Cardioprotective Therapies Research Articles

Temporal trends in medical cardioprotective treatment in patients with abdominal aortic aneurysms: A population-based national cohort study

Background and Aims : Patients with abdominal aortic aneurysmal (AAA) disease suffer high morbidity and mortality, driven mainly by cardiovascular comorbidity, and not the aneurysmatic disease itself. Initiation of cardioprotective therapy with statin and antiplatelets is recommended at AAA diagnosis. However, the implementation of recommendations over time is not well described. We aimed to provide up-to-date insights on temporal trends in the use of cardioprotective therapy in patients diagnosed with AAA.

Novel Anti-Cancer Therapies and Cardiac Outcomes :Systematic Reviews

Background Noval oncological therapies as chemotherapeutic drugs, immunotherapeutic, olecular target therapy and radiotherapies have improve cancer survivorship by potentially life-saving. These noval anti-neoplastic therapies have a significant adverse outcomes, particularly cardiotoxicity which prevent patients from complete receiving cancer treatment and so increase morbidity and mortality rate. Cardiovascular disease is the leading cause of noncancer deaths. Cardiovascular disease and cancer consider as the first and second most common cause of the burden of disease and death. Nowadays they are highly recognized and its drawback prevention remains challenging in cancer survivorship . Development of cadiovascular affection is associated with multiple modifiable risk factors including obesity, hypertension , diabetes, alcohol consumption, smoking, age, chronic kidney disease. Pre-assessment of those patients most likely to be given the cardioprotective therapy to improve cardiac outcomes in patients with preexisting heart disease . Objective to thorough the light on the importance of assessment of cardiac status before beginning in anti-cancer therapies to avoid cardiotoxicity . Methods a systematic literature review depends on collecting data from an evidence-based studies.Searches were made of forty electronic databases: the Cochrane Oral Health Group’s Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, PsycINFO, Scopus and Web of science, MEDLINE(PubMed). Results Systematic reviews have demonstrated correlation between anti cancer therapies and cardiovascular diseases (cardiotoxicity) especially with patients have a pre-existing risk factors . Conclusions Close collaboration among oncologists, hematologist , cardiologists, and primary care physicians to work together in a multidisciplinary setting for effective management of patients.

Abstract LB515: Cardiovascular risk assessed by aptamer-based proteomics is increased in early breast cancer

Abstract Background: Cancer patients with a high risk for cardiovascular (CV) disease may be susceptible to cardiotoxic injury during cancer therapy. Accordingly, CV risk assessment may help in identifying candidates for preventive cardioprotective treatment. Since existing CV risk scores may lack the sensitivity and granularity to reflect the changes in CV risk that is associated with early cancer, we hypothesized that a CV risk score based on aptamer-based proteomics would permit discrimination of CV risk between patients with early breast cancer and age-, sex- and risk factor-matched healthy subjects. Moreover, we hypothesized that CV risk as assessed by aptamer-based proteomics first increases during and subsequently decreases after anthracycline-containing chemotherapy. Methods: We included 120 women with early breast cancer participating in the 2x2 factorial, randomized, placebo-controlled Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA) trial who were assigned to candesartan vs placebo and metoprolol vs placebo. Blood samples were obtained serially at: Visit 1 (ie, post-surgery but prior to epirubicin), following the first cycle of epirubicin (Visit 2), after the completion of epirubicin therapy (Visit 3), following adjuvant therapy (Visit 4), and 1-2 years after completion of adjuvant and blinded therapy (Visit 5). Age-, sex-, and risk factor-matched subjects (n = 500) from the Fenland study served as controls. We used highly multiplexed modified aptamer-based proteomics to measure ~5000 plasma proteins. A validated 27-protein CV risk model (CVD) that provides information on absolute risk of myocardial infarction, stroke, heart failure or mortality over a 4-year period was used as the dependent variable. Results: The CVD risk probability was significantly higher at Visit 1 than in the age-, sex- and risk-factor matched control group (p < 0.001). The CVD risk probability increased significantly from baseline to completion of epirubicin therapy (p < 0.001) and dropped below baseline levels for subsequent timepoints after the completion of epirubicin treatment. The mean CVD risk increased from 15.9% at Visit 2 to 24.6% at Visit 3, resulting in the percentage of subjects in the medium-high risk bin increasing from 9% at Visit 2 to 28% at Visit 3. The CVD risk distribution at the end of study was similar to the initial distribution at baseline and Visit 2. Conclusion: Using a novel CVD risk proteomics model, we observed that (1) The CVD risk of patients with early breast cancer is increased compared to age-, sex- and risk factor-matched individuals from the general population; (2) CVD risk increases during adjuvant epirubicin-containing chemotherapy, and (3) after completed adjuvant cancer therapy CVD risk returns to pre-chemotherapy level. Use of the CVD risk score may represent a novel tool to identify and monitor cancer patients who may benefit from preventive cardioprotective therapy. Citation Format: Torbjørn Omland, Jessica Chadwick, Ragnhild Røysland, Geeta Gulati, David Astling, Siri L. Heck, Victoria Vinje, Rachel Ostroff, Peter Ganz, Jürgen Geisler, Steve Williams. Cardiovascular risk assessed by aptamer-based proteomics is increased in early breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB515.

