Investigation of periodontal disease development and Porphyromonas gulae FimA genotype distribution in small dogs.

In dogs, Porphyromonas gulae is a major periodontal pathogen with 41-kDa proteins polymerizing to form a filamentous structure called fimbriae or pili, termed FimA. FimA is classified into three genotypes: A, B, and C, and there are combinations of types A, B, C, A/B, A/C, B/C, and A/B/C. Periodontal disease is the most common oral disease in small dogs, but the periodontal disease status and P. gulae colonization at each dog age and breed remain unclear. In this study, we stratified 665 small dogs and analyzed the periodontal status and distribution of P. gulae with each FimA genotype. Dogs with periodontal disease and FimA genotype tended to increase with age. The dogs with at least one FimA genotype had significantly more severe periodontal disease compared with P. gulae-negative dogs (P < 0.01). Additionally, periodontal status was significantly associated with specific FimA genotype distribution in Toy Poodles and Chihuahuas (P < 0.05), whereas there was no such association in Dachshunds. These results suggest that the onset of periodontal disease and P. gulae colonization are related and progress with age. The relationship between periodontal disease and FimA genotype may differ depending on the dog breeds.

A novel method of transapical ProtekDuo rapid deployment cannula as temporary left ventricular assist device.

Peripheral extracorporeal membrane oxygenation (ECMO) is one of the most common strategies for cardiogenic shock. ECMO cannulation is associated with an increased risk of complications. We describe a minimally invasive, off-pump technique to provide adequate hemodynamic support and left ventricular unloading. A 54-year-old male with nonischemic cardiomyopathy and severe peripheral vascular disease with cardiogenic shock was initially supported with inotropes and an intra-aortic balloon pump. Despite continued support, he continued to deteriorate, and we escalated to a temporary left ventricular support with a CentriMag, using a transapical ProtekDuo Rapid Deployment cannula via mini left-thoracotomy. This approach provides adequate hemodynamic support, left ventricular unloading and early ambulation. After 9 days, the patient's functional status was improved and was medically optimized. The patient received a left ventricular assist device as destination therapy. He was discharged home, resumed his normal activities and has been doing well for more than 27 months.

HLA Sensitization in Patients Bridged to Lung Transplantation With Extracorporeal Membrane Oxygenation.

Lung transplantation is a definitive therapy for many end-stage lung pathologies. Extracorporeal membrane oxygenation (ECMO) is increasingly being used as a bridge to lung transplantation (BTT). HLA sensitization is a major barrier to lung transplantation. The development of HLA sensitization while undergoing ECMO support as a BTT has recently been reported in a 2-patient series. Methods: We performed a retrospective analysis of patients undergoing ECMO as a BTT at a single large academic medical center from January 2016 to April 2022. The study was approved by the institutional review board. We selected patients who had undergone ECMO support for at least 7 d with either negative HLA before cannulation or initial negative HLA on ECMO (3 patients). Results: We identified 27 patients bridged to lung transplantation with available HLA data. Of this group, 8 patients (29.6%) developed significant HLA sensitization (>10%). We did not identify any factors predisposing to sensitization, including infection episodes or blood product transfusion. Sensitized patients demonstrated a trend toward an increased primary graft dysfunction rate, a need for posttransplant ECMO support, and a decreased 1-y survival; however, these did not meet statistical significance. Conclusions: Our study is the largest series today describing the association between HLA sensitization and ECMO therapy. We suggest that interaction between the immune system and ECMO circuit contributes to allosensitization pretransplant, similar to that occurring with ventricular assist device. Further work is needed to better characterize the incidence of HLA sensitization in a multicenter cohort and to identify potentially modifiable factors associated with HLA sensitization.

Bilateral Lung Transplantation With Donor Positive for COVID-19 Infection on Bronchoalveolar Lavage: A Case Report.

