Publications by authors named "Lorenzo Braghieri"

5 Publications

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Levels of Trimethylamine N-Oxide Remain Elevated Long Term After Left Ventricular Assist Device and Heart Transplantation and Are Independent From Measures of Inflammation and Gut Dysbiosis.

Circ Heart Fail 2021 Jun 15;14(6):e007909. Epub 2021 Jun 15.

Department of Epidemiology, Mailman School of Public Health (S.M., R.T.D.), Columbia University Irving Medical Center, New York, NY.

Background: Trimethylamine N-oxide (TMAO)-a gut-derived metabolite-is elevated in heart failure (HF) and linked to poor prognosis. We investigated variations in TMAO in HF, left ventricular assist device (LVAD), and heart transplant (HT) and assessed its relation with inflammation, endotoxemia, oxidative stress, and gut dysbiosis.

Methods: We enrolled 341 patients. TMAO, CRP (C-reactive protein), IL (interleukin)-6, TNF-α (tumor necrosis factor alpha), ET-1 (endothelin-1), adiponectin, lipopolysaccharide, soluble CD14, and isoprostane were measured in 611 blood samples in HF (New York Heart Association class I-IV) and at multiple time points post-LVAD and post-HT. Gut microbiota were assessed via 16S rRNA sequencing among 327 stool samples. Multivariable regression models were used to assess the relationship between TMAO and (1) New York Heart Association class; (2) pre- versus post-LVAD or post-HT; (3) biomarkers of inflammation, endotoxemia, oxidative stress, and microbial diversity.

Results: ln-TMAO was lower among HF New York Heart Association class I (1.23 [95% CI, 0.52-1.94] µM) versus either class II, III, or IV (1.99 [95% CI, 1.68-2.30], 1.97 [95% CI, 1.71-2.24], and 2.09 [95% CI, 1.83-2.34] µM, respectively; all <0.05). In comparison to class II-IV, ln-TMAO was lower 1 month post-LVAD (1.58 [95% CI, 1.32-1.83] µM) and 1 week and 1 month post-HT (0.97 [95% CI, 0.60-1.35] and 1.36 [95% CI, 1.01-1.70] µM). ln-TMAO levels in long-term LVAD (>6 months: 1.99 [95% CI, 1.76-2.22] µM) and HT (>6 months: 1.86 [95% CI, 1.66-2.05] µM) were not different from symptomatic HF. After multivariable adjustments, TMAO was not associated with biomarkers of inflammation, endotoxemia, oxidative stress, or microbial diversity.

Conclusions: TMAO levels are increased in symptomatic HF patients and remain elevated long term after LVAD and HT. TMAO levels were independent from measures of inflammation, endotoxemia, oxidative stress, and gut dysbiosis.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210465PMC
June 2021

Right Ventricular Pressure-Volume Analysis During Left Ventricular Assist Device Speed Optimization Studies: Insights Into Interventricular Interactions and Right Ventricular Failure.

J Card Fail 2021 May 12. Epub 2021 May 12.

Division of Cardiology, Columbia University Medical Center-New York Presbyterian Hospital in New York, New York, New York; Cardiovascular Research Foundation in New York, New York.

Background: Interventricular interaction, which refers to the impact of left ventricular (LV) function on right ventricular (RV) function and vice versa, has been implicated in the pathogenesis of RV failure in LV assist device (LVAD) recipients. We sought to understand more about interventricular interaction by quantifying changes in the RV systolic and diastolic function with varying LVAD speeds.

Methods And Results: Four patients (ages 22-69 years, 75% male, and 25% with ischemic cardiomyopathy) underwent a protocolized hemodynamic ramp test within 12 months of LVAD implantation where RV pressure-volume loops were recorded with a conductance catheter. The end-systolic PV relationship and end-diastolic PV relationship were compared using the V and V indices (volumes at which end-systolic PV relationship and end-diastolic PV relationship reach a pressure of 20 and 10 mm Hg, respectively). The ∆V and ∆V refer to the change in V and V from the minimum to maximum LVAD speeds. RV PV loops demonstrated variable changes in systolic and diastolic function with increasing LVAD speed. The end-systolic PV relationship changed in 1 patient (patient 2, ∆V = 23.5 mL), reflecting a decrease in systolic function with increased speed, and was unchanged in 3 patients (average ∆V = 7.4 mL). The end-diastolic PV relationship changed with increasing speed in 3 of 4 patients (average ∆V = 12.5 mL), indicating an increase in ventricular compliance, and remained unchanged in one participant (patient 1; ∆V = 4.0 mL).

Conclusions: Interventricular interaction can improve RV compliance and impair systolic function, but the overall effect on RV performance in this pilot investigation is heterogeneous. Further research is required to understand which patient characteristics and hemodynamic parameters influence the net impact of interventricular interaction.
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http://dx.doi.org/10.1016/j.cardfail.2021.04.019DOI Listing
May 2021

Association of preoperative infections, nasal Staphylococcus aureus colonization and gut microbiota with left ventricular assist device outcomes.

Eur J Heart Fail 2021 May 8. Epub 2021 May 8.

Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.

