New record of Gracilariaphuquocensis (Gracilariaceae, Rhodophyta) in the Philippines.

While reliance on morphology has been at the expense of clearly distinguishing gracilarioid species, molecular data have proven to be more reliable in discriminating between taxa. Gracilariaphuquocensis was originally described, based on materials collected from Vietnam. Since it was described in 2020, there have been no further reports of this species. Meanwhile, a question has been raised as to whether the identity of a rhodophyte gracilarioid alga collected from the Philippines that has been referred to as an unidentified species of Gracilaria, could be G.phuquocensis. Based on comparative morpho-anatomical features and a molecular phylogeny based on rbcL gene sequences, establishing the identity of the Philippine material has led to the finding of the new record of G.phuquocensis outside its type locality. In addition to the discovery of G.phuquocensis in the Philippines, the species here is also identified as a newly-reported host for the adelphoparasite resembling Gracilariababae.

Effects of Lifestyle Modification on Psychosocial Function in Patients With Resistant Hypertension: SECONDARY OUTCOMES FROM THE TRIUMPH RANDOMIZED CLINICAL TRIAL.

PURPOSE: In a secondary analysis of the TRIUMPH clinical trial, psychological outcomes in patients with resistant hypertension (RH) receiving a diet and exercise intervention delivered in a cardiac rehabilitation setting were compared with those receiving a similar prescription of diet and exercise provided in a single counseling session by a health educator. METHODS: One hundred forty patients with RH were randomly assigned to a 4-mo program of dietary counseling, behavioral weight management, and exercise (C-LIFE) or a single counseling session providing standardized education and physician advice (SEPA). Participants completed a battery of questionnaires to assess psychological functioning before and after the intervention. A global measure of psychological functioning was derived from the General Health Questionnaire (GHQ), Perceived Stress Scale (PSS), Medical Outcomes Study 36-item Short Form Health Survey, Spielberger State-Trait Anxiety Inventory, Hospital Anxiety and Depression Scale (HADS), Beck Depression Inventory-II, and Patient-Reported Outcomes Measurement Information System (PROMIS) Anger scale. RESULTS: Participants in the C-LIFE intervention achieved greater improvements in psychological functioning compared with SEPA (C-LIFE: 58.9 [56.1, 61.8] vs SEPA: 66.5 [62.1, 70.9]; P = .024). Greater improvements were especially evident for the GHQ, PSS, and HADS. Examination of mediation revealed that greater weight loss ( B =-0.17, P = .004) and improved oxygen uptake ( B =-0.12, P = .044) were associated with improved psychological functioning. CONCLUSION: Compared with standard education and physician advice, a structured program of diet and exercise not only reduced blood pressure but also improved psychological functioning in patients with RH.

Docking Studies and Molecular Dynamics Simulations of Potential Inhibitors from the Brown Seaweed Sargassum polycystum (Phaeophyceae) against PLpro of SARS-CoV-2.

The COVID-19 disease is a major problem affecting human health all over the world. Consequently, researchers have been trying to find solutions to treat this pandemic-scale disease. Even if there are vaccines and approved drugs that could decrease the spread of this pandemic, multidisciplinary approaches are still needed to identify new small molecules as alternatives to combat COVID-19, especially those from nature. In this study, we employed computational approaches by screening 17 natural compounds from the tropical brown seaweed Sargassum polycystum known to have anti-viral properties that benefit human health. This study assessed some seaweed natural products that are bound to the PLpro of SARS-CoV-2. By employing pharmacophore and molecular docking, these natural compounds from S. polycystum showed remarkable scores for protein targets with competitive scores compared to X-ray crystallography ligands and well-known antiviral compounds. This study provides insightful information for advanced study and further in vitro examination and clinical investigation for drug development prospects of abundant yet underexploited tropical seaweeds.

Exercise and Escitalopram in the Treatment of Anxiety in Patients with Coronary Heart Disease: One Year Follow-Up of the UNWIND Randomized Clinical Trial.

