Left Ventricular Adaptation to Exercise Training via Magnetic Resonance Imaging: Studies of Twin Responses to Understand Exercise THerapy.

PURPOSE: Changes in left ventricular mass (LVM) and end-diastolic volume (EDV) in response to exercise training are important determinants of functional capacity in health and disease, but the impact of different exercise modalities remains unclear. METHODS: Using a randomized crossover design we studied the impact of resistance (RES) and endurance (END) training using cardiac magnetic resonance imaging in previously untrained monozygotic (MZ) and dizygotic (DZ) twin pairs (n = 72; 22 MZ pairs, 14 DZ same-sex pairs; 26.1 ± 5.4 yr). Twins, as pairs, undertook 3 months of RES and 3 months of END training (order randomized), separated by a 3-month washout. RESULTS: Group results revealed that END increased LVM (P < 0.001) and EDV (P = 0.007), whereas RES did not (P > 0.05). A higher proportion of individuals responded to END than RES for LVM (72% vs 38%, P < 0.001) and EDV (67% vs 40%, P = 0.003). Baseline cross-sectional intraclass correlations were higher for MZ than DZ twin pairs for all variables (e.g., LVM heritability = 0.42), but no significant correlations were apparent between pairs for change in any variable in response to either RES or END (P > 0.05). CONCLUSIONS: Our findings indicate that cardiac adaptation in response to exercise is modality-specific and that low responders to one mode of exercise can be high responders to an alternative. Heritability estimates based on cross-sectional data, which suggested a genetic contribution to LVM, do not accord with estimates based on training effects, which indicated limited genetic impact on adaptation in this 3-month study of exercise training. This study has implications for understanding the physiological and health impacts of typically used exercise modalities on cardiac adaptation in previously untrained individuals.

Sex Differences in Cardiac Adaptation to Distinct Modalities of Exercise: A Cardiac Magnetic Resonance Study.

PURPOSE: No previous study has described sex differences in chronic cardiac adaptation in response to distinct modalities of exercise training in humans. METHODS: Cardiac magnetic resonance imaging (1.5 T) was used to assess left ventricular (LV) outcomes in 78 untrained subjects (46F, 26 M; 26.1 ± 5.4 yr). Subjects underwent 3 months of closely supervised and monitored resistance (RES) and endurance (END) training, separated by a 3-month washout period. RESULTS: LV mass (LVM) increased in response to END in both sexes (females △3.98 ± 7.98 g, P = 0.002; males △5.99 ± 10.67 g, P = 0.005), whereas LV end-diastolic volume (EDV) increased in males (△7.48 ± 11.91 mL, P = 0.002) but not females (△1.54 ± 10.49 mL, P = 0.373). In response to RES, LVM and EDV did not increase in either sex. The proportion of subjects exhibiting a positive response to training (i.e., a change >0) for LVM and EDV did not differ between sexes for either training modality. CONCLUSION: Eccentric hypertrophy in response to END training was more apparent in males than females, whereas there were no notable cardiac changes between sexes for RES training. The proportion of low versus high responders to training was not sex specific for LVM or EDV in response to either commonly prescribed exercise training modality.

Management options to treat gastrointestinal bleeding in patients supported on rotary left ventricular assist devices: a single-center experience.

