Heart Failure in Non-Caucasians, Women, and Older Adults: A White Paper on Special Populations From the Heart Failure Society of America Guideline Committee.

The presentation, natural history, clinical outcomes, and response to therapy in patients with heart failure differ in some ways across populations. Women, older adults, and non-Caucasian racial or ethnic groups compose a substantial proportion of the overall heart failure population, but they have typically been underrepresented in clinical trials. As a result, uncertainty exists about the efficacy of some guideline-directed medical therapies and devices in specific populations, which may result in the under- or overtreatment of these patients. Even when guideline-based treatments are prescribed, socioeconomic, physical, or psychologic factors may affect non-Caucasian and older adult patient groups to a different extent and affect the application, effectiveness, and tolerability of these therapies. Individualized therapy based on tailored biology (genetics, proteomics, metabolomics), socioeconomic and cultural considerations, and individual goals and preferences may be the optimal approach for managing diverse patients. This comprehensive approach to personalized medicine is evolving, but in the interim, the scientific community should continue efforts focused on intensifying research in special populations, prescribing guideline-directed medical therapy unless contraindicated, and implementing evidence-based strategies including patient and family education and multidisciplinary team care in the management of patients.

Advanced (stage D) heart failure: a statement from the Heart Failure Society of America Guidelines Committee.

We propose that stage D advanced heart failure be defined as the presence of progressive and/or persistent severe signs and symptoms of heart failure despite optimized medical, surgical, and device therapy. Importantly, the progressive decline should be primarily driven by the heart failure syndrome. Formally defining advanced heart failure and specifying when medical and device therapies have failed is challenging, but signs and symptoms, hemodynamics, exercise testing, biomarkers, and risk prediction models are useful in this process. Identification of patients in stage D is a clinically important task because treatments are inherently limited, morbidity is typically progressive, and survival is often short. Age, frailty, and psychosocial issues affect both outcomes and selection of therapy for stage D patients. Heart transplant and mechanical circulatory support devices are potential treatment options in select patients. In addition to considering indications, contraindications, clinical status, and comorbidities, treatment selection for stage D patients involves incorporating the patient's wishes for survival versus quality of life, and palliative and hospice care should be integrated into care plans. More research is needed to determine optimal strategies for patient selection and medical decision making, with the ultimate goal of improving clinical and patient centered outcomes in patients with stage D heart failure.

Acute decompensated heart failure: update on new and emerging evidence and directions for future research.

Acute decompensated heart failure (ADHF) is a complex clinical event associated with excess morbidity and mortality. Managing ADHF patients is challenging because of the lack of effective treatments that both reduce symptoms and improve clinical outcomes. Existing guideline recommendations are largely based on expert opinion, but several recently published trials have yielded important data to inform both current clinical practice and future research directions. New insight has been gained regarding volume management, including dosing strategies for intravenous loop diuretics and the role of ultrafiltration in patients with heart failure and renal dysfunction. Although the largest ADHF trial to date (ASCEND-HF, using nesiritide) was neutral, promising results with other investigational agents have been reported. If these findings are confirmed in phase III trials, novel compounds, such as relaxin, omecamtiv mecarbil, and ularitide, among others, may become therapeutic options. Translation of research findings into quality clinical care can not be overemphasized. Although many gaps in knowledge exist, ongoing studies will address issues around delivery of evidence-based care to achieve the goal of improving the health status and clinical outcomes of patients with ADHF.

Fatty infiltration of right ventricle (adipositas cordis): an unrecognized cause of early graft failure after cardiac transplantation.

Fatty infiltration of the right ventricle is usually an incidental finding at post-mortem, but may have clinical significance at times of physiologic stress. We report a case of fatal right ventricular dysfunction immediately after cardiac transplantation secondary to massive fatty infiltration of the donor right ventricle. Ante-mortem diagnosis of fatty infiltration may be difficult to determine despite non-invasive cardiac evaluation. If the diagnosis of fatty infiltration is suspected at time of donor harvest, the relative risks and benefits of proceeding with transplantation should be carefully assessed.

Association of angiotensin converting enzyme gene polymorphism with tachycardia cardiomyopathy.

Despite incessant tachycardia, not all patients develop tachycardia-mediated cardiomyopathy. The cardiac renin-angiotensin system may be involved in cardiac remodelling and fibrosis. The level of angiotension-converting enzyme (ACE) in the serum is associated with a 287 bp insertion (I)/deletion (D) polymorphism in intron 16 of the ACE gene. The DD genotype is associated with increased serum ACE levels and a higher incidence of idiopathic dilated and ischemic cardiomyopathy. The objective of this study was to assess whether the ACE gene I/D polymorphism is responsible for development of tachycardia-mediated cardiomyopathy. We identified 20 consecutive patients with persistent tachycardia and cardiomyopathy who showed significant improvement in ejection fraction after rate control (group A, tachycardia cardiomyopathy group). We compared the I/D genotype frequency of group A with the gene frequency of a separate group of 20 patents who, despite rapid atrial arrhythmias had preserved left ventricular ejection fraction (group B, tachycardia without cardiomyopathy group). These two groups were then compared with 24 healthy normal volunteers (group C). After a mean follow-up of 30 months, group A patients showed improvement in ejection fraction from 20+/-7 to 43+/-9% (p<0.001). Group A had a significantly higher frequency of the DD genotype than groups B and C (p-value <0.035 and <0.009 respectively). The profile of group B patients was intermediate between normal and patients with tachycardia-mediated cardiomyopathy. I/D polymorphism of the ACE gene may account for cardiomyopathy secondary to tachycardia.

