Does echocardiography accurately reflect CMR-determined changes in left ventricular parameters following exercise training? A prospective longitudinal study.

Cardiac adaptation in response to exercise has historically been described using echocardiography. Cardiac magnetic resonance (CMR), however, has evolved as a preferred imaging methodology for cardiac morphological assessment. While direct imaging modality comparisons in athletes suggest that large absolute differences in cardiac dimensions exist, it is currently unknown whether changes in cardiac morphology in response to exercise training are comparable when using echocardiography and CMR. Twenty-two young men were randomly assigned to undertake a supervised and intensive endurance or resistance exercise-training program for 24 wk. Echocardiography and CMR assessment of left ventricular (LV) mass, LV end-diastolic volume, internal cavity dimensions, and wall thicknesses were completed before and after training. At baseline, pooled data for all cardiac parameters were significantly different between imaging methods, while LV mass (r = 0.756, P < 0.001) and volumes (LV end-diastolic volume, r = 0.792, P < 0.001) were highly correlated across modalities. Changes in cardiac morphology data with exercise training were not significantly related when echocardiographic and CMR measures were compared. For example, posterior wall thickness increased by 8.3% (P < 0.05) when assessed using echocardiography, but decreased by 2% when using CMR. In summary, echocardiography and CMR imaging modalities produce findings that differ with respect to changes in cardiac size and volume following exercise training.

A comparison of the acute haemodynamic response to aerobic and resistance exercise in subjects with exercise-induced pulmonary arterial hypertension.

BACKGROUND: Exercise-induced pulmonary arterial hypertension (EIPAH) is associated with reduced exercise capacity and abnormal central haemodynamic responses to maximal aerobic exercise. Aerobic and resistance exercise training are commonly employed to treat reduced exercise capacity; however, the haemodynamic response to aerobic and resistance exercise, at training intensities, in subjects with EIPAH is unknown. METHODS: Fourteen subjects (11 with scleroderma, 12 females) with EIPAH underwent cardiopulmonary exercise testing on a cycle ergometer, a one-repetition maximum (1RM) strength test and resistance exercise at 40% and 60% of maximum on a bilateral leg press machine. All tests were performed with a pulmonary artery catheter in situ. Haemodynamic and symptomatic responses to aerobic and resistance exercise, performed at 40% of peak oxygen consumption and 40% of 1RM, and at 60% of peak oxygen consumption and 60% of 1RM, were compared. For maximal exercise, the highest haemodynamic responses recorded during the cycling and 1RM tests were compared. RESULTS: There were no differences in haemodynamic or symptomatic responses between the two modalities of submaximal exercise. At maximal exercise, all haemodynamic and symptomatic responses were lower during resistance compared with aerobic exercise (p < 0.05). CONCLUSIONS: At the intensities studied, lower-limb resistance exercise was well tolerated and was mostly associated with similar or lower haemodynamic responses compared with aerobic exercise, in subjects with EIPAH.

Multicenter evaluation of an intrapericardial left ventricular assist system.

OBJECTIVES: The aim of this study was to conduct an initial clinical evaluation of the new HeartWare Ventricular Assist System (HeartWare, Inc., Framingham, Massachusetts) in a multicenter, prospective, nonrandomized single-arm clinical trial. BACKGROUND: Heart failure is a worldwide epidemic. The effectiveness of heart transplantation and medical therapy is limited, resulting in the emergence of mechanical circulatory support as a primary treatment for end-stage heart disease. Left ventricular assist devices that use rotary pumps are small and durable, which might reduce morbidity and mortality during support. METHODS: Fifty heart transplant candidates with New York Heart Association functional class IV symptoms were supported at 5 international centers by the HeartWare System for 180 days, until heart transplant, myocardial recovery and device explant, or death. Patients who continue to be supported have been followed for a minimum of 2 years. RESULTS: Of the 50 patients, 20 (40%) received transplants, 4 (8%) had the pump explanted after myocardial recovery, and 17 (34%) continue support at 2 years. Nine (18%) patients died during support from sepsis (n = 3), multiple organ failure (n = 3), or hemorrhagic stroke (n = 3). The actual survival at 6, 12, and 24 months was 90%, 84%, and 79%, respectively. In the survivors, measures of quality of life showed a significant improvement over baseline values. Significant improvements were found for recognition memory at 3 months after implant (p = 0.006). The most frequent adverse events were infection and bleeding. CONCLUSIONS: Patients with end-stage heart failure can be safely and effectively supported by the HeartWare Ventricular Assist System with improved quality of life and neurocognitive function.

