Decrease In Left Ventricular Volume Research Articles

Beyond heart rhythm: 12 months in the echocardiographic evaluation of cardiac resynchronization

Abstract Introduction Cardiac resynchronization therapy (CRT) is recommended in patients with heart failure (HF), but 1/3 of patients are "non-responders". More recent resynchronization algorithms promote electrical optimization by dynamically adjusting atrioventricular intervals, reducing QRS duration. However, their impact on left ventricular function parameters remains unclear. Objectives The following echocardiographic parameters were evaluated and compared pre-CRT and at 12 months follow-up: left ventricular (LV) diastolic and systolic volume; ejection fraction (LVEF), global longitudinal myocardial strain (GLS), left atrial (LA) volume; and analytical parameters: NT-ProBNP. Methods Retrospective, comparative study of patients who underwent CRT. All patients underwent echocardiographic study and clinical analysis before CRT implantation and at 12 months follow-up. The following echocardiographic parameters were assessed post-procedure: LVEF (Simpson biplane method); LV volumes and LA volumes indexed to body surface area and GLS (GE Echopac). NT-ProBNP values were collected. Results 50 patients (74 ± 1.3 years, 66% men) were studied, 50% with ischemic heart disease. In the comparative analysis before CRT and at 12-month follow-up, statistically significant differences were observed in LV diastolic and systolic volumes (96.5 ± 4.3 ml/m2 vs. 78. 2 ± 4 ml/m2, p=0.001; 65 ± 3 ml/m2 vs. 48 ± 3 ml/m2, p=0.001), with a significant improvement in LVEF at follow-up (33% ± 1.1 vs. 40% ± 1.4, p=0.001) as well as GLS (-7.8% ± 0.3 vs. -11.5% ± 1, p=0.003). LA volume also showed a significant decrease at follow-up (87 ± 4 ml vs. 71 ±3.8 ml). Reverse remodeling was more evident in patients without a history of ischemic heart disease, with a decrease in LV volumes, improved LVEF and GLS. NT-ProBNP levels also decreased significantly at follow-up (1945 ± 294 pg/mL vs. 783 ± 134 pg/mL, p=0.001). Conclusions CRT implantation is a therapeutic option for patients with HF refractory to medical treatment. Recent resynchronization algorithms show good results in reducing LV volumes as well as improving left ventricular function, and the prognosis of these patients.

Metabolome and microbiome analyses reveal the efficacy of Shen-Fu formula in treating heart failure.

Improvement of strategies to treat heart failure (HF) has been a longstanding global goal and challenge. Shen-Fu formula (SF), as a classic herbal preparation, has demonstrated efficacy in treating HF in clinical settings. However, further understanding of the therapeutic mechanisms of SF is required. In this study, metabolomics and 16S rDNA sequencing were used to analyze the effects of SF on metabolic profiling and gut microbiota in HF rats. After 4 weeks of SF treatment, the cardiac function of HF rats showed improvement, with a significant increase in ejection fraction and fractional shortening, as well as a significant decrease in left ventricular volume and mass. Metabolomics study revealed that SF regulates the levels of substances related to energy metabolism, primarily involving lysophosphatidylcholines and polyunsaturated fatty acids. In addition, we found that SF regulates the structure of the microbial community in HF rats and modulates the balance between probiotic and pathogenic bacteria. Furthermore, the SF combination exhibited a superior effect that was better than the use of each herb separately. These results demonstrate the potential of SF therapy in the management of HF and highlight the role of SF in regulating fatty acid metabolism and gut microbiome during HF.

Relationship between changes in the electrical axis of the heart during inspiration and the structural and functional state of the heart according to echocardiography in patients with precapillary pulmonary hypertension

