Restricted Cusp Motion in Newly Implanted Tricuspid Bioprostheses: Incidence, Predictors, and Impact on Survival.

OBJECTIVE: This study aimed to investigate the occurrence of restricted cusp motion (RCM) at the time of bioprosthetic tricuspid valve replacement (TVR) and analyzed associated risk factors and outcomes. METHODS: This study involved adult patients who underwent TVR with a bioprosthesis at our institution between 2012 and 2022. Bioprosthetic cusp motion was analyzed de-novo through a detailed review of intraoperative transesophageal echocardiograms (TEE). Two models of porcine valves were implanted, the Hancock II bioprosthesis (Medtronic, Inc, Minneapolis, Minnesota) and the St. Jude Epic bioprosthesis (St. Jude Medical, St. Paul, Minnesota). RESULTS: Among the 476 patients who met the inclusion criteria, RCM was identified on the immediate post-bypass TEE in 150 (31.5%); there was complete immobility of the cusp in 63 patients (13.2%) and limited movement of a cusp in 87 patients (18.3%). In a multivariable logistic regression analysis, the Hancock II model (OR 6.15, p<0.001), a larger orifice area (per IQR increase, OR 1.58, p=0.017), a smaller body surface area (per IQR increase, OR 0.68, p=0.040), and a lower ejection fraction (per IQR increase, OR 0.60, p=0.033) were independently associated with having RCM. Cox regression adjusting for 15 covariates revealed that RCM at time of TVR was independently associated with an increased risk of mortality (HR 1.35, p=0.049). CONCLUSIONS: This study revealed a high incidence of restricted cusp motion in bioprosthetic valves in the tricuspid position detected shortly post-implantation, which was associated with increased late mortality. To reduce the probability of restricted cusp motion, it is important to select the appropriate prosthesis model and size, particularly in small patients.

Calf rEF: Impact of Calf Muscle Pump Dysfunction With Reduced Ejection Fraction on All-Cause Mortality.

OBJECTIVE: To evaluate mortality outcomes by varying degrees of reduced calf muscle pump (CMP) ejection fraction (EF). PATIENTS AND METHODS: Consecutive adult patients who underwent venous air plethysmography testing at the Mayo Clinic Gonda Vascular Laboratory (January 1, 2012, through December 31, 2022) were divided into groups based on CMP EF for the assessment of all-cause mortality. Other venous physiology included measures of valvular incompetence and clinical venous disease (CEAP [clinical presentation, etiology, anatomy, and pathophysiology] score). Mortality rates were calculated using the Kaplan-Meier method. RESULTS: During the study, 5913 patients met the inclusion criteria. During 2.84-year median follow-up, there were 431 deaths. Mortality rates increased with decreasing CMP EF. Compared with EF of 50% or higher, the hazard ratios (95% CIs) for mortality were as follows: EF of 40% to 49%, 1.4 (1.0 to 2.0); EF of 30% to 39%, 1.6 (1.2 to 2.4); EF of 20% to 29%, 1.7 (1.2 to 2.4); EF of 10% to 19%, 2.4 (1.7 to 3.3) (log-rank P≤.001). Although measures of venous valvular incompetence did not independently predict outcomes, venous disease severity assessed by CEAP score was predictive. After adjusting for several clinical covariates, both CMP EF and clinical venous disease severity assessed by CEAP score remained independent predictors of mortality. CONCLUSION: Mortality rates are higher in patients with reduced CMP EF and seem to increase with each 10% decrement in CMP EF. The mortality mechanism does not seem to be impacted by venous valvular incompetence and may represent variables intrinsic to muscular physiology.

Hemodynamic Comparison of the On-X and Top Hat Mechanical Aortic Valve Prostheses.

