Lene Holmvang

Effect of high-intensity statin therapy on atherosclerosis in non-infarct-related coronary arteries (IBIS-4): a serial intravascular ultrasonography study

AIM The effect of long-term high-intensity statin therapy on coronary atherosclerosis among patients with acute ST-segment elevation myocardial infarction (STEMI) is unknown. The aim of this study was to quantify the impact of high-intensity statin therapy on plaque burden, composition, and phenotype in non-infarct-related arteries of STEMI patients undergoing primary percutaneous coronary intervention (PCI). METHODS AND RESULTS Between September 2009 and January 2011, 103 STEMI patients underwent intravascular ultrasonography (IVUS) and radiofrequency ultrasonography (RF-IVUS) of the two non-infarct-related epicardial coronary arteries (non-IRA) after successful primary PCI. Patients were treated with high-intensity rosuvastatin (40 mg/day) throughout 13 months and serial intracoronary imaging with the analysis of matched segments was available for 82 patients with 146 non-IRA. The primary IVUS end-point was the change in per cent atheroma volume (PAV). After 13 months, low-density lipoprotein cholesterol (LDL-C) had decreased from a median of 3.29 to 1.89 mmol/L (P < 0.001), and high-density lipoprotein cholesterol (HDL-C) levels had increased from 1.10 to 1.20 mmol/L (P < 0.001). PAV of the non-IRA decreased by -0.9% (95% CI: -1.56 to -0.25, P = 0.007). Patients with regression in at least one non-IRA were more common (74%) than those without (26%). Per cent necrotic core remained unchanged (-0.05%, 95% CI: -1.05 to 0.96%, P = 0.93) as did the number of RF-IVUS defined thin cap fibroatheromas (124 vs. 116, P = 0.15). CONCLUSION High-intensity rosuvastatin therapy over 13 months is associated with regression of coronary atherosclerosis in non-infarct-related arteries without changes in RF-IVUS defined necrotic core or plaque phenotype among STEMI patients.

Takotsubo cardiomyopathy, a two-stage recovery of left ventricular systolic and diastolic function as determined by cardiac magnetic resonance imaging

AIMS Takotsubo cardiomyopathy (TTC) is an entity mimicking acute myocardial infarction, characterized by transient severe systolic heart failure. Echocardiographic studies suggest that diastolic dysfunction is present in TTC at presentation; however, no reports exist regarding the time course of left ventricular (LV) recovery. This study describes the recovery of LV systolic and diastolic function in TTC. We hypothesized that, in TTC, there is diastolic dysfunction at admission, and that recovery is delayed compared with systolic function. METHODS AND RESULTS We enrolled (consecutively 2010-12) 16 patients (mean age 66, range 39-84 years) diagnosed with TTC and 20 healthy matched controls. We performed cardiac magnetic resonance imaging (CMR) at admission, pre-discharge, and 3-month follow-up. Diastolic function was assessed by LV peak filling rate (LVPFR) and left atrial (LA) emptying volumes. At admission, LV ejection fraction was low, increased at pre-discharge (37 ± 6 vs. 58 ± 6%, P < 0.001), and normalized at follow-up (to 65 ± 5%, P = 0.01). LVPFR did not increase during hospitalization (80 ± 3 vs. 89 ± 4 mL/s/m(2), P = 0.21), but was normalized at follow-up (to 206 ± 19, P < 0.001; controls, 214 ± 13, P = 0.23). During hospitalization, LA passive emptying volume remained low (6 ± 2 vs. 8 ± 3 mL/m(2), P = 0.05) and LA active emptying volume remained high (17 ± 3 vs. 16 ± 3 mL/m(2), P = 0.71), whereas LA conduit volume increased (7 ± 3 vs. 23 ± 4 mL/m(2), P < 0.001). T2-weighted imaging demonstrated non-coronary distributed apical oedema without contrast enhancement. CONCLUSION Patients with TTC undergo fast systolic recovery. However, at discharge, profound diastolic dysfunction is demonstrated by CMR. At follow-up, both LV systolic and diastolic function is normalized in patients with recovered TTC.

Risk factors of late cardiogenic shock and mortality in ST-segment elevation myocardial infarction patients

Background: The incidence of cardiogenic shock (CS) in patients with ST-segment elevation myocardial infarction (STEMI) is as high as 10%. The majority of patients are thought to develop CS after admission (late CS), but the incidence in a contemporary STEMI cohort admitted for primary percutaneous intervention remains unknown. Aim: The aim of this study was to assess the incidence and time of CS onset in patients with suspected STEMI admitted in two high-volume tertiary heart centres and to assess the variables associated with the development of late CS. Methods: We included consecutive patients admitted for acute coronary angiography with suspected STEMI in a 1-year period. Cardiogenic shock was based on clinical criteria and subdivided into patients with shock on admission, patients developing shock during catheterisation and patients developing shock later during hospitalisation. Follow-up for all-cause mortality was done using registries. Results: A total of 2247 patients with suspected STEMI were included, whereof 225 (10%) developed CS. The majority (56%) had CS on admission, 16% developed CS in the catheterisation laboratory and 28% developed late CS. Thirty-day mortality was 3.1% versus 47% in non-CS versus CS patients (plogrank < 0.0001). Age, stroke, time from symptom onset to intervention, anterior STEMI, heart rate/systolic blood pressure ratio and being comatose after resuscitation from cardiac arrest were independently associated with the development of late CS. Conclusion: In this study, 10% of patients admitted with suspected STEMI for acute coronary angiography presented with or developed CS. Most were in shock on admission. Irrespective of the timing of shock, mortality was high.

