Obesity in heart failure with preserved ejection fraction: Insights from the REDUCE LAP-HF II trial.

AIMS: Obesity is causally related to the development of heart failure with preserved ejection fraction (HFpEF) but complicates the diagnosis and treatment of this disorder. We aimed to determine the relationship between severity of obesity and clinical, echocardiographic and haemodynamic parameters in a large cohort of patients with documented HFpEF. METHODS AND RESULTS: The REDUCE LAP-HF II trial randomized 626 patients with ejection fraction ≥40% and exercise pulmonary capillary wedge pressure (PCWP) ≥25 mmHg to atrial shunt or sham procedure. We tested for associations between body mass index (BMI), clinical characteristics, cardiac structural and functional abnormalities, physical limitations, quality of life and outcomes with atrial shunt therapy. Overall, 60.9% of patients had BMI ≥30 kg/m2 . As the severity of obesity increased, symptoms (Kansas City Cardiomyopathy Questionnaire score) and 6-min walk distance worsened. More severe obesity was associated with lower natriuretic peptide levels despite more cardiac remodelling, higher cardiac filling pressures, and higher cardiac output. Lower cut points for E/e' were needed to identify elevated PCWP in more obese patients. Strain measurements in all four chambers were maintained as BMI increased. Pulmonary vascular resistance at rest and exercise decreased with higher BMI. Obesity was associated with more first and recurrent heart failure events. However, there was no significant interaction between obesity and treatment effects of the atrial shunt. CONCLUSIONS: Increasing severity of obesity was associated with greater cardiac remodelling, higher right and left ventricular filling pressures, higher cardiac output and increased subsequent heart failure events. Despite significant obesity, many HFpEF patients have preserved right heart and pulmonary vascular function and thus, may be appropriate candidates for atrial shunt therapy.

Impact of Left Ventricular Assist Devices on Days Alive and Out of Hospital in Hemodynamically Stable Patients with End-Stage Heart Failure: A Propensity Score Matched Study.

The two main surgical options to treat end-stage heart failure are heart transplantation (HTx) or left ventricular assist device (LVAD) implantation. In hemodynamically stable patients, the decision for HTx listing with or without LVADs is challenging. We analyzed the impact of both options on days alive and out of hospital (DAOH) and survival. This retrospective study screened all patients with HTx or LVAD implantation between 2010 and 2020. The main inclusion criterion was hemodynamic stability defined as independence of intravenous inotropic/vasoactive support at decision. Propensity score matching (PSM) was performed. The primary endpoint was DAOH within one year after the decision. Secondary endpoints included survival, duration until HTx, and hospitalizations. In total, 187 patients received HTx and 227 patients underwent LVAD implantation. There were 21 bridge-to-transplant (BTT)-LVAD patients (implantation less than a month after HTx listing or listing after implantation) and 44 HTx-waiting patients included. PSM identified 17 matched pairs. Median DAOH at one year was not significantly different between the groups (BTT-LVAD: median 281, IQR 89; HTx waiting: median 329, IQR 74; p = 0.448). Secondary endpoints did not differ significantly. Our data suggest that BTT-LVAD implantation may not be favorable in terms of DAOH within one year for hemodynamically stable patients compared to waiting for HTx. Further investigations on quality of life and long-term outcomes are warranted.

Cardiovascular magnetic resonance T2* mapping for the assessment of cardiovascular events in hypertrophic cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is associated with an increased risk of adverse cardiac events. Beyond classic risk factors, relative myocardial ischaemia and succeeding myocardial alterations, which can be detected using either contrast agents or parametric mapping in cardiovascular magnetic resonance (CMR) imaging, have shown an impact on outcome in HCM. CMR may help to risk stratify using parametric T2* mapping. Therefore, the aim of the present study was to evaluate the association of T2* values or fibrosis with cardiovascular events in HCM. Methods: The relationship between T2* with supraventricular, ventricular arrhythmia or heart failure was retrospectively assessed in 91 patients with HCM referred for CMR on a 1.5T MR imaging system. Fibrosis as a reference was added to the model. Patients were subdivided into groups according to T2* value quartiles. Results: 47 patients experienced an event of ventricular arrhythmia, 25 of atrial fibrillation/flutter and 17 of heart failure. T2*≤28.7 ms yielded no association with ventricular events in the whole HCM cohort. T2* of non-obstructive HCM showed a significant association with ventricular events in univariate analysis, but not in multivariate analysis. For the combined endpoint of arrhythmic events, there was already an association for the whole HCM cohort, but again only in univariate analyses. Fibrosis stayed the strongest predictor in all analyses. There was no association for T2* and fibrosis with heart failure. Conclusions: Decreased T2* values by CMR only provide a small association with arrhythmic events in HCM, especially in non-obstructive HCM. No information is added for heart failure.

Coronary Angiography With Pressure Wire and Fractional Flow Reserve.