Initial experience with lung transplant of COVID-19-positive donors was marked by disappointing results, including a reported case of mortality through donor to recipient transmission of infection. However, since that time a number of improvements in preventative and therapeutic measures against COVID-19 have been developed. We present the case of a 51-year-old woman with scleroderma-associated interstitial lung disease who was awaiting lung transplant. A potential donor with excellent lung physiology was located; however, initial testing on bronchoalveolar lavage (BAL) was positive for COVID-19. The donor had tested positive 2 weeks prior and had symptomatically recovered. Our patient had been fully vaccinated but not seroconverted. Given the history of a donor with recovering COVID infection and a fully immunized recipient, our multidisciplinary team elected to proceed with the transplant. The patient successfully underwent bilateral lung transplant with standard induction immunosuppression. Bebtelovimab was given post-transplant day 1 because the recipient remained seronegative to COVID-19. Serial bronchoalveolar lavages post transplant have been negative for COVID-19. The patient has done well after transplant. She was seen in the clinic 2 months post transplant and is ambulatory without supplemental oxygen requirements. To our knowledge, this represents the first reported successful case of lung transplant with a donor positive for COVID-19 on lower respiratory tract sampling.

NT-proBNP and D-Dimer in acute decompensated heart failure: assessment of diagnostic accuracy and correlation with echocardiographic parameters.

PURPOSE: Abnormalities in coagulation and inflammation exist in heart failure. This study compares the diagnostic accuracy of NT-proBNP and D-Dimer and the correlation of these biomarkers with echocardiographic parameters in acute decompensated heart failure. METHODS: A retrospective cross-sectional/observational study was performed using 162 patients with acute decompensated heart failure and 253 age-matched controls. Patients were ruled out for a pulmonary embolus by CT or VQ scans. The study protocol was approved by Institutional Review Board, Lubbock, TX. Correlation of NT-proBNP and D-Dimer values was done with echocardiographic parameters. Statistical significance was assumed at p < 0.05. RESULTS: D-Dimer showed a positive correlation with NT-proBNP (r = 0.665, p = 001). The AUC for NT-proBNP, D-Dimer and a combination of D-Dimer plus NT-proBNP were 0.963, 0.928 and 0.982 respectively. The AUC value for D-Dimer versus the combination of D-Dimer and NT-roBNP was not significant (p = 0.21). Correlation of NT-proBNP was significant with the echocardiographic parameters but D-Dimer did not significantly correlate with any of the echocardiographic parameters studied. CONCLUSIONS: Comparison of the AUC values for D-Dimer versus the combination of D-Dimer and NT-proBNP showed no significance suggestive of comparable diagnostic accuracy in the study population. The lack of correlation between D-Dimer and echocardiographic parameters suggests an independent pathophysiological mechanism underlying upregulation of D-Dimer in acute decompensated heart failure. Further systematic studies are needed to define mechanism of D-Dimer increase in heart failure.

State of the art - Extracorporeal membrane oxygenation as a bridge to thoracic transplantation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has revolutionized the treatment of refractory cardiac and respiratory failure, and its use continues to increase, particularly in adults. However, ECMO-related morbidity and mortality remain high. MAIN TEXT: In this review, we investigate and expand upon the current state of the art in thoracic transplant and extracorporeal life support (ELS). In particular, we examine recent increase in incidence of heart transplant in patients supported by ECMO; the potential changes in patient care and selection for transplant in the years prior to updated United Network for Organ Sharing (UNOS) organ allocation guidelines versus those in the years following, particularly where these guidelines pertain to ECMO; and the newly revived practice of heart-lung block transplants (HLT) and the prevalence and utility of ECMO support in patients listed for HLT. CONCLUSIONS: Our findings highlight encouraging outcomes in patients bridged to transplant with ECMO, considerable changes in treatment surrounding the updated UNOS guidelines, and complex, diverse outcomes among different centers in their care for increasingly ill patients listed for thoracic transplant.

Risk Prediction Model for Survival of Wait-List Patients on Axial CF-LVAD: A UNOS Database Analysis.

