Oral Metolazone Versus Intravenous Chlorothiazide as an Adjunct to Loop Diuretics for Diuresis in Acute Decompensated Heart Failure With Reduced Ejection Fraction.

Background: Thiazide diuretics are often utilized to overcome loop diuretic resistance when treating acute decompensated heart failure (ADHF). In addition to a large cost advantage, several pharmacokinetic advantages exist when administering oral metolazone (MTZ) compared with intravenous (IV) chlorothiazide (CTZ), yet many providers are reluctant to utilize an oral formulation to treat ADHF. The purpose of this study was to compare the increase in 24-hour total urine output (UOP) after adding MTZ or CTZ to IV loop diuretics (LD) in patients with heart failure with reduced ejection fraction (HFrEF). Methods and Results: From September 2013 to August 2016, 1002 patients admitted for ADHF received either MTZ or CTZ in addition to LD. Patients were excluded for heart failure with preserved ejection fraction (HFpEF) (n = 469), <24-hour LD or UOP data prior to drug initiation (n = 129), or low dose MTZ/CTZ (n = 91). A total of 168 patients were included with 64% receiving CTZ. No significant difference was observed between the increase in 24-hour total UOP after MTZ or CTZ initiation (1458 [514, 2401] mL vs 1820 [890, 2750] mL, P = .251). Conclusions: Both MTZ and CTZ similarly increased UOP when utilized as an adjunct to IV LD. These results suggest that while thiazide agents can substantially increase UOP in ADHF patients with HFrEF, MTZ and CTZ have comparable effects.

Evaluation of Clinical Outcomes with Phosphodiesterase-5 Inhibitor Therapy for Right Ventricular Dysfunction After Left Ventricular Assist Device Implantation.

Few studies have evaluated the use of phosphodiesterase-5 inhibitors (PDE5-i) for right ventricular (RV) dysfunction after left ventricular assist device (LVAD) implantation. The study purpose was to examine the impact of postoperative inpatient PDE5-i therapy on clinical outcomes in patients with LVADs. This single-center, retrospective cohort study screened 445 LVAD recipients between January 2011 and May 2015 for eligibility. Subjects receiving post-LVAD PDE5-i were compared with those who did not. The primary outcome was the proportion of all-cause hospital readmission at 30 days. Additional outcomes assessed included duration of intravenous inotrope or inhaled epoprostenol therapy, length of stay, duration of mechanical ventilation, overall survival, and improvement in the degree of postoperative RV dysfunction. Comparative analyses were performed before and after propensity score (PS) matching. Three-hundred and eighteen patients were included; 208 received post-LVAD inpatient PDE5-i and 110 patients did not. There was no difference in the rate of readmission at 30 days before or after PS matching. No significant differences were found between groups with regard to inotrope or epoprostenol duration, lengths of stay, duration of mechanical ventilation, overall survival, or improvement in the degree of RV dysfunction after PS matching. In the current study, the use of PDE5-i for adjunctive treatment of post-LVAD RV dysfunction was not associated with improved clinical outcomes.

Vasopressin antagonism for decompensated right-sided heart failure.

BACKGROUND: Targeted treatment for decompensated right heart failure (RHF) with or without left heart failure is lacking. Vasopressin antagonists (vaptans) may offer an option by increasing urine output and fluid mobilization when used in acute decompensated RHF without impacting blood pressure or renal function, both common complications of loop diuretics. METHODS AND RESULTS: We searched electronic medical records from 2 institutions over 4 years for patients with RHF treated with vaptans. Urine output, creatinine, BUN and sodium, 1 day pre- versus 1 day post-vaptan initiation were compared. Baseline (admission) pre-vaptan values for patients with RHF who met inclusion criteria (n = 112) were RAP, median (interquartile range) = 19 (13-24) mmHg; cardiac index, mean ±â€¯standard deviation = 1.8 ±â€¯0.4 L/min/m2; BNP, 1078 (523-1690) pg/ml; creatinine clearance of 51 (39-69) ml/min, BUN, 37 (26-54) mg/dl, and serum [Na+] 132 (126-135) mEq/L. Most patients (n = 103/112) received intravenous inotrope (prior to vaptan, n = 91). Overall length of stay was 27 (16-43) days. Vaptan treatment (90% tolvaptan, 10% conivaptan) was associated with increased 24 h urine output, 1517 (906-2394) vs 2337 (1425-3744) mL, p = 0.005, and [Na+], 127 (124-130) vs 130 (126-135) mEq/L, p = 0.001, without significant change in Cr or BUN. Furosemide IV dose equivalent decreased or remained unchanged in 75% of patients at 24 h and 64% at 72 h compared to the 24 h prior to vaptan use. CONCLUSION: Vaptans were associated with a significant increase in urine output and serum sodium with an apparent reduction or stabilization of furosemide equivalent dosing in the early treatment period in patients with decompensated RHF. Vaptans may offer a management option for patients failing conventional diuretic-based treatment.

