Variation in Risk-Standardized Acute Admission Rates Among Patients With Heart Failure in Accountable Care Organizations: Implications for Quality Measurement.

Background Accountable care organizations (ACOs) aim to improve health care quality and reduce costs, including among patients with heart failure (HF). However, variation across ACOs in admission rates for patients with HF and associated factors are not well described. Methods and Results We identified Medicare fee-for-service beneficiaries with HF who were assigned to a Medicare Shared Savings Program ACO in 2017 and survived ≥30 days into 2018. We calculated risk-standardized acute admission rates across ACOs, assigned ACOs to 1 of 3 performance categories, and examined associations between ACO characteristics and performance categories. Among 1 232 222 beneficiaries with HF, 283 795 (mean age, 81 years; 54% women; 86% White; 78% urban) were assigned to 1 of 467 Medicare Shared Savings Program ACOs. Across ACOs, the median risk-standardized acute admission rate was 87 admissions per 100 people, ranging from 61 (minimum) to 109 (maximum) admissions per 100 beneficiaries. Compared to the overall average, 13% of ACOs performed better on risk-standardized acute admission rates, 72% were no different, and 14% performed worse. Most ACOs with better performance had fewer Black beneficiaries and were not hospital affiliated. Most ACOs that performed worse than average were large, located in the Northeast, had a hospital affiliation, and had a lower proportion of primary care providers. Conclusions Admissions are common among beneficiaries with HF in ACOs, and there is variation in risk-standardized acute admission rates across ACOs. ACO performance was associated with certain ACO characteristics. Future studies should attempt to elucidate the relationship between ACO structure and characteristics and admission risk.

Outpatient intravenous diuresis in a rural setting: safety, efficacy, and outcomes.

Purpose: To evaluate the safety, efficacy, and outcomes of outpatient intravenous diuresis in a rural setting and compare it to urban outcomes. Methods: A single-center study was conducted on 60 patients (131 visits) at the Dartmouth-Hitchcock Medical Center (DHMC) from 1/2021-12/2022. Demographics, visit data, and outcomes were collected and compared to urban outpatient IV centers, and inpatient HF hospitalizations from DHMC FY21 and national means. Descriptive statistics, T-tests and chi-squares were used. Results: The mean age was 70 ± 13 years, 58% were male, and 83% were NYHA III-IV. Post-diuresis, 5% had mild-moderate hypokalemia, 16% had mild worsening of renal function, and 3% had severe worsening of renal function. No hospitalizations occurred due to adverse events. The mean infusion-visit urine output was 761 ± 521 ml, and post-visit weight loss was -3.9 ± 5.0 kg. No significant differences were observed between HFpEF and HFrEF groups. 30-day readmissions were similar to urban outpatient IV centers, DHMC FY21, and the national mean (23.3% vs. 23.5% vs. 22.2% vs. 22.6%, respectively; p = 0.949). 30-day mortality was similar to urban outpatient IV centers but lower than DHMC FY21 and the national means (1.7% vs. 2.5% vs. 12.3% vs. 10.7%, respectively; p < 0.001). At 60 days, 42% of patients had ≥1 clinic revisit, 41% had ≥1 infusion revisit, 33% were readmitted to the hospital, and two deaths occurred. The clinic avoided 21 hospitalizations, resulting in estimated cost savings of $426,111. Conclusion: OP IV diuresis appears safe and effective for rural HF patients, potentially decreasing mortality rates and healthcare expenses while mitigating rural-urban disparities.

Real-World Characteristics of Patients with Wild-Type Transthyretin Amyloid Cardiomyopathy: An Analysis of Electronic Healthcare Records in the United States.

