Transcatheter transplantation of autologous skeletal myoblasts in postinfarction patients with severe left ventricular dysfunction.

PURPOSE: To report a case-controlled safety and feasibility study of transcatheter transplantation of autologous skeletal myoblasts as a stand-alone procedure in patients with ischemic heart failure. METHODS: Six men (mean age 66.2+/-7.2 years) were eligible for transcatheter transplantation of autologous skeletal myoblasts cultured from quadriceps muscle biopsies. Six other men (mean age 65.7+/-6.3 years) were selected as matched controls (no muscle biopsies). A specially designed injection catheter was advanced through a femoral sheath into the left ventricle cavity, where myoblasts in solution (0.2 mL/injection) were injected into the myocardium via a 25-G needle. At baseline and in follow-up, both groups underwent Holter monitoring, a 6-minute walk test, New York Heart Association (NYHA) class determination, and echocardiography with dobutamine challenge. RESULTS: Skeletal myoblast transplantation was technically successful in all 6 patients with no complications; 19+/-10 injections were performed per patient (210 x 10(6)+/-150 x 10(6) cells implanted per patient). Left ventricular ejection fraction (LVEF) rose from 24.3%+/-6.7% at baseline to 32.2%+/-10.2% at 12 months after myoblast implantation (p=0.02 versus baseline and p<0.05 versus controls); in matched controls, LVEF decreased from 24.7%+/-4.6% to 21.0%+/-4.0% (p=NS). Walking distance and NYHA functional class were significantly improved at 1 year (p=0.02 and p=0.001 versus baseline, respectively), whereas matched controls were unchanged. CONCLUSIONS: Transcatheter transplantation of autologous skeletal myoblasts for severe left ventricular dysfunction in postinfarction patients is feasible, safe, and promising. Scrutiny with randomized, double-blinded, multicenter trials appears warranted.     

Functional recovery after coronary artery bypass grafting in patients with severe left ventricular dysfunction and preserved myocardial viability in the left anterior descending arterial territory as assessed by thallium-201 myocardial perfusion imaging.

To evaluate the functional recovery after coronary bypass surgery in patients with severe left ventricular (LV) dysfunction (ejection fraction (EF) < or = 35%), 100 consecutive patients with viable myocardium in the territory supplied by the left anterior descending artery (LAD) underwent coronary bypass grafting. In addition, cardiac catheterization and single-photon emission computed tomography (SPECT) perfusion imaging with thallium-201 were repeated 1-year postoperatively. Although 12 patients with severe LV dysfunction were preoperatively in a worse New York Heart Association functional class (3.1+/-0.7 vs 2.4+/-0.8; p<0.01), had a higher incidence of heart failure (10/12 vs 14/88; p<0.001) and had a worse LVEF (29+/-5 vs 61+/-14%; p<0.001) compared with 88 patients without severe LV dysfunction, the operative mortality was similar in the 2 groups (1/12 vs 2/88; p=NS). The postoperative NYHA functional class in the patients with severe LV dysfunction was similar to that in the patients without such dysfunction (1.6+/-0.7 vs 1.3+/-0.6; p=NS). In addition, the 1-year postoperative study revealed a significant improvement in the thallium defect score in both the LAD territory (1.7+/-1.2 to 0.7+/-1.0, p=0.01) and all the territories (5.2+/-2.2 to 3.2+/-1.9, p=0.002) in patients with severe LV dysfunction, whereas no improvement in defect score was found in either of these territories in those without severe LV dysfunction (LAD: 0.6+/-1.4 to 0.4+/-1.2, p=NS; All: 1.9+/-2.2 to 1.8+/-2.0, p=NS). Furthermore, a marked 1-year postoperative improvement (15-24%; 95% confidence interval) in LVEF (29+/-5 to 48+/-10%, p<0.001) was demonstrated in patients with severe LV dysfunction, but not in those without such dysfunction (60+/-13 to 61+/-11%, p=NS). These results indicate that myocardial viability in the LAD territory, as demonstrated by thallium-201 SPECT perfusion imaging, predicts a significant improvement in functional class and LVEF of at least 10% or more after coronary artery bypass grafting in patients with severe LV dysfunction.     

