Introduction of Lazy Luna an automatic software-driven multilevel comparison of ventricular function quantification in cardiovascular magnetic resonance imaging.

Cardiovascular magnetic resonance imaging is the gold standard for cardiac function assessment. Quantification of clinical results (CR) requires precise segmentation. Clinicians statistically compare CRs to ensure reproducibility. Convolutional Neural Network developers compare their results via metrics. Aim: Introducing software capable of automatic multilevel comparison. A multilevel analysis covering segmentations and CRs builds on a generic software backend. Metrics and CRs are calculated with geometric accuracy. Segmentations and CRs are connected to track errors and their effects. An interactive GUI makes the software accessible to different users. The software's multilevel comparison was tested on a use case based on cardiac function assessment. The software shows good reader agreement in CRs and segmentation metrics (Dice > 90%). Decomposing differences by cardiac position revealed excellent agreement in midventricular slices: > 90% but poorer segmentations in apical (> 71%) and basal slices (> 74%). Further decomposition by contour type locates the largest millilitre differences in the basal right cavity (> 3 ml). Visual inspection shows these differences being caused by different basal slice choices. The software illuminated reader differences on several levels. Producing spreadsheets and figures concerning metric values and CR differences was automated. A multilevel reader comparison is feasible and extendable to other cardiac structures in the future.

Assessment of diastolic dysfunction: comparison of different cardiovascular magnetic resonance techniques.

AIMS: Heart failure with preserved ejection fraction is still a diagnostic and therapeutic challenge, and accurate non-invasive diagnosis of left ventricular (LV) diastolic dysfunction (DD) remains difficult. The current study aimed at identifying the most informative cardiovascular magnetic resonance (CMR) parameters for the assessment of LVDD. METHODS AND RESULTS: We prospectively included 50 patients and classified them into three groups: with DD (DD+, n = 15), without (DD-, n = 26), and uncertain (DD±, n = 9). Diagnosis of DD was based on echocardiographic E/E', invasive LV end-diastolic pressure, and N-terminal pro-brain natriuretic peptide. CMR was performed at 1.5 T to assess LV and left atrial (LA) morphology, LV diastolic strain rate (SR) by tissue tracking and tagging, myocardial peak velocities by tissue phase mapping, and transmitral inflow profile using phase contrast techniques. Statistics were performed only on definitive DD+ and DD- (total number 41). DD+ showed enlarged LA with LA end-diastolic volume/height performing best to identify DD+ with a cut-off value of ≥0.52 mL/cm (sensitivity = 0.71, specificity = 0.84, and area under the receiver operating characteristic curve = 0.75). DD+ showed significantly reduced radial (inferolateral E peak: DD-: -14.5 ± 6.5%/s vs. DD+: -10.9 ± 5.9%/s, P = 0.04; anterolateral A peak: DD-: -4.2 ± 1.6%/s vs. DD+: -3.1 ± 1.4%/s, P = 0.04) and circumferential (inferolateral A peak: DD-: 3.8 ± 1.2%/s vs. DD+: 2.8 ± 0.8%/s, P = 0.007; anterolateral A peak: DD-: 3.5 ± 1.2%/s vs. DD+: 2.5 ± 0.8%/s, P = 0.048) SR in the basal lateral wall assessed by tissue tracking. In the same segments, DD+ showed lower peak myocardial velocity by tissue phase mapping (inferolateral radial peak: DD-: -3.6 ± 0.7 ms vs. DD+: -2.8 ± 1.0 ms, P = 0.017; anterolateral longitudinal peak: DD-: -5.0 ± 1.8 ms vs. DD+: -3.4 ± 1.4 ms, P = 0.006). Tagging revealed reduced global longitudinal SR in DD+ (DD-: 45.8 ± 12.0%/s vs. DD+: 34.8 ± 9.2%/s, P = 0.022). Global circumferential and radial SR by tissue tracking and tagging, LV morphology, and transmitral flow did not differ between DD+ and DD-. CONCLUSIONS: Left atrial size and regional quantitative myocardial deformation applying CMR identified best patients with DD.

Frequency of exercise-induced ST-T-segment deviations and cardiac arrhythmias in recreational endurance athletes during a marathon race: results of the prospective observational Berlin Beat of Running study.

