Degree Of Left Ventricular Dysfunction Research Articles

Quantitative analysis of intraventricular blood flow dynamics by echocardiographic particle image velocimetry in patients with acute myocardial infarction at different stages of left ventricular dysfunction.

Left ventricular (LV) diastolic filling is characterized by the formation of a vortex that supports an efficient transit into systolic ejection. Aim of this study was to assess the intraventricular (IV) blood flow dynamics among patients with ST elevated myocardial infarction (STEMI) at different degrees of LV dysfunction, in the attempt to find novel indicators of LV pump efficiency. Sixty-four subjects, 34 consecutive STEMI patients and 30 healthy controls, underwent before hospital discharge 2D speckle tracking echocardiography to assess global longitudinal strain (GLS), and echo-particle image velocimetry analysis to assess flow energetic parameters. Left ventricular volumes ejection fraction (LVEF) and global wall motion score index (GWMSI) were evaluated by 3D echocardiography. ST elevated myocardial infarction patients were subdivided into three groups according to LVEF. Energy dissipation, vorticity fluctuation, and kinetic energy fluctuation indexes, which characterize the degree of disturbance in the flow, exhibit a biphasic behaviour in STEMI patients when compared with controls, with the highest values in patients with still preserved LV function and progressive lower values with LV function worsening. Significant linear correlations were found between energy dissipation index and both LVEF and GLS (r = 0.57, P < 0.001 and r = -0.61, P = 0.001, respectively). Kinetic energy fluctuation index significantly correlates with both LVEF (r = 0.75, P < 0.001) and GLS (-0.58, P = 0.002). Finally, a significant correlation was observed between GWMSI and energy dissipation index (-0.56, P = 0.008). The present study describes, for the first time, the progression of IV flow energetic properties in patients with acute myocardial infarction at different stages of LV dysfunction when compared with healthy controls. Further data are needed to assess the role of these parameters in the development and maintenance of LV dysfunction.

Left Ventricular Dysfunction in Duchenne Muscular Dystrophy and Genotype

Prognosis in patients with Duchenne muscular dystrophy (DMD) is guarded, and most deaths are due to cardiac or respiratory causes. It is unclear if some DMD gene mutations might be predictive of either mild or severe cardiac dysfunction. We studied 75 patients with DMD followed at our institution. Cardiac function, as assessed by yearly echocardiography, showed marked variability in left ventricular (LV) function. Some patients in their 3rd decade had no or minimal dysfunction, whereas others in their 2nd decade had very severe dysfunction. Therefore, 4 severity groups were defined ranging from no or mild LV dysfunction to severe LV dysfunction using patient age at first abnormal echocardiographic finding and degree of LV dysfunction. Genetic data were collected for all patients. Most patients had mutations from exon 1 to 20 to exon 41 to 55. The distribution of the 4 severity groups of LV dysfunction did not significantly differ between these 2 mutation groups. An analysis based on the number of exons involved (<5 vs ≥5 exons) also found no significant difference in cardiac severity. When patients having identical mutations were compared with their cardiac course, concordance was often not evident. Steroid therapy had no apparent protection for the development of cardiomyopathy. In conclusion, 75 patients with DMD showed marked variability in the severity of LV dysfunction. Neither the age of onset nor the severity of cardiomyopathy correlated with any of the mutation groups.

Exercise-based rehabilitation for heart failure.

