Time Of Heart Failure Research Articles

THE RISKS OF FIRST ONSET PRIMARY HYPERTENSION DIAGNOSIS IN THERMAL-INJURED PATIENTS.

Introduction: Hypertension is a prevalent condition in the United States and leads to an increased risk of developing various comorbidities. However, the impact of new-onset hypertension after severe burns on patient outcomes is not known. We posit that hypertension onset after severe burn is associated with increased risk of developing comorbidities and mortality. Methods: Using the TriNetX database, burned patients diagnosed with essential hypertension after injury were compared with those who did not develop hypertension; neither had prior hypertension. Each cohort was grouped by sex, percent total body surface area (TBSA) burned, and age, then propensity matched for sex, race, ethnicity, and laboratory values. Outcomes assessed were acute kidney injury (AKI), hyperglycemia, heart failure, myocardial infarction (MI), and death. Results: Those diagnosed with hypertension after severe burn were 4.9 times more likely to develop AKI, 3.6 times for hyperglycemia, 5.3 times for heart failure, 4.7 times for acute MI, and 1.5 times for mortality. Sex analysis shows that men were at greater risk for AKI (1.5 times), heart failure (1.1 times), and death (1.4 times). Women were 1.3 times more likely to develop hyperglycemia. Percent TBSA burned grouping showed increased risk for all outcomes with increasing severity. Age grouping indicated an elevated risk of developing AKI, heart failure, acute MI, and death. Conclusion: New-onset hypertension diagnosis in severely burned patients is associated with acute kidney injury, heart failure, acute MI, and death. Overall, males, older patients, and those with a higher % TBSA burned are at a higher risk of developing these comorbidities.

Dysregulation of ventilation at day and night time in heart failure.

Heart failure (HF) is characterized by an increase in ventilatory response to exercise of multifactorial aetiology and by a dysregulation in the ventilatory control during sleep with the occurrence of both central and obstructive apnoeas. In this setting, the study of the ventilatory behaviour during exercise, by cardiopulmonary exercise testing, or during sleep, by complete polysomnography or simplified nocturnal cardiorespiratory monitoring, is of paramount importance because of its prognostic value and of the possible effects of sleep-disordered breathing on the progression of the disease. Moreover, several therapeutic interventions can significantly influence ventilatory control in HF. Also, rest daytime monitoring of cardiac, metabolic, and respiratory activities through specific wearable devices could provide useful information for HF management. The aim of the review is to summarize the main studies conducted at Centro Cardiologico Monzino on these topics.

Prognosis of diabetes mellitus and timing of heart failure in patients with acute myocardial infarction. An analysis of a French nationwide hospital database

Abstract Background Diabetes mellitus (DM) is a factor of increased mortality in patients with acute myocardial infarction (AMI). DM is also associated with a higher risk of heart failure (HF) in patients with coronary artery disease as in the general population. The aim of the present study was to assess the incidence of HF developing at the acute stage of MI and of HF occurring in the year following hospital discharge, according to presence of DM. We also assessed the association between DM, HF and long-term mortality in this AMI population. Methods We used the French administrative hospital-discharge database, including all patients without history of HF admitted for AMI between 2010 and 2019 (n=797,212, mean age 69 years, 66% male). Among them, 520,258 patients (65%) had ST-segment elevation myocardial infarction (STEMI), 276,954 (35%) had non-STEMI, 192,456 patients (24%) had a history of DM. Occurrence of HF during the initial hospital stay was analysed in the whole population. In patients without HF during the index hospitalisation, discharged and alive at day 8 (n=535,813), we collected all hospitalisations for HF occurring during the year after discharge and analysed subsequent long-term mortality in those alive at one year (n=270,534) (length of follow-up 2.0±2.5 years, median 0.9, IQR 0.1–3.5). Results Overall, DM patients were older than non-DM patients (71±12 vs 67±15 years) and had more frequent comorbidities. At the acute stage, DM was associated with a higher risk of HF (28.7% vs 20.5% adjusted OR 1.40, 1.38–1.42, p<0.0001). In patients without HF at the acute stage and discharged alive at day 8, DM was associated with a higher risk of being hospitalised with HF in the first year (5.6% vs 2.8%, adjusted HR 1.52, 1.49–1.56, p<0.0001). In patients alive at one year, rates of all-cause death per year during subsequent follow-up were 2.2% in those without DM or HF during the first year (reference), 3.4% in those with DM and no HF during the first year (adjusted HR 1.22, 1.18–1.25, p<0.0001), 7.7% in those without DM and with HF during the first year (adjusted HR 1.92, 1.83–2.02, p<0.0001) and 8.9% in those with DM hospitalised with HF during the first year (adjusted HR 2.23, 2.09–2.37, p<0.0001) (see figure). Conclusion After AMI, patients with diabetes are at increased risk of heart failure both at the acute stage and in the year following myocardial infarction, compared with non-diabetic patients. Non-fatal HF developing in the year following discharge is associated with noticeably higher subsequent mortality, and the combination of DM and HF is particularly at risk. Improved management is needed in diabetic patients following an AMI to avoid development of heart failure and its longer-term consequences. Funding Acknowledgement Type of funding sources: None.

