Cardiac sequelae of doxorubicin and paclitaxel as induction chemotherapy prior to high-dose chemotherapy and peripheral blood progenitor cell transplantation in women with high-risk primary or metastatic breast cancer

Doxorubicin plus paclitaxel has been shown to be an active regimen for metastatic breast cancer and is now frequently used as adjuvant therapy for high-risk primary breast cancer. Initial studies reported a higher than expected rate of cardiac toxicity with this regimen. We studied 105 patients with either high-risk primary breast cancer or metastatic breast cancer who were treated with doxorubicin (60 mg/m2) and 3-h infusions of paclitaxel (175 mg/m2) cycled every 3 weeks. Patients received three cycles of chemotherapy for high-risk primary or four cycles for metastatic disease. Patients then proceeded to high-dose chemotherapy (HDC) (STAMP I cyclophosphamide, cisplatin and carmustine) and peripheral blood progenitor cell transplantation (PBPCT). Patients underwent radionuclide multi-gated angiograms (MUGA) before and following induction chemotherapy and following HDC. During induction chemotherapy 40 (38%) of the patients had a reduction in left ventricular ejection fraction (LVEF). Fourteen had a decrease of 20% or greater and two were mildly symptomatic from CHF. There was additional reduction in the LVEF after HDC with a median value for LVEF of 59% (range, 20-78%). During HDC 10 patients developed clinical signs of congestive heart failure (CHF). Five patients responded to diuretic therapy and did not require any additional treatment. Four patients responded to vasodilation and/or digoxin with improvement in cardiac function. A clinically significant decrease in cardiac function was found in a small number of patients after induction chemotherapy and HDC with PBPCT. The majority of the patients tolerated this regimen without problems. Although there was a decline in LVEF as measured by radionuclide MUGA this did not prevent the majority of patients from proceeding with HDC. Bone Marrow Transplantation (2000).     

Cardiac Toxicity of High-Dose Cyclophosphamide in Patients with Multiple Myeloma Undergoing Autologous Hematopoietic Stem Cell Transplantation

High-dose cyclophosphamide is a well-known mobilization regimen in patients with multiple myeloma undergoing autologous hematopoietic stem cell transplantation. Highly differing rates of cardiac complications associated with high-dose cyclophosphamide have been reported. To date, no systematic clinical study has investigated high-dose cyclophosphamide mobilization regimens in multiple myeloma patients and evaluated its cardiotoxicity. We administered high-dose cyclophosphamide (4 g/m2) to 23 consecutive multiple myeloma patients and followed the patients for 15 days by serially measuring the cardiotoxicity biomarkers troponin I (TnI), brain natriuretic peptide (BNP), and endothelin 1 (ET-1). Systolic and diastolic left ventricular function was assessed by complete echocardiography before and at 6 to 8 weeks after the therapy. Patients younger than 55 years showed significant differences between basal TnI levels and TnI concentrations determined at 15 days after high-dose cyclophosphamide treatment (P = .028). Significant differences between basal BNP concentrations and BNP levels measured at 8 hours after high-dose cyclophosphamide treatment were found in the entire group of patients as well as in 2 subgroups, patients younger than 55 years and those older than 55 years (P <.0001, P <.001, and P = .001, respectively). ET-1 results for the entire group of patients showed a significant difference between baseline ET-1 values and ET-1 values determined 8 hours after high-dose cyclophosphamide administration (P = .004). Echocardiographic measurements revealed a barely nonsignificant decrease in cardiac output after high-dose cyclophosphamide infusion compared with pretreatment values (P = .06), a result in accord with echocardiographically detected increases in mild functional mitral regurgitation (P = .025). TnI levels at 15 days after the completion of treatment correlated with left ventricular diastolic dysfunction, as indicated by the s/d index (r = 0.61; P = .04). In conclusion, the significant neurohumoral activation of heart failure occurring after high-dose cyclophosphamide treatment is manifested by an increase in BNP and ET-1 levels, yet without concomitant cardiomyocyte necrosis. BNP levels and to a lesser extent ET-1 levels are much more sensitive indicators of myocardial injury than functional tests, such as echocardiography, whereas diastolic functional parameters are more sensitive predictors of early cyclophosphamide-induced cardiotoxicity. Mild functional mitral regurgitation may develop in patients given high-dose cyclophosphamide therapy.     