BACKGROUND: There are limited data comparing hemodynamic valve function in mechanical aortic valve prostheses. This study compared the hemodynamic function of 2 commonly used mechanical aortic valve (AV) prostheses, the On-X (Artivion) and Top Hat (CarboMedics Inc) valves. METHODS: This study was a retrospective analysis of 512 patients who underwent AV replacement with the On-X (n = 252; 49%) or Top Hat (n = 260; 51%) mechanical valves between 2011 and 2019. Patients were matched on the basis of selected variables. Echocardiographic data were collected preoperatively and postoperatively over a median follow-up of 1.39 years. RESULTS: A total of 320 patients were matched, 160 patients in each group. Despite being matched for left ventricular outflow tract diameter, patients in the Top Hat group received a greater prevalence of smaller tissue annulus diameter valves (≤21 mm) (83% vs 38%; P < .001). Patients in the On-X group had longer aortic cross-clamp times (78 minutes vs 64 minutes; P < .001) during isolated aortic valve replacement. Discharge echocardiography showed no difference in the AV area index between both groups (1.00 cm2/m2 vs 1.02 cm2/m2; P = .377). During longer-term echocardiographic follow-up, the AV area index remained stable for both valves within their respective tissue annulus diameter groups (P = .060). CONCLUSIONS: There was no difference between the 2 valves with respect to the AV area index at discharge, and hemodynamic function was stable during longer-term follow-up. The longer aortic cross-clamp time observed in the On-X group may indicate increased complexity of implantation compared with the Top Hat group.

Invasive Cardiac Hemodynamics in Apical Hypertrophic Cardiomyopathy.

BACKGROUND: Symptomatic limitations in apical hypertrophic cardiomyopathy may occur because of diastolic dysfunction with resultant elevated left ventricular filling pressures, cardiac output limitation to exercise, pulmonary hypertension (PH), valvular abnormalities, and/or arrhythmias. In this study, the authors aimed to describe invasive cardiac hemodynamics in a cohort of patients with apical hypertrophic cardiomyopathy. METHODS AND RESULTS: Patients presenting to a comprehensive hypertrophic cardiomyopathy center with apical hypertrophic cardiomyopathy were identified (n=542) and those who underwent invasive hemodynamic catheterization (n=47) were included in the study. Of these, 10 were excluded due to postmyectomy status or incomplete hemodynamic data. The mean age was 56±18 years, 16 (43%) were women, and ejection fraction was preserved (≥50%) in 32 (91%) patients. The most common indication for catheterization was dyspnea (48%) followed by suspected PH (13%), and preheart transplant evaluation (10%). Elevated left ventricular filling pressures at rest or exercise were present in 32 (86%) patients. PH was present in 30 (81%) patients, with 6 (20%) also having right-sided heart failure. Cardiac index was available in 25 (86%) patients with elevated resting filling pressures. Of these, 19 (76%) had reduced cardiac index and all 6 with right-sided heart failure had reduced cardiac index. Resting hemodynamics were normal in 8 of 37 (22%) patients, with 5 during exercise; 3 of 5 (60%) patients had exercise-induced elevation in left ventricular filling pressures. CONCLUSIONS: In patients with apical hypertrophic cardiomyopathy undergoing invasive hemodynamic cardiac catheterization, 86% had elevated left ventricular filling pressures at rest or with exercise, 81% had PH, and 20% of those with PH had concomitant right-sided heart failure.

Progression of Mild Mitral Annulus Calcification to Mitral Valve Dysfunction and Impact on Mortality.

BACKGROUND: Mitral annulus calcification (MAC) represents a degenerative process resulting in calcium deposition in the mitral valve apparatus. Mitral annulus calcification is associated with adverse clinical outcomes. We sought to examine the long-term significance of mild MAC and its relationship to subsequent mitral valve dysfunction (MVD) and mortality in patients without MVD on the initial echocardiogram. METHODS: A total of 1,420 patients with mild MAC and no MVD at baseline and 1 or more follow-up echocardiograms at least 1 year after the baseline echocardiogram were included in the analysis. For patients with >1 echocardiogram during follow-up, the last echocardiogram was used. The same criteria were used to identify 6,496 patients without MAC. Mitral valve dysfunction was defined as mitral regurgitation (MR) and/or mitral stenosis (MS) of moderate or greater severity. Mixed disease was defined as the concurrent presence of both moderate or greater MS and MR. The primary end point was development of MVD, and the secondary end point was all-cause mortality. RESULTS: For patients with mild MAC, age was 74 ± 10 years and 528 (37%) were female. Over a median follow-up of 4.7 (interquartile range, 2.7-6.9) years, 215 patients with mild MAC developed MVD, including MR in 170 (79%), MS in 37 (17%), and mixed disease in 8 (4%). In a multivariable regression model compared to patients without MAC, the presence of mild MAC was independently associated with increased mortality (hazard ratio = 1.43; 95% CI 1.24, 1.66; P < .001). Kaplan-Meier 4-year survival rates were 80% and 90% for patients with mild MAC and no MAC, respectively. CONCLUSIONS: Mild MAC observed on transthoracic echocardiography is an important clinical finding with prognostic implications for both valvular function and mortality.

