Machine learning extracts marks of thiamine's role in cold acclimation in the transcriptome of Vitis vinifera.

Introduction: The escalating challenge of climate change has underscored the critical need to understand cold defense mechanisms in cultivated grapevine Vitis vinifera. Temperature variations can affect the growth and overall health of vine. Methods: We used Self Organizing Maps machine learning method to analyze gene expression data from leaves of five Vitis vinifera cultivars each treated by four different temperature conditions. The algorithm generated sample-specific "portraits" of the normalized gene expression data, revealing distinct patterns related to the temperature conditions applied. Results: Our analysis unveiled a connection with vitamin B1 (thiamine) biosynthesis, suggesting a link between temperature regulation and thiamine metabolism, in agreement with thiamine related stress response established in Arabidopsis before. Furthermore, we found that epigenetic mechanisms play a crucial role in regulating the expression of stress-responsive genes at low temperatures in grapevines. Discussion: Application of Self Organizing Maps portrayal to vine transcriptomics identified modules of coregulated genes triggered under cold stress. Our machine learning approach provides a promising option for transcriptomics studies in plants.

Increased heart rate with sleep disordered breathing in hypertrophic cardiomyopathy.

BACKGROUND: Current guidelines recommend medications with rate control properties for symptomatic patients with hypertrophic cardiomyopathy (HCM) based on the rationale that lowering heart rate (HR) improves their symptoms. Whether sleep disordered breathing (SDB) is associated with increased HR in HCM patients is not known. METHOD: We diagnosed uncontrolled SDB (oxygen desaturation index ≥5) in consecutive echocardiographically confirmed HCM patients seen at Mayo Clinic, Rochester, and analyzed their HR as recorded by a 24-h Holter monitor. We compared mean, minimum, maximum HR between those with vs without SDB. In a pilot subanalysis of HCM patients with SDB who also underwent subsequent diagnostic polysomnography (PSG), we analyzed RR interval changes coinciding with obstructive sleep apnea and hypopnea episodes. RESULTS: Of the 230 HCM patients included in this study (age 54 ± 16 years; 138 male; LVOT pressure gradient at rest 45 ± 39 mmHg), 115 (50%) patients had SDB. HCM patients with SDB were recorded to have higher mean HR (71 vs. 67 bpm; p = .002, adjusted p = .001), and this difference was most pronounced during night hours of 10 PM to 5 AM (61 vs. 67 bpm; p < .001). In the pilot analysis of the available PSG data, the release of obstructive sleep apneas and hypopneas coincided with fluctuation of HR. CONCLUSIONS: SDB is independently associated with higher mean HR in patients with HCM, and this difference is most significant during sleep. Treatment of SDB, which is readily available, should be tested as a complementary modality to the currently recommended pharmacotherapy aimed at lowering HR in patients with symptomatic HCM.

Ventricular asystole in a CRT-D device. What is the mechanism?

We present a case of an 89-year-old man with a left ventricular assist device and cardiac resynchronization therapy device (CRT-D) who presented with multiple presyncopal events. On the night of admission, telemetry revealed a 13-s pause with appropriately timed pacing spikes but with failure to capture, followed by intermittent ventricular contraction with different QRS morphology. What was the mechanism for his ventricular asystole?

Single- and dual-site ventricular pacing entirely through the coronary sinus for patients with prior tricuspid valve surgery.

PURPOSE: Transvenous right ventricular pacing has traditionally been avoided after surgical tricuspid valve repair or replacement because of possible valvular dysfunction. Epicardial pacing has been used but it requires surgical thoracotomy and has higher lead failure rates when compared to transvenous pacing. We evaluated the lead stability and clinical outcomes in patients with isolated coronary sinus (CS) lead due to relative contraindication to transvenous pacing from prior tricuspid valve (TV) surgery. METHODS: We retrospectively examined a single-center cohort of 34 patients with TV disease and/or surgery who underwent permanent pacemaker implantation with a left ventricular CS lead as the only ventricular pacing lead (to avoid crossing the TV). The clinical outcome, echocardiographic data, and pacing thresholds were evaluated at follow-up. RESULTS: We implanted 19 patients with a single-CS lead and 15 patients with dual-CS leads. The average left ventricular ejection fraction was 56 ± 13% prior to lead implantation and remained stable at 2-year follow-up. The tricuspid regurgitation remained mild at follow-up. The average lead pacing threshold was 1.2 ± 0.6 V × ms at implant and 1.1 ± 0.4 V × ms at 2-year follow-up (P = 0.39). For patients with dual-CS leads, the pacing threshold was 1.2 ± 0.7 V × ms at implant and 1.1 ± 0.5 V × ms at 2-year follow-up (P = 0.52). CONCLUSIONS: The use of ventricular pacing entirely through the CS is an effective and minimally invasive method that provides stable pacing for patients with prior TV surgery in whom transvenous lead placement either is not possible or is relatively contraindicated.