Implications of exercise-induced pulmonary arterial hypertension.

PURPOSE: To characterize the hemodynamic and ventilatory responses to exercise in a group of patients with unexplained dyspnea, increased risk for pulmonary arterial hypertension (PAH), and an elevated mean pulmonary artery pressure (mPAP; >30 mm Hg) on exercise. METHODS: A total of 37 symptomatic patients at risk of PAH and 20 healthy controls underwent a cardiopulmonary exercise test and were assessed for quality of life (QOL). Patients had a pulmonary artery catheter in situ during the exercise test. RESULTS: Seventeen subjects had exercise-induced PAH (EIPAH), which we defined as mPAP ≤ 25 mm Hg at rest, and mPAP > 30 mm Hg and pulmonary artery wedge pressure <20 mm Hg on exercise. These subjects had reduced peak exercise cardiac output (72% ± 19% predicted). Further, compared with matched controls, subjects with EIPAH had reduced peak oxygen consumption (1.2 ± 0.4 vs 1.7 ± 0.5 L · min, P < 0.05), an elevated ventilatory equivalent for carbon dioxide (41.0 ± 7.3 vs 31.0 ± 2.9, P < 0.05) and reduced end-tidal carbon dioxide tension (32.6 ± 3.6 vs 39.4 ± 2.7 mm Hg, P < 0.05) at the anaerobic threshold. These exercise abnormalities were associated with impaired QOL (P < 0.05). CONCLUSIONS: Elevated pulmonary artery pressure on exercise can be associated with hemodynamic and ventilatory abnormalities typical of PAH, along with impaired exercise capacity and reduced QOL.

The impact of exercise training on conduit artery wall thickness and remodeling in chronic heart failure patients.

Exercise training is an important adjunct to medical therapy in chronic heart failure, but the extent to which exercise impacts on conduit artery remodeling is unknown. The aim of this study was to evaluate the impact of aerobic and resistance exercise training modalities on arterial remodeling in patients with chronic heart failure. We randomized 36 untrained subjects with chronic heart failure to resistance training (58.8 ± 3.5 years), aerobic training (61.3 ± 2.8 years), or an untrained control group (64.4 ± 2.4 years). Peak oxygen consumption during cycle ergometry increased after 12 weeks in both the resistance and aerobic training (P < 0.001) groups, but not in controls, whereas leg strength only increased after resistance training (P < 0.05). Brachial artery wall thickness decreased in the resistance training group (475 ± 10 versus 443 ± 13 µm; P < 0.01), whereas no changes were apparent in the aerobic or control groups. Brachial diameter increased by ≈6% and ≈5% in the aerobic training and resistance training groups (P < 0.01), with no change evident in the control group. The wall:lumen ratio consequently declined in the resistance training group at 12 weeks (0.121 ± 0.004 versus 0.107 ± 0.004; P < 0.01) and increased in the control group (0.111 ± 0.006 versus 0.121 ± 0.009; P < 0.05). No wall:lumen change was evident in the aerobic training group. Our findings suggest that exercise has a systemic impact on remodeling of conduit arteries in humans and that resistance exercise training may be advantageous in subjects with chronic heart failure in this regard.

Australian perspective regarding recommendations for physical activity and exercise rehabilitation in pulmonary arterial hypertension.

AIM: To determine the opinion of health care professionals within Australia, regarding acceptable levels of exertion and symptoms, and referral for exercise rehabilitation in patients with pulmonary arterial hypertension (PAH). METHOD: In 2010, 76 health care professionals at a specialist pulmonary hypertension meeting in Australia were surveyed using a self-administered questionnaire. The questionnaire included case studies of patients with PAH in World Health Organization (WHO) functional classes II-IV. For each case study, respondents were asked to report their opinion regarding the acceptable level of exertion and symptoms during daily activities, and whether they would refer the patient for exercise rehabilitation. Three additional questions asked about advice in relation to four specific physical activities. RESULTS: The response rate was 70% (n = 53). Overall, 58% of respondents recommended patients undertake daily activities 'as tolerated'. There was no consensus regarding acceptable levels of breathlessness or fatigue, but the majority of respondents considered patients should have no chest pain (73%) and no more than mild light-headedness (92%) during daily activities. Overall, 63% of respondents would have referred patients for exercise rehabilitation. There was little difference in opinion regarding the acceptable level of exertion or symptoms, or referral for exercise rehabilitation, according to functional class. However, the patients' functional class did influence the advice given regarding the specific physical activities. CONCLUSION: In 2010, there were inconsistencies between individual health care professionals within Australia regarding appropriate levels of physical exertion and acceptable symptoms during daily activities. Almost two-thirds of the respondents reported they would refer patients for exercise rehabilitation.

