Quantitative metrics of the LV trabeculated layer by cardiac CT and cardiac MRI in patients with suspected noncompaction cardiomyopathy.

OBJECTIVES: To compare cardiac computed tomography (CCT) and cardiac magnetic resonance (CMR) for the quantitative assessment of the left ventricular (LV) trabeculated layer in patients with suspected noncompaction cardiomyopathy (NCCM). MATERIALS AND METHODS: Subjects with LV excessive trabeculation who underwent both CMR and CCT imaging as part of the prospective international multicenter NONCOMPACT clinical study were included. For each subject, short-axis CCT and CMR slices were matched. Four quantitative metrics were estimated: 1D noncompacted-to-compacted ratio (NCC), trabecular-to-myocardial area ratio (TMA), trabecular-to-endocardial cavity area ratio (TCA), and trabecular-to-myocardial volume ratio (TMV). In 20 subjects, end-diastolic and mid-diastolic CCT images were compared for the quantification of the trabeculated layer. Relationships between the metrics were investigated using linear regression models and Bland-Altman analyses. RESULTS: Forty-eight subjects (49.9 ± 12.8 years; 28 female) were included in this study. NCC was moderately correlated (r = 0.62), TMA and TMV were strongly correlated (r = 0.78 and 0.78), and TCA had excellent correlation (r = 0.92) between CMR and CCT, with an underestimation bias from CCT of 0.3 units, and 5.1, 4.8, and 5.4 percent-points for the 4 metrics, respectively. TMA, TCA, and TMV had excellent correlations (r = 0.93, 0.96, 0.94) and low biases (- 3.8, 0.8, - 3.8 percent-points) between the end-diastolic and mid-diastolic CCT images. CONCLUSIONS: TMA, TCA, and TMV metrics of the LV trabeculated layer in patients with suspected NCCM demonstrated high concordance between CCT and CMR images. TMA and TCA were highly reproducible and demonstrated minimal differences between mid-diastolic and end-diastolic CCT images. CLINICAL RELEVANCE STATEMENT: The results indicate similarity of CCT to CMR for quantifying the LV trabeculated layer, and the small differences in quantification between end-diastole and mid-diastole demonstrate the potential for quantifying the LV trabeculated layer from clinically performed coronary CT angiograms. KEY POINTS: • Data on cardiac CT for quantifying the left ventricular trabeculated layer are limited. • Cardiac CT yielded highly reproducible metrics of the left ventricular trabeculated layer that correlated well with metrics defined by cardiac MR. • Cardiac CT appears to be equivalent to cardiac MR for the quantification of the left ventricular trabeculated layer.

Coronary calcium scoring on virtual non-contrast and virtual non-iodine reconstructions compared to true non-contrast images using photon-counting computed tomography.

OBJECTIVES: To compare coronary artery calcification (CAC) scores measured on virtual non-contrast (VNC) and virtual non-iodine (VNI) reconstructions computed from coronary computed tomography angiography (CCTA) using photon-counting computed tomography (PCCT) to true non-contrast (TNC) images. METHODS: We included 88 patients (mean age = 59 years ± 13.5, 69% male) who underwent a TNC coronary calcium scan followed by CCTA on PCCT. VNC images were reconstructed in 87 patients and VNI in 88 patients by virtually removing iodine from the CCTA images. For all reconstructions, CAC scores were determined, and patients were classified into risk categories. The overall agreement of the reconstructions was analyzed by Bland-Altman plots and the level of matching classifications. RESULTS: The median CAC score on TNC was 27.8 [0-360.4] compared to 8.5 [0.2-101.6] (p < 0.001) on VNC and 72.2 [1.3-398.8] (p < 0.001) on VNI. Bland-Altman plots depicted a bias of 148.8 (ICC = 0.82, p < 0.001) and - 57.7 (ICC = 0.95, p < 0.001) for VNC and VNI, respectively. Of all patients with CACTNC = 0, VNC reconstructions scored 63% of the patients correctly, while VNI scored 54% correctly. Of the patients with CACTNC > 0, VNC and VNI reconstructions detected the presence of coronary calcium in 90% and 92% of the patients. CACVNC tended to underestimate CAC score, whereas CACVNI overestimated, especially in the lower risk categories. According to the risk categories, VNC misclassified 55% of the patients, while VNI misclassified only 32%. CONCLUSION: Compared to TNC images, VNC underestimated and VNI overestimated the actual CAC scores. VNI reconstructions quantify and classify coronary calcification scores more accurately than VNC reconstructions. CLINICAL RELEVANCE STATEMENT: Photon-counting CT enables spectral imaging, which might obviate the need for non-contrast enhanced coronary calcium scoring, but optimization is necessary for the clinical implementation of the algorithms. KEY POINTS: • Photon-counting computed tomography uses spectral information to virtually remove the signal of contrast agents from contrast-enhanced scans. • Virtual non-contrast reconstructions tend to underestimate coronary artery calcium scores compared to true non-contrast images, while virtual non-iodine reconstructions tend to overestimate the calcium scores. • Virtual non-iodine reconstructions might obviate the need for non-contrast enhanced calcium scoring, but optimization is necessary for the clinical implementation of the algorithms.

