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.

Appropriate use criteria for optical coherence tomography guidance in percutaneous coronary interventions : Recommendations of the working group of interventional cardiology of the Netherlands Society of Cardiology.

INTRODUCTION: Optical coherence tomography (OCT) enables detailed imaging of the coronary wall, lumen and intracoronary implanted devices. Responding to the lack of specific appropriate use criteria (AUC) for this technique, we conducted a literature review and a procedure for appropriate use criteria. METHODS: Twenty-one of all 184 members of the Dutch Working Group on Interventional Cardiology agreed to evaluate 49 pre-specified cases. During a meeting, factual indications were established whereupon members individually rated indications on a 9-point scale, with the opportunity to substantiate their scoring. RESULTS: Twenty-six indications were rated 'Appropriate', eighteen indications 'May be appropriate', and five 'Rarely appropriate'. Use of OCT was unanimously considered 'Appropriate' in stent thrombosis, and 'Appropriate' for guidance in PCI, especially in distal left main coronary artery and proximal left anterior descending coronary artery, unexplained angiographic abnormalities, and use of bioresorbable vascular scaffold (BVS). OCT was considered 'Rarely Appropriate' on top of fractional flow reserve (FFR) for treatment indication, assessment of strut coverage, bypass anastomoses or assessment of proximal left main coronary artery. CONCLUSIONS: The use of OCT in stent thrombosis is unanimously considered 'Appropriate' by these experts. Varying degrees of consensus exists on the appropriate use of OCT in other settings.

Impact of the papillary muscles on cardiac magnetic resonance image analysis of important left ventricular parameters in hypertrophic cardiomyopathy.

PURPOSE: The use of cardiac magnetic resonance (CMR) analysis has increased in patients with hypertrophic cardiomyopathy (HCM). Quantification of left ventricular (LV) measures will be affected by the inclusion or exclusion of the papillary muscles as part of the LV mass, but the magnitude of effect and potential consequences are unknown. METHODS: We performed Cine-CMR in (1) clinical HCM patients (n = 55) and (2) subclinical HCM mutation carriers without hypertrophy (n = 14). Absolute and relative differences in LV ejection fraction (EF) and mass were assessed between algorithms with and without inclusion of the papillary muscles. RESULTS: Papillary muscle mass in group 1 was 6.6 ± 2.5 g/m(2) and inclusion of the papillary muscles resulted in significant relative increases in LVEF of 4.5 ± 1.8 % and in LV mass of 8.7 ± 2.6 %. For group 2 these figures were 4.0 ± 0.9 g/m(2), 3.8 ± 1.0 % and 9.5 ± 1.8 %, respectively. With a coefficient of variation of 4 %, this 9 % difference in LV mass during CMR follow-up will be considered a change, while in fact the exact same mass may have been assessed according to two different algorithms. CONCLUSIONS: In clinical HCM patients, CMR quantification of important LV measures is significantly affected by inclusion or exclusion of the papillary muscles. In relative terms, the difference was similar in subjects without hypertrophy. This underscores a general need for a uniform approach in CMR image analysis.

Revealing the impact of local access-site complications and upper extremity dysfunction post transradial percutaneous coronary procedures.

OBJECTIVES: Little is known about local access-site complications and upper extremity dysfunction after transradial percutaneous coronary procedures (TR-PCP). This systematic review study aimed to summarise the current knowledge on the incidences of access-site complications and upper extremity dysfunction after TR-PCP. METHODS: Two independent, trained investigators searched MEDLINE, EMBASE and CENTRAL for eligible studies published before 1 January 2015. Also, they hand-searched the conference proceedings of the annual scientific sessions of the American College of Cardiology, the American Heart Association, European Society of Cardiology, and the Trans-catheter Cardiovascular Therapeutics. Inclusion criteria were cohort studies and clinical trials discussing the incidence of access-site complications and upper extremity function after transradial percutaneous coronary intervention (TR-PCI) and/or transradial coronary angiography (TR-CAG) as endpoints. RESULTS: 176 articles described access-site complications. The incidence is up to 9.6 %. Fourteen articles described upper extremity dysfunction, with an incidence of up to 1.7 %. Upper extremity dysfunction was rarely investigated, hardly ever as primary endpoint, and if investigated not thoroughly enough. CONCLUSION: Upper extremity dysfunction in TR-PCP has never been properly investigated and is therefore underestimated. Further studies are needed to investigate the magnitude, prevention and best treatment of upper extremity dysfunction. Optimising TR-PCP might be achieved by using slender techniques, detection of upper extremity dysfunction and early referral to a hand rehabilitation centre.

Cardiac metastasis of malignant melanoma: a case report.

