Challenges and pitfalls in classification of disproportionate mitral regurgitation.

The concept of disproportionate mitral regurgitation (dispropMR) has been introduced to identify patients with functional mitral regurgitation (MR) who benefit from percutaneous treatment. We aimed to examine echocardiographic characteristics behind this entity. We retrospectively included 172 consecutive patients with reduced left ventricular ejection fraction (LVEF), and more than mild MR referred to clinically indicated echocardiography. According to the proportionality ratio (effective regurgitant orifice area (EROA)/left ventricular end-diastolic volume (LVEDV)) patients were divided into dispropMR and proportionate MR (propMR) group. Potential factors which might affect proportionality definition were analyzed. 55 patients (32%) had dispropMR. Discrepant grading of MR severity was observed when using regurgitant volume (RegVol) by proximal isovelocity surface area (PISA) method or volumetric method, with significant discordance only in dispropMR (p < 0.001). Patients with dispropMR had more frequently left ventricular foreshortened images for LVEDV calculation than patients with propMR (p = 0.003), resulting in smaller LVEDV in dispropMR group. DispropMR group had more substantial dynamic variation of regurgitant flow compared to propMR. Accordingly, EROA was consistently overestimated by standard single-point PISA method compared to serial PISA method. This was more pronounced in dispropMR (bias:10.5 ± 28.3 mm2) compared to propMR group (bias:6.4 ± 12.8 mm2). DispropMR may be found in roughly one third of clinically indicated echocardiographic studies in patients with reduced LVEF and more than mild MR. EROA overestimation due to dynamic variation of regurgitant flow and LVEDV underestimation due to LV foreshortening were more frequently found in dispropMR. Our results indicate that methodological limitations of echocardiographic MR grading could not be neglected in classifying the proportionality of MR.

Prospective multiparametric CMR characterization and MicroRNA profiling of anthracycline cardiotoxicity: A pilot translational study.

Background: Anthracycline cardiotoxicity is a significant clinical challenge. Biomarkers to improve risk stratification and identify early cardiac injury are required. Objectives: The purpose of this pilot study was to prospectively characterize anthracycline cardiotoxicity using cardiovascular magnetic resonance (CMR), echocardiography and MicroRNAs (MiRNAs), and identify baseline predictors of LVEF recovery. Methods: Twenty-four patients (age 56 range 18-75 years; 42 % female) with haematological malignancy scheduled to receive anthracycline chemotherapy (median dose 272 mg/m2 doxorubicin equivalent) were recruited and evaluated at three timepoints (baseline, completion of chemotherapy, and 6 months after completion of chemotherapy) with multiparametric 1.5 T CMR, echocardiography and circulating miRNAs sequencing. Results: Seventeen complete datasets were obtained. CMR left ventricular ejection fraction (LVEF) fell significantly between baseline and completion of chemotherapy (61 ± 3 vs 53 ± 3 %, p < 0.001), before recovering significantly at 6-month follow-up (55 ± 3 %, p = 0.018). Similar results were observed for 3D echocardiography-derived LVEF and CMR-derived longitudinal, circumferential and radial feature-tracking strain. Patients were divided into tertiles according to LVEF recovery (poor recovery, partial recovery, good recovery). CMR-derived mitral annular plane systolic excursion (MAPSE) was significantly different at baseline in patients exhibiting poor LVEF recovery (11.7 ± 1.5 mm) in comparison to partial recovery (13.7 ± 2.7 mm), and good recovery (15.7 ± 3.1 mm; p = 0.028). Furthermore, baseline miRNA-181-5p and miRNA-221-3p expression were significantly higher in this group. T2 mapping increased significantly on completion of chemotherapy compared to baseline (54.0 ± 4.6 to 57.8 ± 4.9 ms, p = 0.001), but was not predictive of LVEF recovery. No changes to LV mass, extracellular volume fraction, T1 mapping or late gadolinium enhancement were observed. Conclusions: Baseline CMR-derived MAPSE, circulating miRNA-181-5p, and miRNA-221-3p were associated with poor recovery of LVEF 6 months after completion of anthracycline chemotherapy, suggesting their potential predictive role in this context. T2 mapping increased significantly on completion of chemotherapy but was not predictive of LVEF recovery.

Radiotherapy-Induced Cardiotoxicity: The Role of Multimodality Cardiovascular Imaging.

