Calcium channel blockers and clinical outcomes in patients with continuous-flow left ventricular assist devices.

AIMS: Current guidelines suggest calcium channel blockers (CCBs) as the second or third option for blood pressure management in patients with left ventricular assist device (LVAD). However, the clinical outcomes of patients with LVAD who receive CCBs remain unclear. Our study aims to analyse the association of CCBs with clinical outcomes in patients after LVAD implantation. METHODS AND RESULTS: This is a retrospective analysis based on the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) from 2006 to 2017, and adult patients who were alive with LVAD and CCB treatment information at 6 months after implantation were included. Among 10 717 patients, 1369 received CCBs 6 months after implantation, and there was an increasing trend of CCB use after LVAD. Patients receiving CCB therapy at 6 months had a similar 5 year survival rate to those not receiving CCB [49.6%, 95% confidence interval (CI): 47.5-51.7% vs. 51.1%, 95% CI: 45.3-56.7%]. In both Cox and competing risk regressions after adjusting for confounding factors, CCB treatment at 6 months after implantation was not associated with long-term mortality [hazard ratio (HR): 1.03, 95% CI: 0.91-1.17, P = 0.624 and subdistribution HR (SHR): 1.07, 95% CI: 0.95-1.22, P = 0.260]. Consistently, in time-varying models, CCB treatment was not linked to long-term mortality (HR: 0.97, 95% CI: 0.87-1.09, P = 0.682 and SHR: 1.05, 95% CI: 0.94-1.18, P = 0.359). This null association remained in subgroup analysis according to device strategy and propensity-matching analyses. Neurological dysfunction, stroke, bleeding, rehospitalization, and renal dysfunction were more likely to occur among those with CCB when compared with those without CCB treatment. CONCLUSIONS: In patients with LVAD, CCB therapy fails to show benefits in long-term survival and is associated with increased incidences of neurological dysfunction, bleeding, renal dysfunction, and rehospitalization.

Heart transplantation surgery in children and young adults with congenital heart disease.

BACKGROUND: Pediatric cardiac transplantation remains a surgical challenge as a variety of cardiac and vessel malformation are present in patients with congenital heart disease (CHD). Despite limited availability and acceptability of donor hearts, the number of heart transplantations remains on a stable level with improved survival and quality of life. OBSERVATION: As treatment options for CHD continue to improve and the chances of survival increase, more adult CHD patients are listed for transplantation. This review focuses on the clinical challenges and modified techniques of pediatric heart transplantations. CONCLUSION: Not only knowledge of the exact anatomy, but above all careful planning, interdisciplinary cooperation and surgical experience are prerequisites for surgical success.

Presence and impact of anemia in patients supported with left ventricular assist devices.

BACKGROUND: Data on anemia and its effects on patients supported with continuous-flow left ventricular assist devices (LVADs) are lacking. OBJECTIVES: This study sought to describe the presence of anemia over time and investigate its association with mortality, quality of life, exercise capacity, and adverse events in LVAD patients. METHODS: Adults receiving durable LVADs between 2008 and 2017 were identified from the INTERMACS database. The full cohort was stratified according to anemia severity (no anemia, mild, and moderate-severe). RESULTS: The analysis of 19,509 patients (females: 21.2%, age: 56.9 ± 12.9 years) showed that moderate-severe anemia affected 45.2% of patients at baseline, 33.5% of them at 6 months, and 32.3% in the fourth year after implantation. The presence of normal hemoglobin was 24.4% before surgery, 32.5% at 6 months, and 36.6% at 4 years after implantation. Multivariable linear mixed-effect regression revealed that the average hemoglobin over time was significantly lower (ß, -0.233, 95% confidence interval (CI): -0.282 to -0.185), and the reduction of hemoglobin over time was bigger (ß, -0.032 95% CI: -0.035 to -0.028) for LVAD nonsurvivors compared with LVAD survivors. Adjusted Cox regression showed that the severity of preimplant anemia was associated with higher mortality (HR, mild: 1.19; 95% CI: 1.05-1.35 and moderate-severe: 1.44; 95% CI: 1.28-1.62), with similar results in competing risk regression. Anemia progression during follow-up was associated with decreased Kansas City Cardiomyopathy Questionnaire scores and shorter 6-minute walk distances. CONCLUSIONS: In patients supported with LVADs, anemia is a frequent comorbidity, and deterioration over time is associated with poor prognosis.