Outcomes and Predictors of Early Infection after Heart Transplantation.

BACKGROUND: Limited data exist on the incidence and outcome of early infection after orthotopic heart transplantation (OHT). The purpose of this study was to describe characteristics and outcomes of OHT recipients with an early infection and to identify predictors of such infections. METHODS: This retrospective, single-center study included patients greater than 18 years of age who underwent OHT from February 2009 to May 2014 and had an infection within 30 days of transplantation. Patient demographics, clinical variables, and outcomes were collected. Multivariable logistic regression was performed to identify independent predictors of infection. RESULTS: Of the 172 eligible OHT recipients, 51 (29.7%) had an early infection. The median time to diagnosis was five days, with gram-negative organisms being slightly more common (58.2%). No differences in mortality rate, rejection, or re-admission were found between the groups. Longer durations of mechanical ventilation and lengths of stay were found in the infection group (p < 0.001). Patients with an early infection also had a higher incidence of mechanical circulatory support, history of drive-line infection, longer duration of mechanical ventilation, continuous renal replacement therapy (CRRT), and delayed chest closure (p < 0.05 for all). Pre-OHT left-ventricular assist device (adjusted odds ratio [AOR] 2.53; 95% confidence interval [CI] 1.015-6.286; p < 0.046), pre-OHT extracorporeal membrane oxygenation (AOR 14.10; 95% CI 1.38-150.5; p = 0.026) and post-OHT CRRT (AOR 3.98; 95% CI 1.67-9.52; p = 0.002) were found to be independent risk factors for an early infection. A total of 90% of the available susceptibility panels for the gram-negative isolates (26/29) were resistant to the standard peri-operative cephalosporin given. CONCLUSIONS: Prior mechanical circulatory support and the acute need for CRRT may predispose OHT patients to an infection early in the post-operative period. Evaluation of peri-operative antimicrobial prophylaxis, based on an individual center's resistance panels, may be warranted.

Use of adenosine diphosphate receptor inhibitor prior to left ventricular assist device implantation is not associated with increased bleeding.

Current guidelines recommend adenosine diphosphate receptor inhibitors (ADPRi) be discontinued 5-7 days prior to cardiac surgery due to increased bleeding events, rates of re-exploration, and transfusions. However, the risks of left ventricular assist device (LVAD) implantation in patients taking an ADPRi have not previously been studied. We retrospectively identified 134 eligible patients with ischemic cardiomyopathy that underwent LVAD implantation between July 2009 and August 2013. The cohorts received an ADPRi ≤5 days of surgery (n = 25) versus >5 days prior or not at all (n = 109). Subgroup analyses adjusted for differences in frequency of redo sternotomy between cohorts, excluded patients that received an ADPRi >1 year prior to surgery, and excluded patients with a redo sternotomy. The ADPRi and control groups did not have significant differences in the primary outcomes, intraoperative PRBC units transfused (3.0 vs. 4.0, p = 0.12) or chest tube output within 24 h of surgery (1.66 L vs. 1.80 L, p = 0.61). After adjusting for differences in frequency of redo sternotomy (ADPRi vs. control, 12 vs. 52%, p ≤ 0.001), no significant difference in PRBC units transfused (3.1 vs. 3.5, p = 0.59) or chest tube output (2.04 L vs. 2.04 L, p = 0.98) was seen. No significant difference in 30-day mortality (8.0 vs. 11.0%, p = 0.63), 90-day mortality (16.4 vs. 23.3%, p = 0.42), or length of stay (29.0 vs. 28.0, p = 0.61) was seen. In this single-center experience, use of an ADPRi ≤5 days prior to LVAD implantation was not associated with increased bleeding, length of stay, or mortality.

Consequences of avoiding ß-lactams in patients with ß-lactam allergies.

