Targeting residual inflammatory risk in coronary disease: to catch a monkey by its tail.

Patients with coronary disease remain at high risk for future cardiovascular events, even with optimal risk factor modification, lipid-lowering drugs and antithrombotic regimens. A myriad of inflammatory pathways contribute to progression of the atherosclerotic burden in these patients. Only in the last few years has the inflammatory biology of atherosclerosis translated into clinical therapeutic options. Low-dose colchicine can provide a clinically relevant reduction in the risk for composite and individual major cardiovascular outcomes in patients with acute and chronic coronary syndromes. Among others, its anti-inflammatory effects in atherosclerosis seem to be related to neutrophil recruitment and adhesion, inflammasome inhibition, and morphological changes in platelets and platelet aggregation. Future research is aimed at further elucidating its particular mechanism of action, as well as identifying patients with the highest expected benefit and evaluating efficacy in other vascular beds. These data will help to formulate the role of colchicine and other anti-inflammatory drugs in patients with coronary disease and atherosclerosis in general in the near future.

The challenge of choosing in cardiovascular risk management.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. For many years guidelines have listed optimal preventive therapy. More recently, novel therapeutic options have broadened the options for state-of-the-art CV risk management (CVRM). In the majority of patients with CVD, risk lowering can be achieved by utilising standard preventive medication combined with lifestyle modifications. In a minority of patients, add-on therapies should be considered to further reduce the large residual CV risk. However, the choice of which drug combination to prescribe and in which patients has become increasingly complicated, and is dependent on both the absolute CV risk and the reason for the high risk. In this review, we discuss therapeutic decisions in CVRM, focusing on (1) the absolute CV risk of the patient and (2) the pros and cons of novel treatment options.

In search of an efficient strategy to monitor disease status of chronic heart failure outpatients: added value of blood biomarkers to clinical assessment.

INTRODUCTION: Blood biomarkers have the potential to monitor the severity of chronic heart failure (CHF). Studies correlating repeated measurements of blood biomarkers with repeatedly assessed New York Heart Association (NYHA) class over a prolonged follow-up period, and concomitantly investigating their associations with clinical endpoints, have not yet been performed. METHODS: Between 2011-2013, 263 CHF patients were included. At inclusion and subsequently every 3 months, we measured N­terminal pro-B-type natriuretic (NT-proBNP), high-sensitivity troponin T (Hs-TnT) and C­reactive protein (CRP), and assessed NYHA class. The primary endpoint comprised heart failure hospitalisation, cardiovascular mortality, cardiac transplantation or left ventricular assist device implantation. Time-dependent Cox models were used. RESULTS: Mean age was 67 ± 13 years, 72% were men and 27% were in NYHA class III-IV. We obtained 886 repeated measures (median 3 [IQR 2-5] per patient). The primary endpoint was reached in 41 patients during a median follow-up of 1.0 [0.6-1.4] year. Repeatedly measured NT-proBNP and Hs-TnT were significantly associated with repeatedly assessed NYHA class, whereas CRP was not (NT-proBNP: ß [95% CI]: 1.56 [1.17-2.06]ln(ng/l) increase per point increase in NYHA class, p = 0.002; HsTNT: ß [95% CI]: 1.58 [1.21-2.07]). Serially measured NT-proBNP (HR [95% CI]:2.86 [1.73-4.73]), CRP (1.69 [1.21-2.34]) and NYHA class (2.33 [1.51-3.62]) were positively and independently associated with the primary endpoint, whereas Hs-TnT lost statistical significance after multivariable adjustment. A model containing serially measured NYHA class and NT-proBNP displayed a C-index of 0.84, while serially measured NYHA class and CRP showed a C-index of 0.82. CONCLUSION: Temporal NT-proBNP, CRP and NYHA class patterns are independently associated with adverse clinical outcome. Serially measured NT-proBNP and NYHA class are best suited for monitoring CHF outpatients.

Independent prognostic value of coronary artery calcium score and coronary computed tomography angiography in an outpatient cohort of low to intermediate risk chest pain patients.