Takotsubo-cardiomyopathy: A case of extremely fast recovery described by multimodality cardiac imaging

A 67-year-old male was admitted on the suspicionof STEMI due to chest pain after strenuous work, lateralST-elevation on ECG and troponin T 523 ng/L (ref.\50 ng/L). He had hypertension, hypercholesterolaemiaand was an ex-smoker but was otherwise healthy. Acutecoronary angiography showed no culprit lesion butapical ballooning on ventriculography (Figure 1A).Several image modalities were performed as part of aresearch protocol:Cardiac SPECT during resting conditions 15 hours afteradmission (Figure 1B) showed a relative perfusionreductionoftheapexandmidventricularpart,extent40%.Cardiac MRI 22 h after admission (Figure 1C) showedapical ballooning and LVEF 40% (ref. 56%-78%) andbasal hypercontractility, but no sign of infarction.Echocardiography 35 h after admission (Figure 1D)showed an akinetic apex and LVEF 50%.A second cardiac MRI 48 hours after admission(Fig. 1E) showed normalized LVEF 70%, but persis-tent apical hypokinesia and edema.N

Review: Gender differences following percutaneous coronary intervention

PCI is effective for reducing symptoms in patients with stable angina pectoris but does not improve prognosis. In earlier trials PCI has been associated with more procedure related complications in women than men, but this difference between genders has been less pronounced in more recent studies. In acute coronary syndromes there is no evidence of gender differences regarding the benefit of primary PCI for ST-segment elevation myocardial infarction. However, several trials of unstable angina and non-ST-segment elevation myocardial infarction indicate that women do not have the similar benefit of a routine, early, invasive treatment strategy compared with men.

Left Ventricular Hypertrophy Is Associated With Increased Infarct Size and Decreased Myocardial Salvage in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

Background Approximately one third of patients with ST‐segment elevation myocardial infarction (STEMI) have left ventricular hypertrophy (LVH), which is associated with impaired outcome. However, the causal association between LVH and outcome in STEMI is unknown. We evaluated the association between LVH and: myocardial infarct size, area at risk, myocardial salvage, microvascular obstruction, left ventricular (LV) function (all determined by cardiac magnetic resonance [CMR]), and all‐cause mortality and readmission for heart failure in STEMI patients treated with primary percutaneous coronary intervention. Methods and Results In this substudy of the DANAMI‐3 trial, 764 patients underwent CMR. LVH was defined by CMR and considered present if LV mass exceeded 77 (men) and 67 g/m2 (women). One hundred seventy‐eight patients (24%) had LVH. LVH was associated with a larger final infarct size (15% [interquartile range {IQR}, 10–21] vs 9% [IQR, 3–17]; P<0.001) and smaller final myocardial salvage index (0.6 [IQR, 0.5–0.7] vs 0.7 [IQR, 0.5–0.9]; P<0.001). The LVH group had a higher incidence of microvascular obstruction (66% vs 45%; P<0.001) and lower final LV ejection fraction (LVEF; 53% [IQR, 47–60] vs 61% [IQR, 55–65]; P<0.001). In a Cox regression analysis, LVH was associated with a higher risk of all‐cause mortality and readmission for heart failure (hazard ratio 2.59 [95% CI, 1.38–4.90], P=0.003). The results remained statistically significant in multivariable models. Conclusions LVH is independently associated with larger infarct size, less myocardial salvage, higher incidence of microvascular obstruction, lower LVEF, and a higher risk of all‐cause mortality and incidence of heart failure in STEMI patients treated with primary percutaneous coronary intervention. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01435408.

Predictors and prognostic value of left atrial remodelling after acute myocardial infarction

Purpose Left atrial (LA) volume is a strong prognostic predictor in patients following ST-segment elevation myocardial infarction (STEMI). However, the change in LA volume over time (LA remodelling) following STEMI has been scarcely studied. We sought to identify predictors for LA remodelling and to evaluate the prognostic importance of LA remodelling. Methods This is a subgroup analysis from a randomised clinical trial that evaluated the cardioprotective effect of exenatide treatment. A total of 160 patients with STEMI underwent a cardiovascular MR (CMR) 2 days after primary angioplasty and a second scan 3 months later. LA remodelling was defined as changes in LA volume or function from baseline to 3 months follow-up. Major adverse cardiac events were registered after a median of 5.2 years. Results Adverse LA minimum volume (LAmin) remodelling was correlated to the presence of hypertension, larger infarct size by CMR, higher peak troponin T, larger area at risk and adverse left ventricular (LV) remodelling. LA maximum volume (LAmax) remodelling was correlated to larger infarct size by CMR, higher peak troponin T, larger area at risk, larger LV mass, impaired LV function and adverse LV remodelling. Kaplan-Meier and Log Rank analyses showed that patients in the highest tertiles of LAmin or LAmax remodelling are at higher risk (0.030 and p=0.018). Conclusions After a myocardial infarction, LA remodelling reflects a parallel ventricular-atrial remodelling. Infarct size is a major determinant of LA remodelling following STEMI and adverse LA remodelling is associated with an unfavourable prognosis.