Usefulness of Heart Rate Control in Atrial Fibrillation Patients With Obstructive Sleep Apnea.

In patients without atrial fibrillation and flutter (AF), obstructive sleep apnea (OSA) is associated with cyclic and often marked changes in heart rate (HR). We aimed to assess whether presence of OSA impacts optimal HR control in patients in AF. We retrospectively correlated diurnal HR patterns (recorded by 24-hour Holter monitoring) in patients with AF who independently also underwent diagnostic polysomnography. Exclusion criteria were paced rhythm or inadequate recordings from polysomnography and Holter monitoring. The relationship between the presence and severity of OSA and the mean, minimum, maximum HR, as well as pauses (>2 seconds) and their diurnal variation were studied. Of the 494 studied patients (age 69 ± 10 years; 26% women) mild-moderate OSA (apnea hypoxia index ≥5 and <20) was present in 171 (34%) and severe OSA (apnea hypoxia index ≥20) in 254 (51%). Mean 24-hour HR in patients with severe OSA and mild-moderate OSA was similar to those without OSA (78 vs 80 vs 79 beats per minute; p = 0.39), and there was no significant difference observed in minimum and maximum HR of these groups. However, the frequency of short pauses was greater in OSA patients (p = 0.009), with a prominent nocturnal distribution. In conclusion, OSA was not associated with increased HR in patients with AF suggesting that adequate HR control was similarly achievable in patients with and without OSA. The increased frequency of nocturnal pauses in OSA patients may function as a clinical hallmark, and the timing of pauses (during sleep vs wakefulness) should be noted before making therapeutic decisions regarding HR control.

Cytokinin signalling regulates organ identity via the AHK4 receptor in Arabidopsis.

Mutual interactions of the phytohormones, cytokinins and auxin determine root or shoot identity during postembryonic de novo organogenesis in plants. However, our understanding of the role of hormonal metabolism and perception during early stages of cell fate reprogramming is still elusive. Here we show that auxin activates root formation, whereas cytokinins mediate early loss of the root identity, primordia disorganisation and initiation of shoot development. Exogenous and endogenous cytokinins influence the initiation of newly formed organs, as well as the pace of organ development. The process of de novo shoot apical meristem establishment is accompanied by accumulation of endogenous cytokinins, differential regulation of genes for individual cytokinin receptors, strong activation of AHK4-mediated signalling and induction of the shoot-specific homeodomain regulator WUSCHEL. The last is associated with upregulation of isopentenyladenine-type cytokinins, revealing higher shoot-forming potential when compared with trans-zeatin. Moreover, AHK4-controlled cytokinin signalling negatively regulates the root stem cell organiser WUSCHEL RELATED HOMEOBOX 5 in the root quiescent centre. We propose an important role for endogenous cytokinin biosynthesis and AHK4-mediated cytokinin signalling in the control of de novo-induced organ identity.

Chronic obstructive pulmonary disease as a risk factor for ventricular arrhythmias independent of left ventricular function.

BACKGROUND: The association between chronic obstructive pulmonary disease (COPD) and sudden cardiac death has not been fully elucidated. OBJECTIVE: The purpose of this study was to investigate whether decreased left ventricular ejection fraction (LVEF) can explain the increased rate of ventricular tachycardia (VT) in COPD. METHODS: This retrospective study included consecutive adult patients who underwent pulmonary function testing (PFT), Holter monitoring, and transthoracic echocardiography. COPD was correlated with the frequency of VT in a multivariate analysis that adjusted for known confounders including LVEF. Long-term all-cause mortality of patients with COPD and VT was examined. RESULTS: Of the 6351 patients included in this study (age 66 ± 15 years; 48% woman; 92% Caucasian, LVEF 59% ± 12%), 2800 (44%) had PFT indicative of COPD. VT was nearly twice as likely to occur during Holter monitoring in COPD patients (13% vs 23%; P <.001), and the severity of COPD correlated with the risk of VT (21% vs 28% vs 37% for mild-moderate, severe, and very severe COPD; P <.001). COPD and VT remained independently associated (P <.001) even after adjusting for LVEF, demographics, and comorbidities (age, sex, body mass index, hypertension, chronic kidney disease, coronary artery disease, cancer history, diabetes mellitus). COPD was associated with all-cause mortality independently of LVEF (P <.001). CONCLUSION: COPD patients are at higher risk for VT and mortality. This may not be fully attributed to the confounding effect of systolic heart failure measured by LVEF. Further studies are needed to explore the mechanistic interactions between VT and COPD in order to determine whether antiarrhythmic strategies would apply especially to patients with severe COPD.

