The exercise response in idiopathic dilated cardiomyopathy

In order to more clearly define the exercise response of idiopathic dilated cardiomyopathy (IDC), 20 patients in this study with strictly defined IDC were evaluated with radionuclide ventriculography and invasive hemodynamic monitoring. Severe cardiovascular impairment was present at rest, and peak supine exercise produced progressive left ventricular (LV) dilatation in both diastole and systole (mean±SEM from 172±14 to 212±22 ml/m² at end-diastole and from 137± 14 to 170±22 ml/m² at end-systole; both p<0.03). There were marked increases in LV and right ventricular filling pressure (from 17±2 to 36±3 mmHg and from 7±2 to 15±2 mmHg, respectively; both p<0.0001) and increased pulmonary artery pressure. Mean LV ejection fraction did not change significantly with exercise (22±2 to 23±3%; p>0.8), but individual patients demonstrated substantial variability. Cardiac output rose less than in normals and increases were brought about primarily by subnormal heart rate increases. High resting and exercise systemic and pulmonary vascular resistance were indicative of limited vasodilator reserve. Despite marked hemodynamic abnormalities, 10 of the 20 subjects had well preserved exercise capacity (≥ 12 min exercise duration). These patients as a group had significantly lower resting heart rate and higher exercise cardiac output and lower exercise systemic vascular resistance. However, they did not differ from the other patients with respect to resting LV function. Thus, the exercise response in IDC has specific characteristics that distinguish it from normal and from the exercise response of other causes of LV dysfunction. An interesting subset of patients with IDC has well preserved exercise capacity associated with greater chronotropic and vasodilator reserve. This finding suggests less sympathetic activation in these subjects.     

Mild mitral regurgitation reduces exercise capacity in patients with idiopathic dilated cardiomyopathy

We evaluated 30 patients with dilated cardiomyopathy (New York Heart Association functional Class II or III with medical treatment) to assess the effect of mild mitral regurgitation (MR) on exercise capacity in patients with congestive heart failure. They were classified into two groups based on results of left ventriculography: MR present (n=10) and MR absent (n=20). The severity of the MR by left ventriculography was grade I (mild) in all patients with MR. Steady-state hemodynamic data and angiographic data did not differ significantly between the two groups. Heart rate and systolic blood pressure at rest and in response to symptom-limited exercise testing did not differ between the groups. However, the peak work load was significantly lower in the group with MR than that in the group without MR (101±32 vs. 142±29 W, respectively; p<0.005). Peak oxygen uptake and peak oxygen pulse were also significantly lower in the group with MR than in that without MR (peak oxygen uptake: 18±5 vs. 23±5 ml/min/kg; p<0.05, peak oxygen pulse: 6.6±2.6 vs. 9.5±2.7 ml/min/beat; p<0.01, respectively). Thus, mild MR had a detrimental effect on the exercise capacity in patients with dilated cardiomyopathy.     

Cerebral oxygenation during exercise in cardiac patients

BACKGROUND: Until recently, compensatory mechanisms have been believed to regulate adequately cerebral blood flow in humans. However, this has been called into question by a series of new investigations suggesting that patients with left ventricular dysfunction suffer from cerebral hypoperfusion. We compared cerebral oxygenation during incremental exercise between patients with valvular heart disease and normal subjects. METHODS: Thirty-three patients with valvular disease and 33 normal subjects performed a symptom-limited incremental exercise test using a cycle ergometer. Oxyhemoglobin at the forehead was continuously monitored during exercise using near-infrared spectroscopy. Respiratory gas measurements were performed on a breath-by-breath basis. RESULTS: The increase in oxyhemoglobin during exercise was significantly lower in the patients with valvular disease than in normal subjects. The change in oxyhemoglobin during exercise (DeltaO(2)Hb) at the forehead was negatively correlated with the slope of the increase in minute ventilation to the increase in carbon dioxide output (DeltaE/DeltaCO(2)), and positively correlated with the peak oxygen uptake (O(2)), gas exchange threshold (GET), and slope of the increase in O(2) to the increase in the work rate (DeltaO(2)/DeltaWR). Among the patients with valvular disease, 15 patients showed a decrease in oxyhemoglobin at the forehead during exercise. When compared with the patients with increased oxyhemoglobin, those with decreased levels exhibited a higher DeltaE/DeltaCO(2) and a lower peak O(2), GET, and DeltaO(2)/DeltaWR. CONCLUSIONS: The present findings strongly suggest that cerebral oxygenation during exercise is dependent on the cardiovascular and pulmonary systems. The study also indicated the presence of cerebral hypoperfusion during exercise in cardiac patients whose cardiac output fails to increase normally.     

