care group (HR 0·82 [0·54-1·24]; p=0·36), and cardiovascular-related emergency department visits occurred in 17 (4%) patients in the low sodium diet group and 15 (4%) patients in the usual care group (HR 1·21 [0·60-2·41]; p=0·60). No safety events related to the study treatment were reported in either group. INTERPRETATION: In ambulatory patients with heart failure, a dietary intervention to reduce sodium intake did not reduce clinical events. FUNDING: Canadian Institutes of Health Research and the University Hospital Foundation, Edmonton, Alberta, Canada, and Health Research Council of New Zealand.

Outcomes following heart or bilateral-lung transplantation from donors who died of drug toxicity in British Columbia, Canada.

INTRODUCTION: The illicit drug toxicity (overdose) crisis has worsened across Canada; between 2016 and 2021, more than 28,000 individuals have died of drug toxicity. Organ donation from persons who experience drug toxicity death (DTD) has increased in recent years. This study examines whether survival after heart or bilateral-lung transplantation differed by donor cause of death. METHODS: We studied transplant recipients in British Columbia who received heart (N = 110) or bilateral-lung (N = 223) transplantation from deceased donors aged 12-70 years between 2013 and 2019. Transplant recipient survival was compared by donor cause of death from drug toxicity or other. Five-year Kaplan-Meier estimates of survival and 3-year inverse probability treatment weighted Cox proportional hazards models were conducted. RESULTS: DTD donors made up 36% (40/110) of heart and 24% (54/223) of bilateral-lung transplantations. DTD donors were more likely to be young, white, and male. Unadjusted 5-year recipient survival was similar by donor cause of death (heart: 87% for DTD and 86% for non-DTD, p = .75; bilateral- lung: 80% for DTD and 76% for non-DTD, p = .65). Adjusted risk of mortality at 3-years post-transplant was similar between recipients of DTD and non-DTD donor heart (hazard ratio [HR]: .94, 95% confidence interval (CI): .22-4.07, p = .938) and bilateral-lung (HR: 1.06, 95% CI: .41-2.70, p = .908). CONCLUSION: Recipient survival after heart or bilateral-lung transplantation from DTD donors and non-DTD donors was similar. Donation from DTD donors is safe and should be considered more broadly to increase organ donation.

Stroke in Patients with Left Ventricular Assist Devices.

BACKGROUND: Left ventricular assist devices (LVADs) are artificial pumps used in end-stage heart failure to support the circulatory system. These cardiac assist devices work in parallel to the heart, diverting blood from the left ventricle through an outflow graft and into the ascending aorta. LVADs have allowed patients with end-stage heart failure to live longer and with improved quality of life compared to best medical therapy alone. However, they are associated with significant risks related to both thrombosis and bleeding in this medically complex patient population. As LVADs continue to be used more widely, stroke neurologists need to become familiar with the unique physical exam and vascular imaging findings associated with this population. SUMMARY: Reported rates of LVAD-associated stroke at 2 years post-implantation range from 10 to 30%, which is significantly higher than in age-matched controls. There are approximately equal rates of ischemic and hemorrhagic strokes, and rates are highest during the peri-implantation period and in the first year of therapy. Risk factors associated with ischemic and hemorrhagic stroke in this cohort can be grouped into treatment-related factors, including specific devices and antithrombotic/anticoagulation strategy, and patient-related factors. Evidence for reperfusion therapy for acute stroke in this population is limited. Intravenous tissue plasminogen activator (IV-tPA) is often contraindicated as events may occur in the perioperative setting, or in the context of therapeutic anticoagulation. Endovascular therapy with successful recanalization is reported, but there is little experience documented in the published literature. Key messages: LVAD use is increasingly common. Given the high associated risks of stroke, neurologists will need to become increasingly familiar with an approach to assessment and therapy for LVAD patients with cerebrovascular issues.

