Patterns of post-MI left ventricular volume changes - clinical implications

BACKGROUND: Left ventricular (LV) enlargement - the main discriminant of postinfarction remodelling - is dynamic and not necessarily progressive. The magnitude of the remodelling process is directly proportional to infarct size (IS), although it is significantly influenced by other factors. AIM: To assess the clinical implications of different patterns of LV volume changes in 1-year echocardiographic follow-up after myocardial infarction (MI) and to determine early predictors of adverse remodelling. METHODS: The study group consisted of 132 patients (pts) (mean age 55.7+/-12 years) with their first MI (STEMI) (67% pts treated with fibrinolysis). In the consecutive ECHO examinations (S1, first day; S2, at discharge; S3, 6 months; and S4, one year after MI) the following parameters were assessed: WMSI, EDVI, ESVI, LVEF, LV sphericity index (WSF), index of infarct expansion (EXP), restrictive pattern of mitral flow (RP), grade of mitral regurgitation (MR). The criterion of significant LV dilatation was EDVI > or =85 ml/m2 and/or DEDVI > or =20% between two succeeding ECHO. At S3 pts were classified into groups: group 1 with no LV dilatation (n=68), group 2 with early transient LV dilatation (S1 and/or S2) (n=26), group 3 with progressive (S1 - S2 - S3) LV dilatation (n=28). The prognostic value of the following parameters was assessed: anterior infarct location, Q-wave MI, Killip-Kimball class ?2, lack of noninvasive assessed reperfusion R(-), EXP(+), CK > or =3000 IU, WMSIS2 > or =1.5, EDVIS2 > or=80 ml/m2, ESVIS2 > or =40 ml/m2, EFS2 <45%, RPS2 and baseline LV hypertrophy (S1). RESULTS: Patients in group 3 had significantly larger IS (WMSI) than in group 1 (p <0.01) and group 2 (p <0.05). Infarct expansion was found only in group 3. One year after MI in group 3 compared to groups 1 and 2 adverse remodelling was observed: lower EFS4 (p <0.001), more spherical LV (WSFS4) (p <0.001), higher rate of MRS4 > or =2 (p <0.001) and RPS4 (p <0.001). Within each group LVEFS1-S4 was stable in one-year follow-up. In group 3 incidence of heart failure (HF) was significantly higher than in groups 1 and 2 (respectively 57 vs. 2 vs. 4%; p <0.001). Cardiac death (CD) was observed only in group 3 (25% of pts). Increased EDVI > or =80 ml/m2 at discharge was the most powerful independent predictor of progressive LV dilatation. Large IS (CK >/=3000 IU and/or WMSI > or =1.5) was not an independent predictor of adverse remodelling. CONCLUSIONS: 1) During the first 6 months after MI the progression of LV dilatation was a useful sign identifying adverse remodelling, even in the absence of LVEF evolutionary changes. Progressive LV dilatation was associated with more spherical LV and higher rate of MR > or =2 degrees . 2) Patients with progressive LV were at higher risks of HF and CD in one-year follow-up. 3) Increased EDVI > or =80 ml/m2 at discharge was the most powerful independent predictor of adverse postinfarction remodelling. Large IS was not an independent predictor. 4) Echocardiographic monitoring after MI is of great clinical importance - it enables pts at higher risk of HF and CD to be identified.     

Plasma and pericardial fluid natriuretic peptide levels in postinfarction ventricular dysfunction

AIMS: In the present study we examined plasma and pericardial fluid ANP and BNP concentrations in postinfarction ventricular dysfunction. The association of peptide levels to left ventricular (LV) dysfunction and to the localization of the myocardial infarction (MI) was studied. METHODS AND RESULTS: Plasma and pericardial fluid samples were obtained from 37 patients undergoing coronary bypass surgery. According to the ECG and preceding coronary angiography, the patients were divided into three groups: previous anterior myocardial infarction (MI) (n=12), previous inferior/posterior MI (n=15) and no history of MI (n=10). When compared to the control group with no MI, the patients with anterior MI had elevated plasma ANP and BNP (134+/-13 vs. 81+/-15 pg/ml, P<0.01 and 95+/-10 pg/ml vs. 26+/-8 pg/ml, P<0.01, respectively) and pericardial fluid BNP (473+/-60 pg/ml vs. 57+/-8 pg/ml, P<0.001) levels. The plasma natriuretic peptide concentrations were not increased in the patients with inferior/posterior MI, but the pericardial fluid BNP concentrations were greater than in the patients with no history of MI (129+/-35 pg/ml vs. 57+/-8 pg/ml, P<0.05). Six of the 12 patients with previous anterior MI had LVEF> or =45%. Despite their normal LV systolic function, these patients had increased plasma and pericardial fluid BNP levels when compared to the group with no history of MI (68+/-18 pg/ml vs. 26+/-8 pg/ml, P<0.05 and 534+/-258 pg/ml vs. 57+/-8 pg/ml, P<0.01, respectively). CONCLUSIONS: Previous anterior myocardial infarction was associated with increased cardiac BNP production even if the LV systolic function was normal (LVEF> or =45%). The high pericardial fluid BNP concentrations in postinfarction patients suggest that the BNP synthesis and release are augmented in the ventricular myocardium independent from the LVEF.     

