Are Sodium-Glucose Cotransporter-2 Inhibitors the Cherry on Top of Cardio-Oncology Care?

The increasing aging of the population combined with improvements in cancer detection and care has significantly improved the survival and quality of life of cancer patients. These benefits are hampered by the increase of cardiovascular diseases being heart failure the most frequent manifestation of cardiotoxicity and becoming the major cause of morbidity and mortality among cancer survivor. Current strategies to prevent cardiotoxicity involves different approaches such as optimal management of CV risk factors, use of statins and/or neurohormonal medications, and, in some cases, even the use of chelating agents. As a class, SGLT2-i have revolutionized the therapeutic horizon of HF patients independently of their ejection fraction or glycemic status. There is an abundance of data from translational and observational clinical studies supporting a potential beneficial role of SGLT2-i in mitigating the cardiotoxic effects of cancer patients receiving anthracyclines. These findings underscore the need for more robust clinical trials to investigate the effect on cardiovascular outcomes of the prophylactic SGLT2-i treatment in patients undergoing cancer treatment.

Direct intramyocardial injection of VEGF mRNA in patients undergoing coronary artery bypass grafting.

Vascular endothelial growth factor A (VEGF-A) has therapeutic cardiovascular effects, but delivery challenges have impeded clinical development. We report the first clinical study of naked mRNA encoding VEGF-A (AZD8601) injected into the human heart. EPICCURE (ClinicalTrials.gov: NCT03370887) was a randomized, double-blind study of AZD8601 in patients with left ventricular ejection fraction (LVEF) 30%-50% who were undergoing elective coronary artery bypass surgery. Thirty epicardial injections of AZD8601 (total 3 mg) or placebo in citrate-buffered saline were targeted to ischemic but viable myocardial regions mapped using quantitative [15O]-water positron emission tomography. Seven patients received AZD8601 and four received placebo and were followed for 6 months. There were no deaths or treatment-related serious adverse events and no AZD8601-associated infections, immune reactions, or arrhythmias. Exploratory outcomes indicated potential improvement in LVEF, Kansas City Cardiomyopathy Questionnaire scores, and N-terminal pro-B-type natriuretic peptide levels, but the study is limited in size, and significant efficacy conclusions are not possible from the dataset. Naked mRNA without lipid encapsulation may provide a safe delivery platform for introducing genetic material to cardiac muscle, but further studies are needed to confirm efficacy and safety in a larger patient pool.

Echocardiographic parameters of cardiac structure and function in the diagnosis of acute myocarditis in adult patients: A systematic review and meta-analysis.

BACKGROUND: Transthoracic echocardiography (TTE) plays a key role in the initial work-up of myocarditis where the identification of pathologic structural and functional changes may assist in its diagnosis and management. The aim of this systematic review was to appraise the evidence for the utility of echocardiographic parameters of cardiac structure and function in the diagnosis of myocarditis in adult populations. METHODS: A systematic literature search of medical databases was performed using PRISMA principles to identify all relevant studies assessing TTE parameters in adult patients with myocarditis (1995-2020; English only; PROSPERO registration CRD42021243598). Data for a range of structural and functional TTE parameters were individually extracted and those with low heterogeneity were then meta-analyzed using a random-effects model for effect size, and assessed through standardized mean difference (SMD). RESULTS: Available data from six studies (with a pooled total of 269 myocarditis patients and 240 controls) revealed that myocarditis can be reliably differentiated from healthy controls using echocardiographic measures of left ventricular (LV) size and systolic function, in particular LV end-diastolic diameter, LV ejection fraction (LVEF) and LV global longitudinal strain (LV-GLS) (p ≤ .01 for all). LV-GLS demonstrated the highest overall effect size, followed by LVEF and LVEDD (SMD: |0.46-1.98|). Two studies also demonstrated that impairment in LV-GLS was associated with adverse cardiovascular outcomes in this population, irrespective of LVEF. CONCLUSIONS: LV-GLS demonstrated the greatest overall effect size and therefore ability to differentiate myocarditis populations from healthy controls. GLS was also shown to be a predictor of adverse cardiovascular outcomes, in this population. HIGHTLIGHTS: What is already known on this subject? Myocarditis is a disease process that is often a diagnosis of exclusion, as it frequently mimics other acute cardiac pathologies. Transthoracic echocardiography is traditionally the initial imaging modality used for noninvasive structural assessment in populations with myocarditis. What might this study add? This study demonstrates that left ventricular (LV) global longitudinal strain, LV ejection fraction and LV end-diastolic diameter can differentiate between myocarditis patients and healthy controls. LV-GLS demonstrated the greatest overall effect size when comparing these two populations, in comparison to the other measures. How might this impact on clinical practice? This study demonstrates that assessment of myocardial deformation indices allows for sensitive discrimination between myocarditis patients from healthy controls. Routine assessment of LV-GLS may serve as an important diagnostic tool in the acute care setting.

