Clinical Syndrome Of Heart Failure Research Articles

The sympathetic nervous system in heart failure revisited.

Several attempts have been made, by the scientific community, to develop a unifying hypothesis that explains the clinical syndrome of heart failure (HF). The currently widely accepted neurohormonal model has substituted the cardiorenal and the cardiocirculatory models, which focused on salt-water retention and low cardiac output/peripheral vasoconstriction, respectively. According to the neurohormonal model, HF with eccentric left ventricular (LV) hypertrophy (LVH) (systolic HF or HF with reduced LV ejection fraction [LVEF] or HFrEF) develops and progresses because endogenous neurohormonal systems, predominantly the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS), exhibit prolonged activation following the initial heart injury exerting deleterious hemodynamic and direct nonhemodynamic cardiovascular effects. However, there is evidence to suggest that SNS overactivity often preexists HF development due to its association with HF risk factors, is also present in HF with preserved LVEF (diastolic HF or HFpEF), and that it is linked to immune/inflammatory factors. Furthermore, SNS activity in HF may be augmented by coexisting noncardiac morbidities and modified by genetic factors and demographics. The purpose of this paper is to provide a contemporary overview of the complex associations between SNS overactivity and the development and progression of HF, summarize the underlying mechanisms, and discuss the clinical implications as they relate to therapeutic interventions mitigating SNS overactivity.

Impact of lung transplantation on diastolic dysfunction in recipients with pretransplant pulmonary hypertension

ObjectivePulmonary hypertension can cause left ventricular diastolic dysfunction through ventricular interdependence. Moreover, diastolic dysfunction has been linked to adverse outcomes after lung transplant. The impact of lung transplant on diastolic dysfunction in recipients with pretransplant pulmonary hypertension is not defined. In this cohort, we aimed to assess the prevalence of diastolic dysfunction, the change in diastolic dysfunction after lung transplant, and the impact of diastolic dysfunction on lung transplant outcomes. MethodsIn a large, single-center database from January 2011 to September 2021, single or bilateral lung transplant recipients with pulmonary hypertension (mean pulmonary artery pressure > 20 mm Hg) were retrospectively identified. Those without a pre- or post-transplant echocardiogram within 1 year were excluded. Diastolic dysfunction was diagnosed and graded according to the American Society of Echocardiography 2016 guideline on assessment of diastolic dysfunction (present, absent, indeterminate). McNemar's test was used to examine association between diastolic dysfunction pre- and post-transplant. Kaplan–Meier and Cox regression analysis were used to assess associations between pre–lung transplant diastolic dysfunction and post–lung transplant 1-year outcomes, including mortality, major adverse cardiac events, and bronchiolitis obliterans syndrome grade 1 or higher–free survival. ResultsOf 476 primary lung transplant recipients, 205 with pulmonary hypertension formed the study cohort (mean age, 56.6 ± 11.9 years, men 61.5%, mean pulmonary artery pressure 30.5 ± 9.8 mm Hg, left ventricular ejection fraction < 55% 9 [4.3%]). Pretransplant, diastolic dysfunction was present in 93 patients (45.4%) (grade I = 8, II = 84, III = 1), absent in 16 patients (7.8%), and indeterminate in 89 patients (43.4%), and 7 patients (3.4%) had missing data. Post-transplant, diastolic dysfunction was present in 7 patients (3.4%) (grade I = 2, II = 5, III = 0), absent in 164 patients (80.0%), and indeterminate in 15 patients (7.3%), and 19 patients (9.3%) had missing data. For those with diastolic dysfunction grades in both time periods (n = 180), there was a significant decrease in diastolic dysfunction post-transplant (148/169 patients with resolved diastolic dysfunction; McNemar's test P < .001). Pretransplant diastolic dysfunction was not associated with major adverse cardiac events (hazard ratio [HR], 1.08, 95% CI, 0.72-1.62; P = .71), bronchiolitis obliterans syndrome–free survival (HR, 0.67, 95% CI, 0.39-1.56; P = .15), or mortality (HR, 0.70, 95% CI, 0.33-1.46; P = .34) at 1 year. ConclusionsDiastolic dysfunction is highly prevalent in lung transplant candidates with normal left ventricular systolic function and pulmonary hypertension, and resolves in most patients after lung transplant regardless of patient characteristics. Pre–lung transplant diastolic dysfunction was not associated with adverse lung or cardiac outcomes after lung transplant. Collectively, these findings suggest that the presence of diastolic dysfunction in lung transplant recipients with pulmonary hypertension has no prognostic significance, and as such diastolic dysfunction and the associated clinical syndrome of heart failure with preserved ejection fraction should not be considered a relative contraindication to lung transplant in such patients.

