PurposeSevere valve lesions require corrective interventions to avoid progression to heart failure (HF) and premature demise. We tested the hypothesis that despite operative risks, corrective valvular interventions will lead to significant improvements in overall cardiac pump function, especially before the onset of cardiac decompensation.MethodsWe compared the cardiopulmonary exercise performance and non-invasive haemodynamics of 46 consecutive patients with severe valvular disease before and after valvular intervention with reference to 101 healthy male and 139 female controls without cardiovascular disease. Cardiac and physical functional reserves were measured with standard respiratory gas analyses and CO2 rebreathing to measure cardiac output non-invasively during peak treadmill exercise. Data are given as mean±SD and statistical significance accepted at P<0.05.ResultsThe entire patient cohort showed no significant improvement in peak O2 consumption (V˙O2max, P=0.74) or in peak cardiac power (CPOmax, P=0.34) after valvular intervention, but we found instead a dichotomous outcome depending on preoperative cardiac function: (i) the pre-operative cardiac decompensatory subgroup (LoW, n=26) showed increased CPOmax (2.63±0.67 to 3.42±0.98W, P<0.0001) and V˙O2max (1.38±0.55 to 1.56±0.59L·min−1, P<0.01); and (ii) the pre-operative non-decompensatory subgroup (HiW) showed reduced CPOmax (4.58±0.96 to 3.84±0.92W, P<0.001) and V˙O2max (2.29±0.72 to 1.97±0.75L·min−1, P<0.01). Changes in NYHA class were found to be discrepant with these objective measurements.ConclusionThis investigation found an unexpected finding that valvular interventions performed in routine clinical practice do not consistently improve cardiac function, especially in those without pre-operative cardiac decompensation. Assessing cardiac functional gains would open up new avenues for future trials of valvular interventions.

Inroduction: People with postural tachycardia syndrome (PoTS) experience orthostatic intolerance in association with orthostatic tachycardia.Current demographic data is largely based on North American populations.The aim of this study is to obtain a profile of UK PoTS patients and is the largest study to date.Method: 1005 PoTS patients completed an online survey designed by healthcare professionals, charity trustees and patients.It was distributed by email and social media.Only those from the UK diagnosed by tilt table test (N ¼ 615, 73%) are included in this report.Results: 84% of responders were aged between 18-50 and 93% were female.Cardiologists were usually first to suggest a diagnosis of PoTS (36% of cases) followed by patient, family or friend (24%) and in only 7% did the GP suggest a PoTS diagnosis.The mean time from presenting with symptoms to a healthcare professional to obtaining a PoTS diagnosis was 3.5 years (range 0.5-28 years).The most common presenting symptoms of PoTS were lightheadedness (91%), tiredness (91%), and palpitations (85%).60% reported blackouts or fainting, which is a much higher proportion than previous studies.Half of the patients were told by a medical professional that their PoTS symptoms were due to a psychiatric or psychological problem, the most common of which was anxiety.Co-morbidities included Ehlers-Danlos hypermobility type (also known as EDS III or joint hypermobility syndrome; 48%), low blood pressure (37%), vasovagal syncope (33%) and chronic fatigue syndrome (27%).85% of respondents perceived a reduction in their quality of life.A fifth were wheelchair users and 11% had lost their driving licence.25% had changed their career, 29% reduced their working hours and 38% had stopped working for the foreseeable future due to PoTS symptoms.42% experienced undefined financial problems.Of interest, 66% were engaged in aerobic exercise at least twice a week at the onset of their PoTS symptoms, which challenges previous suggestions that deconditioning may be a contributing trigger.Currently, the main barriers to exercise are fatigue and feeling unwell during or after exercise.Of the 38% referred for lifestyle or exercise advice, only half of their advisors knew what advice to give a PoTS patient.Conclusions: This survey paints a unique picture of this under and misdiagnosed condition and its impact on patients' lives.Findings highlight a need for the education of a range of healthcare professionals on PoTS diagnosis and multidisciplinary management.PoTS should be considered in patients who present with the triad of presyncope, fatigue, and palpitations.Due to the non-specific and multiple symptoms of PoTS, the development of a screening tool may facilitate and expedite diagnosis.

