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Purpose: The aim of the study was to determine outcomes after heart transplantation for cytomegalovirus (CMV) mismatched patients (D+/R−) who underwent a surveillance and preemptive therapy protocol, compared to nonmismatch patients. Methods: A review of patient records from January 2010 to December 2020 with follow‐up to October 2023 was done. The protocol consisted weekly surveillance with CMV PCR starting 4 weeks after transplant continuing up until the patient seroconverts or up to 3 months posttransplant if the patient does not seroconvert. Valganciclovir was given for 2 weeks to those who seroconverted. Results: Two hundred and twenty‐one patients were included, and 23% were mismatched patients. Overall survival was not different between CMV groups (p = NS). Causes of death and morbidities were also not significantly different (p = NS). Sixty‐six percent of mismatch patients seroconverted, and there was also a significantly older donor age in the seroconverted patients compared to nonseroconverted patients (41 ± 11 vs. 29 ± 12 years, p < 0.005), indicating a higher risk donor profile. A multivariate Cox regression including donor age showed that there was no increase in mortality in the seroconverted mismatches compared to nonmismatch patients (p = NS). Conclusions: There is no significant increased mortality or morbidity using a CMV surveillance and preemptive therapy protocol. The effect of donor age on seroconversion of mismatches requires further validation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Review of electronic hospital records at the Freeman Hospital, Newcastle upon Tyne, United Kingdom. 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). 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. [ABSTRACT FROM AUTHOR]

Despite the advancements in medical treatment, mechanical support, and stem cell therapy, heart transplantation remains the most effective treatment for selected patients with advanced heart failure. However, with an increase in heart failure prevalence worldwide, the gap between donor hearts and patients on the transplant waiting list keeps widening. Ex situ machine perfusion has played a key role in augmenting heart transplant activities in recent years by enabling the usage of donation after circulatory death hearts, allowing longer interval between procurement and implantation, and permitting the safe use of some extended-criteria donation after brainstem death hearts. This exciting field is at a hinge point, with 1 commercially available heart perfusion machine, which has been used in hundreds of heart transplantations, and a number of devices being tested in the pre-clinical and Phase 1 clinical trial stage. However, no consensus has been reached over the optimal preservation temperature, perfusate composition, and perfusion parameters. In addition, there is a lack of objective measurement for allograft quality and viability. This review aims to comprehensively summarize the lessons about ex situ heart perfusion as a platform to preserve, assess, and repair donor hearts, which we have learned from the pre-clinical studies and clinical applications, and explore its exciting potential of revolutionizing heart transplantation. [ABSTRACT FROM AUTHOR]

Summary: Potential heart and lung donors with a history of illicit drugs and/or smoking and alcohol are frequently offered, though there is no clear guidance on when it is safe to use these organs. A review of the literature on effects of drugs, alcohol and smoking on donor outcomes, and the effects of these on the intact heart and lung was undertaken. There has been a marked increase in deaths from opioid abuse in many developed countries, though recent evidence suggests that outcomes after cardiothoracic transplantation are equivalent to nonopioid donor causes of death. For donor smoking, there is an increased risk with lung transplantation; however, that risk is less when compared to further waiting on the transplant list for a nonsmoking alternative. Heavy alcohol consumption does not adversely affect heart transplantation, and there is no clear evidence of adverse outcomes after lung transplantation. There are no overall effects of cannabis or cocaine on survival after heart or lung transplantation. In all these cases, careful donor assessment can establish if a particular organ can be used. In most cases, use of drugs requires careful assessment, but is not in of itself a contraindication to cardiothoracic transplantation. [ABSTRACT FROM AUTHOR]

Keywords: combined thrombotic event; infection; ischaemic stroke; pump thrombosis; ventricular assist device EN combined thrombotic event infection ischaemic stroke pump thrombosis ventricular assist device 462 463 2 03/15/23 20230301 NES 230301 We thank the editors for the opportunity to respond to the Editorial Comment by Dr. Pektok on our article on the relationship between thrombosis and infections in ventricular assist device (VAD) patients.[1] Despite advances in VAD technology, infections and thrombotic events remain potentially life-threatening complications.[2] In brief, we agree with all Dr. Pektok's comments - he highlights well the difficulties in such a large retrospective study looking at events such as infections that may not have clear starting and ending timepoints. To conclude, the pro-thrombotic state secondary to inflammation could have a potential role in thrombotic events in VAD patients, even if the infection was not VAD-related. RELATIONSHIP BETWEEN INFECTION AND THROMBOTIC EVENTS We found that patients with infections had more thrombotic events: 53% of the 125 patients with infections had thrombotic events. [Extracted from the article]

Abstract: Aim: Circadian variation in human ventricular fibrillation (VF) dominant frequency is unknown. If present this would provide evidence of physiological influence on VF. The objective was to quantify the circadian variation in human VF dominant frequency. Methods: Eight-lead Holter ECG recordings were obtained from a patient with severe myocarditis and chronic VF who was supported by a biventricular assist device. Recordings of up to 24h duration were obtained on 6 days with an average interval between recordings of 7 days. Dominant frequency and amplitude were obtained using spectral analysis and assessed for (i) circadian (ii) inter-recording and (iii) inter-lead differences. Results: There was a significant circadian variation in amplitude (night: 0.027±0.004mVHz vs day: 0.044±0.006mVHz, p <0.0001) but not dominant frequency (night: 7.85±0.62Hz vs day: 7.93±0.54Hz, p >0.05). There were significant differences between recordings in dominant frequency which ranged from 6.80±0.29Hz to 8.36±0.38Hz (p <0.0001) and dominant frequency spectral amplitude which ranged from 0.033±0.014mVHz to 0.043±0.017mVHz (p <0.0001). Histograms of dominant frequencies in leads exhibited strikingly different distributions, particularly in V2 that was characterised by a bimodal distribution, while the other leads were characterised by predominantly unimodal distributions. Conclusion: VF dominant frequency spectral amplitude exhibited circadian variability. In a patient with severe myocarditis, supported with a biventricular assist device and in chronic VF, these results provide evidence for modulation of VF, probably induced by changes in posture and physical activity. [Copyright &y& Elsevier]