Anxiety is common among patients with coronary heart disease (CHD) and is associated with a worse prognosis. UNWIND was a 12-week randomized clinical trial comparing exercise and escitalopram to placebo on measures of anxiety, depression, and CHD biomarkers. Primary results of the trial reported that treatment with escitalopram, but not exercise, was associated with significant reductions in anxiety and depression. At 1-year follow-up, participants completed the Hospital Anxiety-Depression Scale-Anxiety (HADS-A) along with the HADS-Depression (HADS-D), the Beck Depression Inventory-II (BDI-II), and the Godin Leisure Time Exercise survey to assess physical activity. Results showed that those patients randomized to escitalopram had lower scores on the HADS-A compared to those randomized to exercise (P = 0.006) and had less depression compared to exercise on the HADS-D (P = 0.004) and BDI-II (P = 0.004). Participants randomized to exercise reported higher levels of physical activity at 1-year compared to those randomized to Placebo (P = 0.039). However, despite reporting being more physically active, those randomized to exercise did not have less anxiety or depression compared to placebo controls. Escitalopram appears to be a safe and effective treatment for anxiety; exercise has many health benefits, but does not appear to be effective in treating anxiety.

Unveiling new perspective of phylogeography, genetic diversity, and population dynamics of Southeast Asian and Pacific chickens.

The complex geographic and temporal origins of chicken domestication have attracted wide interest in molecular phylogeny and phylogeographic studies as they continue to be debated up to this day. In particular, the population dynamics and lineage-specific divergence time estimates of chickens in Southeast Asia (SEA) and the Pacific region are not well studied. Here, we analyzed 519 complete mitochondrial DNA control region sequences and identified 133 haplotypes with 70 variable sites. We documented 82.7% geographically unique haplotypes distributed across major haplogroups except for haplogroup C, suggesting high polymorphism among studied individuals. Mainland SEA (MSEA) chickens have higher overall genetic diversity than island SEA (ISEA) chickens. Phylogenetic trees and median-joining network revealed evidence of a new divergent matrilineage (i.e., haplogroup V) as a sister-clade of haplogroup C. The maximum clade credibility tree estimated the earlier coalescence age of ancestral D-lineage (i.e., sub-haplogroup D2) of continental chickens (3.7 kya; 95% HPD 1985-4835 years) while island populations diverged later at 2.1 kya (95% HPD 1467-2815 years). This evidence of earlier coalescence age of haplogroup D ancestral matriline exemplified dispersal patterns to the ISEA, and thereafter the island clade diversified as a distinct group.

Lifestyle modification and cognitive function among individuals with resistant hypertension: cognitive outcomes from the TRIUMPH trial.

BACKGROUND: Resistant hypertension is associated with increased risk of cognitive decline, stroke, and dementia. Lifestyle modification has been suggested to improve cognitive function through its salutary effects on vascular function. METHODS: Participants included 140 patients with resistant hypertension participating in the TRIUMPH trial. Participants were randomized to a cardiac rehabilitation-based lifestyle program (C-LIFE) or a standardized education and physician advice condition (SEPA). Participants completed a 45-min cognitive test battery consisting of tests of Executive Functioning and Learning, Memory, and Processing Speed. Biomarkers of vascular [flow mediated dilation of the brachial artery (FMD)], microvascular, and cerebrovascular function were also collected, in addition to weight, fitness, and ambulatory blood pressure. RESULTS: Participants averaged 63 years of age, 48% women, 59% black, and obese [mean BMI = 36 kg/m 2 (SD = 4)]. Cognitive performance improved across the entire cohort during the 4-month trial [ t -scores pretreatment = 48.9 (48, 50) vs. posttreatment = 50.0 (49, 51), P  < 0.001]. Postintervention Executive Function/Learning composite performance was higher for participants in C-LIFE compared to SEPA ( d  = 0.37, P  = 0.039). C-LIFE intervention effects on Memory and Processing Speed were moderated by sex and baseline stroke risk, respectively ( P  = 0.026 and P  = 0.043 for interactions), such that males and participants with greater stroke risk showed the greatest cognitive changes. FMD [C-LIFE: +0.3% (-0.3, 1.0) vs. SEPA: -1.4% (-2.5, -0.3), P  = 0.022], and microvascular function [C-LIFE: 97 (65, 130) vs. SEPA: 025 (-75, 23), P  < 0.001] were improved in C-LIFE compared with SEPA, whereas cerebrovascular reactivity was not [C-LIFE: -0.2 (-0.4, 0) vs. SEPA: 0.1 (-0.2, 0.4), P  = 0.197). Mediation analyses suggested that increased executive function/learning was associated with reduced ambulatory SBP levels secondary to weight loss [indirect effect: B  = 0.25 (0.03, 0.71)]. CONCLUSION: Lifestyle modification individuals with resistant hypertension improves cognition, which appeared to be associated with reduced ambulatory SBP changes through weight loss. Cognitive improvements were accompanied by parallel improvements in endothelial and microvascular function.

