Physical Activity, Inactivity and Sleep in Individuals with Hypertrophic Cardiomyopathy.

Physical activity presents an important cornerstone in the management and care of individuals with hypertrophic cardiomyopathy (HCM). Twenty-one individuals with HCM (age: 52±15 years old, body mass index (BMI): 30±7 kg/m2) completed 7-day monitoring using wrist-worn triaxial accelerometers (GENEActiv, ActivInsights Ltd, UK) and were compared to age and sex-matched healthy controls (age: 51±14 years old, BMI: 25±4 kg/m2). For individuals with HCM, clinical parameters (left atrial diameter and volume, peak oxygen consumption, NTproBNP and Minnesota Living with Heart Failure (MLHF)) were correlated with accelerometry. After adjusting for BMI, individuals with HCM spent less time in moderate-vigorous physical activity (MVPA) (86 (55-138) vs. 140 (121-149) minutes/day, p<0.05) compared to healthy controls. Individuals with HCM engaged in fewer MVPA-5 min (6 (2-15) vs. 27 (23-37) minutes/day, p<0.01) and MVPA-10 min bouts (9 (0-19) vs. 35 (17-54) minutes/day, p<0.01) versus healthy controls. For HCM only, peak oxygen consumption was correlated with MVPA (r=0.60, p<0.01) and MVPA-5 min bouts (r=0.47, p<0.05). MLHF score was correlated with sleep duration (r=0.45, p<0.05). Individuals with HCM should be encouraged to engage in moderate-intensity physical activity bouts and reduce prolonged periods of inactivity in order to potentially improve exercise tolerance and reduce disease burden.

Heart rate variability and haemodynamic function in individuals with hypertrophic cardiomyopathy.

OBJECTIVES: Heart rate variability (HRV) is a measure of cardiac autonomic function. This study: (1) evaluated the differences in HRV and haemodynamic function between individuals with hypertrophic cardiomyopathy (HCM) and healthy controls, and (2) determined the relationship between HRV and haemodynamic variables in individuals with HCM. METHODS: Twenty-eight individuals with HCM (n = 7, females; age 54 ± 15 years; body mass index: 29 ± 5 kg/m2 ) and 28 matched healthy individuals (n = 7 females; age 54 ± 16 years; body mass index: 29 ± 5 kg/m2 ) completed 5-min HRV and haemodynamic measurements under resting (supine) conditions using bioimpedance technology. Frequency domain HRV measures (absolute and normalized low-frequency power (LF), high-frequency power (HF) and LF/HF ratio) and RR interval were recorded. RESULTS: Individuals with HCM demonstrated higher vagal activity (i.e., absolute unit of HF power (7.40 ± 2.50 vs. 6.03 ± 1.35 ms2 , p = 0.01) but lower RR interval (914 ± 178 vs. 1014 ± 168 ms, p = 0.03) compared to controls. Stroke volume (SV) index and cardiac index were lower in HCM compared with healthy individuals (SV, 33 ± 9 vs. 43 ± 7 ml /beat /m², p < 0.01; cardiac index,2.33 ± 0.42 vs. 3.57 ± 0.82 L/min/m2 , p < 0.01), but total peripheral resistance (TPR) was higher in HCM (3468 ± 1027 vs. 2953 ± 1050 dyn·s·m2 cm-5 , p = 0.03). HF power was significantly related to SV (r = -0.46, p < 0.01) and TPR (r = 0.28, p < 0.05) in HCM. CONCLUSIONS: Short-term frequency domain indices of HRV provide a feasible approach to assess autonomic function in individuals with HCM. Vagal activity, represented by HF power, is increased, and associated with peripheral resistance in individuals with HCM.

Application of non-invasive bioreactance to assess hemodynamic function in patients with hypertrophic cardiomyopathy.