BACKGROUND: Limited studies report on the additional prognostic value of coronary computed tomography angiography (CCTA) and the coronary artery calcium score (CACS). METHODS: For a median of 637 days, 1551 outpatients with chest pain, without known coronary artery disease (CAD) and low or intermediate pre-test probability of CAD, were followed for major adverse cardiac events (MACE), defined as death, myocardial infarction or late revascularisation. Cox proportional hazard regression was used to evaluate the independent prognostic value of CCTA and CACS. RESULTS: MACE occurred in 23 patients (1.5 %): death (3, 0.2 %), myocardial infarction (4, 0.3 %) and late revascularisation (16, 1.3 %). Multivariate analysis showed an independent prognostic value of CCTA (p < 0.001), CACS of 100-400 (p = 0.035) and CACS of > 400 (p = 0.021). CCTA showed obstructive CAD in 3.1 % of patients with CACS = 0. No events occurred in patients with CACS = 0 without obstructive CAD at CCTA, whereas 2/23 patients (9 %) with CACS = 0 with obstructive CAD had a MACE. CONCLUSIONS: Our study shows that both CCTA and higher CACS categories have independent prognostic value in chest pain patients with low to intermediate pre-test probability of obstructive CAD, in which CCTA is appropriate. Furthermore a non-negligible amount of patients with CACS = 0 have obstructive CAD at CCTA. CCTA can be used in these patients to identify those at risk for MACE.

Trends in incidence of infective endocarditis at the Medical Center of Alkmaar.

INTRODUCTION: Infective endocarditis (IE) is a life-threatening illness with a high morbidity and mortality, and with a rise in incidence in patients with prosthetic valves and cardiac devices. Recently the Dutch guidelines of IE prophylaxis have been revised, limiting IE prophylaxis to the highest-risk population. The aim of the present study was to investigate the incidence of IE and its trend between 2008-2013 in a regional hospital in the Netherlands. METHODS: This is an observational descriptive study of all patients who were admitted with IE to the Medical Center of Alkmaar (MCA) from 1 January 2008 to 31 December 2013. RESULTS: A total of 89 patients with IE, including 7 patients (7.9 %) with a cardiac device IE (CDIE), were identified. In 2008 there were 8 patients with IE, this increased to 26 patients in 2013. Patients with a prosthetic valve IE increased from 25 % in 2008 to 34.6 % in 2013. This increase was not seen in patients with CDIE. CONCLUSION: In the MCA we have observed an increase in patients with IE since 2010. This increase was in part attributable to prosthetic valve IE. A larger observational study is needed to investigate the increase of IE in the Netherlands.

An Update on Inflammation in Atherosclerosis: How to Effectively Treat Residual Risk.

PURPOSE: This study reviewed the contribution of inflammation to atherosclerotic cardiovascular disease (ASCVD), which has gained widespread recognition in recent years. METHODS: This critical review evaluated how recent publications and ongoing clinical trials in atherosclerotic inflammation will affect clinical care. FINDINGS: Key trials, including CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) with canakinumab (interleukin-1ß inhibition), and COLCOT (Colchicine Cardiovascular Outcomes Trial) and LoDoCo2 (Low Dose Colchicine 2) with colchicine, have shown that suppressing inflammation can improve outcomes in ASCVD. Cholesterol crystals play an important role in activating the NOD-, LRR-, and pyrin domain-containing protein 3 inflammasome and subsequent cytokine cascade. Inflammation contributes to significant residual risk after optimal lipid-lowering therapy. High-sensitivity C-reactive protein is a recognized biomarker of residual risk, and newer biomarkers such as the neutrophil to lymphocyte ratio may add additional information. The role of lipoprotein(a) as a proinflammatory agent or possible inflammatory biomarker is under investigation. The contribution of clonal hematopoiesis of indeterminate potential and trained immunity are in the early stages of investigation. Ongoing clinical trials of suppressing inflammation with NOD-, LRR-, and pyrin domain-containing protein 3 inflammasome inhibition (colchicine) and alternative approaches with downstream interleukin-6 ligand inhibition (ziltivekimab) will expand the evidence base for the use of anti-inflammatory agents in ASCVD. IMPLICATIONS: Based on current evidence and ongoing clinical trials, targeting inflammation alongside optimal lipid lowering is likely to be central to the future treatment of ASCVD. (Clin Ther. 2023;45:XXX-XXX) © 2023 Elsevier HS Journals, Inc.

