Sudden cardiac arrest in patients with cancer in the general population: insights from the Paris-SDEC registry.

BACKGROUND: Data on the management of patients with cancer presenting with sudden cardiac arrest (SCA) are scarce. We aimed to assess the characteristics and outcomes of SCA according to cancer history. METHODS: Prospective, population-based registry including every out-of-hospital SCA in adults in Paris and its suburbs, between 2011 and 2019, with a specific focus on patients with cancer. RESULTS: Out of 4069 patients who had SCA admitted alive in hospital, 207 (5.1%) had current or past medical history of cancer. Patients with cancer were older (69.2 vs 59.3 years old, p<0.001), more often women (37.2% vs 28.0%, p=0.006) with more frequent underlying cardiovascular disease (41.1% vs 32.5%, p=0.01). SCA happened more often with a non-shockable rhythm (62.6% vs 43.1%, p<0.001) with no significant difference regarding witness presence and cardiopulmonary resuscitation (CPR) performed. Cardiac causes were less frequent among patients with cancer (mostly acute coronary syndromes, 25.5% vs 46.8%, p<0.001) and had more respiratory causes (pulmonary embolism and hypoxaemia in 34.2% vs 10.8%, p<0.001). Still, no difference regarding in-hospital survival was found after SCA in patients with cancer versus other patients (26.2% vs 29.8%, respectively, p=0.27). Public location, CPR by witness and shockable rhythm were independent predictors of in-hospital survival after SCA in the cancer group. CONCLUSIONS: One in 20 SCA occurs in patients with a history of cancer, yet with fewer cardiac causes than in patients who are cancer-free. Still, in-hospital outcomes remain similar even in patients with known cancer. Cancer history should therefore not compromise the initiation of resuscitation in the context of SCA.

Adverse myocardial and vascular side effects of immune checkpoint inhibitors: a prospective multimodal cardiovascular assessment.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can induce cardiovascular toxicities. OBJECTIVES: To prospectively assess the incidence of major cardiovascular events (MACE) on ICIs in solid cancer patients: myocarditis, pericarditis, acute coronary syndrome, heart failure, high-degree conduction abnormalities or sustained ventricular arrhythmias, or cardiovascular death at 6 weeks (early MACE), including asymptomatic clinical changes by an independent adjudication committee using current recommended diagnostic criteria. The secondary objective was the incidence of the above-mentioned events adding atrial fibrillation (AF) at 6 months (late MACE). RESULTS: Participants underwent pre-ICIs and repeated multimodality cardiac imaging (echocardiogram, cardiac magnetic resonance (CMR)), serum biomarkers (ultrasensitive troponin I), and rhythm surveillance (ambulatory ECG monitoring) at 6 weeks and 6 months. Forty-nine patients (38 (77.6%) male; mean age 64.3 (SD 11.0) years old) were included (June 2020-December 2021). Early MACE were observed in 9 (18.4%) patients at mean 40.1 (SD 5.9) days, with heart failure (HF) in 5 (10.2%), ventricular arrhythmias, or new conduction disorders in 4 (8.2%) patients. History of AF (HR 4.49 (CI 1.11-18.14), P = 0.035) predicted early MACE. At 6 months follow-up, 18 MACE were observed in 15/49 (31%) patients, with 6 (12.2%) HF events, 5 (10.2%) significant ventricular arrhythmias, or conduction disorders, and 4 (8.2%) AF. There was a significant decline in LVEF (P < 0.001) in patients with no MACE (P = 0.003) or HF (P = 0.0028). Higher creatinine at inclusion (HR 0.99 [0.98-1.00], P = 0.006) predicted HF on multivariate analysis. There were no significant T1 or T2 mapping changes in our study cohort on repeated CMR. CONCLUSIONS: Cardiotoxicity on ICIs is more frequent than previously described when using a thorough detection strategy, consisting mainly in HF and asymptomatic rhythm disorders.