We explored the relationship between left ventricular (LV) pressure and intracellular free calcium concentration ([Ca]i) in the isolated perfused mouse heart. [Ca]i (rhod-2) and LV pressure were recorded simultaneously. In response to increases in LV volume (Frank-Starling, FS, protocol), there were increases in developed pressure (up to 250%), with no changes in pressure morphology (rise or relaxation time) or [Ca]i (magnitude and morphology) for up to 10 mm. During transient increases in the stimulus interval at a fixed LV volume (mechanical restitution, MR, protocol), developed pressure increased significantly (31.3 ± 1.2%), with relatively small changes in peak systolic [Ca]i (7.4 ± 1.4%). The relaxation of [Ca]i, however, was prolonged (30.0 ± 5.5%), resulting in prolonged pressure relaxation (21.2 ± 1 .9%) and increased area under the calcium transient that paralleled the increase in developed pressure (1:1 ratio). A model-based analysis showed that changes in LV pressure during the MR protocol could be completely explained by altered [Ca]i it was not necessary to invoke any changes in model parameters (i.e., dynamic processes that link calcium to pressure). For the FS data, the model predicted only a change in the gain parameter; however, this change alone cannot reproduce well-established length-dependent changes in the steady-state force-pCa relationship. In summary, the mouse myocardium appears to be unique in that significant changes in peak developed pressure can occur with little or no change in the peak [Ca]i. Additionally, unlike other mammalian species, load-dependent prolongation of pressure relaxation is absent in the mouse heart, and pressure relaxation is primarily governed by intracellular free calcium relaxation. [ABSTRACT FROM AUTHOR]

Objective:Cardiac Troponin I (cTnI) phosphorylation by protein kinase C (PKC) results in a reduction of maximal actomyosin ATPase activity, an effect that is more marked at higher levels of calcium (Ca2+) and is likely to reduce active force development. We postulated that there would be greater Ca2+-dependent changes in ventricular function in hearts of cTnI transgenic (TG) mice expressing mutant troponin I lacking PKC sites compared to wild-type (WT). Methods:We studied left ventricular function in isolated perfused hearts over a wide range of left ventricular volumes (Frank-Starling relationships) and mechanical restitution at three levels of perfusate Ca2+ (1.5, 2.5, and 3.5 mM). Manganese-enhanced magnetic resonance imaging (MRI) was used to study in-vivo sarcolemmal Ca2+ influx. The phosphorylation status of cTnI was examined by western blot analysis. Results:Systolic contractile function in TG mice was altered in a calcium-dependent manner such that ventricular contractility was significantly greater in TG mice only at 3.5 mM perfusate Ca2+. The relaxation process and passive mechanical properties were unaltered in TG mice. Mechanical restitution parameters were abnormal in TG mice only at 1.5 mM perfusate Ca2+. In-vivo MRI data demonstrated up to 48% reduction in Mn2+-induced contrast enhancement, indicating reduced sarcolemmal Ca2+ influx. Western blot analysis indicated increased cTnI phosphorylation in TG mice. Conclusions:(1) TG mice exhibit calcium-dependent positive inotropy without slowed relaxation and this phenotype is mitigated by concomitant (compensatory) changes of reduced intracellular Ca2+ and increased phosphorylation of remaining cTnI sites. (2) The contractile phenotype in TG mice can be interpreted as an amplification of the normal response to changes in cellular Ca2+ observed in WT mice. Thus, PKC phosphorylation sites on cTnI play a role in attenuating contractile responses to changes in intracellular Ca2+. [Copyright &y& Elsevier]

Investigates the compensatory changes in Ca[sup 2+] and myocardial O[sub 2] consumption in beta-tropomyosin transgenic hearts. Negative force-frequency response in perfused hearts from transgenic mice; Reduction of peak systolic intracellular Ca[sup 2+] in transgenic mice; Effect of inotropic interventions.

Presents information on a study which examined the impact of beta-tropomyosin on myocardial calcium concentration, on oxygen consumption and on blood pressure and heart rates relationship. Background on tropomyosin; Methodology; Results of the study.

Presents information on a study which determined the in vivo functional significance of troponin I protein kinase C phosphorylation sites to ischemic dysfunction. Methods; Results; Discussion.

Determines the in vivo functional significance of troponin I (TnI) protein kinase C phosphorylation sites in transgenic mouse. Replacement of phosphorylation sites at serines-43 and 45 by alanine; Level of systolic and diastolic intracellular calcium; Myocardial oxygen consumption; Energetic effects of mutant TnI.

Determines the significance of elevated levels of interleukin-6 in patients with severe heart failure. Analysis of cytokine measurements for tumor necrosis factor-alpha and interleukin-6; Mean value for interleukin-6; Relationship between interleukin-6 and tumor necrosis factor-alpha; Association between the cytokine cascade and neurohumoral activation.