Impact of tricuspid valve regurgitation on intermediate outcomes of degenerative mitral valve surgery.

BACKGROUND: In patients undergoing mitral valve surgery, optimal management of less-than-severe concomitant tricuspid valve regurgitation (TR) is unclear, as there are few long-term data. This study examines progression of TR, patient survival, and reoperations in patients undergoing mitral valve surgery. METHODS: There were 1588 patients who underwent degenerative mitral valve surgery and had pre- and postoperative echocardiograms for assessment of TR severity and tricuspid annulus diameter. Analysis used repeated-measures ordinal regression to model the longitudinal trends in TR grade and proportional hazards regression for long-term survival and reoperation outcomes. RESULTS: Concomitant tricuspid valve (TV) surgery was performed in 235 (14.8%) patients. In response to surgery, TR grades improved more in patients with concomitant TV intervention regardless of the severity of preoperative TR, and these early trends were sustained over long-term follow-up. Risk of progression to severe TR was not influenced by tricuspid annulus diameter (P = .226). After we adjusted for underlying health characteristics, survival following mitral valve surgery was similar in patients with and without TV intervention. Late TV reoperation was observed in 22 patients (5-year cumulative risk 1.5%), but among these, only 6 patients had severe TR as the primary indication for reoperation; preoperative TR grade and initial concomitant TV surgery were not associated with incidence of reoperation. CONCLUSIONS: Concomitant TV surgery for moderate TR reduces progression of TR but did not influence survival or incidence of reoperation. Among patients with less-than-severe preoperative TR, tricuspid annular diameter was not associated with progression to severe TR.

Recurrence of Pathologically Proven Papillary Fibroelastoma.

BACKGROUND: Papillary fibroelastoma (PFE) is the most common primary benign cardiac tumor. Because PFEs have the potential to embolize, they often are surgically excised. Prior studies have suggested that postoperative recurrence of PFE is rare or does not occur. We aimed to determine the rate at which PFEs recurred after surgical removal and to identify any risk factors associated with recurrence. METHODS: We retrospectively identified all patients from a single center with pathologically proven PFE, treated from January 1995 through December 2018. Patients were included in the study if they had an echocardiographic examination at least 1 year after surgery. We compared echocardiographic images obtained intraoperatively (after excision) and at dismissal with those of the most recent examination to assess the possibility of PFE recurrence. RESULTS: We included 98 patients in the study. The mean duration of follow-up was 5.4 (SD 3.7) years (range, 1 to 17); the median duration of follow-up was 4.3 years (interquartile range, 1.9 to 7.7). Twelve patients (12.2%) had echocardiographically supported PFE recurrence. Three patients had the recurrent lesion surgically reexcised, and pathologic analysis showed that two were recurrent PFEs and one was a Lambl excrescence. Initial clinical presentation of stroke or transient ischemic attack was more common for the recurrence group (for the first PFE) than for the nonrecurrence group (83% vs 26%; P < .001). CONCLUSIONS: Contrary to findings from previous studies, PFEs do recur after surgical excision. These findings emphasize the importance of postoperative follow-up with transesophageal echocardiography for identifying recurrent masses.

Proteomic profiling of soft tissue sarcomas with SWATH mass spectrometry.

