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Background The enterosalivary nitrate-nitrite-nitric oxide (NO3-NO2-NO) pathway generates NO following oral microbiota-mediated production of salivary nitrite, potentially linking the oral microbiota to reduced cardiometabolic risk. Nitrite depletion by oral bacteria may also be important for determining the net nitrite available systemically. We examine if higher abundance of oral microbial genes favoring increased oral nitrite generation and decreased nitrite depletion is associated with a better cardiometabolic profile cross-sectionally. Methods and Results This study includes 764 adults (mean [SD] age 32 [9] years, 71% women) enrolled in ORIGINS (Oral Infections, Glucose Intolerance, and Insulin Resistance Study). Microbial DNA from subgingival dental plaques underwent 16S rRNA gene sequencing; PICRUSt2 was used to estimate functional gene profiles. To represent the different components and pathways of nitrogen metabolism in bacteria, predicted gene abundances were operationalized to create summary scores by (1) bacterial nitrogen metabolic pathway or (2) biochemical product (NO2, NO, or ammonia [NH3]) formed by the action of the bacterial reductases encoded. Finally, nitrite generation-to-depletion ratios of gene abundances were created from the above summary scores. A composite cardiometabolic Z score was created from cardiometabolic risk variables, with higher scores associated with worse cardiometabolic health. We performed multivariable linear regression analysis with cardiometabolic Z score as the outcome and the gene abundance summary scores and ratios as predictor variables, adjusting for sex, age, race, and ethnicity in the simple adjusted model. A 1 SD higher NO versus NH3 summary ratio was inversely associated with a -0.10 (false discovery rate q=0.003) lower composite cardiometabolic Z score in simple adjusted models. Higher NH3 summary score (suggestive of nitrite depletion) was associated with higher cardiometabolic risk, with a 0.06 (false discovery rate q=0.04) higher composite cardiometabolic Z score. Conclusions Increased net capacity for nitrite generation versus depletion by oral bacteria, assessed through a metagenome estimation approach, is associated with lower levels of cardiometabolic risk.

Periodontitis affects up to 50% of individuals worldwide, and 8.5% are diagnosed with diabetes. The high-comorbidity rate of these diseases may suggest, at least in part, a shared etiology and pathophysiology. Changes in oral microbial communities have been documented in the context of severe periodontitis and diabetes, both independently and together. However, much less is known about the early oral microbial markers of these diseases. We used a subset of the ORIGINS project dataset, which collected detailed periodontal and cardiometabolic information from 787 healthy individuals, to identify early microbial markers of periodontitis and its association with markers of cardiometabolic health. Using state-of-the-art compositional data analysis tools, we identified the log-ratio of Treponema to Corynebacterium bacteria to be a novel Microbial Indicator of Periodontitis (MIP), and found that this MIP correlates with poor periodontal health and cardiometabolic markers early in disease pathogenesis in both subgingival plaque and saliva.

• Results indicate that peripheral venous and tissue congestion are mediators of heart failure pathophysiology via induction of inflammation, oxidative stress, neurohormonal and endothelial activation, and suppression of endogenous defense mechanisms. • Treatment of congestion may have a critical role not only in symptom relief, but also in forestalling disease progression. • These results may also justify future testing of new adjuvant therapies (eg, short-term anti-inflammatory and anti-oxidant treatments) in patients with acute heart failure. Venous congestion (VC) is a hallmark of symptomatic heart failure (HF) requiring hospitalization; however, its role in the pathogenesis of HF progression remains unclear. We investigated whether peripheral VC exacerbates inflammation, oxidative stress and neurohormonal and endothelial cell (EC) activation in patients with HF with reduced ejection fraction (HFrEF). Two matched groups of patients with HFrEF and with no peripheral VC vs without recent HF hospitalization were studied. We modeled peripheral VC by inflating a cuff around the dominant arm, targeting ∼ 30 mmHg increase in venous pressure (venous stress test [VST]). Blood and ECs were sampled before and after 90 minutes of VST. We studied 44 patients (age 53 ± 12 years, 32% female). Circulating endothelin-1, tumor necrosis factor-α, interleukin-6, isoprostane, angiotensin II (ang-2), angiopoietin-2, vascular cell adhesion molecule-1, and CD146 significantly increased after the VST. Enhanced endothelin-1 and angiopoietin-2 responses to the VST were present in patients with vs without recent hospitalization and were prospectively associated with incident HF-related events; 6698 messenger ribonucleic acid (mRNA probe sets were differentially expressed in ECs after VST. Experimental VC exacerbates inflammation, oxidative stress, neurohormonal and EC activation and promotes unfavorable transcriptome remodeling in ECs of patients with HFrEF. A distinct biological sensitivity to VC appears to be associated with high risk for HF progression. [Display omitted] [ABSTRACT FROM AUTHOR]