Impact of oral soluble guanylate cyclase stimulators in heart failure: A systematic review and Meta-analysis of randomized controlled trials.

BACKGROUND: Soluble guanylate cyclase (sGC) stimulators are a novel class of medications with emerging role in heart failure (HF). The aim of this study is to evaluate the efficacy and safety of oral sGC stimulators in patients with HF with reduced and preserved ejection fraction (HFrEF and HFpEF) by pooling data from all available randomized control trials (RCT). METHODS: A comprehensive search of electronic databases from 2000-2020 was performed. Seven RCTs, three HFrEF and four HFpEF studies, were identified. The follow-up duration ranged from 1 month to a median of 10.8 months. A random-effects meta-analysis was conducted to summarize the studies. RESULTS: The study population included 7190 patients: 5707 HFrEF and 1483 HFpEF patients. In HFrEF, oral sGC stimulators reduced the composite incidence of HF hospitalization and cardiovascular death (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.78-0.97; I2 = 0%), primarily driven by lower HF hospitalization (HR 0.88, 95% CI 0.78-0.99; I2 = 0%). There was no significant reduction in all-cause death in HFrEF (HR 0.95, 95% CI 0.83-1.09; I2 = 0%). In HFpEF, there were no improvements in Kansas City Cardiomyopathy Questionnaire clinical summary scores (mean difference 0.81, 95% CI -2.16-3.77; I2 = 72%) or 6-minute walk distance (mean difference 3.34 meters, 95% CI -7.86-14.54; I2 = 28%). There was no difference in all-cause mortality in HFpEF (HR 1.94, 95% CI 0.92-4.09; I2 = 0%). Overall, oral sGC stimulators had low medication-related serious adverse events. CONCLUSION: Oral sGC stimulators are well tolerated in HF and reduce the incidence of HF hospitalization but not cardiovascular death among patients with HFrEF. However, there are no apparent benefits in HFpEF.

Cardiac Sarcoidosis multi-center randomized controlled trial (CHASM CS- RCT).

Approximately 5% of patients with sarcoidosis have clinically manifest cardiac involvement. Clinical features of Cardiac Sarcoidosis are dependent on the location, extent, and activity of the disease. First line therapy is usually with prednisone and this is recommended based on clinician experience, expert opinion and small observational cohorts. There are no published clinical trials in cardiac sarcoidosis and multiple experts in the field have called for randomized clinical trials to answer important patient care questions. Corticosteroid are associated with multiple adverse effects including hypertension, diabetes, weight gain, osteoporosis, and increased risk of infections. In contrast Methotrexate is generally well tolerated and is increasingly used in other forms of sarcoidosis. OBJECTIVES: The Cardiac Sarcoidosis Multi-Center Randomized Controlled Trial (CHASM CS-RCT; NCT03593759) is a multicenter randomized controlled trial designed to evaluate the optimal initial treatment strategy for patients with active cardiac sarcoidosis. We hypothesize that (1) a low dose prednisone/methotrexate combination will have non-inferior efficacy to standard dose prednisone and that (2) the low dose prednisone/ methotrexate combination will result in significantly better quality of life than standard dose prednisone, as a result of reduced burden of side effects. METHODS/DESIGN: Eligible study subjects will have active clinically manifest cardiac sarcoidosis presenting with one or more of the following clinical findings: advanced conduction system disease, significant sinus node dysfunction, non-sustained or sustained ventricular arrhythmia, left ventricular dysfunction or right ventricular dysfunction. Subjects will be randomized in a 1:1 ratio to prednisone 0.5 mg/kg/day for 6 months (maximum dose 30 mg daily) OR to prednisone 20 mg daily for 1 month, then 10 mg daily for 1 month, then 5 mg daily for one month then stop AND methotrexate 15-20 mg once weekly for 6 months. The primary endpoint is summed perfusion rest score on 6-month PET (blinded core-lab review). The summed perfusion rest score is measure of myocardial fibrosis/scar. The design is non-inferiority with a sample size of 97 per group. DISCUSSION: Given the multiorgan system potential adverse side effects of prednisone, proving noninferiority of an alternate regimen would be sufficient to make the alternative compare favorably to standard dose steroids. This is the first ever clinical trial in cardiac sarcoidosis and thus in addition to the listed goals of the trial, we will also establish a multi-center, multinational cardiac sarcoidosis clinical trials network. Such a collaborative infrastructure will enable a new era of high quality data to guide physicians when treating cardiac sarcoidosis patients.

