Evaluation of the 2021 ESC recommendations for family screening in hereditary transthyretin cardiac amyloidosis.

AIMS: The 2021 European Society of Cardiology (ESC) screening recommendations for individuals carrying a pathogenic transthyretin amyloidosis variant (ATTRv) are based on expert opinion. We aimed to (i) determine the penetrance of ATTRv cardiomyopathy (ATTRv-CM) at baseline; (ii) examine the value of serial evaluation; and (iii) establish the yield of first-line diagnostic tests (i.e. electrocardiogram, echocardiogram, and laboratory tests) as per 2021 ESC position statement. METHODS AND RESULTS: We included 159 relatives (median age 55.6 [43.2-65.9] years, 52% male) at risk for ATTRv-CM from 10 centres. The primary endpoint, ATTRv-CM diagnosis, was defined as the presence of (i) cardiac tracer uptake in bone scintigraphy; or (ii) transthyretin-positive cardiac biopsy. The secondary endpoint was a composite of heart failure (New York Heart Association class ≥II) and pacemaker-requiring conduction disorders. At baseline, 40/159 (25%) relatives were diagnosed with ATTRv-CM. Of those, 20 (50%) met the secondary endpoint. Indication to screen (≤10 years prior to predicted disease onset and absence of extracardiac amyloidosis) had an excellent negative predictive value (97%). Other pre-screening predictors for ATTRv-CM were infrequently identified variants and male sex. Importantly, 13% of relatives with ATTRv-CM did not show any signs of cardiac involvement on first-line diagnostic tests. The yield of serial evaluation (n = 41 relatives; follow-up 3.1 [2.2-5.2] years) at 3-year interval was 9.4%. CONCLUSIONS: Screening according to the 2021 ESC position statement performs well in daily clinical practice. Clinicians should adhere to repeating bone scintigraphy after 3 years, as progressing to ATTRv-CM without signs of ATTRv-CM on first-line diagnostic tests or symptoms is common.

Cardiac dysfunction during exercise in young adults with bronchopulmonary dysplasia.

Background: Worldwide, 1-2% of children are born premature and at risk for developing bronchopulmonary dysplasia (BPD). Preterm-born adults are at risk for early cardiovascular disease. The role of BPD is unclear. This study aims to examine cardiorespiratory function during submaximal exercise in young adult survivors of extreme prematurity, with or without BPD. Methods: 40 preterm-born young adults, 20 with BPD (median gestational age 27 weeks, interquartile range (IQR) 26-28 weeks) and 20 without BPD (median gestational age 28 weeks, IQR 27-29 weeks) were prospectively compared to age-matched at term-born adults (median gestational age 39 weeks, IQR 38-40 weeks). Participants underwent exercise testing and cardiovascular magnetic resonance with submaximal exercise. Results: Resting heart rate in BPD subjects was higher than in at term-born subjects (69±10 mL versus 61±7 mL, p=0.01). Peak oxygen uptake during maximal cardiopulmonary exercise testing was decreased in BPD subjects (91±18% versus 106±17% of predicted, p=0.01). In BPD subjects, cardiac stroke volume change with exercise was impaired compared to at term-born subjects (11±13% versus 25±10%; p<0.001). With exercise, left ventricular end-diastolic volume decreased more in preterm-born subjects with versus without BPD (-10±8% versus -3±8%; p=0.01) and compared to at term-born subjects (0±5%; p<0.001). Exploratory data analysis revealed that exercise stroke volume and end-diastolic volume change were inversely correlated with oxygen dependency in those born prematurely. Conclusions: In preterm-born young adults, particularly those with BPD, resting cardiac function, exercise performance and cardiac response to exercise is impaired compared to controls. Exercise cardiovascular magnetic resonance may reveal an important predisposition for heart disease later in life.

Higher prevalence of benign tumors in men with testicular tumors and history of treated cryptorchidism.

