Is there a role for cardiovascular magnetic resonance imaging in the assessment of biological aortic valves?

Patients with biological aortic valves (following either surgical aortic valve replacement [SAVR] or trans catheter aortic valve implantation [TAVI]) require lifelong follow-up with an imaging modality to assess prosthetic valve function and dysfunction. Echocardiography is currently the first-line imaging modality to assess biological aortic valves. In this review, we discuss the potential role of cardiac magnetic resonance imaging (CMR) as an additional imaging modality in situations of inconclusive or equivocal echocardiography. Planimetry of the prosthetic orifice can theoretically be measured, as well as the effective orifice area, with potential limitations, such as CMR valve-related artefacts and calcifications in degenerated prostheses. The true benefit of CMR is its ability to accurately quantify aortic regurgitation (paravalvular and intra-valvular) with a direct and reproducible method independent of regurgitant jet morphology to accurately assess reverse remodelling and non-invasively detect focal and interstitial diffuse myocardial fibrosis. Following SAVR or TAVI for aortic stenosis, interstitial diffuse fibrosis can regress, accompanied by structural and functional improvement that CMR can accurately assess.

Current and future options for adult biventricular assistance: a review of literature.

In cardiogenic shock various short-term mechanical assistances may be employed, including an Extra Corporeal Membrane Oxygenator and other non-dischargeable devices. Once hemodynamic stabilization is achieved and the patient evolves towards a persisting biventricular dysfunction or an underlying long-standing end-stage disease is present, aside from Orthotopic Heart Transplantation, a limited number of long-term therapeutic options may be offered. So far, only the Syncardia Total Artificial Heart and the Berlin Heart EXCOR (which is not approved for adult use in the United States unlike in Europe) are available for extensive implantation. In addition to this, the strategy providing two continuous-flow Left Ventricular Assist Devices is still off-label despite its widespread use. Nevertheless, every solution ensures at best a 70% survival rate (reflecting both the severity of the condition and the limits of mechanical support) with patients suffering from heavy complications and a poor quality of life. The aim of the present paper is to summarize the features, implantation techniques, and results of current devices used for adult Biventricular Mechanical Circulatory Support, as well as a glance to future options.

Diuretic dose is a strong prognostic factor in ambulatory patients awaiting heart transplantation.

AIMS: The prognostic value of 'high dose' loop diuretics in advanced heart failure outpatients is unclear. We aimed to assess the prognosis associated with loop diuretic dose in ambulatory patients awaiting heart transplantation (HT). METHODS AND RESULTS: All ambulatory patients (n = 700, median age 55 years and 70% men) registered on the French national HT waiting list between 1 January 2013 and 31 December 2019 were included. Patients were divided into 'low dose', 'intermediate dose', and 'high dose' loop diuretics corresponding to furosemide equivalent doses of ≤40, 40-250, and >250 mg, respectively. The primary outcome was a combined criterion of waitlist death and urgent HT. N-terminal pro-B-type natriuretic peptide, creatinine levels, pulmonary capillary wedge pressure, and pulmonary pressures gradually increased with higher diuretic dose. At 12 months, the risk of waitlist death/urgent HT was 7.4%, 19.2%, and 25.6% (P = 0.001) for 'low dose', 'intermediate dose', and 'high dose' patients, respectively. When adjusting for confounders, including natriuretic peptides, hepatic, and renal function, the 'high dose' group was associated with increased waitlist mortality or urgent HT [adjusted hazard ratio (HR) 2.23, 1.33 to 3.73; P = 0.002] and a six-fold higher risk of waitlist death (adjusted HR 6.18, 2.16 to 17.72; P < 0.001) when compared with the 'low dose' group. 'Intermediate doses' were not significantly associated with these two outcomes in adjusted models (P > 0.05). CONCLUSIONS: A 'high dose' of loop diuretics is strongly associated with residual congestion and is a predictor of outcome in patients awaiting HT despite adjustment for classical cardiorenal risk factors. This routine variable may be helpful for risk stratification of pre-HT patients.