Background The improvement in cardiac physiological parameters after restoration of sinus rhythm in patients with persistent atrial fibrillation (AF) can be challenging to quantify. Overall cardiac function assessment is better assessed by peak cardiac power output (CPOpeak), rather than indirect measures of cardiac performance such as peak oxygen consumption (VO2peak). CPO was used to quantify improvement in cardiac function early and later following electrical cardioversion. Methods and results 29 patients with persistent AF underwent maximal treadmill cardiopulmonary exercise (CPEx) testing within 14 days (±3) 8 weeks (±3) following electrical cardioversion (DCCv). This enabled measurement of VO2peak, cardiac output (COpeak) and calculation of CPOpeak. Quality of life (QoL) data (EQ5D) was also recorded. Three patients attended for 2 CPEx tests and 3 were lost to follow-up (total n = 26). Fourteen were successfully cardioverted and 12 remained in AF. In patients successfully cardioverted exercise duration increased significantly between all tests. CPOpeak, VO2peak, CO peak and QoL were improved significantly between Tests 1 and 2 (p < 0.02) and Tests 1 and 3 (p < 0.05). QoL improved by 15%. Conclusions Restoration of SR confers significant, early and sustained cardiac functional improvement following DCCv with a significant 14% increase in the calculated peak power output of the heart. Such increase in functional reserve suggests that pursuit of a rhythm control strategy in the treatment of AF may be warranted in terms of both improving quality of life and cardiac function with objective improvement of cardiac function.

Purpose: Lowpeak O-2 consumption ((V) over dotO(2max)/kg) has beenwidely used as an indirect indicator of poor cardiac fitness, and often guidesmanagement of patientswith severe heart failure (HF). Wehypothesized that it should be as good an indicator of cardiac dysfunction in obese and non-obese HF patients.Methods: We compared the cardiopulmonary exercise performance and non-invasive hemodynamics of 152 obese (BMI > 34 kg. m(-2)) and 173 non-obese (BMI <= 32) male HF patients in NYHA classes II and III, with reference to 101 healthymale controls. Their physical and cardiac functional reserveswere measured during treadmill exercise testing with standard respiratory gas analyses and CO2 rebreathing to measure cardiac output noninvasively during peak exercise. Data are given as mean +/- SD.Results: Obese HF patients with BMI 40.9 +/- 7.5 kg.m(-2) (age 56.1 +/- 14.0 years, NYHA 2.5 +/- 0.5) exercised to acceptable cardiopulmonary limits (peak RER = 1.07 +/- 0.12), and achieved a mean (V)overdotO(2max)/kg of 18.6 +/- 5.2 ml.kg(-1).min(-1), significantly lower than in non-obese HF counterparts (19.9 +/- 5.6 ml.kg(-1).min(-1), P = 0.02, age 55.8 +/- 10.6 years, BMI 26.6 +/- 3.1, NYHA 2.4 +/- 0.5, peak RER= 1.07 +/- 0.09), with both lower than controls (38.5 +/- 9.7 ml.kg(-1).min(-1), P < 10-6). In contrast, the uncorrected (V)OverdotO(2max) was higher in obese (2.31 +/- 0.69 ml.min(-1)) than non-obese HF patients (1.61 +/- 0.49 ml.min(-1), P < 10-6). When cardiac dysfunction was evaluated directly, peak cardiac power was significantly greater in obese than non-obese HF patients (4.11 +/- 1.21Wvs 2.73 +/- 0.82 W, P b 10-6), with both lower than controls (5.42 +/- 1.04W, P < 10-6).Conclusion: These results demonstrate that (V)over dotO(2max)/kg is not a generally reliable indicator of cardiac fitness in all patients. Instead, we found that despite having lower (V)over dotO(2max)/kg, obese HF patients had stronger hearts capable of generating greater cardiac power than non-obese HF patients of equivalent clinical HF status. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

We would like to thank Krachler et al. [ [1] Krachler B. Savonen K. Komulainen P. Hassinen M. Lakka T.A. Rauramaa R. VO2max/kg is expected to be lower in obese individuals!. Int. J. Cardiol. 2015; 189: 234 Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar ] for their letter regarding our study “Is low VO2max/kg in obese heart failure patients indicative of cardiac dysfunction?” [ [2] Hothi S.S. Tan D.K. Partridge G. Tan L.B. Is low VO2max/kg in obese heart failure patients indicative of cardiac dysfunction?. Int. J. Cardiol. 2015; 184: 755-762 Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar ]. Krachler's group have concluded from their own data that correcting VO2max with total body mass (BM) “systematically underestimates cardiorespiratory fitness in obese individuals”. This conclusion is indeed consistent with our data as shown in Figs. 2 and 3 of our paper. Both Krachler's and our groups have arrived at the same conclusion that VO2max/kg corrected with total BM is untenable, and we accordingly call for the physiology and cardiology communities to discontinue this scientifically unsound practice. In particular, basing life-and-death decision-making (e.g., for cardiac transplantation or ventricular assist device implantation [ [3] Mehra M.R. Kobashigawa J. Starling R. Russell S. Uber P.A. Parameshwar J. Mohacsi P. Augustine S. Aaronson K. Barr M. Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates—2006. J. Heart Lung Transplant. 2006; 25: 1024-1042 Abstract Full Text Full Text PDF PubMed Scopus (793) Google Scholar ]) on VO2max/kg would require urgent updating.