Gestational hypertensive disorders and blood pressure and childhood cardiac outcomes: A prospective cohort study.

OBJECTIVE: To assess whether gestational hypertensive disorders and higher gestational blood pressure were associated with subclinical changes in offspring cardiac structure and function during childhood. DESIGN: Population-based prospective cohort study. SETTING: Rotterdam, the Netherlands. POPULATION: A cohort of 2502 mother-offspring pairs. METHODS: Maternal blood pressure was measured in early, mid and late pregnancy, and information on gestational disorders were obtained from medical records. Offspring cardiac measurements were assessed by Cardiovascular Magnetic Resonance at 10 years. MAIN OUTCOME MEASURES: Left and right ventricular end-diastolic volumes (LVEDVs and RVEDVs), and ejection fractions, and left ventricular mass (LVM). RESULTS: Offspring exposed to pre-eclampsia had a lower right ventricular ejection fraction (RVEF) (difference, -0.31 SDS; 95% CI -0.60, -0.02); however, no associations with other cardiac outcomes were present. Higher maternal diastolic blood pressure (DBP) in early and late pregnancy was associated with lower LVEDVs and RVEDVs (p < 0.05), with the strongest effect in early pregnancy. No associations of systolic blood pressure (SBP) with offspring outcomes were present. These associations persisted after additional adjustment for birth and child factors. Paternal SBP and DBP were not associated with offspring cardiac outcomes. CONCLUSIONS: No consistent associations of gestational hypertensive disorder status with childhood cardiac outcomes were present. Higher maternal DBP throughout pregnancy was associated with lower childhood LVEDVs and RVEDVs. Stronger maternal-offspring rather than paternal-offspring associations were present, which may suggest that suboptimal maternal gestational haemodynamic adaptations affects offspring cardiac structure through direct intrauterine effects. Further studies are needed to replicate these findings and examine the underlying mechanisms.

Exercise and hypoxia unmask pulmonary vascular disease and right ventricular dysfunction in a 10- to 12-week-old swine model of neonatal oxidative injury.

Prematurely born young adults who experienced neonatal oxidative injury (NOI) of the lungs have increased incidence of cardiovascular disease. Here, we investigated the long-term effects of NOI on cardiopulmonary function in piglets at the age of 10-12 weeks. To induce NOI, term-born piglets (1.81 ± 0.06 kg) were exposed to hypoxia (10-12% F iO 2 ${F}_{{\rm{iO}}_{\rm{2}}}$ ), within 2 days after birth, and maintained for 4 weeks or until symptoms of heart failure developed (range 16-28 days), while SHAM piglets were normoxia raised. Following recovery (>5 weeks), NOI piglets were surgically instrumented to measure haemodynamics during hypoxic challenge testing (HCT) and exercise with modulation of the nitric-oxide system. During exercise, NOI piglets showed a normal increase in cardiac index, but an exaggerated increase in pulmonary artery pressure and a blunted increase in left atrial pressure - suggesting left atrial under-filling - consistent with an elevated pulmonary vascular resistance (PVR), which correlated with the duration of hypoxia exposure. Moreover, hypoxia duration correlated inversely with stroke volume (SV) during exercise. Nitric oxide synthase inhibition and HCT resulted in an exaggerated increase in PVR, while the PVR reduction by phosphodiesterase-5 inhibition was enhanced in NOI compared to SHAM piglets. Finally, within the NOI piglet group, prolonged duration of hypoxia was associated with a better maintenance of SV during HCT, likely due to the increase in RV mass. In conclusion, duration of neonatal hypoxia appears an important determinant of alterations in cardiopulmonary function that persist further into life. These changes encompass both pulmonary vascular and cardiac responses to hypoxia and exercise. KEY POINTS: Children who suffered from neonatal oxidative injury, such as very preterm born infants, have increased risk of cardiopulmonary disease later in life. Risk stratification requires knowledge of the mechanistic underpinning and the time course of progression into cardiopulmonary disease. Exercise and hypoxic challenge testing showed that 10- to 12-week-old swine that previously experienced neonatal oxidative injury had increased pulmonary vascular resistance and nitric oxide dependency. Duration of neonatal oxidative injury was a determinant of structural and functional cardiopulmonary remodelling later in life. Remodelling of the right ventricle, as a result of prolonged neonatal oxidative injury, resulted in worse performance during exercise, but enabled better performance during the hypoxic challenge test. Increased nitric oxide dependency together with age- or comorbidity-related endothelial dysfunction may contribute to predisposition to pulmonary hypertension later in life.