Grafts and Patches: Optimized but Not Optimal Materials for Congenital Heart Surgery.

A variety of materials are available for the surgery of children with congenital heart defects. In addition to growth-related mismatch, degeneration of the material in particular frequently leads to reoperation. Therefore, the choice of conduits and patches should be made carefully. This article provides an overview of the most commonly implanted materials in pediatric cardiac surgery.Structural changes can be detected in all available materials. Depending on the age at implantation and the site of implantation, the extent and time course of material degeneration vary. Autologous material is still the gold standard in reconstructive surgery. Biological materials have largely replaced artificial materials in clinical use.The search for the ideal material continues. In pediatric cardiac surgery, there are only optimized but no optimal materials.

Characteristics and Outcome of Patients With a History of Cancer Undergoing Durable Left Ventricular Assist Device Implantation.

BACKGROUND: Patients with cancer (patients with a history of cancer) with advanced heart failure are increasing, but unlikely to be transplanted, and left ventricular assist device (LVAD) is an alternative strategy. This study investigates the characteristics and outcomes of patients with cancer undergoing durable LVAD. METHODS: Adult patients with a history of cancer who received LVADs were identified from INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) registry: 2008 and 2017. Characteristics and outcomes between patients with cancer and those without cancer were compared, and subgroup analyses of cancer therapy-induced cardiomyopathy (CCM) and non-CCM were also conducted. RESULTS: Overall, 1273 (6.5%) patients had a history of cancer, including 289 (22.7%) with CCM and 984 (77.3%) with non-CCM as the primary reason for heart failure. Patients with cancer had shorter median survival (3.72 versus 3.97 years, log-rank P=0.002), and multivariable Cox and competing risk regressions revealed that a history of cancer was associated with reduced survival (hazard ratio, 1.14 [95% CI, 1.04-1.26]; P=0.005; subdistribution hazard ratio, 1.24 [95% CI, 1.13-1.36]; P<0.001) and decreased incidence of heart transplantation. There was no significant difference in mortality between patients with CCM-induced heart failure and patients without cancer. Patients with cancer experienced an increased risk of bleeding, and age, INTERMACS profile, albumin, dialysis, and blood urea nitrogen were associated with mortality in these patients. CONCLUSIONS: A history of cancer is associated with mildly reduced survival, lower incidence of heart transplantation, and increased risk of bleeding after LVAD, whereas the survival in patients with cancer with CCM-induced heart failure is similar to those without cancer. LVAD implantation in patients with cancer is very well possible.

Tricuspid Valve Surgery in Patients Receiving Left Ventricular Assist Devices.

BACKGROUND: Tricuspid regurgitation (TR) is common and related to poor prognosis in patients after left ventricular assist device (LVAD) implantation. The concomitant tricuspid valve surgery (TVS) at the time of LVAD implantation on short and long-term outcomes are controversial in current evidence. METHODS: This is a single-center, observational, retrospective study. We enrolled patients with moderate-to-severe TR who received LVAD implantations from 2009 to 2020. Postoperative right ventricular failure (RVF), right ventricular assist device (RVAD) use, hospital mortality, new-onset renal replacement therapy (RRT), and acute kidney injury (AKI) were evaluated retrospectively. RESULTS: Sixty-eight patients were included, 36 with and 32 without concomitant TVS. Baseline characteristics did not differ between the two groups. Patients receiving TVS had significantly increased incidences of postoperative RVF (52.8 vs. 25.0%, p = 0.019), RVAD implantation (41.7 vs. 18.8%, p = 0.041), and new-onset RRT (22.2 vs. 0%, p = 0.004). No difference in the incidence of AKI and hospital mortality was detected. Besides, these associations remained consistent in patients who underwent LVAD implantation via median sternotomy. During a median follow-up of 2.76 years, Kaplan-Meier analysis and competing-risk analysis showed that TVS was not associated with better overall survival in patients after LVAD implantation compared with the no-TVS group. CONCLUSION: Our study suggests that concomitant TVS failed to show benefits in patients receiving LVAD implantation. Even worse, concomitant TVS is associated with significantly increased incidences of RVF, RVAD use, and new-onset of RRT. Considering the small sample size and short follow-up, these findings warrant further study.

The influence of glutaraldehyde on the microscopic structure of human pericardium.