Cardiac effects within 3 months of BEAC high-dose therapy in non-Hodgkin's lymphoma patients undergoing autologous stem cell transplantation

OBJECTIVES: Limited data are available on the cardiac effects of high-dose cyclophosphamide (CY) in patients with non-Hodgkin's lymphoma (NHL). We prospectively assessed the cardiac effects of high-dose CY in 30 adult NHL patients receiving CY 6 g/m(2) as part of BEAC high-dose therapy (HDT). METHODS: Radionuclide ventriculography (RVG) and plasma natriuretic peptide (NT-proANP, NT-proBNP) measurements were performed simultaneously prior to BEAC at baseline (d - 7), 12 days (d + 12) and 3 months (m + 3) after stem cell infusion (D0). In addition to these time points, natriuretic peptides were measured 2 days before (d - 2) and 1 week (d + 7) after stem cell infusion. RESULTS: Left ventricular ejection fraction (LVEF) decreased from d - 7 (53% +/- 2%) to d + 12 (49% +/- 2%, P = 0.009). However, no significant change in cardiac diastolic function was observed. The LVEF returned towards baseline by m + 3. Plasma NT-proANP and NT-proBNP increased significantly from baseline (445 +/- 65 pmol/L and 129 +/- 33 pmol/L) to d - 2 (1,127 +/- 142 pmol/L, P < 0.001 and 624 +/- 148 pmol/L, P < 0.001, respectively). Thereafter, they started to decrease, but on d + 7 NT-proANP (404 +/- 157 pmol/L, P = 0.048) and NT-proBNP (648 +/- 125 pmol/L, P = 0.015) were still significantly higher than at baseline. On d + 12 and m + 3 they no longer differed from baseline. CONCLUSIONS: Our findings suggest that high-dose CY results in acute, subclinical systolic dysfunction in NHL patients previously treated with anthracyclines. Natriuretic peptides seem to be more sensitive than LVEF to reflect this transient cardiac effect. Serial measurements of natriuretic peptides might be a useful tool to assess cardiac effects of high-dose CY.     

High-dose melphalan and autologous stem cell transplantation as consolidation treatment in patients with chemosensitive ovarian cancer: results of a single-institution randomized trial

The role of high-dose chemotherapy (HDCT) in epithelial ovarian cancer (EOC) remains controversial. This study was initiated to compare the efficacy and tolerability of HDCT as a consolidation approach in women with chemosensitive advanced EOC (FIGO stages IIC-IV). Patients who had achieved their first clinical complete remission after six cycles of conventional paclitaxel and carboplatin combination chemotherapy were randomly assigned to receive or not high-dose melphalan. The primary objective was to compare time to disease progression (TTP). A total of 80 patients were enrolled onto the trial. Patients who were randomized to receive HDCT were initially treated with cyclophosphamide 4 g/m(2) for PBPC mobilization. HDCT consisted of melphalan 200 mg/m(2). Of the 37 patients who were allocated to HDCT, 11 (29.7%) did not receive melphalan either due to patient refusal (n=5) or due to failure of PBPC mobilization (n=6). In an intent-to-treat analysis, there were no significant differences between the two arms in TTP (P=0.059) as well as in overall survival (OS) (P=0.38).     

Intravenous immunoglobulin treatment for acute fulminant inflammatory cardiomyopathy: series of six patients and review of literature

BACKGROUND:

Although an autoimmune mechanism has been postulated for myocarditis and acute-onset inflammatory dilated cardiomyopathy (DCM), immunomodulatory treatment strategies are still under investigation.

METHODS AND RESULTS:

The clinical data of six patients with acute inflammatory DCM referred for evaluation for possible heart transplantation were reviewed. All patients were admitted with acute congestive heart failure and severely impaired left ventricular (LV) function and were treated with high-dose (2 g/kg) intravenous immunoglobulin (IVIG). The diagnosis of acute inflammatory DCM was based on recent onset of congestive heart failure (New York Heart Association functional class III or IV) with severely depressed LV ejection fraction ([LVEF] 30% or lower) occurring shortly after viral-like illness. All patients had inflammation on endomyocardial biopsy or elevated cardiac enzymes, as well as a normal coronary angiogram. All patients were in New York Heart Association class I or II at the time of hospital discharge. The mean LVEF improved from 21.7±7.5% at baseline to 50.3±8.6% at discharge (P=0.005). Four patients had complete recovery (LVEF 50% or higher) and two patients had partial LV recovery. Patients were followed for a median 13.2 months (range two to 24 months) and had a mean LVEF of 53±6% (P not significant versus LVEF at discharge).

