Clinical and genetic predictors of cardiac dysfunction assessed by echocardiography in patients with hereditary hemochromatosis.

PURPOSE: Hereditary hemochromatosis (HH) may cause iron deposition in cardiac tissue. We aimed to describe the echocardiographic findings in patients with HH and identify risk factors for cardiac dysfunction. METHODS: In this retrospective study, we included patients with HH who underwent transthoracic echocardiography at our tertiary care center between August 2000 and July 2022. We defined three primary outcomes for cardiac dysfunction: 1) left ventricular ejection fraction (LVEF) < 55%, 2) ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e') > 15, and 3) global longitudinal strain (GLS) < 18. Multivariable logistic regression was utilized to identify predictors of cardiac dysfunction. RESULTS: 582 patients (median age 57 years, 61.2% male) were included. The frequency of LVEF < 55%, E/e' > 15 and GLS < 18 was 9.0% (52/580), 9.6% (51/534) and 20.2% (25/124), respectively. In multivariable analysis, non-White race, age, and hypertension were associated with E/e' > 15. No specific HFE genetic mutation was associated with LVEF < 55%. A history of myocardial infarction was strongly associated with both LVEF < 55% and E/e' > 15. In patients with LVEF ≥ 55%, the C282Y/H63D genetic mutation was associated with reduced likelihood of E/e' > 15, p = 0.024. Patients with C282Y/H63D had a higher frequency of myocardial infarction. Smoking and alcohol use were significantly associated with GLS < 18 in unadjusted analysis. CONCLUSION: We found the traditional risk factors of male sex, and history of myocardial infarction or heart failure, were associated with a reduced LVEF, irrespective of the underlying HFE genetic mutation. Patients with a C282Y/H63D genetic mutation had a higher frequency of myocardial infarction, yet this mutation was associated with reduced odds of diastolic dysfunction compared to other genetic mutations in patients with a normal LVEF.

Rib Plating Outcomes in Elderly Trauma Patients With Multiple Rib Fractures: A Community Hospital Experience.

Rib fractures in the elderly are one of the most common injuries in trauma patients admitted to the hospital, accounting for over 350,000 patients annually in the United States. Rib plating has been shown to be most beneficial among certain populations. Early surgical intervention is important to utilize approaches that limit the use of pain medications. This is a retrospective data analysis to determine the efficacy of rib plating in elderly trauma patients with rib fractures. A total of 253 patients were seen with rib fractures, 63% were male and 37% were female. The mean age is 64 ± 18.5 years. Of these patients analyzed, 76% had an associated comorbid condition. A majority of patients (95%) presented to the emergency department (ED) with mild GCS range (13-15). Moderate GCS range (9-12) was 4%, and 3% of patients were with severe GCS (3-8.) The mean ISS was 10. The overall mortality rate was 4.5%. Patients were divided into 2 groups: group I consisted of patients who received open reduction and fixation of the fractured ribs, and group II was patients managed conservatively without surgery. Statistical analyses using Student's t-test and Chi-square test were performed. Institutional Review Board approval was obtained for this study. Rib plating in elderly trauma patients with multiple rib fractures has shown to be beneficial in terms of mortality. Furthermore, geriatric patients with comorbidities will benefit from early open reduction and fixation of rib fractures, though a larger study is needed to establish clearer criteria for rib plating.

Factors Favoring the Development of Chronic Subdural Hematoma After Traumatic Acute Subdural Hematoma in the Elderly.