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. 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). 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. 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. • Left ventricle and left atrial strain are lower in HFrEF than HFpEF at rest and exercise compared to healthy controls. • HFpEF show more profound deterioration of peak atrial longitudinal strain with exercise contributing to exercise intolerance. • 1% reduction in peak atrial longitudinal strain is associated with 10 s reduction in exercise time in heart failure patients. [ABSTRACT FROM AUTHOR]

Investigates exercise-related ventilatory abnormalities and survival in congestive heart failure patients. Usefulness of ventilatory abnormalities in determining which patients with severe congestive heart failure are at a high risk for death; Identification of patients which will be prioritized in cardiac transplantation.

Aim: Sacubitril/valsartan treatment reduces mortality and hospitalizations in heart failure with reduced ejection fraction but has limited application in hypertrophic cardiomyopathy (HCM). The aim of this study was to evaluate the effect of sacubitril/valsartan on peak oxygen consumption (VO2) in patients with non‐obstructive HCM. Methods and results: This is a phase II, randomized, open‐label multicentre study that enrolled adult patients with symptomatic non‐obstructive HCM (New York Heart Association class I–III) who were randomly assigned (2:1) to receive sacubitril/valsartan (target dose 97/103 mg) or control for 16 weeks. The primary endpoint was a change in peak VO2. Secondary endpoints included echocardiographic measures of cardiac structure and function, natriuretic peptides and other cardiac biomarkers, and Minnesota Living with Heart Failure quality of life. Between May 2018 and October 2021, 354 patients were screened for eligibility, 115 patients (mean age 58 years, 37% female) met the study inclusion criteria and were randomly assigned to sacubitril/valsartan (n = 79) or control (n = 36). At 16 weeks, there was no significant change in peak VO2 from baseline in the sacubitril/valsartan (15.3 [4.3] vs. 15.9 [4.3] ml/kg/min, p = 0.13) or control group (p = 0.47). No clinically significant changes were found in blood pressure, cardiac structure and function, plasma biomarkers, or quality of life. Conclusion: In patients with HCM, a 16‐week treatment with sacubitril/valsartan was well tolerated but had no effect on exercise capacity, cardiac structure, or function. [ABSTRACT FROM AUTHOR]

An implantable left ventricular assist device (LVAD) is indicated as a bridge to transplantation or recovery in the United Kingdom (UK). The mechanism of action of the LVAD results in a unique state of haemodynamic stability with diminished arterial pulsatility. The clinical assessment of an LVAD recipient can be challenging because non-invasive blood pressure, pulse and oxygen saturation measurements may be hard to obtain. As a result of this unusual situation and complex interplay between the device and the native circulation, resuscitation of LVAD recipients requires bespoke guidelines. Through collaboration with key UK stakeholders, we assessed the current evidence base and developed guidelines for the recognition of clinical deterioration, inadequate circulation and time-critical interventions. Such guidelines, intended for use in transplant centres, are designed to be deployed by those providing immediate care of LVAD patients under conditions of precipitous clinical deterioration. In summary, the Joint British Societies and Transplant Centres LVAD Working Group present the UK guideline on management of emergencies in implantable LVAD recipients for use in advanced heart failure centres. These recommendations have been made with a UK resuscitation focus but are widely applicable to professionals regularly managing patients with implantable LVADs. [ABSTRACT FROM AUTHOR]

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 slee p 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. [ABSTRACT FROM AUTHOR]

The article comments on a study published within the issue which investigated the use of third generation centrifugal left ventricular assist device to reduce pulmonary vascular resistance in heart failure. Results of the study showed that the authors failed to provide additional information on post implantation data on ventricular functions and medications which could be informative in managing the condition.

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·m2cm−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. [ABSTRACT FROM AUTHOR]

Background: Ventricular assist devices (VADs) are a relatively new development in the management of advanced heart failure. In the UK, VAD recipients comprise a unique group of less than 200 patients. This is the first paper to explore the experience of VAD communities, the extent to which communities are developed around the device, and how these influence the experience of living with the VAD. Methods: Qualitative interviews were conducted with 20 VAD recipients (implanted as a bridge to transplantation), 11 interviews also included the VAD recipients’ partners. Interpretive phenomenology was employed as the theoretical basis guiding the analysis of the interviews. Results: Four key themes emerged from the data: the existence of VAD communities; experiential knowledge and understanding; social comparisons; and the impacts of deaths within the VAD community. Many of the interviewees valued the VAD communities and the relationships they had formed with fellow recipients. The beneficial impacts of the VAD communities included offering recently implanted patients a realistic view of what to expect from life with a VAD; this could aid them in accepting and adapting to the changes imparted by the device. However, negative impacts of the VAD communities were also reported, in particular following deaths within the group, which were a source of distress for many of the interviewees. Conclusions: In general, the VAD communities appeared to be a beneficial source of support for the majority of interviewees. Consideration should be given to how these communities could be supported by clinicians. [ABSTRACT FROM AUTHOR]

