United States

BACKGROUND: Coronary microvascular dysfunction (CMD) and left atrial (LA) strain abnormality are more common in patients with Heart Failure with Preserved Ejection Fraction (HFpEF), but the relationship between CMD and LA strain is not well characterized. HFpEF is a major health burden in the United States, representing the number one cause of hospitalization for Americans over 65
years old. (1) Understanding how coronary microvascular dysfunction impacts HFpEF is important because CMD may be an important prognostic sign of deteriorating heart function, particularly in the HFpEF subset of heart failure. Despite CMD’s prognostic potential, it is currently difficult to measure; only invasive techniques can measure CMD.

OBJECTIVE: We undertook a study to see if non-invasive measurements of LA strain could be correlated with invasive measurements of CMD. We additionally looked at differences between HFpEF and control patients to see if LASr and CMD correlations were generalizable across disease states.

METHODS: We performed a retrospective, observational study of 90 patients at the University of Chicago Medical Center who had an indication for coronary angiography with coronary physiology testing from 2010-2021. CMD was defined as having an invasively-determined coronary flow reserve (CFR) ≤ 2.0. Non-invasive echocardiographic auto-strain analysis was used to obtain LA reservoir strain (LASr), LA conduit strain, and LA contractile strain. Univariable and multivariable logistic
regression was performed for HFpEF patients with various degrees of CMD.

RESULTS: For both HFpEF and control patients, lower LASr was more commonly found in patients with abnormal CFR (HFpEF: 22.5% ± 12.1 vs. 30.7% ± 10.7, P = 0.018; control: 26.0% ± 16.4 vs. 31.0% ± 9.8 , P = 0.185). Both a univariable and multivariable logistic regression of HFpEF patients found LASr to be a significant predictor of abnormal CFR (OR: 0.94, P =0.041).

CONCLUSIONS: There were substantially more patients with CFR ≤ 2.0 in the HFpEF group (50%) compared to control (28%). In HFpEF patients, non-invasively measured LASr showed significant correlation with invasively measured CFR, thus emerging as a potential predictive variable for CFR ≤ 2.0 in patients with this form of heart failure.

AMA Research Challenge 2022

Left Atrial Strain Echocardiography May Be Correlated with Coronary Microvascular Dysfunction

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Background: Accumulating evidence suggests hospitalized patients with heart failure (HF) are especially susceptible to COVID-19-related complications and mortality approaches 30%. We hypothesized that Boosted Tree (BT) mortality risk variance explained (VE%) by cardiac injury and putative COVID-19 thrombo-inflammatory biomarkers would be different between survivors and non-survivors in HF patients undergoing index hospitalization for SARS-CoV-2.

Methods: Presentation demographics, anthropometrics, laboratory results (within 8h), and ICD-10 codes were collected. Discrete data summarized as proportions were compared with chi-squared test. Continuous data summarized with median [IQR] were compared using Kruskal-Wallis test. COVID-19 therapy across 6-pandemic surges, demographics, and comorbidities were statistically balanced. Univariate logistic regression tested association (p<.05) of COVID-19 clinical traits putatively linked with mortality risk and provided a receiver operating characteristic (ROC) curve while computing Youden’s cut point. BT algorithm optimized area under ROC curve (AUROC) representing prediction accuracy while providing VE% contributed by each cut point variable.

