Inappropriate use of antiarrhythmic drugs in paroxysmal and persistent atrial fibrillation in a large contemporary international survey: insights from RealiseAF.

AIMS: International atrial fibrillation (AF) guidelines have defined optimal drugs for patients with various underlying diseases, but the extent to which real-life practice complies with these guidelines is unknown. This study aimed to evaluate the appropriate use of antiarrhythmic drugs (AADs) in patients with paroxysmal and persistent AF from the RealiseAF survey, according to the 2006 American College of Cardiology/American Heart Association/European Society of Cardiology AF guidelines. METHODS AND RESULTS: RealiseAF was an international cross-sectional, observational survey of 10 523 eligible patients from 26 countries on 4 continents, with ≥1 AF episode documented by standard electrocardiogram or by Holter monitoring in the last 12 months. Participating physicians were randomly selected during 2009-10 from lists of office-based or hospital-based cardiologists and internists. Overall, 4947 patients with paroxysmal (n = 2606) or persistent AF (n = 2341) were included; mean (standard deviation) age was 64.7 (12.4) and 66.0 (11.8) years, respectively. Class Ic drugs were prescribed in 589 patients (11.9%); however, in 20.0% of these patients, the indication was not consistent with published guidelines. Similarly, for the 219 patients prescribed sotalol (4.4%), 16.0% received treatment for an indication that deviated from the published guidelines. Amiodarone was prescribed as first-line therapy in 1268 patients (25.6%), but 49.9% of these did not have heart failure or hypertension with significant left ventricular hypertrophy. CONCLUSION: The use of AADs for persistent or paroxysmal AF in this large contemporary international survey showed some deviations from international guidelines. The highest discordance came with the use of amiodarone in first line. Clearly, there is a large discrepancy between published guidelines and current practice.

Extracorporeal ultrafiltration vs. conventional diuretic therapy in advanced decompensated heart failure.

Compared with conventional diuretic (CD) therapy, ultrafiltration (UF) is associated with greater weight loss and fewer re-hospitalizations in patients admitted with decompensated heart failure (HF). Concerns have been raised regarding its safety and efficacy in patients with more advanced heart failure. The authors conducted a single-center, prospective, randomized controlled trial in patients with advanced HF admitted to an intensive care unit for hemodynamically guided therapy, comparing UF (n=17) with CD (n=19) at admission. The primary end point was the time required for pulmonary capillary wedge pressure (PCWP) to be maintained at a value of ≤18 mm Hg for at least 4 consecutive hours. Secondary end points included levels of cytokines and neurohormones, as well as several clinical outcomes. In our study cohort, the time to achieve the primary end point was lower in the UF group but did not reach statistical significance (P = .08). UF resulted in greater weight reduction, higher total volume removed, and shorter hospital length of stay. There were no differences in kidney function, biomarkers, or adverse events. In patients with advanced HF under hemodynamically tailored therapy, UF can be safely performed to achieve higher average volume removed than CD therapy without leading to adverse outcomes.

Symptoms, functional status and quality of life in patients with controlled and uncontrolled atrial fibrillation: data from the RealiseAF cross-sectional international registry.

BACKGROUND: Rate control and rhythm control are accepted management strategies for atrial fibrillation (AF). OBJECTIVE: RealiseAF aimed to describe the success of either strategy and the impact of control on symptomatic status of patients with AF. METHODS: This international, observational, cross-sectional survey of patients with any history of AF in the previous year, recorded AF characteristics, management and frequency of control (defined as sinus rhythm or AF with resting heart rate ≤80 bpm). RESULTS: Overall, 9665 patients were evaluable for AF control, with 59.0% controlled (sinus rhythm 26.5%, AF ≤80 bpm 32.5%) and 41.0% uncontrolled. Symptom prevalence in the previous week was lower in controlled than uncontrolled AF (55.7% vs 68.4%; p<0.001) and similar for patients in sinus rhythm versus AF ≤80 bpm (54.8% vs 56.4%; p=0.23). At the visit, AF-related functional impairment (EHRA class >I) was seen in 67.4% of patients with controlled AF and 82.1% of patients with uncontrolled AF (p<0.001). Quality-of-life (QoL, measured using EQ-5D) was better for patients with controlled versus uncontrolled AF using the Visual Analogue Scale (mean (SD) score 67.1 (18.4) vs 63.2 (18.9); p<0.001), single index utility score (median 0.78 vs 0.73; p<0.001), or five dimensions of well-being (all p<0.001). Irrespective of AF control, cardiovascular events had led to hospitalisation in the past year in 28.1%. CONCLUSION: AF control is not optimal. Control appears to be associated with fewer symptoms and better QoL, but even patients with controlled AF have frequent symptoms, functional impairment, altered QoL and cardiovascular events. New treatments are needed to improve control and minimise the functional and QoL burden of AF.