Improvement in exercise performance and hemodynamics by labetalol in patients with idiopathic dilated cardiomyopathy

Labetalol, a combined alpha- and beta-blocking agent, was administered to 12 patients (mean age 55 years) with idiopathic dilated cardiomyopathy to examine its effects on symptomatology and exercise performance. Studies were performed before treatment, after 8 weeks of placebo, and after 8 weeks of labetalol therapy in a randomized, crossover, double-blind design. The mean (+/- SEM) dose of labetalol for the group was 275 +/- 29 mg. Compared to treatment with placebo, the maximum duration of symptom-limited exercise was significantly prolonged with labetalol (580 +/- 72 seconds to 683 +/- 71 seconds; p less than 0.005). Both the resting and peak exercise heart rate and systolic blood pressure were significantly reduced. Ascending aortic blood flow velocity was also measured by continuous-wave Doppler technique during exercise. Compared to placebo, treatment with labetalol conferred no significant change in cardiac output at rest but significantly improved cardiac output at maximum exercise (14 +/- 3%; p less than 0.001). Doppler-derived peak aortic flow velocity, acceleration, and flow velocity integral were also significantly improved at maximum exercise. Systemic vascular resistance, as derived from mean blood pressure/cardiac output, was reduced by 12 +/- 3% and 16 +/- 3% at rest and at maximum exercise, respectively. New York Heart Association functional class was improved (3.2 +/- 0.2 to 2.2 +/- 0.3; p less than 0.005). No major side effects from labetalol were encountered. Thus labetalol improves symptomatology, exercise capacity, and exercise hemodynamics and reduces systemic vascular resistance in patients with idiopathic dilated cardiomyopathy.     

Familial dilated cardiomyopathy in patients transplanted for idiopathic dilated cardiomyopathy

OBJECTIVE: To evaluate the prevalence, clinical features, and pattern of inheritance of familial dilated cardiomyopathy (DCM) in heart transplant patients. PATIENTS AND METHOD: Patients with idiopathic DCM who had undergone heart transplantation were invited to participate. Patients with alcohol abuse were excluded. A clinical evaluation, 12-lead ECG, echocardiogram, blood tests, and DNA extraction were performed in patients and relatives. Familial DCM was defined as the presence of at least one relative with idiopathic DCM. Possible familial DCM was considered when at least one relative had left ventricular enlargement (LVE) (> 112% predicted LVEDD). RESULTS: One hundred and ninety-nine relatives of 43 families were studied. DCM was familial in 11 probands (25.6%) and possibly familial in 11 (25.6%). Fifteen relatives had DCM (7.5%), 26 (13.1%) LVE, and 5 (2.5%) hypertrophic cardiomyopathy. The pattern of inheritance was autosomal dominant in most families. Five probands (3 with familial DCM) had antecedents of consanguinity and possible recessive inheritance. Six probands (14%, 1 with familial DCM) had relatives with conduction system defects. Creatine kinase was moderately increased in 9 relatives (4.5%), 3 of them with LVE. Fifteen patients had at least moderate alcohol intake. Three of them had familial DCM (relatives without alcohol abuse) and 6 had possible familial DCM. CONCLUSIONS: The prevalence of familial DCM is high in patients who undergo heart transplant. Left ventricular enlargement, conduction system abnormalities, and elevated creatine kinase may be early markers of familial disease. Hypertrophic cardiomyopathy is present in some relatives of patients with idiopathic DCM. Familial DCM is present in patients with a previous diagnosis of alcoholic DCM.     

