Discrepancy between cardiac and physical functional reserves in stroke.

BACKGROUND AND PURPOSE: Understanding the physiological limitations to exercise after stroke will assist the development of targeted therapies to improve everyday function. This study defines (1) whether exercise capacity is limited by the cardiovascular system (oxygen supply) or skeletal muscles (oxygen utilization); and (2) cardiac function and pumping capability in people with stroke. METHODS: Twenty-eight male participants with mild ischemic stroke (70 ± 6 years of age, 18 ± 20 months poststroke) and 25 male, age-matched healthy control subjects performed a graded cardiopulmonary exercise test with gas exchange and noninvasive hemodynamic measurements. Maximal oxygen extraction was calculated as the ratio between peak oxygen consumption and peak cardiac output. Cardiac function and pumping capability were assessed by peak exercise cardiac power output (expressed in watts) and cardiac output. RESULTS: Peak oxygen consumption (18.4 ± 4.6 versus 26.8 ± 5.5 mL/kg/min, P<0.01) and arterial-venous O(2) difference (9.3 ± 2.5 versus 12.6 ± 1.9 mlO(2)/100 mL of blood, P<0.01) were both reduced in stroke participants compared with healthy control subjects. In contrast, peak exercise cardiac power output (4.79 ± 0.79 versus 4.51 ± 0.96 W, P=0.49), cardiac output (16.4 ± 3.1 versus 17.1±2.5 L/min, P=0.41), and the pressure-generating capacity of the heart (127±11 versus 125 ± 14 mm Hg, P=0.97) were similar between stroke participants and healthy control subjects. CONCLUSIONS: The ability of skeletal muscles to extract oxygen is diminished after stroke. However, cardiac function and pumping capability are maintained. Appropriate therapies targeting muscle oxygen uptake such as exercise rehabilitation may improve exercise capacity after stroke.

Short-axis 2D strain from speckle tracking predicts echocardiographic response to cardiac resynchronization therapy.

AIMS: Two-dimensional (2D) strain imaging from speckle tracking is a Doppler independent technique allowing assessment of left ventricular (LV) strain (ɛ); systolic strain rate (SRs') and early diastolic strain rate (SRe') in the radial and circumferential planes. We set out to investigate whether (i) these parameters facilitated assessment of dyssynchronous contraction and (ii) these measures could predict response to cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Forty-one patients with severe, symptomatic heart failure on optimal medical therapy were recruited. Thirty-two healthy subjects were used as controls. Time to peak ɛ, SRs', and SRe' of 6 LV segments were measured in the parasternal short axis prior to and 6 weeks post CRT implantation. Time delays between segments were then calculated and ANOVA assessed for prediction of response, classified as reduction in LV end systolic volume of >15%. 2D strain demonstrated significantly more dyssynchronous contraction in the heart failure population at baseline compared to healthy controls. Significant reduction in dyssynchrony was seen in ɛ and SRs' following CRT, largely confined to those with evidence of remodeling. The time delay between peak circumferential SRs' of opposing walls was the best predictor of reverse remodeling. CONCLUSION: 2D strain imaging appears to be a useful measure to predict response to CRT. The time to peak circumferential SR is a new predictor of response.

Reduced cardiac functional reserve and quality of life in adults with GH deficiency.

INTRODUCTION: Patients with severe GH deficiency (GHD) suffer with a reduced quality of life in addition to diverse changes in cardiac size and performance. So far, the cardiac reserve ability to maintain the circulation during peak exercise has not been measured. We tested the hypothesis that patients with severe GHD have reduced cardiac reserve function compared with healthy controls and that this could explain, in part, their reduced quality of life. AIMS: Eighteen patients with severe GHD and an assessment of GHD in adults (AGHDA) score > or =11 (mean 20.0, range 12-25) were studied and compared with 18 age-, sex- and body mass index-matched healthy controls. Peak cardiac power and cardiorespiratory fitness were investigated using noninvasive haemodynamic measurements during maximal cardiopulmonary exercise testing. RESULTS: Compared with matched controls, the cardiac power of GHD patients during exercise to volitional exhaustion was significantly reduced by 15% (mean +/- SD 4.4 +/- 1.0 W vs. 5.2 +/- 1.0 W, P = 0.02). Patients with GHD also had lower cardiac chronotropic reserve (peak heart rate 154 +/- 21/min vs. 174 +/- 11/min, P = 0.001) and a lower cardiac pressure-generating capacity (systolic blood pressure 160 +/- 25 mmHg vs. 200 +/- 15 mmHg, P < 0.0001). We found no correlation between any measure of peak cardiac power or function and the AGHDA score. CONCLUSION: Using this robust noninvasive method of assessing functional cardiac pumping capacity, we have for the first time shown that, while patients with severe GHD have a significantly impaired cardiac functional reserve associated with chronotropic incompetence and impaired pressure-generating capacity, this does not correlate with their reduced quality of life assessed using the current standard AGHDA score.