Introduction. A deep breath causes a whole range of physiological effects that are reflected in the electrocardiogram. The purpose of the study is to assess the position of the electrical axis of the heart during deep inspiration compared to quiet breathing in patients with precapillary pulmonary hypertension and compare these data with echocardiographic characteristics of the structural and functional state of the heart. Materials and methods. The study included 40 patients with idiopathic pulmonary hypertension and 40 patients with chronic thromboembolic pulmonary hypertension. Echocardiography assessed the size of the heart chambers, systolic and diastolic function of the right and left ventricles, pulmonary artery pressure, pulmonary vascular resistance and indicators of cardiovascular coupling. Results. The values of the electrical axis of the heart during free breathing were 106° [84°; 123°], on inspiration – 89° [87°; 120°] (p = 0.68). In 50 (62.5 %) patients, during a deep inspiration, the electrical axis of the heart shifted to the left from the original one, and in 30 (37.5 %) patients – to the right. In patients with a displacement of the electrical axis of the heart to the left from the original, compared with the others, the end-diastolic size of the left ventricle, end-diastolic and end-systolic volumes of the left ventricle, stroke volume, cardiac output were statistically significantly lower, and the eccentricity index, pulmonary vascular resistance and effective aortic stiffness – significantly larger. Conclusion. In patients with precapillary pulmonary hypertension, two variants of changes of the heart electrical axis during deep inspiration were identified: a shift to the right from the original and to the left from the original. Patients with a displacement of the electrical axis to the left from the original were characterized by a significantly greater increase in pulmonary vascular resistance, a decrease in left ventricular volumes, stroke volume and cardiac output.

A New Cardiovascular Mock Loop Driven by Novel Active Capacitance in Normal and Abnormal Conditions.

The hybrid mock circulatory loop (hMCL) serves as a crucial hemodynamic simulation tool, offering exceptional flexibility, controllability, and reproducibility for investigating the mechanisms underlying cardiovascular diseases (CVD) in a controlled environment, circumventing the limitations of live organism studies. This paper introduces a novel design and control strategy for hMCL, introducing a novel left ventricle volume-elastance (LVVE) equation that unifies the autoregulation of the Frank-Starling mechanism (FSM) with left ventricle contractility (LVC). LVVE establishes a dynamic link between left ventricular volume (LVV) and LVC, inherently satisfying the regulatory relationship between left ventricular pressure (LVP) and LVV through a mathematical equation. For the first time, LVVE integration significantly enhances the physiological relevance of hMCL by faithfully replicating FSM responses across diverse conditions, including aortic stenosis (AS), variations in systemic vascular resistance (SVR), and heart rate (HR) variations. Furthermore, this study introduces the stability proofs for the discrete closed-loop hMCL, enabling real-time proportional valve control through discrete feedback linearization-an innovative departure from conventional methods. Notably, FSM emulation is achieved by tracking reference maximum and minimum LVV values, eliminating the reliance on predefined functions or existing data, such as the maximum LV elastance value. Rigorous experimental validation, encompassing numerical simulations and comparative analyses with prior research, attests to the precision and efficacy of the proposed hMCL in faithfully replicating both normal and abnormal CV conditions. Significantly, the hMCL demonstrates that increasing HR enhances LVC while maintaining physiological pressures; however, this increase in LVC corresponds with a decrease in LVV, in alignment with human data and FSM principles. Crucially, the coupling mechanism between the FSM and LVC yields results of enhanced physiological fidelity, significantly advancing the hMCL's utility in physiological research. Moreover, the hMCL's capacity to simulate critical cardiovascular scenarios, including AS, SVR fluctuations, and HR variations, underscores its versatility and substantial potential for investigating complex CV dynamics.

Age-, Sex-, and Race-Based Normal Values for Left Ventricular Circumferential Strain from the World Alliance Societies of Echocardiography Study

Left ventricular (LV) circumferential strain has received less attention than longitudinal deformation, which has recently become part of routine clinical practice. Among other reasons, this is because of the lack of established normal values. Accordingly, we aimed to establish normative values for LV circumferential strain and determine sex-, age- and race-related differences in a large cohort of healthy adults. Complete 2D transthoracic echocardiograms were obtained in 1572 healthy subjects (51% male), enrolled in the World Alliance of Societies of Echocardiography (WASE) Study. Subjects were divided into 3 age groups (<35, 35-55, >55 years) and stratified by sex and by race. Vendor-independent semi-automated speckle tracking software was used to determine LV regional and global circumferential strain (GCS) values. Limits of normal for each measurement were defined as 95% of the corresponding sex and age group falling between the 2.5th and 97.5th percentiles. Intergroup differences were analyzed using unpaired t-tests. Circumferential strain showed a gradient, with lower magnitude at the mitral valve level, increasing progressively towards the apex. Compared to men, women had statistically higher magnitude of regional and global strain. Older age was associated with a stepwise increase in GCS despite an unaffected EF, a decrease in LV volume and a relatively stable GLS in men with a small gradual decrease in women. Asian subjects demonstrated significantly higher GCS magnitudes than whites of both sexes and blacks in women only. In contrast, no significant differences in GCS were found between white and black subjects of either sex. Importantly, despite statistical significance of the above differences across sex-, age- and races, circumferential strain values were similar in all groups, with variations of the order of magnitude of 1-2%. Notably, no differences in GCS were found between brands of imaging equipment. This study established normal values of LV regional and global circumferential strain, and identified sex-, age- and race-related differences, where present.

