European Society of Cardiology quality indicators for the prevention and management of cancer therapy-related cardiovascular toxicity in cancer treatment.

AIMS: To develop quality indicators (QIs) for the evaluation of the prevention and management of cancer therapy-related cardiovascular toxicity. METHODS AND RESULTS: We followed the European Society of Cardiology (ESC) methodology for QI development which comprises (i) identifying the key domains of care for the prevention and management of cancer therapy-related cardiovascular toxicity in patients on cancer treatment, (ii) performing a systematic review of the literature to develop candidate QIs, and (iii) selecting of the final set of QIs using a modified Delphi process. Work was undertaken in parallel with the writing of the 2022 ESC Guidelines on Cardio-Oncology and in collaboration with the European Haematology Association, the European Society for Therapeutic Radiology and Oncology and the International Cardio-Oncology Society. In total, 5 main and 9 secondary QIs were selected across five domains of care: (i) Structural framework, (ii) Baseline cardiovascular risk assessment, (iii) Cancer therapy related cardiovascular toxicity, (iv) Predictors of outcomes, and (v) Monitoring of cardiovascular complications during cancer therapy. CONCLUSION: We present the ESC Cardio-Oncology QIs with their development process and provide an overview of the scientific rationale for their selection. These indicators are aimed at quantifying and improving the adherence to guideline-recommended clinical practice and improving patient outcomes.

Inflammation versus mechanical stretch biomarkers over time in acutely decompensated heart failure with reduced ejection fraction.

Heart failure can be associated with inflammation but it is unclear if inflammation is directly related to hemodynamic worsening or is an independent pathway. Our aim was to investigate inflammation and mechanical stress using serial measurements of biomarkers in acute and chronic heart failure with reduced ejection fraction (AHF and CHF). METHOD: The following biomarkers were measured on admission, at discharge and one month after discharge: B-type natriuretic peptide (BNP), high-sensitivity C-Reactive protein (hsCRP), Tumour Necrosis Factor alpha (TNFα), interleukin 6 (IL6), myeloperoxidase (MPO), suppression of tumorigenicity 2 (ST2), mid-regional pro-adrenomedullin (MR-proADM), galectin 3 (Gal3), Growth differentiating factor 15 (GDF15) and procalcitonin (PCT). RESULTS: In control CHF group (n=20, 69±11y, NYHA 1-2), most biomarker levels were low and stable over time. In AHF (n=55, 71±14y), BNP, ST2 and GDF15 levels were highly increased on admission and then decreased rapidly with clinical improvement; BNP, ST2 and GDF15 levels were statistically correlated (r=0.64, 0.46 and 0.39; p<0.001 for both). Both hsCRP, MPO, TNFα and Gal3 levels were increased in most AHF patients (70, 56, 83 and 98% respectively) with poor change over time. HsCRP, MPO and TNFα levels were correlated. IL6, MR-proADM and PCT levels were slightly increased, without change over time. Highest quartiles of BNP and ST2 were associated with death or readmission at one year (HR 2.33 [95CI 1.13-4.80] and 2.42 [1.27-4.60]). CONCLUSION: AHF is associated with systemic inflammation. This inflammatory response continued up to one month after discharge despite normalisation of mechanical stress-related markers.

Treat-to-target (T2T) recommendations for gout.

OBJECTIVES: The treat-to-target (T2T) concept has been applied successfully in several inflammatory rheumatic diseases. Gout is a chronic disease with a high burden of pain and inflammation. Because the pathogenesis of gout is strongly related to serum urate levels, gout may be an ideal disease in which to apply a T2T approach. Our aim was to develop international T2T recommendations for patients with gout. METHODS: A committee of experts with experience in gout agreed upon potential targets and outcomes, which was the basis for the systematic literature search. Eleven rheumatologists, one cardiologist, one nephrologist, one general practitioner and one patient met in October 2015 to develop T2T recommendations based on the available scientific evidence. Levels of evidence, strength of recommendations and levels of agreement were derived. RESULTS: Although no randomised trial was identified in which a comparison with standard treatment or an evaluation of a T2T approach had been performed in patients with gout, indirect evidence was provided to focus on targets such as normalisation of serum urate levels. The expert group developed four overarching principles and nine T2T recommendations. They considered dissolution of crystals and prevention of flares to be fundamental; patient education, ensuring adherence to medications and monitoring of serum urate levels were also considered to be of major importance. CONCLUSIONS: This is the first application of the T2T approach developed for gout. Since no publication reports a trial comparing treatment strategies for gout, highly credible overarching principles and level D expert recommendations were created and agreed upon.