Temporal trends in abdominal aortic aneurysmal disease: a nationwide cohort study on cardiovascular morbidity and medical cardioprotective therapy.

Abdominal aortic aneurysmal disease is associated with increased risk of cardiovascular morbidity and death, which potentially can be reduced with cardioprotective medical therapy. The aim of this study was to observe temporal trends in prevalence and incidence of cardiovascular comorbidity as well as use of medical cardioprotective treatment in patients diagnosed with abdominal aortic aneurysmal disease. This was a population-based cohort study based on data from national health registries, including all patients diagnosed with abdominal aortic aneurysms between 1998 and 2018. Data were stratified into four time periods (1999-2003, 2004-2008, 2009-2013, and 2014-2018) to illustrate trends over time. Outcome measures were (i) cardiovascular comorbidity and medical cardioprotective therapy at time of diagnosis, (ii) new admissions for atherosclerotic cardiovascular disease, and (iii) all-cause mortality after 2-year follow-up. The study cohort included 33 296 individuals. Mean age was 74 years. Prevalence of atherosclerotic cardiovascular comorbidity at diagnosis decreased from 41.5 to 32.6%. Use of statins increased from 17.9 to 66.9%, antiplatelets from 45.6 to 63.3%, and combined therapy with both antiplatelets and statins from 11.3 to 44.8%, and from 12.1 to 50.7% when anticoagulant therapy was included. Developments in medication use plateaued after 2013. Prevalence and incidence of atherosclerotic cardiovascular disease decreased through all four time periods. The same applied to all-cause mortality, which decreased from 24.3 to 12.4 deaths (per 100 person-years). In patients diagnosed with abdominal aortic aneurysm, cardiovascular comorbidity at diagnosis, risk of future cardiovascular events, and all-cause mortality is decreasing. Nevertheless, cardiovascular burden and mortality rates remain substantial, and medical cardioprotective therapy can be further improved.

Aging, sex and NLRP3 inflammasome in cardiac ischaemic disease

Experimentally, many strong cardioprotective treatments have been identified in different animal models of acute ischaemia/reperfusion injury (IRI) and coronary artery disease (CAD). However, the translation of these cardioprotective therapies for the benefit of the patients into the clinical scenario has been very disappointing. The reasons for this lack are certainly multiple. Indeed, many confounding factors we must deal in clinical reality, such as aging, sex and inflammatory processes are neglected in many experiments. Due to the pivotal role of aging, sex and inflammation in determining cardiac ischaemic disease, in this review, we take into account age as a modifier of tolerance to IRI in the two sexes, dissecting aging and myocardial reperfusion injury mechanisms and the sex differences in tolerance to IRI. Then we focus on the role of the gut microbiota and the NLRP3 inflammasome in myocardial IRI and on the possibility to consider NLRP3 inflammasome as a potential target in the treatment of CAD in relationship with age and sex. Finally, we consider the cardioprotective mechanisms and cardioprotective treatments during aging in the two sexes.

Could allicin alleviate trastuzumab-induced cardiotoxicity in a rat model through antioxidant, anti-inflammatory, and antihyperlipidemic properties?