Validation of the clinical utility of microRNA as noninvasive biomarkers of cardiac allograft rejection: A prospective longitudinal multicenter study.

While studies have shown an association between microRNAs and cardiac rejection, the clinical relevance of a preidentified miRNA signature as a noninvasive biomarker has never been assessed in prospective multicentric unselected cohorts. To address this unmet need, we designed a prospective study (NCT02672683) including recipients from 11 centers between August 2016 to March 2018. The objective was to validate the association between 3 previously identified circulating microRNA (10a, 92a, 155) and the histopathological diagnosis of rejection. Both relative and absolute (sensitivity analysis) quantifications of microRNAs were performed. Overall, 461 patients were included (831 biopsies, 79 rejections). A per-protocol interim analysis (258 biopsies, 49 rejections) did not find any association between microRNA and rejection (microRNA 10a: odds ratio (OR) = 1.05, 95% confidence intervals (CI) = 0.87-1.27, p = 0.61; 92a: OR = 0.98, 95%CI = 0.87-1.10, p = 0.68; 155: OR = 0.91, 95%CI = 0.76-1.10, p = 0.33). These results were confirmed in the sensitivity analysis. The analysis of the remaining sera was stopped for futility. This study shows no clinical utility of circulating microRNAs 10a, 92a, and 155 monitoring in heart allograft recipients.

Chronic kidney disease is a key risk factor for aortic stenosis progression.

BACKGROUND: Rapid progression of aortic stenosis (AS) has been observed in patients undergoing dialysis, but existing cross-sectional evidence is contradictory in non-dialysis-dependent chronic kidney disease (CKD). The present study sought to evaluate whether CKD is associated with the progression of AS over time in a large cohort of patients with AS. METHODS: We retrospectively studied all consecutive patients diagnosed with AS [peak aortic jet velocity (Vmax) ≥2.5 m/s] and left ventricular ejection fraction ≥50% in the echocardiography laboratories of two tertiary centers between 2000 and 2018. The estimated glomerular filtration rate (eGFR) (mL/min/1.73 m2) was calculated from serum creatinine values. Patients were divided into five CKD stages according to the baseline eGFR. Annual rates of change in the aortic valve area (AVA) were determined by a linear mixed-effects model. RESULTS: Among the 647 patients included, 261 (40%) had CKD. After a median follow-up of 2.9 (interquartile range 1.8-4.8) years, the mean overall rate of change in AVA was -0.077 (95% confidence interval -0.082; -0.073) cm2/year. There was an inverse relationship between the progression rate and kidney function. The more severe the CKD stage, the greater the AVA narrowing (P < .001). By multivariable linear regression analysis, the eGFR was also negatively associated (P < .001) with AS progression. An eGFR strata below 45 mL/min/1.73 m2 was associated with higher odds of rapid progression of AS than normal kidney function. During the clinical follow-up, event-free survival (patients free of aortic valve replacement or death) decreased as CKD progressed. Rapid progression of AS in patients with kidney dysfunction was associated with worse outcomes. CONCLUSIONS: Patients with CKD exhibit more rapid progression of AS over time and require close monitoring. The link between kidney dysfunction and rapid progression of AS is still unknown and requires further research.

Quantification of primary mitral regurgitation by echocardiography: A practical appraisal.

