Tolvaptan vs. furosemide-based diuretic regimens in patients hospitalized for heart failure with hyponatremia (AQUA-AHF).

AIMS: Hyponatremia is associated with poorer outcomes and diuretic response in patients hospitalized for heart failure. This study compared a tolvaptan-based vs. furosemide-based diuretic regimen on short-term clinical responses in hyponatremic acute heart failure. METHODS AND RESULTS: Prospective, randomized, open-label, parallel-group, single-centre study comparing oral tolvaptan vs. continuous infusion furosemide. Thirty-three subjects requiring hospitalization for acute congestive heart failure, and a serum sodium < 135 mmol/L, were randomized to tolvaptan 30 mg orally daily or furosemide 5 mg/h intravenously for initial 24 h, after which treatments could be escalated. Median daily dose throughout was tolvaptan 30 mg and furosemide 120 mg, with four subjects in each group requiring dose escalation. Urine output and net fluid balance were not different between groups at 24 h or subsequent time points up to 96 h. Changes in estimated glomerular filtration rate were comparable. Cystatin C improved at 24 h with tolvaptan compared with furosemide (-6.4 ± 11.8 vs. 4.1 ± 17.2% change, P = 0.036), but the effect was transient. No significant between group differences were seen for NT-proBNP, plasma renin activity, or urinary neutrophil gelatinase-associated lipocalin:Cr. Serum sodium, as well as copeptin levels, increased with tolvaptan compared with furosemide. CONCLUSIONS: Oral tolvaptan was associated with similar, but not superior, diuresis compared with intravenous furosemide for acute heart failure with concomitant hyponatremia.

Accuracy, uncertainty, and adaptability of automatic myocardial ASL segmentation using deep CNN.

PURPOSE: To apply deep convolution neural network to the segmentation task in myocardial arterial spin labeled perfusion imaging and to develop methods that measure uncertainty and that adapt the convolution neural network model to a specific false-positive versus false-negative tradeoff. METHODS: The Monte Carlo dropout U-Net was trained on data from 22 subjects and tested on data from 6 heart transplant recipients. Manual segmentation and regional myocardial blood flow were available for comparison. We consider 2 global uncertainty measures, named "Dice uncertainty" and "Monte Carlo dropout uncertainty," which were calculated with and without the use of manual segmentation, respectively. Tversky loss function with a hyperparameter ß was used to adapt the model to a specific false-positive versus false-negative tradeoff. RESULTS: The Monte Carlo dropout U-Net achieved a Dice coefficient of 0.91 ± 0.04 on the test set. Myocardial blood flow measured using automatic segmentations was highly correlated to that measured using the manual segmentation (R2 = 0.96). Dice uncertainty and Monte Carlo dropout uncertainty were in good agreement (R2 = 0.64). As ß increased, the false-positive rate systematically decreased and false-negative rate systematically increased. CONCLUSION: We demonstrate the feasibility of deep convolution neural network for automatic segmentation of myocardial arterial spin labeling, with good accuracy. We also introduce 2 simple methods for assessing model uncertainty. Finally, we demonstrate the ability to adapt the convolution neural network model to a specific false-positive versus false-negative tradeoff. These findings are directly relevant to automatic segmentation in quantitative cardiac MRI and are broadly applicable to automatic segmentation problems in diagnostic imaging.

Use of coronary artery calcium testing to improve coronary heart disease risk assessment in a lung cancer screening population: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Assessment of coronary artery calcium (CAC) during lung cancer screening chest computed tomography (CT) represents an opportunity to identify asymptomatic individuals at increased coronary heart disease (CHD) risk. We determined the improvement in CHD risk prediction associated with the addition of CAC testing in a population recommended for lung cancer screening. METHODS: We included 484 out of 6814 Multi-Ethnic Study of Atherosclerosis (MESA) participants without baseline cardiovascular disease who met U.S. Preventive Service Task Force CT lung cancer screening criteria and underwent gated CAC testing. 10 year-predicted CHD risks with and without CAC were calculated using a validated MESA-based risk model and categorized into low (<5%), intermediate (5%-10%), and high (≥10%). The net reclassification improvement (NRI) and change in Harrell's C-statistic by adding CAC to the risk model were subsequently determined. RESULTS: Of 484 included participants (mean age = 65; 39% women; 32% black), 72 (15%) experienced CHD events over the course of follow-up (median = 12.5 years). Adding CAC to the MESA CHD risk model resulted in 17% more participants classified into the highest or lowest risk categories and a NRI of 0.26 (p = 0.001). The C-statistic improved from 0.538 to 0.611 (p = 0.01). CONCLUSIONS: CHD event rates were high in this lung cancer screening eligible population. These individuals represent a high-risk population who merit consideration for CHD prevention measures regardless of CAC score. Although overall discrimination remained poor with inclusion of CAC scores, determining whether those reclassified to an even higher risk would benefit from more aggressive preventive measures may be important.

