Wideband black-blood late gadolinium enhancement imaging for improved myocardial scar assessment in patients with cardiac implantable electronic devices.

PURPOSE: Wideband phase-sensitive inversion recovery (PSIR) late gadolinium enhancement (LGE) enables myocardial scar imaging in implantable cardioverter defibrillators (ICD) patients, mitigating hyperintensity artifacts. To address subendocardial scar visibility challenges, a 2D breath-hold single-shot electrocardiography-triggered black-blood (BB) LGE sequence was integrated with wideband imaging, enhancing scar-blood contrast. METHODS: Wideband BB, with increased bandwidth in the inversion pulse (0.8-3.8 kHz) and T2 preparation refocusing pulses (1.6-5.0 kHz), was compared with conventional and wideband PSIR, and conventional BB, in a phantom and sheep with and without ICD, and in six patients with cardiac devices and known myocardial injury. ICD artifact extent was quantified in the phantom and specific absorption rate (SAR) was reported for each sequence. Image contrast ratios were analyzed in both phantom and animal experiments. Expert radiologists assessed image quality, artifact severity, and scar segments in patients and sheep. Additionally, histology was performed on the sheep's heart. RESULTS: In the phantom, wideband BB reduced ICD artifacts by 62% compared to conventional BB while substantially improving scar-blood contrast, but with a SAR more than 24 times that of wideband PSIR. Similarly, the animal study demonstrated a considerable increase in scar-blood contrast with wideband BB, with superior scar detection compared with wideband PSIR, the latter confirmed by histology. In alignment with the animal study, wideband BB successfully eliminated severe ICD hyperintensity artifacts in all patients, surpassing wideband PSIR in image quality and scar detection. CONCLUSION: Wideband BB may play a crucial role in imaging ICD patients, offering images with reduced ICD artifacts and enhanced scar detection.

Additional value of cardiac magnetic resonance feature tracking parameters for the evaluation of the arrhythmic risk in patients with mitral valve prolapse.

OBJECTIVES: The identification of patients with mitral valve prolapse (MVP) presenting high arrhythmic risk remains challenging. Cardiovascular Magnetic Resonance (CMR) feature tracking (FT) may improve risk stratification. We analyzed the role of CMR-FT parameters in relation to the incidence of complex ventricular arrhythmias (cVA) in patients with MVP and mitral annular disjunction (MAD). METHODS: 42 patients with MVP and MAD who underwent 1.5 T CMR were classified as MAD-cVA (n = 23, 55%) in case of cVA diagnosed on a 24-h Holter monitoring and as MAD-noVA in the absence of cVA (n = 19, 45%). MAD length, late gadolinium enhancement (LGE), basal segments myocardial extracellular volume (ECV) and CMR-FT were assessed. RESULTS: LGE was more frequent in the MAD-cVA group in comparison with the MAD-noVA group (78% vs 42%, p = 0.002) while no difference was observed in terms of basal ECV. Global longitudinal strain (GLS) was reduced in MAD-cVA compared to MAD-noVA (- 18.2% ± 4.6% vs - 25.1% ± 3.1%, p = 0.004) as well as global circumferential strain (GCS) at the mid-ventricular level (- 17.5% ± 4.7% vs - 21.6% ± 3.1%, p = 0.041). Univariate analysis identified as predictors of the incidence of cVA: GCS, circumferential strain (CS) in the basal and mid infero-lateral wall, GLS, regional longitudinal strain (LS) in the basal and mid-ventricular inferolateral wall. Reduced GLS [Odd ratio (OR):1.56 (confidence interval (CI) 95%: 1.45-2.47; p < 0.001)] and regional LS in the basal inferolateral wall [OR: 1.62 (CI 95%: 1.22-2.13; p < 0.001)] remained independent prognostic factors in multivariate analysis. CONCLUSION: In patients with MVP and MAD, CMR-FT parameters are correlated with the incidence of cVA and may be of interest in arrhythmic risk stratification.

[Cardiovascular magnetic resonance in clinical practice: who, when and why?] / Résonance magnétique cardiovasculaire en pratique clinique : pour qui, quand et pourquoi ?