Prevalence of mechanical dyssynchrony in patients with heart failure and preserved left ventricular function (a report from the Belgian Multicenter Registry on dyssynchrony)

The present study evaluated the prevalence of mechanical inter- and intraventricular dyssynchrony in patients with heart failure and preserved left ventricular (LV) ejection fraction (LVEF). We studied 138 patients with heart failure (age 67+/-11 years; 76% men); 60 patients had preserved LVEF (>40%). Using conventional Doppler echocardiography, an interventricular mechanical delay>or=40 ms was defined as interventricular dyssynchrony. Using pulse-wave tissue Doppler imaging, the time from the beginning of the QRS complex to onset of systolic motion was measured in 4 basal LV segments. A dispersion of >or=60 ms was defined as intraventricular dyssynchrony. The prevalence of inter- and intraventricular dyssynchrony was lower in patients with preserved LVEF than in those with reduced LVEF (17% vs 41%, p<0.01 for interventricular dyssynchrony, 18% vs 36%, p<0.01 for intraventricular dyssynchrony). However, patients with preserved LVEF and a QRS width>or=120 ms had higher values for the parameters for inter- and intraventricular dyssynchrony than patients with a QRS width<120 ms (interventricular mechanical delay 33+/-20 vs 20+/-16 ms, p<0.05; tissue Doppler imaging dispersion 42+/-26 vs 33+/-22 ms, p<0.05). In patients with a QRS width>or=120 ms, the prevalence of inter- and intraventricular dyssynchrony was comparable for patients with preserved and reduced LVEF (42% vs 55%, p=NS for interventricular dyssynchrony and 45% vs 46%, p=NS for intraventricular dyssynchrony). In conclusion, the prevalence of inter- and intraventricular dyssynchrony was low (17% and 18%, respectively) in patients with heart failure and preserved LVEF. However, in the presence of a QRS width of >or=120 ms, this prevalence increased to almost 50%, comparable to that for patients with heart failure and reduced LVEF and a QRS width of >or=120 ms.     

Improvement of left ventricular ejection fraction, heart failure symptoms and prognosis after revascularization in patients with chronic coronary artery disease and viable myocardium detected by dobutamine stress echocardiography.

OBJECTIVES: This study was designed to address, in patients with severe ischemic left ventricular dysfunction, whether dobutamine stress echocardiography (DSE) can predict improvement of left ventricular ejection fraction (LVEF), functional status and long-term prognosis after revascularization. BACKGROUND: Dobutamine stress echocardiography can predict improvement of wall motion after revascularization. The relation between viability, improvement of function, improvement of heart failure symptoms and long-term prognosis has not been studied. METHODS: We studied 68 patients with DSE before revascularization; 62 patients underwent resting echocardiography/radionuclide ventriculography before and three months after revascularization. Long-term follow-up data (New York Heart Association [NYHA] functional class, Canadian Cardiovascular Society [CCS] classification and events) were acquired up to two years. RESULTS: Patients with > or =4 viable segments on DSE (group A, n = 22) improved in LVEF at three months (from 27+/-6% to 33+/-7%, p < 0.01), in NYHA functional class (from 3.2+/-0.7 to 1.6+/-0.5, p < 0.01) and in CCS classification (from 2.9+/-0.3 to 1.2+/-0.4, p < 0.01); in patients with <4 viable segments (group B, n = 40) LVEF and NYHA functional class did not improve, whereas CCS classification improved significantly (from 3.0+/-0.8 to 1.3+/-0.5, p < 0.01). A higher event rate was observed at long-term follow-up in group B versus group A (47% vs. 17%, p < 0.05). CONCLUSIONS: Patients with substantial viability on DSE demonstrated improvement in LVEF and NYHA functional class after revascularization; viability was also associated with a favorable prognosis after revascularization.     

Delisting of infants and children from the heart transplantation waiting list after carvedilol treatment

OBJECTIVES: We performed a prospective, randomized, double-blind, placebo-controlled study of carvedilol effects in children with severe, chronic heart failure (HF), despite the use of conventional therapy. BACKGROUND: Little is known about the effects of carvedilol in youngsters with chronic HF and severe left ventricular (LV) dysfunction. METHODS: We conducted a double-blind, placebo-controlled study of 22 consecutive children with severe LV dysfunction. The children had chronic HF and left ventricular ejection fraction (LVEF) <30%. Patients were randomly assigned to receive either placebo (8 patients) or the beta-blocker carvedilol (14 patients) at 0.01 mg/kg/day titrated up to 0.2 mg/kg/day, followed-up for six months. RESULTS: During the follow-up and the up-titration period in the carvedilol group, four patients died and one underwent heart transplantation. In patients receiving carvedilol evaluated after six months, a significant increase occurred in LVEF, from 17.8% (95% confidence interval [CI], 14.1 to 21.4%) to 34.6% (95% CI, 25.2 to 44.0%); p = 0.001. Modified New York Heart Association (NYHA) functional class improved in nine patients taken off the transplant waiting list. All nine patients were alive at follow-up. In the placebo group, during the six-month follow-up, two patients died, and two underwent heart transplantation. Four patients persisted with HF symptoms (NYHA functional class IV). No significant change occurred in LVEF or fractional shortening. CONCLUSIONS: Carvedilol added to standard therapy may reduce HF progression and improve cardiac function, allowing some youngsters to be removed from the heart transplantation waiting list.     