CONCLUSIONS:

Therapy with intravenous high-dose IVIG may be a potentially useful treatment in selected patients if given early in the course of acute fulminant inflammatory DCM. A randomized, prospective trial is warranted to prove the real benefit of IVIG in this patient population.     

Does left ventricular dyssynchrony immediately after acute myocardial infarction result in left ventricular dilatation?

BACKGROUND: Reverse remodeling of the left ventricle (LV) is one of the advantageous mechanisms of cardiac resynchronization therapy (CRT). Substantial LV dyssynchrony seems mandatory for echocardiographic response to CRT. Conversely, LV dyssynchrony early after acute myocardial infarction may result in LV dilatation during follow-up. OBJECTIVE: The purpose of this study was to evaluate the relation between LV dyssynchrony early after acute myocardial infarction and the occurrence of long-term LV dilatation. METHODS: A total of 124 consecutive patients presenting with acute myocardial infarction who underwent primary percutaneous coronary intervention were included. Within 48 hours of intervention, two-dimensional echocardiography was performed to assess LV volumes, LV ejection fraction (LVEF), and wall motion score index (WMSI). LV dyssynchrony was quantified using color-coded tissue Doppler imaging (TDI). At 6-month follow-up, LV volumes and LVEF were reassessed. RESULTS: Patients with substantial LV dyssynchrony (> or =65 ms) at baseline (18%) had comparable baseline characteristics to patients without substantial LV dyssynchrony (82%), except for a higher prevalence of multivessel coronary artery disease (P = .019), higher WMSI (P = .042), and higher peak levels of creatine phosphokinase (P = .021). During 6 months of follow-up, 91% of the patients with substantial LV dyssynchrony at baseline developed LV remodeling, compared with 2% in the patients without substantial LV dyssynchrony. LV dyssynchrony at baseline was strongly related to the extent of long-term LV dilatation at 6 months of follow-up. CONCLUSION: Most patients with substantial LV dyssynchrony immediately after acute myocardial infarction develop LV dilatation during 6 months of follow-up.     

Influence of amifostine on reconstitution of lymphocyte subpopulations after conventional- and high-dose chemotherapy in patients with germ cell tumor

We assessed the influence of amifostine on immune reconstitution after conventional-dose paclitaxel, ifosfamide, cisplatin and high-dose carboplatin, etoposide and thiotepa followed by autologous peripheral blood progenitor cell (PBPC) rescue in patients with germ cell tumor (GCT). A total of 40 patients were treated with one cycle of paclitaxel and ifosfamide (TI) followed by granulocyte-colony stimulating factor (G-CSF) to mobilize PBPC, three cycles of paclitaxel, ifosfamide and cisplatin (TIP) and one course of high-dose carboplatin, etoposide and thiotepa (CET) plus PBPC rescue. Patients were randomized to receive an absolute dose of 500 mg amifostine (group A, n=20) on each day of chemotherapy or no amifostine (group B, n=20). Prior to each cycle of chemotherapy, after hematologic engraftment from CET, 6 weeks and 3 months after transplantation the subpopulations of lymphocytes were phenotyped. Between the two study groups no statistically significant differences were observed concerning reconstitution of lymphocyte subpopulations. Throughout treatment with TIP or CET lymphocyte counts and their subpopulations remained low without severe clinical complications. Delayed reconstitution of the CD4(+) cell compartment after PBPC rescue was observed in both study groups, but did not result in any severe or atypical infections. Treatment with amifostine administered at this dose did not significantly influence the reconstitution of lymphocyte subpopulations. Low numbers of lymphocytes during chemotherapy and delayed reconstitution of CD4(+) cells and other lymphocyte subpopulations after PBPC rescue had no clinical relevance for patients with GCT.     