Pharmaco-invasive therapy: Early implementation of statins and proprotein convertase subtilisin/kexin type 9 inhibitors after acute coronary syndrome.

Elevated LDL-cholesterol (LDL-C) plays a major role in atheroma formation and inflammation. Medical therapy to lower elevated LDL-C is the cornerstone for reducing the progression of atherosclerotic cardiovascular disease. Statin therapy, and more recently, other drugs such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, have proven efficacy in long-term lowering of LDL-C and therefore diminish cardiovascular risk. During an acute coronary syndrome (ACS), a systemic inflammatory response can destabilize other non-culprit atherosclerotic plaques. Patients with these vulnerable plaques are at high risk of experiencing recurrent cardiovascular events in the first few years post-ACS. Initiating intensive LDL-C lowering therapy in these patients with statins or PCSK9 inhibitors can be beneficial via several pathways. High-intensity statin therapy can reduce inflammation by directly lowering LDL-C, but also through its pleiotropic effects. PCSK9 inhibitors can directly lower LDL-C to recommended guideline thresholds, and could have additional effects on inflammation and plaque stability. We discuss the potential role of early implementation of statins combined with PCSK9 inhibitors to influence these cascades and to mediate the associated cardiovascular risk, over and above the well-known long-term beneficial effects of chronic LDL-C lowering.

Intensive management of hyperglycaemia in acute coronary syndromes. Study design and rationale of the BIOMArCS 2 glucose trial.

BACKGROUND: Elevated admission plasma glucose is associated with increased mortality in patients who are admitted with an acute coronary syndrome. This may be mediated by increased inflammation, apoptosis and coagulation, and by a disturbed endothelial function that can be found in hyperglycaemic patients. Insulin has several characteristics that may potentially counteract these mechanisms. METHODS: The BIOMArCS programme is a multi-centre initiative and currently consists of three different studies. The effects of acute coronary syndrome on acute biomarkers washout are studied in the BIOMArCS pilot and the value of biomarkers in predicting upcoming acute coronary syndrome events is studied in BIOMArCS 1. The third study (BIOMArCS 2 glucose), which will be presented here, investigates the effectiveness and safety of intensive glucose level control compared with conventional glucose management in patients with acute coronary syndrome and an admission plasma glucose of 7.8-16 mmol/l. In BIOMArCS 2 glucose, a total of 300 patients without insulin-treated diabetes mellitus will be randomized in a 1:1 ratio to either intensive or conventional glucose management on top of standard medical care. The primary endpoint is infarct size as expressed by the cardiac troponin T level 72 h after admission. To study the metabolic effects of insulin administration, we will investigate biomarker washout patterns of various metabolic mechanisms up to 7 days after admission. These markers will address inflammation, oxidative stress, hypercoagulability, endothelial activation and vasodilatation. IMPLICATIONS: Current acute coronary syndrome guidelines lack a clear strategy for hyperglycaemia treatment. This study will extend our knowledge on this matter as it may clarify mechanisms and generate hypotheses of if and how myocardial infarct size may be limited by glucose management at admission.

Long-term Clinical Outcome and MIBI SPECT Parameters in Percutaneous Coronary Interventions.

BACKGROUND AND AIM: Primary percutaneous coronary intervention (PCI) is the preferred treatment option for acute myocardial infarction (MI). Off-site PCI reduces time-to-treatment, which could potentially lead to enhanced clinical outcomes. Therefore, we investigated whether off-site PCI improves 5-year clinical outcomes compared with on-site PCI and whether this is related to in-hospital (99m)Tc-sestamibi single photon emission computed tomography (MIBI SPECT) parameters. METHODS: We describe the 5-year follow-up for a combined endpoint of death or re-infarction in 128 patients with acute MI who were randomly assigned to undergo primary PCI at the off-site centre (n = 68) or to transferral to an on-site centre (n = 60). Three days after PCI, MIBI SPECT was performed to estimate infarct size. A multivariate Cox regression model was created to study the relation between MIBI SPECT parameters and long-term clinical outcomes. RESULTS: After a mean follow-up of 5.8 ± 1.1 years, 25 events occurred. Off-site PCI significantly reduced door-to-balloon time compared with on-site PCI (94 ± 54 versus 125 ± 59 min, p = 0.003). However, infarct size (17 ± 15 versus 14 ± 12%, p = 0.34) and 5-year death or infarct rate (21% versus 18%, p = 0.75) were comparable between treatment centres. With multivariate analysis, only Killip class ≥2 and Q wave MI, but not scintigraphic data, predicted long-term clinical outcomes. CONCLUSION: Off-site PCI reduced door-to-balloon time with a comparable 5-year death or infarct rate. Parameters from resting MIBI SPECT on day 3 after MI did not predict long-term clinical outcomes.