Previous systematic reviews and meta-analyses consistently show the positive effect of exercise-based rehabilitation for heart failure (HF) on exercise capacity; however, the direction and magnitude of effects on health-related quality of life, mortality and hospital admissions in HF remain less certain. This is an update of a Cochrane systematic review previously published in 2010. To determine the effectiveness of exercise-based rehabilitation on the mortality, hospitalisation admissions, morbidity and health-related quality of life for people with HF. Review inclusion criteria were extended to consider not only HF due to reduced ejection fraction (HFREF or 'systolic HF') but also HF due to preserved ejection fraction (HFPEF or 'diastolic HF'). We updated searches from the previous Cochrane review. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue1, 2013) from January 2008 to January 2013. We also searched MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO) and PsycINFO (Ovid) (January 2008 to January 2013). We handsearched Web of Science, bibliographies of systematic reviews and trial registers (Controlled-trials.com and Clinicaltrials.gov). Randomised controlled trials of exercise-based interventions with six months' follow-up or longer compared with a no exercise control that could include usual medical care. The study population comprised adults over 18 years and were broadened to include individuals with HFPEF in addition to HFREF. Two review authors independently screened all identified references and rejected those that were clearly ineligible. We obtained full-text papers of potentially relevant trials. One review author independently extracted data from the included trials and assessed their risk of bias; a second review author checked data. We included 33 trials with 4740 people with HF predominantly with HFREF and New York Heart Association classes II and III. This latest update identified a further 14 trials. The overall risk of bias of included trials was moderate. There was no difference in pooled mortality between exercise-based rehabilitation versus no exercise control in trials with up to one-year follow-up (25 trials, 1871 participants: risk ratio (RR) 0.93; 95% confidence interval (CI) 0.69 to 1.27, fixed-effect analysis). However, there was trend towards a reduction in mortality with exercise in trials with more than one year of follow-up (6 trials, 2845 participants: RR 0.88; 95% CI 0.75 to 1.02, fixed-effect analysis). Compared with control, exercise training reduced the rate of overall (15 trials, 1328 participants: RR 0.75; 95% CI 0.62 to 0.92, fixed-effect analysis) and HF specific hospitalisation (12 trials, 1036 participants: RR 0.61; 95% CI 0.46 to 0.80, fixed-effect analysis). Exercise also resulted in a clinically important improvement superior in the Minnesota Living with Heart Failure questionnaire (13 trials, 1270 participants: mean difference: -5.8 points; 95% CI -9.2 to -2.4, random-effects analysis) - a disease specific health-related quality of life measure. However, levels of statistical heterogeneity across studies in this outcome were substantial. Univariate meta-regression analysis showed that these benefits were independent of the participant's age, gender, degree of left ventricular dysfunction, type of cardiac rehabilitation (exercise only vs. comprehensive rehabilitation), mean dose of exercise intervention, length of follow-up, overall risk of bias and trial publication date. Within these included studies, a small body of evidence supported exercise-based rehabilitation for HFPEF (three trials, undefined participant number) and when exclusively delivered in a home-based setting (5 trials, 521 participants). One study reported an additional mean healthcare cost in the training group compared with control of USD3227/person. Two studies indicated exercise-based rehabilitation to be a potentially cost-effective use of resources in terms of gain in quality-adjusted life years (QALYs) and life-years saved. This updated Cochrane review supports the conclusions of the previous version of this review that, compared with no exercise control, exercise-based rehabilitation does not increase or decrease the risk of all-cause mortality in the short term (up to 12-months' follow-up) but reduces the risk of hospital admissions and confers important improvements in health-related quality of life. This update provides further evidence that exercise training may reduce mortality in the longer term and that the benefits of exercise training on appear to be consistent across participant characteristics including age, gender and HF severity. Further randomised controlled trials are needed to confirm the small body of evidence seen in this review for the benefit of exercise in HFPEF and when exercise rehabilitation is exclusively delivered in a home-based setting.

Incremental Prognostic Value of Myocardial Fibrosis in Patients With Non–Ischemic Cardiomyopathy Without Congestive Heart Failure

We conducted a prospective longitudinal study to investigate the yet unknown clinical significance of myocardial fibrosis in patients with non-ischemic cardiomyopathy without history of congestive heart failure (CHF). At 3 tertiary referral centers, 228 patients with non-ischemic cardiomyopathy without history of CHF were studied with cardiovascular magnetic resonance for late gadolinium enhancement (LGE) detection and quantification and prospectively followed up for a median of 23 months. The end point was a composite of cardiac death, onset of CHF, and aborted sudden cardiac death. LGE was detected in 61 (27%) patients. Thirty-one of 61 (51%) patients with LGE reached combined end point when compared with 18 of 167 (11%) patients without LGE (hazard ratio, 5.10 [2.78-9.36]; P<0.001). Patients with LGE had greater risk of developing CHF than patients without LGE (hazard ratio, 5.23 [2.61-10.50]; P<0.001) and higher rate of aborted sudden cardiac death (hazard ratio, 8.31 [1.66-41.55]; P=0.010). Multivariate analysis showed that LGE was associated with high likelihood of composite end point independent of other prognostic determinants, including age; duration of cardiomyopathy; and left ventricular volumes, mass, and ejection fraction (hazard ratio, 4.02 [2.08-7.76]; P<0.001). Improvement χ(2) analysis disclosed that LGE addition to models, including clinical data alone or in combination with parameters of left ventricular remodeling and function, yielded an improvement in outcome prediction (P<0.001). Addition of LGE to age and left ventricular ejection fraction improved risk stratification for composite end point (net reclassification improvement, 29.6%) and onset of CHF (net reclassification improvement, 25.4%; both P<0.001). In patients with non-ischemic cardiomyopathy without history of CHF, myocardial fibrosis is a strong and independent predictor of outcome, providing incremental prognostic information and improvement in risk stratification beyond clinical data and degree of left ventricular dysfunction.