BACKGROUND: The choice of empiric antibiotics for the treatment of gram-negative bacilli (GNB) bloodstream infections (BSIs) in patients presenting with a ß-lactam (BL) allergy is often a difficult decision given that these agents are first-line treatment in many guidelines. OBJECTIVE: We sought to compare rates of clinical failure between patients with a history of BL allergy who received either a BL or a non-ß-lactam (NBL). METHODS: Adult patients with a past medical history of BL allergy and receipt of antibiotics for treatment of a GNB BSI were included from 3 academic medical centers. Treatment groups were classified as BL or NBL groups based on the empiric antibiotics received. Clinical failure was assessed 72 to 96 hours after initiation of empiric antibiotics. Hypersensitivity reactions during receipt of antibiotic therapy for the index BSI were recorded. RESULTS: A total of 552 patients were included for analysis: 433 patients in the BL group and 119 patients in the NBL group. Clinical failure was higher in the NBL group compared with the BL group (38.7% vs 27.4%, P = .030). The most common cause of clinical failure was a temperature of greater than 38.0°C 72 to 96 hours after receipt of empiric antibiotics (NBL group: 22.7% vs BL group: 13.9%, P = .016). Hypersensitivity occurred in 16 (2.9%) of 552 patients. Thirteen (2.5%) of 552 patients experiencing hypersensitivity reactions were exposed to a BL during treatment for GNB BSI. CONCLUSION: Among patients with a BL allergy, use of BL antibiotics is associated with a lower rate of clinical failure. The low rate of hypersensitivity provides further evidence about the risk of cross-reactivity between BL classes. These results support the practice of using a BL from an alternative class for patients in need of gram-negative antibiotic coverage.

Clinical outcomes with use of erythropoiesis stimulating agents in patients with the HeartMate II left ventricular assist device.

OBJECTIVES: This study evaluated clinical outcomes associated with erythropoiesis stimulating agent (ESA) use in left ventricular assist devices (LVAD)-supported patients. BACKGROUND: Use of ESAs in patients with LVADs may minimize blood transfusions and decrease allosensitization. ESAs increase thrombotic events, which is concerning because LVADs are sensitive to pump thrombosis (PT). METHODS: We retrospectively reviewed 221 patients at our center who received a HeartMate II (Thoratec Corp., Pleasanton, California) LVAD between January 1, 2009 and June 6, 2013. Patients were divided into those who received ESAs during index admission (n = 121) and those who did not (n = 100). Suspected PT was defined as evidence of thrombus in the LVAD or severe hemolysis (lactate dehydrogenase >1,000 mg/dl or plasma-free hemoglobin >40 mg/dl). Outcomes were compared between cohorts using inverse probability-weighted analyses. RESULTS: During a mean follow-up of 14.2 ± 11.9 months, suspected PT occurred in 37 patients (ESA 23%, no ESA 12%; p =0.03). The ESA cohort received ESAs 13.9 ± 60.9 days after LVAD implantation. At 180 days, event-free rates for suspected PT were ESA 78.6% versus no ESA 94.5% (p < 0.001). ESA use had higher rates of suspected PT (hazard ratio [HR]: 2.35; 95% confidence interval [CI]: 1.38 to 4.00; p = 0.002). For every 100-unit increase in cumulative ESA dosage, the hazard of suspected PT increased by 10% (HR: 1.10; 95% CI: 1.04 to 1.16; p < 0.001). After inverse probability weighting, ESA use was associated with a significantly higher rate of all-cause mortality (HR: 1.62; 95% CI: 1.12 to 2.33; p = 0.01). CONCLUSIONS: ESA use in LVAD patients is associated with higher rates of suspected PT.

Treatment of hypertension with chronotherapy: is it time of drug administration?