Relationship of ejection fraction and natriuretic peptide trajectories in heart failure with baseline reduced and mid-range ejection fraction

BackgroundThe prognostic importance of trajectories of neurohormones relative to left ventricular function over time in heart failure with reduced and mid-range EF (HFrEF and HFmrEF) is poorly defined. ObjectiveTo evaluate left ventricular ejection fraction (LVEF) and B-type natriuretic peptide (BNP) trajectories in HFrEF and HFmrEF. MethodsAnalyses of LVEF and BNP trajectories after incident HF admissions presenting with abnormal LV systolic function were performed using 3 methods: a Cox proportional hazards model with time-varying covariates, a dual longitudinal-survival model with shared random effects, and an unsupervised analysis to capture 3 discrete trajectories for each parameter. ResultsAmong 1,158 patients (68.9 ± 13.0 years, 53.3% female), both time-varying LVEF measurements (P=.001) and log-transformed BNP measurements (p-values=2 × 10−16) were independently associated with survival during 6 years after covariate adjustment. In the dual longitudinal/survival model, both LVEF and BNP trajectories again were independently associated with survival (P<.0001 in each model); however, LVEF was more dynamic than BNP (P <.0001 for time covariate in LVEF longitudinal model versus P=.88 for the time covariate in BNP longitudinal model). In the unsupervised analysis, 3 discrete LVEF trajectories (dividing the cohort into approximately thirds) and 3 discrete BNP trajectories were identified. Discrete LVEF and BNP trajectories had independent prognostic value in Kaplan-Meier analyses (P<.0001), and substantial membership variability across BNP and LVEF trajectories was noted. ConclusionAlthough LVEF trajectories have greater temporal variation, BNP trajectories provide additive prognostication and an even stronger association with survival times in heart failure patients with abnormal LV systolic function.

Treatment Persistence of Renin-Angiotensin-Aldosterone-System Inhibitors Over Time in Heart Failure with Reduced Ejection Fraction

Clinical practice guidelines support sustained use of renin-angiotensin-aldosterone-system (RAAS) inhibitors over time in heart failure with reduced ejection fraction, yet few data are available regarding the frequency, timing or predictors of early treatment discontinuation in clinical practice. Among prevalent or new users of angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs), and mineralocorticoid receptor antagonists (MRAs) in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry, we estimated the frequency and independent predictors of treatment discontinuation during follow-up. Among sites with > 5 users of a given RAAS inhibitor, we evaluated practice variation in the proportion of patients with treatment discontinuation. Over median follow-up of 18 months, frequency of drug discontinuation of ACEis/ARBs, ARNIs and MRAs was 12.7% (444 of 3509 users), 10.4% (140 of 1352 users), and 20.4% (435 of 2129 users), respectively. An additional, 149 (11.0%) of ARNI users were switched to ACEis/ARBs, and 447 (12.7%) of ACEi/ARB users were switched to ARNIs during follow-up. Across sites, the median proportion of discontinuation of ACEis/ARBs, ARNIs and MRAs was 12.5% (25th-75th percentiles 6.9%-18.9%), 18.8% (25th-75th percentiles 12.5%-28.6%), and 19.6% (25th-75th percentiles 10.7%-27.0%), respectively. Chronic kidney disease was the only independent predictor of increased risk of discontinuation of each of the RAAS inhibitor classes (P < 0.02 for all). Higher Kansas City Cardiomyopathy Questionnaire overall summary scores independently predicted lower risk of discontinuation of ACEis/ARBs and ARNIs (both P < 0.001) but not of MRAs. Investigator clinical experience was predictive of lower risks of discontinuation of ACEis/ARBs and MRAs (P < 0.02) but not of ARNIs. All other independent predictors of discontinuation were unique to individual therapeutic classes. One in 10 patients discontinue ACEis/ARBs or ARNIs, and 1 in 5 discontinue MRAs in routine clinical practice of heart failure with reduced ejection fraction. Unique patient-level and clinician/practice-level factors are associated with premature discontinuation of individual RAAS inhibitors, which may help to guide structured efforts to promote treatment persistence in clinical care.