Results: Among 5,841 consecutive patients discharged from index COVID-19 hospitalization between March 18, 2020, and April 30, 2022, 1039 harbored extant HF. Those with at least 1 high sensitivity troponin (hs-cTnI) assay, 483, were studied. Hospital mortality (n=62, 13%) and survival (n=421, 87%) patient demographics were statically similar with 63% males and 37% females aged 75[64-83] years distributed across Whites (82%), Blacks (11%), and other races (7%). Subsequent results are similarly sequenced. Most prevalent comorbidities were hypertension (81% vs. 92%, p=.007), diabetes (48% vs. 42%, p=.41), obesity (50% vs. 34%, p<.02), renal failure (34% vs. 38%, p=.58), iron deficiency anemia (35% vs. 35%, p=1.0), and chronic coagulation disorder (39% vs 17%, p=.0002). Biomarker cut points were hs-cTnI ≥26 ng/L (71% vs. 53%, p=.006), CRP ≥6.0 mg/dL (63% vs. 22%, p<.0001), d-dimer ≥2.98 ug/mL (45% vs. 26%, p=.015), LDH ≥444 U/L (61% vs. 20%, p<.0001), and ferritin ≥668 ng/mL (68% vs. 26%, p<.0001). BT model demonstrated 38% R2, AUROC=0.86 with VE% contributed by hs-cTnI (41%), CRP (27%), d-dimer (14%), LDH (10%), and ferritin (8%). 

Conclusion: Our training model demonstrates a machine learning strategy to integrate hs-cTnI with putative biomarkers of COVID-19 severity to enhance understanding of host response contributing to mortality risk at presentation in hospitalized HF patients.

Mortality Risk Variance Explained by High Sensitivity Troponin I Exceeds Putative COVID-19 Severity Biomarkers in Heart Failure Patients Hospitalized with Acute SARS-CoV-2 Infection

Cardiac catheter ablation is a useful tool in the treatment of Atrial Fibrillation (AFib). A subset of patients with AFib may also present with low Ejection Fraction (EF). This study seeks to quantify and analyze the impact of ablation on the EF of AFib patients who presented with a pre-operative EF below 50%. Patient data was retrieved from a private practice group, Florida Cardiology. Patients who underwent an ablation from Jan 2019 through Nov 2021, had a pre-operative EF less than 50%, and had a post-operative EF on record were included in this study. Diagnoses of Heart Failure as well as status of AFib recurrence at follow-up were also noted. Following data collection and statistical analysis, cardiac catheter ablation was found to lead to a statistically significant improvement in the EF of AFib patients that presented with low pre-operative EF < 50%. The average change was +13.15% (Std Dev of 10.11%). Ablation also led to resolution of AFib symptoms in 88.24% of patients. Ablation remains an effective and successful treatment modality for the management of Atrial Fibrillation in patients with a decreased EF (< 50%).

Not Too Late To Ablate: Effect of Cardiac Catheter Ablation on Ejection Fraction in Patients with Atrial Fibrillation and Pre-Op Ejection Fraction under 50%