Safety of dobutamine stress echocardiography in patients with aortic stenosis

BACKGROUND AND AIM OF THE STUDY: Aortic valve disease is becoming one of the most important cardiac diseases in western society. Low-dose dobutamine stress echocardiography (DSE) is recommended in patients with low-gradient aortic stenosis (AS) and severe left ventricular (LV) dysfunction. DSE is also used in patients with AS and moderately reduced or normal LV function for diagnostic purposes. The study aim was to assess the safety of DSE in the setting of AS and various degrees of LV dysfunction. METHODS: A total of 75 patients with AS who underwent DSE at the authors' center between 1997 and 2001 was reviewed. Group A patients (n = 20) had severely reduced mean LV ejection fraction (LVEF) of 25 +/- 6% and underwent low-dose DSE; group B patients (n = 55) had moderate to normal LV function (LVEF 51 +/- 8%) and underwent high-dose DSE. The mean pressure gradient, valve area and side effects after DSE were evaluated. RESULTS: Serious cardiac arrhythmias occurred in 10 patients. In group A, four patients (20%) developed non-sustained ventricular tachycardia. In group B, two patients (4%) had non-sustained ventricular tachycardia (VT), four (7%) had paroxysmal supraventricular tachycardias, and two (4%) severe symptomatic hypotension. Among the 20 patients with evidence of ischemia on DSE, three developed adverse side effects (no difference compared with patients without ischemia; p = 0.922). Fourteen patients received atropine during DSE, and 1 of these developed non-sustained VT after atropine administration. CONCLUSION: Serious cardiac arrhythmias occur frequently during both low-dose and high-dose DSE in patients with AS. Adverse side effects do not relate to stress-induced ischemia or atropine addition.     

Superoxide dismutase activity in adriamycin-induced cardiotoxicity in humans: a potential novel tool for risk stratification

BACKGROUND: Oxidative stress has been implicated in Adriamycin cardiotoxicity experimentally. We evaluated whether changes in systemic markers of antioxidant reserve occur and are associated with left ventricular (LV) dysfunction during Adriamycin use in humans. METHODS AND RESULTS: We prospectively evaluated oncology patients eligible for Adriamycin chemotherapy. Blood samples for enzymatic (erythrocyte superoxide dismutase activity [SOD-U SOD/mg protein]) and nonenzymatic antioxidants (total radical trapping antioxidant potential [TRAP-U of Trolox/microL plasma]) were collected at baseline (B), intermediate (I), and final (F) cycles. LV ejection fraction (LVEF) was assessed by radionuclide ventriculography. Fifty-one patients (49 +/- 12 years, 90% female) underwent 5.9 +/- 0.9 chemotherapy cycles and received 301 +/- 52 mg/m 2 of Adriamycin. LVEF decreased from 61 +/- 6% (B) to 56 +/- 7% (F) ( P < .001), but only 6 (12%) patients developed significant LV systolic dysfunction (LVEF < 50%). SOD activity increased significantly during treatment (4.5 +/- 1.8 [B], 6.0 +/- 2.1 [I], 5.6 +/- 2.2 [F]; P < .01), whereas TRAP values were unchanged. Baseline SOD activity from patients who developed LV systolic dysfunction was significantly higher than from those who maintained normal LVEF (5.9 +/- 1.8 versus 4.3 +/- 1.7; P < .05). In multivariate analysis, baseline SOD levels remained independently associated with LV dysfunction ( P = .05). CONCLUSION: Erythrocyte SOD activity increases after Adriamycin treatment and high baseline levels predicts Adriamycin-induced cardiotoxicity in humans.     

Preserved left ventricular ejection fraction following atrioventricular junction ablation and pacing for atrial fibrillation