Long-Term Mortality Associated With Left Ventricular Dysfunction in Mitral Regurgitation Due to Flail Leaflets

Background— Ejection fraction (EF) as a marker of left ventricular (LV) dysfunction and the appropriate thresholds for diagnosing severe or mild/moderate LV dysfunction in mitral regurgitation are doubted and poorly followed in clinical practice. We aimed at assessing the role of EF in a large registry of organic mitral regurgitation to objectively establish thresholds for various degrees of LV dysfunction and to analyze whether mitral surgery remains beneficial in those subsets of patients. Methods and Results— We investigated the relation between EF and mortality in 1875 patients with mitral regurgitation due to flail leaflets in sinus rhythm (65±13 years; median EF, 66% [60%–71%]) enrolled in the Mitral Regurgitation International Database (MIDA) registry. With EF &lt;60%, mortality after diagnosis increased precipitously under medical management (adjusted hazard ratio [HR], 1.59 [1.19–2.12]) and during the entire follow-up (adjusted HR, 1.51 [1.22–1.87]). Severe LV dysfunction, if defined by EF &lt;30%, would affect a minuscule number of patients (0.3%). Conversely, EF &lt;45% was more frequent (2.9%) and was associated with considerable mortality under medical management (adjusted HR, 2.43 [1.50–3.95]) and during the entire follow-up (adjusted HR, 2.46 [1.67–3.61]). The group with EF of 45% to 60% represented a large proportion of patients (23%), exhibited rarely overt symptoms, and had higher mortality compared with EF &gt;60%. Above 60%, no EF threshold further determined survival. The benefit of surgery remained considerable in the groups with EF &lt;45% (adjusted HR, 0.28 [0.17–0.56]) and with EF of 45% to 60% (adjusted HR, 0.34 [0.21–0.64]). Conclusions— EF is valuable in defining presence and severity of LV dysfunction in organic mitral regurgitation. Patients with EF &lt;45% have severe LV dysfunction, catastrophic outcome under medical management, and should not be denied surgery. Although there is no survival gain with EF ranges &gt;60%, with EF dropping &lt;60%, mortality increases precipitously and prompt surgical referral is critical to outcome.

An Unusual Case of Cardiogenic Shock: Common Cause From Uncommon Etiology

Mechanical complications of an acute coronary syndrome can lead to hemodynamic instability out of proportion to the degree of left ventricular dysfunction. We present the case of a patient with cardiogenic shock secondary to severe mitral regurgitation in the setting of an acutely occluded obtuse marginal artery. Echocardiography and pathologic findings revealed an uncommon cause of anterolateral papillary muscle rupture. Using the unique features of this case, we present a clinical self-assessment exercise highlighting the challenges involved in the management of this type of patient.

Autonomic dysfunction predicts poor physical improvement after cardiac rehabilitation in patients with heart failure.