Radiotherapy (RT) is one of the pillars of cancer therapy. High-dose radiation exposure on the thorax is mainly used in the context of adjuvant RT after breast surgery, in lung and esophageal cancer, and as a complement to systemic treatment in lymphoma. Due to the anatomical proximity, the heart inevitably receives some radiation that can result in acute and chronic cardiotoxicity, leading to heart failure, coronary artery disease, pericardial and valvular heart disease. Current evidence suggests there is no safe radiation dose to the heart, which poses a need for early recognition of RT-induced cardiac injury to initiate cardioprotective treatment and prevent further damage. Multimodality cardiac imaging provides a powerful tool to screen for structural and functional abnormalities secondary to RT. Left ventricular ejection fraction, preferably with three-dimensional echocardiography or cardiovascular magnetic resonance (CMR), and global longitudinal strain with speckle-tracking echocardiography are currently the key parameters to detect cardiotoxicity. However, several novel imaging parameters are tested in the ongoing clinical trials. CMR parametric imaging holds much promise as T1, T2 mapping and extracellular volume quantification allow us to monitor edema, inflammation and fibrosis, which are fundamental processes in RT-induced cardiotoxicity. Moreover, the association between serum biomarkers, genetic polymorphisms and the risk of developing cardiovascular disease after chest RT has been demonstrated, providing a platform for an integrative screening approach for cardiotoxicity. The present review summarizes contemporary evidence of RT-induced cardiac injury obtained from multimodality imaging-echocardiography, cardiovascular computed tomography, CMR and nuclear cardiology. Moreover, it identifies gaps in our current knowledge and highlights future perspectives to screen for RT-induced cardiotoxicity.

Cardiovascular magnetic resonance characterisation of anthracycline cardiotoxicity in adults with normal left ventricular ejection fraction.

BACKGROUND: Anthracycline therapy may lead to changes in cardiac structure and function not detectable by solely evaluating left ventricular ejection fraction (LVEF). OBJECTIVES: We hypothesized that cardiovascular magnetic resonance (CMR) would identify structural and functional myocardial abnormalities in anthracycline-treated cancer survivors with normal LVEF, compared to a matched control population. METHODS: Forty-five cancer survivors (56 ± 16 yrs., 60% female) with normal LVEF (59.5 ± 4.1%) were studied a median of 11 months (range 3-36) following administration of 237 ± 83 mg/m2 anthracycline, and compared with forty-five healthy control subjects of similar age and sex (53 ± 16 yrs., 60% female) with normal LVEF (60.8 ± 2.4%) using 1.5 T CMR. RESULTS: Significantly smaller indexed left ventricular mass (45.6 ± 8.7 vs 50.3 ± 10.1 g/m2, p = 0.02) and indexed myocardial cell volume (30.5 ± 5.7 vs 34.8 ± 7.2 ml/m2, p = 0.002) were evident in cancer survivors and the latter was inversely associated with cumulative anthracycline dose (r = -0.31, p = 0.02). Surrogate CMR markers of myocardial fibrosis were significantly increased in cancer survivors (native myocardial T1: 1021 ± 40 vs 996 ± 35 ms, p = 0.002; extracellular volume: 29.5 ± 4.5 vs 27.4 ± 2.3%, p = 0.006). CMR-derived feature-tracking global longitudinal strain (GLS) was significantly impaired in cancer survivors (2D GLS -18.3 ± 2.6 vs -20.0 ± 2.0%, p < 0.001; 3D GLS -14.5 ± 2.3 vs -16.4 ± 2.6%, p < 0.001). Parameters exhibited good to excellent (ICC = 0.86-0.98) inter- and intra-observer reproducibility. CONCLUSIONS: Anthracycline-treated cancer survivors with normal LVEF have significant perturbations of LV mass, myocardial cell volume, native myocardial T1, ECV, CMR-derived 2D and 3D GLS, compared to controls, with good to excellent levels of inter- and intra-observer reproducibility.

Magnetic Resonance Imaging to Detect Cardiovascular Effects of Cancer Therapy: JACC CardioOncology State-of-the-Art Review.

This paper aims to empower and inform cardio-oncologists by providing a practical guide to the clinical application of cardiac magnetic resonance (CMR) in the rapidly evolving field of cardio-oncology. Specifically, we describe how CMR can be used to assess the cardiovascular effects of cancer therapy. The CMR literature, relevant societal guidelines, indication-specific imaging protocols, and methods to overcome some of the challenges encountered in performing and accessing CMR are reviewed.

Myocardial phenotypes and dysfunction in HFpEF and HFrEF assessed by echocardiography and cardiac magnetic resonance.