Cardiovascular magnetic resonance (CMR) is an imaging modality with growing indications in cardiology. The purpose of this article is to illustrate the current clinical applications of CMR across the spectrum of ischemic heart disease, non-ischemic cardiomyopathies, cardiac arrhythmias and valvular or vascular heart disease. The strengths of CMR lie in its ability to comprehensively image, without the need for ionizing radiation, cardiac and vascular anatomy, function, perfusion, viability and physiology, providing a powerful non-invasive tool for patient diagnosis and prognostication.

La résonance magnétique cardiovasculaire (RMC) est une modalité d'imagerie avec des applications croissantes en cardiologie. Le but de cet article est d'illustrer les applications cliniques actuelles de la RMC dans la cardiopathie ischémique, dans le domaine des cardiomyopathies, les troubles du rythme cardiaque et les maladies valvulaires ou vasculaires. Ses points forts résident dans sa capacité à imager de manière complète, sans besoin de rayonnement ionisant, l'anatomie, la fonction, la perfusion, la viabilité et la physiologie cardiaques et vasculaires, offrant un puissant outil non invasif pour le diagnostic et le pronostic des patients.

[Cardiology: what's new in 2022]. / Cardiologie : ce qui a changé en 2022.

The year of 2022 was marked by many novelties in the fields of interventional cardiology, heart failure, electrophysiology, cardiac imaging, and congenital heart disease. These advances will certainly change our daily practice, on top of improving the diagnosis and treatment of many heart conditions. In addition, the European Society of Cardiology has updated its guidelines on pulmonary hypertension, ventricular arrhythmias and sudden death, cardiovascular assessment of patients undergoing non-cardiac surgery. The members of the Cardiology division of Lausanne University Hospital (CHUV) here present the publications which they considered to be the most important of the past year.

L'année 2022 a été marquée par de nombreuses nouveautés dans les domaines de la cardiologie interventionnelle, de l'insuffisance cardiaque, de l'électrophysiologie, de l'imagerie cardiaque et des cardiopathies congénitales. Ces progrès vont certainement faire évoluer notre pratique quotidienne, en plus d'améliorer le diagnostic et le traitement de nombreuses cardiopathies. Par ailleurs, la Société européenne de cardiologie a mis à jour ses recommandations portant sur l'hypertension pulmonaire, les arythmies ventriculaires et la mort subite ainsi que le bilan cardiologique avant une chirurgie non cardiaque. Les membres du Service de cardiologie du CHUV vous présentent ici les travaux qui leur ont semblé être les plus importants de l'année écoulée.

2D cine vs. 3D self-navigated free-breathing high-resolution whole heart cardiovascular magnetic resonance for aortic root measurements in congenital heart disease.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is considered the method of choice for evaluation of aortic root dilatation in congenital heart disease. Usually, a cross-sectional 2D cine stack is acquired perpendicular to the vessel's axis. However, this method requires a considerable patient collaboration and precise planning of image planes. The present study compares a recently introduced 3D self-navigated free-breathing high-resolution whole heart CMR sequence (3D self nav) allowing a multiplanar retrospective reconstruction of the aortic root as an alternative to the 2D cine technique for determination of aortic root diameters. METHODS: A total of 6 cusp-commissure (CuCo) and cusp-cusp (CuCu) enddiastolic diameters were measured by two observers on 2D cine and 3D self nav cross-sectional planes of the aortic root acquired on a 1.5 T CMR scanner. Asymmetry of the aortic root was evaluated by the ratio of the minimal to the maximum 3D self nav CuCu diameter. CuCu diameters were compared to standard transthoracic echocardiographic (TTE) aortic root diameters. RESULTS: Sixty-five exams in 58 patients (32 ± 15 years) were included. Typically, 2D cine and 3D self nav spatial resolution was 1.1-1.52 × 4.5-7 mm and 0.9-1.153 mm, respectively. 3D self nav yielded larger maximum diameters than 2D cine: CuCo 37.2 ± 6.4 vs. 36.2 ± 7.0 mm (p = 0.006), CuCu 39.7 ± 6.3 vs. 38.5 ± 6.5 mm (p < 0.001). CuCu diameters were significantly larger (2.3-3.9 mm, p < 0.001) than CuCo and TTE diameters on both 2D cine and 3D self nav. Intra- and interobserver variabilities were excellent for both techniques with bias of -0.5 to 1.0 mm. Intra-observer variability of the more experienced observer was better for 3D self nav (F-test p < 0.05). Aortic root asymmetry was more pronounced in patients with bicuspid aortic valve (BAV: 0.73 (interquartile (IQ) 0.69; 0.78) vs. 0.93 (IQ 0.9; 0.96), p < 0.001), which was associated to a larger difference of maximum CuCu to TTE diameters: 5.5 ± 3.3 vs. 3.3 ± 3.8 mm, p = 0.033. CONCLUSION: Both, the 3D self nav and 2D cine CMR techniques allow reliable determination of aortic root diameters. However, we propose to privilege the 3D self nav technique and measurement of CuCu diameters to avoid underestimation of the maximum diameter, particularly in patients with asymmetric aortic roots and/or BAV.