Longer term benefits of exercise and escitalopram in the treatment of anxiety in patients with coronary heart disease: Six month follow-up of the UNWIND randomized clinical trial.

BACKGROUND: Anxiety is a common comorbidity in patients with coronary heart disease (CHD) and is associated with worse prognosis. However, effective treatment for anxiety in CHD patients is uncertain. The UNWIND randomized clinical trial showed that 12-week treatment of escitalopram was better than exercise training or placebo in reducing anxiety in anxious CHD patients. The longer-term benefits of treatment for anxiety are not known. METHODS: Patients were randomized to 12 weeks of Escitalopram (up to 20 mg), Exercise (3 times/wk), or placebo pill. At the conclusion of treatment, participants were followed for 6-months to determine the persistence of benefit on the primary anxiety endpoint assessed by the Hospital Anxiety and Depression Scale-Anxiety scale (HADS-A) and to assess the effects of treatment on major adverse cardiac events over a follow-up period of up to 6 years. RESULTS: Of the 128 participants initially randomized, 120 (94%) were available for follow-up. Participants randomized to the Escitalopram condition exhibited lower HADS-A scores (3.9 [3.1, 4.7]) compared to those randomized to Exercise (5.5 [4.6, 6.3]) (P = .007) and Placebo (5.3 [4.1, 6.5]) (P = .053). Over a median follow-up of 3.2 years (IQR: 2.3, 4.5), there were 29 adverse events but no significant between-group differences. CONCLUSION: In the UNWIND trial, 12 weeks of escitalopram treatment was effective in reducing anxiety. These beneficial effects were sustained for 6 months posttreatment. Although moderate or vigorous physical activity has a number of health benefits, exercise was not an effective treatment for anxiety in patients with CHD.

Potential bioactive compounds as SARS-CoV-2 inhibitors from extracts of the marine red alga Halymenia durvillei (Rhodophyta) - A computational study.

The respiratory infection COVID-19 caused by the virus SARS CoV-2 has continued to be a major health problem worldwide and has caused more than a million mortalities. Even if the development of COVID-19 vaccines has shown much progress, efforts to find novel, natural anti-viral drugs should be pursued. Halymenia durvillei is a marine red alga widely distributed around Southeast Asia. This study aimed to develop new anti SARS CoV-2 compounds from ethanolic and ethyl acetate extracts of H. durvillei via a computational approach, focusing onthe inhibitory action against the main protease (3CL-Mpro). In this study, 37 compounds were extracted and identified by GC-MS analysis. The potentials of compounds 1-2 tetradecandiol and E,E,Z-1,3,12-nonadecatriene-5,14-diol were identified for therapeutic purposes based on our pharmacophore study, while cholest-5-En-3-Ol (3.Beta.)- had a high fitness score in molecular docking studies both in monomer and dimer state compared to the N3 inhibitor and remdesivir affinity scores. As these compounds show competitive affinity scores against the 3CL-Mpro, these natural compounds may be effective for the treatment of COVID-19 infection. The ADME and pharmacokinetic studies should also be employed to assess the ability of the natural compounds as oral drugs. These promising results have shown the potentials of H. durvillei as an alternative drug in addressing COVID-19 infection. Accordingly, further studies should explore the effectiveness of these active compounds.

