Heart Failure with Reduced Ejection Fraction and COVID-19, when the Sick Get Sicker: Unmasking Racial and Ethnic Inequities During a Pandemic.

Minoritized racial and ethnic groups have the highest incidence, prevalence, and hospitalization rate for heart failure. Despite improvement in medical therapies and overall survival, the morbidity and mortality of these groups remain elevated. The reasons for this disparity are multifactorial, including social determinant of health (SDOH) such as access to care, bias, and structural racism. These same factors contributed to higher rates of COVID-19 infection among minoritized racial and ethnic groups. In this review, we aim to explore the lessons learned from the COVID-19 pandemic and its interconnection between heart failure and SDOH. The pandemic presents a window of opportunity for achieving greater equity in the health care of all vulnerable populations.

Outcomes in patients with aortic stenosis and severely reduced ejection fraction following surgical aortic valve replacement and transcatheter aortic valve replacement.

BACKGROUND: Patients with severe aortic stenosis (AS) and left ventricular (LV) dysfunction demonstrate improvement in left ventricular injection fraction (LVEF) after aortic valve replacement (AVR). The timing and magnitude of recovery in patients with very low LVEF (≤ 25%) in surgical or transcatheter AVR is not well studied. OBJECTIVE: Determine clinical outcomes following transcatheter aortic valve replacement (TAVR) and surgical aortic valve repair (SAVR) in the subset of patients with severely reduced EF ≤ 25%. METHODS: Single-center, retrospective study with primary endpoint of LVEF 1-week following either procedure. Secondary outcomes included 30-day mortality and delayed postprocedural LVEF. T-test was used to compare variables and linear regression was used to adjust differences among baseline variables. RESULTS: 83 patients were enrolled (TAVR = 56 and SAVR = 27). TAVR patients were older at the time of procedure (TAVR 77.29 ± 8.69 vs. SAVR 65.41 ± 10.05, p < 0.001). One week post procedure, all patients had improved LVEF after both procedures (p < 0.001). There was no significant difference in LVEF between either group (TAVR 33.5 ± 11.77 vs. SAVR 35.3 ± 13.57, p = 0.60). Average LVEF continued to rise and increased by 101% at final follow-up (41.26 ± 13.70). 30-day mortality rates in SAVR and TAVR were similar (7.4% vs. 7.1%, p = 0.91). CONCLUSION: Patients with severe AS and LVEF ≤ 25% have a significant recovery in post-procedural EF following AVR regardless of method. LVEF doubled at two years post-procedure. There was no significant difference in 30-day mortality or mean EF recovery between TAVR and SAVR. TRIAL REGISTRATION: Indiana University institutional review board granted approval for above study numbered 15,322.

Sex Differences in Circulating Biomarkers of Heart Failure.

PURPOSE OF REVSIEW: Evidence is scaling up for sex differences in heart failure; however, clinical relevance of sex-specific differential thresholds for biomarkers is not clearly known. Current ambiguity warrants a further look into the sex-specific studies on cardiac biomarkers and may facilitate understanding of phenotypic presentations, clinical manifestations, and pathophysiologic pathway differences in men and women. RECENT FINDINGS: Recent studies have confirmed the fact that females have differential threshold for biomarkers, with lower troponin and higher NT proBNP levels. Ambiguity continues to exist in the clinical relevance of ST-2, Galectin 3, and other biomarkers. Novel biomarkers, proteomic biomarkers, and circulating micro RNAs with machine learning are actively being explored. Biomarkers in HFpEF patients with higher female representation are evolving. In recent clinical trials, sex-related difference in biomarkers is not seen despite therapeutic intervention being more effective in females compared to males. Sex-related difference exists in the expression of biomarkers in health and in various disease states of heart failure. However, this differentiation has not effectively translated into the clinical practice in terms of diagnostic studies or prognostication. Active exploration to bridge the knowledge gap and novel technologies can shed more light in this area.

Development of Automated Risk Stratification for Sporadic Odontogenic Keratocyst Whole Slide Images with an Attention-Based Image Sequence Analyzer.