Prognostic value of normal stress echocardiogram in patients with suspected coronary artery disease--a British general hospital experience.

AIMS: To determine the prognostic value of a normal stress echocardiogram in the setting of a large district general non-university hospital in the United Kingdom. METHODS: Between January 1996 and December 1999, all patients who had undergone stress echocardiography were identified and those with normal results were studied. Normal stress echocardiograms were found in 252 patients, 19 of whom were lost to follow-up. Deaths and nonfatal myocardial infarctions were considered hard cardiac events and data was collected in the remaining 233 patients. RESULTS: Among the 233 patients, the pre-test probability of coronary artery disease was low in 68 (27.9%) and intermediate or high in 168 (72.1%). During a follow-up period of mean (SD) 2.7 (1.1) years, death occurred in 4 patients of which 3 were consequent to acute myocardial infarctions and 1 was unexplained. One patient sustained a nonfatal infarction. Thus, the annualized mortality and hard event rates were 0.6% per patient/year and 0.8% per patient/year, respectively. CONCLUSIONS: A normal stress echocardiogram portends an excellent prognosis, even in a cohort with a high proportion of patients having intermediate or high pre-test probability of coronary artery disease.

Outcomes in patients with symptomatic cerebrovascular disease undergoing heart transplantation.

OBJECTIVES: We sought to determine outcomes in patients with and without symptomatic cerebrovascular disease (sCVD) undergoing heart transplantation. Second, we sought to determine factors associated with stroke in the perioperative period after heart transplantation. BACKGROUND: sCVD is considered a relative contraindication to heart transplantation. Despite this concern, outcomes in patients with sCVD undergoing heart transplantation have not been well defined. METHODS: Data on all single-organ heart transplants performed in the United States between April 1994 and December 2006 in patients age 40 years or older were analyzed. Survival analysis was performed to examine the effect of sCVD on the combined outcome of stroke or death, stroke, death, and functional decline, adjusting for potential confounding variables over long-term follow-up. In a separate analysis, predictors of perioperative stroke during the transplant-related hospitalization were examined using multiple logistic regression. RESULTS: There were 1,078 patients with and 16,765 patients without sCVD. The annualized rates of stroke or death (11.5% vs. 7.8%; p < 0.001), stroke (4% vs. 1.4%; p < 0.001), death (8.9% vs. 7.4%; p < 0.001), and functional decline (3.7% vs. 3.0%; p = 0.002) were higher in patients with sCVD than in patients without sCVD. In multivariable analysis, patients with sCVD were at increased risk of stroke or death (hazard ratio [HR]: 1.29; 95% confidence interval [CI]: 1.17 to 1.42), stroke (HR: 2.24; 95% CI: 2.02 to 2.87), and functional decline (HR: 1.21; 95% CI: 1.03 to 1.42) compared with those without sCVD. We did not identify a higher risk of death in patients with sCVD (HR: 1.08; 95% CI: 0.98 to 1.20), compared with those without sCVD. sCVD, ventilator use, and ventricular assist device use were the most important predictors of perioperative stroke. CONCLUSIONS: Patients with sCVD are at an increased risk of stroke and functional decline after transplantation independent of other variables, but not death, during long-term follow-up. These results should assist programs in making informed decisions in patients with sCVD who are undergoing evaluation for heart transplantation.

Emerging ventricular assist devices for long-term cardiac support.

Despite major advances in the treatment of heart failure over the past 2 decades improving the natural history of this condition, heart failure continues to be a major source of morbidity and mortality. Although availability of donor hearts for transplantation has declined over the past several years, innovations in ventricular assist device (VAD) technology has provided an alternative therapeutic option for patients with advanced heart failure. Initiated as a mechanical option to 'bridge' critically ill patients awaiting transplantation, VADs are being increasingly deployed as 'destination' devices to provide long-term support. With technical advances resulting in improved mechanical reliability, reduced postoperative morbidity and greater likelihood of patient acceptance, there is interest in expanding the applicability for destination VAD treatment beyond the current indication of severely ill patients who are not candidates for transplant. This Review examines the newer, third-generation VADs for mechanical cardiac support. These devices are at various stages of development and clinical investigation. One or more of these newer devices is likely to emerge as an important development in the treatment of patients with advanced heart failure.

Thyroid nodule and thyroid cancer management pre- and post-cardiac transplantation.