CT-derived fractional flow reserve (FFRct) for functional coronary artery evaluation in the follow-up of patients after heart transplantation.

OBJECTIVES: Invasively measured fractional flow reserve (FFR) is associated with outcome in heart transplant (HTx) patients. Coronary computed tomography angiography (CCTA)-derived FFR (FFRct) provides additional functional information from anatomical CT images. We describe the first use of FFRct in HTx patients. METHODS: HTx patients underwent CCTA with FFRct to screen for cardiac allograft vasculopathy. FFRct was measured distal to each coronary stenosis > 30% and FFRct ≤ 0.8 indicated hemodynamically significant stenosis. FFRct was also measured at the most distal location of each vessel. Overall distal FFRct was calculated as the mean of the distal values in the left, right, and circumflex coronary artery in each patient. RESULTS: Seventy-three patients (age 56 (42-65) years, 63% males) at 11 (8-16) years after HTx were included. Eighteen (25%) patients had a focal hemodynamically significant stenosis (stenosis > 30% with FFRct ≤ 0.8). In the 55 patients without a hemodynamically significant focal FFRct stenosis (FFRct > 0.80), the distal left anterior descending artery FFRct was < 0.90 in 74% of the patients and 10 (18%) patients had ≥ 1 coronary artery with a distal FFRct ≤ 0.8, including 1 with a distal FFRct ≤ 0.8 in all coronaries. Overall distal FFRct in patients without focal stenosis was 0.88 (0.86-0.91), 0.87 (0.86-0.90), and 0.88 (0.86-0.91) (median with 25th-75th percentile) at 5-9, 10-14, or ≥ 15 years post-transplantation, respectively (p = 0.93). CONCLUSIONS: FFRct performed on CCTA scans of HTx patients demonstrated that 25% of patients had a focal coronary stenosis with FFRct ≤ 0.8. Even without a focal stenosis, FFRct values are often abnormal in HTx patients. KEY POINTS: • This is the first report describing the use of FFRct in in heart transplant patients. • FFRct identifies patients after heart transplantation with hemodynamically significant coronary stenosis. • Even without a focal stenosis, FFRct values are often abnormal in heart transplant patients.

Prognostic significance of left atrial strain in sarcomere gene variant carriers without hypertrophic cardiomyopathy.

BACKGROUND: Genetic testing of relatives of hypertrophic cardiomyopathy (HCM) patients has led to a large group of genotype-positive, phenotype-negative (G+/Ph-) subjects. Prediction of progression to overt HCM in these subjects is challenging. While left atrial (LA) strain is reduced in HCM patients it is currently unknown whether this parameter can be used to predict HCM phenotype progression. METHODS: This study includes 91 G+/Ph- subjects and 115 controls. Standard echocardiographic parameters as well as left ventricular global longitudinal strain (LV GLS) and LA reservoir strain (LASr) were assessed for each patient. Logistic and Cox proportional hazard regression analyses were used to investigate predictors of G+/Ph- status and HCM during follow-up. RESULTS: Independent predictors of G+ status included pathological Q waves (OR 1.60 [1.15-2.23], p < .01), maximal wall thickness (MWT: OR 1.10 [1.07-1.14], p < .001), mitral inflow E wave (OR 1.06 [1.02-1.10, p = .001), A wave (OR 1.06 [1.03-1.10], p < .001), LV GLS (OR .96 [.94-.98], p < .001), and LASr (OR .99 [.97-.99], p = .03). In univariable Cox regression analysis, male sex (HR 2.78 [1.06-7.29], p = .04), MWT (HR 1.72 [1.14-2.57], p = .009) and posterior wall thickness (HR 1.65 [1.17-2.30], p = .004) predicted HCM during a median follow-up of 5.9 [3.2-8.6] years, whereas LASr did not (HR .95 [.89-1.02], p = .14). There were no significant predictors of HCM after multivariable adjustment. CONCLUSION: LASr is significantly impaired in G+/Ph- subjects and is an independent predictor of G+/Ph- status, but did not predict HCM development during follow-up.

Impaired pulmonary vasomotor control in exercising swine with multiple comorbidities.

