Paul J. Hauptman

Knowledge and Practices of Generalist and Specialist Physicians Regarding Drug Therapy for Acute Myocardial Infarction

BACKGROUND The respective roles of generalist and specialist physicians in the care of patients is currently a matter of debate. Information is limited about the knowledge and practices of generalist and specialist physicians regarding conditions that both groups treat, such as myocardial infarction. METHODS We therefore surveyed 1211 cardiologists, internists, and family practitioners in the states of New York and Texas about four treatments demonstrated by randomized clinical trials to be associated with improved survival after myocardial infarction (thrombolytic therapy, immediate and long-term use of aspirin, and long-term use of beta-blockers) and two treatments for which such evidence is lacking (diltiazem for patients with pulmonary congestion and prophylactic lidocaine). We asked physicians about the effect of each treatment on survival and the likelihood that they would prescribe each class of drugs. RESULTS For the four beneficial treatments, the cardiologists believed more strongly than the internists and family physicians that survival was improved by the treatment, and they were more likely to prescribe these drugs (P < 0.001). For example, 94.1 percent of cardiologists said they were very likely to prescribe thrombolytic agents to treat an acute myocardial infarction, as compared with 82.0 percent of internists and 77.3 percent of family practitioners. Conversely, for the two treatments for which trials showed no evidence of a survival benefit, cardiologists were less likely than internists and family practitioners to think there was such a benefit and less likely to prescribe the drugs (P < 0.001). For example, 4.7 percent of cardiologists reported that they were very likely to use prophylactic lidocaine, as compared with 13.1 percent of internists, and 16.5 percent of family practitioners. When we used logistic regression to adjust for potential confounders, all the differences between the cardiologists and the internists and family practitioners remained significant (P < 0.02). CONCLUSIONS Internists and family practitioners are less aware of or less certain about key advances in the treatment of myocardial infarction than are cardiologists. This finding underscores the need to improve the dissemination of information from clinical trials to generalist physicians, particularly if they are to have an enlarged role in the evolving health care system.

Adherence to National Guidelines for Drug Treatment of Suspected Acute Myocardial Infarction: Evidence for Undertreatment in Women and the Elderly

BACKGROUND Evidence-based guidelines for the treatment of patients with acute myocardial infarction (AMI) have been published and disseminated by the American College of Cardiology and the American Heart Association. Few studies have examined the rates of adherence to these guidelines in eligible populations and the influence of age and gender on highly effective AMI treatments in community hospital settings. METHODS Medical records of 2409 individuals admitted to 37 Minnesota hospitals between October 1992 and July 1993 for AMI, suspected AMI, or rule-out AMI, and meeting electrocardiographic, laboratory, and clinical criteria suggestive of AMI were reviewed to determine the proportion of eligible patients who received thrombolytic, beta-blocker, aspirin, and lidocaine hydrochloride therapy. The effects of patient age, gender, and hospital teaching status on the use of these treatments were estimated using logistic regression models. RESULTS Eligibility for treatment ranged from 68% (n=1627) for aspirin therapy, 38% (n=906) for lidocaine therapy, and 30% (n=734) for thrombolytic therapy to 19% (n=447) for beta-blocker therapy. Seventy-two percent of patients eligible to receive a thrombolytic agent received this therapy; 53% received beta-blockers; 81% received aspirin; and 88% received lidocaine. Among patients ineligible for lidocaine therapy (n=1503), 20% received this agent. Use of study drugs was lower among eligible elderly patients, especially those older than 74 years (thrombolytic agent: odds ratio, 0.2; 95% confidence interval, 0.1 to 0.4; aspirin: odds ratio, 0.4, 95% confidence interval, 0.3 to 0.6; beta-blocker: odds ratio, 0.4; 95% confidence interval, 0.2 to 0.8). Female gender was associated with lower levels of aspirin use among eligible patients (odds ratio, 0.7; 95% confidence interval, 0.6 to 0.9); and there was a trend toward lower levels of beta-blocker and thrombolytic use among eligible women. CONCLUSIONS Use of lifesaving therapies for eligible patients with AMI is higher than previously reported, particularly for aspirin and thrombolytic use in nonelderly patients. Lidocaine is still used inappropriately in a substantial proportion of patients with AMI. Increased adherence to AMI treatment guidelines is required for elderly patients and women.