Non-invasive technologies have become popular for the clinical evaluation of cardiac function. The present study evaluated hemodynamic response to cardiopulmonary exercise stress testing using bioreactance technology in patients with hypertrophic cardiomyopathy. The study included 29 patients with HCM (age 55 ± 15 years; 28% female) and 12 age (55 ± 14 years), and gender matched (25% female) healthy controls. All participants underwent maximal graded cardiopulmonary exercise stress testing with simultaneous non-invasive hemodynamic bioreactance and gas exchange. At rest, patients with HCM demonstrated significantly lower cardiac output (4.1 ± 1.3 vs. 6.1 ± 1.2 L/min; p < 0.001), stroke volume (61.5 ± 20.8 vs. 89.5 ± 19.8 mL/beat; p < 0.001), and cardiac power output (0.97 ± 0.3 vs. 1.4 ± 0.3watt; p < 0.001), compared to controls. At peak exercise, the following hemodynamic and metabolic variables were lower in HCM patients that is, heart rate (118 ± 29 vs. 156 ± 20 beats/min; p < 0.001), cardiac output (15.5 ± 5.8 vs. 20.5 ± 4.7 L/min; p = 0.017), cardiac power output (4.3 ± 1.6 vs. 5.9 ± 1.8 watts; p = 0.017), mean arterial blood pressure (126 ± 11 vs. 134 ± 10 mmHg; p = 0.039), and oxygen consumption (18.3 ± 6.0 vs. 30.5 ± 8.3 mL/kg/min; p < 0.001), respectively. Peak arteriovenous oxygen difference and stroke volume were not significantly different between HCM patients and healthy controls (11.2 ± 6.4 vs. 11.9 ± 3.1 mL/100 mL, p = 0.37 and 131 ± 50.6 vs. 132 ± 41.9 mL/beat, p = 0.76). There was a moderate positive relationship between peak oxygen consumption and peak heart rate (r = 0.67, p < 0.001), and arteriovenous oxygen difference (r = 0.59, p = 0.001). Functional capacity is significantly reduced in patients with HCM primarily due to diminished central (cardiac) rather than peripheral factors. Application of non-invasive hemodynamic assessment may improve understanding of the pathophysiology and explain mechanisms of exercise intolerance in hypertrophic cardiomyopathy.

Haemodynamic determinants of quality of life in chronic heart failure.

BACKGROUND: Heart failure patients demonstrate reduced functional capacity, hemodynamic function, and quality of life (QOL) which are associated with high mortality and morbidity rate. The aim of the present study was to assess the relationship between functional capacity, hemodynamic response to exercise and QOL in chronic heart failure. METHODS: A single-centre prospective study recruited 42 chronic heart failure patients (11 females, mean age 60 ± 10 years) with reduced left ventricular ejection fraction (LVEF = 23 ± 7%). All participants completed a maximal graded cardiopulmonary exercise test with non-invasive hemodynamic (bioreactance) monitoring. QOL was assessed using Minnesota Living with Heart Failure Questionnaire. RESULTS: The average value of QOL score was 40 ± 23. There was a significant negative relationship between the QOL and peak O2 consumption (r = - 0.50, p ≤ 0.01). No significant relationship between the QOL and selected exercise hemodynamic measures was found, including peak exercise cardiac power output (r = 0.15, p = 0.34), cardiac output (r = 0.22, p = 0.15), and mean arterial blood pressure (r = - 0.08, p = 0.60). CONCLUSION: Peak O2 consumption, but not hemodynamic response to exercise, is a significant determinant of QOL in chronic heart failure patients.

Peak atrio-ventricular mechanics predicts exercise tolerance in heart failure patients.