Pulmonary hypertension is common in heart failure with preserved ejection fraction (HFpEF). Here, we tested the hypothesis that comorbidities [diabetes mellitus (DM, streptozotocin), hypercholesterolemia (HC, high-fat diet) and chronic kidney disease (CKD, renal microembolization)] directly impair pulmonary vasomotor control in a DM + HC + CKD swine model. 6 months after induction of DM + HC + CKD, pulmonary arterial pressure was similar in chronically instrumented female DM + HC + CKD (n = 19) and Healthy swine (n = 18). However, cardiac output was lower both at rest and during exercise, implying an elevated pulmonary vascular resistance (PVR) in DM + HC + CKD swine (153 ± 10 vs. 122 ± 9 mmHg∙L-1∙min∙kg). Phosphodiesterase 5 inhibition and endothelin receptor antagonism decreased PVR in DM + HC + CKD (- 12 ± 12 and - 22 ± 7 mmHg∙L-1∙min∙kg) but not in Healthy swine (- 1 ± 12 and 2 ± 14 mmHg∙L-1∙min∙kg), indicating increased vasoconstrictor influences of phosphodiesterase 5 and endothelin. Inhibition of nitric oxide synthase produced pulmonary vasoconstriction that was similar in Healthy and DM + HC + CKD swine, but unmasked a pulmonary vasodilator effect of endothelin receptor antagonism in Healthy (- 56 ± 26 mmHg∙L-1∙min∙kg), whereas it failed to significantly decrease PVR in DM + HC + CKD, indicating loss of nitric oxide mediated inhibition of endothelin in DM + HC + CKD. Scavenging of reactive oxygen species (ROS) had no effect on PVR in either Healthy or DM + HC + CKD swine. Cardiovascular magnetic resonance imaging, under anesthesia, showed no right ventricular changes. Finally, despite an increased contribution of endogenous nitric oxide to vasomotor tone regulation in the systemic vasculature, systemic vascular resistance at rest was higher in DM + HC + CKD compared to Healthy swine (824 ± 41 vs. 698 ± 35 mmHg∙L-1∙min∙kg). ROS scavenging induced systemic vasodilation in DM + HC + CKD, but not Healthy swine. In conclusion, common comorbidities directly alter pulmonary vascular control, by enhanced PDE5 and endothelin-mediated vasoconstrictor influences, well before overt left ventricular backward failure or pulmonary hypertension develop.

Improvement of late gadolinium enhancement image quality using a deep learning-based reconstruction algorithm and its influence on myocardial scar quantification.

OBJECTIVES: The aim of this study was to assess the effect of a deep learning (DL)-based reconstruction algorithm on late gadolinium enhancement (LGE) image quality and to evaluate its influence on scar quantification. METHODS: Sixty patients (46 ± 17 years, 50% male) with suspected or known cardiomyopathy underwent CMR. Short-axis LGE images were reconstructed using the conventional reconstruction and a DL network (DLRecon) with tunable noise reduction (NR) levels from 0 to 100%. Image quality of standard LGE images and DLRecon images with 75% NR was scored using a 5-point scale (poor to excellent). In 30 patients with LGE, scar size was quantified using thresholding techniques with different standard deviations (SD) above remote myocardium, and using full width at half maximum (FWHM) technique in images with varying NR levels. RESULTS: DLRecon images were of higher quality than standard LGE images (subjective quality score 3.3 ± 0.5 vs. 3.6 ± 0.7, p < 0.001). Scar size increased with increasing NR levels using the SD methods. With 100% NR level, scar size increased 36%, 87%, and 138% using 2SD, 4SD, and 6SD quantification method, respectively, compared to standard LGE images (all p values < 0.001). However, with the FWHM method, no differences in scar size were found (p = 0.06). CONCLUSIONS: LGE image quality improved significantly using a DL-based reconstruction algorithm. However, this algorithm has an important impact on scar quantification depending on which quantification technique is used. The FWHM method is preferred because of its independency of NR. Clinicians should be aware of this impact on scar quantification, as DL-based reconstruction algorithms are being used. KEY POINTS: • The image quality based on (subjective) visual assessment and image sharpness of late gadolinium enhancement images improved significantly using a deep learning-based reconstruction algorithm that aims to reconstruct high signal-to-noise images using a denoising technique. • Special care should be taken when scar size is quantified using thresholding techniques with different standard deviations above remote myocardium because of the large impact of these advanced image enhancement algorithms. • The full width at half maximum method is recommended to quantify scar size when deep learning algorithms based on noise reduction are used, as this method is the least sensitive to the level of noise and showed the best agreement with visual late gadolinium enhancement assessment.

Clinical implementation of coronary computed tomography angiography for routine detection of cardiac allograft vasculopathy in heart transplant patients.