Oscillatory ventilation during exercise in patients with chronic heart failure: clinical correlates and prognostic implications

STUDY OBJECTIVES: Although breathing disorders are often found in patients with chronic heart failure, exertional oscillatory ventilation (EOV) has been occasionally described. The aim of this study was to determine the prevalence, clinical characteristics, and outcome of patients with chronic heart failure and EOV. SETTING: Cardiology division at tertiary-care hospital. STUDY POPULATION: We studied 323 patients with chronic heart failure and left ventricular ejection fraction (LVEF) < or = 40%. MEASUREMENTS AND RESULTS: All patients performed a symptom-limited cardiopulmonary exercise test and were followed up for 22 +/- 11 months (mean +/- SD). EOV was defined as cyclic fluctuations in minute ventilation (E) at rest that persist during effort lasting > or = 60% of the exercise duration, with an amplitude > or = 15% of the average resting value. Patients with EOV (12%), as compared to those without, showed higher New York Heart Association (NYHA) class (p < 0.05) and lower LVEF (p < 0.0001) and peak oxygen consumption (O(2)) [p < 0.0001]. During the follow-up period, 53 patients died or underwent urgent cardiac transplantation; this group showed higher NYHA class (p < 0.05) and E/CO(2) slope (p < 0.0001) and lower LVEF (p < 0.0001), mitral Doppler early deceleration time (p < 0.01), and peak O(2) (p < 0.0001). EOV was more frequent in nonsurvivors than in survivors (28% vs 9%, p < 0.01). Multivariate analysis revealed peak O(2) (chi(2), 51.5; p < 0.0001), EOV (chi(2), 45.4; p < 0.0001), and LVEF (chi(2), 20.6; p < 0.0001) as independent predictors of major cardiac events. CONCLUSIONS: EOV is not unusual in patients with chronic heart failure, and is associated with worse clinical status, cardiac function, and exercise capacity. EOV is a powerful predictor of poor prognosis and, consequently, it may be considered a valuable guide in the management of patients with chronic heart failure and should suggest a more aggressive medical treatment policy when detected.     

Restrictive filling pattern predicts pulmonary hypertension and is associated with increased BNP levels and impaired exercise capacity in patients with heart failure

BACKGROUND: Left ventricular (LV) diastolic dysfunction is a common finding in patients with systolic heart failure (HF). Severe diastolic dysfunction, which is defined as LV restrictive filling pattern (RFP), is associated with more severe HF, increased sympathetic activity and reduced exercise capacity. It has also been shown to be a predictor of lower survival rate in patients with HF. AIM: To evaluate associations between LV diastolic RFP and BNP levels, systolic pulmonary pressure and exercise capacity in patients with clinically stable HF. METHODS: In 56 patients with HF and low LVEF a standard echocardiographic study and cardiopulmonary exercise test were performed. Levels of BNP using RIA method were also measured. RESULTS: Restrictive filling pattern (E/A >2 or 1< E/A <2 and DTE < or =130 ms) was diagnosed in 26 patients. The RFP group showed increased levels of BNP (90.6+/-66 vs. 50.4+/-61 pg/ml; p=0.003), significantly reduced peak VO2 (15.4+/-4.1 vs. 17.8+/-4.9 ml/kg/min; p=0.046), increased VE/VCO2 slope (36.3+/-5.9 vs. 31.9+/-6.3; p=0.01), and elevated PASP (pulmonary artery systolic pressure measured by echo-Doppler) (49.3+/-13.8 vs. 37.2+/-12.6 mmHg; p=0.02). Prevalence of pulmonary hypertension was significantly higher in the RFP group. A significant correlation between DTE and peak VO2 (r=0.28; p=0.02) and inverse correlations between DTE and BNP levels (r=-048; p=0.003), VE/VCO2 slope (r=-0.35; p=0.02) and PASP (r=-0.39; p=0.03) were found. In logistic regression analysis only RFP was independently associated with pulmonary hypertension. CONCLUSIONS: The restrictive filling pattern is an independent predictor of pulmonary hypertension and is associated with increased BNP levels and worse result of cardiopulmonary exercise test.     

The role of exercise ventilation in clinical evaluation and risk stratification in patients with chronic heart failure