PURPOSE: Exercise intolerance is a cardinal symptom of patients with heart failure (HF). We hypothesized that patients with HF with preserved ejection fraction (HFpEF) in comparison with those with reduced ejection fraction (HFrEF) have disproportionate exercise-induced impairment of left atrial (LA) function that may explain the effort intolerance. METHODS: Total 40 HFpEF patients, 40 HFrEF patients, and 20 matched healthy controls underwent resting and exercise stress transthoracic echocardiography using modified Bruce protocol with speckle-tracking derived assessments of peak atrial longitudinal strain (PALS) and left ventricular global longitudinal strain (LVGLS). RESULTS: In comparison to controls, PALS and LVGLS were reduced in HFpEF and HFrEF patients (P < 0.01); however, the strain magnitudes were significantly lower in HFrEF than in HFpEF (P < 0.01). Both HFpEF and HFrEF showed a 28% and 30% reduction in exercise time in comparison with controls (HFpEF, 363 ± 152, HFrEF 352 ± 91, controls, 505 ± 42 s, P < 0.01) and exercise-related rise in E/E' in HFpEF patients. However, during exercise PALS reduced from resting values by 26% (resting 23.1 ± 4.7 and peak 18.5 ± 3.5, P < 0.01) in HFpEF but only 8% in HFrEF (resting 11.5 ± 1.4 and peak 10.5 ± 1.5, P < 0.01), and remained unchanged in controls (resting 34 ± 1.9 and peak 34.4 ± 1.2, P = 0.4). Regression analysis of the combined data from the HF patients and controls revealed that PALS was independently associated with exercise time such that a 1% reduction in PALS was associated with a 10 s reduction in exercise duration (p < 0.01). PALS at baseline and peak exercise differentiated normal from HF patients. LVGLS at baseline and peak exercise differentiated HFpEF from HFrEF and patients of HFpEF showed abnormality of both PALS and LVGLS. CONCLUSION: Although left ventricle and LA strain are lower in HFrEF than HFpEF at rest and exercise compared to healthy controls, patients with HFpEF show more profound deterioration of LA reservoir function with exercise which appears to contribute to exercise intolerance.

Gender differences in the assessment, decision-making and outcomes for ventricular assist devices and heart transplantation: An analysis from a UK transplant center.

PURPOSE: There are marked gender differences in all etiologies of advanced heart failure. We sought to determine whether there is evidence of gender-specific decision making for transplant assessments, and how gender effects outcomes. METHODS: Retrospective analysis of adult heart transplant assessments at a single UK center between April 2015 and March 2020. RESULTS: Females were 32% of referrals (N = 137 females, 285 males), with marked differences between diagnoses - 11% ischemic and 43% of adult congenital. Females were younger, shorter, weighed less, and had lower pulmonary pressures. Females were much less likely to receive a ventricular assist device (13%). Blood type "O" females were relatively more likely compared to males to receive a transplant (45%). Comparing males and females who received a ventricular assist device, both had similar levels of high pulmonary pressures, indicating consistent decision-making based on hemodynamics to implant a device. Overall survival was better for females (in noncongenital patients), and this was due to female patients who were not accepted for transplant or a ventricular assist device being more often "too well for transplant," rather than in males when they were more often "unsuitable." CONCLUSIONS: Marked gender differences exist at all stages of the heart transplant assessment pathway. Appropriate decision-making based on clinical grounds is shown with less transplants in male blood type "O"s and hemodynamic criteria for ventricular assist device implantation in both genders. Further studies are needed to determine if there is a wider community bias in advanced heart failure treatments for females.

Gender Related Differences in the Clinical Presentation of Hypertrophic Cardiomyopathy-An Analysis from the SILICOFCM Database.

Background and Objectives: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease that affects approximately 1 in 500 people. Due to an incomplete disease penetrance associated with numerous factors, HCM is not manifested in all carriers of genetic mutation. Although about two-thirds of patients are male, it seems that female gender is associated with more severe disease phenotype and worse prognosis. The objective of this study was to evaluate the gender related differences in HCM presentation. Materials and Methods: This study was conducted as a part of the international multidisciplinary SILICOFCM project. Clinical information, laboratory analyses, electrocardiography, echocardiography, and genetic testing data were collected for 362 HCM patients from four clinical centers (Florence, Newcastle, Novi Sad, and Regensburg). There were 33% female patients, and 67% male patients. Results: Female patients were older than males (64.5 vs. 53.5 years, p < 0.0005). The male predominance was present across all age groups until the age of 70, when gender distribution became comparable. Females had higher number of symptomatic individuals then males (69% vs. 52%, p = 0.003), most frequently complaining of dyspnea (50% vs. 30%), followed by chest pain (30% vs. 17%), fatigue (26% vs. 13%), palpitations (22% vs. 13%), and syncope (13% vs. 8%). The most common rhythm disorder was atrial fibrillation which was present in a similar number of females and males (19% vs. 13%, p = 0.218). Levels of N-terminal pro-brain natriuretic peptide were comparable between the genders (571 vs. 794 ng/L, p = 0.244). Echocardiography showed similar thickness of interventricular septum (18 vs. 16 mm, p = 0.121) and posterolateral wall (13 vs. 12 mm, p = 0.656), however, females had a lower number of systolic anterior motion (8% vs. 16%, p = 0.020) and other mitral valve abnormalities. Conclusions: Female patients are underrepresented but seem to have a more pronounced clinical presentation of HCM. Therefore, establishing gender specific diagnostic criteria for HCM should be considered.