Case Report of Multiembolic Cerebrovascular Event Associated with Ramp Study Echocardiogram.

The incidence of ramp test echocardiogram-associated embolic events in the setting of therapeutic anticoagulation is likely rare and has not been reported. We present such a case in a patient with a HeartMate II left ventricular assist device (LVAD) whose serial head computed tomography images, deteriorating clinical course, and the multiembolic nature of the event suggest causality. If the pretest probability of pump thrombosis in an individual LVAD patient is sufficiently high, the potential risks of performing a ramp study echocardiogram may not be warranted, even in the setting of adequate anticoagulation.

Heart Failure-Induced Brain Injury.

Heart failure (HF) is a systemic illness with grave implications for bodily functions. The brain, among other vital organs, often suffers insults as a result of HF, and both anatomic and functional brain abnormalities were found in the HF population. This injury was demonstrated across a wide range of clinical conditions and cardiac functions and was shown to affect patients' outcomes. Although reduced cardiac output and high burden of cardiovascular risk factors are the prevailing explanations for these findings, there are data showing the involvement of neurohormonal, nutritional, and inflammatory mechanisms in this complex process. Here, the authors review the suggested pathophysiology behind brain injury in HF, describe its effect on patients' outcomes, offer a diagnostic approach, and discuss possible therapeutic options.

Assessment of segmental myocardial blood flow and myocardial perfusion reserve by adenosine-stress myocardial arterial spin labeling perfusion imaging.

PURPOSE: To determine the feasibility of measuring increases in myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) on a per-segment basis using arterial spin labeled (ASL) magnetic resonance imaging (MRI) with adenosine vasodilator stress in normal human myocardium. MATERIALS AND METHODS: Myocardial ASL scans at rest and during adenosine infusion were incorporated into a routine 3T MR adenosine-induced vasodilator stress protocol and were performed in 10 healthy human volunteers. Myocardial ASL was performed using single-gated flow-sensitive alternating inversion recovery (FAIR) tagging and balanced steady-state free precession (bSSFP) imaging at 3T. A T2 -prep blood oxygen level-dependent (BOLD) SSFP sequence was used to concurrently assess segmental myocardial oxygenation with BOLD signal intensity (SI) percent change in the same subjects. RESULTS: There was a statistically significant difference between MBF measured by ASL at rest (1.75 ± 0.86 ml/g/min) compared to adenosine stress (4.58 ± 2.14 ml/g/min) for all wall segments (P < 0.0001), yielding a per-segment MPR of 3.02 ± 1.51. When wall segments were divided into specific segmental myocardial perfusion territories (ie, anteroseptal, anterior, anterolateral, inferolateral, inferior, and inferoseptal), the differences between rest and stress regional MBF for each territory remained consistently statistically significant (P < 0.001) after correcting for multiple comparisons. CONCLUSION: This study demonstrates the feasibility of measuring MBF and MPR on a segmental basis by single-gated cardiac ASL in normal volunteers. Second, this study demonstrates the feasibility of performing the ASL sequence and T2 -prepared SSFP BOLD imaging during a single adenosine infusion. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:413-420.

Double-gated myocardial ASL perfusion imaging is robust to heart rate variation.