Cardiac allograft vasculopathy (CAV) is an accelerated form of coronary artery disease that affects long-term outcomes in heart transplant (HTx) patients. We prospectively evaluated the feasibility of coronary computed tomography angiography (CCTA) for the detection of CAV during clinical implementation at our center. All consecutive HTx patients >4 years post-transplant were actively converted from myocardial perfusion imaging to CCTA for the annual assessment of CAV. Between February 2018 and May 2019, 129/172 (75%) HTx patients underwent a CCTA. Renal impairment (n = 21/43) was the most frequent reason for patients could not undergo CCTA. CCTA image quality was good-excellent in 118/129 (92%) patients, and the radiation dose was 2.1 (1.6-2.8) mSv. CCTA showed obstructive CAV in 19/129 (15%) patients. Thirteen (10%) patients underwent additional tests, of which 8 patients underwent coronary revascularization within 90 days of CCTA. After 1 year, 3 additional coronary angiograms were performed, resulting in one revascularization in a patient with known severe CAV who developed ventricular tachycardia. One myocardial infarction after coronary stenting and 2 non-cardiac deaths were observed. CCTA can be successfully implemented for routine detection of CAV with good image quality and low radiation dose. CCTA allows CAV evaluation with the limited need for additional invasive testing.

Evaluation of intraventricular flow by multimodality imaging: a review and meta-analysis.

BACKGROUND: The aim of this systematic review was to evaluate current inter-modality agreement of noninvasive clinical intraventricular flow (IVF) assessment with 3 emerging imaging modalities: echocardiographic particle image velocimetry (EPIV), vector flow mapping (VFM), and 4-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR). METHODS: We performed a systematic literature review in the databases EMBASE, Medline OVID and Cochrane Central for identification of studies evaluating left ventricular (LV) flow patterns using one of these flow visualization modalities. Of the 2224 initially retrieved records, 10 EPIV, 23 VFM, and 25 4D flow CMR studies were included in the final analysis. RESULTS: Vortex parameters were more extensively studied with EPIV, while LV energetics and LV transport mechanics were mainly studied with 4D flow CMR, and LV energy loss and vortex circulation were implemented by VFM studies. Pooled normative values are provided for these parameters. The meta- analysis for the values of two vortex morphology parameters, vortex length and vortex depth, failed to reveal a significant change between heart failure patients and healthy controls. CONCLUSION: Agreement between the different modalities studying intraventricular flow is low and different methods of measurement and reporting were used among studies. A multimodality framework with a standardized set of flow parameters is necessary for implementation of noninvasive flow visualization in daily clinical practice. The full potential of noninvasive flow visualization in addition to diagnostics could also include guiding medical or interventional treatment.

Recovery and prognostic value of myocardial strain in ST-segment elevation myocardial infarction patients with a concurrent chronic total occlusion.

OBJECTIVES: Global left ventricular (LV) function is routinely used to assess cardiac function; however, myocardial strain is able to identify more subtle dysfunction. We aimed to determine the recovery and prognostic value of featuring tracking (FT) cardiovascular magnetic resonance (CMR) strain in ST-segment elevation myocardial infarction (STEMI) patients with a concurrent chronic total occlusion (CTO). METHODS: In the randomized EXPLORE trial, there was no significant difference in global LV function after percutaneous coronary intervention (PCI) of the CTO, compared with no-CTO PCI, post-STEMI. In the current study, we included 200 of the 302 EXPLORE patients with a baseline CMR, of which 180 also had 4-month follow-up (serial) CMR. Global longitudinal strain (GLS) was calculated from 3 long-axis views. Global circumferential strain (GCS) and segmental strain were calculated from 3 short-axis views (basal, mid, and apical). RESULTS: Global strain significantly improved at 4 months (GLS ∆ - 1.8 ± 4.3%, p < 0.001; GCS ∆ - 1.7 ± 4.7%, p < 0.001); however, there was no treatment effect of CTO-PCI on strain recovery. GLS was a significant predictor for 4 months of LV ejection fraction (p = 0.006), incremental to other CMR parameters including infarct size. For mortality, infarct size remained the strongest predictor. On regional level, segmental strain independently predicted recovery in the dysfunctional segments (p < 0.001). CONCLUSIONS: Global and segmental myocardial strains significantly improved over time, with no effect of CTO-PCI. Global strain was associated with outcome and segmental strain was an independent predictor for regional LV recovery in the dysfunctional CTO territory. Further research is needed to determine the additional prognostic value of strain beyond routine CMR parameters. KEY POINTS: • In STEMI patients with a concurrent CTO, strain significantly improves over time, regardless of CTO-PCI. • Global strain is an independent predictor for functional recovery, incremental to infarct size, LVEF, and clinical parameters. • Segmental strain was able to predict the recovery of wall thickening, incremental to transmural extent of infarction.

The clinical impact of phase offset errors and different correction methods in cardiovascular magnetic resonance phase contrast imaging: a multi-scanner study.