[Anti-inflammatory therapy in cardiovascular disease; from hypothesis to future guideline?] / Anti-inflammatoire therapie bij hart- en vaatziekten.

Atherosclerosis is a lipid-driven inflammatory disease, in which both lipids and inflammation can be considered treatment targets. The CANTOS-trial, using the IL-1ß monoclonal antibody canakinumab, has proven the concept of targeting inflammation to reduce cardiovascular risk. In contrast, the anti-inflammatory drug methotrexate failed to show cardiovascular benefit. Colchicine is a drug used in gout patients, acting as a non-selective inflammasome inhibitor. The COLCOT-trial uncovered a significant reduction in ischemic cardiovascular events in subjects following an acute myocardial infarction, which was recently confirmed in the larger LoDoCo2-trial in stable coronary heart disease. Guideline committees will have to decide whether the trials have supplied sufficient evidence to implement the routine use of colchicine in the guidelines for cardiovascular risk management. These convincing endpoint trials have paved the way for tailored treatment regimens, comprising anti-inflammatory agents besides currently established treatment modalities in CVRM.

One-year mortality after a first visit to a cardiology outpatient clinic: a useful performance indicator?

PURPOSE: In 2003 the Dutch Health Care Inspectorate introduced performance indicators to monitor and compare quality of care in Dutch hospitals. In 2007, the new performance indicator 'one-year mortality after a first visit to a cardiology outpatient clinic' was introduced. We set out to evaluate this new indicator in three Dutch teaching hospitals. METHODS: Using electronic medical records, information was collected retrospectively of patients aged >/=70 years who visited the cardiology outpatient clinic of Medical Centre Alkmaar, Meander Medical Centre Amersfoort and Deventer Hospital between 1 January 2006 and 31 January 2006. Diagnoses were based on the diagnosis treatment combination (DBC) coding system. RESULTS: 547 patients (mean age 78.0 years, 53% men) were included, 35 (6.4%) of whom had died after one year. Cardiovascular disease was the most frequent cause of death (22/35, 62.9%). The oneyear mortality among the three hospitals varied from 5.0 to 7.3% (NS). CONCLUSION: One-year mortality after the first visit to a cardiology outpatient clinic amounted to 6.4% in patients aged >/=70 years and did not differ significantly between the three Dutch teaching hospitals. The administrative load to obtain the necessary information was considerable. One-year mortality should be regarded as an 'outcome' parameter rather than a 'performance' indicator. (Neth Heart J 2009;17:52-5.).

[Early invasive strategy no better than a selective invasive strategy for patients with non-ST-segment elevation acute coronary syndromes and elevated cardiac troponin T levels: long-term follow-up results of the ICTUS trial]. / Vroeg invasieve behandelstrategie niet beter dan selectiefinvasieve bij patiënten met een acuut coronair syndroom zonder ST-elevatie en met een verhoogde troponinewaarde: langetermijnresultaten van de ICTUS-studie.