Background:Cardiac autonomic dysfunction, clinically expressed by reduced heart rate variability (HRV), is present in patients with congestive heart failure (CHF) and is related to the degree of left ventricular dysfunction. In athletes, HRV is an indicator of ability to improve performance. No similar data are available for CHF.Objectives:The aim of this study was to assess whether HRV could predict the capability of CHF patients to improve physical fitness after a short period of exercise-based cardiac rehabilitation (CR).Patients and Methods:This was an observational, non-randomized study, conducted on 57 patients with advanced CHF, admitted to a residential cardiac rehabilitation unit 32 ± 22 days after an episode of acute heart failure. Inclusion criteria were sinus rhythm, stable clinical conditions, no diabetes and ejection fraction ≤ 35%. HRV (time-domain) and mean and minimum heart rate (HR) were evaluated using 24-h Holter at admission. Patients’ physical fitness was evaluated at admission by 6-minute walking test (6MWT) and reassessed after two weeks of intensive exercise-based CR. Exercise capacity was evaluated by a symptom-limited cardiopulmonary exercise test (CPET).Results:Patients with very depressed HRV (SDNN 55.8 ± 10.0 ms) had no improvement in their walking capacity after short CR, walked shorter absolute distances at final 6MWT (348 ± 118 vs. 470 ± 109 m; P = 0.027) and developed a peak-VO2 at CPET significantly lower than patients with greater HRV parameters (11.4 ± 3.7 vs. an average > 16 ± 4 mL/kg/min). Minimum HR, but not mean HR, showed a negative correlation (ρ = -0.319) with CPET performance.Conclusions:In patients with advanced CHF, depressed HRV and higher minimum HR were predictors of poor working capacity after a short period of exercise-based CR. An individualized and intensive rehabilitative intervention should be considered for these patients.

Unipolar Voltage Abnormality is Associated with Greater Left Ventricular Dysfunction in Ischemic Cardiomyopathy

Following myocardial infarction (MI), left ventricular function is determined by cardiac remodeling occurring in both infarcted and noninfarcted myocardium (NIM). Unipolar voltage mapping may detect remodeling changes in NIM that are associated with the left ventricular ejection fraction (LVEF). We aimed to identify (1) unipolar voltage characteristics in patients with chronic MI, and (2) association of voltage abnormalities with degree of left ventricular dysfunction (LVD). Two groups of patients with ischemic cardiomyopathy (ICM) who underwent LV endocardial mapping during catheter ablation for ventricular tachycardia (VT) between January 2010 and December 2012 were studied. The first group (19 males) had mild to moderate LVD (M-LVD, LVEF >35%) and was matched for age, sex, infarction size, and infarction location with 10 males who had severe LVD (S-LVD, LVEF <35%). Both bipolar and unipolar endocardial abnormal voltage areas were measured and compared between groups. Abnormal bipolar area was comparable in both groups (30 ± 8% in the S-LVD group vs 28 ± 8% in the M-LVD group; P = 0.5). Total abnormal unipolar voltage area was significantly larger in the S-LVD group (57 ± 14% vs 43 ± 13%; P = 0.02). The abnormal unipolar voltage area within the normal bipolar voltage area was greater in the S-LVD group (26 ± 11% vs 15 ± 16%; P = 0.03). In receiver operating characteristic curve analysis, an 18.0% cut-off value for abnormal unipolar area within NIM identified severe LVD, with 90% sensitivity and 79% specificity (area under the curve 0.821). Patients with ICM and severe LVD have larger areas of unipolar voltage abnormality in the noninfarcted tissue than patients with M-LVD.

Abstract 9675: Does the Degree of Left Ventricular Dysfunction or Symptom Status Influence the Risk of Stroke or Systemic Embolism Among Patients With Atrial Fibrillation and Heart Failure?-Results From the ACTIVE Study