OBJECTIVE: To review evidence for dosing antihypertensives at bedtime and possible cardiovascular risk reduction. DATA SOURCES: A PubMed, EMBASE, and Cochrane Controlled Trials database literature search (1990-September 2014) limited to human subjects was performed using the search terms hypertension, chronotherapy, ambulatory blood pressure, morning administration, evening administration, and antihypertensives. Additional references were identified from literature citations. STUDY SELECTION: All prospective studies assessing cardiovascular outcomes or comparing morning to evening administration of antihypertensives were selected. DATA SYNTHESIS: Compared with morning administration, dosing one or more antihypertensive medications at bedtime helps induce a normal circadian blood pressure pattern and reduces the risk of cardiovascular disease morbidity and mortality in individuals with hypertension. Similar results have been reported in high-risk individuals with diabetes, chronic kidney disease, and resistant hypertension. A lack of diversity among studied populations and reliance on subgroup analyses are among the limitations of these data. All antihypertensive medications have not been studied in chronotherapy and do not uniformly achieve desired results. The most substantial evidence exists for medications affecting the renin-angiotensin-aldosterone system. CONCLUSIONS: Despite growing evidence and promise as a cost-effective strategy for reducing cardiovascular risk, chronotherapy is not uniformly recommended in the treatment of hypertension. Careful selection of patients and antihypertensives for chronotherapy is required. Further investigation is needed to evaluate the definitive impact of chronotherapy on cardiovascular outcomes.

Utilization of a computerized clinical surveillance system to increase acute myocardial infarction core measure compliance.

BACKGROUND: Clinical surveillance systems (CSS) are utilized by many health care institutions to help identify at-risk patients, prioritize care, improve the clinical services provided, and increase compliance with the Center for Medicare and Medicaid Services (CMS) core measures. OBJECTIVE: This study will assess the accuracy and practicality of a CMS acute myocardial infarction (AMI) alert, provided by the CSS Theradoc, designed to increase compliance with medications required at discharge in AMI patients. METHODS: This is a single-center, retrospective cohort review to determine the sensitivity and specificity of the Theradoc CMS AMI alert. All patients with a Theradoc CMS AMI alert were analyzed for AMI occurrence and omission of CMS-required discharge medications. Secondary endpoints regarding alert times and quantity were also assessed to address the practicality of implementing the alert. RESULTS: Data were collected on patients with alerts occurring between January 1, 2011, and December 31, 2011 (N = 962). The Theradoc CSS alert was found to have a sensitivity of 100% and specificity of 4.79%, signifying a gross amount of false positives. No modifications to the alert definitions or timing were able to increase the specificity to >10%. CONCLUSIONS: Regardless of the high sensitivity, the Theradoc CMS AMI alert does not have the appropriate level of specificity to utilize at the study institution at this time.

Clinical utility of azilsartan-chlorthalidone fixed combination in the management of hypertension.

Azilsartan-chlorthalidone fixed combination is a new drug in the management of hypertension. Azilsartan has been shown to have greater blood pressure-lowering effects than other angiotensin-receptor blockers (ARBs), and the debate regarding the superiority of chlorthalidone over hydrochlorothiazide has been ongoing for years. The combination is unique because it is the first to partner an ARB with this, possibly more effective, diuretic. This review will address trials involving both components of this drug, as well as phase III trials involving the fixed-combination product. The article will also discuss the benefit of combination therapy in the treatment of hypertension.

Hyperlipidemia medication management in patients admitted for a myocardial infarction / Manejo de la medicación para hiperlipemia en pacientes ingresados por infarto de miocardio

Objectives: The purpose of this study is to determine the percentage of patients admitted for acute myocardial infarction currently prescribed a statin, with low-density lipoprotein (LDL) <100 mg/dL, and high-density lipoprotein (HDL) <50 mg/dL for men and <55 mg/dL for women and evaluate their medication management with a focus on niacin initiation. Methods: This was a retrospective study from 12/07 to 12/09, conducted at a private, community hospital. Inclusion criteria required patients to have an acute myocaridal infarction (AMI) ICD-9 code, troponin >=0.2 ng/dL and lipid panel performed within 96 hours of troponin. Patients with a triglyceride level > 400 mg/dL were excluded. The residual risk population consisted of patients currently taking a statin with LDL <100 mg/dL and HDL <50/55 mg/dL. Patients were excluded from the residual risk population if they were on niacin, had an allergy to or previously failed niacin therapy, or expired within 72 hours. Results: A total of 553 patients experiencing an AMI had lipid panels available for evaluation. The mean LDL was 97.3 +/- 36.0 mg/dL, mean HDL was 33.5 +/- 11.1 mg/dL, and mean triglycerides were 133.1 +/- 71.3 mg/dL. The majority of patients (n=521, 94.2%) had an HDL < 50 or 55 mg/dL respective of gender. Ninety-two (80.0%) residual risk patients had no change in their home lipid medications post AMI. Fifteen (13.0%) residual risk patients had their dose of statin medication increased. Seven (6.1%) residual risk patients were initiated on niacin. Conclusions: The study results confirm an existence of a residual risk population with nearly 25% of AMI patients meeting the criteria. The results also confirm a low incidence of medication intervention in the residual risk population post AMI (20.0%) regarding lipid therapy, including the initiation of niacin in only 6.1% of patients (AU)

