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.

Outcome of patients with prior coronary bypass surgery admitted with an acute coronary syndrome.

BACKGROUND: Patients with prior coronary artery bypass graft surgery (CABG) are at increased risk for recurrent cardiovascular ischaemic events. Advances in management have improved prognosis of patients with acute coronary syndrome (ACS), yet it is not known whether similar trends exist in patients with prior CABG. AIM: Examine temporal trends in the prevalence, treatment and clinical outcomes of patients with prior CABG admitted with ACS. METHODS: Time-dependent analysis of patients with or without prior CABG admitted with an ACS who enrolled in the ACS Israeli Surveys between 2000 and 2016. Surveys were divided into early (2000-2008) and late (2010-2016) time periods. Outcomes included 30 days major adverse cardiac events (30d MACE) (death, myocardial infarction, stroke, unstable angina, stent thrombosis, urgent revascularisation) and 1-year mortality. RESULTS: Among 15 152 patients with ACS, 1506 (9.9%) had a prior CABG. Patients with prior CABG were older (69 vs 63 years), had more comorbidities and presented more with non-ST elevation-ACS (82% vs 51%). Between time periods, utilisation of antiplatelets, statins and percutaneous interventions significantly increased in both groups (p<0.001 for each). The rate of 30d MACE decreased in patients with (19.1%-12.4%, p=0.001) and without (17.4%-9.5%, p<0.001) prior CABG. However, 1-year mortality decreased only in patients without prior CABG (10.5% vs 7.4%, p<0.001) and remained unchanged in patients with prior CABG. Results were consistent after propensity matching. CONCLUSIONS: Despite an improvement in the management and prognosis of patients with ACS in the last decade, the rate of 1-year mortality of patients with prior CABG admitted with an ACS remained unchanged.

Organization of intensive cardiac care units in Europe: Results of a multinational survey.

BACKGROUND: The present survey aims to describe the intensive cardiac care unit organization and admission policies in Europe. METHODS: A total of 228 hospitals (61% academic) from 27 countries participated in this survey. In addition to the organizational aspects of the intensive cardiac care units, including classification of the intensive cardiac care unit levels, data on the admission diagnoses were gathered from consecutive patients who were admitted during a two-day period. Admission policies were evaluated by comparing illness severity with the intensive cardiac care unit level. Gross national income was used to differentiate high-income countries (n=13) from middle-income countries (n=14). RESULTS: A total of 98% of the hospitals had an intensive cardiac care unit: 70% had a level 1 intensive cardiac care unit, 76% had a level 2 intensive cardiac care unit, 51% had a level 3 intensive cardiac care unit, and 60% of the hospitals had more than one intensive cardiac care unit level. High-income countries tended to have more level 3 intensive cardiac care units than middle-income countries (55% versus 41%, p=0.07). A total of 5159 admissions were scored on illness severity: 63% were low severity, 24% were intermediate severity, and 12% were high severity. Patients with low illness severity were predominantly admitted to level 1 intensive cardiac care units, whereas patients with high illness severity were predominantly admitted to level 2 and 3 intensive cardiac care units. A policy mismatch was observed in 12% of the patients; some patients with high illness severity were admitted to level 1 intensive cardiac care units, which occurred more often in middle-income countries, whereas some patients with low illness severity were admitted to level 3 intensive cardiac care units, which occurred more frequently in high-income countries. CONCLUSION: More than one-third of the admitted patients were considered intermediate or high risk. Although patients with higher illness severity were mostly admitted to high-level intensive cardiac care units, an admission policy mismatch was observed in 12% of the patients; this mismatch was partly related to insufficient logistic intensive cardiac care unit capacity.

Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations.