Heart Failure and Pancreas Exocrine Insufficiency: Pathophysiological Mechanisms and Clinical Point of View.

Heart failure is associated with decreased tissue perfusion and increased venous congestion that may result in organ dysfunction. This dysfunction has been investigated extensively for many organs, but data regarding pancreatic (exocrine) dysfunction are scarce. In the present review we will discuss the available data on the mechanisms of pancreatic damage, how heart failure can lead to exocrine dysfunction, and its clinical consequences. We will show that heart failure causes significant impairment of pancreatic exocrine function, particularly in the elderly, which may exacerbate the clinical syndrome of heart failure. In addition, pancreatic exocrine insufficiency may lead to further deterioration of cardiovascular disease and heart failure, thus constituting a true vicious circle. We aim to provide insight into the pathophysiological mechanisms that constitute this reciprocal relation. Finally, novel treatment options for pancreatic dysfunction in heart failure are discussed.

Left ventricular dysfunction with preserved ejection fraction: the most common left ventricular disorder in chronic kidney disease patients.

Chronic kidney disease (CKD) is a risk factor for premature cardiovascular disease. As kidney function declines, the presence of left ventricular abnormalities increases such that by the time kidney replacement therapy is required with dialysis or kidney transplantation, more than two-thirds of patients have left ventricular hypertrophy. Historically, much research in nephrology has focussed on the structural and functional aspects of cardiac disease in CKD, particularly using echocardiography to describe these abnormalities. There is a need to translate knowledge around these imaging findings to clinical outcomes such as unplanned hospital admission with heart failure and premature cardiovascular death. Left ventricular hypertrophy and cardiac fibrosis, which are common in CKD, predispose to the clinical syndrome of heart failure with preserved left ventricular ejection fraction (HFpEF). There is a bidirectional relationship between CKD and HFpEF, whereby CKD is a risk factor for HFpEF and CKD impacts outcomes for patients with HFpEF. There have been major improvements in outcomes for patients with heart failure and reduced left ventricular ejection fraction as a result of several large randomized controlled trials. Finding therapy for HFpEF has been more elusive, although recent data suggest that sodium-glucose cotransporter 2 inhibition offers a novel evidence-based class of therapy that improves outcomes in HFpEF. These observations have emerged as this class of drugs has also become the standard of care for many patients with proteinuric CKD, suggesting that there is now hope for addressing the combination of HFpEF and CKD in parallel. In this review we summarize the epidemiology, pathophysiology, diagnostic strategies and treatment of HFpEF with a focus on patients with CKD.

Novel Mechanisms of Anthracycline-Induced Cardiovascular Toxicity: A Focus on Thrombosis, Cardiac Atrophy, and Programmed Cell Death.

Anthracycline antineoplastic agents such as doxorubicin are widely used and highly effective component of adjuvant chemotherapy for breast cancer and curative regimens for lymphomas, leukemias, and sarcomas. The primary dose-limiting adverse effect of anthracyclines is cardiotoxicity that typically manifests as cardiomyopathy and can progress to the potentially fatal clinical syndrome of heart failure. Decades of pre-clinical research have explicated the complex and multifaceted mechanisms of anthracycline-induced cardiotoxicity. It is well-established that oxidative stress contributes to the pathobiology and recent work has elucidated important central roles for direct mitochondrial injury and iron overload. Here we focus instead on emerging aspects of anthracycline-induced cardiotoxicity that may have received less attention in other recent reviews: thrombosis, myocardial atrophy, and non-apoptotic programmed cell death.