Early identification of left ventricular remodelling after myocardial infarction, assessed by transthoracic 3D echocardiography.

AIMS: The usefulness of 3D echocardiography (3DE) for accurate evaluation of left ventricular (LV) remodelling after acute myocardial infarction (AMI), and early identification of remodelling in the subacute phase, was assessed. METHODS AND RESULTS: Thirty-three AMI patients (21 anterior AMIs) underwent 3DE prospectively at baseline (6+/-4 days) and at 3, 6, and 12 months post-AMI. Remodelling was defined as >20% increase in end-diastolic volume (EDV) at 6 or 12 months in relation to baseline. In patients with remodelling (n = 13) at baseline, EDV and end-systolic volume (ESV), but not ejection fraction (EF), were significantly increased compared to patients without subsequent remodelling (n = 20). At 12 months, EDV and ESV increased further and significantly, and EF was unchanged in patients with remodelling, whilst LV volumes were unchanged and EF slightly increased in patients without remodelling. Clinical, electrocardiographic, and echocardiographic variables were analysed for the early identification of LV remodelling. Of these, at baseline the 3D sphericity index (EDV divided by the volume of a sphere, the diameter of which is the LV major end-diastolic long axis) was, by far, the most predictive variable with a sensitivity, specificity, and positive and negative predictive value for a cutoff value of >0.25 of 100%, 90%, 87% and 100%, respectively. CONCLUSIONS: Three-dimensional echocardiography can differentiate patients with and without subsequent development of LV remodelling accurately and early on the basis of the 3D sphericity index, a new and highly predictive variable.     

Effects of selective matrix metalloproteinase inhibitor (PG-116800) to prevent ventricular remodeling after myocardial infarction: results of the PREMIER (Prevention of Myocardial Infarction Early Remodeling) trial.

OBJECTIVES: We sought to determine whether matrix metalloproteinase (MMP) inhibitor, PG-116800, reduced left ventricular (LV) remodeling after myocardial infarction (MI). BACKGROUND: PG-116800 is an oral MMP inhibitor with significant antiremodeling effects in animal models of MI and ischemic heart failure. METHODS: In an international, randomized, double-blind, placebo-controlled study, 253 patients with first ST-segment elevation MI and ejection fraction between 15% and 40% were enrolled 48+/- 24 h after MI and treated with placebo or PG-116800 for 90 days. Major efficacy end points were changes in LV volumes as determined by serial echocardiography, and clinical and safety outcomes were also collected. RESULTS: In total, 203 patients (80%) completed 90 days of treatment and had evaluable baseline and 90-day echocardiograms. The proportion of patients with anterior MI (78% vs. 81%) and primary percutaneous coronary intervention (90% vs. 91%) along with baseline LV ejection fraction (35.5% vs. 36.8%) did not differ between PG-116800-treated and placebo-treated patients. There was no difference in the change in LV end-diastolic volume index from days 0 to 90 with PG-116800 versus placebo (5.09 +/- 1.45 ml/m(2) vs. 5.48 +/- 1.41 ml/m2, p = 0.42). Changes in LV diastolic volume, LV systolic volume, LV ejection fraction, sphericity index, plus rates of death or reinfarction were not significantly improved with PG-116800. PG-116800 was well tolerated; however, there was increased incidence of arthralgia and joint stiffness without significant increase in overall musculoskeletal adverse events (21% vs. 15%, p = 0.33). CONCLUSIONS: Matrix metalloproteinase inhibition with PG-116800 failed to reduce LV remodeling or improve clinical outcomes after MI.     

Losartan improves diastolic ventricular filling of hypertensive patients with diastolic dysfunction.

To evaluate the role of losartan on left ventricular (LV) function of hypertensive patients. Hypertensive patients (n = 19) underwent evaluation of systolic and diastolic LV function, using radionuclide ventriculography (RVG), before and at 3 mo into the treatment with the angiotensin II antagonist losartan. All patients underwent a baseline 12 lead ECG and an echocardiogram (ECHO), which was also repeated at 3 mo into treatment. Results are expressed as mean +/- SEM and statistics were performed using paired t-test. A p value < or = 0.05 was considered significant. Treatment with losartan for 3 mo had no effect on LV mass measured by echo (141+/-5 vs. 139+/-6 g/m2). The LV ejection fraction, measured by RVG, was unchanged by treatment when compared to the baseline study (58+/-2% vs. 57+/-2%, respectivelly, p = 0.49). Considering all patients involved in the study (n = 19), the LV "Peak Filling Rate" (PFR), a parameter of diastolic function measured by RVG, was also unchanged by treatment when compared to baseline (2.5+/-0.2 EDV/s vs. 2.5+/-0.3 EDV/s, respectively, p = 0.9). However the analysis of those patients with evidence of diastolic dysfunction (n = 12) on the baseline RVG (PFR < 2.5 EVD/s), demonstrated significant improvement of LV filling after therapy with losartan (PFR = 1.8+/-0.1 EDV/s vs. 2.3 +/-0.2 EDV/s, respectively, p = 0.05). This change was associated with improvement of symptoms. Our results demonstrated that hypertensive patients with diastolic dysfunction on radionuclide ventriculography have significant improvement of ventricular filling at 3 mo into treatment with losartan.     