A prospective longitudinal evaluation of the benefits of epicardial lead placement for cardiac resynchronization therapy.

AIMS: Cardiac resynchronization therapy (CRT) is a recognized treatment for appropriate patients. However, placement of the transvenous left ventricular lead is unsuccessful in 5-10% of patients and a further 20% fail to respond. For these groups, epicardial left ventricular lead placement is one alternative. We prospectively evaluated the effects of epicardial vs. transvenous placed CRT. METHODS AND RESULTS: Twenty-three subjects with unsuccessful transvenous coronary sinus lead placement underwent epicardial implantation. The subjects underwent clinical evaluation, cardiopulmonary exercise testing, and echocardiography before 3 and 6 months after. The results were compared with a control group (n = 35) who had received transvenous CRT. In both groups, there were significant improvements in all measures at 3 and 6 months. The improvement in peak VO(2) was delayed in the epicardial group compared with the transvenous group. At 6 months, the improvements seen in all variables showed no difference between the groups. CONCLUSION: Epicardial lead placement is a viable option for patients with unsuccessful coronary sinus lead placement. The improvements in most variables were of a similar magnitude and over a similar time scale compared with transvenous placement. Improvements in peak VO(2) were delayed in the epicardial group, probably as a result of a prolonged recovery time.

Medium-term results of surgical ventricular restoration with papillary muscle realignment: providing additional benefits in enlarged ischemic left ventricle.

In 2001, we described a new surgical technique of surgical ventricular restoration (SVR) in severe heart failure by papillary muscle re-alignment and volume reduction. This procedure has been offered in our institution to patients with severely impaired left ventricular function. Here we examine our mid-term results and also compare them with a similar cohort of patients who had coronary artery bypass grafting (CABG) only. Between 1998 and 2005, 30 patients underwent SVR by papillary muscle realignment with coronary artery revascularization at our institution. A subset of 20 patients had their left ventricular volume measured by echocardiogram and MRI scan, and a maximal cardiopulmonary exercise test was performed before and after the operation. An unselected consecutive cohort of patients with matching age, gender, and hemodynamic status who underwent CABG only without SVR was tested using the same protocol and the results were compared. We noticed that there was a significant advantage for patients who had additional SVR over patients who had CABG only. The observed improvement in those who had SVR may be due to reduced metabolic mismatch as a result of reduced wall tension and normalization of the apical twist of the left ventricle. We believe this would provide a form of surgical treatment for heart failure secondary to ischemic cardiomyopathy at a time of reduced donor organ availability for transplant.

Left Ventricular Assist Device as a Bridge to Recovery for Patients With Advanced Heart Failure.

BACKGROUND: Left ventricular assist devices (LVADs) have been used as an effective therapeutic option in patients with advanced heart failure, either as a bridge to transplantation, as destination therapy, or in some patients, as a bridge to recovery. OBJECTIVES: This study evaluated whether patients undergoing an LVAD bridge-to-recovery protocol can achieve cardiac and physical functional capacities equivalent to those of healthy controls. METHODS: Fifty-eight male patients-18 implanted with a continuous-flow LVAD, 16 patients with LVAD explanted (recovered patients), and 24 heart transplant candidates (HTx)-and 97 healthy controls performed a maximal graded cardiopulmonary exercise test with continuous measurements of respiratory gas exchange and noninvasive (rebreathing) hemodynamic data. Cardiac function was represented by peak exercise cardiac power output (mean arterial blood pressure × cardiac output) and functional capacity by peak exercise O2 consumption. RESULTS: All patients demonstrated a significant exertional effort as demonstrated with the mean peak exercise respiratory exchange ratio >1.10. Peak exercise cardiac power output was significantly higher in healthy controls and explanted LVAD patients compared with other patients (healthy 5.35 ± 0.95 W; explanted 3.45 ± 0.72 W; LVAD implanted 2.37 ± 0.68 W; and HTx 1.31 ± 0.31 W; p < 0.05), as was peak O2 consumption (healthy 36.4 ± 10.3 ml/kg/min; explanted 29.8 ± 5.9 ml/kg/min; implanted 20.5 ± 4.3 ml/kg/min; and HTx 12.0 ± 2.2 ml/kg/min; p < 0.05). In the LVAD explanted group, 38% of the patients achieved peak cardiac power output and 69% achieved peak O2 consumption within the ranges of healthy controls. CONCLUSIONS: The authors have shown that a substantial number of patients who recovered sufficiently to allow explantation of their LVAD can even achieve cardiac and physical functional capacities nearly equivalent to those of healthy controls.