AimsAlthough trastuzumab (TZB)-induced cardiotoxicity is well documented and allicin (one of the main active garlic ingredients) has ameliorating effects against numerous causes of toxicities; however, the influence of allicin on TZB-induced cardiotoxicity has not been investigated yet. Therefore, the current work explored the potential cardioprotective structural, biochemical, and molecular mechanisms of allicin against TZB-induced cardiotoxicity in a rat's model. MethodsForty rats were divided into four equal groups and treated for five weeks. The control group (G1) received PBS, the allicin group (G2) received allicin (9 mg/kg/day), the TZB group (G3) received TZB (6 mg/kg/week), and the allicin+TZB group (G4) received 9 mg of allicin/kg/day +6 mg of TZB/kg/week. Heart specimens and blood samples were processed for histopathological, immunohistochemical, biochemical, and molecular investigations to determine the extent of cardiac injury in all groups. Key findingsThe myocardium of G3 revealed significant increases in the numbers of inflammatory and apoptotic cells and the area percentage of collagen fibers and TNF-α immunoexpression compared with G1 and G2. Besides, qRT-PCR analysis exhibited significant reductions of SOD3, GPX1, and CAT expressions with significant increases in TNFα, IL-1β, IL-6, cTnI, cTnT, and LDH expressions. Additionally, flow cytometry analysis demonstrated a significant elevation in the apoptotic and ROS levels. In contrast, allicin+TZB cotherapy in G4 ameliorated all previous changes compared with G3. SignificanceThe current study proves that allicin could be used as a novel supplementary cardioprotective therapy to avoid TZB-induced cardiotoxicity via its anti-inflammatory, antifibrotic, antioxidant, antihyperlipidemic, and antiapoptotic properties.

P312 A CASE OF TAKOTSUBO CARDIOMYOPATHY IN SARS–COV–2 INFECTION

Cardiovascular complications are a frequent occurrence in Sars–CoV–2 infection. Takotsubo cardiomyopathy is a possible cause of transient ST segment elevation (1–3% of total cases) and is characterized by a reversible left ventricular dysfunction with coronary arteries free from critical stenosis. The predominant echocardiographic pattern is an akinesia of the mid–apical myocardial segments with preserved kinetics of the basal segments. The incidence of Takotsubo cardiomyopathy showed a marked increase during the COVID–19 pandemic. Three factors mainly contribute to the onset of cardiomyopathy in patients with COVID–19: cytokine storm, adrenergic hyperactivation and microvascular dysfunction. A 79–year–old woman was hospitalized in the Pneumology department of our hospital for bilateral interstitial pneumonia Sars–CoV–2 related. In remote medical history: in 2010 diagnosis of breast cancer with negative follow–up for disease recovery, arterial hypertension, hypercholesterolemia and syndrome of reduced mobility as a result of a previous ischemic stroke. Non–invasive mechanical ventilation with c–PAP was started and, for the detection of anterolateral electrocardiographic anomalies (diffuse symmetrical negative T waves) and an increase in myocardionecrosis markers, echocardiographic evaluation was performed, which revealed an akinesia of the mid–apical segments of the left ventricle with preserved kinetics of the basal segments and severely depressed global systolic function (ejection fraction: 30%). BNP (18.100 pg /mL), interleukin–6 (339 pg /mL) and CRP (136 mg /L) were elevated on blood chemistry tests. In the suspicion of Takotsubo cardiomyopathy (InterTAK Score: 67, probability: 79.8%), cardioprotective therapy with ACE inhibitor, beta–blocker, diuretics, low molecular weight heparin, double antiaggregation and statin was started, deferring coronary angiography to improved clinical conditions. In the following days, due to the respiratory and haemodynamic worsening, the patient was transferred to an intensive setting, where she was intubated and treated with levosimendan and noradrenaline. Serial echocardiograms showed a progressive improvement of the global systolic function (ejection fraction at the last checkup: 55%), with complete regression of the kinetic anomalies, confirming of the diagnostic hypothesis of stress cardiomyopathy. For a pulmonary mycotic superinfection, complicated by iatrogenic pneumothorax, in the following days the patient died.