Parasympathetic Nervous System and Heart Failure Pathophysiology and Potential Implications for Therapy

Abundant evidence links sympathetic nervous system activation to outcomes of patients with heart failure (HF).1 In contrast, parasympathetic activation has complex cardiovascular effects that are only beginning to be recognized. In particular, the pathophysiological roles of normal and disordered parasympathetic innervation in patients with HF are not understood as comprehensively.2–5 In the present article, we review cardiovascular responses to parasympathetic activation, address the modulating factors that can affect parasympathetic function, discuss the role of the vagus nerve in ventricular dysfunction, and consider how activation of the parasympathetic nervous system may have important therapeutic implications for patients with congestive HF. The parasympathetic nervous system originates from medial medullary sites (nucleus ambiguous, nucleus tractus solitarius, and dorsal motor nucleus) and is modulated by the hypothalamus. Vagal efferents extend from the medulla to postganglionic nerves that innervate the atria via ganglia located in cardiac fat pads with neurotransmission that is modulated via nicotinic receptors. Postganglionic parasympathetic and sympathetic cholinergic nerves then affect cardiac muscarinic receptors (the Figure).6–8 Figure. Parasympathetic and sympathetic innervation of the heart: anatomy. Efferent fiber (vagus) comprises A-beta, A-delta, and unmyelinated C fibers. Reproduced from Martini FH. Fundamentals of Anatomy and Physiology . 8th ed. 2006. Chapter 20, by permission of Pearson Education, Inc Prentice Hall, copyright

Variation in the Use of Cardiac Procedures after Acute Myocardial Infarction

BACKGROUND There are large geographic differences in the frequency with which coronary angiography and revascularization are performed. We attempted to assess whether differences in case mix or in the treatment of specific groups of patients may explain this variability. We also assessed the consequences of various patterns of treatment. METHODS We studied patients covered by Medicare who were 65 to 79 years of age and were admitted to 478 hospitals with acute myocardial infarctions during 1990 in New York (1852 patients), where the rate of use of cardiac procedures is low, and in Texas (1837 patients), where the rate of use of such procedures is high. We compared the patterns of treatment of clinically similar groups of patients in the two states. We also compared mortality rates and measures of the health-related quality of life. RESULTS Coronary angiography was performed more often in Texas than in New York (45 percent vs. 30 percent, P < 0.001). The frequency of use in Texas was significantly higher than that in New York for all the clinical subgroups of patients analyzed except those at greatest risk for reinfarction. Over a two-year period, the adjusted likelihood of death was lower in New York than in Texas (hazard ratio, 0.87; 95 percent confidence interval, 0.78 to 0.98). Patients from Texas were 41 percent more likely to report angina (P = 0.002) and 62 percent more likely to say they could not perform activities requiring energy expenditure of 5 or more metabolic equivalents than patients from New York approximately two years after infarction (P < 0.001). CONCLUSIONS Physicians in Texas were more likely to perform angiography than physicians in New York for patients whose conditions allowed more discretion in the use of cardiac procedures. On average, there appears to be no advantage with respect to mortality or health-related quality of life to performing the procedures at the higher rate used in Texas.

ACCF/HRS/AHA/ASE/HFSA/SCAI/SCCT/SCMR 2013 appropriate use criteria for implantable cardioverter-defibrillators and cardiac resynchronization therapy

Steven R. Bailey, MD, FACC, FSCAI, FAHA, Moderator Andrea M. Russo, MD, FACC, FHRS, Writing Group Liaison [⁎][1] Suraj Kapa, MD, Writing Group Liaison Michael B. Alexander, MD, FACC[§][2] Steven R. Bailey, MD, FACC, FSCAI, FAHA[∥][3] Ulrika Birgersdotter-Green, MD, FHRS[∥][3] Alan S.

Delayed Hospital Presentation in Patients Who Have Had Acute Myocardial Infarction

