Browsing by Author "Milano, Carmelo A"
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Item Open Access A Case of Rare Inherited Restrictive Cardiomyopathy With Severe Biatrial Enlargement.(JACC. Case reports, 2019-12) Nafissi, Navid A; Fudim, Marat; Milano, Carmelo A; Rosenberg, Paul B; DeVore, Adam D; Agarwal, RichaWe describe a case of inherited restrictive cardiomyopathy in a patient presenting with severe biatrial enlargement. We review the evaluation and management of restrictive cardiomyopathy with a focus on genetic etiologies. (Level of Difficulty: Intermediate.).Item Open Access An isolated working heart system for large animal models.(J Vis Exp, 2014-06-11) Schechter, Matthew A; Southerland, Kevin W; Feger, Bryan J; Linder, Dean; Ali, Ayyaz A; Njoroge, Linda; Milano, Carmelo A; Bowles, Dawn ESince its introduction in the late 19(th) century, the Langendorff isolated heart perfusion apparatus, and the subsequent development of the working heart model, have been invaluable tools for studying cardiovascular function and disease(1-15). Although the Langendorff heart preparation can be used for any mammalian heart, most studies involving this apparatus use small animal models (e.g., mouse, rat, and rabbit) due to the increased complexity of systems for larger mammals(1,3,11). One major difficulty is ensuring a constant coronary perfusion pressure over a range of different heart sizes - a key component of any experiment utilizing this device(1,11). By replacing the classic hydrostatic afterload column with a centrifugal pump, the Langendorff working heart apparatus described below allows for easy adjustment and tight regulation of perfusion pressures, meaning the same set-up can be used for various species or heart sizes. Furthermore, this configuration can also seamlessly switch between constant pressure or constant flow during reperfusion, depending on the user's preferences. The open nature of this setup, despite making temperature regulation more difficult than other designs, allows for easy collection of effluent and ventricular pressure-volume data.Item Open Access Arterial and venous thrombosis complicating coronary artery bypass grafting after use of epoetin alfa-epbx.(JTCVS techniques, 2020-08-04) Murillo-Berlioz, Alejandro; Guinn, Nicole R; Levy, Jerrold H; Milano, Carmelo AItem Open Access Conventional Ultrafiltration During Elective Cardiac Surgery and Postoperative Acute Kidney Injury.(Journal of cardiothoracic and vascular anesthesia, 2021-05) Manning, Michael W; Li, Yi-Ju; Linder, Dean; Haney, John C; Wu, Yi-Hung; Podgoreanu, Mihai V; Swaminathan, Madhav; Schroder, Jacob N; Milano, Carmelo A; Welsby, Ian J; Stafford-Smith, Mark; Ghadimi, KamrouzObjective
Conventional ultrafiltration (CUF) during cardiopulmonary bypass (CPB) serves to hemoconcentrate blood volume to avoid allogeneic blood transfusions. Previous studies have determined CUF volumes as a continuous variable are associated with postoperative acute kidney injury (AKI) after cardiac surgery, but optimal weight-indexed volumes that predict AKI have not been described.Design
Retrospective cohort.Setting
Single-center university hospital.Participants
A total of 1,641 consecutive patients who underwent elective cardiac surgery between June 2013 and December 2015.Interventions
The CUF volume was removed during CPB in all participants as part of routine practice. The authors investigated the association of dichotomized weight-indexed CUF volume removal with postoperative AKI development to provide pragmatic guidance for clinical practice at the authors' institution.Measurements and main results
Primary outcomes of postoperative AKI were defined by the Kidney Disease: Improving Global Outcomes staging criteria and dichotomized, weight-indexed CUF volumes (mL/kg) were defined by (1) extreme quartiles (Q3) and (2) Youden's criterion that best predicted AKI development. Multivariate logistic regression models were developed to test the association of these dichotomized indices with AKI status. Postoperative AKI occurred in 827 patients (50.4%). Higher CUF volumes were associated with AKI development by quartiles (CUF >Q3 = 32.6 v CUF < Q1 = 10.4 mL/kg; odds ratio [OR] = 1.68, 95% CI: 1.19-2.3) and Youden's criterion (CUF ≥ 32.9 v CUF <32.9 mL/kg; OR = 1.60, 95% CI: 1.21-2.13). Despite similar intraoperative nadir hematocrits among groups (p = 0.8), higher CUF volumes were associated with more allogeneic blood transfusions (p = 0.002) and longer lengths of stay (p < 0.001).Conclusions