Heart failure (HF) with either reduced or preserved ejection fraction is an increasingly prevalent condition. Cardiac imaging plays a central role in trying to identify the underlying cause of the underlying systolic and diastolic dysfunction, as the imaging findings have implications for patient's management and individualised treatment. The imaging modalities used more frequently in patients with heart failure in clinical routine are echocardiography and cardiac magnetic resonance. Both techniques keep some strengths and weakness due to their spatial and temporal resolution. Notably, several features in the diagnostic algorithm of heart failure with preserved systolic function (HFpEF) may be improved by an integrated approach. This review focuses on the role of each modality in characterising cardiac anatomy, systolic and diastolic function as well as myocardial tissue characterisation in the most common phenotypes of dilated and hypertrophied hearts.

Determinants of aortic growth rate in patients with bicuspid aortic valve by cardiovascular magnetic resonance.

Objectives: This study aimed to identify determinants of aortic growth rate in bicuspid aortic valve (BAV) patients. We hypothesised that (1) BAV patients with repaired coarctation (CoA) exhibit decreased aortic growth rate, (2) moderate/severe re-coarctation (reCoA) results in increased growth rate, (3) patients with right non-coronary (RN) valve cusps fusion pattern exhibit increased aortic growth rate compared with right-left cusps fusion and type 0 valves. Methods: Starting from n=521 BAV patients with cardiovascular magnetic resonance data, we identified n=145 patients with at least two scans for aortic growth analysis. Indexed areas of the sinuses of Valsalva and ascending aorta (AAo) were calculated from cine images in end-systole and end-diastole. Patients were classified based on dilation phenotype, presence of CoA, aortic valve function and BAV morphotype. Comparisons between groups were performed. Linear regression was carried out to identify associations between risk factors and aortic growth rate. Results: Patients (39±16 years of age, 68% male) had scans 3.7±1.8 years apart; 32 presented with AAo dilation, 18 with aortic root dilation and 32 were overall dilated. Patients with repaired CoA (n=61) showed decreased aortic root growth rate compared with patients without CoA (p≤0.03) regardless of sex or age. ReCoA, aortic stenosis, regurgitation and history of hypertension were not associated with growth rate. RN fusion pattern showed the highest aortic root growth rate and type 0 the smallest (0.30 vs 0.08 cm2/m*year, end-systole, p=0.03). Conclusions: Presence of CoA and cusp fusion morphotype were associated with changes in rate of root dilation in our BAV population.

Effect of diastolic dysfunction on intraventricular velocity behavior in early diastole by flow mapping.

Intraventricular velocity distribution reflects left ventricular (LV) diastolic function and can be measured non-invasively by flow mapping technologies. We designed our study to compare intraventricular velocities and gradients, obtained by vector flow mapping (VFM) technology during early diastole in consecutive patients diagnosed with mild and advanced diastolic dysfunction at echocardiography and a control group with a purpose to validate the hypothesis of relationship between new parameters and severity of diastolic dysfunction and conventional markers of elevated LV filling pressure. Two-dimensional streamline fields were obtained using VFM technology in 121 subjects (57 with normal diastolic function, 38 with mild diastolic dysfunction and 26 with advanced diastolic dysfunction). We measured several velocities and calculated a gradient along the selected streamline, which we compared between groups and correlated them with conventional echocardiographic parameters. Apical intraventricular velocity gradient (GrIV) was the lowest in control group, followed by mild and advanced diastolic dysfunction groups (5.3 ± 1.9 vs. 6.8 ± 2.5 vs. 13.6 ± 5.0/s, p < 0.001) and showed good correlation with E/e' (r = 0.751, p < 000.1). GrIV/e' ratio was the strongest single predictor of severity of diastolic dysfunction. Different degrees of diastolic dysfunction affect the Intraventricular velocity behavior during early diastole obtained by VFM. GrIV could discriminate between groups with different levels of diastolic dysfunction and was closely associated with classical echocardiographic indices of elevated LV filling pressure. GrIV/e' ratio has a potential to become a single parameter needed to assess left ventricular diastolic function.

Connection between the heart and the gut.