OBJECTIVES: To identify if surgically treated cryptorchidism correlated with testicular tumor pathology at presentation. MATERIALS AND METHODS: An institutional database of patients treated for testicular cancer between 2003 and 2020 was reviewed. Inclusion criteria included orchiectomy patients. Exclusion criteria included unknown cryptorchidism history or pathology or laterality of orchiectomy. Data collection included demographics, surgical history, and tumor marker status. RESULTS: A total of 435 patients were included. Thirty-three of these patients had a history of UDT. There was no statistical difference in age at orchiectomy, laterality of orchiectomy, or lymphovascular invasion with regard to UDT history. There was a statistical difference in tumor pathology after orchiectomy, P = 0.03. On secondary analysis, benign pathology was significantly more common in patients with a history of UDT (15.2%) than without (4.7%), P = 0.01. Mixed GCT was also found at a significantly lower rate in patients with a history of UDT (18.2%) compared to those with no history of UDT (37.3%), P = 0.03. There were no statistically significant differences in other pathology. CONCLUSION: Previous studies have shown that there is a greater rate of seminoma in patients with testicular cancer in an undescended testis. This study shows that in patients with a history of UDT compared to those without a history of UDT, there is a greater percentage of patients with benign testicular masses after orchiectomy. Guideline based practices including monthly self-examination and testis-sparing surgery for appropriate patients may reduce rates of radical orchiectomy for benign tumors.

Long term outcome after surgical ASD-closure at young age: Longitudinal follow-up up to 50 years after surgery.

OBJECTIVES: To describe the clinical outcome and quality of life up to 50 years after surgical atrial septal defect (ASD) closure at young age. Primary outcome is defined as MACE (all-cause mortality, cardiac re-interventions, ischemic stroke, endocarditis, heart failure and symptomatic arrhythmia). METHODS: Single-center, longitudinal cohort-study evaluating 135 consecutive patients who underwent ASD-closure before the age of 15 years between 1968 and 1980. Participants were invited for extensive cardiac evaluation and assessment of quality-of-life every 10 years. RESULTS: Eighty patients (86%) of 93 eligible survivors were included in this study (mean age 52 ± 5 years (range 41-63), 40% male). Median follow-up since surgery was 45 years (range 40-51). Cumulative survival after 50 years was 86% and comparable to the normal Dutch population. Cumulative event-free survival after 45 and 50-years was 59% and 46% respectively (re-intervention in 6, symptomatic arrhythmia in 25, and pacemaker implantation in 10 patients). Right ventricular ejection fraction on CMR was diminished in 6%. Exercise capacity was normal in 77%. There was no pulmonary hypertension. NT-proBNP was elevated in 61%. Quality of life was comparable with the general population. No predictors for late events were identified. CONCLUSION: Long-term survival after surgical ASD-closure in childhood is good and not statistically different at 50 years compared to the normal Dutch population. Re-intervention rate is low, there is no pulmonary hypertension. Right ventricular function was diminished in 6%, exercise capacity was good and stable over time with quality of life comparable to the general population. However, supraventricular tachycardia is common.

Infarct severity and outcomes in ST-elevation myocardial infarction patients without standard modifiable risk factors - A multicenter cardiac magnetic resonance study.