BACKGROUND: Cardiovascular magnetic resonance (CMR) phase contrast (PC) flow measurements suffer from phase offset errors. Background subtraction based on stationary phantom measurements can most reliably be used to overcome this inaccuracy. Stationary tissue correction is an alternative and does not require additional phantom scanning. The aim of this study was 1) to compare measurements with and without stationary tissue correction to phantom corrected measurements on different GE Healthcare CMR scanners using different software packages and 2) to evaluate the clinical implications of these methods. METHODS: CMR PC imaging of both the aortic and pulmonary artery flow was performed in patients on three different 1.5 T CMR scanners (GE Healthcare) using identical scan parameters. Uncorrected, first, second and third order stationary tissue corrected flow measurement were compared to phantom corrected flow measurements, our reference method, using Medis QFlow, Circle cvi42 and MASS software. The optimal (optimized) stationary tissue order was determined per scanner and software program. Velocity offsets, net flow, clinically significant difference (deviation > 10% net flow), and regurgitation severity were assessed. RESULTS: Data from 175 patients (28 (17-38) years) were included, of which 84% had congenital heart disease. First, second and third order and optimized stationary tissue correction did not improve the velocity offsets and net flow measurements. Uncorrected measurements resulted in the least clinically significant differences in net flow compared to phantom corrected data. Optimized stationary tissue correction per scanner and software program resulted in net flow differences (> 10%) in 19% (MASS) and 30% (Circle cvi42) of all measurements compared to 18% (MASS) and 23% (Circle cvi42) with no correction. Compared to phantom correction, regurgitation reclassification was the least common using uncorrected data. One CMR scanner performed worse and significant net flow differences of > 10% were present both with and without stationary tissue correction in more than 30% of all measurements. CONCLUSION: Phase offset errors had a significant impact on net flow quantification, regurgitation assessment and varied greatly between CMR scanners. Background phase correction using stationary tissue correction worsened accuracy compared to no correction on three GE Healthcare CMR scanners. Therefore, careful assessment of phase offset errors at each individual scanner is essential to determine whether routine use of phantom correction is necessary. TRIAL REGISTRATION: Observational Study.

Cardiac remodelling in a swine model of chronic thromboembolic pulmonary hypertension: comparison of right vs. left ventricle.

KEY POINTS: Right ventricle (RV) function is the most important determinant of survival and quality of life in patients with chronic thromboembolic pulmonary hypertension (CTEPH). The changes in right and left ventricle gene expression that contribute to ventricular remodelling are incompletely investigated. RV remodelling in our CTEPH swine model is associated with increased expression of the genes involved in inflammation (TGFß), oxidative stress (ROCK2, NOX1 and NOX4), and apoptosis (BCL2 and caspase-3). Alterations in ROCK2 expression correlated inversely with RV contractile reserve during exercise. Since ROCK2 has been shown to be involved in hypertrophy, oxidative stress, fibrosis and endothelial dysfunction, ROCK2 inhibition may present a viable therapeutic target in CTEPH. ABSTRACT: Right ventricle (RV) function is the most important determinant of survival and quality of life in patients with chronic thromboembolic pulmonary hypertension (CTEPH). The present study investigated whether the increased cardiac afterload is associated with (i) cardiac remodelling and hypertrophic signalling; (ii) changes in angiogenic factors and capillary density; and (iii) inflammatory changes associated with oxidative stress and interstitial fibrosis. CTEPH was induced in eight chronically instrumented swine by chronic nitric oxide synthase inhibition and up to five weekly pulmonary embolizations. Nine healthy swine served as a control. After 9 weeks, RV function was assessed by single beat analysis of RV-pulmonary artery (PA) coupling at rest and during exercise, as well as by cardiac magnetic resonance imaging. Subsequently, the heart was excised and RV and left ventricle (LV) tissues were processed for molecular and histological analyses. Swine with CTEPH exhibited significant RV hypertrophy in response to the elevated PA pressure. RV-PA coupling was significantly reduced, correlated inversely with pulmonary vascular resistance and did not increase during exercise in CTEPH swine. Expression of genes associated with hypertrophy (BNP), inflammation (TGFß), oxidative stress (ROCK2, NOX1 and NOX4), apoptosis (BCL2 and caspase-3) and angiogenesis (VEGFA) were increased in the RV of CTEPH swine and correlated inversely with RV-PA coupling during exercise. In the LV, only significant changes in ROCK2 gene-expression occurred. In conclusion, RV remodelling in our CTEPH swine model is associated with increased expression of genes involved in inflammation and oxidative stress, suggesting that these processes contribute to RV remodelling and dysfunction in CTEPH and hence represent potential therapeutic targets.

Estimating Risk of Pneumonia in a Prospective Emergency Department Cohort.