Hypertension is one of the most prevalent chronic diseases in the United States, affecting approximately 1 in every 2 adults. Barriers to control blood pressures in the outpatient setting from a patient’s perspective include lack of understanding of disease, fear of medication adverse effects or dependence, medication affordability, healthy food choices and time required to follow up with medical providers. In HTN, there has been limited work investigating the role of how blood pressure (BP) monitors affect patients taking an active role in disease monitoring, management and risk modification. In this project, we hypothesize that patients will actively use provided BP monitors and will feel more empowered for controlling their hypertension. This in turn will improve medication adherence and positively reinforce patients to make lifestyle modifications. This study was conducted in the Internal Medicine Clinic at Prisma Health, Greenville, SC. 34 patients with a diagnosis of uncontrolled hypertension were enrolled. Patients were provided brachial cuff BP monitors and followed for 4 months while receiving medical therapy. We systemically contacted patients via phone interviews to determine their adherence (using adherence estimator survey), patients’ perspective on the BP monitors and how to use them. These phone interviews were coded independently by two members of the research team and cross-checked for confirmation, reconciling differences by discussion. Codes were grouped according to overarching themes and subthemes. For mixed analysis, the qualitative and quantitative data was merged after it had been independently analyzed to provide a mixed methods data analysis. Our results suggest that when BP monitors are provided to patients, and patients are educated on proper use of them, they are effective tools to help patients take an active role in managing their disease. Of the 34 patients, 23 patients responded to phone interviews. Assessment of the patients’ blood pressure (BP) was done in the clinic at the beginning of the study and then again at the conclusion of the study. Using a paired t-test, Systolic and diastolic blood pressure showed significant difference between the two time points dropping from a mean of 147.2/864 ± 23.3/16.4 mmHg to 133.7/78.7 ± 15.9/11.2 mmHg (± STD, p<0.005). Of the 23 patients, seventeen (77%) patients had high adherence, three (13%) patients had medium and two (9%) had low adherence according to the adherence estimator used. The low adherence was due to lack of conviction of the importance of blood pressure medication to their health. When questioned further about their opinions on home BP monitors, 3 themes arose from talking to patients: helpful, not-helpful, and somewhat-helpful. The subthemes identified within “helpful” category were Reinforcement, Lifestyle modification, and medical care. These themes were reflected in how often participants used their BP monitors. 16 (70%) patients demonstrated regular usage of BP monitors, while 4 (17%) patients demonstrated no usage whatsoever, and 3 (13%) patients demonstrated intermittent usage which matches the thematic analysis that was apparent in their responses of helpful, not-helpful, and somewhat-helpful, respectively (p<0.005). This study explores a unique perspective of hypertension management in the outpatient setting by providing patients with a tangible way to monitor their blood pressures that in turn augmented adherence. By empowering patients to understand the effects of lifestyle modifications and medications on their blood pressures on a regular basis via providing a BP monitor, there was improvement in the BP control. Although a small sample size, this study substantiates the important role the BP monitors can play in empowering patients for their HTN management. By positively impacting patients’ engagement in disease monitoring and risk modification, BP monitor provision has the potential to improve HTN control.

Provision of Blood Pressure Monitors to Improve Hypertension Control and Enhance Patient Self-Management and Empowerment 

Introduction: Coronary artery calcium (CAC) scoring has become an essential tool to help stratify patients at risk for adverse cardiac events. CAC scores vary significantly depending on age, gender, and race. Here, we evaluated racial variations in calcium scores among patients who presented with chest pain to the emergency department at our institution. 

Methods: Demographic and CAC data were obtained in patients who presented to the ED with chest pain between 2014 and 2017. Data was analyzed based upon reported race (white ‘W’ and African-American ‘AA’). The study group included 174 AA patients (59% female) and 512 W patients (48% female). Other racial categories were excluded. These patients were age (+/- 2 years) and gender matched, and mean CAC scores with standard deviations were calculated. Student’s t-test was used to compare the age-gender matched groups. 

Results: The mean CAC score (and standard deviation) for AA males was 33.6 (76.7) Agatston units (AU), while for W males, mean CAC score was 213.6 (549.3) AU. For AA females, mean CAC score was 40.7 (156.0) AU, while for W females, mean CAC score was 101.2 (280.8) AU. The mean AA CAC was 37.8, while the mean W age-gender matched CAC score was 146.8. These results were statistically significant with a p-value of 0.001. Additionally, 68.0% of AA patient had a CAC value of 0, whereas 51.4% of age-gender matched W patients had a CAC value of 0. 

Conclusion: Among patients presenting to the emergency department with chest pain, AA patients were more likely to have a lower CAC score compared to their white counterparts. However, based on larger data sets, AA patients are known to have a greater incidence of coronary artery disease (CAD) and a higher risk of early death from CAD. Our data suggests a necessity to avoid overreliance on CAC score for risk stratification of AA patients. Further larger group-based studies are needed to enhance evaluation of CAD in the AA patient population to improve preventative cardiovascular management. 


Racial Variations in Coronary Artery Calcium Scores among Patients Presenting to the Emergency Department with Chest Pain

Background:
Surgical Aortic Valve Replacement (SAVR) is the current treatment of choice for good surgical candidates with moderate to severe symptomatic. As TAVR showed an improved 1and 2-year all-cause mortality, it has been opted for moderately symptomatic severe AS patients. The purpose of this review was to do a clinical comparison of TAVR vs SAVR and to analyze the Health Index Factor that makes TAVR a treatment of choice in asymptomatic AS patients. 