Ventricular assist devices (VADs) are playing an increasing role in the management of heart failure. VADs are mechanical circulatory devices that support or replace the function of a failing heart. Currently, VADs are only offered in theUnited Kingdom (UK) to patients waiting for a heart transplant; however, the use of these devices is likely to increase in the near future. Presently, there is a dearth of literature exploring the day-to-day realities of living with a VAD, which will become increasingly important as the role of VADs is increased. This paper adopts an interpretive phenomenological approach to uncover the experience of ‘Being’ a VAD recipient. Semi-structured interviews were conducted with 20 VAD recipients. The overarching theme is that life with a VAD is a liminal existence. This comprised four subthemes: the first examines how the VAD imposes limitations on recipients' lives that can precipitate a loss of identity; the second focuses on temporal disruptions, recipients' sense of time changes from authentic to inauthentic; the third explores how the VAD itself is liminal, it is positioned as temporary rather than as the ‘answer’ to the condition; and finally, we discuss VAD recipients' projections to the future and the possibility of an end to the experience of liminality. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Heart rate variability (HRV) is a non-invasive measure of cardiac autonomic function. A clearer understanding as to whether resting autonomic function represented by HRV could be associated with changes in peak exercise cardiac function remains unanswered. This study evaluated the effect of age and sex on HRV, cardiometabolic function, and determined the correlation between HRV and cardiac function in healthy individuals. Sixty-eight participants (age range: 19–78 years old, females, n = 28) were recruited. Participants were stratified according to age (younger (<40 years old, n = 43, females, n = 17) and older age groups (>55 years old, n = 25, females, n = 11). Firstly, HRV was measured using non-invasive impedance cardiography method (TaskForce, CNSystems, Graz, Austria) and recorded at rest (supine position) for 30 min. HRV measures included: low frequency (LF) power, high frequency (HF) power (both normalised (nu) and absolute units (ms2)) and LF/HF ratio. Participants then completed a progressive cardiorespiratory exercise test using a semi-recumbent cycle ergometer (Corival, Lode, Groningen, Netherlands) with simultaneous gas exchange measurements (Metalyzer 3B, Cortex, Leipzig, Germany). Cardiac function was represented by peak exercise cardiac power output index (CPO). After controlling for body mass index and physical activity, males had significantly higher mean vales of RR interval than females (males = 1043 ± 165; females = 952 ± 128 ms, p = 0.02). There was no significant main effect of age, sex or their interaction on any of the other HRV measures. In younger and older females, resting RR interval had a significant relationship with peak exercise CPO (young females: r = 0.54, p < 0.05; old females: r = 0.81, p < 0.01). There was also a significant relationship between resting HF power and peak exercise CPO in younger females (r = 0.70, p < 0.01). HRV was not influenced by age but RR interval was associated with peak exercise CPO in females regardless of age, whilst HF power was significantly associated with CPO in younger females only. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES Ventricular assist device (VAD) for systemic right ventricular (RV) failure patients post-atrial switch, for transposition of the great arteries (TGA), and those with congenitally corrected TGA has proven useful to reduce transpulmonary gradient and bridge-to-transplantation. The purpose of this study is to describe our experience of VAD in systemic RV failure and our move towards concomitant tricuspid valve replacement (TVR). METHODS This is a single-centre retrospective study of consecutive adult patients receiving HeartWare VAD for systemic RV failure between 2010 and 2019. From 2017, concomitant TVR was performed routinely. Demographic, clinical variables and echocardiographic and haemodynamic measurements pre- and post-VAD implantation were recorded. Complications on support, heart transplantation and survival rates were described. RESULTS Eighteen patients underwent VAD implantation. Moderate or severe systemic tricuspid regurgitation was present in 83.3% of patients, and subpulmonic left ventricular impairment in 88.9%. One-year survival was 72.2%. VAD implantation was technically feasible and successful in all but one. Post-VAD, transpulmonary gradient fell from 16 (15–22) to 10 (7–13) mmHg (P = 0.01). Patients with TVR (n = 6) also demonstrated a reduction in mean pulmonary and wedge pressures. Furthermore, subpulmonic left ventricular end-diastolic dimension (44.3 vs 39.6 mm; P = 0.03) and function improved in this group. After 1 year of support, 72.2% of patients were suitable for transplantation. CONCLUSIONS VAD is an effective strategy as bridge-to-candidacy and bridge-to-transplantation in patients with end-stage systemic RV failure. Concomitant TVR at the time of implant is associated with better early haemodynamic and echocardiographic results post-VAD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Purpose: To assess the agreement between cardiac output estimated by two‐dimensional echocardiography and bioreactance methods at rest and during dobutamine stress test in heart failure patients with preserved left ventricular ejection fraction (HFpEF). Methods: Hemodynamic measurements were assessed in 20 stable HFpEF patients (12 females; aged 61 ± 7 years) using echocardiography and bioreactance methods during rest and dobutamine stress test at increment dosages of 5, 10, 15, and 20 μg/kg/min until maximal dose was achieved or symptoms and sign occurred, that is, chest pain, abnormal blood pressure elevation, breathlessness, ischemic changes, or arrhythmia. Results: Resting cardiac output and cardiac index estimated by bioreactance and echocardiography were not significantly different. At peak dobutamine stress test, cardiac output and cardiac index estimated by echocardiography and bioreactance were significantly different (7.06 ± 1.43 vs 5.71 ± 1.59 L/min, P <.01; and 4.27 ± 0.67 vs 3.43 ± 0.87 L/m2/min; P <.01) due to the significant differences in stroke volume. There was a strong positive relationship between cardiac outputs obtained by the two methods at peak dobutamine stress (r =.79, P <.01). The mean difference (lower and upper limits of agreement) between bioreactance and echocardiography cardiac outputs at rest and peak dobutamine stress was −0.45 (1.71 to −2.62) L/min and −1.35 (0.60 to −3.31) L/min, respectively. Conclusion: Bioreactance and echocardiography methods provide different cardiac output values at rest and during stress thus cannot be used interchangeably. Ability to continuously monitor key hemodynamic variables such as cardiac output, stroke volume, and heart rate is the major advantage of bioreactance method. [ABSTRACT FROM AUTHOR]