Analysis of rDNA reveals a high genetic diversity of Halophila major in the Wallacea region.

The genus Halophila shows the highest species diversity within the seagrass genera. Southeast Asian countries where several boundary lines exist were considered as the origin of seagrasses. We hypothesize that the boundary lines, such as Wallace's and Lydekker's Lines, may act as marine geographic barriers to the population structure of Halophila major. Seagrass samples were collected at three islands in Vietnamese waters and analyzed by the molecular maker ITS. These sequences were compared with published ITS sequences from seagrasses collected in the whole region of interest. In this study, we reveal the haplotype and nucleotide diversity, linking population genetics, phylogeography, phylogenetics and estimation of relative divergence times of H. major and other members of the Halophila genus. The morphological characters show variation. The results of the ITS marker analysis reveal smaller groups of H. major from Myanmar, Shoalwater Bay (Australia) and Okinawa (Japan) with high supporting values. The remaining groups including Sri Lanka, Viet Nam, the Philippines, Thailand, Malaysia, Indonesia, Two Peoples Bay (Australia) and Tokushima (Japan) showed low supporting values. The Wallacea region shows the highest haplotype and also nucleotide diversity. Non-significant differences were found among regions, but significant differences were presented among populations. The relative divergence times between some members of section Halophila were estimated 2.15-6.64 Mya.

Effects of Lifestyle Modification on Patients With Resistant Hypertension: Results of the TRIUMPH Randomized Clinical Trial.

BACKGROUND: Although lifestyle modifications generally are effective in lowering blood pressure (BP) among patients with unmedicated hypertension and in those treated with 1 or 2 antihypertensive agents, the value of exercise and diet for lowering BP in patients with resistant hypertension is unknown. METHODS: One hundred forty patients with resistant hypertension (mean age, 63 years; 48% female; 59% Black; 31% with diabetes; 21% with chronic kidney disease) were randomly assigned to a 4-month program of lifestyle modification (C-LIFE [Center-Based Lifestyle Intervention]) including dietary counseling, behavioral weight management, and exercise, or a single counseling session providing SEPA (Standardized Education and Physician Advice). The primary end point was clinic systolic BP; secondary end points included 24-hour ambulatory BP and select cardiovascular disease biomarkers including baroreflex sensitivity to quantify the influence of the baroreflex on heart rate, high-frequency heart rate variability to assess vagally mediated modulation of heart rate, flow-mediated dilation to evaluate endothelial function, pulse wave velocity to assess arterial stiffness, and left ventricular mass to characterize left ventricular structure. RESULTS: Between-group comparisons revealed that the reduction in clinic systolic BP was greater in C-LIFE (-12.5 [95% CI, -14.9 to -10.2] mm Hg) compared with SEPA(-7.1 [-95% CI, 10.4 to -3.7] mm Hg) (P=0.005); 24-hour ambulatory systolic BP also was reduced in C-LIFE (-7.0 [95% CI, -8.5 to -4.0] mm Hg), with no change in SEPA (-0.3 [95% CI, -4.0 to 3.4] mm Hg) (P=0.001). Compared with SEPA, C-LIFE resulted in greater improvements in resting baroreflex sensitivity (2.3 ms/mm Hg [95% CI, 1.3 to 3.3] versus -1.1 ms/mm Hg [95% CI, -2.5 to 0.3]; P<0.001), high-frequency heart rate variability (0.4 ln ms2 [95% CI, 0.2 to 0.6] versus -0.2 ln ms2 [95% CI, -0.5 to 0.1]; P<0.001), and flow-mediated dilation (0.3% [95% CI, -0.3 to 1.0] versus -1.4% [95% CI, -2.5 to -0.3]; P=0.022). There were no between-group differences in pulse wave velocity (P=0.958) or left ventricular mass (P=0.596). CONCLUSIONS: Diet and exercise can lower BP in patients with resistant hypertension. A 4-month structured program of diet and exercise as adjunctive therapy delivered in a cardiac rehabilitation setting results in significant reductions in clinic and ambulatory BP and improvement in selected cardiovascular disease biomarkers. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02342808.