Introduction: Right ventricular apical (RVA) pacing creates ventricular dyssynchrony and may compromise left ventricular ejection fraction (LVEF). The impact of RVA pacing in patients who have undergone atrioventricular junction (AVJ) ablation for atrial fibrillation (AF) is unclear. We sought to determine whether RVA pacing after AVJ ablation for patients with AF compromises LVEF in the short- or long-term.
Methods/Results: We studied 286 patients with AF who underwent AVJ ablation and RVA pacing at our institution between 1990 and 2002. Patients were stratified into a short-term follow-up group (LVEF reassessed by echocardiography within a year after AVJ ablation, n = 134) and a long-term group (LVEF reassessed after a year, n = 152). Among all 286 patients (mean follow-up 20 months), we observed no change in mean LVEF after AVJ ablation and RVA pacing (48% before vs. 48% after, P = 0.42). Short-term follow-up patients had a statistically significant improvement in mean LVEF (46% before vs. 49% after, P = 0.03), whereas there was no statistically significant change in mean LVEF in long-term follow-up patients (49% before vs. 48% after, P = 0.37). Only 9% of short-term patients, 15% of long-term patients, and 1% of patients with baseline LVEF ≤ 40% experienced ≥10% absolute decrease in LVEF. Baseline LVEF > 40% was a multivariate predictor of LVEF decline.
Conclusions: RVA pacing after AVJ ablation does not compromise LVEF in the short- or long-term for the vast majority of patients. Better predictors are needed to help us select patients for biventricular pacing after AVJ ablation.     

Evaluation of eplerenone in the subgroup of EPHESUS patients with baseline left ventricular ejection fraction <or=30%

AIMS: Because of the prognostic importance of LV dysfunction following an AMI and the increasing use of electrical and/or mechanical interventions in patients with LV systolic dysfunction, this retrospective analysis of EPHESUS patients with LVEF 相似文献   

Effect of chronic right ventricular apical pacing on left ventricular function

The determinants of change in left ventricular (LV) ejection fraction (EF) over time in patients with impaired LV function at baseline have not been clearly established. Using a nuclear database to assess changes in LV function over time, we included patients with a baseline LVEF of 25% to 40% on a gated single-photon emission computed tomographic study at rest and only if second-gated photon emission computed tomography performed approximately 18 months after the initial study showed an improvement in LVEF at rest of > or =10 points or a decrease in LVEF at rest of > or =7 points. In all, 148 patients qualified for the EF increase group and 59 patients for the EF decrease group. LVEF on average increased from 33 +/- 4% to 51 +/- 8% in the EF increase group and decreased from 35 +/- 4% to 25 +/- 5% in the EF decrease group. The strongest multivariable predictor of improvement of LVEF was beta-blocker therapy (odds ratio 3.9, p = 0.002). The strongest independent predictor of LVEF decrease was the presence of a permanent right ventricular apical pacemaker (odds ratio 6.6, p = 0.002). Thus, this study identified beta-blocker therapy as the major independent predictor for improvement in LVEF of > or =10 points, whereas a permanent pacemaker (right ventricular apical pacing) was the strongest predictor of a LVEF decrease of > or =7 points.     

肺积1号方防治肺癌紫杉醇化疗相关心脏不良反应的临床观察

目的观察肺积1号方对肺癌紫杉醇化疗引起的心脏不良反应和心功能的干预效果。方法 64例接受紫杉醇化疗的肺癌患者随机分为对照组（n=32）和实验组（n=32）。对照组仅接受化疗,实验组在化疗同时口服肺积1号方煎剂,早晚各1次,200mL,日一剂。治疗前后分别记录心电图和超声心动图中的左心室舒张末期内径（LVDd）、左心室收缩末期内径（LVSd）、舒张早期与晚期充盈速度比值（E/A）、射血分数（LVEF）和短轴缩短率（FS）等各项指标,以及发生心脏不良反应的患者比例。结果实验组心电图异常发生率明显低于对照组（12.5%vs.31.3%,P〈0.05）,实验组化疗后LVDd、LVDs、E/A、LVEF和FS均与化疗前无统计学差异,对照组LVDd和LVDs较化疗前明显增加（P〈0.05）;实验组心脏不良反应的发生率明显低于对照组（13.6%vs.37.5%,P〈0.05）。结论肺积1号方对肺癌紫杉醇化疗所导致的心脏不良反应有一定的防治作用,并可在一定程度上减轻心脏功能下降。     

Peripartum cardiomyopathy: inflammatory markers as predictors of outcome in 100 prospectively studied patients.