Decreased level of melatonin in serum predicts left ventricular remodelling after acute myocardial infarction

Abstract: As experimental studies suggest that melatonin is cardioprotective after myocardial infarction (MI), this study sought to investigate the relationships between circulating levels of melatonin and left ventricular (LV) remodelling in patients after acute MI. This prospective study included 161 patients (age 61 ± 3 yr; 78% men) undergoing primary percutaneous coronary intervention who were assessed echocardiographically at hospital discharge (day 3–7) and at 12 months. LV remodelling was defined as >20% increase in LV end‐diastolic volume at 12‐month follow‐up compared with baseline. Serum melatonin concentrations were measured at admission, during the light period. Twenty‐four patients showed LV remodelling, and 137 had no evidence of LV remodelling. Patients with LV remodelling had lower levels of melatonin at study entry [9.96 (8.28–11.03) versus 16.74 (13.77–19.59) pg/mL, respectively; P < 0.0001]. Multivariate analysis showed that melatonin levels (OR = 2.10, CI 95% 1.547–2.870, P < 0.001) were an independent predictor of LV remodelling at 12‐month follow‐up. Receiver operating characteristic (ROC) analysis showed an area under the curve of 0.959 (CI 95% 0.93–0.98; P < 0.0001). To our knowledge, this is the first study to show the relationship between melatonin and LV remodelling during the chronic phase post‐MI.     

Differences in left ventricular ejection fraction and volumes measured at rest and poststress by gated sestamibi SPECT.

BACKGROUND: Some studies suggested that the poststress left ventricle ejection fraction (LV EF) is lower than rest LV EF in patients with stress-induced ischemia. METHODS AND RESULTS: By using a 2-day protocol and 30 mCi Tc-99m sestamibi, LV EF, end-systolic volume (ESV), and end-diastolic volume (EDV) were measured with gated SPECT. Of 99 eligible patients, 91 had technically adequate studies. Poststress LV EF minus rest LV EF was defined as DeltaLV EF. DeltaEDV and DeltaESV were similarly defined. Rest and poststress LV EF (r = 0.89), EDV (r = 0.78), and ESV (r = 0.93) were highly correlated (P <.001). Rest LV EF, EDV, and ESV were not significantly different between patients with and without stress-induced ischemia. DeltaLV EF was significantly lower in patients with stress-induced ischemia (-3.5% +/- 4.5% vs -1.1% +/- 4.7%, P = .02). Mean LV EF poststress in ischemic patients was 55.0% +/- 10.5% vs 61.2% +/- 10.0% in nonischemic patients (P = .008). However, only 1 patient (3%) with ischemia had DeltaLV EF that exceeded the 95% confidence limit of DeltaLV EF for normal patients. Ischemia was significantly associated with increased DeltaEDV and DeltaESV (P < .01). CONCLUSIONS: Stress-induced ischemia is associated with poststress reduction in LV EF and increased poststress EDV and ESV. However, the effect of ischemia on the difference between poststress and rest EF measurements is modest and rarely exceeds the confidence limits in normal patients undergoing 2-day protocols. In most patients, poststress LV EF is an accurate reflection of rest LV EF.     

Benefits of coronary revascularisation in diabetic and non-diabetic patients with ischaemic cardiomyopathy: role of myocardial viability

BACKGROUND: Diabetes mellitus in patients with coronary artery disease is associated with poor outcome. In this study, the relation between myocardial viability, diabetes, coronary revascularisation and outcome was evaluated. METHODS: 129 patients (31 diabetic, 98 non-diabetic) with ischaemic cardiomyopathy underwent dobutamine stress echocardiography to assess myocardial viability. Patients with >or=4 viable segments were defined as viable and patients with <4 viable segments as nonviable. Left ventricular ejection fraction (LVEF) was assessed before and 9-12 months post-revascularisation. At the same time-points, LV volumes were measured to evaluate LV remodelling. Finally, cardiac events were noted during 5-year follow-up. RESULTS: The extent of viable myocardium was comparable between diabetic and non-diabetic patients. After revascularisation, LVEF increased >or=5% in 44% of diabetic and in 40% of non-diabetic patients. LVEF only improved in patients with viable myocardium. Ongoing LV remodelling occurred in 36% and 35% of diabetic and non-diabetic patients respectively, and was related to non-viability, whereas viability protected against ongoing LV remodelling, both in diabetic and non-diabetic patients. Viability was the only predictor of survival after revascularisation. CONCLUSIONS: Diabetic, viable patients with ischaemic LV dysfunction exhibit improvement in LVEF post-revascularisation with prevention of ongoing LV remodelling, similar to non-diabetic patients. Myocardial viability was also the only predictor of long-term outcome.     

