Torrential mitral regurgitation following right ventricular apical pacing in rheumatic mitral valve disease: a case report.

Background: Mitral regurgitation may develop or worsen following right ventricular apical pacing due to dyssynchronous left ventricular contraction. Pre-existing secondary mitral annular dilation is a well-recognized and important contributing factor. This description of pacing-induced torrential mitral regurgitation in the setting of rheumatic mitral valve disease is a rare case in which a primary mitral valve lesion was the antecedent mechanism. Case summary: A 60-year-old man was admitted with dizziness and pre-syncope. Twelve-lead electrocardiogram showed complete heart block. A dual-chamber pacemaker was implanted and programmed in DDD mode. Transthoracic echocardiography performed a day later demonstrated a left ventricular ejection fraction (LVEF) of 63% and moderate mitral regurgitation. The patient presented 4 months later with breathlessness and orthopnoea. Pacemaker interrogation demonstrated a 98% right ventricular pacing burden. Echocardiography revealed torrential mitral regurgitation secondary to left ventricular dyssynchrony and complete loss of leaflet coaptation with preserved systolic function. Post-capillary pulmonary hypertension was diagnosed following right heart catheterization. The patient underwent metallic mitral valve replacement, tricuspid annuloplasty, and left internal mammary artery grafting to the left anterior descending artery for a severe proximal stenosis. On inspection, the native mitral valve was notably rheumatic in appearance, and this was confirmed histologically. Discussion: It is important to closely monitor the progression of mitral regurgitation in those with primary mitral valve disease undergoing right ventricular pacing. Early follow-up may prevent the adverse haemodynamic consequences of worsening mitral regurgitation, with a greater chance of recovery of left ventricular function following surgery.

Assessment of left ventricular tissue mitochondrial bioenergetics in patients with stable coronary artery disease.

Recurrent myocardial ischemia can lead to left ventricular (LV) dysfunction in patients with coronary artery disease (CAD). In this observational cohort study, we assessed for chronic metabolomic and transcriptomic adaptations within LV myocardium of patients undergoing coronary artery bypass grafting. During surgery, paired transmural LV biopsies were acquired on the beating heart from regions with and without evidence of inducible ischemia on preoperative stress perfusion cardiovascular magnetic resonance. From 33 patients, 63 biopsies were acquired, compared to analysis of LV samples from 11 donor hearts. The global myocardial adenosine triphosphate (ATP):adenosine diphosphate (ADP) ratio was reduced in patients with CAD as compared to donor LV tissue, with increased expression of oxidative phosphorylation (OXPHOS) genes encoding the electron transport chain complexes across multiple cell types. Paired analyses of biopsies obtained from LV segments with or without inducible ischemia revealed no significant difference in the ATP:ADP ratio, broader metabolic profile or expression of ventricular cardiomyocyte genes implicated in OXPHOS. Differential metabolite analysis suggested dysregulation of several intermediates in patients with reduced LV ejection fraction, including succinate. Overall, our results suggest that viable myocardium in patients with stable CAD has global alterations in bioenergetic and transcriptional profile without large regional differences between areas with or without inducible ischemia.

Changes in clinical and imaging variables during withdrawal of heart failure therapy in recovered dilated cardiomyopathy.

AIMS: This study aimed to profile the changes in non-invasive clinical, biochemical, and imaging markers during withdrawal of therapy in patients with recovered dilated cardiomyopathy, providing insights into the pathophysiology of relapse. METHODS AND RESULTS: Clinical, biochemical, and imaging data from patients during phased withdrawal of therapy in the randomized or single-arm cross-over phases of TRED-HF were profiled. Clinical variables were measured at each study visit and imaging variables were measured at baseline, 16 weeks, and 6 months. Amongst the 49 patients [35% women, mean age 53.6 years (standard deviation 11.6)] who withdrew therapy, 20 relapsed. Increases in mean heart rate [7.6 beats per minute (95% confidence interval, CI, 4.5, 10.7)], systolic blood pressure [6.6 mmHg (95% CI 2.7, 10.5)], and diastolic blood pressure [5.8 mmHg (95% CI 3.1, 8.5)] were observed within 4-8 weeks of starting to withdraw therapy. A rise in mean left ventricular (LV) mass [5.1 g/m2 (95% CI 2.8, 7.3)] and LV end-diastolic volume [3.9 mL/m2 (95% CI 1.1, 6.7)] and a reduction in mean LV ejection fraction [-4.2 (95% CI -6.6, -1.8)] were seen by 16 weeks, the earliest imaging follow-up. Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) fell immediately after withdrawing beta-blockers and only tended to increase 6 months after beginning therapy withdrawal [mean change in log NT-proBNP at 6 months: 0.2 (95% CI -0.1, 0.4)]. CONCLUSIONS: Changes in plasma NT-proBNP are a late feature of relapse, often months after a reduction in LV function. A rise in heart rate and blood pressure is observed soon after withdrawing therapy in recovered dilated cardiomyopathy, typically accompanied or closely followed by early changes in LV structure and function.