OBJECTIVES: While regular physical exercise has many health benefits, strenuous physical exercise may have a negative impact on cardiac function. The 'Berlin Beat of Running' study focused on feasibility and diagnostic value of continuous ECG monitoring in recreational endurance athletes during a marathon race. We hypothesised that cardiac arrhythmias and especially atrial fibrillation are frequently found in a cohort of recreational endurance athletes. The main secondary hypothesis was that pathological laboratory findings in these athletes are (in part) associated with cardiac arrhythmias. DESIGN: Prospective observational cohort study including healthy volunteers. SETTING AND PARTICIPANTS: One hundred and nine experienced marathon runners wore a portable ECG recorder during a marathon race in Berlin, Germany. Athletes underwent blood tests 2-3 days prior, directly after and 1-2 days after the race. RESULTS: Overall, 108 athletes (median 48 years (IQR 45-53), 24% women) completed the marathon in 249±43 min. Blinded ECG analysis revealed abnormal findings during the marathon in 18 (16.8%) athletes. Ten (9.3%) athletes had at least one episode of non-sustained ventricular tachycardia, one of whom had atrial fibrillation; eight (7.5%) individuals showed transient ST-T-segment deviations. Abnormal ECG findings were associated with advanced age (OR 1.11 per year, 95% CI 1.01 to 1.23), while sex and cardiovascular risk profile had no impact. Directly after the race, high-sensitive troponin T was elevated in 18 (16.7%) athletes and associated with ST-T-segment deviation (OR 9.9, 95% CI 1.9 to 51.5), while age, sex and cardiovascular risk profile had no impact. CONCLUSIONS: ECG monitoring during a marathon is feasible. Abnormal ECG findings were present in every sixth athlete. Exercise-induced transient ST-T-segment deviations were associated with elevated high-sensitive troponin T (hsTnT) values. TRIAL REGISTRATION: ClinicalTrials.gov NCT01428778; Results.

Influence of spatial resolution and contrast agent dosage on myocardial T1 relaxation times.

OBJECTIVE: Our aim was to study the influence of small variations in spatial resolution and contrast agent dosage on myocardial T1 relaxation time. MATERIALS AND METHODS: Twenty-nine healthy volunteers underwent cardiovascular magnetic resonance at 3T twice, including a modified look-locker inversion recovery (MOLLI) technique-3(3)3(3)5-for T1 mapping. Native T1 was assessed in three spatial resolutions (voxel size 1.4 × 1.4 × 6, 1.6 × 1.6 × 6, 1.7 × 1.7 × 6 mm3), and postcontrast T1 after 0.1 and 0.2 mmol/kg gadobutrol. Partition coefficient was calculated based on myocardial and blood T1. T1 analysis was done per segment, per slice, and for the whole heart. RESULTS: Native T1 values did not differ with varying spatial resolution per segment (p = 0.116-0.980), per slice (basal: p = 0.772; middle: p = 0.639; apex: p = 0.276), and globally (p = 0.191). Postcontrast T1 values were significantly lower with higher contrast agent dosage (p < 0.001). The global partition coefficient was 0.43 ± 0.3 for 0.2 and 0.1 mmol gadobutrol (p = 0.079). CONCLUSION: Related to the tested MOLLI technique at 3T, very small variations in spatial resolution (voxel sizes between 1.4 × 1.4 × 6 and 1.7 × 1.7 × 6 mm3) remained without effect on the native T1 relaxation times. Postcontrast T1 values were naturally shorter with higher contrast agent dosage while the partition coefficient remained constant. Further studies are necessary to test whether these conclusions hold true for larger matrix sizes and in larger cohorts.

High Spatial Resolution Cardiovascular Magnetic Resonance at 7.0 Tesla in Patients with Hypertrophic Cardiomyopathy - First Experiences: Lesson Learned from 7.0 Tesla.