OBJECTIVES: In our study, we investigate the collagen structure of human pericardium microscopically in dependence of glutaraldehyde (GA) concentration and fixation time. METHODS: Pericardial samples were taken from 9 patients aged 40+ years who underwent cardiac surgery, either coronary artery bypass surgery or valve implantation/reconstruction. Specimens were cut in 5 equal pieces and treated with GA at fixed concentrations (0.3125%, 0.625%, or 1.25%) but different exposer times (5 min, 10 min, 20 min, 30 min, and 60 min). Elastica van Gieson (EvG) staining was used for microscopic examination of pericardial collagen structure. RESULTS: The collagen structure studied microscopically depended on both GA incubation time and GA concentration. At low GA concentrations (0.3125%, 0.625%) and short incubation times, individual collagen fibers appeared separately. After one hour incubation period, single collagen fibers could not be distinguished at any GA concentration. For fixed incubation times no differences were seen in the collagen structure when 0.3125% and 0.625% GA were used. However, at a concentration of 1.25% GA fusion of individual collagen fibers was already observed at low incubation times. CONCLUSION: Pericardial collagen structure changes with increasing incubation time and increasing GA concentration by raising fusion of single fibers. For GA concentrations of ≤0.625%, fiber fusion depends plainly on incubation time. That is relevant as this concentration is used in cardiac surgery. At a concentration of 1.25% GA, single collagen fibers could not be separated, even at short incubation times. Fusion of individual collagen fibers and changes in appearance (less undulating) were assumed to be responsible for stiffening of GA-fixed pericardium.

Industrial Processing Induces Pericardial Patch Degeneration.

Background: Autologous pericardium is considered gold standard for various reconstructive surgical procedures in children. However, processed bovine, equine, and porcine pericardial tissue are also widely used. We investigated structural differences and analyzed alterations caused by industrial processing. Additionally human and equine pericardium explants, used during aortic valve reconstruction were analyzed. Methods: Pericardial tissues (native, processed and explanted) were gathered and stained with HE and EvG to visualize collagen as well as elastic fibers. Fiber structures were visualized by light and polarization microscopy. Antibody staining against CD 3, CD 20, and CD 68 was performed to identify inflammation. Results: Native pericardium of different species showed small differences in thickness, with bovine pericardium being the thickest [bovine: 390 µm (± 40.6 µm); porcine: 223 µm (± 30.1 µm); equine: 260 µm (± 28.4 µm)]. Juvenile pericardium was 277 µm (± 26.7 µm). Single collagen bundle diameter displayed variations (~3-20 µm). Parallel collagen fibers were densely packed with small inter-fibrillary space. After industrial tissue processing, loosening of collagen network with inter-fibrillary gapping was observed. Pericardium appeared thicker (mean values ranging from 257-670 µm). Processed tissue showed less birefringence under polarized light. All analyzed tissues showed a small number of elastic fibers. Fibrosis, calcification and inflammatory processes of autologous and equine pericardium were observed in patient explants. Conclusion: None of the analyzed tissues resembled the exact structure of the autologous pericardial explant. Degeneration of pericardium starts during industrial processing, suggesting a potential harm on graft longevity in children. A careful surgical approach prior to the implantation of xenografts is therefore needed.

C-reactive protein predicts early clinical outcomes and long-term mortality after left ventricular assisted device.

OBJECTIVES: Left ventricular assist device (LVAD) implantation has become a reliable therapeutic strategy in patients with advanced heart failure. C-reactive protein (CRP) is a well-established biomarker of inflammation. This study aims to determine the prognostic effect of CRP level on clinical outcomes of patients who undergo LVAD implantation. METHODS: This is a single-center, observational, retrospective study. One hundred fifty-three patients who received continuous-flow LVAD implantation were included and were divided into two groups of high (>3.9 mg/dL) versus low CRP (⩽3.9 mg/dL). RESULTS: Patients with high pre-implant CRP levels were prone to severe preoperative clinical conditions and complicated intraoperative procedures. Compared with patients in the low CRP group, elevated pre-implant CRP was associated with increased hospital mortality (31.4% vs 8.4%, p < 0.001), postoperative right ventricular failure (47.1% vs 30.1%, p = 0.031), right ventricular assist device use (34.3% vs 16.9%, p = 0.013), AKI (70% vs 51.8%, p = 0.022) and significantly prolonged duration of postoperative mechanical ventilation and intensive care unit length of stay. Univariate Cox regression showed that high pre-implant CRP was significantly associated with increased risk of long-term mortality (Hazard ratio (HR) 2.632 95%; CI: 1.657-4.183, p < 0.001), and multivariable Cox regression also revealed the higher risk of long-term mortality in patients with elevated pre-implant CRP (HR, 2.848 95%CI: 1.659-4.888, p < 0.001). These results remained stable when treating pre-implant CRP as a continuous variable. Besides, the prognostic effect of post-implant CRP was also observed. CONCLUSIONS: CRP is a reliable risk-stratification biomarker in patients receiving continuous-flow -LVAD and can be used as a predictor for short- and long-term outcomes.

