Updates in the management of cancer therapy-related hypertension.

PURPOSE OF REVIEW: To provide a comprehensive review of hypertension among patients with cancer. Several cancer therapies cause hypertension which has resulted in a growing and vulnerable population of patients with difficult to control hypertension which has significant downstream effects. RECENT FINDINGS: Hypertension affects up to 50% of cancer patients and higher comorbidity when compared to the general population. Many anticancer therapies can cause hypertension through their treatment effect. Antihypertensive treatment is crucial given cardiovascular mortality is a leading cause of death among cancer patients. It is already known that hypertension is poorly controlled in the general population, and there are additional challenges in management among patients with cancer. Patients with cancer suffer from multimorbidity, are on multiple medications creating concern for drug interactions, and often have blood pressure lability, which can worsen clinical inertia among patients and their providers. It is crucial to effectively treat hypertension in cancer patients to mitigate downstream adverse cardiovascular events. SUMMARY: In recent years, there have been significant changes in management guidelines of hypertension and simultaneously as influx of new cancer therapeutics. We provide an update on hypertension treatment among patients with cancer on different chemotherapeutic agents.

Multimodality cardiovascular imaging in hypertension.

PURPOSE OF THE REVIEW: Hypertension accounts for the largest proportion of cardiovascular (CV) mortality worldwide and its prevalence continues to rise. While prominent CV societies have offered strong recommendations on the management of hypertension in adults, the role of noninvasive CV imaging in the evaluation of hypertensive patients remains incompletely defined. RECENT FINDINGS: Noninvasive imaging is a rapidly expanding field with a growing number of sophisticated and readily applicable modalities to assess how cardiac structure and function changes after periods of sustained, elevated blood pressure. Echocardiography remains the initial modality to screen these patients while developments in nuclear, computed tomography and cardiac magnetic resonance complement and expand investigations for alternative diagnoses that may complement or conflict with the diagnosis of left ventricular hypertrophy. SUMMARY: In this review article, we summarize the application of echocardiography, nuclear imaging, cardiac computed tomography, and cardiac magnetic resonance imaging in the evaluation and management of hypertensive heart disease.

Clinical considerations and pathophysiological associations among obesity, weight loss, heart failure, and hypertension.

PURPOSE OF REVIEW: To describe the relationship between three pandemics: hypertension, obesity, and heart failure. From pathophysiology to treatment, understanding how these disease entities are linked can lead to breakthroughs in their prevention and treatment. The relevance of this review lies in its discussion of novel pharmacological and surgical treatment strategies for obesity and hypertension, and their role in the prevention and treatment of heart failure. RECENT FINDINGS: Novel medications such as GLP-1 agonists have demonstrated sustained weight loss in patients with obesity, and concurrent improvements in their cardiometabolic profile, and possibly also reductions in hypertension-related comorbidities including heart failure. Surgical therapies including laparoscopic bariatric surgery represent an important treatment strategy in obese patients, and recent studies describe their use even in patients with advanced heart failure, including those with ventricular assist devices. SUMMARY: These developments have deep implications on our efforts to understand, mitigate, and ultimately prevent the three pandemics, and offer promising improvements to quality of life, survival, and the cost burden of these diseases.

Pre-existing Systolic Dysfunction is the Most Powerful Predictor of Failed Arteriovenous Fistula Maturation.

BACKGROUND: Patients requiring hemodialysis access creation often have significant comorbid conditions, which may impact access maturation. Underlying cardiac dysfunction likely plays an important role in the maturation of arteriovenous fistulae (AVF). The effect of specific parameters of cardiac function on successful AVF creation has not previously been explored. METHODS: A retrospective chart analysis of patients undergoing first-time AVF creation at a single center from 2011 to 2018 was performed. Patients with a transthoracic echocardiogram within the 12 months prior to surgery were included. Standard demographic and perioperative variables were collected, in addition to echocardiographic and vascular mapping data. The primary outcome was access maturation, defined as the use of the access site for hemodialysis at 3, 6, and 12 months after surgery. RESULTS: A total of 121 patients met inclusion criteria with a cumulative AVF maturation rate of 57% (69/121) in this select population. Patients with pre-existing systolic cardiac dysfunction were more than 5 times less likely to see their AVF mature by one year postsurgery (OR = 0.17, P = 0.018). Preoperative venous diameter, access site location, and the type of fistula did not differ significantly between patients with and without systolic dysfunction. Selection of the cephalic vein as the venous anastomosis and diastolic dysfunction (≥ Grade 2) were also associated with lower rates of access maturation, although these associations were less robust. CONCLUSIONS: Systolic cardiac dysfunction is the most important nonmodifiable variable associated with failed AVF maturation. Patients requiring hemodialysis with significant pre-existing cardiac dysfunction may not be appropriate for permanent access creation, and long-term catheter use should be seriously considered as an alternative.