C50 CARDIO–ONCO–HAEMATOLOGY IN CLINICAL PRACTICE. A “CHANGELING” CASE: MORE THAN PARADOXICAL BUBBLES

Abstract 39–year–old female, without cardiovascular risk factors. At the end of pregnancy she complained of progressive dyspnoea and so she was admitted to the emergency room. Blood tests showed elevated D–dimer and LDH values. A chest CT scan was performed showing a mediastinal mass of about 15 cm encompassing the ascending aorta, the left brachiocephalic trunk and the superior vena cava, both of which appeared thrombosed. Therapy with low molecular weight heparin was started. The patient underwent a mediastinal biopsy, which documented a primary mediastinal non–Hodgkin‘s lymphoma. The baseline cardiological evaluation showed a preserved ejection fraction (60%) at echocardiogram (ECHO). The first cycle of chemotherapy with R–CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine) was started. After an episode of hypoesthesia of the left upper limb, that regressed spontaneously within a few hours, she performed MRI that showed multiple areolas compatible with ischemic disease. Following these results the patient was submitted to an ECHO with saline solution injected through the right brachial vein that documented evidence of early opacification of the left atrium and subsequent opacification of the right sections (after 3 cardiac cycles) (Fig. 1–2). This finding suggested a right–to–left shunting, via the bronchial lower district to the left atrium (pulmonary veins). This suspicion was confirmed by CT angiography, which showed occlusion of the superior vena cava with passage of contrast into azygos and early opacification of peribronchial venous circles (Fig. 3). A patency of foramen ovale was ruled out by injection of saline solution through the femoral vein. After the second cycle of chemotherapy, ECHO showed diffuse hypokinesia and reduced EF to 50%. It was then decided to proceed with the third cycle according to the intensified R–DAEPOCH scheme, except for doxorubicin, because of the cardiotoxicity developed by the patient. A cardioprotective therapy was also started with bisoprolol and ramipril with rapid titration. At subsequent radiological controls, a progressive reduction of the mediastinal mass was found and after just one month, the echocardiogram showed a complete recovery of the EF. Contrast injection confirmed presence of a veno–venous shunt. Cardio–oncology is an intriguing and complex discipline that requires the development of local multidisciplinary teams for challenging situations that patients with cancer may ask us to address.

Tranilast for advanced heart failure in patients with muscular dystrophy: a single-arm, open-label, multicenter study

BackgroundThe transient receptor potential cation channel subfamily V member 2 (TRPV2) is a stretch-sensitive calcium channel. TRPV2 overexpression in the sarcolemma of skeletal and cardiac myocytes causes calcium influx into the cytoplasm, which triggers myocyte degeneration. In animal models of cardiomyopathy and muscular dystrophy (MD), TRPV2 inhibition was effective against heart failure and motor function. Our previous pilot study showed that tranilast, a TRPV2 inhibitor, reduced brain natriuretic peptide (BNP) levels in two MD patients with advanced heart failure. Thus, this single-arm, open-label, multicenter study aimed to evaluate the safety and efficacy of tranilast for heart failure.MethodsThe study enrolled MD patients with advanced heart failure whose serum BNP levels were > 100 pg/mL despite receiving standard cardioprotective therapy. Tranilast was administered orally at 100 mg, thrice daily. The primary endpoint was the change in log (BNP) (Δlog [BNP]) at 6 months from baseline. The null hypothesis was determined based on a previous multicenter study of carvedilol results in a mean population Δlog (BNP) of 0.18. TRPV2 expression on peripheral blood mononuclear cell surface, cardiac events, total mortality, left ventricular fractional shortening, human atrial natriuretic peptide, cardiac troponin T, and creatine kinase, and pinch strength were also assessed.ResultsBecause of the poor general condition of many patients, only 18 of 34 patients were included and 13 patients could be treated according to the protocol throughout the 6-month period. However, there were no serious adverse events related to tranilast except diarrhea, a known adverse effect, and the drug was administered safely. TRPV2 expression on the mononuclear cell surface was elevated at baseline and reduced after treatment. Cardiac biomarkers such as BNP, human atrial natriuretic peptide, and fractional shortening remained stable, suggesting a protective effect against the progression of heart failure. In the per protocol set group, Δlog [BNP] was − 0.2 and significantly lower than that in the null hypothesis.ConclusionsTranilast is safe and effective in inhibiting TRPV2 expression, even in MD patients with advanced heart failure. Further trials are needed to evaluate the efficacy of tranilast in preventing myocardial damage, heart failure, motor impairment, and respiratory failure.Clinical trial registration The study was registered in the UMIN Clinical Trials Registry (UMIN-CTR: UMIN000031965, URL: http://www.umin.ac.jp/ctr/) [March 30, 2018] and the Japan Registry of Clinical Trials (jRCT, registration number: jRCTs031180038, URL: https://jrct.niph.go.jp/) [November 12, 2021]. Patient registration was started in December 19, 2018.

Effectiveness of empiric cardioprotective therapy in patients receiving cardiotoxic chemotherapies: systematic review & bayesian network meta-analysis