AIMS: Peripartum cardiomyopathy (PPCM) is a disorder of unknown aetiology with a course and outcome that is largely unpredictable. We evaluated the prognostic role of multiple inflammatory markers in the plasma of a large cohort of African patients with PPCM. METHODS AND RESULTS: The study of 100 patients with newly diagnosed PPCM was single-centred, prospective, and longitudinal. Clinical assessment, echocardiography, and blood analysis were done at baseline and after 6 months of standard therapy. Inflammatory markers were measured at baseline only. Fifteen patients died. Left ventricular ejection fraction (LVEF) improved from 26.2+/-8.2 to 42.9+/-13.6% at 6 months (P<0.0001). However, normalization of LVEF (>50%) was only observed in 23%. Baseline levels of C-reactive protein correlated positively with baseline LV end-diastolic (rs=0.33, P=0.0026) and end-systolic (rs=0.35, P=0.0012) diameters and inversely with LVEF (rs=-0.27, P=0.015). Patients who died presented with significantly lower mean EF and higher Fas/Apo-1 plasma values (P<0.05). Fas/Apo-1 and New York Heart Association functional class (NYHA FC) predicted mortality at baseline. CONCLUSION: Plasma markers of inflammation were significantly elevated and correlated with increased LV dimensions and lower LVEF at presentation. Baseline Fas/Apo-1 and higher NYHA FC were the only predictors of mortality. Normalization of LVEF was only observed in 23% of this African cohort.     

High-dose chemotherapy followed by stem cell rescue for high-risk germ cell tumors: the Stanford experience

Germ cell tumors carry an excellent prognosis with platinum-based therapy upfront. The patients who either relapse or demonstrate refractoriness to platinum pose a challenge. There exist many reports in the literature on the use of high-dose chemotherapy and stem cell rescue improving the outcome in patients with relapsed germ cell tumors. However, the reports have great variability in the patient selection, prior treatments, the choice of the conditioning regimen and variability of the doses within the same regimen. In this report, we present 37 patients who underwent a uniform protocol of high-dose chemotherapy with stem cell rescue. Stem cell mobilization was performed with high-dose CY (4 g per m(2)) and we were able to collect adequate cells for marrow rescue in all patients. Patients received a high-dose regimen with etoposide (800 mg/m(2) per day) days -6, -5 and -4 as a continuous infusion, carboplatin (667 mg/m(2) per day) on days -6, -5 and -4 as a 1 h infusion, and CY (60 mg/kg per day) on days -3 and -2. In this high-risk group of patients, high-dose chemotherapy with autologous stem cell rescue led to a 3-year overall survival of 57% and a 3-year event-free survival of 49%. The results are reflective of a single procedure. No tandem transplants were performed. The treatment-related mortality was low at 3% in this heavily pretreated group.     

Left ventricular systolic dyssynchrony index by three-dimensional echocardiography in patients with decreased left ventricular function: comparison with tissue Doppler echocardiography

Background: Three‐dimensional echocardiography (3DE) can simultaneously assess left ventricular (LV) regional systolic motion and global LV mechanical dyssynchrony. Methods: We used 3DE to measure systolic dyssynchrony index (SDI) (standard deviation of the time from cardiac cycle onset to minimum systolic volume in 17 LV segments) in 100 patients and analyzed the association of SDI with other parameters for LV systolic function or dyssynchrony. Eighteen patients who underwent cardiac resynchronization therapy (CRT) were also evaluated at 6 months after CRT, and the association of baseline SDI and tissue Doppler imaging (TDI) dyssynchrony index (Ts‐SD) with the change of LV end‐systolic volume (ESV) analyzed. Ts‐SD was calculated using the standard deviation of the time from the QRS complex to peak systolic velocity. Results: There was a significant inverse correlation between LVEF and SDI (r =?0.686, P < 0.0001). QRS duration was also significantly correlated to SDI (r = 0.407, P < 0.0001). There was a significant positive correlation between baseline SDI and the decrease in LVESV after CRT (r = 0.42). Baseline SDI was significantly greater in responders (10 patients) than in nonresponders (16.4 ± 5.1 vs. 7.9 ± 2.4%, P < 0.01), but there was no significant difference in Ts‐SD. SDI > 11.9% predicted CRT response with a sensitivity of 90% and a specificity of 75%. Conclusions: SDI derived from 3DE is a useful parameter to assess global LV systolic dyssynchrony and predict responses to CRT. (Echocardiography 2012;29:346‐352)     