Aortic regurgitation (AR) is a common complication following left ventricular assist device (LVAD) implantation. We evaluated the hemodynamic implications of AR in patients with HeartMate 3 (HM3) LVAD at baseline and in response to speed changes. Clinically stable outpatients supported by HM3 who underwent a routine hemodynamic ramp test were retrospectively enrolled in this analysis. Patients were stratified based on the presence of at least mild AR at baseline speed. Hemodynamic and echocardiographic parameters were compared between the AR and non-AR groups. Sixty-two patients were identified. At the baseline LVAD speed, 29 patients (47%) had AR, while 33 patients (53%) did not. Patients with AR were older and supported on HM3 for a longer duration. At baseline speed, all hemodynamic parameters were similar between the groups including central venous pressure, pulmonary capillary wedge pressure, pulmonary arterial pressures, cardiac output and index, and pulmonary artery pulsatility index (p > 0.05 for all). During the subacute assessment, AR worsened in some, but not all, patients, with increases in LVAD speed. There were no significant differences in 1-year mortality or hospitalization rates between the groups, however, at 1-year, ≥ moderate AR and right ventricular failure (RVF) were detected in higher rates among the AR group compared to the non-AR group (45% vs. 0%; p < 0.01, and 75% vs. 36.8%; p = 0.02, respectively). In a cohort of stable outpatients supported with HM3 who underwent a routine hemodynamic ramp test, the presence of mild or greater AR did not impact the ability of HM3 LVADs to effectively unload the left ventricle during early subacute assessment. Although the presence of AR did not affect mortality and hospitalization rates, it resulted in higher rates of late hemodynamic-related events in the form of progressive AR and RVF. The Hemodynamic Effects of Aortic Regurgitation in Patients Supported with HM3. [Display omitted] [ABSTRACT FROM AUTHOR]

‘BRS Isis' is a new colored seedless table grape tolerant to downy mildew, the main vine disease in subtropical humid areas. This new seedless cultivar is an interspecific hybrid from the crossing of CNPUV 681–29 [Arkansas 1976 X CNPUV 147–3 (‘Niagara Branca' x ‘Venus')] x ‘BRS Linda', and was recently released by Embrapa Grape and Wine, Brazil. The performance of ‘BRS Isis' seedless grape was evaluated in an experimental vineyard in 2016 located in a subtropical area at Marialva city, state of Parana, Brazil. The vines were grafted onto ‘IAC 766 Campinas' rootstock and trained in an overhead trellising system spaced at 2× 5 m. Vines were cane-pruning in late winter of July 2016, and for assessments, 20 representative vines were selected in the area. As ‘BRS Isis' is a very fruitful grape, presenting 4 bunches per shoot, a load adjustment was performed after fruitset removing 50% of bunches per shoot, leaving 2 bunches per shoot, equivalent to a density of 10 bunches.m−2. The duration in days of the main phenological stages from pruning to harvest, and the physicochemical and yield characteristics of ‘BRS Isis' seedless grape were subjected to evaluation. It was determined that the cycle is 144 days. The means of berry and bunch weight was 6.7 ± 1.0 g and 500.0 ± 0.04 g, respectively, and the color index of berries (CIRG) was 4.3 ± 1.3. The means of total soluble solids (TSS), titratable acidity (TA) and maturity index (TSS/TA) observed were 14.2 ± 0.3° Brix, 0.6 ± 0.04% of tartaric acid and 24.1 ± 1.5, respectively, while the yield was 49.0 ± 5.7 tons.ha−1. The yield observed is considered high to keep a sustainable crop over time, thus, in order to obtain grapes of ‘BRS Isis' with regular yield, and possibly, with a higher content of soluble solids, it is desirable to keep only 1 bunch per shoot (5 bunches.m−2) after fruitset.