BACKGROUND: Standard modifiable cardiovascular risk factors (SMuRFs) are well-established players in the pathogenesis of ST-elevation myocardial infarction (STEMI). However, in a significant proportion of STEMI patients, no SMuRFs can be identified, and the outcomes of this subgroup are not well described. OBJECTIVES: To assess the infarct characteristics at myocardial-tissue level and subsequent clinical outcomes in SMuRF-less STEMIs. METHODS: This multicenter, individual patient-data analysis included 2012 STEMI patients enrolled in four cardiac magnetic resonance (CMR) imaging studies conducted in Austria, Germany, Scotland, and the Netherlands. Unstable patients at time of CMR (e.g. cardiogenic shock/after cardiac arrest) were excluded. SMuRF-less was defined as absence of hypertension, smoking, hypercholesterolemia, and diabetes mellitus. All patients underwent CMR 3(interquartile range [IQR]:2-4) days after infarction to assess left ventricular (LV) volumes and ejection fraction, infarct size and microvascular obstruction (MVO). Clinical endpoints were defined as major adverse cardiovascular events (MACE), including all-cause mortality, re-infarction and heart failure. RESULTS: No SMuRF was identified in 185 patients (9%). These SMuRF-less patients were older, more often male, had lower TIMI risk score and pre-interventional TIMI flow, and less frequently multivessel-disease. SMuRF-less patients did not show significant differences in CMR markers compared to patients with SMuRFs (all p > 0.10). During a median follow-up of 12 (IQR:12-27) months, 199 patients (10%) experienced a MACE. No significant difference in MACE rates was observed between SMuRF-less patients and patients with SMuRFs (8vs.10%, p = 0.39). CONCLUSIONS: In this large individual patient-data pooled analysis of low-risk STEMI patients, infarct characteristics and clinical outcomes were not different according to SMuRF status.

Serial RV wall stress measurements: association with right ventricular function in repaired Tetralogy of Fallot patients.

Background: Optimal timing of pulmonary valve replacement (PVR) in Tetralogy of Fallot (TOF) patients remains challenging. Ventricular wall stress is considered to be an early marker of right ventricular (RV) dysfunction. Objectives: To investigate the association of RV wall stresses and their change over time with functional parameters in TOF patients. Methods: Ten TOF patients after surgical repair with moderate/severe pulmonary regurgitation were included. At two timepoints (median follow-up time 7.2 years), patient-specific computational biventricular models for wall stress assessment were created using CMR short-axis cine images and echocardiography-based RV pressures. RV ejection fraction (RVEF), NT-proBNP and cardiopulmonary exercise tests were used as outcome measures reflecting RV function. Associations between regional RV diastolic wall stress and RV function were investigated using linear mixed models. Results: Increased wall stress correlated with lower RV mass (rrm = -0.70, p = 0.017) and lower RV mass-to-volume (rrm = -0.80, p = 0.003) using repeated measures. Wall stress decreased significantly over time, especially in patients with a stable RVEF (p < 0.001). Higher wall stress was independently associated with lower RVEF, adjusted for left ventricular ejection fraction, RV end-diastolic volume and time since initial surgery (decrease of 1.27% RVEF per kPa increase in wall stress, p = 0.029) using repeated measurements. No association was found between wall stress, NT-proBNP, and exercise capacity. Conclusions: Using a computational method to calculate wall stress locally in geometrically complex ventricles, we demonstrated that lower wall stress might be important to maintain ventricular function. RV wall stress assessment can be used in serial follow-up, and is potentially an early marker of impending RV dysfunction.

Multi-staged vs Single-staged Pelvic Osteotomy in the Modern Treatment of Cloacal Exstrophy: Bridging the Gap.