The cardiovascular system is essentially a complex system of pumps and pipes, and as such it belongs to the branch of fluid dynamics in engineering science, the equivalent of which in cardiovascular physiology is haemodynamics, dealing with measureable variables including pressure and flow. Less well known to cardiologists is the study of cardiovascular energetics which obeys the fundamental Law of Conservation of Energy. According to this Law of physics, to prevent the cessation of the circulation owing to dissipation of energy in the vasculature, the cardiac pump needs to generate and impart a continuous supply of hydraulic energy.1 The primary function of the cardiac pump is therefore to convert chemical energy into hydraulic energy to maintain a physiologically viable circulation.1 How good the cardiac pump is can be represented by how well it can impart hydraulic energy to maintain a circulation that can meet the most demanding physiological stresses.2 The variable that represents this entity is cardiac power output (CPO) at peak stress, which can be calculated by the product of cardiac flow and pressure measured, for example, at maximal exercise. The mean value of CPO is approximated by multiplying cardiac output (CO in L/min), with mean arterial pressure (MAP in mmHg), and a factor to convert into watts (cardiac power output, CPO = CO × MAP × 2.22 × 0−3 W).3 Peak cardiac power output (CPOmax) would therefore best represent the extent of the heart's failure to deliver adequate hydraulic energy sufficient to maintain a circulation that copes with any physiological stresses. It is therefore commonly found in multivariate analyses to be a powerful independent predictor of heart failure (HF) prognosis.4 In this issue of the European Journal of Heart Failure, Grodin and colleagues from Cleveland and Belgium5 extended this scheme of conceptual thinking to study heart function, not from the common and near-ubiquitous perspective of left ventricular ejection fraction (LVEF), but by considering the heart's role as a hydraulic pump at rest, quantified as the cardiac power index (CPI), obtained by indexing resting CPO by body surface area (BSA), during invasive haemodynamic assessment. This retrospective cohort study included 495 sequential ambulatory patients with advanced heart failure on evidence-based treatment followed up for a median of 3.3 years. Their demographics included mean age 54 ± 11 years, 76% male, 48% with ischaemic cardiomyopathy, mean LVEF 20%, 91% in New York Heart Association (NYHA) class III, and 39% having an implantable cardioverter defibrillator (ICD) in situ. Resting CPI less than 0.44 W/m2 was associated with increased adverse outcomes (death, transplant or VAD placement) with a hazard ratio of 2.4. An independent association remained after multivariate analyses for age, gender, pulmonary capillary wedge pressure (PCWP), Fick CI, creatinine, LVEF, B-type natriuretic peptide (BNP), and peak oxygen consumption (VO2max). The authors acknowledge a limitation that this was a single-centre, retrospective study, performed mostly in patients with advanced HF. Furthermore, resting CPI is limited by the fact that it is difficult to determine how much of the peak CPO the patient ‘uses’ at rest. Conceivably minor changes in pulse rate or adrenergic activity (related to stress for example) can lead to increases in CPI thus creating the false assessment of a ‘better’ patient prognosis. Although the definition of advanced HF was rather vague, in advanced HF it is likely that the CPO reserve is relatively low and hence resting CPI may correlate well with peak CPO and therefore provide a good representation of near-maximal cardiac pumping capacity. This assumption should not be made in patients with less severe HF, where peak CPO rather than resting CPI should be assessed. Curiously, one of the earliest indicators of HF prognosis was published in a non-cardiological journal in 1948. In it the authors reported that it is ‘justifiable to consider the prognosis as very grave’ in patients with severe HF if normoblasts are found in their blood and their disappearance was ‘concomitant with an improvement in the heart failure’.6 Since then, there has been a marked proliferation of reported HF prognostic indicators (PrI), which pose a problem for clinicians because of the impossibility of adopting the entire range into routine practice. Over the years, multiple determinants of HF prognosis have been found covering many aspects of the HF syndrome, derived with various statistical tools, especially multivariate analysis, and utilized for worthy clinical and research objectives.7 Now that CPIrest has joined a lengthening list of PrIs for