Incremental prognostic value of speckle tracking echocardiography and early follow-up echo assessment in predicting left ventricular recovery after reperfusion for ST-segment elevation myocardial infarction (STEMI).

PURPOSE: Up to 50% of patients do not achieve significant left ventricular ejection fraction (LVEF) recovery after primary percutaneous intervention (PPCI) for STEMI. We aimed to identify the echocardiographic predictors for LVEF recovery and assess the value of early follow-up echocardiography (Echo) in risk assessment of post-myocardial infarction (MI) patients. METHODS: One hundred one STEMI patients undergoing PPCI were enrolled provided EF below 50%. Baseline echocardiography assessed LVEF, volumes, wall motion score index (WMSI), global longitudinal strain (GLS), global circumferential strain (GCS), and E/e'. Follow-up echocardiography after 6 weeks reassessed left ventricular volumes, LVEF and GLS.GCS was not assessed at follow up. Patients were classified into recovery and non-recovery groups. Predictors of LVEF recovery and major adverse cardiovascular events (MACE) at 6 months were analysed. RESULTS: The mean change of EF was 8.04 ± 3.32% in group I versus -.39 ± 5.09 % in group II (p < .001). Recovered patients had better baseline GLS, baseline GCS, E/e', and follow-up GLS. Multivariate regression analysis revealed E/e', GCS, and follow-up GLS after 6 weeks to be strong independent predictors for LVEF recovery. Composite MACE was considerably higher in group II (32.7% vs. 4.1%, p < .001) mainly driven by higher heart failure hospitalisation Multivariate regression analysis revealed baseline GLS, E/e', and ejection fraction (EF) percentage recovery as strong independent predictors for MACE. CONCLUSIONS: Multiparametric echocardiographic approach incorporating LVEF, strain parameters, and diastolic function could allow early optimal risk stratification after STEMI treated with PPCI. Follow-up GLS and LVEF percentage change are the strongest predictors for early LV recovery and long term clinical outcome, respectively.

Left ventricular ejection fraction: time to revise the metric?

In this paper, we highlight the prevalent misconception among patients regarding the normal value of left ventricular ejection fraction in cardiac function assessment. This misconception arises from the proportion dominance effect, wherein individuals tend to judge based on proportions rather than absolute values. We explain how this misunderstanding impacts patient demoralization and medical adherence, leading to worse clinical outcomes. To address this, the concept of "Left Ventricular Ejection Fraction - Proportion of Normal" is introduced, which adjusts left ventricular ejection fraction to a patient-specific normal range. This patient-centric approach aims to enhance comprehension, engagement, and adherence by conveying accurate information through the lens of proportions, thereby potentially improving clinical outcomes.

Association of leadless pacing with ventricular and valvular function.

