Pulmonary Vein Systolic Flow Reversal and Outcomes in Patients From the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT) Trial.

Background: The implications of pulmonary vein (PV) flow patterns in patients with heart failure (HF) and mitral regurgitation (MR) are uncertain. We examined PV flow patterns in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT) trial (NCT01626079), in which patients with HF and moderate-to-severe or severe functional MR were randomized to transcatheter edge-to-edge repair (TEER) with the MitraClip device plus guideline-directed medical therapy (GDMT) vs. GDMT alone. We sought to evaluate the prognostic utility of baseline PV systolic flow reversal (PVSFR) in HF patients with severe MR and to determine whether the presence of PVSFR can discriminate patients most likely to benefit from TEER in COAPT trial patients. Methods: Patients were categorized by the echocardiographic core laboratory-assessed baseline presence of PVSFR. Two-year outcomes were examined according to PVSFR and treatment. Results: Baseline PV flow patterns were evaluable in 526/614(85.7%) patients, 48.9% of whom had PVSFR. Patients with PVSFR had more severe MR, reduced stroke volume and cardiac output, greater right ventricular dysfunction, and worse hemodynamics. By multivariable analysis, PVSFR was not an independent predictor of 2-year all-cause death, or heart failure hospitalization (HFH). The reductions in the 2-year rates of all-cause death and HFH with TEER compared with GDMT alone were similar in patients with and without PVSFR (Pinteraction = 0.40 and 0.12, respectively). The effect of TEER on improving Kansas City Cardiomyopathy Questionnaire scores and 6-minute walk distance were also independent of PVSFR. Conclusions: In the COAPT trial, PVSFR identified HF patients with severe MR and more advanced heart disease. Patients with and without PVSFR had consistent reductions in mortality, HFH, and improved quality-of-life and functional capacity after TEER. Clinical Trial Registration: ClinicalTrial.gov IdentifierNCT01626079.

Benefits of Adding Glucagon-Like Peptide 1 Receptor Agonists to Sodium-Glucose Co-Transporter 2 Inhibitors in Diabetic Patients With Atherosclerotic Disease and Heart Failure.

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) reduce the risk of cardiovascular events and heart failure hospitalization (HFH) in patients with heart failure with reduced ejection fraction (HFrEF), diabetes mellitus type 2 (DM2), and atherosclerotic cardiovascular disease (ASCVD). The role of glucagon-like peptide 1 agonists (GLP1a) in these patients is unclear. We designed this study to assess if the addition of GLP1a to SGLT2i therapy improves outcomes in patients with HFrEF, DM2, and ASCVD. This was a retrospective cohort study of patients with DM2, ASCVD, and HFrEF in the national Veterans Affairs database. Patients on SGLT2i were propensity matched to patients on both SGTL2i and GLP1a. The co-primary outcomes were HFH and the composite of all-cause death, myocardial infarction, and stroke. We assessed them through a Cox regression model including unbalanced baseline characteristics. From a cohort of 5,576 patients, 343 were propensity matched to each study arm. The addition of GLP1a was associated with a 67% reduction in the 1-year risk of a composite event compared with therapy with SGLT2i (confidence interval 0.138 to 0.714, p = 0.007). The risk of HFH was not significantly different between both arms (p = 0.199). Sensitivity analyses in the unmatched dataset confirmed these findings. In conclusion, the addition of GLP1a to SGLT2i may reduce the risk of adverse events in patients with HFrEF who have DM2 and ASCVD, but it does not affect the risk of HFH.

Diagnosing Cardiac Amyloidosis: From Heart Failure to Electrical Storm.

Cardiac amyloidosis is a condition when amyloid fibers are deposited in the extracellular space of the heart causing tachyarrhythmias, heart failure, or sudden cardiac death. We present a 71-year-old woman presenting with dyspnea on admission. Echocardiogram revealed diastolic heart failure and left ventricular hypertrophy with strain pattern concerning for an infiltrative process. She was discharged with diuretic therapy and scheduled for a cardiac magnetic resonance imaging. One week after discharge, she was readmitted with progressive shortness of breath and syncope. She was found to be in shock and had multiple episodes of cardiac arrest with both ventricular tachycardia and pulseless electrical activity. She developed electrical storm and eventually passed within 24 hours. Autopsy revealed gross cardiomegaly and left ventricular hypertrophy with Congo red staining revealing amyloid fibrils with apple-green birefringence. This case demonstrates the rapid progression of cardiac amyloidosis from acute-onset diastolic heart failure to uncontrollable ventricular tachycardia, and eventually death. We review the literature regarding multiple diagnostic modalities that facilitate the confirmation of cardiac amyloidosis.

Prognostic significance of exercise-induced diastolic dysfunction: A systematic review.