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.

Chronic extra-aortic balloon counterpulsation: first-in-human pilot study in end-stage heart failure.

BACKGROUND: Some patients continue to have significant heart failure symptoms despite optimal medical therapy. METHODS: We describe a first-in-human experience with an implantable non-blood-contacting extra-ascending aortic counterpulsation heart assist system (C-Pulse) in 5 end-stage heart failure patients, aged 54 to 73 years. RESULTS: All patients improved by 1 NYHA class and improvements in invasive hemodynamics were documented in 3 patients. Three of 5 patients (60%) had infectious complications. Two patients were explanted at 5 and 7 weeks, respectively, as a result of mediastinal infection related to the implant procedure. One patient was successfully transplanted at 1 month and 1 remained hemodynamically improved on the device at 6 months but suffered infective complications. The device and protocol have been modified as a result of this pilot study with a further multicenter safety study underway. CONCLUSIONS: Although feasibility of this device is suggested by this pilot study, safety and efficacy will need to be examined in a larger cohort with longer follow-up.

Initial clinical experience with a novel left ventricular assist device with a magnetically levitated rotor in a multi-institutional trial.

BACKGROUND: Third-generation rotary blood pumps have magnetically levitated rotors that eliminate mechanical wear over the years. Together with their potential for miniaturization, these pumps seem suitable for long-term support of patients with a wide range of body surface areas (BSA). Recently, the novel HVAD pump (HeartWare Inc, Framingham, MA), a miniaturized centrifugal pump with a hydrodynamic, magnetically levitated rotor, became ready for clinical application. METHODS: In a multi-institutional trial in Europe and Australia, 23 patients (mean age, 47.9 ± 12 years) in end-stage heart failure were enrolled in 5 centers. The primary end point of the bridge-to-transplant study was survival to heart transplant or survival to 180 days on the device, whichever occurred first. Follow-up data at 1 year are presented. The small size of the device allows for intrapericardial placement of the pump. RESULTS: Implant procedures were generally fast and uneventful. Mean duration of support was 167 ± 143 days (range, 13-425 days), and mean blood flow provided by the pump was 6.1 ± 1.1 liters/min. At the 180-day end point, 2 patients had undergone successful transplant at 157 and 175 days, 2 patients died while on the device, and 19 patients continued pump support for more than 180 days. Actuarial survival after 6 months was 91% and was 86% at the 1-year follow-up. CONCLUSIONS: The design of the HVAD pump enables a quick and less invasive implantation. The results to date demonstrate satisfactory long-term survival with excellent quality of life in this cohort of 23 patients of the initial multi-institutional Conformité Européene (CE) mark trial.

Increase in circadian variation after continuous-flow ventricular assist device implantation.

The circadian rhythm of varying blood pressure and heart rate is attenuated or absent in patients with severe heart failure. In 28 patients supported by a left ventricular assist device (LVAD) for at least 30 days, a restoration of the circadian rhythm was demonstrated by a consistent nocturnal decrease, and then increase, of the LVAD flow while at a constant LVAD speed. The return of the circadian rhythm has implications for cardiac recovery, and the observation indicates that the continuous-flow LVAD has an intrinsic automatic response to physiologic demands.

Nitric oxide is not obligatory for radial artery flow-mediated dilation following release of 5 or 10 min distal occlusion.

This study investigated the nitric oxide (NO) dependence of radial artery (RA) flow-mediated dilation (FMD) in response to three different reactive hyperemia (RH) shear stimulus profiles. Ten healthy males underwent the following three RH trials: 1) 5 min occlusion (5 trial), 2) 10 min occlusion (10 trial), and 3) 10 min occlusion with cuff reinflation at 30 s (10-30 trial). Trials were performed during saline infusion and repeated during N(G)-monomethyl-L-arginine (L-NMMA) infusion in the brachial artery. RA blood flow velocity was measured with Doppler ultrasound, and B-mode RA images were analyzed using automated edge detection software. Shear rate estimation of shear stress was calculated as the blood flow velocity/vessel diameter. L-NMMA decreased baseline vascular conductance by 35%. L-NMMA infusion did not affect the peak shear rate stimulus (P = 0.681) or the area under the curve (AUC) of shear rate to peak FMD (P = 0.088). The AUC was significantly larger in the 10 trial vs. the 10-30 or 5 trial (P < 0.001). Although percent FMD (%change in diameter) in the 10 trial was larger than that in the 5 trial (P = 0.035), there was no significant difference in %FMD between the saline and L-NMMA conditions in any trial: 5 trial, 5.62 +/- 1.48 vs. 5.63 +/- 1.27%; 10 trial, 9.07 +/- 1.16 vs. 11.22 +/- 2.21%; 10-30 trial, 6.52 +/- 1.43 vs. 7.98 +/- 1.51% for saline and L-NMMA, respectively (P = 0.158). We conclude the following: 1) RH following 10 min of occlusion results in an enhanced stimulus and %FMD compared with 5 min of occlusion. 2) When the occlusion cuff is reinflated 30 s postrelease of a 10 min occlusion, it does not result in an enhanced %FMD compared with that which results from RH following 5 min of occlusion. 3) The lack of effect of L-NMMA on FMD suggests that NO may not be obligatory for radial artery FMD in response to either 5 or 10 min of occlusion in healthy volunteers.