The Increase in Paraoxonase 1 Is Associated With Decrease in Left Ventricular Volume in Kidney Transplant Recipients.

Background: Patients on dialysis have impaired cardiac function, in part due to increased fluid volume and ventricular stress. Restored kidney function through transplantation reduces left ventricular volume in both systole and diastole. We previously reported that the decrease in NT-proB-type natriuretic peptide (NT-proBNP) was associated with a decrease in adiponectin. Paraoxonase 1 (PON1) has been inversely associated with cardiovascular outcomes. We now report the association of changes in PON1 with changes in left ventricular volume and left ventricular mass after kidney transplantation.Design: Patients on dialysis were assessed at baseline and 12 months after kidney transplantation (n = 38). A comparison group of patients on dialysis who were not expected to receive a transplant in the next 24 months were studied (n = 43) to determine if the change of PON1 with kidney transplantation achieved a significance greater than that due to biologic variation. Left ventricular volume and mass were determined by cardiac magnetic resonance imaging. PON1 was measured by arylesterase activity and by mass.Results: PON1 mass and activity were not different between the groups at baseline. Both PON1 mass and activity were increased post-kidney transplantation (p < 0.0001 for change). The change in PON1 mass (p = 0.0062) and PON1 arylesterase activity (p = 0.0254) were inversely correlated with the change in NT-proBNP for patients receiving a kidney transplant. However, only the change in the PON1 mass, and not the change in PON1 arylesterase, was inversely correlated with the change in left ventricular volume (ml/m2.7) (p = 0.0146 and 0.0114 for diastolic and systolic, respectively) and with the change in hemoglobin (p = 0.0042).Conclusion: Both PON1 mass and arylesterase activity are increased by kidney transplantation. The increase in PON1 mass is consistent with a novel relationship to the increase in hemoglobin and decrease in left ventricular volume and NT-proBNP seen when kidney function is restored.

Reverse remodeling against the background of cardiac contractility modulation therapy in patients with heart failure and atrial fibrillation

Aim. To study myocardial remodeling in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and atrial fibrillation (AF) against the background of cardiac contractility modulation (CCM) therapy.Material and methods. In a group of 100 patients with HFrEF and AF, transthoracic echocardiography was performed before CCM device implantation and after 2, 6 and 12 months. All patients received longterm optimal medical therapy for HF before surgery.Results. Against the background of CCM therapy, there was a significant increase in left ventricular (LV) ejection fraction, a decrease in LV volume and linear dimensions, a decrease in left atrial volume in patients with coronary and non-coronary HFrEF, with an initial LVEF &lt; and &gt;35%, and also regardless of AF type.Conclusion. CCM therapy in patients with HFrEF and AF led to favorable myocardial remodeling changes. Further study of CCM effect on echocardiographic parameters in randomized clinical trials is needed.

Age-related longitudinal change in cardiac structure and function in adults at increased cardiovascular risk.

