The comorbidity conundrum: a focus on the role of noncardiovascular chronic conditions in the heart failure patient.

The rapid aging of the US population combined with improvements in modern medicine has created a new public health concern of comorbidity, a chronic condition that co-exists with a primary illness. Over 141 million Americans suffer from one or more comorbid conditions. In the heart failure (HF) patient, this comorbidity burden is particularly high, with over 40% of patients having five or more chronic conditions. These comorbidities can vary from being a risk factor to a cause of HF progression or even a precipitating factor for decompensation. Comorbidities, particularly the noncardiovascular conditions, have been associated with greater health resource utilization, poor health outcomes, and increased mortality. To minimize the negative impact that these comorbidities have on patient outcomes, appropriate attention should be paid to identifying, prioritizing, and managing each condition; minimizing medication complexity and polypharmacy; and improving overall coordination of care between providers and patients.

Carvedilol for the treatment of benign prostatic hypertrophy in patients with heart failure?

Heart failure (HF) and benign prostatic hypertrophy (BPH) are two conditions that commonly coexist in men 60 years and older. Carvedilol is the only ß-adrenergic blocker approved for HF that also has additional α1-adrenergic blockade. As α1-adrenergic blockers are used in the treatment of BPH, it is intuitive that carvediolol could improve BPH symptoms. We present a case where carvedilol was replaced with bisoprolol resulting in acute urinary retention. When carvediolol was reinstituted, the patient's symptoms of BPH resolved. Benign prostatic hypertrophy was later diagnosed by digital rectal exam. Six month after reinstituting the carvediolol, the patient remains free of his BPH symptoms. This case suggests that carvedilol may be considered for the management of HF with systolic dysfunction in patients with concomitant BPH thus eliminating the need for an α1-adrenergic blockers.

Clopidogrel desensitization: case report and review of published protocols.

The antiplatelet drug clopidogrel is an oral thienopyridine derivative that has been extensively used for the treatment and secondary prevention of a variety of cardiovascular diseases. Although clopidogrel is well tolerated by most patients, rare but serious hypersensitivity reactions have been documented, including cutaneous reactions and angioedema. An alternative thienopyridine that may be substituted for clopidogrel is ticlopidine; however, deleterious side effects from ticlopidine may occur, including diarrhea, neutropenia, and thrombocytopenia purpura, and cross-reactivity has been documented between these two thienopyridines. In cases of bare-metal stent deployment, cilostazol may be a safe and effective alternative; however, limited therapeutic data are available. In such cases, providers may need to administer a clopidogrel desensitization protocol; three clopidogrel desensitization protocols have been published. We describe a 58-year-old man who developed a generalized diffuse rash along his abdomen within 2 weeks of exposure to clopidogrel after drug-eluting stent placement. Clopidogrel was discontinued, and ticlopidine was begun. The rash resolved within 3 days of clopidogrel discontinuation. Using the Naranjo adverse drug reaction probability scale, we determined that the probability of clopidogrel causing the rash was probable (score of 8). Ticlopidine was subsequently discontinued due to severe diarrhea. Because of the patient's implanted stent and high risk for possible thrombosis, an 8-hour clopidogrel desensitization protocol was devised and successfully used in this patient, who continued to receive clopidogrel over the next year without rash recurrence. Based on our experience and the literature reviewed, administration of a clopidogrel desensitization protocol in patients with a history of isolated cutaneous hypersensitivity reactions, including angioedema, to clopidogrel can be a safe therapeutic alternative to ticlopidine or cilostazol.

Restless legs syndrome induced by escitalopram: case report and review of the literature.