How do different indicators of cardiac pump function impact upon the long-term prognosis of patients with chronic heart failure?

BACKGROUND: The prognosis of patients with mild-moderate chronic heart failure (CHF) over a long-term follow-up period is more difficult to predict than for patients with more severe CHF in the short term. This study assessed the prognostic value of various indicators of cardiac pump function to gain insight into how different aspects of organ function impact upon prognosis. METHODS: Unselected, consecutive patients with CHF (n = 219, 166 men, mean [+/-SD] age 56 +/- 13 years) who underwent symptom limited cardiopulmonary treadmill exercise testing with noninvasive estimation of cardiac output using carbon dioxide rebreathing techniques were followed up for a median period of 8.6 +/- 1.0 years in survivors. Cardiac power output (CPO) was calculated from the product of cardiac output and mean arterial pressure and cardiac reserve was estimated by subtracting resting from peak exercise CPO or cardiac output (CO). RESULTS: All-cause mortality was 36% (78 deaths). Survivors had a significantly greater cardiac pumping reserve with the greatest difference seen in CPO reserve (+57%) and CO reserve (+49%) (both P < .001). Although various direct and indirect indicators of cardiac function were predictive of outcome on univariate analyses, multivariate analysis using the Cox proportional hazards model identified CO reserve to be the independent variable predictive of all-cause mortality, with a hazard ratio (95% CI) of 0.682 (0.612-0.757, P < .001) for each L/min increase in cardiac output reserve. Survival at 10 years in patients with tertiles of good, moderate, or poor cardiac output reserve was 89%, 63%, and 36.1%, respectively (P < .001). CONCLUSION: In this long-term follow-up study involving a cohort of unselected ambulatory patients with mild-moderate CHF, cardiac pumping reserve measured noninvasively by cardiopulmonary exercise testing was found to be the strongest independent predictor of prognosis.

Comparison and relation of indirect and direct dynamic indexes of cardiac pumping capacity in chronic heart failure.

Cardiac power output (CPO), the product of cardiac output (CO) and mean arterial pressure (MAP), is a direct measure of cardiac pumping capability and is strongly indicative of prognosis and exercise ability in patients with chronic heart failure (CHF). However, it is not as easily measured as indirect indicators of cardiac function, such as peak oxygen consumption (VO(2)) or peak "circulatory power" (CircP), the product of VO(2) and MAP. The relation between direct and indirect indexes of cardiac pumping capacity was evaluated in 219 ambulatory patients with CHF. CircP was found to have a direct and consistent relation with CPO, overall (R = 0.93, p <0.0001) and at peak exercise (R = 0.84, p < 0.0001). The results suggest CircP to be an adequate measure of cardiac pumping capacity when the more directly measured CPO is not available.

beta2-Adrenergic receptor stimulation in vivo induces apoptosis in the rat heart and soleus muscle.