Background: Heart failure (HF) is a major component of widely applied stroke risk stratification schemes in atrial fibrillation (AF). However, data regarding the relationship between left ventricular (LV) dysfunction or HF symptoms and risk of stroke/systemic embolism among HF patients remains sparse. Methods: A total of 3487 participants from the Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE) trials with HF at baseline were randomized to anti-platelet therapy. Patients with HF were categorized as having preserved vs reduced ejection fraction (PEF ≥ 0.50, REF &lt; 0.50). If reduced, the degree of LV dysfunction was classified as mild, moderate or severe. HF symptoms were assessed using New York Heart Association (NYHA) class I-IV. Cox proportional-hazards models were used to estimate hazard ratios (HR, 95% CI) for stroke/systemic embolism across categories of LV dysfunction and NYHA class. Results: At baseline, 875 (47%) had HF-PEF, 982 (53%) had HF-REF; the degree of LV dysfunction was classified as mild in 25%, moderate in 25% and severe in 14%. During 3.6 years of follow-up, 211 patients had stroke/systemic embolism. In multivariable analysis, independent predictors of stroke were age ≥ 75 years (HR 2.83, 1.80-4.44), diabetes (HR 1.45, 1.03-2.03), diastolic blood pressure (per 1 mmHg, HR 1.02, 1.01-1.04), peripheral arterial disease(HR 1.94, 1.10-3.41), female(HR 1.48, 1.07-2.05) and prior stroke/transient ischemic attack (HR 1.77, 1.23-2.54) however EF &lt; 0.50, LV dysfunction or NYHA class were not predictors. Compared to those with HF-REF, patients with HF-PEF exhibited similar risk of stroke/systemic embolism: 4.18% vs. 3.83% per year, HR 0.89, 95% CI 0.65-1.22 after controlling for AF risk factors. Compared to normal LV function, there was no significant trend across categories of LV systolic dysfunction (p for trend, 0.57). The risk of stroke/systemic embolism was similar in HF patients with NYHA class I (4.0% per year, referent category), II (4.0%, HR 0.87, 0.60-1.26), III (3.9%, HR 0.62, 0.38-1.02), or IV (2.8%, 0.60, 0.14-2.55). Conclusion: Among patients with a history of HF, the presence or absence of LV dysfunction or severity of HF symptoms did not influence the risk of stroke/systemic embolism.

Predictors of mineralocorticoid receptor antagonist utilization in patients with left ventricular dysfunction following acute myocardial infarction: real world data from the acute coronary syndrome IS

Background: Following the EPHESUS trial, published in 2003, mineralocorticoid receptor antagonist (MRA) therapy among acute MI patients with left ventricular dysfunction and heart failure or diabetes mellitus received a class I indication in this high risk population. We sought to assess predictors for the implementation of this indication in a real world setting following the trial. Methods: The study population comprised 955 patients enrolled in the Acute Coronary Syndrome Israeli Surveys (ACSIS) 2004-2010 who met the guideline criteria for treatment with MRA including serum creatinine I or diabetes mellitus. Results: Among 7,696 patients enrolled in the ACSIS surveys from 2004, 955 (12%) were eligible for MRA treatment. In this population MRA therapy has increased from 20.6% to 25.4% over the six-year period, whereas utilization of other guideline recommended drugs, including ACE-I/ARBs and beta-blockers, was >3-fold higher. In a multivariate-adjusted logistic regression analysis, independent predictors of MRA prescription included a higher degree of left ventricular dysfunction (and a higher Killip class on admission, whereas there was no significant difference in creatinine level between patients with and without MRA treatment (Figure). ![Figure][1] Conclusions: In a real world setting, approximately one quarter of acute MI patients eligible for treatment with an MRA received this mode of medical therapy. MRA prescription in this population was associated with lower risk clinical characteristics, suggesting underutilization of MRAs in higher risk eligible patients. [1]: pending:yes

Mineralocorticoid receptor antagonist use in eligible patients following acute myocardial infarction: Real world data from the Acute Coronary Syndrome Israeli Surveys: 2004–2010

Following the EPHESUS trial in 2003, mineralocorticoid receptor antagonist (MRA) therapy received a class I indication for the management of eligible high-risk post-MI patients. Our goal was to examine temporal trends in MRA use in eligible post-myocardial infarction (MI) patients. We investigated temporal trends and factors associated with MRA utilization among eligible patients enrolled in the biannual Acute Coronary Syndrome Israeli Surveys (ACSIS) 2004-2010. Among 7696 patients enrolled in the ACSIS surveys from 2004, 955 (12%) were eligible for MRA therapy. In this population, prescription of MRAs at discharge from the index event showed a modest increase from 21% to 25% over the six-year period, whereas utilization of other guideline recommended drugs, including angiotensin converting enzyme inhibitors/receptor blockers and β-blockers was >2-fold higher. Multivariate logistic regression analysis showed that independent predictors of MRA prescription at discharge included a higher degree of left ventricular dysfunction (LVEF ≤30% vs. 31-40%: OR = 2.19; p = 0.02), history of heart failure prior to admission (OR = 1.92; p <0.004), admission Killip≥II (OR = 1.78; p = 0.004), and an anterior location of the index MI (OR = 1.54; p = 0.03). MRA utilization was not associated with an increased risk for adverse events or rehospitalization at 30 days of follow-up. In a real world setting, approximately one quarter of eligible post-MI patients are treated with an MRA following the index event, without a significant time-dependent change in this management strategy. MRAs are more likely to be underutilized in eligible lower-risk patients.

