Clinical features of myocardial triglyceride in different types of cardiomyopathy assessed by proton magnetic resonance spectroscopy: comparison with myocardial creatine

BackgroundMyocardial lipid overstorage may produce cardiomyopathy, leading to dysfunction, but advanced heart failure may cause lipolysis via sympathetic nerve activation. In the failing heart, the creatine kinase system may also be impaired. The aims of this study were to assess myocardial triglyceride (TG) and creatine (CR) in different types of cardiomyopathy and to investigate whether they are related to the severity of cardiac dysfunction.Methods and ResultsIn patients with hypertrophic cardiomyopathy (HCM, n = 8), dilated cardiomyopathy (DCM, n = 12) or ischemic cardiomyopathy (ICM, n = 10), and normal subjects (NML, n = 22), myocardial TG and CR were evaluated using proton magnetic resonance spectroscopy. To assess cardiac sympathetic nerve activity, myocardial MIBG (a radioactive guanethidine analog) uptake was measured in DCM. Myocardial TG was significantly lower in hypertrophic cardiomyopathy (HCM) (1.92 ± 0.99 μmol/g), but higher in ICM (7.59 ± 4.36 μmol/g) than in NML hearts (4.05 ± 1.94 μmol/g). There was no significant difference in TG between DCM (4.84 ± 6.45 μmol/g) and NML. Myocardial CR in HCM (20.4 ± 8.4 μmol/g), DCM (14.8 ± 4.8 μmol/g), and ICM (19.4 ± 6.3 μmol/g) was significantly lower than that in NML hearts (27.1 ± 4.3 μmol/g). Overall, myocardial CR correlated positively with the severity of heart failure estimated by ejection fraction or myocardial BMIPP (a radioactive fatty acid analog) uptake, but TG did not. In DCM, myocardial TG correlated with body mass index, but not with MIBG uptake.ConclusionsMyocardial TG may be related to the specific cause of disease rather than the severity of cardiac dysfunction. In contrast, myocardial CR reflects the severity of heart failure despite different pathoetiologic mechanisms of dysfunction. In DCM, myocardial TG may be affected by an overweight state rather than cardiac sympathetic nerve dysfunction. Thus, myocardial CR has a closer relationship to heart failure severity than does myocardial TG.     

Endothelial Function and Arterial Compliance are not Impaired in Subjects With Heart Failure of Non-Ischemic Origin

BackgroundPatients with heart failure and underlying ischemic heart disease (IHD) exhibit both endothelial dysfunction and increased arterial stiffness. We investigated whether this is also the case in heart failure of nonischemic etiology.Methods and ResultsEleven patients with heart failure and IHD, 12 patients with heart failure from angiographically verified idiopathic nonischemic dilated cardiomyopathy (DCM), and 16 healthy subjects of similar age and sex were compared. Endothelium-dependent and independent function were evaluated by ultrasonic measurement of flow-mediated dilatation (FMD) and glyceryl trinitrate (GTN)-induced dilatation of the brachial artery respectively. Vascular compliance was assessed by carotid-femoral pulse wave velocity (PWV) and augmentation index (AIx). Heart failure severity was similar in IHD and DCM patients. FMD was impaired in the subjects with IHD as compared with control subjects (4.8 ± 0.3 vs. 8.0 ± 3.6 %, P < .01), but not in those with DCM. GTN-induced vasodilatation was not different in patients and controls. PWV was also increased in IHD patients compared with controls (12.1 ± 3.6 vs. 8.0 ± 1.6 m/s, P < .01), but not in DCM patients. AIx was similar in patients and controls.ConclusionHeart failure of nonischemic etiology is not associated with abnormalities of endothelium-mediated dilatation or of arterial compliance. The findings of our study now need to be confirmed in larger studies.     