Correlation Between Echocardiographic and Hemodynamic Variables in Cardiothoracic Intensive Care Unit.

OBJECTIVES: The echocardiographic indices have not been validated in critically ill population. The authors investigated the correlation between some echocardiographic and hemodynamic parameters. DESIGN: Prospective, spontaneous, noninterventional observational study. SETTING: Adult cardiothoracic intensive care unit, single center (Royal Brompton Hospital, London, United Kingdom). PARTICIPANTS: Consecutive adult patients admitted to the cardiothoracic intensive care unit for severe respiratory failure, primary cardiocirculatory failure, and post-aortic surgery. INTERVENTIONS: Clinical hemodynamic parameters (stroke volume [SV], cardiac output [CO], mean arterial pressure [MAP], and cardiac power index [CPI]) and echocardiographic indices of ventricular function (left ventricular total isovolumic time [t-IVT], mitral annular plane systolic excursion [MAPSE], and left ventricular fraction [LVEF]) were evaluated offline. MEASUREMENTS AND MAIN RESULTS: The study comprised 117 patients (age 57.2 ± 19; 60.6% male). The t-IVT showed an inverse correlation with SV, CO, MAP, and CPI (r -67%; -38%; -45%; -51%, respectively). MAPSE exhibited a positive correlation with SV, CO, MAP, and CPI (r 43%; 44%; 34%; 31%, respectively). LVEF did not show any correlation. In the multivariate analysis the association between t-IVT and hemodynamics was confirmed for SV, CO, MAP, and CPI, with the highest partial correlation between t-IVT and MAP (R = -58%). CONCLUSIONS: MAPSE and t-IVT are 2 reproducible and reliable echocardiographic indices of systolic function and ventricular efficacy associated with hemodynamic variables in cardiothoracic critically ill patients, whereas LVEF did not show any correlation.

Cardiac structure and function in patients with schizophrenia taking antipsychotic drugs: an MRI study.

Cardiovascular disease (CVD) is a major cause of excess mortality in schizophrenia. Preclinical evidence shows antipsychotics can cause myocardial fibrosis and myocardial inflammation in murine models, but it is not known if this is the case in patients. We therefore set out to determine if there is evidence of cardiac fibrosis and/or inflammation using cardiac MRI in medicated patients with schizophrenia compared with matched healthy controls. Thirty-one participants (14 patients and 17 controls) underwent cardiac MRI assessing myocardial markers of fibrosis/inflammation, indexed by native myocardial T1 time, and cardiac structure (left ventricular (LV) mass) and function (left/right ventricular end-diastolic and end-systolic volumes, stroke volumes, and ejection fractions). Participants were physically fit, and matched for age, gender, smoking, blood pressure, BMI, HbA1c, ethnicity, and physical activity. Compared with controls, native myocardial T1 was significantly longer in patients with schizophrenia (effect size, d = 0.89; p = 0.02). Patients had significantly lower LV mass, and lower left/right ventricular end-diastolic and stroke volumes (effect sizes, d = 0.86-1.08; all p-values < 0.05). There were no significant differences in left/right end-systolic volumes and ejection fractions between groups (p > 0.05). These results suggest an early diffuse fibro-inflammatory myocardial process in patients that is independent of established CVD-risk factors and could contribute to the excess cardiovascular mortality associated with schizophrenia. Future studies are required to determine if this is due to antipsychotic treatment or is intrinsic to schizophrenia.

Can we remove scar and fibrosis from adult human myocardium?

The pathological processes leading to heart failure are characterized by the formation of fibrosis and scar, yet the dynamics of scar production and removal are incompletely understood. Spontaneous disappearance of myocardial collagen is reported in infancy but doubted in adulthood where scar volume constitutes a better prognostic indicator than the conventional parameters of ventricular function. Whilst certain drugs are known to attenuate myocardial fibrosis evidence is emerging that stem cell therapy also has the potential to reduce scar size and improve myocardial viability. Both animal studies and clinical trials support the concept that, as in infancy, cellular processes can be triggered to remove collagen and regenerate injured myocardium. The molecular mechanisms likely involve anti-fibrotic cytokines growth factors and matrix-metalloproteinases. Autologous cardiac, bone-marrow and adipose tissue derived stem cells have each shown efficacy. Specific immune privileged mesenchymal stem cells and genetically modified immunomodulatory progenitor cells may in turn provide an allogenic source for the paracrine effects. Thus autologous and allogenic cells both have the potential through paracrine action to reduce scar volume, boost angiogenesis and improve ventricular morphology. The potential benefit of myocardial cell therapy for routine treatment of heart failure is an area that requires further study.

Improving the management of iron deficiency in ambulatory heart failure patients.