Effect of Exercise, Escitalopram, or Placebo on Anxiety in Patients With Coronary Heart Disease: The Understanding the Benefits of Exercise and Escitalopram in Anxious Patients With Coronary Heart Disease (UNWIND) Randomized Clinical Trial.

Importance: Anxiety is common among patients with coronary heart disease (CHD) and is associated with worse health outcomes; however, effective treatment for anxiety in patients with CHD is uncertain. Objective: To determine whether exercise and escitalopram are better than placebo in reducing symptoms of anxiety as measured by the Hospital Anxiety and Depression-Anxiety Subscale (HADS-A) and in improving CHD risk biomarkers. Design, Setting, and Participants: This randomized clinical trial was conducted between January 2016 and May 2020 in a tertiary care teaching hospital in the US and included 128 outpatients with stable CHD and a diagnosed anxiety disorder or a HADS-A score of 8 or higher who were older than 40 years, sedentary, and not currently receiving mental health treatment. Interventions: Twelve weeks of aerobic exercise 3 times per week at an intensity of 70% to 85% heart rate reserve, escitalopram (up to 20 mg per day), or placebo pill equivalent. Main Outcomes and Measures: The primary outcome was HADS-A score. CHD biomarkers included heart rate variability, baroreflex sensitivity, and flow-mediated dilation, along with 24-hour urinary catecholamines. Results: The study included 128 participants. The mean (SD) age was 64.6 (9.6) years, and 37 participants (29%) were women. Participants randomized to the exercise group and escitalopram group reported greater reductions in HADS-A (exercise, -4.0; 95% CI, -4.7 to -3.2; escitalopram, -5.7; 95% CI, -6.4 to -5.0) compared with those randomized to placebo (-3.5; 95% CI, -4.5 to -2.4; P = .03); participants randomized to escitalopram reported less anxiety compared with those randomized to exercise (-1.67; 95% CI, -2.68 to -0.66; P = .002). Significant postintervention group differences in 24-hour urinary catecholamines were found (exercise z score = 0.05; 95% CI, -0.2 to 0.3; escitalopram z score = -0.24; 95% CI, -0.4 to 0; placebo z score = 0.36; 95% CI, 0 to 0.7), with greater reductions in the exercise group and escitalopram group compared with the placebo group (F1,127 = 4.93; P = .01) and greater reductions in the escitalopram group compared with the exercise group (F1,127 = 4.37; P = .04). All groups achieved comparable but small changes in CHD biomarkers, with no differences between treatment groups. Conclusions and Relevance: Treatment of anxiety with escitalopram was safe and effective for reducing anxiety in patients with CHD. However, the beneficial effects of exercise on anxiety symptoms were less consistent. Exercise and escitalopram did not improve CHD biomarkers of risk, which should prompt further investigation of these interventions on clinical outcomes in patients with anxiety and CHD. Trial Registration: ClinicalTrials.gov Identifier: NCT02516332.

Origin and Demographic History of Philippine Pigs Inferred from Mitochondrial DNA.

The Philippines is a mega-diverse country that lies at the crossroads of past human migrations in the Asia-Pacific region and is believed to have never been connected to the Asian continent, even during the major sea-level subsidence of the Quaternary. As a result, the history of pig dispersal in the Philippines remains controversial, due to limited molecular studies and absence of archaeological evidence of pig domestication. This study provides the first comprehensive analysis of 184 complete mitochondrial DNA D-loop region from Philippine pigs to elucidate their early dispersal history by performing a phylogenetic comparison with wild boars and domestic pigs worldwide. The results showed a demographic signal of the ancestry of Philippine pigs that had a close genetic relationship with those from the mainland Southeast Asia and Northeast Asia, suggesting gene flow that may have resulted from human migration and trade. Here we have suggested two possible dispersal routes. One parallels the Neolithic expansion in Island Southeast Asia and Oceania via Northeast Asia, the other from the mainland Southeast Asia, into Palawan and Sulu Archipelago as early as prehistoric times via the Sundaic Region. Despite geographic barriers to migration, numerous genetic lineages have persisted across the Philippine islands, even justifying the recognition of a Philippine Lanyu subclade. The prehistoric population history suggests a demographic expansion that coincided with the interglacial periods of the Pleistocene and may have spread from the southern regions into the eastern and central regions of the Philippines. The intriguing signal of discrepancy discovered between the ancestral pattern and distribution range of the numerous endemic Philippine wild pigs opens a challenging new approach to illuminate complexity among these animals. Our study has contributed significantly towards completing the sparse molecular studies on Philippine pigs, an essential for creating win-win conservation measures.