BACKGROUND: Cardiovascular Magnetic Resonance (CMR) provides valuable information in patients with hypertrophic cardiomyopathy (HCM) based on myocardial tissue differentiation and the detection of small morphological details. CMR at 7.0T improves spatial resolution versus today's clinical protocols. This capability is as yet untapped in HCM patients. We aimed to examine the feasibility of CMR at 7.0T in HCM patients and to demonstrate its capability for the visualization of subtle morphological details. METHODS: We screened 131 patients with HCM. 13 patients (9 males, 56 ±31 years) and 13 healthy age- and gender-matched subjects (9 males, 55 ±31years) underwent CMR at 7.0T and 3.0T (Siemens, Erlangen, Germany). For the assessment of cardiac function and morphology, 2D CINE imaging was performed (voxel size at 7.0T: (1.4x1.4x2.5) mm3 and (1.4x1.4x4.0) mm3; at 3.0T: (1.8x1.8x6.0) mm3). Late gadolinium enhancement (LGE) was performed at 3.0T for detection of fibrosis. RESULTS: All scans were successful and evaluable. At 3.0T, quantification of the left ventricle (LV) showed similar results in short axis view vs. the biplane approach (LVEDV, LVESV, LVMASS, LVEF) (p = 0.286; p = 0.534; p = 0.155; p = 0.131). The LV-parameters obtained at 7.0T where in accordance with the 3.0T data (pLVEDV = 0.110; pLVESV = 0.091; pLVMASS = 0.131; pLVEF = 0.182). LGE was detectable in 12/13 (92%) of the HCM patients. High spatial resolution CINE imaging at 7.0T revealed hyperintense regions, identifying myocardial crypts in 7/13 (54%) of the HCM patients. All crypts were located in the LGE-positive regions. The crypts were not detectable at 3.0T using a clinical protocol. CONCLUSIONS: CMR at 7.0T is feasible in patients with HCM. High spatial resolution gradient echo 2D CINE imaging at 7.0T allowed the detection of subtle morphological details in regions of extended hypertrophy and LGE.

Impact of surgical correction of pectus excavatum on cardiac function: insights on the right ventricle. A cardiovascular magnetic resonance study†.

OBJECTIVES: Pectus excavatum (PE) is often regarded as a cosmetic disease, while its effect on cardiac function is under debate. Data regarding cardiac function before and after surgical correction of PE are limited. We aimed to assess the impact of surgical correction of PE on cardiac function by cardiovascular magnetic resonance (CMR). METHODS: CMR at 1.5 T was performed in 38 patients (mean age 21 ± 8.3; 31 men) before and after surgical correction to evaluate thoracic morphology, indices and its relation to three-dimensional left and right ventricular cardiac function. RESULTS: Surgery was successful in all patients as shown by the Haller Index ratio of maximum transverse diameter of the chest wall and minimum sternovertebral distance [pre: 9.64 (95% CI 8.18-11.11) vs post: 3.0 (2.84-3.16), P < 0.0001]. Right ventricular ejection fraction (RVEF) was reduced before surgery and improved significantly at the 1-year follow-up [pre: 45.7% (43.9-47.4%) vs 48.3% (46.9-49.5%), P = 0.0004]. Left ventricular ejection fraction was normal before surgery, but showed a further improvement after 1 year [pre: 61.0% (59.3-62.7%) vs 62.7% (61.3-64.2%), P = 0.0165]. Cardiac compression and the asymmetry index changed directly after surgery and were stable at the 1-year follow-up [3.93 (3.53-4.33) vs 2.08 (1.98-2.19) and 2.36 (2.12-2.59) vs 1.38 (1.33-1.44), respectively; P < 0.0001 for both]. None of the obtained thoracic indices were predictors of the improvement of cardiac function. A reduced preoperative RVEF was predictive of RVEF improvement. CONCLUSIONS: PE is associated with reduced RVEF, which improves after surgical correction. CMR has the capability of offering additional information prior to surgical correction.

Clinical effects of phosphodiesterase 3A mutations in inherited hypertension with brachydactyly.