End-of-life care in patients with advanced heart failure.

PURPOSE OF REVIEW: With an aging population with heart failure, there is a growing need for end-of-life care in this population, including a focus on symptom management and quality-of-life considerations. RECENT FINDINGS: Targeted therapies focusing on symptom control and improving quality of life is the cornerstone of providing care in patients with heart failure near the end of life. Such therapies, including the use of inotropes for palliative purposes, have been shown to improve symptoms without an increase in mortality. In addition, recent evidence shows that implementing certain strategies in planning for end of life, including advance care planning and palliative care involvement, can significantly improve symptoms and quality of life, reduce hospitalizations, and ensure care respects patient values and preferences. SUMMARY: Shifting focus from prolonging life to enhancing quality of life in heart failure patients approaching the end of life can be achieved by recognizing and managing end-stage heart failure-related symptoms, advanced care planning, and a multidisciplinary care approach.

Mechanical circulatory support in the heart failure population.

PURPOSE OF REVIEW: Use of durable left ventricular assist devices (LVADs) has increased considerably in recent years because of the insufficient supply of donor hearts for cardiac transplantation and improvement in outcomes from refinements in technology. This review examines clinical utility of these devices and summarizes the most recent evidence supporting the use of LVAD therapy. RECENT FINDINGS: There continues to be significant advancements made in LVAD technology, which has resulted in improvements in the rates of adverse events and overall patient quality of life. Specifically, less invasive and improved surgical techniques have resulted in fewer incidence of pump thrombosis and stringent blood pressure management have been shown to significantly decrease stroke rates. SUMMARY: The continued advances in LVAD therapy have resulted in significant improvement in overall survival; however, complication rates remain relatively high. Future work will focus on improvements in adverse outcomes and ultimately the possibility that LVADs will be a viable alternative to transplantation in patients with end-stage heart failure.

Update on the management of acute heart failure.

PURPOSE OF REVIEW: We provide a concise review of recent studies focusing on the management of patients with acute heart failure (AHF). RECENT FINDINGS: In well designed randomized trials, no mortality benefit has been observed with the use of diuretics, ultrafiltration, inotropes and vasodilators in AHF. Recent trials examining the role of novel inotropes and vasodilators as well as the role of mineralocorticoid receptor antagonists in the AHF population, is reviewed. SUMMARY: The focus of therapy in AHF should be directed towards symptom management. No mortality benefit has been observed despite good quality studies.

Enumerateblood - an R package to estimate the cellular composition of whole blood from Affymetrix Gene ST gene expression profiles.

BACKGROUND: Measuring genome-wide changes in transcript abundance in circulating peripheral whole blood is a useful way to study disease pathobiology and may help elucidate the molecular mechanisms of disease, or discovery of useful disease biomarkers. The sensitivity and interpretability of analyses carried out in this complex tissue, however, are significantly affected by its dynamic cellular heterogeneity. It is therefore desirable to quantify this heterogeneity, either to account for it or to better model interactions that may be present between the abundance of certain transcripts, specific cell types and the indication under study. Accurate enumeration of the many component cell types that make up peripheral whole blood can further complicate the sample collection process, however, and result in additional costs. Many approaches have been developed to infer the composition of a sample from high-dimensional transcriptomic and, more recently, epigenetic data. These approaches rely on the availability of isolated expression profiles for the cell types to be enumerated. These profiles are platform-specific, suitable datasets are rare, and generating them is expensive. No such dataset exists on the Affymetrix Gene ST platform. RESULTS: We present 'Enumerateblood', a freely-available and open source R package that exposes a multi-response Gaussian model capable of accurately predicting the composition of peripheral whole blood samples from Affymetrix Gene ST expression profiles, outperforming other current methods when applied to Gene ST data. CONCLUSIONS: 'Enumerateblood' significantly improves our ability to study disease pathobiology from whole blood gene expression assayed on the popular Affymetrix Gene ST platform by allowing a more complete study of the various components of this complex tissue without the need for additional data collection. Future use of the model may allow for novel insights to be generated from the ~400 Affymetrix Gene ST blood gene expression datasets currently available on the Gene Expression Omnibus (GEO) website.