BACKGROUND: Patients with chronic heart failure (CHF) are characterised by an increased ventilatory response to exercise. The role of exercise ventilation in the risk stratification and evaluation of patients with CHF has not yet been established. AIM: To examine the relationship between exercise ventilation indices and clinical parameters of CHF and to assess the prognostic value of the ventilatory response to exercise. METHODS: The study group consisted of 87 patients with CHF (72 males, mean age 58 years) with a mean left ventricular ejection fraction of 32%. Ten patients were in NYHA class I, 38 - in NYHA class II, 34 - in NYHA class III, and 5 - in NYHA class IV. The control group consisted of 20 patients without CHF (13 males, mean age 58 years, mean LVEF - 61%). All studied subjects underwent maximal exercise test with gas-exchange measurement. The following parameters were analysed: peak exercise oxygen consumption [peak VO(2) (ml/kg/min)], VE-VCO(2) index [a coefficient of linear regression analysis depicting an association between ventilation (VE) and carbon dioxide production (VCO(2)) during exercise] and VE/VCO(2) ratio at peak exercise to VE/VCO(2) ratio while at rest (VE/VCO(2 peak/rest)). RESULTS: Ventilatory response indices were significantly higher in patients with CHF compared with controls: VE-VCO(2) - 37.9+/-11.1 vs 27.1+/-4.1; VE-VCO(2 peak/rest) - 0.89+/-0.14 vs 0.75+/-0.10 (p<0.001). In CHF patients a significant positive correlation between ventilatory response parameters and NYHA class (VE-VCO(2) - r=0.52; VE/VCO(2 peak/rest) - r=0.47) and a negative correlation with peak VO(2) (VE-VCO(2) - r=-0.52; VE/VCO(2 peak/rest) - r=-0.49) were noted (p<0.0001 for all correlations). No correlation was found between ventilatory parameters and echocardiographic variables or CHF aetiology. During the follow-up period lasting at least 12 months, 17 (22%) patients died. In the univariate Cox model, NYHA class III-IV, decreased peak VO(2) and increased VE-VCO(2) and VE/VCO(2 peak/rest) values were significantly associated with the risk of death. The multivariate analysis revealed that VE/VCO(2 peak/rest) > or =1.0 was the adverse prognostic factor, independent of peak VO(2) (p=0.02) and NYHA class (p=0.01). The Kaplan-Meier analysis showed that prognosis during the 18-month follow-up period in patients with enhanced exercise ventilation was worse than in the remaining patients (59% survival in patients with VE/VCO(2 peak/rest) > or =1.0 59% vs 91% survival in patients with VE/VCO(2 peak/rest) <1.0, p=0.001). CONCLUSIONS: In patients with stable CHF simple exercise ventilation parameters may provide important clinical and prognostic information.     

Comparison of the effects of cardiac resynchronization therapy in patients with class II versus class III and IV heart failure (from the InSync/InSync ICD Italian Registry)

Cardiac resynchronization therapy (CRT) is recommended for patients with New York Heart Association (NYHA) class III or IV heart failure and wide QRS complexes. The aim of this study was to compare the effects of CRT in patients in NYHA class II with those in NYHA class III or IV. Nine hundred fifty-two patients (188 in NYHA class II) consecutively implanted with biventricular devices and enrolled in a national observational registry were studied. Clinical outcomes were estimated after 12 months of CRT, and long-term survival was assessed. At a median follow-up of 16 months, significantly fewer major cardiovascular events were reported in patients in NYHA class II compared with NYHA class III or IV (rate 13 vs 23 per 100 patient-years of follow-up, p<0.001). The percentage of patients who improved in NYHA class status after 12 months of CRT was lower in those in class II than in those in class III or IV (34% vs 69%, p<0.001), whereas the absolute increase in the ejection fraction was similar (8+/-9% vs 9+/-11%, p=NS), as well as the reductions in end-diastolic diameter (-3+/-8 vs -3+/-8 mm, p=NS) and end-systolic diameter (-4+/-10 vs -6+/-10 mm, p=NS). The NYHA class II group experienced lower all-cause mortality (log-rank test p=0.018). In the 2 groups, patients with major cardiovascular events during follow-up exhibited less or no reverse remodeling compared with those with better long-term clinical outcomes. In conclusion, the results of this study indicate that CRT induced similar improvements in ventricular function in the 2 groups, whereas the improvement in functional status was significantly lower for patients in NYHA class II than for those in class III or IV. A positive effect of CRT on cardiac dimensions was associated with a long-term beneficial effect on disease progression in patients in NYHA class II.     

Impaired glucose tolerance worsens exercise capacity and ventilatory response to exercise in patients with chronic heart failure

BACKGROUND: There is increasing evidence for the importance of peripheral abnormalities in the pathogenesis and progression of heart failure (HF). Recently, glucose and insulin metabolism abnormalities have been intensively investigated in patients with HF. AIM: To investigate whether coexistence of impaired glucose tolerance (IGT) may decrease exercise tolerance and influence ventilatory response to exercise in patients with systolic HF. METHODS: Maximal cardiopulmonary exercise test with evaluation of peak VO2 and VE/VCO2 slope and oral glucose tolerance test were performed in 64 clinically stable patients with HF and LVEF <45%. RESULTS: Impaired glucose tolerance was diagnosed in 26 (41%) patients and normal glucose tolerance (NGT) in 38 (59%) patients. There were no significant differences in baseline clinical characteristics or LVEF between groups. There were significant differences in peak VO2 between IGT and NGT (15.4+/-4.1 vs. 18.7+/-4.2 ml/kg/min respectively; p=0.003) and VE/VCO2 slope (35.7+/-7.3 vs. 31.8+/-5.7 respectively; p=0.02). The IGT was independently related to peak VO2 and VE/VCO2 slope in multivariate regression analysis. CONCLUSION: The IGT is associated with worse exercise capacity and ventilatory response to exercise in patients with HF.     