BACKGROUND: Approximately 800 000 coronary angiography procedures are per- formed in Germany each year, mainly in order to identify coronary artery stenoses. As a rule, revascularization is indicated only when coronary artery stenoses cause relevant ischemia, but this cannot be determined unequivocally by angiography alone. Pressure wire measurement and the measurement of fractional flow reserve (FFR) enable direct evaluation of the hemodynamic relevance of coronary artery stenoses during diagnostic coronary angiography. METHODS: This review is based on publications retrieved by a selective search in PubMed focusing especially on large randomized trials, registry studies, and meta- analyses on either pressure wire measurement or FFR. RESULTS: According to a registry study from France, the hemodynamic evaluation of a stenosis during coronary angiography affected decisions about revascularization in 43% of cases. Randomized multicenter trials have shown that a combined end- point consisting of death, myocardial infarction, or revascularization arose signifi- cantly less commonly in the FFR group than in the group receiving angiography without FFR (13.2% versus 18.3%; p = 0.02), and that patients with one or more hemodynamically significant coronary artery stenoses (FFR ≤ 0.80) benefited more from revascularization than from medical management alone (event rate, 8.1% versus 19.5%; p <0.001). It was also shown that revascularization yields no benefit if relevant ischemia has been ruled out, even if the angiogram shows high-grade coronary artery stenoses. CONCLUSION: All cardiac catheter laboratories should be capable of performing pres- sure wire measurements and measurements of FFR and should do so regularly if ischemia due to coronary artery stenosis cannot be demonstrated non-invasively. A pathological FFR measurement is an indication for revascularization.

Retrospective phase-based gating for cardiac proton spectroscopy with fixed scan time.

BACKGROUND: Respiratory motion is a major limiting factor for spectral quality and duration of in vivo proton MR spectroscopy of the heart. Prospective navigator gating is frequently applied to minimize the effects of respiratory motion, but scan durations are subject-dependent and hence difficult to predict. PURPOSE: To implement cardiac proton MRS with fixed scan time by employing retrospective phase-based gating and to compare the proposed method to conventional navigator-gated MRS. STUDY TYPE: Prospective. SUBJECTS: Eighteen healthy volunteers (29.7 ± 7.8 years). FIELD STRENGTH/SEQUENCE: 1.5, navigator-gated (16 averages without, 96 with water suppression [WS]) data acquisition as reference and navigator-free data acquisition with a fixed scan time (48 without WS, 304 with WS), cardiac-triggered point-resolved spectroscopy (PRESS). ASSESSMENT: Navigator-free data acquisition with retrospective phase-based gating was compared with prospective navigator-gating. Navigator-free acquisition was repeated in 10 subjects to assess reproducibility. Scan time was assessed for prospective and retrospective gating. Retrospective phase-based gating was performed using a threshold based on the standard deviation (SD) of individual water (W) and triglyceride (TG) phases. STATISTICAL TESTS: T-tests and Bland-Altman analysis. RESULTS: The duration of the prospective navigator-gated scans ranged from 6:09 minutes to 21:50 minutes (mean 10:05 ± 3:46 min, gating efficiency 40.4 ± 10.5%), while data acquisition for retrospective phase-based gating had a fixed scan time of 11:44 minutes. Retrospective phase-based gating using a threshold of 1 × SD yielded a gating efficiency of 72.7 ± 4.3% and a coefficient of variation (CoV) of triglyceride-to-water ratios of 9.8% compared with the navigated reference. The intrasubject reproducibility of retrospective gating revealed a CoV of 9.5%. DATA CONCLUSION: Cardiac proton MRS employing retrospective phase-based gating is feasible and provides reproducible assessment of TG/W in a fixed scan time. Since scan time is independent of respiratory motion, retrospective phase-based gating offers an approach to motion compensation with predictable exam time for proton MRS of the heart. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1973-1981.

Myocardial triglycerides in cardiac amyloidosis assessed by proton cardiovascular magnetic resonance spectroscopy.