The heart is regularly involved in metastatic neoplasms with cardiac metastases being found in up to 20 % of autopsies. We present a case about a 42-year-old Caucasian female with a fatal metastatic melanoma to the heart. The five- year survival rate for stage IV melanoma (melanoma with metastases to other organs) is 15 to 20 %. If patients with malignant melanoma present with new onset of cardiac symptoms, clinicians should always be aware of the possibility of cardiac metastases and perform further investigations.

Right-to-left atrial shunting with normal intracardiac pressures following cardiac surgery: pathophysiology and management.

We present a case of acute respiratory insufficiency with right-to-left atrial shunting under normal intracardiac pressures discovered several days after aortic surgery for aortic dissection. We discuss the possible mechanisms and management of right-to-left atrial shunting through an atrial septum defect with normal intracardiac pressures following cardiac surgery.

Systemic embolisation as presentation and recurrence of cardiac myxoma two years after surgery.

Primary cardiac tumours are rare when compared with metastatic involvement. The majority of primary cardiac tumours are benign and in adults the majority of these masses are myxomas. The treatment is surgical removal because of the risk of embolisation and/or cardiovascular complications. We describe a female presenting with systemic embolisation and recurrence of cardiac myxoma after surgery. Recurrence of myxoma is rare after surgery in case of solitary tumours but more frequent in patients with familial myxomas in association with the Carney complex. Genetic analysis revealed a mutation in the PRKAR1A gene that has never been described before. (Neth Heart J 2010;18:499502.).

A microcosting study of diagnostic tests for the detection of coronary artery disease in The Netherlands.

OBJECTIVE: The primary aim of the present study was to calculate the actual costs of four diagnostic tests for the detection of coronary artery disease in the Netherlands using a microcosting methodology. As a secondary objective, the cost effectiveness of eight diagnostic strategies was examined, using microcosting and reimbursement fees subsequently as the cost estimate. DESIGN: A multicenter, retrospective cost analysis from a hospital perspective. SETTING: The study was conducted in three general hospitals in the Netherlands for 2006. INTERVENTIONS: Exercise electrocardiography (exECG), stress echocardiography (sECHO), single-photon emission computed tomography (SPECT) and coronary angiography (CA). RESULTS: The actual costs of exECG, sECHO, SPECT and CA were 33, 216, 614 and 1300 euro respectively. For all diagnostic tests, labour and indirect cost components (overheads and capital) together accounted for over 75% of the total costs. Consumables played a relatively important role in SPECT (14%). Hotel and nutrition were only applicable to SPECT and CA. Diagnostic services were solely performed for CA, but their costs were negligible (2%). Using microcosting estimates, exECG-sECHO-SPECT-CA was the most and CA the least cost effective strategy (397 and 1302 euro per accurately diagnosed patient). Using reimbursement fees, exECG-sECHO-CA was most and SPECT-CA least cost effective (147 and 567 euro per accurately diagnosed patient). CONCLUSIONS: The use of microcosting estimates instead of reimbursement fees led to different conclusions regarding the relative cost effectiveness of alternative strategies.

[An 80-year-old woman with dyspnoea caused by cardiac myxoma]. / Een 80-jarige vrouw met kortademigheid door myxoma cordis.

An 80-year-old woman presented with general malaise and dyspnoea that has persisted for 2 months. Physical examination, laboratory tests, chest X-ray and ECG were normal, but tachycardia was not. A CT scan of the thorax performed due to suspicion of pulmonary embolism revealed a lesion in the right atrium and no other abnormalities. Echocardiography confirmed the presence of the tumour and also showed pulmonary hypertension. Cardiac myxoma was considered and the tumour was surgically removed. The patient recovered completely but the dyspnoea persisted. Cardiac myxoma is often difficult to confirm. Clinical presentation of a myxoma is determined by its location, size and mobility. Symptoms are a result of mechanical obstruction, embolism or constitutional effects. Treatment consists of surgical removal of the myxoma due to the associated risk of embolism and sudden death.

A patient with four artificial heart valves after ergotamine therapy.

A 67-year-old female was evaluated in the out-patient clinic because of shortness of breath on exertion and regular spells of fever. She had been taking ergotamine tartrate to treat migraine for more than 30 years. The patient had undergone aortic-valve replacement for aortic insufficiency three years before. On echocardiographic evaluation, severe retraction and insufficiency of the remaining native heart valves was demonstrated. Endocarditis and carcinoid syndrome were excluded. The mitral, tricuspid and pulmonary valves were all replaced by a mechanical valvular prosthesis. Pathological-anatomical evaluation of the three replaced valves and the aortic valve replaced three years earlier disclosed identical findings, compatible with long-term ergotamine use. Nine months after surgery, a sick sinus syndrome developed necessitating implantation of a DDDR pacemaker with a right atrial and a coronary sinus lead. Functional class according to the New York Heart Association improved from class III to I. After stopping the ergotamine, the fever disappeared. However, the migraine spells reoccurred which are now being treated with paracetamol.