Impact of cardiopulmonary bypass surgery on cytokines in epicardial adipose tissue: comparison with subcutaneous fat.

BACKGROUND: Cardiac surgery and cardiopulmonary bypass (CPB) have been shown to stimulate a systemic inflammatory response which has been associated with adverse postoperative outcomes. Adipose tissue, both epicardial (EAT) and subcutaneous (SAT), is a known source of inflammatory cytokines, but its role in the pathophysiology of surgery- and CPB-induced systemic inflammatory response has not been fully elucidated. Therefore, we conducted a study to establish levels of selected cytokines in EAT and SAT prior to and after surgery with CPB. METHODS: Adipose tissue samples were obtained from patients undergoing planned cardiac surgery on CPB. Samples from EAT and SAT were collected before and immediately after CPB. Levels of tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), adipocyte fatty acid-binding protein (AFABP), leptin and adiponectin were determined by ELISA, which were adjusted for a total concentration of proteins in the individual samples. RESULTS: Samples from 77 patients (mean age 67.68 ± 11.5 years) were obtained and analysed. Leptin, adiponectin, TNF-α and AFABP were shown to decrease their concentrations statistically significantly in the EAT after CPB while no statistically significant drop was observed in the SAT. On the contrary, IL-6 showed only a slight and statistically insignificant decrease in the EAT after CPB and it was in the SAT where a statistically significant drop was observed. DISCUSSION: One of the most relevant findings of this study was the marked decrease in EAT levels of TNF-α, AFABP, leptin and adiponectin after the CPB termination. Our results suggest that EAT might serve as a pool of cytokines which are released into the circulation in reaction to surgery with CPB. Should these novel findings be confirmed, new strategies to assess and possibly reduce EAT contribution on adverse outcomes of cardiac surgery may be developed.

Predictors of Elevated Defibrillation Threshold with the Subcutaneous Implantable Cardioverter-defibrillator.

There are limited data regarding defibrillation thresholds (DFTs) for the subcutaneous implantable cardioverter-defibrillator (S-ICD), and factors associated with elevated DFTs remain incompletely understood. The objective of this study was to determine the factors associated with elevated DFTs in patients undergoing S-ICD implantation. A retrospective cross-sectional analysis of all patients undergoing S-ICD implantation at our institution between 2013 and 2016 who underwent step-down DFT testing was performed. Factors associated with a higher DFT were analyzed. In total, 56 patients (mean age: 49.3 ± 13.1 years, mean left ventricular ejection rate: 31.1% ± 13.7%) underwent S-ICD implantation in the study period. Full DFT testing was performed in 31 of the 56 patients (55%), with an average DFT of 46.4 joules (J) ± 25.9 J found among this cohort. The DFT was > 65 J in five of the 31 patients (16%). A high DFT was associated with increased body mass index (BMI) (37.7 kg/m2 versus 29.4 kg/m2; p = 0.02) and either increased septal or posterior wall thickness (1.5 cm versus 1.0 cm; p = 0.0003 and 1.4 cm versus 1.1 cm; p= 0.003, respectively). Patients with high DFTs also had higher failed shock impedance values (138 Ω versus 71 Ω; p = 0.005). Renal failure did not appear to affect DFT (51.4 J versus 51.7 J; p = 0.99). BMI, body surface area (BSA), and septal and posterior left ventricular wall thickness predicted elevated DFT on univariate analysis, although findings were not significant with multivariate analysis due to the small sample size. Thus, elevated S-ICD DFT appears to be associated with increased BMI, BSA, and septal or posterior wall thickness. In contrast, dialysis-dependent renal failure is not associated with elevated DFT. Further investigation is necessary in order to better characterize and predict which patients are at-risk for high DFTs.

Elevation of cardiac troponin T in patients with amyotrophic lateral sclerosis.