Acute heart failure and cardiogenic shock: a multidisciplinary practical guidance.

PURPOSE: Acute heart failure (AHF) causes high burden of mortality, morbidity, and repeated hospitalizations worldwide. This guidance paper describes the tailored treatment approaches of different clinical scenarios of AHF and CS, focusing on the needs of professionals working in intensive care settings. RESULTS: Tissue congestion and hypoperfusion are the two leading mechanisms of end-organ injury and dysfunction, which are associated with worse outcome in AHF. Diagnosis of AHF is based on clinical assessment, measurement of natriuretic peptides, and imaging modalities. Simultaneously, emphasis should be given in rapidly identifying the underlying trigger of AHF and assessing severity of AHF, as well as in recognizing end-organ injuries. Early initiation of effective treatment is associated with superior outcomes. Oxygen, diuretics, and vasodilators are the key therapies for the initial treatment of AHF. In case of respiratory distress, non-invasive ventilation with pressure support should be promptly started. In patients with severe forms of AHF with cardiogenic shock (CS), inotropes are recommended to achieve hemodynamic stability and restore tissue perfusion. In refractory CS, when hemodynamic stabilization is not achieved, the use of mechanical support with assist devices should be considered early, before the development of irreversible end-organ injuries. CONCLUSION: A multidisciplinary approach along the entire patient journey from pre-hospital care to hospital discharge is needed to ensure early recognition, risk stratification, and the benefit of available therapies. Medical management should be planned according to the underlying mechanisms of various clinical scenarios of AHF.

Trends in death attributed to myocardial infarction, heart failure and pulmonary embolism in Europe and Canada over the last decade.

BACKGROUND: Worldwide, cardiovascular diseases and cancer account for ∼40% of deaths. Certain reports have shown a progressive decrease in mortality. Our main objective was to assess mortality trends related to myocardial infarction (MI), heart failure (HF) and pulmonary embolism (PE). METHODS: MI, HF and PE were studied as cause of death based on the analysis of death certificates in Canada (C), England and Wales (E), France (F) and Sweden (S). We also used a multiple cause approach. Age-standardized death rates (SDR) were calculated. RESULTS: The SDR for MI, HF or PE as the underlying cause of death, all decreased during the last decade. The decrease in SDR secondary to MI exceeded that for HF or PE. Concerning multiple cause of death, a greater decrease was also found for MI, compared with HF or PE. CONCLUSIONS: We confirm the beneficial trends in SDR with MI, HF or PE both as underlying or multiple causes in the studied countries. For HF and PE, multiple cause approach seems more accurate to describe the burden of these two pathologies. Our study also suggests that more efforts should be dedicated to HF and PE in order to achieve similar trends than in MI.

Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular risk factors: recommendations from the EACPR. Part II.

In a previous paper, as the first of a series of three on the importance of characteristics and modalities of physical activity (PA) and exercise in the management of cardiovascular health within the general population, we concluded that, in the population at large, PA and aerobic exercise capacity clearly are inversely associated with increased cardiovascular disease risk and all-cause and cardiovascular mortality and that a dose­response curve on cardiovascular outcome has been demonstrated in most studies. More and more evidence is accumulated that engaging in regular PA and exercise interventions are essential components for reducing the severity of cardiovascular risk factors, such as obesity and abdominal fat, high BP, metabolic risk factors, and systemic inflammation. However, it is less clear whether and which type of PA and exercise intervention (aerobic exercise, dynamic resistive exercise, or both) or characteristic of exercise (frequency, intensity, time or duration, and volume) would yield more benefit for each separate risk factor. The present paper, therefore, will review and make recommendations for PA and exercise training in the management of cardiovascular health in individuals with cardiovascular risk factors. The guidance offered in this series of papers is aimed at medical doctors, health practitioners, kinesiologists, physiotherapists and exercise physiologists, politicians, public health policy makers, and individual members of the public. Based on previous and the current literature overviews, recommendations from the European Association on Cardiovascular Prevention and Rehabilitation are formulated regarding type, volume, and intensity of PA and regarding appropriate risk evaluation during exercise in individuals with cardiovascular risk factors.

Use of tamoxifen in a German shepherd dog with sclerosing encapsulating peritonitis.

