Papillary muscle rupture: small life-threatening myocardial infarction.

We report the case of a 70 years old man admitted to our coronary care unit because of atrial fibrillation, non-ST-elevation myocardial infarction and cardiogenic shock. Emergency coronary angiography showed a 99 % stenosis of the circumflex coronary that was successfully treated with a bare metal stent. Atrial fibrillation was cardioverted to sinus rhythm. Nevertheless, no hemodynamic benefit was observed. Transesophageal echocardiography (TEE) showed rupture of the papillary muscle (PM). The patient underwent emergent mitral valve replacement. Surgical visualization of the mitral valve confirmed the rupture of the antero-lateral PM. The postoperative course was uneventful and the patient recovered fully. This case highlights that even small myocardial infarction may have dramatic clinical presentations such as PM rupture with cardiogenic shock. Clinical suspicion and rapid confirmation of the diagnosis by TEE are essential requirements for successful treatment.

Prognosis of patients with ischaemic cardiomyopathy after coronary revascularisation: relation to viability and improvement in left ventricular ejection fraction.

BACKGROUND: In patients with ischaemic cardiomyopathy and viable myocardium, left ventricular ejection fraction (LVEF) does not always improve after revascularisation. Whether this may affect prognosis is unclear. OBJECTIVE: To evaluate the prognosis of viable patients with and without improvement of LVEF after coronary revascularisation. METHODS: Before revascularisation, radionuclide ventriculography (RNV) and dobutamine stress echocardiography were performed to assess LVEF and myocardial viability, respectively. Nine to 12 months after revascularisation, LVEF improvement was assessed by RNV. Patients were divided into three groups: group 1, viable patients with LVEF improvement (n = 27); group 2, viable patients without LVEF improvement (n = 15), group 3, non-viable patients (n = 48). Cardiac events were evaluated during a 4-year follow-up. RESULTS: After revascularisation, the mean (SD) LVEF improved from 32 (9)% to 42 (10)% in group 1, but did not change significantly in group 2 and in group 3, p<0.001 by analysis of variance (ANOVA). Heart failure symptoms improved in both groups 1 (mean (SD) NYHA class from 3.1 (0.9) to 1.7 (0.7)) and 2 (from 3.2 (0.7) to 1.7 (0.9)), but not in group 3 (from 2.8 (1.0) to 2.7 (0.5)), p<0.001 by ANOVA. During follow-up, the cardiac event rate was low (4%) in group 1, intermediate (21%) in group 2 and high (33%) in group 3 (p = 0.01). CONCLUSION: The best prognosis after revascularisation may be expected in those viable patients whose LVEF improves. Conversely, viable patients without functional improvement have an intermediate prognosis.

Outcome after redo coronary artery bypass grafting in patients with ischaemic cardiomyopathy and viable myocardium.

BACKGROUND: Repeat coronary artery bypass grafting (redo-CABG) in patients with ischaemic cardiomyopathy is associated with high perioperative risk and worse long-term outcome compared with patients undergoing their first CABG. OBJECTIVE: To assess whether patients with viable myocardium undergoing redo-CABG have a better outcome. METHODS: 18 patients with ischaemic cardiomyopathy underwent redo-CABG and 34 underwent their first CABG; all had substantial viability (> or =25% of the left ventricle) on dobutamine stress echocardiography (DSE). Left ventricular ejection fraction (LVEF) and heart failure symptoms were assessed before and 9-12 months after revascularisation. Cardiac event rate was assessed during the follow-up period (median 4 years, 25-75th centile 2.8-4.9 years). RESULTS: The extent of viable myocardium on DSE was comparable in the two groups (11.3 (3.9) segments in patients who underwent redo-CABG v 12.8 (3.0) in patients who underwent their first CABG; p = NS). LVEF improved from 32% (9%) to 39% (12%); p = 0.01, in patients who underwent redo-CABG and from 30% (7%) to 36% (7%); p<0.01, in those who underwent their first CABG; New York Heart Association class improved from 2.5 (1.1) to 1.9 (0.8); p = 0.03, and from 2.7 (1.0) to 1.8 (0.70); p<0.01, respectively. In patients who underwent redo-CABG, the perioperative mortality was 0, post-surgery inotropic support was needed in 11% of the patients and mid-term (4-year) survival was 100%, with a total event rate of 28%. All these variables were not statistically different from patients who underwent their first CABG (p = 0.50, 0.90, 0.08 and 0.81, respectively). CONCLUSION: Patients with ischaemic cardiomyopathy and substantial viability undergoing redo-CABG benefit from revascularisation in terms of improvement in LVEF, heart failure symptoms, angina and mid-term prognosis.