BACKGROUND: Continuous flow left ventricular assist devices (CF-LVADs) have become a viable option for patients with end-stage heart failure as a bridge to transplantation or the destination therapy. METHODS: Adult patients listed for heart transplantation (2010-2015) with an axial CF-LVAD on the wait list were obtained from the UNOS database. The multivariate Cox regression model was used to predict the probability of survival after listing. Patients were divided into derivation (80%) and validation (20%) groups. Receiver operating characteristics curves and area under curves were used to define the strength of the model. RESULTS: Risk factors on multivariate analyses were diabetes type I (hazard ratio [HR], 2.5; P = .018), presence of inotropes (HR, 1.6; P = .005), creatinine at listing (HR, 1.2; P < .001). No significant differences were observed between the derivation and validation groups for any of the variables. The area under the curve at 3, 6, and 12 months on the wait list was 0.69, 0.65, 0.63, respectively in the training set and 0.71, 0.65, 0.60, respectively in the validation set. Survival analyses showed that patients implanted with Heartmate II before listing had a better survival than those who were implanted after being on the wait list (HR, 0.78; P = .048). CONCLUSION: To our knowledge, this was the first time a risk prediction model was generated for wait-list survival of Heartmate II patients. A significant difference in survival was noted between patients who received their Heartmate II before being put on a wait list vs those who were implanted while on the list.

Expert Opinions on the Debate of Pericardial Reconstruction in Cardiovascular Surgery: To Close or Not to Close?

BACKGROUND: As of 2019, pericardial closure was performed in only a small portion of the over 320,000 cardiac surgeries performed annually. However, evidence regarding the benefits of pericardial closure or reconstruction has been accruing, particularly with the publication of the RECON study in 2019.  Methods: This group of authors convened to try to arrive at consensus expert opinion regarding pericardial reconstruction. Structured topic questions initially were used to stimulate discussion. Subsequently, a survey of proposed expert opinion statements was conducted among the authors. Based on that survey, consensus expert opinion statements and recommendations were compiled. RESULTS: The expert opinions encompass various topics relating to pericardial reconstruction, including definitions, benefits/risks, and technique. Observed benefits include reductions in: (1) adhesions; (2) postoperative pericardial effusion, atrial fibrillation, and bleeding; and (3) readmissions and length of hospital stay. Expert opinion recommendations regarding surgical technique are compiled into a single chart. Complete pericardial reconstruction should be performed, using native pericardial tissue if available and viable; if not feasible, a patch may be used. Patches that stimulate the formation of site-specific tissue in situ (such as natural extracellular matrix) may have additional benefits (including bioregenerative properties and lack of inflammatory response). Closure should be taut, but tension-free. Adequate drainage of the closed pericardium must be ensured. CONCLUSIONS: Based on available data and collective surgical experience, we endorse pericardial reconstruction as standard approach in appropriately selected patients. We also endorse adoption of standardized pericardial reconstruction techniques to optimize patient outcomes and improve evidence quality in future studies.

A Risk Assessment Model for Stroke in the Early Post-Transplant Period in Adult Cardiac Allograft Recipients: A UNOS Database Analysis.

BACKGROUND: Stroke risk in adult cardiac allograft recipients in the early postoperative period remains less defined. This study attempts to develop a risk assessment model in this population. METHODS: Patients (≥18 years of age) between 2005 and 2015 who underwent cardiac transplantation were selected from the United Network for Organ Sharing database. The final study cohort had 20,915 patients. Risk factors were identified and multivariate logistic regression was used to test associations. SAS software was used for analyses. RESULTS: Male recipients had a lower risk (odds ratio [OR] 0.7 [0.6-0.92]; P < .05) for stroke. Prolonged ischemic time (OR 1.2 [1.1-1.3), mechanical ventilation (OR 1.6 [1.2-1.9]), left ventricular assist device support (OR 1.8 [1.4-2.3]), black or Hispanic ethnicity (OR 1.33 [1.04-1.7]), days in status 1A (OR 1.05 [1.01-1.1]), recipient creatinine (OR 1.2 [1.02-1.4]), and type 2 diabetes (OR 1.4 [1.1-1.7]) were significant risk factors. A risk score was generated. Patients with a score of 8 had a 5-fold increase in event rate as compared with those with a score of 0. The c-statistic for this model was 0.65. CONCLUSIONS: For the first time, a weighted risk score GIMVECH (female gender, ischemic time, mechanical ventilation, left ventricular assist device support, ethnicity, clinical history) was generated to assess stroke in the early post-transplant period.