Removal of weight-indexed CUF volumes > 32 mL/kg increased the risk for postoperative AKI development. Importantly, CUF volume removal of any amount did not mitigate allogeneic blood transfusion during elective cardiac surgery. Prospective studies are needed to validate these findings.Item Open Access Durability and Efficacy of Tricuspid Valve Repair in Patients Undergoing Left Ventricular Assist Device Implantation.(JACC. Heart failure, 2019-12-03) Barac, Yaron D; Nicoara, Alina; Bishawi, Muath; Schroder, Jacob N; Daneshmand, Mani A; Hashmi, Nazish K; Velazquez, Eric; Rogers, Joseph G; Patel, Chetan B; Milano, Carmelo AOBJECTIVES:This study sought to determine the durability of tricuspid valve repair (TVr) performed concurrently with left ventricular assist device (LVAD) implantation and its association with the development of late right heart failure (RHF). BACKGROUND:Surgical management of tricuspid regurgitation (TR) at the time of LVAD implantation is performed in an attempt to reduce the occurrence of postoperative RHF. Limited data exist regarding the durability of TVr in patients with LVAD as well as its impact on development of late RHF. METHODS:A retrospective review was conducted of consecutive adult patients who underwent durable LVAD implantation and concurrent TVr at the authors' institution between 2009 and 2017. Late RHF was defined as readmission for HF requiring inotropic or diuretic therapy. TVr failure was defined as moderate or severe TR at any follow-up echocardiographic examination after LVAD implantation. RESULTS:A total of 156 patients underwent LVAD and concurrent TVr during the study. Of the total, 59 patients (37.8%) had a failed TVr. The mean duration of echocardiographic follow-up was 23 ± 22 months. Of the 146 patients who were discharged after the index hospitalization, 53 patients (36.3%) developed late RHF. Multivariate Cox proportional hazard analysis demonstrated that TVr failure was an independent predictor of late RHF development (hazard ratio: 2.62; 95% confidence interval: 1.38 to 4.96; p = 0.003). CONCLUSION:Failure of TVr in this cohort occurred at a significant rate. Failure of TVr is an independent risk factor for development of late RHF. Future studies should investigate strategies to reduce recurrence of significant TR.Item Open Access Genome-wide association study of acute kidney injury after coronary bypass graft surgery identifies susceptibility loci.(Kidney Int, 2015-10) Stafford-Smith, Mark; Li, Yi-Ju; Mathew, Joseph P; Li, Yen-Wei; Ji, Yunqi; Phillips-Bute, Barbara G; Milano, Carmelo A; Newman, Mark F; Kraus, William E; Kertai, Miklos D; Shah, Svati H; Podgoreanu, Mihai V; Duke Perioperative Genetics and Safety Outcomes (PEGASUS) Investigative TeamAcute kidney injury (AKI) is a common, serious complication of cardiac surgery. Since prior studies have supported a genetic basis for postoperative AKI, we conducted a genome-wide association study (GWAS) for AKI following coronary bypass graft (CABG) surgery. The discovery data set consisted of 873 nonemergent CABG surgery patients with cardiopulmonary bypass (PEGASUS), while a replication data set had 380 cardiac surgical patients (CATHGEN). Single-nucleotide polymorphism (SNP) data were based on Illumina Human610-Quad (PEGASUS) and OMNI1-Quad (CATHGEN) BeadChips. We used linear regression with adjustment for a clinical AKI risk score to test SNP associations with the postoperative peak rise relative to preoperative serum creatinine concentration as a quantitative AKI trait. Nine SNPs meeting significance in the discovery set were detected. The rs13317787 in GRM7|LMCD1-AS1 intergenic region (3p21.6) and rs10262995 in BBS9 (7p14.3) were replicated with significance in the CATHGEN data set and exhibited significantly strong overall association following meta-analysis. Additional fine mapping using imputed SNPs across these two regions and meta-analysis found genome-wide significance at the GRM7|LMCD1-AS1 locus and a significantly strong association at BBS9. Thus, through an unbiased GWAS approach, we found two new loci associated with post-CABG AKI providing new insights into the pathogenesis of perioperative AKI.Item Open Access Indications for and outcomes of therapeutic plasma exchange after cardiac transplantation: A single center retrospective study.