The accurate quantification of primary mitral regurgitation (MR) and its consequences on cardiac remodeling is of paramount importance to determine the best timing for surgery in these patients. The recommended echocardiographic grading of primary MR severity relies on an integrated multiparametric approach. It is expected that the large number of echocardiographic parameters collected would offer the possibility to check the measured values regarding their congruence in order to conclude reliably on MR severity. However, the use of multiple parameters to grade MR can result in potential discrepancies between one or more of them. Importantly, many factors beyond MR severity impact the values obtained for these parameters including technical settings, anatomic and hemodynamic considerations, patient's characteristics and echocardiographer' skills. Hence, clinicians involved in valvular diseases should be well aware of the respective strengths and pitfalls of each of MR grading methods by echocardiography. Recent literature highlighted the need for a reappraisal of the severity of primary MR from a hemodynamic perspective. The estimation of MR regurgitation fraction by indirect quantitative methods, whenever possible, should be central when grading the severity of these patients. The assessment of the MR effective regurgitant orifice area by the proximal flow convergence method should be used in a semi-quantitative manner. Furthermore, it is crucial to acknowledge specific clinical situations in MR at risk of misevaluation when grading severity such as late-systolic MR, bi-leaflet prolapse with multiple jets or extensive leak, wall-constrained eccentric jet or in older patients with complex MR mechanism. Finally, it is debatable whether the 4-grades classification of MR severity would be still relevant nowadays, since the indication for mitral valve (MV) surgery is discussed in clinical practice for patients with 3+ and 4+ primary MR based on symptoms, specific markers of adverse outcome and MV repair probability. Primary MR grading should be seen as a continuum integrating both quantification of MR and its consequences, even for patients with presumed "moderate" MR.

The evolving role of cardiovascular magnetic resonance in the assessment of mitral valve prolapse.

Mitral valve prolapse (MVP), characterized by a displacement > 2 mm above the mitral annulus of one or both bileaflets, with or without leaflet thickening, is a common valvular heart disease, with a prevalence of approximately 2% in western countries. Although this population has a generally good overall prognosis, MVP can be associated with mitral regurgitation (MR), left ventricular (LV) remodeling leading to heart failure, ventricular arrhythmia, and, the most devastating complication, sudden cardiac death, especially in myxomatous bileaflet prolapse (Barlow's disease). Among several prognostic factors reported in the literature, LV fibrosis and mitral annular disjunction may act as an arrhythmogenic substrate in this population. Cardiac magnetic resonance (CMR) has emerged as a reliable tool for assessing MVP, MR severity, LV remodeling, and fibrosis. Indeed, CMR is the gold standard imaging modality to assess ventricular volume, function, and wall motion abnormalities; it allows accurate calculation of the regurgitant volume and regurgitant fraction in MR using a combination of LV volumetric measurement and aortic flow quantification, independent of regurgitant jet morphology and valid in cases of multiple valvulopathies. Moreover, CMR is a unique imaging modality that can assess non-invasively focal and diffuse fibrosis using late gadolinium enhancement sequences and, more recently, T1 mapping. This review describes the use of CMR in patients with MVP and its role in identifying patients at high risk of ventricular arrhythmia.

Role of Cardiovascular Magnetic Resonance in Native Valvular Regurgitation: A Comprehensive Review of Protocols, Grading of Severity, and Prediction of Valve Surgery.

Valvular regurgitation is common in developed countries with an increasing prevalence due to the aging of the population and more accurate diagnostic imaging methods. Echocardiography is the gold standard method for the assessment of the severity of valvular heart regurgitation. Nonetheless, cardiovascular magnetic resonance (CMR) has emerged as an additional tool for assessing mainly the severity of aortic and mitral valve regurgitation in the setting of indeterminate findings by echocardiography. Moreover, CMR is a valuable imaging modality to assess ventricular volume and flow, which are useful in the calculation of regurgitant volume and regurgitant fraction of mitral valve regurgitation, aortic valve regurgitation, tricuspid valve regurgitation, and pulmonary valve regurgitation. Notwithstanding this, reference values and optimal thresholds to determine the severity and prognosis of valvular heart regurgitation have been studied lesser by CMR than by echocardiography. Hence, further larger studies are warranted to validate the potential prognostic relevance of the severity of valvular heart regurgitation determined by CMR. The present review describes, analyzes, and discusses the use of CMR to determine the severity of valvular heart regurgitation in clinical practice.

Prognosis value of Forrester's classification in advanced heart failure patients awaiting heart transplantation.