Disease Progression of Hypertrophic Cardiomyopathy: Modeling Using Machine Learning.

BACKGROUND: Cardiovascular disorders in general are responsible for 30% of deaths worldwide. Among them, hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease that is present in about 1 of 500 young adults and can cause sudden cardiac death (SCD). OBJECTIVE: Although the current state-of-the-art methods model the risk of SCD for patients, to the best of our knowledge, no methods are available for modeling the patient's clinical status up to 10 years ahead. In this paper, we propose a novel machine learning (ML)-based tool for predicting disease progression for patients diagnosed with HCM in terms of adverse remodeling of the heart during a 10-year period. METHODS: The method consisted of 6 predictive regression models that independently predict future values of 6 clinical characteristics: left atrial size, left atrial volume, left ventricular ejection fraction, New York Heart Association functional classification, left ventricular internal diastolic diameter, and left ventricular internal systolic diameter. We supplemented each prediction with the explanation that is generated using the Shapley additive explanation method. RESULTS: The final experiments showed that predictive error is lower on 5 of the 6 constructed models in comparison to experts (on average, by 0.34) or a consortium of experts (on average, by 0.22). The experiments revealed that semisupervised learning and the artificial data from virtual patients help improve predictive accuracies. The best-performing random forest model improved R2 from 0.3 to 0.6. CONCLUSIONS: By engaging medical experts to provide interpretation and validation of the results, we determined the models' favorable performance compared to the performance of experts for 5 of 6 targets.

Does infection predispose to thrombosis during long-term ventricular assist device support?

BACKGROUND: Infections and thrombotic events remain life-threatening complications in patients with ventricular assist devices (VAD). METHODS: We describe the relationship between both events in our cohort of patients (n = 220) supported with the HeartWare VAD (HVAD). This is a retrospective analysis of patients undergoing HVAD implantation between July 2009 and March 2019 at the Freeman Hospital, Newcastle upon Tyne, United Kingdom. RESULTS: Infection was the most common adverse event in HVAD patients, with 125 patients (56.8%) experiencing ≥ one infection (n = 168, 0.33 event per person year (EPPY)), followed by pump thrombosis (PT) in 61 patients (27.7%, 0.16 EPPY). VAD-specific infections were the largest group of infections. Of the 125 patients who had an infection, 66 (53%) had a thrombotic event. Both thrombotic events and infections were related to the duration of support, though there was only limited evidence that infections predispose to thrombosis. Those with higher than median levels of C-reactive protein during the infection were more likely to have an ischaemic stroke (IS) (34.5% vs 16.7%, p = .03), though not PT or a combined thrombotic event (CTE: first PT or IS). However, in multivariate analysis, there was no significant effect of infection predisposing to CTE. CONCLUSIONS: Infection and thrombotic events are significant adverse events related to the duration of support in patients receiving HVADs. Infections do not clearly predispose to thrombotic events.

Feasibility of the cardiac output response to stress test in suspected heart failure patients.