PURPOSE: Staged pelvic osteotomy has been shown in the past to be an effective tool in the closure of the extreme pubic diastasis of cloacal exstrophy. The authors sought to compare orthopedic complications between non-staged pelvic osteotomies and staged pelvic osteotomies in cloacal exstrophy. METHODS: A prospectively maintained exstrophy-epispadias complex database of 1510 patients was reviewed for cloacal exstrophy bladder closure events performed with osteotomy at the authors' institution. Bladder closure failure was defined as any fascial dehiscence, bladder prolapse, or vesicocutaneous fistula within one year of closure. There was a total of 172 cloacal exstrophy and cloacal exstrophy variant patients within the database and only closures at the authors' institution were included. RESULTS: 64 closure events fitting the inclusion criteria were identified in 61 unique patients. Staged osteotomy was performed in 42 closure events and non-staged in 22 closures. Complications occurred in 46/64 closure events, with 16 grade III/IV complications. There were no associations between staged osteotomy and overall complication or grade III/IV complications (p = 0.6344 and p = 0.1286, respectively). Of the 46 total complications, 12 were orthopedic complications with 6 complications being grade III/IV. Staged osteotomy closure events experienced 10/42 orthopedic complications while non-staged osteotomy closures experienced 2/22 orthopedic complications, however this did not reach significance (p = 0.1519). Of the 64 closure events, 57 resulted in successful closure with 6 failures and one closure with planned cystectomy. CONCLUSION: This study confirms, in a larger series, superior outcomes when using staged pelvic osteotomy in cloacal exstrophy bladder closure. Staged osteotomy was shown to be a safe alternative to non-staged osteotomy that can decrease the risk of closure failure in this group. Staged pelvic osteotomy should be considered in all patients undergoing cloacal exstrophy bladder closure. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: Level III.

Multimodality Imaging of Cardiac Paragangliomas.

Paragangliomas are rare neuroendocrine tumors of extra-adrenal autonomic paraganglia origin. Paragangliomas rarely involve the heart, and they account for less than 1% of primary cardiac tumors. Most cardiac paragangliomas are incidentally detected at echocardiography or CT or during the workup of symptomatic patients with high catecholamine levels. Paragangliomas are typically located around the great vessels, coronary arteries (atrioventricular groove), or the atria, which can be explained by the tumor origin from the paraganglia and the distribution of the cardiac plexus. At MRI, cardiac paragangliomas typically have low to intermediate signal on T1-weighted images and high signal on T2-weighted images. The tumors are strongly vascularized, with high uptake on first-pass perfusion images and a heterogeneous pattern on late gadolinium enhancement images. Functional imaging is indicated for diagnostic confirmation and to screen for additional tumor locations or metastatic disease. Surgical excision is the only curative treatment. Cardiac CT angiography or invasive angiography should be performed preoperatively to precisely delineate tumor vascularization. In particular, its relation with the coronary arteries should be determined, as paragangliomas can be perfused by the coronary arteries, posing additional surgical challenges and the need for coronary revascularization. This imaging essay reviews the characteristics of paragangliomas and the use of multimodality imaging for diagnosis and treatment. Keywords: CT Angiography, Molecular Imaging, MR Imaging, PET/CT, Cardiac, Heart, Neoplasms-Primary © RSNA, 2023.

COVID-19-related myocarditis post-heart transplantation.

This report describes the first heart transplantation recipient with acute biventricular heart failure symptoms caused by a post-myocarditis state, late after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. No other viral pathogens could be detected. Computed tomography angiography did not show cardiac allograft vasculopathy, and myocardial biopsy demonstrated no clinically relevant rejection. Subsequent cardiovascular magnetic resonance imaging revealed extensive epicardial delayed enhancement without myocardial edema. Heart failure medication was initiated and an implantable cardioverter defibrillator was implanted (due to non-sustained ventricular tachycardias), leading to a partial recovery of the ejection fraction. Further studies are needed to investigate the number of heart transplant recipients with myocardial damage after a SARS-CoV-2 infection.

Influence of sex and phenotype on cardiac outcomes in patients with Fabry disease.