BACKGROUND: Cardiac involvement of amyloidosis leads to left-ventricular (LV) wall thickening with progressive heart failure requiring rehospitalization. Cardiovascular magnetic resonance (CMR) is a valuable tool to non-invasively assess myocardial thickening as well as structural changes. Proton CMR spectroscopy (1H-CMRS) additionally allows assessing metabolites including triglycerides (TG) and total creatine (CR). However, opposing results exist regarding utilization of these metabolites in LV hypertrophy or thickening. Therefore, the aim of this study was to measure metabolic alterations using 1H-CMRS in a group of patients with thickened myocardium caused by cardiac amyloidosis. METHODS: 1H-CMRS was performed on a 1.5 T system (Achieva, Philips Healthcare, Best, The Netherlands) using a 5-channel receive coil in 11 patients with cardiac amyloidosis (60.5 ± 11.4 years, 8 males) and 11 age- and gender-matched controls (63.2 ± 8.9 years, 8 males). After cardiac morphology and function assessment, proton spectra from the interventricular septum (IVS) were acquired using a double-triggered PRESS sequence. Post-processing was performed using a customized reconstruction pipeline based on ReconFrame (GyroTools LLC, Zurich, Switzerland). Spectra were fitted in jMRUI/AMARES and the ratios of triglyceride-to-water (TG/W) and total creatine-to-water (CR/W) were calculated. RESULTS: Besides an increased LV mass and a thickened IVS concomitant to the disease characteristics, patients with cardiac amyloidosis presented with decreased global longitudinal (GLS) and circumferential (GCS) strain. LV ejection fraction was preserved relative to controls (60.0 ± 13.2 vs. 66.1 ± 4.3%, p = 0.17). Myocardial TG/W ratios were significantly decreased compared to controls (0.53 ± 0.23 vs. 0.80 ± 0.26%, p = 0.015). CR/W ratios did not show a difference between both groups, but a higher standard deviation in patients with cardiac amyloidosis was observed. Pearson correlation revealed a negative association between elevated LV mass and TG/W (R = - 0.59, p = 0.004) as well as GCS (R = - 0.48, p = 0.025). CONCLUSIONS: A decrease in myocardial TG/W can be detected in patients with cardiac amyloidosis alongside impaired cardiac function with an association to the degree of myocardial thickening. Accordingly, 1H-CMRS may provide an additional diagnostic tool to gauge progression of cardiac amyloidosis along with standard imaging sequences. TRIAL REGISTRATION: EK 2013-0132.

Cardiac- versus diaphragm-based respiratory navigation for proton spectroscopy of the heart.

OBJECTIVES: To study inter-individual differences of the relation between diaphragm and heart motion, the objective of the present study was to implement respiratory navigation on the heart and compare it against the established method of navigator gating on the diaphragm for single-voxel cardiac 1H-MRS. MATERIALS AND METHODS: 1H-MRS was performed on a 1.5T system in 19 healthy volunteers of mixed age (range 24-75 years). Spectra were recorded in a 6-8 ml voxel in the ventricular septum using a PRESS (point-resolved spectroscopy) sequence and ECG gating. Water-unsuppressed data acquired with pencil beam navigation on the heart were compared to data with navigation on the diaphragm. Water-suppressed data were obtained to assess triglyceride-to-water ratios. RESULTS: Water phase and amplitude fluctuations for cardiac versus diaphragm navigation did not reveal significant differences. Both navigator positions provided comparable triglyceride-to-water ratios and gating efficiencies (coefficient of variation (CoV) 7.0%). The cardiac navigator showed a good reproducibility (CoV 5.2%). DISCUSSION: Respiratory navigation on the heart does not convey an advantage over diaphragm-based navigator gating for cardiac 1H-MRS, but also no disadvantage. Consequently, cardiac and diaphragm respiratory navigation may be used interchangeably.

Secondary right heart failure due to haemodynamically relevant iatrogenic atrial septal defect: does the sequence of structural interventions sometimes matter? A case report.

BACKGROUND: Edge-to-edge mitral valve repair is a common procedure for treating severe symptomatic mitral valve regurgitation in patients not eligible for surgery. CASE SUMMARY: After necessary transseptal puncture during the MitraClip procedure, an iatrogenic atrial septal defect (iASD) routinely remains and closes spontaneously in most cases. We present a case in which this shunt persisted due to increased left heart pressure, causing repeated rehospitalization, and ultimately requiring interventional closure: after successful transcatheter edge-to-edge repair of severe, symptomatic mitral regurgitation, the iASD persisted presumably due to underestimated paradoxical low-flow, low-gradient aortic valve stenosis. Despite transcatheter aortic valve implantation, the iASD became haemodynamically relevant requiring successful interventional iASD closure in the end after a long period of rehospitalizations. We evaluated the symptoms, haemodynamic, and functional characteristics of the patient using several diagnostic tools, as well as the comorbidities of the patient, in terms of their potential to favour the persistence and haemodynamic relevance of iASDs. DISCUSSION: The combination of sophisticated diagnostic tools, such as cardiac magnetic resonance imaging and transoesophageal echocardiography (TOE), physical examination, and symptoms can be used to identify patients vulnerable to the development of a haemodynamic-relevant iASD that will need early interventional treatment.

Performing and Interpreting Fractional Flow Reserve Measurements in Clinical Practice: An Expert Consensus Document.

Fractional flow reserve (FFR) measurements can determine the haemodynamic relevance of coronary artery stenoses. Current guidelines recommend their use in lesions in the absence of non-invasive proof of ischaemia. The prognostic impact of FFR has been evaluated in randomised trials, and it has been shown that revascularisation can be safely deferred if FFR is >0.80, while revascularisation of stenoses with FFR values ≤0.80 results in significantly lower event rates compared to medical treatment. Left main stenoses, aorto-ostial lesions, as well as patients with left ventricular hypertrophy and severely-impaired ejection fraction, have been excluded from large, randomised trials. While FFR measurements are relatively straightforward to perform, uncertainty about procedural logistics, as well as data acquisition and interpretation in specific situations, could explain why they are not widely used in clinical practice. We summarise the clinical data in support of FFR measurements, and provide recommendations for performing and interpreting the procedure.