Left ventricular systolic function in middle-aged patients with diabetes mellitus

In cross-sectional studies of asymptomatic diabetic patients, multiple abnormalities in left ventricular (LV) function have been found. Long-term significance of these abnormalities is unknown because follow-up studies have not been previously performed. LV ejection fraction (EF) by radionuclide angiocardiography was examined in middle-aged control Subjects (n = 44), in patients with insulin-dependent (IDDM) (n = 32) and non-insulin-dependent (NIDDM) (n = 32) diabetes mellitus at baseline and after 4-year follow-up. At baseline, all study subjects were free from cardiovascular disease. LVEF at rest did not differ between the groups at baseline. The decrease in LVEF at rest during follow-up was 1.1 ± 1.1% (mean ± SEM) in control subjects, 3.1 ± 1.3% (p = NS, compared with control subjects) in patients with IDDM, and 7.2 ± 1.4% (p <0.01) in patients with NIDDM. At follow-up examination, abnormally low LVEF at rest (<50%) was found in 7% of control subjects, 13% of patients with IDDM (p = NS), and in 31% of patients with NIDDM (p <0.05). Compared with control subjects, the prevalence of an abnormal LVEF response to exercise (an increase by <5%, or a decrease) was higher in diabetic groups at both examinations. This prevalence increased in control subjects from 10% at baseline to 26% at follow-up examination. In patients with IDDM, the respective increase was from 43% to 52% (p = NS, compared With control subjects), and in patients with NIDDM from 53% to 73% (p = NS). Duration and metabolic control of diabetes, presence of diabetic complications, and LVEF at rest or during exercise at baseline did not differ in either diabetic group between the patients who had normal or abnormal LVEF at rest or in response to exercise at follow-up examination. No study subject experienced clinical heart failure during follow-up, but 7% of control subjects, 37% of patients (p <0.001) with IDDM, and 34% of patients (p <0.01) with NIDDM had coronary artery disease at follow-up examination. In conclusion, LVEF at rest deteriorated significantly during 4-year follow-up in patients with NIDDM but not in patients with IDDM. A high prevalence of subclinical LV systolic dysfunction became evident both in patients with IDDM and patients with NIDDM as an abnormal LVEF response to exercise both at baseline and follow-up examinations.     

Relationship between left ventricular dysfunction and depression following myocardial infarction: data from the MIND-IT.

AIMS: Depression in patients following myocardial infarction (MI) is associated with an increased risk of mortality, but this association may be confounded by cardiac disease severity. We explored the relationship between left ventricular ejection fraction (LVEF) and depression in MI patients. METHODS AND RESULTS: In the Myocardial Infarction and Depression-Intervention Trial (MIND-IT), 1989 MI patients were assessed for depressive symptoms [Beck Depression Inventory (BDI) t = 0, 3, 6, 9, and 12 months post-MI]. Patients with BDI score > or =10 were assessed for the presence of International Classification of Diseases, 10th revision (ICD-10) depressive disorder (t = 3, 6, 9, and 12 months post-MI). Patients were divided into categories according to their LVEF during hospitalization, i.e. LVEF <30%, LVEF 30-45%, LVEF 45-60%, and LVEF > or = 60%. During hospitalization, presence of depressive symptoms was higher in patients with LV dysfunction. A relationship was found between LVEF and ICD-10 depressive disorder, i.e. a lower LVEF was associated with a higher rate of depression from 3-12 months post-MI (P < 0.01). Levels of LVEF inversely correlated with the BDI score at 3 months post-MI. Associations persisted after adjustment for demographics, risk factors for coronary artery disease, co-morbidity, Killip class, and baseline BDI score. CONCLUSION: In MI patients, the rate of depression and the severity of depressive symptoms are significantly related to the severity of LV dysfunction. The association between depression and LV dysfunction must be acknowledged when evaluating the prognostic effects of depression in cardiac patients.     

The presence of contractile reserve has no predictive value for the evolution of left ventricular function following atrio-ventricular node ablation in patients with permanent atrial fibrillation.