The impact of COVID-19: variations in volumes and characteristics of retina surgeries.

BACKGROUND: In concordance with medical recommendations in response to COVID-19, Emory Healthcare limited surgical procedures starting March 16, 2020. We investigated the impact of these recommendations on the number, types, and urgency of surgical retina cases. METHODS: We conducted a retrospective review of all surgical patients at the Retina division of the Emory Eye Center from February 17-April 12, 2020 and during the same time period in 2019 and 2018. The demographics of patients and the number, types and urgency of retina surgeries were collected. Descriptive statistics for each variable were reported. Univariate analysis was carried out using the chi-square test or Fisher's exact test for categorical covariates. RESULTS: From February 17-March 15 to March 16-April 12, 2020, total surgeries decreased from 87 to 34. Emergent cases, occurring within 7 days of surgical order placement, decreased from 23 to 18 (p = 0.0056), and urgent cases, occurring within 21 days of surgical order placement, decreased from 26 to 4 (p = 0.0380). From March 16-April 12, 2019 there were 62 surgeries: 21 emergent (34%), 14 urgent (23%). From March 16-April 12, 2018 there were 68 surgeries: 15 emergent (22%), 21 urgent (30%). After March 16, 2020, average patient age decreased from 39.4 to 25.7 years. There were no statistically significant differences in racial make-up or insurance coverage for those having surgery prior to versus after March 16, 2020. CONCLUSION: National recommendations for ophthalmologic surgeries during COVID-19 disproportionately affected older patients and patients with urgent cases at our tertiary care academic medical center. These results may inform the ophthalmologic field of the potential effects of pandemics such as COVID-19 on the surgical retina care of patients.

Safety of same-day discharge after uncomplicated, minimalist transcatheter aortic valve replacement in the COVID-19 era.

OBJECTIVES: We sought to evaluate the safety, efficacy and feasibility of same-day discharge after uncomplicated, minimalist TAVR. BACKGROUND: At the start of the COVID-19 pandemic, we created a same-day discharge (SDD) pathway after conscious sedation, transfemoral (minimalist) TAVR to help minimize risk of viral transmission and conserve hospital resources. Studies support that next-day discharge (NDD) for carefully selected patients following minimalist TAVR is safe and feasible. There is a paucity of data regarding the safety of SDD after TAVR. METHODS: In-hospital and 30 day outcomes of consecutive patients meeting pre-specified criteria for SDD after minimalist TAVR at our institution between March and July of 2020 were reviewed. Outcomes were compared to a NDD cohort from July 2018 through July 2020 that would have met SDD criteria. Primary endpoints were mortality, delayed pacemaker placement, stroke and cardiovascular readmission at 30 days. RESULTS: Twenty nine patients were discharged via the SDD pathway after TAVR. 128 prior NDD patients were identified who met all criteria for SDD. The STS scores were similar between the two groups (SDD 2.6% ±1.5 vs. NDD 2.3% ± 1.2). There were no deaths at 30 days in either group. There was no significant difference in delayed pacemaker placement (SDD 0% vs. NDD 0.8%, p > .99) or cardiovascular readmission (SDD 0% vs. NDD 5.5%, p = .35) at 30 days. CONCLUSIONS: Same day discharge following uncomplicated, minimalist TAVR in selected patients appears to be safe, achieving similar 30 day outcomes as a cohort of next day discharge patients.

Evaluating Outcomes and Weight Loss After Panniculectomy.