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardioprotective therapies represent an important avenue to reduce these limiting toxicities, including serious heart failure (HF) events. However, due to conflicting isolated reports, the true efficacy and optimal cardioprotective therapy at the time of anticancer treatment initiation is unclear. Therefore, we undertook a network meta-analysis to elucidate the most effective therapies at cardiotoxic HF prevention. Purpose To determine the efficacy, and optimal cardioprotective strategy in patients receiving cardiotoxic chemotherapies. Methods Leveraging the MEDLINE/Pubmed, CENTRAL, and clinicaltrials.gov databases, we identified all randomized controlled trials (RCTs) investigating cardioprotective therapies from inception to November 2021. Eligible cardioprotective classes included ACEIs, ARBs, Beta-blockers, dexrazoxane (DEX), statins, and mineralocorticoid receptor antagonists (MRA). The primary endpoint was the prevention of new-onset HF. The secondary outcomes were the mean difference in left ventricular ejection fraction (LVEF) change, the incidence of hypotension, and all-cause mortality. Network meta-analyses were used to assess the cardioprotective effects of each therapy to deduce the most effective therapies. Both analyses were undertaken using a Bayesian random-effects model to estimate risk ratios (RR) and 95% credible intervals (95% CrI). Results Overall, from 726 articles, 39 studies evaluating 5,931 participants (38.0±19.1 years, 72.0% females) were identified. Over a median follow-up of 6 months, use of any cardioprotective strategy was associated with a significant reduction in new-onset HF (RR:0.32; 95% CrI:0.19-0.55), improved LVEF (mean difference: 3.92%; 95% CrI:2.81-5.07), and increased hypotension (RR:3.27; 95% CrI:1.38-9.87); there was no difference in mortality (RR:1.03; 95% CrI:0.84-1.22). Based on the median risk of incident HF in the control groups being 3.28%, the number need to treat (NNT) for "any" cardioprotective therapy to prevent one incident HF event was 45 patients. For dexrazoxane and neurohormonal agents, the median NNT was 36 and 53 patients, respectively. In this network analysis, dexrazoxane was most effective at HF prevention [Surface Under the Cumulative Ranking curve (SUCRA): 81.47%] and MRA most effective at preserving LVEF (SUCRA: 99.22%). ARBs most greatly increased hypotension (RR:7.20; 95% CrI:2.46-26.94). Conclusion Cardiotoxicity remains a challenge for cancer patients requiring life-saving cancer therapies. The initiation of a cardioprotective strategy reduces incident HF. Additional head-to-head trials are needed to confirm the optimal preventative strategy.

Role of Myocardial Strain Imaging in Cancer Therapy-Related Cardiac Dysfunction.

This review aims to provide a contemporary perspective on the role of myocardial strain imaging in the management of patients on cardiotoxic therapy. Risk/benefit evaluation of cardiotoxic cancer treatment remains challenging, weighing life-saving cancer therapy with fatal cardiac dysfunction potentially caused by cancer therapy. The serial change in left ventricular ejection fraction (LVEF) was conventionally used for the detection of cancer therapy-related cardiac dysfunction (CTRCD). Peak systolic global longitudinal strain (GLS) by speckle-tracking echocardiography has turned into a vital pre- and post-chemotherapy assessment for the early detection of cardiotoxicity. Complexity in cardiotoxic therapy regimen, different definition of CTRCD by LVEF, variations in GLS values, timings, and variable cutoffs make it challenging to standardize the protocol for the detection of CTRCD. GLS > 15% relative reduction from baseline has been widely used. Evidence suggests that GLS could predict early subclinical LV dysfunction, and initiation of cardioprotective therapy led to less decline of LV function. Most of the studies used an echocardiographic endpoint, and the impact of GLS on the long-term clinical outcome is not established. GLS has emerged as a reliable measure to identify early subclinical LV dysfunction by detecting myocardial deformation in patients on cardiotoxic chemotherapy. To date, a significant decline in GLS suggests the initiation of cardioprotective therapy with close monitoring. Interruption of prognostically important cardiotoxic chemotherapies requires a multidisciplinary team approach guided mainly by LVEF and other clinical factors. Further randomized control trials with hard clinical endpoints and longer follow-ups may help to determine the role of GLS in CTRCD.

FGF21-FGFR4 signaling in cardiac myocytes promotes concentric cardiac hypertrophy in mouse models of diabetes.

Fibroblast growth factor (FGF) 21, a hormone that increases insulin sensitivity, has shown promise as a therapeutic agent to improve metabolic dysregulation. Here we report that FGF21 directly targets cardiac myocytes by binding β-klotho and FGF receptor (FGFR) 4. In combination with high glucose, FGF21 induces cardiac myocyte growth in width mediated by extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. While short-term FGF21 elevation can be cardio-protective, we find that in type 2 diabetes (T2D) in mice, where serum FGF21 levels are elevated, FGFR4 activation induces concentric cardiac hypertrophy. As T2D patients are at risk for heart failure with preserved ejection fraction (HFpEF), we propose that induction of concentric hypertrophy by elevated FGF21-FGFR4 signaling may constitute a novel mechanism promoting T2D-associated HFpEF such that FGFR4 blockade might serve as a cardio-protective therapy in T2D. In addition, potential adverse cardiac effects of FGF21 mimetics currently in clinical trials should be investigated.