In response to a growing number of patients on the UK urgent heart transplant waiting list, the UK donor heart allocation scheme was revised in October 2016 with the introduction of a new super-urgent category. Patients with temporary mechanical circulatory support (tMCS) became eligible for super-urgent registration. The aim of this study was to compare activity, indications, and outcomes before and after the change. Data on adult (aged ≥16 years) heart transplant registrations and recipients in the 2 years before (Era 1: July 1, 2014–June 30, 2016) and after (Era 2: January 2017–December 2018) the introduction of the new scheme were extracted from the UK Transplant Registry and analyzed using competing risks analysis, Kaplan–Meier analysis, and Cox proportional-hazards regression. There were 525 waiting-list registrations in Era 1 and 594 in Era 2, including 14% super-urgent registrations, with 90% having some form of tMCS. Median waiting time to transplant was 41 days for all urgent registrations in Era 1 compared with 17 days for super-urgent registrations and 71 days for urgent registrations in Era 2. Numbers of non-urgent transplants were not affected. Deaths on the waiting list significantly decreased from 5% to 2% at 6 months between Era 1 and Era 2 (adjusted hazard ratio = 0.29, 95% CI = 0.13–0.62). In addition, total number of patients with tMCS were not different between both eras, suggesting no significant change in this area of clinical decision making. Post-transplant survival at 1 year for super-urgent recipients was not significantly different from post-transplant survival at 1 year for other categories. The Introduction of a super-urgent heart allocation scheme in the UK reduces waiting time to transplant for the sickest patients, with comparable post-transplant survival while reducing deaths on the waiting list. [ABSTRACT FROM AUTHOR]

Objectives: Heart rate variability (HRV) and haemodynamic response to exercise (i.e. peak cardiac power output) are strong predictors of mortality in heart failure. The present study assessed the relationship between measures of HRV and peak cardiac power output.Design: In a prospective observational study of 33 patients (age 54 ± 16 years) with chronic heart failure with reduced left ventricular ejection fraction (29 ± 11%), measures of the HRV (i.e. R-R interval and standard deviation of normal R-R intervals, SDNN) were recorded in a supine position. All patients underwent maximal graded cardiopulmonary exercise testing with non-invasive (inert gas rebreathing) cardiac output assessment. Cardiac power output, expressed in watts, was calculated as the product of cardiac output and mean arterial blood pressure.Results: The mean RR and SDNN were 837 ± 166 and 96 ± 29 ms, peak exercise cardiac power output 2.28 ± 0.85 watts, cardiac output 10.34 ± 3.14 L/min, mean arterial blood pressure 98 ± 14 mmHg, stroke volume 91.43 ± 40.77 mL/beat, and oxygen consumption 19.0 ± 5.6 mL/kg/min. There was a significant but only moderate relationship between the RR interval and peak exercise cardiac power output (r = 0.43, p = .013), cardiac output (r = 0.35, p = .047), and mean arterial blood pressure (r = 0.45, p = .009). The SDNN correlated with peak cardiac power output (r = 0.42, p = .016), mean arterial blood arterial (r = 0.41, p = .019), and stroke volume (r = 0.35, p = .043).Conclusions: Moderate strength of the relationship between measures of HRV and cardiac response to exercise suggests that cardiac autonomic function is not good indicator of overall function and pumping capability of the heart in chronic heart failure. [ABSTRACT FROM AUTHOR]

Aim: The present study assessed the effect of high intensity interval training on cardiac function during prolonged submaximal exercise in patients with type 2 diabetes.Methods: Twenty-six patients with type 2 diabetes were randomized to a 12 week of high intensity interval training (3 sessions/week) or standard care control group. All patients underwent prolonged (i.e. 60 min) submaximal cardiopulmonary exercise testing (at 50% of previously assess maximal functional capacity) with non-invasive gas-exchange and haemodynamic measurements including cardiac output and stroke volume before and after the intervention.Results: At baseline (prior to intervention) there was no significant difference between the intervention and control group in peak exercise oxygen consumption (20.3 ± 6.1 vs. 21.7 ± 5.5 ml/kg/min, p = 0.21), and peak exercise heart rate (156.3 ± 15.0 vs. 153.8 ± 12.5 beats/min, p = 0.28). During follow-up assessment both groups utilized similar amount of oxygen during prolonged submaximal exercise (15.0 ± 2.4 vs. 15.2 ± 2.2 ml/min/kg, p = 0.71). However, cardiac function i.e. cardiac output during submaximal exercise decreased significantly by 21% in exercise group (16.2 ± 2.7-12.8 ± 3.6 L/min, p = 0.03), but not in the control group (15.7 ± 4.9-16.3 ± 4.1 L/min, p = 0.12). Reduction in exercise cardiac output observed in the exercise group was due to a significant decrease in stroke volume by 13% (p = 0.03) and heart rate by 9% (p = 0.04).Conclusion: Following high intensity interval training patients with type 2 diabetes demonstrate reduced cardiac output during prolonged submaximal cardiopulmonary exercise testing. Ability of patients to maintain prolonged increased metabolic demand but with reduced cardiac output suggests cardiac protective role of high intensity interval training in type 2 diabetes.Trial registration: ISRCTN78698481. Registered 23 January 2013, retrospectively registered. [ABSTRACT FROM AUTHOR]