Aims: Infections are common following left ventricular assist device (LVAD) implantation and predict adverse events. Infections are frequent prior to LVAD implantation although their impact on postoperative outcomes remains unknown. Gut and nasal microbial imbalance may predispose to mucosal colonization with pathogens. Herein, we investigated the predictive role of pre-LVAD infections, and explored the association of nasal Staphylococcus aureus (SA) colonization and gut microbiota, on postoperative outcomes.

Methods And Results: Overall, 254 LVAD patients were retrospectively categorized based on pre-LVAD infection status: Group 1, bacterial/fungal bloodstream infection (BSI); Group 2, other bacterial/fungal; Group 3, viral; and Group 4, no infection. In a subset of patients, nasal SA colonization (n = 140) and pre-LVAD stool (n = 25) were analysed using 16S rRNA sequencing. A total of 75 (29%) patients had a pre-LVAD infection [Group 1: 22 (29%); Group 2: 41 (55%); Group 3: 12 (16%)]. Pre-LVAD BSIs were independent predictors of 1-year postoperative mortality and infections [Group 1 vs. 4: hazard ratio (HR) 2.70, P = 0.036 vs. HR 1.8, P = 0.046]. In an unadjusted analysis, pre-LVAD infections other than BSIs, INTERMACS profile ≤2, higher serum creatinine, lower serum albumin and nasal SA colonization were also significantly associated with postoperative infections. Patients with early post-LVAD infections exhibited decreased microbial diversity (P < 0.05).

Conclusions: Pre-LVAD infections are common. BSIs independently predict postoperative mortality and infections. Additional studies are needed to confirm our findings that pre-LVAD SA nasal colonization and gut microbial composition can help stratify patients' risk for infectious complications after LVAD implantation.
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http://dx.doi.org/10.1002/ejhf.2215DOI Listing
May 2021

Angiotensin receptor neprilysin inhibitor use in patients with left ventricular assist devices: A single-center experience.

Int J Artif Organs 2021 Jan 19:391398821989066. Epub 2021 Jan 19.

Division of Cardiology, Department of Medicine, New York Presbyterian Hospital, Columbia University, New York, NY, USA.

Though left ventricular assist devices (LVADs) are an increasingly common therapy for ACC/AHA Stage D heart failure, the optimal medical therapy for patients with LVADs is not known. We sought to evaluate the safety and efficacy of angiotensin receptor neprilysin inhibitor (ARNi) therapy in our single center LVAD patient experience. We evaluated patients implanted with LVADs at Columbia University Irving Medical Center between August 2010 and May 2019, and who were treated with an ARNi for at least 3 months. Thirty patients met this criteria. Eighteen (60%) patients transitioned to an ARNi from an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB), while all were on a beta blocker (BB) at the time of ARNi initiation. The primary outcome, NT-proBNP levels at time of initiation and 3 and 6 month follow up, significantly decreased from a median of 1265 pg/mL at initiation to 750 pg/mL at 3 months and 764 pg/mL at 6 months ( = 0.01). No significant change was seen in serum creatinine, BUN, or potassium levels.
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http://dx.doi.org/10.1177/0391398821989066DOI Listing
January 2021

Interplay Between Genetic Substrate, QTc Duration, and Arrhythmia Risk in Patients With Long QT Syndrome.

J Am Coll Cardiol 2018 04;71(15):1663-1671

Molecular Cardiology, Istituti Clinici Scientifici Maugeri, Istituto di Ricovero e Cura a Carattere Scientifico, Pavia, Italy; Department of Molecular Medicine, University of Pavia, Pavia, Italy; Molecular Cardiology, Fundación Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain. Electronic address:

Background: Long QT syndrome (LQTS) is a common inheritable arrhythmogenic disorder, often secondary to mutations in the KCNQ1, KCNH2, and SCN5A genes. The disease is characterized by a prolonged ventricular repolarization (QTc interval) that confers susceptibility to life-threatening arrhythmic events (LAEs).

Objectives: This study sought to create an evidence-based risk stratification scheme to personalize the quantification of the arrhythmic risk in patients with LQTS.

Methods: Data from 1,710 patients with LQTS followed up for a median of 7.1 years (interquartile range [IQR]: 2.7 to 13.4 years) were analyzed to estimate the 5-year risk of LAEs based on QTc duration and genotype and to assess the antiarrhythmic efficacy of beta-blockers.

Results: The relationship between QTc duration and risk of events was investigated by comparison of linear and cubic spline models, and the linear model provided the best fit. The 5-year risk of LAEs while patients were off therapy was then calculated in a multivariable Cox model with QTc and genotype considered as independent factors. The estimated risk of LAEs increased by 15% for every 10-ms increment of QTc duration for all genotypes. Intergenotype comparison showed that the risk for patients with LQT2 and LQT3 increased by 130% and 157% at any QTc duration versus patients with LQT1. Analysis of response to beta-blockers showed that only nadolol reduced the arrhythmic risk in all genotypes significantly compared with no therapy (hazard ratio: 0.38; 95% confidence interval: 0.15 to 0.93; p = 0.03).

Conclusions: The study provides an estimator of risk of LAEs in LQTS that allows a granular estimate of 5-year arrhythmic risk and demonstrate the superiority of nadolol in reducing the risk of LAEs in LQTS.
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http://dx.doi.org/10.1016/j.jacc.2018.01.078DOI Listing
April 2018