Tetralogy of Fallot: prognostic factors after surgical repair.

INTRODUCTION AND OBJECTIVE: Corrective surgery for tetralogy of Fallot (TF) has led to excellent survival. However; several years after surgery, the majority of patients have right ventricular (RV) dilatation, and 10% will need reoperation of the RV outflow tract due to limited exercise capacity, ventricular arrhythmias or symptoms of heart failure (HF). Our aim was to identify predictive factors of adverse outcome: moderate to severe RV dilatation, HF, reoperation of the RV outflow tract and cardiac death. METHODS: Eighty-eight adult patients with TF were operated between January 1977 and July 2001; 22 were lost to follow-up and 66 were followed for 18 +/- 6 years. We analyzed clinical, electrocardiographic and echocardiographic variables. RV dilatation was considered to exist if the inlet measurement at end-diastole in 4-chamber apical view was more than 35 mm, being classified as moderate when > or = 50 and < 60 mm and severe when > or = 60 mm. RESULTS: Of the 66 patients, 25 (37.9%) had undergone previous palliative shunt (PS) at the age of 4 +/- 5 years. Mean age at surgical correction was 10 +/- 8 years (range: < 1 to 38 years; median: 6.5 years). Transannular patching was used in 65% of patients, patch closure of a right ventriculotomy in 91%, and in 53% of patients a pulmonary commissurotomy was performed. At the end of follow-up, 3 patients were in NYHA class III-IV and one patient was successfully reoperated with implantation of a biological pulmonary valve. Prevalence of RV dilatation was 97% (57/59), being moderate to severe in 69% (36/52). In patients with moderate to severe RV dilatation we found previous PS (18.8 vs. 50.0%; p = 0.03), transannular patching (37.5 vs. 75.0%; p 0.01) and wide QRS (160 ms) (6.7 vs. 45.7%, p = 0.01) to be more frequent. These patients reported more palpitations (0 vs. 22.2%; p 0.05), but there were no differences in arrhythmic events (18.8 vs. 33.3%; p = 0.28); maximal heart rate on exercise was lower (86.2 +/- 10.9 vs. 79.9 +/- 8.6; p = 0.04), but exercise time and functional capacity were similar between the groups. Follow-up time and use of RV patching were similar. Transannular patching was associated with previous PS at an older age (0.9 +/- 0.7 vs. 4.9 +/- 5.7 years; p = 0.01), a higher grade of pulmonary regurgitation (III-IV) (22.7 vs. 57.5%; p = 0.01), wide QRS (160 ms) (9.5 vs. 41.0%, p = 0.01), and greater RV dilatation. No mortality was reported. CONCLUSION: Transannular patching and performance of previous PS were predictive factors of severe RV dilatation, and pulmonary regurgitation seems to be its physiological mechanism. Despite this, long-term prognosis is favorable and patients have good functional capacity.     

Predischarge low-dose dobutamine test and prediction of left ventricular function at 1 year in patients with a first anterior myocardial infarction

BACKGROUND: It is unclear whether spontaneous improvement in contractility following acute myocardial infarction (AMI) is related to severity of predischarge systolic dysfunction and can be predicted by isotopic ventriculography with a low-dose dobutamine test (DBT). HYPOTHESIS: Spontaneous improvement in contractility would be similar in patients with more preserved and those with depressed ventricular function, and a DBT test could predict it. METHODS: Left ventricular ejection fraction (LVEF), regional contractility score (RCS), and left ventricular end-diastolic volume index (EDVI) at predischarge, during DBT, and at 1 year were analyzed in 43 patients with a first anterior ST-elevation AMI. RESULTS: Changes produced by DBT in patients with LVEF < 40%, RCS > or = 3, or EDVI > or = 70 ml/m2 were smaller than in those observed at 1 year (LVEF: 30 +/- 5-35 +/- 7%, p < 0.001, vs. 39 +/- 10%, p = 0.005; RCS: 4.9 +/- 1.4-4.6 +/- 2.0, NS, vs. 3.4 +/- 2.0, p < 0.02; EDVI: 92 +/- 14-86 +/- 22, NS, vs. 78 +/- 23 ml/m2, p < 0.03). In contrast, in patients with EF > or = 40%, RCS < 3 or EDVI < 70 ml/m2, changes with DBT tended to be greater than those observed at 1 year (LVEF: 52 +/- 8-57 +/- 11%, p < 0.004 vs. 55 +/- 11%, p < 0.04); RCS: 1.1 +/- 0.9-0.8 +/- 0.8, NS, vs. 1.1 +/- 1.1, NS; and EDVI: 51 +/- 9-47 +/- 11, p < 0.005, vs. 54 +/- 13 ml/m2, NS). CONCLUSIONS: Among patients with a first anterior AMI, spontaneous improvement in contractility at 1 year was greatest in those with a more depressed ventricular function or a dilated ventricle, but its magnitude was underestimated by a predischarge DBT test.     