Barriers to Goals of Care Discussions With Patients Who Have Advanced Heart Failure: Results of a Multicenter Survey of Hospital-Based Cardiology Clinicians.

BACKGROUND: Conversations about goals of care in hospital are important to patients who have advanced heart failure (HF). METHODS: We conducted a multicenter survey of cardiology nurses, fellows, and cardiologists at 8 Canadian teaching hospitals. The primary outcome was the importance of barriers to goals-of-care discussions in hospital (1 = extremely unimportant; 7 = extremely important). We also elicited perspectives on roles of different practitioners in having these conversations. RESULTS: Questionnaires were returned by 770/1024 (75.2%) eligible clinicians. The most important perceived barriers were: family members' and patients' difficulty in accepting a poor prognosis (mean [SD] score 5.9 [1.1] and 5.7 [1.2], respectively), family members' and patients' lack of understanding about the limitations and harms of life-sustaining treatments (5.8 [1.1] and 5.7 [1.2], respectively), and lack of agreement among family members about goals of care (5.8 [1.2]). Interprofessional team members were viewed as having different but important roles in goals-of-care discussions. CONCLUSIONS: Cardiology clinicians perceive family and patient-related factors as the most important barriers to goals-of-care discussions in hospital. Many members of the interprofessional team were viewed as having important roles in addressing goals of care. These findings can inform the design of future interventions to improve communication about goals of care in advanced HF.

Qualitative Analysis of Patient Decisional Needs for Medications to Treat Heart Failure.

BACKGROUND: The development of tools to support shared decision-making should be informed by patients' decisional needs and treatment preferences, which are largely unknown for heart failure (HF) with reduced ejection fraction (HFrEF) pharmacotherapy decisions. We aimed to identify patients' decisional needs when considering HFrEF medication options. METHODS: This was a qualitative study using semi-structured interviews. We recruited patients with HFrEF from 2 Canadian ambulatory HF clinics and clinicians from Canadian HF guideline panels, HF clinics, and Canadian HF Society membership. We identified themes through inductive thematic analysis. RESULTS: Participants included 15 patients and 12 clinicians. Six themes and associated subthemes emerged related to HFrEF pharmacotherapy decision-making: (1) patient decisional needs included lack of awareness of a choice or options, difficult decision timing and stage, information overload, and inadequate motivation, support and resources; (2) patients' decisional conflict varied substantially, driven by unclear trade-offs; (3) treatment attribute preferences-patients focused on both benefits and downsides of treatment, whereas clinicians centered discussion on benefits; (4) quality of life-patients' definition of quality of life depended on pre-HF activity, though most patients demonstrated adaptability in adjusting their daily activities to manage HF; (5) shared decision-making process-clinicians' described a process more akin to informed consent; (6) decision support-multimedia decision aids, virtual appointments, and primary-care comanagement emerged as potential enablers of shared decision-making. CONCLUSIONS: Patients with HFrEF have several decisional needs, which are consistent with those that may respond to decision aids. These findings can inform the development of HFrEF pharmacotherapy decision aids to address these decisional needs and facilitate shared decision-making.