Milestones in Heart Failure: How Far We Have Come and How Far We Have Left to Go

Heart failure is a clinically complex syndrome that results due to the failure of the ventricles to function as pump and oxygenate end organs. The repercussions of inadequate perfusion are seen in the form of sympathetic overactivation and third spacing, leading to clinical signs of increased blood pressure, dyspnea, fatigue, palpitations, etc. This article provided a brief overview of the clinical syndrome of heart failure; its epidemiology, risk factors, symptoms, and staging; and the mechanisms involved in disease progression. This article also described several landmark trials in heart failure that tested the efficacy of first-line drugs such as beta-blockers, angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and the latest drugs in the field of heart failure: angiotensin receptor neprilysin inhibitors. Most studies described in this article were guideline-setting trials that revolutionized the practice of medicine and cardiology.

Gender variability in the clinical phenotype of hypertrophic cardiomyopathy

Abstract Introduction Hypertrophic cardiomyopathy (HCM) is a structural heart disease defined by an increase in left-ventricular (LV) wall thickness, that may be complicated with a clinical syndrome of heart failure, arrhythmia and death. Purpose To characterize the clinically significant factors for female HCM patients and bring forward the awareness to gender-based differences in HCM. Methods We reviewed the patient records of 1297 patients age ≥18 years, diagnosed with HCM, from two tertiary medical centers in Spain and Israel, and analyzed 748 male and female patients matched for age ≥60 years at admission, BMI, hypertension, diabetes and obstructive HCM. Results Female patients were older at original diagnosis [median 54 years (38–66) vs. 50 years (35–60), p=0.007], and had higher rates of family history of both HCM (46% vs. 37%, p=0.01) and sudden cardiac death (23% vs. 15%, p=0.02). Female patients had lower rates of active smoking (11% vs. 25%, p&amp;lt;0.001) and coronary disease (3% vs. 8%, p=0.007). In echocardiographic studies, females had a smaller LV cavity both during diastole [median 42mm (39–46) vs. 46 (42–50), p&amp;lt;0.001] and during systole [median 24 (21–29) vs. 27 (23–31), p&amp;lt;0.001]. Female patients had higher rates of significant mitral insufficiency (37% vs. 19%, p&amp;lt;0.001), and despite no significant differences in the rates of obstructive HCM, diastolic dysfunction, left-atrial enlargement, atrial fibrillation, ventricular tachyarrhythmia or pulmonary disease, they also had more significant pulmonary hypertension (≥45mmHg, 29% vs. 14%, p&amp;lt;0.001). Women had a lower functional capacity (p&amp;lt;0.001 for differences in NYHA, see fig.), and lower exercise capacity [median 7.0 METs (5–10) vs. 10.0 (7–12), p&amp;lt;0.001) and more abnormal blood pressure response to exercise (35% vs. 26%, p=0.03). Electrocardiographic features were similar across genders, except for a non-clinically significant shorter QRS duration in females. No significant differences were seen in 5-year mortality follow-up, which was ∼3% in the entire cohort. Conclusions Female patients suffering from HCM have a clinical phenotype defined by slightly later presentation (and shorter time until admission to a tertiary-center cardiomyopathy clinic), smaller LV cavity size, higher severity of mitral insufficiency and pulmonary hypertension and worse functional and exercise capacities. Genders did not differ in 5-year mortality, which was relatively low. Functional and exercise capacity Funding Acknowledgement Type of funding source: None

The Spectrum of Pregnancy-Associated Heart Failure Phenotypes: An Echocardiographic Study.