BACKGROUND: Tafamidis was approved for the treatment of hereditary and wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) in May 2019, based on findings from the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT). METHODS: This retrospective cohort study evaluated the factors associated with tafamidis prescription after diagnosis of ATTRwt-CM in the real world. Between May 2019 and December 2020, 430 patients with 6 months' database activity were indexed from the de-identified US Optum electronic healthcare records at first diagnosis of ATTRwt-CM or prescription of tafamidis, then followed until last activity or death. Of these, 209 patients were prescribed tafamidis during follow-up, 167 (80%) within 1 month, 98% by 6 months, and 100% by 9 months. Median time from index to tafamidis prescription, calculated using the Kaplan-Meier method, was 5.8 months (95% confidence interval [CI] 2.4-not evaluable). RESULTS: Factors associated with tafamidis prescription in a multivariable Cox proportional hazards regression (hazard ratio [95% CI]) included age ≥ 65 years (2.1 [1.07-4.05]), male sex (1.6 [1.07-2.28]), having heart failure/cardiomyopathy (2.4 [1.54-3.82]), and having had technetium-99m pyrophosphate myocardial scintigraphy (1.7 [1.28-2.28]). CONCLUSIONS: The clinical characteristics of patients with ATTRwt-CM who were prescribed tafamidis in the real world were broadly comparable with those who took part in ATTR-ACT. Further studies are needed to evaluate hereditary and ATTRwt-CM patient populations in the real world and assess the long-term outcomes associated with disease management pathways. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT01994889.

Real-world safety of neurohormonal antagonist initiation among older adults following a heart failure hospitalization.

AIMS: To optimize guideline-directed medical therapy for heart failure, patients may require the initiation of multiple neurohormonal antagonists (NHAs) during and following hospitalization. The safety of this approach for older adults is not well established. METHODS AND RESULTS: We conducted an observational cohort study of 207 223 Medicare beneficiaries discharged home following a hospitalization for heart failure with reduced ejection fraction (HFrEF) (2008-2015). We performed Cox proportional hazards regression to examine the association between the count of NHAs initiated within 90 days of hospital discharge (as a time-varying exposure) and all-cause mortality, all-cause rehospitalization, and fall-related adverse events over the 90 day period following hospitalization. We calculated inverse probability-weighted hazard ratios (IPW-HRs) with 95% confidence intervals (CIs) comparing initiation of 1, 2, or 3 NHAs vs. 0. The IPW-HRs for mortality were 0.80 [95% CI (0.78-0.83)] for 1 NHA, 0.70 [95% CI (0.66-0.75)] for 2, and 0.94 [95% CI (0.83-1.06)] for 3. The IPW-HRs for readmission were 0.95 [95% CI (0.93-0.96)] for 1 NHA, 0.89 [95% CI (0.86-0.91)] for 2, and 0.96 [95% CI (0.90-1.02)] for 3. The IPW-HRs for fall-related adverse events were 1.13 [95% CI (1.10-1.15)] for 1 NHA, 1.25 [95% CI (1.21-1.30)] for 2, and 1.64 [95% CI (1.54-1.76)] for 3. CONCLUSIONS: Initiating 1-2 NHAs among older adults within 90 days of HFrEF hospitalization was associated with lower mortality and lower readmission. However, initiating 3 NHAs was not associated with reduced mortality or readmission and was associated with a significant risk for fall-related adverse events.

Estimation of Out-of-Pocket Costs for Guideline-Directed Medical Therapy for Heart Failure Under Medicare Part D and the Inflation Reduction Act.

This cross-sectional study estimates out-of-pocket costs of heart failure with reduced ejection fraction medication regimens in Medicare Part D under current law and the Inflation Reduction Act.

The Association Between Beta-blocker and Renin-Angiotensin System Inhibitor Use After Heart Failure With Reduced Ejection Fraction Hospitalization and Outcomes in Older Patients.