BACKGROUND: Diagnostic tools available to support general practitioners diagnose heart failure (HF) are limited. OBJECTIVES: (i) Determine the feasibility of the novel cardiac output response to stress (CORS) test in suspected HF patients, and (ii) Identify differences in the CORS results between (a) confirmed HF patients from non-HF patients, and (b) HF reduced (HFrEF) vs HF preserved (HFpEF) ejection fraction. METHODS: Single centre, prospective, observational, feasibility study. Consecutive patients with suspected HF (N = 105; mean age: 72 ± 10 years) were recruited from specialized HF diagnostic clinics in secondary care. The consultant cardiologist confirmed or refuted a HF diagnosis. The patient completed the CORS but the researcher administering the test was blinded from the diagnosis. The CORS assessed cardiac function (stroke volume index, SVI) noninvasively using the bioreactance technology at rest-supine, challenge-standing, and stress-step exercise phases. RESULTS: A total of 38 patients were newly diagnosed with HF (HFrEF, n = 21) with 79% being able to complete all phases of the CORS (91% of non-HF patients). A 17% lower SVI was found in HF compared with non-HF patients at rest-supine (43 ± 15 vs 51 ± 16 mL/beat/m2, P = 0.02) and stress-step exercise phase (49 ± 16 vs 58 ± 17 mL/beat/m2, P = 0.02). HFrEF patients demonstrated a lower SVI at rest (39 ± 15 vs 48 ± 13 mL/beat/m2, P = 0.02) and challenge-standing phase (34 ± 9 vs 42 ± 12 mL/beat/m2, P = 0.03) than HFpEF patients. CONCLUSION: The CORS is feasible and patients with HF responded differently to non-HF, and HFrEF from HFpEF. These findings provide further evidence for the potential use of the CORS to improve HF diagnostic and referral accuracy in primary care.

Heart failure (HF) is a global pandemic affecting 26 million people worldwide with an estimated 1 million people in the United Kingdom. Accurate early diagnosis of HF and the initiation of evidence-based treatment is essential to reduce morbidity and mortality and the associated burden on healthcare. As there are no state-of-the-art approaches, early diagnosis is challenging and often inaccurate, as initial signs and symptoms are nonspecific. We have developed an innovative test, named CORS (cardiac output response to stress test), to help general practitioners identify HF, which uses a method similar to an electrocardiogram and measures heart function at rest and during short step exercise. We recruited suspected HF patients from specialist HF diagnostic clinics in secondary care to complete the CORS test. We successfully demonstrated that 79% of patients with newly diagnosed HF (n = 38) and 91% of non-HF patients (n = 67) were able to complete all phases of the CORS test. Our findings demonstrate that newly diagnosed HF patients are able to complete this test, which provides further evidence for the potential use of the CORS test to improve HF diagnostic and referral accuracy in primary care.

LVAD decommissioning for myocardial recovery: Long-term ventricular remodeling and adverse events.

BACKGROUND: Left ventricular assist devices (LVADs) mechanically unload the heart and coupled with neurohormonal therapy can promote reverse cardiac remodeling and myocardial recovery. Minimally invasive LVAD decommissioning with the device left in place has been reported to be safe over short-term follow-up. Whether device retention reduces long-term safety, or sustainability of recovery is unknown. METHODS: This is a dual-center retrospective analysis of patients who had achieved responder status (left ventricular ejection fraction, LVEF ≥40% and left ventricular internal diastolic diameter, LVIDd ≤6.0 cm) and underwent elective LVAD decommissioning for myocardial recovery from May 2010 to January 2020. All patients had outflow graft closure and driveline resection with the LVAD left in place. Emergent LVAD decommissioning for an infection or device thrombosis was excluded. Patients were followed with serial echocardiography for up to 3-years. The primary clinical outcome was survival free of heart failure hospitalization, LVAD reimplantation, or transplant. RESULTS: During the study period 515 patients received an LVAD and 29 (5.6%) achieved myocardial recovery, 12 patients underwent total device explantation or urgent device decommissioning, 17 patients underwent elective LVAD decommissioning, and were included in the analysis. Median age of patients at LVAD implantation was 42 years (interquartile range, IQR: 25-54 years), all had a nonischemic cardiomyopathy, and 5 (29%) were female. At LVAD implantation, median LVEF was 10% (IQR: 5%-15%), and LVIDd 6.6 cm (IQR: 5.8-7.1 cm). There were 11 hydrodynamically levitated centrifugal-flow (65%), and 6 axial-flow LVADs (35%). The median duration of LVAD support before decommissioning was 28.7 months (range 13.5-36.2 months). As compared to the turndown study parameters, 1-month post-decommissioning, median LVEF decreased from 55% to 48% (p = 0.03), and LVIDd increased from 4.8 cm to 5.2 cm (p = 0.10). There was gradual remodeling until 6 months, after which there was no statistical difference on follow-up through 3-years (LVEF 42%, LVIDd 5.6 cm). Recurrent infections affected 41% of patients leading to 3 deaths and 1 complete device explant. Recurrent HF occurred in 1 patient who required a transplant. Probability of survival free of HF, LVAD, or transplant was 94% at 1-year, and 78% at 3-years. CONCLUSIONS: LVAD decommissioning for myocardial recovery was associated with excellent long-term survival free from recurrent heart failure and preservation of ventricular size and function up to 3-years. Reducing the risk of recurrent infections, remains an important therapeutic goal for this management strategy.