Heart Failure with Supra-normal Left Ventricular Ejection Fraction - State of the Art.

ResumoEm 2019, um artigo publicado no European Heart Journal reconheceu pela primeira vez a insuficiência cardíaca (IC) com fração de ejeção do ventrículo esquerdo (FEVE) ≥ 65% como um novo fenótipo de IC, ou a insuficiência cardíaca com fração de ejeção supranormal (ICFEsn), com o objetivo principal de promover a investigação desta nova categoria. Eles analisaram a mortalidade em pessoas com IC e descobriram que havia uma relação em forma de U entre a mortalidade e a FEVE. Sendo assim, os pacientes com ICFEsn tinham uma mortalidade geral mais alta em comparação com outros pacientes diagnosticados com IC com fração de ejeção preservada (ICFEp). Este artigo descreve a situação atual da ICFEsn e discute as perspectivas futuras com base nos resultados preliminares de nosso grupo. Para melhor tratar os pacientes com ICFEsn, é fundamental que cardiologistas e médicos entendam as diferenças e semelhanças desse novo fenótipo.

The significance of left ventricular ejection time in heart failure with reduced ejection fraction.

Left ventricular ejection time (LVET) is defined as the time interval from aortic valve opening to aortic valve closure, and is the phase of systole during which the left ventricle ejects blood into the aorta. LVET has been used for several decades to assess left ventricular function and contractility. However, there is a recent interest in LVET as a measure of therapeutic action for novel drugs in patients with heart failure with reduced ejection fraction (HFrEF), since LVET is shortened in these patients. This review provides an overview of the available information on LVET including methods of measuring LVET, mechanistic understanding of LVET, association of LVET with outcomes, mechanisms behind shortened LVET in HFrEF and the potential implications of drugs that affect and normalize LVET.

Cognitive decline and conversion to MCI and dementia in heart failure: A 12‐year follow‐up study

AbstractBackgroundCognitive decline and development of mild cognitive impairment (MCI) and dementia over time in heart failure (HF) have not been fully examined. The purpose of this study was to compare (1) cognitive decline and (2) time to convert to MCI or dementia between people with and without HF.MethodData were retrieved from the National Alzheimer’s Coordinating Center database in September 2017. People with baseline dementia were excluded. Cognitive decline was assessed using changes in age, education, and gender‐adjusted z‐scores of verbal memory (Logical Memory Test delayed recall), attention (Digit Span Forward, Trail Making Test A), executive function (Trail Making B, Digit Symbol Test), and language (Category Fluency, Boston Naming Test) over 12 years. Time to convert was assessed using diagnosis of cognitive status by neurologists at each visit. Statistical analyses were conducted using multivariable Cox Proportional Hazards Models after adjusting for covariates (e.g., comorbidity, APOE carrier status).ResultAmong 4,149 participants, 87 had HF (66 with normal cognition, 21 with MCI) at baseline Median years of follow‐up was 6 (SD=2; range = 1‐12). At baseline, compared with non‐HF participants, HF participants were significantly older, had less education and more comorbidities, and were more likely to have MCI. Compared with non‐HF participants, HF participants had faster decline in attention (time by group interaction b=‐0.059, p=.0007), executive function (b=‐0.095, p=.0006) and language (b=‐0.051, p=.0137) but not memory (b=‐0.055, p=.0595) over 12 years after controlling for covariates and baseline cognitive status. Time to convert from normal cognition to MCI was not significantly different between participants with and without HF. Similarly, time to convert from MCI to dementia did not differ between the groups. The small number of HF participants may have limited the ability to detect 50% survival probability.ConclusionParticipants with HF had accelerated cognitive decline, especially in the domains of attention, executive function, and language compared with people without HF. The effect of HF on time to convert needs to be tested in larger samples.