Impact of cardiac fibrosis and collagens on right ventricular failure and acute kidney injury in patients after continuous-flow left ventricular assist devices.

OBJECTIVES: We aim to investigate the impact of cardiac fibrosis and collagens on right ventricular failure (RVF) and acute kidney injury (AKI) in patients receiving continuous flow left ventricular assist devices. METHODS: Heart tissues from 34 patients were obtained from continuous flow left ventricular assist device insertion sites and corresponding clinical data were collected. The participants were divided into 2 groups according to the extent of the cardiac fibrosis or collagens. RESULTS: Overall, 18 patients developed RVF with 14 receiving right ventricular assist device (RVAD), and 22 patients developed AKI with 12 needing new-onset renal replacement therapy. Higher collagen I (Col1) was significantly associated with increased incidences of RVF (76.5% vs 29.4%, P = 0.015), RVAD support (64.7% vs 17.6%, P = 0.013) and stage 3 AKI (58.8% vs 17.6%, P = 0.032), and patients with higher Col1 were more prone to renal replacement therapy (52.9% vs 17.6%, P = 0.071). Receiver operating characteristic curves showed that Col1 had good predictive effects on RVF [area under the curve (AUC) = 0.806, P = 0.002], RVAD support (AUC = 0.789, P = 0.005), stage 3 AKI (AUC = 0.740, P = 0.020) and renal replacement therapy (AUC = 0.731, P = 0.028) after continuous-flow left ventricular assist device. Moreover, patients with higher Col1 had significantly longer postoperative duration of mechanical ventilation, duration of intensive care unit stay and hospital length of stay (all P < 0.05). Cardiac fibrosis, collagen III (Col3) and Col1/Col3 shared similar results or trends with Col1. CONCLUSIONS: Cardiac fibrosis and related collagens in the apical left ventricular tissue are associated with increased risks of RVF, RVAD use and worse renal function. Further study is warranted owing to the small sample size.

Myocardial oxygen consumption during histidine-tryptophan-ketoglutarate cardioplegia in young human hearts.

OBJECTIVES: Energy demand and supply need to be balanced to preserve myocardial function during paediatric cardiac surgery. After a latent aerobic period, cardiac cells try to maintain energy production by anaerobic metabolism and by extracting oxygen from the given cardioplegic solution. Myocardial oxygen consumption (MVO2) changes gradually during the administration of cardioplegia. METHODS: MVO2 was measured during cardioplegic perfusion in patients younger than 6 months of age (group N: neonates; group I: infants), with a body weight less than 10 kg. Histidine-tryptophan-ketoglutarate crystalloid solution was used for myocardial protection and was administered during a 5-min interval. To measure pO2 values during cardioplegic arrest, a sample of the cardioplegic fluid was taken from the inflow line before infusion. Three fluid samples were taken from the coronary venous effluent 1, 3 and 5 min after the onset of cardioplegia administration. MVO2 was calculated using the Fick principle. RESULTS: The mean age of group N was 0.2 ± 0.09 versus 4.5 ± 1.1 months in group I. The mean weight was 3.1 ± 0.2 versus 5.7 ± 1.6 kg, respectively. MVO2 decreased similarly in both groups (min 1: 0.16 ± 0.07 vs 0.36 ± 0.1 ml/min; min 3: 0.08 ± 0.04 vs 0.17 ± 0.09 ml/min; min 5: 0.05 ± 0.04 vs 0.07 ± 0.05 ml/min). CONCLUSIONS: We studied MVO2 alterations after aortic cross-clamping and during delivery of cardioplegia in neonates and infants undergoing cardiac surgery. Extended cardioplegic perfusion significantly reduces energy turnover in hearts because the balance procedures are both volume- and above all time-dependent. A reduction in MVO2 indicates the necessity of a prolonged cardioplegic perfusion time to achieve optimized myocardial protection.