Autosomal-dominant hypertension with brachydactyly is a salt-independent Mendelian syndrome caused by activating mutations in the gene encoding phosphodiesterase 3A. These mutations increase the protein kinase A-mediated phosphorylation of phosphodiesterase 3A resulting in enhanced cAMP-hydrolytic affinity and accelerated cell proliferation. The phosphorylated vasodilator-stimulated phosphoprotein is diminished, and parathyroid hormone-related peptide is dysregulated, potentially accounting for all phenotypic features. Untreated patients die prematurely of stroke; however, hypertension-induced target-organ damage is otherwise hardly apparent. We conducted clinical studies of vascular function, cardiac functional imaging, platelet function in affected and nonaffected persons, and cell-based assays. Large-vessel and cardiac functions indeed seem to be preserved. The platelet studies showed normal platelet function. Cell-based studies demonstrated that available phosphodiesterase 3A inhibitors suppress the mutant isoforms. However, increasing cGMP to indirectly inhibit the enzyme seemed to have particular use. Our results shed more light on phosphodiesterase 3A activation and could be relevant to the treatment of severe hypertension in the general population.

Insulin resistance in heart failure: differences between patients with reduced and preserved left ventricular ejection fraction.

AIMS: Insulin resistance (IR) is a characteristic feature of heart failure (HF) pathophysiology that affects symptoms and mortality. Differences in the pathophysiological profile of IR in HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) are not characterized in detail. The aim of this study was to evaluate features of IR in HFpEF vs. HFrEF. METHODS AND RESULTS: We included 18 patients with HFrEF (EF 30 ± 11%, body mass index (BMI) 26.5 ± 3.3 kg/m(2)), 22 HFpEF patients (EF 63 ± 7%, BMI 28.6 ± 4.8 kg/m(2)), and 20 healthy controls of similar age, all without diabetes mellitus. Patients were in stable ambulatory condition and on stable medical regimens for HF. IR was assessed at fasting steady state by the homeostasis model assessment (HOMA) index and within the physiological range of insulin-glucose interactions by the short insulin sensitivity test (SIST). Fasting-state IR was observed in HFpEF and in HFrEF in comparison with controls (HOMA 1.9, interquartile range (IQR) 1.5-3.6 vs. HOMA 3.1, IQR 1.4-3.7 vs. controls 1.2, IQR 1.8-0.9, respectively; analysis of variance P < 0.001), but no statistical difference was observed between HFpEF and HFrEF. The dynamic test over the physiological range of insulin-glucose interactions revealed a more severe IR in HFrEF as compared with HFpEF. Thus, glucose levels remained the highest in HFrEF (76 (64-89) mg/dL) at the end of the SIST compared with HFpEF and controls (68 (58-79) and 56 (44-66) mg/dL, respectively, P < 0.001). CONCLUSION: IR is present in non-diabetic patients with HFpEF and HFrEF. However, distinct differences in the insulin sensitivity characteristics in HFpEF and HFrEF become apparent by more advanced testing. Patients with HFrEF showed more severe IR.

Self-rated health predicts adverse events during ß-blocker treatment: the CIBIS-ELD randomised trial analysis.

BACKGROUND: Self-rated health (SRH) predicts outcome in patients with heart failure. Beta-blockers are known to improve health-related quality of life and reduce mortality in such patients. We aimed to evaluate the relation between SRH and adverse events during titration of beta-blockers in elderly patients with heart failure. METHODS: The cardiac insufficiency bisoprolol study in the elderly (CIBIS-ELD) is a multicentre, double-blind trial, in which 883 patients aged ≥ 65 years with chronic heart failure (73 ± 6 years, 38% women, left ventricular ejection fraction [LVEF] 42% ± 14%) were randomised to bisoprolol or carvedilol. SRH was assessed at baseline and after 12 weeks, using a 5-grade descriptive scale: excellent, very good, good, fair, and poor. RESULTS: Median SRH at baseline and follow-up was good, but more patients reported fair/poor SRH at baseline (36% vs. 30%, p = 0.012). Women, beta-blocker-naïve patients, patients in NYHA class III/IV and those with PHQ-9 score ≥ 12 were more likely to report fair/poor baseline SRH (p < 0.001 for all). During follow-up, SRH improved in 34% of patients and worsened in 8% (p < 0.001). Adverse events were experienced by 64% patients and 38% experienced > 1 adverse event or serious adverse event, with higher prevalence in lower SRH categories. In a multivariate logistic regression model, SRH, age, distance achieved on the 6-min walk test and LVEF >45% predicted adverse events (p < 0.05 for all). CONCLUSIONS: SRH is an independent predictor of adverse events during titration of beta-blockers and correlates with the proportion and number of adverse events per patient.