Клінічний випадок «невидимої» гігантської неорганної заочеревинної пухлини

SummaryBackground. The problem of verification of abdominal and retroperitoneal spacegiant tumors deserves special attention. At first glance, such verification should not bedifficult, but real clinical practice suggests otherwise. Often such a tumor can remainundetected for a long time, despite repeated examinations. This is especially true forliposarcomas, which have a heterogeneous structure, can be perceived duringultrasound as the intestine, which worsens visualization due to flatulence. As a result,patients receive treatment for a long time for various pathologies, the size of the tumorincreases, the prognosis of such patients deteriorates.Materials and methods. The case of a patient with giant retroperitonealliposarcoma is presented in order to draw attention to the importance of cancervigilance for timely diagnosis of the tumor.Results. A 77-year-old male patient was treated for a long time for heart failure(HF) and was repeatedly hospitalized for HF decompensation. The main complaintswere an increase in abdominal volume, flatulence, shortness of breath, impaired qualityof life and decreased tolerance to exercise. Ultrasound examination of the abdominalcavity and retroperitoneal space was performed repeatedly, poor visualization wasexplained by severe flatulence. During the last hospitalization, a very large tumor wasdetected by multidetector spiral computed tomography (MSCT). According to theautopsy, the liposarcoma of gigantic size (approximately 8 kg) was found. The diagnosiswas confirmed histologically.Conclusion. Computed tomography and MSCT is a useful diagnostic tool to verifygiant «invisible» tumors in the abdomen.

Long-term PM2.5 exposure as a risk factor for 30-day hospital readmissions among heart failure patients

Background: Hospital readmissions represent a health and economic burden to patients and the healthcare system. We understand little about the relationship between long-term environmental exposures and hospital readmission risk. Here, we use electronic health records linked to exposure data (EPA CARES) to quantify the associations between long-term PM2.5 exposure at the time of heart failure (HF) diagnosis and the number of hospital readmissions – a key outcome metric for quality of care for hospitals and healthcare systems. Methods: Annual average PM2.5 was estimated at 1x1 km resolution for each primary residence. We used stabilized inverse probability weights to account for imbalanced confounder distributions and the competing risk of death. We adjusted for age at HF diagnosis, race, sex, year of HF diagnosis, and neighborhood socioeconomic status in quasi-Poisson regression models with an offset of log(follow-up time). Associations are presented as the percent increase from the mean and associated 95% confidence interval (CI). Results: Among 34,459 HF patients, 18,078 had an inpatient or emergency admission, thus qualifying them to have a readmission and enter this analysis. A 1 µg/m3 increase in annual average PM2.5 was associated with an 11% (95% CI = 6 – 16) increase in 30-day readmissions; independent of short-term (5-day average) exposures prior to the readmissions. PM2.5 exposure was also associated with a 13% (95% CI = 4 – 22) and 14% (95% CI = 10 – 18) increase in 7 and 90 day readmissions, respectively. Conclusion: Long-term PM2.5 exposure is associated with increased hospital readmissions, including 30-day readmissions, a closely tracked metric by which hospitals and healthcare systems are evaluated. Associations were independent of short-term variations in PM2.5 prior to readmission, indicating that long-term exposures may be an important contributor to hospital readmission risk that should be further explored. This abstract does not necessarily represent EPA policy.

Podsumowanie roku 2019 w niewydolności serca z obniżoną frakcją wyrzutową lewej komory

The last years it is a good time in heart failure for innovative therapy. The results of new trials which were published after the last 2016 guidelines for heart failure need the systematic approach and present the practical guide based on EBM. For that reason in the last year 2019 the experts of Heart Failure Association (HFA) European Society of Cardiology published the consensus. The present article summarized the main issues regarding heart failure with reduced ejcetion fraction together with comennt based on the HFA expert consensus.