Compare echocardiographic phenotypes of women presenting with peripartum heart failure. A retrospective case-control study of pregnant women (n = 86) presenting with PP-HF symptoms (i.e., dyspnea, PND, orthopnea) and objective examination and laboratory findings (lung congestion, elevated JVP and/or HJR, elevated brain natriuretic peptide [BNP] and pulmonary edema on chest X-ray). Three distinct phenotypes based on echocardiographically-defined LVEF were identified: (a) PP-HF with preserved ejection fraction (PP HFpEF, LVEF: > 50%); (b) PP-HF with midrange ejection fraction (PP HFmrEF, LVEF: 40-50%); c) PP-HF with reduced ejection fraction (PP HFrEF, LVEF: < 40%); these were compared with 17 pregnant subjects without PP-HF symptoms/findings. Most patients were African American (n = 63; 73%), with low prevalence of hypertension (n = 15, 17%) or diabetes mellitus (n = 5, 5%); pre-eclampsia was highly prevalent (n = 52, 60%). Echocardiographically-defined phenotypes (HFpEF, n = 37; HFmrEF, n = 18; HFrEF, n = 31) showed progressively worse abnormalities in LV remodeling (LV enlargement, LV hypertrophy), LV diastolic function, and right ventricular function; the three PP-HF groups had comparable abnormalities in increased left atrial size and estimated peak tricuspid valve regurgitation velocity. Compared to controls, all three groups had significantly increased filling pressures, LV mass index and left atrial volume index. Peripartum women presenting with the clinical syndrome of heart failure exhibit a spectrum of echocardiographic phenotypes. Significant abnormalities in LV structure, diastolic function, LA size, peak TR velocity and RV function were identified in women with preserved and mid-range EFs, suggesting pregnancy-related cardiac pathophysiologic derangements.

Defining cardiotoxicity of doxorubicin and trastuzumab.

e23097 Background: Doxorubicin and trastuzumab have been described to cause clinical heart failure and asymptomatic declines in left ventricular ejection fraction (LVEF). Initial studies of doxorubicin in the 1970’s defined cardiotoxicity by the clinical syndrome of heart failure without imaging for LVEF determination. Trials with adjuvant trastuzumab used various LVEF cut-offs that were arbitrarily determined. This study aims to compare the predictive value of commonly used definitions of cardiotoxicity associated with chemotherapy for the development of clinical heart failure. Methods: A retrospective chart review was performed on an IRB approved cohort of 638 patients with breast cancer who received doxorubicin, trastuzumab, or both and who had baseline and follow up echocardiograms, collecting LVEF values for each echocardiogram. Clinical heart failure was determined by formal cardiology evaluations denoting clinical heart failure in patients. Four different definitions of cardiotoxicity were compared; American Society of Echocardiography (ASE), Cardiac Review and Evaluation Committee (CREC), Alexander et al, and Schwartz et al (Table). Results: Only 8 patients (1.25%) developed clinical heart failure. The sensitivity, specificity, positive predictive value, and negative predictive value of each definition of cardiotoxicity are listed in the table. Conclusions: Overall there is a low threshold for detection of clinical heart failure in breast cancer therapy. While the ASE definition has the highest combination of sensitivity, specificity, and positive predictive value, it has a sensitivity of only 62.5%. Thus, cardiologists and oncologists should collaborate to develop a definition of cardiotoxicity better correlated to clinical outcomes. [Table: see text]

Treatment of Heart Failure With Preserved Ejection Fraction (HFpEF): the Phenotype-Guided Approach.

The syndrome of heart failure with preserved ejection (HFpEF) continues to rise in prevalence without persuasive evidence of current pharmacologic interventions that can reduce mortality. Clinical trials thus far have generally enrolled "all-comers" with the clinical syndrome of heart failure and objective evidence of a preserved ejection fraction. However, HFpEF is increasingly understood to be a heterogeneous syndrome likely borne from the interplay of genetic predisposition, lifestyle factors, and high burden of associated comorbidities with each contributing to a variety of incompletely understood pathophysiologic abnormalities. Complicating management further, such abnormalities appear to be present to varying degrees among individual patients. Ongoing studies, along with the use of computational statistics/machine learning, offer the hope of clarifying the pathophysiological substrates giving rise to the syndrome of HFpEF in different patient subsets. With better understanding of the syndrome's underpinnings, there will be the potential for development of truly targeted therapies. However, for now, there is substantial evidence for the use of currently available pharmacologic device and lifestyle therapy for the optimized management of patients. Such therapy can be tailored to presently identifiable patient clusters-called "phenotypes"-distinguished by both the presence of predominant presenting symptoms and/or predominant comorbidity profiles. Examples of clinical presentation phenotypes include lung congestion, chronotropic incompetence, pulmonary hypertension, or skeletal muscle weakness as predominant features. Additionally, such patients may have underlying metabolic syndrome, systemic (arterial) hypertension, renal dysfunction, atrial fibrillation, and/or coronary artery disease as principal underlying comorbidities. Here, we review a "phenotype-guided" approach to the management of patients with HFpEF, based on a stepwise method of making the HFpEF diagnosis, identifying the prominent sources of organ dysfunction, and treating accordingly.