Prognostic Value of Peak Oxygen Uptake in Patients Supported With Left Ventricular Assist Devices (PRO-VAD).

OBJECTIVES: The purpose of this study was to examine whether peak oxygen uptake (pVO2) and other cardiopulmonary exercise test (CPET)-derived variables could predict intermediate-term mortality in stable continuous flow LVAD recipients. BACKGROUND: pVO2 is a cornerstone in the selection of patients for heart transplantation, but the prognostic power of pVO2 obtained in patients treated with a left ventricular assist device (LVAD) is unknown. METHODS: We collected data for pVO2 and outcomes in adult LVAD recipients in a retrospective, multicenter study and evaluated cutoff values for pVO2 including: 1) values above or below medians; 2) grouping patients in tertiles; and 3) pVO2 ≤14 ml/kg/min if the patient was not treated with beta-blockers (BB) or pVO2 ≤12 ml/kg/min if the patient was taking BB therapy. RESULTS: Nine centers contributed data from 450 patients. Patients were 53 ± 13 years of age; 78% were male; body mass index was 25 ± 5 kg/m2 with few comorbidities (stroke: 11%; diabetes: 18%; and peripheral artery disease: 4%). The cause of heart failure (HF) was most often nonischemic (66%). Devices included were the HeartMate II and 3 (Abbott); and Heartware ventricular assist devices Jarvik and Duraheart (Medtronic). The index CPET was performed at a median of 189 days (154-225 days) after LVAD implantation, and mean pVO2 was 14.1 ± 5 ml/kg/min (47% ± 14% of predicted value). Lower pVO2 values were strongly associated with poorer survival regardless of whether patients were analyzed for absolute pVO2 in ml/kg/min, pVO2 ≤12 BB/14 ml/kg/min, or as a percentage of predicted pVO2 values (P ≤ 0.001 for all). For patients with pVO2 >12 BB/14 and ventilation/carbon dioxide relationship (VE/VCO2) slope <35, the 1-year survival was 100%. CONCLUSIONS: Even after LVAD implantation, pVO2 has prognostic value, similar to HF patients not supported by mechanical circulatory support devices. (PROgnostic Value of Exercise Capacity Measured as Peak Oxygen Uptake [pVO2] in Recipients of Left Ventricular Assist Devices [PRO-VAD]; NCT04423562).

A machine learning-based risk stratification model for ventricular tachycardia and heart failure in hypertrophic cardiomyopathy.