Effects of Pimobendan on Prolonging Time to Rehospitalization or Frequency of Rehospitalization in Patients with Heart Failure: A Retrospective Cohort Study Using a Medical Administrative Database (PREFER Study).

BackgroundAs approximately 24% of patients with chronic heart failure are rehospitalized within 1 year and heart failure is aggravated by repeated hospitalizations, greater importance was attached to the prevention of hospitalization.ObjectiveThe objective of this study was to investigate the influence of pimobendan on rehospitalization of patients with advanced heart failure using a Japanese medical administrative database.MethodsFrom January 2010 to February 2018, patients hospitalized two or more times for heart failure were selected for analysis. The primary endpoint was the incidence of hospitalizations for heart failure during the follow-up period, which was compared between pimobendan prescription and non-prescription groups after propensity score matching.ResultsThe total number of patients with heart failure included during the study period was 1 421 110 and we matched 276 patients in both groups. The incidence of rehospitalization throughout the period to completion of follow-up was 365.23/1000 people/yr (95% confidence interval [CI]: 327.78–402.69) in the pimobendan prescription group and 537.81/1000 people/yr (95% CI: 492.36–583.27) in the non-prescription group. The cumulative incidence at 365 days was significantly lower in the pimobendan prescription group (pimobendan prescription group: 35.4% (95% CI: 29.8–41.8), non-prescription group: 51.2% (95% CI: 45.1–57.7), (P < 0.001). The adjusted hazard ratio in the pimobendan prescription group was 0.556 (95% CI: 0.426–0.725, P < 0.001).ConclusionPimobendan was suggested to extend the time to rehospitalization for patients with advanced heart failure. It is necessary to verify the results of this study by performing a prospective study. In addition, the influence of pimobendan on general heart failure patients must be examined.

Pulmonary hypertension detection by computed tomography pulmonary transit time in heart failure with reduced ejection fraction.

To evaluate the relationships between pulmonary transit time (PTT), cardiac function, and pulmonary haemodynamics in patients with heart failure with reduced ejection fraction (HFrEF) and to explore how PTT performs in detecting pulmonary hypertension (PH). In this prospective study, 57 patients with advanced HFrEF [49 men, 51 years ± 8, mean left ventricular (LV) ejection fraction 26% ± 8] underwent echocardiography, right heart catheterization, and cardiac computed tomography (CT). PTT was measured as the time interval between peaks of attenuation in right ventricle (RV) and LV and was compared between patients with or without PH and 15 controls. PTT was significantly longer in HFrEF patients with PH (21 s) than in those without PH (11 s) and controls (8 s) (P < 0.001) but not between patients without PH and controls (P = 0.109). PTT was positively correlated with pulmonary artery wedge pressure (PAWP) (r = 0.74), mean pulmonary artery pressure (r = 0.68), N-terminal pro-B-type natriuretic peptide (r = 0.60), mitral (r = 0.54), and tricuspid (r = 0.37) regurgitation grades, as well as with LV, RV, and left atrial volumes (r from 0.39 to 0.64) (P < 0.01). PTT was negatively correlated with cardiac index (r = -0.63) as well as with LV (r = -0.66) and RV (r = -0.74) ejection fractions. PAWP, cardiac index, mitral regurgitation grade, and RV end-diastolic volume were all independent predictors of PTT. PTT value ≥14 s best-detected PH with 91% sensitivity and 88% specificity (area under the receiver operating characteristic curve: 0.95). In patients with HFrEF, PTT correlates with cardiac function and pulmonary haemodynamics, is determined by four independent parameters, and performs well in detecting PH.