2023 World Heart Federation guidelines for the echocardiographic diagnosis of rheumatic heart disease.

Rheumatic heart disease (RHD) is an important and preventable cause of morbidity and mortality among children and young adults in low-income and middle-income countries, as well as among certain at-risk populations living in high-income countries. The 2012 World Heart Federation echocardiographic criteria provided a standardized approach for the identification of RHD and facilitated an improvement in early case detection. The 2012 criteria were used to define disease burden in numerous epidemiological studies, but researchers and clinicians have since highlighted limitations that have prompted a revision. In this updated version of the guidelines, we incorporate evidence from a scoping review, an expert panel and end-user feedback and present an approach for active case finding for RHD, including the use of screening and confirmatory criteria. These guidelines also introduce a new stage-based classification for RHD to identify the risk of disease progression. They describe the latest evidence and recommendations on population-based echocardiographic active case finding and risk stratification. Secondary antibiotic prophylaxis, echocardiography equipment and task sharing for RHD active case finding are also discussed. These World Heart Federation 2023 guidelines provide a concise and updated resource for clinical and research applications in RHD-endemic regions.

Outcomes of latent rheumatic heart disease: External validation of a simplified score in patients with and without secondary prophylaxis.

BACKGROUND: Secondary antibiotic prophylaxis reduces progression of latent rheumatic heart disease (RHD) but not all children benefit. Improved risk stratification could refine recommendations following positive screening. We aimed to evaluate the performance of a previously developed echocardiographic risk score to predict mid-term outcomes among children with latent RHD. METHODS: We included children who completed the GOAL, a randomized trial of secondary antibiotic prophylaxis among children with latent RHD in Uganda. Outcomes were determined by a 4-member adjudication panel. We applied the point-based score, consisting of 5 variables (mitral valve (MV) anterior leaflet thickening (3 points), MV excessive leaflet tip motion (3 points), MV regurgitation jet length ≥ 2 cm (6 points), aortic valve focal thickening (4 points) and any aortic regurgitation (5 points)), to panel results. Unfavorable outcome was defined as progression of diagnostic category (borderline to definite, mild definite to moderate/severe definite), worsening valve involvement or remaining with mild definite RHD. RESULTS: 799 patients (625 borderline and 174 definite RHD) were included, with median follow-up of 24 months. At total 116 patients (14.5%) had unfavorable outcome per study criteria, 57.8% not under prophylaxis. The score was strongly associated with unfavorable outcome (HR = 1.26, 95% CI 1.16-1.37, p < 0.001). Unfavorable outcome rates in low (≤6 points), intermediate (7-9 points) and high-risk (≥10 points) children at follow-up were 11.8%, 30.4%, and 42.2%, (p < 0.001) respectively (C-statistic = 0.64 (95% CI 0.59-0.69)). CONCLUSIONS: The simple risk score provided an accurate prediction of RHD status at 2-years, showing a good performance in a population with milder RHD phenotypes.

Primary prevention of cancer-associated venous thrombosis: Rationale and challenges in clinical practice.

Cancer-associated venous thrombosis (CAT) is a common, multifactor event known to complicate the course of cancer and jeopardize a patient's prognosis. The current guidelines regarding the prevention of CAT are sometimes considered insufficiently precise about specific situations, or are poorly applied. The expected benefits of thromboprophylaxis are balanced by the risk of major bleeding induced by anticoagulation, which implies a need to accurately identify ambulatory patients at high risk of thrombosis or hemorrhage. The Khorana score is commonly used for this, but is limited by the non-reproducibility of predicted performance across cancer types, and by the fact that antitumor treatment and cardiovascular risks are not included. The COMPASS-CAT score, which includes those two aspects, was found to be a more accurate predictor of venous thromboembolism in patients with lung cancer, and to better distinguish between patients at low or high risk of thrombosis. The frailty of patients with cancer is also a major issue, and should be taken into account when thromboprophylaxis is considered. According to current guidelines, CAT prophylaxis should be considered for hospitalized patients, those for whom surgery is scheduled, or those with pancreatic cancers. In ambulatory patients, decisions should be made according to patient, cancer and antitumoral treatment characteristics. Low molecular weight heparin is the gold standard of CAT prophylaxis. Despite increased risks of bleeding or drug-drug interactions in cancer patients, direct oral anticoagulants could be alternate options for high-risk ambulatory patients that should be accompanied by a careful global analysis of benefits, harms, and patient preferences.