INTRODUCTION: Beta-blockers (BB) and renin-angiotensin system inhibitors (RASi) are foundational for the treatment of heart failure with reduced ejection fraction (HFrEF). However, given the increased risk of side effects in older patients, uncertainty remains as to whether, on net, older patients benefit as much as the younger patients studied in trials. METHODS AND RESULTS: Using the Get With The Guidelines-Heart Failure registry linked with Medicare data, overlap propensity weighted Cox proportional hazard models were used to examine the association between BB and RASi use at hospital discharge and 30-day and 1-year outcomes among patients with HFrEF. Among the 48,711 patients (aged ≥65 years) hospitalized with HFrEF, there were significant associations between BB and/or RASi use at discharge and lower rates of 30-day and 1-year mortality, including those over age 85 (30-day hazard ratio 0.56, 95% confidence interval 0.45-0.70; 1-year hazard ratio 0.69, 95% confidence interval 0.61-0.78). In addition, the magnitude of benefit associated with BB and/or RASi use after discharge did not decrease with advancing age. Even among the oldest patients, those over age 85, with hypotension, renal insufficiency or frailty, BB and/or RASi use at discharge was still associated with lower 1-year mortality or readmission. CONCLUSIONS: Among older patients hospitalized with HFrEF, BB and/or RASi use at discharge is associated with lower rates of 30-day and 1-year mortality across all age groups and the magnitude of this benefit does not seem to decrease with advancing age. These data suggest that, absent a clinical contraindication, BB and RASi should be considered in all patients hospitalized with HFrEF before or at hospital discharge, regardless of age.

The association between beta-blockers and outcomes in patients with heart failure and concurrent Alzheimer's disease and related dementias.

BACKGROUND: Contemporary patients with heart failure with reduced ejection fraction (HFrEF) are older and have a higher prevalence of cognitive impairment than those studied in trials. The risk/benefit trade-off of routine beta-blocker (BB) use in patients with HFrEF and Alzheimer's disease and related dementias (ADRD) has not been explored. This study aimed to determine the association between BB use and outcomes among patients with HFrEF and ADRD. METHODS: Using a random 40% sample of Medicare Parts A, B, and D data we identified patients with ≥1 hospitalization for HFrEF between 2008 and 2018. Each patient was classified based on BB use prior to admission and after discharge. Outcomes include 90-day and 1-year mortality and readmission. RESULTS: Between 2008 and 2018, we identified 357,030 patients hospitalized with HFrEF; 12.7% had ADRD. Patients with HFrEF and ADRD had higher 90-day and 1-year mortality compared to patients with HFrEF-only. Among patients admitted on a BB, 60.5% of patients with HFrEF-only were continued on therapy after discharge, compared to 56.8% of patients with HFrEF and ADRD. Discontinuing BB was associated with a 2.2-fold higher risk of 90-day mortality (p < 0.001) among patients with HF-only and a 2.- fold higher risk of 90-day mortality (p < 0.001) among patients with HFrEF + ADRD. Not starting a BB was associated with a 1.8-fold higher risk of 90-day mortality (p < 0.001) among patients with HFrEF-only and a 1.7-fold higher risk of 90-day mortality (p < 0.001) among patients with HFrEF + ADRD. Similar risks were seen at 1 year. CONCLUSIONS: BB therapy is associated with significantly lower short and long-term mortality rates among all patients with HFrEF; the magnitude of these associated benefits appear at least as large in patients with HFrEF and ADRD compared to patients with HFrEF-only.

Coverage with evidence development: where are we now?

OBJECTIVES: CMS' coverage with evidence development (CED) policy allows Medicare beneficiaries to access promising therapies and services while additional data are collected. CED program characteristics are mostly unreported, and qualities associated with retirement of CED data collection requirements are unknown. We aimed to review and systematically describe CED program history and components and report programmatic elements correlated with retirement of CED data collection requirements, while identifying areas for policy improvement. STUDY DESIGN: Systematic review. METHODS: We extracted CED information from the CMS website, ClinicalTrials.gov, PubMed, internet searches, and communication with CMS. RESULTS: There were 27 CED determinations from 2005 to 2022 in 8 therapeutic areas, with the most for cardiovascular diseases (8/27; 30%). Duration of CED programs (range, 1-16 years) and the number of related registries and clinical trials (range, 0-34) were widely variable. Only 4 CEDs have had data collection requirements with continued National Coverage Determination (NCD); 3 relate to cardiovascular therapies, and all have some public availability of findings resulting from CED-related data collection mechanisms. There were 2 instances of NCD revocation and deferral to local coverage decisions. CONCLUSIONS: Changes in the CED program through improving program predictability and transparency with regard to outstanding questions, roles of relevant stakeholders, and requirements for reporting and reevaluation would strengthen the program's effectiveness. Ultimately, these improvements would provide incentives for stakeholder participation in data collection to achieve the goal of increasing access to beneficial therapies and improving clinical outcomes.