AimHeart failure (HF) incidence increases markedly with age. We examined age‐associated longitudinal change in cardiac structure and function, and their prediction by age and cardiovascular disease (CVD) risk factors, in a community‐based cohort aged ≥60 years at increased CVD risk but without HF.Methods and resultsCVD risk factors were recorded in 3065 participants who underwent a baseline echocardiographic examination, of whom 2358 attended a follow‐up examination 3.8 [median, inter‐quartile range (IQR) 3.5, 4.2] years later. Median age was 71 (IQR 67, 76) years and 55% of participants were male. Age was associated with longitudinal increase in left ventricular (LV) mass index (LVMI); decrease in LV volumes; increase in LV ejection fraction; decrease in mitral annular systolic velocity; decrease in diastolic function (decreased mitral early diastolic annular velocity (e′); and increase in left atrial volume index, mitral peak early diastolic flow velocity (E)/e′ ratio, and tricuspid regurgitant velocity (TRVmax) in men and women, except for TRVmax in men). In multivariable analysis, longitudinal increase in LVMI was explained by CVD risk factors alone, whereas age, together with CVD risk factors, independently predicted longitudinal change in all other echocardiographic parameters. CVD risk factors were differentially associated with longitudinal change in different echocardiographic parameters.ConclusionsWhereas the increase in LVMI with age was explained by CVD risk factors alone, age, together with risk factors, independently predicted longitudinal change in all other echocardiographic parameters, providing evidence for age‐specific mechanisms of change in cardiac structure and function as people age. Age‐associated change in LVMI, LV volumes, and diastolic function resembled what might be expected for the evolution of HF with preserved ejection fraction. Given the differential association of different CVD risk factors with longitudinal change in different echocardiographic parameters, therapies aimed at attenuation of age‐associated change in cardiac structure and function, and HF evolution, will likely need to address multiple CVD risk factors.

P703 A breathtaking heart. The loeffler"s endocarditis

Abstract This is a 72 year-old man known for idiopathic HES with endomyocardial fibrosis and moderate aortic regurgitation, treated with corticosteroids and antithrombotics. Two months prior to admission, he develops progressive exertional dyspnea reaching NYHA 3 class, with concomitant peripheral edema and rise in NT-proBNP. Cardiac transthoracic work-up shows a preserved left ventricular ejection fraction, but more marked dilatation with decrease in left ventricular volume due to a large echodense mass in the apex. The transmitral flow is restrictive, and the aortic regurgitation moderate. In view of this rapid evolution, resection of the left ventricular mass with concomitant aortic valve replacement is performed. Pathology confirmed eosinophilic infiltration. First described in 1975, hypereosinophilic syndrome (HES) is a rare pathology that is defined as an absolute eosinophil count (&amp;gt;1,5 G/L) in the peripheral blood with eosinophil-mediated organ damage and /or dysfunction. We know three mains categories; primary (or neoplastic), secondary (or reactive) and idiopathic. Cardiac involvement is uncertain and cardiac injury does not clearly correlate with degree of peripheral eosinophilia. Heart tissue damage evolves through three stages (necrotic, intermediate and fibrotic). Endomyocardial fibrosis and eosinophilic myocarditis, also known as "Loeffler’s endocarditis", are major causes of morbidity and mortality among patients with HES. Echocardiography plays a crucial role in initial diagnosis of endomyocardial fibrosis, displaying myocardial wall thickening, signs of restriction (mitral inflow with large E wave and small A wave; E/A ratio greater than 2, short deceleration time less than 150 ms) and intracardiac thrombus (fixed mass embedding left ventricular apex). Valve regurgitation is another possible complication due to entrapment of the chordae tendinae and/or leaflets during the fibrotic stage of this disease. Cardiac MRI is another important diagnostic tool for precising cardiac involvement. Despite of steadily improving noninvasive diagnostic imaging methods, endomyocardial biosy still remains the gold standard exam and ultrasounds work-up is crucial for follow-up. In conclusion, endomyocardial fibrosis is a rare cause of restrictive cardiomyopathy characterized by echocardiographic sign of elevated filling pressure, progressive endomyocardial thickening, valve regurgitation and possible intracardiac thrombus formation. This case underlines the importance of echocardiography in initial diagnosis and regular follow-up of this type of patients, in order to adapt medical treatment and monitor hemodynamic evolution of the restrictive physiology and of valvular damage. Abstract P703 Figure. HES-3

Assessment of left ventricular systolic function after VSD transcatheter device closure using speckle tracking echocardiography