(1) Background: The categorization of recurrent and non-recurrent odontogenic keratocyst is complex and challenging for both clinicians and pathologists. What sets this cyst apart is its aggressive nature and high likelihood of recurrence. Despite identifying various predictive clinical/radiological/histopathological parameters, clinicians still face difficulties in therapeutic management due to its inherent aggressive nature. This research aims to build a pipeline system that accurately detects recurring and non-recurring OKC. (2) Objective: To automate the risk stratification of OKCs as recurring or non-recurring based on whole slide images (WSIs) using an attention-based image sequence analyzer (ABISA). (3) Materials and methods: The presented architecture combines transformer-based self-attention mechanisms with sequential modeling using LSTM (long short-term memory) to predict the class label. This architecture leverages self-attention to capture spatial dependencies in image patches and LSTM to capture sequential dependencies across patches or frames, making it suitable for this image analysis. These two powerful combinations were integrated and applied on a custom dataset of 48 labeled WSIs (508 tiled images) generated from the highest zoom level WSI. (4) Results: The proposed ABISA algorithm attained 0.98, 1.0, and 0.98 testing accuracy, recall, and area under the curve, respectively, whereas VGG16, VGG19, and Inception V3, standard vision transformer attained testing accuracies of 0.80, 0.73, 0.82, 0.91, respectively. ABISA used 58% fewer trainable parameters than the standard vision transformer. (5) Conclusions: The proposed novel ABISA algorithm was integrated into a risk stratification pipeline to automate the detection of recurring OKC significantly faster, thus allowing the pathologist to define risk stratification faster.

Intensive Cardiac Rehabilitation Outcomes in Patients with Heart Failure.

INTRODUCTION: Cardiac rehabilitation (CR) has proven to be beneficial for patients with heart failure (HF), potentially reducing morbidity and mortality while improving fitness and psychological outcomes. Intensive cardiac rehabilitation (ICR) represents an emerging form of CR that has demonstrated advantages for patients with various cardiovascular diseases. Nevertheless, the specific outcomes of ICR in patients with HF remain unknown. OBJECTIVES: The purpose of this study is to assess the effectiveness of ICR in patients with HF. METHODS: This retrospective study involved 12,950 patients who participated in ICR at 46 centers from January 2016 to December 2020. Patients were categorized into two groups: the HF group, comprising 1400 patients (11%), and the non-HF group, consisting of 11,550 patients (89%). The primary endpoints included the ICR completion rate, changes in body mass index (BMI), exercise minutes per week (EMW), and depression scores (CESD). A t-test was employed to compare variables between the two groups. RESULTS: The HF group comprises older patients, with 37% being females (compared to 44% in the non-HF group). The ICR completion rate was higher in the non-HF group. After ICR completion, adjusted analyses revealed that patients without HF demonstrated a greater improvement in BMI. There were no differences in fitness, as measured via EMW, or in depression scores, as measured via CESD, between the two groups. CONCLUSIONS: Despite the lower baseline functional status and psychosocial scores of HF patients compared to non-HF patients, patients with HF were able to attain similar or even better functional and psychosocial outcomes after ICR.

Building Automation Pipeline for Diagnostic Classification of Sporadic Odontogenic Keratocysts and Non-Keratocysts Using Whole-Slide Images.