Opposing forces of cardiogenic shock: left ventricular outflow obstruction, severe mitral regurgitation, and left ventricular dysfunction in Takotsubo cardiomyopathy.

Rates of stress (Takotsubo) cardiomyopathy have increased during the coronavirus pandemic due to social stressors, even in patients who are not infected with the virus. At times, Takotsubo cardiomyopathy (TC) may present as cardiogenic shock. Herein, we present a case during the pandemic of shock from TC secondary to left ventricular outflow tract obstruction (LVOTO), mitral regurgitation (MR), and left ventricular (LV) dysfunction. The contrasting management strategy of LVOTO, MR, and LV failure was cause for clinical challenge, and we highlight the balance of treating these opposing forces.

Sacubitril/valsartan vs ACEi/ARB at hospital discharge and 5-year survival in older patients with heart failure with reduced ejection fraction: A decision analysis approach.

BACKGROUND: In clinical trials, sacubitril/valsartan has demonstrated significant survival benefits compared to angiotensin converting enzyme inhibitors or angiotensin receptor blockers (ACEi/ARB). Whether older patients with heart failure with reduced ejection fraction (HFrEF) benefit as much, due to higher rates of comorbidities, frailty and drug discontinuation, is unknown. METHODS AND RESULTS: Using a cohort of Medicare beneficiaries hospitalized with HFrEF between 2016 and 2018, we determined all-cause mortality and HF-readmission rates among patients not given ACEi/ARB or sacubitril/valsartan at hospital discharge, by age. We then used risk reductions from the SOLVD, PARADIGM-HF and PIONEER-HF trials to estimate the benefits of ACEi/ARB and sacubitril/valsartan. We then incorporated age-specific estimates of drug discontinuation from Medicare. A Markov decision process model was used to simulate 5-year survival and estimate number needed to treat, comparing discharge on ACEi/ARB vs sacubitril/valsartan by age. After accounting for drug discontinuation rates, which were surprisingly slightly higher among those discharged on ACEi/ARB (2.3%/month vs 1.9%/month), there was a small but significant survival advantage to discharge on sacubitril/valsartan over 5 years (+0.81 months [95% CI 0.80, 0.81]). The benefit of sacubitril/valsartan over ACEi/ARB did not decrease with increasing age - the number needed to treat among 66 to 74-year-old patients was 84 and among 85+ year-old patients was 67. CONCLUSIONS: Even after accounting for "real world" rates of drug discontinuation, discharge on sacubitril/valsartan after conferred a small, but significant, survival advantage which does not appear to wane with increasing age.

Association of early electrical changes with cardiovascular outcomes in immune checkpoint inhibitor myocarditis.