Abstract The present study evaluated the effect of age on glucose tolerance and cardiac function and assessed the relationship between metabolic control and cardiac function and performance. Thirty-four healthy women aged 40 to 81 years were divided into two age groups: younger (≤50 years of age, N = 19) and older (≥60 years of age, N = 15). Participants performed an oral glucose tolerance test and a graded cardiopulmonary exercise test with non-invasive haemodynamic measurements. Compared to younger, older women demonstrated significantly higher 2-hour glucose (4.67 ± 1.01 vs 6.08 ± 1.54 mmol/l, P < 0.01), but lower peak exercise O 2 consumption (1.96 ± 0.44 vs 1.38 ± 0.26 l/min, P < 0.01) and cardiac power output (4.06 ± 0.76 vs 3.35 ± 0.73 W, P = 0.01). When data from all study participants were combined, there was a significant negative relationship between 2-hour glucose and peak cardiac power (r = −0.39, P = 0.02), and peak O 2 consumption (r = −0.40, P = 0.02). The strength of these relationships was affected by age, with moderate negative relationship identified between 2-hour glucose and peak cardiac power output in younger compared to older participants (r = −0.38, P = 0.11 vs. r = −0.09, P = 0.75). Metabolic control and cardiac function decline with age. The lack of relationship between glucose control and cardiac power may suggest that metabolic control does not influence cardiac function and performance in older women. Highlights • Age is the major risk factor for development of cardiovascular and metabolic diseases. • Cardiac function and glucose control decline with age. • Cardiac function is not associated with glucose control in older women. [ABSTRACT FROM AUTHOR]

The present study evaluated reproducibility of the inert gas rebreathing method to estimate cardiac output at rest and during cardiopulmonary exercise testing. Thirteen healthy subjects (10 males, 3 females, ages 23-32 years) performed maximal graded cardiopulmonary exercise stress test using a cycle ergometer on 2 occasions (Test 1 and Test 2). Participants cycled at 30-watts/ 3-min increments until peak exercise. Hemodynamic variables were assessed at rest and during different exercise intensities (i. e., 60, 120, 150, 180 watts) using an inert gas rebreathing technique. Cardiac output and stroke volume were not significantly different between the 2 tests at rest 7.4 (1.6) vs. 7.1 (1.2) liters min-1, p = 0.54; 114 (28) vs. 108 (15) ml beat-1, p = 0.63) and all stages of exercise. There was a significant positive relationship between Test 1 and Test 2 cardiac outputs when data obtained at rest and during exercise were combined (r = 0.95, p < 0.01 with coefficient of variation of 6.0 %), at rest (r = 0.90, p < 0.01 with coefficient of variation of 5.1 %), and during exercise (r = 0.89, p < 0.01 with coefficient of variation 3.3 %). The mean difference and upper and lower limits of agreement between repeated measures of cardiac output at rest and peak exercise were 0.4 (-1.1 to 1.8) liter min-1 and 0.5 (-2.3 to 3.3) liter min-1, respectively. The inert gas rebreathing method demonstrates an acceptable level of test-retest reproducibility for estimating cardiac output at rest and during cardiopulmonary exercise testing at higher metabolic demands. [ABSTRACT FROM AUTHOR]

Cardiac failure is a major cause of mortality in patients with Duchenne muscular dystrophy (DMD). Antisense-mediated exon skipping has the ability to correct out-of-frame mutations in DMD to produce truncated but functional dystrophin. Traditional antisense approaches have however been limited by their poor uptake into cardiac muscle. The addition of cell-penetrating peptides to antisense molecules has increased their potency and improved their uptake into all muscles, including the heart. We have investigated the efficacy of the Peptide-conjugated phosphodiamidate morpholino oligomer (P-PMO) Pip6a-PMO, for restoration of cardiac dystrophin and functional rescue in DMD mice- the mdx mouse and the less well characterised Cmah-/-mdx mouse (which carry a human-like mutation in the mouse Cmah gene as well as a mutation in DMD). In our first study male mdx mice were administered Pip6a-PMO, i.v, fortnightly from 12 to 30 weeks of age alongside mock-injected age-matched mdx and C57BL10 controls. Mice received 4 doses of 18 mg/kg followed by 8 doses of 12.5 mg/kg. The cardiac function of the mice was analysed 2 weeks after their final injection by MRI followed by conductance catheter and their muscles were harvested for dystrophin quantification. In the second study, male Cmah-/-mdx mice, received 12.5 mg/kg Pip6a-PMO, i.v fortnightly from 8 to 26 weeks and assessed by MRI at 3 time points (12, 18 and 28 weeks) alongside mock-injected age-matched mdx, C57BL10 and Cmah-/-mdx controls. The mice also underwent MEMRI and conductance catheter at 28 weeks. This allowed us to characterise the cardiac phenotype of Cmah-/-mdx mice as well as assess the effects of P-PMO on cardiac function. Pip6a-PMO treatment resulted in significant restoration of dystrophin in mdx and Cmah-/-mdx mice (37.5% and 51.6%, respectively), which was sufficient to significantly improve cardiac function, ameliorating both right and left ventricular dysfunction. Cmah-/-mdx mice showed an abnormal response to dobutamine stress test and this was completely ameliorated by PIP6a-PMO treatment. These encouraging data suggest that total restoration of dystrophin may not be required to significantly improve cardiac outcome in DMD patients and that it may be realistic to expect functional improvements with modest levels of dystrophin restoration which may be very achievable in future clinical trials. [ABSTRACT FROM AUTHOR]

