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.

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.

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.

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.

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.

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.

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.

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.

Cardiac functional reserve is diminished in growth hormone-deficient adults.

Various studies have shown that patients with severe growth hormone deficiency (GHD) have diverse changes in left ventricular (LV) size or performance but so far there is no direct indication of cardiac reserve ability to maintain the circulation during peak exercise. We tested the hypothesis that patients with severe GHD have reduced cardiac reserve function compared with healthy controls. Eighteen patients with severe GHD were studied and compared with 18 age-, sex-, and body mass index (BMI)-matched healthy controls. Peak cardiac power and cardiorespiratory fitness were investigated using noninvasive hemodynamic measurements during maximal cardiopulmonary exercise testing. 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 watts (W) vs. 5.2 +/- 1.0 W, P= 0.02), despite attaining similar aerobic exercise peaks (VO(2max), GHD: 2390 +/- 822 mL/min vs. controls: 2461 +/- 872 mL/min, P= 0.80) and similar peak respiratory exchange ratios. The lower peak cardiac power could not be accounted for by peripheral alterations because both groups reached similar peak exercise systemic vascular resistances. Patients with GHD also had lower cardiac chronotropic reserve (peak heart rate: 154 +/- 21 bpm vs. 174 +/- 11 bpm, P= 0.001) and a lower cardiac pressure-generating capacity (systolic blood pressure [SBP] 160 +/- 25 mmHg vs. 200 +/- 15 mmHg, P < 0.0001). Using this robust noninvasive method of assessing functional cardiac pumping capacity we have for the first time shown that patients with severe GHD have a significantly impaired cardiac functional reserve associated with chronotropic incompetence and impaired pressure-generating capacity.

A mechanistic investigation into how long-term resynchronization therapy confers ongoing cardiac functional benefits and improved exercise capacity.

The exact mechanisms underpinning the longer term benefits of cardiac resynchronization therapy (CRT) were not fully understood. It was still unclear whether there was any ongoing functional benefit conferred by the partial resynchronization of ventricular contraction. To resolve this, a randomized controlled double-blind crossover trial was conducted to investigate the impact of temporary cessation of CRT on cardiac function both at rest and during peak exercise. Fifteen patients with severe heart failure and a CRT device implanted at least 3 months previously were randomly assigned to have the CRT mode switched to either off or on during exercise tests with central hemodynamic measurements (including noninvasive cardiac output measured using rebreathing methods), then crossed over on separate days to the opposite CRT mode. There were no significant changes in hemodynamic variables at rest with either mode of CRT. When CRT was acutely turned off, there was 19% lower peak exercise cardiac power (2.10 +/- 0.46 vs 2.59 +/- 0.75 W; p <0.005), 6% lower mean arterial pressure (92 +/- 12 vs 98 +/- 13 mm Hg; p <0.05), and 11.5% lower peak cardiac output (10.4 +/- 1.9 vs 11.8 +/- 2.5 L/min; p <0.05). Exercise capacity was also diminished with lower peak oxygen uptake (15.7 +/- 4.3 vs 17.2 +/- 4.9 ml/kg/min; p <0.01) and shorter exercise duration (542 +/- 204 vs 587 +/- 212 seconds; p <0.05). These changes were seen without differences in peak respiratory exchange ratio and peak systemic vascular resistance. In conclusion, these observations provided evidence that after CRT, left ventricular resynchronization continued to confer cardiac functional benefits manifest during peak exercise, but imperceptible at rest.

A study of presbycardia, with gender differences favoring ageing women.