Impact of mechanical circulatory support on post-transplant stroke risk.

The effect of type of mechanical circulatory support on stroke risk during the early post-transplant period remains undefined in patients bridged to transplant. This study assesses if the type of circulatory support device affects stroke risk in this population. The study cohort of 4257 adult patients bridged with mechanical support to cardiac transplant were derived from the UNOS transplant registry data. Risk factors assessed were age, gender, ischemic time, diabetes (recipient), durable mechanical support at listing and mechanical ventilation pre-transplant. Descriptive statistics were used to describe characteristics of the study cohort. Univariate logistic regression was used to test if there is a significant association between stroke event and all the potential risk factors. Multivariate logistic regression was used to test such associations while adjusting for all other risk factors. Odds ratios (ORs) and their 95% confidence intervals (CIs) in parenthesis, were calculated. p < 0.05 was considered significant. Patients on Extracorporeal membrane oxygenation (ECMO) had the highest risk of stroke immediately post-transplant prior to discharge (OR 3.03, {1.16, 7.95}) followed by Total Artificial Heart (TAH) (OR 2.03, {1.01, 4.07) as compared to those only on a Left Ventricular Assist Device (LVAD). Ischemic time (OR 1.3 {1.09, 1.45}) and diabetes (OR 1.8 {1.29, 2.51}) were significant risk factors. Patients on ECMO and TAH had a 203% and 103% increase respectively in the odds of having a stroke prior to discharge as compared to those only on LVADS.

Risk Prediction Model for Basal Cell Carcinoma in Cardiac Allograft Recipients.

BACKGROUND: Basal cell carcinoma (BCC) is the second most common skin cancers in posttransplant patients. Long-term immunosuppression predisposes the patients to higher risk. This study was undertaken to develop a risk prediction model using the United Network for Organ Sharing (UNOS) database. MATERIALS AND METHODS: Heart transplant recipients (2000~2015) from the UNOS database were analyzed. The Cox proportional hazards model was applied to screen the predictors associated with the development of BCC. Stepwise forward selection with Akaike information criterion was done to obtain the multivariate model. Area under the curve was derived from the receiver operating characteristics curve to assess the quality of the prediction model. A risk scoring system was developed to stratify patients into different risk groups, and the occurrence rates of posttransplant BCC among different groups were compared. RESULTS: There were 24,374 patients who received heart transplantation within this study period, and 1211 recipients have been reported with BCC. The multivariate model provides area under the curves at 5, 8, and 10 years posttransplant of 0.77, 0.76, and 0.76, respectively, in the derivation set and 0.75, 0.74, and 0.74, respectively, in the validation set. The predicted and observed probabilities of developing BCC in 5 years agree well across different risk groups. Kaplan-Meier survival curves were generated, which demonstrate significant differences between subjects in different risk groups. CONCLUSION: A risk prediction model has been generated for the first time for BCC with a c-statistic of ≥0.74 in both derivation and validation sets, making it a good tool for risk stratification.

Risk prediction model for cutaneous squamous cell carcinoma in adult cardiac allograft recipients.

BACKGROUND: Heart transplant recipients are at higher risk of developing skin cancer than the general population due to the long-term immunosuppression treatment. Cancer has been reported as one of the major causes of morbidity and mortality for patients after heart transplantation. Among different types of skin cancers, cutaneous squamous cell carcinoma (cSCC) is the most common one, which requires timely screening and better management. AIM: To identify risk factors and predict the incidence of cSCC for heart transplant recipients. METHODS: We retrospectively analyzed adult heart transplant recipients between 2000 and 2015 extracted from the United Network for Organ Sharing registry. The whole dataset was randomly divided into a derivation set (80%) and a validation set (20%). Uni- and multivariate Cox regression were done to identify significant risk factors associated with the development of cSCC. Receiver operating charac-teristics curves were generated and area under the curve (AUC) was calculated to assess the accuracy of the prediction model. Based on the selected risk factors, a risk scoring system was developed to stratify patients into different risk groups. A cumulative cSCC-free survival curve was generated using the Kaplan-Meier method for each group, and the log-rank test was done to compare the inter-group cSCC rates. RESULTS: There were 23736 heart-transplant recipients during the study period, and 1827 of them have been reported with cSCC. Significant predictors of post-transplant cSCC were older age, male sex, white race, recipient and donor human leukocyte antigen (HLA) mismatch level, malignancy at listing, diagnosis with restrictive myopathy or hypertrophic myopathy, heart re-transplant, and induction therapy with OKT3 or daclizumab. The multivariate model was used to predict the 5-, 8- and 10-year incidence of cSCC and respectively provided AUC of 0.79, 0.78 and 0.77 in the derivation set and 0.80, 0.78 and 0.77 in the validation set. The risk scoring system assigned each patient with a risk score within the range of 0-11, based on which they were stratified into 4 different risk groups. The predicted and observed 5-year probability of developing cSCC match well among different risk groups. In addition, the log-rank test indicated significantly different cSCC-free survival across different groups. CONCLUSION: A risk prediction model for cSCC among heart-transplant recipients has been generated for the first time. It offers a c-statistic of ≥ 0.77 in both derivation and validation sets.

