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.

2D-echocardiography vs cardiac MRI strain: a prospective cohort study in patients with HER2-positive breast cancer undergoing trastuzumab.

BACKGROUND: We aimed to study the predictive value of early two-dimensional echocardiography (2DE) speckle tracking (ST) for left ventricular ejection fraction (LVEF) changes during trastuzumab treatment for HER2-positive breast cancer. METHODS: HER2-positive breast cancer patients receiving trastuzumab, with or without anthracycline, underwent 2DE-ST at baseline and after 3 and 6 months (m) trastuzumab. Cardiac magnetic resonance (CMR) imaging (with ST) was performed at baseline and 6 m. We studied the correlation between 2DE-ST- and CMR-derived global longitudinal strain (GLS) and global radial strain (GRS) measured at the same time. Additionally, we associated baseline and 3 m 2DE-ST measurements with later CMR-LVEF, and with cardiotoxicity, defined as CMR-LVEF < 45% and/or absolute decline > 10% during trastuzumab. RESULTS: Forty-seven patients were included. Median baseline LVEF was 60.4%. GLS measurements based on 2DE-ST and CMR showed weak correlation (Pearson's r = 0.33; p = 0.041); GRS measurements were uncorrelated (r = 0.09; p = 0.979). 2DE-LVEF at baseline and 3 m, and 2DE-ST-GLS at 3 m were predictive of CMR-LVEF at 6 m. In contrast, the change in 2DE-ST-GLS at 3 m was predictive of the change in CMR-LVEF at 6 m, whereas the change in 2DE-LVEF was not. Importantly, the 11 patients who developed cardiotoxicity (28%) had larger 2DE-ST-GLS change at 3 m than those who did not (median 5.2%-points versus 1.7%-points; odds ratio for 1% difference change 1.81, 95% confidence interval 1.11-2.93; p = 0.016; explained variance 0.34). CONCLUSIONS: Correlations between 2DE-ST and CMR-derived measurements are weak. Nevertheless, ST-measurements appeared useful to improve the performance of 2DE in predicting LVEF changes after 6 m of trastuzumab treatment.

Brachial Artery Thrombosis as a Presentation of Non-Small Cell Pulmonary Carcinoma Growing Into the Left Atrium.

We present a case of a thrombus in the left brachial artery as a cardioembolic presentation of pulmonary carcinoma. There have been few reports describing this clinical presentation, but if present, prognosis is very poor. Therefore, a cardioembolic event should be borne in mind as an atypical presentation of pulmonary carcinoma. (Level of Difficulty: Beginner.).

Usefulness of High-Sensitivity Cardiac Troponin T to Predict Long-Term Outcome in Patients with Hypertrophic Cardiomyopathy.

Since the first report of an association between cardiac troponin (cTn) and adverse outcome in hypertrophic cardiomyopathy (HD), there is a paucity in confirmative data. We performed a prospective, prespecified 5-year follow-up cohort study of 135 HC patients who participated in a national multicenter project and underwent clinical evaluation, MRI (cine, LGE and T2-weighted imaging) and biomarker assessment (high-sensitivity cTnT (hs-cTnT), N-terminal pro-B-type natriuretic peptide, soluble tumorgenicity suppressor-2, Galectin-3, Growth differentiation factor-15, C-terminal Propeptide of Type I Collagen (CICP)). An elevated hs-cTnT concentration was defined as ≥14ng/L. Follow-up was systematically performed for the primary endpoint: a composite of sudden cardiac death, heart failure related death, stroke-related death, heart failure hospitalization, hospitalization for stroke, spontaneous sustained ventricular tachycardia (VT) or appropriate ICD discharge, and progression to NYHA class III-IV. Elevated hs-cTnT was present in 33 of 135 (24%) HC patients. During a median follow-up of 5.0 years (IQR: 4.9-5.1) 18 patients reached the primary endpoint. Using Cox regression analysis, elevated hs-cTnT was univariately associated with the primary endpoint (HR: 3.4 (95%CI: 1.4-8.7, p=0.009). Also female sex, previous syncope, previous non-sustained VT, reduced LV ejection fraction (<50%) and CICP were associated with the primary endpoint. In multivariable analysis, elevated hs-cTnT remained independently associated with outcome (aHR: 4.7 (95%CI: 1.8-12.6, p = 0.002). In conclusion, this 5-year follow-up study is the first to prospectively confirm the association of elevated hs-cTnT and adverse outcomes. In addition to established clinical variables, cTn seems the biomarker of interest to further improve risk prediction in HC, which should be evaluated in larger prospective registries.

Cardiac monitoring in HER2-positive patients on trastuzumab treatment: A review and implications for clinical practice.

Trastuzumab prolongs progression-free and overall survival in patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer. However, trastuzumab treatment is hampered by cardiotoxicity, defined as a left ventricular ejection fraction (LVEF) decline with a reported incidence ranging from 3 to 27% depending on variable factors. Early identification of patients at increased risk of trastuzumab-induced myocardial damage is of great importance to prevent deterioration to irreversible cardiotoxicity. Although current cardiac monitoring with multi gated acquisition (MUGA) scanning and/or conventional 2D-echocardiography (2DE) have a high availability, their reproducibility are modest, and more sensitive and reliable techniques are needed such as 3D-echocardiography (3DE) and speckle tracking echocardiography (STE). But which other diagnostic imaging modalities are available for patients before and during trastuzumab treatment? In addition, what is the optimal frequency and duration of cardiac monitoring? At last, which biomarker monitoring strategies are currently available for the identification of cardiotoxicity in patients treated with trastuzumab?