Pre- and postoperative assessment of left ventricular function by magnetic resonance imaging and 2-D-echocardiography in patients undergoing left ventricular aneurysmectomy

BACKGROUND: Left ventricular (LV) aneurysms may complicate myocardial infarctions. Reliable quantification of LV functional parameters is mandatory to predict clinical outcome in patients undergoing LV aneurysmectomy. We compared global LV function measured by magnetic resonance (MR) and 2-D-echocardiography in patients before and after aneurysmectomy. METHODS: 31 patients (23 male), mean age 64 (range 35 - 85) years with an LV aneurysm (25/31 anterior MI, 5/31 inferior MI, 1/31 both) were enrolled. MR and echocardiography were performed directly before and 3 - 65 (median 8) days after surgery. MR studies were performed on a 1.5 Tesla scanner. End-diastolic and end-systolic volumes and diameters (EDV/ESV, EDD/ESD), ejection fraction (EF) and stroke volume (SV) were determined. Echocardiography was performed to determine EF, EDD and ESD. NYHA class was assessed before and 3 months after surgery. RESULTS: After aneurysmectomy MR analysis showed a decrease in EDV (255 +/- 68 ml to 202 +/- 59 ml) ( p < 0.001) and ESV (186 +/- 71 ml to 134 +/- 53 ml; p < 0.001); EF increased (28 +/- 10 % to 35 +/- 12 %; p < 0.001); EDD/ESD decreased ( p < 0.01). Compared to echocardiography, a low correlation was found in EF before/after surgery r = 0.76/r = 0.69 and ESD r = 0.43/r = 0.60, respectively. In EDD a good correlation was found before surgery (r = 0.81), and a lower correlation after surgery (r = 0.72). NYHA class improved from 3.0 +/- 0.5 before to 1.8 +/- 0.8 after operation ( p < 0.001). CONCLUSION: Resection of an LV aneurysm results in a mean improvement of 25 % in LV function, and improved clinical outcome. In asymmetric ventricles with aneurysms MR proved to be superior as a sensitive and non-invasive tool compared to conventional 2-D-echocardiography.     

Impact of left ventricular lead position in cardiac resynchronization therapy on left ventricular remodelling. A circumferential strain analysis based on 2D echocardiography.

Aims: To assess if myocardial deformation imaging allows definition of an optimal left ventricular (LV) lead position with improved effectiveness of cardiac resynchronization therapy (CRT) on LV reverse remodelling. METHODS: Circumferential strain imaging based on tracking of acoustic markers within 2D echo images (GE Ultrasound) was performed in 47 heart failure patients (59 +/- 9 years, 28 men) at baseline, one day postoperatively, 3 and 10 months after initiation of CRT. Myocardial deformation imaging was used to determine(1) the segment with latest peak negative systolic circumferential strain prior to CRT, and(2) the segment with maximal temporal difference of peak strain before-to-on CRT as the segment with greatest benefit of CRT and assumed LV lead position. Anatomic LV lead position was determined by fluoroscopy. Optimal LV lead position was defined as concordance or immediate neighbouring of the segment with latest systolic strain prior to CRT and segment with assumed LV lead position. RESULTS: Agreement of assumed LV lead position based on strain analysis and LV lead position defined by fluoroscopy were high (kappa = 0.847). At 10 month follow-up, there was greater increase of EF (12 +/- 3 vs. 7 +/- 4%, P < 0.001), greater decrease of left ventricular end-diastolic volume (LVEDV) (23 +/- 8 vs. 13 +/- 7 mL, P < 0.001) and left ventricular end-systolic volume (LVESV) (42 +/- 10 vs. 27 +/- 8 mL, P < 0.001), and greater increase of VO(2)max (2.8 +/- 0.8 vs. 1.9 +/- 1.0 mL/kg/min, P = 0.035) in the optimal (n = 28 patients) compared to the non-optimal LV lead position group (n = 19 patients). The distance between segment with latest systolic strain prior to CRT and segment with assumed LV lead position was the only independent predictor of DeltaLVEDV and DeltaLVESV at 10 month follow-up (R(2) = 0.2175, P = 0.0197) and (R(2) = 0.3774, P = 0.0054), respectively. CONCLUSION: Detailed analysis of the myocardial contraction sequence using circumferential strain imaging allows determination of the LV lead position in CRT. Optimal LV lead position in CRT defined by circumferential strain analysis results in greater improvement in LV function and more LV reverse remodelling than non-optimal LV lead position.     

Differential change in left ventricular mass and regional wall thickness after cardiac resynchronization therapy for heart failure.