Factors Impacting Physician Prognostic Accuracy in Heart Failure Patients With Reduced Left Ventricular Ejection Fraction.

BACKGROUND: A recent study showed that the accuracy of heart failure (HF) cardiologists and family doctors to predict mortality in outpatients with HF proved suboptimal, performing less well than models. OBJECTIVES: The authors sought to evaluate patient and physician factors associated with physician accuracy. METHODS: The authors included outpatients with HF from 11 HF clinics. Family doctors and HF cardiologists estimated patient 1-year mortality. They calculated predicted mortality using the Seattle HF Model and followed patients for 1 year to record mortality (or urgent heart transplant or ventricular assist device implant as mortality-equivalent events). Using multivariable logistic regression, the authors evaluated associations among physician experience and confidence in estimates, duration of patient-physician relationship, patient-physician sex concordance, patient race, and predicted risk, with concordant results between physician and model predictions. RESULTS: Among 1,643 patients, 1-year event rate was 10% (95% CI: 8%-12%). One-half of the estimates showed discrepant results between model and physician predictions, mainly owing to physician risk overestimation. Discrepancies were more frequent with increasing patient risk from 38% in low-risk to ∼75% in high-risk patients. When making predictions on male patients, female HF cardiologists were 26% more likely to have discrepant predictions (OR: 0.74; 95% CI: 0.58-0.94). HF cardiologist estimates in Black patients were 33% more likely to be discrepant (OR: 0.67; 95% CI: 0.45-0.99). Low confidence in predictions was associated with discrepancy. Analyses restricted to high-confidence estimates showed inferior calibration to the model, with risk overestimation across risk groups. CONCLUSIONS: Discrepant physician and model predictions were more frequent in cases with perceived increased risk. Model predictions outperform physicians even when they are confident in their predictions. (Predicted Prognosis in Heart Failure [INTUITION]; NCT04009798).

Predicting 1-Year Mortality in Outpatients With Heart Failure With Reduced Left Ventricular Ejection Fraction: Do Empiric Models Outperform Physician Intuitive Estimates? A Multicenter Cohort Study.

BACKGROUND: Many studies have demonstrated that physicians often err in estimating patient prognosis. No studies have directly compared physician to model predictive performance in heart failure (HF). We aimed to compare the accuracy of physician versus model predictions of 1-year mortality. METHODS: This multicenter prospective cohort study on 11 HF clinics in 5 provinces in Canada included consecutive consented outpatients with HF with reduced left ventricular ejection fraction (<40%). By collecting clinical data, we calculated predicted 1-year mortality using the Seattle HF Model (SHFM), the Meta-Analysis Global Group in Chronic HF score, and the HF Meta-Score. HF cardiologists and family doctors, blinded to model predictions, estimated patient 1-year mortality. During 1-year follow-up, we recorded the composite end point of mortality, urgent ventricular assist device implant, or heart transplant. We compared physicians and model discrimination (C statistic), calibration (observed versus predicted event rate), and risk reclassification. RESULTS: The study included 1643 patients with ambulatory HF with a mean age of 65 years, 24% female, and mean left ventricular ejection fraction of 28%. Over 1-year follow-up, 9% had an event. The SHFM had the best discrimination (SHFM C statistic 0.76; HF Meta-Score 0.73; Meta-Analysis Global Group in Chronic Heart Failure 0.70) and calibration. Physicians' discrimination differed little (0.75 for HF cardiologists and 0.73 for family doctors) but both physician groups substantially overestimated risk by >10% in both low- and high-risk patients (poor calibration). In risk reclassification analysis, among patients without events, the SHFM better classified 51% in comparison to HF cardiologists and 43% in comparison to family doctors. In patients with events, the SHFM erroneously assigned lower risk to 44% in comparison to HF cardiologists and 34% in comparison to family doctors. CONCLUSIONS: Family doctors and HF cardiologists showed adequate risk discrimination, with however substantial overestimation of absolute risk. Predictive models showed higher accuracy. Incorporating models in family and HF cardiology practices may improve patient care and resource use in HF with reduced left ventricular ejection fraction. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04009798.