PURPOSE: Cardiac motion is a dominant source of physiological noise (PN) in myocardial arterial spin labeled (ASL) perfusion imaging. This study investigates the sensitivity to heart rate variation (HRV) of double-gated myocardial ASL compared with the more widely used single-gated method. METHODS: Double-gating and single-gating were performed on 10 healthy volunteers (n = 10, 3F/7M; age, 23-34 years) and eight heart transplant recipients (n = 8, 1F/7M; age, 26-76 years) at rest in the randomized order. Myocardial blood flow (MBF), PN, temporal signal-to-noise ratio (SNR), and HRV were measured. RESULTS: HRV ranged from 0.2 to 7.8 bpm. Double-gating PN did not depend on HRV, while single-gating PN increased with HRV. Over all subjects, double-gating provided a significant reduction in global PN (from 0.20 ± 0.15 to 0.11 ± 0.03 mL/g/min; P = 0.01) and per-segment PN (from 0.33 ± 0.23 to 0.21 ± 0.12 mL/g/min; P < 0.001), with significant increases in global temporal SNR (from 11 ± 8 to 18 ± 8; P = 0.02) and per-segment temporal SNR (from 7 ± 4 to 11 ± 12; P < 0.001) without significant difference in measured MBF. CONCLUSION: Single-gated myocardial ASL suffers from reduced temporal SNR, while double-gated myocardial ASL provides consistent temporal SNR independent of HRV. Magn Reson Med 77:1975-1980, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

ST Segment Elevation ECG Changes During Pharmacologic Stress With Regadenoson.

Regadenoson is a pharmacologic stress agent that has been widely adopted as an alternative over other pharmacologic vasodilator agents due to its ease of use, patient tolerance, and safety profile. We report the case of dynamic ST-segment elevation electrocardiogram changes after regadenoson injection during an inpatient single-photon emission computed tomography myocardial perfusion stress test, with subsequent coronary angiography revealing the presence of hemodynamically significant coronary artery disease. Our findings confirm that transient regadenoson-induced ST-segment elevations are a marker for hemodynamically significant disease even in the setting of low-risk SPECT perfusion images.

Pan-Cardiac Cycle Fixed Mitral Valve Opening in an LVAD Patient Presenting with Hemorrhagic Shock.

We present the case of a patient with a HeartMate II left ventricular assist device (LVAD) who underwent an elective cholecystectomy and abruptly decompensated on postoperative day 9. We highlight the uncommon echocardiogram finding of mitral valve leaflets fixed widely open throughout the cardiac cycle during an LVAD suction event. Bedside echocardiographic confirmation of a suction event enabled the rapid diagnosis and intervention for hemorrhagic shock before blood tests and radiographic results were available. Acoustic image quality can be limited in LVAD patients, and awareness of this uncommon finding may increase specificity for the echocardiographic diagnosis of LVAD suction events.

Noninvasive measurement and clinical relevance of myocardial twist and torsion.

Left ventricular (LV) torsion (twisting) and untwisting results in equalization of wall stress and augmentation of pressure generated for a given shortening of sarcomere during the systolic contraction and aids early diastolic relaxation. This is attributed to the dynamic interaction of epicardial and endocardial helical myocardial fibers. Recent advances in noninvasive imaging techniques have enabled us to quantify torsion accurately and reliably in health and disease. LV torsional mechanics are altered in range of clinical conditions from those that cause minimal cardiac architectural changes as seen in hypertension, diabetes mellitus or older age to advanced cardiac remodeling as seen dilated or hypertrophic cardiomyopathy. Therefore, assessment of LV rotational mechanics may be a potentially sensitive marker of cardiac dysfunction and may provide important insights into the pathophysiology of heart failure.

Left ventricular torsional mechanics in uncomplicated pregnancy.

BACKGROUND: Alterations in left ventricular (LV) twist (torsion) and untwist have been described for a variety of physiologic and pathologic conditions. Little information is available regarding changes in these parameters during normal pregnancy. HYPOTHESIS: Pregnancy is associated with significant changes in LV torsional mechanics. METHODS: Left ventricular twist and untwist was measured in 32 pregnant females (mean gestation 199 ± 48 d) and 23 nonpregnant controls using speckle-tracking echocardiography. RESULTS: Left ventricular ejection fraction (68 ± 5% vs 66 ± 5%) was similar between the groups (P not significant). There was a significant increase in peak LV twist from nonpregnant controls (9.4 ± 3.7 degrees) to second-trimester (12.0 ± 4.2 degrees) and third-trimester subjects (12.6 ± 5.9 degrees, all P<0.05). Peak LV twist velocity was also increased in second- and third-trimester groups compared with controls (94 ± 24 degrees/sec and 93 ± 30 vs 64 ± 21 degrees/sec, respectively, both P<0.05). Both peak untwist velocity and time to peak untwist velocity were not significantly different between groups (P not significant). Multiple regression analysis indicate that only systolic blood pressure (r = 0.394, P = 0.005) was an independent predictor for increased LV torsion. CONCLUSIONS: There are significant changes in LV torsional indices during the course of pregnancy, whereas untwist parameters remain unchanged. Blood pressure is independently associated with increased torsion during pregnancy.