Heart failure and the prognostic impact and incidence of new-onset of diabetes mellitus: a nationwide cohort study

BackgroundPrevalent diabetes at the time of heart failure (HF) diagnosis is associated with a higher risk of death, but the incidence and prognostic importance of new-onset diabetes in patients with established HF remains unknown.MethodsPatients with a first hospitalization for HF in the period 2003–2014 were included and stratified according to history of diabetes. Annual incidence rates of new-onset diabetes were calculated and time-dependent multivariable Cox regression models were used to compare the risk of death in patients with prevalent and new-onset diabetes with patients without diabetes as reference. The model was adjusted for age, sex, duration of HF, educational level and comorbidity. Covariates were continuously updated throughout follow-up.ResultsA total of 104,522 HF patients were included in the study, of which 21,216 (19%) patients had diabetes at baseline, and 8164 (10%) developed new-onset diabetes during a mean follow-up of 3.9 years. Patients with new-onset diabetes and prevalent diabetes were slightly younger than patients without diabetes (70 vs. 74 and 77, respectively), more likely to be men (62% vs. 60% and 54%), and had more comorbidities expect for ischemic heart disease, hypertension and chronic kidney disease which were more prevalent among patients with prevalent diabetes. Incidence rates of new-onset diabetes increased from around 2 per 100 person-years in the first years following HF hospitalization up to 3 per 100 person-years after 5 years of follow-up. A total of 61,424 (59%) patients died during the study period with event rates per 100 person-years of 21.5 for new-onset diabetes, 17.9 for prevalent diabetes and 13.9 for patients without diabetes. Compared to patients without diabetes, new-onset diabetes was associated with a higher risk of death (adjusted HR 1.47; 95% CI 1.42–1.52) and prevalent diabetes was associated with an intermediate risk (HR 1.19; 95% CI, 1.16–1.21).ConclusionFollowing the first HF hospitalization, the incidence of new-onset diabetes was around 2% per year, rising to 3% after 5 years of follow-up. New-onset diabetes was associated with an increased risk of death, compared to HF patients with prevalent diabetes (intermediate risk) and HF patients without diabetes.

Heart Failure and the Prognostic Impact and Incidence of New-Onset of Diabetes Mellitus: A Nationwide Cohort Study

Prevalent diabetes at the time of heart failure (HF) diagnosis is associated with a higher risk of death, but the incidence and prognostic importance of new-onset diabetes in patients with established HF remains unknown. Patients with a first hospitalization for HF in the period 2003–2014 were included and stratified according to history of diabetes. Annual incidence rates of new-onset diabetes were calculated and time-dependent multivariable Cox regression models were used to compare the risk of death in patients with prevalent and new-onset diabetes with patients without diabetes as reference. The model was adjusted for age, sex, duration of HF, educational level and comorbidity. Covariates were continuously updated throughout follow-up. A total of 104,522 HF patients were included in the study, of which 21,216 (19%) patients had diabetes at baseline, and 8164 (10%) developed new-onset diabetes during a mean follow-up of 3.9 years. Patients with new-onset diabetes and prevalent diabetes were slightly younger than patients without diabetes (70 vs. 74 and 77, respectively), more likely to be men (62% vs. 60% and 54%), and had more comorbidities expect for ischemic heart disease, hypertension and chronic kidney disease which were more prevalent among patients with prevalent diabetes. Incidence rates of new-onset diabetes increased from around 2 per 100 person-years in the first years following HF hospitalization up to 3 per 100 person-years after 5 years of follow-up. A total of 61,424 (59%) patients died during the study period with event rates per 100 person-years of 21.5 for new-onset diabetes, 17.9 for prevalent diabetes and 13.9 for patients without diabetes. Compared to patients without diabetes, new-onset diabetes was associated with a higher risk of death (adjusted HR 1.47; 95% CI 1.42–1.52) and prevalent diabetes was associated with an intermediate risk (HR 1.19; 95% CI, 1.16–1.21). Following the first HF hospitalization, the incidence of new-onset diabetes was around 2% per year, rising to 3% after 5 years of follow-up. New-onset diabetes was associated with an increased risk of death, compared to HF patients with prevalent diabetes (intermediate risk) and HF patients without diabetes.