BACKGROUND: Recent guidelines recommend diastolic stress testing among patients with unexplained dyspnea. Previous studies have reported exercise related change in diastolic parameters as a prognostic marker for worse outcomes. However, the role of exercise-induced diastolic dysfunction (DD) in predicting adverse outcomes has not been fully established. METHOD: We conducted a meta-analysis to explore the prognostic significance of exercise-induced DD. PUBMED/EMBASE/SCOPUS databases were searched for studies reporting adverse outcomes in patients undergoing exercise echocardiography based on diastolic response during exercise. Exercise-induced DD was defined as an increase in E/e' or E/A ratio with stress. Outcomes of interest were cardiovascular mortality or hospitalizations. RESULTS: A total of 8 studies were identified, including 4,462 patients who underwent exercise stress echocardiography. The follow-up ranged from 13 months to 5 years. The major indication for stress testing was exertional dyspnea. All studies reported cardiac mortality and hospitalization in the composite outcome. Meta-analysis conducted using random-effects model showed that exercise-induced DD was associated with a higher likelihood of cardiovascular mortality or hospitalization (HR = 1.32, P < .05). Significant heterogeneity was noted among the studies. CONCLUSIONS: Exercise-induced DD is associated with worse cardiovascular outcomes. Changes in echocardiographic parameters such as e' with exercise might be useful for risk stratification and identification of high-risk patients.

In-Hospital and Long-Term Outcomes of Beta-Blocker Treatment in Cocaine Users: A Systematic Review and Meta-analysis.

BACKGROUND: Although ß-blocker treatment is generally contraindicated in patients presenting with acute cocaine intoxication due to concern for unopposed α-receptor stimulation, some studies have reported that ß-blocker treatment did not increase adverse events in these patients. As this treatment is still controversial, we performed a meta-analysis of observational studies on this topic. METHODS: By searching three electronic databases (MEDLINE, EMBASE, and the Cochrane Library) from their inception to June 11, 2018, we identified eight observational studies with 2,048 patients who presented to hospital with cocaine-associated chest pain or after recent cocaine use. Outcomes of interest were myocardial necrosis or infarction (MI) and death during hospital stay or follow-up. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated by using a random-effects meta-analysis based on the DerSimonian-Laird method. RESULTS: Among patients presenting with cocaine-associated chest pain or recent cocaine use, there was no significant difference in in-hospital all-cause mortality (RR, 0.59; 95% CI, 0.24 - 1.47) and MI (RR, 1.24; 95% CI, 0.74 - 2.06) between patients who did and did not receive ß-blocker treatment during their hospital stay. During long-term follow-up (mean 2.6 years), there was no significant difference in all-cause mortality (RR, 0.79; 95% CI, 0.44 - 1.41) and MI (RR, 0.96; 95% CI, 0.40 - 2.33) between the two groups. CONCLUSIONS: These results suggest that ß-blocker treatment in patients presenting with cocaine intoxication may not be as harmful as originally believed. Further clinical studies are needed to investigate this topic.

Novel method versus the Friedewald method for estimating low-density lipoprotein cholesterol in determination of the eligibility for statin treatment for primary prevention in the United States.

Although the Friedewald method has been used as the clinical standard to estimate low-density lipoprotein cholesterol (LDL-C) levels, a novel method with better accuracy was suggested and is now being adopted in real practice. We investigated the effect of this novel method on determining the eligibility for statin treatment for primary prevention in the United States.In this cross-sectional study, we determined the discordance in the statin-eligible population for primary prevention according to the 2 different LDL-C estimating methods based on the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines. Using data from the National Health and Nutrition Examination Survey 2005-2014, we included 5302 nationally representative US adults aged between 40 and 75 years without history of atherosclerotic cardiovascular disease (ASCVD). Sampling weights were used in all statistical analyses to account for complex sampling design and nonresponse.If the Friedewald method is replaced by the novel method for analysis of the fasting samples, 0.2% (95% confidence interval [CI], 0.0-0.8) and 0.4% (95% CI, 0.3-0.6) of the population would no longer be eligible or would become newly eligible for statin treatment, respectively. Among the individuals with a TG level ≥150 mg/dL and LDL-C level estimated using the Friedewald method <70 mg/dL, 11.6% (95% CI, 4.0-29.3) would become newly eligible for the statin treatment when using the novel method.The use of the novel method for estimating LDL-C instead of the Friedewald method would be associated with a small net increase in statin eligible/needed US adults for primary prevention based on the 2013 ACC/AHA guidelines. Reassessment of individuals' statin eligibility using the novel method may be beneficial, particularly when their TG level is 150 mg/dL or higher and LDL-CF level is lower than 70 mg/dL.

Trends in the prevalence of metabolic syndrome and its components in the United States 2007-2014.