New options in noninvasive assessment of left ventricular torsion.

The complex, intricate 3D pattern of ventricular torsion has both fascinated and perplexed scientists for centuries. The identity of the underlying anatomic myocardial unit responsible for this pattern of contraction continues to be an arena of debate. While the complicated wringing motions involved in torsion are difficult to quantify, several techniques have been demonstrated to be effective in the noninvasive assessment of left ventricular (LV) torsion. Magnetic resonance tissue-tagging with dynamic MRI is the gold standard for the noninvasive quantitative evaluation of torsion with high spatial and temporal resolution. However, this is a technically involved and potentially time-consuming process. Echocardiography is another alternative noninvasive method. Both tissue Doppler imaging and speckle-tracking imaging have been shown to be sufficiently accurate and reliable alternatives to MRI in the noninvasive assessment of LV torsion. While the potential applications of these techniques to assess LV torsion appears boundless, further studies are needed to validate measures of LV torsion by the additional, but most important, test of demonstrating its clinical utility as a predictor of prognosis.

The effect of beta-blockers on the diagnostic accuracy of vasodilator pharmacologic SPECT myocardial perfusion imaging.

BACKGROUND: The effect of beta (beta) blockers on the accuracy, particularly the sensitivity, of vasodilator radionuclide myocardial perfusion imaging (MPI) is not entirely clear. This study aimed to further assess the effect of beta-blockers on the ability of MPI to identify significant and high-risk coronary artery disease (CAD). METHODS AND RESULTS: For 555 patients who underwent vasodilator MPI and had coronary angiography within 90 days, global and per-vessel sensitivities and specificities were calculated, and were found to be similar between patients taking beta-blockers and those who were not. beta-blockers did not decrease the ability to detect patients with multivessel disease. Summed stress scores and summed rest scores were likewise similar in both groups. To account in part for catheterization referral bias and the potential of false-negative MPI studies in patients receiving beta-blockers, survival analysis was performed on 2646 patients with normal MPI studies who did not undergo cardiac catheterization and failed to demonstrate significant mortality difference related to the taking of beta-blockers. CONCLUSIONS: beta-blocker therapy does not diminish the ability of vasodilator stress MPI to detect clinically significant CAD, nor hide the mortality risk of patients with normal studies not referred for catheterization.

Heart-brain interactions in mental stress-induced myocardial ischemia.

Myocardial ischemia that results from emotional provocation occurs in as many as 30% to 50% of patients with coronary artery disease during the discourse of their lives. This emotionally provoked or mental stress ischemia is associated with poor prognosis, with emerging treatment strategies. This article outlines the conceptual constructs that support the pathophysiologic underpinnings, and biobehavioral aspects associated with this mental stress ischemia. We review a biobehavioral model in which cognitive stress is transduced in the brain. The response of the brain to psychosocial stress is a highly sophisticated and integrated process by which sensory inputs are evaluated and appraised for their importance in relation to previous experience and current goals. The biologic consequences of such stress transduced in the central nervous system has its effect on cardiovascular flow and function through changes in autonomic balance, which result in various biologic processes that culminate in the perturbation of flow and function of the heart.

Usefulness of myocardial perfusion echocardiography to identify obstructive coronary artery disease in patients with abnormal ventricular septal motion.

Twenty-three patients who had septal wall motion abnormalities and who underwent angiography within 2 weeks were evaluated by myocardial perfusion echocardiography. Mean perfusion score (plateau video intensity times the wash-in rate) was lower in segments that were supplied by obstructed coronary arteries in real time (7.5 vs 22.6 dB/s, p <0.005) and with end-systolic triggering (8.6 vs 20.9 dB/s, p <0.001). Lower mean septal perfusion scores (<12 dB/s) were seen in 14 of 16 patients who had obstructive septal coronary artery disease, and normal mean septal perfusion scores were seen in 6 of 7 patients who did not have obstructive septal coronary artery disease.