Cerebral blood flow as a marker for recovery of left ventricular systolic dysfunction in patients with idiopathic dilated cardiomyopathy

BackgroundThis study was intended to investigate whether cerebral blood flow (CBF) could predict the recovery of left ventricular (LV) systolic dysfunction in patients with idiopathic dilated cardiomyopathy (DCMP).Methods and ResultsBetween July 2001 and March 2009, 107 patients who had been diagnosed with idiopathic DCMP underwent radionuclide angiography to assess their CBF. The recovery of LV systolic dysfunction was defined as recovery of the ejection fraction (EF) measured by transthoracic echocardiography to a level of 40% or greater and an increase of 10% or greater in its absolute value during follow-up. The EF was followed for at least 36 months if it did not recover. Thirty-four patients (31.8%) recovered and had greater CBF than the nonrecovered patients (41.9 ± 3.4 vs. 37.1 ± 4.9 mL/min/100g, P < .001). On multivariate logistic analysis, CBF (odds ratio 1.216) and symptom duration (odds ratio 0.952) were independent predictors of the recovery of LV systolic dysfunction. There was also a weak negative correlation between CBF and symptom duration (r = ?0.334, P < .001). Furthermore, CBF was associated with LVEF improvement seen at the 1- and 2-year follow-up times according to multiple linear regression analysis.ConclusionsCBF was associated with recovery of LV systolic dysfunction in patients with idiopathic DCMP. Therefore, measurement of CBF would be helpful to predict the clinical course of their disease.     

Different response of patients with idiopathic and ischaemic dilated cardiomyopathy to exercise training

We looked at the benefits and complications of a home-based exercise programme in patients with ischaemic and idiopathic dilated cardiomyopathy. Twenty-four patients with left ventricular end-diastolic dimension >6.5 cm and fractional shortening <25% entered a cross-over trial of 8 weeks training versus 8 weeks rest. Echocardiography, electrocardiogram and cardiopulmonary exercise testing were performed at baseline, after training and after detraining. Training resulted in a higher peak oxygen consumption (26.5 versus 21.3 ml/kg/min, P=0.004), a higher peak heart rate (161 versus 152 bpm, P=0.02) and improved well-being. Patients with idiopathic dilated cardiomyopathy showed a significant increase in exercise time (879 versus 828 s, P=0.03) and peak oxygen consumption (31.3 versus 24.3 ml/kg/min, P=0.02) and a decrease in left ventricular end-diastolic dimension (6.4 versus 6.9 cm, P=0.01) and end-systolic dimension (5.3 versus 5.8 cm, P=0.04) in contrast to those with coronary artery disease, who developed a reduction in septal excursion and shortening rate following training. Complications of training were more common in those patients with ischaemic cardiomyopathy, greater left ventricular dimensions, poorer exercise tolerance and greater ventilation drive at baseline, and included fluid retention and exercise-induced ventricular tachycardia. We found that this group of patients with a dilated, poorly functioning left ventricle can safely derive benefit from a home-based exercise programme, particularly those of idiopathic origin, but they should be closely monitored for the development of complications.     

T-lymphocyte subsets in patients with idiopathic dilated cardiomyopathy

T-cell subsets were measured in the peripheral blood of 33 patients with heart failure from idiopathic dilated cardiomyopathy, 22 patients with heart failure from other causes, and 33 normal controls. Mean T-suppressor cell percentage was 30% in normals, 21% in patients with idiopathic dilated cardiomyopathy whose duration of symptoms was less than 1 year (P = 0.0005), and 26% in those with symptoms for greater than 1 year (P = 0.05). Similarly, percentage of T-suppressor cells in the group with heart failure from causes other than idiopathic dilated cardiomyopathy was significantly lower (23%; P = 0.005) in those with short duration of symptoms. When both heart failure groups were combined those with symptoms for less than 1 year had significantly lower T-suppressor frequencies (22%) than those with symptoms for more than 1 year (P = 0.015). Multivariate analysis identified duration of symptoms and age as the only independent predictors of T-suppressor cell frequencies. Decreased percentage of T-suppressor cells in patients with idiopathic dilated cardiomyopathy may be an epiphenomenon related to duration of heart failure. This should be taken into account in assigning an etiologic mechanism for T-suppressor cells in idiopathic dilated cardiomyopathy.     