Methods:
An extensive literature review of PubMed, Cochrane, and Embase databases was performed using the key words “Aortic stenosis”, “SAVR”, “TAVR”, and “Asymptomatic”. A total of 45 prospective randomized clinical trials in English language that were published from year 2000 onwards were included in the final analysis. 

Results:
Strang G et al found that 59.3% of the asymptomatic AS patients are likely to die in the next 5 years without proactive treatment. Multiple studies have proven that early intervention with aortic valve replacement is superior to conservative treatment in severe asymptomatic AS, however, the choice between SAVR and TAVR is not well established. NOTION Trial, SURTAVI Trail, and PARTNER 3 study showed non-inferiority of TAVR over SAVR, within a 1-year follow-up for low surgical risk patients. Evolut Low-risk study is the only prospective study performed to date that enrolled patients with asymptomatic severe AS. The Trial demonstrated that there was no difference in all-cause mortality at 30 days (1.3% vs 4.8%. p=0.23), and 12 days (1.3% vs 6.5%, p=0.11). Additionally, TAVR also decreases the risk of post-procedural atrial fibrillation,acute kidney injury rehospitalization and has shown significant improvement in mean trans-aortic pressure gradient. TAVR also showed marked improvement in 30 day Quality of Life (QOL) index, where SAVR didn’t report any significant change in the QOL index.

Conclusion:
TAVR has consistently shown a statistically non-significant difference in case mortality, risk of stroke, and rehospitalization in patients with high and moderate surgical risk, whereby recent initial trials have shown significant improvement in the QOL index and hemodynamic index for patients with asymptomatic disease. More extensive studies are required to prove the feasibility and long term outcomes of the TAVR in asymptomatic patients.





Role of Trans-Catheter Aortic Valve Replacement in Asymptomatic Aortic Stenosis- Feasibility Analysis

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT-2Is) have proven their efficacy in managing patients with heart failure (HF), yet within this broad family identifying an effective single agent is still controversial. Therefore, we conducted a network meta-analysis to investigate which SGLT-2Is is more effective in patients with HF.

Methods: PubMed, Web of Science, Scopus, and Embase, were systematically searched from inception to February 2022. We included randomized controlled trials (RCTs) that investigated the usage of SGLT-2Is versus placebo in heart failure patients. Main outcomes were all-cause, cardiovascular mortality, serious adverse events, and hospitalization due to HF. The random-effects method model and inverse variance statistics were used to calculate the odds ratio (OR) with a 95% confidence interval (CI).

Results: Our study included 12 RCTs with a total number of 69,024 patients (37,923 in the SGLT2 inhibitors group and 31,101 in the placebo group). Five RCTs used Empagliflozin, four used Dapagliflozin, and one used Canagliflozin, Ertugliflozin, and Sotagliflozin, respectively. Our analysis showed that Empagliflozin has a statistically significant lowest odds for both cardiovascular mortality and serious adverse effects (OR: 0.80 with 95% CI [0.67-0.96]) and (OR: 0.84 with 95% CI [0.76-0.93]), respectively compared to other SGLT-2Is. All SGLT-2Is have been associated with the same lower odds without preferences for one over the others in regard to all-cause mortality. Furthermore, the rate of hospitalization due to HF showed a statistically significant decrease with all of our SGLT-2Is except for canagliflozin, which showed insignificant results with (OR: 0.63 with 95% CI [0.39-1.01]).

Conclusion: Empagliflozin had the lowest odds of cardiovascular mortality and serious adverse effects. Canagliflozin was the only SGLT-2Is that was non-superior to placebo for risk of hospitalization for HF. Meanwhile, no differences between the included SGLT-2Is were observed in terms of all-cause mortality.