Long-term effectiveness of empiric cardio-protection in patients receiving cardiotoxic chemotherapies: A systematic review & bayesian network meta-analysis

BackgroundCardioprotective therapies represent an important avenue to reduce treatment-limiting cardiotoxicities in patients receiving chemotherapy. However, the optimal duration, strategy and long-term efficacy of empiric cardio-protection remains unknown. MethodsLeveraging the MEDLINE/Pubmed, CENTRAL and clinicaltrials.gov databases, we identified all randomised controlled trials investigating cardioprotective therapies from inception to November 2021 (PROSPERO-ID:CRD42021265006). Cardioprotective classes included ACEIs, ARBs, Beta-blockers, dexrazoxane (DEX), statins and mineralocorticoid receptor antagonists. The primary end-point was new-onset heart failure (HF). Secondary outcomes were the mean difference in left ventricular ejection fraction (LVEF) change, hypotension and all-cause mortality. Network meta-analyses were used to assess the cardioprotective effects of each therapy to deduce the most effective therapies. Both analyses were performed using a Bayesian random effects model to estimate risk ratios (RR) and 95% credible intervals (95% CrI). ResultsOverall, from 726 articles, 39 trials evaluating 5931 participants (38.0 ± 19.1 years, 72.0% females) were identified. The use of any cardioprotective strategy associated with reduction in new-onset HF (RR:0.32; 95% CrI:0.19–0.55), improved LVEF (mean difference: 3.92%; 95% CrI:2.81–5.07), increased hypotension (RR:3.27; 95% CrI:1.38–9.87) and no difference in mortality. Based on control arms, the number-needed-to-treat for ‘any’ cardioprotective therapy to prevent one incident HF event was 45, including a number-needed-to-treat of 21 with ≥1 year of therapy. Dexrazoxane was most effective at HF prevention (Surface Under the Cumulative Ranking curve: 81.47%), and mineralocorticoid receptor antagonists were most effective at preserving LVEF (Surface Under the Cumulative Ranking curve: 99.22%). ConclusionCardiotoxicity remains a challenge for patients requiring anticancer therapies. The initiation of extended duration cardioprotection reduces incident HF. Additional head-to-head trials are needed.

Cardio-oncology in Austria: cardiotoxicity and surveillance of anti-cancer therapies : Position paper of the Heart Failure Working Group of the Austrian Society of Cardiology.

Survival in cancer is continuously improving due to evolving oncological treatment. Therefore, cardiovascular short-term and long-term side effects gain crucial importance for overall outcome. Cardiotoxicity not only presents as heart failure, but also as treatment-resistant hypertension, acute coronary ischemia with plaque rupture or vasospasm, thromboembolism, arrhythmia, pulmonary hypertension, diastolic dysfunction, acute myocarditis and others. Recent recommendations have proposed baseline cardiac risk assessment and surveillance strategies. Major challenges are the availability of monitoring and imaging resources, including echocardiography with speckle tracking longitudinal strain (GLS), serum biomarkers such as natriuretic peptides (NT-proBNP) and highly sensitive cardiac troponins. This Austrian consensus encompasses cardiotoxicity occurrence in frequent antiproliferative cancer drugs, radiotherapy, immune checkpoint inhibitors and cardiac follow-up considerations in cancer survivors in the context of the Austrian healthcare setting. It is important to optimize cardiovascular risk factors and pre-existing cardiac diseases without delaying oncological treatment. If left ventricular ejection fraction (LVEF) deteriorates during cancer treatment (from >10% to <50%), or myocardial strain decreases (>15% change in GLS), early initiation of cardioprotective therapies (angiotensin-converting enzyme inhibitors, angiotensin or beta receptor blockers) is recommended, and LVEF should be reassessed before discontinuation. Lower LVEF cut-offs were recently shown to be feasible in breast cancer patients to enable optimal anticancer treatment. Interdisciplinary cardio-oncology cooperation is pivotal for optimal management of cancer patients.

The rationale for the need to study sodium-glucose co-transport 2 inhibitor usage in peritoneal dialysis patients.