The microscopic diagnostic differentiation of odontogenic cysts from other cysts is intricate and may cause perplexity for both clinicians and pathologists. Of particular interest is the odontogenic keratocyst (OKC), a developmental cyst with unique histopathological and clinical characteristics. Nevertheless, what distinguishes this cyst is its aggressive nature and high tendency for recurrence. Clinicians encounter challenges in dealing with this frequently encountered jaw lesion, as there is no consensus on surgical treatment. Therefore, the accurate and early diagnosis of such cysts will benefit clinicians in terms of treatment management and spare subjects from the mental agony of suffering from aggressive OKCs, which impact their quality of life. The objective of this research is to develop an automated OKC diagnostic system that can function as a decision support tool for pathologists, whether they are working locally or remotely. This system will provide them with additional data and insights to enhance their decision-making abilities. This research aims to provide an automation pipeline to classify whole-slide images of OKCs and non-keratocysts (non-KCs: dentigerous and radicular cysts). OKC diagnosis and prognosis using the histopathological analysis of tissues using whole-slide images (WSIs) with a deep-learning approach is an emerging research area. WSIs have the unique advantage of magnifying tissues with high resolution without losing information. The contribution of this research is a novel, deep-learning-based, and efficient algorithm that reduces the trainable parameters and, in turn, the memory footprint. This is achieved using principal component analysis (PCA) and the ReliefF feature selection algorithm (ReliefF) in a convolutional neural network (CNN) named P-C-ReliefF. The proposed model reduces the trainable parameters compared to standard CNN, achieving 97% classification accuracy.

Heart Failure with Reduced Ejection Fraction and COVID-19, when the Sick Get Sicker: Unmasking Racial and Ethnic Inequities During a Pandemic.

Minoritized racial and ethnic groups have the highest incidence, prevalence, and hospitalization rate for heart failure. Despite improvement in medical therapies and overall survival, the morbidity and mortality of these groups remain elevated. The reasons for this disparity are multifactorial, including social determinant of health (SDOH) such as access to care, bias, and structural racism. These same factors contributed to higher rates of COVID-19 infection among minoritized racial and ethnic groups. In this review, we aim to explore the lessons learned from the COVID-19 pandemic and its interconnection between heart failure and SDOH. The pandemic presents a window of opportunity for achieving greater equity in the health care of all vulnerable populations.

No Evidence for Oversizing Hearts and Donor Size Impact on 1-Year Survival in Heart Failure Patients With Left Ventricular Assist Device.

The predicted heart mass (PHM) ratio has recently emerged as a better metric for donor-to-recipient size-matching than weight ratios. It is unknown whether this applies to transplant candidates on left ventricular assist device (LVAD) support. Our study examines if PHM ratio is optimal for size-matching specifically in the LVAD patient population. Patients with LVAD who received a heart transplant from January 1997 to December 2020 in the Scientific Registry of Transplant Recipients database were studied. We compared 5 size-matching metrics, including donor-recipient ratios of weight, height, body mass index, body surface area, and PHM. Single and multivariable Cox proportional hazards models for 1-year mortality were calculated. Our sample consisted of 11,891 patients. In our multivariate analysis, we found that patients in the undersized group with PHM ratios <0.83 had a hazard ratio for 1-year mortality of 1.34 (95% confidence interval 1.08 to 1.65, p = 0.007) suggestive of increased mortality with the use of undersized donors. There was no statistical difference in mortality between the matched (PHM ratio 0.83 to 1.2) and oversized group (PHM ratio ≥1.2). In heart transplant recipients on LVAD support, the PHM ratio provides better risk stratification than other metrics. Use of undersized donor hearts with PHM ratio <0.83 confers higher 1-year mortality. Using oversized donor hearts for transplantation in recipients on LVAD support has no benefit.

Using Sacubitril/Valsartan to Decrease Health care Costs in Population Health Patients.

Value-based care is the foundation of population health. The Health care Economic Efficiency Ratio (HEERO) scoring system is a promising new tool to measure the cost benefits of care in our Accountable Care Organization. HEERO score compares actual costs spent (utilizing insurance claims) and expected costs spent (estimated using the Centers for Medicare/Medicaid Services Risk score). Scores <1 suggest economic benefit. Sacubitril/valsartan has been shown to decrease readmissions for patients with heart failure (HF) and decrease health care costs. We explored the utility of sacubitril/valsartan in reducing HEERO scores and decreasing overall health care expenditure in patients with HF. Patients with HF in the population health cohort were enrolled. HEERO score was calculated for patients taking sacubitril/valsartan and other HF medications at 3-month intervals up to a year. We compared the average and total health care expenditure and inpatient days for patients on sacubitril/valsartan, spironolactone, ß blocker (BB) along with spironolactone, BB and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. For patients on sacubitril/valsartan, HEERO scores and inpatient days decreased (decreased health care expenditure) as the number of days of utilization increased (p <0.0001). In total, 270+ days of sacubitril/valsartan decreased health care costs by 22%. This cost reduction was mainly attributed to decreased inpatient days. Additionally, the combination of sacubitril/valsartan, spironolactone, and BB showed decreased HEERO score and inpatient days compared with spironolactone, BB and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker in male patients. Sacubitril/valsartan use beyond 270 days resulted in decreased health care expenditure in a population health cohort compared with other HF medications. This economic benefit is achieved through the reduction in hospitalizations. Sacubitril/valsartan is an integral part of value-based care providing high-value, cost-effective care, and bolstering the economic wellbeing of patient care. Payor sources should consider this in subsidizing the cost of the medicine.