Exercise training improves exercise capacity and diastolic function in patients with heart failure with preserved ejection fraction: results of the Ex-DHF (Exercise training in Diastolic Heart Failure) pilot study.

OBJECTIVES: We sought to determine whether structured exercise training (ET) improves maximal exercise capacity, left ventricular diastolic function, and quality of life (QoL) in patients with heart failure with preserved ejection fraction (HFpEF). BACKGROUND: Nearly one-half of patients with heart failure experience HFpEF, but effective therapeutic strategies are sparse. METHODS: A total of 64 patients (age 65 ± 7 years, 56% female) with HFpEF were prospectively randomized (2:1) to supervised endurance/resistance training in addition to usual care (ET, n = 44) or to usual care alone (UC) (n = 20). The primary endpoint was the change in peak Vo(2) after 3 months. Secondary endpoints included effects on cardiac structure, diastolic function, and QoL. RESULTS: Peak Vo(2) increased (16.1 ± 4.9 ml/min/kg to 18.7 ± 5.4 ml/min/kg; p < 0.001) with ET and remained unchanged (16.7 ± 4.7 ml/min/kg to 16.0 ± 6.0 ml/min/kg; p = NS) with UC. The mean benefit of ET was 3.3 ml/min/kg (95% confidence interval [CI]: 1.8 to 4.8, p < 0.001). E/e' (mean difference of changes: -3.2, 95% CI: -4.3 to -2.1, p < 0.001) and left atrial volume index (milliliters per square meter) decreased with ET and remained unchanged with UC (-4.0, 95% CI: -5.9 to -2.2, p < 0.001). The physical functioning score (36-Item Short-Form Health Survey) improved with ET and remained unchanged with UC (15, 95% CI: 7 to 24, p < 0.001). The ET-induced decrease of E/e' was associated with 38% gain in peak Vo(2) and 50% of the improvement in physical functioning score. CONCLUSIONS: Exercise training improves exercise capacity and physical dimensions of QoL in HFpEF. This benefit is associated with atrial reverse remodeling and improved left ventricular diastolic function. (Exercise Training in Diastolic Heart Failure-Pilot Study: A Prospective, Randomised, Controlled Study to Determine the Effects of Physical Training on Exercise Capacity and Quality of Life [Ex-DHF-P]; ISRCTN42524037).

Titration to target dose of bisoprolol vs. carvedilol in elderly patients with heart failure: the CIBIS-ELD trial.

AIMS: Various beta-blockers with distinct pharmacological profiles are approved in heart failure, yet they remain underused and underdosed. Although potentially of major public health importance, whether one agent is superior in terms of tolerability and optimal dosing has not been investigated. The aim of this study was therefore to compare the tolerability and clinical effects of two proven beta-blockers in elderly patients with heart failure. METHODS AND RESULTS: We performed a double-blind superiority trial of bisoprolol vs. carvedilol in 883 elderly heart failure patients with reduced or preserved left ventricular ejection fraction in 41 European centres. The primary endpoint was tolerability, defined as reaching and maintaining guideline-recommended target doses after 12 weeks treatment. Adverse events and clinical parameters of patient status were secondary endpoints. None of the beta-blockers was superior with regards to tolerability: 24% [95% confidence interval (CI) 20-28] of patients in the bisoprolol arm and 25% (95% CI 21-29) of patients in the carvedilol arm achieved the primary endpoint (P= 0.64). The use of bisoprolol resulted in greater reduction of heart rate (adjusted mean difference 2.1 b.p.m., 95% CI 0.5-3.6, P= 0.008) and more, dose-limiting, bradycardic adverse events (16 vs. 11%; P= 0.02). The use of carvedilol led to a reduction of forced expiratory volume (adjusted mean difference 50 mL, 95% CI 4-95, P= 0.03) and more, non-dose-limiting, pulmonary adverse events (10 vs. 4%; P < 0.001). CONCLUSION: Overall tolerability to target doses was comparable. The pattern of intolerance, however, was different: bradycardia occurred more often in the bisoprolol group, whereas pulmonary adverse events occurred more often in the carvedilol group. This study is registered with controlled-trials.com, number ISRCTN34827306.