(Journal of clinical apheresis, 2018-08) Onwuemene, Oluwatoyosi A; Grambow, Steven C; Patel, Chetan B; Mentz, Robert J; Milano, Carmelo A; Rogers, Joseph G; Metjian, Ara D; Arepally, Gowthami M; Ortel, Thomas LINTRODUCTION:Limited data are available describing indications for and outcomes of therapeutic plasma exchange (TPE) in cardiac transplantation. METHODS:In a retrospective study of patients who underwent cardiac transplantation at Duke University Medical Center from 2010 to 2014, we reviewed 3 TPE treatment patterns: a Single TPE procedure within 24 h of transplant; Multiple TPE procedures initiated within 24 h of transplant; and 1 or more TPE procedures beginning >24 h post-transplant. Primary and secondary outcomes were overall survival (OS) and TPE survival (TS), respectively. RESULTS:Of 313 patients meeting study criteria, 109 (35%) underwent TPE. TPE was initiated in 82 patients within 24 h, 40 (37%) receiving a single procedure (Single TPE), and 42 (38%) multiple procedures (Multiple TPE). Twenty-seven (25%) began TPE >24 h after transplant (Delayed TPE). The most common TPE indication was elevated/positive panel reactive or human leukocyte antigen antibodies (32%). With a median follow-up of 49 months, the non-TPE treated and Single TPE cohorts had similar OS (HR 1.08 [CI, 0.54, 2.14], P = .84), while the Multiple and Delayed TPE cohorts had worse OS (HR 2.62 [CI, 1.53, 4.49] and HR 1.98 [CI, 1.02, 3.83], respectively). The Multiple and Delayed TPE cohorts also had worse TS (HR 2.59 [CI, 1.31, 5.14] and HR 3.18 [CI, 1.56, 6.50], respectively). Infection rates did not differ between groups but was independently associated with OS (HR 2.31 [CI, 1.50, 3.54]). CONCLUSIONS:TPE is an important therapeutic modality in cardiac transplant patients. Prospective studies are needed to better define TPE's different roles in this patient population.Item Open Access Inhaled Epoprostenol Compared With Nitric Oxide for Right Ventricular Support After Major Cardiac Surgery.(Circulation, 2023-07) Ghadimi, Kamrouz; Cappiello, Jhaymie L; Wright, Mary Cooter; Levy, Jerrold H; Bryner, Benjamin S; DeVore, Adam D; Schroder, Jacob N; Patel, Chetan B; Rajagopal, Sudarshan; Shah, Svati H; Milano, Carmelo A; INSPIRE-FLO InvestigatorsBackground
Right ventricular failure (RVF) is a leading driver of morbidity and mortality after major cardiac surgery for advanced heart failure, including orthotopic heart transplantation and left ventricular assist device implantation. Inhaled pulmonary-selective vasodilators, such as inhaled epoprostenol (iEPO) and nitric oxide (iNO), are essential therapeutics for the prevention and medical management of postoperative RVF. However, there is limited evidence from clinical trials to guide agent selection despite the significant cost considerations of iNO therapy.Methods
In this double-blind trial, participants were stratified by assigned surgery and key preoperative prognostic features, then randomized to continuously receive either iEPO or iNO beginning at the time of separation from cardiopulmonary bypass with the continuation of treatment into the intensive care unit stay. The primary outcome was the composite RVF rate after both operations, defined after transplantation by the initiation of mechanical circulatory support for isolated RVF, and defined after left ventricular assist device implantation by moderate or severe right heart failure according to criteria from the Interagency Registry for Mechanically Assisted Circulatory Support. An equivalence margin of 15 percentage points was prespecified for between-group RVF risk difference. Secondary postoperative outcomes were assessed for treatment differences and included: mechanical ventilation duration; hospital and intensive care unit length of stay during the index hospitalization; acute kidney injury development including renal replacement therapy initiation; and mortality at 30 days, 90 days, and 1 year after surgery.Results
Of 231 randomized participants who met eligibility at the time of surgery, 120 received iEPO, and 111 received iNO. Primary outcome occurred in 30 participants (25.0%) in the iEPO group and 25 participants (22.5%) in the iNO group, for a risk difference of 2.5 percentage points (two one-sided test 90% CI, -6.6% to 11.6%) in support of equivalence. There were no significant between-group differences for any of the measured postoperative secondary outcomes.Conclusions
Among patients undergoing major cardiac surgery for advanced heart failure, inhaled pulmonary-selective vasodilator treatment using iEPO was associated with similar risks for RVF development and development of other postoperative secondary outcomes compared with treatment using iNO.Registration
URL: https://www.Clinicaltrials