Summary: Purpose: This study assessed the agreement between cardiac output estimated by inert gas rebreathing and bioreactance methods at rest and during exercise. Methods: Haemodynamic measurements were assessed in 20 healthy individuals (11 females, nine males; aged 32 ± 10 years) using inert gas rebreathing and bioreactance methods. Gas exchange and haemodynamic data were measured simultaneously under rest and different stages (i.e. 30, 60, 90, 120, 150 and 180 W) of progressive graded cardiopulmonary exercise stress testing using a bicycle ergometer. Results: At rest, bioreactance produced significantly higher cardiac output values than inert gas rebreathing (7·8 ± 1·4 versus 6·5 ± 1·7 l min−1, P = 0·01). At low‐to‐moderate exercise intensities (i.e. 30–90 W), bioreactance produced significantly higher cardiac outputs compared with rebreathing method (P<0·05). At workloads of 120 W and above, there was no significant difference in cardiac outputs between the two methods (P = 0·10). There was a strong relationship between the two methods (r = 0·82, P = 0·01). Bland–Altman analysis including rest and exercise data showed that inert gas rebreathing reported 1·95 l min−1 lower cardiac output than bioreactance, with lower and upper limits of agreement of −3·1–7·07 l min−1. Analysis of peak exercise data showed a mean difference of 0·4 l min−1 (lower and upper limits of agreement of −4·9–5·7 l min−1) between both devices. Conclusion: Bioreactance and inert gas rebreathing methods show acceptable levels of agreement for estimating cardiac output at higher levels of metabolic demand. However, they cannot be used interchangeably due to strong disparity in results at rest and low‐to‐moderate exercise intensity. [ABSTRACT FROM AUTHOR]

Objectives: Both aging and hypertension are significant risk factors for heart failure in the elderly. The purpose of this study was to determine how aging, with and without hypertension, affects left ventricular function. Methods: Cross-sectional study of magnetic resonance imaging and 31P spectroscopy-based measurements of left ventricular structure, global function, strains, pulse wave velocity, high energy phosphate metabolism in 48 normal subjects and 40 treated hypertensive patients (though no other cardiovascular disease or diabetes) stratified into 3 age deciles from 50–79 years. Results: Normal aging was associated with significant increases in systolic blood pressure, vascular stiffness, torsion, and impaired diastolic function (all P<0.05). Age-matched hypertension exacerbated the effects of aging on systolic pressure, and diastolic function. Hypertension alone, and not aging, was associated with increased left ventricular mass index, reduced energetic reserve, reduced longitudinal shortening and increased endocardial circumferential shortening (all P<0.05). Multiple linear regression analysis showed that these unique hypertensive features were significantly related to systolic blood pressure (P<0.05). Conclusions: 1) Hypertension adds to the age-related changes in systolic blood pressure and diastolic function; 2) hypertension is uniquely associated with changes in several aspects of left ventricular structure, function, systolic strains, and energetics; and 3) these uniquely hypertensive-associated parameters are related to the level of systolic blood pressure and so are potentially modifiable. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background This study examined whether aortic valve opening (AVO) and other echocardiographic parameters influence outcomes in patients on left ventricular (LV) assist device (LVAD) support. Pump thrombosis (PT) and ischemic stroke (IS) are known complications of LVAD, but mechanisms that could influence them are not completely understood. Methods This was a retrospective analysis of 147 patients who received a HeartWare Ventricular Assist Device ( HeartWare International) as a bridge to transplant or to candidacy between July 2009 and August 2015, of whom 126 had at least 30 days of follow-up before the first event (30-days-out cohort). Outcomes included survival, PT, IS, and PT+IS (combined thrombotic event; CTE). Results Median time on support was 518 days. Of the 30-days-out cohort, 29% had a first PT and 19% a first IS. AVO was associated with longer survival on device (1,081 vs 723 days; p = 0.01) in the entire cohort. In the 30-days-out cohort, the aortic valve was more frequently closed in patients with lower ejection fractions on support (14% ± 6% vs 18% ± 9%; p = 0.009), more dilated pre-event echocardiogram (LV end-diastolic diameter, 66 ± 12 mm vs 62 ± 10 mm; p = 0.04), and pre-implant LV end-diastolic diameter (70 ± 10 mm vs 66 ± 9 mm; p = 0.06). CTE-free survival on the device was lower with a closed aortic valve (897 vs 1,314 days; p = 0.003) as was PT-free survival on the device (1,070 vs 1,457 days; p = 0.02). Cox regression analysis showed that AVO was an independent predictor of CTE ( p = 0.03) Conclusions Thrombotic events are relatively frequent in patients on long-term LVAD support. A closed aortic valve was associated with decreased overall survival, thrombosis-free survival, and poorer LV function on support. These are high-risk patients, so whether they require more intense anti-coagulation or prioritizing for transplantation requires further research. [ABSTRACT FROM AUTHOR]

Background In normal ageing, both vascular and ventricular properties change, and how these affect left ventricular function is not clear. Methods 96 subjects (ages 20–79) without cardiovascular disease underwent cardiac magnetic resonance (MR) imaging for measurement of global function, diastolic function (E/A ratio), MR tagging for measurement of torsion to shortening ratio (TSR, ratio of epicardial torsion to endocardial circumferential shortening, with increase in TSR suggesting subendocardial dysfunction relative to the subepicardium), and phase contrast MR imaging measurement of central aortic pulse wave velocity (PWV). The Vicorder device was used to measure carotid to femoral PWV. Results Univariate correlations established that the 4 principal age-related changes in the left ventricular function were: 1) diastolic function: E/A ratio (r: − 0.61, p < 0.00001); 2) global systolic function: cardiac output (r: − 0.49, p < 0.00001), 3) structure: end-diastolic volume index (r: − 0.39, p < 0.0001), and 4) systolic strains: TSR (r: 0.49, p < 0.0001). Multiple linear regression analysis showed that age was the dominant factor in predicting changes in cardiac output and E/A ratio (both p < 0.01). Increased TSR was significantly related to reduced cardiac output and end-diastolic volume index (p < 0.05 and p < 0.01 respectively). Measures of vascular stiffness were not significantly related to any of these variables, but increased effective arterial elastance (afterload) was significantly related to reduced E/A ratio (p < 0.05). Conclusions In this group of normal ageing subjects, afterload but not vascular stiffness is significantly related to diastolic dysfunction. Increased TSR, suggesting relative subendocardial dysfunction, has a significant role in reductions of cardiac output and end-diastolic volume index. [ABSTRACT FROM AUTHOR]