BACKGROUND: Machine learning (ML) and artificial intelligence are emerging as important components of precision medicine that enhance diagnosis and risk stratification. Risk stratification tools for hypertrophic cardiomyopathy (HCM) exist, but they are based on traditional statistical methods. The aim was to develop a novel machine learning risk stratification tool for the prediction of 5-year risk in HCM. The goal was to determine if its predictive accuracy is higher than the accuracy of the state-of-the-art tools. METHOD: Data from a total of 2302 patients were used. The data were comprised of demographic characteristics, genetic data, clinical investigations, medications, and disease-related events. Four classification models were applied to model the risk level, and their decisions were explained using the SHAP (SHapley Additive exPlanations) method. Unwanted cardiac events were defined as sustained ventricular tachycardia occurrence (VT), heart failure (HF), ICD activation, sudden cardiac death (SCD), cardiac death, and all-cause death. RESULTS: The proposed machine learning approach outperformed the similar existing risk-stratification models for SCD, cardiac death, and all-cause death risk-stratification: it achieved higher AUC by 17%, 9%, and 1%, respectively. The boosted trees achieved the best performing AUC of 0.82. The resulting model most accurately predicts VT, HF, and ICD with AUCs of 0.90, 0.88, and 0.87, respectively. CONCLUSIONS: The proposed risk-stratification model demonstrates high accuracy in predicting events in patients with hypertrophic cardiomyopathy. The use of a machine-learning risk stratification model may improve patient management, clinical practice, and outcomes in general.

The effect of age on mechanisms of exercise tolerance: Reduced arteriovenous oxygen difference causes lower oxygen consumption in older people.

OBJECTIVE: To assess the effect of age on mechanisms of exercise tolerance. METHODS: Prospective observational study recruited 71 healthy individuals divided into two groups according to their age i.e. younger (≤40 years of age, N = 43); and older (≥55 years of age, N = 28). All participants underwent maximal graded cardiopulmonary exercise stress testing using cycle ergometer with simultaneous non-invasive gas-exchange and central haemodynamic measurements. Using the Fick equation, arteriovenous O2 difference was calculated as the ratio between measured O2 consumption and cardiac output. RESULTS: The mean age of younger and older participants was 26.0 ± 5.7 years, and 65.1 ± 6.6 years respectively. Peak O2 consumption was significantly lower in older compared to the younger age group (18.8 ± 5.2 vs 34.4 ± 9.8 mL/kg/min, p < 0.01). Peak exercise cardiac output and cardiac index were not significantly different between the younger and older age groups (22.7 ± 5.0 vs 22.1 ± 3.9 L/min, p = 0.59; and 12.4 ± 2.9 vs 11.8 ± 1.9 L/min/m2, p = 0.29). Despite demonstrating significantly lower peak heart rate by 33 beats/min (129 ± 18.3 vs 162 ± 19.9, p < 0.01), older participants demonstrated significantly higher stroke volume and stroke volume index compared to the younger age group (173 ± 41.5 vs 142 ± 34.9 mL/min, p < 0.01; and 92.1 ± 18.1 vs 78.3 ± 19.5 mL/m2, p < 0.01). Arteriovenous O2 difference was significantly lower in older compared to younger age group participants (9.01 ± 3.0 vs 15.8 ± 4.3 mlO2/100 mL blood, p < 0.01). CONCLUSION: Ability of skeletal muscles to extract delivered oxygen represented by reduced arteriovenous O2 difference at peak exercise appears to be the key determinant of exercise tolerance in healthy older individuals.

Using existing technology better: Improving outcomes with the HeartWare left ventricular assist device.

BACKGROUND: The HeartWare left ventricular assist device has been in use for over 12 years. We sought to determine how outcomes at our centre have improved over time. METHODS: Review of electronic hospital records at the Freeman Hospital, Newcastle upon Tyne, United Kingdom. RESULTS: A total of 255 first time adult implants were divided into 2 eras: Era 1: 2009-2015 (N = 154) and Era 2: 2016-2020 (N = 101). We prospectively aimed to avoid higher risk Intermacs Classifications in Era 2, which resulted in significant changes in Intermacs class to lower risk in Era 2 (P < 0.001). There was a significant improvement in survival in Era 2, with 1 year survival increasing from 70 to 80% (P < 0.05). This was particularly associated with lower 30 day mortality in Era 2 (1.7 ± 2.3 vs 15.5 ± 7%, P < 0.005). This was associated with better right ventricular function in Era 2, and there was a trend to more temporary right ventricular assist devices used in Era 2 (28 ± 13 vs 12 ± 14%, P = 0.06). Deaths from intracranial haemorrhage, sepsis and right heart failure were unchanged between eras, though there was a trend towards less deaths in Era 2 from combined thromboses deaths (stroke and device thrombosis; 3.3 ± 5.4 vs 11.1 ± 7.4%, P = 0.07). CONCLUSIONS: Better patient selection in association with more use of temporary right ventricular assist support has resulted in a significant improvement in survival. Intracranial haemorrhage, sepsis and right heart failure remain significant problems.