The wave of kidney and heart outcome trials, showing multiple potential benefits for sodium-glucose co-transport 2 (SGLT2) inhibitors, have excluded patients with an estimated glomerular filtration rate below 25 ml/min/1.73 m2. However, dialysis patients are at the highest risk of cardiovascular disease and would benefit most from effective cardioprotective therapies. There is emerging evidence from experimental studies and post hoc analyses of randomised clinical trials that SGLT2 inhibitors are well tolerated and may also be effective in preventing cardiovascular and mortality outcomes in patients with severe chronic kidney disease, including patients receiving dialysis. As such, extending the usage of SGLT2 inhibitors to dialysis patients could provide a major advancement in their care. Peritoneal dialysis (PD) patients have an additional unmet need for effective pharmacotherapy to preserve their residual kidney function (RKF), with its associated mortality benefits, and for treatment options that help reduce the risk of transfer to haemodialysis. Experimental data suggest that SGLT2 inhibitors, via various mechanisms, may preserve RKF and protect the peritoneal membrane. There is sound physiological rationale and an urgent clinical need to execute robust randomised control trials to study the use of SGLT2 inhibitors in PD patients to answer important questions of relevance to patients and healthcare systems.

Changing the Trajectory of Heart Failure and Kidney Disease: A Call for Action.

Changing the Trajectory of Heart Failure and Kidney Disease: A Call for Action.

Cardiotoxicity of Anticancer Drugs: Molecular Mechanisms and Strategies for Cardioprotection.

Chemotherapy and targeted therapies have significantly improved the prognosis of oncology patients. However, these antineoplastic treatments may also induce adverse cardiovascular effects, which may lead to acute or delayed onset of cardiac dysfunction. These common cardiovascular complications, commonly referred to as cardiotoxicity, not only may require the modification, suspension, or withdrawal of life-saving antineoplastic therapies, with the risk of reducing their efficacy, but can also strongly impact the quality of life and overall survival, regardless of the oncological prognosis. The onset of cardiotoxicity may depend on the class, dose, route, and duration of administration of anticancer drugs, as well as on individual risk factors. Importantly, the cardiotoxic side effects may be reversible, if cardiac function is restored upon discontinuation of the therapy, or irreversible, characterized by injury and loss of cardiac muscle cells. Subclinical myocardial dysfunction induced by anticancer therapies may also subsequently evolve in symptomatic congestive heart failure. Hence, there is an urgent need for cardioprotective therapies to reduce the clinical and subclinical cardiotoxicity onset and progression and to limit the acute or chronic manifestation of cardiac damages. In this review, we summarize the knowledge regarding the cellular and molecular mechanisms contributing to the onset of cardiotoxicity associated with common classes of chemotherapy and targeted therapy drugs. Furthermore, we describe and discuss current and potential strategies to cope with the cardiotoxic side effects as well as cardioprotective preventive approaches that may be useful to flank anticancer therapies.

The efficacy and safety of cardio-protective therapy in patients with 5-FU (Fluorouracil)-associated coronary vasospasm.

BackgroundCoronary vasospasm is a known side effect of 5-FU (fluorouracil) therapy. Beyond switching to non-5FU-based chemotherapy, there are no established treatments for 5-FU associated coronary vasospam. Our objective was to assess the safety and efficacy of re-challenge with 5-FU after pre-treatment with calcium channel blockers (CCBs) and long-acting nitrates among patients 5-FU associated coronary vasospasm.MethodsWe conducted a retrospective study of patients with 5-FU coronary vasospasm at a single academic center. By protocol, those referred to cardio-oncology received pre-treatment with either combination [nitrates and CCBs] or single-agent therapy [nitrates or CCBs]) prior to re-challenge with 5-FU. Our primary outcome was overall survival. Other important outcomes included progression-free survival and safety.ResultsAmong 6,606 patients who received 5-FU from January 2001 to Dec 2020, 115 (1.74%) developed coronary vasospasm. Of these 115 patients, 81 patients continued 5-FU therapy, while 34 stopped. Of the 81 who continued, 78 were referred to cardio-oncology and prescribed CCBs and/or nitrates prior to subsequent 5-FU, while the remaining 3 continued 5-FU without cardiac pre-treatment. Of the 78, 56.4% (44/78) received both nitrates and CCBs, 19.2% (15/78) received CCBs alone, and 24.4% (19/78) received nitrates alone. When compared to patients who stopped 5-FU, those who continued 5-FU after pre-treatment (single or combination therapy) had a decreased risk of death (HR 0.42, P = 0.005 [95% CI 0.23–0.77]) and a trend towards decreased cancer progression (HR 0.60, P = 0.08 [95% CI 0.34–1.06]). No patient in the pre-treatment group had a myocardial infarct after re-challenge; however, chest pain (without myocardial infarction) recurred in 19.2% (15/78) among those who received cardiac pre-treatment vs. 66.7% (2/3) among those who did not (P = 0.048). There was no difference in efficacy or the recurrence of vasospasm among patients who received pre-treatment with a single agent (nitrates or CCBs) or combination therapy (14.7% (5/34) vs. 25.0% (11/44), P = 0.26).ConclusionRe-challenge after pre-treatment with CCBs and nitrates guided by a cardio-oncology service was safe and allowed continued 5-FU therapy.

