Gender disparities and predictors of in-hospital mortality with Takotsubo cardiomyopathy.

BACKGROUND: Takotsubo cardiomyopathy (TCM) is classically associated with significant gender disparities, such that it is more prevalent in females, but the clinical outcomes are worse for male patients. The goal of this study was to assess contemporary gender disparities in clinical outcomes of TCM hospitalizations and to determine predictors of male in-hospital mortality. METHODS: This was a retrospective analysis involving adult hospitalizations for TCM in the U.S between 2016 and 2020. Multivariable Logistic regression was used to estimate Odds Ratio (OR) for in-hospital mortality between the two genders. Univariable Cox regression was performed to identify predictors associated with in-hospital mortality for male hospitalizations. All factors from the univariable analysis with p < 0.20 were included in a multivariable Cox regression model. RESULTS: A total of 199,920 patients with TCM were identified. Female patients with TCM had 50% lower risk of in-hospital mortality compared to male patients (Adjusted OR 0.50, 95% CI 0.46-0.55, p < 0.001). Older age, higher Charlson comorbidity index, history of intracranial hemorrhage, cardiac arrest, need for vasopressor agents, mechanical intubation, and cardiogenic shock without the use of temporary mechanical circulatory support (MCS) were associated with higher in-hospital male mortality. CONCLUSIONS: Although TCM is more prevalent among females, gender disparities exist in the clinical outcomes of TCM patients. Cardiac arrest and cardiogenic shock without the use of temporary MCS were found to be the most significant predictors of male in-hospital mortality. Cardiogenic shock with use of temporary MCS did not lead to higher male in-hospital mortality.

Etiologies and Predictors of 30-Day Readmission in Heart Failure: An Updated Analysis.

Background and Objectives: Readmissions in heart failure (HF), historically reported as 20%, contribute to significant patient morbidity and high financial cost to the healthcare system. The changing population landscape and risk factor dynamics mandate periodic epidemiologic reassessment of HF readmissions. Methods: National Readmission Database (NRD, 2019) was used to identify HF-related hospitalizations and evaluated for demographic, admission characteristics, and comorbidity differences between patients readmitted vs. those not readmitted at 30-days. Causes of readmission and predictors of all-cause, HF-specific, and non-HF-related readmissions were analyzed. Results: Of 48,971 HF patients, the readmitted cohort was younger (mean 67.4 vs. 68.9 years, p≤0.001), had higher proportion of males (56.3% vs. 53.7%), lowest income quartiles (33.3% vs. 28.9%), Charlson comorbidity index (CCI) ≥3 (61.7% vs. 52.8%), resource utilization including large bed-size hospitalizations, Medicaid enrollees, mean length of stay (6.2 vs. 5.4 days), and disposition to other facilities (23.9% vs. 20%) than non-readmitted. Readmission (30-day) rate was 21.2% (10,370) with cardiovascular causes in 50.3% (HF being the most common: 39%), and non-cardiac in 49.7%. Independent predictors for readmission were male sex, lower socioeconomic status, nonelective admissions, atrial fibrillation, chronic obstructive pulmonary disease, chronic kidney disease, anemia, and CCI ≥3. HF-specific readmissions were significantly associated with prior coronary artery disease and Medicaid enrollment. Conclusions: Our analysis revealed cardiac and noncardiac causes of readmission were equally common for 30-day readmissions in HF patients with HF itself being the most common etiology highlighting the importance of addressing the comorbidities, both cardiac and non-cardiac, to mitigate the risk of readmission.

Left Ventricular Pseudoaneurysm: An Overview of Diagnosis and Management.