Cerebral oxygenation during exercise in patients with terminal lung disease

STUDY OBJECTIVES: In patients with terminal lung disease who were exercising, we assessed whether improved arterial O2 saturation with an increased fraction of inspired oxygen (FIO2) affects cerebral oxygenation. DESIGN: Randomized, crossover. PATIENTS AND METHODS: The cerebral changes in oxyhemoglobin (DeltaHbO2) and changes in deoxyhemoglobin (DeltaHb) levels were evaluated using near-infrared spectrophotometry and the middle cerebral artery (MCA) mean velocity (V(mean)) was determined by transcranial Doppler ultrasonography in 13 patients with terminal lung disease (New York Heart Association class III-IV). Patients were allocated to an FIO2 of either 0.21 or 0.35 during incremental exercise with 15 min between trials. RESULTS: Peak exercise intensity (mean [+/- SE], 26 +/- 4 W) reduced the arterial O2 pressure (at rest, 64 +/- 3 mm Hg; during exercise, 56 +/- 3 mm Hg) and the arterial oxygen saturation (SaO2) [at rest, 92 +/- 2%; 87 +/- 2%; p < 0.05], while the arterial CO2 pressure was not significantly affected. The MCA V(mean) increased from 49 +/- 5 to 63 +/- 7 cm/s (p < 0.05) as did the DeltaHb, while the DeltaHbO2 remained unaffected by exercise. With an elevated FIO2, the SaO2 level (at rest, 95.8 +/- 0.7%; during exercise, 96.0 +/- 1.0%) and arterial O2 pressure (at rest, 102 +/- 11 mm Hg; during exercise, 100 +/- 8 mm Hg) were not significantly affected by exercise, and the levels of blood oxygenation remained higher than the values established at normoxia (p < 0.05). The MCA V(mean) increased to a level similar to that achieved during control exercise (ie, to 70 +/- 11 cm/s). In contrast to control exercise, DeltaHb decreased while DeltaHbO2 increased during exercise with 35% O2 (p < 0.05). CONCLUSION: An O2-enriched atmosphere enabled patients with terminal lung disease to maintain arterial O2 saturation during exercise. An exercise-induced increase in cerebral perfusion was not affected by hyperoxia, whereby the enhanced availability of oxygenated hemoglobin increases cerebral oxygenation. The clinical implication of the study is that during physical activity patients with terminal lung disease are recommended to use an elevated FIO2 to protect cerebral oxygenation.     

Differences in pulmonary function and exercise capacity in patients with idiopathic dilated cardiomyopathy and idiopathic pulmonary arterial hypertension

Objectives

We observed the pulmonary function and exercise capacity of idiopathic dilated cardiomyopathy (IDCM) and idiopathic pulmonary arterial hypertension (IPAH) patients using cardiopulmonary exercise testing (CPX). We evaluated and compared the two groups.

Background

Pulmonary abnormalities and decreased exercise capacity are common in IDCM and IPAH. Little is known about the differences in these two syndromes.

Methods

Sixty-three patients were involved the study, 23 with IDCM and 40 with IPAH. All patients underwent pulmonary function testing at rest and CPX.