Restless legs syndrome (RLS) is a sensorimotor disorder characterized by distressing sensations deep inside the limbs, typically occurring at bedtime or rest. These paresthesias involve an irresistible urge to move the limb, which provides temporary relief but at the expense of sleep and quality of life. The pathophysiology of RLS has been related to dopaminergic pathway dysfunction, thereby aligning it closely with depression from both pathophysiologic and treatment perspectives. Certain antidepressant drugs, including the selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), may induce or exacerbate RLS. We describe the case of a 34-year-old woman with no history of RLS who came to the emergency department with acute decompensated heart failure. After 7 days of hospitalization, she was waitlisted to receive a heart transplant. Her mood became depressed, and she requested a psychiatric consultation; escitalopram 10 mg at bedtime was started. Within 2 days of starting therapy, she developed very severe (determined by a score based on an RLS symptom rating scale) RLS symptoms, warranting the discontinuation of escitalopram. Within 2 days of stopping therapy, her RLS symptoms improved considerably (rated as mild). One week later, the patient was rechallenged with a lower dose of escitalopram, and her very severe RLS symptoms reappeared. Within 2 days of stopping escitalopram, her RLS symptoms again improved, with complete resolution 1 week later. Using the Naranjo adverse drug reaction probability scale, which assesses the probability of a drug causing an adverse event, the patient's score was 9, indicating a definite adverse drug reaction. Although published case reports have linked fluoxetine, sertraline, citalopram, paroxetine, and mirtazapine to RLS, this is the first report, to our knowledge, of escitalopram as a cause of RLS. Based on this case and additional data published with other SSRIs and SNRIs, we believe that escitalopram should be added to the list of agents that can induce RLS.

An alternative salvage regimen for Helicobacter pylori-resistant patients with heart failure.

Helicobacter pylori infects over 50% of the worldwide population. For eradication, European, Canadian, and American guidelines recommend a regimen consisting of a proton pump inhibitor, clarithromycin, and metronidazole or amoxicillin dosed twice daily for at least 7 days. When this treatment strategy fails, a complex, multidosed bismuth-based quadruple regimen is recommended. Unfortunately, for patients with heart failure, this salvage regimen can be potentially hazardous due to the drug-drug interaction with tetracycline and digoxin, as well as the large salicylate content with bismuth subsalicylate. As H. pylori infection is so prevalent, providers will most likely encounter such a therapeutic dilemma. A safe, effective, and simplistic alternative is a 10-day fluoroquinolone-based regimen consisting of a proton pump inhibitor, levofloxacin and either clarithromycin or amoxicillin. Levofloxacin demonstrates excellent bioavailability, widespread tissue and fluid distribution, extended half-life, limited drug interaction profile, low incidence of side effects, and remarkable activity against H. pylori with minimal primary resistance. Compared to the 7-day quadruple regimen, a 10-day levofloxacin-based regimen demonstrated a greater eradication rate, better tolerability, and a lower rate of therapy discontinuation. We briefly provide a summary of the data regarding this levofloxacin-based regimen and two successful cases from our heart failure clinic.

Elucidating the mechanism of action and potential interactions of MAO-B inhibitors.

A critical enzyme in neurotransmitter metabolism is monoamine oxidase (MAO). MAO occurs in two isoforms, MAO-A and MAO-B. MAO inhibitors are classified as selective for a particular subtype of MAO or nonselective and can be reversible or irreversible. Nonselective MAO inhibitors originally were studied as antidepressants. Newer MAO-B selective irreversible inhibitors are indicated for use in treatment of Parkinson's disease. MAO-B inhibitors offer modest antiparkinsonian effects, as they do not inhibit brain MAO-A effectively at the dose used in treating Parkinson's disease. In this article, the mechanism of action of MAO-B inhibitors, their potential neuroprotective effects, interactions such as the cheese reaction, and serotonin syndrome are discussed.

Effect of cost-sharing for prescription medications on health outcomes in older adults: a critical review of the literature and potential implications for managed care.