The impact of left ventricular reconstruction on survival in patients with ischemic cardiomyopathy.

OBJECTIVE: Left ventricular reconstruction (LVR) is performed to improve the morphologic structure and function of the heart in patients with heart failure. This procedure has been performed at the Cleveland Clinic Foundation since 1997. We assessed mortality, functional status, and predictors of outcome in these patients. METHODS: Data were extracted from multiple prospectively acquired datasets on demographic, clinical, and operative details of 220 consecutive patients who underwent LVR between July 1997 and July 2003, where the indication for surgery was heart failure (of whom 66% had New York Heart Association (NYHA) functional class III or IV symptoms). Mortality, functional status, and postoperative complications were ascertained by reference to the clinical record, social security death index, and by phone contact. Mean preoperative left ventricular ejection fraction (LVEF) was 21.5+/-7.3% and mean left ventricular end-diastolic diameter was 6.4+/-1.0 cm. The mean age was 61.4+/-9.0 years and 80% were male. The majority (86%) of patients underwent concomitant coronary artery bypass grafting and 49% underwent mitral valve surgery. RESULTS: Thirty-day mortality was 1% and survival at 1, 3, and 5 years was 92%, 90%, and 80%, respectively. Of the survivors for whom data on NYHA functional class were available, 85% were in NYHA functional class I or II. Mortality was predicted by reduced preoperative ejection fraction <20% (unadjusted hazard ratio 1.53, p = 0.02), body mass index < or = 24 kg/m2 (unadjusted hazard ratio 1.69, p = 0.01), QRS duration > or = 130 ms (unadjusted hazard ratio 1.66, p = 0.01) and the requirement for renal replacement therapy postoperatively (unadjusted hazard ratio 3.85, p < 0.01). Mean LVEF improved to 24.7+/-8.86% (p < 0.01) and left ventricular volumes were also significantly reduced. CONCLUSIONS: In selected patients with heart failure, LVR, in conjunction with revascularization and valve surgery, is associated with excellent survival, improved symptoms, and improved LVEF and left ventricular dimensions.

Mycophenolate mofetil and risk of developing malignancy after orthotopic heart transplantation: analysis of the transplant registry of the International Society for Heart and Lung Transplantation.

BACKGROUND: Malignancy after organ transplantation has been described as the "price of immunotherapy." Evolving strategies aimed at effective immunosuppression could have differing effects on the likelihood of developing malignancy. We analyzed data from the transplant registry of the International Society for Heart and Lung Transplantation (ISHLT) to ascertain which factors are associated with the development of malignancy after orthotopic heart transplantation (OHT). METHODS: Multivariate modeling was performed to determine factors predictive of first post-transplant malignancy in patients taking standard immunosuppressive regimens, defined as cyclosporine or tacrolimus and azathioprine or mycophenolate mofetil (MMF), who underwent OHT between January 1, 1995 and December 31, 1997. RESULTS: Of the 3,895 transplants described in the cohort, 703 (18%) developed post-transplant malignancy at any time during the follow-up period, and 549 (14%) developed malignancy within the first 5 years post-transplant. The breakdown of malignancy was as follows: skin: 47%; post-transplant lymphoproliferative disease: 10%; other malignancies: 24%; combination of types: 10%; and unreported: 10%. Multivariate modeling revealed that independent predictors of increased risk were prior malignancy and increased age, whereas the use of MMF as part of a standard immunosuppressive regimen was associated with an adjusted relative risk (RR) = 0.73 (95% confidence interval 0.56 to 0.95). Relative to a recipient age of 55 years, the risk of malignancy for 30, 45 and 60 years of age was 0.32, 0.46 and 1.37, respectively. Although the use of tacrolimus appeared protective in the univariate analysis, it was not significant according to multivariate analysis. Female gender appeared to be protective. Neither OKT3 nor anti-thymocyte globulin (ATG) use was associated with a significantly increased risk of malignancy. CONCLUSIONS: The choice of immunosuppressive regimen may affect the likelihood of developing malignancy after OHT. Induction immunosuppression does not appear to increase the risk of subsequent malignancy. The use of MMF in standard immunosuppressive regimens is associated with a significantly lower risk of developing malignancy.