Secondary Antibiotic Prophylaxis for Latent Rheumatic Heart Disease.

BACKGROUND: Rheumatic heart disease affects more than 40.5 million people worldwide and results in 306,000 deaths annually. Echocardiographic screening detects rheumatic heart disease at an early, latent stage. Whether secondary antibiotic prophylaxis is effective in preventing progression of latent rheumatic heart disease is unknown. METHODS: We conducted a randomized, controlled trial of secondary antibiotic prophylaxis in Ugandan children and adolescents 5 to 17 years of age with latent rheumatic heart disease. Participants were randomly assigned to receive either injections of penicillin G benzathine (also known as benzathine benzylpenicillin) every 4 weeks for 2 years or no prophylaxis. All the participants underwent echocardiography at baseline and at 2 years after randomization. Changes from baseline were adjudicated by a panel whose members were unaware of the trial-group assignments. The primary outcome was echocardiographic progression of latent rheumatic heart disease at 2 years. RESULTS: Among 102,200 children and adolescents who had screening echocardiograms, 3327 were initially assessed as having latent rheumatic heart disease, and 926 of the 3327 subsequently received a definitive diagnosis on the basis of confirmatory echocardiography and were determined to be eligible for the trial. Consent or assent for participation was provided for 916 persons, and all underwent randomization; 818 participants were included in the modified intention-to-treat analysis, and 799 (97.7%) completed the trial. A total of 3 participants (0.8%) in the prophylaxis group had echocardiographic progression at 2 years, as compared with 33 (8.2%) in the control group (risk difference, -7.5 percentage points; 95% confidence interval, -10.2 to -4.7; P<0.001). Two participants in the prophylaxis group had serious adverse events that were attributable to receipt of prophylaxis, including one episode of a mild anaphylactic reaction (representing <0.1% of all administered doses of prophylaxis). CONCLUSIONS: Among children and adolescents 5 to 17 years of age with latent rheumatic heart disease, secondary antibiotic prophylaxis reduced the risk of disease progression at 2 years. Further research is needed before the implementation of population-level screening can be recommended. (Funded by the Thrasher Research Fund and others; GOAL ClinicalTrials.gov number, NCT03346525.).

Rheumatic heart disease in The Gambia: clinical and valvular aspects at presentation and evolution under penicillin prophylaxis.

BACKGROUND: Rheumatic heart disease (RHD) remains the leading cause of cardiac-related deaths and disability in children and young adults worldwide. In The Gambia, the RHD burden is thought to be high although no data are available and no control programme is yet implemented. We conducted a pilot study to generate baseline data on the clinical and valvular characteristics of RHD patients at first presentation, adherence to penicillin prophylaxis and the evolution of lesions over time. METHODS: All patients registered with acute rheumatic fever (ARF) or RHD at two Gambian referral hospitals were invited for a clinical review that included echocardiography. In addition, patients were interviewed about potential risk factors, disease history, and treatment adherence. All clinical and echocardiography information at first presentation and during follow-up was retrieved from medical records. RESULTS: Among 255 registered RHD patients, 35 had died, 127 were examined, and 111 confirmed RHD patients were enrolled, 64% of them females. The case fatality rate in 2017 was estimated at 19.6%. At first presentation, median age was 13 years (IQR [9; 18]), 57% patients had late stage heart failure, and 84.1% a pathological heart murmur. Although 53.2% of them reported history of recurrent sore throat, only 32.2% of them had sought medical treatment. A history suggestive of ARF was reported by 48.7% patients out of whom only 15.8% were adequately treated. Two third of the patients (65.5%) to whom it was prescribed were fully adherent to penicillin prophylaxis. Progressive worsening and repeated hospitalisation was experienced by 46.8% of the patients. 17 patients had cardiac surgery, but they represented only 18.1% of the 94 patients estimated eligible for cardiac surgery. CONCLUSION: This study highlights for the first time in The Gambia the devastating consequences of RHD on the health of adolescents and young adults. Our findings suggest a high burden of disease that remains largely undetected and without appropriate secondary prophylaxis. There is a need for the urgent implementation of an effective national RHD control programto decrease the unacceptably high mortality rate, improve case detection and management, and increase community awareness of this disease.