Results

Patients with IPAH had a higher peak respiratory frequency (32.40 ± 7.88 vs 29.60 ± 6.50 b/min), peak dead space volume/tidal volume (29.33 ± 4.55 vs 26.30  ± 3.31%), peak end-tidal partial pressure of O₂ (125.18 ± 5.88 vs 115.17 ± 6.06 mm Hg), peak minute ventilation/CO₂ production (50.14 ± 13.26 vs 33.50 ± 6.80 L/min/L/min), and a lower peak oxygen uptake (1262.70 ± 333.34 vs 742.76 ± 194.72 ml/min), peak minute ventilation (38.20 ± 13.07 vs 45.33 ± 12.31 L), peak oxygen uptake/heart rate (5.11 ± 1.47 vs 9.43 ± 2.79 ml/b) and peak end-tidal partial pressure of CO₂ (23.73 ± 5.39 vs 35.30 ± 5.45 mm Hg) during exercise.

Conclusions

Compared to IDCM, patients with IPAH had worse pulmonary function and exercise capacity resulting from severe ventilation/perfusion mismatching and gas exchange abnormalities.     

Circulating tenascin-C levels in patients with idiopathic dilated cardiomyopathy

Circulating serum tenascin-C (an extracellular matrix glycoprotein) levels in patients with idiopathic dilated cardiomyopathy (IDC) were measured. Serum tenascin-C levels were increased in proportion to the severity of left ventricular dysfunction in patients with IDC. The associations of serum tenascin-C levels with serum troponin T and procollagen type III aminoterminal peptide levels suggest that increased levels of serum tenascin-C indicate ongoing replacement fibrosis after myocardial damage in IDC.     

Abnormal contractile responses during dobutamine stress echocardiography in patients with idiopathic dilated cardiomyopathy

BACKGROUND: In chronic heart failure augmented wall stress leads to increased energy demand. Supply, however, may be reduced due to coronary vasoconstriction and endothelial dysfunction. This might lead to a mismatch between demand and supply. In the present study we further explored the effect of increased demand during dobutamine stress echocardiography. METHODS AND RESULTS: Sixteen patients with idiopathic dilated cardiomyopathy (mean age 44+/-13 years, New York Heart Association class II-III, mean left ventricular ejection fraction 0.27+/-0.10) underwent dobutamine stress echocardiography (5-40 microg/min per kg bodyweight+atropine if required). Wall motion and thickening was assessed in 16 segments using a four-point scale. Eleven patients (69%) showed regions with worsening of wall motion or a biphasic response during dobutamine infusion. Of the remaining five patients one patient did not show any wall motion changes and one patient showed a partial improvement while only in three patients wall motion improvement in the whole heart was found. CONCLUSION: A majority of patients with idiopathic dilated cardiomyopathy showed decreased wall motion during increased demand, i.e. ischemia-like myocardial contractile responses during dobutamine stress echocardiography. These findings further support the concept that an energy mismatch between demand and supply might play a pathophysiological role in idiopathic dilated cardiomyopathy.     

Cardiovascular reserve in idiopathic dilated cardiomyopathy as determined by exercise response during cardiac catheterization

Simultaneous right- and left-sided cardiac high-fidelity hemodynamic measurements were obtained at rest and supine exercise during cardiac catheterization in 27 patients (mean age 32 +/- 10 years) with idiopathic dilated cardiomyopathy to investigate the hemodynamic exercise response and possible mechanisms for the wide variation in exercise tolerance observed clinically. There were no significant differences in other rest hemodynamic variables between group 1, patients with a normal exercise factor (more than 600, n = 10), and group 2, patients with an abnormal exercise factor (less than 600, n = 17). A greater increase in stoke volume index (12 +/- 6 vs 2 +/- 8 ml/beats/m2, mean +/- standard deviation) and a greater decrease in systemic vascular resistance with exercise occurred in group 1 than in group 2 (-614 +/- 304 vs -406 +/- 291 dynes cm-5). Elevation of right ventricular end-diastolic pressure with exercise was significantly greater in group 2 than in group 1 (7 +/- 5 vs 1 +/- 4 mm Hg, respectively, p less than 0.05). A maintained cardiac reserve in patients with idiopathic dilated cardiomyopathy appears to be largely dependent on 2 primary factors: preservation of normal right ventricular function during exercise; and preservation of systemic vasodilator capability sufficient to produce a significant degree of afterload reduction during exercise.     