Left ventricular pseudoaneurysm is a rare but life-threatening disorder that is frequently reported secondary to myocardial infarction or cardiac surgery. In this article, we chronicle the case of a patient with no prior risk factors who presented with a 2-week history of nonexertional atypical left chest pain. Apical 2-chamber transthoracic echocardiography revealed an unexpected outpouching of basal inferoseptal wall of the left ventricle, which had a narrow neck and relatively wide apex. The patient was diagnosed with left ventricular pseudoaneurysm and medical therapy was initiated. He refused to undergo the surgical intervention and subsequently, he was discharged from the hospital in stable condition. This article illustrates that physicians should be vigilant for atypical presentations of left ventricular pseudoaneurysm, and a high index of suspicion should be maintained for this stealth killer while performing appropriate diagnostic imaging. Additionally, we review the currently available approaches to diagnosis and management in these patients.

Outpatient Emergencies: Acute Heart Failure.

Heart failure is an epidemic in the United States and a major health problem worldwide. The syndrome of acute heart failure is marked by a recent onset of symptoms usually in terms of days to a few weeks of worsening fatigue, shortness of breath, orthopnea, swelling, and sudden onset of weight gain. Physicians caring for patients with heart failure must know the risk factors for this disease, pathophysiology, symptomatology, important examination findings, key diagnostic tests, and management approach so as to improve symptoms and reduce mortality.

Effect of Early Intervention With Positive Airway Pressure Therapy for Sleep Disordered Breathing on Six-Month Readmission Rates in Hospitalized Patients With Heart Failure.

Rehospitalization for congestive heart failure (CHF) is high within 6 months of discharge. Sleep disordered breathing (SDB) is common and underdiagnosed condition in patients with CHF. We hypothesized that early recognition and treatment of SDB in hospitalized patients with CHF will reduce hospital readmissions and emergency room visits. Patients admitted for CHF underwent overnight polysomnography within 4 weeks of discharge. Patients diagnosed with SDB were provided therapy with positive airway pressure therapy. Patients were identified as having good compliance if the device use was for a minimum of 4 hours 70% of the time for a minimum of 4 weeks during the first 3 months of therapy. Hospital admissions for 6 months before therapy were compared with readmission within 6 months after therapy in patients with good and poor compliance. A total of 70 patients were diagnosed with SDB after discharge. Of the 70 patients, 37 (53%) were compliant with positive airway pressure therapy. Compliant patients were more likely to be older (64 ± 12 vs 58 ± 11 years) and women (54% vs 33%) and less likely to be patient with diabetes (40% vs 67%) versus noncompliant patients. Although both groups experienced a decrease in total readmissions, compliant patients had a significant reduction (mean ± SE: -1.5 ± 0.2 clinical events vs -0.2 ± 0.3; p <0.0001). In this single-center analysis, identification and treatment of SDB in admitted patients with CHF with SDB is associated with reduced readmissions over 6 months after discharge. Adherence to the treatment was associated with a greater reduction in clinical events.

Photoplethysmographic Signal to Screen Sleep-Disordered Breathing in Hospitalized Heart Failure Patients: Feasibility of a Prospective Clinical Pathway.

OBJECTIVES: The purpose of this study was to evaluate the plethysmographic signal-derived oxygen desaturation index (ODI) as an inpatient screening strategy to identify sleep-disordered breathing (SDB) in patients with congestive heart failure (CHF). BACKGROUND: SDB is highly prevalent among patients hospitalized with CHF but is widely underdiagnosed. We evaluated overnight photoplethysmography as a possible screening strategy for hospitalized patients with CHF. METHODS: Consecutively admitted heart failure patients with high clinical suspicion of SDB and ODI ≥5 were offered outpatient polysomnography (PSG), which was completed within 4 weeks of discharge. PSG was considered positive if the apnea hypoxia index (AHI) was ≥5. A Bland-Altman plot was used to assess agreement between ODI and AHI. Receiver-operator characteristics were determined for ODI ≥5 and AHI ≥5. RESULTS: A screening questionnaire identified 246 of 282 consecutive patients with positive symptoms for SDB. Of these patients, 105 patients were offered further evaluation and 86 had ODI ≥5 (mean ODI 17 ± 17). Among these 86 patients, 68 underwent outpatient PSG within 4 weeks of discharge. PSG showed that 64 (94%) had SDB, with a mean AHI of 28. Inpatient ODI correlated well with PSG-derived AHI. The area under the curve was 0.82 for AHI ≥5. The Bland-Altman plot revealed no major bias. Matthew's correlation coefficient revealed that the optimal cut-off for ODI is 5. CONCLUSIONS: Screening hospitalized patients with heart failure using targeted inpatient ODI identifies a cohort of patients with a high prevalence of SDB. Our screening strategy provides a potentially cost-effective method for early detection and treatment of SDB.

Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: the ROSE acute heart failure randomized trial.

IMPORTANCE: Small studies suggest that low-dose dopamine or low-dose nesiritide may enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction; however, neither strategy has been rigorously tested. OBJECTIVE: To test the 2 independent hypotheses that, compared with placebo, addition of low-dose dopamine (2 µg/kg/min) or low-dose nesiritide (0.005 µg/kg/min without bolus) to diuretic therapy will enhance decongestion and preserve renal function in patients with acute heart failure and renal dysfunction. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, double-blind, placebo-controlled clinical trial (Renal Optimization Strategies Evaluation [ROSE]) of 360 hospitalized patients with acute heart failure and renal dysfunction (estimated glomerular filtration rate of 15-60 mL/min/1.73 m2), randomized within 24 hours of admission. Enrollment occurred from September 2010 to March 2013 across 26 sites in North America. INTERVENTIONS: Participants were randomized in an open, 1:1 allocation ratio to the dopamine or nesiritide strategy. Within each strategy, participants were randomized in a double-blind, 2:1 ratio to active treatment or placebo. The dopamine (n = 122) and nesiritide (n = 119) groups were independently compared with the pooled placebo group (n = 119). MAIN OUTCOMES AND MEASURES: Coprimary end points included 72-hour cumulative urine volume (decongestion end point) and the change in serum cystatin C from enrollment to 72 hours (renal function end point). RESULTS: Compared with placebo, low-dose dopamine had no significant effect on 72-hour cumulative urine volume (dopamine, 8524 mL; 95% CI, 7917-9131 vs placebo, 8296 mL; 95% CI, 7762-8830 ; difference, 229 mL; 95% CI, -714 to 1171 mL; P = .59) or on the change in cystatin C level (dopamine, 0.12 mg/L; 95% CI, 0.06-0.18 vs placebo, 0.11 mg/L; 95% CI, 0.06-0.16; difference, 0.01; 95% CI, -0.08 to 0.10; P = .72). Similarly, low-dose nesiritide had no significant effect on 72-hour cumulative urine volume (nesiritide, 8574 mL; 95% CI, 8014-9134 vs placebo, 8296 mL; 95% CI, 7762-8830; difference, 279 mL; 95% CI, -618 to 1176 mL; P = .49) or on the change in cystatin C level (nesiritide, 0.07 mg/L; 95% CI, 0.01-0.13 vs placebo, 0.11 mg/L; 95% CI, 0.06-0.16; difference, -0.04; 95% CI, -0.13 to 0.05; P = .36). Compared with placebo, there was no effect of low-dose dopamine or nesiritide on secondary end points reflective of decongestion, renal function, or clinical outcomes. CONCLUSION AND RELEVANCE: In participants with acute heart failure and renal dysfunction, neither low-dose dopamine nor low-dose nesiritide enhanced decongestion or improved renal function when added to diuretic therapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01132846.

Cardiovascular toxicities of cancer chemotherapy.

Cancer chemotherapy has improved over the years with the advent of newer agents, including more targeted chemotherapeutic drugs, resulting in better patient survival. However, with continued use and patient exposure to these drugs, important cardiovascular adverse effects are becoming realized, such as left ventricular dysfunction and heart failure, myocardial ischemia, hypertension, arrhythmias, and pulmonary arterial hypertension. In this article, we review the most common cardiovascular toxicities and their related pathophysiology that occur with the use of these agents.

Recurrent orthostatic syncope due to left atrial and left ventricular collapse after a continuous-flow left ventricular assist device implantation.