Thyroid nodules are common in the adult population. Widespread use of sensitive imaging studies often leads to their incidental discovery. Recent guidelines recommend thyroid-stimulating hormone determination and ultrasonography during initial nodule evaluation. Fine-needle aspiration is often performed to detect malignancy. However, the management of thyroid nodules in cardiac transplantation patients has not been directly addressed by recent guidelines. Confounding medications such as amiodarone and anti-coagulants present a management dilemma. The timing of fine-needle aspiration is crucial because (1) malignancy diagnosed pre-operatively usually precludes organ transplantation, and (2) patients undergoing solid-organ transplantation are at increased risk of developing de novo malignancies, including thyroid. With the rising incidence of thyroid cancer, donor-related malignancy will likely become a more prominent issue. This review addresses thyroid nodule management in the cardiac transplant population and provides recommendations for organ donation and transplantation in donors and recipients with thyroid cancer.

The effect of ventricular assist devices on post-transplant mortality an analysis of the United network for organ sharing thoracic registry.

OBJECTIVES: This study sought to determine the relationship between pre-transplant ventricular assist device (VAD) support and mortality after heart transplantation. BACKGROUND: Increasingly, VADs are being used to bridge patients to heart transplantation. The effect of these devices on post-transplant mortality is unclear. METHODS: Patients 18 years or older who underwent first-time, single-organ heart transplantation in the U.S. between 1995 and 2004 were included in the analyses. This study compared 1,433 patients bridged with intracorporeal and 448 patients bridged with extracorporeal VADs with 9,455 United Network for Organ Sharing status 1 patients not bridged with a VAD with respect to post-transplant mortality. Because the proportional hazards assumption was not met, hazard ratios (HRs) for different time periods were estimated. RESULTS: Intracorporeal VADs were associated with an HR of 1.20 (95% confidence interval [CI]: 1.02 to 1.43; p = 0.03) for mortality in the first 6 months after transplant and an HR of 1.99 (95% CI: 1.44 to 2.75; p < 0.0001) beyond 5 years. Between 6 months and 5 years, the HRs were not significantly different from 1. Extracorporeal VADs were associated with an HR of 1.91 (95% CI: 1.53 to 2.37; p < 0.0001) for mortality in the first 6 months and an HR of 2.93 (95% CI: 1.19 to 7.25; p = 0.02) beyond 5 years. The HRs were not significantly different from 1 between 6 months and 5 years, except for an HR of 0.23 (95% CI: 0.06 to 0.91; p = 0.04) between 24 and 36 months. CONCLUSIONS: Extracorporeal VADs are associated with higher mortality within 6 months and again beyond 5 years after transplantation. Intracorporeal VADs are associated with a small increase in mortality in the first 6 months and a clinically significant increase in mortality beyond 5 years. These data do not provide evidence supporting VAD implantation in stable United Network for Organ Sharing status I patients awaiting heart transplantation.

Influence of donor cocaine use on outcome after cardiac transplantation: analysis of the United Network for Organ Sharing Thoracic Registry.

Heart transplantation from donors with a history of cocaine abuse remains controversial. Therefore, we examined the consequence of donor cocaine-use history on all-cause mortality and the development of coronary artery disease after heart transplantation. Using the United Network for Organ Sharing Thoracic Registry we identified 9,217 first-time heart-only adult transplant recipients between January 1999 and December 2003, and then divided this cohort into sub-groups based on the reported history of donor cocaine use. Multivariate analysis revealed no difference in mortality or development of coronary artery disease at 1 and 5 years between transplant recipients who received an organ from donors with a history of cocaine use when compared with donors having no history of cocaine use.

Device therapy for the management of advanced heart failure.

Rapid advances have been made over the last decade in the nonpharmacological treatment of patients with advanced heart failure. This article reviews the current application of device therapy including cardiac resynchronization, defibrillators, cardiac restraint devices and mechanical ventricular support in patients with advanced heart failure.

Contemporary Medical, Surgical, and Device Therapies for End-stage Heart Failure.

Despite recent advances in medical therapy, mortality remains high following the diagnosis of heart failure (HF). Cardiac transplantation is still the standard surgical treatment option for highly selected patients with severe end-stage HF; however, it is only available to a small percentage of patients. The small number of available donor hearts is an inherent limitation on the ability of cardiac transplantation to greatly impact the management of advanced HF. The increased incidence and prevalence of HF in an ever aging and medically complex population has paved the way for alternative surgical and device treatment strategies. Some of these treatment options include ventricular reduction/remodeling surgery, mitral valve repair, mechanical ventricular assist device implantation, implantable cardioverter-defibrillators, and cardiac resynchronization therapy. Several recent trials have demonstrated the effectiveness of these therapies with regard to improvement in primary cardiac end points, HF symptoms, and survival. Surgical and device techniques are usually combined with optimal medical management of HF. The total cost and actual cost-effectiveness of employing these new therapeutic modalities in a growing population of HF patients remains to be determined.