AIMS: The value of Forrester's perfusion/congestion profiles assessed by invasive catheter evaluation in non-inotrope advanced heart failure patients listed for heart transplant (HT) is unclear. We aimed to assess the value of haemodynamic evaluation according to Forrester's profiles to predict events on the HT waitlist. METHODS AND RESULTS: All non-inotrope patients (n = 837, 79% ambulatory at listing) registered on the French national HT waiting list between 1 January 2013 and 31 December 2019 with right heart catheterization (RHC) were included. The primary outcome was a combined criteria of waitlist death, delisting for aggravation, urgent HT or left ventricular assist device implantation. Secondary outcome was waitlist death. The 'warm-dry', 'cold-dry', 'warm-wet', and 'cold-wet' profiles represented 27%, 18%, 27%, and 28% of patients, respectively. At 12 months, the respective rates of primary outcome were 15%, 17%, 25%, and 29% (P = 0.008). Taking the 'warm-dry' category as reference, a significant increase in the risk of primary outcome was observed only in the 'wet' categories, irrespectively of 'warm/cold' status: hazard ratios, 1.50; 1.06-2.13; P = 0.024 in 'warm-wet' and 1.77; 1. 25-2.49; P = 0.001 in 'cold-wet'. CONCLUSIONS: Haemodynamic assessment of advanced HF patients using perfusion/congestion profiles predicts the risk of the combine endpoint of waitlist death, delisting for aggravation, urgent heart transplantation, or left ventricular assist device implantation. 'Wet' patients had the worst prognosis, independently of perfusion status, thus placing special emphasis on the cardinal prominence of persistent congestion in advanced HF.

Left ventricular assist device inflow cannula implantation: Why a "Step sideways" technique can be helpful.

Preservation of right ventricle vascularization that is dependent on left coronary network collateral development is essential during left ventricular assist device implantation to avoid postoperative right heart failure. Our technique was performed on a patient who underwent implantation as a bridge to transplantation; the technique is characterized by providing a moderate lateral and inferior displacement of the inflow cannula position, which achieves both the objectives of respecting the apical course of a left anterior descending coronary artery supplying an occluded right coronary and of maintaining a sufficient orientation degree toward the plane of the mitral valve for correct left ventricular unloading.

Successful Terbinafine Treatment for Cutaneous Phaeohyphomycosis Caused by Trematosphaeria grisea in a Heart Transplanted Man: Case Report and Literature Review.

Phaeohyphomycosis is a chronic infectious disease caused by dematiaceous fungi. It is characterized by the presence of pigmented septate mycelia within tissues. In the case of superficial infection, the lesion(s) chronically evolve(s) toward painless pseudo-tumor(s) of the soft parts. We report herein the original case of a heart transplanted man who exhibited phaeohyphomycosis of the left hand, with no mention of travels in endemic areas. Trematosphaeria grisea was identified as the causative agent, which is quite innovative since this species has been rather described in mycetoma. The antifungal treatment initially based on isavuconazole alone was not sufficient to cure the patient. In contrast, its association with local terbinafine ointment allowed total clinical improvement. This finding is unusual as diagnosis of phaeohyphomycosis caused by T. grisea is uncommon in nontropical countries, and as the outcome appeared successful by the means of add-on therapeutic strategy with terbinafine.

Cardiac magnetic resonance for assessment of cardiac involvement in Takotsubo syndrome: Do we still need contrast administration?