OBJECTIVE: To review the literature addressing the relationship between increased cost-sharing of prescription medications within a managed care setting and health outcomes in older adults. DATA SOURCE: A Medline/preMedline search (1950 to August 21, 2007) was conducted to identify pertinent peer-review studies with robust study designs specifically addressing cost-sharing of prescription medications and health outcomes. STUDY SELECTION AND DATA EXTRACTION: Studies were selected if they were conducted within a managed care environment, evaluated prescription medications, provided specifics regarding health outcomes, and did not focus on a solitary chronic disease state or medication class. Studies had to employ study designs with claims-based data sources in which cross-sectional or longitudinal variation in amount of co-payments or coinsurance occurred. DATA SYNTHESIS: From 61 articles, seven studies were selected, five addressing beneficiaries > or =65 years of age and two addressing those <65 years of age. Increases in cost-sharing in managed care organizations, particularly for the elderly, can result in greater use of health care services (e.g., emergency department visits and hospital admissions), with a possible increase in mortality. CONCLUSION: Based on the limited number of studies published, increased cost-sharing of prescription medications for elderly beneficiaries appears to exert negative effects on health outcomes and may be related to an increase in utilization of other health care services. If managed care organizations continue with their current policy of multi-tiered increases, the future may remain bleak for both the managed care organizations and their geriatric beneficiaries.

Posaconazole as salvage therapy in a patient with disseminated zygomycosis: case report and review of the literature.

Zygomycosis refers to any fungal infection originating from the class Zygomycetes and the order Mucorales. In immunocompromised patients, these fungi produce a relatively rapid, violently destructive, and highly fatal infection. Treatment approaches include both aggressive antifungal pharmacotherapy and surgical intervention. Unfortunately, even with optimal therapy, morbidity and mortality rates remain relatively high. As failure rates are elevated with commercial antifungals, new treatment options are needed. Posaconazole is an orally available, extended-spectrum triazole antifungal being investigated in phase III clinical trials for the treatment and prevention of invasive fungal infections, including zygomycosis. We report the case of a 26-year-old Vietnamese man with a medical history of acute lymphocytic leukemia who had undergone consolidation chemotherapy and had neutropenic fever when he came to the emergency department. The patient was admitted to the hospital and treated with broad-spectrum antibiotics and caspofungin. Two weeks into his admission, however, abscesses in the pelvis, prostate, and musculature surrounding the hip were detected radiographically; these abscesses eventually cultured for Mucor sp. Disseminated zygomycosis was diagnosed. Caspofungin was immediately discontinued, and high-dose liposomal amphotericin B 10 mg/kg/day was begun. Over the next month, infection spread to the right lung, left kidney, middle thoracic spine, and epidural space. As a result, oral posaconazole 200 mg 4 times/day was added to the liposomal amphotericin B. Significant clinical, hematologic, mycologic, and radiologic improvements were demonstrated as early as 10 days after start of posaconazole therapy and continued through 41 days of inpatient treatment. Liposomal amphotericin B was discontinued after 3 weeks of posaconazole, and the patient was discharged on hospital day 92 receiving oral posaconazole, with no major adverse events reported. Five months after discharge, the patient had no evidence of fungal disease recurrence or progression. Posaconazole appears to be a well-tolerated and effective salvage treatment for zygomycosis, including disseminated disease.

Should beta-blockers be used in the treatment of cocaine-associated acute coronary syndrome?

OBJECTIVE: To critically evaluate the 30 year debate of beta-blocker use in cocaine-induced acute coronary syndrome (CIACS). DATA SOURCES: An Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, and Ovid MEDLINE (1966-August 21, 2007) search of the medical literature was conducted using the key terms cocaine, myocardial infarction, acute coronary syndrome, and adrenergic beta-antagonists. STUDY SELECTION AND DATA EXTRACTION: All clinical trials, case reports, national cardiovascular guidelines, and reviews published in English were evaluated. Case reports were included based on whether (1) acute coronary syndrome was suspected, (2) a beta-blocker was used during the treatment course, and (3) objective and subjective patient-specific information was documented. DATA SYNTHESIS: Three case reports and 2 placebo-controlled trials were identified that used 4 beta-blockers (atenolol, labetalol, metoprolol, propranolol). Three national guidelines addressed beta-blocker use. Although published data are limited, propranolol and labetalol exert minimal to no effect on alleviating cocaine-induced coronary vasoconstriction. None of the evaluated national guidelines recommends beta-blockers as first-line agents in CIACS management. CONCLUSION: Beta-blockers should not be considered first-line agents for controlling chest pain in patients with documented CIACS. If long-term beta-blockade is warranted, its benefits should be weighed against recurrent use of cocaine and possible exacerbation of acute coronary syndrome. Given that carvedilol exhibits ancillary pharmacologic proprieties beneficial in CIACS, and post-myocardial infarction mortality data are available regarding its use, this agent could be considered to be appropriate therapy.