[Right ventricle metastasis from a colonic cancer: Diagnosis by using endomyocardial biopsy]. / Métastase ventriculaire droite d'un adénocarcinome colique : diagnostic par biopsie endomyocardique.

The diagnosis of cardiac tumors has been dramatically improved by modern cardiac imaging. In cases presenting with right intracavitary mass the diagnosis can rely on right endomyocardial biopsy. We report here a case of right ventricle tumor whose diagnosis was established as a colonic metastasis by using right endomyocardial biopsy.

Acute Stress Cardiomyopathy: Heart of pheochromocytoma.

Stress cardiomyopathy (SCM) is a syndrome characterized by transient regional systolic dysfunction of the left ventricle in the absence of angiographic evidence of coronaropathy. This abnormality is associated with high levels of catecholamines. Stress cardiomyopathy is also called Takotsubo (TS) cardiomyopathy. Pheochromocytoma crisis can occur spontaneously or can be precipitated by manipulation of the tumor, trauma, certain medications or stress for example during non-adrenal surgery. The main drugs leading to pheochromocytoma crisis include D2 dopamine receptor antagonists, noncardioselective ß-adrenergic receptor blockers, tricyclic antidepressants and related neurotransmitter uptake blockers, sympathomimetics, certain peptide and steroid hormones and several agents used during induction of anesthesia. Patients can develop symptoms of heart failure associated with tachyarrhythmia, cardiogenic shock with hypotension and collapse, or apparent acute coronary syndromes. This review describes pathophysiology, epidemiology, diagnosis criteria and management of SCM.

The inter-rater reliability and individual reviewer performance of the 2012 world heart federation guidelines for the echocardiographic diagnosis of latent rheumatic heart disease.

BACKGROUND: In 2012, the World Heart Federation (WHF) published guidelines for the echocardiographic diagnosis of rheumatic heart disease (RHD). This study assesses individual reviewer performance and inter-rater agreement and reliability on the presence of any RHD, as well classification of RHD based on the 2012 WHF criteria. METHODS: Four cardiologists individually reviewed echocardiograms in the context of a randomized clinical trial (ClinicalTrials.gov:NCT03346525) and participated in a blinded adjudication panel. Panel decision was the reference standard for diagnosis. Performance of individual reviewers to panel adjudication was compared through sensitivity and specificity analyses and inter-rater reliability was assessed between individual panelists using Fleiss free marginal multirater kappa. RESULTS: Echocardiograms from 784 children had two independent reports and panel adjudication. The accuracy of independent reviewers for any RHD had high sensitivity (94%, 95% CI 93-95%) and moderate specificity (62%, 95% CI 53-70%). Sensitivity and specificity for definite RHD was 61.3 (95% CI, 55.3-67.1) and 93.1 (95% CI, 91.6-94.4), with 86.8 (84.7-88.7) and 65.8 (61.0-70.4) for borderline RHD. There was moderate inter-rater agreement (κ = 0.66) on the presence of any RHD while agreement for specific 2012 WHF classification was only fair (κ = 0.51). CONCLUSIONS: The 2012 WHF guidelines are moderately reproducible when used by expert cardiologists. More cases of RHD were diagnosed by an consensus panel than by individual reviewers. A revision to the criteria is now warranted to further increase the reliability of the WHF criteria.

Contemporary Diagnosis and Management of Rheumatic Heart Disease: Implications for Closing the Gap: A Scientific Statement From the American Heart Association.