Left ventricular assist devices (LVADs) have become an established treatment for patients with advanced heart failure as a bridge to transplantation or for permanent support as an alternative to heart transplantation. Continuous-flow LVADs have been shown to improve outcomes, including survival, and reduce device failure compared with pulsatile devices. Although LVADs have been shown to be a good option for patients with end-stage heart failure, unanticipated complications may occur. We describe dynamic left atrial and left ventricular chamber collapse related to postural changes in a patient with a recent continuous-flow LVAD implantation.

Change in intrathoracic impedance measures during acute decompensated heart failure admission: results from the Diagnostic Data for Discharge in Heart Failure Patients (3D-HF) Pilot Study.

BACKGROUND: Despite the high number of admissions for acute decompensated heart failure (ADHF), there are no specific criteria for discharge readiness. A number of patients have implantable devices that might provide data to assist in determining readiness for discharge. METHODS AND RESULTS: The 3D-HF (Diagnostic Data for Discharge in Heart Failure Patients) study was a prospective observational pilot study enrolling HF patients with Optivol-capable cardiac devices within 48 hours of a hospital admission characterized by worsening HF symptoms. The primary end point was the difference in times from admission to 50% improvement in impedance and to when patient was medically ready for discharge. The nonparametric sign test was used to determine if the difference was significant. A total of 20 subjects were enrolled over a 24-month period. The median ADHF length of stay was 7 days. Of the 20 subjects, 18 achieved the intrathoracic impedance improvement threshold before discharge. The time to reach the threshold for improvement was 2.5 days (interquartile range 2.0-6.0). The difference between days to 50% impedance and days to provider's discharge decision was 3.0 (P = .0072). CONCLUSIONS: Intrathoracic impedance changes were evident over a short duration in the majority of patients admitted for ADHF and may be a potential criterion for discharge readiness.

Reporting of clinical trials: publication, authorship, and trial registration.

Transparency is the foundation on which all of research integrity rests. The public trust from patients, providers, and policy makers depends on fidelity to the mandates of accountability and access. Two important foundational practices for maintaining transparency in research and the reporting of clinical trials discussed in this review concern manuscript authorship and clinical trial registry, recognizing recent controversies regarding honorary and ghost authorship in the publication of industry-sponsored studies.

Dynamic changes in lymphocyte GRK2 levels in cardiac transplant patients: a biomarker for left ventricular function.

G protein-coupled receptor kinase 2 (GRK2), which is upregulated in the failing human myocardium, appears to have a role in heart failure (HF) pathogenesis. In peripheral lymphocytes, GRK2 expression has been shown to reflect myocardial levels. This study represents an attempt to define the role for GRK2 as a potential biomarker of left ventricular function in HF patients. We obtained blood from 24 HF patients before and after heart transplantation and followed them for up to 1 year, also recording hemodynamic data and histological results from endomyocardial biopsies. We determined blood GRK2 protein by Western blotting and enzyme-linked immunosorbent assay. GRK2 levels were obtained before transplant and at first posttransplant biopsy. GRK2 levels significantly declined after transplant and remained low over the course of the study period. After transplantation, we found that blood GRK2 significantly dropped and remained low consistent with improved cardiac function in the transplanted heart. Blood GRK2 has potential as a biomarker for myocardial function in end-stage HF.

Valvular heart disease in osteogenesis imperfecta: presentation of a case and review of the literature.

Osteogenesis imperfecta (OI) is a rare inheritable disorder of connective tissue. While musculoskeletal abnormalities are well known, cardiovascular involvement is rare. Aortic root dilation is the most common cardiovascular manifestation. OI preferentially affects the left-sided heart valves, for unclear reasons, leading to aortic and mitral regurgitation. Valve replacement surgery carries a unique set of issues in this population, and fewer than 40 cases have been reported. We report a case of chronic severe aortic regurgitation in a patient with OI complicated by the development of a flail aortic valve leaflet and presenting with a transient ischemic attack. The patient subsequently underwent successful combined bioprosthetic aortic valve replacement and coronary artery bypass grafting. We review the literature on valvular disease and other cardiovascular manifestations in OI and the related surgical considerations relevant to this patient population.