CLINICAL INTRODUCTION: A 45-year-old man with ulcerative colitis was admitted with bloody diarrhoea and chest pain. Inflammatory markers and high-sensitivity troponin were elevated (C reactive protein 57 mg/L, white cell count 10.65×109/L, neutrophil 6.6×109/L, Troponin-I 663 mmol/L). The ECG showed inferior ST-elevation. Urgent coronary angiography revealed unobstructed coronary arteries. Inpatient cardiovascular magnetic resonance (CMR) was arranged to determine the aetiology of the myocardial infarction with non-obstructive coronary arteries. The imaging protocol at 1.5 T included balanced steady-state free precession cine images, T2-weighted oedema sequences, and early and late gadolinium enhancement (LGE). Native T1 and T2 mapping images provided advanced tissue characterisation (figure 1). QUESTION: What is the most likely diagnosis based on the MRI findings? Multiple embolic myocardial infarctions in the right coronary artery territory.Acute autoimmune myocarditis.Cardiac sarcoidosis.Stress (Takotsubo) cardiomyopathy.Multiple embolic myocardial infarctions in the left circumflex coronary artery territory. heartjnl;105/15/1148/F1F1F1Figure 1(A) Balanced steady-state free precession (bSSFP) left ventricular long-axis, three-chamber view. (B) T2 short-tau inversion recovery. (C) Early gadolinium enhancement demonstrating high signal intensity indicative of hyperaemia with capillary leakage (arrowed). (D) Late gadolinium enhancement with high signal intensity indicative of increased extracellular space (arrowed). (E) bSSFP left ventricular short-axis view. (F) Native myocardial T1 mapping with elevated native T1 mapping values in the inferior wall (arrowed). (G) Native myocardial T2 mapping with elevated native T2 values in the inferior wall, indicative of oedema (arrowed). (H) Late gadolinium enhancement with high signal intensity indicative of increased extracellular space (arrowed).

Overview of mitral regurgitation in Europe: results from the European Registry of mitral regurgitation (EuMiClip).

Aims: To determine the prevalence of mitral regurgitation (MR) in a large cohort of consecutive patients undergoing clinically indicated echocardiography and to examine the distribution of primary and secondary MR. Methods and results: All patients undergoing an echocardiographic study in 19 European centres within a 3-month period were prospectively included. MR assessment was performed as recommended by the European Association of Cardiovascular Imaging (EACVI). MR was classified according to mechanism as primary or secondary and aetiologies were reported. A total of 63 463 consecutive echocardiographic studies were reviewed. Any degree of MR was described in 15 501 patients. Concomitant valve disease of at least moderate grade was present in 28.5% of patients, being tricuspid regurgitation the most prevalent. In the subgroup of moderate and severe MR (n = 3309), 55% of patients had primary MR and 30% secondary MR. Both mechanisms were described in 14% of the studies. According to Carpentier's classification, 26.7% of MR were classified as I, 19.9% of MR as II, 22.4% of MR as IIIa, and 31.1% of MR as IIIb. Conclusion: To date, this is the largest echocardiography-based study to analyse the prevalence and aetiology distribution of MR in Europe. The burden of secondary MR was higher than previously described, representing 30% of patients with significant MR. In our environment, degenerative disease is the most common aetiology of primary MR (60%), whereas ischaemic is the most common aetiology of secondary MR (51%). Up to 70% of patients with severe primary MR may have a Class I indication for surgery. However, the optimal therapeutic approach for secondary MR remains uncertain.

Mitral-Aortic Flow Reversal in Cardiac Resynchronization Therapy: Coupling With Ejection and Impact of Variations in Atrioventricular Delay.

BACKGROUND: Flow entering the left ventricle is reversed toward the outflow tract through rotating reversal flow around the mitral valve. This was thought to facilitate early ejection, but had not been proved to date. We hypothesized that perfect coupling between reversal and ejection flow would occur at optimal atrioventricular delay (AVD), contributing to its hemodynamic superiority, and evaluated its applicability for AVD optimization. METHODS AND RESULTS: Forty consecutive patients with cardiac resynchronization therapy underwent intracardiac flow analysis and AVD optimization. Reversal and ejection flow curves were studied. The presence and duration of reversal-ejection discontinuity were assessed for all programmed AVD. Reproducibility of each optimization method was evaluated through interobserver variability. Discontinuity between reversal and ejection flow was observed in all patients with longer than optimal AVD, increasing linearly with excess duration in AVD (linear R2=0.976, P<0.001). Longer discontinuities implied progressive decreases in pre-ejection flow velocity in the left ventricular outflow tract, with consequent loss of flow momentum. The equation optimal AVD=programmed AVD-[1.2(discontinuity duration)]+4 accurately predicted optimal AVD. Short AVD systematically compromised reversal flow because of premature ejection. Agreement over optimal AVD was superior when assessed by flow reversal method (intraclass correlation coefficient =0.931; P<0.001) over both iterative and aortic velocity-time integral methods. CONCLUSIONS: Perfect coupling between mitral-aortic flow reversal and ejection flow in the left ventricle occurs at optimal AVD. As a result, full blood momentum in the outflow tract is used to facilitate early ejection. This can be measured and provides a new method for AVD optimization.