BACKGROUND: Immune-checkpoint inhibitor-associated myocarditis (ICI-myocarditis) often presents with arrhythmias, but the prognostic value of early electrocardiogram findings is unclear. Although ICI-myocarditis and acute cellular rejection (ACR) following cardiac transplantation use similar treatment strategies, differences in arrhythmia burden are unknown. OBJECTIVE: To evaluate the association of electrocardiogram findings in ICI-myocarditis with myocarditis-related mortality and life-threatening arrhythmia. METHODS: A total of 125 cases of ICI-myocarditis were identified retrospectively across 49 hospitals worldwide; 50 cases of grade 2R or 3R ACR were included as comparators. Two cardiologists blinded to clinical data interpreted electrocardiograms. Associations between electrocardiogram features, myocarditis-related mortality and the composite of myocarditis-related mortality and life-threatening arrhythmias were examined. Adjusted hazard ratios (aHRs) were calculated. RESULTS: The cohort had 78 (62.4%) men; median (interquartile range) age was 67 (58-76) years. At 30 days, myocarditis-related mortality was 20/124 (16.1%), and 28/124 (22.6%) met the composite endpoint. Patients who developed complete heart block (aHR by subdistribution hazards model [aHR(sh)] 3.29, 95% confidence interval [CI] 1.24-8.68; P=0.02) or life-threatening cardiac arrhythmias (aHR(sh) 6.82, 95% CI: 2.87-16.21; P<0.001) had a higher risk of myocarditis-related mortality. Pathological Q waves (aHR(sh) 3.40, 95% CI: 1.38-8.33; P=0.008), low QRS voltage (aHR(sh) 6.05, 95% CI: 2.10-17.39; P<0.001) and Sokolow-Lyon index (aHR(sh)/mV 0.54, 95% CI: 0.30-0.97; P=0.04) on admission electrocardiogram were also associated with increased risk of myocarditis-related mortality. These associations were mirrored in the composite outcome analysis. Compared with ACR, ICI-myocarditis had a higher incidence of life-threatening cardiac arrhythmias (15/125 [12.0%] vs 1/50 [2%]; P=0.04) and third-degree heart block (19/125 [15.2%] vs 0/50 [0%]; P=0.004). CONCLUSIONS: Electrocardiograms in ICI-myocarditis with ventricular tachycardias, heart block, low-voltage and pathological Q waves were associated with myocarditis-related mortality and life-threating arrhythmia. Arrhythmia burden in ICI-myocarditis exceeds that of ACR after heart transplant.

Complications and Mortality Following CRT-D Versus ICD Implants in Older Medicare Beneficiaries With Heart Failure.

OBJECTIVES: This study sought to assess the comparative effectiveness of cardiac resynchronization therapy with defibrillator (CRT-D) over implantable cardioverter-defibrillator (ICD) alone in older Medicare patients with heart failure with reduced ejection fraction (HFrEF). BACKGROUND: Despite growing numbers of older patients with HFrEF, the benefits of cardiac resynchronization therapy (CRT) in this group are largely unknown. METHODS: A cohort of fee-for-service Medicare beneficiaries ≥65 years of age with HFrEF and enrolled in Medicare Part D who underwent CRT-D or ICD implantation from January 2008 to August 2015 was identified. Beneficiaries were divided by age (65-74, 75-84, and 85+ years), and outcomes were compared between the CRT-D and ICD groups after inverse probability weighting. RESULTS: Compared with the ICD group, the CRT-D group was older and more likely to be White, be female, and have left bundle branch block. After weighting, overall complications were high across age and device groups (14%-20%). The 1-year mortality was high across all groups. In the 2 oldest age strata, the hazard of death was lower in the CRT-D group (HR: 0.90; 95% CI: 0.86-0.95 and HR: 0.81; 95% CI: 0.72-0.90, respectively; P < 0.001); the hazard of heart failure hospitalization was lower for CRT-D vs ICD in the 85+ years age group (HR: 0.82; 95% CI: 0.74-0.92; P < 0.001). CONCLUSIONS: In older Medicare beneficiaries undergoing ICD with or without CRT, complications and 1-year mortality were high. Compared with ICD alone, CRT-D was associated with a lower hazard of mortality in patients ≥74 years of age and lower hazard of HF hospitalization in those ≥85 years of age. These findings support the use of CRT in eligible older patients undergoing ICD implantation.

Trends in Mortality Rates Among Medicare Enrollees With Alzheimer Disease and Related Dementias Before and During the Early Phase of the COVID-19 Pandemic.