Long term prognostic value of myocardial viability and ischaemia during dobutamine stress echocardiography in patients with ischaemic cardiomyopathy undergoing coronary revascularisation.

OBJECTIVE: To evaluate the relative merits of viability and ischaemia for prognosis after revascularisation. METHODS: Low-high dose dobutamine stress echocardiography (DSE) was performed before revascularisation in 128 consecutive patients with ischaemic cardiomyopathy (mean (SD) left ventricular ejection fraction (LVEF) 31 (8)%). Viability (defined as contractile reserve (CR)) and ischaemia were assessed during low and high dose dobutamine infusion, respectively. Cardiac death was evaluated during a five year follow up. Clinical, angiographic, and echocardiographic data were analysed to identify predictors of events. RESULTS: Univariable predictors of cardiac death were the presence of multivessel disease (hazard ratio (HR) 0.21, p < 0.001), baseline LVEF (HR 0.90, p < 0.0001), wall motion score index (WMSI) at rest (HR 4.02, p = 0.0006), low dose DSE (HR 7.01, p < 0.0001), peak dose DSE (HR 4.62, p < 0.0001), the extent of scar (HR 1.39, p < 0.0001), and the presence of CR in > or = 25% of dysfunctional segments (HR 0.34, p = 0.02). The best multivariable model to predict cardiac death included the presence of multivessel disease, WMSI at low dose DSE, and the presence of CR in > or = 25% of the severely dysfunctional segments (HR 9.62, p < 0.0001). Inclusion of ischaemia in the model did not provide additional predictive value. CONCLUSION: The findings of the present study illustrate that in patients with ischaemic cardiomyopathy, the extent of viability (CR) is a strong predictor of long term prognosis after revascularisation. Ischaemia did not add significantly in predicting outcome.

Long term outcome in patients with silent versus symptomatic ischaemia during dobutamine stress echocardiography.

OBJECTIVES: To compare the long term prognosis of patients having silent versus symptomatic ischaemia during dobutamine stress echocardiography (DSE). DESIGN: Observational study. SETTING: Tertiary referral centre. PATIENTS: 931 patients who experienced stress induced myocardial ischaemia during DSE. RESULTS: Silent ischaemia was present in 643 of 931 patients (69%). The number of dysfunctional segments at rest (mean (SD) 9.6 (5.1) v 8.8 (5.0), p = 0.1) and of ischaemic segments (3.5 (2.2) v 3.8 (2.1), p = 0.2) was comparable in both groups. During a mean (SD) follow up of 5.5 (3.3) years, there were 169 (18%) cardiac deaths and 86 (9%) non-fatal infarctions. Multivariable Cox regression analysis showed age (hazard ratio (HR) 1.1, 95% confidence interval (CI) 1.02 to 1.05), previous myocardial infarction (HR 1.4, 95% CI 1.1 to 2.0), and number of ischaemic segments during the test (HR 2.0, 95% CI 1.0 to 3.7) as independent predictors of cardiac death and myocardial infarction. For every additional ischaemic segment there was a twofold increment in risk of late cardiac events. The annual cardiac death or myocardial infarction rate was 3.0% in patients with symptomatic ischaemia and 4.6% in patients with silent ischaemia (p < 0.01). Silent induced ischaemia was an independent predictor of cardiac death and myocardial infarction (HR 1.7, 95% CI 1.1 to 2.0). During follow up symptomatic patients were treated more often with cardioprotective therapy (p < 0.01) and coronary revascularisation (145 of 288 (50%) v 174 of 643 (27%), p < 0.001). CONCLUSIONS: Patients with silent ischaemia had a similar extent of myocardial ischaemia during DSE compared to patients with symptomatic ischaemia but received less cardioprotective treatment and coronary revascularisation and experienced a higher cardiac event rate.