Multivariate miRNA signatures as biomarkers for non-ischaemic systolic heart failure

Non-ischaemic heart failure is one of the today's most prevalent cardiovascular disorders. Since modern pharmacotherapy has proved to be very effective in delaying disease progression and preventing death, imaging modalities and molecular biomarkers play an important role in early identification and clinical management as well as risk assessment of patients. The present study evaluated for the first time whole peripheral blood miRNAs as novel biomarker candidates for non-ischaemic heart failure with reduced ejection fraction (HF-REF). We assessed genome-wide miRNA expression profiles in 53 HF-REF patients and 39 controls. We could identify and validate several miRNAs that show altered expression levels in non-ischaemic HF-REF, discriminating cases from controls both as single markers or when combined in a multivariate signature. In addition, we demonstrate that the miRNAs of this signature significantly correlate with disease severity as indicated by left ventricular ejection fraction. Our data further denote that miRNAs are potential biomarkers for systolic heart failure. Since their detection levels in whole blood are also related to the degree of left ventricular dysfunction, they may serve as objective molecular tools to assess disease severity and prognosis.

NEW BIOMARKER STRATEGY “BRAIN NATRIURETIC PEPTIDE /TROPONIN I- RATIO” FOR DETECTING ACUTE MYOCARDIAL INFARCTION FROM PATIENTS WITH CHEST SYMPTOMS AT EMERGENCY DEPARTMENT

The accurate diagnosis of acute myocardial infarction (acute-MI) is important to improve life prognosis. The ratio of brain natriuretic peptide (BNP) to troponin I (Tnl) level (BNP/Tnl-ratio) reflects the degree of left ventricular dysfunction and myocardial injury. We assessed the hypothesis that

Idiopathic giant cell myocarditis and cardiac sarcoidosis

Idiopathic giant cell myocarditis (GCM) and cardiac sarcoidosis (CS) are rare disorders that cause cardiomyopathy, often with ventricular arrhythmias or heart block. Infection, autoimmune processes, and genetics have all been implicated in the pathogenesis of these diseases, but the etiology for both diseases is likely a complex multifactorial process. Both GCM and CS are generally progressive despite treatment with standard heart failure and arrhythmia therapies. Making the diagnosis of GCM or CS on initial clinical presentation is possible in only a small percentage of patients, so myocardial tissue diagnosis is required. The use of multiple noninvasive imaging modalities may aid in diagnosis and assessment of response to treatment. Establishing the diagnosis of GCM or CS early is crucial, as tailored immunosuppressive treatment may significantly alter the clinical course of these patients. The prognosis of patients with GCM is poor, while the prognosis for patients with CS varies according to degree of left ventricular dysfunction.

Cardiomyopathie du péripartum : une entité multiple

Peripartum cardiomyopathy (PPCMP) is a dilated and hypokinetic cardiomyopathy occurring during pregnancy or after delivery, with an estimated incidence between 1/1000 and 1/4000 births. It has been defined as a new onset of heart failure in the month preceding or following delivery, without demonstrated aetiology nor previously known heart disease, and with echocardiographic evidences of left ventricular (LV) dysfunction (LV ejection fraction<0.45). It's a multifactorial disease, immunologic, hormonal, and possibly viral mechanisms playing a determinant pathophysiological role. The classical clinical presentation is a rapid and unexpected onset of heart failure in a previously healthy woman, echocardiography being the key examination for positive and differential diagnosis, prognostication, therapeutic decision-making, and follow-up. The potential severity of PPCMP, and its unpredictable evolution in the first days following diagnosis, require that patients be referred to a tertiary care centre with a high skill in intensive cardiology care. Therapeutic management of PPCMP does not offer any specificity when compared to other causes of acute or chronic heart failure (from diuretics to extracorporeal life support), except for ACE-inhibitors, that are contraindicated before delivery. The high incidence of thrombo-embolic complications observed in the disease requires however rapid and curative anticoagulation, and immuno-suppressive treatment has been proposed in fulminant and highly inflammatory presentation, but its efficacy remains controversial. Very recently, promising results have been reported with bromocriptin-a prolactin secretion inhibitor-for reducing 6-month morbidity and mortality, but these findings have to be confirmed in larger scale randomised trials. As for the long-term evolution, approximately half of the patients will heal, while half of the women will keep some degree of LV dysfunction, 25% of them developing moderate to severe chronic heart failure.