Heart Failure–Specific Relationship Between Muscle Sympathetic Nerve Activity and Aortic Wave Reflection

BackgroundReflected arterial waves contribute to left ventricular (LV) afterload. Heart failure patients with reduced ejection fraction (HFrEF) are afterload sensitive and sympathetically activated. We tested the hypothesis that HFrEF patients exhibit a positive relationship between sympathetic vasoconstrictor discharge and aortic wave reflection.MethodsSixteen treated patients with HFrEF (61 ± 9 years of age, left ventricular ejection fraction 30 ± 7%, 3 women) and 16 similar-aged healthy control subjects (57 ± 7 years of age, 4 women) underwent noninvasive measurements of radial pulse waveforms (applanation tonometry) to calculate central blood pressures and aortic wave reflection characteristics: augmentation pressure (AP), augmentation index (AI_x), and AI_x corrected to a heart rate of 75 beats/min (AI_x@75). Muscle sympathetic nerve activity (MSNA) burst frequency was recorded from the fibular nerve (microneurography).ResultsHFrEF patients had higher AI_x (26 ± 9 vs 17 ± 15%; P < .05) and MSNA burst frequency (48 ± 7 vs 39 ± 11 bursts/min; P < .05) and lower central diastolic pressure than control subjects (64 ± 8 vs 70 ± 9 mm Hg; P = 0.05). There were no between-group differences in heart rate, other measures of blood pressure (brachial and central; P > .05), AP (11 ± 5 vs 7 ± 8 mm Hg; P = 0.11), or AI_x@75 (19 ± 9 vs 13 ± 11%,-P = 0.14). MSNA correlated positively with AP (r = 0.50; P < .05), AI_x (r = 0.51; P < .05), and AI_x@75 (r = 0.54; P < .05) in HFrEF patients but not in control subjects (r = 0.002–0.18; P > 0.49).ConclusionsIn patients with HFrEF, but not similarly aged healthy subjects, indices of aortic wave reflection correlate positively with MSNA. By increasing LV afterload, such neurovascular coupling could impair LV performance and worsen heart failure symptoms. Therapies that attenuate neurogenic vasoconstriction may benefit HFrEF patients by diminishing arterial wave reflection.     

Ischemic Cardiomyopathy Affects the Thioredoxin System in the Human Myocardium

Background

Oxidative stress due to reactive oxygen species (ROS) production is a key factor in the development of heart failure (HF). This study investigated the thioredoxin (Trx) system, which plays a major role in antioxidant defense, in patients suffering from ischemic (ICM) or dilated (DCM) cardiomyopathy.

Losartan improves heart rate variability and heart rate turbulence in heart failure due to ischemic cardiomyopathy

BackgroundHeart rate variability (HRV) and heart rate turbulence are known to be disturbed and associated with excess mortality in heart failure. The aim of this study was to investigate whether losartan, when added on top of β-blocker and angiotensin-converting enzyme inhibitor (ACEI) therapy, could improve these indices in patients with systolic heart failure.Methods and ResultsSeventy-seven patients (mean age 60.4 ± 8.0, 80.5% male) with ischemic cardiomyopathy (mean ejection fraction 34.5 ± 4.4%) and New York Heart Association Class II-III heart failure symptoms, already receiving a β-blocker and an ACEI, were randomly assigned to either open-label losartan (losartan group) or no additional drug (control group) in a 2:1 ratio and the patients were followed for 12 weeks. The HRV and heart rate turbulence indices were calculated from 24-hour Holter recordings both at the beginning and at the end of follow-up. The baseline clinical characteristics, HRV, and heart rate turbulence indices were similar in the 2 groups. At 12 weeks of follow-up, all HRV parameters except pNN50 increased (SDNN: 113.2 ± 34.2 versus 127.8 ± 24.1, P = .001; SDANN: 101.5 ± 31.7 versus 115.2 ± 22.0, P = .001; triangular index: 29.9 ± 11.1 versus 34.2 ± 7.9, P = .008; RMSSD: 29.1 ± 20.2 versus 34.3 ± 23.0, P = .009; NN50: 5015.3 ± 5554.9 versus 6446.7 ± 6101.1, P = .024; NN50: 5.65 ± 6.41 versus 7.24 ± 6.99, P = .089; SDNNi: 45.1 ± 13.3 versus 50.3 ± 14.5, P = .004), turbulence onset decreased (−0. 61 ± 1.70 versus −1.24 ± 1.31, P = .003) and turbulence slope increased (4.107 ± 3.881 versus 5.940 ± 4.281, P = .004) significantly in the losartan group as compared with controls.ConclusionsA 12-week-long losartan therapy significantly improved HRV and heart rate turbulence in patients with Class II-III heart failure and ischemic cardiomyopathy already on β-blockers and ACEI.     

