Pulmonary perfusion and NYHA classification improve after cardiac resynchronization therapy.

BACKGROUND: Evaluation of cardiac resynchronization therapy (CRT) often includes New York Heart Association (NYHA) classification, and echocardiography. However, these measures have limitations. Perfusion gradients from ventilation/perfusion single-photon emission computed tomography (V/P SPECT) are related to left-heart filling pressures and have been validated against invasive right-heart catheterization. The aim was to assess if changes in perfusion gradients are associated with improvements in heart failure (HF) symptoms after CRT, and if they correlate with currently used diagnostic methods in the follow-up of patients with HF after receiving CRT. METHODS AND RESULTS: Nineteen patients underwent V/P SPECT, echocardiography, NYHA classification, and the quality-of-life scoring system "Minnesota living with HF" (MLWHF), before and after CRT. CRT caused improvement in perfusion gradients from V/P SPECT which were associated with improvements in NYHA classification (P = .0456), whereas improvements in end-systolic volume (LVESV) from echocardiography were not. After receiving CRT, the proportion of patients who improved was lower using LVESV (n = 7/19, 37%) than perfusion gradients (n = 13/19, 68%). Neither change in perfusion gradients nor LVESV was associated with changes in MLWHF (P = 1.0, respectively). CONCLUSIONS: Measurement of perfusion gradients from V/P SPECT is a promising quantitative user-independent surrogate measure of left-sided filling pressure in the assessment of CRT response in patients with HF.

The association between plasma miR-122-5p release pattern at admission and all-cause mortality or shock after out-of-hospital cardiac arrest.

BACKGROUND: Data suggests that the plasma levels of the liver-specific miR-122-5p might both be a marker of cardiogenic shock and a prognostic marker of out-of-hospital cardiac arrest (OHCA). Our aim was to characterize plasma miR-122-5p at admission after OHCA and to assess the association between miR-122-5p and relevant clinical factors such all-cause mortality and shock at admission after OHCA. METHODS: In the pilot trial, 10 survivors after OHCA were compared to 10 age- and sex-matched controls. In the main trial, 167 unconscious survivors of OHCA from the Targeted Temperature Management (TTM) trial were included. RESULTS: In the pilot trial, plasma miR-122-5p at admission after OHCA was 400-fold elevated compared to controls. In the main trial, plasma miR-122-5p at admission was independently associated with lactate and bystander cardiopulmonary resuscitation. miR-122-5p at admission was not associated with shock at admission (p = 0.14) or all-cause mortality (p = 0.35). Target temperature (33 °C vs 36 °C) was not associated with miR-122-5p levels at any time point. CONCLUSIONS: After OHCA, miR-122-5p demonstrated a marked acute increase in plasma and was independently associated with lactate and bystander resuscitation. However, miR-122-5p at admission was not associated with all-cause mortality or shock at admission.

The brain-enriched microRNA miR-124 in plasma predicts neurological outcome after cardiac arrest.

INTRODUCTION: Early prognostication after successful cardiopulmonary resuscitation is difficult, and there is a need for novel methods to estimate the extent of brain injury and predict outcome. In this study, we evaluated the impact of the cardiac arrest syndrome on the plasma levels of selected tissue-specific microRNAs (miRNAs) and assessed their ability to prognosticate death and neurological disability. METHODS: We included 65 patients treated with hypothermia after cardiac arrest in the study. Blood samples were obtained at 24 hours and at 48 hours. For miRNA-screening purposes, custom quantitative polymerase chain reaction (qPCR) panels were first used. Thereafter individual miRNAs were assessed at 48 hours with qPCR. miRNAs that successfully predicted prognosis at 48 hours were further analysed at 24 hours. Outcomes were measured according to the Cerebral Performance Category (CPC) score at 6 months after cardiac arrest and stratified into good (CPC score 1 or 2) or poor (CPC scores 3 to 5). RESULTS: At 48 hours, miR-146a, miR-122, miR-208b, miR-21, miR-9 and miR-128 did not differ between the good and poor neurological outcome groups. In contrast, miR-124 was significantly elevated in patients with poor outcomes compared with those with favourable outcomes (P < 0.0001) at 24 hours and 48 hours after cardiac arrest. Analysis of receiver operating characteristic curves at 24 and 48 hours after cardiac arrest showed areas under the curve of 0.87 (95% confidence interval (CI) = 0.79 to 0.96) and 0.89 (95% CI = 0.80 to 0.97), respectively. CONCLUSIONS: The brain-enriched miRNA miR-124 is a promising novel biomarker for prediction of neurological prognosis following cardiac arrest.