BACKGROUND: Traditional transvenous pacemakers are associated with worsening tricuspid valve function due to lead-related leaflet impingement, as well as ventricular dysfunction related to electromechanical dyssynchrony from chronic right ventricular (RV) pacing. The association of leadless pacing with ventricular and valvular function has not been well established. We aimed to assess the association of leadless pacemaker placement with changes in valvular regurgitation and ventricular function. METHODS AND RESULTS: Echocardiographic features before and after leadless pacemaker implant were analyzed in consecutive patients who received a leadless pacemaker with pre- and postprocedure echocardiography at Duke University Hospital between November 2014 and November 2019. Valvular regurgitation was graded ordinally from 0 (none) to 3 (severe). Among 54 patients, the mean age was mean age was 70.1 ± 14.3 years, 24 (44%) were women, and the most frequent primary pacing indication was complete heart block in 24 (44%). The median RV pacing burden was 45.4 (interquartile range [IQR] 3.5-97.0). On echocardiogram performed 8.9 months (IQR 4.5-14.5) after implant, there was no change in the average severity of tricuspid regurgitation (mean change 0.07 ± 1.15, p = .64) from pre-procedure echocardiogram. We observed a decrease in the average left ventricular ejection fraction (LVEF) (52.3 ± 9.3 to 47.9 ± 12.1, p = .0019) and tricuspid annular plane systolic excursion (TAPSE) (1.8 ± 0.6 to 1.6 ± 0.4, p = .0437). Thirteen patients (24%) had absolute drop in LVEF of ≥10%. CONCLUSION: We did not observe short term worsening valvular function in patients with leadless pacemakers. However, consistent with the pathophysiologic impact of RV pacing, leadless pacing was associated with a reduction in biventricular function.

ACEI/ARB and beta-blocker therapies for preventing cardiotoxicity of antineoplastic agents in breast cancer: a systematic review and meta-analysis.

Anthracyclines and trastuzumab are widely used to treat breast cancer but increase the risk of cardiomyopathy and heart failure. With the use of trastuzumab and anthracycline-containing medications, this study intends to evaluate the effectiveness and security of current treatments against cardiotoxicity. We conducted a systematic review of randomized controlled trials (RCTs), which used at least one angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), or beta-blocker (BB) to prevent cardiotoxicity of antineoplastic agents for breast cancer, in 4 databases (PubMed, Cochrane Library, EMBASE, Web of Science) from inception to 11 May 2022, without language restrictions. The outcome of interest was left ventricular ejection fraction (LVEF) and adverse events. Stata 15 and R software 4.2.1 were used to perform all statistical analyses. The Cochrane version 2 of the risk of bias tool was used to assess the risk of bias, and the grading of recommendations assessment, development, and evaluation (GRADE) assessment was used to appraise the quality of the evidence. Fifteen randomized clinical studies with a total of 1977 patients were included in the analysis. The included studies demonstrated statistically significant LVEF in the ACEI/ARB and BB treatment groups (χ2 = 184.75, I2 = 88.6%, p = 0.000; SMD 0.556, 95% CI 0.299 to 0.813). In an exploratory subgroup analysis, the benefit of experimental agents on LVEF, whether anthracyclines or trastuzumab, was prominent in patients treated with ACEIs, ARBs, and BBs. Compared to placebo, ACEI/ARB and BB treatments in breast cancer patients protect against cardiotoxicity after trastuzumab and anthracycline-containing medication treatment, indicating a benefit for both.

Value of Speckle Tracking Echocardiography Combined with Stress Echocardiography in Predicting Surgical Outcome of Severe Aortic Regurgitation with Markedly Reduced Left Ventricular Function.