Residual high incidence of ventricular arrhythmias after left ventricular reconstructive surgery.

OBJECTIVE: Left ventricular reconstruction is performed in patients with ischemic cardiomyopathy and akinetic or dyskinetic left ventricular regions. These patients may remain at risk for malignant ventricular arrhythmias and hence may benefit from prophylactic implantable cardioverter-defibrillators. Specific guidelines for electrophysiologic testing and implantable cardioverter-defibrillator implantation in patients undergoing left ventricular reconstruction are lacking. We aimed to assess the residual risk and timing of ventricular arrhythmias after left ventricular reconstruction to determine whether electrophysiologic risk stratification or implantable cardioverter-defibrillator implantation can be safely deferred. METHODS: Data were prospectively gathered on 217 consecutive patients with left ventricular ejection fractions less than 40% undergoing left ventricular reconstruction at our institution from 1997 to 2002. Patients were divided into 3 groups: group 1, implantable cardioverter-defibrillator present before surgery; group 2, implantable cardioverter-defibrillator implanted early after surgery; and group 3, no implantable cardioverter-defibrillator implanted. End points were all-cause mortality (censored for cardiac transplantation) and appropriate implantable cardioverter-defibrillator therapies. RESULTS: Of 217 patients (mean age, 61 +/- 10 years [mean +/- SD]), survival after a median follow-up of 381 days was 90%. Electrophysiologic studies successfully identified patients at low risk. Appropriate implantable cardioverter-defibrillator therapies occurred in 20% of group 1 and 12% of group 2. The median time to the first implantable cardioverter-defibrillator therapy from the time of left ventricular reconstruction was 43 days, and most first therapies (67%) occurred within the first 63 days. CONCLUSIONS: The early event rates (occurring in the first 90 days after left ventricular reconstruction) support the use of predischarge electrophysiologic studies, implantation of implantable cardioverter-defibrillators before discharge from the hospital, or both.

Peak oxygen consumption as a predictor of death in patients with heart failure receiving beta-blockers.

BACKGROUND: Peak oxygen uptake (peak VO2) is a strong predictor of mortality and is commonly used in the evaluation of patients for cardiac transplantation. Beta-blockers reduce mortality in patients with heart failure, without influencing peak VO2, raising the possibility that peak VO2 is no longer suitable as an indicator of prognosis in these patients. METHODS AND RESULTS: We analyzed prospectively gathered data on 2105 patients referred for cardiopulmonary testing for all-cause mortality and for occurrence of death or transplantation. Patients receiving beta-blockers were younger, more likely to have coronary disease, and had a greater mean ejection fraction but had a similar peak VO2. There were 555 deaths (26%) and 194 (9%) transplants during a median follow-up of 3.5 years. Peak VO2 was a predictor of mortality irrespective of beta-blocker use; a decrease of 1 mL x kg(-1) x min(-1) resulted in an adjusted hazard ratio (HR) of 1.13 (95% CI 1.09 to 1.17, P<0.0001) in patients not receiving beta-blockers and 1.27 (95% CI 1.18 to 1.36, P<0.0001) in patients receiving beta-blockers. Similar findings were noted when considering death or transplantation as an end point. Beta-blocker use was associated with better outcomes until peak VO2 values became very low (approximately 10 mL x kg(-1) x min(-1)), at which level survival rates were equally poor. CONCLUSION: Peak VO2 is a determinant of survival in patients in heart failure even in the setting of beta-blockade. Because of improved survival in patients treated with beta-blockers, the cut point value of 14 mg x kg(-1) x min(-1) for referral for cardiac transplantation in these patients requires reevaluation, and a lower cut point may be more appropriate.