[The year in cardiology : 2018]. / Cardiologie.

This review article provides a broad overview of the novelties in cardiology in 2018. Advances in interventional cardiology and cardiovascular prevention, heart failure, electrophysiology and non-invasive cardiovascular imaging have provided important new insights in the pathophysiology, diagnosis and treatment of ischemic and valvular heart disease, heart failure, rhythm disorders and cardiomyopathies. This article provides an overview of the most relevant articles published in 2018.

L'année 2018 a été riche en nouveautés dans les domaines de la cardiologie interventionnelle, de l'insuffisance cardiaque, de l'électrophysiologie et de l'imagerie cardiaque. Les progrès dans ces domaines respectifs ont fourni de nouveaux outils pour le diagnostic et le traitement des cardiopathies ischémiques et valvulaires, de l'insuffisance cardiaque à fraction d'éjection réduite ou préservée, des troubles du rythme et des cardiomyopathies. Cet article fournit un aperçu des articles les plus pertinents publiés en 2018.

European Cardiovascular Magnetic Resonance (EuroCMR) registry--multi national results from 57 centers in 15 countries.

BACKGROUND: The EuroCMR registry sought to evaluate indications, image quality, safety and impact on patient management of clinical routine CMR in a multi-national European setting. Furthermore, interim analysis of the specific protocols should underscore the prognostic potential of CMR. METHODS: Multi-center registry with consecutive enrolment of patients in 57 centers in 15 countries. More than 27000 consecutive patients were enrolled. RESULTS: The most important indications were risk stratification in suspected CAD/Ischemia (34.2%), workup of myocarditis/cardiomyopathies (32.2%), as well as assessment of viability (14.6%). Image quality was diagnostic in more than 98% of cases. Severe complications occurred in 0.026%, always associated with stress testing. No patient died during or due to CMR. In 61.8% CMR findings impacted on patient management. Importantly, in nearly 8.7% the final diagnosis based on CMR was different to the diagnosis before CMR, leading to a complete change in management. Interim analysis of suspected CAD and risk stratification in HCM specific protocols revealed a low rate of adverse events for suspected CAD patients with normal stress CMR (1.0% per year), and for HCM patients without LGE (2.7% per year). CONCLUSION: The most important indications in Europe are risk stratification in suspected CAD/Ischemia, work-up of myocarditis and cardiomyopathies, as well as assessment of viability. CMR imaging is a safe procedure, has diagnostic image quality in more than 98% of cases, and its results have strong impact on patient management. Interim analyses of the specific protocols underscore the prognostic value of clinical routine CMR in CAD and HCM.

Case report: Acute pericarditis following hepatic microwave ablation for liver metastasis.

Hepatic microwave ablation (MWA) is a growing treatment modality in the field of primary and secondary liver cancer. One potential side effect is thermal damage to adjacent structures, including the pericardium if the hepatic lesion is located near the diaphragm. Hemorrhagic cardiac tamponade is known to be a rare but potentially life-threatening complication. Here we present the first case of cardiac complication following MWA treatment in a 55-year-old man who presented with late cardiac tamponade. Adequate and timely management is essential, and clinicians should be fully aware of the need to perform early transthoracic echocardiography to detect signs of pericardial effusion when cardiac involvement is suspected.