gov; Unique identifier: NCT03081052.Item Open Access Longitudinal Changes in Regional Cerebral Perfusion and Cognition Following Cardiac Surgery.(The Annals of thoracic surgery, 2018-09-22) Smith, Patrick J; Browndyke, Jeffrey N; Monge, Zachary A; Harshbarger, Todd B; James, Michael L; Gaca, Jeffrey G; Alexander, John H; Berger, Miles M; Newman, Mark F; Milano, Carmelo A; Mathew, Joseph P; Neurologic Outcomes Research Group (NORG)Cardiac surgery has been associated with increased risk of postoperative cognitive decline, as well as dementia risk in the general population. Few studies, however, have examined the impact of coronary revascularization or valve replacement / repair surgery on longitudinal cerebral perfusion changes or their association with cognitive function.We examined longitudinal changes in cerebral perfusion among 54 individuals with cardiac disease; 27 undergoing cardiac surgery and 27 matched controls. Arterial spin labeling (ASL) magnetic resonance perfusion imaging was used to quantify cerebral blood flow within the anterior communicating artery (ACA), middle cerebral artery (MCA), and posterior communicating artery (PCA) vascular territories prior to surgery and postoperatively at 6-weeks and 1-year. Cognitive performance was examined during the same intervals using a battery of tests tapping memory, executive, information processing and upper extremity motor functions. Repeated measures, mixed models were used to examine for perfusion changes and the association between perfusion changes and cognition.Significant postoperative increases in perfusion were observed at 6-weeks within the MCA vascular territory following cardiac surgery (P = .035 for interaction). Perfusion changes were most notable in distal territories of the MCA and PCA at 6-weeks, with no additional changes at 1-year. Postoperative increases in MCA perfusion at 6-weeks were associated with improved psychomotor speed (β = 0.35, P = .016); whereas, no significant differences were found between groups in vascular territory perfusion and cognition at 1-year.Cardiac surgery is associated with significant short-term increases in MCA perfusion with associated improvements in psychomotor speed.Item Open Access Phosphoproteomic profiling of human myocardial tissues distinguishes ischemic from non-ischemic end stage heart failure.(PLoS One, 2014) Schechter, Matthew A; Hsieh, Michael KH; Njoroge, Linda W; Thompson, J Will; Soderblom, Erik J; Feger, Bryan J; Troupes, Constantine D; Hershberger, Kathleen A; Ilkayeva, Olga R; Nagel, Whitney L; Landinez, Gina P; Shah, Kishan M; Burns, Virginia A; Santacruz, Lucia; Hirschey, Matthew D; Foster, Matthew W; Milano, Carmelo A; Moseley, M Arthur; Piacentino, Valentino; Bowles, Dawn EThe molecular differences between ischemic (IF) and non-ischemic (NIF) heart failure are poorly defined. A better understanding of the molecular differences between these two heart failure etiologies may lead to the development of more effective heart failure therapeutics. In this study extensive proteomic and phosphoproteomic profiles of myocardial tissue from patients diagnosed with IF or NIF were assembled and compared. Proteins extracted from left ventricular sections were proteolyzed and phosphopeptides were enriched using titanium dioxide resin. Gel- and label-free nanoscale capillary liquid chromatography coupled to high resolution accuracy mass tandem mass spectrometry allowed for the quantification of 4,436 peptides (corresponding to 450 proteins) and 823 phosphopeptides (corresponding to 400 proteins) from the unenriched and phospho-enriched fractions, respectively. Protein abundance did not distinguish NIF from IF. In contrast, 37 peptides (corresponding to 26 proteins) exhibited a ≥ 2-fold alteration in phosphorylation state (p<0.05) when comparing IF and NIF. The degree of protein phosphorylation at these 37 sites was specifically dependent upon the heart failure etiology examined. Proteins exhibiting phosphorylation alterations were grouped into functional categories: transcriptional activation/RNA processing; cytoskeleton structure/function; molecular chaperones; cell adhesion/signaling; apoptosis; and energetic/metabolism. Phosphoproteomic analysis demonstrated profound post-translational differences in proteins that are involved in multiple cellular processes between different heart failure phenotypes. Understanding the roles these phosphorylation alterations play in the development of NIF and IF has the potential to generate etiology-specific heart failure therapeutics, which could be more effective than current therapeutics in addressing the growing concern of heart failure.Item Open Access Right Minithoracotomy Versus Median Sternotomy for Mitral Valve Surgery: A Propensity Matched Study.(The Annals of thoracic surgery, 2015-08) Tang, Paul; Onaitis, Mark; Gaca, Jeffrey G; Milano, Carmelo A; Stafford-Smith, Mark; Glower, DonaldBackground