Improvement of stress LVEF rather than rest LVEF after coronary revascularisation in patients with ischaemic cardiomyopathy and viable myocardium.

OBJECTIVE: To evaluate prospectively the response of left ventricular ejection fraction (LVEF) to high dose dobutamine infusion in patients showing substantial viability, with and without improved resting LVEF after revascularisation. METHODS: Before and 9-12 months after revascularisation, 50 patients with ischaemic cardiomyopathy (LVEF 32 (8)%) and substantial myocardial viability (> or = 4 viable segments) underwent radionuclide ventriculography and dobutamine stress echocardiography. Patients were divided into group 1, patients with, and group 2, patients without significant improvement in resting LVEF (> or = 5% by radionuclide ventriculography) after revascularisation. The response of LVEF during dobutamine stress echocardiography was compared in these two groups. RESULTS: Groups 1 and 2 were comparable in baseline characteristics, resting LVEF, and number of viable segments (mean (SD) 7 (4) v 6 (2), not significant). After revascularisation, the LVEF response during dobutamine stress echocardiography improved significantly in both groups (group 1, 34 (10)% to 56 (8)%; group 2, 32 (10)% to 46 (11)%; both p < 0.001). Interestingly, although resting LVEF did not improve in group 2, peak stress LVEF after revascularisation did (p < 0.001). Group 1 patients had, however, a greater increase in peak stress LVEF (group 1, 22 (10)%; group 2, 13 (9)%; p < 0.01). New York Heart Association and Canadian Cardiovascular Society classes decreased in both groups. CONCLUSIONS: Although patients with viable myocardium did not always have improved rest LVEF after revascularisation, peak stress LVEF improved. Assessment of improvement of resting function may not be the ideal end point to evaluate successful revascularisation.

Assessment of myocardial viability in chronic ischemic heart disease: current status.

Assessment of myocardial viability is clinically important in the work-up of patients with ischemic cardiomyopathy. Numerous studies in the past 2 decades demonstrated that revascularization improves left ventricular ejection fraction (LVEF), heart failure symptoms and prognosis in patients with viable myocardium. Conversely patients without viable tissue do not benefit from revascularization. Also, a substantial amount of viable myocardium (at least 25% of the left ventricle) is needed to result in improvement of LVEF. Hence, both identification and quantification of the extent of viable myocardium are required for a careful selection of candidates for revascularization. Indeed, the presence of a substantial amount of viable myocardium decreases the risk of surgery in patients with reduced LVEF. Several diagnostic techniques are available to identify myocardial viability. Positron emission tomography (PET), myocardial perfusion imaging, and stress echocardiography are considered the traditional techniques to evaluate myocardial viability. Recently, newer techniques including cardiac magnetic resonance (CMR), myocardial contrast echocardiography (MCE) and electromechanical mapping have been introduced. In this manuscript the status of the currently available techniques to assess viability was reviewed. Also the relative merits of each technique for prediction of functional recovery and prognosis was addressed. The available retrospective data support the clinical use of viability assessment. Patients with ischemic cardiomyopathy should undergo viability testing to determine therapeutic strategy. In the presence of substantial amount of viable myocardium, patients should undergo revascularization since benefits in terms of left ventricular function, remodeling, symptoms and prognosis may be anticipated. However, prospective randomized trial are needed to confirm these data.

Prognostic value of dobutamine stress echocardiography in patients with previous coronary revascularisation.

OBJECTIVE: To assess the prognostic value of dobutamine stress echocardiography (DSE) in patients with previous myocardial revascularisation. DESIGN: Prospective study. SETTING: Tertiary referral centre in Rotterdam, the Netherlands. PATIENTS: 332 consecutive patients with previous percutaneous or surgical coronary revascularisation underwent DSE. Follow up was successful for 331 (99.7%) patients. Thirty eight patients who underwent early revascularisation (

Pulsed wave tissue Doppler imaging for the quantification of contractile reserve in stunned, hibernating, and scarred myocardium.