Long-Term Consequences of COVID-19: A 1-Year Analysis.

Long-lasting symptoms after SARS-CoV-2 infection have been described many times in the literature and are referred to as Long COVID. In this prospective, longitudinal, monocentric, observational study, we collected the health complaints of 474 patients (252 ambulatory and 222 hospitalized) at Lausanne University Hospital 1 year after COVID-19 diagnosis. Using a self-reported health survey, we explored cardiopulmonary, vascular, neurological, and psychological complaints. Our results show that age, Charlson comorbidity index, and smoking habits were associated with hospital admission. Regarding the vascular system, we found that having had thromboembolism before SARS-CoV-2 infection was significantly associated with a higher risk of recurrence of thromboembolism at 1 year. In the neurologic evaluation, the most frequent symptom was fatigue, which was observed in 87.5% of patients, followed by "feeling slowed down", headache, and smell disturbance in 71.5%, 68.5%, and 60.7% of cases, respectively. Finally, our cohort subjects scored higher overall in the STAI, CESD, Maastricht, and PSQI scores (which measure anxiety, depression, fatigue, and sleep, respectively) than the healthy population. Using cluster analysis, we identified two phenotypes of patients prone to developing Long COVID. At baseline, CCS score, prior chronic disease, stroke, and atrial fibrillation were associated with Long COVID. During COVID infection, mechanical ventilation and five neurological complaints were also associated with Long COVID. In conclusion, this study confirms the wide range of symptoms developed after COVID with the involvement of all the major systems. Early identification of risk factors associated with the development of Long COVID could improve patient follow-up; nevertheless, the low specificity of these factors remains a challenge to building a systematic approach.

Cost evaluation of cardiovascular magnetic resonance versus coronary angiography for the diagnostic work-up of coronary artery disease: application of the European Cardiovascular Magnetic Resonance registry data to the German, United Kingdom, Swiss, and United States health care systems.

BACKGROUND: Cardiovascular magnetic resonance (CMR) has favorable characteristics for diagnostic evaluation and risk stratification of patients with known or suspected CAD. CMR utilization in CAD detection is growing fast. However, data on its cost-effectiveness are scarce. The goal of this study is to compare the costs of two strategies for detection of significant coronary artery stenoses in patients with suspected coronary artery disease (CAD): 1) Performing CMR first to assess myocardial ischemia and/or infarct scar before referring positive patients (defined as presence of ischemia and/or infarct scar to coronary angiography (CXA) versus 2) a hypothetical CXA performed in all patients as a single test to detect CAD. METHODS: A subgroup of the European CMR pilot registry was used including 2,717 consecutive patients who underwent stress-CMR. From these patients, 21% were positive for CAD (ischemia and/or infarct scar), 73% negative, and 6% uncertain and underwent additional testing. The diagnostic costs were evaluated using invoicing costs of each test performed. Costs analysis was performed from a health care payer perspective in German, United Kingdom, Swiss, and United States health care settings. RESULTS: In the public sectors of the German, United Kingdom, and Swiss health care systems, cost savings from the CMR-driven strategy were 50%, 25% and 23%, respectively, versus outpatient CXA. If CXA was carried out as an inpatient procedure, cost savings were 46%, 50% and 48%, respectively. In the United States context, cost savings were 51% when compared with inpatient CXA, but higher for CMR by 8% versus outpatient CXA. CONCLUSION: This analysis suggests that from an economic perspective, the use of CMR should be encouraged as a management option for patients with suspected CAD.

In postmenopausal women, lower limb peripheral arterial disease, assessed by ankle-brachial index, may be a strong predictor of cardiovascular risk.