Based on clinical trial data patients with heart failure (HF) and evidence of iron deficiency should be offered intravenous (iv) iron with the aim of improving exercise capacity and symptoms. Baseline measurement in outpatient HF clinics demonstrated that only 50% of patients who may be eligible for iv iron were investigated with iron studies. Our aim was to make sure that 90% of the patients attending our heart failure clinics who were symptomatic and had an ejection fraction (EF) ≤45% should have their iron studies checked within the last six months. In an effort to increase the proportion of suitable patients in whom iron studies are requested, we carried out three plan-do-study-act (PDSA) cycles each with a different intervention. These interventions included a presentation of the clinical trial evidence at a HF multidisciplinary meeting, email reminders prior to clinic and stickers in the patient notes (repeated twice). The effect of each intervention was measured with the outcome being the proportion of eligible patients in whom iron studies were documented within the previous 6 months. The interventions increased the number of suitable patients who had iron studies checked, to as high as 100%, however this effect was not sustained. Root cause analysis revealed that clinicians were unenthusiastic to continue performing iron studies due to inefficiency in the process of admitting patients and giving them iv iron. For example median in-hospital stay of seven hours for an infusion that is given over 15 minutes. In an attempt to improve patient and physician satisfaction we piloted an ambulatory outpatient service to deliver iv iron. We demonstrated that this service was feasible and more efficient as less time was required waiting for a bed or spent in hospital and was less costly. In summary we have demonstrated interventions which can increase the identification of patients who would benefit from iv iron and piloted a new time and cost efficient system of administration of iv iron.

Ursodeoxycholic acid in patients with chronic heart failure: a double-blind, randomized, placebo-controlled, crossover trial.

OBJECTIVES: This study sought to assess the effects of ursodeoxycholic acid (UDCA) on endothelial function and inflammatory markers in patients with chronic heart failure (CHF). BACKGROUND: Endothelial dysfunction is commonly observed in patients with CHF, and it contributes to the limitation in exercise capacity that accompanies this condition. Bacterial lipopolysaccharide may trigger proinflammatory cytokine release and promote further endothelial dysfunction. UDCA, a bile acid used in the treatment of cholestatic liver disease, has anti-inflammatory and cytoprotective properties and may contribute to the formation of mixed micelles around lipopolysaccharide. These properties may help to improve peripheral blood flow in patients with CHF. METHODS: We performed a prospective, single-center, double-blind, randomized, placebo-controlled crossover study of UDCA in 17 clinically stable male patients with CHF (New York Heart Association functional class II/III, left ventricular ejection fraction <45%). Patients received in random order 500 mg UDCA twice daily for 4 weeks and placebo for another 4 weeks. The primary endpoint was post-ischemic peak peripheral arm blood flow as assessed by strain-gauge plethysmography. RESULTS: Sixteen patients completed the study. UDCA was well tolerated in all patients. Compared with placebo, UDCA improved peak post-ischemic blood flow in the arm (+18%, p = 0.038), and a trend for improved peak post-ischemic blood flow in the leg was found (+17%, p = 0.079). Liver function improved: compared with placebo, levels of γ-glutamyl transferase, aspartate transaminase, and soluble tumor necrosis factor α receptor 1 were lower after treatment with UDCA than after placebo (all p < 0.05). There was no change in 6-min walk test or New York Heart Association functional class, and levels of tumor necrosis factor α and interleukin-6 were unchanged or increased compared with placebo. CONCLUSIONS: UDCA is well tolerated in patients with CHF. UDCA improves peripheral blood flow and is associated with improved markers of liver function.

Rapidly growing left atrial myxoma: a case report.

INTRODUCTION: Left atrial myxomas are rare benign tumors of the heart. They vary widely in size, and very little is known about their growth rate. The reported growth rates of left atrial myxomas from several published case reports appears to vary from no growth, to between 1.3 to 6.9 mm/month in diameter within patients with established myxoma who have not undergone surgery. CASE PRESENTATION: We present the case of a rapidly growing pedunculated left atrial myxoma in a 62-year-old asymptomatic Caucasian woman found incidentally during routine transthoracic echocardiography. Our patient was attending her annual valve clinic assessment for moderate aortic regurgitation, and her two previous consecutive transthoracic echocardiography scans performed 12 and 24 months prior to this appointment had demonstrated a clear left atrium and aortic regurgitation of moderate severity. CONCLUSIONS: To the best of our knowledge, our case is the first to provide images of absence and presence of myxoma from transthoracic echocardiography scans taken a year apart, with estimated growth rate of 2.2 mm/month. Rapidly growing myxoma may be mistaken for thrombus, and may require urgent surgical excision to reduce the risk of associated complications such as thrombo-embolic events, sudden cardiac death and removal of a possibly malignant tumor. The potential for rapid growth should be considered if there is a plan to delay surgery. Furthermore, it would be pertinent to consider annual echocardiography in patients presenting with clinical features suggestive of cardiac myxoma such as constitutional symptoms, as these tumors may be rapid growing and may only become apparent on subsequent echocardiography.