Regulatory T Cell Biomarkers Identify Patients at Risk of Developing Acute Cellular Rejection in the First Year Following Heart Transplantation.

BACKGROUND: Acute cellular rejection (ACR), an alloimmune response involving CD4+ and CD8+ T cells, occurs in up to 20% of patients within the first year following heart transplantation. The balance between a conventional versus regulatory CD4+ T cell alloimmune response is believed to contribute to developing ACR. Therefore, tracking these cells may elucidate whether changes in these cell populations could signal ACR risk. METHODS: We used a CD4+ T cell gene signature (TGS) panel that tracks CD4+ conventional T cells (Tconv) and regulatory T cells (Treg) on longitudinal samples from 94 adult heart transplant recipients. We evaluated combined diagnostic performance of the TGS panel with a previously developed biomarker panel for ACR diagnosis, HEARTBiT, while also investigating TGS' prognostic utility. RESULTS: Compared with nonrejection samples, rejection samples showed decreased Treg- and increased Tconv-gene expression. The TGS panel was able to discriminate between ACR and nonrejection samples and, when combined with HEARTBiT, showed improved specificity compared with either model alone. Furthermore, the increased risk of ACR in the TGS model was associated with lower expression of Treg genes in patients who later developed ACR. Reduced Treg gene expression was positively associated with younger recipient age and higher intrapatient tacrolimus variability. CONCLUSIONS: We demonstrated that expression of genes associated with CD4+ Tconv and Treg could identify patients at risk of ACR. In our post hoc analysis, complementing HEARTBiT with TGS resulted in an improved classification of ACR. Our study suggests that HEARTBiT and TGS may serve as useful tools for further research and test development.

Brain, heart, and sudden death.

During the past 30 years, rate of coronary artery disease (CAD), as the main cause of sudden death (SD), has decreased more than rate of SD. Likewise, cause of SD remains elusive in not a trivial portion of its victims. One possible reason is attention to only one organ, the heart, as the cause of SD. In fact, SD literature focuses more on the heart, less on the brain, and seldom on both. A change is required. In this paper, we first review the pathological findings seen in heart autopsies of SD victims after psychological stressors such as physical assault victims without internal injuries. Then, we summarize new studies investigating brain areas, like the insula, whose malfunctions and injuries are related to SD. Next, we review prototypes of neurological diseases and psychological stressors associated with SD and look at heart failure (HF)-related SD providing evidence for the brain-heart connection. Finally, we propose a new look at SD risk factors considering both brain and heart in their association with SD, and review strategies for prevention of SD from this perspective.

COVID-19-positivity in a heart transplant recipient-antibody-mediated rejection or SARS-CoV-2-associated cardiac injury?

Through the ongoing and heightening coronavirus disease 2019 (COVID-19) pandemic, the heart has been implicated as a central target of injury associated with significantly increased morbidity and mortality. Correspondingly, heart transplant recipients are a vulnerable population for which insufficient research has been conducted. Pathologic antibody-mediated rejection (pAMR) of cardiac allografts shares many characteristics with COVID-19-associated cardiac injury. In this case study, we investigate a 57-year-old female who contracted COVID-19 11 days postheart transplant and was observed to have pAMR while positive for laboratory-confirmed COVID-19, resulting in a diagnostic conundrum.

Does Opium Consumption Have Shared Impact on Atherosclerotic Cardiovascular Disease and Cancer?