Femoral venoarterial extracorporeal membrane oxygenation using a novel biatrial cannula for venous drainage and left ventricular venting.

Extracorporeal life support (ECLS) is an expanding technology for patients in cardiogenic shock. The majority of patients requiring ECLS can be managed with percutaneous venoarterial (VA) femoral cannulation. Despite sufficient extracorporeal circulatory support, a unclear number of patients develop left ventricular distension which can result in increased wall tension and stress as well as worsening pulmonary edema. Indications to vent the left ventricle can be controversial. When venting is indicated, a number of additional procedures may be considered including inotropic support, intra-aortic balloon pump, impella, balloon atrial septostomy, or placement of a transseptal cannula. We present a unique case of a femoral VA extracorporeal membrane oxygenation as a bridge to transplant with left-sided venting using a Bio-Medicus NextGen cannula (Medtronic) with a transseptal approach.

Temporary Circulatory Support With Ventricular Assist Devices: Update on Surgical and Percutaneous Strategies.

PURPOSE OF REVIEW: The available platforms for temporary circulatory support (TCS) have expanded to include impeller technologies in addition to the traditional approaches with centrifugal pumps and intra-aortic counterpulsation. We review the evidence for competing technologies, relative risk, and benefit of individual TCS platforms and provide a consensus opinion in the context of our institutional experience. RECENT FINDINGS: Trans-aortic axial flow devices (Impella) have significantly impacted the support of patients with cardiogenic shock. Despite the absence of prospective randomized data, the use of both percutaneous and surgical Impella devices is ubiquitous among heart failure centers and rapidly evolving. Extracorporeal centrifugal pumps remain the technology of last resort. Despite the increasing use of new TCS platforms, there is little empirical evidence that outcomes have been impacted. Increasingly, systems of care-rather than technology-are seen as the more important variable in the management of patients with cardiogenic shock.

Stem cell therapy in heart failure: Where do we stand today?

Heart failure is a global epidemic that drastically cuts short longevity and compromises quality of life. Approximately 6 million Americans ≥20 years of age carry a diagnosis of heart failure. Worldwide, about 40 million adults are affected. The treatment of HF depends on the etiology. If left untreated it rapidly progresses and compromises quality of life. One of the newer technologies still in its infancy is stem cell therapy for heart failure. This review attempts to highlight the clinical studies done in ischemic cardiomyopathy, dilated cardiomyopathy and restrictive cardiomyopathy. A combined approach of simultaneous revascularization and stem cell therapy appears to produce maximum benefit in ischemic cardiomyopathy. Treatment of dilated cardiomyopathy with stem cells also holds promise but needs more definition with regards to timing, route of cell delivery and type of cell used to achieve reproducible results. The variability noted in response to stem cell therapy in patients could also be secondary to their co-morbidities. Abnormalities of glucose metabolism and diabetes in particular impair stem cell and angiogenic cell mobilization. This opens up a whole new area of investigation into exploring the biochemical microenvironment which could influence the efficacy of stem cell therapy. This article is part of a Special Issue entitled: Stem Cells and Their Applications to Human Diseases edited by Hemachandra Reddy.