Predicting the Development of Reduced Left Ventricular Ejection Fraction in Patients With Left Bundle Branch Block.

Left bundle branch block (LBBB) increases the likelihood of developing reduced left ventricular (LV) ejection fraction (EF) but predicting which patients with LBBB and normal LVEF will develop decreased LVEF remains challenging. Fifty patients with LBBB and normal LVEF were retrospectively identified. Clinical, electrocardiographic, and echocardiographic variables were compared between patients who developed a decreased LVEF and those who did not. A total of 16 of 50 patients developed reduced LVEF after 4.3 (SD = 2.8) years of follow-up. Baseline patient and electrocardiographic variables were similar between patients who did and did not develop decreased LVEF. Baseline LVEF was lower in patients who developed decreased LVEF than in those who did not (51.9% [SD = 2.2%] vs 54.9% [SD = 4.4%], p <0.01). Diastolic filling time (DFT) accounted for a significantly smaller percentage of the cardiac cycle in patients who developed decreased LVEF than in those who did not (35.9%, [SD = 6.9%] vs 44.4% [SD = 4.5%] p <0.01). In univariable logistic regression, DFT had a C-statistic of 0.86 (p <0.0001) for prediction of development of decreased LVEF. In conclusion, patients in whom DFT accounted for <38% of the cardiac cycle had a relative risk of developing decreased LVEF of 7.0 (95% confidence interval 3.0 to 16.0) compared to patients with DFT accounting for ≥38% of the cardiac cycle.

Allelopathic effects of macroalgae on Pocillopora acuta coral larvae.

Allelopathy has been proposed as a key mechanism mediating coral-algal interactions; however, few studies have tested macroalgal allelochemicals on coral larvae. In this study, we examined the effects of crude extracts from four macroalgal species on Pocillopora acuta larvae under different exposure conditions. Larval mortality increased considerably with increasing concentrations of Bryopsis sp., Endosiphonia horrida, and Lobophora sp. extracts. Increasing E. horrida and Lobophora sp. extract concentrations also substantially decreased larval settlement. No detectable effects on larvae were observed in Hypnea pannosa extracts. Further, while larval mortality increased with exposure duration to Lobophora sp. extracts, larval settlement was enhanced at 12 h exposure, but reduced at shorter and longer durations. Our results emphasize that macroalgal chemical effects are highly dependent on macroalgal species and exposure conditions. On reefs dominated by allelopathic macroalgae, the survivorship and settlement of coral larvae are potentially constrained, thereby limiting the recovery of degraded reefs.

Lifestyle and neurocognition in older adults with cognitive impairments: A randomized trial.

OBJECTIVE: To determine the independent and additive effects of aerobic exercise (AE) and the Dietary Approaches to Stop Hypertension (DASH) diet on executive functioning in adults with cognitive impairments with no dementia (CIND) and risk factors for cardiovascular disease (CVD). METHODS: A 2-by-2 factorial (exercise/no exercise and DASH diet/no DASH diet) randomized clinical trial was conducted in 160 sedentary men and women (age >55 years) with CIND and CVD risk factors. Participants were randomly assigned to 6 months of AE, DASH diet nutritional counseling, a combination of both AE and DASH, or health education (HE). The primary endpoint was a prespecified composite measure of executive function; secondary outcomes included measures of language/verbal fluency, memory, and ratings on the modified Clinical Dementia Rating Scale. RESULTS: Participants who engaged in AE (d = 0.32, p = 0.046) but not those who consumed the DASH diet (d = 0.30, p = 0.059) demonstrated significant improvements in the executive function domain. The largest improvements were observed for participants randomized to the combined AE and DASH diet group (d = 0.40, p = 0.012) compared to those receiving HE. Greater aerobic fitness (b = 2.3, p = 0.049), reduced CVD risk (b = 2.6, p = 0.042), and reduced sodium intake (b = 0.18, p = 0.024) were associated with improvements in executive function. There were no significant improvements in the memory or language/verbal fluency domains. CONCLUSIONS: These preliminary findings show that AE promotes improved executive functioning in adults at risk for cognitive decline. CLINICALTRIALSGOV IDENTIFIER: NCT01573546. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for adults with CIND, AE but not the DASH diet significantly improves executive functioning.