AIMS: LV reverse remodelling has been shown to be a favourable response after cardiac resynchronization therapy (CRT) in many clinical trials. This study investigated whether left ventricular (LV) reverse remodelling after CRT has any structural benefit, which include the improvement of LV mass or regional wall thickness. METHODS AND RESULTS: Fifty patients (66 +/- 11 years) receiving CRT were followed up for at least 3 months. Echocardiography with tissue Doppler imaging was performed serially before and at day 1 and 3 months after CRT. Although LV end-systolic volume (LVESV) was decreased at day 1 after CRT (141 +/- 74 vs. 129 +/- 71 cm(3), P < 0.001), further LV reverse remodelling was observed at 3 months (110 +/- 67 cm(3), P < 0.001 vs. day 1). LV ejection fraction increased at day 1 (26.5 +/- 9.3 vs. 28.5 +/- 9.1%, P < 0.005) and was further improved at 3 months (34.2 +/- 10.5%, P < 0.001 vs. day 1). However, reduction of LV mass (231 +/- 67 vs. 213 +/- 59 g, P < 0.001) and regional wall thickness was only observed at 3 months, but not at day 1. The improvement of LV mass correlated with the change in LVESV (r = 0.66, P < 0.001) and the baseline systolic asynchrony index (Ts-SD) (r = -0.52, P < 0.001). LV mass was only decreased significantly in responders of LV reverse remodelling (245 +/- 66 vs. 207 +/- 61 g, P < 0.001), but increased in non-responders (209 +/- 64 vs. 223 +/- 56 g, P = 0.02). Responders had significant decrease in thickness of all the four walls for -6 to -11% (all P < or =0.02), whereas non-responders had increased thickness in septal and lateral walls for +11% (both P < 0.05). CONCLUSION: The acute reduction in LV volume after CRT is mediated by haemodynamic and geometric benefits without actual changes in LV mass. However, at 3-month follow-up, reduction in LV mass and regional wall thickness was demonstrated, which represents structural reverse remodelling. Such benefit was only observed in volumetric responders but was worsened in non-responders.     

Effects of long-term therapy with bosentan on the progression of left ventricular dysfunction and remodeling in dogs with heart failure

OBJECTIVES: In this study, we examined the effects of long-term therapy with bosentan on the progression of LV dysfunction and remodeling in dogs with moderate HF. BACKGROUND: Acute intravenous administration of bosentan, a mixed endothelin-1 type A and type B receptor antagonist, was shown to improve left ventricular (LV) function in patients and dogs with heart failure (HF). METHODS: Left ventricular dysfunction was induced by multiple, sequential intracoronary microembolizations in 14 dogs. Embolizations were discontinued when LV ejection fraction (EF) was between 30% and 40%. Dogs were randomized to three months of therapy with bosentan (30 mg/kg twice daily, n = 7) or no therapy at all (control, n = 7). RESULTS: In untreated dogs, EF decreased from 35 +/- 1% before initiating therapy to 29 +/- 1% at the end of three months of therapy (p = 0.001), and LV end-diastolic volume (EDV) and end-systolic volume (ESV) increased (EDV: 71 +/- 3 vs. 84 +/- 8 ml, p = 0.08; ESV: 46 +/- 2 vs. 60 +/- 6 ml, p = 0.03). By contrast, in dogs treated with bosentan, EF tended to increase from 34 +/- 2% before initiating therapy to 39 +/- 1% at the end of three months of therapy (p = 0.06), and EDV and ESV decreased (EDV: 75 +/- 3 vs. 71 +/- 4 ml, p = 0.05; ESV: 48 +/- 2 vs. 43 +/- 3 ml, p = 0.01). Furthermore, compared with untreated dogs, dogs treated with bosentan showed significantly less LV cardiomyocyte hypertrophy and LV volume fraction of interstitial fibrosis. CONCLUSIONS: In dogs with moderate HF, long-term therapy with bosentan prevents the progression of LV dysfunction and attenuates LV chamber remodeling. The findings support the use of mixed endothelin-1 receptor antagonists as adjuncts to the long-term treatment of HF.     

Long-term effects of non-excitatory cardiac contractility modulation electric signals on the progression of heart failure in dogs

OBJECTIVE: We previously showed that acute delivery of non-excitatory cardiac contractility modulation (CCM) electric signal during the absolute refractory period improved LV function in dogs with chronic heart failure (HF). In the present study we examined the long-term effects of CCM signal delivery on the progression of LV dysfunction and remodeling in dogs with chronic HF. METHODS: Chronic HF was produced in 12 dogs by multiple sequential intracoronary microembolizations. The CCM signal was delivered using a lead implanted in the distal anterior coronary vein. A right ventricular and a right atrial lead were implanted and used for timing of CCM signal delivery. In six dogs, CCM signals were delivered continuously for 6 h daily with an average amplitude of 3.3 V for 3 months. Six HF dogs did not have leads implanted and served as controls. RESULTS: In control dogs, LV end-diastolic volume (EDV) and LV end-systolic volume (ESV) increased (64+/-5 ml vs. 75+/-6 ml, P=0.003; 46+/-4 ml vs. 57+/-4 ml, P=0.003; respectively), and ejection fraction (EF) decreased (28+/-1% vs. 23+/-1%, P=0.001) over the course of 3 months of follow-up. In contrast, CCM-treated dogs showed a smaller increase in EDV (66+/-4 vs. 73+/-5 ml, P=0.01), no change in ESV, and an increase in EF from 31+/-1 to 34+/-2% (P=0.04) after 3 months of therapy. CONCLUSIONS: In dogs with HF, long-term CCM therapy prevents progressive LV dysfunction and attenuates global LV remodeling. These findings provide compelling rationale for exploring the use of CCM for the treatment of patients with chronic HF.     