Comparison of ventricular tachyarrhythmia characteristics in patients with idiopathic dilated or ischemic cardiomyopathy and defibrillators implanted for primary prevention

Background:

Implantable cardioverter‐defibrillator (ICD) therapy for primary prevention is well established in ischemic cardiomyopathy (ICM). Data on the role of ICDs in patients with dilated cardiomyopathy (DCM) and no history of ventricular tachyarrhythmia (VT/VF) are more limited.

Hypothesis:

DCM patients with an impaired left ventricular ejection fraction (LVEF) still represent a low arrhythmic risk subgroup in clinical practice.

Methods:

ICD stored data of DCM patients with an LVEF ≤35% was compared to data of ICM patients meeting Multicenter Automatic Defibrillator Implantation Trial (MADIT) eligibility criteria. VT/VF occurrences and electrical storm (ES) events were analyzed.

Results:

There were 652 patients followed for 50.9 ± 33.9 months. There were 1978 VT and 241 VF episodes analyzed in 66 out of 203 patients (32.5%) with DCM and in 118 out of 449 patients (26.3%, P = 0.209) with ICM. Freedom of appropriate ICD treatment due to VT/VF or ES events did not differ in both patient populations (log‐rank, P>0.05). In patients presenting with VT/VF episodes, mean event rates were comparable in both patient populations (3.2 ± 14.1 for DCM and VT vs 3 ± 13.9 for ICM and VT [P = 0.855], 0.4 ± 1.3 for DCM and VF vs 0.4 ± 1.8 for ICM and VF [P = 0.763], and 0.2 ± 0.7 for DCM and ES vs 0.2 ± 1 for ICM and ES [P = 0.666]).

Conclusions:

DCM patients with prophylactic ICDs implanted due to heart failure and patients fulfilling MADIT criteria reveal comparable patterns of VT/VF/ES events during long‐term follow‐up. Incidence, mean number of events, and time to first event did not differ significantly. Findings support the current guidelines for prophylactic ICD therapy in DCM patients with heart failure. © 2011 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.     

The L-Arginine–Asymmetric Dimethylarginine Ratio is an Independent Predictor of Mortality in Dilated Cardiomyopathy

BackgroundAsymmetric dimethylarginine (ADMA) is associated with increased mortality in patients with chronic heart failure but it remains unclear if the etiology of heart failure influences the prognostic value of dimethylarginines.Methods and ResultsL-Arginine, ADMA, and symmetric dimethylarginine (SDMA) were measured by liquid chromatography–tandem mass spectrometry in 341 patients with chronic heart failure due to dilated cardiomyopathy (DCM; n = 226) or ischemic cardiomyopathy (ICM; n = 115). Median (interquartile range [IQR]) ADMA and SDMA plasma levels were higher, L-arginine and the L-arginine–ADMA ratio were lower in patients with severe forms of heart failure (New York Heart Association (NYHA) functional class III or IV) compared with milder forms (NYHA functional class I or II) (ADMA 0.57 (0.14) μmol/L vs 0.54 (0.12) μmol/L [P < .001]; SDMA 0.47 (0.27) μmol/L vs 0.37 (0.13) μmol/L [P < .001]; L-arginine 81.8 (39.1) μmol/L vs 92.6 (39.3) μmol/L [P < .01]), but no significant differences were observed between the different etiologies. The L-arginine–ADMA ratio was associated with outcome only in patients with DCM. In multivariate analysis, the mortality risk of DCM patients was significantly lower for those in the highest quartile compared with the lowest quartile during a median observation time of 3.3 years (hazard ratio 0.31, 95% CI 0.11–0.88; P = .028, adjusted for other risk factors).ConclusionsDCM patients with unfavourable L-arginine–ADMA ratio are at increased risk for death.     