The efficacy of conventional median sternotomy versus a right minithoracotomy (RT) approach to mitral valve surgery was evaluated in a single high-volume institution.Methods
A retrospective analysis of a single institution's experience was performed using propensity matching of 1,694 patients who underwent mitral valve surgery during a 15-year period. Patients who had procedures that were not usually performed through an RT approach were excluded. Using 1:1 propensity score matching, we obtained 215 matched patients in each group for outcomes analysis.Results
There was no difference in the median year of operation between the two groups (2002 versus 2001; p = 0.142). The RT approach was not a predictor of postoperative mortality. Predictors of mortality included increasing age, diabetes, smoking, preoperative dialysis, lung disease, advanced congestive heart failure class, and peripheral vascular disease. The RT approach was associated with less new-onset atrial fibrillation (8% versus 16%; p = 0.018), pneumonia (1% versus 5%; p = 0.049), respiratory failure (3% versus 8%; p = 0.036), and acute renal failure (2% versus 7%; p = 0.006), lower chest tube output (350 versus 840 mL; p < 0.001), and fewer red blood transfusions (2 versus 3 units; p = 0.001).Conclusions
Right minithoracotomy compared with median sternotomy for mitral valve surgery was associated with less postoperative atrial fibrillation, respiratory complications, acute renal failure, chest tube output, and use of packed red blood cells. Given study limitations, the RT approach for mitral valve surgery may have advantages over median sternotomy in selected patients.Item Open Access Use of an inverted On-X mitral valve in the aortic position in a resource limited setting.(Journal of cardiac surgery, 2020-08-25) Jimenez Contreras, Fabian; Murillo-Berlioz, Alejandro; Anand, Jatin; Aksamit, Claire; Orellana, Hugo; Milano, Carmelo A; Williams, Adam RImplanting an inverted aortic valve prosthesis in the mitral position has shown to be a viable solution for a small mitral annulus. We describe a case of implanting an inverted in the mitral prosthesis in the aortic position in a patient with an excessively large aortic annulus. A 46-year-old male with severe aortic insufficiency underwent aortic valve replacement during a surgical outreach program in Tegucigalpa, Honduras. Aortic valve annulus measured 30 mm on preoperative echocardiogram. An inverted On-X mechanical mitral heart valve with Conform-X sewing ring 25/33 mm was implanted with an excellent hemodynamic result and no paravalvular leak. To the best of our knowledge, this case demonstrates the first inverted mitral prosthesis implanted in the aortic valve position.Item Open Access Using a Regent Aortic Valve in a Small Annulus Mitral Position Is a Viable Option.(The Annals of thoracic surgery, 2018-04) Barac, Yaron D; Zwischenberger, Brittany; Schroder, Jacob N; Daneshmand, Mani A; Haney, John C; Gaca, Jeffrey G; Wang, Andrew; Milano, Carmelo A; Glower, Donald DBACKGROUND:Outcome of mitral valve replacement in extreme scenarios of small mitral annulus with the use of the Regent mechanical aortic valve is not well documented. METHODS:Records were examined in 31 consecutive patients who underwent mitral valve replacement with the use of the aortic Regent valve because of a small mitral annulus. RESULTS:Mean age was 60 ± 14 years. Mitral stenosis or mitral annulus calcification was present in 30 of 31 patients (97%). Concurrent procedures were performed in 17 of 31 patients (55%). Median valve size was 23 mm. Mean mitral gradient coming out of the operating room was 4.2 ± 1.5 mm Hg and at follow-up echocardiogram performed at a median of 32 months after the procedure was 5.8 ± 2.4 mm Hg. CONCLUSIONS:A Regent aortic mechanical valve can be a viable option with a larger orifice area than the regular mechanical mitral valve in a problematic situation of a small mitral valve annulus. Moreover, the pressure gradients over the valve are acceptable intraoperatively and over time.Item Open Access VAD therapy 20/20: moving beyond the myopic view of a nascent therapy.(Ann Cardiothorac Surg, 2014-11) DeVore, Adam D; Milano, Carmelo A; Rogers, Joseph GThe past five years have seen remarkable growth in the use of durable, continuous flow left ventricular assist devices (LVAD) with associated improvements in mortality, quality of life, functionality and end-organ function. To sustain the growth of this important therapy, the LVAD community must now address key issues focused around the costs of LVAD care, refined patient selection, and reducing complications associated with this therapy. In this perspective piece, we discuss many of these issues.