The global burden of rheumatic heart disease continues to be significant although it is largely limited to poor and marginalized populations. In most endemic regions, affected patients present with heart failure. This statement will seek to examine the current state-of-the-art recommendations and to identify gaps in diagnosis and treatment globally that can inform strategies for reducing disease burden. Echocardiography screening based on World Heart Federation echocardiographic criteria holds promise to identify patients earlier, when prophylaxis is more likely to be effective; however, several important questions need to be answered before this can translate into public policy. Population-based registries effectively enable optimal care and secondary penicillin prophylaxis within available resources. Benzathine penicillin injections remain the cornerstone of secondary prevention. Challenges with penicillin procurement and concern with adverse reactions in patients with advanced disease remain important issues. Heart failure management, prevention, early diagnosis and treatment of endocarditis, oral anticoagulation for atrial fibrillation, and prosthetic valves are vital therapeutic adjuncts. Management of health of women with unoperated and operated rheumatic heart disease before, during, and after pregnancy is a significant challenge that requires a multidisciplinary team effort. Patients with isolated mitral stenosis often benefit from percutaneous balloon mitral valvuloplasty. Timely heart valve surgery can mitigate the progression to heart failure, disability, and death. Valve repair is preferable over replacement for rheumatic mitral regurgitation but is not available to the vast majority of patients in endemic regions. This body of work forms a foundation on which a companion document on advocacy for rheumatic heart disease has been developed. Ultimately, the combination of expanded treatment options, research, and advocacy built on existing knowledge and science provides the best opportunity to address the burden of rheumatic heart disease.

Cardiovascular Toxicity Related to Cancer Treatment: A Pragmatic Approach to the American and European Cardio-Oncology Guidelines.

The considerable progress made in the field of cancer treatment has led to a dramatic improvement in the prognosis of patients with cancer. However, toxicities resulting from these treatments represent a cost that can be harmful to short- and long-term outcomes. Adverse events affecting the cardiovascular system are one of the greatest challenges in the overall management of patients with cancer, as they can compromise the success of the optimal treatment against the tumor. Such adverse events are associated not only with older chemotherapy drugs such as anthracyclines but also with many targeted therapies and immunotherapies. Recognizing this concern, several American and European governing societies in oncology and cardiology have published guidelines on the cardiovascular monitoring of patients receiving potentially cardiotoxic cancer therapies, as well as on the management of cardiovascular toxicities. However, the low level of evidence supporting these guidelines has led to numerous discrepancies, leaving clinicians without a consensus strategy to apply. A cardio-oncology expert panel from the French Working Group of Cardio-Oncology has undertaken an ambitious effort to analyze and harmonize the most recent American and European guidelines to propose roadmaps and decision algorithms that would be easy for clinicians to use in their daily practice. In this statement, the experts addressed the cardiovascular monitoring strategies for the cancer drugs associated with the highest risk of cardiovascular toxicities, as well as the management of such toxicities.

Radiotherapy in Patients With a Cardiac Implantable Electronic Device.

Recently, the Heart Rhythm Society published recommendations on management of patients with cardiac implantable electronic device (CIED) who require radiotherapy (RT). We aimed to report the experience of a teaching hospital, and discuss our practice in the context of recently published guidelines. We identified all consecutive CIED recipients (12,736 patients) who underwent RT between March 2006 and June 2017. Among them, 90 (1%) patients (78.2 ± 10 years, 73% male) had a CIED: 82 pacemakers and 8 implantable cardioverter-defibrillators. Two patients required CIED extraction prior to RT for ipsilateral breast cancer (no device replacement in 1 patient). Four patients (5%) were considered at high-risk, 35 (39%) at intermediate-risk, and the remaining 50 (56%) at low-risk for CIED dysfunction. Overall, only a minority of patients followed recommended local protocol during RT delivery (31%) and during follow-up (56%). CIED malfunction was detected in 5 patients (6%), mainly back-up mode resetting (80%), with 4 (including 3 pelvic cancer location) patients initially classified as being at intermediate-risk and 1 at low-risk. Four out of the 5 patients with CEID malfunction had received neutron producing beams. In conclusion, our findings underline the lack of rigorous monitoring of patients undergoing RT (though CIED malfunction appears to be rare and relatively benign in nature), and emphasize the interest of considering neutron producing beam for risk stratification as recommended in recent guidelines. Optimization of patient's management requires a close collaboration between both CIED clinicians and radiation oncologists, and more systematic remote CIED monitoring may be helpful.