AIMS: Transcatheter ablation of the atrio-ventricular (AV) node followed by ventricular pacing has been shown to improve symptoms and quality of life (QOL) of patients with permanent atrial fibrillation (AF). In a considerable number of patients, cardiac function deteriorates after AV node ablation. We aimed to determine whether the absence of contractile reserve assessed by low dose dobutamine stress echocardiography (LDDSE) could identify those patients whose left ventricular (LV) function deteriorates after AV node ablation. METHODS: All 25 patients studied had permanent AF for at least 12 months. LVEF was determined 6 days and 3 months after AV node ablation by radionuclide ventriculography (RNV), at a paced rate of 80 beats/min. Deterioration in cardiac function was defined as a decrease in LVEF>5%. LDSE was performed in all patients before and after ablation. The presence of contractile reserve was defined as an improvement in regional function of >or=1 grade at low dose dobutamine in at least 4 segments. QOL measurements were taken using Minnesota, NHBP and MPWB questionnaires. RESULTS: LVEF showed no improvement in the overall group (52.8+/-11.1% vs. 51.8+/-9.8%, p=NS). QOL showed significant improvement in all questionnaires (Minnesota: 4.1+/-2.1 vs. 2.5+/-2, p=0.001; NHBP: 54.8+/-43.3 vs. 34.2+/-34.3, p=0.002; MPWB: 22.2+/-4.6 vs. 19.4+/-6.2, p=0.03). There was no significant difference in change of LVEF between patients with and without contractile reserve (-0.4+/-8.7 vs. 1.6+/-11.3, p=NS). However, patients with a preserved LVEF at baseline showed more frequently a reduced LVEF after AV node ablation (62.2+/-10.4% vs. 47.5+/-7.6%, p=0.001). CONCLUSIONS: (1) The absence of contractile reserve does not predict deterioration of cardiac function after AV node ablation. (2) AV node ablation results in a significant improvement in QOL, which is not necessarily associated with improvement of LVEF. (3) Higher baseline LVEF predicts deterioration of cardiac function. These data suggest that although AV node ablation is an excellent way of controlling symptoms, it should be avoided in patients with normal LV function.     

多普勒超声心动图检测慢性心力衰竭患者心肌生物能量消耗水平的变化及临床意义

目的 分析慢性心力衰竭(心衰)患者的多普勒超声指标心肌生物能量消耗(MEE)与左心室结构指标及其收缩、舒张、整体功能指标及心衰严重程度(NYHA心功能分级)、C反应蛋白(CRP)、N末端B型利钠肽原(NT-proBNP)之间的关系,探讨MEE用于评估慢性心衰心功能状况的临床价值.方法 选择慢性心衰住院患者99例,据左室射血分数(LVEF)值分为LVEF正常的心衰(HFNEF)组37例,LVEF降低的心衰(HFREF)组62例(其中LVEF>35%、<50%及≤35%分别为30例及32例);据NYHA心功能分级分为Ⅱ级(26例)、Ⅲ级(42例)、Ⅳ级(31例);对照组30例.采用多普勒超声心动图检测并计算MEE及常规结构指标,左心室收缩(LVEF、LVFS)、舒张(E/A、EDT、IVRT)及整体功能指标(Tei指数),并测定各组血清CRP、血浆NT-proBNP水平,分析各组间各参数的差异,探讨MEE与上述指标间的相关性.结果 HFNEF组患者MEE水平与对照组差异无统计学意义(P>0.05),HFREF组患者MEE水平较对照组明显增加(P<0.01);慢性心衰组MEE随LVEF的降低及NYHA心功能分级级别的升高而显著增加(P<0.05);双变量相关分析显示,MEE与心室结构及收缩、舒张、整体功能指标、NYHA心功能分级及血清CRP、血浆NT-proBNP水平之间均具有相关性,其中关系最密切的是左心室收缩功能指标,即MEE与LVEF、LVFS均呈明显负相关[分别为r=-0.540、P<0.01,r=-0.454、P<0.01].结论 随左心室收缩功能障碍及心衰程度的加重,慢性心衰患者的MEE水平逐步升高,MEE与现有的心功能评价指标(如LVEF值、NYHA分级、NT-proBNP 等)均呈明显相关,特别与左心室收缩功能指标关系密切.MEE可从心肌生物能量学角度有效评定慢性心衰患者的心功能状况.