Cancer and cardiovascular (CV) disease are the most prevalent diseases in the developed world. Evidence increasingly shows that these conditions are interlinked through common risk factors, coincident in an ageing population, and are connected biologically through some deleterious effects of anticancer treatment on CV health. Anticancer therapies can cause a wide spectrum of short- and long-term cardiotoxic effects. An explosion of novel cancer therapies has revolutionised this field and dramatically altered cancer prognosis. Nevertheless, these new therapies have introduced unexpected CV complications beyond heart failure. Common CV toxicities related to cancer therapy are defined, along with suggested strategies for prevention, detection and treatment. This ESMO consensus article proposes to define CV toxicities related to cancer or its therapies and provide guidance regarding prevention, screening, monitoring and treatment of CV toxicity. The majority of anticancer therapies are associated with some CV toxicity, ranging from asymptomatic and transient to more clinically significant and long-lasting cardiac events. It is critical however, that concerns about potential CV damage resulting from anticancer therapies should be weighed against the potential benefits of cancer therapy, including benefits in overall survival. CV disease in patients with cancer is complex and treatment needs to be individualised. The scope of cardio-oncology is wide and includes prevention, detection, monitoring and treatment of CV toxicity related to cancer therapy, and also ensuring the safe development of future novel cancer treatments that minimise the impact on CV health. It is anticipated that the management strategies discussed herein will be suitable for the majority of patients. Nonetheless, the clinical judgment of physicians remains extremely important; hence, when using these best clinical practices to inform treatment options and decisions, practitioners should also consider the individual circumstances of their patients on a case-by-case basis.

Incidence, predictors and prognostic implications of dyspnea at admission among acute coronary syndrome patients without heart failure.

BACKGROUND: Among patients with stable coronary artery disease, effort-related dyspnea is associated with a larger ischemic territory and worse outcome. Whether dyspnea, not related to heart failure, is also associated with adverse outcome among patients with acute coronary syndromes (ACS) has not been fully elucidated. METHODS: We studied ACS patients enrolled in the biennial Acute Coronary Syndrome Israeli Surveys (ACSIS) during 2010-2013 who were classified as Killip 1. A retrospective comparative analysis was performed between patients with chest pain alone (n = 2017) and those with chest pain with dyspnea (n = 417). RESULTS: Patients with dyspnea were older (64.4 ±â€¯13 vs.61.8 ±â€¯12, p < 0.001), more frequently women (81% vs. 75% p < 0.001) and had higher rates of multiple comorbidities. Statistically significant predictors for dyspnea as a presenting symptom were female sex [HR 1.47 (1.11, 1.89)], chronic kidney disease [HR 1.81 (1.30, 2.52)], chronic obstructive pulmonary disease [HR 1.59 (1.045, 2.429)] and angina ≥24 h [HR 1.46 (1.147, 1.86)]. Patients presenting with dyspnea were less likely to undergo primary reperfusion (31% vs. 42%, p < 0.001) and overall coronary intervention (71% vs. 78%, p < 0.001) during their hospitalization. Mortality rates were significantly higher among patients presenting with dyspnea both at 30-day (3% vs. 2%, p = 0.017) and at 1-year follow-up (9% vs. 4%, p < 0.001). Dyspnea was as an independent predictor of 1-year mortality. CONCLUSION: The presence of dyspnea is frequent and associated with adverse outcome among patients with ACS without signs of heart failure. Early identification of this higher-risk cohort of patients may allow intensifying treatment and careful follow-up may be warranted.

Repetitive use of levosimendan for treatment of chronic advanced heart failure: clinical evidence, practical considerations, and perspectives: an expert panel consensus.

BACKGROUND: The intravenous inodilator levosimendan was developed for the treatment of patients with acutely decompensated heart failure. In the last decade scientific and clinical interest has arisen for its repetitive or intermittent use in patients with advanced chronic, but not necessarily acutely decompensated, heart failure. Recent studies have suggested long-lasting favourable effects of levosimendan when administered repetitively, in terms of haemodynamic parameters, neurohormonal and inflammatory markers, and clinical outcomes. The existing data, however, requires further exploration to allow for definitive conclusions on the safety and clinical efficacy of repetitive use of levosimendan. METHODS AND RESULTS: A panel of 30 experts from 15 countries convened to review and discuss the existing data, and agreed on the patient groups that can be considered to potentially benefit from intermittent treatment with levosimendan. The panel gave recommendations regarding patient dosing and monitoring, derived from the available evidence and from clinical experience. CONCLUSIONS: The current data suggest that in selected patients and support out-of-hospital care, intermittent/repetitive levosimendan can be used in advanced heart failure to maintain patient stability. Further studies are needed to focus on morbidity and mortality outcomes, dosing intervals, and patient monitoring. Recommendations for the design of further clinical studies are made.