The time from the onset of symptoms of acute myocardial infarction to hospital presentation has long been observed to correlate with in-hospital and long-term mortality [1]. With the advent of the thrombolytic era, delayed hospital presentation has been recognized as both the largest contributor to postponed treatment of acute myocardial infarction and a critical determinant of the initial management strategy. The findings of the large clinical trials of thrombolysis in acute myocardial infarction have consistently shown a relation between early treatment and improvements in short-term survival [2]. In the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries (GUSTO-1) trial [3], the 30-day mortality rates were 5.6% in patients who came to the hospital within 1 hour of symptom onset and 8.6% in patients who delayed presentation for more than 4 hours. The time between symptom onset and presentation is often the most important determinant of eligibility for thrombolytic therapy. Several population-based studies have confirmed a strong inverse association between the length of delay and the use of thrombolytic agents [4, 5]. For example, findings from the Worcester heart Attack Study [6] have indicated that patients arriving at the emergency department within 1 hour of the onset of acute symptoms are more than six times more likely to receive thrombolytic therapy than are patients presenting more than 6 hours after symptom onset. The identification of factors contributing to delayed hospital presentation in patients who have had acute myocardial infarction is essential to the development of appropriate patient-directed educational interventions to reduce delay. To examine this issue, we studied 2409 patients in whom acute myocardial infarction was suspected at the time of admission to 37 hospitals in Minnesota between October 1992 and July 1993. Methods Setting The Minnesota Clinical Comparison and Assessment Program is a quality improvement program of the Healthcare Education and Research Foundation that involves hospitals throughout Minnesota; the 45 participating hospitals account for 60% of all hospital admissions statewide. Of these hospitals, 37 participated in our study. Fifty-four percent of the study hospitals were located in urban areas. Fifty-one percent had fewer than 100 beds; 43% had 100 to 500 beds; and 5% had 500 or more beds. Two hospitals were academic medical centers, and the rest were community hospitals. Study Sample To define a sample of patients in whom acute myocardial infarction was suspected at the time of hospital presentation, all admissions to the study hospitals from October 1992 to July 1993 were retrospectively screened for the following admission diagnoses: acute myocardial infarction, rule-out acute myocardial infarction, and suspected acute myocardial infarction [7]. Information on clinical symptoms at the time of hospital presentation, as well as electrocardiographic results and serum enzyme levels during the first 24 hours of hospitalization, was obtained from medical records. Patients were included if they met two of the following clinical criteria: 1) typical symptoms of acute myocardial infarction [chest discomfort, arm or shoulder pain, diaphoresis, dyspnea, nausea or vomiting, and neck or jaw pain]; 2) explicit medical record documentation by a physician that electrocardiographic findings were considered compatible with acute myocardial infarction; and 3) elevated serum creatine kinase and MB isoenzyme levels that were above the upper limit of normal (as specified by the laboratory at each participating hospital). Of 4968 persons with the specified admission diagnoses, 2559 were excluded for the following reasons: failure to meet clinical criteria (44.4%); transfer from a nonstudy hospital (30.5%); inability to access the medical record (22.0%); history of myocardial infarction during the 2 weeks before the hospital admission of interest (2.7%); and death by the time of arrival at the hospital (0.4%). Length of Delay The amount of time that elapsed between the onset of symptoms suggestive of an acute coronary event and hospital presentation was categorized as follows: less than 2 hours, 2 to 6 hours, more than 6 hours to 12 hours, more than 12 hours to 24 hours, more than 24 hours to 72 hours, and more than 72 hours. Delay categories were defined a priori to be clinically relevant to making decisions about the management of acute myocardial infarction, particularly the use of thrombolytic therapy. Patients whose medical records indicated that they had developed symptoms within the day of admission but gave no additional information on timing were placed in a separate category. For analyses of the relation between various demographic and clinical factors and delay, we considered these patients to have presented to the hospital more than 12 hours to 24 hours after symptom onset; this time category was outside the window during which benefit could be achieved from thrombolytic therapy [2]. Patient Characteristics Demographic and socioeconomic variables of interest were age (<55, 55 to 64, 65 to 74, 75 to 84, or 85 years), sex, marital status (married, never married, widowed, or divorced), living arrangement (not alone, alone, or residing in a long-term care facility), location of residence based on ZIP code (urban or rural), employment status (employed, unemployed, or retired), and health insurance status (Medicare, health maintenance organization, or other commercial coverage; Medicaid; or no insurance). Each patient was also characterized according to the median income of the ZIP code of residence for 1993, obtained from U.S. census data. Use of emergency medical transport was determined from information in the medical record. Clinical characteristics noted at the time of admission included a history of hypercholesterolemia, hypertension, diabetes mellitus, angina, myocardial infarction, congestive heart failure, mechanical revascularization (percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery), family history of coronary artery disease, and previous use of sublingual nitroglycerin. Patients were characterized according to the presence or absence of chest discomfort as a symptom of acute myocardial infarction. We used the Index of Co-existent Disease to characterize the burden of comorbid disease among the study patients. Details on the development of this index and scoring guidelines have been described elsewhere [8, 9]. The index consists of two dimensions: 1) severity of coexisting medical conditions and 2) degree of physical impairment. These dimensions were determined on the basis of information contained in the medical record at the time of hospital admission. The assessments for both dimensions were condensed into a single composite index consisting of four levels that ranged from no coexisting disease or no significant physical impairment to severe coexisting disease or severe physical impairment (none, mild, moderate, severe). The day of symptom onset was characterized according to whether it was a weekday or occurred on a weekend. The time of day during which symptoms developed was categorized as follows: 6:00 a.m. to 11:59 a.m., noon to 5:59 p.m., 6:00 p.m. to 11:59 p.m., and midnight to 5:59 a.m. To determine the time-of-day category for a particular patient, the number of hours reflecting the midpoint of the delay category for that patient was subtracted from the time of hospital presentation. This measure was determined only for patients with delays of 24 hours or less because the relevance of this factor for patients with delays of more than 1 day was believed to be questionable. Data Collection and Integrity All information that was relevant to our study was abstracted from medical records. Trained nurse abstracters collected all data. Abstracters were required to show ongoing inter-rater agreement with a criterion review of 95% or higher. A random sample of 10% of each abstracters completed cases was retrospectively audited to ensure that this standard was met. Statistical Analysis Patients were classified according to whether the delay between onset of symptoms suggestive of acute myocardial infarction and hospital presentation was 6 hours or less or more than 6 hours. Factors potentially associated with a delay of more than 6 hours were first examined by using chi-square statistics. Logistic regression models were used to determine factors that were independently associated with delay of more than 6 hours. Regression models initially included terms for patient age, sex, marital status, living arrangement, location of residence, employment status, health insurance status, median income, presence of chest discomfort as a symptom, medical history (hypercholesterolemia, hypertension, diabetes mellitus, angina, myocardial infarction, congestive heart failure, mechanical revascularization, family history of coronary artery disease, and use of sublingual nitroglycerin), and Index of Co-existent Disease category. A term was also included in the model to indicate the day of the week on which symptoms developed. To examine the independent effect on delay of the time of day at which symptoms occurred, an analysis was done only for patients whose symptoms had lasted 24 hours or less. Final models were constructed by using the standard stepwise regression procedure available in SAS PROC LOGIST (SAS Institute, Cary, North Carolina) [10]; all dummy variables associated with a unique study characteristic were forced into the final model if any of the dummy variables was associated with a P value of 0.05 or less. Selected variables (age and sex) were forced into the models regardless of the significance level. Odds ratios and 95% CIs were calculated directly from the estimated regression coefficients and their SEs. Results Length of delay could be assigned for all but 5 of the 2409 patients (99.8%)