BACKGROUND: Recent trends in the prevalence of metabolic syndrome (MetS) and its components among U.S. adults are not known. METHODS: We performed an updated analysis using the National Health and Nutrition Examination Survey 2007-2014 data to investigate the latest trends of prevalence of MetS and its components. MetS was defined based on the modified National Cholesterol Education Program-Adult Treatment Panel III criteria. Multiple regression models were used to assess linear trends over the years, after adjusting for sex, age, and race/ethnicity, as appropriate. Sampling weights were considered to account for complex sampling design, and all estimates were adjusted by age by a direct method. RESULTS: During 2007-2014, the age-adjusted weighted prevalence (±standard error) of MetS among U.S. adults was 34.3 ±â€¯0.8%. In age-stratified analysis, 54.9 ±â€¯1.7% of elderly population aged 60 and over had MetS. When evaluating trends from 2007 to 2014, the prevalence of MetS remained stable in all sex, age, and race/ethnicity groups (P-trends > 0.100 for all). Among the components of MetS, the prevalence of hypertriglyceridemia and fasting hyperglycemia decreased (P-trend <0.050). However, the prevalence of abdominal obesity significantly increased, especially in women (P-trend = 0.009). The prevalence of elevated blood pressure and low high-density lipoprotein cholesterol level remained stable. CONCLUSIONS: The prevalence of MetS remained stable during 2007-2014. However, it was still prevalent in the U.S., especially among the elderly population. The prevalence of abdominal obesity continued to increase in women for which more efforts should be made.

Progressive Multifocal Leukoencephalopathy and Monoclonal Antibodies: A Review.

Progressive multifocal leukoencephalopathy (PML) is a viral infection predominantly seen in patients with HIV infection. However, with the increased use of monoclonal antibodies (MAB) for various lymphoproliferative disorders, we are now seeing this infection in non-HIV patients on drugs such as natalizumab, rituximab, and so on. The aim of this article is to review the relationship between the occurrence of PML and MAB used in the treatment of hematological malignancies and autoimmune diseases. Review of articles from PubMed-indexed journals which study PML in relation to the use of MAB. Relevant literature demonstrated an increased risk of reactivation of latent John Cunningham polyomavirus (JCV) resulting in development of PML in patients on long-term therapy with MAB. The highest incidence of 1 PML case per 1000 treated patients and 1 case per 32 000 was observed in patients treated with natalizumab and rituximab, respectively. Serological and polymerase chain reaction tests for the detection of JCV can be helpful in risk stratification of patients for the development of PML before and during therapy with MAB. Treatment with MAB can result in development of PML. Clinicians should include PML in differential diagnosis in patients treated with these agents if they manifest central nervous system symptoms.

Primary Gangrenous Cutaneous Mold Infections in a Patient With Cancer and Neutropenia.

BACKGROUND: Opportunistic fungal infections caused by Aspergillus and Candida followed by infections with Fusarium, Rhizopus, Mucor, and Alternaria species are an important cause of morbidity and mortality in patients with hematological malignancies. Cutaneous mucormycosis infections are rare, and the incidence, outcomes, and factors associated with survival in the setting of hematological malignancies are not clear. METHODS: A literature search was conducted for all cases of primary cutaneous mold infections in patients with hematological malignancy, of which 50 cases were found. Our case of a patient with a hematological malignancy who sustained a cat bite that in turn caused a primary cutaneous mold infection is also included. RESULTS: In the 51 cases identified, 66.7% were neutropenic upon presentation, and 54.9% were male with an average age of 32 years. Aspergillus species (33.3%) was the most cited followed by Rhizopus species (19.6%). Overall mortality rate was 29.4% and was observed more frequently in patients with neutropenia (60.0%) and without surgical intervention (73.3%). Survival rate was higher (35.3%) for cases utilizing both antifungal and surgical intervention. The antifungal agent with the highest survival rate was amphotericin B and its formulations (58.8%). CONCLUSIONS: Neutropenia within hematological malignancies demonstrate a risk for developing severe cutaneous fungal infections, of which primary cutaneous mucormycosis can carry significant mortality. Combination antifungal therapy and surgical debridement appears to be associated with higher survival outcomes and warrants further investigation.

Marijuana Smoking in Patients With Leukemia.

Worldwide, marijuana (cannabis) is a widely used drug. The incidence of marijuana smoking is increasing and is second only to tobacco as the most widely smoked substance in the general population. It is also the second most commonly used recreational drug after alcohol. Some adverse effects of marijuana smoking have been documented; however, the number of studies on the pulmonary effects of marijuana in individuals with leukemia is limited. In our case series, we report on 2 men with acute myeloid leukemia with miliary nodular lung patterns on computed tomography of the chest due to heavy marijuana use. We also report on 2 patients with acute lymphocytic leukemia who had a history of smoking marijuana and then developed lung opacities consistent with mold infection.