INTRODUCTION: Traumatic acute subdural hematoma (TASDH) is by far the most common traumatic brain injury in elderly patients presented to the emergency department, and a number of those treated conservatively will develop chronic subdural hematoma (CSDH). The factors contributing to chronicity were not well studied in the elderly; therefore, we retrospectively analyzed our elderly patients with acute subdural hematomas to identify the risk factors which might contribute to the development of subsequent CSDH. METHODS: A retrospective analysis of 254 patients with TASDH admitted between 2012 and 2016 to our level 2 trauma department in a community hospital was collected. Data include age, sex, comorbid conditions, CT findings, anticoagulant therapy, surgical interventions, disposition after discharge, and mortality. Data on those readmitted within the first 2 months with the diagnosis of CSDH were also studied (group A), and compared to those not readmitted (group B). Multiple logistic regression was used to determine the risk factors associated with readmission at P ≤ .05. Institutional review board approval was obtained for this study. RESULTS: There were 254 patients who were admitted with TASDH, 144 male (56.7%) and 110 female (43.3%), with the mean age of 71.4 (SD ± 19.38) years. Only 37 patients (14.6%) went for surgery in their initial admission. A total of 14 patients (5.6%) were readmitted subsequently with the diagnosis of CSDH within two months of initial discharge (group A). Only four patients (28.5%) were on anticoagulant therapy and these patients went for emergency craniotomy for evacuation of hematoma. All 14 patients had a history of coronary artery disease and hypertension and only 5 (35.7%) were diabetic. Review of head CT on initial admission of those patients revealed 4 patients (28.5%) had multiple lesions and 4 (28.5%) had tentorial/falax bleeding and 4 (28.5%) had a shift. The initial size and thickness of the bleeding was 1.4-5 mm. The adjusted model identified diabetes, race, and initial disposition as significant risk factors (P < .05). CONCLUSION: Risk associated with the transformation of TASDH to CSDH is difficult to assess in those group of elderly patients because of the small number; however, diabetes, race, and initial disposition to home pointed toward a risk for future development of CSDH and those patients should be followed clinically and radiographically over the next few months after discharge, particularly those on anticoagulant therapy.

Impact of raising serum myoglobin on resuscitation of trauma patients with high injury severity score (ISS).

INTRODUCTION: Recent studies recommend limiting the amount of crystalloid perfused during resuscitation for trauma patients. Severely injured patients sustain extensive muscle damage with subsequent high serum myoglobin levels precipitating acute renal injury if not treated immediately. To timely identify patients at risk of acute renal injury, we proposed determining the strength of the correlation between the American College of Surgeons-defined injury severity score with serum and urine myoglobin level in the early hours of arrival to the emergency department to determine the patient at higher risk of raising serum myoglobin level and subsequent renal injury. METHOD: A retrospective analysis was conducted at a 400-bed community teaching hospital with a level 2 trauma section and annual admission of 750-800 patients using the data in the trauma registry (2010-2017). Patients with an injury severity score of 15 or above were selected, and Student t test and Pearson correlation 2-tailed analysis were used to identify the relationship with serum myoglobin. RESULT: There were 306 patients total, with 200 men (70.3%) and 106 women (29.7%) and a mean age of 60.64 (SD = 23.6) (range 18-96) years. The mean injury severity score was 22.3 (SD = 8.5) (range 16-75). The median level of serum myoglobin in the first 24 hours of admission was 848.56 ng/mL (range 22-11,197). There was a strong and significant correlation between the 2 variables (r = 0.397, P < .0001). CONCLUSION: The appearance of urine myoglobin with serum level of 39 ng/mL suggests that with higher injury severity score, the potential for acute kidney injury is likely and should be addressed early in the patient management.

Eosinophillic Myocarditis Secondary to Metastatic Melanoma.

Eosinophilic myocarditis is a rare form of myocarditis that may manifest from cancer-mediated inflammation. A case of eosinophilic myocarditis secondary to metastatic melanoma is described; metastatic melanoma can cause a T helper type 2 lymphocyte-mediated increase in circulating levels of interleukin-5, which is known to stimulate eosinophil proliferation resulting in myocardial inflammation and fibrosis. Cardiac imaging with transesophageal echocardiography revealed a large immobile left ventricular apical thrombus. Cardiac MRI was then performed and revealed enhancing fibrosis along the endocardial surface. © RSNA, 2019 Supplemental material is available for this article.

Eosinophillic Myocarditis Secondary to Metastatic Melanoma.

Eosinophilic myocarditis is a rare form of myocarditis that may manifest from cancer-mediated inflammation. A case of eosinophilic myocarditis secondary to metastatic melanoma is described; metastatic melanoma can cause a T helper type 2 lymphocyte-mediated increase in circulating levels of interleukin-5, which is known to stimulate eosinophil proliferation resulting in myocardial inflammation and fibrosis. Cardiac imaging with transesophageal echocardiography revealed a large immobile left ventricular apical thrombus. Cardiac MRI was then performed and revealed enhancing fibrosis along the endocardial surface. © RSNA, 2019 Supplemental material is available for this article.