Sodium-glucose transporter 2 inhibitors in patients with heart failure: a network meta-analysis

Background
Aortic stenosis (AS) etiologies include degenerative calcific change, bicuspid aortic valve, and systolic dysfunction. Left ventricular systolic dysfunction decreases blood flow across the aortic valve. There are limited data on low-flow aortic stenosis (stroke volume index (SVI) < 35 mL/m2) following aortic valve replacement (AVR) in patients with systolic dysfunction (LVEF < 50%). We hypothesized that patients with low-flow aortic stenosis and systolic dysfunction perform poorly after AVR compared to those patients with normal flow (SVI ≥ 35 mL/m2) and systolic dysfunction.

Methods
We reviewed AVR cases at a high-volume structural heart center in western New York from 2012 to 2017. Of the 120 patients, 70 patients had low flow aortic stenosis. Stroke volume index was calculated at the level of the left ventricular outflow tract from the transthoracic echocardiographic examination prior to AVR. We performed Receiver operator characteristics and Cox regression analyses to examine the accuracy of the SVI model in predicting the postoperative outcome of the patients undergoing AVR procedure with existing left ventricular dysfunction.

Results
Both five-year survival and overall mortality following AVR were decreased in patients with low flow aortic stenosis. 63% of patients with low-flow aortic stenosis compared to 30% with normal flow aortic stenosis were deceased five years post-AVR. ROC curve indicated SVI to be a clinical predictor of both 5 year (AUC .732, 95% CI: 0.641 - 0.823, p < 0.001) and overall mortality (AUC .728, 95% CI: 0.633 - 0.823, p < 0.001). A comparison of survivors and non-survivors showed that diabetes with an odds ratio of 3.18 [1.45-6.99]; (p = 0.005) and low-flow stroke volume with an odds ratio of 4.44 (2.05-9.66); (p < 0.001) were significant clinical risk factors for patient mortality. 

Conclusion
Patients with low flow aortic stenosis and systolic dysfunction had decreased 5-year survival rates and increased overall mortality post-AVR. This highlights the importance of monitoring blood flow across the aortic valve prior to AVR. Diabetes and low flow stroke volume were notable risk factors for patient mortality. Additional studies are in progress to assess other clinical predictors like energy loss index for patient mortality following AVR.

Stroke Volume Index Predicts Mortality Following Aortic Valve Replacement

Background
Hidradenitis suppurativa (HS) is a chronic, inflammatory skin condition of the follicular epithelium that impacts 1-4% of the population. HS presents clinically as recurrently inflamed nodules and sinus tracts, located in intertriginous areas of the body. The nodules can become infected and inflamed, leading to abscesses, pain, and scarring; all of which can have debilitating consequences on a patient’s quality of life. This study aims to improve HS outcomes by analyzing which pathogens are most frequently cultured based on lesion location and pathogen sensitivity profiles. These findings will allow physicians to tailor empiric antibiotic treatment based on HS lesion location. 

Methods
A retrospective medical chart review of patients who were seen at The University of Texas Medical Branch with a diagnosis of HS from 2006-2021 was conducted. 485 patients were seen over 600 patient visits from 2006-2021.

Results
Of the 485 patients seen with documented HS lesions, 75% were female and cultures were performed 47% of the time. Staphylococcus aureus was the most commonly cultured bacteria in general, and, was the most frequently cultured bacteria in the axilla, buttocks, and groin. Proteus mirabilis was the second most commonly cultured bacteria. P. mirabilis and Enterococcus spp. were the most common bacteria cultured in the inframammary region.

Sensitivity analysis of Staphylococcus aureus showed sensitivity to clindamycin in 70% of the cultures, rifampin in 93%, tetracycline in 89%, and trimethoprim-sulfamethoxazole (TMP/SMX) in 93%. A majority of Staphylococcus aureus was found to be resistant to erythromycin (59%) and oxacillin (55%). For P. mirabilis, ampicillin and levofloxacin were both found to be 100% sensitive. Lastly, Enterococcus spp. were found to be sensitive to ampicillin in 95% of the cultures.