IMPORTANCE: The COVID-19 pandemic fundamentally altered the delivery of health care in the United States. The associations between these COVID-19-related changes and outcomes in vulnerable patients, such as among persons with Alzheimer disease and related dementias (ADRD), are not yet well understood. OBJECTIVE: To determine the association between regional rates of COVID-19 infection and excess mortality among individuals with ADRD. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cross-sectional study used data from beneficiaries of 100% fee-for-service Medicare Parts A and B between January 1, 2019, and December 31, 2020, to assess age- and sex-adjusted mortality rates. Participants were 53 640 888 Medicare enrollees 65 years of age or older categorized into 4 prespecified cohorts: enrollees with or without ADRD and enrollees with or without ADRD residing in nursing homes. EXPOSURES: Monthly COVID-19 infection rates by hospital referral region between January and December 2020. MAIN OUTCOMES AND MEASURES: Mortality rates from March through December 2020 were compared with those from March through December 2019. Excess mortality was calculated by comparing mortality rates in 2020 with rates in 2019 for specific, predetermined groups. Means were compared using t tests, and 95% CIs were estimated using the delta method. RESULTS: This cross-sectional study included 26 952 752 Medicare enrollees in 2019 and 26 688 136 enrollees in 2020. In 2019, the mean (SD) age of community-dwelling beneficiaries without ADRD was 74.1 (8.8) years and with ADRD was 82.6 (8.4) years. The mean (SD) age of nursing home residents with ADRD (83.6 [8.4] years) was similar to that for patients without ADRD (79.7 [8.8] years). Among patients diagnosed as having ADRD in 2019, 63.5% were women, 2.7% were Asian, 9.2% were Black, 5.7% were Hispanic, 80.7% were White, and 1.7% were identified as other (included all races or ethnicities other than those given); the composition did not change appreciably in 2020. Compared with 2019, adjusted mortality in 2020 was 12.4% (95% CI, 12.1%-12.6%) higher among enrollees without ADRD and 25.7% (95% CI, 25.3%-26.2%) higher among all enrollees with ADRD, with even higher percentages for Asian (36.0%; 95% CI, 32.6%-39.3%), Black (36.7%; 95% CI, 35.2%-38.2%), and Hispanic (40.1%; 95% CI, 37.9%-42.3%) populations with ADRD. The hospital referral region in the lowest quintile for COVID-19 infections in 2020 had no excess mortality among enrollees without ADRD but 8.8% (95% CI, 7.5%-10.2%) higher mortality among community-dwelling enrollees with ADRD and 14.2% (95% CI, 12.2%-16.2%) higher mortality among enrollees with ADRD living in nursing homes. CONCLUSIONS AND RELEVANCE: The results of this cross-sectional study suggest that the COVID-19 pandemic may be associated with excess mortality among older adults with ADRD, especially for Asian, Black, and Hispanic populations and people living in nursing homes, even in areas with low COVID-19 prevalence.

Oncocytic Papillary Cystadenoma, an Unusual Variant Presenting as a Laryngeal Ventricular Cyst.

Cystadenoma arising from the larynx is a rare benign minor salivary gland tumor that can show mucinous or papillary morphology. The epithelial lining of the salivary gland tumor can present with oncocytic features, which is attributed to an increased number of mitochondria. We present a rare case of oncocytic papillary cystadenoma (OPC) of the larynx which has a combination of these features. The WHO defines OPC tumors as entities which closely resemble Warthin tumor, but lack its classic lymphoid component. The immunohistochemical profile and molecular genetic features are largely unknown. We present an 84-year-old female, former smoker, who presented with progressive dysphonia, dysphagia, and shortness of breath. Laryngoscopy revealed a large, smooth mass originating from the ventricle of the right vocal fold. Subsequent biopsy demonstrated cyst wall fragments lined by a bilayer of large columnar to cuboidal oncocytic cells that had granular eosinophilic cytoplasm, round to oval nuclei with finely dispersed chromatin, and small but distinct nucleoli. The surrounding stroma was slightly fibrotic with scant lymphoid elements. No nuclear pleomorphism, increased mitosis, or necrosis was identified. In the larynx, benign salivary gland tumors are rare and less frequent than malignant neoplasms. Awareness of rare benign entities like OPC help ensure proper management and aid in avoiding unnecessary therapy.

Comparative effectiveness of cardiac resynchronization therapy in older patients with heart failure: Systematic review and meta-analysis.