Left ventricular remodeling can be predicted with left ventricular volume response during dobutamine echocardiography after acute myocardial infarction

OBJECTIVES: This study was performed to evaluate the significance of left ventricular (LV) volume response during dobutamine stress echocardiography (DSE) in the prediction of LV volume change during follow-up (F/U) in patients with acute myocardial infarction (AMI). METHODS: Forty-five patients with AMI (male 39, age 57+/-10 y, anterior myocardial infarction [MI] 29) underwent DSE 6+/-4 d after AMI. Revascularization of the infarct-related artery was performed if severe stenosis was present. A F/U echocardiography was performed 7.5+/-3.4 mo after DSE. The LV end-diastolic volume (EDV) and end-systolic volume (ESV) using the modified Simpson's method were measured at baseline echocardiography, low-dose (10 microg x kg(-1) x min(-1)) DSE, and F/U echocardiography. RESULTS: Patients were divided into 2 groups; Group I (n = 21) with an abnormal response (<10% decrease) in LVEDV during low-dose DSE; Group II (n = 24) with a normal response (> or =10% decrease) in LVEDV during low-dose DSE. At F/U echocardiography, the (%) change of LVEDV was significantly different between the 2 groups (-2.0+/-16.7 versus - 22.6+/-24.7%, p<0.01). Using multivariate analysis, the response of LVEDV (%) at low-dose DSE was the only significant independent predictor of the change of LVEDV (%) during F/U (y = 0.85 x - 0.03, r = 0.63, p<0.001). CONCLUSIONS: The response of LVEDV during DSE can be used as a predictor for the LV volume change after AMI.     

Freehand three-dimensional echocardiography with rotational scanning for measurements of left ventricular volume and ejection fraction in patients with coronary artery disease

BACKGROUND: Measurement of left ventricular (LV) volumes and ejection fraction (EF) is important in managing patients with coronary artery disease (CAD). Introduction of free-hand three-dimensional echocardiography (3DE) system which is equipped with small magnetic tracking system and average rotational geometry for LV volumes may provide easy and accurate quantification of LV systolic function in CAD patients. PURPOSE: To evaluate the feasibility and accuracy of LV volumes and EF measurement by free-hand 3DE with rotational geometry in patients with CAD. METHODS AND RESULTS: The study subjects consisted of consecutive 25 patients with CAD who were scheduled for quantitative gated single-photon emission computed tomography (QGS). LV end-diastolic volume (EDV), end-systolic volume (ESV), and EF were determined by conventional two-dimensional echocardiography (2DE), 3DE, and QGS. Three-dimensional echocardiography data acquisition and analysis were possible in 22 of 25 subjects (feasibility 88%). In this 3DE system, image acquisition time was 2 minutes, and 5 minutes were needed for off-line analysis of LV volumes and EF. Correlations and the limits of agreement between 3DE and QGS (r = 0.97, 0.0 +/- 9.1 ml for EDV, r = 0.99, 0.0 +/- 5.0 ml for ESV, and r = 0.97, 0.5 +/- 3.3% for EF, respectively) were superior to those between 2DE and QGS (r = 0.85, 12.6 +/- 26.8 ml for EDV, r = 0.85, 9.7 +/- 26.1 ml for ESV, and r = 0.90, -1.3 +/- 6.9% for EF, respectively). Inter- and intra-observer variabilities of 3DE were smaller than that of 2DE (5% vs 10%, 5% vs 10% for EDV, 6% vs 13%, 5% vs 9% for ESV, and 4% vs 11%, 4% vs 6% for EF, respectively). CONCLUSION: Three-dimensional echocardiography using magnetic tracking system and average rotational geometry offered a feasible and accurate method for quantification of LV volumes and EF in patients with CAD.     