OBJECTIVE: The objective of this study was to evaluate long-term outcomes and weight loss after panniculectomy. METHODS: A retrospective chart review study was performed on 225 consecutive patients who had undergone panniculectomy from 2002 and 2020. Demographic variables including smoking status, medical comorbidities, and prior history of weight loss/bariatric surgery were collected for 173 patients. Preoperative and postoperative body mass index (BMI) were calculated in addition to postoperative outcomes. RESULTS: The study population was 85% female with a mean age of 57 years and an average follow-up of 3.9 years. Relevant comorbidities included obesity (88%), hypertension (65%), diabetes (37%), and smoking (8%), and the majority (53%) of patients had undergone prior bariatric surgery. The overall complication rate was 40%. Twenty percent of patients required reoperation or readmission, and 20% had minor complications addressed in an outpatient setting. Patients who had higher preoperative BMI experienced a significant long-term reduction in BMI. In addition, patients who did not undergo prior bariatric surgery tended to lose weight more often and by larger amounts than patients who had prior bariatric surgery (71.6% vs 57.6, P = 0.023). Complications were not uncommon and included infection (17%), delayed wound healing (16%), seroma (8%), and hematoma (3%). Patients who had prior bariatric surgery were at reduced risk of any complication (P = 0.012). Smoking increased the incidence of infection (38.5% of smokers vs 15.6% of nonsmokers, P = 0.039). Concomitant hernia repair increased the risk of overall complications (64.3% vs 35.9%, P = 0.003) and delayed wound healing (39.2% vs 11.7%, P < 0.001). In the subgroup of patients who did not lose weight, a panniculus weight greater than 5 kg was associated with an increased complication rate (61.5% vs 27%, P = 0.03). CONCLUSIONS: Patients who underwent a panniculectomy tended to lose weight postoperatively, particularly those who had not undergone previous bariatric surgery. Complications were not uncommon, especially in patients with a smoking history. Prior bariatric surgery patients had a significant decrease in postoperative complications but tended to lose less weight after panniculectomy than those without prior bariatric surgery. Concomitant hernia repair put patients at an increased risk of complications.

Coronary Atherosclerotic Plaque Burden Assessment by Computed Tomography and Its Clinical Implications.

Recent studies have demonstrated that coronary plaque burden carries greater prognostic value in predicting adverse atherosclerotic cardiovascular disease outcomes than myocardial ischemia, thereby challenging the existing paradigm. Advances in plaque quantification through both noncontrast and contrast-enhanced computed tomography (CT) methods have led to earlier and more cost-effective detection of coronary disease compared with traditional stress testing. The 2 principal techniques of noninvasive coronary plaque quantification assessment are coronary artery calcium scoring by noncontrast CT and coronary CT angiography, both of which correlate with disease burden on invasive angiography. Plaque quantification from these imaging modalities has shown utility in risk stratification and prognostication of adverse cardiovascular events, leading to increased incorporation into clinical practice guidelines and preventive care pathways. Furthermore, due to their expanding clinical value, emerging technologies such as artificial intelligence are being integrated into plaque quantification platforms, placing more advanced measures of plaque burden at the forefront of coronary plaque evaluation. In this review, we summarize recent clinical data on coronary artery calcium scoring and coronary CT angiography plaque quantification in the evaluation of adverse atherosclerotic cardiovascular disease in patients with and without chest pain, highlight how these methods compare to invasive quantification approaches, and directly compare the performance characteristics of coronary artery calcium scoring and coronary CT angiography.

Outcomes of Patients With Left Ventricular Assist Devices Requiring Intermittent Hemodialysis: Single-Center Cohort, Systematic Review, and Individual-Participant Data Meta-Analysis.

Patients with left ventricular assist devices (LVADs) who require intermittent hemodialysis (iHD) are considered to have a poor prognosis despite a paucity of supportive evidence, mostly from small single-center cohorts and extrapolations from studies of patients who received continuous renal replacement therapy but no iHD. We conducted a systematic review and individual-participant-data meta-analysis of the literature including our single-center cohort to examine the outcomes of patients initiated on iHD following LVAD implantation. Sixty-four patients from 5 cohorts met selection criteria (age 57.5 [46-64.5] years, 87% HeartMate II, mostly bridge to transplantation). Follow-up after iHD initiation was 87.5 (38.5-269.5) days, although it was considerably longer in our center than in other cohorts (601.5 [93-1559] days vs 65 [26-180] days, P = 0.0007). The estimated median survival was 308 (76-912.5) days and varied significantly among cohorts, ranging from 60 (57-65) to 838 (103-1872) days (P = 0.0096). Twelve (18.8%) patients achieved either heart transplantation (HT) or remission during follow-up. Patients who received HT had an 8-fold longer estimated median survival (1972 [799-1972] days vs 244 [64-838] days, P = 0.0112). Being from a more recent cohort was associated with better 1-year survival. Renal recovery occurred in eight patients (13.1%) at 30 days and its cumulative incidence increased to 73% (27/37 patients with available data) at 1 year. Most patients initiated on iHD after LVAD experienced renal recovery within the first year after implantation. Improved survival was observed for patients who received HT and in those from more recent cohorts. Some patients were able to survive on LVAD and iHD support for several years.