Soft tissue sarcomas (STS) are a group of rare and heterogeneous cancers. While large-scale genomic and epigenomic profiling of STS have been undertaken, proteomic analysis has thus far been limited. Here we utilise sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) for proteomic profiling of formalin fixed paraffin embedded (FFPE) specimens from a cohort of STS patients (n = 36) across four histological subtypes (leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma). We quantified 2951 proteins across all cases and show that there is a significant enrichment of gene sets associated with smooth muscle contraction in leiomyosarcoma, RNA splicing regulation in synovial sarcoma and leukocyte activation in undifferentiated pleomorphic sarcoma. We further identified a subgroup of STS cases that have a distinct expression profile in a panel of proteins, with worse survival outcomes when compared to the rest of the cohort. Our study highlights the value of comprehensive proteomic characterisation as a means to identify histotype-specific STS profiles that describe key biological pathways of clinical and therapeutic relevance; as well as for discovering new prognostic biomarkers in this group of rare and difficult-to-treat diseases.

Pazopanib in advanced soft tissue sarcomas.

Pazopanib is the first and only tyrosine kinase inhibitor currently approved for the treatment of multiple histological subtypes of soft tissue sarcoma (STS). Initially developed as a small molecule inhibitor of vascular endothelial growth factor receptors, preclinical work indicates that pazopanib exerts an anticancer effect through the inhibition of both angiogenic and oncogenic signaling pathways. Following the establishment of optimal dosing and safety profiles in early phase studies and approval for the treatment of advanced renal cell carcinoma, pazopanib was investigated in STS. A landmark phase III randomized study demonstrated improved progression-free survival with pazopanib compared to that with placebo in pretreated patients with STS of various subtypes. The efficacy of pazopanib in specific STS subtypes has been further described in real-world-based case series in both mixed and subtype-specific STS cohorts. At present, there are no clinically validated predictive biomarkers for use in selecting patients with advanced STS for pazopanib therapy, limiting the clinical effectiveness and cost-effectiveness of the drug. In this review, we summarize the preclinical and clinical data for pazopanib, outline the evidence base for its effect in STS and explore reported studies that have investigated putative biomarkers.

Clinical Characteristics and efficacy of chemotherapy in sclerosing epithelioid fibrosarcoma.

BACKGROUND: Sclerosing epithelioid fibrosarcoma (SEF) is a very rare soft tissue sarcoma subtype. Clinically it is an aggressive tumour; however, to our knowledge there are no published reports regarding the efficacy of chemotherapy in SEF. Therefore, the aim of this study was to document the outcome of a series of patients with SEF treated at a single referral centre with reference to systemic therapy. METHODS: A retrospective search of a prospectively maintained database was performed to identify all patients diagnosed with SEF between 1990 and 2017. The diagnosis was confirmed in each case by a dedicated soft tissue sarcoma pathologist. We analysed those with recurrent disease and the effect of systemic chemotherapy in the metastatic setting. RESULTS: Thirteen patients were identified, median overall survival from diagnosis and metastasis were 47.3 (95% CI 25.0-131.9) and 16.3 (95% CI 5.3-20.6) months, respectively. In total, 12 (92.3%) patients developed metastatic disease of which 10 died of disease, 1 was lost to follow-up and 1 had recently commenced palliative treatment. Among the 10 patients with metastatic disease, 7 received palliative chemotherapy. Palliative chemotherapy resulted in partial response in 1 patient, stable disease in 3 patients and progressive disease in 3 patients. Median time to disease progression was 2.7 (95% CI 1.2-4.4) months. Two of 13 patients were treated with adjuvant chemotherapy, receiving 6 cycles of liposomal doxorubicin and 1 cycle of doxorubicin, respectively, with a metastasis-free survival of 28.2 and 7.1 months, respectively. CONCLUSION: SEF is an aggressive sarcoma subtype with a poor outcome and with limited responsiveness to conventional chemotherapy. Patients with this subtype should be considered for participation in clinical trials with novel agents. Further investigation into the biology of this rare disease is required to improve outcomes.

2018 ESMO Sarcoma and GIST Symposium: 'take-home messages' in soft tissue sarcoma.

The 7th edition of the 'ESMO Sarcoma and GIST Symposium' was held in Milan in February 2018. For the first time, the Symposium brought together representatives from the European Reference Network on rare adult solid cancer (EURACAN) joined by sarcoma experts from the USA, Japan and patient advocacy groups, to share insights and discuss future directions in this rare condition. This commentary will summarise the highlights in soft tissue sarcomas.

Preoperative Low-Dose Aspirin Exposure and Outcomes After Emergency Neurosurgery for Traumatic Intracranial Hemorrhage in Elderly Patients.