Impact of preoperative atrial fibrillation in patients with left ventricular assist device: A systematic review and meta-analysis.

Atrial fibrillation (AF) is a common finding in patients evaluated for left ventricular assist device (LVAD). There is conflicting data regarding the mortality risk as well as the thromboembolic risk in patients with preoperative AF who undergo LVAD implantation. We examined these risks by performing a meta-analysis. We performed a literature search of Pubmed, EMBASE, SCOPUS, and Cochrane from inception to February 2018. The eligible studies were used to compare mortality rate and thromboembolic risk between AF and Non-AF (NAF) groups after LVAD implantation. We obtained 391 articles from our search strategy. Seven retrospective studies were included and accounted for 5823 LVAD patients (AF 1589; NAF 4234). The median follow-up duration ranged from 7-24 months. The pooled analysis revealed a significantly increased risk of mortality in preoperative AF patients who underwent LVAD operation compared to those with NAF (Risk Ratio [RR] 1.16, 95% CI 1.05-1.28, I2 = 0%). Five studies reported thromboembolism events involving 1359 preoperative AF and 3893 NAF patients. The pooled analysis did not show a statistically significant association between risk of thromboembolic event and preoperative AF (Risk Ratio [RR] 1.08, 95% CI 0.86-1.36, I2 = 76.2%). Our study shows that preoperative AF may be associated with a higher mortality rate. This study is limited by the fact that the data are pooled from retrospective studies. Further prospective studies are warranted in order to validate these results.

Correlations of GDF-15 with sST2, MMPs, and worsening functional capacity in idiopathic dilated cardiomyopathy: Can we gain new insights into the pathophysiology?

Growth and differentiation factor-15 (GDF-15) has been implicated in fibrosis, inflammation, and ventricular remodeling. The role of GDF-15 in the regulation of cardiac remodeling in idiopathic dilated cardiomyopathy (DCM) remains poorly defined. This study attempts to analyze the molecular interactions between GDF-15 and markers of fibrosis as well as its positive correlations with worsening functional capacity. The study population consisted of 24 DCM patients and 8 control subjects. All DCM patients had normal coronary angiographic studies. Plasma levels of GDF-15, matrix metalloproteinase-2 (MMP2), MMP3, MMP9, tissue inhibitor of MMP 1 (TIMP1), and soluble suppression of tumorigenicity-2 protein (sST2) were determined by enzyme-linked immunosorbent assays. Brain Natriuretic Peptide (BNP) was measured as per core laboratory protocol assay at Scott and White Memorial Hospital core laboratory. Correlation analysis was performed between GDF-15 and each of the MMPs-MMP2, MMP3, MMP9, and TIMP as well as New York Heart Association (NYHA) class and echocardiographic parameters (left ventricular ejection fraction (LVEF) and left ventricular internal dimension in diastole (LVIDd)). LVEF and LVIDd were obtained by two-dimensional echocardiography. The protocol was approved by Scott and White Memorial Hospital Institutional Review Board (S&W IRB). Correlation analysis of control versus all DCM patients showed a strong correlation of GDF-15 with TIMP1 (r = 0.83, p < 0.0001) and weaker correlation with MMP3 (r = 0.41, p = 0.011) and MMP2 (r = 0.47, p = 0.003). MMP9 showed poor correlation with GDF-15 (r = 0.3036, p = 0.046). GDF-15 correlated negatively with MMP2/TIMP1 ratio (r = -0.47, p = 0.006). sST2 correlated strongly with GDF-15 (r = 0.7, p < 0.0001). GDF-15 correlated negatively with LVEF (r = -0.49, p = 0.004) and positively with LVIDd (r = 0.58, p = 0.0006). GDF-15 showed significant positive correlation with NYHA functional class (r = 0.71, p < 0.00001) and BNP (r = 0.86, p < 0.00001). Significant associations of GDF-15 with MMPs, sST2, LVIDd, LVEF, and NYHA class reported here for the first time in nonischemic dilated hearts may open up new avenues of investigations to better understand molecular mechanisms controlling cardiac remodeling. This study is limited by its small size and needs validation in larger populations.