Gastrointestinal (GI) bleeding in ventricular assist devices (VADs) has been reported with rotary devices. The pathophysiological mechanisms and treatments are in evolution. We performed a retrospective review of GI bleeding episodes for all VADs implanted at our institution. Five male patients experienced GI bleeding-age 63.6 ± 3.64 years. VAD type VentrAssist n = 1, Jarvik 2000 n = 2, and HeartWare n = 2. All patients were anticoagulated as per protocol with antiplatelet agents (aspirin and/or clopidogrel bisulfate [Plavix] and warfarin (therapeutic international normalized ratio 2.0-3.5). There was no prior history of gastric bleeding in this group. Ten episodes of bleeding requiring blood transfusion occurred in five patients. Some patients had multiple episodes (1 × 5, 1 × 2, 3 × 1). The events occurred at varying times post-VAD implantation (days 14, 21, 26, 107, 152, 189, 476, 582, 669, and 839). Octreotide (a long-acting somatostatin analogue that reduces splanchnic arterial and portal blood flow) was administered subcutaneously or intravenously. Three patients received infusions of adrenaline at 1 µg/min to enhance pulsatility. Anticoagulation was interrupted during bleeding episodes but successfully introduced post bleeding event. GI bleeding is a significant complication of VAD therapy. In this article, we discuss diagnosis and management options.

Physical Activity Is Higher in Patients with Left Ventricular Assist Device Compared with Chronic Heart Failure.

PURPOSE: Left ventricular assist devices (LVAD) are associated with an increased aerobic capacity in patients with chronic heart failure (CHF). However, studies evaluating the impact of LVAD implantation on physical activity (PA) are lacking. The aim of this study was to compare daily PA levels in participants with LVAD with well-matched CHF participants. METHODS: Sixteen participants with an LVAD (age, 59.1 ± 10.8 yr) were case-matched to 16 participants with advanced CHF (age, 58.3 ± 8.7 yr), who were listed or being considered for cardiac transplantation. Participants underwent a cardiopulmonary exercise test to determine peak oxygen consumption (V˙O2 peak). Physical activity was monitored continuously for seven consecutive days with an Actiheart monitor. RESULTS: V˙O2 peak in the CHF group (12.3 ± 3.5 mL·kg·min) was not significantly different to the LVAD group before LVAD implantation (10.4 ± 2.1 mL·kg·min), but was lower than in the LVAD group after implantation (15.8 ± 4.3 mL·kg·min; P < 0.05). Physical activity was higher in the LVAD (19.7 ± 6.4 kJ·kg·d) compared with the CHF group (11.6 ± 6.9 kJ·kg·d; P = 0.001). The LVAD participants spent more time performing moderate-intensity PA than their CHF counterparts (median, 26 min·d; interquartile range, 24-40 min·d vs median, 12 min·d; interquartile range, 9-16 min·d; P < 0.001). Physical activity was correlated with V˙O2 peak (r = 0.582; P = 0.001) across participants in the CHF and LVAD groups. CONCLUSIONS: Higher levels of PA were observed in participants with LVAD compared with patients with advanced CHF. This may be due to a higher V˙O2 peak, resulting in an improved capacity to perform activities of daily living with less symptoms.

Cerebral Blood Flow during Exercise in Heart Failure: Effect of Ventricular Assist Devices.

INTRODUCTION: In healthy individuals, cerebral blood flow (CBF) increases during exercise, but few studies have compared changes in CBF during exercise in patients with heart failure (HF) to healthy controls (CTRL) or assessed the effects of left ventricular assist devices (LVAD). We hypothesized that subjects implanted with LVAD would exhibit impaired cerebrovascular responses to cycle exercise when compared with age- and sex-matched healthy CTRL subjects but would have enhanced responses relative to subjects with HF. METHODS: Internal carotid artery (ICA) blood flow and intracranial middle (MCAv) and posterior cerebral (PCAv) artery velocities were measured continuously using Doppler ultrasound, alongside cardiorespiratory measures at rest and in response to an incremental submaximal cycle ergometer exercise protocol in nine LVAD participants (58 ± 15 yr, 87 ± 16 kg, 172 ± 8 cm, six females), nine age- and sex-matched subjects with HF (58 ± 8 yr, 84 ± 11 kg, 177 ± 6 cm), and nine CTRL (55 ± 14 yr, 74 ± 16 kg, 168 ± 10 cm). RESULTS: At rest, ICA hemodynamics (velocity, shear rate, and flow) were greater in CTRL and LVAD than that in HF (P < 0.05). Higher MCAv (+5.52 ± 1.59 cm·s, P = 0.003) and PCAv (+5.82 ± 1.41 cm·s, P = 0.001) were also observed in LVAD subjects than healthy CTRL. During exercise, ICA flow increased at all workloads in CTRL, but not in HF or LVAD groups. MCAv increased from baseline in both HF and CTRL participants (P = 0.0001), but not in LVAD subjects. Nonetheless, CTRL and LVAD showed higher MCAv (P = 0.006) and PCAv (P < 0.0001) values throughout exercise than HF. CONCLUSION: Our findings indicate that LVAD subjects exhibit higher CBF at rest and during exercise than matched HF participants but attenuated brain blood flows during exercise when compared with healthy subjects. CBF should be considered when designing exercise training interventions in patients with HF and LVAD.