Assessment of Device-Related Thrombus and Associated Clinical Outcomes With the WATCHMAN Left Atrial Appendage Closure Device for Embolic Protection in Patients With Atrial Fibrillation (from the PROTECT-AF Trial).

Left atrial appendage closure with the WATCHMAN device is an alternative to anticoagulation for stroke prevention in selected patients with atrial fibrillation (AF). LA device-related thrombus (DRT) is poorly defined and understood. We aimed to (1) develop consensus echocardiographic diagnostic criteria for DRT; (2) estimate the incidence of DRT; and (3) determine clinical event rates in patients with DRT. In phase 1 (training), a training manual was developed and reviewed by 3 echocardiographers with left atrial appendage closure device experience. All available transesophageal (TEE) studies in the WATCHMAN left atrial appendage system for embolic protection in patients with atrial fibrillation (PROTECT-AF) trial patients with suspected DRT were reviewed in 2 subsequent phases. In phase 2 (primary blind read), each reviewer independently scored each study for DRT, and final echo criteria were developed. Unanimously scored studies were considered adjudicated, whereas all others were reevaluated by all reviewers in phase 3 (group adjudication read). DRT was suspected in 35 of 485 patients by the site investigator, the echocardiography core laboratory, or both; 93 of the individual TEE studies were available for review. In phase 2, 3 readers agreed on 67 (72%) of time points. Based on phases 1 and 2, 5 DRT criteria were developed. In phase 3, studies without agreement in phase 2 were adjudicated using these criteria. Overall, at least 1 TEE was DRT positive in 27 (5.7%) PROTECT-AF patients. Stroke, peripheral embolism, or cardiac/unexplained death occurred in subjects with DRT at a rate of 3.4 per 100 patient-years follow-up. In conclusion, DRT were identified on at least 1 TEE in 27 PROTECT-AF patients, indicating a DRT incidence of 5.7%. Primary efficacy events in patients with DRT occurred at a rate of 3.4 per 100 patient-years follow-up, intermediate in frequency between event rates previously reported for the overall device and warfarin arms in PROTECT-AF.

An Approach to Improve the Negative Predictive Value and Clinical Utility of Transthoracic Echocardiography in Suspected Native Valve Infective Endocarditis.

BACKGROUND: In patients with suspected native valve infective endocarditis, current guidelines recommend initial transthoracic echocardiography (TTE) followed by transesophageal echocardiography (TEE) if clinical suspicion remains. The guidelines do not account for the quality of initial TTE or other findings that may alter the study's diagnostic characteristics. This may lead to unnecessary TEE when initial TTE was sufficient to rule out vegetation. METHODS: The objective of this study was to determine if the use of a strict definition of negative results on TTE would improve the performance characteristics of TTE sufficiently to exclude vegetation. A retrospective analysis of patients at a single institution with suspected native valve endocarditis who underwent TTE followed by TEE within 7 days between January 1, 2007, and February 28, 2014, was performed. Negative results on TTE for vegetation were defined by either the standard approach (no evidence of vegetation seen on TTE) or by applying a set of strict negative criteria incorporating other findings on TTE. Using TEE as the gold standard for the presence of vegetation, the diagnostic performance of the two transthoracic approaches was compared. RESULTS: In total, 790 pairs of TTE and TEE were identified. With the standard approach, 661 of the transthoracic studies had negative findings (no vegetation seen), compared with 104 studies with negative findings using the strict negative approach (meeting all strict negative criteria). The sensitivity and negative predictive value of TTE for detecting vegetation were substantially improved using the strict negative approach (sensitivity, 98% [95% CI, 95%-99%] vs 43% [95% CI, 36%-51%]; negative predictive value, 97% [95% CI, 92%-99%] vs 87% [95% CI, 84%-89%]). CONCLUSIONS: The ability of TTE to exclude vegetation in patients is excellent when strict criteria for negative results are applied. In patients at low to intermediate risk with strict negative results on TTE, follow-up TEE may be unnecessary.