A German shepherd dog was diagnosed with sclerosing encapsulating peritonitis after an episode of peritonitis caused by a free intra-abdominal foreign body (stick). The foreign body had initially been treated by surgical removal and abdominal lavage. Postoperatively, peritoneal effusion persisted despite the use of methylprednisolone for 1 month and a second surgical exploration and abdominal lavage. After a third surgery at our institution (to breakdown abdominal adhesions) followed by open abdominal drainage, treatment with tamoxifen orally was initiated and within 2 weeks the dog's condition improved dramatically. Two months later, no fluid was present in the abdomen. The only apparent adverse reaction to tamoxifen therapy was swelling of the vulva. In humans, sclerosing encapsulating peritonitis is a known life-threatening complication following peritoneal dialysis. In veterinary medicine, most animals with sclerosing encapsulating peritonitis die because of chronic weight loss, peritoneal effusion and progression of concurrent disease. This dog's condition was unresponsive to methylprednisolone alone but was successfully treated with aggressive surgery including enterolysis and open abdominal lavage and the addition of tamoxifen.

[Treating heart failure with carvedilol in private practice (initiating treatment and follow-up at one year. The KEOPS study]. / Traitement par carvedilol dans l'insuffisance cardiaque en pratique libérale (initiation du traitement et suivi à un an). Etude KEOPS.

AIMS: This study aimed at describing usual conditions of carvedilol use in heart failure (HF) patients. METHODS: KEOPS was a one-year, multi-centre, prospective pharmaco-epidemiological study in carvedilol treated HF patients recruited by private cardiologists. RESULTS: Two thousand nine patients (mean age: 68) with heart failure were included by 401 cardiologists. 64% of patients were in class II of NYHA and 27% in class III, 87% of patients presented stable heart failure for at least four weeks. Contraindication to beta blocking was observed in 24% of patients, mean left ventricular fraction of ejection was 39% and only 39% of patients had mean left ventricular fraction of ejection<35%. Co-medications included a diuretic agent, ACE inhibitor or ARB in 68% of cases. Eighty three percent of patients had a titration of carvedilol (median duration=1 20 days). Thirty percent reached the recommended maximal dose. The dose of carvedilol at the titration's visit for all the patients (patient in stop included) was on average 30.5 +/- 22.1 mg/day with a median on 25 [confidence interval: 23-27] During the year of follow-up, 10% of patients have stopped the treatment (3% of patients having reached the maximum recommended dose of carvedilol versus 13% for the others), for cardiovascular reasons in 50% of patients (aggravation of heart failure: 28%, symptomatic arterial hypotension: 9%, symptomatic bradycardia: 5%). Finally, symptomatology of patients has improved during the study (59% of patients in class mild to severe at inclusion, versus 36% at the end of the observation), especially for the 30% of patients followed at one year and having reached the maximum recommended dose of carvedilol. Only in univariate analysis, patients with an inclusion high weight (>85 kg) were likely less to reach recommended maximal dose (37.2 versus 8.7%, p-value<0.0001), the patients with systolic heart failure had more chance than the patients with diastolic heart failure to reach the recommended maximal dose (31 versus 17.4%, p-value=0.006), in the same way, the lack of auricular supported more the reach of recommended maximal dose (31.2 versus 24.1%, p-value=0.018) CONCLUSION: KEOPS study suggests an improvement of usual conditions of carvedilol compared to the last investigation but the persistence of prescription outside medical authorization and less dosage of this product compared with clinical studies.

[Diabetes and heart failure, a fatal association]. / Diabète et insuffisance cardiaque, une association morbide.

The prevalence of heart failure and diabetes are both increasing: 25 to 30% of patients with heart failure suffer from diabetes, and the latter aggravates heart failure. The presence of macro- or micro-angiopathy, cardiac neuropathy or renal failure worsens the clinical pattern and disturbs treatment strategies. Doppler-echocardiography and the dosage of BNP can probably help to detect and consequently to treat prematurely heart failure in the diabetic patient. The usual treatments in heart failure have similar or lower efficacy in the diabetic patient, and treatment intolerance is frequent. Treatments used for diabetes can be handled with difficulty in case of heart failure (metformin, glitazones). In the future, it is therefore extremely important: 1--to prevent the occurrence of diabetes in patients with glucose intolerance; 2--in diabetic patients, to prematurely detect cardiac dysfunction and optimally control diabetes, in order to avoid its occurrence; 3--and finally, in diabetic patients with heart failure, to optimize the medical treatment, in order that these patients have similar benefits compared to non-diabetic patients with heart failure. The ACE-inhibitors and angiotensin-2 antagonists seem to have an important role. Treatments breaking the glycation bridges, as well as statins, appear as interesting therapeutic options. Finally, the exact role of myocardial revascularization, either by angioplasty or surgery, might probably be important.

Treatment practices in heart failure with preserved left ventricular ejection fraction: a prospective observational study.