Magnetic resonance imaging muscle lesions in presumptive canine fibrocartilaginous embolic myelopathy.

This retrospective cohort study reports the observation of magnetic resonance imaging (MRI) epaxial muscle hyperintensity in dogs diagnosed with presumptive fibrocartilaginous embolic myelopathy (FCEM) (n = 61). It further reports the observation of vertebral column hyperesthesia lasting > 12 hours. The hypothesis tested was that the finding of MRI epaxial muscle hyperintensity correlated with dogs presenting with hyperesthesia. Client-owned dogs diagnosed with presumptive FCEM by specific MRI criteria were included. Statistical analysis was performed using Fisher's exact test. Twenty-three percent (14/61) of MRIs displayed abnormal muscle hyperintensity and 43% (26/61) exhibited vertebral column hyperesthesia. No relationship was found between muscle hyperintensity and pain persisting beyond 12 hours. The muscle hyperintensity remains of unknown significance. That 43% of presumptive FCEM cases have prolonged signs of pain is a higher prevalence than previously reported, and may affect clinical differential diagnoses. This is especially significant in cases in which MRI is not possible and a presumptive diagnosis must be based on the clinical signs.

Imagerie par résonance magnétique des lésions des muscles dans la myélopathie embolique fibrocartilagineuse canine présumée. Cette étude rétrospective de cohorte signale les observations de l'imagerie par résonance magnétique (IRM) pour l'hyperintensité du muscle épaxial chez les chiens diagnostiqués avec une myélopathie embolique fibrocartilagineuse (MEFC) présumée (n = 61). Elle signale aussi l'observation de l'hyperesthésie de la colonne vertébrale durant > 12 heures. L'hypothèse qui a été testée était qu'il y avait une corrélation entre l'observation de l'hyperintensité du muscle épaxial par IRM et les chiens présentés avec de l'hyperesthésie. Les chiens appartenant à des clients pour lesquels un diagnostic présomptif de MEFC avait été posé à l'aide du critère spécifique de l'IRM ont été inclus. L'analyse statistique a été réalisée en utilisant le test exact de Fisher. Vingt-trois pour cent (14/61) des IRM affichaient une hyperintensité anormale du muscle et 43 % (26/61) présentaient de l'hypersthésie de la colonne vertébrale. Aucun lien n'a été trouvé entre l'hyperintensité musculaire et la douleur persistant au-delà de 12 heures. La signification de l'hyperintensité musculaire est toujours inconnue. Le taux de 43 % de cas présomptifs de MEFC affichant des signes de douleur prolongée représente une prévalence supérieure aux données déjà signalées et pourrait affecter les diagnostics cliniques différentiels. Ce fait revêt une importance particulière lorsque l'IRM n'est pas possible et qu'un diagnostic présomptif doit se baser sur les signes cliniques.(Traduit par Isabelle Vallières).

Juvenile cellulitis in a 7-week-old golden retriever dog.

A 7-week-old golden retriever puppy was presented with acute onset of marked facial inflammation and pustular dermatitis, markedly enlarged submandibular lymph nodes, and pyrexia. Treatment included high-dose corticosteroids and antibiotics. One week after presentation the puppy showed a significant decrease in inflammation and healing pustules.

Cellulite juvénile chez un chien Golden retriever âgé de 7 semaines. Un chiot Golden retriever âgé de 7 semaines a été présenté suite à l'apparition aiguë d'une inflammation faciale marquée et de dermatite pustuleuse, de ganglions lymphatiques sous-maxillaires significativement enflés et de pyrexie. Le traitement a inclus des fortes doses de corticostéroïdes et d'antibiotiques. Une semaine après la présentation, le chiot a manifesté une réduction significative de l'inflammation et des pustules en voie de guérison.(Traduit par Isabelle Vallières).

Structures and Energetics of Protonated Clusters of Methylamine with Phenylalanine Analogs, Characterized by Infrared Multiple Photon Dissociation Spectroscopy and Electronic Structure Calculations.