Findings on 3D speckle tracking echocardiography in asymptomatic methamphetamine abusers

To detect potential cardiac abnormalities in asymptomatic methamphetamine abusers using three-dimensional speckle tracking echocardiography (3D STE). Fifty-three male methamphetamine abusers, free of cardiac symptoms/signs, were enrolled in this study. A control group of 53 age-matched male normal subjects was studied for comparison. Standard 3D, flow and tissue Doppler echo with measurements of left ventricular end-diastolic volume (LVEDV), end-systolic volume (LVESV), ejection fraction (LVEF), the ratio of the early to late diastolic transmitral filling velocity (E/A), the ratio of the early diastolic transmitral filling velocity to the early diastolic septal tissue velocity (E/E') and 3D STE with measurements of global area strain (GAS), global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS) were performed, respectively. These echocardiographic parameters were compared between methamphetamine abusers and normal subjects, and receiver operating characteristic curve (ROC) analysis was done to differentiating methamphetamine abusers from normal subjects. LVESV, LVEDV, LVEF, E/A, E/E' ratios and GRS were not significantly different between methamphetamine abusers and normal subjects (p > 0.05). However, GAS, GLS and GCS were significantly less in methamphetamine abusers than in normal subjects (p < 0.05). The areas under ROC (AUC) for GAS were greatest among all the 3D STE derived LV global strains (GAS vs. GLS, GCS and GRS, 0.95 vs. 0.76, 0.69 and 0.61, respectively). The cutoff value with - 30.3% of GAS had sensitivity of 91.8%, specificity of 91.6% and accuracy of 91.3% for differentiating methamphetamine abusers from normal subjects. The potential myocardial function abnormalities can be detected by 3D STE in asymptomatic methamphetamine abusers, and GAS is a good indicator for indentifying methamphetamine abusers from normal population, which can be used to screening and monitor methamphetamine abuse, detect subclinical LV dysfunction, predict potential methamphetamine-related cardiotoxicity, and to initiate early cardioprotective therapy before the onset of overt heart failure in time.

Psychological stress and short-term hospitalisations or death in patients with heart failure

ObjectiveStandard predictors do not fully explain variations in the frequency and timing of heart failure (HF) adverse events (AEs). Psychological stress can trigger acute cardiovascular (CV) events, but it is...

54. Prevention of Sensory Ataxia in a Novel Mouse Model of Friedreich Ataxia Using Gene Therapy Approach

Friedreich's ataxia (FRDA), the most common autosomal recessive ataxia, is characterized by a sensory and spinocerebellar ataxia, hypertrophic cardiomyopathy and increase incidence of diabetes. FRDA is caused by reduced levels of frataxin (FXN), an essential mitochondrial protein involved in the biosynthesis of iron-sulfur (Fe-S) clusters. Impaired mitochondrial oxidative phosphorylation, bioenergetics imbalance, deficit of Fe-S cluster enzymes and mitochondrial iron overload occur in individuals with FRDA. Proprioceptive neurons within the dorsal root ganglia (DRG) and cardiomyocytes are the most affected tissues in FRDA patients. To date there are not effective treatment for FRDA. We have previously established the primary proof-of-concept for developing gene therapy of FRDA cardiomyopathy and showed that adeno-associated virus (AAV) rh. 10 vector expressing human FXN injected intravenously not only prevented the onset of the cardiac disease in a faithful FRDA cardiac mouse model, but also, when administered at the time of heart failure, rapidly and completely reversed the cardiac disease. To date, there were unfortunately no adequate neuronal mouse model to address the possibility of gene therapy for the neuronal aspects of FRDA. We therefore recently generated a novel mouse model that recapitulates faithfully the sensory ataxia associated to FRDA using the conditional approach to delete frataxin specifically in the proprioceptive neurons of the DRG. By behavioural analysis, the mice exhibit an ataxic phenotype beginning at 3 weeks of age, which is rapidly progressive. Electrophysiological studies reveal a significant decrease of sensory wave already at 4.5 weeks and almost a complete loss at 8 weeks of age. A significant loss of sensory neurons within dorsal root ganglia is observed at 17.5 weeks of age compare to age matched controls. Ultrastructural analysis of sciatic and saphenous nerves showed abnormalities at early time points. Using this mouse model, we have developed an AAV gene therapy approach based on an intravenous delivery of AAV9-CAG-hFXN-HA vector at an early symptomatic stage of the disease. Mice displayed a complete prevention of the ataxic phenotype and electrophysiological analysis showed maintenance of the sensory wave in the treated animals. Histological studies revealed a complete prevention of neuronal loss in the DRG as well as a normal ultrastructure of saphenous and sciatic nerve. As results are encouraging, we plan to evaluate the potential therapeutical effect at a more advanced stage of the disease.