BACKGROUND: This study evaluated the ability of T1 and T2 mapping cardiovascular magnetic resonance to assess myocardial involvement in Takotsubo syndrome (TTS). We hypothesized that non-contrast mapping techniques can be accurate and sufficient. METHODS: We prospectively analysed 30 patients with TTS and 34 controls. CMR was performed a mean 5 days after the onset of symptoms and after a mean 3 month follow-up. RESULTS: On admission, compared to controls, TTS patients had significantly higher global T2 values (59 ± 8 ms vs 51 ± 4 ms, p < 0.001), native T1 (1053 ± 75 ms vs 960 ± 61 ms, p < 0.001) and extracellular volume (ECV) fraction (29% ± 5 vs 23% ±3, p < 0.001). The sensitivity and specificity for T2 (cut off: 56 ms) were 62% and 97% respectively; for native T1: (cut off 1011 ms) were 72% and 91% respectively; and for ECV (cut off: 27%) were 72% and 97% respectively. Combining T2 and native T1 provided the best sensitivity (91.7%) with a good specificity (88.2%). No patients had late gadolinium enhancement. Segmental analysis showed that T2, native T1 and ECV values were significantly higher in regions with wall motion abnormalities (WMA) compared to normokinetic segments (62 ± 9 ms vs 55 ± 5 ms, p < 0.001; 1060 ± 65 ms vs 1025 ± 56 ms, p = 0.02; and 34% ± 5 vs 29% ± 1, p = 0.02). At follow up, native T1 and ECV values did not normalized. CONCLUSION: In TTS patients, a non-contrast mapping technique provides a high diagnostic accuracy allowing identification of acute and persistent myocardial injury. Segmental analysis showed that myocardial injury is preferably detected in segments with WMA.

Sarcoidosis diagnosed on granulomas in the explanted heart after transplantation: Results of a French nationwide study.

BACKGROUND: Cardiac sarcoidosis (CS) is a challenging diagnosis. Patients may progress to end-stage congestive heart failure and require cardiac transplantation without ever having been diagnosed. Characteristics and outcomes of patients with granulomas in the explanted hearts are unknown. METHODS: All French heart transplantation centers were contacted to participate in the study. Each center searched through local databases for the cases of non-caseating granuloma in the explanted hearts between 2000 and 2017. Data before and after transplantation were recorded from medical charts. Survival of CS and all- cause heart transplantation patients were compared. RESULTS: Fifteen patients (10 men, 5 women) received a diagnosis of CS based on pathologic data of the explanted heart and were recruited for the study. All patients were diagnosed as non-ischemic dilated or hypertrophic cardiomyopathy and presented congestive heart failure. Eight patients (53%) had ventricular rhythm disturbances, and 3 (20%) a complete heart block. Ten out of 13 patients (77%) had extracardiac radiological signs compatible with sarcoidosis on chest computed tomography (CT) scans. One patient died 3 months after transplantation from infectious complications. The 14 remaining patients were still alive at the end of the study (median follow-up of 28.8 months). One patient had a second heart transplantation 5 years later because of chronic allograft vasculopathy. One patient presented a relapse of CS confirmed by myocardial biopsies 9 years after transplantation, requiring an escalation of immunosuppressive therapy. CONCLUSION: CS may be undiagnosed before heart transplantation. In 77% of cases, sarcoidosis could have been detected before transplantation with non-invasive imaging techniques.

Galectin-3 predicts response and outcomes after cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) reduces symptoms, morbidity and mortality in chronic heart failure patients with wide QRS complexes. However, approximately one third of CRT patients are non-responders. Myocardial fibrosis is known to be associated with absence of response. We sought to see whether galectin-3, a promising biomarker involved in fibrosis processes, could predict response and outcomes after CRT. METHODS: Consecutive patients eligible for implantation of a CRT device with a typical left bundle branch block ≥ 120 ms were prospectively included. Serum Gal-3 level, Selvester ECG scoring, and cardiac magnetic resonance with analysis of late gadolinium enhancement (LGE) were ascertained. Response to CRT was defined by a composite endpoint at 6 months: no death, nor hospitalization for major cardiovascular event, and a significant decrease in left ventricular end-systolic volume of 15% or more. RESULTS: Sixty-one patients were included (age 61 ± 5 years, ejection fraction 27 ± 5%), 59% with non-ischemic cardiomyopathy. At 6 months, 49 patients (80%) were considered responders. Responders had a lower percentage of LGE (8 ± 13% vs 22 ± 16%, p = 0.006), and a trend towards lower rates of galectin-3 (16 ± 6 ng/mL vs 19 ± 8 ng/mL, p = 0.13). LGE ≥ 14% and Gal-3 ≥ 22 ng/mL independently predicted response to CRT (OR = 0.17 [0.03-0.62], p = 0.007, and OR = 0.11 [0.02-0.04], p < 0.001, respectively). At 48 months of follow-up, 12 patients had been hospitalized for a major cardiovascular event or had died. Galectin-3 level predicted long-term outcomes (HR = 3.31 [1.00-11.34], p = 0.05). CONCLUSIONS: Gal-3 serum level predicts the response to CRT at 6 months and long-term outcomes in chronic heart failure patients.