Effects of growth hormone on circulating cytokine network, and left ventricular contractile performance and geometry in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: Recent experimental and clinical data indicate that abnormal central and peripheral immune reactions contribute to the progression of chronic heart failure, and that immunomodulation may be an important therapeutic approach in this syndrome.Aims We sought to study the effects of growth hormone (GH) administration on circulating pro-inflammatory/anti-inflammatory cytokine balance, and to investigate whether these GH-induced immunomodulatory effects are associated with the improvement of left ventricular (LV) contractile performance in idiopathic dilated cardiomyopathy (DCM) patients. METHODS: Plasma pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF) and its soluble receptor (sGM-CSFR), chemotactic cytokine macrophage chemoattractant protein-1 (MCP-1), soluble adhesion molecules intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1), and, finally, anti-inflammatory cytokines interleukin-10 (IL-10) and transforming growth factor-beta2 (TGF-beta2) were measured (ELISA method) in 12 patients with DCM (NYHA class III; LV ejection fraction: 23.6+/-1.7%) before and after a 3-month subcutaneous administration of GH 4IU every other day (randomized crossover design). Peak oxygen uptake (VO2 max), LV dimensions, LV mass index, end-systolic wall stress (ESWS), mean velocity of circumferential fibre shortening (Vcfc), and contractile reserve (change of ratio Vcfc/ESWS after dobutamine administration) were also determined at the same period. RESULTS: Treatment with GH produced a significant reduction in plasma TNF-alpha (7.8+/-1.1 vs 5.5+/-0.9pg/ml, P=0.013), IL-6 (5.7+/-0.5 vs 4.7+/-0.4pg/ml, P=0.043), GM-CSF (27.3+/-1.7 vs 23.3+/-1.8pg/ml, P=0.042), sGM-CSFR (4.0+/-0.4 vs 3.2+/-0.4ng/ml, P=0.039), MCP-1 (199+/-5 vs 184+/-6pg/ml, P=0.048), sICAM-1 (324+/-34 vs 274+/-27ng/ml, P=0.008) and sVCAM-1 (1238+/-89 vs 1043+/-77ng/ml, P=0.002) in DCM patients. A significant increase in ratios IL-10/TNF-alpha (1.9+/-0.3 vs 3.5+/-0.9, P=0.049), IL-10/IL-6(2.6+/-0.6 vs 3.2+/-0.5, P=0.044) and TGF-beta2/TNF-alpha (3.1+/-0.6 vs 4.4+/-0.6, P=0.05) was alsofound with GH therapy. A significant reduction in ESWS (841+/-62 vs 634+/-48gr/cm(2), P=0.0026) and LV end-systolic volume index (LVESVI, 128+/-12 vs 102+/-12ml, P=0.035) as well as a significant increase in posterior wall thickness (PWTH, 9.2+/-0.5 vs 10.3+/-0.6mm, P=0.034), contractile reserve (0.00029+/-0.0001 vs 0.00054+/-0.0001circ*cm(2)/gr*s, P=0.00028) and VO2max (15.3+/-0.7 vs 17.1+/-0.9ml/kg/min, P=0.002) were observed after GH administration. Good correlations were found between GH-induced increase in contractile reserve and the increases in VO2max (r=0.63, P=0.028), IL-10/TNF-alpha (r=0.69, P=0.011) and TGF-beta2/TNF-alpha (r=0.58, P=0.046) ratios, as well as the reduction in plasma TNF-alpha levels (r=-0.86, P=0.0004). CONCLUSIONS: GH administration modulates beneficially circulating cytokine network and soluble adhesion molecules in patients with DCM, whilst enhancing contractile reserve and diminishing LV volumes. These GH-induced anti-inflammatory effects may be associated with the improvement in LV contractile performance and exercise capacity as well as with the reverse of LV remodelling of patients with DCM.     

Circulating levels of hepatocyte growth factor and left ventricular remodelling after acute myocardial infarction (from the REVE-2 study)

Aim As experimental studies suggest that hepatocyte growth factor (HGF) is cardioprotective after myocardial infarction (MI), this study sought to investigate relationships between circulating levels of HGF and left ventricular (LV) remodelling in patients after acute MI. METHODS AND RESULTS: This prospective multicentre study included 246 patients with a first anterior Q-wave MI. Serial echocardiographic studies were performed at hospital discharge and 3 and 12 months after MI; quantitative analysis was performed at a core echocardiography laboratory. Blood samples to measure HGF, brain natriuretic peptide (BNP), and C-reactive protein were obtained at discharge and at the 1, 3, and 12 month follow-up visits. Plasma HGF levels were high at baseline, decreased at 1 month, and remained stable thereafter. In the post-MI period (at 3 and 12 months), HGF levels were positively associated with LV volumes, wall motion systolic index, E/Ea, and BNP; and negatively with LV ejection fraction. High HGF levels were associated with higher C-reactive protein levels. Multivariate analysis showed that both BNP (P < 0.0001) and C-reactive protein (P < 0.0001) were independently associated with HGF levels at 3 and 12 months. Patients who died or were rehospitalized for heart failure during follow-up had higher HGF levels at 1 month (P = 0.0006), 3 months (P = 0.018), and 1 year (P = 0.006) after MI. CONCLUSIONS: Circulating HGF levels correlate with all markers of LV remodelling after MI and are associated with rehospitalization for heart failure.     

Prediction of functional recovery of the left ventricle after coronary revascularization in patients with prior anterior myocardial infarction: a myocardial integrated backscatter study.