HF, where does it rank amongst other competing PrIs? With so many PrIs already reported in the literature, frequent emergence of newly reported PrIs and questions raised over previously advocated PrIs, practising clinicians are overwhelmed and in danger of becoming inattentive to newer PrIs. The time has come to reappraise and draw a shortlist of PrIs that are worthy of being adopted into routine clinical practice. A major handicap with testing and selecting the best PrI is that, unlike symptoms and functional capacities, it is impossible to measure the prognosis of an individual patient and measure how it is altered by certain therapeutic interventions in that individual.8 Prognosis of HF can only be determined in a cohort of patients over a period of time and the PrIs derived thereby would then require validation in different HF populations to verify their general applicability.9 However, HF populations are changing significantly over time, for example, with evolving demographics such as rising proportions of older patients with preserved LVEF and degenerative valve disease, and with progressively improving pharmacological, device, and interventional therapies. Each multiparametric combination set of PrIs will therefore require periodical redevelopment ad infinitum, followed by validation iteratively in different HF populations. Are there alternative and better ways of selecting PrIs for clinicians? Table 1 lists proposed methods for the classification of HF PrIs. In statistics, it is axiomatic that ‘Bigger is Better’, implying that the larger the sample size, the greater the power, confidence, and generalizability of the PrIs. An ideal approach would be to conduct a mega-study involving millions of consecutive HF patients and entering all known candidate PrIs into conclusive multivariate analyses. However, this approach may not be practical, as it will be necessary to repeat such a mega-study every few years, especially if there are significant drifts in HF management options. An alternative approach would be to test PrIs in smaller studies using a priori hypothesis. They could, for example, be considered according to pathophysiological mechanisms. The HF syndrome is caused by a combination of the cardiac pump's failure to maintain a physiological circulation1 and downstream derangements consequential upon tissue hypoperfusion, congestion, and neurohormonal and inflammatory activation, giving rise to measureable markers. Thus, PrIs can be divided into those pertaining to the primary causes of HF (structural and functional defects) and those pertaining to downstream effects. One might therefore speculate that PrIs related to the primary cardiac dysfunction4 will be more prognostic than PrIs derived from downstream consequences, especially in patients with advanced HF irrespective of aetiology. In this context, measuring CPIrest, and even more so peak CPO, would accurately assess the cardiac pumping capacity and, hence, be strongly associated with outcomes, as shown by Grodin et al.5 Another important consideration when assessing PrIs is to ‘stress’ them longitudinally to verify whether any improvement in their values, however biologically achieved (and not caused by differences in measurement techniques), are accompanied by concordant improvements in HF status and prognosis. For example, applying such a stress test to BNP, it would appear that any alteration in the rates of BNP synthesis, metabolism, or excretion would alter plasma BNP levels unaccompanied by actual alterations in cardiac status and prognosis. This may partly explain why trials of BNP-guided HF therapy have so far produced rather mixed results.10 Peak CPO or resting CPI were not assessed previously in such a study examining their changes with therapies. However, conceivably, resting CPI could be altered by therapies such as inotropes that have not been shown to improve outcomes,11 adding to the caution needed in applying it to clinical practice. What constitutes an optimal and useful PrI? It is one that not only predicts prognosis well, but is also generally applicable to heterogeneous HF patients worldwide and would respond to interventions that change prognosis in a way that correlates with the intervention's effect while not responding to interventions that do not change or worsen prognosis. The selection process for such HF PrIs should now be undertaken in earnest. In addition, as in drug development, where new agents in an existing class are required to demonstrate superiority before approval, the onus should now be on investigators claiming a newly discovered HF PrI to provide evidence of its superiority over existing PrIs. Conflict of interest: none declared.