Although atherosclerotic cardiovascular disease (ASCVD) and cancer are seemingly different types of disease, they have multiple shared underlying mechanisms and lifestyle-related risk factors like smoking, unhealthy diet, excessive alcohol consumption, and inadequate physical activity. Opium abuse is prevalent in developing countries, especially the Middle East region and many Asian countries. Besides recreational purposes, many people use opium based on a traditional belief that opium consumption may confer protection against heart attack and improve the control of the risk factors of ASCVD such as diabetes mellitus, hypertension, and dyslipidemia. However, scientific reports indicate an increased risk of ASCVD and poor control of ASCVD risk factors among opium abusers compared with nonusers. Moreover, there is accumulating evidence that opium consumption exerts potential carcinogenic effects and increases the risk of developing various types of cancer. We conducted a review of the literature to review the current evidence on the relationship between opium consumption and ASCVD as well as various kinds of cancer. In addition, we will discuss the potential shared pathophysiologic mechanisms underlying the association between opium abuse and both ASCVD and cancer.

Non-culprit coronary artery percutaneous coronary intervention during acute ST-segment elevation myocardial infarction: insights from the APEX-AMI trial.

AIMS: To examine the incidence of and propensity for non-culprit interventions performed at the time of the primary percutaneous coronary intervention (PCI) and its association with 90-day outcomes. METHODS AND RESULTS: We examined the incidence, propensity for, and associated 90-day outcomes following non-culprit interventions performed at the time of primary PCI among ST-elevation myocardial infarction patients with multi-vessel coronary artery disease (MVD). Of the 5373 patients who underwent primary PCI in the APEX-AMI trial, 2201 had MVD. Of those, 217 (9.9%) underwent non-infarct-related arteries (IRA) PCI, whereas 1984 (90.1%) underwent PCI of the IRA alone. Ninety-day death and death/CHF/shock were higher in the non-IRA group compared with the IRA-only PCI group (12.5 vs. 5.6%, P (log-rank) < 0.001 and 17.4 vs. 12.0%, P (log-rank) = 0.020, respectively). After adjusting for patient and procedural characteristics as well as propensity for performing non-IRA PCI, this procedure remained independently associated with an increased hazard of 90-day mortality [adjusted hazard ratio 2.44, 95% CI (1.55-3.83), P < 0.001]. CONCLUSION: Non-culprit coronary interventions were performed at the time of primary PCI in 10% of MVD patients and were significantly associated with increased mortality. Our data support current guideline recommendations discouraging the performance of such procedures in stable primary PCI patients. Prospective randomized study of this issue may be warranted.

The State of the Heart Biopsy: A Clinical Review.

Endomyocardial biopsy (EMB) is an invaluable and underused diagnostic tool for myocardial disease. The primary indications are surveillance of cardiac allograft rejection and the diagnosis of inflammatory and infiltrative cardiomyopathies. EMB is typically performed by sampling the right ventricular septum via the right internal jugular vein using fluoroscopic guidance. The diagnostic yield of EMB is improved by sampling both ventricles and with the use of guidance from imaging or electroanatomic mapping. The risk of major cardiac complications is operator dependent and < 1% in experienced centres. EMB is the gold standard and most common form of cardiac allograft rejection surveillance, whereas advanced cardiac imaging and donor-specific antibody quantification provide complementary information. Gene expression profiling is an alternative surveillance strategy to EMB for low-risk patients. EMB is recommended for myocarditis and can guide therapy for giant-cell myocarditis, necrotizing eosinophilic myocarditis, sarcoidosis, and immune checkpoint inhibitor myocarditis. There is growing interest in using EMB to guide therapy for viral myocarditis, although the uptake of this approach is limited to specialized centres. EMB has been replaced as a first-line test for infiltrative cardiomyopathy by nonbiopsy diagnostic techniques, but is still useful to clarify the diagnosis or disease subtype. The miniaturization of bioptomes and advances in laboratory techniques such as microarrays promises to improve the safety and yield of EMB. We review the contemporary use of EMB for cardiac allograft rejection, inflammatory cardiomyopathy, and infiltrative cardiomyopathy.