Inverse correlation of CD3 & vascular endothelial growth factor in incisional oral squamous cell carcinoma biopsies predicts nodal metastasis & poor survival of patients.

Background & objectives: Oral squamous cell carcinoma (OSCC) is widely prevalent in the Indian subcontinent mainly due to habit-associated aetiologies. Immune regulation and angiogenesis are the part of tumourigenesis that play a crucial role in metastasis and survival. However, the concurrent expression of vascular endothelial growth factor (VEGF) and CD3 (immune regulator receptor on T-lymphocyte) in the same OSCC tissue samples has not been reported in the Indian population. The present study evaluated the expression of CD3+ T-cells and VEGF in OSCC tissue samples and studied the clinicopathological correlation and survival analysis in an Indian population. Methods: This was a retrospective study conducted on 30 formalin-fixed and paraffin embedded sections which were histologically diagnosed as OSCC cases comprising of 15 metastatic OSCC and 15 non-metastatic OSCC with available clinical data and survival status. Results: Reduced expression of CD3+ T-cells and increased VEGF expression were observed in metastatic OSCC samples. The correlation of expression of CD3+ T-cells and VEGF with clinicopathological parameters showed a significant association between these markers with age, nodal status, site of the lesion and survival. Interpretation & conclusions: Reduced expression of CD3+ T-cells in OSCC was found to be associated with a significantly poor survival. VEGF was found to be over expressed in metastatic OSCC as compared to that in non-metastatic OSCC. The study findings suggest that the evaluation of CD3 and VEGF in incisional OSCC biopsies can be considered for predicting the survival outcome and metastasis.

PCSK9 Inhibition in Patients After Heart Transplantation: a Retrospective Review and Literature Analysis.

PURPOSE OF REVIEW: Following cardiac transplantation, patients have an increased risk of developing cardiac allograft vasculopathy and atherosclerotic cardiovascular disease. Therefore, aggressive lipid management is indicated. Some patients do not achieve optimal lipid profiles with statin monotherapy, however, or discontinue statins due to intolerance. In this review, we investigated the use of PCSK9 inhibitors as an alternative treatment for hyperlipidemia following cardiac transplantation. RECENT FINDINGS: Nine published articles were identified that included 110 patients treated with alirocumab or evolocumab after cardiac transplantation. PCSK9 inhibitors were tolerated by all patients, and each study demonstrated an effective reduction of low-density lipoprotein ranging from 40 to 87% decrease from baseline. In our study, the 110 patients from literature review were added to a cohort of 7 similar patients from our institution for combined analysis. This report supports that PCSK9 inhibitors should be considered following cardiac transplantation when conventional medial therapy is not tolerated or ineffective.

Aortic Thrombosis in Patients on Mechanical Circulatory Support: A Systematic Literature Review.