OBJECTIVE: To determine whether routine coronary angiography followed by revascularisation where appropriate is better than initial drug treatment in patients with non-ST-segment elevation acute coronary syndromes (nSTE-ACS) and elevated troponin T concentrations. DESIGN: Multicentre randomised clinical trial (www.controlled-trials. com, number: SRCTN82153174). METHOD: Patients with nSTE-ACS and elevated cardiac troponin were randomly assigned to an early invasive strategy or a selective invasive strategy. The early invasive strategy consisted of coronary angiography and revascularisation as indicated within 48 hours. The selective invasive strategy consisted of initial drug therapy; catheterisation was performed if the patient developed refractory angina or recurrent ischaemia. The main endpoints were a composite of death, recurrent myocardial infarction and rehospitalisation for anginal symptoms within 3 years, and all-cause mortality within 4 years. RESULTS: A total of 1200 patients were enrolled from 42 hospitals in the Netherlands. The in-hospital revascularisation rate was 76% in the early invasive group and 40% in the selective invasive group. After 3 years, the cumulative rate for the composite endpoint was 30.0% in the early invasive group and 26.0% in the selective invasive group (hazard ratio 1.21; 95% CI: 0.97-1.50; p = 0.09). The 4-year all-cause mortality rate was similar in both treatment groups (7.9% vs 7.7%; p = 0.62). CONCLUSION: Long-term follow-up of this trial suggests that an early invasive strategy is not better than a selective invasive strategy in patients with nSTE-ACS and elevated cardiac troponin. Therefore, implementation of either strategy is acceptable in these patients.

[Two patients with Eisenmenger syndrome treated with novel agents that target vasodilation of the pulmonary capillary bed]. / Twee patiënten met het syndroom van Eisenmenger behandeld met nieuwe medicijnen gericht op vasodilatatie van het longvaatbed.

Two women with Eisenmenger syndrome, aged 63 and 45 years, presented with different symptoms: the first patient had peripheral oedema, proteinuria, progressive fatigue and cyanosis and the other had increasing dyspnoea and blue lips. The first patient was successfully treated with diuretics but experienced a collum fracture that occurred after hypovolemic collapse caused by diuretic use. She was given sildenafil and underwent hip surgery with spinal anaesthesia 10 days later. In the following weeks, the patient was haemodynamically stable but then died suddenly; no autopsy was performed. The second patient was given oxygen therapy at home and bosentan. After 6 months the symptoms of dyspnoea resolved and her 6-minute walking distance increased from 453 to 512 m. The life expectancy of patients with congenital heart disorders such as Eisenmenger syndrome has improved dramatically, due in part to the efficacy of novel agents that inhibit endothelial-cell proliferation. With these advances, treatment of these patients is no longer restricted to tertiary-care centres. Therefore, community cardiologists, pulmonologists and internists should be aware of these congenital heart disorders and the available treatment options.

[A man with the combination of dry and wet beriberi]. / Een man met de combinatie van droge en natte beriberi.

A 34-year-old alcoholic man had neurological and cardiac symptoms. The patient was admitted to the hospital for acute painful sensory disturbances and severe weakness of the feet. Neurological and electrophysiological investigation revealed axonal sensorimotor polyneuropathy that was most prominent in the legs. Cardiac assessment showed signs and symptoms of heart failure due to a high-output state. Blood analysis showed a low thiamine concentration of 58 nmol/l (lower reference limit: 80). Therefore, a diagnosis of combined wet beriberi with cardiomyopathy and dry beriberi with axonal polyneuropathy was made. The treatment of beriberi is simple and effective and consists of thiamine supplementation in conjunction with diuretic treatment. With this approach, the patient recovered fully. Patients with beriberi have a good prognosis, particularly when the diagnosis is made at an early stage.

Time course of functional recovery of stunned and hibernating segments after surgical revascularization.

BACKGROUND: Recovery of function is possible in patients with ischemic cardiomyopathy when left ventricular dysfunction is caused by stunning or hibernation. It is plausible that recovery of function after revascularization may take a longer time in hibernating myocardium compared with stunned myocardium. Accordingly, the time courses of functional recovery in hibernating and stunned myocardium were compared. METHODS AND RESULTS: Patients (n=26) with ischemic cardiomyopathy undergoing surgical revascularization were studied; regional perfusion (resting (201)Tl single-photon emission CT), glucose utilization ((18)F-2-deoxyglucose single-photon emission CT), and contractile function (2D echocardiography) were assessed before revascularization. Dysfunctional segments with normal perfusion/glucose utilization were considered to be stunned, and dysfunctional segments with reduced perfusion/preserved glucose utilization were considered to be hibernating. Contractile function was reevaluated 3 months (early) and 14 months (late) after revascularization. Of the 266 dysfunctional segments, 57 (22%) were stunned, 62 (23%) were hibernating, and 147 (55%) were scar tissue. In stunned myocardium, contractile function improved significantly at 3 months, without further improvement at 14 months; 61% of the stunned segments improved at 3 months, and 9% improved at 14 months. In hibernating myocardium, contractile function improved at 3 months, with a further improvement at 14 months; 31% of the hibernating segments improved at 3 months, and 61% showed (additional) recovery at 14 months. CONCLUSIONS: Stunned myocardium is likely to demonstrate early recovery of function, whereas hibernating myocardium may take a longer time to (fully) recover in function after revascularization.