Sympathetic rhythmicity in cardiac transplant recipients

BACKGROUND: Variability of R-R interval and muscle sympathetic nerve activity (MSNA) occurs predominantly at a low frequency (LF, +/-0.1 Hz) and a high frequency (HF, +/-0.25 Hz) in normal humans. Increased sympathetic drive in normal humans is associated with an increased LF component of the R-R interval and MSNA. Patients with severe heart failure have high sympathetic activity but decreased or absent LF power of both R-R and MSNA. We tested the hypothesis that this dysfunction in autonomic modulation in heart failure can be reversed by heart transplantation. METHODS AND RESULTS: We performed spectral analysis of resting MSNA, R-R interval, and respiration in 9 patients with heart transplants, 9 chronic heart failure patients, and 9 normal control subjects, all closely matched for age, sex, and body mass index. MSNA (bursts per minute) was higher in patients with heart transplants (74+/-3) than either patients with heart failure (56+/-6) or normal subjects (40+/-4) (P<0.001). LF variability in the R-R interval was reduced in both heart transplant recipients and heart failure patients compared with the control subjects (P<0.01). The LF variability in MSNA was also nearly absent in the heart failure patients (P<0.01). However, the LF and HF oscillations in MSNA in patients with heart transplants were comparable to those evident in the control subjects. CONCLUSIONS: Cardiac transplantation does not reduce MSNA. However, LF oscillations in sympathetic activity are restored after transplantation such that the MSNA oscillatory profile is similar to that observed in normal subjects.     

The Presence of Electromechanical Mismatch In Nonischemic Dilated Cardiomyopathy Is Associated With Ventricular Repolarization Instability

BackgroundWe analyzed electromechanical mismatch (EMM) and its relationship to ventricular repolarization in patients with nonischemic dilated cardiomyopathy (DCM).Methods and ResultsIn 39 DCM patients with left ventricular ejection fraction (LVEF) <40% and New York Heart Association functional class ≥III, electroanatomic mapping was used to quantify areas of EMM. High-resolution electrocardiograph was used to measure heart rate variability (HRV) and QT variability index (QTVI). EMM was present in 22 patients (56%, group 1), whereas 17 patients presented no mismatched segments (44%, group 2). The groups did not differ in age (56 ± 10 years in group 1 vs 57 ± 7 years in group 2; P = .82), sex (male: 82% vs 94%; P = .40), LVEF (27 ± 8% vs 25 ± 6%; P = .18), or N-terminal pro–B-type natriuretic peptide (2,350 pg/mL vs 2,831 pg/mL; P = .32). Although heart rate and HRV were similar in both groups (rate: 80 ± 20 beats/min in group 1 vs 74 ± 19 beats/min in group 2 [P = .47]; standard deviation of normal-to normal RR intervals: 106 ± 79 vs 88 ± 115 [P = .61]), we found significantly higher QTVI values in patients from group 1 (−1.15 ± 0.46 vs −1.62 ± 0.51 in group 2; P = .005). In patients with implantable cardioverter-defibrillators, ventricular arrhythmias recorded ≤1 year before enrollment were more frequent in group 1 than in group 2 (58% vs 13%; P = .02).ConclusionsEMM is present in a majority of patients with DCM and is associated with ventricular repolarization instability.     

Serum matrix metalloproteinase-3 as a novel marker for risk stratification of patients with nonischemic dilated cardiomyopathy

BackgroundSelective induction of myocardial matrix metalloproteinases (MMPs) has been reported to occur in human nonischemic dilated cardiomyopathy (DCM). We aimed to evaluate the utility of serum MMPs for risk stratification of patients with DCM.Methods and ResultsWe measured serum levels of MMP-2, MMP-3, and MMP-9 using enzyme-linked immunosorbent assay in 71 patients with mild to moderate DCM (left ventricular ejection fraction = 28.3 ± 11.5%). The primary end point was the composite incidence of cardiac death and hospitalizations for worsening heart failure. During the follow-up period (mean, 28 ± 16 months), 19 patients had major cardiac events with sudden cardiac death in 6 cases and hospitalizations for worsening heart failure in 13 cases. Multivariate analysis revealed that MMP-3 and B-type natriuretic peptide were significant independent predictors of cardiac events in patients with DCM (hazard ratio 1.41, P = .012; hazard ratio 2.72, P = .048, respectively). According to the Kaplan-Meier analyses of cumulative cardiac event-free rates of the two groups that were based on the median levels of MMPs, the differences in the cardiac event-free curves were significant only for MMP-3 (P = .009). Moreover, patients with elevations of both MMP-3 and B-type natriuretic peptide were found to have the poorest prognosis.ConclusionOur results may address the utility of serum MMP-3 for risk stratification of patients with DCM.     