特发性扩张型心肌病与HLA-A*基因的关联研究

目的探讨特发性扩张型心肌病（idiopathic dilated cardiomyopathy，IDC）易感的分子机制和确立一种人类主要组织相容性复合体（HLA—A＊）基因的检测方法。方法采用聚合酶链式反应和顺序特异性引物（PCR—SSP）基因分析方法，对31例特发性扩张型心肌病患者及29例无血缘关系的健康人的HIA—A＊各等位基因及亚基因进行检测分析，并将该方法与其他检测HIA等位基因的方法进行对比。结果HIA—A＊ 03基因与IDC呈正相关（RR=4．697，P〈0．05），其他HIA—A＊各等位基因未见异常。结论HIA—A＊03基因可能是北方汉族人IDC的致病易感基因之一。采用的方法（PCR—SSP）具有快速、简便、敏感、准确和可靠等优点，值得推广。     

Assessments of left ventricular function during exercise in patients with dilated cardiomyopathy: comparison with ischemic cardiomyopathy

Responses to supine bicycle ergometer exercise were assessed in a study population consisting of 26 patients with dilated cardiomyopathy (DCM) and 23 patients with ischemic cardiomyopathy (ICM). Left ventricular ejection fraction (LVEF) and regional wall motion were analyzed at rest and during supine bicycle ergometer exercise with radionuclide ventriculography. Although the same degree of LVEF between DCM (23 +/- 8%) and ICM (26 +/- 4%) occurred at rest, the left ventricular regional wall motion abnormality was more prominent in DCM. LVEF during the peak exercise stage in DCM was almost unchanged (24 +/- 8%), but in ICM it decreased significantly (22 +/- 5%). Exercise-induced regional wall motion abnormalities were detected in nine patients (35%) in DCM and 13 patients (57%) in ICM. Although patients with DCM are believed to have diffuse hypokinesis of the left ventricle, severe regional wall motion abnormalities (akinesis or dyskinesis) were frequently observed. During the follow-up period of up to six years, eight patients with DCM died of congestive heart failure. In eight patients with DCM who showed decreased LVEF during exercise, five patients died. However, only three of 18 patients without decreased LVEF during exercise died. Exercise-induced left ventricular dysfunction in DCM seems to be a poor prognostic sign.     

Carnitine deficiency in patients with coeliac disease and idiopathic dilated cardiomyopathy

BACKGROUND AND AIMS: Idiopathic dilated cardiomyopathy (IDCM) and coeliac disease (CD) are two pathological conditions which may lead, by different mechanisms, to malabsorption of various micronutrients, including carnitine, active in cardiac metabolism. The aim of the present investigation was primarily to evaluate differences in serum concentrations of total carnitine between IDCM patients and patients with IDCM associated with CD and then also to evaluate, in the latter, the effect of a gluten-free diet on serum concentrations of total carnitine. METHOD AND RESULTS: Serum carnitine was determined by enzymatic spectrophotometric assay in three groups of individuals: group A, 10 patients (5 males, 5 females), mean age 46.5+/-10.8 years, presenting isolated IDCM; group B, 3 patients (2 males, 1 female), mean age 34+/-8 years, with IDCM+CD; and group C, 10 healthy subjects (5 males, 5 females), mean age 38.6+/-11.1 years. All patients with IDCM belonged to class NYHA I-II. Mean concentrations of total serum carnitine in the group of patients with isolated IDCM (group A) were found to be lower than in the controls (group C). The concentrations in patients with IDCM associated with CD (group B) were lower than in the control group and also lower than in the isolated IDCM (group A). After 2 years on a gluten-free diet, patients presenting IDCM associated with CD showed a progressive increase in mean serum carnitine levels compared to values observed prior to the diet. CONCLUSIONS: Patients presenting IDCM associated with CD show a greater decrease in serum total carnitine levels than patients presenting the isolated form of IDCM. A gluten-free diet, in these patients, leads to a progressive increase in serum levels of this substance.