Causes of death and rehospitalization in patients hospitalized with worsening heart failure and reduced left ventricular ejection fraction: Results from efficacy of vasopressin antagonism in heart failure outcome study with tolvaptan (EVEREST) program

BACKGROUND The postdischarge rehospitalization and death rates are high in patients with acute heart failure (HF) syndromes despite optimization of standard therapy for chronic HF. To the best of our knowledge, there has been no systematic analysis of the causes of death and rehospitalization in this patient population. METHODS This was a prespecified analysis of adjudicated cause-specific all-cause mortality and cardiovascular (CV) hospitalization in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial, a randomized, double-blind, placebo-controlled study in patients hospitalized with worsening HF and left ventricular ejection fraction < or =40% comparing tolvaptan, an oral vasopressin receptor antagonist to placebo, in addition to standard care. RESULTS Of the 4,133 randomized, there were 5,239 rehospitalizations and 1,080 deaths during a median of 9.9 months. Of all deaths, 41.0% were due to HF, 26.0% due to sudden cardiac death (SCD), 2.6% due to acute myocardial infarction (MI), 2.2% due to stroke, and 13.2% due to non-CV causes. Of all hospitalizations, 39.2% were non-CV, whereas 46.3% were for HF, and a minority of hospitalizations was due to stroke, MI, arrhythmia, or other CV causes. CONCLUSIONS Despite close follow-up and evidence-based therapy within a clinical trial, rehospitalization and death remain high. Although most deaths were from HF, one quarter of patients had SCD. In addition, there were almost as many non-CV hospitalizations as HF hospitalizations. Knowledge of the causes of death and rehospitalization may be essential for proper management and early initiation of therapy.

Rationale and study design of the increase of vagal tone in heart failure study: INOVATE-HF.