Impact of inactivity and exercise on the vasculature in humans.

The effects of inactivity and exercise training on established and novel cardiovascular risk factors are relatively modest and do not account for the impact of inactivity and exercise on vascular risk. We examine evidence that inactivity and exercise have direct effects on both vasculature function and structure in humans. Physical deconditioning is associated with enhanced vasoconstrictor tone and has profound and rapid effects on arterial remodelling in both large and smaller arteries. Evidence for an effect of deconditioning on vasodilator function is less consistent. Studies of the impact of exercise training suggest that both functional and structural remodelling adaptations occur and that the magnitude and time-course of these changes depends upon training duration and intensity and the vessel beds involved. Inactivity and exercise have direct "vascular deconditioning and conditioning" effects which likely modify cardiovascular risk.

Anti-thymocyte globulin as an adjunct to treatment of fulminant lymphocytic myocarditis.

There is much debate over the role of immunosuppression in the treatment of acute and fulminant myocarditis. The low incidence of the condition prevents large numbers of cases for study, and treatment protocols vary greatly between institutions. In this study we add our experience with anti-thymocyte globulin as an adjunct to standard medical therapy for 5 patients presenting with cardiogenic shock due to fulminant myocarditis. All cases were associated with rapid and dramatic improvement in hemodynamic and electrophysiologic abnormalities, returning patients to NYHA Class I and cardiac function to normal or near normal by discharge.

Observations from non-invasive measures of right heart hemodynamics in left ventricular assist device patients.

BACKGROUND: Left ventricular assist devices (LVADs) reduce pulmonary vascular resistance (PVR) in patients with severe heart failure. The aim of this study was to noninvasively assess the effect of LVAD implantation on PVR and right-heart function. METHODS: In 21 patients with HeartMate II LVADs, serial echocardiograms were reviewed prior to implantation and 1 and 6 months after implantation. Echocardiographic and Doppler indices of right-heart structure and function were measured along with LVAD settings, hemodynamics, and biochemistry, and the Minnesota Living With Heart Failure Questionnaire (MLHFQ) and 6-minute walk test were administered. RESULTS: Comparing values before and 1 month after implantation, there were reductions in PVR (3.51 +/- 0.9 vs 2.0 +/- 0.5 Wood units, P < .0001), right ventricular (RV) systolic pressure (49 +/- 11 vs 34 +/- 7 mm Hg, P < .0001), and tricuspid regurgitation severity, with no change in RV size, RV fractional area change, or tricuspid annular plane systolic excursion. Patients with larger PVR reductions had better clinical status (MLHFQ score, 28 +/- 12 vs 60 +/- 29, P = .04; 6-minute walking distance, 1706 +/- 71 vs 1141 +/- 387 ft, P = .04). Patients with significant deteriorations in RV function had poorer clinical status (MLHFQ score, 79 +/- 13 vs 51 +/- 27, P = .04; 6-minute walking distance, 480 +/- 275 vs 1030 +/- 437 ft, P = .04). CONCLUSIONS: Echocardiographically detected changes in right-heart hemodynamics were associated with symptomatic status after LVAD implantation.

Resistance training and diastolic myocardial tissue velocities in obese children.