BackgroundThis is a case-control study conducted on 30 children, 15 with VSD who performed VSD transcatheter device closure (group A) and 15 controls of matching age and gender (group B), in the period between September 2015 and February 2018. We aimed to assess the global left ventricular (LV) systolic function by 2D speckle tracking before and after ventricular septal defect (VSD) transcatheter closure, in comparison to normal controls. All patients were subjected to full history taking; general and cardiac examination; ECG; CXR; full transthoracic echocardiographic examination, including VSD number, size, and site; LV dimensions and volumes; estimated pulmonary artery pressure; right ventricular size and function; left ventricular circumferential; and radial strain imaging by 2D speckle tracking. Patients who had ventricular septal defect closed were reassessed by transthoracic echocardiography after 3 months.ResultsThe study included 15 children with VSD: 3 males and 12 females; their age ranged from 2 to 13 years; all had subaortic VSD except for 1 who had apical muscular VSD: VSD size ranged from 3 to 8 mm; PFM coil was used to close defect in all patients except for 2 patients who had an Amplatzer duct occlude I (ADOI) device, and 1 patient needed an additional vascular plug after significant hemolysis. Pre-procedurally, group A had a significantly higher LVEDD, LVESD, and LVEDV than group B. Mean circumferential strain was significantly higher (more negative) in group A than that in group B either pre- or post-procedure. Post-procedurally, there was a significant decrease in circumferential strain (less negative) and a significant increase in radial strain (more positive).ConclusionFollowing transcatheter VSD closure, there is a significant decrease in LV circumferential strain and a significant increase in LV radial strain, which conclude a decrease in LV volume overload with the improvement of its contractility.

Clinical manifestations following intramuscular exposure of mice to a lethal dose of ricin

Abstract Ricin a plant toxin derived from seeds of Ricinus communis, irreversibly inactivates ribosomes by site-specific depurination, thereby arresting cell protein synthesis, while its clinical manifestations following intramuscular exposure have not yet been investigated in depth. Here we report an extensive pathological study of intramuscular intoxication with a lethal dose of ricin in a murine model. Ricin injection caused neutrophilia, thrombocytopenia and coagulopathy. Although histopathological alternations including hemorrhages, vessel congestion and focal necrosis were observed in various organs, major insults were limited to the spleen, bone marrow (BM) and cardiovascular system. Intensive atrophy, evident in the BM and splenic white pulps, were accompanied be severe depletion of megakaryocytes in both organs. Moreover, splenic T and B lymphocytes, NK cells, macrophages and dendritic cells decreased significantly. The most striking damage was in the heart, where we observed diffuse hemorrhages, myocyte disconnection, loss of striation, interstitial edema, collagen deposition and elevated levels of serum cardiac troponin. Finally, echocardiography revealed marked thickening of the walls, along with sequential decrease in left ventricular volume. These were accompanied by a significant reduction in stroke volume and cardiac output, while the ejection fraction remained unaltered. Measurements of the toxin direct catalytic performance in the spleen, BM and heart of the ricin-intoxicated mice revealed no substantial 28S rRNA depurination. The lack of measurable ricin catalytic activity in conjunction with the striking clinical disorders observed, suggests that ricin affects these organs in an indirect manner.

RF63 PROSPECTIVE EVALUATION OF VENTRICULAR LOADING TREND IN PEDIATRIC PATIENTS WITH PULSATILE FLOW LVAD

Aim: The aim of this study was to describe the echocardiographic trend of left ventricular (LV) and right ventricular (RV) function after implantation of a pulsatile flow left ventricular assist device (LVAD) in children. Methods: From 2013 to 2016, we prospectively evaluated 13 consecutive pediatric Berlin Heart EXCOR LVAD patients. Clinical and echocardiographic data were collected at baseline, within 24 h after implantation and monthly until LVAD explant. Results: Median age and weight at the implantation was 8 (4–23) months and 5 (4.6–8.3) kg at the time of implantation, respectively. All were affected by dilated cardiomyopathy. Average LVAD support time was 226.2 ± 121.2 days. Nine (70%) were transplanted, 4 (30%) died. LV end-systolic and end-diastolic volumes were reduced until the follow up of two months (P = 0.019 and P = 0.001). A progressive increase in RV dimensions was observed. After 4 months of follow up, RV fractional area change worsening was statistically related with the deterioration of LV unloading (P = 0.0036). Four patients needed prolonged inotropic support for RV failure. Conclusion: Pulsatile LVAD in pediatrics is followed by an early and mid-term LV unloading, as expressed by a decrease in LV volumes and diameters at echocardiogram. The effects of unloading do not remain stable at long term follow up. RV function improved in the acute phase, but a progressive dilatation of RV was noted over time. In some patients, RV failure might lead to the need of an increase of inotropic support at long term follow up.