Clinicians recognise that heart failure (HF) patients suffer from exercise intolerance to varying degrees, and those with the worst organ failure such as cardiogenic shock have the greatest limitation. Exercise duration has been shown to correlate well with cardiac pump dysfunction [ [1] Bain R.J. Tan L.B. Murray R.G. Davies M.K. Littler W.A. The correlation of cardiac power output to exercise capacity in chronic heart failure. Eur. J. Appl. Physiol. Occup. Physiol. 1990; 61: 112-118 Crossref PubMed Scopus (25) Google Scholar ]. Nowadays, exercise intolerance is usually quantified as aerobic exercise capacity measured as peak O2 consumption (VO2max) during cardiopulmonary exercise testing (CPX), previously introduced into cardiology by Weber and colleagues as a tool to evaluate patients with HF [ [2] Weber K.T. Kinasewitz G.T. Janicki J.S. Fishman A.P. Oxygen utilization and ventilation during exercise in patients with chronic cardiac failure. Circulation. Jun 1982; 65: 1213-1223 Crossref PubMed Scopus (721) Google Scholar ]. The authors described it as “an objective, reproducible and safe non-invasive method for characterizing cardiac reserve and functional status in patients with chronic cardiac failure”. This association and in terms of clinical use, perceived equivalence with cardiac reserve led to the finding that VO2max/kg is a strong predictor of HF prognosis [ [3] Mancini D.M. Eisen H. Kussmaul W. Mull R. Edmunds Jr., L.H. Wilson J.R. Value of peak exercise oxygen consumption for optimal timing of cardiac transplantation in ambulatory patients with heart failure. Circulation. Mar 1991; 83: 778-786 Crossref PubMed Scopus (1433) Google Scholar ] and this has subsequently been adopted as a key selection criterion for cardiac transplantation [ 4 Mehra M.R. Kobashigawa J. Starling R. Russell S. Uber P.A. Parameshwar J. Mohacsi P. Augustine S. Aaronson K. Barr M. Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates—2006. J. Heart Lung Transplant. Sep 2006; 25: 1024-1042 Abstract Full Text Full Text PDF PubMed Scopus (747) Google Scholar , 5 Hunt S.A. Abraham W.T. Chin M.H. Feldman A.M. Francis G.S. Ganiats T.G. Jessup M. Konstam M.A. Mancini D.M. Michl K. Oates J.A. Rahko P.S. Silver M.A. Stevenson L.W. Yancy C.W. 2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation. Apr 14 2009; 119: e391-e479 Crossref PubMed Scopus (1401) Google Scholar , 6 Heart Failure Society of America Lindenfeld J. Albert N.M. Boehmer J.P. Collins S.P. Ezekowitz J.A. Givertz M.M. Katz S.D. Klapholz M. Moser D.K. Rogers J.G. Starling R.C. Stevenson W.G. Tang W.H. Teerlink J.R. Walsh M.N. HFSA 2010 comprehensive heart failure practice guideline. J. Card. Fail. Jun 2010; 16: e1-e194 Abstract Full Text Full Text PDF PubMed Scopus (874) Google Scholar ]. Subsequently, direct methods of measuring cardiac reserve and pumping capability became available [ 7 Tan L.B. Cardiac pumping capability and prognosis in heart failure. Lancet. Dec 13 1986; 328: 1360-1363 Abstract Scopus (126) Google Scholar , 8 Cooke G.A. Marshall P. al-Timman J.K. Wright D.J. Riley R. Hainsworth R. Tan L.B. Physiological cardiac reserve: development of a non-invasive method and first estimates in man. Heart. Mar 1998; 79: 289-294 Crossref PubMed Scopus (94) Google Scholar ], and whenever entered into multivariate analyses together with VO2max, peak cardiac power (CPOmax) emerged consistently as the stronger predictor of HF prognosis [ 9 Williams S.G. Cooke G.A. Wright D.J. Parsons W.J. Riley R.L. Marshall P. Tan L.B. Peak exercise cardiac power output; a direct indicator of cardiac function strongly predictive of prognosis in chronic heart failure. Eur. Heart J. Aug 2001; 22: 1496-1503 Crossref PubMed Scopus (170) Google Scholar , 10 Lang C.C. Karlin P. Haythe J. Lim T.K. Mancini D.M. Peak cardiac power output, measured noninvasively, is a powerful predictor of outcome in chronic heart failure. Circ. Heart Fail. 2009; 2: 33-38 Crossref PubMed Scopus (90) Google Scholar ]. These findings are unsurprising since CPOmax is a direct representation of cardiac organ pump function in maintaining the circulation [ [11] Tan L.B. Williams S.G. Tan D.K.H. Cohen-Solal A. So many definitions of heart failure: are they all universally valid? A critical appraisal. Expert. Rev. Cardiovasc. Ther. Feb 2010; 8: 217-228 Crossref PubMed Scopus (48) Google Scholar ]. In cross-sectional studies in healthy subjects [ [12] Goldspink D.F. George K.P. Chantler P.D. Clements R.E. Sharp L. Hodges G. Stephenson C. Reilly T.P. Patwala A. Szakmany T. Tan L.B. Cable N.T. A study of presbycardia, with gender differences favoring ageing women. Int. J. Cardiol. Nov 12 2009; 137: 236-245 Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar ] and HF patients [ [13] Hothi S.S. Tan D.K.H. Partridge G. Tan L.B. Is low V ˙ O2max/kg in obese heart failure patients indicative of cardiac dysfunction?. Int. J. Cardiol. 2015; 184: 755-762 Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar ], instantaneous comparisons of VO2max and CPOmax have also been found to be significantly correlated as shown in Fig. 1a .