Purpose Successful pregnancy following cardiac transplantation has been described, although outcome data from individual centers are relatively sparse. We investigated maternal and fetal outcomes including change in left ventricular ( LV) function and calcineurin inhibitor ( CNI) dose in women who became pregnant from our institution. Methods We identified every female patient <49 years at the time of transplant who survived >3 months post-surgery, between 1985 and 2014. Those who conceived had a review of their medical records and transplant charts. Those currently alive were interviewed. Results There were 22 pregnancies in 17 women with 20 live births (91%). Mean time from transplantation was 98±62.4 months. Rejection complicated one pregnancy, and LV function remained normal in all others. Hypertension complicated 3 (13.6%), preeclampsia 3 (13.6%), and cholestasis 1 (4.5%). Mean birthweight was 2447±608 grams at 34.1±3.6 weeks. Four women died following pregnancy. A significant increase in total daily dose of tacrolimus and cyclosporine A was required to maintain therapeutic levels through pregnancy (CyA, P<.001; and Tac, P=.001), with no deterioration in serum creatinine. Conclusions We report a 91% live birth rate post-cardiac transplantation. Meticulous individualized care with frequent monitoring of CNI levels and LV function is necessary to optimize the maternal and fetal outcomes. [ABSTRACT FROM AUTHOR]

Background In this study we investigated the development of aortic incompetence (AI) and change in aortic root and left ventricular dimensions after implantation of the continuous-flow HeartWare ventricular assist device (HVAD) in our adult patient cohort. Methods A retrospective analysis of serial echocardiograms was performed on patients implanted with an HVAD between July 2009 and July 2013. Data from echocardiograms performed before and at 1 and 2 years (±3 months) were analyzed. Patients with native aortic valves (AoVs) with no previous intervention and HVAD in situ for ≥6 months were included. Results A total of 73 HVADs in 71 patients with a mean duration of support of 624 ± 359 days were included in our study. One patient developed moderate AI at 1 year (1.9%). Mild or greater AI was more likely in those with a closed or intermittently opening AoV at 1 year ( p = 0.005). Aortic annulus dimensions increased significantly at 1 and 2 years, regardless of extent of AI. At 2 years, in those with mild or worse AI, the sinuses of Valsalva were also larger ( p = 0.002). Left ventricular end-diastolic dimension (LVEDD) was significantly reduced in those with no or trace AI at 1 and 2 years ( p = 0.012 and p = 0.008, respectively), but remained unchanged in those with AI at both time-points. Conclusions The development of more than mild AI is rare in HVAD patients at our center. When encountered, it is more common with a closed AoV. Dilation of the aortic annulus, and root dilation in those with mild or more AI, is seen with HVAD support over time. [ABSTRACT FROM AUTHOR]

Background: Both non-alcoholic fatty liver disease (NAFLD) and Type 2 diabetes increase the risk of developing cardiovascular disease. The metabolic processes underlying NAFLD and Type 2 diabetes are part of an integrated mechanism but little is known about how these conditions may differentially affect the heart. We compared the impact of NAFLD and Type 2 diabetes on cardiac structure, function and metabolism. Methods: 19 adults with Type 2 diabetes (62 ± 8 years), 19 adults with NAFLD (54 ± 15 years) and 19 healthy controls (56 ± 14 years) underwent assessment of cardiac structure, function and metabolism using high resolution magnetic resonance imaging, tagging and spectroscopy at 3.0 T. Results: Adults with NAFLD and Type 2 diabetes demonstrate concentric remodelling with an elevated eccentricity ratio compared to controls (1.05 ± 0.3 vs. 1.12 ± 0.2 vs. 0.89 ± 0.2 g/ml; p < 0.05). Despite this, only the Type 2 diabetes group demonstrate significant systolic and diastolic dysfunction evidenced by a reduced stroke index (31 ± 7vs. controls, 38 ± 10, p < 0.05 ml/m²) and reduced E/A (0.9 ± 0.4 vs. controls, 1.9 ± 1.4, p < 0.05) respectively. The torsion to shortening ratio was higher in Type 2 diabetes compared to NAFLD (0.58 ± 0.16 vs. 0.44 ± 0.13; p < 0.05). Significant associations were observed between fasting blood glucose/HbA1c and diastolic parameters as well as the torsion to shortening ratio (all p < 0.05). Phosphocreatine/adenosine triphosphate ratio was not altered in NAFLD or Type 2 diabetes compared to controls. Conclusions: Changes in cardiac structure are evident in adults with Type 2 diabetes and NAFLD without overt cardiac disease and without changes in cardiac energy metabolism. Only the Type 2 diabetes group display diastolic and subendocardial dysfunction and glycemic control may be a key mediator of these cardiac changes. Therapies should be explored to target these preclinical cardiac changes to modify cardiovascular risk associated with Type 2 diabetes and NAFLD. [ABSTRACT FROM AUTHOR]