Accuracy of currently available techniques for prediction of functional recovery after revascularization in patients with left ventricular dysfunction due to chronic coronary artery disease: comparison of pooled data.

OBJECTIVES: This study evaluated the relative merits of the most frequently used techniques for predicting improvement in regional contractile function after coronary revascularization in patients with left ventricular dysfunction due to chronic coronary artery disease. BACKGROUND: Several techniques have been proposed for predicting improvement in regional contractile function after revascularization, including thallium-201 (Tl-201) stress-redistribution-reinjection, Tl-201 rest-redistribution, fluorine-18 fluorodeoxyglucose with positron emission tomography, technetium-99m sestamibi imaging and low dose dobutamine echocardiography (LDDE). METHODS: A systematic review of all reports on prediction of functional recovery after revascularization in patients with chronic coronary artery disease (published between 1980 and March 1997) revealed 37 with sufficient details for calculating the sensitivity and specificity of each imaging modality. From the pooled data, 95% and 99% confidence intervals were also calculated. RESULTS: Sensitivity for predicting regional functional recovery after revascularization was high for all techniques. The specificity of both Tl-201 protocols was significantly lower (p < 0.05) and LDDE significantly higher (p < 0.01) than that of the other techniques. CONCLUSIONS: Pooled analysis of 37 studies showed that although all techniques accurately identify segments with improved contractile function after revascularization, the Tl-201 protocols may overestimate functional recovery. The evidence available thus far indicates that LDDE appears to have the highest predictive accuracy.

Quantitative angiographic measurements of isolated left anterior descending coronary artery stenosis. Correlation with exercise echocardiography and technetium-99m 2-methoxy isobutyl isonitrile single-photon emission computed tomography.

OBJECTIVES: This study sought to assess the value of quantitative coronary arteriography in predicting an ischemic response at exercise echocardiography and technetium-99m 2-methoxy isobutyl isonitrile (mibi) single-photon emission computed tomography (SPECT) in patients with single-vessel disease of the left anterior descending coronary artery. BACKGROUND: The relation between severity of coronary stenosis and ischemic response to exercise echocardiography and perfusion scintigraphy in patients with single-vessel left anterior descending coronary artery disease is not well established. METHODS: Thirty-one patients without a previous myocardial infarction who had isolated stenosis of varying degrees in the proximal or midportion of the left anterior descending coronary artery were studied. Quantitative arteriographic analysis was used for measurements of percent diameter stenosis and minimal lumen diameter. Exercise-induced wall motion abnormalities by echocardiography and transient perfusion defects by mibi SPECT were considered a positive response. The analysis of sensitivity/specificity and receiver operating characteristic curves was applied to establish the diagnostic power of quantitative coronary arteriography to predict an ischemic response to exercise echocardiography and mibi SPECT: RESULTS: The "best" angiographic cutoff values for predicting a positive exercise echocardiographic and scintigraphic response were similar (diameter stenosis 52%, minimal lumen diameter 1.12 mm for echocardiography; diameter stenosis 49%, minimal lumen diameter 1.20 mm for SPECT). However, the sensitivity/specificity at the cross point was slightly higher (even if not statistically significant) for echocardiography than for SPECT, both for diameter stenosis (81% vs. 67%) and minimal lumen diameter (81% vs. 74%), suggesting that quantitative coronary arteriographic measurements are more closely related to echocardiographic than scintigraphic exercise test results. CONCLUSIONS: The functional significance of a proximal/mid-left anterior descending coronary artery stenosis measured by quantitative coronary arteriography is slightly better related to echocardiographic than scintigraphic markers of exercise-induced myocardial ischemia.

Prognostic value of dobutamine-atropine stress technetium-99m sestamibi perfusion scintigraphy in patients with chest pain.