BackgroundTiming of aortic valve replacement in patients with severe asymptomatic aortic stenosis (VD) is controversial. Exercise testing may uncover symptoms and early cardiac dysfunction. However there is little information on the value of cardiopulmonary exercise (CPX) testing combined with haemodynamic assessment during exercise in this patient group. We report preliminary results of CPX and haemodynamic data in this patient cohort.Methods21 consecutive patients with severe VD underwent maximal CPX tests. Central haemodynamics including cardiac output were measured non-invasively at rest and during peak exercise. The results were compared to normal values from a cohort of healthy controls and depicted as % of predicted for normal healthy controls.ResultsThe following preliminary observations were made and are depicted on the graphs: (1) All patients except one (5%) had peak oxygen consumption (VO2max) within the ranges for healthy controls. (2) Five patients (24%) had cardiac power output (CPOmax) below the range for healthy controls. (3) When plotted together relative to healthy controls the CPOmax of patients with severe VD were lagging below the VO2max, suggesting measurement of VO2max alone may not pick out the ones with early cardiac dysfunction.ConclusionHaemodynamic assessment during exercise using direct indicators of cardiac function may be more sensitive than conventional cardiopulmonary exercise parameters in detecting early cardiac dysfunction in patients with severe asymptomatic aortic stenosis.

Purpose: Low peak O2 consumption (VO2max) has been widely used as an indirect indicator of poor cardiac function. Thus, VO2max≤14 ml/kg/min is a criterion warranting transplant consideration (Circulation 2010; 122:173). We hypothesized that it should be as good an indicator in obese versus non-obese heart failure (HF) patients. Methods: We compared the cardiopulmonary exercise performance and non-invasive haemodynamics of obese (BMI >34 kg/m2) and non-obese (BMI ≤30) male HF patients in NYHA Classes II and III, with healthy male controls with no known cardiovascular diseases (n=101, age 43.2±18.1 years, BMI 26.0±3.1). Their physical and cardiac functional reserves were measured during treadmill exercise testing with standard respiratory gas analyses and CO2 rebreathing to non-invasively measure cardiac output during peak exercise. Data are given as mean±SD. Results: Obese HF patients with BMI=44.9±6.8 (n=69, age 52.3±10.0 years, NYHA 2.6±0.5) managed to exercise to acceptable cardiopulmonary limits (peak RER=1.04±0.12), and achieved a mean VO2max of 18.4±5.5 ml/kg/min which was significantly lower than in controls (37.0±10.7 mls/kg/min, P<10-6) and non-obese HF counterparts (19.8±5.4 ml/kg/min, P<0.01, n=102, age 58.2±14.1 years, BMI 26.1±3.0, NYHA 2.5±0.5) (Fig. 1A). In contrast, the direct measure of cardiac function, peak cardiac power output (CPOmax), was greater in obese HF patients (4.16±1.51 W) than in non-obese HF patients (2.40±0.68 W, P<0.001) (Fig. 1B). Figure 1. VO2max and CPOmax versus BMI Conclusion: These results argue against and question the widely held assumption that VO2max in ml/kg/min is a reliable indirect indicator of cardiac dysfunction in all HF patients. Indeed, they suggest that the common cardiological practice of scaling VO2max with body weight can be clinically misleading and should be abandoned.

Purpose: Uraemia is associated with increased cardiac morbidity and mortality. The present study aimed to test the hypothesis that patients with chronic kidney disease (CKD) without any known cardiovascular disease or diabetes mellitus have impaired cardiac and physical functional reserves compared to controls. Methods: We compared the cardiopulmonary exercise performance and non-invasive haemodynamics of 30 male patients with late CKD (stages 4&5) and 20 patients with early CKD (stages 2&3) against 101 healthy male volunteers. Physical and cardiac functional reserves were measured during treadmill exercise testing with standard respiratory gas analyses and a CO2-rebreathing method of non-invasively measuring cardiac outputs during peak exercise. As positive controls, data from 39 age- and gender-matched heart failure (HF) patients in NYHA class II&III were also obtained. The results are presented as mean±SD. Result: The mean eGFRs of early and late CKD patients were 54.4±18.2 and 16.2±5.8 ml/min respectively. Compared to healthy controls, the CKD patients showed a graded reduction in peak cardiac power output (CPOmax) with 92.4±12.2% (P<0.05) of predicted CPOmax in early CKD and 81.4±13.2% (P<0.001) of predicted CPOmax in late CKD, whereas their peak O2 uptake (VO2max) was preserved in early CKD (98.8±11.8% of predicted VO2max, P=NS) and mildly reduced in late CKD (87.6±18.1% of predicted VO2max, P<0.01). These values were not as impaired as in HF patients who had 58.2±14.4% and 45.5±10.7% of predicted VO2max and CPOmax respectively (both P<0.001). Conclusion: This novel study shows that CKD per se causes impaired cardiac functional reserve, thus confirming the identity of Uraemic Cardiomyopathy which requires further cardio-renal collaborative research.