La biopsie endomyocardique est un outil diagnostique sous-utilisé et très utile en cas de maladie myocardique. Ses principales indications sont la surveillance du rejet d'une allogreffe cardiaque et le diagnostic des cardiomyopathies restrictives (infiltrantes) et inflammatoires. La biopsie endomyocardique est généralement réalisée en prélevant un échantillon du septum ventriculaire droit par la veine jugulaire interne droite, sous guidage fluoroscopique. Le succès diagnostique de la biopsie endomyocardique est amélioré en prélevant un échantillon des deux ventricules et en utilisant le guidage par imagerie ou cartographie électroanatomique. Le risque de complications cardiaques majeures varie en fonction de la personne qui effectue l'intervention, et est de moins de 1 % dans les centres où cette intervention est courante. La biopsie endomyocardique est la norme de référence et la forme la plus courante de surveillance du rejet d'une allogreffe cardiaque, tandis que les techniques avancées d'imagerie cardiaque et la quantification des anticorps spécifiques au donneur fournissent de l'information complémentaire. Le profil d'expression génétique est une stratégie de surveillance qui peut être utilisée plutôt que la biopsie endomyocardique chez les patients à faible risque. La biopsie endomyocardique est recommandée pour la myocardite et peut guider le traitement dans les cas de myocardite à cellules géantes, de myocardite nécrosante éosinophilique, de sarcoïdose et de myocardite induite par les inhibiteurs du point de contrôle immunitaire. La biopsie endomyocardique est de plus en plus utilisée pour guider le traitement de la myocardite virale, même si l'adoption de cette approche n'est observée que dans les centres spécialisés. En première intention, la biopsie endomyocardique a été remplacée par des techniques diagnostiques n'ayant pas recours à la biopsie dans les cas de cardiomyopathie restrictive, mais demeure néanmoins utile pour préciser le diagnostic ou le sous-type de maladie. La miniaturisation des bioptomes et les progrès en matière de techniques de laboratoire, comme les microréseaux, devraient améliorer l'innocuité et l'efficacité de la biopsie endomyocardique. Nous avons passé en revue l'utilisation faite à l'heure actuelle de la biopsie endomyocardique en ce qui concerne le rejet de l'allogreffe cardiaque, la cardiomyopathie inflammatoire et la cardiomyopathie restrictive.

Corticosteroid and Immunosuppressant Therapy for Cardiac Sarcoidosis: A Systematic Review.

Background Corticosteroid therapy for the treatment of clinically manifest cardiac sarcoidosis is generally recommended. Our group previously systematically reviewed the data in 2013; since then, there has been increasing quality and quantity of data and also interest in nonsteroid agents. Methods and Results Studies were identified from MEDLINE, EMBASE, Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, and the National Institutes of Health ClinicalTrials.gov database. The quality of included articles was rated using Scottish Intercollegiate Guidelines Network 50. Outcomes examined were atrioventricular conduction, left ventricular function, ventricular arrhythmias, and mortality. A total of 3527 references were retrieved, and 34 publications met the inclusion criteria. There were no randomized trials, and only 2 studies were rated good quality. In the 34 reports (total of 1297 patients), 1125 patients received corticosteroids, 235 received additional or other immunosuppressant therapy, and 97 patients received no therapy. There were 178 patients treated for atrioventricular conduction disease, with 76/178 (42.7%) improving. In contrast, 21 patients were not treated with corticosteroids and/or immunosuppressant therapy, and none of them improved. Therapy was associated with the prevention of deterioration in left ventricular function. A total of 8 publications reported on ventricular arrhythmia burden, and 19 reported on mortality; the data quality was too limited to draw conclusions for the latter 2 outcomes. Conclusions The best quality data relate to atrioventricular nodal conduction and left ventricular function recovery. In both situations, therapy with corticosteroids and/or immunosuppressant therapy were sometimes associated with positive outcomes. The data quality is too limited to draw conclusions for ventricular arrhythmias and mortality.