Evaluation of physical therapists' knowledge, attitudes, and professional use of dietary supplements: implications for practice and education.

PURPOSE: The objective of this cross-sectional study was to better define physical therapists' (PTs) knowledge, attitudes, and professional reported use of dietary supplements (DSs). METHODS: This study was approved by University of Colorado Investigational Review Board. A survey was developed and piloted to evaluate knowledge of supplement indications and serious side effects; comfort in performing medication and supplement histories and making therapeutic recommendations; and current practice and attitudes of supplement use and resource information. Therapists were identified through the Colorado Board of Physical Therapy. Five hundred surveys were mailed. Analysis of the survey items consisted of descriptive statistics and qualitative analysis of free text for themes and concepts. RESULTS: One-hundred eighty-four surveys were returned (38% response rate). Eighty-two percent were female. Forty-nine percent had a baccalaureate degree, 38 % master's degree, and 1.6 % Doctor of Physical Therapy. Over 50% practiced in an ambulatory setting. While 46% believed they were adequately educated on DS, only 50% of respondents could identify the correct indication for the designated supplement, while less than 6% one correct serious side effect, once efedra was excluded. For supplement information, more than 90% turned to non-peered review materials. Forty percent of therapist indicated that they were currently recommending DSs to their patients. Glucosamine, glucosamine with chondroitin, and methyl-sulfonylmethane comprised the top supplements suggested. CONCLUSIONS: PTs are recommending DS within their practice. While many therapists noted they were adequately educated, gaps in knowledge base were apparent. As physical therapy curricula continue to evolve, the addition of DS instruction should be considered a priority, as well as, steps put in place to provide additional education for practicing therapists.

Possible heart failure exacerbation associated with rosiglitazone: case report and literature review.

Increasing evidence suggests that neurohumoral manifestations of heart failure may lead to insulin resistance, predisposing patients with heart failure to the development of glucose intolerance or worsening of existing diabetes. Theoretically, insulin-sensitizing thiazolidinediones (TZDs) should be beneficial in this patient population. A 74-year-old man with well-compensated systolic dysfunction and longstanding type 2 diabetes mellitus treated with glyburide began therapy with rosiglitazone 4 mg/day, which was increased to 8 mg/day after 1 month. Two weeks later he was seen with a 5-kg weight gain, shortness of breath, bibasilar rales, +S3 gallop, and increased jugular venous distention. Twelve days later symptoms worsened, with pulmonary edema on chest radiograph, continued weight gain, and +4 pitting edema resistant to oral diuretics. The patient was admitted to the hospital for exacerbation of heart failure. Five days after discharge he was readmitted for similar symptoms, including an 11.8-kg weight gain. He reported adherence to drug therapy and diet. Rosiglitazone was immediately discontinued and 11 days later the man's weight stabilized to 79 kg and remained between 79 and 80 kg 2 and 3 months after discharge. This case demonstrates that TZDs may precipitate weight gain and pulmonary and peripheral edema in patients with stable heart failure. Earlier reports documented similar symptoms in patients without a history of heart failure. Although current recommendations state that TZDs should not be administered to patients with New York Heart Association class III or IV disease, practitioners should be aware that these adverse effects also may occur in patients with milder forms heart failure as well as those without heart failure.

QT interval prolongation and the risk of torsades de pointes: essentials for clinicians.