BACKGROUND: The impact of ageing on the human cardiovascular system has been the subject of several studies in recent years, but with insufficient emphasis on defining sex-specific differences. To rectify this, gender-specific differences in structure and function in the human cardiovascular system were studied in a European population during natural ageing. METHODS: Cardiac power output (CPO) was measured and integrated with changes in left ventricular (LV) mass, diastolic, systolic and limb blood flow, blood pressure and exercise capacity in 93 health-screened men and 122 women, aged 20 to 75 years. RESULTS: Correlating with a 21% loss of LV mass, maximum cardiac pumping (i.e. CPOmax=QmaxxMAPmax) and reserve (CR=CPOmax-CPOrest) capacities decreased 20-25% with age in male hearts. In contrast, CPOmax, CR and LV mass were all preserved in ageing women. Maximum cardiac output (Qmax; 26-32%), peak forearm blood flow (FBFpeak; 61%) and exercise capacity (40-50%) all decreased, but more so in men than women. In contrast, systemic vascular resistance (68-75%) and mean arterial pressure (MAPmax; 14-26%) increased in both sexes. CPOrest decreased 27% in men, but was unchanged in women, despite lower early:late diastolic filling (48-51%), Qrest (19-23%) and FBFrest (56%) in both sexes. CONCLUSIONS: Understanding sex-specific differences in cardiovascular ageing is important for public health and biomedical research, given increasingly larger older populations and the need to prevent and treat cardiovascular disease.

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.

Confusion over thiazolidinedione-induced heart failure: need for a better definition of heart failure.

Evaluation of: Erdmann E, Wilcox RG. Weighing up the cardiovascular benefits of thiazolidinedione therapy: the impact of increased risk of heart failure. Eur. Heart J. 29(1), 12-20 (2008). Thiazolidinediones (TZDs) reduce insulin resistance through the modulation of peroxisome proliferator-activated receptor (PPAR)-gamma activity and are, therefore, used for the treatment of individuals with Type 2 diabetes. TZDs have been blamed for inducing heart failure (HF) and are contraindicated in patients with impaired ventricular function. Whether precipitation of HF by TZDs is overestimated or not remains hotly debated in the scientific community. One message from the TZD-HF debacle is that current definitions of HF lack scientific rigour as they fail to assess cardiac organ function directly using a representative and reliable method. Once cardiologists reappraise and update the current definition of HF, appropriate steps can then be taken to answer the question of whether TZDs really induce true HF.

Efficacy of lifestyle intervention on peak exercise cardiac power output and reserve in premenopausal obese females: a randomised pilot study.

BACKGROUND: Clinically obese women have a two-fold increased risk for the development of heart failure. Among younger premenopausal females, obesity has been associated with cardiac remodelling and impaired resting systolic and diastolic function. However, few studies have evaluated cardiorespiratory and cardiac responses to maximal exertion among obese premenopausal females. DESIGN: A randomised pilot study was conducted to investigate the effects of a 3-month lifestyle intervention programme on weight management and maximal cardiorespiratory function in healthy clinically obese premenopausal females. Within this study, thirteen selected participants performed both graded and single-stage V. *O2peak exercise tests, the latter integrating the non-invasive measurement of cardiac output (CO2 rebreathing method), peak cardiac power output (CPO(peak)) and physiological cardiac reserve. Six participants were randomly assigned to 3-months of lifestyle intervention and 7 served as waiting list controls. RESULTS: Trends were evident for improvement in the traditional weight-adjusted V. *O2peak (ml kg(-1) min(-1)) measure among the lifestyle group compared with a modest reduction in the controls (test for interaction, P=0.059). CPO(peak) showed a modest, non-significant increase in the lifestyle group and tended to decrease in the control (test for interaction, P=0.166). Physiological cardiac reserve also improved (2.63+/-0.54 to 2.92+/-0.43 W) in the lifestyle group and declined (2.69+/-0.24 to 2.56+/-0.28 W) in the control group (test for interaction, P=0.091). V. *O2peak (ml min(-1)) increased non-significantly on graded maximal exercise in the lifestyle group compared with control. The larger within group changes in the lifestyle group failed to achieve statistical significance (test for interaction, P=0.131). CONCLUSIONS: In the absence of significant weight reduction, clinically obese premenopausal females derived modest benefits in maximal cardiorespiratory capacity and cardiac functional reserve from a 3-month lifestyle intervention incorporating supervised exercise.