OBJECTIVE: To improve the prediction of pediatric pneumonia by developing a series of models based on clinically distinct subgroups. We hypothesized that these subgroup models would provide superior estimates of pneumonia risk compared with a single pediatric model. STUDY DESIGN: We conducted a secondary analysis of a prospective cohort being evaluated for radiographic pneumonia in an urban pediatric emergency department (ED). Using multivariate modeling, we created 4 models across subgroups stratified by age and presence of wheezing to predict the risk of pneumonia. RESULTS: A total of 2351 patients were included in the study. In this series, the prevalence of pneumonia was 8.5%, and 21.6% were hospitalized. The highest prevalence of pneumonia was in children aged >2 years without wheezing (13.3%). Children aged <2 years with wheezing had the lowest prevalence of pneumonia (4.0%). The most accurate model was for children aged <2 years with wheezing (area under the curve [AUC], 0.80), and the poorest performing model was for those aged <2 years without wheezing (AUC, 0.64). The AUC of a combination of the 4 subgroup models was 0.76 (95% CI, 0.72-0.80). The precision of the models' estimates (expected vs observed) was ± 3.7%. CONCLUSIONS: Using 4 complementary prediction models for pediatric pneumonia, an accurate risk of pneumonia can be calculated. These models can provide the basis for clinical decision making support to guide the use of chest radiographs and promote antibiotic stewardship.

Myocardial fibrosis predicts adverse outcome after MitraClip implantation.

BACKGROUND: High-risk patients with mitral regurgitation (MR) may be treated by a percutaneous mitral valve repair with the MitraClip, but identification of patients who may benefit remains difficult. We aimed to determine whether myocardial fibrosis predicts outcome in MR patients undergoing MitraClip implantation and is beneficial in clinical decision making. METHODS: Preprocedural to the MitraClip implantation, myocardial fibrosis was analyzed with cardiovascular magnetic resonance (CMR) through late gadolinium enhancement. The CMR data were core-lab adjudicated measured before the MitraClip implantation. Adverse outcome was defined as New York Heart Association (NYHA) class III or IV after 1 month or death within 1 month after the MitraClip implantation. RESULTS: In total, 23 patients underwent preprocedural CMR, mean age 80 ± 9 years, 45% male, 64% atrial fibrillation and 73% NYHA class III or IV at baseline. Myocardial fibrosis was present in 55% of the patients with degenerative MR and in 64% of the patients with functional MR. An adverse outcome occurred in 69% of the patients with myocardial fibrosis and in 11% of the patients without myocardial fibrosis (P = 0.01). CONCLUSIONS: Our hypothesis-generating study showed that the presence of myocardial fibrosis predicts adverse outcome in patients undergoing MitraClip implantation. After confirmation with larger sample size, identification of myocardial fibrosis might contribute to assess prognosis and to clinical decision making.

Behavioral Economic Purchase Tasks to Estimate Demand for Novel Nicotine/tobacco Products and Prospectively Predict Future Use: Evidence From The Netherlands.

INTRODUCTION: The demand for alternative nicotine/tobacco products is not well established. This paper uses a behavioral economic approach to test whether smokers have differential demand for conventional factory-made, electronic, and very low nicotine content cigarettes (FMCs/ECs/VLNCs) and uses the prospective cohort design to test the predictive validity of demand indices on subsequent use of commercially available FMCs and ECs. METHODS: Daily smokers (≥16 years) from the Netherlands completed an online survey in April 2014 (N = 1215). Purchase tasks were completed for FMCs, ECs, and VLNCs. Participants indicated the number of cigarettes they would consume in 24 h, across a range of prices (0-30 euro). The relationship between consumption and price was quantified into four indices of demand (intensity, Pmax, breakpoint, and essential value). A follow-up survey in July 2015 measured FMC and EC use. RESULTS: At baseline, greater demand was observed for FMCs relative to ECs and VLNCs across all demand indices, with no difference between ECs and VLNCs. At follow-up, greater baseline FMC demand (intensity, essential value) was associated with lower quit rates and higher relapse. EC demand (Pmax, breakpoint, essential value) was positively associated with any EC use between survey waves, past 30 day EC use, and EC purchase between waves. CONCLUSIONS: Smokers valued FMCs more than ECs or VLNCs, and FMCs were less sensitive to price increases. Demand indices predicted use of commercially available products over a 15 month period. To serve as viable substitutes for FMCs, ECs and VLNCs will need to be priced lower than FMCs. IMPLICATIONS: Purchase tasks can be adapted for novel nicotine/tobacco products as a means to efficiently quantify demand and predict use. Among current daily smokers, the demand for ECs and VLNCs is lower than FMCs.

Multiplane/3D transesophageal echocardiography monitoring to improve the safety and outcome of complex transvenous lead extractions.