Troponin Levels and the Severity of COVID-19 Pneumonia.

IntroductionIn late 2019, a novel coronavirus was identified as the pathogen responsible for a cluster of pneumonia cases in Wuhan, a city in the Hubei Province of China. Elevated cardiac troponin is a marker of myocardial injury, which is commonly seen in hospitalized patients with COVID-19 due to unclear reasons. The frequency of elevated troponin levels in patients with COVID-19 is variable and is reported in up to 7-36% of patients. The troponin level may be associated with the severity of COVID-19, and mild cases of COVID-19 tend to have a normal troponin level. This study aims to determine the frequency of patients with COVID-19 who had elevated troponin levels on presentation to the ED and determine the factors associated with elevated troponin levels. Additionally, the study aims to identify the association of elevated troponin and the outcome of COVID-19.MethodologyA retrospective study wherein the factors associated with elevated troponin levels in COVID-19 pneumonia were evaluated. The study was conducted in King Fahd Hospital of the Imam Abdulrahman Bin Faisal University. The Hospital Information System was used to identify all visits to the ED from March 2020 to November 2020 for patients who tested positive for SARS-CoV-2. In addition, a structured data collection form was used to collect data from the electronic health records. The data collection was conducted by emergency medicine physicians who were given a detailed explanation of the purpose of the study and had training and supervision by the principal investigator.ResultsThe study involved 214 patients who presented to the ED and had positive results on the SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) test and had troponin-I levels measured. Patients with elevated troponin levels were more likely to require supplementary oxygen compared with those with normal troponin levels (88.0 vs. 58.5%; P < 0.01). In total, 36 (76.6%) patients with elevated troponin levels required admission to the ICU compared with 58 (45.0%) patients with normal troponin levels (P < 0.01). Multivariable binary logistic regression analysis was used to identify the predictors of elevated troponin levels on presentation. The model revealed that being admitted in the ICU was the single independent predictor (P = 0.02).ConclusionThe study demonstrated that the troponin level on presentation to the ED was a viable independent prognostic factor in COVID-19 pneumonia. However, further studies are needed to investigate targeted therapeutic interventions among patients with elevated troponin levels, such as cardioprotective therapies like corticosteroids, immunosuppressants, antivirals, or immunoglobulins.

Effect of Oral Semaglutide on Cardiovascular Parameters and Their Mechanisms in Patients with Type 2 Diabetes: Rationale and Design of the Semaglutide Anti-Atherosclerotic Mechanisms of Action Study (SAMAS).

IntroductionType 2 diabetes (T2D) management has reached a point where not only optimal glycaemic control is necessary, but also additional interventions with proven cardiovascular risk reduction benefit. Subcutaneous semaglutide has been shown to provide cardiovascular protection, but its use may be limited by its injection formulation. To overcome this limitation, an oral semaglutide tablet has been developed, which could potentially be of the same value as its injection counterpart, but in a much wider group of patients with T2D, thereby allowing for broader cardiovascular risk reduction in this vulnerable patient population.MethodsA total of 100 consecutive patients with T2D and a disease duration of up to 10 years, without manifest cardiovascular disease, who are treated with metformin (± sulphonylurea) and optimal cardioprotective therapy, will be recruited in a single-blinded, randomized trial named “Semaglutide Anti-atherosclerotic Mechanisms of Action Study (SAMAS).” After 1:1 randomization, patients will receive either oral semaglutide 14 mg daily or placebo for 1 year. The primary outcome comprises changes in atherosclerosis-related structural and functional characteristics of the arterial wall, namely: reduction of the carotid intima-media thickness, improvement of endothelial function and decrease in arterial stiffness. Secondary outcomes are changes in atherogenic small dense low-density lipoproteins, glucose control (HbA1c) and inflammatory markers (hsCRP). Possible correlations between primary endpoints and changes in lipids, HbA1c and high-sensitivity C-reactive protein will be sought.DiscussionThis is the first study to investigate the direct and indirect anti-atherosclerotic mechanisms of oral semaglutide. The results are expected to confirm the position of oral semaglutide in the multifactorial management of T2D with an emphasis on cardiovascular disease prevention.Trial RegistrationClinicalTrials.gov Identifier: NCT05147896.