BACKGROUND: Lower limb peripheral arterial disease (PAD) is a leading atherosclerotic disease in the elderly. However, awareness of the disease is poor, particularly in women. METHODS: In this retrospective, cross-sectional study, postmenopausal women referred to our Angiology Division were tested for PAD, defined as an "ankle-brachial index" (ABI) ≤0.9 or ≥1.4 (in the latter case with a "toe-brachial index" <0.7), or a history of lower limb arterial revascularization. Aim of our study was to assess cardiovascular (CV) risk profile in postmenopausal women with and without PAD, and to evaluate the role of PAD and six classic CV risk factors (CVRFs), namely age, current smoking, hypertension, dyslipidaemia, severe chronic renal failure, and diabetes in predicting CV disease (CVD), defined as coronary artery disease and/or cerebrovascular disease. RESULTS: Overall, 850 patients were included, 39.4% of whom with PAD. Compared with women without PAD, those with PAD were older (75.2 vs 66 years, respectively; p <0.001), and displayed higher rates of other CVRFs (p <0.001 for each). A personal history of CVD was reported in 18.8% of women with PAD and in 6.1% of those without PAD (p <0.001). At multivariate regression analysis, PAD (odds ratio [OR]: 2.15; 95% confidence interval [CI]: 1.33-3.47), and hypertension (OR: 2.20; 95%CI: 1.24-3.88) were the strongest factors associated with CVD presence. CONCLUSIONS: PAD is a strong marker of CVD in this selected series of postmenopausal women. If confirmed in the general population, PAD screening through ABI calculation may be considered for CV risk assessment in postmenopausal women.

Acute cardiac manifestations under immune checkpoint inhibitors-beware of the obvious: a case report.

BACKGROUND: Immune checkpoint inhibitors (ICI) have revolutionized the management of many cancer types by drastically improving the median survival rate of patients. However, this efficiency comes at the cost of a high rate of immune-related adverse events, including lethal cardiac manifestations. Rapidly fatal cases of ICI-induced myocarditis have been reported and drawn considerable attention over the past years. However, it is essential to bear in mind that not all cardiac events occurring under ICI therapy are necessarily myocarditis. CASE SUMMARY: A 61-year-old female treated with pembrolizumab for a stage IV melanoma was admitted for chest pain leading to the diagnosis of ICI-related myocarditis based on the description of a discrete left ventricular subepicardial late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging. ICI were suspended and intravenous methylprednisolone initiated. A second line anti-MEK therapy was initiated. After a month of treatment, similar chest pain occurred. CMR revealed a midventricular stress cardiomyopathy and no LGE was detected. A posteriori interrogation revealed emotional stressors preceding both episodes. Review of the first CMR, performed 2 weeks after symptom onset, indicated a pattern compatible with the recovery phase of a stress cardiomyopathy and the presence of LGE was questioned. ICI were reintroduced without recurrence of cardiac events. DISCUSSION: Not all cardiac manifestations occurring under ICI therapy are drug-related adverse events, therefore differential diagnoses must systematically be considered as the contraindication of ICI may have a major impact on patient prognosis. Cardiac imaging should be performed early and plays a key role in the management strategy.

Cell-based therapy for myocardial repair in patients with acute myocardial infarction: rationale and study design of the SWiss multicenter Intracoronary Stem cells Study in Acute Myocardial Infarction (SWISS-AMI).