Mechanical alternans in human idiopathic dilated cardiomyopathy is caused with impaired force–frequency relationship and enhanced poststimulation potentiation

Mechanical alternans (MA) is frequently observed in patients with heart failure, and is a predictor of cardiac events. However, there have been controversies regarding the conditions and mechanisms of MA. To clarify heart rate-dependent contractile properties related to MA, we performed incremental right atrial pacing in 17 idiopathic dilated cardiomyopathy (DCM) patients and in six control patients. The maximal increase in left ventricular dP/dt during pacing-induced tachycardia was assessed as the force gain in the force–frequency relationship (FG-FFR), and the maximal increase in left ventricular dP/dt of the first post-pacing beats was examined as the force gain in poststimulation potentiation (FG-PSP). As a result, MA was induced in 9 DCM patients (DCM MA(+)) but not in the other 8 DCM patients (DCM MA(?)), and not in any of the control patients. DCM MA(+) had significantly lower FG-FFR (34.7 ± 40.9 vs 159.4 ± 103.9 mmHg/s, P = 0.0091) and higher FG-PSP (500.0 ± 96.8 vs 321.9 ± 94.9 mmHg/s, P = 0.0017), and accordingly a wider gap between FG-PSP and FG-FFR (465.3 ± 119.4 vs 162.5 ± 123.6 mmHg/s, P = 0.0001) than DCM MA(?) patients. These characteristics of DCM MA(+) showed clear contrasts to those of the control patients. In conclusion, MA is caused with an impaired force–frequency relationship despite significant poststimulation potentiation, suggesting that MA reflects ineffective utilization of the potentiated intrinsic force during tachycardia.     

Effect of Adaptive Servoventilation on Muscle Sympathetic Nerve Activity in Patients With Chronic Heart Failure and Central Sleep Apnea

BackgroundAdaptive servoventilation (ASV) improves cardiac function and sympathetic nerve activity in patients with heart failure (HF). However, the mechanisms underlying these improvements remain obscure.Methods and ResultsWe compared muscle sympathetic nerve activity (MSNA) and cardiorespiratory polygraphy and echocardiography findings at baseline and at 3.5 ± 0.8 months’ follow-up in 32 patients with HF (New York Heart Association functional class II or III; ejection fraction <45%) and central sleep apnea (CSA; apnea-hypopnea index [AHI] ≥15/h) who consented (n = 20; ASV group) or declined (n = 12; non-ASV group) to undergo ASV treatment. Compliance with ASV and changes in AHI were determined from data collected by integral counters in devices and from cardiorespiratory polygraphic findings, respectively. Ejection fraction and MSNA significantly changed in the ASV (both P < .001) but not the non-ASV group. Although changes in AHI and MSNA correlated, the average use of ASV did not. In contrast, changes in AHI and the average use of ASV were independent predictors of changes in ejection fraction (both P < .01).ConclusionsASV decreases MSNA and improves cardiac function in association with suppression of CSA in patients with HF.     

Comparison of Heart Transplantation Outcomes: Adult Congenital Heart Disease vs Matched Cardiac Patients in a Quaternary Reference Centre