Background: Predicting outcomes of surgical aortic valve replacement (AVR) in patients with chronic severe aortic regurgitation (AR) and markedly reduced left ventricular (LV) function remains a challenge. This study aimed to explore the preoperative echocardiographic index that could predict the recovery of LV systolic function after surgery in patients with chronic severe AR and reduced left ventricular ejection fraction (LVEF). Methods: The study group consisted of 50 patients diagnosed with chronic severe AR ( > 6 months) and significantly reduced LVEF (18~35%, average 26.2 ± 5.3%). Low-dose dobutamine stress echocardiography (DSE) was performed before surgery. Only patients with an absolute increase in LVEF ≥ 8% during DSE were referred for surgical AVR. During following up (over six months to one year after surgery), the patients were divided into two groups by postoperative LVEF ( > or ≤ 40%). DSE- and speckle tracking echocardiography (STE)-derived LV functional parameters were compared between groups to identify predictors of post-operative improvement in LVEF. Results: A total of 38 patients underwent AVR. One patient died before discharge. Post-surgical LV size and LVEF improved markedly after surgery in all patients (n = 37). Pre-surgical LV end-systolic diameter, baseline global longitudinal strain (GLS) and peak GLS were better in the group with LVEF > 40% (n = 18; p < 0.05, t test). Baseline GLS and peak GLS correlated moderately with post-surgery LVEF (R = -0.581, p < 0.001; R = -0.596, p < 0.001; respectively). Logistic regression analysis demonstrated baseline GLS and peak GLS were the independent predictors of post-surgery improvement of LVEF. Peak GLS had the highest prediction value (area under the curve = 0.895, sensitivity and specificity: 89.5% and 77.8%, respectively), with a cutoff value of -9.4%. Conclusions: This study shows that STE combined with DSE can provide sensitive quantitative indices for predicting improvement of LV systolic function after AVR in patients with chronic severe AR and significantly decreased LVEF.

Clinical and echocardiographic outcomes with new-onset left bundle branch block after SAPIEN-3 transcatheter aortic valve replacement.

BACKGROUND: New-onset left bundle branch block (LBBB) can develop after transcatheter aortic valve replacement (TAVR) resulting in worse outcomes. AIMS: Describe clinical and echocardiographic outcomes with new-onset LBBB after TAVR. METHODS: We included consecutive patients who underwent transfemoral-TAVR with SAPIEN-3 (S3) valve between April 2015 and December 2018. Exclusion criteria included pre-existing LBBB, right BBB, left anterior hemiblock, left posterior hemiblock, wide QRS ≥ 120ms, prior permanent pacemaker (PPM), and nontransfemoral access. RESULTS: Among 612 patients, 11.4% developed new-onset LBBB upon discharge. The length of stay was longer with new-onset LBBB compared with no LBBB [3 (2-5) days versus 2 (1-3) days; p < 0.001]. New-onset LBBB was associated with higher rates of 30-day PPM requirement (18.6% vs. 5.4%; p < 0.001) and 1-year heart failure hospitalizations (10.7% vs. 4.4%; p = 0.033). There was no difference in 3-year mortality between both groups (30.9% vs. 30.6%; p = 0.829). Further, new-onset LBBB was associated with lower left ventricular ejection fraction (LVEF) at both 30 days (55.9 ± 11.4% vs. 59.3 ± 9%; p = 0.026) and 1 year (55 ± 12% vs. 60.1 ± 8.9%; p = 0.002). These changes were still present when we stratified patients according to baseline LVEF (≥50% or <50%). New-onset LBBBs were associated with a higher 1-year LV end-diastolic volume index (51.4 ± 18.6 vs. 46.4 ± 15.1 ml/m2 ; p = 0.036), and LV end-systolic volume index (23.2 ± 14.1 vs. 18.9 ± 9.7 ml/m2 ; p = 0.009). Compared with resolved new-onset LBBB, persistent new-onset LBBB was associated with worse LVEF and higher PPM at 1 year. CONCLUSIONS: New-onset LBBB after S3 TAVR was associated with higher PPM requirement, worse LVEF, higher LV volumes, and increased heart failure hospitalizations, with no difference in mortality.

Impact of donor ventricular function on heart transplantation outcomes.