Comprehensive Assessment of Mitral Valve Geometry and Cardiac Remodeling With 3-Dimensional Echocardiography After Percutaneous Mitral Valve Repair

MitraClip is a validated treatment for significant mitral regurgitation (MR) in high-risk patients. Aims of the study were to evaluate immediate changes in mitral valve (MV) geometry induced by MitraClip and correlations between baseline geometry and cardiac remodeling. Eighty patients who underwent MitraClip for primary (48%) or secondary (52%) MR were enrolled. Intraoperative transesophageal echocardiographic 3D images were acquired immediately before and after the procedure for MV annulus (MVA) morphology analysis. Transthoracic 3D echocardiography was performed preoperatively and at 6 months follow-up (6MFU). Patients were classified on the basis of MR reduction (ΔMR) at 6MFU as Optimal (ΔMR ≥ 2) or Suboptimal (ΔMR < 2). An optimal result was reached in 60 (75%) patients, whereas 20 subjects showed a ΔMR< 2 at 6MFU. The Optimal showed significantly smaller baseline MVA (antero-posterior diameter 4.05 ± 0.59 vs 4.43 ± 0.68 cm; anterolateral-posteromedial diameter 4.38 ± 0.56 vs 4.70 ± 0.73 cm; MVA circumference 14.1 ± 1.7 vs 15.1 ± 2.3 cm; and 3D area 14.8 ± 3.9 vs 17.4 ± 5.3 cm2), lower sphericity index and nonplanar angle compared with Suboptimal. A value of antero-posterior diameter ≥4.44cm was identified (receiver-operating characteristic curve) as a possible cut-off for preoperative identification of Suboptimal patients. Postoperatively, MitraClip induced reduction of MVA flattening (nonplanar angle), sphericity index, and size (as expressed by antero-posterior diameter, MVA circumference and area). At 6MFU, the Optimal showed significant decrease in left ventricular volumes and pulmonary artery systolic pressure. In conclusion, MitraClip induces remarkable changes in MVA geometry and favorable left ventricular remodeling is detected in patients with optimal mid-term outcome; a preprocedural antero-posterior diameter <4.44cm seems to be a potential predictor of mid-term optimal result.

Evolution of Biventricular Loading Condition in Pediatric LVAD Patient: A Prospective and Observational Study.

The aim of this study was to describe the echocardiographic trend of left ventricular (LV) and right ventricular (RV) function after implantation of a pulsatile flow left ventricular assist device (LVAD) in children. From 2013 to 2016, we prospectively evaluated 13 consecutive pediatric Berlin Heart EXCOR LVAD patients. Clinical and echocardiographic data were collected at baseline, within 24 h after implantation and monthly until LVAD explant. Median age and weight at the implantation was 8 (4-23) months and 5 (4.6-8.3) kg at the time of implantation, respectively. All were affected by dilated cardiomyopathy. Average LVAD support time was 226.2 ± 121.2 days. Nine (70%) were transplanted, 4 (30%) died. LV end-systolic and end-diastolic volumes were reduced until the follow up of two months (P = 0.019 and P = 0.001). A progressive increase in RV dimensions was observed. After 4 months of follow up, RV fractional area change worsening was statistically related with the deterioration of LV unloading (P = 0.0036). Four patients needed prolonged inotropic support for RV failure. Pulsatile LVAD in pediatrics is followed by an early and mid-term LV unloading, as expressed by a decrease in LV volumes and diameters at echocardiogram. The effects of unloading do not remain stable at long term follow up. RV function improved in the acute phase, but a progressive dilatation of RV was noted over time. In some patients, RV failure might lead to the need of an increase of inotropic support at long term follow up.

Physiologic Changes in the Heart Following Cessation of Mechanical Ventilation in a Porcine Model of Donation After Circulatory Death: Implications for Cardiac Transplantation.