Limited evidence suggests that specificity of cardiac troponin T (cTnT), a highly sensitive biomarker of myocardial injury, is reduced in patients with skeletal myopathies. Whether amyotrophic lateral sclerosis (ALS)-the most common motor neuron disease-could be also associated with abnormal plasma or serum cTnT levels remains unclear. Our objective was to assess cTnT levels in patients with ALS without known cTnT elevating conditions. Among ALS patients seen at our institution until 2012 we identified those who had their cTnT measured. Patients who suffered from conditions known to elevate cTnT were excluded. A case-control analysis comparing cTnT levels of these ALS patients to matched non-ALS controls fulfilling the same inclusion criteria was performed. We included 40 ALS patients of whom 27 (68 %) patients had a positive cTnT. In the control group (n = 40), 2 (5 %) tested as cTnT positive (p < 0.001). Among the ALS patients who underwent cTnT evaluation on more occasions (n = 7; median follow-up = 1.08 years), 2 (29 %) patients tested positive during the initial measurement while 6 (86 %) of them had positive cTnT at the subsequent evaluations. ALS patients with increased cTnT had been diagnosed with ALS significantly earlier than those without the elevation. Our findings raise the possibility that ALS may cause cTnT elevations. Further studies are needed to confirm these findings, clarify the pathophysiological mechanism, and establish the significance of cTnT elevations in patients with ALS.

Phosphodiesterase 5 Inhibitor Use in Men With Hypertrophic Cardiomyopathy.

The prevalence of sexual dysfunction (SD) in men with hypertrophic cardiomyopathy (HC) remains unknown, yet its clinical relevance may be high given that its treatment-phosphodiesterase 5 inhibitors (PDE5i)-can increase the left ventricular outflow tract pressure gradient. In this retrospective study, we evaluated the medical records of consecutively seen men with HC for the evidence of SD (defined as SD diagnosis noted in the medical record, the use of medications unique for SD, or SD reported by the patient on a routine clinical questionnaire). Of the 283 consecutively seen men with HC (mean age 52.9 ± 14.1 years), 63 patients (22%) with SD were identified. Of those with SD, 38% were recorded as regularly using PDE5i. In conclusion, SD and the use of PDE5i present a relatively common occurrence in men with HC, and further studies are needed to develop an evidence-guided algorithm for safe implementation of SD therapies in this most common inherited cardiomyopathy.

Decrease in longitudinal strain in heart transplant recipients is associated with rejection.

BACKGROUND: Around 20-40% of heart transplant patients experience moderate to severe rejection within the first year after heart transplantation. Endomyocardial biopsy (EMB) is a gold standard for diagnosing heart transplant rejection. There is a need for non-invasive alternatives that allow for early, safe and reliable diagnosis of acute graft rejection prior to the onset of clinical symptoms. AIMS: Our aim was to investigate the potential of speckle tracking derived strain analysis in the diagnosis of acute graft rejection. METHODS: Patients indicated for EMB consented to a trans-thoracic echocardiography examination (TTE) within 2 hours of the EMB. Of this cohort, those with at least 2 EMBs separated ≥ 1 week, and whose TTE could be analyzed for strain, were included. The relationship between strain and EMB results was evaluated. RESULTS: Of the 43 patients included (mean age 51.33±1.79, 67% male), 23 had findings of rejection identified on at least one EMB and at least one EMB without rejection for comparison. A significant deterioration in the longitudinal strain during rejection compared to non-rejection was found on apical 4-chamber views (-11.51±0.91 vs -13.48±0.96, P=0.025) and apical 2-chamber views (-11.84±0.78 vs -14.43±0.83, P=0.002). In the patients in whom no rejection was identified on either EBM, there was no significant change in longitudinal strain values at two different time points. CONCLUSION: Worsening of longitudinal strain was associated with acute cellular rejection. Routine TTE-based strain analysis could help in early detection of cardiac rejection and timing of EMB.

Endomyocardial biopsy-integrating electrode at the bioptome tip.