OBJECTIVE: This study describes the influence of sex and disease phenotype on the occurrence of cardiac events in Fabry disease (FD). METHODS: Cardiac events from birth to last visit (median age 50 years) were recorded for 213 patients with FD. Patients were categorised as follows : men with classical FD (n=57), men with non-classical FD (n=26), women with classical FD (n=98) and women with non-classical FD (n=32), based on the presence of classical FD symptoms, family history (men and women), biomarkers and residual enzyme activity (men). Event rates per 1000 patient-years after the age of 15 years and median event-free survival (EVS) age were presented. Influence of disease phenotype, sex and their interaction was studied using Firth's penalised Cox regression. RESULTS: The event rates of major cardiovascular events (combined endpoint cardiovascular death (CVD), heart failure (HF) hospitalisation, sustained ventricular arrhythmias (SVAs) and myocardial infarction) were 11.0 (95% CI 6.6 to 17.3) in men with classical FD (EVS 55 years), 4.4 (95% CI 2.5 to 7.1) in women with classical FD (EVS 70 years) and 5.9 (95% CI 2.6 to 11.6) in men with non-classical FD (EVS 70 years). None of these events occurred in women with non-classical FD. Sex and phenotype significantly influenced the risk of major adverse cardiovascular event. CVD was the leading cause of death (75%) to which HF contributed most (42%). The overall rate of SVA was low (14 events in nine patients (4%)). CONCLUSIONS: Sex and phenotype greatly influence the risk and age of onset of cardiac events in FD. This indicates the need for patient group-specific follow-up and treatment.

Impact of sex on timing and clinical outcome of septal myectomy for obstructive hypertrophic cardiomyopathy.

BACKGROUND: Sex disparities are common in hypertrophic cardiomyopathy (HCM). Previous research has shown that at time of myectomy, women are older, have greater impairment of diastolic function and more advanced cardiac remodeling. The clinical impact of these differences is unknown. METHOD: This study included 162 HCM patients (61% men) who underwent septal myectomy. Time to treatment was calculated in relation to symptom onset and diagnosis. Pre- and post-operative echocardiographic data were collected. Sex differences were assessed at baseline and in time-to-event survival analyses for the composite endpoint of all-cause mortality, cardiac transplantation, re-intervention and aborted sudden cardiac death. RESULTS: Women were generally older at time of myectomy (57 vs. 49 years, p < 0.01), with similar time to treatment as measured from symptom onset (2.3 [1.3-6.0] vs. 2.8 [1.1-5.3] years, p > 0.05), but a shorter time since diagnosis compared to men (2.6 [1.2-7.0] vs. 4.3 [2.4-8.3] years, p = 0.02). Mean wall thickness and left atrial diameter were the same for men and women, but were higher in women when correcting for body surface area (absolute: 20 vs. 19 mm, 48 vs 46 mm, p ≥ 0.05; corrected: 9.7 vs. 11.2 mm/m2, 23.4 vs. 26.3 mm/m2, p < 0.01). After 5.9 [3.0-9.1] years, 15% of men and 8% of women had reached the composite endpoint (p > 0.05). CONCLUSION: In conclusion, although women present later in life and seem to have more advanced disease on echocardiography, time until myectomy was similar and clinical outcomes after myectomy are favourable for both men and women.

Detection of Subclinical Cardiovascular Disease by Cardiovascular Magnetic Resonance in Lymphoma Survivors.

BACKGROUND: Long-term survivors of Hodgkin lymphoma (HL) and mediastinal non-Hodgkin lymphoma experience late adverse effects of radiotherapy and/or anthracycline-containing chemotherapy, leading to premature cardiovascular morbidity and mortality. OBJECTIVES: The aim of this study was to identify markers for subclinical cardiovascular disease using cardiovascular magnetic resonance (CMR) in survivors of HL and non-Hodgkin lymphoma. METHODS: CMR was performed in 80 lymphoma survivors treated with mediastinal radiotherapy with or without anthracyclines, and results were compared with those among 40 healthy control subjects matched for age and sex. RESULTS: Of the 80 lymphoma survivors, 98% had histories of HL, the mean age was 47 ± 11 years, and 54% were male. Median radiotherapy dose was 36 Gy (interquartile range: 36-40 Gy), and radiotherapy was combined with anthracyclines in 70 lymphoma survivors (88%). Mean time between diagnosis and CMR was 20 ± 8 years. Significantly lower left ventricular (LV) ejection fraction (53% ± 5% vs 60% ± 5%; P < 0.001) and LV mass (47 ± 10 g/m2 vs 56 ± 8 g/m2; P < 0.001) and higher LV end-systolic volume (37 ± 8 mL/m2 vs 33 ± 7 mL/m2; P = 0.013) were found in lymphoma survivors. LV global strain parameters were also significantly worse in lymphoma survivors (P < 0.02 for all). Native myocardial T1 was significantly higher in lymphoma survivors compared with healthy control subjects (980 ± 33 ms vs 964 ± 25 ms; P = 0.007), and late gadolinium enhancement was present in 11% of the survivors. CONCLUSIONS: Long-term lymphoma survivors have detectable changes in LV function and native myocardial T1 on CMR. Further longitudinal studies are needed to assess the implication of these changes in relation to treatment and clinical outcome.