OBJECTIVES: To assess whether quantification of myocardial systolic velocities by pulsed wave tissue Doppler imaging can differentiate between stunned, hibernating, and scarred myocardium. DESIGN: Observational study. SETTING: Tertiary referral centre. PATIENTS: 70 patients with reduced left ventricular function caused by chronic coronary artery disease. METHODS: Pulsed wave tissue Doppler imaging was done close to the mitral annulus at rest and during low dose dobutamine; systolic ejection velocity (Vs) and the difference in Vs between low dose dobutamine and the resting value (DeltaVs) were assessed using a six segment model. Assessment of perfusion (with Tc-99m-tetrofosmin SPECT) and glucose utilisation (by 18F-fluorodeoxyglucose SPECT) was used to classify dysfunctional regions (by resting cross sectional echocardiography) as stunned, hibernating, or scarred. RESULTS: 253 of 420 regions (60%) were dysfunctional. Of these, 132 (52%) were classified as stunned, 25 (10%) as hibernating, and 96 (38%) as scarred. At rest, Vs in stunned, hibernating, and scar tissue was, respectively, 6.3 (1.8), 6.6 (2.2), and 5.5 (1.5) cm/s (p = 0.001 by ANOVA). There was a gradual decline in Vs during low dose dobutamine infusion between stunned, hibernating, and scar tissue (8.3 (2.6) v 7.8 (1.5) v 6.8 (1.9) cm/s, p < 0.001 by ANOVA). DeltaVs was higher in stunned (2.1 (1.9) cm/s) than in hibernating (1.2 (1.4) cm/s, p < 0.05) or scarred regions (1.3 (1.2) cm/s, p = 0.001). CONCLUSIONS: Quantitative tissue Doppler imaging showed a gradual reduction in regional velocities between stunned, hibernating, and scarred myocardium. Dobutamine induced contractile reserve was higher in stunned regions than in hibernating and scarred myocardium, reflecting different severities of myocardial damage.

Relation between left ventricular contractile reserve during low dose dobutamine echocardiography and plasma concentrations of natriuretic peptides.

BACKGROUND: In ischaemic cardiomyopathy, raised plasma concentrations of natriuretic peptides are associated with a poor long term prognosis, while the presence of contractile reserve is a favourable sign. OBJECTIVE: To assess the relation between plasma natriuretic peptides and contractile reserve. DESIGN: Prospective observational study. SETTING: Tertiary referral centre. PATIENTS: 66 consecutive patients undergoing low dose dobutamine stress echocardiography to evaluate contractile reserve in regions with contractile dysfunction at rest, divided into two groups: group 1, 31 patients with ischaemic cardiomyopathy (left ventricular ejection fraction < or = 40%) and heart failure symptoms; group 2, 35 patients with normal left ventricular function. MAIN OUTCOME MEASURES: Plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), measured using immunoradiometric assays. Contractile reserve was defined as an improvement in segmental wall motion score during infusion of low dose dobutamine. RESULTS: Plasma ANP and BNP concentrations were higher in group 1 than in group 2 (mean (SD): ANP, 17.8 (32.8) v 7.2 (9.7), p < 0.005; BNP, 24.4 (69.0) v 5.0 (14.3) pmol/l, respectively; p < 0.001). In group 1, the presence of contractile reserve was inversely related to ANP and BNP levels; however, patients with contractile reserve had lower ANP and BNP concentrations than patients without contractile reserve (ANP, 14.2 (9.1) v 24.2 (44.2), p < 0.05; BNP, 20.2 (25.5) v 37.5 (93.8) pmol/l, respectively; p < 0.05). CONCLUSIONS: Plasma natriuretic peptide concentrations are raised in patients with left ventricular dysfunction, but in the presence of preserved myocardial contractile reserve, relatively low levels of ANP and BNP are present.