BACKGROUND: The addition of electroanatomic mapping to a standard echo-guided endomyocardial biopsy could identify areas of abnormal pathology and increase the diagnostic yield of the procedure. METHODS AND RESULTS: In this demonstration of a novel technique, a 45-year-old woman with clinical suspicion for cardiac sarcoidosis underwent right ventricular bipolar electroanatomical mapping with identification of areas of signal fractionation and low voltage. A bioptome, configured to record an electrogram from the tip, was then visualized on the three-dimensional electroanatomic mapping (3DEAM) system, and directed to these areas. The biopsy was assisted by the use of a steerable introducer sheath, and by recording unipolar and extended bipolar signals from the bioptome tip. A prominent change in the signal was detected by the electrode at the bioptome tip when the jaws closed on the endomyocardial tissue. Patient tolerated the procedure without complications, and the biopsied samples were appropriate for pathological analysis. CONCLUSIONS: Using existing technology, the 3DEAM, which integrates unipolar and bipolar signal from the bioptome tip, is feasible, and can be safely added to a standard echocardiographically guided endomyocardial biopsy. Future studies should investigate whether such a technique could increase the safety and diagnostic yield of endomyocardial biopsies in patients with suspected cardiomyopathies.

Correlation of geomagnetic activity with implantable cardioverter defibrillator shocks and antitachycardia pacing.

OBJECTIVE: To investigate a potential relationship between implantable cardioverter defibrillator (ICD) therapies and daily geomagnetic activity (GMA) recorded in a large database. PATIENTS AND METHODS: The ALTITUDE database, derived from the Boston Scientific LATITUDE remote monitoring system, was retrospectively analyzed for the frequency of ICD therapies. Daily GMA was expressed as the planetary K-index and the integrated A-index and was graded as levels I (quiet), II (unsettled), III (active), and IV (storm). RESULTS: A daily mean ± SD of 59,468±11,397 patients were monitored between January 1, 2009, and May 15, 2012. The distribution of days according to GMA was as follows: level I, 924/1231 (75%); level II, 226/1231 (18%); level III, 60/1231 (5%); and level IV, 21/1231 (2%). The daily mean ± SD numbers of ICD shocks received per 1000 active patients in the database were 1.29±0.47, 1.17±0.46, 1.03±0.37, and 0.94±0.29 on level I, II, III, and IV days, respectively; the daily mean ± SD sums of shocks and antitachycardia pacing therapies were 9.29±2.86, 8.46±2.45, 7.92±1.80, and 7.83±2.28 on quiet, unsettled, active, and storm days, respectively. A significant inverse relationship between GMA and frequency of ICD therapies was identified, with the most pronounced difference between level I and level IV days (P<.001 for shocks; P=.008 for shocks + antitachycardia pacing). CONCLUSION: In a large-scale cohort analysis, ICD therapies were delivered less frequently on days of higher GMA, confirming the previous pilot data and suggesting that higher GMA does not pose an increased risk of arrhythmias using ICD therapies as a surrogate marker. Further studies are needed to gain an in-depth understanding of the underlying mechanisms.

Decreased exercise capacity and sleep-disordered breathing in patients with hypertrophic cardiomyopathy.

BACKGROUND: Mechanisms of decreased exercise capacity in patients with hypertrophic cardiomyopathy (HCM) are not well understood. Sleep-disordered breathing (SDB) is a highly prevalent but treatable disorder in patients with HCM. The role of comorbid SDB in the attenuated exercise capacity in HCM has not been studied previously. METHODS: Overnight oximetry, cardiopulmonary exercise testing, and echocardiographic studies were performed in consecutive patients with HCM seen at the Mayo Clinic. SDB was considered present if the oxygen desaturation index (number of ≥ 4% desaturations/h) was ≥ 10. Peak oxygen consumption (VO2 peak) (the most reproducible and prognostic measure of cardiovascular fitness) was then correlated with the presence and severity of SDB. RESULTS: A total of 198 patients with HCM were studied (age, 53 ± 16 years; 122 men), of whom 32% met the criteria for the SDB diagnosis. Patients with SDB had decreased VO2 peak compared with those without SDB (16 mL O2/kg/min vs 21 mL O2/kg/min, P < .001). SDB remained significantly associated with VO2 peak after accounting for confounding clinical variables (P < .001) including age, sex, BMI, atrial fibrillation, and coronary artery disease. CONCLUSIONS: In patients with HCM, the presence of SDB is associated with decreased VO2 peak. SDB may represent an important and potentially modifiable contributor to impaired exercise tolerance in this unique population.

Percutaneous ablation and retrieval of a right atrial myxoma.

We report the first case of percutaneous myxoma ablation and retrieval from the right atrium. This novel procedure may reduce the need for repeat surgical excisions in patients with Carney Complex and other recurrent myxoma syndromes.