Introduction Clinicians often feel apprehensive when managing pregnant patients with heart disease. To complement current evaluation, we have developed a new method of directly assessing the individual patient9s cardiac functional reserve through stress testing. Pregnant mothers with and without heart disease were studied to test the hypothesis that pregnant cardiac patients who possess cardiac reserve equivalent to that of controls can tolerate the usual demands of pregnancy, labour and puerperium. Methods Fifty-one pregnant women with heart disease (mean age 30.7±6.5 (range 21–42), mean gestation 25.6±8.6 weeks) and 102 healthy pregnant women (mean age 31.4±5.0, (range 19–41), mean gestation 25.1±9.2 weeks) underwent maximal symptom-limited treadmill cardiopulmonary exercise testing. Fifty-nine non-pregnant women (mean age 32.7±5.1 (range 20–41) years) were similarly tested and used as a control group. Cardiac output (CO) was measured at peak exercise using the CO2 re-breathing method. Cardiac power output (CPO) was calculated as the product of CO and mean arterial pressure. A composite endpoint including maternal death, fetal death, emergency caesarean section for maternal distress and significant morbidities was determined. Results All tests were performed without significant complications. Employing data from a previous study of haemodynamics during labour in healthy women, the mean CPO required during peak labour is 2.6 W. This value was adopted for investigation as the minimum required for an average woman to cope with the circulatory demands of normal labour. The healthy controls had a mean peak CPO (PkCPO) of 3.79±0.6 W and all non-pregnant women had PkCPO exceeding 2.6 W. The majority of heart disease patients were able to achieve PkCPO values overlapping their healthy counterparts. Only a small proportion of the cardiac patients had PkCPO values lower than the 2.6 W cutoff. Women were significantly more likely to have uncomplicated pregnancy, labour and puerperium if able to achieve PkCPO>2.6 W (OR 8.1, 95% CI 1.8 to 37.0, p=0.023). Pregnant women in NYHA class I had PkCPO values indistinguishable from controls (mean 3.98±0.77 W, NS); whereas symptomatic pregnant women had significantly lower values (mean 3.15±0.71W, p<0.005). Conclusions Direct measurement of cardiac functional reserve capacity can be performed by maximal cardiopulmonary exercise testing with non-invasive assessment of PkCPO, which can be safely undertaken during pregnancy. A cutoff value of PkCPO 2.6 W was identified as the lower limit for healthy women, corresponding to that required for normal labour. Most cardiac patients studied had PkCPO values comfortably above this cutoff, and all asymptomatic (NYHA I) and low risk cardiac patients had PkCPO values similar to controls. Measurement of PkCPO allows pregnant patients to be further classified into those with adequate vs limited cardiac reserve, supplementary to existing risk stratification methods.

Lymphedema often responds to compression therapy which can also cause undesirable cardiac overload if heart failure coexists. We hypothesized that the biomarker B-type natriuretic peptide (BNP) can be used to screen lymphedema patients for undetected cardiac dysfunction. We studied unselected consecutive patients with lymphedema to determine their BNP status and compared these data with those obtained from healthy subjects without known cardiovascular diseases. Out of a total of 305 subjects with lymphedema screened, 102 (33%) consented to take part in this study. The majority (87%) were female with a mean age of 60.5 +/- 13.2 (SD) years, and 47% had just lower limb swelling. The groups were equally divided between cancer and non-cancer related causes. There were 45 females and 4 males under 60 years old, and 44 female and 9 male patients over 60 years old. Median (IQR) BNP (ng/L) were as follows: <60 years females = 17.9 (15.2) (median [RR: 3 - 64] and males = 12.4 (14.7) [RR: 0.2 - 44], >60 years females = 35.8 (57.9) [RR: 2 -247)] and males = 47.2 (44.1) [RR: 2 - 238]. For this population, the BNP concentration 100 ng/L was adopted as the value to exclude heart failure. Using this definition, 7 lymphedema subjects had BNP concentrations of 120 (19.8) ng/L, and all were found to have cardiac abnormalities on echocardiography. This study demonstrated that 93% of unselected subjects with lymphedema had BNP concentrations that exclude a diagnosis of heart failure. Those subjects with elevated BNP were found on subsequent echocardiography to have cardiac abnormalities. The use of a BNP assay is of potential value in screening patients who are more likely to have cardiac failure. Indicative factors include bilateral leg swelling, over the age of 50 years, breathlessness, where there is no known cause for the swelling. A BNP assay using a BNP concentration threshold of 100 ng/L (29 pmol/L) will identify those patients who require more detailed investigations.