BACKGROUND: Some heart transplant (HTx) centers have expanded their donor eligibility criteria in response to the organ shortage; one area of active interest involves utilizing hearts with ventricular dysfunction. Our study seeks to identify if a relationship exists between donor left ventricular ejection fraction (LVEF) and ischemic time or donor age on HTx outcomes. METHODS: We performed a retrospective analysis on adult patients who had a HTx between 1996 and 2021 (n = 46,936). Donor LVEF (dLVEF) values were categorized into three groups: <50%, 50%-70%, and >70%. Ischemic time and donor age were stratified into four groups: ≤2.0, 2.1-3.0, 3.1-4.0, >4.0 h, and ≤30, 31-40, 41-50, >50 years, respectively. The outcome of interest was long-term survival. RESULTS: Multivariable survival analysis found a slight increase in overall mortality risk for patients with donor ejection fractions <50% (HR = 1.16, p = .013). However, subsequent subgroup investigation discovered that this elevated hazard was only applicable when ischemic time was prolonged to >3.0 h (3.1-4.0 h: HR = 1.23, p = .024; > 4.0 h: HR = 1.52, p < .001). There was no significant difference in survival between dLVEF groups when ischemic time was limited to ≤3.0 h or when stratified by donor age. CONCLUSION: HTx patients with a low donor ejection fraction have comparable survival to recipients with a normal dLVEF when ischemic time is limited to ≤3.0 h. Reduced dLVEF does not appear to be sensitive to advanced donor age. The clinical implications of our study may encourage the recruitment of more donor hearts for transplantation.

Best ablation strategy in patients with premature ventricular contractions with multiple morphology: a single-centre experience.

AIMS: This study aimed to examine the clinical benefits of targeted ablation of all Premature ventricular complex (PVC) morphologies vs. predominant PVC only. METHODS AND RESULTS: A total of 171 consecutive patients with reduced left ventricular ejection fraction (LVEF) and ≥2 PVC morphology with high burden (>10%/day) undergoing their first ablation procedure were included in the analysis. At the initial procedure, prevalent PVC alone was ablated in the majority. However, at the redo, all PVC morphologies were targeted for ablation. : At the first procedure, 152 (89%) patients received ablation of the dominant PVC only. In the remaining 19 (11%) patients, all PVC morphologies were ablated. At two years, high PVC burden was detected in 89 (52%) patients. Repeat procedure was performed in 78 of 89, where all PVC morphologies were ablated. At 5 years after the repeat procedure, 71 (91%) had PVC burden of <5% [3.8 ± 1.1% vs. 15.4 ± 4.3% in successful vs. failed subjects (P < 0.001)]. In patients with low PVC burden after the initial procedure, LVEF improved from 37.5% to 41.6% [mean difference (MD): 3.39 ± 2.9%, P < 0.001], whereas a reduction in LVEF from 39.8% to 34.5% (MD: 6.45 ± 4.7%, P < 0.001) was recorded in patients with high PVC burden. One year after the repeat procedure, LVEF improved from 36.2% to 41.7% (MD: 5.5 ± 4.3%, P < 0.001) in patients with successful ablation. CONCLUSION: In this observational series, ablation of all PVC morphologies was associated with significantly lower PVC burden and improvement of LVEF at long-term follow-up, compared with ablation of the dominant morphology only.

Comparing Renin-Angiotensin-Aldosterone Blockade Regimens for Long-Term Chemotherapy-Related Cardiac Dysfunction: A Network Meta-Analysis.

PURPOSE: Cancer therapies including trastuzumab and anthracyclines are cardiotoxic and cause cardiac dysfunction. To prevent cardiotoxicity, pharmacological agents used in heart failure have been administered concomitantly with cardiotoxic cancer therapy, but few studies to date have performed a head-to-head comparison of these different agents. This systematic review and network meta-analysis of randomized-controlled trials aims to evaluate the efficacy of renin-angiotensin-aldosterone system (RAAS) blockers, namely angiotensin-converting enzyme inhibitors (ACE-Is), aldosterone receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs), in primary prevention against chemotherapy-related cardiac dysfunction in patients receiving anthracyclines and/or trastuzumab. METHODS: A systematic search was performed in major web databases for studies from inception to 15 September 2022. A Bayesian network meta-analysis model was used to assess the relative effects of competing treatments on the primary outcomes of risk of significant decline in left ventricular ejection fraction (LVEF) and mean LVEF decline. Secondary outcomes included left ventricular diastolic function, global longitudinal strain, and cardiac biomarkers. This study is registered with PROSPERO, CRD42022357980. RESULTS AND CONCLUSION: Nineteen studies reported the effects of 13 interventions (N = 1905 patients). Only enalapril (RR 0.05, 95% CI 0.00-0.20) was associated with reduced risk of patients developing significant decline in LVEF relative to placebo. Subgroup analysis showed that the beneficial effect of enalapril was driven by protection against anthracycline-associated toxicity. In addition, no RAAS-inhibiting agents showed efficacy in protection against treatment with both anthracycline and trastuzumab. The use of RAAS inhibition therapy did not conclusively impact on other markers of cardiac function, including left ventricular diastolic function and cardiac biomarkers.