[Cancer treatment and risk of heart failure]. / Traitement des cancers et risque d'insuffisance cardiaque.

Cancer treatment and risk of heart failure. As new advancements in oncology have radically changed the prognosis in millions of cancer patients, these have become at high risk of multiple cardiovascular complications. Heart failure is likely the most common cardiovascular side effect of cancer therapies. Definition of heart failure induced by cancer treatment resides in the reduction of left ventricular ejection fraction under 50%. Biomarkers as the reduction of left ventricular longitudinal function or troponin raise are associated with the advent of heart failure. Risk of cardiotoxicity includes traditional cardiovascular risk factors, lifestyle and cancer treatment(s). In addition to anthracyclins, which may lead to persistent heart failure, target therapies, radiotherapy and immune checkpoint inhibitors may be responsible for cardio-toxicity. Early screening of drug related heart failure may lead to medical treatment thus enabling the continuation of cancer cardiotoxic drugs when no other alternative is available. Cardio-oncology, a new discipline, guides decision making in these complex patients.

Traitement des cancers et risque d'insuffisance cardiaque. Les avancées thérapeutiques en cancérologie ont amélioré le pronostic de millions de patients, soulevant ainsi l'impact de leurs complications cardiovasculaires. L'insuffisance cardiaque en est probablement la plus fréquente et la mieux caractérisée, définie par une baisse de la fraction d'éjection ventriculaire gauche inférieure à 50 %. Les biomarqueurs de cardiotoxicité, associés à la survenue ultérieure d'une insuffisance cardiaque, sont la baisse relative des indices de déformation longitudinale ventriculaire gauche (« strain ¼ global longitudinal) et l'élévation de la troponine. Le risque de cardiotoxicité est plurifactoriel, relatif aux facteurs de risque cardiovasculaires traditionnels, au mode de vie et aux traitements oncologiques administrés. Outre les anthracyclines pouvant se compliquer d'insuffisance cardiaque pérenne, des thérapies ciblées, la radiothérapie et plus rarement l'immunothérapie sont pourvoyeurs d'insuffisance cardiaque. Un dépistage précoce permet de traiter l'insuffisance cardiaque et de poursuivre, en l'absence d'alternative thérapeutique, le traitement oncologique cardiotoxique. La cardio-oncologie, spécialité transversale émergente, est née de ce constat et permet la prise en charge de ces patients complexes.

Correction to: Pericardial effusion under nivolumab: case-reports and review of the literature.

Following publication of the original article [1], the authors reported that authors' given and family names haven been incorrectly tagged.

Pericardial effusion under nivolumab: case-reports and review of the literature.

BACKGROUND: Nivolumab, a programmed death-1 (PD-1) inhibitor, is an immune checkpoint inhibitor particularly used in the treatment of malignant melanoma, non-small cell lung cancer and renal cell carcinoma. Immune-related adverse events are frequent under immunotherapies. Cardiotoxic side effects, initially thought to be rare, are more often encountered paralleling the expanding use of immune checkpoint blockade. Among them, pericardial effusion and tamponade deserve attention as they may present with unusual symptomatology. CASE PRESENTATION: We report three cases of pericardial effusion under nivolumab for lung adenocarcinoma. Two cases of early and late-onset pericardial effusion were symptomatic with tamponade and one case occurred without any symptoms. Pericardiocentesis with pericardial biopsy was performed in symptomatic pericardial effusion followed by the administration of a corticotherapy. Pericardial biopsies showed infiltration of T-lymphocytes, mostly CD4+. Nivolumab was stopped in two cases and resumed for one patient. Pericardial effusion evolved positively in all cases with or without treatment. CONCLUSIONS: We review the literature on pericardial effusion under nivolumab to further discuss the hallmarks of pericardial effusion under nivolumab and the management of nivolumab therapy in this situation. In conclusion, pericardial effusion as an immune-related adverse event under nivolumab appears less rare than initially thought and may require particular attention.