BACKGROUND: Current guidelines for treatment of patients with heart failure (HF) and preserved left ventricular ejection fraction (LVEF) are empirical. One of the objectives of the ETICS study was to evaluate medical treatment at discharge and after 1 year in patients hospitalised for a first episode of HF in 2000. We report the results concerning treatment of patients with preserved LVEF at discharge and at 1 year. METHODS: Two hundred and sixty three consecutive patients (75+/-10 years, 47 males) with LVEF >50% hospitalised for a first episode of HF were prospectively included. Mean LVEF was 63+/-8%. The main aetiology was hypertension (61%) followed by ischaemic heart disease (29%). Atrial fibrillation and diabetes were present in 34% and 27% of cases, respectively. Medical treatment records were complete at discharge and at 1 year after discharge. RESULTS: At discharge, as at 1 year after discharge, diuretics were the drugs most commonly prescribed (81% and 78%), followed by ACE inhibitors (49% and 46%), amiodarone (32% and 28%), beta-blockers (27% and 29%), nitrates (28% and 27%), calcium channel blockers (27% and 26%), spironolactone (21% and 25%), cardiac glycosides (19% and 24%), and angiotensin II receptor antagonists (4% and 6%). Once prescribed at hospital discharge, drug prescription rates and daily doses did not change significantly over time. Age did not influence drug prescription rates at discharge or at 1 year, except for the spironolactone prescription rate, which decreased at 1 year in patients > or =75 years of age. At discharge, ACE inhibitor and beta-blocker daily doses were lower in older patients, while, at 1 year, no differences in daily doses of these drugs were observed between patients above and below the age of 75 years. CONCLUSION: Loops diuretics are largely prescribed in HF with preserved LVEF, followed by ACE inhibitors. Future large multicentre trials are required to define the background standard treatment in addition to treatment of aetiological factors.

[Exercise training in cardiac patients: usefulness of the cardiopulmonary exercise test]. / Réadaptation des patients porteurs d'une cardiopathie: intérêt de la mesure des echanges gazeux a l'effort (VO2).

Exercise training is currently including in the treatment of coronary arterial disease patients, in patients with left ventricular dysfunction as well as in patients who underwent cardiac transplantation or cardiac surgery. However methods of prescribing exercise-training programs are difficult to determine and must be adapted for each patient Exercise test with gas analysis through the determination of anaerobic threshold may help to understand the physiopathological mechanism related to exercise limitation in these patients. Exercise test may help to precise exercise intensity during cardiac rehabilitation and may assess the benefits on exercise tolerance.

[Massive pulmonary embolism and stroke due to thrombus across the foramen ovale]. / Thrombus enclavé dans le foramen ovale responsable d'embolie pulmonaire et d'accident vasculaire cérébral.

We report the case of a man admitted for massive pulmonary embolism. Transthoracic echocardiography showed a serpentine thrombus in the right atrium across the foramen oval. Because of an acute worsening of the circulatory insufficiency, an intravenous thrombolysis was prescribed and the patient recovered progressively. An early control echocardiography showed the disappearing of the intracardiac thrombus and no evidence of abnormality of interatrial septum. While there was no evidence of venous thrombosis in legs, a renal cancer was diagnosed by echography. Silent stroke were highlighted at the scanner. This clinical case leads to discuss the origin of thrombus (in situ formation or thrombus migration) as well as the treatment (heparinotherapy, thrombolysis, surgical embolectomy, definitive closure of the foramen oval).

Cardiac resynchronisation therapy reduces functional mitral regurgitation during dynamic exercise in patients with chronic heart failure: an acute echocardiographic study.

OBJECTIVES: To assess non-invasively the acute effects of cardiac resynchronisation therapy (CRT) on functional mitral regurgitation (MR) at rest and during dynamic exercise. METHODS: 21 patients with left ventricular (LV) systolic dysfunction and functional MR at rest, treated with CRT, were studied. Each patient performed a symptom-limited maximal exercise with continuous two dimensional Doppler echocardiography twice. The first exercise was performed with CRT; the second exercise was performed without CRT. Mitral regurgitant flow volume (RV), effective regurgitant orifice area (ERO) and LV dP/dt were measured at rest and at peak exercise. RESULTS: CRT mildly reduced resting mitral ERO (mean 8 (SEM 2) v 11 (2) mm(2) without CRT, p = 0.02) and RV (13 (3) v 18 (3) ml without CRT, p = 0.03). CRT attenuated the spontaneous increase in mitral ERO and RV during exercise (1 (1) v 9 (2) mm(2), p = 0.004 and 1 (1) v 8 (2) ml, p = 0.004, respectively). CRT also significantly increased exercise-induced changes in LV dP/dt (140 (46) v 479 (112) mm Hg/s, p < 0.001). CONCLUSION: Attenuation of functional MR, induced by an increase in LV contractility during dynamic exercise, may contribute to the beneficial clinical outcome of CRT in patients with chronic heart failure and LV asynchrony.