NT-proBNP correlates with LVEF decline in HER2-positive breast cancer patients treated with trastuzumab.

BACKGROUND: Early identification of cardiac dysfunction by non-invasive imaging in HER2-positive breast cancer patients treated with trastuzumab is challenging. In particular multigated acquisition (MUGA) scan, which is most widely used, is unable to detect subclinical cardiac changes. The use of N-terminal pro-brain natriuretic peptide (NT-proBNP), a serum biomarker of myocardial stress, might improve timely diagnosis. METHODS: This prospective, single-center, cohort study included patients with HER2-positive breast cancer who started trastuzumab therapy. Echocardiography was scheduled at regular intervals every 3 months during one year follow-up for cardiac function monitoring. For research purposes, NT-proBNP was determined at the same time points. Trastuzumab-induced cardiotoxicity (TIC) was the primary study endpoint, defined as a left ventricular ejection fraction (LVEF) < 45%, and/or an absolute decline in LVEF > 10% since inclusion, and/or the incidence of a clinical cardiac event. RESULTS: A total of 135 patients were enrolled between April 2008 and June 2016, with a median age of 54 years (IQR: 47-61). By three-dimensional echocardiography (3DE), the median LVEF at baseline was 62% (IQR: 58-65). At a median of 6 months (IQR: 5-11), 45 patients (33%) reached the study endpoint of TIC. Patients with TIC had a mean change of - 9.5% in LVEF (95% CI -7.2 to - 11.7; p = 0.001) during 1 year of trastuzumab treatment. Both NT-proBNP at baseline (HR 1.04, 95% CI 1.02-1.07; p = 0.003) and LVEF decline during anthracycline treatment prior to the start of trastuzumab (HR 1.16, 95% CI 1.07-1.25; p < 0.001) were independently associated with development of TIC. The level of NT-proBNP during follow-up was associated too with development of TIC (HR 1.06 per 10 pmol/l difference, 95% CI 1.02-1.10; p = 0.008). No steadily or sudden increase in NT-proBNP prior to TIC was observed. CONCLUSIONS: NT-proBNP cannot be used as a surrogate monitoring tool for trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients during the first year of treatment. Patients showing an LVEF decline during anthracycline pre-treatment appeared vulnerable for trastuzumab-induced cardiotoxicity.

Obstructive giant cardiac tumour in a patient with chest pain and acute respiratory insufficiency.

A 77-year-old woman presented with dyspnoea and respiratory-related thoracic pain, which was accompanied by dizziness and fatigue but no syncopal attacks. Auscultation of the heart disclosed an opening snap with mid-diastolic murmur. Laboratory assessment revealed no abnormalities but an elevated D-dimer level (1.49 mg/l). Electrocardiography was normal. The chest radiograph showed an enlarged heart without other abnormalities. Computed tomography (CT) scan for a suspected diagnosis of pulmonary embolism was performed. The CT scan did not reveal pulmonary embolism, but a large cardiac tumour in the left atrium.

Computed tomography unmasks a phantom tumour.

We describe a patient with left sided congestive heart failure and a round-shaped mass on the chest X-ray. Using computed tomography, the mass is diagnosed as a phantom tumour consisting of loculated effusion in the interlobular fissure that vanishes after treatment for heart failure is initiated.

Sustained improvement after combined anterior mitral leaflet extension and myectomy in hypertrophic obstructive cardiomyopathy.

BACKGROUND: Mitral leaflet extension (MLE) combined with septal myectomy is a new surgical approach to treat hypertrophic obstructive cardiomyopathy (HOCM) and an enlarged mitral leaflet area. The study presents the long-term clinical results and outcome of this technique. METHODS AND RESULTS: MLE entails grafting a glutaraldehyde-preserved autologous pericardial patch onto the center portion of the anterior mitral valve leaflet. Twenty-nine patients with HOCM were studied. Mean follow-up (+/-SD) was 3.4+/-2.1 years (range 3 months to 7.7 years). The preoperative calculated mitral leaflet area was 16.7+/-3.4 cm2. New York Heart Association functional class improved significantly from 2.8+/-0.4 to 1.3+/-0.4 (P<0.05), width of the interventricular septum decreased from 23+/-4 to 17+/-2 mm (P<0.05), left ventricular outflow tract gradient decreased from 100+/-20 to 17+/-14 mm Hg (P<0.01), severity of mitral regurgitation graded on a scale from 0 to 4+ decreased from 2.5+/-0.9 to 0.5+/-0.6 (P<0.01), and severity of the systolic anterior motion of the mitral valve graded on a scale from 0 to 3+ decreased from 2.9+/-0.3 to 0.5+/-0.7 (P<0.01) postoperatively. There were no deaths associated with surgery. CONCLUSIONS: Long-term follow-up shows sustained improvement in functional status, reduction of outflow tract obstruction, and attenuation of mitral regurgitation and systolic anterior motion of the mitral valve. In this respect, the new technique widens the surgical applications in HOCM.