Gas-phase clusters of protonated methylamine and phenylalanine (Phe) derivatives have been studied using infrared multiple photon dissociation (IRMPD) spectroscopy in combination with electronic structure calculations at the MP2/aug-cc-pVTZ//B3LYP/6-311+G(d,p) level of theory. Experiments were performed on several Phe derivatives including 4-chloro-l-phenylalanine (4Chloro-Phe), 4-nitro-l-phenylalanine (4Nitro-Phe), 3-cyano-l-phenylalanine (3Cyano-Phe), and 3-trifluoromethyl-l-phenylalanine (3CF3-Phe). Through comparisons between experimental IRMPD spectra and stimulated spectra obtained by electronic structure calculations, charge-solvated structures were found to be prevalent in both 4Chloro-Phe and 4Nitro-Phe, whereas 3Cyano-Phe favored zwitterionic structures and 3-CF3-Phe likely have both zwitterionic and charge-solvated structures present.

Structural investigation of protonated azidothymidine and protonated dimer.

Infrared multiple photon dissociation (IRMPD) spectroscopy experiments and quantum chemical calculations have been used to explore the possible structures of protonated azidothymidine and the corresponding protonated dimer. Many interesting differences between the protonated and neutral forms of azidothymidine were found, particularly associated with keto-enol tautomerization. Comparison of computational vibrational and the experimental IMRPD spectra show good agreement and give confidence that the dominant protonated species has been identified. The protonated dimer of azidothymidine exhibits three intramolecular hydrogen bonds. The IRMPD spectrum of the protonated dimer is consistent with the spectrum of the most stable computational structure. This work brings to light interesting keto-enol tautomerization and exocyclic hydrogen bonding involving azidothymidine and its protonated dimer. The fact that one dominant protonated species is observed in the gas phase, despite both the keto and enol structures being similar in energy, is proposed to be the direct result of the electrospray ionization process in which the dominant protonated dimer structure dissociates in the most energetically favorable way.

Consecutive fragmentation mechanisms of protonated ferulic acid probed by infrared multiple photon dissociation spectroscopy and electronic structure calculations.

Protonated ferulic acid and its principle fragment ion have been characterized using infrared multiple photon dissociation spectroscopy and electronic structure calculations at the B3LYP/6-311 + G(d,p) level of theory. Due to its extensively conjugated structure, protonated ferulic acid is observed to yield three stable fragment ions in IRMPD experiments. It is proposed that two parallel fragmentation pathways of protonated ferulic acid are being observed. The first pathway involves proton transfer, resulting in the loss of water and subsequently carbon monoxide, producing fragment ions m/z 177 and 149, respectively. Optimization of m/z 177 yields a species containing an acylium group, which is supported by a diagnostic peak in the IRMPD spectrum at 2168 cm(-1). The second pathway involves an alternate proton transfer leading to loss of methanol and rearrangement to a five-membered ring.

Tridentate ionic hydrogen-bonding interactions of the 5-fluorocytosine cationic dimer and other 5-fluorocytosine analogues characterized by IRMPD spectroscopy and electronic structure calculations.

Ionic hydrogen-bonding interactions have been found in several clusters formed by 5-fluorocytosine (5-FC). The chloride and trimethylammonium cluster ions, along with the cationic (proton-bound) dimer have been characterized by infrared multiple-photon dissociation (IRMPD) spectroscopy and electronic structure calculations performed at the B2PLYP/aug-cc-pVTZ//B3LYP/6-311+G(d,p) level of theory. IRMPD action spectra, in combination with calculated spectra and relative energetics, indicate that it is most probable that predominantly a single isomer exists in each experiment. For the 5-FC-trimethylammonium cluster specifically, the calculated spectrum of the lowest-energy isomer convincingly matches the experimental spectrum. Interestingly, the cationic dimer of 5-FC was found to have a single energetically relevant isomer (Cationic-IV) involving a tridentate ionic hydrogen-bonding interaction. The three sites of intermolecular ionic hydrogen bonds in this isomer interact very efficiently, leading to a significant calculated binding energy of 180 kJ/mol. The magnitude of the calculated binding energy for this species, in combination with the strong correlation between the simulated and IRMPD spectra, suggests that a tridentate-proton-bound dimer was observed predominantly in the experiments. Comparison of the calculated relative Gibbs free energies (298 K) for this species and several of the other isomers considered also supports the likelihood of the dominant protonated dimer existing as Cationic-IV.