High doses of the beta2-adrenergic receptor (AR) agonist clenbuterol can induce necrotic myocyte death in the heart and slow-twitch skeletal muscle of the rat. However, it is not known whether this agent can also induce myocyte apoptosis and whether this would occur at a lower dose than previously reported for myocyte necrosis. Male Wistar rats were given single subcutaneous injections of clenbuterol. Immunohistochemistry was used to detect myocyte-specific apoptosis (detected on cryosections via a caspase 3 antibody and confirmed with annexin V, single-strand DNA labeling, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling). Myocyte apoptosis was first detected at 2 h and peaked 4 h after clenbuterol administration. The lowest dose of clenbuterol to induce cardiomyocyte apoptosis was 1 microg/kg, with peak apoptosis (0.35 +/- 0.05%; P < 0.05) occurring in response to 5 mg/kg. In the soleus, peak apoptosis (5.8 +/- 2%; P < 0.05) was induced by the lower dose of 10 microg/kg. Cardiomyocyte apoptosis was detected throughout the ventricles, atria, and papillary muscles. However, this damage was most abundant in the left ventricular subendocardium at a point 1.6 mm, that is, approximately one-quarter of the way, from the apex toward the base. beta-AR antagonism (involving propranolol, bisoprolol, or ICI 118551) or reserpine was used to show that clenbuterol-induced myocardial apoptosis was mediated through neuromodulation of the sympathetic system and the cardiomyocyte beta1-AR, whereas in the soleus direct stimulation of the myocyte beta2-AR was involved. These data show that, when administered in vivo, beta2-AR stimulation by clenbuterol is detrimental to cardiac and skeletal muscles even at low doses, by inducing apoptosis through beta1- and beta2-AR, respectively.

Relative toxicity of cardiotonic agents: some induce more cardiac and skeletal myocyte apoptosis and necrosis in vivo than others.

We sought to determine the relative myotoxicity of a sample of cardiotonic (catecholaminergic and PDE Inhibitory) agents currently available for clinical use. Male Wistar rats (292 +/- 24 g) were administered single subcutaneous injections of 20 mmol kg(-1) of each agent. Myocyte apoptosis (caspase-3 and annexin-V) and necrosis (anti-myosin antibody) were detected immunohistochemically on cryosections of the heart and soleus muscle. All of the cardiotonic agents except dopamine produced significant amounts of cardiomyocyte death compared with the vehicle controls, with necrosis (range 2-8%, p < 0.01) approximately one order of magnitude greater in extent than apoptosis (range 0.06-0.5%, p < 0.05). The incidence of necrosis induced by norepinephrine (8%) was approximately twice that of epinephrine and isoproterenol (4 %) and four times that of dobutamine and milrinone (2%). All agents were also toxic to the soleus muscle (range 0.1-8%), but isoproterenol (8%, p < 0.05) and epinephrine (4%, p < 0.05) were the most significant. No cell death was detected in control animals treated with only the vehicle. A majority of cardiotonic agents currently in clinical use are toxic to cardiac and skeletal myocytes. These observations suggest that judicious clinical use of such agents requires careful weighing of potential benefits against the harm via accelerated cumulative loss of myocytes.

Comparison of plasma N-brain natriuretic peptide, peak oxygen consumption, and left ventricular ejection fraction for severity of chronic heart failure.

We investigated whether a simple blood test of plasma N-brain natriuretic peptide (N-BNP), compared with echocardiographic left ventricular ejection fraction (LVEF), both measured at rest, correlated well with aerobic exercise capacity (peak oxygen consumption [VO(2)]) in patients with chronic heart failure. Plasma N-BNP was found to significantly correlate with peak VO(2) (p <0.001) and exercise duration (p = 0.001), whereas LVEF showed very poor correlations with peak VO(2) and exercise duration (both p >0.3). The results suggest that N-BNP actually reflects functional cardiac impairment better than LVEF.

Is plasma N-BNP a good indicator of the functional reserve of failing hearts? The FRESH-BNP study.

AIMS: Whether plasma N-terminal brain natriuretic peptide (N-BNP) is useful in the diagnosis of heart failure (HF) depends traditionally on whether it is as good as the putative 'gold-standard', left ventricular ejection fraction (LVEF), in indicating cardiac dysfunction. However, since HF is primarily an impairment of function of the cardiac pump, we explored the relationship between N-BNP and direct and indirect indicators of cardiac pump dysfunction. METHODS AND RESULTS: Eighty-six HF patients (mean age 56 years) with a range of LVEF's (mean 36.9+/-15.2%, range 15-66%) and 10 age-matched healthy controls were recruited into the study and had resting N-BNP measured. Cardiopulmonary exercise testing was performed to assess peak oxygen consumption (Vo(2)). A subgroup of 23 subjects underwent further exercise haemodynamic assessment to evaluate peak cardiac power output (CPO). The CHF group had significantly higher N-BNP (median [interquartile range]) levels (299 [705] fmol/ml) than the control group (7 [51] fmol/ml, P<0.005). Significant correlations between N-BNP and peak Vo(2), and N-BNP and peak CPO were observed (R> or =0.5, P<0.005). Although significant correlation was observed between N-BNP and LVEF (R=0.34, P=0.01), the correlations between LVEF and peak Vo(2) or peak CPO (all R<0.3, P>0.3) were not significant. Multivariate analysis identified plasma N-BNP and NYHA class, but not LVEF, as independent predictors of peak Vo(2). CONCLUSIONS: We have found that N-BNP was surprisingly good as a simple indicator of cardiac pump dysfunction. Since heart failure is an inadequacy of function, these results strongly support the notion that N-BNP is a useful blood test in estimating the extent of cardiac pump dysfunction and helpful in establishing positive diagnosis of heart failure.