Kinetics of mononuclear cell infiltration and cytokine expression in iodine-induced thyroiditis in the NOD-H2h4 mouse.

Mononuclear cell infiltration of the thyroid gland is a common histologic feature of chronic lymphocytic thyroiditis. Although the infiltrating mononuclear cells have been implicated in the destruction of the thyroid, information concerning the progression of infiltration into the thyroid is limited. In this report, we examine the composition and kinetics of mononuclear cell infiltration in the thyroid and the expression of major histocompatibility complex class II (I-Ak), IL-12, and IFN-gamma in the thyroid of the NOD-H2h4 mouse, a model of spontaneous autoimmune thyroiditis accelerated by the administration of excess dietary iodine. Mice were given a low dose of 0.015% NaI in their drinking water for 2, 4, 6, 8, and 16 weeks, and thyroids were removed, serially sectioned, and stained in an avidin-biotin peroxidase assay. The thyroid infiltrate included CD4+ and CD8+ T cells, F4/80+ macrophages, and B220+ B cells. After 2 weeks of iodine treatment, CD4+ T cells were the first seen in the thyroid, followed by CD8+ T cells and F4/80+ macrophages. B220+ B cells entered the thyroid after 4 weeks of iodine treatment. IL-12 and IFN-gamma positive cells were located in the thyroid early in disease and were up-regulated in the focal accumulations of infiltrating cells. Thyrocytes clearly expressed I-Ak after 4 weeks of iodine treatment near the location of mononuclear cell infiltration.

Iodine: an environmental trigger of thyroiditis.

Like most autoimmune diseases of humans, chronic lymphocytic (Hashimoto's) thyroiditis results from the combination of a genetic predisposition and an environmental trigger. A body of clinical and epidemiologic evidence points to excessive ingestion of iodine as an environmental agent. In genetically determined thyroiditis in animals, iodine enrichment has been shown to increase the incidence and severity of disease. Its mechanism of action is still uncertain. Using a new animal model of autoimmune thyroiditis, the NOD.H2(h4) mouse, we have been able to show that iodine enhances disease in a dose-dependent manner. Immunochemical studies suggest that iodine incorporation in the thyroglobulin may augment the antigenicity of this molecule by increasing the affinity of its determinants for the T-cell receptor or the MHC-presenting molecule either altering antigen processing or by affecting antigen presentation.

Adhesion molecules as susceptibility factors in spontaneous autoimmune thyroiditis in the NOD-H2h4 mouse.

Mononuclear cell infiltration of the thyroid is a prominent feature of chronic lymphocytic thyroiditis. Adhesion molecules play a major role in determining the localization of inflammatory mononuclear cells in the thyroid. Previous reports from animal models and human studies have described the thyroidal expression of adhesion molecules only late in clinical disease. In this study, we examined the distribution and kinetics of expression of E-selectin, VCAM-1, LFA-1, and ICAM-1 in the NOD-H2h4 mouse, a model of spontaneous autoimmune thyroiditis accelerated by dietary iodine. Mice were fed 0.015% NaI in their drinking water for 2, 4, 6, 8, and 16 weeks, and thyroids were removed, serially sectioned, and stained in an avidin-biotin-peroxidase assay. We found a dramatic increase in E-selectin and VCAM-1 expression on intrathyroidal endothelial cells after 16 weeks of iodine treatment. In addition, we describe for the first time that thyrocytes from the NOD-H2h4 mouse, and the parental NOD, constitutively express ICAM-1 independent of iodine treatment and prior to mononuclear cell infiltration of the thyroid gland. ICAM-1 was not detected on the thyrocytes of other untreated strains of mice, implicating expression of this adhesion molecule as a critical event in the recruitment of inflammatory mononuclear cells to the thyroid.