Hearts donated following circulatory death (DCD) may represent an additional source of organs for transplantation; however, the impact of donor extubation on the DCD heart has not been well characterized. We sought to describe the physiologic changes that occur following withdrawal of life-sustaining therapy (WLST) in a porcine model of DCD. Physiologic changes were monitored continuously for 20 min following WLST. Ventricular pressure, volume, and function were recorded using a conductance catheter placed into the right (N = 8) and left (N = 8) ventricles, and using magnetic resonance imaging (MRI, N = 3). Hypoxic pulmonary vasoconstriction occurred following WLST, and was associated with distension of the right ventricle (RV) and reduced cardiac output. A 120-fold increase in epinephrine was subsequently observed that produced a transient hyperdynamic phase; however, progressive RV distension developed during this time. Circulatory arrest occurred 7.6±0.3 min following WLST, at which time MRI demonstrated an 18±7% increase in RV volume and a 12±9% decrease in left ventricular volume compared to baseline. We conclude that hypoxic pulmonary vasoconstriction and a profound catecholamine surge occur following WLST that result in distension of the RV. These changes have important implications on the resuscitation, preservation, and evaluation of DCD hearts prior to transplantation.

Interaction between respiration and right versus left ventricular volumes at rest and during exercise: a real-time cardiac magnetic resonance study

Breathing-induced changes in intrathoracic pressures influence left ventricular (LV) and right ventricular (RV) volumes, the exact nature and extent of which have not previously been evaluated in humans. We sought to examine this "respiratory pump" using novel real-time cardiac magnetic resonance (CMR) imaging. Eight healthy subjects underwent serial multislice real-time CMR during normal breathing, breath holding, and the Valsalva maneuver. Subsequently, a separate cohort of nine subjects underwent real-time CMR at rest and during incremental exercise. LV and RV end-diastolic volume (EDV) and end-systolic volume (ESV) and diastolic and systolic eccentricity indexes were determined at peak inspiration and expiration. During normal breathing, inspiration resulted in an increase in RV volumes [RVEDV: +18 ± 8%, RVESV: +14 ± 12%, and RV stroke volume (SV): +21 ± 10%, P < 0.01] and an opposing decrease in LV volumes (P < 0.0001 for interaction). During end-inspiratory breath holding, RV SV decreased by 9 ± 10% (P = 0.046), whereas LV SV did not change. During the Valsalva maneuver, volumes decreased in both ventricles (RVEDV: -29 ± 11%, RVESV: -16 ± 14%, RV SV: -36 ± 14%, LVEDV: -22 ± 17%, and LV SV: -25 ± 17%, P < 0.01). The reciprocal effect of respiration on LV and RV volumes was maintained throughout exercise. The diastolic and systolic eccentricity indexes were greater during inspiration than during expiration, both at rest and during exercise (P < 0.0001 for both). In conclusion, ventricular volumes oscillate with respiratory phase such that RV and LV volumes are maximal at peak inspiration and expiration, respectively. Thus, interpretation of RV versus LV volumes requires careful definition of the exact respiratory time point for proper interpretation, both at rest and during exercise.

Efficacy and safety of bisoprolol fumarate compared with carvedilol in Japanese patients with chronic heart failure: results of the randomized, controlled, double-blind, Multistep Administration of bisoprolol IN Chronic Heart Failure II (MAIN-CHF II) study

Bisoprolol fumarate (bisoprolol) is a β-blocker widely used to treat chronic heart failure (CHF). However, few studies have compared its efficacy and safety with those of the widely used β-blocker carvedilol in Japanese patients with CHF. We designed a confirmatory trial of bisoprolol using carvedilol as a control drug; however, the trial was discontinued after an off-label use of bisoprolol was approved during the study. Bisoprolol and carvedilol were administered for 32 weeks in 31 and 28 patients, respectively. The mean maintenance doses of bisoprolol and carvedilol were 3.3 and 13.6 mg/day, respectively, and the mean durations of treatment were 188.2 and 172.9 days, respectively. Heart-rate changes were similar in both groups. The mean changes from baseline to Week 32 in left ventricular (LV) ejection fraction (EF) (bisoprolol vs carvedilol groups; 11.7 % ± 8.6 % vs 10.1 % ± 10.5 %), LV end-diastolic volume (-37.5 ± 48.7 vs -24.7 ± 29.4 ml), and LV end-systolic volume (-41.9 ± 43.0 vs -29.3 ± 25.9 ml) revealed a decrease in LV volume and an increase in LVEF in both groups. The cumulative event-free rate for a composite of cardiovascular death or admissions to hospital for worsening of CHF was 92.4 % and 94.7 % in the bisoprolol and carvedilol groups, respectively. Overall, 90.3 % and 85.7 % of patients were titrated up to the maintenance doses of bisoprolol and carvedilol, respectively. Bisoprolol, at half the dose used in other countries, is well tolerated and is as effective as carvedilol for treating Japanese patients with mild to moderate CHF.