Diagnostic accuracy of left atrial function and strain for differentiating between acute and chronic myocardial infarction.

BACKGROUND: The cardiac magnetic resonance tissue tracking (CMR-TT) technique was used to obtain left atrial strain and strain rate in patients with myocardial infarction (MI) and to evaluate the utility of this technique in the quantitative assessment of myocardial infarction for distinguishing acute from chronic myocardial infarction. METHODS: We retrospectively analyzed 36 consecutive patients with acute myocardial infarction (AMI) and 29 patients with chronic myocardial infarction (CMI) who underwent CMR and 30 controls. Left atrial (LA) and ventricular functions were quantified by volumetric, and CMR-TT derived strain analysis from long and short left ventricular view cines. Receiver Operating Characteristics (ROC) analysis was used to determine the diagnostic accuracy of CMR-TT strain parameters for discriminating between acute and chronic myocardial infarction. RESULTS: AMI and CMI participants had impaired LA reservoir function, conduit function and LA booster pump dysfunction compared to the controls. LA strain was more sensitive than LV global strain for the assessment of the MI stage. Peak late-negative SR yielded the best areas under the ROC curve (AUC) of 0.879, showing differentiation between acute and chronic myocardial infarction of all the LA strain parameters obtained. The highest significant differences between chronic myocardial infarction and normal myocardium were also found in the LV strain (p < 0.001) and LA functional parameters (p < 0.001), but there was no difference between AMI and normals. CONCLUSIONS: CMR-TT-derived LA strain is a potential and robust tool in demonstrating impaired LA mechanics and quantifying LA dynamics, which have high sensitivity and specificity in the differential diagnosis of acute versus chronic myocardial infarction. Their use is thus worth popularizing in clinical application.

Possible heart failure caused by osimertinib in a lung cancer patient.

INTRODUCTION: Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) indicated for the treatment of epidermal growth factor receptor mutated non-small cell lung cancer (NSCLC). It has demonstrated better results concerning effectiveness than other TKIs for the same indication. However, despite a good safety profile, it could produce some cardiotoxicity that does not occur with other drugs of the same group. CASE REPORT: We report the evolution and management of a female patient diagnosed with NSCLC who developed a grade 3 cardiotoxicity due to treatment with osimertinib. This patient suffered from a left bundle branch block, dyslipidemia, and hypertension as cardiovascular risk factors. After a long period of treatment with osimertinib, she developed a severe heart failure (HF) with an important decrease in left ventricular ejection fraction (LVEF), which triggered an admission to the oncology unit for eight days. MANAGEMENT AND OUTCOMES: Treatment with osimertinib was first suspended and then resumed after stabilization of the HF. She also developed atrial fibrillation during admission and has required narrow cardiac monitoring and management since the debut of the HF. After evaluating the benefit-risk balance, osimertinib was reintroduced and the patient continues in treatment at the moment, although the baseline LVEF is not recovered. DISCUSSION: There is scarce evidence in the literature concerning HF and important LVEF decrease due to osimertinib. However, its severity and repercussion for the patient justify the thorough screening of cardiovascular risk factors before starting the therapy.

Adiponectin - stratification biomarker in diastolic cardiac dysfunction.

This study does not propose to elucidate how adiponectin secretion is regulated, but how its adiponectin concentration is an indicator of heart disease. About adiponectin, it is not known whether it is functionally an enzyme, or very likely a cytokine/chemokine/hormone, secreted by fat cells/adipocytes in the abdomen. Abdominal fat secretes 67 hormones, and all of which cause disease. For example, adiponectin generates diabetes and ischaemic heart disease via dyslipidemia. Based on clinical symptoms, electrocardiographic and echocardiographic parameters, a group of 208 patients with diastolic cardiac dysfunction with or without preserved systolic function, developed on a background of painful chronic ischaemic heart disease, stable angina on exertion, was constituted. The serum levels of adiponectin, total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides were measured. Using the identified values, it was appreciated whether adiponectin correlates with the type of any of the two conditions, so that it can be recognised as a diagnostic and risk stratification marker.