Background Peak O2 consumption (Vo2max) of ≤14 ml/kg/min has been widely accepted as being indicative of poor cardiac function warranting consideration for transplantation (Circulation 2010; 122:173). We examined whether this variable is a good indicator of cardiac function in overweight heart failure (HF) patients. Methods We compared the cardiopulmonary exercise performance and non-invasive haemodynamics of overweight (BMI >34 kg/m2) and non-overweight (BMI ≤30) male heart failure patients in NYHA Classes II and III, with those of healthy male volunteers with no known cardiovascular diseases (n=101, age 43.2±18.1(SD) years, BMI 26.0±3.1) as controls. Their physical and cardiac functional reserves were measured during treadmill exercise testing with standard respiratory gas analyses and rebreathing method of non-invasively measuring cardiac outputs during peak exercise. Results Consecutive overweight HF were screened and 24 patients (age 49±8(SD) years, BMI 44.9±6.8, NYHA 2.50±0.50) managed to exercise to acceptable cardiopulmonary limits (peak RER=1.01±0.12), and achieved Vo2max of 16.8±4.6 mls/kg/min which was significantly lower than controls (37.0±10.7 mls/kg/min, p<10−6) and also lower than those of 30 non-overweight HF counterparts (20.0±3.7 mls/kg/min, p=0.0019, age 49±15 years, BMI 25.0±2.9, NYHA 2.48±0.51). As shown in Abstract 99 figure 1, the overweight HF patients had Vo2max values which distributed around the 14 mls/kg/min cut-off value, and 9 of whom were indeed below this cut-off value. However, the uncorrected Vo2max were higher than those of non-overweight counterparts (Overweight: 2575±748 vs 1594±325 mls/min, p<10−6), and its range of 1485–4210 mls/min overlapped with the range of 1244–5774 mls/min in controls. The peak cardiac power output (CPOmax, 4.5±1.6 W, minimum 2.7 W) of overweight HF patients were clearly above those of non-overweight (2.4±0.6 W, p<10−6, Abstract 99 figure 2) and all above the transplant cut-off value of 1.5 W. Conclusion These results indicate that in principle Vo2max in ml/kg/min as an indirect indicator of cardiac function or for cardiac transplantation selection is unreliable when applied to overweight heart failure patients. Extending this concept to the entire spectrum of body weights, the practice of correcting Vo2max by body weight in cardiological practice would also require urgent reconsideration.

Background Previous received dogma has propagated the concept that heart failure (HF) patients have compromised vasodilatory capacity during exercise through various vascular mechanisms, thereby reducing their exercise capacity through peripheral (vascular) factors rather than central (cardiac) factors. We tested whether such a concept is still valid in modern HF patients receiving current standard HF therapies. Methods and Results We recruited 150 female participants (133 normal healthy controls, age 48.5±13.1 (SD) years; 17 DCM patients, age 41.5±14.2 years) with no known coronary or other vascular diseases, and compared their central haemodynamic responses during volitional maximal exercise. The exercise capacity of controls spanned the same ranges as those of the HF patients. All patients performed symptom-limited cardiopulmonary exercise testing (CPX) with breath-by-breath analyses of respiratory gases and non-invasive haemodynamic measurements employing standard auscultatory sphygmomanometric and rebreathing methods. The patients performed a total of 30 CPX9s. The peak O2 consumption spanned from 1.20 to 2.45 L/min in DCM patients and from 1.15 to 2.44 L/min in controls. As shown in the figure, at peak exercise the systemic vascular resistances (SVR) of DCM patients were lower (532±154 dyn.s.cm-5) than those of controls (654±118 dyn.s.cm-5). Conclusion With modern HF therapy, the lower peak exercise SVR in HF patients compared to normal healthy controls demonstrates that there is no evidence of compromised systemic vasodilatory capacities in HF patients. The long-held dogma of vasodilatory incapacity in HF propagated >3 decades ago is no longer valid nowadays.