Role of arterial hypertension in the cardiac involvement of acromegaly

Cardiac disease is common in acromegaly. Several mechanisms have been implicated: hypertension, coronary artery disease, valvular heart disease, endocrinopathies including "acromegalic cardiomyopathy". Fifteen consecutive patients with acromegaly, aged 48 +/- 13 years and treated for 4 +/- 5 years, underwent Doppler echocardiography. The patients had no cardiovascular symptoms: 6 had hypertension for 10 +/- 7 years and were compared with a group of 10 control subjects of the same age (48 +/- 17 years). The myocardial mass index (MMI) was higher in acromegaly (110 +/- 32 vs 82 +/- 12 g/m2, p = 0.02), left ventricular enddiastolic dimensions where comparable (48 +/- 7 vs 48 +/- 5 mm, NS) fractional shortening was slightly greater (0.37 +/- 0.04 vs 0.34 +/- 0.04, p = 0.07) as was velocity of shortening (NS) and the ratio of systolic time intervals (NS). The mitral EF slope was decreased (80 +/- 21 vs 101 +/- 30 ms; p less than 0.02); the ratio of the amplitudes of the E and A waves was a little decreased and the isovolumic relaxation phase was increased (92 +/- 13 vs 69 +/- 16 ms; p less than 0.01). Hypertensives (N = 6) had higher MMI (133 +/- 27 vs 94 +/- 24 g/m2, p = 0.02). Normotensive patients had larger isovolumic relaxation periods than control subjects (90 +/- 11 vs 69 +/- 16 ms, p less than 0.05). These results show that in the infraclinical phase, the heart in acromegaly is hypertrophied, not dilated. Hypertension plays a significant role in the development of this hypertrophy. Left ventricular systolic function is normal but diastolic function is impaired.     

Diagnostic and prognostic value of urine NT-proBNP levels in heart failure patients

BACKGROUND: Plasma NT-proBNP levels are sensitive markers of ventricular dysfunction. However, studies of natriuretic peptides in urine are limited. AIMS: To compare urine and plasma NT-proBNP levels and to investigate the diagnostic and prognostic value of urine levels in heart failure (HF). METHODS: Urinary and plasma NT-proBNP levels were measured in 96 HF patients and 20 control subjects. The patients were functionally classified according to the NYHA criteria. RESULTS: Urine NT-proBNP was higher in HF patients than in control subjects (94+/-31 pg/ml vs. 67+/-6 pg/ml, p<0.0001), correlating with plasma NT-proBNP levels (r=0.78, p<0.0001). Urinary levels were elevated in the more severe functional classes and diminished in obese patients. Urine NT-proBNP was a good tool for diagnosis of HF, the area under the curve (AUC) being 0.96+/-0.02 (p<0.0001), and for predicting 12-month cardiac events (p=0.011). To determine the prognostic power of urinary NT-proBNP in detecting 12-month cardiac mortality, we obtained an AUC of 0.75+/-0.10 (p=0.015). CONCLUSION: Urinary NT-proBNP, a relatively simple non-invasive test, is a new candidate marker for the diagnosis and evaluation of prognosis in HF and for the characterization of functional status in these patients.     

Dobutamine as bridge to angiotensin-converting enzyme inhibitor-nitrate therapy in endstage heart failure

BACKGROUND: Intravenous inotropic intervention in congestive heart failure is generally associated with a poor prognosis and is largely used as a "bridge" to mechanical support or heart transplantation. HYPOTHESIS: We hypothesized that the inotropic support afforded by dobutamine may serve as a bridge to the introduction and intensification of angiotensin-converting enzyme (ACE) inhibitor-nitrate therapy. METHODS: We studied the efficacy of transitioning inotrope-dependent patients in endstage heart failure from intravenous dobutamine to high-dose ACE inhibitor-nitrates, with 1-year follow-up. Forty-nine sequential dobutamine-dependent patients with left ventricular ejection fraction (LVEF) 17+/-17% were treated with increasing lisinopril (1.9+/-1.5 to 46+/-28 mg/day) and isosorbide dinitrate (7+/-6 to 229+/-161 mg/day). Outpatient dobutamine was continued or repeat infusions pursued, as indicated, and dobutamine was tapered when feasible. RESULTS: During the following year, 14 of 49 patients required repeat dobutamine, with home treatment with dobutamine for 6.3+/-3.7 months (n = 5). At 1 year, New York Heart Association (NYHA) classification improved from 3.6+/-0.5 to 1.9+/-1.0, p < 0.0001; yearly hospitalizations fell from 2.7+/-2.3 to 1.2+/-3.0, p = 0.02; and LVEF rose from 17+/-7% to 24+/-11%, p < 0.0001. At 1 year, 14 patients who remained dobutamine dependent had significantly more severe symptoms than dobutamine-independent patients (n = 35). Transplant or death occurred in 7 of 14 patients with follow-up dobutamine, and in 5 of 35 patients free of subsequent dobutamine, p = 0.03. Patients with poor outcome (transplant n = 10, death n = 12) continued to be more limited (NYHA 2.7+/-0.9 vs. 1.7+/-0.9, p = 0.0002), with more follow-up hospitalizations (3.6+/-5.4 vs. 0.6+/-0.8, p = 0.0004), and no improvement in LVEF (17+/-8vs. 28+/-11%, p = 0.003). CONCLUSIONS: Of the patients on dobutamine inotropic support, 70% were successfully transitioned to ACE inhibitor-nitrate therapy, with improved symptoms and LVEF, and with reduced hospitalizations and follow-up dobutamine or transplant. Thirty percent of patients with continued need for dobutamine had a significantly poorer 1-year clinical outcome.     