Quantification of regional left ventricular function in Q wave and non-Q wave dysfunctional regions by tissue Doppler imaging in patients with ischaemic cardiomyopathy.

OBJECTIVE: To quantify regional left ventricular (LV) function and contractile reserve in Q wave and non-Q wave regions in patients with previous myocardial infarction. DESIGN: An observational study. SETTING: Tertiary care centre. PATIENTS: 81 patients with previous myocardial infarction and depressed LV function. INTERVENTIONS: All patients underwent surface ECG at rest and pulsed wave tissue Doppler imaging at rest and during low dose dobutamine infusion. The left ventricle was divided into four major regions (anterior, inferoposterior, septal, and lateral). Severely hypokinetic, akinetic, and dyskinetic regions on two dimensional echocardiography at rest were considered dysfunctional. MAIN OUTCOME MEASURES: Regional myocardial systolic velocity (Vs) at rest and the change in Vs during low dose dobutamine infusion (DeltaVs) in dysfunctional regions with and without Q waves on surface ECG. RESULTS: 220 (69%) regions were dysfunctional; 60 of these regions corresponded to Q waves and 160 were not related to Q waves. Vs and DeltaVs were lower in dysfunctional than in non-dysfunctional regions (mean (SD) Vs 6.2 (1.9) cm/s v 7.1 (1.7) cm/s (p < 0.001), and DeltaVs 1.9 (1.9) cm/s v 2.6 (2.5) cm/s (p = 0.009), respectively). There were no significant differences in Vs and DeltaVs among dysfunctional regions with and without Q waves (Q wave regions: Vs 6.2 (1.8) cm/s, DeltaVs 1.6 (2.2) cm/s; non-Q wave regions: Vs 6.3 (1.9) cm/s, DeltaVs 2.0 (2.0) cm/s). CONCLUSIONS: Quantitative pulsed wave tissue Doppler demonstrated that, among dysfunctional regions, Q waves on the ECG do not indicate more severe dysfunction, and myocardial contractile reserve is comparable in Q wave and non-Q wave dysfunctional myocardium.

C-reactive protein and primary prevention of ischemic heart disease.

C-reactive protein (CRP) is the prototype acute phase reactant and therefore a marker of systemic inflammation. In the last decades, accumulating data have demonstrated the role of inflammation in the pathogenesis of ischemic heart disease. High CRP levels, measured by high-sensitivity methods, on admission have a short-term negative prognostic value and are associated with a worse outcome. In epidemiological studies, minor elevations of CRP are associated with future risk of myocardial infarction, stroke and peripheral vascular disease. This increased risk is independent of other biochemical and clinical risk factors, and the association between high CRP and an abnormal cholesterol ratio significantly increases the risk in the individual patient. Finally, the observation of an increased level of CRP may be of clinical utility in primary prevention, because these subjects favourably benefit from statin therapy.

Enhanced response of blood monocytes to in vitro lipopolysaccharide-challenge in patients with recurrent unstable angina.

BACKGROUND: C-reactive protein (CRP) plasma levels have been associated with short- and long-term occurrence of coronary events. We investigated whether circulating inflammatory cell responsiveness to low-grade stimuli could contribute to the reported association between CRP and coronary events. METHODS AND RESULTS: We studied 32 patients with unstable angina who were followed for 24 months and were free of symptoms for 6 months (group 1): 19 patients had persistently high CRP levels (>0.3 mg/dL) (group 1A); 13 patients had normal CRP levels (group 1B). During the follow-up, 12 (63%) group 1A but no group 1B patients developed an infarction or recurrence of unstable angina (P<0.001). Eighteen patients with chronic stable angina (group 2) and 18 healthy subjects (group 3) were studied as controls. Interleukin (IL)-6 production (median, range) by peripheral blood mononuclear cells after 4 hours of in vitro stimulation with 1 ng/mL lipopolysaccharide (LPS) was significantly higher in group 1A (4526 pg/mL, 3042 to 10 583 pg/mL) than in group 1B (1752 pg/mL, 75 to 3981 pg/mL), group 2 (707 pg/mL, 41 to 3275 pg/mL), and group 3 (488 pg/mL, 92 to 3503 pg/mL) (all P<0.001). No significant differences were observed among the other groups. IL-6 production after LPS-challenge was correlated with baseline CRP levels (r=0.42, P=0.005). CONCLUSIONS: Mononuclear cells of patients with recurrent phases of instability exhibit an enhanced production of IL-6 in response to low-dose of LPS, correlated with baseline CRP levels, 6 months after the last acute event. This persisting enhanced acute-phase responsiveness may help explain the association between CRP and acute coronary events.