Discrimination of ST deviation caused by acute coronary occlusion from normal variants and other abnormal conditions, using computed electrocardiographic imaging based on 12-lead ECG.

BACKGROUND: Many graphical methods for displaying ST-segment deviation in the ECG have been tried for enhancing decision-making in patients with suspected acute coronary syndromes. Computed electrocardiographic imaging (CEI), based on a mathematical inverse solution, has been recently applied to transform ST-J point measurements made in conventional 12-lead ECG into a display of epicardial potentials in bull's-eye format. The purpose of this study is to assess utility of CEI in the clinical setting. METHODS: In 99 patients with stable coronary disease, 12-lead ECGs were recorded during elective percutaneous coronary intervention (PCI), first before balloon-catheter insertion and then when an intracoronary balloon blocked blood supply to a region of myocardium for more than 4minutes (typically 5minutes). Four groups of patients were additionally studied, namely those with preexcitation, pericarditis, early repolarization syndrome (ERS), and left ventricular hypertrophy (LVH) with strain. Comparisons between performances of published criteria for ST-elevation myocardial infarction (STEMI) and quantitative as well as visual assessment of CEI images were based on sensitivities and specificities. RESULTS: Visual assessment of CEI outperformed STEMI criteria. This was especially evident for the capability of detecting LCx occlusion with sensitivities for STEMI criteria=35% and for visual assessment of CEI by 2 physicians=71%, i. e. twice as many patients were correctly identified by CEI. False positive rates for CEI were low in patients with LVH with strain as well as with preexcitation for both methods. For pericarditis and ERS, visual as well as quantitative assessment of CEI performed better than STEMI criteria. CONCLUSION: Visual assessment of CEI is a promising method for increasing the accuracy of ECG-based triage to PCI or conservative care.

Increased pulmonary blood volume variation in patients with heart failure compared to healthy controls: a noninvasive, quantitative measure of heart failure.

Variation of the blood content of the pulmonary vascular bed during a heartbeat can be quantified by pulmonary blood volume variation (PBVV) using magnetic resonance imaging (MRI). The aim was to evaluate whether PBVV differs in patients with heart failure compared with healthy controls and investigate the mechanisms behind the PBVV. Forty-six patients and 10 controls underwent MRI. PBVV was calculated from blood flow measurements in the main pulmonary artery and a pulmonary vein, defined as the maximum difference in cumulative PBV over one heartbeat. PBVV was indexed to stroke volume (SV) in the main pulmonary artery (PBVVSV). Patients displayed higher PBVVSV than controls (58 ± 14 vs. 43 ± 7%, P < 0.001). The change in PBVVSV could be explained by left ventricular (LV) longitudinal contribution to SV (R2 = 0.15, P = 0.02) and the phase shift between in- and outflow (R2 = 0.31, P < 0.001) in patients. Both variables contributed to the multiple regression analysis model and predicted PBVVSV (R2 = 0.38); however, the phase shift alone explained ~30% of the variation in PBVVSV. No correlation was found between PBVVSV and large vessel area. In conclusion, PBVVSV was higher in patients compared with controls. Approximately 40% of the variation of PBVVSV in patients can be explained by the LV longitudinal contribution to SV and the phase shift between pulmonary in- and outflow, where the phase shift alone accounts for ~30%. The remaining variation (60-70%) most likely occurs on a small vessel level. Future studies are needed to show the clinical added value of PBVVSV compared with right-heart catheterization.NEW & NOTEWORTHY This study shows that the pulmonary blood volume variation indexed to the stroke volume is higher in patients with heart failure compared with controls. The mechanisms behind this are lack of systolic suction from the left ventricular atrioventricular plane descent and increased phase shift between the in- and outflow to the pulmonary circulation (~40%), where the phase shift alone accounts for ~30%. The remaining variation (60-70%) is suggested to occur on a small vessel level.

Diagnosing and grading heart failure with tomographic perfusion lung scintigraphy: validation with right heart catheterization.