The effect of trastuzumab on cardiac function in patients with HER2-positive metastatic breast cancer and reduced baseline left ventricular ejection fraction.

We investigated the effect of trastuzumab on cardiac function in a real-world historic cohort of patients with HER2-positive metastatic breast cancer (MBC) with reduced baseline left ventricular ejection fraction (LVEF). Thirty-seven patients with HER2-positive MBC and baseline LVEF of 40% to 49% were included. Median LVEF was 46% (interquartile range [IQR] 44%-48%) and median follow-up was 18 months (IQR 9-34 months). During this period, the LVEF did not worsen in 24/37 (65%) patients, while 13/37 (35%) patients developed severe cardiotoxicity defined as LVEF <40% with median time to severe cardiotoxicity of 7 months (IQR 4-10 months) after beginning trastuzumab. Severe cardiotoxicity was reversible (defined as LVEF increase to a value <5%-points below baseline value) in 7/13 (54%) patients, partly reversible (defined as absolute LVEF increase ≥10%-points from nadir to a value >5%-points below baseline) in 3/13 (23%) patients and irreversible (defined as absolute LVEF increase <10%-points from nadir and to a value >5%-points below baseline) in 3/13 (23%) patients. Likelihood of reversibility was numerically higher in patients who received cardio-protective medications (CPM), including ACE-inhibitors, beta-blockers and angiotensine-2 inhibitors, compared to those who did not receive any CPM (71% vs 13%, P = .091). Sixty-five percent of patients who received trastuzumab for HER2-positive MBC did not develop severe cardiotoxicity during a median follow-up of 18 months, despite having a compromised baseline LVEF. If severe cardiotoxicity occurred, it was at least partly reversible in more than two-thirds of the cases. Risks and benefits of trastuzumab use should be balanced carefully in this vulnerable population.

Predictors and prognostic impact of left ventricular ejection fraction trajectories in patients with ST-segment elevation myocardial infarction.

BACKGROUND: There is little evidence on left ventricular ejection fraction (LVEF) trajectories after ST-segment elevation myocardial infarction (STEMI). AIM: We aim to identify the LVEF trajectories after STEMI and explore their predictors and association with prognosis. METHODS: This is a retrospective, observational study of STEMI patients. The LVEF trajectories were identified by the latent class trajectory model in patients with baseline LVEF < 50%. We used logistic regression analysis to investigate the predictors for LVEF trajectories. The Cox proportional hazard model was used to assess the impact of LVEF trajectories on prognosis. The primary outcomes were cardiovascular mortality and heart failure (HF) rehospitalization. RESULTS: 572 of 1179 patients presented with baseline normal LVEF (≥ 50%) and 607 with baseline reduced LVEF (< 50%). Two distinct LVEF trajectories were identified in patients with baseline reduced LVEF: recovered LVEF group and persistently reduced LVEF group. Higher baseline LVEF, lower peak troponin T, non-anterior MI, and lower heart rates were all found to be independently associated with LVEF recovery. After multivariate adjustments, patients with persistently reduced LVEF experienced an increased risk of cardiovascular mortality (HR 7.49, 95% CI 1.94-28.87, P = 0.003) and HF rehospitalization (HR 3.54, 95% CI 1.56-8.06 P = 0.003) compared to patients with baseline normal LVEF. Patients with recovered LVEF, on the other hand, showed no significant risk of cardiovascular mortality and HF rehospitalization. CONCLUSION: Our study indicated two distinct LVEF trajectories after STEMI and that the persistently reduced LVEF trajectory was related to poor prognosis. In addition, several baseline characteristics can predict LVEF recovery.

Advanced Echocardiographic Techniques in Cardio-Oncology: the Role for Early Detection of Cardiotoxicity.