Both transesophageal echocardiography (TEE) and intracardiac echocardiography have been used to assist transvenous lead extractions. The clinical utility of continuous echocardiographic monitoring during the procedure is still debated, with different reports supporting opposite findings. In cases where the procedure is expected to be difficult, we propose adding a continuous TEE monitoring using a static 3D/multiplane probe in mid-esophageal position, with digital remote manipulation of the field of view. This approach may improve the chances of a successful extraction, increase safety, or even guide the entire intervention. We present here a short case series where continuous monitoring by TEE played an important role.

Elevated monocyte-specific type I interferon signalling correlates positively with cardiac healing in myocardial infarct patients but interferon alpha application deteriorates myocardial healing in rats.

Monocytes are involved in adverse left ventricular (LV) remodelling following myocardial infarction (MI). To provide therapeutic opportunities we aimed to identify gene transcripts in monocytes that relate to post-MI healing and evaluated intervention with the observed gene activity in a rat MI model. In 51 MI patients treated by primary percutaneous coronary intervention (PCI), the change in LV end-diastolic volume index (EDVi) from baseline to 4-month follow-up was assessed using cardiovascular magnetic resonance imaging (CMR). Circulating monocytes were collected at day 5 (Arterioscler Thromb Vasc Biol 35:1066-1070, 2015; Cell Stem Cell 16:477-487, 2015; Curr Med Chem 13:1877-1893, 2006) after primary PCI for transcriptome analysis. Transcriptional profiling and pathway analysis revealed that patients with a decreased LV EDVi showed an induction of type I interferon (IFN) signalling (type I IFN pathway: P value < 0.001; false discovery rate < 0.001). We subsequently administered 15,000 Units of IFN-α subcutaneously in a rat MI model for three consecutive days following MI. Cardiac function was measured using echocardiography and infarct size/cardiac inflammation using (immuno)-histochemical analysis. We found that IFN-α application deteriorated ventricular dilatation and increased infarct size at day 28 post-MI. Moreover, IFN-α changed the peripheral monocyte subset distribution towards the pro-inflammatory monocyte subset whereas in the myocardium, the presence of the alternative macrophage subset was increased at day 3 post-MI. Our findings suggest that induction of type I IFN signalling in human monocytes coincides with adverse LV remodelling. In rats, however, IFN-α administration deteriorated post-MI healing. These findings underscore important but also contradictory roles for the type I IFN response during cardiac healing following MI.

Strain analysis is superior to wall thickening in discriminating between infarcted myocardium with and without microvascular obstruction.

OBJECTIVES: The aim of the present study was to evaluate the diagnostic performances of strain and wall thickening analysis in discriminating among three types of myocardium after acute myocardial infarction: non-infarcted myocardium, infarcted myocardium without microvascular obstruction (MVO) and infarcted myocardium with MVO. METHODS: Seventy-one patients with a successfully treated ST-segment elevation myocardial infarction underwent cardiovascular magnetic resonance imaging at 2-6 days after reperfusion. The imaging protocol included conventional cine imaging, myocardial tissue tagging and late gadolinium enhancement. Regional circumferential and radial strain and associated strain rates were analyzed in a 16-segment model as were the absolute and relative wall thickening. RESULTS: Hyperenhancement was detected in 418 (38%) of 1096 segments and was accompanied by MVO in 145 (35%) of hyperenhanced segments. Wall thickening, circumferential and radial strain were all significantly diminished in segments with hyperenhancement and decreased even further if MVO was also present (all p < 0.001). Peak circumferential strain (CS) surpassed all other strain and wall thickening parameters in its ability to discriminate between hyperenhanced and non-enhanced myocardium (all p < 0.05). Furthermore, CS was superior to both absolute and relative wall thickening in differentiating infarcted segments with MVO from infarcted segments without MVO (p = 0.02 and p = 0.001, respectively). CONCLUSIONS: Strain analysis is superior to wall thickening in differentiating between non-infarcted myocardium, infarcted myocardium without MVO and infarcted myocardium with MVO. Peak circumferential strain is the most accurate marker of regional function. KEY POINTS: • CMR can quantify regional myocardial function by analysis of wall thickening on cine images and strain analysis of tissue tagged images. • Strain analysis is superior to wall thickening in differentiating between different degrees of myocardial injury after acute myocardial infarction. • Peak circumferential strain is the most accurate marker of regional function.

Reexpansion Pulmonary Edema in Pediatrics.

Reexpansion pulmonary edema is a rare complication that may occur after drainage of pneumothorax or pleural effusion. A number of factors have been identified that increase the risk of developing reexpansion pulmonary edema, and pathophysiologic mechanisms have been postulated. Patients may present with radiographic findings alone or may have signs or symptoms that prompt evaluation and diagnosis. Clinical presentations range from mild cough to respiratory failure and hemodynamic compromise. Treatment strategies are supportive, and should be tailored to match the severity of the condition.