Vitamin D Deficiency, Inflammation, and Diminished Endogenous Regenerative Capacity in Coronary Heart Disease.

Background: Vitamin D deficiency (VDD) is associated with coronary heart disease (CHD) and poor outcomes, but supplementation does not improve prognosis. VDD has been implicated in and may promote greater risk through inflammation and impaired progenitor cell function. Objectives: The authors examined VDD, high-sensitivity C-reactive protein (hsCRP), circulating progenitor cell (CPC) counts, and outcomes in patients with CHD. They hypothesized that the higher risk with VDD is mediated by inflammation and impaired regenerative capacity. Methods: A total of 5,452 individuals with CHD in the Emory Cardiovascular Biobank had measurement of 25-hydroxyvitamin D, subsets of whom had hsCRP measurements and CPCs estimated as CD34-expressing mononuclear cell counts. Findings were validated in an independent cohort. 25-hydroxyvitamin D <20 ng/mL was considered VDD. Cox and Fine-Gray models determined associations between marker levels and: 1) all-cause mortality; 2) cardiovascular mortality; and 3) major adverse cardiovascular events, a composite of adverse CHD outcomes. Results: VDD (43.6% of individuals) was associated with higher adjusted cardiovascular mortality (HR: 1.57, 95% CI: 1.09-2.28). There were significant interactions between VDD and hsCRP and CPC counts in predicting cardiovascular mortality. Individuals with both VDD and elevated hsCRP had the greatest risk (HR: 2.82, 95% CI: 2.16-3.67). Only individuals with both VDD and low CPC counts were at high risk (HR: 2.25, 95% CI: 1.46-3.46). These findings were reproduced in the validation cohort. Conclusions: VDD predicts adverse outcomes in CHD. Those with VDD, inflammation and/or diminished regenerative capacity are at a significantly greater risk of cardiovascular mortality. Whether targeted supplementation in these high-risk groups improves risk warrants further study.

Diagnostic Tools for Cardiac Amyloidosis: A Pragmatic Comparison of Pathology, Imaging and Laboratories.

Cardiac amyloidosis (CA) is a complex disease considered to be the most common underdiagnosed form of restrictive cardiomyopathy. Accumulation of misfolded proteins called amyloid fibrils in the extracellular space results in clinical deterioration and late diagnosis is associated with morbidity and mortality. Both types of this disease, light chain CA and transthyretin-related CA share many cardiac and extracardiac features that compromise multiple organs such as kidneys, musculoskeletal system, autonomic nervous system, and gastrointestinal tract. Early diagnosis and detection of CA are imperative. Clinicians should maintain a high degree of suspicion among patients with unexplained diastolic heart failure to implement different disease-altering therapies at the early stages of the disease. In this article, we provided a comprehensive review of multiple invasive and non-invasive cardiac imaging modalities with their respective degrees of sensitivities and specificity.

U-shaped relationship between apolipoprotein A1 levels and mortality risk in men and women.

BACKGROUND: Apolipoprotein A1 (ApoA1) is the principal protein component of high-density lipoprotein (HDL). Although low HDL cholesterol (HDL-C) levels are known to be associated with greater cardiovascular risk, recent studies have also shown heightened mortality risk at very high HDL-C levels. AIMS: To investigate the sex-specific association between elevated ApoA1 levels and adverse outcomes, and their genetic basis. METHODS: A prospective cohort study of United Kingdom Biobank participants without coronary artery disease at enrollment was performed. The primary exposure was serum ApoA1 levels. The primary and secondary outcome measures were cardiovascular and all-cause death, respectively. RESULTS: In 402 783 participants followed for a median of 12.1 years, there was a U-shaped relationship between ApoA1 levels and both cardiovascular as well as all-cause mortality, after adjustment for traditional cardiovascular risk factors. Individuals in the highest decile of ApoA1 levels (1.91-2.50 g/L) demonstrated higher cardiovascular (HR 1.21, 95% CI 1.07-1.37, P < 0.0022) and all-cause mortality (HR 1.14, 95% CI 1.07-1.21, P < 0.0001) compared with those within the lowest risk eighth decile (1.67-1.75 g/L). The U-shaped relationship was present in both sexes, though more pronounced in men. Sensitivity analyses showed that cardiovascular mortality rates were higher in those with greater alcohol intake (P < 0.004). Adjustment for polygenic variation associated with higher ApoA1 levels did not attenuate the effect of very high ApoA1 levels on mortality. In the sub-group with very elevated HDL-C levels (> 80 mg/dL in men, > 100 mg/dL in women), there was no association between ApoA1 levels and mortality. CONCLUSION: Both very low and very elevated ApoA1 levels are associated with higher cardiovascular and all-cause mortality.