Validity of Hemodynamic Monitoring Using Inert Gas Rebreathing Method in Patients With Chronic Heart Failure and Those Implanted With a Left Ventricular Assist Device.

OBJECTIVE: The present study assessed agreement between resting cardiac output estimated by inert gas rebreathing (IGR) and thermodilution methods in patients with heart failure and those implanted with a left ventricular assist device (LVAD). METHODS AND RESULTS: Hemodynamic measurements were obtained in 42 patients, 22 with chronic heart failure and 20 with implanted continuous flow LVAD (34 males, aged 50 ± 11 years). Measurements were performed at rest using thermodilution and IGR methods. Cardiac output derived by thermodilution and IGR were not significantly different in LVAD (4.4 ± 0.9 L/min vs 4.7 ± 0.8 L/min, P = .27) or patients with heart failure (4.4 ± 1.4 L/min vs 4.5 ± 1.3 L/min, P = .75). There was a strong relationship between thermodilution and IGR cardiac index (r = 0.81, P = .001) and stroke volume index (r = 0.75, P = .001). Bland-Altman analysis showed acceptable limits of agreement for cardiac index derived by thermodilution and IGR, namely, the mean difference (lower and upper limits of agreement) for patients with heart failure -0.002 L/min/m2 (-0.65 to 0.66 L/min/m2), and -0.14 L/min/m2 (-0.78 to 0.49 L/min/m2) for patients with LVAD. CONCLUSIONS: IGR is a valid method for estimating cardiac output and should be used in clinical practice to complement the evaluation and management of chronic heart failure and patients with an LVAD.

Noninvasive Assessment of Cardiac Output in Advanced Heart Failure and Heart Transplant Candidates Using the Bioreactance Method.

OBJECTIVES: The aim of the present study was to assess the validity and trending ability of the bioreactance method in estimating cardiac output at rest and in response to stress in advanced heart failure patients and heart transplant candidates. DESIGN: This was a prospective single-center study. SETTING: This study was conducted at the heart transplant center at the Freeman Hospital, Newcastle upon Tyne, UK. PARTICIPANTS: Eighteen patients with advanced chronic heart failure due to reduced left ventricular ejection fraction (19 ± 7%), and peak oxygen consumption 12.3 ± 3.9 mL/kg/min. INTERVENTIONS: Participants underwent right heart catheterization using the Swan-Ganz catheter. MEASUREMENTS AND MAIN RESULTS: Cardiac output was measured simultaneously using thermodilution and bioreactance at rest and during active straight leg raise test to volitional exertion. There was no significant difference in cardiac index values obtained by the thermodilution and bioreactance methods (2.26 ± 0.59 v 2.38 ± 0.50 L/min, p > 0.05) at rest and peak straight leg raise test (2.92 ± 0.77 v 3.01 ± 0.66 L/min, p > 0.05). In response to active leg raise test, thermodilution cardiac output increased by 22% and bioreactance by 21%. There was also a strong relationship between cardiac outputs from both methods at rest (r = 0.88, p < 0.01) and peak straight leg raise test (r = 0.92, p < 0.01). Cartesian plot analysis showed good trending ability of bioreactance compared with thermodilution (concordance rate = 93%) CONCLUSIONS: `Cardiac output measured by the bioreactance method is comparable to that from the thermodilution method. Bioreactance method may be used in clinical practice to assess hemodynamics and improve management of advanced heart failure patients undergoing heart transplant assessment.