Junctional rhythm quantity and duration during slow pathway radiofrequency ablation in patients with atrioventricular nodal re-entry supraventricular tachycardia.

AIM: The occurrence of accelerated junctional rhythm during radiofrequency energy delivery at the region of the slow pathway is a well-recognized marker of successful treatment of atrioventricular nodal re-entry tachycardia (AVNRT). Our aim was to evaluate if the quantity and duration of accelerated junctional rhythm during radiofrequency ablation of the slow pathway is correlated with residual slow pathway conduction. METHODS AND RESULTS: Forty consecutive patients with AVNRT undergoing radiofrequency ablation of slow pathway who developed accelerated junctional rhythm during ablation were included. We compared accelerated junctional rhythm quantity and duration between two groups: group A, without echo beats and group B, with echo beats on post-ablation electrophysiology study. The total amount of accelerated junctional rhythm was significantly greater in group A than in group B [75.0 (63.5-165.0) vs. 36.0 (24.0-65.0), P=0.006], as well as total duration of accelerated junctional rhythm [47.0(33.5-81.0) s vs. 23.0 (16.0-42.0) s, P=0.006]. The cycle length of accelerated junctional rhythm did not differ between the two groups [510.0 (445.0-545.0) ms vs. 500.0 (450.0-585.0) ms, P=0.5). CONCLUSIONS: The amount and duration of accelerated junctional rhythm is correlated with the total abolishment abolition of slow pathway conduction. A higher amount and duration of accelerated junctional rhythm during radiofrequency applications may be an additional marker of successful ablation.

The effects of streptokinase and hydroxyethyl starch on in vitro clot disruption by ultrasound.

BACKGROUND: In vitro studies showed that low-frequency ultrasound (US) causes blood clot dissolution. This effect is augmented with thrombolytics, microbubbles and microparticles. However, in animal models of transcutaneous delivery, US alone is not effective, probably due to attenuation of US energy by overlying skin. When combined with thrombolytics or microbubbles, transcutaneous US is highly effective. PURPOSE: To assess the synergistic effect of low-intensity low-frequency US and saline, hydroxyethyl starch (HAES) (a non-gas filled microparticle containing solution), streptokinase (STK), and their combination on blood clot disruption. METHODS: Human blood clots from 4 healthy donors, 2-4 hours old, were immersed for 0, 15, or 30 min in 37 degrees C in 10 ml of the above-mentioned solutions, and then were randomized to 10 sec of 20 kHz US or no US. The % difference in weight was calculated. RESULTS: Immersion for 30 min without US resulted in 13.8 +/- 1.2% clot lysis in saline, and 22.0 +/- 1.3%, 21.7 +/- 2.1%, and 23.2 +/- 1.9% in STK, HAES, and STK + HAES, respectively (p = 0.002). US augmented clot lysis in all groups and at all time points. With low-intensity US, HAES was not better than saline. However, the combination of HAES + STK with US resulted in larger clot disruption at 15 sec incubation time (46.7 +/- 3.2%) than with saline (29.6 +/- 2.1%), HAES (29.6 +/- 2.5%), and STK (32.8 +/- 3.6%) (p < 0.001). CONCLUSION: low-frequency, low-intensity US combined with HAES and STK resulted in greater clot disruption at short incubation times. This combination may assist in achieving faster reperfusion in in vivo models.

There is synergism between high-intensity, low-frequency ultrasound and streptokinase but not with eptifibatide, heparin, and aspirin. Differential effects on fresh and aged blood clots. An in vitro study.