De novo aortic insufficiency (AI) is a common adverse event after continuous-flow left ventricular assist device (LVAD) placement and is associated with morbidity and mortality. This study aims to compare the development of de novo AI between HeartMate 3 (Abbott) and HeartMate II LVAD recipients. A retrospective review was conducted of clinical characteristics and serial echocardiograms (1 month, 6 months, and 1 year postimplantation) of HeartMate 3 patients implanted between November 2014 and March 2019 and of HeartMate II patients implanted between April 2004 and December 2015 at Columbia University Irving Medical Center. One hundred twenty-two patients were excluded from analysis for a history of aortic valve surgery, concomitant aortic valve surgery with LVAD implant, or more than trace preoperative AI left untreated. De novo AI was defined as development of more than mild AI after LVAD implant. Included in the study were 121 HeartMate 3 patients and 270 HeartMate II patients. After accounting for competing risks of death and transplantation, there was no significant difference in the development of de novo AI by 1 year postimplantation between HeartMate II and HeartMate 3 patients (P =.68). There was no significant difference in severity of AI developed up to 1 year post-implantation between HeartMate II and HeartMate 3 patients. Development of de novo AI is comparable between HeartMate 3 and HeartMate II patients. There is no significant difference in severity of AI between HeartMate II and HeartMate 3 patients. [ABSTRACT FROM AUTHOR]

The intra-aortic balloon pump (IABP) is widely implanted as temporary mechanical circulatory support for cardiogenic shock (CS). However, its use is declining following the results of the IABP-SHOCK II trial, which failed to show a clinical benefit of the IABP in acute coronary syndrome (ACS)-related CS. Acute-on-chronic heart failure has become an increasingly recognized, distinct cause of CS (HF-CS). The pathophysiology of HF-CS differs from that of ACS-CS because it typically represents the progression from a state of congestion (with relatively preserved cardiac output) to a low-output state with hypoperfusion. The IABP is a volume-displacement pump that promotes forward flow from a high-capacitance reservoir to low-capacitance vessels, improving peripheral perfusion and decreasing left ventricular afterload in the setting of high filling pressures. The IABP can improve ventricular-vascular coupling and, therefore, myocardial energetics. Additionally, many patients with HF-CS are candidates for cardiac replacement therapies (left ventricular assist device or heart transplantation) and, therefore, may benefit from a bridge strategy that stabilizes the hemodynamics and end-organ function in preparation for more durable therapies. Notably, the new United Network for Organ Sharing donor heart allocation system has recently prioritized patients on IABP support. This review describes the role of IABP in the treatment of HF-CS. It also briefly discusses new strategies for vascular access as well as fully implantable versions for longer duration of support. [ABSTRACT FROM AUTHOR]