Focused Treatment of Heart Failure with Reduced Ejection Fraction Using Sacubitril/Valsartan.

The clinical syndrome of heart failure (HF) can be described as the reduced capacity of the heart to deliver blood throughout the body. To compensate for inadequate tissue perfusion, the renin–angiotensin aldosterone system (RAAS) and the sympathetic nervous system (SNS) become activated, resulting in increased blood pressure, heart rate, and blood volume. Consequent activation of the natriuretic peptide system (NPS) typically balances these effects; however, the NPS is unable to sustain compensation for excessive neurohormonal activation over time. Until recently, mortality benefits have been provided to patients with HF only by therapies that target the RAAS and SNS, including angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists, and beta-blockers. Sacubitril/valsartan, the first-in-class angiotensin receptor/neprilysin inhibitor (ARNI), targets both the NPS and RAAS to further improve clinical outcomes. This review discusses the focused management of patients with HF with reduced ejection fraction (HFrEF) and suggests changes to current management paradigms. From this assessment, the evidence supports favoring sacubitril/valsartan over ACEIs or ARBs, and this therapy should be used in conjunction with beta-blockers to further decrease morbidity and mortality in patients with HFrEF.

Recognition, Diagnosis, and Management of Heart Failure with Preserved Ejection Fraction

The clinical syndrome of heart failure with preserved ejection fraction (HFpEF) is unique in terms of etiologies, diagnostic criteria, costs, and treatment modalities when compared to heart failure with reduced ejection fraction. There is an emerging paradigm shift that recognizes the clinical syndrome of HFpEF and its various phenotypes. Understanding these HFpEF phenotypes is crucial to understanding the pathophysiology of HFpEF, which in turn can further guide our management strategies. This review outlines the diagnostic criteria, introduces the common clinical phenotypes, and discusses treatments currently utilized in practice for the management of HFpEF.

Long-term management of end-stage heart failure.

End-stage heart failure manifests as severe and often relentless symptoms that define the clinical syndrome of heart failure, namely congestion and hypoperfusion. These patients suffer from dyspnea, fatigue, abdominal discomfort, and ultimately cardiac cachexia. Renal and hepatic dysfunction frequently further complicates the process. Recurrent hospitalizations, cardiac arrhythmias, and intolerance to standard heart failure therapies are common as the disease progresses. Management focuses on controlling symptoms, correcting precipitants, avoiding triggers, and maximizing therapies with demonstrable survival benefit. Among appropriate candidates, advanced therapies such as orthotopic heart transplant (OHT) can significantly extend survival and improve the quality of life. Left ventricular assist devices have been used with increasing frequency as a bridge to OHT or as a destination therapy in appropriately selected candidates where they have a demonstrable mortality benefit over medical therapy. Importantly, a multidisciplinary patient-centered approach is crucial when considering these advanced therapies.

The kidney in heart failure: an update.