OBJECTIVE: Ultrasound is emerging as a promising modality for recanalization of acutely thrombosed blood vessels, especially when associated with fibrinolytics. We assessed the efficacy of ultrasound combined with saline, heparin, eptifibatide, aspirin, and streptokinase in disruption of fresh as well as aged human blood clots, using an in vitro model. METHODS: Blood clots from five donors, 2-4 or 48 hours old, were cut into 250-400 mg slices and immersed for 1, 15, or 30 min in 10 ml saline containing either heparin, eptifibatide, aspirin, streptokinase, or saline alone. Clots were then randomized to 10 s of 20 kHz ultrasound or immersion alone. After treatment, the percentage difference in weight was calculated. RESULTS: Immersion of fresh clots without ultrasound in eptifibatide and heparin resulted in significantly more clot lysis than immersion in saline, aspirin, and streptokinase. Immersion of aged thrombi without ultrasound in heparin, eptifibatide, and aspirin had no additive effect over immersion in saline. Ultrasound enhanced clot disruption in all five solutions, in each immersion time and both in fresh and aged clots. Heparin and aspirin had no additive effect, compared with saline, on ultrasound disruption of both fresh and aged clots, whereas eptifibatide was less effective than saline. In contrast, streptokinase greatly enhanced disruption of both fresh (P=.004) and aged (P<.001) thrombi by ultrasound. The combinations of ultrasound with saline, heparin, eptifibatide, and aspirin were less effective on aged than fresh thrombi, whereas the combination of ultrasound with streptokinase was equally effective on fresh and aged thrombi. CONCLUSIONS: Using a simple in vitro model, we found that the combination of streptokinase and low-frequency ultrasound had a synergistic effect on disruption of both fresh and aged blood clots. Further studies are needed to assess the role of heparin and antiplatelet agents in augmenting clot disruption by ultrasound in in vivo models of acute and subacute thrombosis.

Relation of nonobstructive aortic valve calcium to carotid arterial atherosclerosis.

Recently it was shown that subjects with aortic valve calcium (AVC) are at increased risk for future cardiovascular disease including stroke. We hypothesized that the increased risk of stroke may be due to an association with carotid artery atherosclerotic disease. Between 1995 and 1999 our laboratory made a diagnosis of AVC without significant stenosis in 3,949 patients. Of those, 279 patients without other cardiac structural exclusion criteria (148 men and 131 women; mean age 73 +/- 9 years, range 45 to 90) underwent carotid artery duplex ultrasound for various indications, and formed the study group. Age- and sex-matched patients without AVC (n = 277), who underwent carotid artery duplex ultrasound during the same period and for the same indications, served as the control group. Compared with the control group, the AVC group had a significantly higher prevalence of carotid stenosis (> 40% to 60%, 89% vs 78% [p < 0.001]; >60% to 80%, 43% vs 23% [p <0.001];and > 80% to 100%, 32%vs 14% [p < 0.001]). The AVC group had a similar, significantly higher prevalence of > or = 2-vessel disease and bilateral carotid stenosis (stenosis levels of > 20% to 40%, >40% to 60%, > 60% to 80%, and > 80% to 100%). In multivariate analysis, AVC, but not traditional risk factors, was the only independent predictor of severe carotid atherosclerotic disease (stenosis > 80% to 100%; p = 0.0001). Thus, there is a significant association between the presence of AVC and carotid atherosclerotic disease.

Microparticle-containing oncotic solutions augment in-vitro clot disruption by ultrasound.

Echocardiographic contrast agents enhance blood clot disruption by ultrasound. It has been suggested that the microbubbles add nuclei for the enhancement of cavitation by ultrasound. However, microbubbles are rapidly destroyed by the ultrasound energy. We assessed whether non-gas filled colloidal solutions (hyperoncotic medium molecular hydroxyethyl starch and degraded gelatin polypeptides) will facilitate clot disruption by ultrasound. In two separate experiments human blood clots, 200-400 mg in weight, were weighed and then immersed for 15 seconds in 10 ml normal saline solution containing 0%, 0.1%, 1%, 2%, and 5% of hyperoncotic medium molecular hydroxyethyl starch or 0%, 0.035%, 0.175%, 0.35%, and 0.7% degraded gelatin polypeptides. Clots were randomized to 10 seconds 20 kHz ultrasound or immersion without ultrasound. After treatment, the clots were reweighed, and the percent difference in weight was calculated. Non-gas filled microparticle-containing solutions such as hyperoncotic medium molecular hydroxyethyl starch and degraded gelatin polypeptides significantly augmented blood clot disruption by ultrasound. The effect is dependent on the colloidal solution concentration with maximal effect achieved with 1% hyperoncotic medium molecular hydroxyethyl starch and 0.35% degraded gelatin polypeptides.