BACKGROUND: Antiplatelet medications are usually discontinued before elective neurosurgery, but this is not an option for emergent neurosurgery. We performed a retrospective cohort study to examine whether preoperative aspirin use was associated with worse outcomes after emergency neurosurgery in elderly patients. METHODS: We analyzed all cases of emergency neurosurgical procedures for traumatic intracranial hemorrhage from 2008 to 2012 at a level 1 trauma center. Demographics, comorbidities, and outcomes were compared for patients ≥65 years by preoperative aspirin exposure. Exclusion criteria were: (1) polytrauma, (2) concomitant use of other preoperative anticoagulants or antiplatelet agents, (3) surgical indication other than subdural, extradural, or intraparenchymal hemorrhage, and (4) repeat neurosurgical procedures within a single admission. Estimated intraoperative blood loss, postprocedural intracranial bleeding requiring reoperation, death in hospital, intensive care unit, and hospital lengths of stay and perioperative blood product transfusion from 48 hours before 48 hours after surgery were the study outcomes. We also examined whether platelet transfusion had an impact on outcomes for patients on aspirin. RESULTS: The cohort included 171 patients. Patients receiving preoperative aspirin (n = 87, 95% taking 81 mg/day) were the same age as patients not receiving aspirin (n = 84; 78.3 ± 7.8 vs 75.9 ± 7.9 years, P > .05), had slightly higher admission Glasgow Coma Scale scores (12.8 ± 3.4 vs 11.4 ± 4, P = .02) and tended to have more coronary artery disease (P< .05). Adjusted for Glasgow Coma Scale and coronary artery disease, patients receiving preoperative aspirin had a higher odds of perioperative platelet transfusion (adjusted odds ratio 9.89, 95% confidence interval, 4.24-26.25). There were no other differences in outcomes between the 2 groups. Preoperative or intraoperative platelet transfusion was not associated with better outcomes among aspirin patients. CONCLUSIONS: In patients age ≥65 years undergoing emergency neurosurgery for traumatic intracranial hemorrhage, preoperative low-dose aspirin treatment was not associated with increased perioperative bleeding, hospital lengths of stay, or in-hospital mortality.

Intravenous Tissue Plasminogen Activator Administration for Ischemic Stroke 1 Hour After Epidural Catheter Removal: A Case Report.

Anticoagulation after a recent neuraxial procedure poses risk for development of spinal hematoma. Clinical evidence supports prompt IV tissue plasminogen activator administration after onset of ischemic stroke. There is an absence of data regarding emergency fibrinolytic therapy for patients experiencing a stroke with recent neuraxial procedures, resulting in highly disparate, nonevidence-based guidelines. This report describes a patient who developed ischemic stroke when receiving postoperative epidural analgesia. Tissue plasminogen activator was emergently administered 1 hour after epidural catheter removal with a favorable recovery. The patient and his family reviewed the manuscript, and written consent to publish this case report was obtained from the patient.

High Dose, Prolonged Epsilon Aminocaproic Acid Infusion, and Recombinant Factor VII for Massive Postoperative Retroperitoneal Hemorrhage following Splenectomy.

The antifibrinolytic agent ε-aminocaproic acid is used to decrease procedural blood loss in a variety of high risk surgeries. The utility of recombinant factor VII administration in massive hemorrhage has also been reported in a variety of settings, though the impact in a surgical context remains unclear. We describe the case of a patient who underwent massive open splenectomy and developed diffuse retroperitoneal bleeding on postoperative day one. Massive transfusion was initiated, but attempts to control hemorrhage with surgical and interventional radiology approaches were unsuccessful, as was recombinant factor VII administration. Commencement of a high dose aminocaproic acid infusion was followed by a prominent rise in fibrinogen levels and stabilization of the hemorrhage. Indications, dosages, and adverse effects of ε-aminocaproic acid as described in the literature are reviewed.

Diagnosing the cause of vertigo: a practical approach.