Uterine bioimpedance combined with artificial intelligence as a means of cancer detection.

This study hypothesised that benign and tumour-bearing uterine tissue could be differentiated by their unique electrical bioimpedance patterns, with the aid of artificial intelligence. Twenty whole, ex-vivo uterine specimens were obtained at the time of hysterectomy. A total of 11 benign and 9 malignant specimens were studied. A uterine bioimpedance probe was designed to measure the tissue between the endometrial and serosal layers of the uterus. The impedance data was then analysed with multiple instance learning and principal component analysis, forms of artificial intelligence. Final pathology results for the specimens included uterine sarcoma, adenocarcinoma, carcinosarcoma, and high-grade serous carcinoma. The analysis correctly identified 78% (7/9) of the malignant specimens and 82% (9/11) of the benign specimens. The overall accuracy of our analysis was 80%. Our results demonstrate distinction between electrical impedance properties of malignant and benign uterine specimens. Bioimpedance and artificial intelligence may have potential implications in risk assessment of patients and may subsequently guide surgical decision-making regarding route of organ removal.

Actin at stereocilia tips is regulated by mechanotransduction and ADF/cofilin.

Stereocilia on auditory sensory cells are actin-based protrusions that mechanotransduce sound into an electrical signal. These stereocilia are arranged into a bundle with three rows of increasing length to form a staircase-like morphology that is required for hearing. Stereocilia in the shorter rows, but not the tallest row, are mechanotransducing because they have force-sensitive channels localized at their tips. The onset of mechanotransduction during mouse postnatal development refines stereocilia length and width. However, it is unclear how actin is differentially regulated between stereocilia in the tallest row of the bundle and the shorter, mechanotransducing rows. Here, we show actin turnover is increased at the tips of mechanotransducing stereocilia during bundle maturation. Correspondingly, from birth to postnatal day 6, these stereocilia had increasing amounts of available actin barbed ends, where monomers can be added or lost readily, as compared with the non-mechanotransducing stereocilia in the tallest row. The increase in available barbed ends depended on both mechanotransduction and MYO15 or EPS8, which are required for the normal specification and elongation of the tallest row of stereocilia. We also found that loss of the F-actin-severing proteins ADF and cofilin-1 decreased barbed end availability at stereocilia tips. These proteins enriched at mechanotransducing stereocilia tips, and their localization was perturbed by the loss of mechanotransduction, MYO15, or EPS8. Finally, stereocilia lengths and widths were dysregulated in Adf and Cfl1 mutants. Together, these data show that actin is remodeled, likely by a severing mechanism, in response to mechanotransduction.

The Purinergic Receptor P2rx3 is Required for Spiral Ganglion Neuron Branch Refinement during Development.

The mammalian cochlea undergoes a highly dynamic process of growth and innervation during development. This process includes spiral ganglion neuron (SGN) branch refinement, a process whereby Type I SGNs undergo a phase of "debranching" before forming unramified synaptic contacts with inner hair cells. Using Sox2CreERT2 and R26RtdTomato as a strategy to genetically label individual SGNs in mice of both sexes, we report on both a time course of SGN branch refinement and a role for P2rx3 in this process. P2rx3 is an ionotropic ATP receptor that was recently implicated in outer hair cell spontaneous activity and Type II SGN synapse development (Ceriani et al., 2019), but its function in Type I SGN development is unknown. Here, we demonstrate that P2rx3 is expressed by Type I SGNs and hair cells during developmental periods that coincide with SGN branching refinement. P2rx3 null mice show SGNs with more complex branching patterns on their peripheral synaptic terminals and near their cell bodies around the time of birth. Loss of P2rx3 does not appear to confer general changes in axon outgrowth or hair cell formation, and alterations in branching complexity appear to mostly recover by postnatal day (P)6. However, when we examined the distribution of Type I SGN subtypes using antibodies that bind Calb2, Calb1, and Pou4f1, we found that P2rx3 null mice showed an increased proportion of SGNs that express Calb2. These data suggest P2rx3 may be necessary for normal Type I SGN differentiation in addition to serving a role in branch refinement.