Conclusion
The authors recommend TMP/SMX or tetracyclines as empiric therapy for axillary, buttocks and groin lesions. For only inframammary lesions, use of ampicillin should be strongly considered. For patients with multiple sites including the inframammary area, TMP/SMX should be used to ensure Gram (+) and Gram (–) coverage. Tetracyclines may be used as first line empiric therapy for multiple sites without inframammary involvement. 


An Updated Reference for Empiric Antibiotic Therapy in Hidradenitis Suppurativa

Background: Post-transplant lymphoproliferative disorder (PTLD) is a rare but deadly complication seen in patients after solid organ transplants as well as hematopoietic stem cell transplants. Current research suggests the underlying etiology of disease progression is likely secondary to a viral reactivation in the setting of immunosuppression such as the Epstein-Barr Virus (EBV). Cutaneous findings are rare but can range from ulcerated plaques to focal alopecia, with mycosis fungoides being the most frequent manifestation of the cutaneous T-cell lymphoma category. The objective of this study was to investigate the epidemiology and various clinical features of cutaneous manifestations of PTLD. 
Methods: A systematic review of published literature regarding cutaneous post-transplant lymphoproliferative disorders was conducted with inclusion of papers that reported individual patient characteristics and clinical courses. The prevalence of cutaneous PTLD for each specific transplantation was adjusted using the respective total transplantation rates conducted in the United States of America. 
Results: 82 cutaneous PTLD patients had a mean (SD) age at diagnosis of 50.9 (20.8) years, onset from transplant to disease presentation of 7.5 (5.8) years, and males comprised 74.4% of reported patients. When adjusted for total number of transplantation types, cutaneous manifestations of PTLD were most prevalent in renal transplants (77.9%) followed by HSCT (9.1%), liver (6.6%), and cardiac (5.1%). The most common areas of skin lesions were the lower extremities (33.8%), the trunk (18.8%), and the head and neck (11.3%). 
Conclusion: Renal transplant patients comprised the highest proportion of transplantations that developed cutaneous PTLD, which was surprising given cardiac transplant patients usually undergo more intense immunosuppressive regimens. Males appear to be predominantly affected, and the onset of cutaneous PTLD can range widely from shortly after transplantation to several years afterwards, emphasizing the important role clinicians have in being diligent within this patient population. Careful examination of cutaneous findings in these high-risk patients is especially important for timely diagnosis and therapeutic interventions, and further studies are needed to characterize the specific risk factors in cutaneous PTLD patients.

Clinical Characteristics of Post-Transplant Lymphoproliferative Disorder Involving the Skin

Venous leg ulcers, the most common leg ulcer, occur in patients with chronic venous
insufficiency due to venous hypertension. Evidence supports the conservative treatment with lower extremity compression, ideally within the range of 30-40 mm Hg. Pressures in this range provide enough force to partially collapse lower extremity veins without restricting arterial flow in patients in patients without peripheral arterial disease. There are many options for applying such compression, and those who apply these devices have varying levels of training and backgrounds. In this quality improvement study, a single observer utilized a reusable pressure monitor to compare pressures applied using different devices by individuals in wound clinics with diverse training from specialties of dermatology, podiatry, and general surgery. Average compression was higher in the dermatology wound clinic compared to the general surgery clinic (p=.004), and wraps applied by clinic staff were nearly twice as likely as a self-applied wrap to have pressures greater than 40 mm Hg (p = .03). Pressures were also dependent upon the specific compression device used (p=.008). These results indicate that the device-provided pressure may be dependent on both the compression device and on the background and training of the applicator. We propose that standardization in the training of compression application and increased use of a point of care pressure monitor may improve the consistency of applied compression, thus improving adherence to treatment and outcomes in patients with chronic venous insufficiency.

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Mortality Risk Variance Explained by High Sensitivity Troponin I Exceeds Putative COVID-19 Severity Biomarkers in Heart Failure Patients Hospitalized with Acute SARS-CoV-2 Infection

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