Heart and kidney are closely related in the clinical syndrome of heart failure (HF). It is now sufficiently clear that renal dysfunction occurs frequently in all phenotypes of HF, and when present, it is associated with higher mortality and morbidity. While the pathophysiology is multifactorial, the most important factors are a reduced renal perfusion and venous congestion. Recent interest has focused on worsening renal function (WRF), a situation strongly related to mortality, but seemingly only when HF status deteriorates. Unfortunately, to date clinicians are unable to identify specifically those patients with a grim prognosis following WRF. Although much has been learned on cardiorenal interaction in HF, still more questions have been left unanswered. The coming decade should provide us with more dedicated epidemiologic, mechanistic, and controlled trials in HF patients with reduced renal function. An updated classification of the cardiorenal syndrome that incorporates recent evidence and points towards areas of interest and uncertainties, and areas where progress is needed could facilitate this process. Ultimately, this should lead to preventive and treatment strategies that can preserve renal function and associated outcome in patients with HF.

Epidemiology and prognosis of heart failure

Heart failure (HF) is a major and growing health problem in western communities. Recent data indicate that more than 50% of patients with the clinical syndrome of HF have a preserved left ventricular ejection fraction (HF with preserved ejection fraction, HFpEF). In contrast to the calculated expectations, the observed incidence of HF is rising. Despite the fact that the relative proportion of patients with preserved left ventricular function is also increasing, other factors, such as ageing of the population and the concomitant change of compound risk factors may also contribute to the actual rise in the incidence of HF. Patients with HF suffer from reduced exercise capacity, impaired quality of life and also from recurrent hospitalization due to HF. Over the past decades, an increase of recurrent HF events has been documented. In contrast to earlier reports in which HFpEF was considered to be more benign than HF with reduced ejection fraction (HFrEF), recent data suggest that once hospitalized for HF, patients with HFpEF and those with HFrEF have a comparable prognosis in terms of morbidity and mortality. Despite increasing clinical and economic relevance, no treatment has yet been shown to convincingly reduce mortality in HFpEF. In contrast, strategies for improving survival have now been established for HFrEF. The problem of HF will continue to be major challenge for the healthcare systems in western communities; therefore, consolidated clinical research is necessary to further improve therapeutic strategies for HFrEF and to generally establish treatment options for HFpEF.

‘Hearts and minds’: association, causation and implication of cognitive impairment in heart failure

The clinical syndrome of heart failure is one of the leading causes of hospitalisation and mortality in older adults. An association between cognitive impairment and heart failure is well described but our understanding of the relationship between the two conditions remains limited. In this review we provide a synthesis of available evidence, focussing on epidemiology, the potential pathogenesis, and treatment implications of cognitive decline in heart failure. Most evidence available relates to heart failure with reduced ejection fraction and the syndromes of chronic cognitive decline or dementia. These conditions are only part of a complex heart failure-cognition paradigm. Associations between cognition and heart failure with preserved ejection fraction and between acute delirium and heart failure also seem evident and where data are available we will discuss these syndromes. Many questions remain unanswered regarding heart failure and cognition. Much of the observational evidence on the association is confounded by study design, comorbidity and insensitive cognitive assessment tools. If a causal link exists, there are several potential pathophysiological explanations. Plausible underlying mechanisms relating to cerebral hypoperfusion or occult cerebrovascular disease have been described and it seems likely that these may coexist and exert synergistic effects. Despite the prevalence of the two conditions, when cognitive impairment coexists with heart failure there is no specific guidance on treatment. Institution of evidence-based heart failure therapies that reduce mortality and hospitalisations seems intuitive and there is no signal that these interventions have an adverse effect on cognition. However, cognitive impairment will present a further barrier to the often complex medication self-management that is required in contemporary heart failure treatment.

Peripheral reflex feedbacks in chronic heart failure: Is it time for a direct treatment?

Despite repeated attempts to develop a unifying hypothesis that explains the clinical syndrome of heart failure (HF), no single conceptual paradigm for HF has withstood the test of time. The last model that has been developed, the neurohormonal model, has the great virtue of highlighting the role of the heart as an endocrine organ, as well as to shed some light on the key role on HF progression of neurohormones and peripheral organs and tissues beyond the heart itself. However, while survival in clinical trials based on neurohormonal antagonist drugs has improved, HF currently remains a lethal condition. At the borders of the neurohormonal model of HF, a partially unexplored path trough the maze of HF pathophysiology is represented by the feedback systems. There are several evidences, from both animal studies and humans reports, that the deregulation of baro-, ergo- and chemo-reflexes in HF patients elicits autonomic imbalance associated with parasympathetic withdrawal and increased adrenergic drive to the heart, thus fundamentally contributing to the evolution of the disease. Hence, on top of guideline-recommended medical therapy, mainly based on neurohormonal antagonisms, all visceral feedbacks have been recently considered in HF patients as additional potential therapeutic targets.