OBJECTIVE: QT interval prolongation signifies an increased risk of the life-threatening arrhythmia torsades de pointes (TdP). The purpose of this paper is to review the diverse methods for assessing and monitoring the risk of TdP, discuss risk factors for TdP, and recommend interventions that may mitigate the risk of TdP. METHODS: A non-systematic search of PubMed (through March 2013) was conducted to determine the optimal approach to assessing and monitoring QT interval, prevention of TdP, and to identify risks factors for TdP. Papers known to the authors were included, as were scientific statements. Articles were chosen based on the judgment of the authors. RESULTS: Risk factors for drug-induced TdP include hypokalemia, female sex, drug-drug interactions, advancing age, genetic predisposition, hypomagnesemia, heart failure, bradycardia, and corrected QT (QTc) interval prolongation. Many risk factors, including hypokalemia, use of QT-interval-prolonging drugs, and drug interactions are potentially modifiable and should be corrected in persons at risk for QT interval prolongation. Given the variable onset of TdP following initiation of QT-interval-prolonging drugs, careful and regular monitoring of electrocardiography (EKG) and electrolytes are necessary. Patients at risk for QT interval prolongation should be educated to go directly to the emergency room if they experience palpitations, lightheadedness, dizziness or syncope. When the QTc interval is 470-500 ms for males, or 480-500 ms for females, or the QTc interval increases 60 ms or more from pretreatment values, dose reduction or discontinuation of the offending drug should be considered where possible, and electrolytes corrected as needed. Furthermore, if the QTc interval is ≥500 ms, the offending drug should be discontinued, and continuous EKG telemetry monitoring should be performed, or the 12-lead EKG should be repeated every 2-4 hours, until the QT interval has normalized. CONCLUSIONS: Close monitoring for QTc prolongation is necessary to prevent TdP. The recommendations in this paper are limited by the available evidence and additional studies are needed to better define the approach to monitoring.

A citywide smoking ban reduced maternal smoking and risk for preterm births: a Colorado natural experiment.

BACKGROUND: Few reports exist on the association of a public smoking ban with fetal outcomes and maternal smoking in the United States. We sought to evaluate the effect of a citywide smoking ban in comparison to a like municipality with no such ban in Colorado on maternal smoking and subsequent fetal birth outcomes. METHODS: A citywide smoking ban in Colorado provided a natural experiment. The experimental citywide smoking ban site was implemented in Pueblo, Colorado. A comparison community was chosen that had no smoking ban, El Paso County, with similar characteristics of population, size, and geography. The two sites served as their own controls, as each had a preban and postban retrospective observation period: preban was April 1, 2001, to July 1, 2003; postban was April 1, 2004, to July 1, 2006. Outcomes were maternal smoking (self-report), low birth weight (LBW) (defined as <2500 g or as <3000 g), and preterm births (<37 weeks gestation) in singleton births from mothers residing in these cities and reported to the State Department of Public Health. A difference-in-differences estimator was used to account for site and temporal trends in multivariate models. RESULTS: Compared to El Paso County preban, the odds of maternal smoking and preterm births were, respectively, 38% (p<0.05) and 23% (p<0.05) lower in Pueblo. The odds for LBW births decreased by 8% for <3000 g and increased by 8.4% for <2500 g; however, neither was significant. CONCLUSIONS: This is the first evidence in the United States that population-level intervention using a smoking ban improved maternal and fetal outcomes, measured as maternal smoking and preterm births.

Costs and outcomes associated with clopidogrel discontinuation in Medicare beneficiaries with acute coronary syndrome in the coverage gap.

BACKGROUND: Current guidelines for acute coronary syndrome recommend clopidogrel for an optimal period of 12 months in order to reduce the risk of reinfarction and mortality. Premature clopidogrel discontinuation has been associated with higher rates of rehospitalization, coronary stent thrombosis, and mortality. No data exist regarding the effect of the Medicare Part D coverage gap on medical costs and outcomes in Medicare beneficiaries who discontinue their clopidogrel upon entering the coverage gap. METHODS: Beneficiaries with a Medicare Advantage plan in 2009 who had a diagnosis of acute coronary syndrome were taking clopidogrel 75 mg daily, and reached the gap in the same year representing the study sample. From this cohort, those who filled at least two prescriptions for clopidogrel (continued) versus those that did not (discontinued) while in the gap were compared with regard to outcomes related to acute coronary syndrome and expenditure 30 days after the last prescription was filled and during any time while in the gap. Descriptive and multivariate analyses were used to compare these differences. RESULTS: A total of 1365 beneficiaries with acute coronary syndrome met the inclusion criteria, of which 705 beneficiaries entered into the coverage gap, wherein 103 (14.6%) and 602 (85.4%) of beneficiaries discontinued and continued clopidogrel, respectively. Compared with those who continued clopidogrel during the gap, beneficiaries who discontinued clopidogrel showed a higher trend in the number of hospitalizations related to acute coronary syndrome and emergency room visits, albeit not statistically significant. Those who discontinued clopidogrel showed a higher mean adjusted cost per member per month in hospitalizations ($3604) related to acute coronary syndrome and outpatient visits ($1144) related to acute coronary syndrome and total medical costs ($5614), albeit not statistically significant. CONCLUSION: Medicare beneficiaries who face large out-of-pocket costs for clopidogrel while in the coverage gap and discontinue therapy may experience adverse events related to acute coronary syndrome.