Bleeding episodes in “complete, staged” versus “culprit only” revascularisation in patients with multivessel disease and ST-segment elevation myocardial infarction: a DANAMI-3-PRIMULTI substudy

AIMS The aim of this study was to evaluate whether a staged in-hospital complete revascularisation strategy increases the risk of serious bleeding events in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. METHODS AND RESULTS The DANAMI-3-PRIMULTI trial investigated whether a staged in-hospital complete revascularisation strategy improved outcome in patients with STEMI and multivessel disease. In this substudy, we investigated potential bleeding complications related to a second in-hospital procedure. Bleedings were assessed using BARC and TIMI criteria. Six hundred and twenty-seven (627) patients were randomised 1:1 to either PCI of the infarct-related artery (IRA) only (n=313) or complete revascularisation during a staged procedure before discharge (n=314). We found no significant difference in TIMI major+minor bleedings related to the primary PCI. There were neither major nor minor bleedings in relation to the second procedure in the complete revascularisation arm. There were significantly more in-hospital minimal+medical attention bleedings in the group randomised to complete revascularisation (61.5% vs. 49.5% in the IRA-PCI only group, p=0.003), but no difference in admission time or one-year mortality (2.2% complete revascularisation-group vs. 2.6% IRA-PCI only group, p=0.8). CONCLUSIONS In multivessel diseased STEMI patients, a staged complete in-hospital revascularisation strategy or any second in-hospital procedure did not result in an increase in serious bleeding events.

A post hoc analysis of long-term prognosis after exenatide treatment in patients with ST-segment elevation myocardial infarction

AIMS We aimed to assess the effect of exenatide treatment as an adjunct to primary percutaneous coronary intervention (PCI) on long-term clinical outcome. METHODS AND RESULTS We performed a post hoc analysis in 334 patients with a first STEMI included in a previous study randomised to exenatide (n=175) or placebo (n=159) as an adjunct to primary PCI. The primary endpoint was a composite of all-cause mortality and admission for heart failure during a median follow-up of 5.2 years (interquartile range: 5.0-5.5). Secondary endpoints were all-cause mortality and admission for heart failure, individually. The primary composite endpoint occurred in 24% in the exenatide group versus 27% in the placebo group, p=0.44 (HR 0.80, p=0.35). Admission for heart failure was lower in the exenatide (11%) compared to the placebo group (20%) (HR 0.53, p=0.042). All-cause mortality occurred in 14% in the exenatide group versus 9% in the placebo group (HR 1.45, p=0.20). CONCLUSIONS In this post hoc analysis of patients with a STEMI, treatment with exenatide at the time of primary PCI did not reduce the primary composite endpoint or the secondary endpoint of all-cause -mortality. However, exenatide treatment reduced the incidence of admission for heart failure.

Association between QRS duration on prehospital ECG and mortality in patients with suspected STEMI

BACKGROUND QRS duration has previously shown association with mortality in patients with acute myocardial infarction treated with thrombolytics, less is known in patients with suspected ST segment elevation myocardial infarction (STEMI) when assessing QRS duration on prehospital ECG. Thus, the objective was to investigate the prognostic effect of QRS duration on prehospital ECG and presence of classic left and right bundle branch block (LBBB/RBBB) for all-cause mortality in patients with suspected STEMI. METHOD In total 2105 consecutive patients (mean age 64±13years, 72% men) with suspected STEMI were prospectively included. QRS duration was registered from automated QRS measurement on prehospital ECG and patients were divided according to quartiles of QRS duration (<89ms, 89-98ms, 99-111ms and >111ms). Primary endpoint was all-cause 30-day mortality. Predictors of all-cause mortality were assessed using Cox proportional hazards analysis. RESULTS Among all patients median QRS duration was 98ms (IQR 88-112ms). RBBB-morphology was seen in 126 patients (6.0%) and LBBB in 88 patients (4.2%), 80% were treated with percutaneous coronary intervention and the final diagnosis was STEMI in 1777 patients (84%). Thirty-day mortality was 7.6% in patients with suspected STEMI. In multivariable analysis, QRS duration>111ms (hazard ratio (HR) 3.08; 95% confidence interval (CI): 1.71-5.57, p=0.0002), LBBB - morphology (HR 3.0; 95% CI: 1.38-6.53, p=0.006) and RBBB (HR 3.68; 95% CI: 1.95-6.95, p<0.0001) were associated with 30 day all-cause mortality. CONCLUSION In patients with suspected STEMI, QRS prolongation, LBBB, and RBBB on prehospital ECG are associated with increased risk of death.