BACKGROUND: Aortic valve (AV) thrombosis is an uncommon but ominous complication in patients managed with mechanical circulatory support (MCS) devices. In this systematic review, we summarised the data on clinical presentations and outcomes in such patients. METHODS: We searched articles on PubMed and Google Scholar, reporting at least one adult patient with aortic thrombosis on MCS support and where the individual patient data could be extracted. We grouped the patients by the type of MCS (temporary or durable), and the type of the AV (prosthetic, surgically modified, or native) RESULTS: We identified reports on six patients with aortic thrombus on short-term MCS, and on 41 patients on durable left ventricular assist devices (LVADs). On temporary MCS, AV thrombus typically causes no symptoms and is found incidentally pre- or intra-operatively. For those with durable MCS, the occurrence of aortic thrombus forming on prosthetic or surgically modified valves appears to be more related to the intervention on the valve, rather than from the presence of LVAD. The mortality in this group was 18%. In patients with native AV on durable LVAD support, 60% of patients presented with acute myocardial infarction, acute stroke, or acute heart failure, and mortality in this cohort was 45%. In terms of management, heart transplantation was most successful. CONCLUSIONS: While the outcomes of aortic thrombosis were good in patients where temporary MCS was used in the setting of aortic valve surgery, patients with native AV who develop this complication on durable LVAD have high morbidity and mortality. Cardiac transplantation should be strongly considered in eligible candidates because other therapies provide inconsistent results.

Expansion microscopy: A revolution in diagnostic pathology.

Expansion microscopy (ExM) is a recent discovery in diagnostic pathology and microbiology that promotes a physical magnification of the tissue specimen instead of optical magnification. It not only improves the resolution of the specimen but also enhances the diagnostic precision, and permits nanoscale imaging of the specimen. Optical microscopy is routinely used in histopathology and microbiology for ages. Due to its simplicity, compatibility with different types of specimens, and ease of operation it is accepted by pathologists. ExM and its variants have been widely tested in different types of tissue specimens and microbiological specimens and yielded brilliant results.

Aortic root thrombosis leading to STEMI in a Heartmate 3 patient.

Despite left ventricular assist device (LVAD) therapy becoming established for end-stage heart failure (HF), complications remain. Thromboembolic complications are rare with the newest iteration of LVADs. We managed a case of a continuous-flow LVAD-related thromboembolic event that presented as an acute myocardial infarction. A 64-year-old male who underwent Heartmate III® LVAD implantation had crushing substernal chest pain and ventricular tachycardia with acute anterolateral myocardial infarction on electrocardiogram on post-operative day 9. Echocardiography showed closed aortic valve and mild aortic regurgitation, but CT angiography showed thrombus within the left coronary cusp despite full anticoagulation. Continuous suction of blood from the left ventricle despite pulsatile flow into the ascending aorta resulted in a minimally opening aortic valve and stagnation of blood leading to thrombosis on the coronary cusp. Apart from post-operative ventricular tachycardia and right ventricular failure, he had adequate body size (body surface area 2.13 m2) and no post-operative or coagulopathy which could predispose him to thrombosis. Coronary angiography revealed stable severe three-vessel disease and thrombus in left main and proximal circumflex artery, and he had aspiration thrombectomy, and international normalized ratio target was increased to 3-3.5 with aspirin 325 mg daily. He survived to discharge but died 60 days after LVAD implant with multiple low flow alarms, and cardiac arrest. We review the literature and propose a management algorithm for patients with impaired AV opening and aortic root thrombosis.

Donor substance abuse and heart transplantation outcomes.

Heart failure continues to account for millions of cases and deaths worldwide. Heart transplant is the gold standard for treatment of advanced heart failure. Unfortunately, the supply of donor hearts continues to be limited with the increase in demand for heart transplantation. In this review, we aim to explore the safety and efficacy of using hearts from donors with history of substance use. Despite the theoretical effect of cocaine and alcohol on the cardiovascular system, several studies demonstrate no difference in outcomes (overall survival, graft rejection, graft vasculopathy) when using hearts from patients with history of cocaine and alcohol use. The opioid epidemic has expanded the potential donor pool where the current studies have not shown any adverse outcomes when considering donors with history of opioid use. The currently available evidence would support the use of donor hearts from patients with history of alcohol, cocaine, opioids, and marijuana use. Further studies are needed to evaluate the safety of using donor hearts from patients with history of nicotine use.

Don't Break My Heart: A Case Report of Takotsubo Syndrome in a Transplanted Heart.