Cardiovascular magnetic resonance in heart transplant patients: diagnostic value of quantitative tissue markers: T2 mapping and extracellular volume fraction, for acute rejection diagnosis.

BACKGROUND: The diagnosis of acute rejection in cardiac transplant recipients requires invasive technique with endomyocardial biopsy (EMB) which has risks and limitations. Cardiovascular magnetic resonance imaging (CMR) with T2 and T1 mapping is a promising technique for characterizing myocardial tissue. The purpose of the study was to evaluate T2, T1 and extracellular volume fraction (ECV) quantification as novel tissue markers to diagnose acute rejection. METHODS: CMR was prospectively performed in 20 heart transplant patients providing 31 comparisons EMB-CMR. CMR was performed close to EMB. Images were acquired on a 1.5 Tesla scanner including T2 mapping (T2 prepared balanced steady state free precession) and T1 mapping (modified Look-Locker inversion recovery sequences: MOLLI) at basal, mid and apical level in short axis view. Global and segmental T2 and T1 values were measured before and 15 min (for T1 mapping) after contrast administration. RESULTS: Acute rejection was diagnosed in seven patients: six cellular rejections (4 grade IR, 2 grade 2R) and one antibody mediated rejection. Patients with acute rejection had significantly higher global T2 values at 3 levels: 58.5 ms [55.0-60.3] vs 51.3 ms [49.5-55.2] (p = 0.007) at basal; 55.7 ms [54.0-59.7] vs 51.8 ms [50.1-53.6] (p = 0.002) at median and 58.2 ms [54.0-63.7] vs 53.6 ms [50.8-57.4] (p = 0.026) at apical level. The area under the curve (AUC) for each level was 0.83, 0.79 and 0.78 respectively. Patients with acute rejection had significantly higher ECV at basal level: 34.2% [32.8-37.4] vs 27.4% [24.6-30.6] (p = 0.006). The AUC for basal level was 0.84. The sensitivity, specificity and diagnosis accuracy for basal T2 (cut off: 57.7 ms) were 71, 96 and 90% respectively; and for basal ECV: (cut off 32%) were 86, 85 and 85% respectively. Combining basal T2 and basal ECV allowed diagnosing all acute rejection and avoiding 63% of EMB. CONCLUSIONS: In heart transplant patients, a combined CMR approach using T2 mapping and ECV quantification provides a high diagnostic accuracy for acute rejection diagnosis and could potentially decrease the number of routine EMB.

Coronary Toxicities of Anti-PD-1 and Anti-PD-L1 Immunotherapies: a Case Report and Review of the Literature and International Registries.

Immunotherapy medications that target programmed death 1 protein (PD-1) and programmed death-ligand 1 (PD-L1), such as nivolumab, pembrolizumab, and atezolizumab, are currently used in the first- or second-line treatment of non-small cell lung cancers, among other indications. However, these agents are associated with immune-related side effects, the most common of which are endocrinopathies, colitis, hepatitis, and interstitial pneumonitis. In contrast, coronary toxicities are rarely reported and remain poorly understood. Here, we describe the case of a patient who developed an acute coronary syndrome when treated with nivolumab as second-line therapy for metastatic pulmonary adenocarcinoma. A review of the literature, the French pharmacovigilance registry, and the World Health Organization pharmacovigilance database led to the identification of four cases of patients with coronary manifestations attributable to anti-PD1 immunotherapy (with no reported cases of patients undergoing anti-PD-L1 immunotherapy), which we describe herein. The potential mechanisms causing adverse coronary reactions to this type of therapy, which is used to treat lung cancer as well as other solid and hematological neoplastic diseases, are also discussed.