Early markers of cardiovascular injury in childhood leukaemia survivors treated with anthracycline chemotherapy.

BACKGROUND: Cardiovascular disease (CVD) is the leading non-malignant cause of death in childhood cancer survivors. Heightened risk of CVD is often attributable to treatment with anthracycline chemotherapy. Anthracycline-mediated cardiac injury may lie latent for years following cessation of treatment and is therefore often not detected until disease is advanced and aggressive therapy is required. Symptomatic CVD may be preceded by subclinical cardiac and vascular dysfunction. This study aimed to determine whether such dysfunction could be detected in healthy, anthracycline-treated survivors of childhood leukaemia. METHODS: Cardiac magnetic resonance imaging (cMRI) with late gadolinium enhancement and endothelial function were used to characterise pre-clinical stages of CVD. Twenty-two long-term (>5 years survival; age 21 ± 3 years) childhood leukaemia survivors were assessed. All survivors were asymptomatic and had normal resting echocardiography. To exclude potential confounding effects of radiotherapy, no survivors had received this treatment. Twenty-two similarly aged (25 ± 3 years) gender-matched controls were recruited for comparison. RESULTS: Left ventricular ejection fraction was lower in the survivors (55.0 ± 4.6%) compared to the controls (59.4 ± 6.2%; p = 0.010). Further, five survivors (23%) had clinically reduced (<50%) left ventricular ejection fraction. Normalised left ventricular end systolic volume was augmented in survivors (40.0 ± 9.1 mL·m2 vs. 34.5 ± 7.5 mL·m2; p = 0.038). Cardiac MRI did not show any late gadolinium enhancement. High resolution, ultrasound-derived flow mediated dilation was impaired in survivors (6.7 ± 2.1% vs. 8.60 ± 1.91%, p = 0.005). CONCLUSIONS: We detected subclinical changes in cardiovascular structure and function indicative of early disease in anthracycline-treated childhood leukaemia survivors with normal echocardiography. Early detection and characterisation of underlying disease allows for timely intervention and improved outcomes in this at-risk population.

Eccentric Cycling: A Promising Modality for Patients with Chronic Heart Failure.

PURPOSE: Chronic heart failure (CHF) is characterized by dyspnea and poor exercise tolerance, which decreases aerobic capacity (V˙O2peak), a measure strongly correlated with quality of life and mortality. In healthy populations, eccentric (ECC) cycling can be performed at a lower oxygen demand for matched workload, compared with concentric (CON) cycling, but few studies have previously investigated ECC cycling in CHF. We hypothesized that, when matched for external workload (W), an ECC cycling bout would be performed at a lower cardiorespiratory load (V˙O2) than CON in patients with CHF. METHODS: Eleven CHF patients (10 males) with impaired left ventricular systolic function (ejection fraction 31% ± 12%) completed a CON V˙O2peak test, with the subsequent ECC and CON protocols set at 70% of individual maximal CON power (W). Oxygen consumption (V˙O2), RER, minute ventilation (V˙E), HR, and rate pressure product were compared between conditions. RESULTS: ECC was performed at a lower V˙O2 (12.3 ± 1.3 vs 14.1 ± 0.8 mL·kg·min, P = 0.01), RER (0.92 ± 0.02 vs 0.96 ± 0.01, P = 0.01), and V˙E (36.5 ± 4.4 vs 40.2 ± 2.0 L·min, P = 0.04) in comparison with CON, despite both conditions being performed at matched workloads. HR (101 ± 5 vs 96 ± 1 bpm, P = 0.06) and rate pressure product (13,539 ± 788 vs 11,911 ± 227 bpm·mm Hg, P = 0.15) were not significantly different between conditions. CONCLUSION: When matched for external workload, ECC cycling can be performed with a lower oxygen demand than CON in patients with CHF. Eccentric cycling is a promising modality for cardiac rehabilitation in severely deconditioned patients with CHF.