AIMS: Pulmonary congestion remains a diagnostic challenge in patients with heart failure (HF). The recommended method, chest X-ray (CXR), lacks in accuracy, whereas quantitative tomographic lung scintigraphy [ventilation/perfusion single-photon emission computed tomography (V/P SPECT)] has shown promising results but needs independent validation. The aim of this study is to evaluate V/P SPECT as a non-invasive method to assess and quantify pulmonary congestion in HF patients, using right heart catheterization as reference method. The secondary objective was to investigate the performance of V/P SPECT in the clinical setting compared with CXR. METHODS AND RESULTS: Forty-six consecutive patients with HF that were under consideration for heart transplantation were studied prospectively. All participants were examined with V/P SPECT, CXR, and right heart catheterization. Pulmonary artery wedge pressure served as reference method. Quantitative perfusion gradients were derived from V/P SPECT images. Ventilation/perfusion single-photon emission computed tomography images were also assessed both by expert readers and clinical nuclear medicine physicians. Expert readers correctly identified 87% of all patients with an elevated pulmonary artery wedge pressure > 15 mmHg. The average sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for V/P SPECT assessed by the expert readers were 87%, 72%, 85%, and 75%, respectively. In the clinical nuclear medicine setting, V/P SPECT had 87% sensitivity, 63% specificity, 81% PPV, and 71% NPV. Clinically, V/P SPECT outperformed CXR, which had 27% sensitivity, 75% specificity, 67% PPV, and 35% NPV. CONCLUSIONS: Ventilation/perfusion single-photon emission computed tomography can be used as a non-invasive method to diagnose and quantify pulmonary congestion in patients with HF and is more accurate than CXR in diagnosing pulmonary congestion in the clinical setting.

Automatic lung segmentation in functional SPECT images using active shape models trained on reference lung shapes from CT.

OBJECTIVE: Image segmentation is an essential step in quantifying the extent of reduced or absent lung function. The aim of this study is to develop and validate a new tool for automatic segmentation of lungs in ventilation and perfusion SPECT images and compare automatic and manual SPECT lung segmentations with reference computed tomography (CT) volumes. METHODS: A total of 77 subjects (69 patients with obstructive lung disease, and 8 subjects without apparent perfusion of ventilation loss) performed low-dose CT followed by ventilation/perfusion (V/P) SPECT examination in a hybrid gamma camera system. In the training phase, lung shapes from the 57 anatomical low-dose CT images were used to construct two active shape models (right lung and left lung) which were then used for image segmentation. The algorithm was validated in 20 patients, comparing its results to reference delineation of corresponding CT images, and by comparing automatic segmentation to manual delineations in SPECT images. RESULTS: The Dice coefficient between automatic SPECT delineations and manual SPECT delineations were 0.83 ± 0.04% for the right and 0.82 ± 0.05% for the left lung. There was statistically significant difference between reference volumes from CT and automatic delineations for the right (R = 0.53, p = 0.02) and left lung (R = 0.69, p < 0.001) in SPECT. There were similar observations when comparing reference volumes from CT and manual delineations in SPECT images, left lung (bias was - 10 ± 491, R = 0.60, p = 0.005) right lung (bias 36 ± 524 ml, R = 0.62, p = 0.004). CONCLUSION: Automated segmentation on SPECT images are on par with manual segmentation on SPECT images. Relative large volumetric differences between manual delineations of functional SPECT images and anatomical CT images confirms that lung segmentation of functional SPECT images is a challenging task. The current algorithm is a first step towards automatic quantification of wide range of measurements.

Effect of exercise on the plasma vesicular proteome: a methodological study comparing acoustic trapping and centrifugation.

Extracellular vesicles (EVs) are a heterogeneous group of actively released vesicles originating from a wide range of cell types. Characterization of these EVs and their proteomes in the human plasma provides a novel approach in clinical diagnostics, as they reflect physiological and pathological states. However, EV isolation is technically challenging with the current methods having several disadvantages, requiring large sample volumes, and resulting in loss of sample and EV integrity. Here, we use an alternative, non-contact method based on a microscale acoustic standing wave technology. Improved coupling of the acoustic resonator increased the EV recovery from 30% in earlier reports to 80%, also displaying long term stability between experiment days. We report a pilot study, with 20 subjects who underwent physical exercise. Plasma samples were obtained before and 1 h after the workout. Acoustic trapping was compared to a standard high-speed centrifugation protocol, and the method was validated by flow cytometry (FCM). To monitor the device stability, the pooled frozen plasma from volunteers was used as an internal control. A key finding from the FCM analysis was a decrease in CD62E+ (E-selectin) EVs 1 h after exercise that was consistent for both methods. Furthermore, we report the first data that analyse differential EV protein expression before and after physical exercise. Olink-based proteomic analysis showed 54 significantly changed proteins in the EV fraction in response to physical exercise, whereas the EV-free plasma proteome only displayed four differentially regulated proteins, thus underlining an important role of these vesicles in cellular communication, and their potential as plasma derived biomarkers. We conclude that acoustic trapping offers a fast and efficient method comparable with high-speed centrifugation protocols. Further, it has the advantage of using smaller sample volumes (12.5 µL) and rapid contact-free separation with higher yield, and can thus pave the way for future clinical EV-based diagnostics.