Assessment and management of aortic valve disease in patients with left ventricular dysfunction

The onset of symptoms or left ventricular systolic dysfunction heralds a poor prognosis for patients with either aortic stenosis or aortic regurgitation. Echocardiography is the primary imaging modality for assessment of aortic valvular lesions. Cardiac catheterization is indicated to determine the severity of the aortic valve lesion when there is a discrepancy between the clinical findings and the results of echocardiography in patients with either symptoms or left ventricular dysfunction. For patients with low-gradient, low-output aortic stenosis, dobutamine provocation should be used to differentiate truly severe aortic stenosis from patients with a primary cardiomyopathy and low aortic valve area due to low forward flow. Aortic valve surgery improves myocardial performance by relief of ventricular afterload in both patients with severe stenosis and those with severe regurgitation. Surgery should be pursued in both patients with severe aortic stenosis and those with severe regurgitation regardless of the degree of left ventricular dysfunction.

AMP Activated Protein Kinase-α2 Regulates Expression of Estrogen-Related Receptor-α, a Metabolic Transcription Factor Related to Heart Failure Development

The normal expression of myocardial mitochondrial enzymes is essential to maintain the cardiac energy reserve and facilitate responses to stress, but the molecular mechanisms to maintain myocardial mitochondrial enzyme expression have been elusive. Here we report that congestive heart failure is associated with a significant decrease of myocardial estrogen-related receptor-α (ERRα), but not peroxisome proliferator-activated receptor-γ coactivator 1α, in human heart failure samples. In addition, chronic pressure overload in mice caused a decrease of ERRα expression that was significantly correlated to the degree of left ventricular dysfunction, pulmonary congestion, and decreases of a group of myocardial energy metabolism-related genes. We found that the metabolic sensor AMP activated protein kinase (AMPK) regulates ERRα expression in vivo and in vitro. AMPKα2 knockout decreased myocardial ERRα (both mRNA and protein) and its downstream targets under basal conditions, with no change in myocardial peroxisome proliferator-activated receptor-γ coactivator 1α expression. Using cultured rat neonatal cardiac myocytes, we found that overexpression of constitutively active AMPKα significantly induced ERRα mRNA, protein, and promoter activity. Conversely, selective gene silencing of AMPKα2 repressed ERRα and its target gene levels, indicating that AMPKα2 is involved in the regulation of ERRα expression. In addition, overexpression of ERRα in AMPKα2 knockout neonatal cardiac myocytes partially rescued the repressed expression of some energy metabolism-related genes. These data support an important role for AMPKα2 in regulating the expression of myocardial ERRα and its downstream mitochondrial enzymes.

Relationship Between Components of Heart Rate Variability and Doppler Echocardiographic Indices of Left Ventricular Systolic Performance in Patients with Coronary Artery Disease

Decreased heart rate variability (HRV) has been reported as prognostic predictor in coronary artery disease population. The aim of the study was to assess the relationship between cardiac autonomic tone disturbances and the degree of left ventricular dysfunction, estimated by 2-dimensional and Doppler echocardiography, in patients with coronary artery disease. Forty patients with angiographically proven coronary artery disease and 15 age-and sex-matched healthy subjects were included into the study (Group I and II, respectively). Routine clinical examinations, electrocardiography, coronary angiography, and 2-dimensional and Doppler echocardiography with assessment of LV systolic performance were done in all the patients and control subjects. Cardiac autonomic function was assessed by means of frequency-domain analysis of heart rate variability. The powers of LF and HF bands (P1 and P2), their ratio (P1/P2), and the logarithmic expression of powers were measured. The patients (Group I) had lower values of parasympathetic band of HRV and higher sympathetic activity than the healthy population (Group II) (p < 0.0002 for P2 and p < 0.04 for P1/P2 ratio). A positive significant correlation was seen between parasympathetic band of HRV and ejection fraction (r = 0.61, p < 0.0001), and mean acceleration of aortal flow (r = 0.56, p < 0.0001), whereas P1/P2 ratio inversely and significantly correlated with the same parameters (r = -0.46, p < 0.002 and r = -0.41, p < 0.008).