BACKGROUND Imbalance between the parasympathetic and sympathetic nervous systems is a recognized contributor to progression of chronic heart failure. Current therapy with beta adrenergic antagonists is designed to moderate the up-regulation of norepinephrine and sympathetic effects; however, to date, there are no therapies that specifically address the withdrawal of parasympathetic influences on cardiac function and structure. METHODS/RESULTS In order to evaluate the impact of vagus nerve stimulation, an international multi-center randomized clinical trial (INOVATE-HF) has been designed to assess safety and efficacy of vagus nerve stimulation in symptomatic patients with heart failure on optimal medical therapy using the CardioFit System (BioControl Medical, Yehud, Israel). Up to 650 patients from 80 sites will be recruited and randomized in a 3:2 ratio to receive active treatment or standard optimal medical therapy. Inclusion criteria include left ventricular systolic dysfunction, the presence of New York Heart Association Class III symptoms, sinus rhythm, and QRS width less than 120 milliseconds. The study is powered to detect differences in the primary efficacy end point of all-cause mortality and heart failure hospitalization and 2 safety end points. CONCLUSION Vagal nerve stimulation with CardioFit as a treatment for symptomatic heart failure is under active investigation as a novel approach to restore balance between the sympathetic and parasympathetic nervous systems. If shown to be safe and effective in decreasing heart failure events and mortality, this novel approach will impact the treatment paradigm for heart failure.

Anxiety disorders increase risk for incident myocardial infarction in depressed and nondepressed Veterans Administration patients.

BACKGROUND Depression is a risk factor for incident myocardial infarction (MI), but little is known about the independent or additive risk from anxiety disorders. METHODS In a 7-year retrospective cohort design, we identified a cohort free of cardiovascular disease in fiscal years 1999 and 2000 that contained 96,612 patients between 25 and 80 years of age who had an International Classification of Diseases, Ninth Revision, Clinical Modification code indicating a diagnosis of depression in 2000 (baseline) and 259,387 patients without depression. Cox proportional hazards models stratified by depression were computed to test for a main effect of anxiety disorder unspecified, generalized anxiety disorder, panic disorder, social phobia, obsessive-compulsive disorder, and posttraumatic stress disorder (PTSD) on risk of incident MI. The models were adjusted for multiple MI risk factors and sociodemographics. RESULTS Depressed as compared to nondepressed Veterans Administration patients were at increased risk for incident MI (HR 1.39; 95% CI 1.34-1.45). In nondepressed patients those with anxiety disorder unspecified (HR 1.34; 95% CI 1.21-1.47), panic disorder (HR 1.43; 95% CI 1.11-1.83), and PTSD (HR 1.25; 95% CI 1.16-1.36) were at increased risk for incident MI. The independent risk associated with anxiety disorders was reduced in patients comorbid for depression. CONCLUSIONS In Veterans Administration patients free of heart disease in 1999 and 2000, those with depression, anxiety disorder unspecified, panic disorder, and PTSD were at increased risk of incident MI. Anxiety disorders are independent risk factors for MI. Depression partially accounts for the effect of anxiety disorders on risk of MI in patients with both conditions.

Implantable Cardiac Device Procedures in Older Patients: Use and In-Hospital Outcomes

BACKGROUND Although the effectiveness of implantable cardioverter defibrillators (ICDs) and cardiac resynchronization therapy (CRT) alone or in combination is well established, limited data are available on device use and short-term outcomes in older patients. We sought to characterize age-specific practices and outcomes among patients with heart failure undergoing device implantation using a large nationally representative administrative database. METHODS The cohort comprised patients older than 18 years with a diagnosis of heart failure who underwent implantation of an ICD or CRT between January 1, 2004, and December 31, 2005. Data included patient demographics, comorbidities, type of device, procedural complications, length of stay, total cost of hospitalization, and hospital characteristics. Multivariate stepwise logistic regression analysis was used to identify risk factors for in-hospital mortality. RESULTS We identified 26 887 patients who received an implantable device. The median age was 70.0 years (17.5% were > or =80 years), 72.6% were male, and 31.3% were of nonwhite race/ethnicity. Compared with younger patients, those 80 years or older were more likely to receive CRT alone. In-hospital mortality increased from 0.7% among patients younger than 80 years to 1.2% among those aged 80 to 85 years and 2.2% among those older than 85 years (P < .001). Independent predictors of in-hospital mortality included age 80 years or older, elevated comorbidity score, inotrope use, and procedure-related complications. CONCLUSIONS Despite the fact that most device trials have excluded patients 80 years or older, more than one-fifth of ICD and CRT devices are implanted in this age group. Advanced age is an independent predictor of in-hospital mortality following device implantation, suggesting that additional study is needed to define criteria for appropriate device use in older patients.