Differential Effects of Dobutamine Versus Treadmill Exercise on Left Ventricular Volume and Wall Stress

Dobutamine and exercise echocardiography are well-validated modalities used for the evaluation of patients with suspected myocardial ischemia. Patients undergoing dobutamine stress echocardiography (DSE), however, experience less angina, ST-segment depressions, and wall motion abnormalities. Other than the effect on heart rate, the physiologic and volumetric differences between pharmacologic and exercise-induced stress that affect myocardial oxygen demand are not well defined. The aim of this study was to test the hypothesis that in the absence of ischemia, dobutamine reduces left ventricular (LV) volume, wall tension (WTN), and peak systolic stress (PSS) compared with exercise. Seventy patients without ischemia were prospectively enrolled (35 underwent exercise echocardiography and 35 DSE), and various hemodynamic parameters were measured and LV volumes calculated (using the Simpson and Teichholz formulas). Systolic WTN and PSS were determined at rest and stress. LV end-diastolic volume index fell significantly more with dobutamine than with exercise (-34% vs -9%, P < .0001), as did mean end-systolic volume index (-55% vs -37%, P = .07). Systolic blood pressure increased more with exercise (41 ± 22 vs 1 ± 33 mm Hg, P < .0001), as did cardiac index (2.5 ± 0.7 vs 1.0 ± 0.8 L/min/m(2), P < .0001). Systolic WTN increased with exercise by 24% (P < .0001) but decreased with dobutamine by 18% (P < .0001). PSS increased with exercise by 21% (P < .0001) but decreased with dobutamine by 23% (P < .0001). The degree of stress achieved with DSE appears to be considerably different than with exercise. DSE produces greater reductions in LV end-diastolic and end-systolic volumes than exercise and decreases rather than increases in WTN and PSS. The lower WTN and PSS were related to both a decrease in LV volume and lower systolic blood pressure with dobutamine. These observations support recommendations favoring exercise stress testing in patients able to exercise and reinforce the notion that high-risk echocardiographic features of ischemia such as stress-induced LV dilatation may be less striking or absent with DSE.

Absence of Myocardial Thyroid Hormone Inactivating Deiodinase Results in Restrictive Cardiomyopathy in Mice

Cardiac injury induces myocardial expression of the thyroid hormone inactivating type 3 deiodinase (D3), which in turn dampens local thyroid hormone signaling. Here, we show that the D3 gene (Dio3) is a tissue-specific imprinted gene in the heart, and thus, heterozygous D3 knockout (HtzD3KO) mice constitute a model of cardiac D3 inactivation in an otherwise systemically euthyroid animal. HtzD3KO newborns have normal hearts but later develop restrictive cardiomyopathy due to cardiac-specific increase in thyroid hormone signaling, including myocardial fibrosis, impaired myocardial contractility, and diastolic dysfunction. In wild-type littermates, treatment with isoproterenol-induced myocardial D3 activity and an increase in the left ventricular volumes, typical of cardiac remodeling and dilatation. Remarkably, isoproterenol-treated HtzD3KO mice experienced a further decrease in left ventricular volumes with worsening of the diastolic dysfunction and the restrictive cardiomyopathy, resulting in congestive heart failure and increased mortality. These findings reveal crucial roles for Dio3 in heart function and remodeling, which may have pathophysiologic implications for human restrictive cardiomyopathy.

The STICH trial unravelled

The STICH trial unravelled