Regional and global ventricular systolic function in isolated ventricular non-compaction: Pathophysiological insights from magnetic resonance imaging

BackgroundIsolated ventricular non-compaction (IVNC) is frequently, but not invariably, associated with left ventricular (LV) systolic dysfunction. Factors impacting on regional and global LV function are unknown. The aim of the study was to apply magnetic resonance imaging (MRI) to evaluate the impact of extent and severity of ventricular non-compaction on LV systolic function in patients with IVNC. MethodsSixteen adult patients with IVNC as defined by previously validated MRI criteria [ratio between end-diastolic thickness of non-compacted and compacted myocardium (NC/C ratio)>2.3 in ≥1 LV segment] were enrolled. Short-axis cine images were employed for analysis. Applying a 16-segment LV model, regional systolic performance was assessed qualitatively (wall motion score, WMS; 1 = normal, 2 = mild hypokinesia, 3 = moderate-to-severe hypokinesia, and 4 = a/dyskinesia) as well as quantitatively [fractional wall thickening, FWT (%)=100×(end-diastolic wall thickness−end-systolic wall thickness)/end-diastolic wall thickness)]. ResultsMean LV ejection fraction was 43.8±15.4% (range, 17–68%). Regional disease severity, as expressed by the NC/C ratio, revealed a significant correlation with WMS (r=0.26; p=0.018) and FWT (r=−0.30; p=0.006). The total number of non-compacted segments/patient (NoNC) as an index of disease extent was a significant independent correlate of LV ejection fraction by multivariate regression analysis (β=−5.24; p=0.038) and an excellent predictor of global LV dysfunction (ROC analysis, AUC=0.98; p<0.0001). ConclusionsIn patients with IVNC, disease severity correlates with the degree of LV dysfunction at a regional level. The extent of myocardial non-compaction is an independent predictor of global LV dysfunction.

184 Predictive factors of difficult implantation procedure in cardiac resynchronization therapy

No studies have been published regarding factors related to difficult CRT implantation procedure and primary left ventricular (LV) lead implant failure. The aim of this prospective study was twofold: (1) to evaluate the prevalence and predictive factors of prolonged CRT implantation procedure; (2) to identify the predictive factors of primary LV lead implantation failure. Between November 2008 and September 2009, 106 pts underwent primo CRT implantation. Population characteristics were a mean age of 69 ± 10 years; 28.3% female; NYHA class 3.2 ± 0.3; LVEF (29 ± 6%); QRS width 146 ± 23 ms. Primo CRT implantation was obtained in 96/106 pts (90.5% primary success). A second procedure was successfully attempted in 6/10 pts with a second more experienced operator (5.7%). Among the remaining 4 pts, 1 pt required an epicardial LV lead implantation, and the implantation was not reattempted in the other 3 pts. The overall success rate of CRT implantation was 96.2% (102/106 pts). Procedure parameters were as follows: LV threshold (1.4 ± 0.9V); LV wave amplitude (15 ± 8 mV); LV impedance (874 ± 215 Ohms); median procedure time (skin to skin), 55 min. [45–80] and median of procedure fluoroscopy time, 11 min. [6.2–29]. In 24 patients (22.6%), difficult procedures requiring 85 min of implantation duration occurred. By univariate analysis, predictive factors of difficult implantation were LV ejection fraction (25.6 ± 6 vs. 30.2 ± 8%; p = 0.02), LVEDD (72.4 ± 11 vs. 66 ± 11 mm; p = 0.01), LVESD (62 ± 12 vs. 56 ± 12 mm; p = 0.04) and the operator's experience (very experienced operator vs. less experienced operator; p = 0.006). By multivariate analysis, only primary LV lead implantation failure, LVESD and operator's experience were independently associated with difficult procedures. In this patient subset with primary LV lead implant failure (n = 10), the only independent predictive factor was the LVESV (p = 0.03). In this study, the rate of difficult CRT device implantation procedures approached 25%. Both the degree of LV dysfunction and the operator's experience were independent predictors of surgical difficulties.