Lifestyle modification for resistant hypertension: The TRIUMPH randomized clinical trial.

BACKGROUND: Resistant hypertension (RH) is a growing health burden in this country affecting as many as 1 in 5 adults being treated for hypertension. Resistant hypertension is associated with increased risk of adverse cardiovascular disease (CVD) events and all-cause mortality. Strategies to reduce blood pressure (BP) in this high-risk population are a national priority. METHODS: TRIUMPH is a single-site, prospective, randomized clinical trial to evaluate the efficacy of a center-based lifestyle intervention consisting of exercise training, reduced sodium and calorie Dietary Approaches to Stop Hypertension eating plan, and weight management compared to standardized education and physician advice in treating patients with RH. Patients (n = 150) will be randomized in a 2:1 ratio to receive either a 4-month supervised lifestyle intervention delivered in the setting of a cardiac rehabilitation center or to a standardized behavioral counseling session to simulate real-world medical practice. The primary end point is clinic BP; secondary end points include ambulatory BP and an array of CVD biomarkers including left ventricular hypertrophy, arterial stiffness, baroreceptor reflex sensitivity, insulin resistance, lipids, sympathetic nervous system activity, and inflammatory markers. Lifestyle habits, BP, and CVD risk factors also will be measured at 1-year follow-up. CONCLUSIONS: The TRIUMPH randomized clinical trial (ClinicalTrials.gov NCT02342808) is designed to test the efficacy of an intensive, center-based lifestyle intervention compared to a standardized education and physician advice counseling session on BP and CVD biomarkers in patients with RH after 4 months of treatment and will determine whether lifestyle changes can be maintained for a year.

High-risk percutaneous coronary intervention is associated with reverse left ventricular remodeling and improved outcomes in patients with coronary artery disease and reduced ejection fraction.

BACKGROUND: Therapies that reverse pathologic left ventricular (LV) remodeling are often associated with improved outcomes. The incidence and impact of reverse LV remodeling after high-risk percutaneous coronary intervention (PCI) are unknown. METHODS: The PROTECT II study was a multicenter trial in patients with complex, multivessel coronary artery disease and reduced ejection fraction (EF) that revealed an increase in visual EF after high-risk PCI. Among patients with quantitative echocardiography (LV volumes and biplane EF), we assessed the extent and predictors of reverse LV remodeling, defined as improved systolic function with an absolute increase in EF ≥5% and correlated these findings with clinical events. RESULTS: Quantitative echocardiography was performed in 184 patients at baseline and longest follow-up. Mean EF at baseline was 27.1%. Ninety-three patients (51%) demonstrated reverse LV remodeling with an absolute increase in EF of 13.2% (P < .001). End-systolic volume decreased from 137.7 to 106.6 mL (P = .002). No significant change in EF or end-systolic volume was seen among non-remodelers. Reverse LV remodeling occurred more frequently in patients with more extensive revascularization (odds ratio, 7.52; 95% CI [1.31-43.25]) and was associated with significantly fewer major adverse events (composite of death/myocardial infarction/stroke/transient ischemic attack): 9.7% versus 24.2% (P = .009). There was also a greater reduction in New York Heart Association class III/IV heart failure among reverse LV remodelers (66.7% to 24.0%) than non-remodelers (56.3% to 34.4%), P = .045. CONCLUSIONS: Reverse LV remodeling can occur after high-risk PCI in patients with complex coronary artery disease and reduced EF and is associated with improved clinical outcomes.