Usefulness of the severity and extent of wall motion abnormalities as prognostic markers of an adverse outcome after a first myocardial infarction treated with thrombolytic therapy

The prognostic value of wall motion score index (WMSI), assessed at predischarge after a first acute myocardial infarction (AMI) in the thrombolytic era, is still not well known. One-hundred forty-four consecutive patients with a first AMI treated with thrombolytic therapy underwent exercise testing and echocardiography at rest before discharge and were followed-up for a mean period of 18 months. During follow-up, there were 32 cardiac events (12 patients had cardiac deaths, 8 had unstable angina pectoris, 1 had nonfatal reinfarction, and 11 patients had congestive heart failure). The patients who experienced any cardiac event had a higher WMSI (1.67+/-0.15 vs. 1.30+/-0.16, p<0.0001), a higher end-systolic volume (75.1+/-34 vs. 59.5+/-22 ml, p<0.01), and a lower ejection fraction (47+/-16% vs. 55+/-10%, p<0.001) at predischarge than patients without events. The incidence of a positive predischarge exercise testing did not differ between patients with and without cardiac events (22% vs. 24%, p = NS). Multivariate Cox regression analysis, including clinical, exercise results, and echocardiographic parameters, showed that the most powerful predictor of a subsequent event was a resting WMSI > or =1.50 before discharge (chi-square 17.8, p<0.0001). Thus, in patients with a first AMI who underwent thrombolysis, the severity and extent of echocardiographically detected wall motion abnormalities are important independent predictors of cardiac events.     

Influence of etiology on ventilatory expired gas and prognosis in heart failure

BACKGROUND: Mechanisms leading to heart failure (HF) are numerous. Etiology-based differences are, however, frequently not taken into account when assessing results of an exercise test. The purpose of this investigation is to: (1) compare subject characteristics and ventilatory expired gas measures demonstrating clinical value between subjects with ischemic and non-ischemic HF. (2) Examine the prognostic value of HF etiology. METHODS: 71 subjects (44 male/27 female) diagnosed with compensated HF underwent exercise testing with ventilatory expired gas analysis. Mean age and ejection fraction (EF) were 51.3% (+/-12.8) and 27.0% (+/-12.5%) for the entire group. HF etiology was ischemic in 30 subjects (16 male/14 female) and non-ischemic in 41 (28 male/13 female). RESULTS: Age (57.5+/-10.7 vs. 46.7+/-12.5, p<0.001), minute ventilation-carbon dioxide production (VE/VCO2) slope (39.5+/-9.1 vs. 32.6+/-7.7, p=0.001), and duration of phase 1 kinetics in seconds (46.0+/-23.0 vs. 30.0+/-15.6, p=0.001) were significantly higher while peak oxygen consumption (VO2) in ml O2 kg(-1) min(-1) (12.5+/-4.7 vs. 16.0+/-5.2, p=0.006) and partial pressure of end-tidal CO2 (P(ET)CO2) in mm Hg at rest (32.1+/-4.8 vs. 36.1+/-8.0, p=0.02) and peak exercise (31.7+/-4.3 vs. 36.2+/-5.9, p=0.001) were significantly lower in the ischemic group. Difference in EF did not reach statistical significance (28.4% +/-12.5%-ischemic vs. 26.1%+/-12.5%-non-ischemic, p=0.44). Ischemic etiology was additionally a significant predictor of cardiac-related events (p=0.04). CONCLUSIONS: These findings demonstrate noninvasive indicators of cardiac function and prognosis is poorer in subjects with ischemic HF etiology. Consideration of HF etiology may therefore be prudent, particularly when considering prognosis.     

Osteopontin expression of circulating T cells and plasma osteopontin levels are increased in relation to severity of heart failure.