Behavioral Economic Purchase Tasks to Estimate Demand for Novel Nicotine/tobacco Products and Prospectively Predict Future Use: Evidence From The Netherlands.

INTRODUCTION: The demand for alternative nicotine/tobacco products is not well established. This paper uses a behavioral economic approach to test whether smokers have differential demand for conventional factory-made, electronic, and very low nicotine content cigarettes (FMCs/ECs/VLNCs) and uses the prospective cohort design to test the predictive validity of demand indices on subsequent use of commercially available FMCs and ECs. METHODS: Daily smokers (≥16 years) from the Netherlands completed an online survey in April 2014 (N = 1215). Purchase tasks were completed for FMCs, ECs, and VLNCs. Participants indicated the number of cigarettes they would consume in 24 h, across a range of prices (0-30 euro). The relationship between consumption and price was quantified into four indices of demand (intensity, Pmax, breakpoint, and essential value). A follow-up survey in July 2015 measured FMC and EC use. RESULTS: At baseline, greater demand was observed for FMCs relative to ECs and VLNCs across all demand indices, with no difference between ECs and VLNCs. At follow-up, greater baseline FMC demand (intensity, essential value) was associated with lower quit rates and higher relapse. EC demand (Pmax, breakpoint, essential value) was positively associated with any EC use between survey waves, past 30 day EC use, and EC purchase between waves. CONCLUSIONS: Smokers valued FMCs more than ECs or VLNCs, and FMCs were less sensitive to price increases. Demand indices predicted use of commercially available products over a 15 month period. To serve as viable substitutes for FMCs, ECs and VLNCs will need to be priced lower than FMCs. IMPLICATIONS: Purchase tasks can be adapted for novel nicotine/tobacco products as a means to efficiently quantify demand and predict use. Among current daily smokers, the demand for ECs and VLNCs is lower than FMCs.

Elevated monocyte-specific type I interferon signalling correlates positively with cardiac healing in myocardial infarct patients but interferon alpha application deteriorates myocardial healing in rats.

Monocytes are involved in adverse left ventricular (LV) remodelling following myocardial infarction (MI). To provide therapeutic opportunities we aimed to identify gene transcripts in monocytes that relate to post-MI healing and evaluated intervention with the observed gene activity in a rat MI model. In 51 MI patients treated by primary percutaneous coronary intervention (PCI), the change in LV end-diastolic volume index (EDVi) from baseline to 4-month follow-up was assessed using cardiovascular magnetic resonance imaging (CMR). Circulating monocytes were collected at day 5 (Arterioscler Thromb Vasc Biol 35:1066-1070, 2015; Cell Stem Cell 16:477-487, 2015; Curr Med Chem 13:1877-1893, 2006) after primary PCI for transcriptome analysis. Transcriptional profiling and pathway analysis revealed that patients with a decreased LV EDVi showed an induction of type I interferon (IFN) signalling (type I IFN pathway: P value < 0.001; false discovery rate < 0.001). We subsequently administered 15,000 Units of IFN-α subcutaneously in a rat MI model for three consecutive days following MI. Cardiac function was measured using echocardiography and infarct size/cardiac inflammation using (immuno)-histochemical analysis. We found that IFN-α application deteriorated ventricular dilatation and increased infarct size at day 28 post-MI. Moreover, IFN-α changed the peripheral monocyte subset distribution towards the pro-inflammatory monocyte subset whereas in the myocardium, the presence of the alternative macrophage subset was increased at day 3 post-MI. Our findings suggest that induction of type I IFN signalling in human monocytes coincides with adverse LV remodelling. In rats, however, IFN-α administration deteriorated post-MI healing. These findings underscore important but also contradictory roles for the type I IFN response during cardiac healing following MI.