Brain natriuretic peptide levels do not correlate with acute cellular rejection in De Novo orthotopic heart transplant recipients.

BACKGROUND: The changes in brain natriuretic peptide (BNP) levels after orthotopic heart transplantation have not been previously described. The use of brain natriuretic peptide levels as a surrogate marker for cellular rejection remains controversial, with conflicting data. METHODS: We prospectively evaluated the potential utility of BNP levels in the first 6 months after transplantation and sought correlation with histologic grade of rejection and hemodynamic status. RESULTS: Thirty-five patients and 265 biopsy samples were included in the study. BNP levels did not correlate with histologic grade of rejection. They showed good correlation with central venous pressure and pulmonary capillary wedge pressure. BNP levels were elevated after transplant and showed a steep time-dependent decline. BNP levels correlated with echocardiographically derived indices of diastolic dysfunction. CONCLUSIONS: BNP levels are not a surrogate marker for rejection in the first 2 months after orthotopic heart transplantation and do not obviate the necessity for endomyocardial biopsy. Whether BNP levels have long-term prognostic significance is unclear and remains the subject of ongoing prospective study.

Is there an association between ephedra and heart failure? a case series.

BACKGROUND: Ephedra is a sympathomimetic commonly used for the purposes of athletic performance enhancement and weight loss. It is known to be associated with gastrointestinal and psychiatric manifestations. We report here on 6 cases of dilated cardiomyopathy associated with ephedra use. METHODS AND RESULTS: Over a period of 18 months, 6 patients attending our outpatient department with new onset heart failure were noted to have exposure to ephedra. The case record was reviewed and detailed clinical and echocardiographic data were extracted. All 6 patients (4 males) had left ventricular dysfunction at presentation (mean ejection fraction 20 +/- 5%) and were treated with conventional heart failure pharmacotherapy. All patients discontinued ephedra use as advised. New York Heart Association class improved from class III in 5 patients (class II in 1 patient) to class I, within a median of 6 months (range 3-96). Ejection fraction improved to a mean of 47 +/- 6%. CONCLUSIONS: Ephedra may be associated with left ventricular systolic dysfunction. Withdrawal of this agent, in conjunction with proven pharmacotherapy, results in a significant improvement in functional status and left ventricular ejection fraction. We recommend specific enquiry into the use of over-the-counter supplements, particularly ephedra and its derivatives, when being evaluated with heart failure symptoms. These cases illustrate the potential risk of ephedra and provide additional support for the recent decision to ban this supplement.

Contemporary outcomes of outpatients referred for cardiac transplantation evaluation to a tertiary heart failure center: impact of surgical alternatives.

BACKGROUND: The growing epidemic of congestive heart failure in the setting of limited donor-organ availability has mandated continued development and increased utilization of medical and surgical alternatives to cardiac transplantation. We sought to assess current disposition and outcomes of patients recently referred for transplant evaluation to a single high-throughput tertiary referral center. METHODS AND RESULTS: We performed a retrospective observational review of consecutive patients with advanced heart failure who were assessed initially in an outpatient setting by a heart failure cardiologist, with a view to transplant or nontransplant surgical alternatives between 1995 and 2000. Of 1174 consecutive referrals (mean age 55.1 [+/-12.7], 74% male), 588 (50%) were recommended for medical treatment (mean age 55.3 [+/-12.4], 72% male) and 200 (17%) for nontransplant surgery, principally coronary artery bypass grafting, mitral valve repair, infarct exclusion, partial left ventriculectomy, or combinations thereof (mean age 57.8 [+/-10.6], 76% male). A minority, 418 (36%), were initially listed for cardiac transplantation (mean age 53.5 [+/-13.9], 80% male). Of these, 74 (18% of listed) died waiting (34 on left ventricular assist device support), 45 were delisted (27 for improved clinical status), and 217 (18% of referred group) have been transplanted. The 3-year survival (Kaplan-Meier) was equivalent (82%) in the transplanted and nontransplant surgery groups (excluding partial left ventriculectomy patients). CONCLUSION: In current clinical practice less than one fifth of transplant referrals are ultimately transplanted, reflecting both a limited donor supply and the application of alternative, nontransplant strategies. Medium-term survival in patients suitable for alternative surgical strategies equals that of cardiac transplantation.