A call to action: responding to the future forecasting of cardiovascular disease in america.

BACKGROUND: Cardiovascular disease (CVD) continues to be a leading cost driver for payers in the United States.1 The American Heart Association estimates that more than 75 million individuals nationwide have some form of CVD. Individuals aged 20 to 45 years are developing CVD at higher rates than ever before. OBJECTIVES: To discuss the alarming increase in the rate of CVD in young adults (aged 18-45 years) previously only seen in older adults (aged ≥65 years) and describe the 5 primary risk factors (smoking, obesity, hypertension, diabetes, and dyslipidemia) that contribute to this new trend in the working-age population. DISCUSSION: Using Medical Expenditure Panel Survey data, this article outlines the increased prevalence of the 3 primary components of CVD-stroke, heart failure, and myocardial infarction-in younger adults and the cost impact on payers and on US society. The examples provided in this article highlight the need for increased efforts by all healthcare stakeholders, and by payers in particular, to develop prevention strategies for CVD risk factors targeted at young adults to curb the alarming rise in CVD among this age-group. CONCLUSION: This article provides compelling evidence for the need to institute prevention measures to curb the growing prevalence of CVD risk factors among younger adults in the United States.

Effect of intravenous ondansetron on QT interval prolongation in patients with cardiovascular disease and additional risk factors for torsades: a prospective, observational study.

BACKGROUND: The 5-hydroxytryptamine type 3 antagonists, or setrons (eg, ondansetron), are commonly used for nausea and vomiting in the hospital setting. In 2001, droperidol was given a black box warning because it was found to prolong the QT interval and induce arrhythmias. The setrons share with droperidol the same potential proarrhythmic mechanisms, but limited data exist concerning their effects on the QT interval in individuals at high risk for torsades de pointes. METHODS: Forty hospitalized patients admitted for heart failure or acute coronary syndromes with one or more risk factors for torsades de pointes and an order for intravenous ondansetron 4 mg were enrolled in this prospective, observational study. The QT interval corrected for heart rate (QTc) was obtained via a 12-lead electrocardiogram on admission and again 120 minutes after the first dose of ondansetron in order to determine the mean change in QTc following ondansetron exposure. RESULTS: The mean time interval between obtaining the baseline electrocardiogram and the second electrocardiogram following ondansetron administration was 3.5 ± 2.14 hours. In the total population, the QTc interval was prolonged by 19.3 ± 18 msec (P < 0.0001) 120 minutes after ondansetron administration. For patients with an acute coronary syndrome and those with heart failure, QTc was prolonged by 18.3 ± 20 msec (P < 0.0001) and 20.6 ± 20 msec (P < 0.0012), respectively. Following ondansetron exposure, 31% and 46% in the heart failure and acute coronary syndromes groups, respectively, met gender-related thresholds for a prolonged QTc. CONCLUSION: Our study found QTc prolongation due to ondansetron administration similar to that found in previous studies. When used in patients with cardiovascular disease (eg, heart failure or acute coronary syndromes) with one or more risk factors for torsades de pointes, ondansetron may significantly increase the QTc interval for up to 120 minutes after administration. From a patient safety perspective, patients who are at high risk for torsades de pointes and receiving ondansetron should be followed via telemetry when admitted to hospital.