PURPOSE: The primary purpose of this study was to determine the effects of resistance exercise training on early diastolic myocardial velocities (E') in an obese pediatric population. METHODS: Twenty-three obese adolescents were selected to participate in either a resistance-based training program (RT; n = 13, 12.2 +/- 0.4 yr, body mass index [BMI] = 32.5 +/- 1.9 kg m(-2)) or a nonexercise control intervention (n = 10, 13.6 +/- 0.7 yr, BMI = 30.2 +/- 2.6 kg m(-2)) for 8 wk. All subjects had repeated echocardiographic assessments to determine left ventricular (LV) geometry, early transmitral flow velocity (E), and E'. RESULTS: LV mass and wall thicknesses did not significantly change with training or in controls. RT improved E' (11.9 +/- 0.5 to 13.3 +/- 0.5 cm s(-1), P< 0.01) in the presence of a decrease in E/E' (8.17 +/- 0.39 to 7.06 +/- 0.30 cm s(-1), P < 0.01), a marker of left atrial pressure. No changes were evident in the inactive control subjects. CONCLUSIONS: A supervised 8-wk RT exercise program improved early diastolic tissue velocity in obese children, independent of changes in LV morphology.

Successful treatment of rotary pump thrombus with the glycoprotein IIb/IIIa inhibitor tirofiban.

Despite advances in blood pump technology, thrombus formation within left ventricular assist devices (LVADs) is a life-threatening complication with few therapeutic options. A 38-year-old woman who underwent rotary LVAD implantation as a bridge to cardiac transplant developed labile flows (4 to >10 liters), associated with power spikes (4 to 12 watts) and an increase in plasma free hemoglobin (0.86 g/liter), consistent with pump thrombus at Day 140 post-LVAD implantation, despite thromboprophylaxis with aspirin and warfarin. Within 12 hours of commencing an intravenous infusion of tirofiban at a rate of 0.1 mug/kg/min, there were signs of improvement of pump dysfunction, and complete resolution was evident at Day 4 with, stable flows, power consumption and normalization of plasma free hemoglobin. Tirofiban may be considered as an alternative thrombolytic treatment strategy in rotary pump thrombus to avoid the need for LVAD replacement.

First successful bridge to myocardial recovery with a HeartWare HVAD.

In this report we describe the first successful bridge to myocardial recovery with the HeartWare HVAD. Assessment for explantation included serial echocardiography, hemodynamic monitoring, metabolic analysis and manipulation of pump speed, both at rest and during exercise. A protocol for assessing the degree of myocardial recovery without stopping the device is described.

The athlete's heart: a contemporary appraisal of the 'Morganroth hypothesis'.

As early as 1975, Morganroth and colleagues hypothesized that the cardiac morphological adaptation observed in athletes corresponded with the nature of the haemodynamic stimulus imposed on the ventricles during repeated exercise bouts. Endurance training purportedly leads to an eccentric form of cardiac hypertrophy, principally characterized by increased left ventricular (LV) cavity dimension, and thus LV mass (LVM), as a consequence of prolonged repetitive volume overload. In contrast, strength training is supposedly associated with a concentric form of hypertrophy where increased ventricular wall thickness, with no change in cavity size, underpins the elevated LVM as a consequence of the pressure overload produced during strenuous resistive exercise. The 'Morganroth hypothesis' has been broadly adopted in the scientific and medical literature, partly as a consequence of a large body of cross-sectional evidence suggesting that endurance athletes have greater cavity dimensions than control subjects or resistance athletes. However, in conflict with the 'Morganroth hypothesis', several studies suggest that LV wall thickness is increased more in endurance-, than strength-trained athletes and others have reported no morphological changes in resistance-trained athletes. Such controversial data may reflect variability in the training stimuli, with little obvious attempt to quantify these issues in previous research. Further reflection on the 'Morganroth hypothesis' may also be pertinent as more sensitive technologies, such as magnetic resonance imaging, are now being employed for the assessment of cardiac morphology. Finally, the process of scaling (or normalizing) cardiac size for between-subject differences in body size and composition has further complicated the description and understanding of cardiac morphology in athletes. Specifically, it is possible that the increased LVM observed in some athletes may merely reflect a 'larger than normal' body size. These considerations emphasise the limitations of the predominance of cross-sectional comparisons in the available literature, which assume that differences between groups are due to a training effect per se rather than other between-subject differences. The small number of longitudinal training studies undertaken in athletes suggest that individuals with athlete's heart can exhibit further cardiac adaptation in response to training resumption. Longitudinal training studies undertaken in previously sedentary subjects generally indicate that exercise results in enlargement of LV cavity size, increases in wall thickness or LVM following training. However, there are currently limited longitudinal data available to comment on the effects of different modalities of exercise training on LV cavity dimension and wall thickness. In summary, significant caveats related to cross-sectional literature, the relative insensitivity of echocardiographic measurements and the paucity of evidence from longitudinal exercise training studies, warrant ongoing research to verify the 'Morganroth hypothesis'.