Myotoxic effects of clenbuterol in the rat heart and soleus muscle.

Myocyte-specific necrosis in the heart and soleus muscle of adult male Wistar rats was investigated in response to a single subcutaneous injection of the anabolic beta(2)-adrenergic receptor agonist clenbuterol. Necrosis was immunohistochemically detected by administration of a myosin antibody 1 h before the clenbuterol challenge and quantified by using image analysis. Clenbuterol-induced myocyte necrosis occurred against a background of zero damage in control muscles. In the heart, the clenbuterol-induced necrosis was not uniform, being more abundant in the left subendocardium and peaking 2.4 mm from the apex. After position (2.4 mm from the apex), dose (5 mg clenbuterol/kg), and sampling time (12 h) were optimized, maximum cardiomyocyte necrosis was found to be 1.0 +/- 0.2%. In response to the same parameters (i.e., 5 mg of clenbuterol and sampled at 12 h), skeletal myocyte necrosis was 4.4 +/- 0.8% in the soleus. These data show significant myocyte-specific necrosis in the heart and skeletal muscle of the rat. Such irreversible damage in the heart suggests that clenbuterol may be damaging to long-term health.

Fiftieth anniversary of aldosterone: from discovery to cardiovascular therapy.

Half a century after the elucidation of its molecular structure, aldosterone is generating the greatest interest, not in the fields of endocrinology or renal medicine but in cardiology-where aldosterone over-activation is now perceived as detrimental in heart failure (HF) and ischaemic heart disease. Clinically, excess aldosterone is associated with higher morbidity and mortality after myocardial infarction (MI) and HF. The Randomised Aldactone Evaluation Study (RALES) study in severe chronic heart failure and the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival (EPHESUS) study in post-MI heart failure have shown that use of non-selective and selective aldosterone receptor antagonists, respectively, improves prognosis. The pathophysiological mechanisms underpinning these damaging aldosterone-mediated cardiovascular effects are still being elucidated, but prime candidates include cardiomyocyte necrosis and apoptosis, and myocardial fibrosis resulting in adverse cardiac remodelling, coronary vasculopathy, tachyarrhythmia and positive feedback activation of the renin-angiotensin-aldosterone system. Practical points for consideration when instigating therapy include preferential use of aldosterone receptor antagonists to maintain electrolyte balance whenever loop or thiazide diuretics are used (vulnerable HF patients require higher ranges of potassium and magnesium to minimise propensity for tachyarrthythmia), for renoprotection and for counteracting aldosterone breakthrough despite adequate ACE inhibition; use of the minimum doses of loop diuretics required to lessen activation of the renin-angiotensin-aldosterone system in HF; use of selective aldosterone receptor antagonists to avoid gynaecomastia/mastalgia and impotence; and prophylactic use of aldosterone receptor antagonists to improve prognosis.

Characterisation of isoprenaline myotoxicity on slow-twitch skeletal versus cardiac muscle.