Cyclic variation (CV) of myocardial integrated backscatter (IBS), which reflects intrinsic contractile performance, can predict myocardial viability in patients with a reperfused acute myocardial infarction (MI), but the use of this method has not been validated for chronic left ventricular (LV) dysfunction. The aim of this study was to examine whether myocardial IBS was useful for predicting LV functional recovery after coronary revascularization in 17 patients with prior anterior MI and LV dysfunction (ejection fraction <50%). Within 24 h of the revascularization procedure (percutaneous transluminal coronary angioplasty or coronary stenting), IBS curves were obtained by placing the region of interest on the anterior wall on the short-axis IBS image. The patients had repeat left heart catheterization at 3 or 6 months after the revascularization procedure, and were grouped according to the patterns of the IBS curve within the anterior wall. In 8 patients (group A), the IBS curve had a synchronized pattern with the magnitude of CV > or = 3.5, and in the remaining 9 patients (group B), the curve had either an asynchronized pattern or the magnitude of CV was less than 3.5 dB even in the case of synchronized pattern, or both. At baseline, there were no significant differences in LV functional indices between the 2 groups. After the follow-up period, the LV end-systolic volume decreased (75 +/- 21 ml to 56 +/- 20ml, p = 0.05), LV ejection fraction increased (35 +/- 12% to 50 +/- 14%, p = 0.014), and LV end-diastolic pressure decreased (19 +/- 10 mmHg to 13 +/- 6 mmHg, p = 0.02) in group A, whereas only the LV ejection fraction increased (34 +/- 9% to 40 +/- 11%, p = 0.03) in group B; LV end-systolic volume (72 +/- 19 ml to 66 +/- 16 ml, p = 0.126) and LV end-diastolic pressure (18 +/- 12 mmHg to 14 +/- 8 mmHg, p = 0.184) showed no significant changes. In conclusion, IBS is valuable for predicting LV functional recovery after coronary revascularization in patients with LV dysfunction caused by a remote anterior MI. A large-scale study is be needed to establish these data.     

Serum C-reactive protein elevation in left ventricular remodeling after acute myocardial infarction--role of neurohormones and cytokines

BACKGROUND: We previously reported that increased peak serum C-reactive protein (CRP) level after acute myocardial infarction (AMI) was a major predictor of cardiac rupture and long-term outcome. The aim of this study was to clarify the role of serum CRP elevation as a possible marker of left ventricular (LV) remodeling after AMI. METHODS: We prospectively studied 31 patients who underwent primary angioplasty for a first anterior Q-wave AMI. Peak serum CRP level was determined by serial measurements after admission. LV volume and the plasma levels of various neurohormones and cytokines were measured on admission, and 2 weeks and 6 months after AMI. RESULTS: Patients with higher peak CRP levels (above the median) had a greater increase in LV end-diastolic volume during 2 weeks after AMI (+21+/-14 vs. +5+/-6 ml/m(2), P=0.001) and a lower ejection fraction (45+/-11 vs. 53+/-7%, P=0.02) than those with lower CRP levels, associated with a higher incidence of pump failure, atrial fibrillation, and LV aneurysm. Plasma levels of norepinephrine, brain natriuretic peptide, and interleukin-6 2 weeks after AMI were higher in the high CRP group than in the low CRP group. CONCLUSIONS: Increased peak serum CRP level was associated with a greater increase in LV volume after anterior AMI. Plasma norepinephrine and interleukin-6 levels were increased in patients with higher CRP levels, suggesting a possible role of sympathetic activation and enhanced immune response in the development of LV remodeling after AMI.     

Right and left ventricular volume characteristics in common atrioventricular canal

Right (RV) and left (LV) ventricular volume characteristics were determined from biplane cineangiography in 29 patients with atrioventricular canal (AVC). The patients were classified into two groups: group I (N = 19), uncomplicated AVC; group II (N = 10), AVC associated with RV obstruction. In group I, LV end-diastolic volume (EDV) [177 +/- 9 (SEM)% of normal] and RVEDV (125 +/- 9%) both were greater than normal (P is less than 0.001 and less than 0.01, respectively). LV ejection fraction (EF) was decreased (0.59 +/- 0.02, P is less than 0.001) but RVEF was normal (0.58 +/- 0.03). LV stroke volume index (SVI) was increased (48 +/- 3 ml/m2, P is less than 0.005), and RVSVI was normal (34 +/- 3 ml/m2). One patient had a markedly small RVEDV (45%). In group II, LVEDV and RVEDV were not different from normal (119 +/- 11% and 97 +/- 15%, respectively). LVEF was depressed (0.52 +/- 0.04, P is less than 0.001) and RVEF was normal (0.55 +/- 0.05). LVSVI was normal (38 +/- 5 ml/m2) and RVSVI was slightly decreased (29 +/- 4 ml/m2, P is less than 0.025). Two patients had a markedly small RVEDV (31%, 55%). EDV correlated with the pulmonary-to-systemic flow ratio (LV, r = 0.71; RV, r = 0.68). The data show that in most patients with AVC, LV and RV are enlarged in the uncomplicated form but not in the form with RV obstruction. LV function is more compromised than RV in both groups. RV hypoplasia is rare but was documented in both uncomplicated forms and forms with RV obstruction.