Objetivos: El propósito de este estudio es determinar el porcentaje de pacientes ingresados por un infarto agudo de miocardio que tienen actualmente prescrita una estatina, con lipoproteínas de baja densidad (LDL) <100mg/dL, y lipoproteínas de alta densidad (HDL) <50 mg/dL para hombres y <55 mg/dL para mujeres, y evaluar el manejo de su medicación centrándose en la iniciación a niacina. Métodos: Este fue un estudio retrospectivo de 12/07 a 12/09, realizado en un hospital comunitario privado. Los criterios de inclusión requerían que los pacientes tuviesen un código CIE-9 de infarto agudo de miocardio (IAM), troponina >=0.2 ng/dL y un panel lipídico realizado en las 96 horas de la troponina. Los pacientes con nivel de triglicéridos >400 mg/dL fueron excluidos. La población de riesgo residual consistió en pacientes que tomaban actualmente estatinas con LDL<100 mg/dL y HDL<50/55 mg/dL. Se excluía a los pacientes de la población de riesgo residual si estaban con niacina, tenían alergia o fallo previo a la niacina, o fallecieron en las 72 horas. Resultados: Un total de 553 pacientes que sufrieron un IAM tenían un perfil lipídico disponible para evaluación. La media de LDL fue de 97,3 (DE=36,0) mg/dL, la media de HDL fue de 33,5 (DE=11,1) mg/dL, y la media de triglicéridos fue de 133,1 (DE=71,3) mg/dL. La mayoría de los pacientes (n=521, 94.2%) tenían HDL<50 o 55 mg/dL, respectivamente del su género. 92 (80,0%) pacientes de riesgo residual no tuvo cambios en su medicación domiciliaria de lípidos después del IAM. A 15 (13,0%) pacientes de riesgo residual se le aumentó la dosis de estatinas. En 7 (6,1) pacientes de riesgo residual se inició la niacina. Conclusiones: Los resultados del estudio confirman la existencia de una población de riesgo residual de cerca del 25% de pacientes con IAM que satisface los criterios. Los resultados también confirman la baja incidencia de intervención en la población de riesgo residual post-IAM (20,0%) en relación al tratamiento para los lípidos, incluyendo la iniciación de niacina en sólo el 6,1% de los pacientes (AU)

Hyperlipidemia medication management in patients admitted for a myocardial infarction.

OBJECTIVES: The purpose of this study is to determine the percentage of patients admitted for acute myocardial infarction currently prescribed a statin, with low-density lipoprotein (LDL) <100 mg/dL, and high-density lipoprotein (HDL) <50 mg/dL for men and <55 mg/dL for women and evaluate their medication management with a focus on niacin initiation. METHODS: This was a retrospective study from 12/07 to 12/09, conducted at a private, community hospital. Inclusion criteria required patients to have an acute myocaridal infarction (AMI) ICD-9 code, troponin ≥0.2 ng/dL and lipid panel performed within 96 hours of troponin. Patients with a triglyceride level > 400 mg/dL were excluded. The residual risk population consisted of patients currently taking a statin with LDL <100 mg/dL and HDL <50/55 mg/dL. Patients were excluded from the residual risk population if they were on niacin, had an allergy to or previously failed niacin therapy, or expired within 72 hours. RESULTS: A total of 553 patients experiencing an AMI had lipid panels available for evaluation. The mean LDL was 97.3 ± 36.0 mg/dL, mean HDL was 33.5 ± 11.1 mg/dL, and mean triglycerides were 133.1 ± 71.3 mg/dL. The majority of patients (n=521, 94.2%) had an HDL < 50 or 55 mg/dL respective of gender. Ninety-two (80.0%) residual risk patients had no change in their home lipid medications post AMI. Fifteen (13.0%) residual risk patients had their dose of statin medication increased. Seven (6.1%) residual risk patients were initiated on niacin. CONCLUSIONS: The study results confirm an existence of a residual risk population with nearly 25% of AMI patients meeting the criteria. The results also confirm a low incidence of medication intervention in the residual risk population post AMI (20.0%) regarding lipid therapy, including the initiation of niacin in only 6.1% of patients.