Severe frequent ventricular ectopy after exercise as a predictor of death in patients with heart failure.

OBJECTIVES: The study was done to determine the prognostic importance of frequent ventricular ectopy in recovery after exercise among patients with systolic heart failure (HF). BACKGROUND: Although ventricular ectopy during recovery after exercise predicts death in patients without HF, its prognostic importance in patients with significant ventricular dysfunction is unknown. METHODS: Systematic electrocardiographic data during rest, exercise, and recovery were gathered on 2,123 consecutive patients with left ventricular systolic ejection fraction

PET abnormalities in patients with nonischemic cardiomyopathy.

BACKGROUND: The abnormalities in dilated cardiomyopathy (DCM) are generally considered diffuse and to affect the left ventricle in a global manner. However, regional wall motion abnormalities and metabolic defects may also occur to varying, but unclear degrees. QRS width and metabolic defects on positron emission tomography (PET) correlate with survival. We sought to ascertain the prevalence of regional defects in DCM by multiple imaging modalities and to establish the relationship between QRS width and these defects. METHODS: In consecutive patients with advanced nonischemic DCM, undergoing cardiac transplant evaluation, we reviewed multiple imaging modalities (PET, 2-dimensional echocardiography, and radionuclide ventriculography) to quantify the incidence of regional metabolic and wall motion abnormalities and correlate them with clinical and electrocardiographic parameters. RESULTS: Of 44 patients studied, PET imaging revealed scar in 91% of patients, with a mean of 25 +/- 18% of the left ventricle involved, predominantly in the distribution of the left anterior descending artery. Regional wall motion abnormalities occurred in 51% of patients who underwent echocardiography and 59% of patients who underwent nuclear scintigraphy (with only 70% concordance). QRS duration on the surface electrocardiogram correlated positively with the degree of scarring (r=.52, P=.0007). CONCLUSIONS: The presence of scar (matched perfusion and metabolic defects) on PET scanning in patients with advanced DCM is not always indicative of coronary disease. Thus coronary angiography is usually required to define the etiology of systolic dysfunction. The extent of scar correlates with QRS duration. This may have implications for the application of cardiac resynchronization therapy.

Recent advances in the diagnosis of heart failure.

Heart failure has reached epidemic proportions and the prevalence is increasing. The accurate and efficient diagnosis of heart failure remains problematic, as signs and symptoms are neither sensitive nor specific. Recent advances in the diagnosis of this condition include a conceptual change in what constitutes heart failure, a greater understanding of heart failure with preserved systolic function, and an abundance of data supporting the use of neurohormonal assays, particularly brain-type natriuretic peptide. These factors will help facilitate earlier diagnosis and targeted treatment of patients with this malady.

Surgical Remodeling in Ischemic Cardiomyopathy.

Ischemic cardiomyopathy has a very poor prognosis, despite significant advances in pharmacologic therapy in the past decade. Orthotopic heart transplantation is an option for only a small minority of patients. Due to donor shortage and a finite outcome after transplant, nontransplant surgical intervention should be intensively investigated. Coronary artery bypass grafting improves survival in patients with demonstrated myocardial viability. Despite this, patients with the greatest left ventricular volumes do not show an improvement in outcomes. Surgical remodeling results in an improved stress-strain relationship and favorable myocardial remodeling. This may lead to improved survival, improvement in ventricular anatomy, and better quality of life. Surgical remodeling is often combined with revascularization, valve repair, and cardiac resynchronization therapy, along with optimal pharmacologic regimens, to provide a comprehensive therapeutic strategy for patients with this infirmity.