Interaction between pulse wave velocity, augmentation index, pulse pressure and left ventricular function in chronic heart failure.

Pulse wave velocity (PWV), the carotid augmentation index (AIx), and pulse pressure (PP) may be prognostic factors in heart failure, but the possible influence of the ejection fraction (EF) and other simple haemodynamic variables on them has not been investigated in this setting. Noninvasive methods were used to measure carotid-radial (CR), carotid-femoral (CF) PWV and AIx, and brachial PP, in 135 consecutive patients with stable symptomatic chronic heart failure. The patients were divided into two groups, with preserved (>or=40%) or reduced (<40%) EF. CF-PWV, AIx and PP were lower in the decreased EF group (8.85+/-2.77 versus 10.60+/-2.75 m/s, P<0.001; 121+/-21 versus 132+/-24, P=0.009 and 41+/-19 versus 67+/-17 mmHg, P<0.001), but CR-PWV values were similar regardless of the EF status. These results were not modified after adjustment for age and sex. Multiple regression analysis showed that AIx and PP were systematically related to time domain parameters (heart rate or ejection duration) and EF, whatever the group. CF-PWV was weakly related to time domain values and unrelated to mean blood pressure (BP) or EF in the preserved EF group, whereas it was related to both mean BP and EF in the low EF group. In conclusion, whatever the EF level, PP and AIx were strongly modulated in the time domain, by pressure and by the EF level. The same relationships were found with CF-PWV, but only in the reduced EF group. Whether CF-PWV is the best prognostic factor in patients with 'diastolic' heart failure must be confirmed in a prospective study.

[Heart failure and cachexia]. / Insuffisance cardiaque et cachexie.

Cachexia is related to a malnutrition state related to hypercatabolism. Initially described in cancer, it is also related to several chronic diseases including heart failure. Defined by an unintentional weight loss exceeding 7.5% of body mass during more than 6 months, it is presented by the association of nutritional deficiencies, digestive and/or urinary losses as well as metabolic abnormalities causing fat and lean mass loss and is associated to a poor prognosis. The pathophysiology of cachexia and heart failure presented some similarities associating especially neuro-hormonal activation, a cortisol/DHEA ratio imbalance, as well as pro-inflammatory cytokines activation. Currently the treatment of cachexia is mainly preventive, based on ACE-inhibitors and beta-blockers therapy and physical reconditioning. The benefits of hormonal and nutritional substitutes remains to be evidenced.

[Anaemia, cardiac failure and erythropoietin]. / Anémie, insuffisance cardiaque et érythropoïétine.

Anaemia is common in severe cardiac failure due to systolic dysfunction. The mechanisms are varied. Anaemia is a negative prognostic factor. Treatment with erythropoietin seems to improve the quality of life, functional status, effort tolerance and systolic function of these patients. Large scale clinical trials are on-going.

Heart failure due to left ventricular systolic dysfunction: treatment at discharge from hospital and at one year.

BACKGROUND: The treatment of heart failure (HF) due to left ventricular systolic dysfunction has been defined in recent guidelines, but these guidelines are not always applied in routine clinical practice. One of the objectives of the ETICS study was to evaluate medical treatment at discharge and after 1 year in patients hospitalised for a first episode of congestive HF due to left ventricular systolic dysfunction in 2000. METHODS: One hundred and seventy nine patients (63% males, mean age of 69+/-13 years) with an ejection fraction < or = 40% were prospectively included. The main aetiology was ischaemic heart disease (44%). RESULTS: The drugs prescribed at discharge and at one year, respectively, were loop diuretics in 95% and 91% of cases, angiotensin-converting enzyme (ACE) inhibitors in 82% and 75%, spironolactone in 35% and 37%, beta-blockers in 25% and 41%, digitalis glycosides in 34% and 30% of cases, and nitrates in 20% and 16% of cases. ACE inhibitors were prescribed at discharge and at 1 year at dosages reaching 64+/-29% and 72+/-30% of the recommended doses, respectively, and beta-blockers were prescribed at 26+/-16% and 35+/-25% of recommended doses, respectively. CONCLUSION: Diuretics and ACE inhibitors are largely prescribed in HF due to left ventricular systolic dysfunction, followed by spironolactone. Beta-blockers are still underused both in terms of the rate of patients receiving them and the daily doses. These results highlight the value of continuing to widely circulate official practice guidelines in order to improve the management of HF due to left ventricular systolic dysfunction.