BACKGROUND: Pivotal CRT trials enrolled patients with HFrEF significantly younger than the typical contemporary patient with HFrEF. Thus, the risks and benefits in this older population with HFrEF are largely unknown. We sought to perform meta-analyses comparing safety and effectiveness of cardiac resynchronization therapy (CRT) in older vs younger patients with heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: PubMed, The Cochrane Library, Scopus, and Web of Science were queried for comparative effectiveness studies of CRT in older patients with HFrEF. Title, abstract, and full-text screening was performed to identify studies comparing at least 1 prespecified end point between older and younger adult patients with at least 50 participants. Random effects meta-analysis in the left ventricular ejection fraction (LVEF) mean difference (older minus younger) and the relative risk (RR) of death, improvement in New York Heart Association (NYHA) functional class, and complications are reported along with estimates of heterogeneity. In 7 studies, there was similar LVEF improvement between groups (mean difference 1.14, 95% confidence interval [CI] -0.04 to 2.32, P = .06, I2 = 53%). Older patients were equally likely as younger patients to see an improvement in NYHA functional class of at least 1 in 6 studies (RR 0.99, 95% CI 0.93-1.06, P = .76, I2 = 25%). No significant differences in the incidence of hematoma, pneumothorax, lead dislodgment, cardiac perforation, or infection requiring explant was observed. The RR of mortality in 11 studies demonstrated higher risk of all-cause mortality in older patients (RR 1.05, 95% CI 1.03-1.08, P < .01, I2 = 0%). CONCLUSIONS: Compared with younger patients, older patients receiving CRT were equally likely to experience improvement in LVEF, left ventricular end-diastolic diameter, and NYHA functional class. There was no difference in procedural complications. The higher rate of all-cause mortality in older patients likely reflects a greater underlying risk of death from competing causes.

How Do I Optimize Heart Failure Medications for Patients with Hypotension or Chronic Kidney Disease?

HF Medications for Hypotension or CKDThe cornerstone of treatment for HF with reduced ejection fraction is GDMT; however, safely delivering maximal therapy is often hampered by low blood pressure, labile renal function, or both. Reviewing the physiologic basis of GDMT and exploring each drug's mechanism of action and unique properties can enable careful initiation and titration of therapy, even in patients with hypotension or CKD.

Prognostic Value of Lymph Node Ratio in Cutaneous Melanoma: A Systematic Review.

The prognosis of cutaneous melanoma (CM) is based on the histological characteristics of the primary tumor, such as Breslow depth, ulceration, and mitotic rate. The lymph node ratio (LNR) is the ratio of the involved lymph nodes (LNs) divided by the total number of LNs removed during regional LN dissection. LNR is a prognostic factor for many solid tumors; however, controversies exist regarding CM. This study sought to analyze the role of LNR as a prognostic factor in CM. An extensive literature search was conducted using PubMed, Google Scholar, Medline, and the Cochrane Central Registry of Controlled Trials from January 1966 to July 2015. The keywords included in the search were CM and inclusion of the ratio of positive to the total number of LNs as a prognostic factor. The outcomes analyzed included the number of patients with positive LNs, type of survival analysis, and results from the multivariate analysis. A total of 11 studies involving 12,011 patients with positive LNs were evaluated. No previous randomized controlled trials, meta-analyses, or systematic reviews were identified in the Cochrane database on the prognostic value of LNR in CM. The primary electronic database search resulted in 333 full-text articles. The LN location examined was the cervical, axillary, and inguinal regions in all studies except for one that examined only the inguinal region. All studies except three studied the prognostic value of the LNR as a categorical variable rather than a continuous variable. LNR was categorized as A (≤0.1), B (0.11-0.25), and C (>0.25). All studies identified LNR as an independent predictor of overall survival (OS), disease-free survival (DFS), or disease-specific survival (DSS). The hazard ratio (HR) and confidence interval (CI) associated with either DFS or OS were available only in a few studies. Moreover, pooled HR for OS was 2.08 (95% CI: 1.48 2.92), for DFS was 1.364 (95% CI: 0.92-2.02), and for DSS was 1.643 (95% CI: 0.89-3.0). The LNR provides superior prognostic stratification among patients with CM. Additional adequately powered prospective studies are needed to further define the role of LNR and be included in the staging system of CM and direct adjuvant therapy.