PURPOSE OF REVIEW: Implementation of advanced echocardiographic techniques in cardio-oncology is a growing need as they are the cornerstone of early detection of cancer therapy-related cardiovascular toxicity (CTR-CVT). RECENT FINDINGS: Three-dimensional echocardiography and myocardial deformation techniques have shown more accuracy and reproducibility than classic 2D measurements in detecting cardiovascular adverse effects in patients undergoing anticancer therapies. Application of advanced echo techniques to daily monitoring of patients with cancer helps to identify those at risk of developing CTR-CVT during and after cancer treatment. Furthermore, advanced echo parameters improve early initiation of cardioprotective treatments in order to minimize cardiovascular events and cancer treatment interruption.

Delayed Improvement of Left Ventricular Function in Newly Diagnosed Heart Failure Depends on Etiology-A PROLONG-II Substudy.

In patients with newly diagnosed heart failure with reduced ejection fraction (HFrEF), three months of optimal therapy are recommended before considering a primary preventive implantable cardioverter-defibrillator (ICD). It is unclear which patients benefit from a prolonged waiting period under protection of the wearable cardioverter-defibrillator (WCD) to avoid unnecessary ICD implantations. This study included all patients receiving a WCD for newly diagnosed HFrEF (n = 353) at our center between 2012 and 2017. Median follow-up was 2.7 years. From baseline until three months, LVEF improved in patients with all peripartum cardiomyopathy (PPCM), myocarditis, dilated cardiomyopathy (DCM), or ischemic cardiomyopathy (ICM). Beyond this time, LVEF improved in PPCM and DCM only (10 ± 8% and 10 ± 12%, respectively), whereas patients with ICM showed no further improvement. The patients with newly diagnosed HFrEF were compared to 29 patients with a distinct WCD indication, which is an explantation of an infected ICD. This latter group had a higher incidence of WCD shocks and poorer overall survival. All-cause mortality should be considered when deciding on WCD prescription. In patients with newly diagnosed HFrEF, the potential for delayed LVEF recovery should be considered when timing ICD implantation, especially in patients with PPCM and DCM.

Cardiotoxicity during long-term trastuzumab use in patients with HER2-positive metastatic breast cancer: who needs cardiac monitoring?

PURPOSE: Patients with HER2-positive metastatic breast cancer (MBC) usually receive many years of trastuzumab treatment. It is unknown whether these patients require continuous left ventricular ejection fraction (LVEF) monitoring. We studied a real-world cohort to identify risk factors for cardiotoxicity to select patients in whom LVEF monitoring could be omitted. METHODS: We included patients with HER2-positive MBC who received > 1 cycle of trastuzumab-based therapy in eight Dutch hospitals between 2000 and 2014. Cardiotoxicity was defined as LVEF < 50% that declined > 10%-points and was categorized into non-severe cardiotoxicity (LVEF 40-50%) and severe cardiotoxicity (LVEF < 40%). Multivariable Cox and mixed model analyses were performed to identify risk factors associated with cardiotoxicity. Additionally, we explored the reversibility of cardiotoxicity in patients who continued trastuzumab. RESULTS: In total, 429 patients were included. Median follow-up for cardiotoxicity was 15 months (interquartile range 8-31 months). The yearly incidence of non-severe + severe cardiotoxicity in the first and second year was 11.7% and 9.1%, respectively, which decreased thereafter. The yearly incidence of severe cardiotoxicity was low (2.8%) and stable over time. In non-smoking patients with baseline LVEF > 60% and no cardiotoxicity during prior neoadjuvant/adjuvant treatment, the cumulative incidence of severe cardiotoxicity was 3.1% after 4 years of trastuzumab. Despite continuing trastuzumab, LVEF decline was reversible in 56% of patients with non-severe cardiotoxicity and in 33% with severe cardiotoxicity. CONCLUSIONS: Serial cardiac monitoring can be safely omitted in non-smoking patients with baseline LVEF > 60% and without cardiotoxicity during prior neoadjuvant/adjuvant treatment.