Clinical use of C-reactive protein for the prognostic stratification of patients with ischemic heart disease.

C-reactive protein (CRP), the prototypic acute phase reactant and a sensitive marker of inflammation, consistently predicts new coronary events, including myocardial infarction and death, in patients with ischemic heart disease. The data are very consistent with regard to the long-term outcome, but in many studies are also significant for in-hospital events. The predictive value of CRP is, in the majority of the studies, independent of and additive to that of the troponins. Moreover recent data suggest that CRP may be a reliable marker of the risk of restenosis after percutaneous coronary interventions and that its levels can be modulated by statins. Taken together, all these data suggest that CRP, probably with different cut-offs, should be used as a marker of risk and as a guide to therapy in patients hospitalized for acute coronary syndromes and in outpatients suffering from ischemic heart disease.

Role of inflammation in the pathogenesis of unstable coronary artery diseases.

Inflammation has been shown to play a pivotal role in ischemic heart disease, in particular unstable angina. The instability that characterizes this syndrome is related to the waxing and waning of ischemic stimuli, especially thrombotic ones. Angiographically and autoptically the severity of the atherosclerotic background in unstable angina does not differ from that in chronic stable angina, but in the former mural thrombi are often found and coronary atherosclerotic plaques are characterized by an inflammatory infiltrate, mostly consisting of activated lymphocytes, macrophages and mast-cells. In addition to these local findings, systemic evidence also suggests the importance of the role of inflammation in unstable angina as platelets, neutrophils and monocytes are activated, and elevated levels of serum markers of inflammation, e.g. C-Reactive Protein, have been consistently found. CRP has been demonstrated to be a reliable marker of prognosis in coronary heart disease. The consequences of inflammation are a disruption in the dynamic balance between antithrombotic and prothrombotic activities, an altered extracellular matrix metabolism, hyper-reactivity of cells such as monocytes and smooth muscle cells, all important features of unstable angina. These findings have important prognostic implications, since markers of inflammation are associated to a worse prognosis, and may also have therapeutic implications in the near future.

In vitro hyperreactivity to lipopolysaccharide in patients with history of unstable angina is not associated with seropositivity for Cytomegalovirus, Helicobacter pylori and Chlamydia pneumoniae.

BACKGROUND: Inflammation and possibly chronic infections are associated with acute coronary syndromes; however, the mechanisms responsible for this association are not yet fully elucidated. The aim of this study was to assess whether the hyperreactivity of the inflammatory system, that we have shown in unstable patients with persistently elevated C-reactive protein and with recurrence of symptoms, was associated with chronic infection. METHODS: In 20 unstable angina patients seropositivity and antibody levels vs Cytomegalovirus, Helicobacter pylori and Chlamydia pneumoniae were measured and correlated with the interleukin-6 production in vivo in 1 ml of whole blood stimulated with 0.1 microgram lipopolysaccharide for 4 hours. RESULTS: No positive correlation was found between antibody titer and interleukin-6 levels. No correlation was also found between seropositivity to Cytomegalovirus, Helicobacter pylori or Chlamydia pneumoniae and interleukin-6 levels. CONCLUSIONS: Our study suggests that seropositivity for infective agents, including Chlamydia pneumoniae, does not affect the monocyte response to lipopolysaccharide and thus cannot account for the enhanced interleukin-6 production observed in unstable angina patients with raised levels of C-reactive protein and worse prognosis, and suggests the predominant role of the individual response to different stimuli.