Appropriately testing patients with intermediate risk for coronary artery disease: how well are we doing?

BACKGROUND: Cardiovascular risk assessment and stratification of stable coronary artery disease represents a pivotal component of coronary artery disease management. The introduction of risk stratification tools has advanced the detection of patients with intermediate to high risk for coronary artery events. These patients will ultimately undergo non-invasive and invasive cardiovascular testing. OBJECTIVE: To synthesise evidence illustrating risk stratification tools and non-invasive testing for patients with intermediate risk for coronary artery disease and suggest a simple method for clinicians to follow prior to ordering non-invasive cardiovascular testing. STUDY SELECTION: Literature review of PubMed and MEDLINE Central on studies and evidence highlighting the appropriate use criteria for radionuclide myocardial perfusion imaging. FINDINGS AND CONCLUSIONS: Overtestingusing myocardial perfusion imaging is well documented in several studies in the literature. Few studies highlighted the importance of the appropriate use criteria for radionuclide myocardial perfusion imaging, which can reduce unnecessary testing in patients with suspected coronary artery disease. Herein, we propose 'Simple Steps to Follow' to be considered by clinicians prior to ordering radionuclide myocardial perfusion imaging. The target audience of this article is internal and family medicine primary care physicians and other non-cardiologist physicians.

Effect of intra-operative single dose of dexamethasone for control of post-operative nausea and vomiting on the control of glucose levels in diabetic patients.

BACKGROUND: Dexamethasone adds a unique challenge to glycemic control, and it may complicate patient care if there is an association between intra-operative dexamethasone and blood glucose levels. METHODS: We analyzed 396 diabetic patients who underwent general anesthesia for various surgical procedures and were hospitalized post-operatively for at least 24 h between January 2015 and June 2016. Patients were classified into two groups-those who received dexamethasone intra-operatively and those who did not. The groups were analyzed for blood glucose changes during and following their procedure. RESULTS: A total of 396 diabetic patients (152 (38.8%) dexamethasone group; 244 (62.2%) control) were included. The dexamethasone group had significantly lower preoperative blood glucose (135.5 mmol/L) compared to the control group (144.4 mmol/L) (p = 0.04) and significantly lower proportion of patients who had received insulin during surgery (14.9%) compared to the control group (23.4%) (p = 0.04). Overall, glucose levels declined from pre-op to post-op day 1 by 9.6 (62.9) (p = 0.007). CONCLUSION: Diabetic patients receiving dexamethasone for control of post-operative nausea during surgery are at greater risk for increasing blood glucose levels and difficult glycemic control during and after surgery compared to patients receiving other medications to control post-operative nausea.

Visit-to-Visit Office Blood Pressure Variability and Cardiovascular Outcomes in SPRINT (Systolic Blood Pressure Intervention Trial).

Studies of visit-to-visit office blood pressure (BP) variability (OBPV) as a predictor of cardiovascular events and death in high-risk patients treated to lower BP targets are lacking. We conducted a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial), a well-characterized cohort of participants randomized to intensive (<120 mm Hg) or standard (<140 mm Hg) systolic BP targets. We defined OBPV as the coefficient of variation of the systolic BP using measurements taken during the 3-,6-, 9-, and 12-month study visits. In our cohort of 7879 participants, older age, female sex, black race, current smoking, chronic kidney disease, and coronary disease were independent determinants of higher OBPV. Use of thiazide-type diuretics or dihydropyridine calcium channel blockers was associated with lower OBPV whereas angiotensin-converting enzyme inhibitors or angiotensin receptor blocker use was associated with higher OBPV. There was no difference in OBPV in participants randomized to standard or intensive treatment groups. We found that OBPV had no significant associations with the composite end point of fatal and nonfatal cardiovascular events (n=324 primary end points; adjusted hazard ratio, 1.20; 95% confidence interval, 0.85-1.69, highest versus lowest quintile) nor with heart failure or stroke. The highest quintile of OBPV (versus lowest) was associated with all-cause mortality (adjusted hazard ratio, 1.92; confidence interval, 1.22-3.03) although the association of OBPV overall with all-cause mortality was marginal (P=0.07). Our results suggest that clinicians should continue to focus on office BP control rather than on OBPV unless definitive benefits of reducing OBPV are shown in prospective trials. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01206062.