BACKGROUND: T cells in peripheral blood reflect the systemic inflammatory response in patients with heart failure (HF). In a rat model of HF, osteopontin is dramatically increased in the left ventricular myocardium, so the association between osteopontin and HF was examined in the present study. METHODS AND RESULTS: Peripheral blood was collected from 93 patients with heart disease and 38 controls. Left ventricular ejection fraction (LVEF) was calculated using a modified Simpson's rule. The 93 patients were classified into 3 classes according to the New York Heart Association (NYHA) functional classification. Osteopontin-expressing CD4+ T cells were quantified by flow cytometry. Plasma osteopontin levels (ng/ml) and the frequencies of osteopontin-expressing CD4+ T cells (%) were higher in patients with HF than in controls (800+/-554, 575+/-229, p=0.016 and 27.3+/-12.2, 16.7+/-10.0, p<0.001). Furthermore, the plasma osteopontin levels and the frequencies of osteopontin-expressing CD4+ T cells increased in proportion to the severity of the NYHA functional class. The frequencies of osteopontin-expressing CD4+ T cells were significantly correlated with LVEF (r=-0.336, p=0.0048) and log plasma brain natriuretic peptide levels (r=0.305, p=0.0025). CONCLUSIONS: Osteopontin expression of circulating CD4+ T cells and plasma osteopontin levels reflect the severity of HF. Osteopontin could be a new target in the assessment of HF.     

Atriobiventricular pacing improves exercise capacity in patients with heart failure and intraventricular conduction delay

OBJECTIVES: We sought to assess the efficacy of biventricular pacing with respect to both peak and submaximal measures of exercise in patients with New York Heart Association class III heart failure (HF) and intraventricular conduction delay in a randomized, blinded study. BACKGROUND: Submaximal and maximal changes in exercise capacity need evaluating in this patient population with this novel therapy. METHODS: Graded exercise and 6-min walk tests were performed in patients randomized to three months each of active (atrio-biventricular) and inactive pacing. Minute ventilation (VE), oxygen uptake (VO(2)), ventilated carbon dioxide (VCO(2)) and heart rate were measured in patients achieving a respiratory quotient >1 (n = 30). Oxygen pulse, anaerobic threshold (AT) and ventilatory efficiency (VE/VCO(2)) were calculated. RESULTS: Active biventricular pacing increased peak VO(2) (15.8 +/- 4.3 vs. 14.4 +/- 4.6 ml/kg/min, p = 0.02), exercise time (501 +/- 223 s vs. 437 +/- 233 s, p < 0.001) and oxygen pulse (9.3 +/- 2.8 vs. 8.1 +/- 3.1 ml/beat, p < 0.01) compared with inactive pacing. The submaximal measures of exercise capacity significantly increased with active pacing: AT (11.2 +/- 4.1 ml/kg/min vs. 9.5 +/- 2.3 ml/kg/min, p = 0.02) and 6-min walk (414 +/- 94 m vs. 359 +/- 94 m, p = 0.001). Minute ventilation/ventilated carbon dioxide improved (32 +/- 9 vs. 36 +/- 11, p = 0.03) with normalization of the VE/VCO(2) slope in 59% of patients (chi-square test, p = 0.002) with active pacing. CONCLUSIONS: Biventricular pacing may improve maximal and submaximal exercise capacity in patients with advanced HF and intraventricular conduction delay.     

非糖尿病扩张型心肌病心力衰竭患者胰岛素抵抗、血清ST2与心功能相关性及临床意义

目的探讨非糖尿病扩张型心肌病慢性心力衰竭患者胰岛素抵抗（IR）、血清ST2水平与心功能相关性及临床意义。方法入选56例非糖尿病扩张型心肌病患者,冠状动脉造影排除缺血性心肌病。按NYHA心功能分级分为三组（心功能Ⅱ级、心功能Ⅲ级、心功能Ⅳ级组）。健康对照组48例。用葡萄糖氧化酶法测定空腹血糖,放射免疫法测定空腹胰岛素,并计算出胰岛素抵抗指数（HOMA-IR）;酶联免疫方法测定NT-proBNP、ST2水平结果 1.心衰组HOMA-IR、ST2均高于正常对照组（P〈0.05）;2.不同心功能组HOMA-IR、ST2有显著性差异（P〈0.05）,随心衰程度加重而进行性升高;3.HOMA-IR与LVEF呈负相关（r=-0.524p〈0.01）;与LVEDd呈正相关（r=0.329p〈0.01）;与NT-proBNP呈正相关（r=0.466p〈0.01）;4.血清ST2水平与LVEF呈负相关（r=-0.258p〈0.01）;与LVED呈正相关（r=0.234p〈0.01）;与NT-proBNP呈正相关（r=0.359p〈0.01）;5.HOMA-IR与血清ST2水平呈正相关（r=0.287p〈0.01）。结论非糖尿病扩张型心肌病心力衰竭患者HOMA-IR、血清ST2水平与心功能密切相关,且随心功能恶化而升高;IR可能与ST2存在内在联系;IR可能是HF的易患因素之一。