BackgroundThe number of transplantations performed for adult congenital heart disease (ACHD) patients is increasing. We sought to compare survival and post-transplantation complications, including graft failure, rejection, dialysis, and use of a right ventricular assist device, between ACHD and a cohort of dilated (DCM) and ischemic (ICM) cardiomyopathy patients matched by age and year of transplantation.MethodsWe retrospectively reviewed our single-institution heart transplantation database and selected all patients who had surgery from 1988 to 2017. In our primary analysis, we looked at survival and post-transplantation complications across cardiomyopathy groups. Our secondary analysis was matched to mitigate era effects as well as differences in age at transplant.ResultsWe analyzed a cohort consisting of 303 heart transplant patients with cardiomyopathy due to either 1) ACHD (n = 38), 2) ICM (n = 110), or 3) DCM (n = 155). Kaplan-Meier analysis and a multivariable Cox proportional hazard regression model were used for all-cause mortality, and cause-specific hazard regression for cause-specific mortality and morbidity. There was no statistically significant survival difference across groups. The 1-year survival was 68.5% for ACHD, 85.4% for ICM, and 85.5% for DCM. In multivariable analysis, ICM and DCM patients showed a 66% lower risk of death relative to the ACHD group. The matched analysis showed no significant difference in survival across groups.ConclusionsACHD patients represent a growing high-risk patient cohort referred for transplantation. To improve survival outcomes we need to address modifiable risk factors.     

Global hypothermia for neuroprotection after cardiac arrest

Abstract

Levosimendan is a new inodilatory agent with calcium sensitizing activity. A major concern regarding the use of inotropic agent in heart failure is their effect on the sympathetic tone. This effect could explain increase in short term mortality with other inotropes. We aimed to assess the effect of levosimendan on sympathetic tone measured directly by microneurogra-phy. In a group of acute decompensated heart failure patients, we assessed cardiac performance by digital plethysmography measurement. Sympathetic tone was assessed through recording of muscle sympathetic nerve activity (MSNA) by micro-neurography. Recording were done blindly, for each patient after dobutamine perfusion was stopped (baseline) and 48 h after levosimendan infusion. Clinical, biological and morphological data were collected. We compared cardiac parameters and MSNA before and after administration of levosimendan. 13 patients were recruited (48 ± 3.6 years). Systolic blood pressure and rate pressure product (mmHg × Beat/min) decreased significantly after levosimendan infusion (P< 0.05). Cardiac output and stroke volume were significantly increased after levosimendan infusion (P< 0.05). A significant decrease of MSNA activity is observed after levosimendan infusion (P< 0.01). Levosimendan induced improvement of cardiac performance, associated with a decreased in MSNA. This study show for the first time that levosimendan has no direct detrimental effect on the sympathetic nervous system.     

Cardiorenal anemia syndrome in chronic heart failure contributes to increased sympathetic nerve activity

Background

We sought to assess whether cardiorenal anemia syndrome (CRAS) in chronic heart failure (CHF) patients contributes to sympathetic overactivity through modulation of sympathetic reflexes.

Methods and results

We prospectively studied 15 patients with CRAS and CHF and 15 control CHF patients, matched for age, gender distribution, type of cardiomyopathy, left ventricular ejection fraction (LVEF) and BMI. We compared muscle sympathetic nerve activity (MSNA) and the effect of peripheral chemoreflex deactivation on MSNA in both groups. We also compared sympathetic baroreflex function, assessed by the slope of the relationship between MSNA and diastolic blood pressure in both groups and while peripheral chemoreflexes were (by breathing 100% oxygen for 15 min) or not deactivated. Baseline MSNA was significantly elevated in CHF patients with CRAS compared with control CHF patients (83.1 ± 4.6 versus 64.9 ± 2.9 bursts/100 heart beats; P < 0.05) and sympathetic baroreflex impaired (2.69 ± 0.44 vs 5.25 ± 0.60% bursts/mm Hg; P < 0.01). Chemoreflex deactivation with administration of 100% oxygen led to a significant decrease in muscle sympathetic nerve activity (77.8 ± 4.7 versus 82.1 ± 4.9 bursts/100 heart beats; P < 0.01) and to an increase in sympathetic baroreflex function (2.77 ± 0.45 vs 5.63 ± 0.73% bursts/mm Hg; P < 0.01) in patients with CRAS and CHF. In contrast, neither room air nor 100% oxygen changed MSNA, hemodynamic or sympathetic baroreflex function in control CHF patients.

Conclusions

CRAS in CHF patients is associated with elevated sympathetic activity mediated by both tonic activation of peripheral chemoreflex and baroreflex impairment.     