Melanoma Differentiation-associated Gene 7/IL-24 Exerts Cytotoxic Effects by Altering the Alternative Splicing of Bcl-x Pre-mRNA via the SRC/PKCδ Signaling Axis.

Melanoma differentiation-associated gene 7 (MDA-7/IL-24) exhibits cytotoxic effects on tumor cells while sparing untransformed cells, and Bcl-x(L) is reported to efficiently block the induction of cell death by MDA-7/IL-24. The expression of Bcl-x(L) is regulated at the level of RNA splicing via alternative 5' splice site selection within exon 2 to produce either the pro-apoptotic Bcl-x(s) or the anti-apoptotic Bcl-x(L). Our laboratory previously reported that Bcl-x RNA splicing is dysregulated in a large percentage of human non-small cell lung cancer (NSCLC) tumors. Therefore, we investigated whether the alternative RNA splicing of Bcl-x pre-mRNA was modulated by MDA-7/IL-24, which would suggest that specific NSCLC tumors are valid targets for this cytokine therapy. Adenovirus-delivered MDA-7/IL-24 (Ad.mda-7) reduced the viability of NSCLC cells of varying oncogenotypes, which was preceded by a decrease in the ratio of Bcl-x(L)/Bcl-x(s) mRNA and Bcl-x(L) protein expression. Importantly, both the expression of Bcl-x(L) and the loss of cell viability were "rescued" in Ad.mda-7-treated cells incubated with Bcl-x(s) siRNA. In addition, NSCLC cells ectopically expressing Bcl-x(s) exhibited significantly reduced Bcl-x(L) expression, which was again restored by Bcl-x(s) siRNA, suggesting the existence of a novel mechanism by which Bcl-x(s) mRNA restrains the expression of Bcl-x(L). In additional mechanistic studies, inhibition of SRC and PKCδ completely ablated the ability of MDA-7/IL-24 to reduce the Bcl-x(L)/(s) mRNA ratio and cell viability. These findings show that Bcl-x(s) expression is an important mediator of MDA-7/IL-24-induced cytotoxicity requiring the SRC/PKCδ signaling axis in NSCLC cells.

Coronary Interventions before Liver Transplantation Might Not Avert Postoperative Cardiovascular Events.

Percutaneous coronary intervention and coronary artery bypass grafting may be performed before orthotopic liver transplantation (OLT) to try to improve the condition of patients who have severe ischemic heart disease. However, data supporting improved outcomes are lacking. We reviewed the medical records of 2,010 patients who underwent OLT at our hospital from 2000 through 2010. The 51 patients who underwent coronary artery angiography within 6 months of transplantation were included in this study: 28 had mild coronary artery disease, 10 had moderate disease, and 13 had severe disease. We compared all-cause and cardiac-cause mortality rates. We found a significant difference in cardiac deaths between the groups (P <0.001), but none in all-cause death (P=0.624). Of the 10 patients who had moderate coronary artery disease, one underwent pre-transplant coronary artery bypass grafting. Of 13 patients with severe disease, 3 underwent percutaneous coronary intervention, and 6 underwent coronary artery bypass grafting. Overall, 50% of patients who underwent either intervention died of cardiac-related causes, whereas no patient died of a cardiac-related cause after undergoing neither intervention (P <0.0001). We conclude that, despite coronary intervention, mortality rates remain high in OLT patients who have severe coronary artery disease.

Use of a melody pulmonary valve in transcatheter valve-in-valve replacement for tricuspid valve bioprosthesis degeneration.