Abstract 14708: Prothrombin Time is a Novel Marker for Congestion in Acute Decompensated Heart Failure Patients Without Anticoagulants

Background: Where prothrombin time is widely used to monitor anticoagulation in cardiology patients, it is also a classical marker of liver damage. However, the clinical significance of prothrombin time in heart failure patients without anticoagulants is unknown. Therefore, we investigated the prevalence, relationship with clinical characteristics, and prognostic value of prothrombin time in acute decompensated heart failure (ADHF). Method: We prospectively studied 651 consecutive patients admitted for ADHF. Prothrombin time internationalized normalized ratio (PT-INR) was measured on admission in all patients. By excluding patients with oral anticoagulants, acute coronary syndrome and liver diseases, 308 patients were assessed. We assessed the relationship between PT-INR and blood tests, echocardiogram, and hemodynamic parameters from right heart catheterization. Cox regression hazard analysis was performed to assess prognostic value of PT-INR on all-cause mortality and cardiovascular mortality. Results: Of the 308 patients (75±13 years, 192 male), the mean PT-INR value was 1.10. Patients with prolonged PT-INR(&gt;1.10, n=104) had significantly higher total bilirubin, alkaline phosphatase and gamma-glutamyl transpeptidase (all p&lt;0.05), however, had similar LVEF, blood urea nitrogen, creatinine, and BNP compared to those with less PT-INR(≦1.10, n=204). PT-INR value had strong correlation with pulmonary capillary wedge pressure (r=-0.61, p&lt;0.01) and right atrial pressure (r=-0.59, p&lt;0.01), but not with cardiac index (r=0.23, p=ns.). Twenty-two patients (7%) died during a mean follow up of 317 days, and Cox proportional hazards analysis showed that PT-INR was an independent predictor of both all-cause mortality (HR=1.14, p&lt;0.05) and cardiovascular mortality (HR=1.12, p&lt;0.05) even after adjusted by age, sex, LVEF, creatinine, BNP and hemoglobin. Conclusion: Prolonged PT-INR in ADHF patients without anticoagulants was associated with clinical markers of hepatic congestion and elevated right sided pressure. It was also an independent predictor of all-cause and cardiovascular mortality.

Abstract 13262: Right to Left Ventricular Interdependence at Rest and During Exercise Assessed by the Ratio Between Pulmonary Systolic to Diastolic Time in Heart Failure Reduced Ejection Fraction

Background: The ratio between the duration of right ventricular (RV) systole and diastole (S:D ratio) has been proposed as an index of RV performance in a pediatric population with pulmonary arterial hypertension in whom it may predict prognosis and functional capacity. In heart failure (HF) S:D may provide relevant insights in the exercise response. Aim: to analyze the correlation between rest and peak exercise S:D and functional and cardiac parameters in HFrEF. Methods: 94 HFrEF patients (mean age 66±11 y, male 70%, ischemic etiology 71%, mean LVEF 34±9%) underwent a symptom-limited cardiopulmonary exercise testing (incremental ramp protocol) combined with exercise-echo. RV S:D was assessed by echo at rest and peak exercise. Results: A good correlation was found between rest and peak S:D and CPET indexes of exercise capacity, such as peak oxygen consumption (VO2) (Sperman’s rho -0.40 and 0.38 respectively, p= 0.02 and 0.023) and maximal workload (Rho= -0.42 and -0.45, p=0.031 and 0.034). An higher S:D also correlated with more impaired ventilatory efficiency or higher VE/VCO2 slope (Rho 0.49 and 0.32, p=0.019 and 0.024). Looking at echo phenotype, interestingly S:D is associated with parameters of mitral regurgitation (MR) severity, such as effective regurgitant orifice (Rho rest 0.63, peak 0.35, p&lt;0.01) and pulmonary artery systolic pressure (PASP, rho rest 0.53, peak 0.35, p&lt;0.01) particularly at rest. S:D also correlated with right RV fractional area change at rest and peak exercise (-0.39 and -0.39, p=0.035 and 0.04). Conclusions: In HFrEF population the assessment of S:D at rest and peak exercise predicts functional status and is related to more advanced hemodynamic impairment (increased PASP and MR) as expression of more unfavorable ventricular interdependence.