BACKGROUND: Recent studies report that intracoronary administration of autologous bone marrow mononucleated cells (BM-MNCs) may improve remodeling of the left ventricle after acute myocardial infarction (AMI). Subgroup analysis suggest that early treatment between days 4 and 7 after AMI is probably most effective; however, the optimal time point of intracoronary cell administration has never been addressed in clinical trials. Furthermore, reliable clinical predictors are lacking for identifying patients who are thought to have most benefit from cellular therapy. STUDY DESIGN: In a multicenter trial, 192 patients with AMI successfully treated by percutaneous coronary intervention (PCI) of the infarct-related artery will be randomized in a 1:1:1 pattern to 1 control and 2 BM-MNC treatment groups. The control group will be treated with state-of-the-art medical management. The treatment groups will receive intracoronary administration of autologous BM-MNC at 5 to 7 days or 3 to 4 weeks after the initial event, respectively. Left ventricular function as well as scar size, transmural extension, and regional wall motion score will be assessed by cardiac magnetic resonance (CMR) studies at baseline and after 4 and 12 months. METHODS: Fifty milliliters of bone marrow will be harvested by aspiration from the iliac crest and then carried by courier to a centralized cell processing facility. The mononucleated cell fraction will be isolated by density gradient centrifugation, washed, and resuspended in 10 mL of injection medium. The cells will be characterized by fluorescence-activated cell sorting analysis and tested for sterility and potency both "in vitro" and "in vivo." Bone marrow MNC will then be reinfused directly in the infarct-related coronary artery. END POINTS: The primary end point is the change in global left ventricular (LV) ejection fraction by CMR at 4 months as compared to baseline. Comparisons will then be made between each of the prespecified therapy subgroups (early and late after AMI) and the control group. Secondary end points include change in infarct size, change in regional myocardial thickness, and wall motion at 4 and 12 months compared to baseline. Infarct extension (size and transmural extension), time delay to PCI, and coronary flow characteristics after PCI will be assessed as potential predictors of LV remodeling and change after cell therapy. Major adverse cardiac events (MACE) (death, myocardial infarction, coronary revascularization, rehospitalization for heart failure) will be assessed at 4, 12, and 24 months and time to MACE will be estimated. DISCUSSION: With the present study, we aim to determine the optimal time point of intracoronary administration of autologous BM-MNC after AMI on LV remodeling.

Early or deferred cardiovascular magnetic resonance after ST-segment-elevation myocardial infarction for effective risk stratification.

AIMS: In ST-segment-elevation myocardial infarction (STEMI), cardiovascular magnetic resonance (CMR) holds the potentiality to improve risk stratification in addition to Thrombolysis in Myocardial Infarction (TIMI) risk score. Nevertheless, the optimal timing for CMR after STEMI remains poorly defined. We aim at comparing the prognostic performance of three stratification strategies according to the timing of CMR after STEMI. METHODS AND RESULTS: The population of this prospective registry-based study included 492 reperfused STEMI patients. All patients underwent post-reperfusion (median: 4 days post-STEMI) and follow-up (median: 4.8 months post-STEMI) CMR. Left ventricular (LV) volumes, function, infarct size, and microvascular obstruction extent were quantified. Primary endpoint was a composite of all-death and heart failure (HF) hospitalization. Baseline-to-follow-up percentage increase of LV end-diastolic (EDV; ΔLV-EDV) ≥20% or end-systolic volumes (ESV; ΔLV-ESV) ≥15% were tested against outcome. Three multivariate models were developed including TIMI risk score plus early post-STEMI (early-CMR) or follow-up CMR (deferred-CMR) or both CMRs parameters along with adverse LV remodelling (paired-CMRs). During a median follow-up of 8.3 years, the primary endpoint occurred in 84 patients (47 deaths; 37 HF hospitalizations). Early-CMR, deferred-CMR, and paired-CMR demonstrated similar predictive value for the primary endpoint (C-statistic: 0.726, 0.728, and 0.738, respectively; P = 0.663). ΔLV-EDV ≥20% or ΔLV-ESV ≥15% were unadjusted outcome predictors (hazard ratio: 2.020 and 2.032, respectively; P = 0.002 for both) but lost their predictive value when corrected for other covariates in paired-CMR model. CONCLUSION: In STEMI patients, early-, deferred-, or paired-CMR were equivalent stratification strategies for outcome prediction. Adverse LV remodelling parameters were not independent prognosticators.

CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy international registry: Design and rationale of the DERIVATE study.