Muscle size explains low passive skeletal muscle force in heart failure patients.

BACKGROUND: Alterations in skeletal muscle function and architecture have been linked to the compromised exercise capacity characterizing chronic heart failure (CHF). However, how passive skeletal muscle force is affected in CHF is not clear. Understanding passive force characteristics in CHF can help further elucidate the extent to which altered contractile properties and/or architecture might affect muscle and locomotor function. Therefore, the aim of this study was to investigate passive force in a single muscle for which non-invasive measures of muscle size and estimates of fiber force are possible, the soleus (SOL), both in CHF patients and age- and physical activity-matched control participants. METHODS: Passive SOL muscle force and size were obtained by means of a novel approach combining experimental data (dynamometry, electromyography, ultrasound imaging) with a musculoskeletal model. RESULTS: We found reduced passive SOL forces (∼30%) (at the same relative levels of muscle stretch) in CHF vs. healthy individuals. This difference was eliminated when force was normalized by physiological cross sectional area, indicating that reduced force output may be most strongly associated with muscle size. Nevertheless, passive force was significantly higher in CHF at a given absolute muscle length (non length-normalized) and likely explained by the shorter muscle slack lengths and optimal muscle lengths measured in CHF compared to the control participants. This later factor may lead to altered performance of the SOL in functional tasks such gait. DISCUSSION: These findings suggest introducing exercise rehabilitation targeting muscle hypertrophy and, specifically for the calf muscles, exercise that promotes muscle lengthening.

MR imaging in ischemic heart disease.

This article reviews the current MR imaging literature with respect to ischemic heart disease and focuses on the clinical practicalities of cardiac MR imaging today.

A cardiac magnetic resonance imaging study of electrocardiographic Q waves in type 2 diabetes: the Fremantle Diabetes Study.

To investigate the evolution and significance of Q waves in type 2 diabetes, we studied 36 patients of mean (+/-S.D.) age 69.9+/-7.1 years from the longitudinal observational Fremantle Diabetes Study (FDS). All had (i) neither history/symptoms of coronary heart disease (CHD) nor pathological Q waves at FDS recruitment between 1993 and 1996, (ii) five consecutive annual assessments by FDS close-out in 2001, and (iii) contrast-enhanced cardiac magnetic resonance imaging in 2005. At this latter assessment, there were (i) 9 with no history of CHD or Q waves during follow-up (Group 1), (ii) 13 with Q waves on >/=1 electrocardiogram but no CHD history/symptoms (Group 2), and (iii) 14 with CHD history/symptoms irrespective of electrocardiographic status (Group 3). Of 20 episodes of new Q waves in 17 Group 2 or Group 3 patients during FDS follow-up, 17 (85%) resolved within 2 years. A myocardial infarction (MI) was detected by CMR in three patients (8.3%; one subendocardial in Groups 1 and 3, one non-full-thickness in Group 3) but these did not correlate with electrocardiographic appearances. Q waves may have unreliable pathological significance in type 2 diabetes, including as a marker of silent MI.