Dizziness is among the commonest of chief complaints. It often presents a significant challenge to the attending physician, because the symptoms and signs are often vague and non-specific. However, a robust systematic approach can usually arrive at the diagnosis. Maintaining balance requires sensory inputs from the vestibular, visual, and somatosensory systems and the cerebellum fine-tunes inaccurate motor outputs. Causes of vertigo are most commonly otological, followed by central, somatosensory, and visual. The first question in approaching patients with dizziness is to categorise dizziness into one of the four groups: lightheadedness, pre-syncope, disequilibrium, and vertigo. Secondly, central vertigo has to be differentiated with peripheral vertigo. For peripheral vertigo, the most common cause is benign paroxysmal positional vertigo and should be specifically looked for. The tempo of the vertiginous attacks and other associated symptoms can help differentiate the other causes of peripheral vertigo, including Meniere's disease, vestibular neuronitis, labyrinthitis, and a perilymph fistula.

Hearing impairment and depressive symptoms in an older chinese population.

OBJECTIVE: To investigate the association of objectively measured hearing loss and depression in an older Chinese population. DESIGN: Cross-sectional study. SETTING: Screening service provided to the elderly as part of a charity program in collaboration with a local group of medical and audiologic professionals. METHODS: A cross-sectional study was conducted on community-dwelling people aged 60 years or above using pure-tone audiometry in a soundproof environment together with a validated Cantonese version of the Geriatric Depression Scale. The association of hearing loss and depression, together with a number of predisposing factors, was examined with multivariate analysis. The effect of hearing aid use was investigated in some subjects. MAIN OUTCOME MEASURES: The effect of both self-reported hearing impairment and objectively measured hearing loss on depressive symptoms, together with a number of predisposing factors, was examined with multivariate analysis. RESULTS: Excluding those suffering from dementia, 914 people were included. Logistic regression showed that the main predicting factors of depression were poor self-perceived health, measured hearing loss, and female gender. Measured hearing loss gave an odds ratio of 1.649 (95% CI 1.048-2.595). The association of self-reported hearing loss with depression was shown in univariate analysis but not in multivariate analysis. Hearing aid use showed a tendency toward reducing depressive symptom scores. CONCLUSIONS: There is an independent association between depression and measured hearing loss in older Chinese but not between depression and self-reported hearing loss. Self-reported hearing impairment should not replace audiometry in estimating risks of hearing impairment. The use of hearing aids could improve the general well-being of our older population.

Alveolar capillary dysplasia with congenital misalignment of pulmonary vessels.

Alveolar capillary dysplasia with misalignment of pulmonary vessels is an uncommon congenital cause of persistent pulmonary hypertension of the newborn. It is universally fatal, and diagnosis is entirely dependent upon surgical lung biopsy. We present a case of alveolar capillary dysplasia with misalignment of pulmonary vessels occurring in a full-term neonate, emphasizing that early involvement of the thoracic surgeon for a histological diagnosis allows expensive and ineffective treatments to be avoided.

Severe acute respiratory syndrome complicated by spontaneous pneumothorax.

Severe acute respiratory syndrome (SARS) presents an unprecedented diagnostic and therapeutic challenge to clinicians. Despite recent progress in identifying and analyzing the coronavirus that is responsible for it, few reports have addressed the clinical complications of SARS. The present study was a two-center retrospective cohort study. All patients in the study had SARS, were managed in the two major Hong Kong hospitals (ie, Prince of Wales Hospital and United Christian Hospital), and had developed spontaneous pneumothorax during their hospitalization between March 10, 2003, and April 28, 2003. Spontaneous pneumothorax was reported in 6 of 356 SARS patients who were treated at the two hospitals during the period. This represents an incidence of 1.7%. None of the six patients had a history of smoking or pulmonary disease. The rate of admission to the ICU was 66.7% and the crude mortality rate was 33.3% in this group of patients. There was a trend for the mean neutrophil count in these patients to be higher than in previously reported cohorts of comparable SARS patients (14.5 x 10(9) vs 4.6 x 10(9) neutrophils per liter, respectively). Conservative measures like tube thoracostomy or observation alone offered satisfactory initial symptomatic management in five of six patients. Spontaneous pneumothorax is a specific and potentially life-threatening complication in SARS patients. Patients with extensive lung injury, as indicated by severe clinical courses, and in particular high neutrophil counts, appear to be most at risk. The benefits of surgical management must be balanced against the potential risks to health-care workers.