Validity of the distance between mitral leaflets coaptation point and annular plane in differentiation between ischemic and dilated cardiomyopathy

Background: Identification of patients with ischemic cardiomyopathy (ICM) from those with idiopathic dilated cardiomyopathy (DCM) is important therapeutically and prognostically.Objective: To assess the validity of the distance between the mitral leaflets coaptation point and the mitral annular plane (CPMA) at low dose dobutamine stress echocardiography (DSE) for differentiation between ICM and DCM.Patients and methods: Echocardiographic indices and CPMA were measured at baseline and during dobutamine infusion for 50 patients who were presenting with heart failure and reduced ejection fraction (EF). Patients were divided into two groups depending on coronary angiographic findings, group I (ICM with significant coronary artery disease) and group II (DCM with normal coronary arteries).Results: Compared with baseline values, the CPMA at low dose DSE decreased significantly in ICM patients (11.8 ± 2.2 vs 8 ± 1.2 mm, P < 0.01) while it showed non-significant change in patients with DCM (11.66 ± 2.3 vs 11.99 ± 2.22 mm, P > 0.05). At low dose DSE ICM group showed a high statistically significant negative correlation between CPMA and both EF (r = ?0.749, P < 0.0001) and viability index (r = ?0.782, P < 0.0001) and significant positive correlation with WMSI (r = 0.79, P < 0.0001). Receiver operating characteristic (ROC) CPMA cut-off value ? 9 mm at low dose DSE, had sensitivity of 76.92%, specificity of 85.71% in detecting patients with ICM.Conclusion: Measurement of CPMA at low dose DSE might help in identifying patients with ICM from those with DCM.     

Heart rate variability in idiopathic dilated cardiomyopathy: relation to disease severity and prognosis.

OBJECTIVE: To assess the clinical importance of heart rate variability (HRV) in patients with idiopathic dilated cardiomyopathy (DCM). PATIENTS AND METHODS: Time domain analysis of 24 hour HRV was performed in 64 patients with DCM, 19 of their relatives with left ventricular enlargement (possible early DCM), and 33 healthy control subjects. RESULTS: Measures of HRV were reduced in patients with DCM compared with controls (P < 0.05). HRV parameters were similar in relatives and controls. Measures of HRV were lower in DCM patients in whom progressive heart failure developed (n = 28) than in those who remained clinically stable (n = 36) during a follow up of 24 (20) months (P = 0.0001). Reduced HRV was associated with NYHA functional class, left ventricular end diastolic dimension, reduced left ventricular ejection fraction, and peak exercise oxygen consumption (P < 0.05) in all patients. DCM patients with standard deviation of normal to normal RR intervals calculated over the 24 hour period (SDNN) < 50 ms had a significantly lower survival rate free of progressive heart failure than those with SDNN > 50 ms (P = 0.0002, at 12 months; P = 0.0001, during overall follow up). Stepwise multiple regression analysis showed that SDNN < 50 ms identified, independently of other clinical variables, patients who were at increased risk of developing progressive heart failure (P = 0.0004). CONCLUSIONS: HRV is reduced in patients with DCM and related to disease severity. HRV is clinically useful as an early non-invasive marker of DCM deterioration.     

Immunohistochemical study of remodeling of myocardial lymphatic and blood microvascular structures in terminal heart failure: differences between ischemic and dilated cardiomyopathy

This study investigated (cardiac) remodeling of the myocardial microvasculature in patients with terminal heart failure due to ischemic (ICM) and dilative (DCM) cardiomyopathy. Seventeen transmural left-ventricular (LV) biopsies (9 ICM and 8 DCM), taken from heart transplant recipients at transplantation (n=4) or during ventricular assist device implantation (n=13) were investigated by immunohistostaining for VEGFR-1 and VEGFR-2 as capillary markers and VEGFR-3, D2-40, PROX-1 and LYVE-1 as lymphatic markers. Results were compared to LV biopsies from 7 donor hearts (control). Compared to control, DCM hearts showed a significantly higher density of LYVE-1 positive lymphatics (p < 0.05), whereas no difference was seen for other markers. ICM hearts showed a significantly higher density of D2-40 positive lymphatics (p < 0.01) and a lower density of VEGFR-2 capillaries compared to control (p < 0.05). In comparison to normal donor hearts, ICM and DCM hearts showed a significantly different pattern of microvascular receptor expression. As distinct patterns were seen in ICM and DCM, the effect of microvascular remodeling may be substantially different between two clinically important causes of cardiomyopathy. Further research should be aimed at defining the impact of extracellular matrix composition and VEGF-related angiogenesis on the myocardial microvasculature at various stages of heart failure.     