Defining and Measuring a Standard Set of Patient-Relevant Outcomes in Coronary Artery Disease.

Systematic outcome measurement enables to continuously improve treatment results and stimulates dissemination of best practices. For patients with coronary artery disease, no examples yet exist of standard sets of patient-relevant outcome measures that have already been fully implemented at a large scale in clinical care. The aim of this paper is twofold: (1) to share the standard set of outcome measures as developed by Meetbaar Beter, and (2) to show how the standard set is presented and published to support improvement of cardiac care. A step-wise approach was followed by an expert panel to construct a standard set of outcome measures. This resulted in a comprehensive set of relevant outcome measures, comprising 4 generic and 11 treatment-specific outcomes. Both short-term and long-term outcomes measures up to 5 years of follow-up were included. Relevant initial conditions were selected to enable case-mix adjustment. The standard set has been implemented in 21 hospitals across the Netherlands. The results and experiences have been used to fine-tune the set in 4 reporting cycles in 2012 to 2016, using an annual maintenance cycle. Currently about 83,000 percutaneous coronary interventions and 30,000 coronary artery bypass graftings are included in the dataset, covering the majority of all percutaneous coronary interventions and coronary artery bypass graftings in the Netherlands. In conclusion, Meetbaar Beter has defined and implemented a comprehensive set of patient-relevant outcome measures for coronary artery disease, and the variation of the results among the centers indicates that there are sufficient opportunities to further improve cardiac care in the Netherlands.

A Novel Method for Evaluating the Acceptability of Substitutes for Cigarettes: The Experimental Tobacco Marketplace.

OBJECTIVES: The current study tests the substitutability of nicotine replacement therapy (NRT), electronic cigarettes (ECs), and very low nicotine cigarettes (VLNCs) in the context of an online experimental tobacco marketplace (ETM) that was designed to mimic the choices of smokers under 4 policy scenarios. METHODS: Dutch cigarette smokers (N = 840) completed an online survey in July 2015. The ETM was comprised of conventional cigarettes, VLNCs, ECs (disposable/cartridge/tank systems), and NRT (lozenges/patches/tabs). All participants completed a scenario in which conventional cigarettes were banned. To test additional policy scenarios participants were randomized to one of 3 experiments: 1) no VLNCs, 2) all products available, or 3) no ECs. Hypothetical weekly purchases were made when the cost for conventional cigarettes was ½ market price (MP), MP, 2x MP, and 4x MP. Substitutability was measured by the change in estimated consumption as cigarette prices increased. RESULTS: Tank and cartridge ECs and VLNCs were stronger cigarette substitutes than disposable ECs and NRT products. Substitution of ECs and NRT for cigarettes was dampened when VLNCs were available. CONCLUSIONS: The ETM offers a method to predict how smokers might respond to policies that alter the availability of potentially substitutable products available in the marketplace.

Long term outcome after mononuclear bone marrow or peripheral blood cells infusion after myocardial infarction.