BACKGROUND: Implantable cardioverter defibrillator (ICD) represents the most valuable sudden cardiac death (SCD) prophylactic strategy in patients with heart failure and severely reduced left ventricular ejection fraction (LVEF). To date, it is still unknown how to integrate the information given by cardiac magnetic resonance (CMR) into clinical and transthoracic echocardiography (TTE) work-up of non-ischemic cardiomyopathy (NICM) and ischemic cardiomyopathy (ICM) patients for accurate risk stratification. METHODS AND RESULTS: DERIVATE is a prospective, international, multicenter, observational registry of NICM and ICM patients with chronic heart failure and reduced LVEF who will undergo clinical evaluation, TTE and CMR. The registry will enrol cohorts from 34 sites. Complete risk factor, clinical presentation, TTE and CMR data will be collected and each patient will be followed-up for outcomes. Primary end point of the study is all-cause mortality. Secondary end points are: cardiovascular death, SCD, aborted SCD, sustained ventricular tachycardia (VT), and major adverse cardiac events (MACE) defined as a composite endpoint of SCD, aborted SCD, and sustained VT. Specifically, we will determine CMR findings that predict outcomes, with incremental value over LVEF and NYHA classification. Secondary aims consist in providing a comprehensive clinical and imaging score and testing the contribution of machine learning to determine prognostic CMR parameters. CONCLUSIONS: The final objective of the study consists in the identification of prognostic CMR parameters in a large prospective cohort for a better selection of patients with heart failure being worthy of primary prevention ICD therapy. (clinicaltrials.gov registration: RTT# NCT03352648).

Rationale and design of the 'F.I.R.E.' study. A multicenter, double-blind, randomized, placebo-controlled study to measure the effect of FX06 (a fibrin-derived peptide Bbeta(15-42)) on ischemia-reperfusion injury in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention.

Immediate reopening of acutely occluded coronary arteries via primary percutaneous coronary intervention (PCI) is the treatment of choice to salvage the ischemic myocardium in the setting of ST-segment elevation myocardial infarction (STEMI). However, the sudden re-initiation of blood flow achieved with PCI can lead to a local acute inflammatory response with further endothelial and myocardial damage. This phenomenon, described as 'reperfusion injury', has been recognized for several decades, yet no pharmacologic intervention has so far succeeded in reducing myocardial damage linked to reperfusion. FX06 is a naturally occurring peptide derived from the neo-N-terminus of fibrin (Bbeta(15-42)). It prevents leukocyte migration through the gap junctions of endothelial cells. Experimental studies have shown that FX06 inhibits the binding of the proinflammatory fibrin E1 fragment to VE-cadherin expressed in the adherence junction. It represents a novel approach to reducing local and systemic inflammation, including myocardial reperfusion injury, in the adherens junction. The present multicenter, double-blind, randomized, placebo-controlled study is designed to test the hypothesis that FX06 injection during and immediately after primary PCI can reduce infarct size in patients with STEMI. The primary outcome measure of efficacy in this study is the degree of myocardial salvage calculated as the difference between the perfusion defect before and after PCI, determined by myocardial perfusion scintigraphy during rest. Further, infarct size at the end of the index hospitalization, as well as at 4 months, will be measured by cardiac magnetic resonance imaging. The present position paper describes the rationale, design and the methods utilized in this trial.

Effect of phosphodiesterase-5 inhibition with Tadalafil on SystEmic Right VEntricular size and function - A multi-center, double-blind, randomized, placebo-controlled clinical trial - SERVE trial - Rational and design.

BACKGROUND: Patients with a systemic right ventricle (RV) have a compromised late outcome caused by ventricular dysfunction. Standard medical heart failure therapy has not been shown to improve RV function and survival in these patients. Phosphodiesterase (PDE)-5 inhibition increases contractility in experimental models of RV hypertrophy, but not in the normal RV. In clinical practice, the effects of PDE-5 inhibition on systemic RV function and exercise capacity in adults with a systemic RV have not been tested. METHODS: The SERVE protocol is a double-blind, randomized placebo-controlled multicenter superiority trial to study the effect of PDE-5 inhibition with Tadalafil on RV volumes and function in patients with either D-transposition of the great arteries repaired with an atrial switch procedure or with congenitally corrected transposition of the great arteries. Tadalafil 20mg or placebo will be given over a study period of 3years. The primary endpoint is the change in mean end-systolic RV volumes from baseline to study end at 3years of follow-up (or at the time of permanent discontinuation of the randomized treatment if stopped before 3- years of follow-up), and will be measured by cardiovascular magnetic resonance imaging (CMR) or by cardiac computed tomography in patients with contraindications for CMR. Secondary endpoints are changes in RV ejection fraction, VO2max and NT-proBNP. CONCLUSION: The objective of this study is to assess the effect of PDE-5 inhibition with Tadalafil on RV size and function, exercise capacity and neurohumoral activation in adults with a systemic RV over a 3-year follow-up period.