Bioprosthetic heart valves can degenerate and fail over time. Repeat surgery as a means of replacement increases morbidity and mortality rates, and some patients are not candidates for reoperation. A newer treatment, percutaneous transcatheter valve-in-valve implantation, might delay or substitute for invasive procedures. We present the case of a 51-year-old woman, a poor candidate for surgery who had prosthetic tricuspid valve degeneration and stenosis. We successfully performed valve-in-valve placement of a Melody(®) valve, using a procedure originally intended to treat pulmonary valve conduit obstruction or regurgitation. To our knowledge, this is among the first case reports to describe the use of the Melody pulmonary valve in transcatheter valve-in-valve replacement for prosthetic tricuspid stenosis that was otherwise not correctable. Additional data and longer follow-up periods are necessary to gain an understanding of ideal indications and selection of patients for the percutaneous transcatheter treatment of tricuspid valve stenosis.

Cardiac troponin elevation predicts mortality in patients undergoing orthotopic liver transplantation.

Introduction. While patients undergoing orthotopic liver transplantation (OLT) have high cardiovascular event rates, preoperative risk stratification may not necessarily predict those susceptible patients. Troponin T (TnT) may help predict patients at risk for cardiovascular complications. Methods. Consecutive patients undergoing OLT at Mayo Clinic in Florida between 1998 and 2010 who had TnT obtained within 10 days following surgery were included. Three groups were compared based on TnT level: (1) normal (TnT ≤0.01 ng/mL), (2) intermediate (TnT 0.02-0.11 ng/mL), and (3) elevated (TnT >0.11 ng/mL). Overall and cardiovascular mortality was assessed. Results. Of the 78 patients included, there was no difference in age, gender, severity of liver disease, and echocardiographic findings. Patients in the normal and intermediate TnT groups had a lower overall mortality rate (14.3% and 0%, resp.) when compared with those with elevated TnT (50%; P = 0.001). Patients in the elevated TnT group had a cardiovascular mortality rate of 37.5% compared with 1.4% in the other groups combined (P < 0.01). The elevated TnT group had a much higher mortality rate when compared with those in the intermediate group (P < 0.0001). Conclusion. TnT may accurately help risk stratify patients in the early postoperative setting to better predict cardiovascular complications.

A heart of stone: a case of acute development of cardiac calcification and hemodynamic collapse.

Acute cardiac calcification is a clinical entity that may develop over days to months and is usually localized to areas of healed myocardial infarction, cardiac surgery or trauma. We present an unusual case of rapidly developing non-ischemic cardiac calcification in the setting of sepsis and end stage renal disease resulting in acute diastolic dysfunction and cardiac collapse diagnosed by computed tomography (CT) and confirmed by autopsy. We propose that dedicated cardiac CT may provide the most accurate means to detect cardiac calcification.

Radiation dose in cardiac imaging: how should it affect clinical decisions?

OBJECTIVE: The purpose of this article is to discuss whether and how the risks of exposure to ionizing radiation should affect clinical decision making in patients with known or suspected cardiovascular disease. CONCLUSION: Although the prevalence of cardiovascular disease and frequency of diagnostic testing has risen dramatically, cardiovascular mortality has declined. Earlier and more accurate detection of cardiovascular disease may play an important role. Concerns regarding excessive radiation exposure from cardiovascular imaging have been raised. Efforts to reduce exposure have included selection of appropriate patients for cardiovascular testing, technologic advances, educational resources, and a directed patient-centered approach to testing.

Diffuse diseases of the myocardium: MRI-pathologic review of nondilated cardiomyopathies.

OBJECTIVE: This article will present correlation of the key radiologic findings with gross and microscopic pathology for the characterization of diffuse myocardial diseases using advanced imaging techniques. Our goal is to provide a focused and in-depth review of the pathophysiology underlying each entity and to emphasize the structural basis for the corresponding imaging characteristics. This article is limited to those disorders characterized by ventricular wall thickening without chamber dilatation, including hypertrophic cardiomyopathy, hypertensive cardiomyopathy, and cardiac amyloidosis. CONCLUSION: For the characterization of diffuse myocardial diseases using advanced imaging techniques, it is essential to understand the underlying pathologic changes in the heart. With these techniques, such as cardiac MRI, the various cardiomyopathies can be differentiated accurately, which may potentially obviate invasive testing and endomyocardial biopsy.

Indexes of von Willebrand factor as biomarkers of aortic stenosis severity (from the Biomarkers of Aortic Stenosis Severity [BASS] study).