OBJECTIVES: This study reports the long-term follow-up of the randomised controlled HEBE trial. The HEBE study is a multicentre trial that randomised 200 patients with large first acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention to either intracoronary infusion of bone marrow mononuclear cells (BMMCs) (n=69), peripheral blood mononuclear cells (PBMCs) (n=66) or standard therapy (n=65). METHODS: In addition to 3-5 days, and 4 months after AMI, all patients underwent cardiac MRI after 2 years. A follow-up for 5 years after AMI was performed to assess clinical adverse events, including death, myocardial reinfarction and hospitalisation for heart failure. RESULTS: Of the 200 patients enrolled, 9 patients died and 12 patients were lost to follow-up at 5 years after AMI. BMMC group showed less increase in LV end-diastolic volume (LVEDV) (3.5±16.9 mL/m(2)) compared with (11.2±19.8 mL/m(2), p=0.03) in the control group, with no difference between the PBMC group (9.2±20.9 mL/m(2)) and controls (p=0.69). Moreover, the BMMC group showed a trend for decrease in LV end systolic volume (-1.8±15.0 mL/m(2)) as compared with controls (3.0±16.3 mL/m(2), p=0.07), with again no difference between PBMC (3.3±18.8 mL/m(2)) and controls (p=0.66). The combined endpoint of death and hospitalisation for heart failure was non-significantly less frequent in the BMMC group compared with the control group (n=4 vs n=1, p=0.20), with no difference between PBMC and controls (n=6 vs n=4, p=0.74). The composite endpoint of death or recurrent myocardial infarction was significantly higher in the PBMC group compared with controls (14 patients vs 3 patients, p=0.008), with no difference between the BMMC group and controls (2 vs 3 patients, p=0.67). CONCLUSIONS: Long-term follow-up of the HEBE trial showed that increase in LVEDV was lower in the BMMC group. This study supports the long-term safety of intracoronary BMMC therapy. However, major clinical cardiovascular adverse events were significantly more frequent in the PBMC group. TRIAL REGISTRATION NUMBER: The Netherlands Trial Register #NTR166 (http://www.trialregister.nl) and the International Standard Randomised Controlled Trial, #ISRCTN95796863 (http://isrctn.org).

Cell therapy in reperfused acute myocardial infarction does not improve the recovery of perfusion in the infarcted myocardium: a cardiac MR imaging study.

PURPOSE: To investigate the effects of cell therapy on myocardial perfusion recovery after treatment of acute myocardial infarction (MI) with primary percutaneous coronary intervention (PCI). MATERIALS AND METHODS: In this HEBE trial substudy, which was approved by the institutional review board (trial registry number ISRCTN95796863), the authors assessed the effects of intracoronary infusion with bone marrow-derived mononuclear cells (BMMCs) or peripheral blood-derived mononuclear cells (PBMCs) on myocardial perfusion recovery by using cardiac magnetic resonance (MR) imaging after revascularization. In 152 patients with acute MI treated with PCI, cardiac MR imaging was performed after obtaining informed consent-before randomization to BMMC, PBMC, or standard therapy (control group)-and repeated at 4-month follow-up. Cardiac MR imaging consisted of cine, rest first-pass perfusion, and late gadolinium enhancement imaging. Perfusion was evaluated semiquantitatively with signal intensity-time curves by calculating the relative upslope (percentage signal intensity change). The relative upslope was calculated for the MI core, adjacent border zone, and remote myocardium. Perfusion differences among treatment groups or between baseline and follow-up were assessed with the Wilcoxon signed rank or Mann-Whitney U test. RESULTS: At baseline, myocardial perfusion differed between the MI core (median, 6.0%; interquartile range [IQR], 4.1%-8.0%), border zone (median, 8.4%; IQR, 6.4%-10.2%), and remote myocardium (median, 12.2%; IQR, 10.5%-15.9%) (P < .001 for all), with equal distribution among treatment groups. These interregional differences persisted at follow-up (P < .001 for all). No difference in perfusion recovery was found between the three treatment groups for any region. CONCLUSION: After revascularization of ST-elevation MI, cell therapy does not augment the recovery of resting perfusion in either the MI core or border zone.