BACKGROUND: Elevated catecholamines are known to be cardiotoxic, but their potential injurious effects on skeletal muscles are largely unknown. We have investigated whether isoprenaline induces in vivo myocyte necrosis in rat soleus muscle, and characterised the time-course, dose-response, spatial distribution and adrenoceptor involvement of its myotoxicity, in comparison with effects on cardiomyocytes in the same animals. MATERIAL AND METHODS: Myocyte necrosis in response to subcutaneous isoprenaline was detected in vivo using a monoclonal anti-myosin antibody. Secondary immunoperoxidase staining (in vitro) facilitated the localisation of the damage and quantitative image analysis. RESULTS: Using this sensitive technique we report a novel observation that isoprenaline induces significant myocyte necrosis (5-10%) in the soleus muscle. This toxic damage was initiated at lower doses of isoprenaline than in the myocardium (1 vs. 10 microg kg(-1) s.c.), and peaked earlier (at 12 vs. 18 h post injection). Damage was distributed throughout the soleus muscle, whereas cardiomyocyte necrosis was most marked in left ventricular subendocardium where it was approximately 10 and three times greater than in the subepicardium and atria, respectively. Using selective adrenoceptor (AR) antagonism, we found that isoprenaline myotoxicity was mediated via beta(2)-AR in the soleus and via beta(1)-AR in the myocardium. CONCLUSION: The results show that the myopathic effects of isoprenaline are not confined to the heart. The involvement of skeletal muscle with different characteristics and mechanisms may have important implications in elucidating and treating the generalised myopathic processes seen in heart failure patients who have elevated levels of circulating catecholamines.

Is uremic cardiomyopathy a direct consequence of chronic kidney disease?

Heart failure is a major cause of morbidity and mortality in chronic kidney disease (CKD). Rather than merely secondary to traditional vascular factors, CKD is also an independent risk factor for heart failure, termed uremic cardiomyopathy (UCM). Echocardiography commonly reveals structural left ventricular hypertrophy in CKD, without clarifying whether it is adaptive or maladaptive. Corresponding functional assessments have been mostly conducted at rest. To unravel the extents and mechanisms UCM, a next step involves the adoption of direct measurements of CKD-induced cardiac pumping incapacity at peak exercise. This could potentially lead to future novel interventions to ameliorate or reverse UCM.

Principles governing heart failure therapy re-examined relative to standard evidence-based medicine-driven guidelines.

Although all aspects of clinical work nowadays are modified by the pervading influence of evidence-based medicine (EBM) and multiplicative guidelines, not many clinicians realize that the underlying premise of EBM-driven guidelines is a particular strain of consequentialist ideology. Subservience to this ideology has transformed modern medical practice, but there is a real risk of distorting good medical practice, of belittling clinical judgement, of disempowering clinicians, and subjecting patients to skewed medical reality and treatment options. With so many heart failure (HF) guidelines issued by various august bodies, it is therefore timely to reappraise principles governing modern HF therapy with a fresh examination of the hierarchy of medical imperatives, the role of alternatives to consequentialism including deontological principles in HF therapy. In addition, other ideology worth re-examining, aside from EBM, are the principle of appropriate definition of HF underlying therapeutic goals and the principle of prioritizing objectives of HF therapy. Even within standard EBM, there are many questions to reconsider: about what types of evidence are admissible, different interpretations of available evidence, emphasizing patient-centered outcome measures instead of randomized controlled trials quantifiable therapeutic outcomes, how to prescribe drugs for prognostic versus symptomatic benefits, and how to deliver HF therapy based on pathophysiological features through mechanistic considerations and not just confined to randomized controlled trials or meta-analytical statistical imperatives. Through re-examination of these fundamental principles of HF therapy, it is hoped that clinicians will be empowered to manage HF patients more holistically and better deliver HF therapies in the best interest of each individual patient.

So many definitions of heart failure: are they all universally valid? A critical appraisal.

Defining heart failure (HF) is a matter of finding the most appropriate words to formulate the definiens for HF that will be universally applicable in all specific circumstances pertaining to the nature of HF. Currently available definitions of HF contain ambiguities and notable deficiencies such that non-heart failure medical conditions can become mislabelled as heart failure. Principles of how best to formulate definitions have been employed to provide a guide on how to appraise published definitions of HF. A fundamental requirement of a good definition is that it should be universal, and by this criterion, we need to question the validity of a conventional dogma that a collection of clinical diagnostic features are equivalent to HF definitions. A long-standing deficiency in HF definitions is the inability to take into account the quantifiable extent of functional impairment of the heart. Other traditional misconceptions surrounding HF definitions have also been addressed. In line with Derek Gibson's proposal, we have rephrased William Harvey's description of the cardiac role in maintaining the circulation in terms of Newtonian physics and of the Law of Conservation of Energy to reach a more universal and less ambiguous definition of HF, with the objective of advancing the science of HF and the treatment of this distressing condition.