We correlated von Willebrand factor (VWF) activity indexes and brain natriuretic peptide (BNP) with measures of aortic stenosis (AS) severity, bleeding, symptoms, and freedom from death or aortic valve replacement. Patients with AS (n = 66 [16 mild, 20 moderate, and 30 severe]) and aortic valve replacement (n = 21) were assessed with VWF antigen, VWF latex agglutination immunoturbidic activity, platelet function analyzer collagen plus adenosine diphosphate (PFA-CADP), VWF multimer ratio, and BNP level after echocardiography. In patients with AS, the mean gradient correlated with BNP (Spearman r = 0.29, p = 0.02), VWF latex agglutination immunoturbidic activity/VWF antigen ratio (r = -0.41, p <0.001), PFA-CADP (r = 0.49, p <0.001), and VWF multimer ratio (r = -0.76, p <0.001). The area under the curve for detection of severe AS was 0.62 (95% confidence interval [CI] 0.48 to 0.77) by elevated BNP, 0.81 (95% CI 0.69 to 0.92) by PFA-CADP closure time, 0.69 (95% CI 0.55 to 0.82) by VWF latex agglutination immunoturbidic activity/VWF antigen ratio, and 0.86 (95% CI 0.76 to 0.95) by VWF multimer ratio. For the VWF multimer ratio, a threshold of 0.15 yielded a sensitivity and specificity for severe AS of 77% and positive predictive value of 74%. Bleeding (in 14%) was associated with a prolonged PFA-CADP time and reduced VWF latex agglutination immunoturbidic activity/VWF antigen ratio. Symptoms were associated with elevated BNP and low Duke Activity Status Index score. In 66 patients with AS, freedom from death (n = 4) or aortic valve replacement (n = 22) was associated with PFA-CADP (p = 0.003), VWF high-molecular-weight multimers (p = 0.009), and VWF latex agglutination immunoturbidic activity/VWF antigen ratio (p <0.001) but not BNP (p = 0.32). In severe AS versus aortic valve replacement, the PFA-CADP and VWF multimer ratio differed (p <0.001), but BNP and the VWF latex agglutination immunoturbidic activity/VWF antigen ratio did not. In conclusion, the VWF activity indexes were associated with AS severity and bleeding and were predictive of cardiovascular outcomes.

The Proto-oncogene PKCι regulates the alternative splicing of Bcl-x pre-mRNA.

Two splice variants derived from the Bcl-x gene via alternative 5' splice site selection (5'SS) are proapoptotic Bcl-x(s) and antiapoptotic Bcl-x(L). Previously, our laboratory showed that apoptotic signaling pathways regulated the alternative 5'SS selection via protein phosphatase-1 and de novo ceramide. In this study, we examined the elusive prosurvival signaling pathways that regulate the 5'SS selection of Bcl-x pre-mRNA in cancer cells. Taking a broad-based approach by using a number of small-molecule inhibitors of various mitogenic/survival pathways, we found that only treatment of non-small cell lung cancer (NSCLC) cell lines with the phosphoinositide 3-kinase (PI3K) inhibitor LY294002 (50 µmol/L) or the pan-protein kinase C (PKC) inhibitor Gö6983 (25 µmol/L) decreased the Bcl-x(L)/(s) mRNA ratio. Pan-PKC inhibitors that did not target the atypical PKCs, PKCι and PKCζ, had no effect on the Bcl-x(L)/(s) mRNA ratio. Additional studies showed that downregulation of the proto-oncogene, PKCι, in contrast to PKCζ, also resulted in a decrease in the Bcl-x(L)/(s) mRNA ratio. Furthermore, downregulation of PKCι correlated with a dramatic decrease in the expression of SAP155, an RNA trans-acting factor that regulates the 5'SS selection of Bcl-x pre-mRNA. Inhibition of the PI3K or atypical PKC pathway induced a dramatic loss of SAP155 complex formation at ceramide-responsive RNA cis-element 1. Finally, forced expression of Bcl-x(L) "rescued" the loss of cell survival induced by PKCι siRNA. In summary, the PI3K/PKCι regulates the alternative splicing of Bcl-x pre-mRNA with implications in the cell survival of NSCLC cells.