Cardiogenic shock after heart transplant, could be due to acute rejection, cardiac allograft vasculopathy, or myocarditis. Stress cardiomyopathy (CM) in a denervated transplanted heart is unusual. A 56-year-old man with a history of ischemic heart disease and a seizure disorder underwent orthotropic heart transplant. He had breakthrough seizures posttransplant while on levetiracetam (Keppra) and was admitted for status epilepticus. A transthoracic echocardiogram (TTE) was done for hypotension (BP 90/60). TTE showed a severely reduced left ventricular ejection fraction (LVEF) of 15%, hyperkinetic base, and apical ballooning that are consistent with stress CM. Electrocardiogram with T wave inversion in precordial leads. Troponin was elevated to 1.77. The patient had cardiogenic shock and needed an intra-aortic balloon pump and multiple pressors. He was treated for status epilepticus and the LVEF completely recovered in 1 week. The patient had a normal TTE, coronary angiography, and biopsy with no rejection 8 days before admission. Stress CM was the diagnosis of exclusion, confirmed with a complete recovery of the LVEF. There are only 5 case reports of stress CM after heart transplant, with most presenting 9 to 10 years afterwards. We describe an unusual case of cardiogenic shock from stress CM triggered by status epilepticus in a denervated heart only 1 year posttransplant. The mechanism is elusive, and some hypotheses suggest exaggerated sensitivity to a plasma catecholamine surge from parasympathetic denervation. In a denervated heart, autonomic re-innervation can be seen as early as 1 year posttransplant.

Special Considerations in the Care of Women With Advanced Heart Failure.

Advanced heart failure (AHF) is associated with increased morbidity and mortality, and greater healthcare utilization. Recognition requires a thorough clinical assessment and appropriate risk stratification. There are persisting inequities in the allocation of AHF therapies. Women are less likely to be referred for evaluation of candidacy for heart transplantation or left ventricular assist device despite facing a higher risk of AHF-related mortality. Sex-specific risk factors influence progression to advanced disease and should be considered when evaluating women for advanced therapies. The purpose of this review is to discuss the role of sex hormones on the pathophysiology of AHF, describe the clinical presentation, diagnostic evaluation and definitive therapies of AHF in women with special attention to pregnancy, lactation, contraception and menopause. Future studies are needed to address areas of equipoise in the care of women with AHF.

Ensemble Deep-Learning-Based Prognostic and Prediction for Recurrence of Sporadic Odontogenic Keratocysts on Hematoxylin and Eosin Stained Pathological Images of Incisional Biopsies.

(1) Background: Odontogenic keratocysts (OKCs) are enigmatic developmental cysts that deserve special attention due to their heterogeneous appearance in histopathological characteristics and high recurrence rate. Despite several nomenclatures for classification, clinicians still confront challenges in its diagnosis and predicting its recurrence. This paper proposes an ensemble deep-learning-based prognostic and prediction algorithm, for the recurrence of sporadic odontogenic keratocysts, on hematoxylin and eosin stained pathological images of incisional biopsies before treatment. (2) Materials and Methods: In this study, we applied a deep-learning algorithm to an ensemble approach integrated with DenseNet-121, Inception-V3, and Inception-Resnet-V3 classifiers. Around 1660 hematoxylin and eosin stained pathologically annotated digital images of OKC-diagnosed (60) patients were supplied to train and predict recurrent OKCs. (3) Results: The presence of SEH (p = 0.004), an incomplete epithelial lining, (p = 0.023), and a corrugated surface (p = 0.049) were the most significant histological parameters distinguishing recurrent and non-recurrent OKCs. Amongst the classifiers, DenseNet-121 showed 93% accuracy in predicting recurrent OKCs. Furthermore, integrating and training the traditional ensemble model showed an accuracy of 95% and an AUC of 0.9872, with an execution time of 192.9 s. In comparison, our proposed model showed 97% accuracy with an execution time of 154.6 s. (4) Conclusions: Considering the outcome of our novel ensemble model, based on accuracy and execution time, the presented design could be embedded into a computer-aided design system for automation of risk stratification of odontogenic keratocysts.