Sex- and gender-specific research priorities for the emergency management of heart failure and acute arrhythmia: proceedings from the 2014 Academic Emergency Medicine Consensus Conference Cardiovascular Research Workgroup.

The emergency department (ED) is the point of first contact for patients with acute heart failure and arrhythmias, with 1 million annual ED visits in the United States. Although the total numbers of men and women living with heart failure are similar, female patients are underrepresented in clinical studies, with current knowledge predominantly based on data from male patients. This has led to an underappreciation of the sex-specific differences in clinical characteristics and pathophysiology-based management of heart failure. Similar disparities have been found in management of acute arrhythmias, especially atrial arrhythmias that lead to an increased risk of stroke in women. Additionally, peripartum and postpartum cardiomyopathy represent a diagnostic and treatment dilemma. This article is the result of a breakout session in the cardiovascular and resuscitation work group of the 2014 Academic Emergency Medicine consensus conference "Gender-Specific Research in Emergency Medicine: Investigate, Understand, and Translate How Gender Affects Patient Outcomes." A nominal group technique was used to identify and prioritize themes and research questions using electronic mail, monthly conference calls, in-person meetings, and Web-based surveys between June 2013 and May 2014. Consensus was achieved through three rounds of nomination followed by the meeting on May 13, 2014, and resulted in seven priority themes that are essential to the common complex clinical syndrome of heart failure for both men and women and include the areas of pathophysiology; presentation and symptomatology; and diagnostic strategies using biomarkers, treatment, and mortality, with special consideration to arrhythmia management and pregnancy.

Racial and Ethnic Differences in Heart Failure Etiology, Prognosis, and Management

Heart failure (HF) remains a major health care burden for the USA. Racial/ethnic groups in the USA are at increased risk for developing HF and incur higher rates of morbidity. Understanding the variations in the clinical syndrome of HF among different racial/ethnic groups is fundamental to addressing how to effectively treat these sub-groups. Despite evidence-based guideline-recommended medical and device therapy for HF, eligible patients from various racial/ethnic groups suffer disparities in receiving guideline-based HF therapy. The initiation of performance improvement programs has improved adherence to guideline-based therapy. The racial/ethnic differences that exist regarding the etiology and responses to medical therapy are fundamental to addressing ways to improve access to care, adherence, and overall survival in these at-risk groups. The review outlines racial/ethnic variations in the etiology, prognosis, and management with medical and device therapy for HF.

Myocardial Mechanics in Cardiomyopathies

Cardiomyopathies are a heterogeneous group of diseases that can be phenotypically recognized by specific patterns of ventricular morphology and function. The authors summarize recent clinical observations that mechanistically link the multidirectional components of left ventricular (LV) deformation with morphological phenotypes of cardiomyopathies for offering key insights into the transmural heterogeneity of myocardial function. Subendocardial dysfunction predominantly alters LV longitudinal shortening, lengthening and suction performance and contributes to the phenotypic patterns of heart failure (HF) with preserved ejection fraction (EF) seen with hypertrophic and restrictive patterns of cardiomyopathy. On the other hand, a more progressive transmural disease results in reduction of LV circumferential and twist mechanics leading to the phenotypic pattern of dilated cardiomyopathy and the clinical syndrome of HF with reduced (EF). A proper characterization of LV transmural mechanics, energetics, and space-time distributions of pressure and shear stress may allow recognition of early functional changes that can forecast progression or reversal of LV remodeling. Furthermore, the interactions between LV muscle and fluid mechanics hold the promise for offering newer mechanistic insights and tracking impact of novel therapies.