Among left ventricular assist device patients, the most commonly infected component is the drive line, which can be managed with antibiotics and local debridement. Infection of intrathoracic device components is less common but more difficult to manage. Herein we describe the incidence of deep device infection (DDI) at our center as well as management and outcomes. We retrospectively reviewed 658 patients who underwent implantable left ventricular assist device insertion with HeartMate 2 (Abbott) or HeartMate 3 (Abbott) devices between January 2004 and June 2021. DDI was defined according to radiographic and clinical criteria. Cumulative incidence was calculated using a Fine-Gray subdistribution model; survival analysis was performed using the method of Kaplan and Meier. There were 32 (4.8%) DDIs during this study period. Drive line infection and re-exploration for bleeding were associated with development of DDI. Cumulative incidence of DDI increased over time, affecting 11% (7%-18%) at 5 years. The dominant microbes involved in DDI were Pseudomonas aeruginosa (19%) and methicillin-resistant Staphylococcus aureus (13%). Nineteen patients (59%) with device infection underwent device exchange, 6 (19%) underwent initial transplant, and 7 (22%) were treated solely with debridement and antibiotics. Of those who underwent device exchange, 12 (63%) developed reinfection of their new device and 6 underwent subsequent heart transplant. Patients who underwent transplantation for management of device infection had improved 5-year survival (80% vs 11%; P =.01) but 3 patients (25%) developed deep sternal wound infection after transplant. DDI is a rare but challenging complication in this destination era. Heart transplantation is the preferred management strategy for eligible patients but infectious complication is common. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: There is a paucity of data on depression, anxiety and post-traumatic stress disorder after left ventricular assist device (LVAD) implantation. We designed an observational study to integrate these with functional capacity and health-related quality of life (HR-QOL) in surviving LVAD patients.Methods and Results: Consenting patients between 1 month and 9 years after LVAD implantation (n = 121) were screened for functional capacity (World Health Organization Disability Assessment Schedule 2.0 [WHODAS 2.0)]); HR-QOL (European Quality of Life [EQ-5D] and Visual Assessment Scales [EQ-VAS]), depression (Patient Health Questionnaire [PHQ-9], anxiety (Generalized Anxiety Disorder Scale [GAD-7]) and post-traumatic stress disorder (Impact of Event Scale Revised [IES-R]). Of the 94% of patients who consented, 34.7% reported impaired functional capacity (WHODAS 2.0 score of ≥25%), 23.1%-34.7% HR-QOL problems (domain EQ-5D of ≥3), 10.7% "poor health" (EQ-VAS of ≤40), 14.9% depression (PHQ-9 of >14), 11.7% suicidal ideation and 17.5% anxiety (GAD-7 of >10). Among these patients, 23.5% had a positive screen for post-traumatic stress disorder (IES-R of ≥24). An EQ-VAS of 80 or greater predicted good functional capacity (P < .001).Conclusions: One-third of discharged LVAD patients reported impaired function, HR-QOL, and psychological issues. A standardized evaluation before and after LVAD implantation could facilitate psychologic prehabilitation, inform decision-making, and identify indications for mental health intervention. [ABSTRACT FROM AUTHOR]

Background: Heart failure predisposes to intracardiac thrombus (ICT) formation. There are limited data on the prevalence and impact of preexisting ICT on postoperative outcomes in left ventricular assist device patients. We examined the risk for stroke and death in this patient population.Methods and Results: We retrospectively studied patients who were implanted with HeartMate (HM) II or HM3 between February 2009 and March 2019. Preoperative transthoracic echocardiograms, intraoperative transesophageal echocardiograms and operative reports were reviewed to identify ICT. There were 525 patients with a left ventricular assist device (median age 60.6 years, 81.8% male, 372 HMII and 151 HM3) included in this analysis. An ICT was identified in 44 patients (8.4%). During the follow-up, 43 patients experienced a stroke and 55 died. After multivariable adjustment, presence of ICT increased the risk for the composite of stroke or death at 6-month (hazard ratio [HR] 1.82, 95% confidence interval [CI] 1.00-3.33, P = .049). Patients with ICT were also at higher risk for stroke (HR 2.45, 95% CI 1.14-5.28, P = .021) and death (HR 2.36, 95% CI 1.17-4.79 P = .016) at 6 months of follow-up.Conclusions: The presence of ICT is an independent predictor of stroke and death at 6 months after left ventricular assist device implantation. Additional studies are needed to help risk stratify and optimize the perioperative management of this patient population. [ABSTRACT FROM AUTHOR]