Regional myocardial ischemia in hypertrophic cardiomyopathy: impact of myectomy.

OBJECTIVE: Chest pain is a common finding in patients with hypertrophic cardiomyopathy and can be observed in 40% to 50% of all patients. However, the pathogenesis of these ischemia-like symptoms is still unclear. METHODS: Twenty-two patients with hypertrophic cardiomyopathy and 15 controls underwent positron emission tomography for evaluation of regional myocardial perfusion and coronary flow reserve (hyperemic/baseline myocardial blood flow). Myocardial perfusion (mL/min/g) was measured using [(13)N]ammonia at rest and during hyperemia with dipyridamole (0.56 mg/kg intravenously). Regional coronary flow reserve was assessed in 3 planes (apical, midventricular, basal) in 4 regions (septal, anterior, lateral, inferior). Patients were divided into 2 groups: group 1 consisted of 11 patients treated with surgical myectomy (age 56 +/- 10 years) and group 2 consisted of 11 patients treated medically (age 53 +/- 13 years). RESULTS: Mean global coronary flow reserve was 3.87 +/- 0.92 in controls but 2.31 +/- 0.40 in operated (P <.001 vs controls) and 1.76 +/- 0.58 in medically treated patients (P <.001 vs controls, P <.05 vs operated). Similarly, septal coronary flow reserve was 4.19 +/- 1.22 in controls but significantly reduced in operated patients (2.26 +/- 0.48, P <.001 vs controls) and in medically treated patients (1.76 +/- 0.58; P <.001 vs controls). However, septal flow reserve was significantly higher in operated patients than in patients with medically treated hypertrophic cardiomyopathy (+37%, P <.05), mainly due to a reduced resting myocardial perfusion. CONCLUSIONS: Global and regional myocardial perfusion is reduced in patients with hypertrophic cardiomyopathy. However, myectomy may have a beneficial effect on septal perfusion and flow reserve. Thus, ischemia seems to play an important role in the symptomatology and pathophysiology of hypertrophic cardiomyopathy.

Fluorine-19 magnetic resonance angiography of the mouse.

PURPOSE: To implement and characterize a fluorine-19 ((19)F) magnetic resonance imaging (MRI) technique and to test the hypothesis that the (19)F MRI signal in steady state after intravenous injection of a perfluoro-15-crown-5 ether (PCE) emulsion may be exploited for angiography in a pre-clinical in vivo animal study. MATERIALS AND METHODS: In vitro at 9.4T, the detection limit of the PCE emulsion at a scan time of 10 min/slice was determined, after which the T(1) and T(2) of PCE in venous blood were measured. Permission from the local animal use committee was obtained for all animal experiments. 12 µl/g of PCE emulsion was intravenously injected in 11 mice. Gradient echo (1)H and (19)F images were obtained at identical anatomical levels. Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were determined for 33 vessels in both the (19)F and (1)H images, which was followed by vessel tracking to determine the vessel conspicuity for both modalities. RESULTS: In vitro, the detection limit was ∼400 µM, while the (19)F T(1) and T(2) were 1350±40 and 25±2 ms. The (19)F MR angiograms selectively visualized the vasculature (and the liver parenchyma over time) while precisely coregistering with the (1)H images. Due to the lower SNR of (19)F compared to (1)H (17±8 vs. 83±49, p<0.001), the (19)F CNR was also lower at 15±8 vs. 52±35 (p<0.001). Vessel tracking demonstrated a significantly higher vessel sharpness in the (19)F images (66±11 vs. 56±12, p = 0.002). CONCLUSION: (19)F magnetic resonance angiography of intravenously administered perfluorocarbon emulsions is feasible for a selective and exclusive visualization of the vasculature in vivo.