扩张型心肌病患者心率变异性的临床分析

目的探讨心率变异性(HRV)在扩张型心肌病(DCM)患者中的变化规律及其对扩张型心肌病患者心血管事件的预测价值。方法对90例扩张型心肌病患者和50例健康人行24h动态心电图心率变异性对比分析及随访。心率变异性(HRV)分析包括正常RR间期标准差(SDNN),5min平均RR间期标准差(SDANN)等。90例扩张型心肌病患者平均随访21.2±7.3个月(10天～32个月),确定有无心血管事件发生。计算心率变异性(HRV)指标在预测扩张型心肌病患者发生心血管事件中的比值比(OR)和95%可信区间(95%CI)。结果健康人的心率变异性有明显的昼夜变化规律,心率变异性夜间>白天;扩张型心肌病患者的心率变异性明显低于健康组,昼夜节律性丧失,且与病情及心功能明显相关;11例扩张型心肌病患者发生心血管事件。心率变异性时域指标SDNN<100ms和SDANN<100ms发生心血管事件的比值比(OR)和95%可信区间(95%CI)分别为6.05和1.98～18.47及5.00和1.43～17.54。对性别和年龄进行校正后,SDNN<100ms的比值比(OR)和95%可信区间(95%CI)为3.13和1.16～8.47。结论扩张型心肌病患者在总体心率变异性显著降低的基础上,以迷走神经张力低下和心率变异性昼夜节律丧失为突出表现;扩张型心肌病合并心力衰竭患者心率变异性的变化,反映患者病情变化;24h心率变异性的SDNN可能是预测扩张型心肌病患者发生心血管事件的独立危险因素。     

Improvement of peripheral endothelial dysfunction by acute vitamin C application: different effects in patients with coronary artery disease,ischemic, and dilated cardiomyopathy

Background

Endothelial dysfunction has been described in patients with coronary artery disease (CAD) or chronic heart failure (CHF). Vitamin C administration leads to an improvement of endothelial function by reducing elevated levels of reactive oxygen species. It remains unclear, however, whether the degree of endothelial dysfunction caused by oxidative stress differs between CAD and CHF because of ischemic (ICM) or dilated cardiomyopathy (DCM).

Methods

In patients with CAD (n = 9; left ventricular ejection fraction [LVEF], 64% ± 3%), ICM (n = 9; LVEF, 25% ± 4%), DCM (n = 9; LVEF, 25% ± 3%), and healthy subjects (HS; n = 5; LVEF, 66% ± 5%) a change in internal radial artery diameter in response to acetylcholine (Ach; 15 and 30 μg/min) was measured with high-resolution ultrasound scanning during a co-infusion of normal saline or vitamin C (25 mg/min).

Results

Ach-mediated vasodilation was blunted in patients with CHF (DCM, 90 ± 20 μm; ICM, 86 ± 20 μm) and patients with CAD (336 ± 20 μm) as compared with HS (496 ± 43 μm; P <.05 vs patients with DCM, ICM, CAD). Vitamin C co-infusion increased Ach-mediated vasodilation by 180 ± 35 μm (to 270 ± 30 μm) in DCM (P <.05 vs CAD, HS) and by 294 ± 40 μm (to 380 ± 20 μm) in ICM (P <.05 vs DCM, CAD, HS). In patients with CAD, vitamin C increased Ach-mediated vasodilation by 146 ± 35 μm to normal values, whereas vascular diameter remained unchanged in HS (14 ± 20 μm; P = not significant).

Conclusions

Acute vitamin C administration restored peripheral endothelial function in patients with CAD to normal values, whereas endothelial function remained attenuated in CHF, in particular in patients with DCM. These results suggest that in patients with CHF, factors other than oxidative stress (eg, cytokines) contribute to the pathologic endothelial function.