OBJECTIVES: This study investigated the prognostic value of dobutamine-atropine technetium-99m (Tc-99m) sestamibi single-photon emission computed tomographic (SPECT) myocardial perfusion imaging. BACKGROUND: Dobutamine-atropine Tc-99m sestamibi SPECT imaging is an accurate method for the detection of coronary disease. However, the prognostic value of this stress modality has not been assessed. METHODS: Three hundred ninety-two consecutive patients with chest pain (mean [+/- SD] age 60 +/- 12 years; 220 men, 190 with a previous myocardial infarction) underwent a dobutamine-atropine Tc-99m sestamibi SPECT scintigraphic study. Patients were followed up for 22 +/- 13 months to determine the univariate and multivariate variables associated with hard cardiac events (cardiac death, nonfatal myocardial infarction), to define their event-free survival and to determine whether the extent and severity of reversible perfusion defects correlated with events. RESULTS: Forty-four patients (11%) had hard cardiac events. Multivariate models demonstrated that older age (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.0 to 4.4), history of heart failure (OR 2.6, 95% CI 1.3 to 5.2), abnormal sestamibi scan results (OR 10.0, 95% CI 2.3 to 43.0) and reversible perfusion defects (OR 3.2, 95% CI 1.6 to 6.4) had independent predictive value. Patients without perfusion defects, with fixed defects alone, reversible defects alone and fixed plus reversible defects had annual hard cardiac event rates of 0.8%, 6.8%, 8.1% and 11.6%, respectively. Patients with increasing reversible defect scores had increasing annual event rates of 2.1%, 5.0%, 5.5%, 13.0% and 14.6%, respectively. CONCLUSIONS: Dobutamine-atropine stress Tc-99m sestamibi SPECT imaging provides excellent prognostic information. The single most important independent predictor for future hard cardiac events is an abnormal pattern, and a reversible defect provides additional, independent prognostic information. Moreover, the extent and severity of reversible defects are major determinants for prognosis.

Prediction of recovery of myocardial dysfunction after revascularization. Comparison of fluorine-18 fluorodeoxyglucose/thallium-201 SPECT, thallium-201 stress-reinjection SPECT and dobutamine echocardiography.

OBJECTIVES: We compared three techniques to predict functional recovery after revascularization. BACKGROUND: Recently, fluorine-18 (F-18) fluorodeoxyglucose in combination with single-photon emission computed tomography (SPECT) has been proposed to identify viable myocardium, Thallium-201 reinjection and low dose dobutamine echocardiography are used routinely for this purpose. METHODS: Seventeen patients (mean [+/- SD] left ventricular ejection fraction 36 +/- 11%) were studied. Regional and global ventricular function were evaluated before and 3 months after revascularization by echocardiography and radionuclide ventriculography, respectively. Myocardial F-18 fluorodeoxyglucose uptake (during hyperinsulinemic glucose clamping) was compared with rest perfusion assessed with early thallium-201 SPECT. On a separate day, low dose dobutamine echocardiography and post-stress thallium-201 reinjection SPECT were simultaneously performed. RESULTS: The sensitivities for F-18 fluorodeoxyglucose/thallium-201, thallium-201 reinjection and low dose dobutamine echocardiography to assess recovery were 89%, 93% and 85%, respectively; specificities were 77%, 43% and 63%, respectively. Stepwise logistic regression indicated that F-18 fluorodeoxyglucose/ thallium-201 was the best predictor. In hypokinetic segments, the combination of F-18 fluorodeoxyglucose/thallium-201 and low dose dobutamine echocardiography was the best predictor. Global function improved (left ventricular ejection fraction increased > 5%) in 6 patients and remained unchanged in 11. All three techniques correctly identified five of six patients with improvement. Fluorine-18 fluorodeoxyglucose/thallium-201 identified all patients without improvement; low dose dobutamine echocardiography identified 9 of 11 without improvement; and thallium-201 reinjection identified 6 of 11 patients without improvement. CONCLUSIONS: Fluorine-18 fluorodeoxyglucose/thallium-201 SPECT was superior to the other techniques in assessing functional recovery. Integration of metabolic and functional data is necessary, particularly in hypokinesia, for optimal prediction of improvement of regional function.